Antibiotics

Biotechnol Bioeng, 1998 Jun 20, 58(6), 625 - 32
Plasmid maintenance in Escherichia coli recombinant cultures is dramatically, steadily, and specifically influenced by features of the encoded proteins; Corchero JL et al.; A set of eight closely related plasmid constructs carrying CI857-controlled recombinant genes has been used as a model to study plasmid stability in Escherichia coli, in the absence of antibiotic selection . Plasmid loss rates and relative interdivision times of plasmid-bearing cells and plasmid-free cells have been analyzed throughout prolonged cultures . Whereas the calculated plasmid loss rates are not consistent for a given plasmid and set of conditions, the relative growth fitness of plasmid-bearing cells is highly reproducible . In the absence of gene expression, plasmid maintenance is influenced by the length of the cloned segment, the growth temperature, and the plasmid copy number, but not by the plasmid size . At high, inducing temperatures, the effects of the metabolic burden are eclipsed by the toxicity exhibited by the different proteins produced, which is determined by structural features . Despite the multifactorial nature of the negative pressures acting independently on plasmid-bearing cells, the relative cell fitness in a mixed cell population is very reproducible for a given vector, resulting in a monotonous spread of the plasmid-free cells in recombinant cultures .

Nervenarzt, 1999 Feb, 70(2), 167 - 71
{Neuroborreliosis with extensive cerebral vasculitis and multiple cerebral infarcts}; Schmitt AB et al.; We report on a patient who suffered from borreliosis-induced severe cerebral vasculitis accompanied by multiple cerebral infarctions leading to hemiparesis, hemianopsia and reduced consciousness . Despite antibiotic and immunosuppressive therapy with ceftriaxon and prednisolone the patients condition deteriorated . Cerebral angiography showed multiple stenoses of large arteries of the posterior circulation and ubiquitous irregularities of small vessel wails . General reduced perfusion reflected an increased peripheral resistance . After 4 weeks of additional immunosuppressive treatment with cyclophosphamide the neurological status and angiographic findings improved dramatically.

Instr Course Lect, 1999, 48, 177 - 82
Cementless fixation issues in revision total knee arthroplasty; Whiteside LA; Although massive solid allografts can be expected to vascularize and form new bone, variable amounts of replacement as well as collapse and necrosis may be prominent features of these large block allografts . Immunocompatibility seems to be an important factor in allograft healing and incorporation . Large block allograft of the acetabulum appears to be more likely to succeed if autograft is used . Rejection appears to be a significant factor in survival of large allografts . Although bone itself is not highly immunogenic, the role of marrow elements in the cancellous bone graft may be crucial . When possible, marrow contents should be washed carefully from the interstices of cancellous bone to remove cellular elements that do not contribute to osteoinduction but do produce an inflammatory immune response that can compromise healing and bone formation . Washing and soaking the components in antibiotic solution has the additional benefit of making available a reservoir of antibiotic that is released slowly during the postoperative period . Morcellized cancellous bone, rather than finely ground bone which tends to be destroyed by phagocytosis, is the best available choice for reconstructing large volumes of deficient bone stock . Fixation is completely dependent on the existing bone, so that massive defects must be protected until sufficient rigidity develops in the grafted material to allow sharing of weightbearing loads . Clinical experience has shown that migration of the tibial component after reconstruction with morcellized allograft is rare during the first 2 to 5 years after surgery (Fig . 8) . These results are surprising in light of reported experience with structural allografts of the acetabulum . Jasty and Harris reported loosening of acetabular components after 4 years in 32% of their cases . The biologic behavior of morcellized allograft differs from that of block allograft, however . Vascularization and ossification are rapid and a permanent, competent loadbearing structure is achieved by filling large deficient areas . The biologic response obtained with the correct technique appears to be early and vigorous . It does not seem likely that progressive collapse would occur after remodeling and healing have been established (Fig . 9) . Bone graft handling probably is crucial to the success of grafting of the knee . Antibiotic soaking and washing, removal of bone marrow, and adequate support of the implants are all necessary factors for consistent success of this technique . The results of this salvage procedure have been encouraging . The grafting technique appears to provide long-term support for the implants, so that repeat revision is unlikely.

Ter Arkh, 1999, 71(1), 47 - 50
{Masks of subacute infectious endocarditis}; Taranova MV et al.; AIM: Formulation of approaches to differential diagnosis and treatment policy for subacute infectious endocarditis (SIE) when it is masked by another monoorganic or systemic disease . MATERIALS AND METHODS: The course of SIE was analysed in 132 patients of whom 74(56%) had erroneous admittance diagnoses . Rheumocarditis was not confirmed in 34 patients, 24 patients had nonspecific reactions masking SLE (4 cases), glomerulonephritis (7 cases), myocarditis (4 cases), hemorrhagic vasculitis, nodular periarteritis, polymyositis (9 cases) . RESULTS: The "masks" made the SIE diagnosis more difficult, resulted in late or invalid treatment--monotherapy with steroid hormones, in particular . This complicated the diagnostic process and aggravated the disease course . CONCLUSION: To detect SIE it is necessary besides analysis of case record and symptoms to performe echocardiography in dynamics, because of possible late development of valvular defect . High-dose antibiotic therapy is justified for diagnosis of ex juvantibus when the diagnosis remains controversial.

J Nat Prod, 1999 Mar, 62(3), 495 - 6
KR025, a new cytotoxic compound from Myxococcus fulvus; Ahn JW et al.; A new bithiazole, KR-025 (1), was isolated from Myxococcus fulvus . Its structure was elucidated by spectroscopic analysis . In addition to 1, the strain produced relatively large quantities of a second, closely related antibiotic, myxothiazol . These compounds demonstrated potent cytotoxicity against human tumor cells.

Int Surg, 1998 Oct-Dec, 83(4), 277 - 9
Carcinoma of the oesophagus . Anastomotic leaks after manual sutures--incidence and treatment; Baulieux J et al.; Progress in the development of suture materials results in a lower rate of fistulas . Modern techniques for the diagnosis of leakage (contrast study, CT-scan) allow for an early diagnosis and adequate therapy: if possible conservative therapy with drainage of the abscess, adapted antibiotic therapy and parenteral and enteral nutrition are the best methods . In the case of necrosis of the transplant, reoperation permits enables extra time for reconstruction . All the technical possibilities of reconstruction must be known . It is necessary to apply prophylactic precautions to avoid leakage of the anastomosis on the oesophagus.

Biomed Environ Sci, 1998 Dec, 11(4), 363 - 9
Protective efficacy of calcium channel blockers in sulphur mustard poisoning; Mazumder PK et al.; The present study was designed to ascertain the in vivo protective efficacy of Ca(2+)-channel blockers against dermally applied sulphur mustard (SM) . Male albino mice were exposed to 1.5 LD50 of SM (232 mg/kg) percutaneously and the control group received an equal volume of vehicle (polyethylene glycol 300) . Prior to SM application, the animals were administered nifedipine and dextrose saline containing antibiotic by intraperitoneal route . The protection assessed by the mean survival time (MST) was determined by Dunnett's method . The MST was significantly increased in nifedipine treated group . The characteristic biochemical indices of SM intoxication, i.e . lipid peroxidation and reduced glutathione (GSH) were determined in liver from animals sacrificed at 24, 48 and 72 h after exposure . SM application (1 LD50) caused a reduction in GSH level which was restored in nifedipine treated group . SM-induced lipid peroxidation was also prevented by nifedipine administration . The protective effect of nifedipine may be related to its capacity of attenuating SM-induced lipid peroxidation and glutathione depletion.

Antibiot Khimioter, 1999, 44(1), 6 - 10
{Effect of calcium gluconate on the toxicity and antitumor of doxorubicin in mice}; Bogush TA et al.; The effect of calcium gluconate on the toxicity and specific activity of the anthracycline antibiotic doxorubicin was studied on mice with transplanted hemoblastosis La or plasmocytoma MOPS-406 . In both cases after the animal exposure to nontoxic therapeutic doses of doxorubicin no influence of calcium gluconate on the antibiotic antitumor activity was observed . When doxorubicin was used in toxic (and even lethal) doses the antitoxic effect of calcium gluconate and an increase of the antibiotic therapeutic activity were stated . The combination of calcium gluconate and doxorubicin made it possible to significantly increase the maximum therapeutic effect of doxorubicin (higher levels of the animal survival and some cures) and to widen the ranges of the drug therapeutic doses at the account of decreasing the toxicity of the antibiotic and increasing its dose . The results suggested that the antitoxic modifier calcium gluconate could be used for increasing anticancer efficacy of doxorubicin which is given now at the total dose limit of 550 mg/m2 even in cases with preserved tumor sensitivity to the drug.

Eur J Pediatr, 1999 Mar, 158(3), 238 - 42
A detailed analysis of changes in serum C-reactive protein levels in neonates treated for bacterial infection; Ehl S et al.; A prospective study was undertaken to characterize the rate of increase, time of peak values and rates of decrease in serum concentrations of C-reactive protein (CRP) in a group of infants treated for neonatal bacterial infection . A total of 176 consecutively admitted neonates with birth weight > 1500 g and without mechanical ventilation or central lines in situ, who received antibiotic therapy for suspected bacterial infection, were enrolled . The changes in serum CRP concentration in 60 of 63 infants who had CRP values above 20 mg/l 24-48 h after the beginning of treatment were analysed in detail . Initial increase rates in serum CRP levels of up to 4.5 mg/l per h were documented peak were reached at a mean of 19.5 h after antibiotic therapy had been initiated, but in some patients an increase in serum CRP levels occurred up to 40-48 h after the beginning of treatment . The mean serum half-life of CRP in infected neonates was 21 h (range 11.2-38 h) . CONCLUSION: In neonates with bacterial infection (defined by a combination of clinical signs and increased C-reactive protein and immature-total quotient values) no differences in the overall pattern nor in any of the particular phases of the C-reactive protein response curves could be observed between neonates with positive (n = 13) or negative blood cultures (n = 47).

Scand Cardiovasc J, 1999, 33(1), 5 - 8
The significance of oral health and dental treatment for the postoperative outcome of heart valve surgery; Hakeberg M et al.; The objective of this study was to evaluate the significance of preoperative dental treatment for the development of complications in the form of infections during the first postoperative weeks after heart valve surgery . In one group of patients (n = 149), oral health was examined and dental treatment performed 3-6 months prior to heart valve surgery . In a second group (n = 104), oral health was examined postoperatively and these patients did not receive any dental treatment before surgery . Infections were recorded for all patients during the first three weeks after surgery and correlated to the dental status at the time of surgery . Sepsis or endocarditis occurred in 5.4% of the first group and in 1.9% of the second group . Freedom from all infections for the two groups was 55% and 56%, respectively . The results did not reveal any significant differences between the groups regarding patients' oral health at the primary oral examination . The frequencies of postoperative complications such as focal infections, fever and increased CRP were also found to be similar for both groups . The combined scores of complications were 2.1% and 1.8%, respectively . Data from the present study do not support the suggestion that dental intervention will decrease the rate of early complications following heart valve surgery.

Cancer Prev Control, 1998 Aug, 2(4), 179 - 90
Use of granulocyte colony-stimulating factor (G-CSF) in patients receiving myelosuppressive chemotherapy for the treatment of cancer . Provincial Systemic Treatment Disease Site Group; Rusthoven J et al.; GUIDELINE QUESTIONS: 1) Does G-CSF reduce the incidence of important adverse clinical outcomes due to infections in patients with cancer treated with myelosuppressive therapy? 2) Does G-CSF allow maintenance of the chemotherapy dose with the goal of improving survival? OBJECTIVE: To evaluate the evidence for the role of G-CSF in patients receiving myelosuppressive chemotherapy for the treatment of cancer . OUTCOMES: Clinical outcomes reflecting events that may affect quality of life and/or resource utilization (e.g., rates and duration of hospitalization, antibiotic use); outcomes reflecting the effect of treatment on infection rates, tumour response and survival and those related to the biological effect of G-CSF . PERSPECTIVE (VALUES): Evidence was selected, reviewed and synthesized by members of the Provincial Systemic Treatment Disease Site Group (DSG) of the Cancer Care Ontario Practice Guidelines Initiative . Drafts of this document have been circulated and reviewed by members of the Systemic Treatment DSG . The DSG comprises medical oncologists, pharmacists, supportive care personnel and administrators . Evaluation by clinicians was considered in the final practice guideline . Community representatives did not participate in the development of this report but will in future reports . Guidelines approval does require participation by community representatives . QUALITY OF EVIDENCE: Two published guidelines and an update of one guideline were identified . Ten eligible randomized controlled trials published in English were included . BENEFITS: A meta-analysis of data from 8 trials showed that the odds of experiencing febrile neutropenia with G-CSF were significantly reduced (odds ratio 0.38; 95% confidence interval {CI} 0.27 to 0.52; p < 0.00001) . G-CSF reduced the risk of febrile neutropenia by 34% (risk ratio 0.66; 95% CI 0.51 to 0.86; p = 0.0015) . The use of G-CSF was associated with a significant reduction in antibiotic usage and days spent in hospital in 2 trials and had no effect in the other 4 in which it was measured . Five trials reported no difference in overall median survival, with 2 small trials detecting a significant increase related to G-CSF . However, further research is necessary to confirm these results . HARMS: The toxic effects of G-CSF are relatively mild . The most consistent clinical symptom attributed to G-CSF is bone pain, reported in incidence rates ranging from 20% to 50% in 3 trials . Except for one case, reported bone pain was mild . PRACTICE GUIDELINE: In cancer patients receiving myelosuppressive chemotherapy, granulocyte colony-stimulating factor (G-CSF) may be beneficial for some patients . If a reduction in the number of febrile neutropenic episodes, or in the duration of such episodes, is expected to improve quality of life, then G-CSF is a reasonable treatment option for selected patients . A clear justification for the use of G-CSF should be stated . If the objective of using G-CSF is to maintain dose intensity of antitumour agents, then G-CSF can be recommended where reduction in dose intensity has been shown in randomized controlled trials to reduce survival or disease-free survival . Although the evidence is weaker, the Systemic Treatment DSG would support the practice endorsed by other guidelines (American Society of Clinical Oncology, Ontario Drug Benefit Plan) and would recommend G-CSF for patients receiving potentially curative chemotherapy: i) as primary prophylaxis; that is, where dose reductions below a specified level are required because of a known high risk of febrile neutropenia, or ii) as secondary prophylaxis in patients receiving chemotherapy of established efficacy who have suffered a prior serious episode of febrile neutropenia due to the same chemotherapy regimen . The exact cut-off for dose reductions is unknown at this time and ought to be left to the judgement of the clinician . In general, the use of G-CSF for dose reductions lower than 20% is not recommended . (ABSTRACT TRUNCATED)

Dtsch Med Wochenschr, 1999 Feb 26, 124(8), 213 - 6
{Kikuchi-Fusimoto disease: the differential diagnosis of cervical lymphadenitis with recurrent attacks of fever}; Kosch M et al.; HISTORY AND CLINICAL FINDINGS: A 49-year-old, otherwise healthy woman had recurrent fever and lymphadenopathy with leukopenia for nineteen years . Her symptoms prompted successless antibiotic therapy and extensive evaluations of fever of unknown origin . At admission there were several enlarged cervical lymph nodes and subfebrile temperatures . INVESTIGATIONS: Neither laboratory findings nor imaging did show an infectious, rheumatologic or hematologic cause of her symptoms . Histopathological examination of an lymph node biopsy revealed histiocytic, necrotizing lymphadenitis (Kikuchi-Fusimoto disease) as the underlying disease . TREATMENT AND COURSE: After spontaneous resolution without specific therapy the patient is now symptomless and well 9 months after diagnosis . CONCLUSION: Kikuchi-Fusimoto disease is a cause of benign and usually self-limiting lymphadenopathy . Clinicians and pathologists should be aware of this uncommon differential diagnosis since early histologic recognition will minimize potentially and unnecessary evaluations and treatments.

J Colloid Interface Sci, 1999 Apr 15, 212(2), 275 - 279
Drug-Cyclodextrin Association Constants Determined by Surface Tension and Surface Pressure Measurements; Angelova A et al.; The complexation reaction between the amphiphilic peptide antibiotic polymyxin B and naturally occurring cyclodextrins, used as potential drug carriers, was quantitatively evaluated from surface tension measurements at various drug concentrations . The association constant, Ka, of polymyxin B:beta-cyclodextrin inclusion complex formation of 1:1 stoichiometry was determined from the change in the drug interfacial activity upon the addition of beta-cyclodextrin at the excess solution concentration (10(-3) M) . The obtained Ka value is discussed in terms of molecular matching of the host cyclodextrin cavity and the guest drug molecule .

Compr Ther, 1999 Feb, 25(2), 73 - 81
Treatment of bacterial meningitis; Hasbun R et al.; Major epidemiological changes have altered the empiric therapy of patients with bacterial meningitis, a disease with significant morbidity and mortality . We offer recommendations for empiric management decisions and specific antibiotic choices for patients with bacterial meningitis.

Prev Med, 1999 Apr, 28(4), 437 - 44
Preventing tuberculosis among HIV-infected persons: a survey of physicians' knowledge and practices; DeRiemer K et al.; BACKGROUND: Guidelines exist for screening, diagnosing, and preventing tuberculosis (TB) among HIV-infected persons, but their application and utility are unknown . METHODS: We conducted a survey of knowledge and practices among 1,300 physicians in the San Francisco Bay area to assess their practices towards TB among HIV-infected persons . RESULTS: Of 630 respondents, 350 (56%) provided care for HIV-infected persons . Thirty-four percent of the respondents had seen the most recent guidelines for preventing tuberculosis among HIV-infected persons; 65% routinely provide information to HIV-infected patients about the risks of exposure to Mycobacterium tuberculosis; 39% provide annual tuberculin skin testing (TST) to HIV-infected patients without a history of a positive test; 86% knew that >/=5-mm induration is considered a positive TST result in HIV-infected persons; and 47% provide a 12-month regimen of chemoprophylaxis for HIV-infected persons who have a positive TST but not active tuberculosis . Physician specialty and experience with HIV-infected persons were not strongly correlated; experience was a better predictor of correct knowledge and practices . CONCLUSIONS: Many physicians were not aware of the standards of care for preventing tuberculosis among HIV-infected patients, even in a geographic area with a high prevalence of M . tuberculosis and HIV .

J Membr Biol, 1999 Mar 15, 168(2), 183 - 97
Determination of the individual electrical and transport properties of the plasmalemma and the tonoplast of the giant marine alga Ventricaria ventricosa by means of the integrated perfusion/charge-pulse technique: evidence for a multifolded tonoplast; Ryser C et al.; The charge-pulse relaxation spectrum of nonperfused and perfused (turgescent) cells of the giant marine alga Ventricaria ventricosa showed two main exponential decays with time constants of approximately 0.1 msec and 10 msec, respectively, when the cells were bathed in artificial sea water (pH 8) . Variation of the external pH did not change the relaxation pattern (in contrast to other giant marine algae) . Addition of nystatin (a membrane-impermeable and pore-forming antibiotic) to the vacuolar perfusion solution resulted in the disappearance of the slow exponential, whereas external nystatin decreased dramatically the time constant of the fast one . This indicated (by analogy to corresponding experiments with Valonia utricularis, J . Wang, I . Spiess, C . Ryser, U . Zimmermann, J . Membrane Biol . 157: 311-321, 1997) that the fast relaxation must be assigned to the RC-properties of the plasmalemma and the slow one to those of the tonoplast . Consistent with this, external variation of {K+}o or of {Cl-}o as well as external addition of K+- or Cl--channel/carrier inhibitors (TEA, Ba2+, DIDS) affected only the fast relaxation, but not the slow one . In contrast, addition of these inhibitors to the vacuolar perfusion solution had no measurable effect on the charge-pulse relaxation spectrum . The analysis of the data in terms of the "two membrane model" showed that K+- and (to a smaller extent) Cl--conducting elements dominated the plasmalemma conductance . The analysis of the charge-pulse relaxation spectra also yielded the following area-specific data for the capacitance and the conductance for the plasmalemma and tonoplast (by assuming that both membranes have a planar surface): (plasmalemma) Cp = 0.82 * 10(-2) F m-2, Rp = 1.69 * 10(-2) Omega m2, Gp = 5.9 * 10(4) mS m-2, (tonoplast) Ct = 7 . 1 * 10(-2) F m-2, Rt = 14.9 * 10(-2) Omega m2 and Gt = 0.67 * 10(4) mS m-2 . The electrical data for the tonoplast show that (in contrast to the literature) the area-specific membrane resistance of the tonoplast of these marine giant algal cells is apparently very high as reported already for V . utricularis . The exceptionally high value of the area-specific capacitance could be explained - among other interpretations - by assuming a 9-fold enlargement of the tonoplast surface . The hypothesis of a multifolded tonoplast was supported by transmission electronmicroscopy of cells fixed under maintenance of turgor pressure and of the electrical parameters of the membranes . This finding indicates that the tonoplast of this species exhibited a sponge-like appearance . Taking this result into account, it can be easily shown that the tonoplast exhibits a high-resistance (1.1 Omega m2) . Vacuolar membrane potential measurements (performed in parallel with charge-pulse relaxation studies) showed that the potential difference across the plasmalemma was mainly controlled by the external K+-concentration which suggested that the resting membrane potential of the plasmalemma is largely a K+-diffusion potential . After permeabilization of the tonoplast with nystatin the potential of the intact membrane barrier dropped from about slightly negative or positive (-5.1 to +18 mV, n = 13) to negative values (-15 up to -68 mV; n = 8) . This indicated that the cytoplasm of V . ventricosa was apparently negatively charged relative to the external medium . Permeabilization of the plasmalemma by addition of external nystatin resulted generally in an increase in the potential to slightly more positive values (-0.8 to +4.3 mV; n = 5), indicating that the vacuole is positively charged relative to the cytoplasm . These findings apparently end the long-term debate about the electrical properties of V . ventricosa . The results presented here support the findings of Davis (Plant Physiol . 67: 825-831, 1981), but are contrary to the results of Lainson and Field (J . Membrane Biol . 29: 81-94, 1976).

Am J Ophthalmol, 1999 Mar, 127(3), 288 - 93
Visual and anatomic outcomes associated with posterior segment complications after ganciclovir implant procedures in patients with AIDS and cytomegalovirus retinitis; Lim JI et al.; PURPOSE: To determine anatomic and visual acuity outcomes of posterior segment complications after ganciclovir implant surgery . METHODS: We reviewed the medical records of 63 patients with acquired immunodeficiency syndrome who had active cytomegalovirus retinitis in 82 eyes and who underwent 110 consecutive ganciclovir implant procedures . Preoperative and postoperative visual acuity, type of postoperative complication, treatment, and lines of visual acuity change were determined . RESULTS: Thirty-eight eyes of 19 patients had bilateral ganciclovir implant procedures, and 25 eyes of 19 patients underwent two or more ganciclovir implant procedures . Thirteen (12%) of 110 ganciclovir implant procedures developed posterior segment complications: rhegmatogenous retinal detachment in six, vitreous hemorrhage in four, endophthalmitis in two, and cystoid macular edema with epiretinal membrane in one . Treatment included pars plana vitrectomy with silicone oil in two cases and without silicone oil in three cases, scleral buckling in one, intravitreal antibiotic injection in two, and laser photocoagulation in two . Overall, median visual acuity was 20/25 preoperatively . Median follow-up was 6 months for all eyes and 7 months for eyes with complications . Postoperative median visual acuity was 20/25 for eyes without complications vs 20/40 at 1 month, 20/60 at 3 and 6 months, and 20/100 at 12 months in eyes with complications (P < .001) . More eyes with than without complications lost 2 or more lines of visual acuity (P < .001) . CONCLUSION: Postoperative complications occurred in 12% of the ganciclovir implant procedures and were associated with decreased visual acuity despite treatment.

J Pediatr Orthop, 1999 Mar-Apr, 19(2), 143 - 50
Pyomyositis in children and adolescents: report of 12 cases and review of the literature; Spiegel DA et al.; Pyomyositis initially was observed more commonly in the developing world but now is reported with increasing frequency in the United States . The presentation is nonspecific and the differential diagnoses are many . We found the clinical history, laboratory findings, and response to treatment similar to those observed in different areas of the world . Magnetic resonance imaging (MRI) with gadolinium injection, in addition to helping to make the diagnosis, may help differentiate between early and late stages that help guide treatment . Coexisting bone changes (58%) may represent either the sensitivity of MRI to reactive inflammatory changes or the presence of a coexisting osteomyelitis . All patients responded to antibiotics and drainage if abscesses were present . Although the optimal duration of antibiotic therapy remains unclear, a shorter course should be considered in patients with a good clinical response, even when MRI shows nonspecific bony abnormalities . Percutaneous drainage was successful in five cases and may represent an alternative to the traditional surgical approach.

Eur Radiol, 1999, 9(3), 454 - 6
Hemorrhagic necrosis due to peliosis hepatis: imaging findings and pathological correlation; Vignaux O et al.; Peliosis hepatis is an uncommon liver condition characterized by blood-filled cavities . We report the CT, angiographic and MR features of a case of peliosis hepatis with no obvious etiology and spontaneously regressing hemorrhagic necrosis . Helical CT showed multiple peripheral low-density regions with foci of spontaneous high density suggesting the presence of blood component . On MR imaging, the multiple peripheral lesions were hypointense on T1-weighted and hyperdense on T2-weighted images, with bright foci on all sequences suggesting subacute blood . Angiography showed no evidence of tumor or vascular malformation; multiple nodular vascular lesions filling in the parenchymal phase and persisting in the venous phase suggested blood-filled cavities . Pathological examination showed blood-filled spaces with no endothelial lining, characteristic of the parenchymal type of peliosis . Knowledge of the imaging features of hemorrhagic necrosis due to peliosis hepatis is important since it can be responsive to antibiotic therapy . Furthermore, differentiating hemorrhagic necrosis from hepatic abscess avoids dangerous and sometimes fatal percutaneous drainage.

Chest, 1999 Mar, 115(3), 635 - 41
Pharmacoeconomic evaluation of a combination of ipratropium plus albuterol compared with ipratropium alone and albuterol alone in COPD; Friedman M et al.; STUDY OBJECTIVE: To conduct a post hoc pharmacoeconomic evaluation of two double-blind, randomized, prospective, parallel group studies comparing the long-term efficacy and safety of ipratropium combined with albuterol in a single inhalational canister against either bronchodilator agent alone in patients with COPD . Patients: One thousand sixty-seven patients with COPD . METHODS: The dose of each bronchodilator was two puffs four times a day (42 microg of ipratropium bromide, 240 microg of albuterol sulfate) . Pulmonary function testing was performed on days 1, 29, 57, and 85 of treatment . Outcomes, health-care resource consumption, and costs were compared for the three treatment groups over the 85-day study period . A total of 1,067 patients were randomized in the two studies (albuterol alone, n = 347; ipratropium alone, n = 362; albuterol plus ipratropium, n = 358) . RESULTS: Improvement in FEV1 and area under the FEV1 response-time curve from time 0 to 4 h (FEV1AUC0-4) was significantly greater for the combination of albuterol plus ipratropium than either agent alone on all test days . Compared with albuterol, patients receiving ipratropium and ipratropium plus albuterol experienced significantly fewer COPD exacerbations and patient-days of exacerbation . In addition, the increased frequency of exacerbations observed in the albuterol group was associated with a significant increase in the number of patient hospital days and antibiotic and corticosteroid use . As a result, the total cost of treatment over the study period was significantly less for ipratropium ($156 per patient) and ipratropium plus albuterol ($197 per patient) than for albuterol ($269 per patient) . Increased cost-effectiveness, defined as total estimated treatment cost per mean change in FEV1AUC0-4, was observed in both treatment arms containing ipratropium . CONCLUSIONS: The inclusion of ipratropium in a pharmacologic treatment regimen is associated with a lower rate of exacerbations in COPD . The result is lower total treatment costs and improved cost-effectiveness.

Pediatr Transplant, 1997 Nov, 1(2), 124 - 9
Prophylaxis and therapy using liposomal amphotericin B (AmBisome) for invasive fungal infections in children undergoing organ or allogeneic bone-marrow transplantation; Ringden O et al.; Sixty-one children with a median age of 6 years (range 1-16) were given prophylaxis/therapy for 78 courses of treatment with liposomal amphotericin (AmBisome) and were reviewed retrospectively . Thirty-six received allogeneic bone marrow, 22 a liver transplant, 2 kidneys and 1 a liver and kidney . AmBisome was given as prophylaxis in 30 episodes, as treatment for suspected invasive fungal infections (IFI) in 33 and for a verified IFI in 15 . AmBisome prophylaxis was given for a median of 14 days in a dose of 1 mg/kg/day . The median dose of AmBisome was 2.1 mg/kg/day (range 0.9-5.0) . The median duration of therapy was 10 days in children with suspected IFI and 20 days in children with verified IFI . The total dose ranged from 0.025 g up to a maximum of 3.95 g . Proven and probable side effects of AmBisome were a decrease in the level of serum potassium (30/78 cases), renal toxicity (22), an increase in the alkaline phosphatases (24), back pain (2), fever and abdominal pain (2), anaphylactic reaction (1), an increase in the bilirubin level (1), nausea (1), chest pain (1) and fever (1) . Of 31 children with suspected IFI, fever disappeared in 21 (68%) . In 14 verified or suspected IFI cases treated for 5 days or more, the clinical cure rate was 12 (86%) . Eradication of fungi from a deep site was verified in 8/10 and the survival rate from 1 1/2 years to more than 7 years was 7/12 (58%) . We conclude that AmBisome was well tolerated as prophylaxis and therapy in transplanted children, few acute toxic side effects were seen and the cure rate in verified IFI was high.

J Glaucoma, 1999 Feb, 8(1), 46 - 50
Quantification of intraoperative administration of mitomycin-C in filtering surgery with surgical sponge material; Larrosa JM et al.; PURPOSE: To determine the absorption and release of mitomycin-C 0.4 and 0.2 mg/mL from sponge-like specimens of Spongostan film (Ferrosan, Copenhagen, Denmark) and the scleral and conjunctival impregnation in an experimental model of filtering surgery . METHODS: The maximum amount of mitomycin per volume unit that Spongostan is able to absorb was determined physically as the difference between dry weight and soaked weight . Mitomycin-C activity in known volumes of Spongostan after mitomycin-C release in vitro also was determined at 0, 1, 10, and 30 seconds and 1, 3, 5, 10, 15, and 30 minutes . Antibiotic activity of the specimens was evaluated by means of bioassay . Millimeters of inhibition of bacterial growth were related to microg of mitomycin activity according to a reference curve obtained from known amounts of mitomycin-C . Finally, 10 eyes of 10 rabbits underwent filtering surgery with intraoperative application of mitomycin by means of the Spongostan film . The Spongostan implants then were removed and tested for mitomycin activity . Scleral and conjunctival specimens were obtained for bioassay . RESULTS: The maximum capacity of 25 mm2 x 0.5 mm thick Spongostan films saturated in 0.4 and 0.2 mg/mL solutions of mitomycin-C were 8.49 microg and 4.23 microg, respectively . Biologic activity (bioassay determination) was 8.24 microg and 4.19 microg of mitomycin-C, respectively . In vitro release of mitomycin was gradual until 30 minutes . In vivo mitomycin release from Spongostan after 5 minutes was 6.91 microg . Impregnation with the antimitotic was better in conjunctiva than sclera . CONCLUSION: Bioassay permits quantification of mitomycin-C activity . The release from sponge specimens is gradual, and impregnation was better in conjunctiva than sclera.

Clin Exp Rheumatol, 1999 Jan-Feb, 17(1), 81 - 7
Tuberculosis prophylaxis in patients with steroid treatment and systemic rheumatic diseases . A case-control study; Hernandez-Cruz B et al.; OBJECTIVE: The aim of this study was to assess the impact of isoniazid prophylaxis in patients with systemic rheumatic diseases who attended a teaching hospital in Mexico City between 1987 and 1992 . METHODS: In this case-control study, patients with systemic rheumatic diseases and tuberculosis (cases) were compared with patients with systemic rheumatic diseases without tuberculosis (controls) . The groups were matched by year of hospital admission and rheumatic disease . Clinical charts were reviewed for: 1) isoniazid prophylaxis, defined as the administration of isoniazid 300 mg/day for 6 or more months in patients with exposure to steroids (prophylaxis with isoniazid was defined as complete, incomplete or any prophylaxis); 2) exposure to steroids: defined as the administration of prednisone > 15 mg/day (or its equivalent of another steroid) for 3 or more months before tuberculosis or recruitment into the study; 3) exposure to immunosuppressants, defined as the administration of any dose of azathioprine, methotrexate, cyclophosphamide, and/or 6-mercaptopurine, before tuberculosis in the cases or recruitment date in the controls; 4) reactivity to PPD; and 5) other relevant variables . RESULTS: Twenty cases and 66 controls were studied . A 70% decrease in the risk of developing tuberculosis was found among patients who received any prophylaxis with isoniazid as compared to controls: OR 0.31, 95% CI 0.09-0.98, p = 0.03 . A 97% decrease was seen in those patients who received complete prophylaxis: OR 0.034, 95% CI 0.0001-0.216, p < 0.0001 . The protective effect of complete prophylaxis persisted even after controlling for other potential confounders, such as age, gender, rheumatic disease, duration of rheumatic symptoms, and exposure to steroids and/or immunosuppressants . CONCLUSION: The results of this study suggest that in countries with a high prevalence of tuberculosis the use of isoniazid (300 mg/day for 6 months) in rheumatic patients with exposure to prednisone (> 15 mg/day for three or more months) may be useful to prevent tuberculosis, independently of the results of the PPD reactivity test . However, a controlled clinical trial will be required to confirm these results.

Vestn Otorinolaringol, 1998, (6), 34 - 6
{Bronchopulmonary complications in patients with laryngeal cancer: features of preoperative care}; Smetanin IG et al.; 582 case records of patients with cancer of the larynx have been examined for associated bronchopulmonary disease . Bronchopulmonary complications were registered in 90.7, 38.9% of patients with tracheostoma and without it, respectively, in 21.3% of control patients . The original trial included 80 patients of the study group and 50 control patients . The study of blood gases and acid-base balance, external respiration function has revealed compensated acidosis in both groups (more pronounced in the study group before operation), respiratory distress in the study group . The removal of the tumor resulted in improvement of the external respiration and normalization of blood gases and acid-base balance . A complex of diagnostic, therapeutic and prophylactic measures is proposed against bronchopulmonary complications in laryngeal cancer.

Vet Res, 1999 Jan-Feb, 30(1), 39 - 47
Pharmacokinetics, bioavailability and dosage regimen of sulphadimidine in camels (Camelus dromedarius) under hot, arid environmental conditions; Kumar R et al.; A two-way crossover study was conducted in young Bikaneri camels (aged between 12 and 18 months) during the hot summer season to determine the bioavailability, pharmacokinetics and dosage regimens of sulphadimidine (SDM) . A dose of 100 mg.kg-1 of SDM was used to study both the intravenous and oral pharmacokinetics of the drug . Analysis of the intravenous data according to a two-compartment pharmacokinetic model revealed that SDM was well distributed in the body (Vd(area):0.862 L.kg-1), had an overall body clearance of 0.035 +/- 0.019 L.h-1.kg-1 and the elimination of half-lives was in the range of 14.2 to 20.6 h . The mean maximum plasma SDM concentration following oral administration was 63.23 +/- 2.33 micrograms.mL-1, which was achieved 24 h after the oral administration . The mean bioavailability of SDM following oral administration was approximately 100% . To achieve and maintain the therapeutically satisfactory plasma sulphadimidine levels of > or = 50 micrograms.mL-1, the optimum dosage regimen for camels following either intravenous or oral administration would be 110 mg.kg-1 as the priming dose and 69 mg.kg-1 as the maintenance dose, to be repeated at 24 h intervals.

Biopolymers, 1999 Apr, 49(4), 329 - 40
Identification of unusual amino acids in peptides using automated sequential Edman degradation coupled to direct detection by electrospray-ionization mass spectrometry; Walk TB et al.; The determination of the primary structure of peptides and proteins is routine in many laboratories; however, many of the obtained sequences are incomplete or can be misinterpreted when the samples contain unusual amino acids . Here we report the development of an automated peptide sequenator coupled to an electrospray-ionization (ESI) mass spectrometer (MS) that, in conjunction with minor modifications to the sequencing conditions and, in some cases, prior derivatization of amino acids, allows the detection of the phenylthiohydantoin (PTH) derivatives of a number of unusual amino acids . Using the coupled sequenator-ESI-MS system we were able to determine the complete sequence of the lantibiotic gallidermin, a partial sequence of the calcium-dependent peptide antibiotic CDA2 as well as the pool sequence of a mixture of synthetic peptides containing nonproteinogenic amino acids . In addition to the 20 proteinogenic amino acids, the procedure was able to detect PTH derivatives of hydroxyphenylglycine, 2,3-didehydroasparagine, 3-methylglutamic acid, oxytryptophan, ornithine, N-methylglycine, dihydroxyphenylalanine, and alpha-aminoisobutyric acid . Similarly, after a simple derivatization procedure, we were also able to correctly identify educts of 2,3-didehydroalanine, 2,3-didehydrobutyrine, lanthionine, and 3-methyllanthionine.

J Am Coll Cardiol, 1999 Mar, 33(3), 788 - 93
A critical appraisal of the quality of the management of infective endocarditis; Delahaye F et al.; OBJECTIVES: The purpose of this study was to assess the quality of the management of infective endocarditis . BACKGROUND: Although many guidelines on the management of infective endocarditis exist, the quality of this management has not been evaluated . METHODS: We collected data on all patients (116) hospitalized with infective endocarditis over 1 year in all hospitals in the Rhone-Alpes region (France) . RESULTS: Prophylactic antibiotics were not given before infective endocarditis to 8/11 cardiac patients at risk and who underwent an at risk procedure . Among the 55 cardiac patients at risk and with fever and who consulted a physician, blood cultures were not performed before antibiotic therapy was initiated for 32 patients . In-hospital antibiotic therapy was incorrect for 23 patients . The portal of entry was not treated for 16/61 patients with an accessible portal of entry . Among the 19 patients who had severe heart failure or fever persisting more than 2 weeks in spite of antibiotic therapy and who could have undergone early surgery, surgery was delayed for five, and not performed for three . Overall, the average score was 15/20 . CONCLUSIONS: More information on the management of infective endocarditis should be widely disseminated to the physicians' and the dentists' communities and to the patients at risk.

Aust N Z J Ophthalmol, 1999 Feb, 27(1), 75 - 8
Lacrimal gland abscess: two case reports; McNab AA; BACKGROUND: Bacterial dacryoadenitis is rare and suppuration leading to abscess formation within the lacrimal gland has been very rarely reported in the antibiotic era . METHODS: The medical records and investigation results, including computed tomography (CT), of two patients with lacrimal gland abscess were reviewed . RESULTS: Two cases of lacrimal gland abscess, one a 28-year-old male and the other a 64-year-old female, are described . Both demonstrated a characteristic low-density area within an enlarged lacrimal gland on CT . The first case had been treated with antibiotics and the abscess, when drained, was sterile . The second case settled spontaneously . Neither patient suffered any sequelae of dry eye . CONCLUSIONS: Although rare, lacrimal gland abscess may still occur and may require surgical drainage if spontaneous resolution does not occur.

J Microencapsul, 1999 Mar-Apr, 16(2), 181 - 94
Cephradin-plaga microspheres for sustained delivery to cattle; Ustariz-Peyret C et al.; In the field of controlled drug delivery, most of the reported work is aimed at introducing new systems, or at providing basic information on the critical parameters which affect release profiles in vitro and occasionally in vivo . The situation is totally different when one wants to fulfil the specific requirements imposed by the marketing of a sustained release device to be used in humans or in animals eaten by human beings . The control of the release characteristics is then a difficult challenge . In this work, attempts were made to combine cephradin, a hydrophilic beta-lactam antibiotic, and bioresorbable polymeric matrices of a poly(alpha-hydroxy acid) in the form of microspheres with the aim of delivering the antibiotic to cattle at a dose rate of 4-5 mg/kg/day over a 3-4 days period after i.m . injection . PLAGA aliphatic polyesters were selected because they are already FDA approved as matrices . The solvent evaporation technique using PVA as the emulsion stabilizer was selected because it is efficient and can be extended to an industrial scale . Various experimental conditions were used in order to obtain the highest encapsulation yields compatible with the desired specifications . Decreasing the volume of the aqueous phase and adding a water-miscible organic solvent/non-solvent of cephradin failed . In contrast, microspheres containing up to 30% cephradin were prepared after addition of sodium chloride to the aqueous dispersing phase . The amount of entrapped drug was raised to 40% by decreasing the temperature and the pressure . Preliminary investigations using dogs showed that 20% cephradin microspheres prepared under these conditions extended the presence of cephradin in the blood circulation up to 48 h . Increasing the load led to higher blood concentrations but shorter sustained release . The fact that the microspheres were for cattle limited the volume of the injection and thus the amount of microspheres to be administered . The other limiting factors were related to microsphere morphology.

Chest Surg Clin N Am, 1999 Feb, 9(1), 113 - 24, ix
Noninfectious immunologic disorders in adults; Bensch G et al.; This article covers a variety of immunologic defects and discusses their potential side effects, with an emphasis on immunodeficiencies with survival into adulthood . To organize the approach to immunodeficiencies, the immune system is broken down broadly into four major components: the complement cascade, antibody (B cell)-mediated immunity, cellular (T cell)-mediated immunity, and phagocytosis.

Chest Surg Clin N Am, 1999 Feb, 9(1), 19 - 38
The initial pulmonary evaluation of the immunocompromised patient; Walsh FW et al.; Practical approaches to the initial evaluation of solid organ transplant patients, BMT patients, and HIV-infected patients with pulmonary disease are summarized in Figures 2, 3, and 4 . These algorithms are meant to be used as guidelines for the clinician . The clinical setting will ultimately determine the extent and speed of the evaluation . Patients who are recipients of solid organ transplants and have pulmonary symptoms may have focal or diffuse changes or may have normal chest radiographs . In all these groups, sputum is obtained by expectation . If a pathogen is found in any of the groups, it is treated . When no pathogen is found on sputum examination in patients with focal disease, empiric antibiotic therapy is given . If the patients do not improve on the empiric antibiotics, then bronchoscopy is performed . Some centers proceed directly to bronchoscopy before antibiotics are started in the hope of directing antibiotic therapy . Patients who have a normal CXR or diffuse infiltrates and no identified pathogen on examination of sputum undergo bronchoscopy, and the protocol is followed until a diagnosis is made (see Fig . 2) . Patients who have received a BMT and who present with pulmonary symptoms are treated as shown in Figure 3 . The CXR will reveal if the infiltrate is focal or diffuse . Those with focal infiltrates are treated with broad-spectrum antibiotics for 48 to 72 hours . If the symptoms and signs do not show some resolution, then bronchoscopy is usually performed . The effect of diffuse infiltrates in BMT patients depends to a large extent how far along in recovery from the transplant the patient is when they develop the infiltrates . During the first 30 days posttransplant, pulmonary edema commonly occurs, and the infiltrates may resolve with diuresis . If the patient is not clinically fluid overloaded or they do not respond to the diuretic therapy, then bronchoscopy with BAL is indicated . Finally, many HIV-infected patients may present with pulmonary symptoms . They may have a normal CXR or a diffuse or focal pattern (Fig . 4) . All patients are subjected to sputum induction to identify a pathogen . If one is identified, it is treated . Should the patient not respond to treatment adequately or a pulmonary pathogen is not found, then bronchoscopy with BAL, protected specimen brush, or a transbronchial biopsy is attempted . The above schema is a general guideline to the initial evaluation of pulmonary disorders in the ICP . The respiratory abnormality is found in most of the cases if these algorithms are closely followed . If the patient does not improve or deteriorates further, additional diagnostic procedures such as video-assisted thorascopic lung biopsy or CT-directed transthoracic needle biopsy may be needed.

Antibiot Khimioter, 1998, 43(12), 8 - 11
{Organofluorine derivatives of amphotericin B: synthesis and antifungal activity}; Shenin IuD et al.; Reactions of amphotericin B, a polyene macrolide antibiotic, with acyl perfluorides resulted in formation of its N-perfluoroacyl derivatives . Physicochemical and medicobiological properties of the derivatives were studied . The biological study revealed that the acute toxity (LD50) of the derivatives was 2 times as low as that of the starting antibiotic . The derivatives showed high antifungal activity against a great number of the test cultures.

JAMA, 1999 Mar 10, 281(10), 927 - 30
A cluster of transfusion-associated babesiosis cases traced to a single asymptomatic donor; Dobroszycki J et al.; CONTEXT: The risk of acquiring babesiosis by blood transfusion is largely unknown since in areas where it is endemic it is often an asymptomatic infection . OBJECTIVE: To investigate and treat a cluster of blood transfusion-associated babesiosis cases . DESIGN: Case series and epidemiologic investigation . SETTING: Urban inner-city hospital . PATIENTS: Six persons who received Babesia microti-infected blood components from a donor . MAIN OUTCOME MEASURE: Diagnosis and successful therapy of babesiosis following transfusion . RESULTS: Six individuals (1 adult, 1 child, and 4 neonates) were exposed to products from a single blood donation by an asymptomatic Babesia-infected donor . Three of the 6 exposed patients became parasitemic . Polymerase chain reaction testing, animal inoculation studies, and indirect immunofluorescent antibody testing were used to confirm the presence of Babesia microti in the donor's blood and to establish the presence of infection in 3 of the 6 recipients . The 3 infected recipients and 1 additional recipient were treated without incident . CONCLUSION: Physicians should consider babesiosis in the differential diagnosis of a febrile hemolytic disorder after blood transfusion . Prompt diagnosis is important since babesiosis is responsive to antibiotic therapy and, untreated, can be a fatal disease in certain risk groups.

Cancer Gene Ther, 1999 Jan-Feb, 6(1), 37 - 44
Regression of intracerebral rat glioma isografts by therapeutic subcutaneous immunization with interferon-gamma, interleukin-7, or B7-1-transfected tumor cells; Visse E et al.; Progress in the definition of the roles of various costimulators and cytokines in determining the type and height of immune responses has made it important to explore genetically altered tumor cells expressing such molecules for therapeutic immunizations . We have studied the effect of therapeutic subcutaneous (s.c.) immunizations on the growth of preexisting intracerebral brain tumor isografts in the rat . Transfectant glioma cell clones expressing either rat interferon-gamma (IFN-gamma), rat interleukin-7 (IL-7), or rat B7-1 were selected . After irradiation (80 Gy) the clones were used for immunization (administered in up to four s.c . doses in a hind leg over 14-day intervals starting 1 day after the intracranial isografting of the parental tumor) . Significant growth inhibition of the intracerebral parental tumors was induced by transfectants expressing IFN-gamma and IL-7, respectively . The strongest effect was observed with IFN-gamma-expressing cells, resulting in cures in 37% of the males and in 100% of the females . Immunization with IL-7 had a similar, strong initial effect, with significantly prolonged survival in the majority of the rats but a lower final cure rate (survival for >150 days) . The B7-1-expressing tumor clones induced cures in seven of eight female rats; however, no cures were seen in the male rats . It was also shown that the B7-1-expressing cells were themselves strongly immunogenic in female rats, requiring high cell numbers to result in a progressively growing tumor upon s.c . isografting; this was not the case in male rats . As a whole, the results imply that despite the unfavorable location of intracerebral tumors, therapeutic s.c . immunizations with certain types of genetically altered tumor cells can induce complete regressions with permanent survival and without gross neurological or other apparent signs of brain damage . The present results demonstrate complete regressions when immunizations are initiated shortly after intracranial isografting, when the intracerebral tumor is small.

J Chemother, 1999 Feb, 11(1), 40 - 5
Influence of fever on cefazolin pharmacokinetics; Beovic B et al.; The influence of fever on the pharmacokinetics of cefazolin was investigated in patients with acute febrile diseases . Nine patients were included in the study . Antibiotic serum concentrations were determined using high performance liquid chromatograpy (HPLC) . An analog computer and the SIMULINK software package were used to identify the pharmacokinetic model and PCNONLIN software package to obtain the secondary parameters . In 6 patients a two-compartment pharmacokinetic model of cefazolin was observed during fever and after defervescence . In 2 patients a two-compartment model changed to a one-compartment after defervescence, and a one-compartment model was observed in one patient during both periods . Cefazolin-treated patients with a two-compartment model (6/9) had higher Cmax, mean steady state serum concentrations (Css), and area under the plasma concentration-time curve (AUC(0-->infinity)), smaller central compartment volume (V1), and lower clearance (Cl) during fever . The varying distribution of antibiotics during fever probably reflects different hemodynamic responses to fever.

Jpn J Antibiot, 1998 Dec, 51(12), 746 - 58
{Clinical efficacy of sulbactam/ampicillin in comparison with cefotiam in the treatment of elderly patients with pneumonia}; Ishibashi T et al.; Clinical efficacy and safety of pareteral sulbactam/ampicillin (SBT/ABPC) was compared with cefotiam (CTM) in a randomized clinical trial of pneumonia in the elderly at 13 National Hospitals of Kyushu island . 37 patients received SBT/ABPC 3 g i.v., b.i.d., and 31 patients received CTM 1 g i.v., b.i.d . for 7 to 14 days . 1 . 68 patients (37 for SBT/ABPC and 31 for CTM) were evaluated for safety . No statistical differences were noted in the patients' backgrounds of either group . 2 . The clinical efficacy of SBT/ABPC was 96.3% (26/27 cases) while CTM was 75.2% (17/23 cases) . This was found to be statistically significant (Fisher's exact test: p < 0.05) . 3 . 100% of evaluated cases (10 for SBT/ABPC and 4 for CTM) showed bacterial elimination . 4 . No side effects were observed in the study . 5 . Abnormal laboratory findings were noted in 10.8% (4/37 cases) for SBT/ABPC and 3.2% (1/31 cases) for CTM . The major adverse events were mild elevation of GOT, GPT and A1-P for SBT/ABPC, and mild platelets overproduction for CTM . No statistical differences were noted in both groups . These results are consistent with SBT/ABPC as a highly effective antibiotic in the treatment of elderly patients with pneumonia.

Heart Lung, 1999 Mar-Apr, 28(2), 134 - 41
Stenotrophomonas maltophilia infection and colonization in the intensive care units of two community hospitals: A study of 143 patients; Gopalakrishnan R et al.; Study Objective: To study the epidemiology of Stenotrophomonas maltophilia infections in the intensive care units (ICUs) of community general hospitals . DESIGN: Retrospective chart review of 143 patients with cultures positive for S . maltophilia over a 2-year period . SETTING: Intensive care units of 2 community general hospitals . RESULTS: Patients with S . maltophilia infection or colonization were elderly (mean age 62.4 years), intubated for a mean of 11.8 days, and had a mean Acute Physiology and Chronic Health Evaluation II (APACHE II) score of 16.6 . A tracheostomy was present in 22.4%, and underlying chronic respiratory disease and malignancy were found in 25.9% and 15.4%, respectively . Only 2 patients (1.4%) were neutropenic . Most isolates (89.5%) were from the respiratory tract and were part of a polymicrobial culture in 52 . 5% of patients . Only a slightly higher APACHE II score (mean = 18.0, SD 7.8 vs mean = 15.6, SD 6.2, P = 0.052) differentiated patients with infection from those with colonization . All but 2 patients were exposed to antibiotics before their positive culture . Crude mortality rate was 41.3% overall and was significantly higher in those with an APACHE II score of 15 or more (48.8% vs 30.5%, P = 0 . 028) . CONCLUSION: S . maltophilia is emerging as an important cause of nosocomial infection, especially pneumonia, in ICUs of community general hospitals . Patients tend to be elderly, intubated for a mean of about 12 days, have high APACHE II scores, and frequently have a tracheostomy or underlying chronic respiratory disease . In contrast to earlier reports, neutropenia and underlying malignancy are uncommon in our ICU population . We found prior antibiotic exposure was almost universal and similar to previous reports, but use of imipenem was much less common in our community hospital patients . Patients with a high APACHE II score should be considered infected rather than colonized, but differentiation of infection from colonization remains problematic . Isolation of S . maltophilia from a patient carries a crude mortality rate of 41.3%, and patients with an APACHE II score of 15 or more have a significantly higher mortality rate than those with lesser scores, approaching 50% . Trimethoprim-sulfamethoxazole (TMP-SMX) remains the drug of choice for infections caused by S . maltophilia.

Biochim Biophys Acta, 1999 Feb 4, 1449(1), 25 - 40
Cycloheximide and 4-OH-TEMPO suppress chloramphenicol-induced apoptosis in RL-34 cells via the suppression of the formation of megamitochondria; Karbowski M et al.; Toxic effects of chloramphenicol, an antibiotic inhibitor of mitochondrial protein synthesis, on rat liver derived RL-34 cell line were completely blocked by a combined treatment with substances endowed with direct or indirect antioxidant properties . A stable, nitroxide free radical scavenger, 4-hydroxy-2,2,6, 6-tetramethylpiperidine-1-oxyl, and a protein synthesis inhibitor, cycloheximide, suppressed in a similar manner the following manifestations of the chloramphenicol cytotoxicity: (1) Oxidative stress state as evidenced by FACS analysis of cells loaded with carboxy-dichlorodihydrofluorescein diacetate and Mito Tracker CMTH2MRos; (2) megamitochondria formation detected by staining of mitochondria with MitoTracker CMXRos under a laser confocal microscopy and electron microscopy; (3) apoptotic changes of the cell detected by the phase contrast microscopy, DNA laddering analysis and cell cycle analysis . Since increases of ROS generation in chloramphenicol-treated cells were the first sign of the chloramphenicol toxicity, we assume that oxidative stress state is a mediator of above described alternations of RL-34 cells including MG formation . Pretreatment of cells with cycloheximide or 4-hydroxy-2,2, 6,6-tetramethylpiperidine-1-oxyl, which is known to be localized into mitochondria, inhibited the megamitochondria formation and succeeding apoptotic changes of the cell . Protective effects of cycloheximide, which enhances the expression of Bcl-2 protein, may further confirm our hypothesis that the megamitochondria formation is a cellular response to an increased ROS generation and raise a possibility that antiapoptotic action of the drug is exerted via the protection of the mitochondria functions.

Ann Vasc Surg, 1999 Mar, 13(2), 130 - 40
Comparison of healing in fresh and preserved arterial allografts in the dog; Marois Y et al.; The use of aortic allografts for the management of vascular prosthetic infections has recently been reintroduced . Impressive results have been obtained; however, the possibility of late degeneration remains a major concern . The healing behavior of aortic allografts, either fresh or preserved, in antibiotic-supplemented nutrient medium at 4 degrees C for 1 week and used as thoracic aorta substitutes in dogs was investigated after 6 months of implantation . Four dogs received a fresh aortic allograft from four different donors, and four dogs received a preserved allograft from two different donors . Autografts in two dogs were performed as controls . The in vivo investigation was conducted to describe (1) the histological characteristics of the arterial wall, (2) the macroscopic and thrombogenic aspect of the luminal surface, (3) the integrity of the endothelial lining by scanning electron microscopy, and (4) its biochemical function by prostacyclin (PGI2) and thromboxane A2 (TXA2) secretion . Immune-mediated reactions directed toward the grafts were measured by sequential screening of donor-specific serum antibody development . All donor-recipient pairs of dogs were major histocompatibility complex (MHC)-incompatible according to a mixed lymphocyte reaction (MLR) assay . From the results of this study we concluded that although preserved arterial allografts exhibited similar surface characteristics as those of fresh allografts in terms of re-endothelialization and long-term graft function, an elicited immune response, a degenerative process in the media, and a hyperplasic reaction in the intima could not be prevented using this method of preservation.

N Engl J Med, 1999 Mar 11, 340(10), 764 - 71
Liposomal amphotericin B for empirical therapy in patients with persistent fever and neutropenia . National Institute of Allergy and Infectious Diseases Mycoses Study Group; Walsh TJ et al.; BACKGROUND: In patients with persistent fever and neutropenia, amphotericin B is administered empirically for the early treatment and prevention of clinically occult invasive fungal infections . However, breakthrough fungal infections can develop despite treatment, and amphotericin B has substantial toxicity . METHODS: We conducted a randomized, double-blind, multicenter trial comparing liposomal amphotericin B with conventional amphotericin B as empirical antifungal therapy . RESULTS: The mean duration of therapy was 10.8 days for liposomal amphotericin B (343 patients) and 10.3 days for conventional amphotericin B (344 patients) . The composite rates of successful treatment were similar (50 percent for liposomal amphotericin B and 49 percent for conventional amphotericin B) and were independent of the use of antifungal prophylaxis or colony-stimulating factors . The outcomes were similar with liposomal amphotericin B and conventional amphotericin B with respect to survival (93 percent and 90 percent, respectively), resolution of fever (58 percent and 58 percent), and discontinuation of the study drug because of toxic effects or lack of efficacy (14 percent and 19 percent) . There were fewer proved breakthrough fungal infections among patients treated with liposomal amphotericin B (11 patients {3.2 percent}) than among those treated with conventional amphotericin B (27 patients {7.8 percent}, P=0.009) . With the liposomal preparation significantly fewer patients had infusion-related fever (17 percent vs . 44 percent), chills or rigors (18 percent vs . 54 percent), and other reactions, including hypotension, hypertension, and hypoxia . Nephrotoxic effects (defined by a serum creatinine level two times the upper limit of normal) were significantly less frequent among patients treated with liposomal amphotericin B (19 percent) than among those treated with conventional amphotericin B (34 percent, P<0.001) . CONCLUSIONS: Liposomal amphotericin B is as effective as conventional amphotericin B for empirical antifungal therapy in patients with fever and neutropenia, and it is associated with fewer breakthrough fungal infections, less infusion-related toxicity, and less nephrotoxicity.

Anesth Analg, 1999 Mar, 88(3), 654 - 8
Rabbits treated with chronic isepamicin are resistant to mivacurium and rocuronium; Kim KS et al.; We compared the dose-response relationships and the neuromuscular blocking effects of mivacurium and rocuronium after chronic isepamicin therapy for 7 days in 56 anesthetized rabbits . Train-of-four stimuli were applied every 10 s to the common peroneal nerve, and the force of contraction of the tibialis anterior muscle was measured . Chronic isepamicin therapy is associated with a rightward shift of the mivacurium and rocuronium dose-response curves . The effective dose for 50% twitch depression of mivacurium and rocuronium increased significantly, from 16.9 +/- 4.8 and 56.5 +/- 5.3 microg/kg, respectively, with placebo to 30.6 +/- 5.3 and 75.6 +/- 4.7 microg/kg, respectively, during isepamicin therapy . The isepamicin rabbits receiving mivacurium 0.18 mg/kg or rocuronium 0.6 mg/kg had an accelerated recovery from neuromuscular blockade compared with those receiving placebo . The results of this study show that mivacurium and rocuronium have both a decreased effect and a shorter duration of action in rabbits when used during concurrent isepamicin therapy . IMPLICATIONS: We studied the dose-response relationships and the neuromuscular blocking effects of mivacurium and rocuronium during chronic isepamicin therapy in rabbits . Mivacurium and rocuronium have both a decreased effect and a shorter duration of action during chronic aminoglycoside antibiotic therapy in rabbits.

Br J Urol, 1993 Nov, 72(5 Pt 1), 605 - 10
Fluid absorption and circulating endotoxins during transurethral resection of the prostate; Sohn MH et al.; Recent publications report increased cardiovascular morbidity and mortality after transurethral prostatic resection (TURP) . Repeated breath-ethanol monitoring with a new infrared device permits a highly sensitive peroperative registration of fluid absorption . A prospective study in 52 patients revealed surprisingly high rates of intravascular fluid loads without clinical manifestations . Only 4 patients developed clinical signs of the TUR syndrome . Immunological work-up in 41 patients demonstrated circulating endotoxins and significant rise of endogenous tumour necrosis factor (TNF) in 3 of these patients . In 11 patients transient endotoxins could be detected during resection under prophylactic parenteral antibiosis . In the face of less invasive approaches to benign prostatic hyperplasia, close intraoperative monitoring and antibiotic coverage should be demanded as a routine procedure during TURP . Elective surgery should be delayed until appropriate antibiotic therapy has been given.

J Med Entomol, 1999 Jan, 36(1), 108 - 12
Detection of Escherichia coli O157:H7 from Musca domestica (Diptera: Muscidae) at a cattle farm in Japan; Iwasa M et al.; Enterohemorrhagic Escherichia coli (EHEC) O157:H7 was isolated for the first time from Musca domestica L . A total of 310 fly samples was collected from 4 different farms in Obihiro-City, Hokkaido, in the summer and autumn of 1997;5 samples carried E . coli serotype O157:H7 . Using ELISA and Vero cell cytotoxicity assay, 3 isolates from 1 cattle farm produced both active Shiga-toxin type 1 (Stx1) and 2 (Stx2) . These isolates also carried hemolysin and eaeA genes and harbored the 90-kb virulence plasmid of EHEC O157:H7 . Based on plasmid profiles, antibiotic patterns, polymerase chain reaction (PCR)-based DNA finger printing analysis using random amplified polymorphic DNA, pulsed field gel electrophoresis analysis, and DNA sequences of stx1 and stx2, all 3 isolates from fly samples were identical . These results indicate that the house fly is capable of carrying the toxigenic EHEC O157:H7 involved in human disease.

Int J Hematol, 1999 Feb, 69(2), 81 - 8
Effect of granulocyte-colony stimulating factor on empiric therapy with flomoxef sodium and tobramycin in febrile neutropenic patients with hematological malignancies . Kan-etsu Hematological Disease and Infection Study Group; Yoshida M et al.; The clinical effects of concomitant use of granulocyte-colony stimulating factor (G-CSF) on empiric antibiotic therapy in febrile neutropenic patients were evaluated in a randomized fashion . Two hundred and fourteen neutropenic febrile episodes (neutrophil counts < 1.0 x 10(9)/l) were treated with flomoxef sodium and tobramycin with or without G-CSF . The resolution of fever at day 4 (excellent response) or at day 7 (good response) was deemed effective . Among 157 evaluable episodes, the observed excellent responses were 31 (38.8%) and the good responses were 20 (25.0%) in the G-CSF group; those in the control group were 26 (33.8%) and 25 (32.5%), respectively . The overall efficacy rate was 63.8% (51/80) in the G-CSF group and 66.2% (51/77) in the control group (not significant) . The initial neutrophil count was 0.186 +/- 0.249 x 10(9)/l in the G-CSF group and 0.235 +/- 0.290 x 10(9)/l in the control group, and rose to 2.889 +/- 4.198 x 10(9)/l and 0.522 +/- 0.844 x 10(9)/l, respectively, at day 7 . These results indicate that G-CSF does not affect the rate of response to empiric antibiotic therapy in febrile neutropenic patients, although a significant effect of G-CSF was observed on neutrophil recovery.

Rev Gastroenterol Mex, 1998 Apr-Jun, 63(2), 66 - 71
{Comparison of 2 schedules based on pantoprazole for eradication of Helicobacter pylori in patients with active duodenal ulcer}; Dehesa M et al.; OBJECTIVE: To compare the efficacy and tolerability of a triple vs dual pantoprazole based therapy to eradicate Helicobacter pylori (H . pylori) in mexican patients with florid duodenal ulcer . BACKGROUND: The treatment of peptic ulcer disease was revolutionized by the fact that H . pylori generally induces chronic gastritis and peptic ulcer disease and that the cure of the infection prevents ulcer relapses . MATERIAL AND METHODS: 74 H . pylori positive patients with florid duodenal ulcer were randomized to receive either pantoprazole 40 mg bid in combination with clarithromycin 500 mg tid and amoxicillin 1 g bid (triple regimen PAC) or pantoprazole in combination with clarithromycin and placebo (dual regimen PC) during 14 days . To ensure complete ulcer healing all patients received an additional 2 weeks treatment with pantoprazole 40 mg od . 14C Urea Breath test (UBT) was the main criteria used to determine eradication rate with < 150 disintegrations per minute (DPM) to consider a patient eradicated . In all patients culture, antibiotic susceptibility (E-test) and histology were performed . RESULTS: In the per protocol analysis (n = 66) the eradication rate was: PAC 93.5% vs PC 54.3% (p < 0.001) . 76% of H . pylori strains were resistant to metronidazole . Tolerance and compliance were excellent in both groups . CONCLUSIONS: Triple therapy (PAC) was shown to be superior to dual therapy (PC) for H . pylori eradication in mexican patients with florid duodenal ulcer.

Mol Genet Metab, 1999 Feb, 66(2), 117 - 21
Complementation studies in human and feline Niemann-Pick type C disease; Somers KL et al.; Complementation studies were performed to determine if the gene responsible for the major form of human Niemann-Pick type C disease (NPC) and a feline model of NPC are orthologous . Cell fusions between human NPC and feline NPC fibroblasts were conducted to assess whether the multinucleated heterokaryons that were formed showed a reversal of the NPC phenotype . Cultured fibroblasts from NPC-affected humans and NPC-affected cats were hybridized and then analyzed for complementation by challenging the cells with low-density lipoprotein (LDL) and subsequently staining with the fluorescent antibiotic filipin to visualize any abnormal accumulation of unesterified cholesterol . All of the multinucleated cells formed from these fusions retained the NPC staining phenotype, indicating an absence of complementation and suggesting that the underlying defect in the major form of human NPC and this feline model of NPC involve orthologous genes .

Clin Diagn Lab Immunol, 1999 Mar, 6(2), 260 - 5
Cytokines and inflammatory mediators do not indicate acute infection in cystic fibrosis; Wolter JM et al.; Various treatment regimens and difficulties with research design are encountered with cystic fibrosis (CF) because no standard diagnostic criteria exist for defining acute respiratory exacerbations . This study evaluated the role of serial monitoring of concentrations of selected cytokines and inflammatory mediators in serum and sputum as predictors of respiratory exacerbation, as useful outcome measures for CF, and to guide therapy . Interleukin-8 (IL-8), tumor necrosis factor alpha (TNF-alpha), neutrophil elastase-alpha-1-protease inhibitor complex (NE complex), protein, and alpha-1-protease inhibitor (alpha-1-PI) were measured in serum and sputum collected from CF patients during respiratory exacerbations and periods of well-being . Levels of NE complex, protein, and alpha-1-PI in sputum rose during respiratory exacerbations and fell after institution of antibiotic therapy (P = 0.078, 0.001, and 0.002, respectively) . Mean (+/- standard error of the mean) levels of IL-8 and TNF-alpha were extremely high in sputum (13,780 +/- 916 and 249.4 +/- 23.5 ng/liter, respectively) but did not change significantly with clinical deterioration of the patient (P > 0.23) . IL-8 and TNF-alpha were generally undetectable in serum, and therefore these measures were unhelpful . Drop in forced expiratory volume in 1 s was the only clinical or laboratory parameter that was close to being a determinant of respiratory exacerbation (P = 0.055) . This study provides evidence of intense immunological activity occurring continually within the lungs of adult CF patients . Measurement of cytokines and inflammatory mediators in CF sputum is not helpful for identifying acute respiratory exacerbations.

Science, 1999 Mar 5, 283(5407), 1530 - 4
Exon shuffling by L1 retrotransposition; Moran JV et al.; Long interspersed nuclear elements (LINE-1s or L1s) are the most abundant retrotransposons in the human genome, and they serve as major sources of reverse transcriptase activity . Engineered L1s retrotranspose at high frequency in cultured human cells . Here it is shown that L1s insert into transcribed genes and retrotranspose sequences derived from their 3' flanks to new genomic locations . Thus, retrotransposition-competent L1s provide a vehicle to mobilize non-L1 sequences, such as exons or promoters, into existing genes and may represent a general mechanism for the evolution of new genes.

Ned Tijdschr Geneeskd, 1998 Dec 19, 142(51), 2773 - 7
{Acute management of patients bitten by poisonous snakes}; Carels RA et al.; The management of poisonous snake bites includes first aid and clinical medical treatment . First aid consists of reassurement of the patient, immobilisation of the bitten limb and rapid transport to the nearest hospital to monitor the vital functions . In no case suction, incision or tight bandages should be applied . The degree of envenomation can be classified in three categories depending on the spread of the symptoms: no symptoms, only local non-progressive symptoms, and systemic or local rapidly progressive symptoms (severe envenomation) . Antivenin therapy is indicated in severe envenomation . Because of the risk of anaphylactic reactions or serum sickness, antivenin should be given with great caution . Antibiotic therapy and tetanus prophylaxis are advised in all cases . Immediate consultation with the National Intoxication Centre of the Rijksinstitut voor Volksgezondheid en Milieu (RIVM) is always warranted; telephone: 030-2748888 . In a national protocol, which is available at the RIVM, the Harbour Hospital Rotterdam, the Academic Medical Centre and Artis Zoo Amsterdam, the correct management of snake bites is described . An overview of all antivenins available in the Netherlands is also given in this protocol.

Ned Tijdschr Geneeskd, 1998 Dec 12, 142(50), 2724 - 8
{Vertical HIV-I-transmission . II . HIV-diagnosis in a child}; Orendi JM et al.; In newborn children from HIV-infected women early establishment of HIV infection is of importance for optimal therapy of HIV-infected children and avoidance of unnecessary medication in uninfected children . A more than 95% reliable diagnosis of HIV infection can now be obtained at the age of four weeks by polymerase chain reaction (PCR) technology . Before this age a positive PCR result is relevant since it necessitates additional investigation such as measuring anti-HIV drug resistance and may lead to modification of anti-HIV treatment . Prophylaxis against Pneumocystis carinii is not needed if HIV infection can not be demonstrated by PCR after the age of four weeks.

J Pediatr, 1999 Mar, 134(3), 304 - 9
Postsplenectomy course in homozygous sickle cell disease; Wright JG et al.; OBJECTIVE: To determine whether children with homozygous sickle cell (SS) disease and splenectomy are at greater risk of death, overwhelming septicemia, or other complications . METHODS: A total of 130 patients with SS treated by splenectomy (46 recurrent acute splenic sequestration, 84 chronic hypersplenism) over a 22.5-year period at the Sickle Cell Clinic of the University Hospital of the West Indies, Kingston, Jamaica, were compared with a control group matched for sex, age, and duration of follow-up in a retrospective review . Deaths and bacteremias were examined over the whole study period . Painful crises, acute chest syndromes, and febrile episodes were compared in the 90 patients completing 5 years of postsplenectomy follow-up . FINDINGS: Mortality and bacteremic episodes did not differ between the splenectomy and control groups . Painful crises were more common in the splenectomy group than in the control group (P =.01) but did not differ between splenectomy indications . Acute chest syndrome was more common in the splenectomy group than in the control group (P <.01) and was more common in the acute splenic sequestration group than in the hypersplenism group (P =.01) . Febrile events did not differ between the groups or between the indications for splenectomy . CONCLUSION: Splenectomy does not increase the risk of death or bacteremic illness in patients with SS disease and, if otherwise indicated, should not be deferred for these reasons.

Clin Infect Dis, 1999 Feb, 28(2), 274 - 8
Cat-scratch disease with paravertebral mass and osteomyelitis; Robson JM et al.; The case of a 9-year-old girl with cat-scratch disease (CSD) complicated by development of a paravertebral mass and osteomyelitis is presented . Following multiple scratches and inguinal lymphadenopathy, she developed back pain, and imaging demonstrated a paravertebral mass with evidence of osteomyelitis involving vertebra T9 . The diagnosis was made on the basis of detection of Bartonella henselae by use of molecular techniques on an aspirate from the vertebral column and supportive serology for infection with B . henselae . Eleven other cases of this unusual manifestation associated with CSD have been reported in the literature and are reviewed . The patient was treated with gentamicin, followed by rifampicin and trimethoprim-sulfamethoxazole, orally and made a favorable recovery over 7 months . This is comparable with other case reports, regardless of the choice of antibiotic therapy . CSD in immunocompetent hosts is not always self-limiting, and tissues beyond the lymph nodes can be involved.

Clin Infect Dis, 1999 Feb, 28(2), 192 - 4
Respiratory tract infections as a public health challenge; Douglas RM; Acute respiratory infections have everywhere become the province of clinicians and the pharmaceutical industry . A public health approach is needed with systematic efforts to minimize transmission, maximize prevention, and harness the research and surveillance effort to decrease their incidence and severity . These infections have a huge incidence, morbidity burden, and economic impact in all societies . Several factors now demand renewed attention to prevention . They include the growing costs and potentially limited benefits of an expanded pharmacotherapeutic approach; the serious change in antibiotic susceptibility of the common respiratory pathogens; the advances made in vaccinology in recent years; and the need to promote equity and share limited health resources across the world's population . Care should not be restricted to those in affluent countries who can afford increasingly expensive treatment.

J Hosp Infect, 1999 Feb, 41(2), 87 - 99
Diagnosis of ventilator-associated pneumonia; Flanagan PG; The diagnosis of ventilator-associated pneumonia (VAP) is problematic despite numerous attempts at defining acceptable diagnostic criteria and the optimal technique for routine respiratory sampling . Clinical criteria have imperfect diagnostic reliability in ventilated patients, but remain crucial for defining those patients who may require respiratory sampling . Quantitative clinical scoring systems may improve the accuracy of clinical diagnosis in some ventilated patients . Review of published studies suggest that fibreoptic bronchoscopic techniques have greater diagnostic reliability than qualitative endotracheal aspirates, despite inconsistent results when comparing the same techniques in different centres . However, the cost and invasive nature of bronchoscopic methods precludes their use as first-line techniques in VAP . Non-bronchoscopic, non-directed techniques are cheaper, safer and more widely available alternatives to fibreoptic bronchoscopy techniques and have comparable accuracy . Quantitation of respiratory tract cultures is useful in excluding VAP in patients with equivocal signs of pneumonia . The diagnostic threshold of bacterial load that defines the presence of VAP should vary according to the pre-test probability of pneumonia, length of ventilation, antibiotic administration and immunocompetence of the patient.

Korean J Intern Med, 1999 Jan, 14(1), 85 - 7
A case of pancytopenia secondary to low-dose pulse methotrexate therapy in a patient with rheumatoid arthritis and renal insufficiency; Park GT et al.; Most reports on serious MTX toxicity have focused on hepatic abnormalities, while other effects, including hematologic reactions, have not been emphasized . We experienced a case of pancytopenia secondary to MTX therapy in a patient with RA and renal insufficiency . A 67-year-old woman with a 12-year history of active seropositive RA that was a response to non-steroidal anti-inflammatory drugs, hydroxychloroquinine and intra-articular steroid injections, had been followed up and was diagnosed as early chronic renal failure in October, 1993 . Recently, because of significant morning stiffness and polyarthralgia, the decision was made to institute MTX treatment . This was begun as a single oral dose of 5mg/week . After 2 doses, the patient was admitted to the hospital with general weakness . Laboratory tests showed a hemoglobin level of 7.9 g/dl, WBC count 1800/mm3 and platelet count of 64000/mm3 . The serum creatinine level was 6.1 mEq/dl and the BUN level was 82 mEq/dl . Liver function test results were normal, but the serum albumin level was 2.7 g/dl . The patient subsequently developed fever and blood transfusions, granulocyte colony stimulating factor (G-CSF) and intravenous prophylactic antibiotic therapy were required . Her condition was improved . In summary, Low-dose MTX-related adverse hematologic side effects, including fatal pancytopenia, are rare but are a cause of increasing concern in patients with RA and renal insufficiency . Close monitoring of associated risk factors, particularly impaired renal function, should be mandatory for all patients who are receiving MTX therapy.

J Antimicrob Chemother, 1998 Dec, 42(6), 831 - 4
Incorporation rates, stabilities, cytotoxicities and release of liposomal tetracycline and doxycycline in human serum; Sangare L et al.; Tetracycline and doxycycline were encapsulated in cationic, anionic and neutral liposomes . The amounts of antibiotic encapsulated, the stability of each preparation at 4 degrees C for 4 weeks, and the kinetics of the release of entrapped drug into human sera were assessed by high-performance liquid chromatography . The toxicities of the liposome preparations on human erythrocytes and HeLa 229 cells were evaluated in vitro . The results showed that doxycycline was entrapped more efficiently than tetracycline, and that doxycycline-entrapped liposomes were more stable at 4 degrees C and in human sera, and less cytotoxic than tetracycline-entrapped liposomes.

Can Vet J, 1998 Feb, 39(2), 103 - 6
The effect of streptomycin, oxytetracycline, tilmicosin and phenylbutazone on spermatogenesis in bulls; Barth AD et al.; To determine whether declining semen quality associated with health problems may be due to certain antibiotic or anti-inflammatory treatments, semen was collected 3 times per week for up to 42 d from 6 normal bulls after treatment with oxytetracycline, tilmicosin, dihydrostreptomycin, or phenylbutazone . No adverse effects on semen quality were observed.

Ther Drug Monit, 1999 Feb, 21(1), 63 - 73
Impact of goal-oriented and model-based clinical pharmacokinetic dosing of aminoglycosides on clinical outcome: a cost-effectiveness analysis; van Lent-Evers NA et al.; The benefits of a pharmacy-based, active therapeutic drug monitoring (TDM) service (ATM) on outcomes were examined in a prospective study at four hospitals . ATM involved pharmacokinetic dosage optimization at the start of treatment, subsequent Bayesian adaptive control, and frequent patient evaluation . Cost-effectiveness was calculated based on real costs . The ATM group comprised 105 patients and 127 patients with nonguided TDM who were followed up as controls . Forty-eight of the ATM and 62 of the nonguided TDM patients had an infection on admission . Peak concentrations in ATM patients were significantly higher (10.6+/-2.9 mg/L; nonguided TDM, 7.6+/-2.2 mg/L; p < 0.01) . Trough levels in the ATM group were significantly lower (p < 0.01) . There was a trend toward lower mortality in the ATM group (nine of 105 versus 18 of 127; p = 0.26) that was significant for patients with an infection on admission (one of the 48 ATM patients died versus nine of the 62 nonguided TDM patients; p = 0.023) . ATM reduced the length of hospital stay for all patients in the study (20.0+/-1.4 days; nonguided TDM, 26.3+/-2.9 days; p = 0.045) and for patients admitted with an infection (12.6+/-0.8 days; nonguided TDM, 18.0+/-1.4; p < 0.001) . The incidence of nephrotoxicity was reduced from 13.4% (nonguided TDM) to 2.9% (p < 0.01) . With ATM, total costs were lower for all patients (Dutch guilders {DFL}, 13,125+/-9,267; nonguided TDM, DFL 16,862+/-17,721; p < 0.05) and for patients admitted with an infection (DFL 8,883+/-3,778; nonguided TDM, DFL 11,743+/-7,437; p < 0.01) . Goal-oriented, model-based dosing of aminoglycosides resulted in higher antibiotic efficacy, shorter hospitalization, and reduced incidence of nephrotoxicity . By combining efficacy with savings, ATM offered a significant alternative to usual care.

Anim Genet, 1999 Feb, 30(1), 1 - 9
A synteny map of the horse genome comprised of 240 microsatellite and RAPD markers; Shiue YL et al.; To generate a domestic horse genome map we integrated synteny information for markers screened on a somatic cell hybrid (SCH) panel with published information for markers physically assigned to chromosomes . The mouse-horse SCH panel was established by fusing pSV2neo transformed primary horse fibroblasts to either RAG or LMTk mouse cells, followed by G418 antibiotic selection . For each of the 108 cell lines of the panel, we defined the presence or absence of 240 genetic markers by PCR, including 58 random amplified polymorphic DNA (RAPD) markers and 182 microsatellites . Thirty-three syntenic groups were defined, comprised of two to 26 markers with correlation coefficient (r) values ranging from 0.70 to 1.0 . Based on significant correlation values with physically mapped microsatellite (type II) or gene (type I) markers, 22 syntenic groups were assigned to horse chromosomes (1, 2, 3, 4, 6, 9, 10, 11, 12, 13, 15, 18, 19, 20, 21, 22, 23, 24, 26, 30, X and Y) . The other 11 syntenic groups were provisionally assigned to the remaining chromosomes based on information provided by heterologous species painting probes and work in progress with type I markers.

Pediatrics, 1999 Mar, 103(3), 594 - 8
Once- versus twice-daily gentamicin dosing in neonates >/=34 Weeks' gestation: cost-effectiveness analyses; Thureen PJ et al.; OBJECTIVES: To compare performance and cost analysis of two gentamicin regimens in infants >/=34 weeks' gestation requiring antibiotics for a 72-hour rule-out sepsis evaluation . A once-daily dosing (ODD) regimen of 4 mg/kg was compared with a standard twice-daily dosing (TDD) regimen of 2.5 mg/kg every 12 hours . SETTING AND DESIGN: Infants at two university-affiliated Level III nurseries were prospectively temporally allocated to receive ODD (n = 27) or TDD (n = 28) as part of their 72-hour empirical antibiotic regimen . Performance of dosing regimens was based on target serum gentamicin concentrations (SGC) established prospectively as a peak of 5 to 10 microgram/mL and a trough of </=2 microgram/mL . SGC were determined by fluorescence polarization immunoassay on day 3 of therapy . Cost data were obtained by distributing a questionnaire to 15 pediatric pharmacy practice sites . Inquiries were made regarding hospital cost of drug acquisition, drug supplies, drug preparation and administration, and serum concentration analysis . Performance and cost data were then used to do a cost-effectiveness analysis . RESULTS: Mean peak concentrations were higher with ODD (7.9 +/- 0.2 microgram/mL) than TDD (6.7 +/- 0.3 microgram/mL) . Half of the patients in the TDD group had trough concentrations >2 microgram/mL, compared with none in the ODD group . Overall, 57% of the SGCs in the TDD group were outside the target concentration range versus 7% in the ODD group . Based on questionnaire results, a total 72-hour process cost of ODD versus TDD was compared for regimens with and without use of SGC analysis . If SGCs are obtained, more than 75% of the cost associated with gentamicin therapy is attributable to SGC analysis . Based on a cost-effectiveness analysis, ODD was the dominant dosing strategy in all categories analyzed . CONCLUSIONS: ODD of gentamicin at 4 mg/kg in neonates >/=34 weeks' gestation is the preferable treatment strategy based on: 1) significantly improved SGC performance compared with TDD; 2) elimination of the need for routine SGC collection in infants on short courses of therapy; and 3) significant antibiotic-associated hospital cost savings when compared with conventional therapy of TDD and SGC analysis.

Appl Environ Microbiol, 1999 Mar, 65(3), 1036 - 44
A phosphonate-induced gene which promotes Penicillium-mediated bioconversion of cis-propenylphosphonic acid to fosfomycin; Watanabe M et al.; Penicillium decumbens is able to epoxidize cis-propenylphosphonic acid (cPA) to produce the antibiotic fosfomycin {FOM; also referred to as phosphonomycin and (-)-cis-1,2-epoxypropylphosphonic acid}, a bioconversion of considerable commercial significance . We sought to improve the efficiency of the process by overexpression of the genes involved . A conventional approach of isolating the presumed epoxidase and its corresponding gene was not possible since cPA epoxidation could not be achieved with protein extracts . As an alternative approach, proteins induced by cPA were detected by two-dimensional gel electrophoresis . The observation that a 31-kDa protein (EpoA) was both cPA induced and overaccumulated in a strain which more efficiently converted cPA suggested that it might take part in the bioconversion . EpoA was purified, its amino acid sequence was partially determined, and the corresponding gene was isolated from cosmid and cDNA libraries with oligonucleotide probes . The DNA sequence for this gene (epoA) contained two introns and an open reading frame encoding a peptide of 277 amino acids having some similarity to oxygenases . When the gene was subcloned into P . decumbens, a fourfold increase in epoxidation activity was achieved . epoA-disruption mutants which were obtained by homologous recombination could not convert cPA to FOM . To investigate the regulation of the epoA promoter, the bialaphos resistance gene (bar, encoding phosphinothricin acetyltransferase) was used to replace the epoA-coding region . In P . decumbens, expression of the bar reporter gene was induced by cPA, FOM, and phosphorous acid but not by phosphoric acid.

Regul Toxicol Pharmacol, 1998 Dec, 28(3), 212 - 21
Pharmaceuticals in the environment--a human risk?
Christensen FM.
Pharmaceuticals in the environment and their potential toxic effects are emerging research areas, which is also reflected in the drug approval regulation . This far, focus has mainly been directed toward potential effects on nature and wildlife . In this paper, human risk as a consequence of exposure via the environment has been addressed and assessed . The synthetic estrogen 17alpha-ethinylestradiol (EE2), the antibiotic phenoxymethylpenicillin (Pen V), and the antineoplastic drug cyclophosphamide (CP) were chosen as modeling substances based on criteria of receptor specificity, elevated risk for human population groups for which the pharmaceuticals are not therapeutically intended, different modes of action, and prescription frequency . Attention has been focused on emissions from the use phase and subsequent diffuse release via the sewer systems . A reasonable worst-case environmental fate and human exposure were estimated using the software EUSES on worst-case emission quantities . The results indicate a negligible human risk connected to the environmental exposure for these substances . Danish conditions have been used as the modeling area, but the results are assumed to be valid for regions with similar drug consumption profiles .

Gastrointest Endosc, 1999 Mar, 49(3 Pt 1), 297 - 301
Unsedated transnasal EGD: an alternative approach to conventional esophagogastroduodenoscopy for documenting Helicobacter pylori eradication; Saeian K et al.; BACKGROUND: The aim of this study was to assess the yield of antral biopsies performed via unsedated transnasal esophagogastroduodenoscopy, a technique that does not require conscious sedation with its concomitant costs and complications, for documentation of Helicobacter pylori eradication . METHODS: Nineteen patients who were previously CLO test positive on conventional esophagogastroduodenoscopy and subsequently treated for H pylori infection were enrolled . The subjects had not received antibiotic therapy in the prior month and had no prior gastric surgery . By using a GIF-N30 fiberoptic endoscope and a tiny cup biopsy forceps (1.8 mm diameter), unsedated transnasal endoscopy was performed and antral biopsy specimens were taken for a CLO test, histologic analysis (Dieterle stain), and tissue culture . On the same day, the subjects underwent a carbon 13-labeled area urea breath test . All subjects completed a visual analog scale, rating the acceptability of the unsedated transnasal examination and the previous sedated conventional esophagogastroduodenoscopy . RESULTS: There was no statistically significant difference between the results of the CLO tests (5/19 positive) versus the 13C-urea breath test (4/19 positive) (p = 0.96), the CLO tests versus histologic findings (5/19 positive) (p = 0.71), or the 13C-urea breath test versus histologic findings (p = 0.96) . All tissue culture results were negative . The overall acceptability of unsedated transnasal esophagogastroduodenoscopy was similar to that of sedated conventional esophagogastroduodenoscopy . CONCLUSION: Unsedated transnasal esophagogastroduodenoscopy, a technique that eliminates the costs and complications associated with conscious sedation, is a feasible and accurate alternative to conventional esophagogastroduodenoscopy when documentation of H pylori eradication and confirmation of gastric ulcer healing are both indicated.

Wien Klin Wochenschr, 1998 Dec 23, 110(24), 894 - 7
Human ehrlichiosis in central Europe; Lotric-Furlan S et al.; Ehrlichioses are tick-transmitted diseases associated with illnesses of animals for decades, but recently recognised to be emerging human diseases . In the last ten years increasing number of cases of human infections caused by Ehrlichia chaffeensis and granulo-cytic ehrlichia were described in the United States . Several reports also indicate the presence of infection with the human granulocytic ehrlichiosis (HGE) agent in Europe . The first confirmed acute human disease caused by HGE agent was reported from Slovenia . Until 1997, five patients have been discovered in a prospective study on the etiology of febrile illnesses occurring within six weeks following a tick bite, conducted at the Department of Infectious Diseases, University Medical Centre, Ljubljana, Slovenia . The diagnosis of acute HGE was established by seroconversion to the HGE agent and/or molecular identification of ehrlichial organisms . None of the patients had detectable morulae on blood smear examination . Clinical characteristics and laboratory findings were similar to those reported from the United States, although the disease course was relatively mild in the Slovenian cases . All patients recovered rapidly and without sequelae, although only three patients received antibiotic therapy (of whom only two were treated with doxycycline) . Many ehrlichiosis cases could go undetected due to a lack of physician awareness, lack of public knowledge, or limited investigation . HGE should now be also included in the differential diagnosis of febrile illnesses occurring after a tick bite in Europe.

Klin Monatsbl Augenheilkd, 1998 Dec, 213(6), 351 - 4
{Pars plana vitrectomy in Borrelia burgdorferi endophthalmitis}; Meier P et al.; BACKGROUND: Ocular manifestations of Lyme borreliose present with unusual forms of conjunctivitis, keratitis, optic nerve disease, uveitis, vitritis and rarely endophthalmitis . CASE REPORT: A 57-year-old man working as logger in Sax-ony-Anhalt suffering from an endophthalmitis on his left eye was referred to us . The vision of his left eye was intact light perception and hand motions . The slit-lamp examination revealed severe inflammation of the anterior chamber with hypopyon, posterior synechiae, and opacity of the posterior lens capsule . Funduscopy showed no red reflex, no retinal details . In the local hospital serum analysis was performed and showed in Western-Blot IgM- and IgG-antibodies against Borrelia burgdorferi . Despite of intravenous application of ceftriaxon for 14 days panuveitis persisted, and endophthalmitis developed when antibiotic therapy was finished . RESULTS: During pars plana vitrectomy a sharply delineated cystic lesion containing yellowish fluid was revealed, and creamy yellow fluid was aspirated . Microscopically in hematoxylineosin stained slides of the aspirate structures consistent with Borrelia burgdorferi were found . Postoperatively vision increased to 1/15 . Despite of a second intravenous ceftriaxon treatment for 14 days we observed a retinal vasculitis in the follow up of 6 months . CONCLUSIONS: Despite intravenous ceftriaxon-therapy borrelia burgdorferi must have survived in the vitreous body . Further investigations are required with respect to the use of other antibiotics or immunosuppressives.

Thyroid, 1999 Jan, 9(1), 29 - 31
Granulocyte colony-stimulating factor (G-CSF) does not improve recovery from antithyroid drug-induced agranulocytosis: a prospective study; Fukata S et al.; Agranulocytosis is the most serious side effect of antithyroid drug (ATD) therapy . We conducted prospective and randomized studies to examine whether granulocyte colony-stimulating factor (G-CSF) is actually effective for ATD-induced agranulocytosis . Twenty-four patients with Graves' disease who developed agranulocytosis during ATD therapy were randomly divided into a G-CSF group (n = 14) and an untreated group (n = 10) . Subcutaneous injection of G-CSF (100 to 250 microg) was given daily until neutrophil counts rose to greater than 1000/microL . The untreated group received antibiotic therapy only . Recovery time, which is defined as the number of days required for neutrophil counts to exceed 500/microL, was monitored by daily complete blood count (CBC) . Recovery time in the G-CSF-treated group did not differ from that of the untreated group in those patients with moderate and severe agranulocytosis; thus, prolonged use of G-CSF treatment is generally ineffective for ATD-induced agranulocytosis.

Microbiol Immunol, 1998, 42(12), 871 - 4
Heterogeneity of phenotypic and genotypic traits including organic-acid resistance in Escherichia coli O157 isolates; Horii T et al.; We undertook an epidemiologic study for the sensitivity of both Shiga-like toxin (Slt)-producing Escherichia coli (STEC) O157 and non-STEC O157 strains isolated from different patients with diarrhea to hydrochloric acid (HCl) and organic acids such as acetate, propionate, butyrate and lactate, and other pathogenic factors . The E . coli O157 isolates examined showed a wide variety of organic-acid susceptibility patterns . E . coli O157 isolates resistant to HCl or acetate were found more frequently than those resistant to other organic acids . These isolates also showed diverse pathogenicity patterns for the presence of the virulence genes, antibiotic susceptibility and plasmid profile.

Kyobu Geka, 1999 Feb, 52(2), 168 - 71
{A case report of pleural empyema treated by video-assisted thoracoscopic surgery in an elder patient receiving hemodialysis}; Inoue N et al.; A 79-year-old male who had the treatment of renal failure with hemodialysis was admitted to our hospital for the management of right pleural empyema . We performed thoracoscopic debridement and pleural irrigation in the management of empyema thoracis, because both chest tube drainage and antibiotic therapy had failed . Postoperatively pleural irrigation was performed for three weeks and the chest drains were removed after four weeks . He was successfully transferred to our department of internal medicine at four weeks after the operation . Thoracoscopic debridement and pleural irrigation for the elder patient with pleural empyema is safe, effective and minimally invasive surgical procedure.

Rev Rhum Engl Ed, 1999 Jan, 66(1), 24 - 8
Nonsurgical treatment of osteoarticular tuberculosis . A retrospective study in 143 adults; Pertuiset E et al.; OBJECTIVE AND METHODS: Data are sparse on nonsurgical treatments currently used for osteoarticular tuberculosis in industrialized countries . We conducted a multicenter retrospective study in the Paris urban area, France, in 206 cases of osteoarticular tuberculosis documented by examination of a local specimen . This article reports our findings in the 143 patients who were followed up at least until treatment completion . RESULTS: Mean follow-up after treatment completion was 16 months . Seventy-five (52%) patients had spondylitis and 68 (48%) did not . The number of antituberculous agents used during the initial treatment phase was four in 65% of cases and three in 35% . In the spondylitis subgroup, mean (+/- SD) antibiotic therapy duration was 14.7 +/- 3.4 months, and 25% of patients required surgery; 3% of patients died, 1% suffered a relapse, and 96% achieved a full recovery with no relapse . In the nonspondylitis subgroup, mean antibiotic therapy duration was 13 +/- 3 months and 29% of patients required surgery . The only HIV-positive patient had osteitis of the calcaneus with a relapse that led to discovery of secondary rifampin resistance . CONCLUSION: Based on our findings and on data from the literature, we believe that 12 months is a reasonable duration for antituberculous therapy in osteoarticular tuberculosis, including tuberculous spondylitis.

Am J Respir Cell Mol Biol, 1999 Mar, 20(3), 481 - 92
Effects of cyclosporin A and dinactin on T-cell proliferation, interleukin-5 production, and murine pulmonary inflammation; Umland SP et al.; We compared the effects of cyclosporin A (CSA) and a macrotetrolide antibiotic, dinactin, on human T-cell proliferation and cytokine production induced by stimulation of the T-cell receptor alone (monoclonal antibody {mAb} directed against CD3) or in combination with costimulatory signals (mAbs directed against CD3 and CD28) . These agents were also examined in a murine model of interleukin (IL)-5-mediated pulmonary inflammation . Dinactin inhibited T-cell proliferation induced by IL-2, by mAb to CD3, and by mAbs to CD3 plus alpha-CD28 with identical dose-response curves (IC50 = 10-20 ng/ml) . Dinactin inhibited cytokine production with IC50 values of 10 ng/ml for IL-4 and IL-5 and 30 or 60 ng/ml for interferon-gamma or IL-2, respectively . Unlike CSA, exogenous IL-2 did not alter the dinactin-mediated effects on T cells, and nuclear run-on and steady-state messenger RNA (mRNA) analysis showed that dinactin inhibited cytokine production through a post-transcriptional mechanism . CSA selectively blocked T-cell receptor-induced T-cell proliferation and cytokine production (IC50 = 10 ng/ml) . Under costimulatory conditions, IL-5 synthesis was only minimally inhibited by high concentrations of CSA, and at CSA concentrations of less than 125 ng/ml, IL-5 was significantly increased above control values . Dinactin and CSA reduced pulmonary eosinophilia when administered within 1 d of airway antigen challenge . Of the cytokine mRNAs examined in the lungs of CSA-pretreated, antigen-challenged mice, IL-5 mRNA levels were the least reduced, paralleling the resistance of IL-5 to CSA observed in vitro and suggesting a role for CD28 in the in vivo induction of IL-5.

Aust N Z J Surg, 1999 Feb, 69(2), 117 - 20
Surgical wound infection surveillance: the importance of infections that develop after hospital discharge; Mitchell DH et al.; BACKGROUND: The aim of this study was to evaluate two methods of post-discharge surgical wound surveillance and to compare the incidence and outcomes of wound infections that develop prior to patients' discharge with those that develop after hospital discharge . METHODS: One thousand, three hundred and sixty inpatients who underwent major elective surgery in an 800-bed teaching hospital in western Sydney between February 1996 and July 1997 were followed prospectively . Pre-discharge wound surveillance was performed by clinical assessment by an independent researcher on the fifth (or later) postoperative day . Post-discharge wound surveillance was performed by a mail out of questionnaires completed independently by patients and surgeons . RESULTS: Overall, 138 wound infections were diagnosed (incidence 10.1%), of which fewer than one-third (n = 44) were diagnosed before discharge (average 10.4 days postoperatively) and the remainder (n = 94) after discharge (average 20.6 days postoperatively) . Seven hundred and eighty-two (57.5%) post-discharge survey forms were returned by patients and 680 (50.0%) by surgeons . When forms were returned by both surgeons and patients for the same wound (641 cases), there was substantial agreement in diagnosing infection or no infection (kappa = 0.73) . CONCLUSIONS: The majority of nosocomial surgical wound infections develop after the patients' discharge from hospital . A post-discharge surveillance programme including self-reporting of infections by patients and return of questionnaires by patients and surgeons is feasible in an Australian hospital setting . However, such a programme is labour and resource intensive and strategies to increase return of questionnaires are required.

Shock, 1999 Feb, 11(2), 82 - 6
Low-dose intramuscular polymyxin B improves survival of septic rats; Mayumi T et al.; Polymyxin B (PLB) is a cationic antibiotic that also stoichiometrically neutralizes the lipid A moiety of endotoxin . We examined effects of a small dose of PLB on the mortality of rats with cecal ligation and puncture, on LPS-stimulated nitric oxide (NO) production, and on tumor necrosis factor alpha (TNF alpha) production by isolated rat Kupffer cells . MATERIALS AND METHODS: In vivo studies: Cecal ligation and puncture (CLP) was performed under anesthesia in 28 rats . One hour after CLP, either 600 U/kg of PLB or saline was administered intramuscularly every 6 h (PLB group: n = 12; control group: n = 16) . Plasma endotoxin was measured at 3 and 24 h after the CLP by the Endospecy test . This was compared with survival . In vitro studies: Kupffer cells were isolated from the normal rat liver . The cells were incubated with LPS or LPS + PLB . After 24 h, NO and TNF alpha content were measured using the Griess and ELISA methods, respectively . RESULTS: Low dose PLB significantly decreased the endotoxin levels at both 3 and 24 h (5.5 +/- 2.1 pg/mL vs . 32.8 +/- 3.6 at 3 h; 26.1 +/- 6.1 vs . 49.1 +/- 5.6 at 24 h (p < .05) after CLP . PLB significantly improved survival of CLP rats (68.8% in the control group vs . 100% in the PLB treated group on 3 days after CLP, p < .001) . PLB also attenuated NO and TNF alpha production from the Kupffer cells . CONCLUSION: Intramuscular PLB administered in low doses may improve the mortality of sepsis.

Fogorv Sz, 1999 Jan, 92(1), 3 - 10
{Analysis of secretion into the saliva of cefoxitin (Mefoxin), imipenem (Tienam) and meropenem (Meronem)}; Kelentey B et al.; The salivary excretion of cefoxitin (Mefoxin), a second-generation beta-lactam antibiotic of the cefalosporin group, which shows enhanced anti-anaerobic effect was investigated in oral surgery patients . In animal experiments the saliva levels of imipenem (Tienam) and meropenem (Meronem), which also belong to the betalactam carbapenem group were studied . The antibiotics were administered parenterally in single therapeutic doses, then blood samples were taken first after half an hour then hourly, and mixed saliva was collected for 6 hours . Cefoxitin was found to reach top level in the 1st hour, then this level decreased rapidly, and in the 4th hour it was no longer measurable . Out of the carbapenems imipenem showed highest level in the 2nd hour and in the 4th hour its concentration in the saliva was minimal . Meropenem reached a higher level in the saliva (1,5-2 times higher than the serum level) in the 2nd hour after administration, which persisted even in the 6th hour . The experimental results justify the administration of these antibiotics in dentistry and oral surgery.

J Foot Ankle Surg, 1999 Jan-Feb, 38(1), 55 - 60
Recurrent mycetoma of the foot; Davis JD et al.; Mycetoma, also known as madura foot, is a local, chronic, slowly progressive disease with the classic presentation involving tumefaction, multiple draining sinuses, and grain-filled pus . It is primarily produced by either a bacteria (actinomycetoma) or a fungal (eumycetoma) organism . Determining the causative organism is fundamental to the treatment process . All types of mycetoma infections should be treated with early surgical debridement and tissue culture . Tissue should be sent for gross, microscopic, and histopathologic evaluation . In addition to surgical management, these patients should be managed adjunctively with a prolonged course of chemotherapy . Patients with actinomycetoma are treated with an antibiotic and can expect to have a clinical cure with little chance for recurrence, whereas, patients with eumycetoma are treated with an antifungal agent and usually do poorly with a high rate of recurrence . The case presented involved an infection due to Actinomadura madurae (Nocardiaform madurae) and demonstrates successful treatment with surgical resection and prolonged doxycycline chemotherapy.

Arzneimittelforschung, 1999 Jan, 49(1), 44 - 50
Experimental studies on the influence of surfactants on intestinal absorption of drugs . Cefadroxil as model drug and sodium taurocholate as natural model surfactant: studies in rat colon and in rat duodenum; Carmona-Ibanez G et al.; The influence of the natural bile acid surfactant sodium taurocholate (CAS 81-24-3) on colic and duodenal (i.e . the proximal third of the small intestine) absorption of cefadroxil (CAS 50370-12-2) was studied using the in situ rat gut technique, and compared with the effect of sodium lauryl sulfate (CAS 151-21-3), the most widely used synthetic anionic surfactant . Previously, the stability, compatibility, and micelle-solubilization characteristics of taurocholate were assessed in order to correct, when necessary, the absorption results . White the passive absorption rate constants (kf, h-1) determined in colon in the presence of increasing lauryl sulfate concentrations showed an asymptotic value about 7-fold higher than that of cefadroxil alone, only a 2-fold higher value was obtained in the presence of taurocholate at similar concentrations . Therefore the natural surfactant would increase the polarity of the colic absorbent membrane much less than lauryl sulfate does (about 3.5 times) . The effects of taurocholate on the duodenal absorption of cefadroxil, which is the sum of a single passive process and a simultaneous carrier-mediated transport, can be summarized as follows: 1 . When the working concentration of cefadroxil is far from carrier saturation (0.1 mg/ml) a slight but clear net decrease in the apparent kf value is observed in the presence of increasing concentrations of the natural surfactant (from 3.0 to 2.3 h-1) 2 . When the concentration of the antibiotic in the working fluid is above carrier saturation (10 mg/ml) the picture is reversed, and a slight net increase in kf in the presence of increasing concentrations of taurocholate (from 0.8 to 1.2 h-1) is found . This means that the effect of taurocholate as a noncompetitive inhibitor of active cefadroxil transport is very much smaller than that observed with lauryl sulfate . Moreover, the increase in passive absorption relative to the synthetic surfactant is also much smaller . On the basis of allometric considerations it could be concluded that for practical purposes taurocholate does not act as a substantial absorption modifier for cefadroxil, at least in the small intestine, the main absorption site of the antibiotic . It can, however, not be considered an inert ingredient, and therefore oral administration of cefadroxil far from that of taurocholate-containing preparations, and even from lipid-rich meals should be strongly recommended.

Fundam Clin Pharmacol, 1999, 13(1), 59 - 66
Role of the calcium/calmodulin-dependent protein kinase II in the regulation of the renal basolateral PAH and dicarboxylate transporters; Gabriels G et al.; The aim of the present study was to investigate whether the activities of the renal basolateral organic anion transporter (PAH transporter) and the sodium-dependent dicarboxylate transporter are modulated by the calcium/calmodulin-dependent multifunctional protein kinase II (CaM kinase II) . The studies were performed on isolated S2 segments of proximal tubules microdissected from rabbit kidneys without the use of enzymatic agents . 3H-PAH was used as marker substance of the anion transporter, and 14C-glutarate as a marker of the sodium/dicarboxylate cotransporter . Because the tubules were not perfused, and hence were collapsed, the tubular uptake of the marker substances reflects transport across the basolateral cell membrane . To obtain uptake rates most closely related to initial transport rates, 30 s tubular uptake measurements were performed . The results show that a selective inhibitor of CaM kinase II, KN93, inhibited tubular PAH uptake . The smallest effective dose was 10(-7) M . An inactive analogue of KN93, KN92, was without effect, even at the high concentration of 10(-5) M . In contrast to PAH transport, tubular 14C-glutarate uptake was not affected by KN93 (10(-5) M) . PAH transport was also inhibited after elevation of intracellular Ca2+ by the Ca(2+)-ionophore A 23187 and by the polycationic antibiotic neomycin, but not by the intracellular Ca2+ modulators thapsigargin and ryanodine . The effect of the Ca(2+)-ionophore could be abolished by KN93, but not by Rp-cAMPs, an inhibitor of protein kinase A, indicating that this event was mediated by CaM kinase II, but not by PKA . The results provide the first evidence that, in addition to the protein kinases A and C (previous studies from this lab), CaM kinase II has a role in the regulation of the renal basolateral PAH transporter, whereas the renal basolateral dicarboxylate transporter does not depend on CaM kinase II activity.

Heart, 1999 Mar, 81(3), 232 - 8
Chlamydia pneumoniae and atherosclerosis; Wong YK et al.; OBJECTIVE: To review the literature for evidence that chronic infection with Chlamydia pneumoniae is associated with atherosclerosis and acute coronary syndromes . DATA SOURCES: MEDLINE and Institute of Science and Information bibliographic databases were searched at the end of September 1998 . Indexing terms used were chlamydi*, heart, coronary, and atherosclerosis . Serological and pathological studies published as papers in any language since 1988 or abstracts since 1997 were selected . DATA EXTRACTION: It was assumed that chronic C pneumoniae infection is characterised by the presence of both specific IgG and IgA, and serological studies were examined for associations that fulfilled these criteria . Pathological studies were also reviewed for evidence that the presence of C pneumoniae in diseased vessels is associated with the severity and extent of atherosclerosis . DATA SYNTHESIS: The majority of serological studies have shown an association between C pneumoniae and atherosclerosis . However, the number of cases in studies that have reported a positive association when using strict criteria for chronic infection is similar to the number of cases in studies which found no association . Nevertheless, the organism is widely found in atherosclerotic vessels, although it may not be at all diseased sites and is not confined to the most severe lesions . Rabbit models and preliminary antibiotic trials suggest that the organism might exacerbate atherosclerosis . CONCLUSION: More evidence is required before C pneumoniae can be accepted as playing a role in atherosclerosis . Although use of antibiotics in routine practice is not justified, large scale trials in progress will help to elucidate the role of C pneumoniae.

Biochemistry, 1999 Feb 9, 38(6), 1902 - 11
UDP-3-O-(R-3-hydroxymyristoyl)-N-acetylglucosamine deacetylase of Escherichia coli is a zinc metalloenzyme; Jackman JE et al.; The enzyme UDP-3-O-(R-3-hydroxymyristoyl)-GlcNAc deacetylase (LpxC) catalyzes the committed step in the biosynthesis of lipid A and is therefore a potential antibiotic target . Inhibition of this enzyme by hydroxamate compounds {Onishi, H . R.; Pelak, B . A.; Gerckens, L . S.; Silver, L . L.; Kahan, F . M.; Chen, M . H.; Patchett, A . A.; Stachula, S . S.; Anderson, M . S.; Raetz, C . R . H . (1996) Science 274, 980-982} suggested the presence of a metal ion cofactor . We have investigated the substrate specificity and metal dependence of the deacetylase using spectroscopic and kinetic analyses . Comparison of the steady-state kinetic parameters for the physiological substrate UDP-3-O-(R-3-hydroxymyristoyl)-GlcNAc and an alternative substrate, UDP-GlcNAc, demonstrates that the ester-linked R-3-hydroxymyristoyl chain increases kcat/KM (5 x 10(6))-fold . Metal-chelating reagents, such as dipicolinic acid (DPA) and ethylenediaminetetraacetic acid, completely inhibit LpxC activity, implicating an essential metal ion . Plasma emission spectroscopy and colorimetric assays directly demonstrate that purified LpxC contains bound Zn2+ . This Zn2+ can be removed by incubation with DPA, causing a decrease in the LpxC activity that can be restored by subsequent addition of Zn2+ . However, high concentrations of Zn2+ also inhibit LpxC . Addition of Co2+, Ni2+, or Mn2+ to apo-LpxC also activates the enzyme to varying degrees while no additional activity is observed upon the addition of Cd2+, Ca2+, Mg2+, or Cu2+ . This is consistent with the profile of metals that substitute for catalytic zinc ions in metalloproteinases . Co2+ ions stimulate LpxC activity maximally at a stoichiometry of 1:1 . These data demonstrate that E . coli LpxC is a metalloenzyme that requires bound Zn2+ for optimal activity.

Biochem J, 1999 Mar 1, 338 ( Pt 2), 561 - 8
Regulation of UDP-N-acetylglucosamine:dolichyl-phosphate N-acetylglucosamine-1-phosphate transferase by retinoic acid in P19 cells; Meissner JD et al.; UDP-N-acetylglucosamine:dolichyl-phosphate N-acetylglucosamine-1-phosphate transferase (GPT) is the first enzyme in the dolichol pathway of protein N-glycosylation, and is implicated in the developmental programmes of a variety of eukaryotes . In the present study we describe the effects of all-trans-retinoic acid (RA) on the levels of GPT protein and enzymic activity, and on the transcription rate of the GPT gene, in mouse P19 teratocarcinoma cells . RA caused a dose-dependent and protein-synthesis-dependent induction of enzyme activity . The maximum induction of GPT activity (about 3-fold) required 2 days of exposure to 1 microM RA . Induced GPT activity also resulted in an increase in the rate of incorporation of {3H}mannose into Glc3Man9GlcNAc2 . Enzymic activities paralleled GPT gene expression . The GPT gene was induced (2-fold) after 7 h of RA treatment . An approx . 3-fold increase in a 48 kDa GPT protein and approx . 4-fold increases in the levels of three GPT transcripts (1.8, 2.0 and 2.2 kb) were observed after 2 days of RA treatment . The enhanced levels of GPT protein and mRNAs began to decline 3 days after the initiation of differentiation, and GPT expression was down-regulated during cellular differentiation . GPT activity decreased about 2 . 8-fold to a constant level in differentiated P19 cells . The results indicate that the RA-induced enzyme activity was mainly determined by increased transcription of the GPT gene . RA-treated P19 cells were about 4-fold more resistant to tunicamycin, a fungal antibiotic which inhibits GPT, than were control cells . In addition, GPT activity in membranes from RA-treated P19 cells exhibited approx . 4-fold increased resistance to tunicamycin compared with activity in membranes from untreated control cells, demonstrating that resistance to tunicamycin is correlated with induced GPT activity . Furthermore, increased GPT activity had regulatory significance with regard to the rate of incorporation of {3H}mannose into Glc3Man9GlcNAc2-P-P-dolichol and into glycoproteins . Together, the data provide additional insights into the hormonal regulation of GPT and present evidence that the RA-mediated induction of GPT has a regulatory impact on the dolichol pathway.

Poult Sci, 1999 Jan, 78(1), 70 - 4
Calcium dependency of interleukin-1 secretion by a chicken macrophage cell line; Cieszynski JA et al.; The role of calcium in transducing the signal for interleukin-1 (IL-1) secretion was examined in the MQ-NCSU chicken macrophage cell line . Cells were maintained in RPMI 1640 medium supplemented with 5% chicken serum and antibiotic-antimycotic solution at 40 C and 5% CO2 . The effects of stimulation with lipopolysaccharide (LPS), calcium ionophore A23187, or a combination of both on IL-1 secretion were examined . Calcium ionophore A23187 did not replace LPS in MQ-NCSU stimulation but the LPS + A23187 combination stimulated more IL-1 than ionophore alone in these cells . The combination of LPS and ionophore did not increase IL-1 secretion above the levels observed with LPS alone . No synergistic effects between LPS and A23187 were evident . In order to demonstrate that IL-1 secretion by the MQ-NCSU cells is a calcium-dependent process, ethylene glycol bis(beta-aminoethyl ether)N,N,N',N'-tetraacetic acid (EGTA) was used to chelate free calcium in the cultures . Incorporation of 5 mM EGTA in the cultures lowered IL-1 stimulated by LPS + A23187 to control levels . Addition of 5 mM CaC12 to EGTA-suppressed cultures restored IL-1 secretion . These results indicate that the calcium ionophore, A23187, augments IL-1 secretion by LPS-stimulated MQ-NCSU macrophages and that IL-1 secretion by these cells is a calcium-dependent process.

Curr Genet, 1999 Feb, 35(1), 41 - 50
The role of an extracellular chitinase from Trichoderma virens Gv29-8 in the biocontrol of Rhizoctonia solani; Baek JM et al.; The role of extracellular chitinase in the biocontrol activity of Trichoderma virens was examined using genetically manipulated strains of this fungus . The T . virens strains in which the chitinase gene (cht42) was disrupted (KO) or constitutively over-expressed (COE) were constructed through genetic transformation . The resulting transformants were stable and showed patterns similar to the wild-type (WT) strain with respect to growth rate, sporulation, antibiotic production, colonization efficiency on cotton roots and growth/survival in soil . Biocontrol activity of the KO and COE strains were significantly decreased and enhanced, respectively against cotton seedling disease incited by Rhizoctonia solani when compared with the WT strain.

Bioorg Med Chem Lett, 1999 Jan 18, 9(2), 227 - 32
Preparation and immunosuppressive activity of 32-(O)-acylated and 32-(O)-thioacylated analogues of ascomycin; Hersperger R et al.; A series of 32-(O)-acylated and 32-(O)-thioacylated derivatives of the antibiotic ascomycin (1) have been synthesized . These readily accessible analogues exhibit potent immunosuppressive activity in vitro, as measured by an interleukin-2 reporter gene assay and the mixed lymphocyte reaction . Such molecules are expected to have a therapeutic potential in chronic inflammatory diseases of the airways such as asthma.

Eur J Biochem, 1998 Dec 15, 258(3), 1059 - 67
The StrQ protein encoded in the gene cluster for 5'-hydroxystreptomycin of Streptomyces glaucescens GLA.0 is a alpha-D-glucose-1-phosphate cytidylyltransferase (CDP-D-glucose synthase); Beyer S et al.; The gene strQ was identified as the last gene of a putative transcription unit, strB1FGHPQ, located in the gene cluster for the production of 5'-hydroxy-streptomycin (OH-Sm) in Streptomyces glaucescens GLA.0 . {In contrast, the corresponding operon in the str/sts-gene cluster of the Sm-producer Streptomyces griseus, strB1FGHIK, differs in the two distal genes; Mansouri, K . & Piepersberg, W . (1991) Mol . Gen . Genet . 228, 459-469} . The deduced StrQ protein exhibited similarities to members of the enzyme family of hexose-1-phosphate nucleotidylyltransferases (NDP-hexose synthases or pyrophosphorylases), with the strongest similarity to the subfamily of alpha-D-glucose-1-phosphate cytidylyltransferases (CDP-D-glucose synthases) . The StrQ protein was heterologously expressed in Escherichia coli . The purified protein revealed an enzyme activity of that of a CDP-D-glucose synthase and a substrate specificity restricted to CTP and alpha-D-glucose 1-phosphate . The K(m) and Vmax values determined for CTP are 44 microM and 920 microM and for alpha-D-glucose 1-phosphate 195 microM and 1.06 mM, respectively . The CDP-D-glucose synthase activity was also detected in cells of S . glaucescens under the conditions of antibiotic production, but was absent from cells of the streptomycin producer S . griseus N2-3-11 . Also, the genomes of several strains of S . griseus did not seem to possess strQ-related genes . In contrast, hybridisation experiments indicated that genes homologous to strQ were probably present in various other actinomycetes producing aminoglycosides . A possible function of the StrQ protein in the OH-Sm biosynthetic pathway of GLA.0 is discussed.

Biol Pharm Bull, 1999 Jan, 22(1), 55 - 60
Sustained release liquid preparation using sodium alginate for eradication of Helicobacter pyroli; Katayama H et al.; We prepared a new liquid preparation for eradication of Helicobacter pylori (HP), and examined drug release in vitro and in vivo . The liquid preparation mainly consisted of a sodium alginate (AG) aqueous solution containing ampicillin (ABPC), an antibiotic drug, or methylene blue, a dye . Drug release was retarded by Ca pre-treatment (0.10 M, 20 s) of the AG preparation in in vitro drug release studies due to gel-formation at the liquid surface . In in vivo experiments, the AG preparations were administered orally to rats . The rats were divided into two groups, with or without pre-administration of ranitidine hydrochloride (RH, an H2-blocker) . The total remaining % of ABPC in the stomach was high in the rats administered the AG preparation compared to the ABPC solution . The AG preparation might float in the stomach without adhering to the gastric wall in the rats without pre-administration of RH . The total remaining % of ABPC at 30 min was almost 100% in the RH pre-administration rats administered the AG preparation, and about 80% of the drug existed in fraction 2 (implying adhesion of the preparation on the gastric mucus) . At 60 min, the total remaining % in the AG preparation plus Ca (mean 87%) increased about 2-fold compared to that in the AG preparation alone (mean 44%) . In this case, a large portion of the remaining ABPC also existed in fraction 2 . This preparation may be useful for eradication of HP.

Arch Intern Med, 1999 Feb 8, 159(3), 266 - 70
Doxycycline is a cost-effective therapy for hospitalized patients with community-acquired pneumonia; Ailani RK et al.; BACKGROUND: Doxycycline has a high degree of activity against many common respiratory pathogens and has been used in the outpatient management of lower respiratory tract infections, including pneumonia . OBJECTIVE: To evaluate the efficacy of intravenous doxycycline as empirical treatment in hospitalized patients with mild to moderately severe community-acquired pneumonia . PATIENTS AND METHODS: We conducted a randomized prospective trial to compare the efficacy of intravenous doxycycline with other routinely used antibiotic regimens in 87 patients admitted with the diagnosis of community-acquired pneumonia . Forty-three patients were randomized to receive 100 mg of doxycycline intravenously every 12 hours while 44 patients received other antibiotic(s) (control group) . The 2 patient groups were comparable in their clinical and laboratory profiles . RESULTS: The mean+/-SD interval between starting an antibiotic and the clinical response was 2.21+/-2.61 days in the doxycycline group compared with 3.84+/-6.39 days in the control group (P = .001) . The mean+/-SD length of hospitalization was 4.14+/-3.08 days in the doxycycline group compared with 6.14+/-6.65 days in the control group (P = .04) . The median cost of hospitalization was $5126 in the doxycycline group compared with $6528 in the control group (P = .04) . The median cost of antibiotic therapy in the doxycycline-treated patients ($33) was significantly lower than in the control group ($170.90) (P<.001) . Doxycycline was as efficacious as the other regimens chosen for the treatment of community-acquired pneumonia . CONCLUSION: Doxycycline is an effective and inexpensive therapy for the empirical treatment of hospitalized patients with mild to moderately severe community-acquired pneumonia.

Am J Obstet Gynecol, 1999 Feb, 180(2 Pt 1), 410 - 5
Treatment of toxoplasmosis during pregnancy: a multicenter study of impact on fetal transmission and children's sequelae at age 1 year; Foulon W et al.; OBJECTIVE: Toxoplasmosis during pregnancy can cause fetal infection, with unpredictable sequelae in later life . We measured the effects of prenatal antibiotic therapy on the fetomaternal transmission of Toxoplasma gondii and on the appearance of sequelae in the congenitally infected child at age 1 year . STUDY DESIGN: In a multicenter study we investigated consecutive women with Toxoplasma seroconversion during pregnancy . Data were obtained from 144 women recruited in 5 different Toxoplasma reference centers . Through multivariate analysis we assessed the association between transmission and appearance of sequelae as a function of the following parameters: estimated gestational age at infection, administration of antibiotic therapy, duration of antibiotic therapy, and time lapse between infection and the start of antibiotic therapy . RESULTS: Sixty-four of the 144 women (44%) gave birth to a congenitally infected infant . Multivariate analysis showed that transmission was predicted neither by whether antibiotics had been administered nor by the time lapse between infection and the start of antibiotic therapy, but only by the gestational age at which maternal infection occurred (P <.0001) . Sequelae were found in 19 children (13%), 9 of whom (6%) had severe sequelae . Administration of antibiotics was predictive of the absence of sequelae (P =.026, odds ratio 0.30, 95% confidence interval 0.104-0.863), in particular the absence of severe sequelae (P =.007, odds ratio 0.14, 95% confidence interval 0.036-0.584) . The sooner antibiotics were given after the infection, the less frequently sequelae were seen (P = . 021) . CONCLUSION: Prenatal antibiotic therapy after toxoplasmosis during pregnancy had no impact on the fetomaternal transmission rate but reduced the rate of sequelae among the infected infants . The early start of treatment resulted in a significant reduction in the number of severely affected infants.

Pediatr Nurs, 1998 May-Jun, 24(3), 205 - 12, 225
Prevention of infective endocarditis in the pediatric congenital heart population; Estlow MM; In 1997, the American Heart Association updated recommendations for the prevention of sub-acute bacterial endocarditis (SBE) or infective endocarditis (IE) occurring in the pediatric population with congenital heart disease (Dajani, et al., 1997) . Although uncommon, endocarditis remains an important cause of morbidity and mortality in children with cardiovascular disease, which constitutes the primary population at risk . Through comprehensive discharge planning and teaching, the advanced practice nurse (APN) and the pediatric cardiovascular nurse may contribute significantly toward preventing IE in this population . Nursing's role and responsibility is to convey the appropriate information to patients, families, and the staff who care for children with heart disease.

Khirurgiia (Sofiia), 1998, 51(3), 14 - 5
{Intra-arterial therapy as a treatment method in acute pancreatitis}; Petrov P et al.; Intra-arterial therapy has a definite place in the complex management of pancreatitis . Drug infusion into the celiac trunk and a . mesenterica superior is a procedure bringing about the highest concentration (16-18 times) in the pathological focus (Briskinikol), inactivation of vasoactive and toxic products, interference with autolysis of the gland, allowing in turn the administration of smaller drug amounts . Intraarterial therapy (IT) is carried out in 18 patients presenting destructive pancreatitis: total necrosis--2, focal necrosis--8 and hemorrhagic pancreatitis--8, with ages ranging from 25 to 65 years, in a poor general condition . IT is conducted after catheterization of truncus celiacus and celiacography, with infusion effected through single time introduction of 0.5 per cent novocain solution, heparin, kontrikal, Petphtoruracil, antibiotic and atropine.

Anesth Analg, 1999 Feb, 88(2), 268 - 70
Endobronchial intubation causes an immediate increase in peak inflation pressure in pediatric patients; Campos C et al.; Our purpose was to determine whether endobronchial intubation always causes an immediate increase in peak inflation pressure and, if so, the magnitude of the increase . Fourteen children scheduled for central line placement for prolonged antibiotic administration comprised the study group . After routine premedication and induction of anesthesia (halothane in oxygen), an endotracheal tube was inserted, and its position was verified by auscultation and fluoroscopy . Children were mechanically ventilated using a preset volume pressure-limited ventilator with a 5-L fresh gas flow . All children received a constant tidal volume using a similar circuit, similar tubing, and a similar compression volume . The lowest peak inflation pressure to deliver a tidal volume of 15 mL/kg was used . After adjusting the respiratory rate (end-tidal CO2 30 mm Hg) and anesthetic level (halothane end-tidal 1.2%), the peak inflation pressure at this endotracheal position was recorded . The endotracheal tube was advanced into a bronchus, the position was verified as above, and peak inflation pressure was recorded . The endobronchial tube was then pulled back into the trachea, and placement of the central line proceeded . The peak inflation pressure at the endobronchial position was significantly greater than the peak inflation pressure at the endotracheal position (P < 0.0001) . The increase was instantaneous at the endobronchial position . Monitoring peak inflation pressure while inserting an endotracheal tube and during anesthesia can help to diagnose endobronchial intubation . Implications: Monitoring peak inflation pressure while inserting an endotracheal tube and during anesthesia can help to diagnose endobronchial intubation.

Ann Pharmacother, 1999 Jan, 33(1), 22 - 6
Torsade de pointes induced by cisapride/clarithromycin interaction; Piquette RK; OBJECTIVE: To highlight a case of torsade de pointes ventricular arrhythmia induced by the concomitant use of cisapride and clarithromycin . CASE SUMMARY: A 77-year-old white woman was admitted to the hospital with a diagnosis of pneumonia and exacerbation of congestive heart failure . In addition to her usual medications, which included cisapride, the patient was prescribed trimethoprim/sulfamethoxazole and clarithromycin for pneumonia . Within 48 hours, the patient had documented episodes of symptomatic torsade de pointes arrhythmia, which eventually responded to therapy . Both cisapride and clarithromycin were discontinued, and the patient did not have any recurring episodes during a 32-month follow-up . DISCUSSION: Cisapride has been implicated in causing adverse cardiac events, including torsade de pointes arrhythmia . In most cases, the patients had preexisting risk factors for torsade de pointes and/or were receiving other medications known to inhibit the hepatic CYP3A4 enzyme system and the metabolism of cisapride . There is evidence that clarithromycin, a relatively new macrolide antibiotic, also inhibits the isoenzyme CYP3A4 . The resulting accumulation of cisapride caused by concomitant clarithromycin therapy was believed to have been the cause of the torsade de pointes arrhythmia in this patient . CONCLUSIONS: Concomitant use of cisapride and clarithromycin may cause torsade de pointes arrhythmia.

Adv Dent Res, 1998 Nov, 12(2), 136 - 43
Tetracycline derivatives induce apoptosis selectively in cultured monocytes and macrophages but not in mesenchymal cells; Bettany JT et al.; Evidence for a non-antibiotic activity displayed by certain tetracycline derivatives is presented . This activity is a selective cytotoxicity toward cells of the monocytic lineage (the human histiocytic lymphoma U937 cell line and the mouse macrophage line RAW264) but not toward various cells of a mesenchymal lineage (including primary ovine articular chondrocytes and meniscal cells, murine calvarial osteoblasts and MG-63 osteosarcoma cells, and primary human neonatal foreskin fibroblasts) . Cells were incubated with various chemically modified tetracycline derivatives (CMTs) or doxycycline for 24 hrs at a range of concentrations between zero and 50 micrograms/mL in both serum-containing and serum-free culture conditions . Assessment of cell viability by means of the MTT assay demonstrated a potent dose-dependent cytotoxic effect induced by compound CMT-3 and a less potent effect induced by doxycycline, but no apparent cytotoxic effect in the presence of either CMT-2 or CMT-5 . Cytospin preparations analyzed by the labeling of DNA fragments indicated the same trends and suggested that cell death was via an apoptotic mechanism . The cytotoxic potency of these tetracyclines toward cells of the monocytic lineage could be diminished but not abolished by either the presence of 10% fetal calf serum within the culture medium, or pre-treatment with phorbol esters to promote a more macrophage-like phenotype . These data provide evidence that, in addition to well-characterized antibiotic and MMP-inhibitory characteristics, tetracyclines may function by a novel mechanism to induce selective apoptosis.

Plant Physiol, 1999 Feb, 119(2), 565 - 74
Rhizosphere bacteria enhance selenium accumulation and volatilization by indian mustard
de Souza MP, Chu D, Zhao M, Zayed AM, Ruzin SE, Schichnes D, Terry N.
Indian mustard (Brassica juncea L.) accumulates high tissue Se concentrations and volatilizes Se in relatively nontoxic forms, such as dimethylselenide . This study showed that the presence of bacteria in the rhizosphere of Indian mustard was necessary to achieve the best rates of plant Se accumulation and volatilization of selenate . Experiments with the antibiotic ampicillin showed that bacteria facilitated 35% of plant Se volatilization and 70% of plant tissue accumulation . These results were confirmed by inoculating axenic plants with rhizosphere bacteria . Compared with axenic controls, plants inoculated with rhizosphere bacteria had 5-fold higher Se concentrations in roots (the site of volatilization) and 4-fold higher rates of Se volatilization . Plants with bacteria contained a heat-labile compound in their root exudate; when this compound was added to the rhizosphere of axenic plants, Se accumulation in plant tissues increased . Plants with bacteria had an increased root surface area compared with axenic plants; the increased area was unlikely to have caused their increased tissue Se accumulation because they did not accumulate more Se when supplied with selenite or selenomethionine . Rhizosphere bacteria also possibly increased plant Se volatilization because they enabled plants to overcome a rate-limiting step in the Se volatilization pathway, i.e . Se accumulation in plant tissues.

Dig Dis Sci, 1999 Jan, 44(1), 108 - 15
Attenuation of hydrophobic phospholipid barrier is an early event in Helicobacter felis-induced gastritis in mice; Lichtenberger LM et al.; Helicobacter pylori infection has been linked to the development of gastritis which can then progress to a number of disease entities including peptic ulcer disease and gastric cancer . Since the pathogenic mechanism by which the bacteria causes gastritis is unresolved, we employed a model system, the H . felis-infected mouse to investigate the temporal relationship between bacterially-induced alterations in the hydrophobic phospholipid barrier of the stomach and the development of gastritis . In the present study, C57BL/6 mice were inoculated with 10(9) CFU of H . felis and the changes in gastric wet weight, histology, surface hydrophobicity, phospholipid/phosphatidylcholine concentration, phospholipase A2 activity, and the pH of collected gastric juice were measured 0.5-2 months postinoculation . In related experiments, we investigated the effects of treating H . felis infected mice with antibiotic/ bismuth therapy on the above gastric properties . It was determined that both gastric surface hydrophobicity and phospholipid composition were significantly attenuated as early as 2-4 weeks postinfection, preceding signs of mucosal inflammation and glandular atrophy as indicated by increases in gastric wet weight, pH and a disappearance in parietal cells . These early H . felis-induced changes in gastric surface hydrophobicity and phospholipid concentration were reversed by antibiotic/bismuth therapy . Based on these results we conclude that H . felis infection induces an early transformation of the stomach from a hydrophobic to an acid-sensitive hydrophilic state that may trigger the subsequent development of gastritis.

Hepatogastroenterology, 1998 Nov-Dec, 45(24), 2190 - 2
Successful conservative treatment for esophageal perforation by a fish bone associated with mediastinitis; Nozoe T et al.; A 74 year-old man presenting with esophageal perforation associated with mediastinitis due to the swallowing of a fish bone is reported herein . Conservative treatment, including starvation therapy and the injection of antibiotic drugs, proved to be successful for this patient . Although the optimal treatment for esophageal perforation remains controversial, it is important to choose the appropriate strategies when treating cases of esophageal perforation with mediastinitis.

Clin Pharmacol Ther, 1999 Jan, 65(1), 50 - 7
Pharmacokinetics of meropenem in critically ill patients with acute renal failure undergoing continuous venovenous hemofiltration; Tegeder I et al.; OBJECTIVE: Meropenem is a broad-spectrum antibiotic used for severe infections . In patients with chronic end-stage renal failure, meropenem clearance is reduced and doses must be adjusted according to the creatinine clearance . The aim of this study was to assess pharmacokinetic data of meropenem in patients with acute renal failure and to determine the amount of drug removed by continuous venovenous hemofiltration, an often-used renal replacement therapy in patients with acute renal failure . METHODS: Nine critically ill anuric patients with acute renal failure undergoing continuous venovenous hemofiltration received 500 mg meropenem 2 or 3 times daily . Plasma and hemofiltrate concentrations were determined during 1 dosing interval at steady state . Pharmacokinetic parameters were calculated for a 2-compartment open model and dose requirements were calculated . RESULTS: The total meropenem clearance was 52.0 +/- 8.4 mL/min, with a hemofiltration clearance of 22.0 +/- 4.7 mL/min and a nonrenal-nonhemofiltration clearance of 29.9 +/- 5.4 mL/min; 235.9 +/- 88.6 mg, or 47.2% +/- 17.7%, of the dose were removed through continuous venovenous hemofiltration . The terminal elimination half-life was 8.7 +/- 3.5 hours and the volume of distribution at steady state was 12.4 +/- 1.8 L . Peak and trough concentrations for a dosing interval of 12 hours were 38.9 +/- 9.7 mg/L and 7.3 +/- 1.3 mg/L, respectively . The corresponding concentrations for a dosing interval of 8 hours were 44.7 +/- 10.4 mg/L and 11.9 +/- 0.7 mg/L, respectively . CONCLUSION: Pharmacokinetic data of anuric patients with acute renal failure were similar to those of patients with end-stage renal failure . Because hemofiltration contributes significantly to meropenem elimination, the recommended dose for critically ill anuric patients receiving continuous venovenous hemofiltration should be increased by 100% to avoid potential underdosing.

Arch Esp Urol, 1998 Dec, 51(10), 1041 - 4
{Fournier gangrene: our experience}; Jimenez Verdejo J et al.; OBJECTIVE: Fournier's gangrene is a necrotizing fasciitis involving the genitoperineal region caused by the synergistic action of aerobic and anaerobic pathogens . It is a rapidly progressing disease and carries a high mortality . Our experience with Fournier's gangrene is presented . METHODS: Herein we describe 11 cases of Fournier's gangrene that were diagnosed and treated from 1991 to 1996 . The most important predisposing factor was diabetes mellitus and the most common triggering factor was a perianal condition . RESULTS/CONCLUSIONS: The survival rate was high (81%) and can be ascribed to early diagnosis, aggressive and rapid surgical treatment with debridement, resection of the necrotic areas, drainage, simultaneous broad spectrum antibiotic therapy and frequent local treatment.

Oncology, 1999, 56(2), 97 - 102
Complications of subcutaneous infusion port in the general oncology population; Ballarini C et al.; Subcutaneous infusion ports (SIPs) represent a valid method for long-term chemotherapy . The SIPs have several advantages over other methods of venous access: they are easy to implant under local anaesthesia, have less discomfort for the patients, allow low costs, can be implanted in day hospital, and can be managed ambulatorily . However, SIPs have delayed complications, frequently related to clinical conditions of the neoplastic patients, and immediate complications, often due to the placement technique . From March 1992 to March 1997 we placed, under local anaesthesia and under fluoroscopic control, 102 SIPs in 99 general oncology patients for long-term chemotherapy (88% solid, 12% haematological tumours) . The percutaneous venous access devices were in the subclavian vein in 96% of the cases and in the internal jugular vein in 4% of them . Immediate complications were: 1 haemopneumothorax, which required thoracic aspirations and two blood transfusions, 1 loop of the tunneled part of the catheter without alterations in SIP function, and 1 left jugular thrombosis in a patient with subclavian veins already thrombosed . The venous access was in the subclavian vein in the first 2 cases, and it was not necessary to suspend the therapeutic program . In the third instance, implanted in jugular vein, it was necessary to remove the SIP . Delayed complications were: 1 necrosis of the skin over the port, 1 infection of subcutaneous pocket, 2 infections of the system, 1 catheter deconnection, and 3 catheter ruptures with embolization of the catheter tip . The SIPs were removed in all cases but 1 in whom infection was successfully treated by appropriate antibiotic therapy . Embolization of the catheter required removal from the pulmonary artery under fluoroscopic guidance in the cardiac catheterization laboratory . In conclusion, infection and thrombosis are the two major complications of SIP in general oncology patients . In these cases it is not necessary to remove systematically the system, but a correct therapy (antibiotic, fibrinolytic agents) can be utilized with good results . The catheter rupture is often due to the wear over the costoclavicular angle . The interventional radiology is the method of choice in the treatment of the catheter embolization by rupture or dislocation . The experience of the surgical and nursing staff is probably the most important factor in decreasing the total rate of complications.

Eur J Pediatr, 1999 Jan, 158(1), 32 - 7
Isoprinosine does not protect against frequent respiratory tract infections in childhood; Litzman J et al.; Isoprinosine, an in vitro immuno-enhancing agent principally acting by stimulating T-lymphocytes, is one of a number of agents sometimes used in an attempt to prevent recurrent respiratory infections in children, although there are no formal trials for this particular drug . We performed a placebo-controlled double-blind trial to assess the efficacy of isoprinosine (50 mg/kg per day) for 6 weeks followed by 50 mg/kg per day twice weekly for 6 weeks in the prevention of frequent acute respiratory tract infections in 102 children aged 4-8 years . A total of 43 children treated with isoprinosine and 41 with placebo finished the study . Despite a transient increase in the total number of CD3+, CD4+ and CD8+ T-lymphocytes after 6 weeks of daily isoprinosine treatment, there was no difference in the number and length of duration of acute respiratory infections, number of antibiotic courses and number of days with cough, pharyngitis, rhinitis and increased body temperature (> or = 37.0 degrees C and > or = 38.0 degrees C) . There were no changes in markers of T- or B-lymphocyte activation (CD25, HLA-DR, CD45RA/RO, CD23) . CONCLUSION: Attempts at immunomodulation using isoprinosine in the dose and for the duration used may increase the total numbers of both CD4 and CD8 T-lymphocytes but is ineffective in prevention of respiratory tract infections in childhood.

Int J Cancer, 1999 Jan 18, 80(2), 279 - 84
Inhibition of N-linked glycosylation by tunicamycin enhances sensitivity to cisplatin in human head-and-neck carcinoma cells; Noda I et al.; Tunicamycin (TM), a naturally occurring antibiotic, blocks the first step in the biosynthesis of N-linked oligosaccharides in cells . In this study, we investigated whether changes in N-linked glycosylation affect the sensitivity of head-and-neck carcinoma cell lines to cis-diaminedichloroplatinum(II) (cisplatin) in vitro and in vivo . In vitro treatment of the IMC-3 and KB cell lines with TM significantly decreased the 50% inhibitory concentration (IC50) of cisplatin, as determined by the MTT assay (24.15 to 10.97 microg/ml, p < 0.05) . In addition, TM significantly decreased the IC50 of cisplatin against established cisplatin-resistant IMC-3/CR cells (>100 to 14.4 microg/ml, p < 0.05) to levels similar to those against parental IMC-3 cells . TM treatment decreased the number of Con A- and L-PHA-binding sites on the surface of tumor cells but had no effect on the intracellular platinum concentration . Induction of apoptosis in vitro by TM plus cisplatin in combination was increased compared with that by cisplatin alone . Furthermore, in vivo administration of TM plus cisplatin in combination significantly inhibited local tumor growth in the cisplatin-resistant in vivo C3H/He mouse model as compared with the control group (p < 0.05) and increased in vivo apoptosis of tumor cells . Our results suggest that the manipulation of glycosylation by TM in tumor cells might be a useful therapeutic strategy for successful chemotherapy using cisplatin against head-and-neck cancer.

Int J Cancer, 1999 Jan 18, 80(2), 257 - 64
Over-production of parathyroid hormone-related peptide results in increased osteolytic skeletal metastasis by prostate cancer cells in vivo; Rabbani SA et al.; Prostate carcinoma is one of the most common malignancies affecting males, resulting in a high rate of morbidity and mortality . This hormone-dependent malignancy is characteristically associated with a high incidence of osteoblastic skeletal lesions . However, osteolytic lesions invariably accompany blastic ones . In the current study, we assessed the role of parathyroid hormone-related peptide (PTHRP), a potent bone-resorbing agent, in contributing to bone breakdown and prostatic skeletal metastasis using a syngeneic rat prostate cancer model . The full-length cDNA encoding rat PTHRP was subcloned as a Hind III insert in the sense orientation into the mammalian expression vector pRc-CMV to generate the expression vector pRc-PTHRP-S . Both control and experimental plasmids were stably transfected into low PTHRP-producing Dunning R3227, Mat Ly Lu rat prostate cancer cells . Following antibiotic selection, monoclonal cell lines expressing the highest amount of PTHRP mRNA and immunoreactive PTHRP were selected as experimental tumor cells for further analysis . Increased PTHRP production by these cells had no significant effect in vitro on the invasive capacity of these cells . Control and experimental cells were inoculated s.c . into the right flank or by the intracardiac (i.c.) route into the left ventricle of inbred male Copenhagen rats . No skeletal metastases occurred after s.c . injection with either cells . In contrast, i.c . inoculation led to lumbar vertebra metastasis and consequent hind-limb paralysis . Furthermore, histological examination of skeletal metastases in experimental animals showed a marked increase in osteoclastic activity . Our results demonstrate that PTHRP can increase osteoclastic osteolysis in the presence of focal osseous prostate cancer metastases and may contribute to the lytic lesions which generally accompany osteoblastic lesions in prostate cancer.

Ophthalmic Res, 1999, 31(2), 140 - 2
Animal study on the effects of catalin on aftercataract and posterior capsule opacification; Biswas NR et al.; PURPOSE: To find out the role of Catalin in the prevention of posterior capsular opacification (PCO), we undertook this experimental study in rabbits . METHODS: Twenty rabbits (10 for the Catalin group and 10 for the placebo group) were operated on for extracapsular clear lens extraction in an aseptic environment . In all cases, capsulorrhexis of 8 mm diameter was carried out . Both the test drug and placebo were given at a dose of 4 times/day from the first postoperative day for 8 weeks . Common drugs in both groups were topical corticosteroid, antibiotic and cycloplegic drops . Periodic slitlamp examinations and photographic documentations were carried out to find any evidence of aftercataract . At the end ot 8 weeks, histopathological examination was carried out to document any evidence of aftercataract . RESULT: Overall, evidence of aftercataract was seen in 6 rabbits in the control group and 3 in the Catalin group; the degree of PCO was higher in the placebo group . CONCLUSION: We found that Catalin played some role in preventing PCO.

Am J Surg, 1998 Dec, 176(6A Suppl), 32S - 38S
The pharmacokinetic effects of coadministration of morphine and trovafloxacin in healthy subjects; Vincent J et al.; BACKGROUND: Morphine and antibiotics are frequently coadministered in the surgical setting . These agents may interact, reducing the efficacy of the antibiotic or increasing the toxicity of morphine . It is therefore important to determine whether antibiotics that might be used for surgical prophylaxis have the potential to change the pharmacokinetics of morphine . It is equally important to learn whether morphine affects the plasma levels of antibiotics and thus may potentially influence their efficacy or tolerability . METHODS: This open, randomized, placebo-controlled, three-treatment, three-period cross-over study enrolled 19 healthy volunteers . Oral trovafloxacin (200 mg), a novel fluoroquinolone antibiotic, and intravenous morphine (0.15 mg/kg) were coadministered, and the effects on the pharmacokinetics of each drug and on changes in the pharmacologic action of morphine, estimated from its effects on respiratory rate and level of sedation, were examined . RESULTS: When trovafloxacin was coadministered with morphine, the half-life of trovafloxacin was unchanged; however, the ratio of the area under the serum concentration versus time curve (AUC(0-infinity)) estimates for trovafloxacin/morphine versus trovafloxacin/placebo was 63.8% (95% confidence interval {CI}, 40.7% to 100.3%), indicating a 36% reduction in the bioavailability of trovafloxacin . The ratio of the mean maximum serum concentration (Cmax) estimates of trovafloxacin for the two treatments was 53.8% (95% CI: 36.1% to 80.1%), indicating a 46% reduction in Cmax . The time to Cmax was delayed by 4 hours . With trovafloxacin coadministration, there were no statistically significant changes in either the mean relative bioavailability of morphine or that of its metabolite, 6beta-glucuronide-morphine . Coadministration of trovafloxacin did not exacerbate the reduction in respiratory rate or increase the number of side effects associated with morphine administration . CONCLUSIONS: Coadministration of trovafloxacin and morphine reduces the bioavailability and maximum serum concentrations of trovafloxacin . However, elimination of oral trovafloxacin is not impaired, suggesting that the efficacy of trovafloxacin could be maintained in many patients who receive concomitant morphine . Morphine plasma levels and pharmacologic effects are not significantly altered by coadministration of trovafloxacin . Despite their similar metabolic pathways, the trovafloxacin/morphine combination neither exacerbates the respiratory depressant effects of morphine nor increases the frequency of side effects when compared with placebo/morphine treatment . These results suggest that the efficacy of trovafloxacin may be maintained when coadministered with morphine . Concurrent administration of trovafloxacin and morphine is unlikely to alter the pharmacologic effects of morphine.

Am J Surg, 1998 Dec, 176(6A Suppl), 23S - 26S
The bioavailability of nasogastric versus tablet-form oral trovafloxacin in healthy subjects; Vincent J et al.; BACKGROUND: Patients in the hospital, as well as those in home care settings, often require nutritional supplementation with enteral feeding solutions . In addition, patients with serious infections who are clinically unstable often cannot maintain adequate intake by mouth and may require an alternative to oral antibiotic administration . However, delivery of crushed oral formulations of drugs via nasogastric tubes is often carried out without adequate bioavailability data, and this method of administration may not always be equivalent to oral drug delivery . METHODS: In an open-label, randomized, four-period, four-treatment, cross-over study, 24 healthy volunteers were given one dose of each of the following treatments, with a 7-day wash-out between dosing periods: Treatment A: two 100-mg trovafloxacin tablets given orally with 240 mL water; Treatment B: two crushed 100-mg trovafloxacin tablets suspended in water and administered through a nasogastric tube into the stomach; Treatment C: two crushed 100-mg trovafloxacin tablets suspended in water and administered through a nasogastric tube into the duodenum; or Treatment D: two crushed 100-mg trovafloxacin tablets suspended in water and given through a nasogastric tube into the stomach concomitantly with an enteral feeding solution (240 mL full-strength Osmolite) . RESULTS: Pharmacokinetic analyses showed that the bioavailability of trovafloxacin after administration of crushed tablets into the stomach with or without concomitant enteral feeding was not significantly different from that of the orally administered whole tablets: the 90% confidence limits of the area under the concentration-time curve (AUC(0-infinity)) for Treatment B versus Treatment A (91.3%, 109.5%) and Treatment D versus Treatment A (91.6%, 109.9%) were well within the bioequivalence criteria of 80% to 125% . Results of analysis of variance (ANOVA) indicated no significant sequence, period, or treatment-by-period interaction effects . Administration of trovafloxacin into the duodenum (Treatment C) resulted in reduced systemic exposure to trovafloxacin, with a 31% decrease in AUC(0-infinity) and a 30% decrease in peak serum concentration (Cmax) compared to oral administration . Time to peak serum concentration (Tmax) was 1.7 hours after oral administration of trovafloxacin and 1.1 hours after administration directly into the stomach or duodenum through a nasogastric tube in the absence of concomitant enteral feeding . All four treatments were well tolerated; no participant discontinued the study due to adverse events and no serious adverse events were reported . CONCLUSIONS: These results showed that administration of crushed trovafloxacin tablets through a nasogastric tube into the stomach, with or without concomitant enteral feeding, achieves absorption and tolerability comparable to those of orally administered trovafloxacin tablets.

Perit Dial Int, 1998 Nov-Dec, 18(6), 583 - 9
Nystatin prophylaxis: its inability to prevent fungal peritonitis in patients on continuous ambulatory peritoneal dialysis; Thodis E et al.; OBJECTIVE: To evaluate the potential effectiveness of nystatin as prophylaxis for fungal peritonitis (FP) in patients on continuous ambulatory peritoneal dialysis (CAPD) . DESIGN: This historically controlled study was designed to investigate the effectiveness of nystatin in the prevention of FP . For this purpose we compared the incidence of FP among 240 (new and prevalent) CAPD patients between January 1996 and November 1996 (period A) with its incidence in 240 new and prevalent CAPD patients in our program between January 1997 and November 1997 (period B) when nystatin prophylaxis was used . There were 2400 patient-months in each period . Nystatin (500,000 IU four times per day), was given orally at the beginning of other antibiotic therapy (usually for peritonitis) and continued for 5 days after the end of the antibiotic therapy . RESULTS: During period A, 133 peritonitis episodes were recorded, and during period B, 99 episodes were recorded . Six episodes of FP were identified in over 2400 patient-months of period A, and 12 in over 2400 patient-months of period B . This difference was not statistically significant . Three episodes of antibiotic-related FP were seen in period A, and four in period B . The remaining episodes arose de novo, that is, unrelated to the use of antibiotics . We observed no side effects for nystatin . CONCLUSION: In CAPD patients the use of nystatin, a nonabsorbable antifungal agent, as prophylaxis in every instance of peritonitis or other indications for antibiotics, did not lower the incidence of fungal peritonitis.

Langenbecks Arch Chir Suppl Kongressbd, 1998, 115, 1197 - 9
{Instillation vacuum sealing--report of initial experiences}; Moch D et al.; Patients with acute (n = 13) or chronic (n = 14) infections were treated by the novel technique of instillation vacuum-sealing, which uses the PVA sponge as a drug-release system for antibiotic and antiseptic solutions . During a follow-up of 4.2 (3-14) months there was one recurrence of infection in a patient with chronic osteomyelitis.

Langenbecks Arch Chir Suppl Kongressbd, 1998, 115, 647 - 54
{The problem of interactions in perioperative prophylaxis: reducing the risk or increasing the risk?}; Lorenz W et al.; Risk research and risk analysis have to be modeled as a fairly complex system including multivariate regression modeling for risk factors in etiology, Markov models in pathogenesis, and a construct of mechanistic and hermeneutic variables for clinical outcome analysis . The McPeek index is proposed as an example . Several prophylaxes for risk reduction in the perioperative period produce risk reduction as well as risk augmentation in different types of outcome . These unexpected findings were observed not only in clinical trials, but also in animal experiments and in isolated tissues . This demonstrates a basic problem of handling complexity in the real clinical setting.

Eksp Klin Farmakol, 1998 Nov-Dec, 61(6), 45 - 7
{The morphological and functional status of the ovaries in rats administered antitumor preparations}; Gol'dberg ED et al.; Experiments were performed on Wistar rats to evaluate comparatively the morphological and functional state of the ovaries in the early and late-term periods after a single injection of a platinum-containing cytostatic drug platidiam and an antibiotic of the anthracycline series farmorubicin . It was found that the antineoplastic agents caused a similar toxic effect on the animal's sexual glands . The number of generative elements in the ovaries decreased in this case and the duration of the estrous cycle, the indices of embryonal death, and the pregnancy index increased.

Eksp Klin Farmakol, 1998 Nov-Dec, 61(6), 39 - 41
{Immunity during ampicillin administration against a background of immunosuppression}; Sakaeva DD et al.; The effect of 50 and 100 mg/kg doses of ampicillin, immunocompromised by cyclophan and azathioprine, on immunity of intact mice was studied . Ampicillin did not change the number of antibody-forming cells (AFC) and delayed hypersensitivity (DHS) in immunosuppression . It inhibited spontaneous oxidant metabolism of neutrophils and macrophages against the background of azathioprine . The therapeutic effect of ampicillin was maintained under such conditions . In intact animals the antibiotic did not change the number of AFC, increased DHS expression, and reduced the spontaneous index of macrophage activation in the nitroblue tetrazolium test.

Radiat Med, 1998 Nov-Dec, 16(6), 457 - 60
Effects of right hemithoracic irradiation on ceftazidime penetration into the alveolar space in rats; Murata T et al.; The effect of thoracic irradiation on antibiotic penetration into the alveolar space was determined in a hemithoracic irradiation rat model to evaluate radiation-induced acute alveolar injury at various time intervals . The results of this investigation may be summarized as follows: (1) The transfer of ceftazidime (CAZ: Modacin) from blood to lung tissue, that is, the permeability of pulmonary capillary epithelium, and the transfer of ceftazidime from lung tissue to bronchoalveolar lavage fluid, that is, the permeability of the alveolar epithelium, peaked at 4 to 5 weeks after thoracic irradiation; (2) the time course of change in the absolute concentration of ceftazidime in lung tissue showed a significant increase not only in the irradiated lung but also in the contralateral non-irradiated lung 3 days or more after irradiation . The finding that the administration of antibiotics may cause a significant increase in drug concentration in lung tissue even in the contralateral lung at 3 days after irradiation suggests that the change induced at the alveolar level immediately after irradiation affects the non-irradiated lung field through an as yet unknown mechanism.

Am Surg, 1999 Feb, 65(2), 147 - 50
Puerperal ovarian vein thrombosis with extension into the inferior vena cava; Clarke CS et al.; The incidence of puerperal ovarian vein thrombosis is estimated to range between 1 in 600 and 1 in 2000 deliveries . The cardinal signs of puerperal ovarian vein thrombosis include fever, leukocytosis, and right lower quadrant abdominal pain, most often in a recently delivered female patient . These patients are classically described as failing to improve with intravenous antibiotic therapy alone; resolution of symptoms and presumptive diagnosis is made on defervescence with the addition of intravenous heparin therapy . Objective diagnostic modalities include venography, ultrasound, laparoscopy, and MRI, although CT remains the gold standard for the identification of this under-diagnosed entity . We present a case report of a 20-year-old female treated at our facility for puerperal ovarian vein thrombosis . She was transferred to our vascular surgery service after developing the classic signs of puerperal ovarian vein thrombosis and undergoing CT demonstrating ovarian vein thrombosis with extension of free-floating thrombus into her inferior vena cava (IVC) . This degree of thrombosis was particularly concerning when one considers the 3 to 33 per cent rate of pulmonary embolism reported in patients with puerperal ovarian vein thrombosis . Treatment modalities for such extensive degrees of thrombosis are described in the literature and range from hysterectomy and thrombectomy to ligation of the IVC . In our case, we prophylactically placed a suprarenal IVC Greenfield filter to protect against pulmonary embolism and proceeded with the standard regimen of anticoagulation and antibiotics . This treatment approach has been reported only twice previously in the literature, to our knowledge.

J La State Med Soc, 1998 Dec, 150(12), 629 - 37
New therapies for cystic fibrosis; Simakajornboon N et al.; In the decade since the gene responsible for cystic fibrosis (CF) was identified, our understanding of the pathophysiology of CF pulmonary disease has significantly improved . The current model for CF lung disease suggests several levels at which clinical interventions may be made in an attempt to alter the natural course of disease progression . The first part of this review highlights some of the progress made in novel forms of therapy directed at earlier portions of the pathophysiologic cascade such as gene therapy, protein therapy, and ion-transport regulatory therapy . New developments in well-established modes of therapy such as mucolytic therapy, airway clearance therapy, and antibiotic therapy are discussed next . The review concludes with a look at the use of two forms of therapy that have been adapted to CF care, anti-inflammatory therapy and lung transplantation.

J Mol Biol, 1999 Feb 5, 285(5), 2069 - 78
Major groove binding of the tRNA/mRNA complex to the 16 S ribosomal RNA decoding site; VanLoock MS et al.; We propose a detailed three-dimensional model, with atomic detail, for the structure of the Escherichia coli 16 S rRNA decoding site in a complex with mRNA and the A and P-site tRNAs . Model building began with four primary assumptions: (1) A and P-site tRNA conformations are identical with those seen in the tRNA crystal structure; (2) A and P-site tRNAs adopt an S-type orientation upon binding mRNA in the ribosome; (3) A1492 and A1493 bind non-specifically to the mRNA through a series of hydrogen bonds; and (4) C1400 lies in close proximity to the P-site tRNA wobble base in order to satisfy a UV-induced photocrosslink formed between the two residues . We have models with both major groove and minor groove binding of the tRNA/mRNA complex to the decoding site RNA, and conclude that major groove binding is more likely . Both classes of models maintain structural features reported in the NMR structure of the A-site region of the decoding site RNA with bound paromomycin . We also present models for the tRNA/mRNA complex bound to the decoding site RNA in the presence of the aminoglycoside paromomycin . We discuss possible mechanisms for ribosomal proof reading and antibiotic disruption of this proofreading .

Eur J Pharm Sci, 1998 Apr, 6(2), 145 - 52
In vitro studies of teicoplanin binding to rat tissues and erythrocytes; Reinoso RF et al.; Teicoplanin is a large polar antibiotic with a large distribution volume (Vss = 1.2-2.8 l/kg) despite extensive binding to plasma albumin . To understand this observation, binding of 3H-teicoplanin to 10% rat tissue homogenates was determined in vitro by ultracentrifugation in the presence of teicoplanin (1-30 microg/ml) . Binding and efflux from erythrocytes were also studied . The in vitro total-to-unbound tissue concentration ratio (Kpu) differed widely but for each tissue was concentration independent . Upon correction for the plasma unbound fraction, there was discrepancy between the in vitro and in vivo tissue-to-plasma concentration ratios (KP), the latter calculated from previously published tissue and plasma concentration-time data using the area method . Moreover, calculation of Vss from in vitro Kp (8.10 l/kg) overestimated the in vivo value . These results suggest that in vivo teicoplanin binds to cell membranes and enters some but not all cells, such as erythrocytes.

Int J Parasitol, 1998 Dec, 28(12), 1885 - 8
Intestinal Cryptosporidium sp . infection in the Egyptian tortoise, Testudo kleinmanni; Graczyk TK et al.; An adult Egyptian tortoise (Testudo kleinmanni) presented with clinical signs of enteritis and died 5 weeks after initiation of antibiotic therapy . Histological examination of the small intestine revealed heavy infection with Cryptosporidium sp.; over 80% of epithelial cells harboured the pathogen . No Cryptosporidium developmental stages were present in the stomach or the lungs . The intestinal lamina propria and mucosa were infiltrated by heterophils, lymphocytes and macrophages . The present study constitutes the first report of Cryptosporidium sp . infection in T . kleinmanni, and the first histological documentation of intestinal cryptosporidiosis in Chelonia.

Acta Neurol Scand, 1999 Jan, 99(1), 26 - 35
Parkinsonism: siblings share Helicobacter pylori seropositivity and facets of syndrome; Charlett A et al.; OBJECTIVE: Given a history of peptic ulcer is more frequent in parkinsonism, to investigate the role of Helicobacter pylori in its pathogenesis and of cross-infection in familial aggregation . METHODS: Facets of parkinsonism were quantified in 33 elderly subjects with idiopathic parkinsonism and in their 39 siblings with double the number of controls, all obeying inclusion/exclusion criteria . Specific-IgG antibody was assayed . RESULTS: Siblings, compared with controls, had brady/hypokinesia of gait (P< or =0.002), bradykinesia of hands (P = 0.01), abnormal posture (P = 0.001), rigidity (P < 0.001) and seborrhoea/seborrhoeic dermatitis (P = 0.02) . Both parkinsonians and siblings differed from controls in the odds of being H . pylori seropositive {odds ratios 3.04 (95% C.I.: 1.22, 7.63) and 2.94 (1.26, 6.86) respectively, P < 0.02}, seropositivity being found in 0.70 of sufferers . CONCLUSION: Familial transmission of chronic infection plus part of syndrome links Helicobacter with causality . Seropositivity not being universal throughout parkinsonism, consequent on gastric atrophy +/- sporadic antibiotic exposure, might explain less aggressive disease in older sufferers.

J Pept Res, 1998 Dec, 52(6), 477 - 81
First record of host defence peptides in tadpoles . The magnificent tree frog Litoria splendida; Wabnitz PA et al.; Tadpoles of the Magnificent Tree Frog Litoria splendida produce host defence peptides early in their development and well before metamorphosis . Peptides were identified and characterized using high performance liquid chromatography and electrospray mass spectrometry . No host defence peptides were identified in the eggs . The neuropeptide caerulein was detected 10 d after egg deposition, and the antibiotic peptides caerin 1.1, caerin 1.6 and caerin 3.1 first appeared at 14 d . The concentration of peptides increases with the onset of metamorphosis at 84 d, when the host-defence peptide profile is the same as that of the adult.

Eur J Clin Microbiol Infect Dis, 1998 Nov, 17(11), 801 - 6
Three cases of tuberculosis after heart transplantation in Spain; Munoz RM et al.; Three cases are presented of tuberculosis occurring in a series of 410 heart transplant recipients in a Spanish hospital, representing a rate of 0.73% . Twenty-eight cases reported in the literature are also reviewed . In most series reported, tuberculosis occurred in a small percentage of heart transplant recipients, the average rate being 1.25% . Compared to the general population, a higher percentage (28%) of extrapulmonary and disseminated forms of the disease is seen in these patients . Although a cure without recurrence can usually be achieved with a conventional anti-tuberculous antibiotic regimen, the disease is still associated with a significant mortality rate of 11% . Guidelines for the early diagnosis and treatment of these patients are discussed.

Cancer, 1999 Jan 1, 85(1), 9 - 17
Mucosa-associated lymphoid tissue lymphoma of the stomach: long term outcome after local treatment; Fung CY et al.; BACKGROUND: Although antibiotic therapy is emerging as effective initial treatment for patients with gastric lymphoma of mucosa-associated lymphoid tissue (MALT), there is a subset of patients for whom antibiotics are ineffective or inappropriate . Surgical resection can be curative, but total gastrectomy may be required for the eradication of all disease . To identify the optimal nonantibiotic therapy for early stage gastric MALT lymphoma, the authors retrospectively evaluated the Massachusetts General Hospital experience with gastric MALT lymphoma . METHODS: Disease patterns and treatment outcomes were retrospectively analyzed in data from 21 consecutive patients with gastric MALT lymphoma who were treated between 1978 and 1995 at the Massachusetts General Hospital . RESULTS: Sixteen patients were Stage IE, and 5 were in higher stages . Treatment consisted of resection with or without radiation or chemotherapy (14 patients), radiation alone (4 patients), or radiation plus chemotherapy (2 patients) . Thirteen Stage IE patients received local therapy only . The 10-year actuarial relapse free survival rate for Stage IE patients was 93%, with 1 relapse among 15 treated patients . Because the patient who relapsed was treated successfully with chemotherapy, the 10-year cancer free survival was 100% . Overall survival for Stage IE patients was 93% at 5 years and 58% at 10 years, with no deaths from lymphoma . CONCLUSIONS: These data indicate that a high probability of long term remission can be achieved with only local treatment of patients with Stage I gastric MALT lymphoma . Preliminary results suggest that radiation therapy is well tolerated and effective and may well be the optimal nonantibiotic treatment for patients with localized gastric MALT lymphoma.

J Bacteriol, 1999 Feb, 181(3), 1043 - 4
Escherichia coli cells exposed to streptomycin display a mutator phenotype; Ren L et al.; Mistranslation mediated by the mutA and mutC tRNA alleles elicits a strong mutator phenotype (H . S . Murphy and M . Z . Humayun, J . Bacteriol . 179:7507-7514, 1997; M . M . Slupska, C . Baikalov, R . Lloyd, and J . H . Miller, Proc . Natl . Acad . Sci . USA 93:4380-4385, 1996) . Here, we show that exposure to streptomycin, an antibiotic known to promote mistranslation, induces a recA- and umuDC-independent mutator phenotype detected as enhanced mutagenesis at a 3, N4-ethenocytosine lesion borne on transfected M13 single-stranded DNA.

N Engl J Med, 1999 Jan 28, 340(4), 260 - 4
Prevalence of various respiratory viruses in the middle ear during acute otitis media; Heikkinen T et al.; BACKGROUND: Vaccines against respiratory viruses may be able to reduce the frequency of acute otitis media . Although the role of respiratory viruses in the pathogenesis of acute otitis media is well established, the relative importance of various viruses is unknown . METHODS: We determined the prevalence of various respiratory viruses in the middle-ear fluid in 456 children (age, two months to seven years) with acute otitis media . At enrollment and after two to five days of antibiotic therapy, specimens of middle-ear fluid and nasal-wash specimens were obtained for viral and bacterial cultures and the detection of viral antigens . The viral cause of the infections was also assessed by serologic studies of serum samples obtained during the acute illness and convalescence . RESULTS: A specific viral cause of the respiratory tract infections was identified in 186 of the 456 children (41 percent) . Respiratory syncytial virus was the most common virus identified in middle-ear fluid: it was detected in the middle-ear fluid of 48 of the 65 children (74 percent) infected by this virus (P< or =0.04 for the comparison with any other virus) . Parainfluenza viruses (15 of 29 children {52 percent}) and influenzaviruses (10 of 24 children {42 percent}) were detected in the middle-ear fluid significantly more often than enteroviruses (3 of 27 children {11 percent}) or adenoviruses (1 of 23 children {4 percent}) (P< or =0.01 for all comparisons) . CONCLUSION: Respiratory syncytial virus is the principal virus invading the middle ear during acute otitis media . An effective vaccine against upper respiratory tract infections caused by respiratory syncytial virus may reduce the incidence of acute otitis media in children.

J Pharmacol Toxicol Methods, 1998 Jul, 40(1), 1 - 12
Therapeutic applications of implantable drug delivery systems; Dash AK et al.; In the past, drugs were frequently administered orally, as liquids or in powder forms . To avoid problems incurred through the utilization of the oral route of drug administration, new dosage forms containing the drug(s) were introduced . As time progressed, there was a need for delivery systems that could maintain a steady release of drug to the specific site of action . Therefore, drug delivery systems were developed to optimize the therapeutic properties of drug products and render them more safe, effective, and reliable . Implantable drug delivery systems (IDDS) are an example of such systems available for therapeutic use . The application of currently available implantable drug delivery systems is the main focus of this review . IDDS can be classified into three major categories: biodegradable or nonbiodegradable implants, implantable pump systems, and the newest atypical class of implants . Biodegradable and nonbiodegradable implants are available as monolithic systems or reservoir systems . The release kinetics of drugs from such systems depend on both the solubility and diffusion coefficient of the drug in the polymer, the drug load, as well as the in vivo degradation rate of the polymer, especially, in the case of the biodegradable systems . Controlled release of drug from the implantable pump is generally achieved utilizing the microtechnology of electronic systems and remote-controlled flow rate manipulation through the maintenance of a constant pressure difference . The third atypical class includes those which have been recently developed such as ceramic hydroxyapatite antibiotic systems used in the treatment of bone infections, intraocular implants for the treatment of glaucoma, and transurethral implants utilized in the treatment of impotence . The major advantages of these systems include targeted local delivery of drugs at a constant rate, less drug required to treat the disease state, minimization of possible side effects, and enhanced efficacy of treatment . Also, these forms of delivery systems are capable of protecting drugs which are unstable in vivo and that would normally require a frequent dosing intervals . Due to the development of such sustained release formulations, it is now possible to administer unstable drugs once a week to once a year that in the past required frequent daily dosing . Preliminary studies using these systems have shown superior effectiveness over conventional methods of treatment . However, one limitation of these newly developed drug delivery systems is the fact that their cost-to-benefit ratio (cost/benefit) is too high which restricts their use over conventional dosage forms . Hopefully, in the future, new implantable systems can be developed at a lower cost, thereby minimizing the cost-to-benefit ratio and therefore, be used extensively in standard therapeutic practice . Some of the most recently discovered implants are in the early developmental stages and more rigorous clinical testing is required prior to their use in standard practice.

J Pharm Biomed Anal, 1998 Dec, 18(4-5), 579 - 83
Derivative spectrophotometric determination of the triethylammonium salt of cefotaxime in presence of related compounds from the synthesis; Nuevas L et al.; Cefotaxime sodium is a broad spectrum third generation antibiotic . It is obtained by reaction of 7-aminocephalosporanic acid (7-ACA) and S-(2-benzothiazolyl)2-amino-alpha-(methoxyimino)-4-thiazoleethanethio ate . 2-Mercaptobenzothiazole is a by-product of this reaction . A derivative spectrophotometric determination of cefotaxime is proposed for its determination in a reaction mixture in the presence of the related compounds from synthesis . With this method Beer's law is obeyed over a concentration range from 0.005 to 0.080 mg ml(-1) at 276.8 nm (r = 0.9995) . This technique is accurate, precise (RSD = 0.4%), and has a sensitivity of 1.2% (differences in analytical response of 0.74 microg ml(-1) could be detected) . Recovery experiments of cefotaxime from reaction mixtures include 100% for all assayed concentrations . For these reasons, this technique is found valid for the intended purposes.

Ophthalmology, 1999 Jan, 106(1), 86 - 90
Periocular atypical mycobacterial infections; Chang WJ et al.; OBJECTIVE: To examine the clinical characteristics and management of periocular infections caused by atypical mycobacteria . DESIGN: Retrospective, noncomparative case series . PARTICIPANTS: Six patients were identified with periocular atypical mycobacterial infections: four with Mycobacterium chelonae and two with Mycobacterium fortuitum . INTERVENTION: The treatment of these infections included removal of the foreign bodies with debridement of the lesions . Specimens were sent for histopathologic examination, routine cultures, and fresh tissue for culture after homogenization . MAIN OUTCOME MEASURES: A retrospective review of culture-proven atypical mycobacterial infections involving the periocular tissues was performed . Charts were reviewed for age, gender, infectious organism, medical history, surgical history, presenting symptoms, clinical features, and treatment . RESULTS: Four associations with infection were identified in these patients: immunosuppression, nasolacrimal duct obstruction, the presence of a foreign body, and a history of recent surgery . All six of the patients had at least one of these associations and five of the patients had at least two . Clinical characteristics that may distinguish atypical mycobacterial infections from acute bacterial infections include subacute presentation, firm nodular lesions, mild erythema, mild tenderness, and minimal purulent discharge . All patients had resolution of their infections after debridement and several weeks of systemic antibiotic therapy guided by susceptibility testing . CONCLUSIONS: Periocular atypical mycobacterial infections are uncommon . The clinical history and examination can raise the suspicion of this infection by revealing the clinical characteristics of these infections . Treatment includes removal of foreign bodies, debridement, and long-term systemic antibiotic therapy.

Melanoma Res, 1998 Dec, 8(6), 493 - 8
Tyrosinase transfection produces melanin synthesis and growth retardation in glioma cells; Singh MV et al.; Tyrosinase is the key enzyme in melanin biosynthesis in pigmented cells . We transfected 9L rat glioma cells with human tyrosinase cDNA that had been cloned in a high expression vector . Stable transfectants were selected by their resistance to the antibiotic G418 . More than a dozen G418-resistant clones were isolated and were screened for tyrosinase expression using dopa-oxidase activity . The clone with the highest tyrosinase activity was selected and expanded for further studies . Northern blot analyses of total RNA from cells showed that the transfected cells had relatively more tyrosinase transcript than SK-MEL-23 human melanotic melanoma cells . The melanin content of the transfected cells was dependent on the concentration of L-tyrosine in the culture medium . In addition, the growth of transfected cells was inhibited when grown in a medium containing high concentrations of L-tyrosine . These results suggest that tyrosinase activity is cytotoxic in a substrate-dependent manner . This may have far reaching therapeutic use for glioma tumours.

Clin Obstet Gynecol, 1998 Dec, 41(4), 842 - 8
Tocolytic therapy in preterm PROM; Allen SR; Preterm premature rupture of the membranes nearly always leads to preterm labor and delivery . Preterm delivery accounts for most of the morbidity attributable to PPROM . Antibiotic and corticosteroid treatment may modify the outcome of pregnancy after PPROM . The extent of morbidities attributable to PPROM also justifies consideration of the use of tocolysis, at least for a limited period of time (48 hours) after preterm amniorrhexis . When begun after the onset of contractions following PPROM, tocolysis generally does not prolong the latency period, although some prolongation may occur before 28 weeks gestational age . Prophylactic tocolysis begun before the onset of labor increases the likelihood of delaying the onset of labor for 1-2 days, but not beyond . Aggressive long-term tocolysis may increase the maternal risk of chorioamnionitis and endometritis . None of the reviewed randomized studies demonstrated a significant neonatal risk . None of these studies showed an improvement in neonatal outcome, although they have not tested the combination of tocolysis and corticosteroid use with appropriate controls . The hypothesis that PROM remote from term should be managed with 1-2 days of prophylactic tocolysis and corticosteroids to enhance fetal pulmonary maturity is attractive, yet it remains inadequately evaluated.

Clin Obstet Gynecol, 1998 Dec, 41(4), 832 - 41
Antenatal corticosteroids in preterm premature rupture of membranes; Chen B et al.; It is clear that there is no unequivocal indication for the use of antenatal corticosteroids in the preterm gestation with PROM . Extrapolating the effects seen in gestations with intact membranes, however, there are potential benefits in reduction of neonatal respiratory disease and intracranial hemorrhage at the expense of increased risks of maternal postpartum infection . Because the lifetime harm from the neonatal grave and the sequelae of infection in the mother are usually mild, we recommend that antenatal corticosteroids be administered to patients with PPROM between the gestational ages of 24-33 weeks in the absence of frank maternal or fetal infection or fetal compromise . With the increasing acceptance of antenatal corticosteroid therapy, it is unlikely that any further prospective randomized trials will be possible because withholding corticosteroids may expose patients to unacceptable potential harm . Therefore, clinical judgments may have to made based solely on the limited data presently available . Hopefully, future clinical investigations will provide useful information about the relation between antenatal corticosteroids and perinatal infections of the mother and infant in the setting of prophylactic antibiotic exposure . Additionally, there is also a need for information establishing a clinical profile for the patient with PPROM that accurately predicts when she is likely to enter spontaneous labor, thus allowing clinicians to increase the likelihood of appropriately administering corticosteroids within 1 week of delivery to maximize potential neonatal benefit.

Pediatrics . 1999 Jan;103(1):E2.
Epidemic of gastrointestinal tract infection including hemorrhagic colitis attributable to Shiga toxin 1-producing Escherichia coli O118:H2 at a junior high school in Japan; Hashimoto H et al.; BACKGROUND: An epidemic of gastrointestinal disturbances related to food ingestion occurred at a junior high school in Komatsu, Japan, and was caused by specifically Shiga toxin (Stx) 1-producing Escherichia coli O118:H2, which has not been reported previously in humans . No outbreak of E coli-producing Stx 1 alone had occurred . METHODS: A total of 526 students and 35 adult staff members who ate the same food at lunch in the school were investigated . Questionnaires about food consumption at lunch were given to all 561 subjects as well as to clinics and hospitals that had treated 79 patients . Stool specimens from 525 subjects, and food, water, and environmental specimens, including cooking utensils, were collected in an attempt to identify the pathogen . RESULTS: A total of 126 subjects (22.5%) developed a diarrheal illness . The pathogen was isolated from the stool in 131 subjects, 49 of which were asymptomatic, and from a dipper . Salads served over several days were identified as high-risk from food analysis . Gastrointestinal symptoms resembled those associated with previous infections of Stx-producing E coli, but were mild . No cases of the hemolytic-uremic syndrome developed . Headache was present in 87 patients . Three patients underwent surgery for acute appendicitis during this epidemic . Four of five carriers had received an antibiotic effective against the pathogen . CONCLUSIONS: This outbreak of E coli O118:H2 demonstrated the clinical and epidemiologic features of infection by E coli that produces Stx 1 alone . Infections with such organisms are being recognized increasingly, and the pattern of disease observed may differ from the pattern observed with E coli O157:H7.

Curr Opin Hematol, 1999 Jan, 6(1), 3 - 7
Granulocyte transfusion therapy; Schiffer CA; Transfusions of granulocytes have been used for many decades to treat serious infections in patients with sustained periods of granulocytopenia . The benefit has been limited somewhat by the technical problems of obtaining adequate doses of granulocytes from normal donors and by histocompatibility issues in alloimmunized recipients . The introduction of granulocyte colony-stimulating factor (G-CSF) as a means to induce granulocytosis in donors has rekindled interest in this therapy, particularly for the treatment of invasive fungal infections . Granulocyte yields after G-CSF stimulation are routinely 3 to 4 times higher than have been used in the past and have resulted in posttransfusion increments for more than 24 hours after transfusion . Studies in progress should help define the utility of these higher dose transfusions in patients with infections refractory to antibiotic therapy.

Prog Urol, 1998 Dec, 8(6), 1077 - 9
{Current role of aminoglycosides in the treatment of acute pyelonephritis}; Caron F; In view of the very great efficacy of 3rd generation cephalosporins and fluoroquinolones used as monotherapy in the treatment of uncomplicated acute pyelonephritis, the addition of an aminoglycoside is not currently recommended, because of the unfavourable balance of the advantages and disadvantages of this antibiotic class . However, a brief course of aminoglycosides may nevertheless be useful during the initial phase of treatment, especially in hospitalised subjects . The authors analyse the contribution of three recently published studies to this debate.

J Card Surg, 1998 Jan, 13(1), 1 - 8; discussion 9-10
Aortic valve replacement with biological substitute; Choudhary SK et al.; In the quest for an ideal aortic valve substitute, homografts and autografts are well-established options . We reviewed our results with homografts and autografts for aortic valve replacement during the last 5 years . From March 1992 through July 1997, 189 patients (138 male and 51 female), age 8 months to 68 years (mean 31.0+/-4.2 years), underwent aortic valve replacement with a human biological substitute . Of these, 93 patients received a cryopreserved or antibiotic-preserved aortic/pulmonary homograft, whereas 96 patients underwent a Ross procedure . Etiology was rheumatic in 143 (75.6%) patients, bicuspid aortic valve in 40 (21.2%), Marfan's disease in 5 (2.6%), and myxomatous aortitis in 1 (0.5%) . Among the homograft group, a scalloped subcoronary implantation technique was used in 54 patients, whereas 32 patients underwent root replacement . Five patients required aortic root and ascending aortia replacement for annuloaortic ectasia . In all patients undergoing the Ross procedure, a root replacement technique was used . Operative mortality was 7.4% (14 patients) . Late mortality was 5.3% (10 patients) . Follow-up ranged from 1 to 46 months postoperatively . In patients with homograft aortic valve replacement, 76 patients (91.5%) had trivial to mild aortic regurgitation, while 7 patients (8.4%) had important aortic regurgitation . In patients with the Ross procedure, 78 patients (89.6%) had trivial to mild regurgitation . Moderate to severe aortic regurgitation was present in 9 patients (10.3%), all of whom had rheumatic heart disease and were young (< 30 years at surgery) . We conclude that homografts and autografts provide an excellent substitute for the diseased aortic valve . Young age (< 30 years) with rheumatic etiology is a major risk factor for early progressive aortic regurgitation in patients undergoing the Ross procedure.

J Eur Acad Dermatol Venereol, 1998 Sep, 11 Suppl 1, S2 - 7; discussion S28-9
Immunomodulatory effects of tretinoin in combination with clindamycin; Wauben-Penris PJ et al.; BACKGROUND: Since acne is a multifactorial skin disease, therapies affecting several etiologic factors can have a higher than expected effectiveness . A combination of the antibiotic clindamycin phosphate and the retinoic acid tretinoin was developed . OBJECTIVE: Anti-inflammatory and immunomodulatory effects of tretinoin in vitro were studied on human keratinocytes and peripheral blood mononuclear cells (PBMCs) . Effects of clindamycin phosphate on tretinoin effects were studied . METHODS: Anti-inflammatory effects on keratinocytes were assessed using an in vitro model with PMA (phorbol ester)-stimulated A431 cells (human epidermoid carcinoma) . Immunomodulatory effects were measured on superantigen (SEB) stimulated PBMCs . RESULTS: Tretinoin showed very potent inhibition of PMA-stimulated IL-6 (interleukin 6) release by A431 cells . The addition of clindamycin phosphate did not interfere with this effect . Tretinoin very potently stimulated IL-5 release, and inhibited IFN gamma release by SEB-stimulated human PBMCs . This indicates an immunomodulatory effect, stimulating Th2, and inhibiting Th1 dominated responses . These features have been related to the healing of acne lesions . The addition of clindamycin phosphate did not interfere with the immunomodulatory effects of tretinoin . CONCLUSION: The combination of tretinoin and clindamycin phosphate can be expected to be very effective in acne therapy.

Biochem Mol Biol Int, 1998 Dec, 46(6), 1219 - 25
Role of reducing co-factor in cerulenin-insensitivity of 6-hydroxymellein synthase in carrot cell extract; Kurosaki F et al.; The activity of 6-hydroxymellein synthase, a multifunctional polyketide biosynthetic enzyme of carrot, was not inhibited by cerulenin in the presence of NADPH . However, cerulenin showed a marked inhibitory activity to the synthase if the reducing co-factor was omitted from the assay mixture . The synthase was also sensitive to the antibiotic even in the presence of NADPH when the acyl condensation site and the reducing domain at the reaction center of the enzyme were dissociated under the high ionic strength condition . In addition, the synthase activity was appreciably inhibited when NADH was employed instead of NADPH . These observations strongly suggest that a phosphate group attached to 2'-position of adenosyl moiety of NADPH molecule plays an important role in the apparent insensitivity of 6-hydroxymellein synthase toward cerulenin.

Rheum Dis Clin North Am, 1998 Nov, 24(4), 737 - 51, viii
Prognosis, course of disease, and treatment of the spondyloarthropathies; Leirisalo-Repo M; Prognosis in the majority of patients with acute reactive arthritis is usually good, with most patients recovering in a few months . In about 15% to 30% of such patients, the disease progresses, and spondyloarthropathy and even ankylosing spondylitis develop in the following 10 to 20 years . A recurrent attack of reactive arthritis is common in patients with chlamydia-triggered arthritis, but it is rare in patients who have had enteroarthritis . In patients with chronic spondyloarthropathy without evidence of preceding infection, the disease can progress slowly into ankylosing spondylitis . When reactive chlamydia arthritis is indicated, a prolonged course of antibiotics is needed . For other forms of reactive arthritis, solid evidence in favor of antibiotic therapy is still lacking . Presence of hip pain, decreased mobility of thoracic cervical or thoracic spine, heel pain, inflammatory gut lesions, high erythrocyte sedimentation rate, positive family history, and presence of human leukocyte antigen B27 are indicators for chronicity . Sulfasalazine might be of use in chronic arthritis and ankylosing spondylitis, especially if the patient has peripheral arthritis.

Dermatol Clin, 1998 Oct, 16(4), 735 - 8, xi-xii
Urethritis treatment; Erbelding EJ et al.; This article reviews most common sexually transmitted causes of urethritis in men . Outlined are clinical presentation, approach, diagnostic work-up, and treatment for the most common pathogens, as well as the cost issues related to antibiotic therapy . Common management problems in urethritis are also discussed.

Anticancer Res, 1998 Nov-Dec, 18(6A), 4163 - 9
Neomycin inhibition of intestinal putrescine uptake; Hardy A et al.; Enhanced intestinal polyamine uptake was confirmed in tumor-bearing rats . Intestinal brush border membrane from rats bearing a Mat Lylu prostatic adenocarcinoma exhibited 46% increase in 14C putrescine uptake . After oral ingestion of 14C putrescine, radioactivity was recovered in the tumor (about 2% of total amount ingested) and was enhanced in liver and in blood . Radioactivity in tumor-bearing rat red blood cells (RBC) was two-fold higher than in healthy control rats indicating that polyamines originating in food can contribute to the enhancement of RBC polyamine levels observed after tumor development . Neomycin-induced inhibition of intestinal putrescine absorption was observed both in vitro and in vivo . In intestinal brush border membrane 500 microM neomycin inhibited putrescine uptake by 30-35% . In vivo, a single dose of neomycin given per os modified final 14C radioactivity distribution: a) The final accumulation of radioactivity in the tumor was reduced by 50% . b) Neomycin treatment lowered the high levels of radioactivity in the blood of cancerous animals . This reduction was correlated with a significant reduction of RBC polyamine levels . c) Radioactivity accumulated in the colon after neomycin treatment in both healthy and cancerous rats . The role of neomycin as an intestinal antibiotic and the presently described effect of this drug on intestinal polyamine uptake emphasize the importance of neomycin in polyamine deprivation treatments.

Biochemistry, 1999 Jan 5, 38(1), 235 - 42
Replication block by an enediyne drug-DNA deoxyribose adduct; Kappen LS et al.; Under anaerobic conditions neocarzinostatin chromophore, an enediyne antibiotic, forms a covalent drug-DNA adduct on the 5' carbon of deoxyribose at a specific single site in a 2-nucleotide bulge, rather than strand cleavage, by a mechanism involving general base-catalyzed intramolecular drug activation to a reactive radical species . We have taken advantage of the selectivity of this reaction to prepare a single-stranded oligonucleotide containing a single drug adduct at a T residue and to study its effect on the template properties of the oligonucleotide in replicative synthesis, as followed by 5'-32P-labeled primer extension by several DNA polymerases . With the Klenow fragment of Escherichia coli DNA polymerase I, synthesis stops at the base immediately 3' to the adduct . The same enzyme, but lacking 3' to 5' exonuclease activity, permits synthesis to proceed by one additional nucleotide . This effect is enhanced when Mn2+ is substituted for Mg2+ . T4, herpes simplex virus, and cytomegalovirus DNA polymerases all act like Klenow polymerase . Sequenase (exo-minus T7 DNA polymerase) is qualitatively similar to exo-minus Klenow polymerase but is more efficient in inserting a nucleotide opposite the lesion . With the small-gap-filling human DNA polymerase beta, which lacks intrinsic exonucleolytic activity, primer extension proceeds to the nucleotide opposite the lesion . However, when a gap was created opposite the lesion, polymerase beta adds as many as two additional nucleotides 5' to the adduct site . The fidelity of base incorporation opposite the lesion was not impaired, in contrast with adducts on DNA bases.

Biochemistry, 1999 Jan 5, 38(1), 191 - 8
Tetracycline-chelated Mg2+ ion initiates helix unwinding in Tet repressor induction; Orth P et al.; The homodimeric tetracycline repressor (TetR) regulates resistance to the antibiotic tetracycline at the transcriptional level . TetR binds in the absence of Tc to palindromic operator sequences utilizing two helix-turn-helix (HTH) motifs . If the tetracycline-Mg2+ complex {MgTc}+ enters two identical binding tunnels buried within the TetR homodimer, a conformational change takes place, and the induced {TetR/{MgTc}+}2 complex releases operator DNA . To demonstrate the contribution of Mg2+ to {MgTc}+ binding and TetR induction, the Mg2+ concentration in the induced TetR homodimer was progressively reduced by addition of EDTA, resulting in two X-ray crystal structures of Mg2+-free and half-occupied TetR(D) . Tc remains bound to the {MgTc}+-binding sites, despite the complete or partial absence of Mg2+ . Together with inducer-free TetR(D), the structures were refined to between 2.2 and 2.7 A resolution and compared with fully induced TetR(D) in complex with two {MgTc}+ . Each inducer binding tunnel has three constituent parts, one hydrophobic and two hydrophilic ones . One of the hydrophilic contact areas binds Tc by hydrogen bonding; the hydrophobic region correctly positions Tc and partially closes the entrance to the binding tunnel; the second hydrophilic region coordinates Mg2+, transduces the induction signal, and completes the process of closing the tunnel entrance . Tc confers binding specificity to TetR while Mg2+ is primarily responsible for induction: After binding to the imidazole Nepsilon of His100, Mg2+ is octahedrally coordinated to the 1,3-ketoenolate group of Tc and to three water molecules . One of these waters forms a hydrogen bond to the hydroxyl group Ogamma of Thr103 . The induced 2.5 A movement of Thr103 results in the partial unwinding of helix alpha6, associated with a lateral shift of helices alpha4 and alpha9 . They simultaneously close the tunnel entrance and cause the DNA-binding domains to adopt a nonbinding conformation, leading to release of operator DNA and expression of the genes responsible for resistance.

Neurobiol Learn Mem, 1999 Jan, 71(1), 80 - 93
Chloramphenicol-induced amnesia for passive avoidance training in the day-old chick; Freeman FM et al.; The antibiotic chloramphenicol, an inhibitor of mitochondrial protein synthesis, was used to investigate the time-related changes in protein synthesis following passive avoidance training in the day-old chick (white leghorn-black Australorp) . Retention of memory for this simple learning task is known to be prevented by an inhibitor of cytosolic protein synthesis, anisomycin, in a biphasic manner, with the first phase of sensitivity occurring up to 90 min post-training and the second phase between 4 and 5 h post-training (Freeman, Rose, & Scholey, 1995) . Birds received bilateral intracranial injections of chloramphenicol (10 microl/hemisphere of a 7.4 mM solution) at various times relative to training and were tested 24 h later . This report shows that at the second phase of anisomycin susceptibility there was a chloramphenicol-sensitive period (5 h post-training) which had an onset time less than 1 h after injection . The effect of chloramphenicol appears not to be due to the mitochondria being energetically compromised since intracranial injections of an uncoupler of mitochondrial oxidative phosphorylation, 2,4-dinitrophenol (0.1 mM), did not disrupt memory formation when injected 5 h after training, even though it did cause amnesia when injected at the earlier time point of 20 min post-training . These results are discussed in the context of what is already known about memory formation in the day-old chick .

J Hand Surg {Br}, 1998 Dec, 23(6), 811 - 2
Mycobacterium malmoense infection . An unusual cause of wrist swelling; Syed AA et al.; We report a case of non-tuberculous tenosynovitis of the wrist caused by Mycobacterium malmoense . The patient presented with a ganglion-like swelling on the flexor aspect of the wrist . The diagnosis was confirmed by fine needle aspiration biopsy . A satisfactory resolution was obtained by antibiotic therapy alone, indicating that radical synovectomy may not be necessary in all cases of M . malmoense infection.

Collegian, 1998 Jul, 5(3), 40 - 1
Helicobacter pylori; Leaver M; H pylori is now recognised as a treatable primary cause of both gastric ulcers and gastric adenocarcinoma . Most infections remain asymptomatic . Persons with signs and symptoms which correlate with potential infection with H pylori should be tested and, if positive, treated with a recognised triple antibiotic regimen . Evaluation of the response to the treatment regimen should be undertaken.

Oncology, 1999, 56(1), 28 - 35
Optimal timing (Preemptive versus supportive) of granulocyte colony-stimulating factor administration following high-dose cyclophosphamide; Koumakis G et al.; PURPOSE: The aim of this study is to compare various time schedules of granulocyte colony-stimulating factor (G-CSF) treatment in a clinical model of patients who received high-dose cyclophosphamide (HDCY 45 g/m2) for the treatment of an underlying malignancy in order to investigate the optimal time (preemptive vs . supportive) of G-CSF initiation upon the incidence and duration of cytopenias and related parameters, such as incidence of febrile episodes, antibiotic use, duration and cost of G-CSF administration and overall clinical benefit and cost effectiveness of various schedules used . PATIENTS AND METHODS: Seventy-two courses were given in a sequential cohort study . G-CSF was administered either 24, 48, 72, 96 h after chemotherapy (preemptive treatment) or upon the onset of leukopenia (WBC </=1,000/ microl) (supportive treatment) . Study parameters were compared among the various groups as well as to a control group who received HDCY without G-CSF support . RESULTS: (1) Patients who received G-CSF early (24, 48 h) had a shorter duration of leukopenia (WBC </=1,000/ microl) compared to those who received G-CSF at a later stage (72, 96 h) or as supportive treatment (p < 0 . 05) . However the duration of neutropenia (ANC </=500/ microl) or thrombocytopenia (platelets </=20,000/ microl) was not affected by the different time schedules of treatment . (2) Patients who received G-CSF early (up to 72 h) had less febrile days with neutropenia in comparison to late treatment (>96 h), supportive and control groups (p < 0.05) . The cost of antibiotics was also in favor of the early treatment group . The median duration of febrile days of the delayed (>72 h) treatment groups and antibiotic cost was similar to those in patients who did not receive G-CSF at all . (3) When G-CSF was given preemptively a shorter time was required to reach normal WBC (5,000/ microl) in comparison to the sup- portive and control group . This was due to a prolonged WBC recovery rather than to an early onset of leukopenia (tail effect) . A delayed leukopenia recovery occurs as administration of G-CSF is delayed . (4) As a result the required length of G-CSF treatment to reach normal WBC (5,000/ microl) was shorter in the early treatment group and the cost from G-CSF use was less in that group in comparison to the late (>72 h) and supportive groups which indicated an increased cost without clinical benefit over controls . CONCLUSIONS: G-CSF administration after HDCY has a similar effect upon the incidence and duration of severe leukopenia and thrombocytopenia . However, severe leukopenia is shorter when G-CSF starts up to 72 h after HDCY . The length of G-CSF administration and its cost is also in favor of early initiation of treatment as well as the number of febrile days and antibiotic use . Delayed (>72 h) or supportive treatment indicate more febrile episodes, antibiotic use and higher cost when compared to the early groups . Late (>72 h) or supportive G-CSF administration in this study indicates no benefit versus no treatment in relation to length of leukopenia, febrile days, antibiotic use and overall treatment cost.

Am J Physiol, 1999 Jan, 276(1 Pt 1), C136 - 44
Squalamine, a novel cationic steroid, specifically inhibits the brush-border Na+/H+ exchanger isoform NHE3; Akhter S et al.; Squalamine, an endogenous molecule found in the liver and other tissues of Squalus acanthias, has antibiotic properties and causes changes in endothelial cell shape . The latter suggested that its potential targets might include transport proteins that control cell volume or cell shape . The effect of purified squalamine was examined on cloned Na+/H+ exchanger isoforms NHE1, NHE2, and NHE3 stably transfected in PS120 fibroblasts . Squalamine (1-h pretreatment) decreased the maximal velocity of rabbit NHE3 in a concentration-dependent manner (13, 47, and 57% inhibition with 3, 5, and 7 micrograms/ml, respectively) and also increased K'{H+}i . Squalamine did not affect rabbit NHE1 or NHE2 function . The inhibitory effect of squalamine was 1) time dependent, with no effect of immediate addition and maximum effect with 1 h of exposure, and 2) fully reversible . Squalamine pretreatment of the ileum for 60 min inhibited brush-border membrane vesicle Na+/H+ activity by 51% . Further investigation into the mechanism of squalamine's effects showed that squalamine required the COOH-terminal 76 amino acids of NHE3 . Squalamine had no cytotoxic effect at the concentrations studied, as indicated by monitoring lactate dehydrogenase release . These results indicate that squalamine 1) is a specific inhibitor of the brush-border NHE isoform NHE3 and not NHE1 or NHE2, 2) acts in a nontoxic and fully reversible manner, and 3) has a delayed effect, indicating that it may influence brush-border Na+/H+ exchanger function indirectly, through an intracellular signaling pathway or by acting as an intracellular modulator.

J Vet Pharmacol Ther, 1998 Dec, 21(6), 444 - 52
Pharmacokinetics and pharmacodynamics of tilmicosin in sheep and cattle; Modric S et al.; Tilmicosin is a long-acting macrolide antibiotic currently approved for treatment of bovine respiratory disease in the USA . Serum pharmacokinetics of tilmicosin were compared between cattle (major species) and sheep (minor species) after subcutaneous injection in order to evaluate a new potential application of the drug in currently nonapproved species . There were no significant differences in the elimination rates, maximum serum concentrations, half-lives (t1/2), areas under the curve (AUC), areas under the first-moment curve (AUMC), and mean residence times . Volume of distribution (Vd(area)) and clearance (Cl), when normalized by body weight, were also similar . The only significantly different parameter was time at which maximum drug concentration was reached (tmax), with sheep having the tmax of 3.9 h, compared to 0.5 h in cattle . Although macrolides are considered to be one of the safest anti-infective drugs, adverse cardiovascular effects of several macrolides have been reported . The cardiopulmonary effects of tilmicosin were monitored in healthy adult sheep after receiving a single subcutaneous (s.c.) injection of tilmicosin at the dose of 10 mg/kg, and no significant changes were found . The study indicates that tilmicosin can be used safely and effectively in sheep at the given dose, with no adverse cardiopulmonary effects.

Singapore Med J, 1998 Oct, 39(10), 456 - 60
Care of elderly patients with DNR orders in Singapore--a descriptive study; Low JA et al.; OBJECTIVE: To describe the demographic profile of a cohort of elderly patients with a 'do-not-resuscitate' (DNR) order at death and to study the specific supportive measures instituted or withdrawn during the DNR period and those in force at the time of death . METHODS: The case notes of patients who died between October 1996 and March 1997 in the Department of Geriatrics, Alexandra Hospital were studied retrospectively by a single observer . RESULTS: Only 95 out of an eligible 102 patients' case notes could be retrieved . Seventy-two (75.8%) patients had a DNR status at death . The racial distribution was as follows: 90.3% Chinese, 5.6% Indians, 2.8% Malays and 1.4% Others while their pre-admission domicile were: own home 79.2%, nursing home 19.4% others 1.4% . Those bedbound constituted 48.6% of the cohort while 29.2% had dementia and 43.1% were totally dependent for their activities of daily living . The commonest cause of death was pneumonia while the average duration patients were on the DNR status was 5.1 days before death . The commonest measures instituted during DNR period were as follows: oxygen therapy (38.9%), nasogastric tube insertion and feeding (30.6% and 33.3% respectively), intravenous fluid administration (33.3%), blood investigations (33.3%), opioid use (33.3%) and antibiotic use (29.2%) . Measures withdrawn were intravenous fluid administration (36.1%), hourly monitoring of parameters (22.2%), antibiotics (13.9%), high dependency care (12.5%) and nasogastric tube feeding (6.9%) . CONCLUSION: The DNR status is decided late in the course of a patient's illness when he may have been too ill to partake in the decision making process . Even if a DNR status was ordered, a patient might still be subjected to CPR at death.

Hand Clin, 1998 Nov, 14(4), 669 - 81, x
Postoperative infection in hand surgery . Cause, prevention, and treatment; Shapiro DB; The consequences of postoperative infection in hand surgery are fortunately uncommon but can lead to severe disability . This article reviews the pathogenesis of infections and the role of antibiotics, skin preparation, and surgical technique in the development and prevention of infection . The final sections discuss the roles that different disease states and different types of surgery have on the risk of postoperative infection.

Hand Clin, 1998 Nov, 14(4), 531 - 45, vii
Nosocomial infections in hand surgery; Calkins ER; The active and experienced hand surgeon should have enough knowledge to recognize both common and uncommon hand infections . Control of hospital-acquired infections, including surgical site infections, requires a knowledge of potential personal risk factors and ongoing surveillance systems to aid in prevention and early detection . Current national trends may soon require that surgical-site infections be diagnosed by specific criteria that will allow comparisons of data from various locations . Although most hand surgery procedures are now performed on an ambulatory basis, it is important for the hand surgeon to be aware of current methodologies for the prevention, control, surveillance, and treatment of hospital-acquired infections . These intriguing aspects of hospital-acquired infections are reviewed in this article.

J Reprod Med, 1998 Dec, 43(12), 1051 - 4
Delayed-interval delivery in a quadruplet pregnancy after intrauterine death of a partial molar pregnancy and preterm delivery . A case report; Marinoff DN et al.; BACKGROUND: Delayed-interval delivery is infrequent in twin gestation and more rare in triplet and quadruplet gestation . Coexistence of a triploid pregnancy with a normal fetus has not previously been reported to have resulted in survival of the normal fetus . CASE: A 26-year-old woman, gravida 2, para 0-0-1-0, was diagnosed with a quadruplet pregnancy . At 16 1/2 weeks' gestation she developed preeclampsia and severe hyperemesis . Ultrasound was consistent with partial molar pregnancy in quadruplet D . Quadruplet D died in utero, and the preeclampsia and hyperemesis resolved . At 19 5/7 weeks, spontaneous rupture of the membranes and preterm labor occurred, and quadruplet A, stillborn female weighing 260 g, was delivered . With the use of antibiotic therapy, tocolysis and bed rest, the remaining two fetuses were maintained in utero until 32 6/7 weeks' gestation, when quadruplet B, a 1,470-g female, and quadruplet C, a 1,700-g female, were delivered . CONCLUSION: This was the first reported case of surviving fetuses coexisting with a partial molar pregnancy . This case was also complicated by preterm delivery and successful delayed-interval birth in a quadruplet pregnancy.

Dis Mon, 1998 Dec, 44(12), 677 - 716
Human immunodeficiency virus infection, Part II; Horowitz HW et al.; The acceptance of highly active antiretroviral therapy (HAART) among patients and health care providers has had a dramatic impact on the epidemiology and clinical characteristics of many opportunistic infections associated with human immunodeficiency virus (HIV) . Previously intractable opportunistic infections and syndromes are now far less common . In addition, effective antibiotic prophylactic therapies have had a profound impact on the risk of patients developing particular infections and on the incidence of these infections overall . Most notable among these are Pneumocystis carinii, disseminated Mycobacterium avium complex, tuberculosis, and toxoplasmosis . Nevertheless, infections continue to cause significant morbidity and mortality among patients who are infected with HIV . The role of HAART in many clinical situations is unquestioned . Compelling data from clinical trials support the use of these therapies during pregnancy to prevent perinatal transmission of HIV . HAART is also recommended for health care workers who have had a "significant" exposure to the blood of an HIV-infected patient . Both of these situations are discussed in detail in this article . In addition, although more controversial, increasing evidence supports the use of HAART during the acute HIV seroconversion syndrome . An "immune reconstitution syndrome" has been newly described for patients in the early phases of treatment with HAART who develop tuberculosis, M avium complex, and cytomegalovirus disease . Accumulating data support the use of hydroxyurea, an agent with a long history in the field of myeloproliferative disorders, for the treatment of HIV . Newer agents, particularly abacavir and adefovir dipivoxil, are available through expanded access protocols, and their roles are being defined and clarified.

Actas Urol Esp, 1998 Oct, 22(9), 794 - 6
{Renal tuberculosis associated with renal adenocarcinoma: unusual association}; Fernandez Arjona M et al.; We present a patient 50 years old, complaining of right lumbar pain and miccional syndrome for three weeks . After analytic and x-ray studies, renal tuberculosis and renal cell carcinoma was the diagnosis . We started with specific antibiotic therapy and a radical nephrectomy was developed . According with the literature revised, just three cases has been published before . Because is an unusual clinic presentation we present these clinical note, we discuss the pathogenic and therapeutic procedures.

J Neurosci, 1999 Jan 15, 19(2), 759 - 74
Identification and characterization of early glial progenitors using a transgenic selection strategy; Chandross KJ et al.; To define the spatiotemporal development of and simultaneously select for oligodendrocytes (OLs) and Schwann cells (SCs), transgenic mice were generated that expressed a bacterial beta-galactosidase (beta-gal) and neomycin phosphotransferase fusion protein (betageo) under the control of murine 2'3'-cyclic nucleotide 3'-phosphodiesterase (muCNP) promoters I and II . Transgenic beta-gal activity was detected at embryonic day 12.5 in the ventral region of the rhombencephalon and spinal cord and in the neural crest . When cells from the rhombencephalon were cultured in the presence of G418, surviving cells differentiated into OLs, indicating that during development this brain region provides one source of OL progenitors . Postnatally, robust beta-gal activity was localized to OLs throughout the brain and was absent from astrocytes, neurons, and microglia or monocytes . In the sciatic nerve beta-gal activity was localized exclusively to SCs . Cultures from postnatal day 10 brain or sciatic nerve were grown in the presence of G418, and within 8-9 d exposure to antibiotic, 99% of all surviving cells were beta-gal-positive OLs or SCs . These studies demonstrate that the muCNP-betageo transgenic mice are useful for identifying OLs and SCs beginning at early stages of the glial cell lineage and throughout their development . This novel approach definitively establishes that the beta-gal-positive cells identified in vivo are glial progenitors, as defined by their ability to survive antibiotic selection and differentiate into OLs or SCs in vitro . Moreover, this experimental paradigm facilitates the rapid and efficient selection of pure populations of mouse OLs and SCs and further underscores the use of cell-specific promoters in the purification of distinct cell types.

Endocr J, 1998 Aug, 45(4), 595 - 600
Recurrent hemithyroiditis: a case report; Nakamura S et al.; We report on a girl with recurrent painful thyroiditis which involved the entire right thyroid lobe, but did not spread to the left thyroid lobe . She occasionally developed pain and swelling of the right side of the neck following symptoms of common cold over several years . During these attacks, the right thyroid lobe was enlarged, tender, and very soft, while the left thyroid lobe was not remarkable . Ultrasonic examination revealed that the entire right thyroid lobe was hypoechoic, but the entire left lobe was normal echoic . Serum C-reactive protein, white blood cell count, and erythrocyte sedimentation rate were increased during the attacks . The thyroiditis responded quickly to treatment with prednisolone and/or anti-inflammatory drugs, but the thyroiditis may have subsided spontaneously since the signs and symptoms of thyroiditis had subsided with only antibiotic therapy . After resolution of the thyroiditis, the echogenicity of the right lobe returned to near normal and the inflammatory findings became negative . During the investigation, thyroid function was normal except for when the thyroiditis was first diagnosed at another hospital with a serum TSH level of 0.1 mU/l . Serum thyroglobulin level was increased but returned to normal or decreased during and after attacks of thyroiditis . The mechanism(s) of the recurrent hemithyroiditis remains unknown, but the underlying disease appeared to be chronic thyroiditis since tests for anti-microsomal or anti-thyroid peroxidase antibodies were consistently positive during the course of her illness . The changes in the titers of these antibodies were not clear during and after the attacks of thyroiditis . In addition, the clinical course suggests that the present hemithyroditis can be induced by recurrent upper respiratory infection.

Biochim Biophys Acta, 1999 Jan 4, 1426(1), 91 - 8
Investigation of the glycosyltransferase enzymes involved in the initial stages of the N-linked protein glycosylation pathway in Aspergillus niger; Wallis GL et al.; A protocol has been developed to produce functional microsomes from mycelium of Aspergillus niger . Using these preparations, radioactive biochemical assays have been designed and optimised to measure the in vitro activities of three of the enzymes of the N-linked dolichol phosphate (Dol-P) glycosylation pathway: UDP-N-GlcNAc:dolichol-P GlcNAc-1-P transferase (GPT), Dol-P mannose synthase (DPMS) and Dol-P glucose synthase (DPGS) . Exogenous Dol-P and Triton X-100 are essential for in vitro activity . All three Dol-P:glycosyl transferases had alkaline pH optima and activity rapidly decreased below neutrality . Characterisation of the glycolipid products by anion-exchange chromatography and TLC showed that they were Dol-P-P-GlcNAc, Dol-P-Glc and Dol-P-Man for GPT, DPGS and DPMS, respectively . The antibiotic tunicamycin completely inhibited GPT activity at a concentration of 100-200 ng ml(-1) and an IC50 of 40 ng ml(-1), but had little effect on the other two enzymes . The ratio of the activity of the three enzymes to each other suggested that DPMS may be involved in other cellular activities and is probably under different control mechanisms than the other two.

Eur Respir J, 1998 Dec, 12(6), 1384 - 7
Do radiographic features of acute infection influence management of lower respiratory tract infections in the community?
Simpson JC, Hulse P, Taylor PM, Woodhead M.
Community-acquired lower respiratory tract infection (LRTI) is a common clinical problem, and a chest radiograph is the most common investigation . This study investigated why general practitioners (GPs) request radiographs and whether radiographic features of LRTI affect management . The 12 month study included GP-requested chest radiographs performed at the Manchester Royal Infirmary . The GPs of patients with radiographic evidence of LRTI were sent a questionnaire . Radiographs (n=2,538) were performed in patients aged >15 yrs . One hundred and eleven (4.4%) chest radiographs showed evidence of LRTI, and 97 (87%) were included in the analysis . Fifty-six (62%) had their radiograph requested at the second or third visit . Forty-five (58%) radiographs were performed to confirm infection . In 47 (48%) of cases the GP felt the radiograph had affected treatment . An effect on treatment was significantly more common in patients not receiving antibiotics prior to the radiograph . Twenty-nine (32%) of GPs felt a normal radiograph would have affected management, most often with respect to antibiotic prescriptions (17 (58%)) . Where the radiologist's report suggested a repeat radiograph or hospital referral, this was significantly more likely to have occurred . The commonest reason for a radiograph in patients with suspected lower respiratory tract infection is to confirm the infection . In the opinion of the general practitioner the results of the radiograph do affect patient treatment . The wording of the radiologists report is associated with patient management.

Clin Imaging, 1998 Nov-Dec, 22(6), 425 - 7
Early CT findings of Fournier's gangrene in a healthy male; Sherman J et al.; Early clinical identification of Fournier's gangrene is imperative to avoid delay in the aggressive surgical debridement, antibiotic therapy, and sometimes hyperbaric oxygen treatments . We report on the early computed tomography findings of a non-gas-forming Fournier's gangrene in a healthy male to aid urologists, surgeons, and radiologists in the recognition of this rapidly progressive and often fatal infection.

Clin Biochem, 1998 Nov, 31(8), 653 - 6
Endothelial cell compatibility of clarithromycin for intravenous use; Vorbach H et al.; OBJECTIVES: Tolerance of intravenously applied clarithromycin has been tested on marginal ear veins of rabbits . Use of human umbilical venous endothelial cells (HUVEC) for testing antibiotic solutions for intravenous compatibility provides a valuable alternate model . DESIGN AND METHODS: In order to evaluate the effect of clarithromycin on intracellular purines, reflecting cell viability, energy production, signal transduction and DNA/RNA synthesis, intracellular adenosine 5' triphosphate (ATP), adenosine 5' diphosphate (ADP), guanosine 5' triphosphate (GTP), and guanosine 5' diphosphate (GDP) levels were measured by means of high performance liquid chromatography (HPLC) . RESULTS: Incubation of cells with 2 mg/mL clarithromycin resulted in a rapid decrease of the intracellular ATP from 12.6 +/- 1.1 to 8.87 +/- 0.82 nmol/million cells or 1.5 +/- 0.6 nmol/million cells, after 20 or 60 min, respectively . In addition, ADP was extensively depleted . Purine nucleotide profiles were markedly different following exposure to 1 mg/mL clarithromycin . There was no significant decline of intracellular high energy phosphate levels after 20 min . CONCLUSION: These results show that clarithromycin has a better endothelial compatibility if diluted to a final concentration of 1 mg/mL . These data are in line with our clinical observations that the occurrence of phlebitis could be minimized by diluting the manufacturers' preparation of clarithromycin to 1 mg/mL.

Ann Pharmacother, 1998 Dec, 32(12), 1317 - 23
Ambulatory management of chemotherapy-induced fever and neutropenia in adult cancer patients; Davis DD et al.; OBJECTIVE: To review the literature on the management of low-risk adults with chemotherapy-induced fever and neutropenia (CIFN) . Included in the review are methods to identify these patients, management options, and economic impact associated with nontraditional treatment options . DATA SOURCES: A MEDLINE and bibliographic search (January 1966-December 1997) for all English-language studies evaluating the identification and treatment of adult, low-risk CIFN patients was completed . Reference lists from identified articles also served as literature sources . STUDY SELECTION AND DATA EXTRACTION: All human studies identified from the data sources were evaluated . Pertinent information, excluding pediatric studies, was selected and critically evaluated for discussion . DATA SYNTHESIS: Alterations in prominent bacterial isolates in CIFN, newer antibiotic choices, enhanced focus on patient comfort, and cost-containment directives have promoted recent research identifying adult cancer patients with low-risk CIFN . Using this information to select low-risk CIFN patients, several investigators have completed trials using antibiotic therapy applicable to the ambulatory setting . Additionally, some investigators have included the use of an oral outpatient antibiotic regimen . Limited data indicate that this approach is a reasonable treatment option for selected patients . CONCLUSIONS: A subset of adult patients with CIFN are at low risk for serious morbidity and mortality when treated with broad-spectrum antibiotics in the ambulatory setting . Managing these patients with this approach requires close patient selection, intense follow-up, data collection, and ongoing evaluation to determine efficacy and patient safety . Currently, ambulatory treatment with oral antibiotics for CIFN is not considered standard of care . Further studies of larger size designed to confirm low-risk patient characteristics and optimal antibiotic selection are required.

JSLS, 1997 Jul-Sep, 1(3), 255 - 8
Video-assisted thoracoscopic management of post-pneumonectomy empyema; Podbielski FJ et al.; BACKGROUND: Post-pneumonectomy empyema is a major therapeutic challenge in thoracic surgery . The presence or absence of a concomitant bronchopleural fistula directs treatment of this condition . When there is no bronchopleural fistula the condition is classically treated with thoracostomy drainage, irrigation and antibiotic instillation with closure . This approach is, however, associated with a significant rate of primary failure . Alternative modified techniques involve opening the thoracic cavity widely with serial debridement followed by interval closure . Multiple surgical procedures often require a protracted hospital stay . METHODS: We describe a technique in three patients utilizing video-assisted thoracoscopic surgery for debridement and closure of the pneumonectomy cavity . CONCLUSION: Advantages of this technique include debridement under direct visualization, low morbidity, and potential for a shorter hospital stay.

JSLS, 1997 Jul-Sep, 1(3), 251 - 3
Video-assisted thoracoscopic surgery in the management of pediatric empyema; Gandhi RR et al.; BACKGROUND: Management of empyema in children has progressed from open thoracotomy to video-assisted thoracoscopic surgery (VATS) . The purpose of the present study was to evaluate the efficacy and safety of VATS in children with multiloculated empyemas . METHODS: Nine children (mean age, 4 years; range, 21 months to 13 years) with empyema, in whom multiple loculations were found on computed tomography, were treated with VATS from January, 1994, to November, 1996 . All patients underwent VATS under general anesthesia, with drainage of the empyemas, decortication, and placement of chest tubes under direct vision . RESULTS: In all nine patients, VATS was successful . Average operating time was 120 minutes . Blood loss was insignificant, except in one patient who needed an intraoperative blood transfusion . This child required extensive decortication, with blood oozing from raw areas . All patients recovered well, with no recurrences to date . An algorithm for the use of VATS in the treatment plan for children with empyema was established . CONCLUSION: VATS provides safe and effective treatment in the management of pediatric empyema . Moreover, it avoids lengthy hospitalization, prolonged intravenous antibiotic therapy, and unnecessary pain and stress secondary to placement of chest tubes without anesthesia.

Drug Dev Ind Pharm, 1998 Jun, 24(6), 583 - 7
Enhancement of bioavailability of griseofulvin by its complexation with beta-cyclodextrin; Dhanaraju MD et al.; Griseofulvin is a poorly soluble antifungal antibiotic drug, the solubility of which can be enhanced by complexation with beta-cyclodextrin . The inclusion complex was prepared by coprecipitation method in various molar ratios of 1:1, 2:1, 3:1, and 1:2 of the drug and beta-cyclodextrin, respectively . The inclusion complex was characterized and evaluated by UV-VIS spectral studies and FTIR . The in vitro drug release studies indicated that the 1:2 molar ratio complex form of the drug significantly increased the dissolution rate when compared to the free form . The acute toxicity studies clearly indicated that the beta-cyclodextrin complex was nontoxic and the safety range was close to other Griseofulvin formulations . The in vivo study of the beta-cyclodextrin was carried out in both animals and human beings by administering in four different rabbits and volunteers, respectively . Pellets made with Griseofulvin-beta-cyclodextrin complex also showed a significant increase in the dissolution of the drug, revealing that beta-cyclodextrin plays an important role in the solubilization of Griseofulvin.

Drug Dev Ind Pharm, 1998 Jul, 24(7), 631 - 5
Effect of various lipid-bile salt mixed micelles on the intestinal absorption of amphotericin-B in rat; Dangi JS et al.; Amphotericin-B (AmB), a lipophilic polyene antibiotic, is the drug of choice in the treatment of many serious mycotic diseases . The solubility and gastrointestinal membrane permeability (Papp) of AmB in mixed micellar systems were examined . Membrane permeability was determined using a rat gut perfusion method . The mixed micellar systems studied contained the bile salt in association with fatty acid . All mixed micellar systems enhanced the absorption of AmB relative to the simple micelle . These results have shown that mixed micelles can enhance the absorption of AmB to a greater extent relative to nonmicellar and simple micellar systems . Maximum enhancement (> 20-fold) in the rate of AmB absorption was obtained with the sodium desoxycholate/soya lecithin 40:40 mM system . These results offer a possible explanation for the reported enhancement in gastrointestinal absorption of AmB when coadministered with lipid-bile salt mixed micelles, and these systems can be used as a vehicle for designing novel drug delivery systems for poorly absorbable drug(s).

J Travel Med, 1998 Dec, 5(4), 221 - 2
Fatal grand mal seizure in a Dutch trekker; Basnyat B; A 35-year-old healthy Dutch woman went on a trek (Lang Tang) in Nepal up to an approximate altitude of about 3800 meters . She had no prior history of any medical problems except attacks of generalized epilepsy when she was 19 years old, which had been controlled with antiepileptic medications . She had had no attacks after the age of 20 . A CT scan done around that time had apparently been normal . On this trek she had developed diarrhea which had been cured with norfloxacin 400 mg two times per day for 3 days . Two days later, while descending, she developed a grand mal seizure at an altitude of 3300 meters, after which she developed a classic postictal phase but gradually recovered . She developed grand mal seizures again the next day, but when she went to a travel clinic in Kathmandu, she had been seizure free for 72 hours . She also revealed that she had not suffered from acute mountain sickness on the trek . She also had a prior history of gastroenteritis at high altitude which improved significantly with norfloxacin, a quinolone antibiotic . This was corroborated by her party . Upon examination she was fully conscious and oriented to person, place and time . Her pulse was 70 beats per minute and her BP was 110/80 mm of Hg . Her fundi and cranial nerves exam were completely normal . Her abstract thinking, gait, power, tone, reflexes and other facets of her neurologic exam revealed absolutely no abnormalities . Her cardiovascular exam revealed a normal rhythm with no murmurs or bruits . The rest of her exam was also normal . She revealed that she played tennis on a regular basis and was an outdoor person . She had not trekked before in the Himalayas and it was uncertain if she had been to high altitude before . She was on no medications at the time . There was no history of drug abuse . She did not smoke and consumed few alcoholic beverages . She had not consumed any alcohol on the trek . She was advised to get a CT scan (she declined as she was going home to Holland in 2 days) and she was prescribed a loading dose of phenytoin 1 g orally spread over several hours and it was recommended she take 300 mg of phenytoin per day . She was going to see her neurologist in Holland on arrival there . She went to her hotel in Kathmandu while her friends went to fill the prescription of phenytoin . When her friends returned to the hotel she was having another grand mal seizure . Medical help was sought, but she died before the doctor arrived to control her seizures . When the doctor did arrive and carried out CPR for half an hour it was to no avail as she continued to have no pulse or blood pressure.

Biophys J, 1999 Jan, 76(1 Pt 1), 552 - 63
Membrane helix orientation from linear dichroism of infrared attenuated total reflection spectra; Bechinger B et al.; Oriented multilamellar systems containing phospholipids and peptides have been formed on a germanium internal reflection element . Attenuated total reflection infrared spectra have been recorded and the linear dichroism of peptide amide I and amide II bands measured . Using peptides for which the orientation had been previously studied under similar experimental conditions by 15N solid-state nuclear magnetic resonance spectroscopy, important conclusions were drawn on the approach to be used to derive secondary structure orientation in a membrane from dichroic ratios . In particular, it is shown that the influence of the film thickness and refractive index on the orientation determination can be evaluated from the value of RATRiso, i.e., the dichroic ratio of a dipole oriented at the magic angle or with isotropic mobility . A series of peptides was used to test the validity of our suggestions on various helix orientations in the membrane . These include magainin 2 and hydrophobic (hPhi20) model peptides, the transmembrane segment of glycophorin (GLY), and LAH4, a designed peptide antibiotic that changes between a transmembrane and an in-plane orientation in a pH-dependent manner.

AIDS, 1998 Dec 24, 12(18), 2447 - 57
Twice weekly tuberculosis preventive therapy in HIV infection in Zambia; Mwinga A et al.; BACKGROUND: A randomized double-blind placebo-controlled trial was conducted to estimate the efficacy of preventive therapy for tuberculosis (TB) in HIV-infected adults in Lusaka, Zambia . The main outcome measures were the incidence of TB, mortality and adverse drug reactions . METHODS: During a 2 year period, 1053 HIV-positive individuals without evidence of clinical TB were randomly assigned to receive 6 months of isoniazid twice a week (H), or 3 months of rifampicin twice a week (R) plus pyrazinamide (Z), or a placebo . Therapy was taken twice a week and was self administered . Subjects presenting with symptoms during the follow-up period were investigated for TB . RESULTS: The 1053 subjects in the study were followed up for a total of 1631 person-years (median = 1.8 years) . Twenty-nine subjects were taken off treatment as a result of adverse drug reactions . A total of 96 cases of TB/probable TB (59 TB and 37 probable TB) were diagnosed during the study period and 185 deaths were reported . One hundred and fifteen subjects (11%) did not return to the study clinic at any time after enrolment . The incidence of TB was lower in those subjects on preventive therapy (H and RZ groups combined) compared with those on placebo (rate ratio = 0.60, 95% CI: 0.36-1.01, P = 0.057), as was the incidence of TB/probable TB (rate ratio = 0.60, 95% CI: 0.40-0.89, P = 0.013) . The effect of preventive therapy was greater in those with a tuberculin skin test (TST) of 5 mm or greater, in those with a lymphocyte count of 2x10(9)/l or higher, and in those with haemoglobin of 10 g/dl or higher . There was no difference in mortality rates between the preventive therapy and placebo groups . The effect of preventive therapy declined after the first year of the study so that by 18 months the rates of TB in the treated groups were similar to that in the placebo group . CONCLUSION: This study has demonstrated that preventive therapy with either twice weekly isoniazid for 6 months or a combination of rifampicin and pyrazinamide for 3 months reduced the incidence of TB in HIV-infected persons in Zambia . No effect was observed on mortality . The effect was greatest in persons who had a positive TST or a lymphocyte count of 2x10(9)/l or greater, indicating that preventive therapy may be more effective in people with less advanced immunosuppression . The limited duration of the protective effect reported in this study raises the question of the need for lifelong preventive therapy or re-prophylaxis.

Arch Pharm Res, 1998 Aug, 21(4), 385 - 90
Sequence selectivity of DNA alkylation by adozelesin and carzelesin; Yoon JH et al.; Adozelesin and carzelesin are synthetic analogues of the extremely potent antitumor antibiotic CC-1065, which alkylates N3 of adenine in a consensus sequence 5'-(A/T)(A/T)A* (A* is the site of alkylation) . We have investigated the DNA sequence selectivity of adozelesin and carzelesin by thermally induced DNA strand cleavage assay using radiolabeled restriction DNA fragments . An analysis of alkylation patterns shows that the consensus sequences for carzelesin and adozelesin have been found to be 5'-(A/T)(A/T)A* and 5'-(A/T)(G/C)(A/T)A* . A new consensus sequence, 5'-(A/T)(A/T)CA*, has been observed to display an additional alkylation site for adozelesin but not for carzelesin . These results indicate that the pattern of sequence selectivity induced by carzelesin is similar but not identical to those induced by adozelesin.

Proc Natl Acad Sci U S A, 1999 Jan 5, 96(1), 127 - 32
Transient and stable gene expression in mammalian cells transduced with a recombinant baculovirus vector; Condreay JP et al.; Recombinant baculoviruses can serve as gene-transfer vehicles for transient expression of recombinant proteins in a wide range of mammalian cell types . Furthermore, by inclusion of a dominant selectable marker in the viral vector, cell lines can be derived that stably express recombinant genes . A virus was constructed containing two expression cassettes controlled by constitutive mammalian promoters: the cytomegalovirus immediate early promoter/enhancer directing expression of green fluorescent protein and the simian virus 40 (SV40) early promoter controlling neomycin phosphotransferase II . Using this virus, efficient gene delivery and expression was observed and measured in numerous cell types of human, primate, and rodent origin . In addition to commonly used transformed cell lines such as HeLa, CHO, Cos-7, and 293, this list includes primary human keratinocytes and bone marrow fibroblasts . In all cases, addition of butyrate or trichostatin A (a selective histone deacetylase inhibitor) to transduced cells markedly enhanced the levels of reporter protein expression observed . When transduced cells are put under selection with the antibiotic G418, cell lines can be obtained at high frequency that stably maintain the expression cassettes of the vector DNA and exhibit stable, high-level expression of the reporter gene . Stably transduced derivatives have been selected from a substantial number of different cell types, suggesting that stable lines can be derived from any cell type that exhibits transient expression.

Res Commun Mol Pathol Pharmacol, 1998 Sep, 101(3), 233 - 40
Effect of clarithromycin on alpha1-acid glycoprotein levels in normal and diabetic rats; Komori T et al.; The elevation of alpha1-acid glycoprotein (AGP) serum level, a member of the acute phase proteins (APP) synthesized by the liver, is induced during inflammation . In this study, we show that clarithromycin (CAM), a 14-membered macrolide antibiotic, causes an increase in the serum levels of AGP in a dose-dependent manner . AGP levels peak at 48h after a single administration with CAM In order to elucidate the mechanism of AGP induction by CAM, the effects of CAM, phenobarbital (PB), ethynylestradiol (EE2) and dexamethasone (DEX) treatments on APP fluctuation patterns were examined . In addition, modulation of the AGP induction by CAM, PB, EE2 and DEX in the diabetic state was examined . In contrast to treatment by PB, CAM treatment increased alpha2-macroglobulin levels to a much lesser extent than that observed during inflammation . On the other hand, albumin levels were unaffected by CAM treatment but decreased during inflammation . In addition, AGP induction by CAM, EE2 and DEX were attenuated in streptozotocin-induced diabetic rats, whereas the PB-induced increase in AGP levels was potentiated in diabetic rats . Thus, CAM and DEX treatments appear to induce similar fluctuations in APP levels . These results suggest that CAM increases AGP levels via a mechanism which may be different from PB and typical inflammatory pathways.

C R Seances Soc Biol Fil, 1998, 192(5), 991 - 6
{Role of cytokines in the pathogenesis of gastrointestinal diseases associated with Helicobacter pylori infection}; Imanishi J et al.; It is well known that Helicobacter pylori can cause gastritis, gastroduodenal ulcers and malignant diseases . The infiltration of polymorphonuclear leukocytes is recognized in the lesions of these diseases, and the infiltration disappears by antibiotic therapy . However, it is not yet clarified how Helicobacter pylori induces the formation of lesions including leukocyte infiltration . Recently, we have confirmed that several kinds of cytokines are expressed in the gastric biopsy specimens of gastroduodenal diseases . Especially, it is conjectured that chemokines such as interleukin-8 (IL-8) which are expressed in the specimens, induce leukocyte infiltration, gastric mucosal inflammation and gastroduodenal ulcers . It is possible that Helicobacter pylori CagA gene is closely related with IL-8 expression because this cytokine is more strongly expressed in the specimens from the patients infected with CagA-positive Helicobacter than those with CagA-negative one.

Am J Med, 1998 Dec, 105(6), 478 - 83
A randomized comparison of fluconazole with amphotericin B as empiric anti-fungal agents in cancer patients with prolonged fever and neutropenia; Malik IA et al.; PURPOSE: Several studies have documented the efficacy of amphotericin B as empiric antifungal therapy in cancer patients with prolonged fever and neutropenia . Amphotericin, however, is a toxic drug . Fluconazole has broad-spectrum antifungal activity with an excellent safety profile . Although prophylactic use of fluconazole is widespread, its efficacy as an empiric antifungal agent has not been extensively investigated . PATIENTS AND METHODS: We randomly assigned 106 patients with absolute neutropenia (< or = 500 cells microL) and persistent fever of undetermined origin (> 38 degrees C) despite 1 week of broad-spectrum antibiotic therapy to receive either fluconazole 400 mg orally daily or amphotericin B 0.5 mg/kg/day . Patients with obvious invasive fungal infections were excluded, as were those with abnormal renal or hepatic function . Success was defined as defervescence with the initially assigned antifungal regimen without development of clinically evident invasive fungal infection . RESULTS: Six patients were excluded from the analysis, mostly because they did not have severe neutropenia . Forty-eight patients received amphotericin B, and 52 received fluconazole . Baseline clinical characteristics and laboratory parameters as well as duration of neutropenia (7.7 versus 6.9 days), duration of fever (7.8 versus 8.1 days), and duration of hospitalization (10.4 versus 8.3 days) were similar between those receiving amphotericin and fluconazole . Treatment success rates and mortality rates were similar in the two groups: 22 (46%) patients in the amphotericin group and 29 (56%) patients in the fluconazole group responded successfully to therapy (P = 0.3), whereas 16 (33%) patients in the amphotericin group and 14 (27%) patients in the fluconazole group died during hospitalization (P = 0.5) . Adverse events such as chills and fever (4 versus 1), bronchospasm (2 versus none), severe hypokalemia (25 versus 12) and nephrotoxicity (9 versus 3) were more frequently observed in patients receiving amphotericin . Adverse prognostic factors included prolonged duration of neutropenia and pneumonia . CONCLUSIONS: These results suggest that fluconazole is an equally effective but less toxic alternative to amphotericin B as empiric antifungal therapy in cancer patients with prolonged fever and neutropenia.

Electrophoresis, 1998 Nov, 19(16-17), 2907 - 11
Two examples of rapid and simple drug analysis in pharmaceutical formulations using capillary electrophoresis: naphazoline, dexamethasone and benzalkonium in nose drops and nystatin in an oily suspension; Raith K et al.; Capillary electrophoresis is a versatile tool in pharmaceutical analysis . In the course of a revision of the "Standardrezepturen", a German formula of standard dispensings for preparation in pharmacies, this technique has been applied to drug analysis in pharmaceutical formulations . The present paper deals with two different examples . First, naphazoline, dexamethasone and the preservative benzalkonium are quantified in nose drops without any sample preparation . Second, the antifungal antibiotic nystatin is quantified using nonaqueous capillary electrophoresis in methanol after sample preparation from an oily suspension.

Electrophoresis, 1998 Nov, 19(16-17), 2890 - 4
Analysis of cefadroxil by micellar electrokinetic capillary chromatography: development and validation; Li YM et al.; A method is developed and validated for analysis of the antibiotic cefadroxil using micellar electrokinetic capillary chromatography . It permits cefadroxil to be completely separated from ten of its known related substances within 15 min (including the washing procedure) . The separation is performed in an acetate buffer (50 mM, pH 5.25) containing sodium dodecyl sulfate (SDS; 110 mM) . The fused-silica capillary was 44 cm long (36 cm effective length), 50 microm ID; the voltage, 18 kV; temperature, 15 degrees C; and the detection wavelength; 254 nm . The influence of the type of buffer, buffer pH and concentration, and of the SDS concentration was investigated . The robustness of the method was examined by means of a full-fraction factorial design . The parameters for validation such as linearity, precision, limit of detection and limit of quantitation are also reported.

Ann Transplant, 1996, 1(4), 67 - 8
Pregnancy and delivery after liver transplantation; Pietrzak B et al.; The first case of pregnancy in a patient after an orthotopic liver transplantation (OLT) in Poland is presented . A 21-year-old woman was liver grafted 3 years prior to the pregnancy . Before having conceived the patient's graft function was stable . The woman was on immunosuppressive therapy with cyclosporine A and prednisolone . During pregnancy no significant changes in biochemical tests of liver function and liver blood flow were noted . Starting at the second trimester, a slight anemia occurred and the quantity of blood platelets continued to decrease, the latter having been observed immediately after the transplantation . The intrauterine growth of the fetus was monitored by ultrasound and the assessment of blood flow to the placenta was made . No abnormality was observed . In the second and third trimester the presence of HCV-RNA in the serum was found . In the 41-st week of pregnancy labor commenced . The threat of intrauterine infection indicated a cesarean delivery . The newborn weighed 4180 g and had an Apgar score of 10 . The cesarean section, as well as puerperium, was normal . The immunosuppressive therapy was continued, and antibiotics were administered for prophylactic reasons . During the first month the infant was treated with antibiotics because of pneumonia and the suspicion of meningitis . Nine months after the delivery, the patient's health is satisfactory and the baby is making normal progress.

J Thorac Cardiovasc Surg, 1999 Jan, 117(1), 77 - 90; discussion 90-1
Primary aortic valve replacement with allografts over twenty-five years: valve-related and procedure-related determinants of outcome; Lund O et al.; OBJECTIVES: Allografts offer many advantages over prosthetic valves, but allograft durability varies considerably . METHODS: From 1969 through 1993, 618 patients aged 15 to 84 years underwent their first aortic valve replacement with an aortic allograft . Concomitant surgery included aortic root tailoring (n = 58), replacement or tailoring of the ascending aorta (n = 56), and coronary artery bypass grafting (n = 87) . Allograft implantation was done by means of a "freehand" subcoronary technique (n = 551) or total root replacement (n = 67) . The allografts were antibiotic sterilized (n = 479), cryopreserved (n = 12), or viable (unprocessed, harvested from brain-dead multiorgan donors or heart transplant recipients, n = 127) . Maximum follow-up was 27.1 years . RESULTS: Thirty-day mortality was 5.0%, and crude survival was 67% and 35% at 10 and 20 years . Ten- and 20-year rates of freedom from complications were as follows: endocarditis, 93% and 89%; primary tissue failure, 62% and 18%; and redo aortic valve replacement, 81% and 35% . Multivariable Cox analyses identified several valve- and procedure-related determinants: rising allograft donor age and antibiotic-sterilized allograft for mortality; donor more than 10 years older than patient for endocarditis; rising donor age minus patient age, rising implantation time (from harvest to aortic valve replacement), and donor age more than 65 years for tissue failure; and rising donor age minus patient age, young patient age, rising implantation time, and subcoronary implantation preceded by aortic root tailoring for redo aortic valve replacement . Estimated 10- and 20-year rates of freedom from tissue failure for a 70-year-old patient with a viable valve from a 30-year-old donor and no other risk factors were 91% and 64%; the figures were 71% and 20% if the donor age was 65 years . The rates of freedom from tissue failure for a 30-year-old patient with a 30-year-old donor were 82% and 39%; the figures were 49% and 3% with a 65-year-old donor . Beneficial influences of a viable valve were largely covered by short harvest time (no delay for allografts from brain dead organ donors or heart transplant recipients) and short implantation time . CONCLUSIONS: Primary allograft aortic valve replacement can give acceptable results for up to 25 years . The late results can be improved by the use of a viable allograft, by matching patient and donor age, and by more liberal use of free root replacement with re-implantation of the coronary arteries rather than tailoring the root to accommodate a subcoronary implantation.

Antimicrob Agents Chemother, 1999 Jan, 43(1), 181 - 4
ADP-ribosylation as an intermediate step in inactivation of rifampin by a mycobacterial gene; Quan S et al.; Mycobacterium smegmatis DSM43756 inactivates rifampin, and the inactivated antibiotic product recovered from culture medium was ribosylated on the 23-OH group . To study this process, the gene responsible for the inactivation was expressed at high levels by the lac promoter in Escherichia coli conferring resistance to >500 microg of antibiotic per ml . Cell homogenates generated a novel derivative designated RIP-TAs; in this study, we determined that RIP-TAs is 23-(O-ADP-ribosyl)rifampin . Our results indicated that RIP-TAs is an intermediate in the pathway leading to ribosylated rifampin and that the previously characterized gene encodes a mono(ADP-ribosyl)transferase which, however, shows no sequence similarity to other enzymes of this class.

Clin Infect Dis, 1998 Dec, 27(6), 1388 - 93
Successful medical therapy for deeply invasive facial infection due to Pythium insidiosum in a child; Shenep JL et al.; Pythiosis occurs in animals and humans who encounter aquatic habitats that harbor Pythium insidiosum . Drug therapy for deeply invasive infections with this organism has been ineffective in humans and animals; patients have been cured only by radical surgical debridement . A 2-year-old boy developed periorbital cellulitis unresponsive to antibiotic and antifungal therapy . The cellulitis extended to the nasopharynx, compromising the airway and necessitating a gastrostomy for feeding . P . insidiosum was isolated from surgical biopsy specimens of the affected tissue . On the basis of in vitro susceptibility studies of the isolate, the patient was treated with a combination of terbinafine and itraconazole . The infection resolved over a period of a few months . The patient remained well 1.5 years after completing a 1-year course of therapy . Cure of deep P . insidiosum infection is feasible with drug therapy.

J Ocul Pharmacol Ther, 1998 Dec, 14(6), 491 - 6
A novel method for controlling the quantity of mitomycin-C applied during filtering surgery for glaucoma; Mehel E et al.; The use of a sponge impregnated with mitomycin-C is an increasingly common practice in glaucoma surgery . The appropriate antibiotic concentration and exposure time have been considered in the literature, but not the exact amount to be used or the size of the sponge . The purpose of this study was to estimate the quantity of mitomycin-C contained in sponges prepared by different surgeons as compared to that in applicators of the type used in Schirmer's test graduation (5 x 5 mm) . Four surgeons each cut and prepared 10 sponges for intraoperative use according to their usual method . The same procedure was performed with 10 Schirmer's test graduations . Each sponge and each graduation was immersed in a solution of mitomycin-C 0.2 mg/ml, and the quantity of antibiotic (microg) in each was calculated as the difference between wet and dry weight . The mean quantity (+/- SEM) of mitomycin-C contained in cut sponges was 9.6 +/- 4.4 microg (range 1.9-17.3), and the differences between surgeons were statistically significant (p<0.0001) . The mean quantity of antibiotic in Schirmer's test graduation was 1.7 +/- 0.3 microg (range 1.1-2.5), and the differences between surgeons were not statistically significant (p=0.79) . The quantities of mitomycin-C contained in sponges prepared for glaucoma surgery differed for a given surgeon and between surgeons . Thus, variations in the doses applied to the sclera could account for certain complications due to mitomycin-C . The use of a Schirmer's test graduation improves predictability for the quantity of mitomycin-C applied to the sclera.

Scand J Gastroenterol Suppl, 1998, 228, 31 - 7
Progress in the management and treatment of infected pancreatic necrosis; Farkas G et al.; Infected pancreatic necrosis and sepsis are the leading causes of mortality in necrotizing pancreatitis . A review has been undertaken of the results of the past two decades relating to different surgical treatments of infected pancreatic necrosis . During the period 1978-85, the surgical treatment of necrotizing pancreatitis and its complications in our department consisted of the 'conventional' therapy (resection of the involved pancreatic tissue, or necrosectomy and drainage) in 61 patients, with a mortality rate of 36% (22 patients died) . Since 1986, we have performed necrosectomy and other surgical interventions combined with continuous widespread lavage in 142 patients with infected pancreatic necrosis . The overall mortality decreased significantly to 6.3% (9 patients died) . This result was achieved by means of aggressive surgical treatment, continuous, prolonged washing and suction drainage and supportive therapy, including immunonutrition, modifying the cytokine production and adequate antibiotic and antifungal medication . This surgical strategy provides the possibility for recovery in cases of necrotizing pancreatitis with septic complications.

Clin Cancer Res, 1998 Dec, 4(12), 2967 - 76
Calphostin C triggers calcium-dependent apoptosis in human acute lymphoblastic leukemia cells; Zhu DM et al.; Recent studies have demonstrated that the naturally occurring perylenequinone antibiotic calphostin C is a potent inhibitor of protein kinase C and can induce apoptosis in some tumor cell lines by an as yet unknown mechanism . Here we demonstrate that calphostin C induces dose-dependent apoptosis in DT40 chicken lymphoma B-cells, and targeted disruption of lyn, syk, btk, PLCgamma2, or IP3R genes does not prevent or attenuate its cytotoxicity . In our study, calphostin C also induced rapid apoptosis in human acute lymphoblastic leukemia (ALL) cell lines ALL-1 (BCR-ABL+ pre-pre-B ALL), RS4;11 (MLL-AF4+ pro-B ALL), NALM-6 (pre-B ALL), DAUDI (Burkitt's/B-cell ALL), MOLT-3 (T-ALL), and JURKAT (T-ALL), whereas other potent PKC inhibitors did not . In biochemical studies, calphostin C was discovered to induce rapid calcium mobilization from intracellular stores of ALL cell lines, and its cytotoxicity against ALL cell lines was well correlated with the magnitude of this calcium signal . Calphostin C-induced apoptosis was markedly suppressed by BAPTA/AM, a cell-permeable Ca2+ chelator as well as NiCl2, an inhibitor of Ca2+/Mg2+-dependent endonucleases . Inhibition of the Ca2+/calmodulin-dependent phosphatase calcineurin with perfluoreperazine dimadeate (a calmodulin antagonist) or cyclosporin A (a specific inhibitor of calcineurin) also reduced the magnitude of calphostin C-induced apoptosis in ALL cell lines . Calphostin C was capable of inducing calcium mobilization and apoptosis in freshly obtained primary leukemic cells from children with ALL . Taken together, our results provide unprecedented evidence that calphostin C triggers a Ca2+-dependent apoptotic signal in human ALL cells.

Dermatol Surg, 1998 Dec, 24(12), 1350 - 3
Tie-over bolster dressings may not be necessary to secure small full thickness skin grafts; Langtry JA et al.; BACKGROUND: The accepted method for securing full thickness skin grafts (FTSG) is with a tie-over bolster dressing, with or without basting sutures . We question the need for tie-over bolster dressings for small FTSGs . OBJECTIVE: We describe our method of FTSG reconstruction and the outcome in a consecutive series . METHODS: Thirty patients with surgical defects following tumour excision from the face24, scalp1, ear2, and finger3 ranging in diameter from 8 to 45 mm (mean 20 mm) were reconstructed with a FTSG . Interrupted monofilament nylon perimeter sutures only were used, with antibiotic ointment at the wound edge with either a light dressing or no dressing . RESULTS: A series of 30 FTSG secured without a tie-over bolster dressing or basting sutures is described, all with good to excellent long term results . In two cases there was early superficial necrosis of the graft, but ultimately 100% graft take . CONCLUSION: We have found tie-over bolster dressings and basting sutures to be unnecessary in our series of small FTSG . This technique saves time and material and minimizes handling of the graft.

Curr Opin Nephrol Hypertens, 1998 Nov, 7(6), 639 - 42
Haemodialysis catheter bacteraemia: evolving strategies; O'Riordan E et al.; This article reviews the new trends in the diagnosis, treatment and prevention of catheter-related bacteraemia in clinical nephrology . Among these are the newer diagnostic techniques of evaluating and obtaining culture specimens from central lines, such as timed cultures and use of the endoluminal brush . In general, attempts to salvage infected haemodialysis lines are unsuccessful . We review the data that pertain to the use of antibiotic-coated catheters in non-dialysis patients and discuss how these observations may be applied to end-stage renal disease patients.

Chirurg, 1998 Nov, 69(11), 1257 - 62
{Reconstruction of severe facial defects due to noma}; Erdmann D et al.; Noma is an ulcerative-necrotizing gingivo-stomatitis eventually leading to severe destruction of the midface, including lips and cheek, maxilla/mandible, nose and rarely the orbit . The defects are usually unilateral . Children from economically underdeveloped countries are predominantly affected . Medically untreated the disease has a high mortality rate, which can be dramatically lowered by adequate antibiotic therapy started in time . Predisposing factors include malnourishment, immunosuppression, and poor oral hygiene . Forty-eight noma patients were surgically treated in Sokoto, Nigeria during October 1997 by an Interplast Germany team sponsored by AWD Stiftung Kinderhilfe . Interdisciplinary surgical strategies and results, e.g . ankylosis release, local flap coverage and 12 pedicled musculocutaneous latissimus dorsi island flaps, as well as a noma classification (NOMAC), are presented.

Ned Tijdschr Geneeskd, 1998 Oct 31, 142(44), 2395 - 9
{A changed pattern of opportunistic infections and malignancies in HIV-seropositive patients after the introduction of intensive anti-HIV-combination therapy}; Borleffs JC et al.; The application of potent combinations of antiretroviral drugs ('highly active antiretroviral therapy' (HAART)) makes effective therapy of HIV infection feasible . Consequently, the pattern of opportunistic infections and other secondary complications has changed . The incidence of infections and mortality due to aids has declined significantly . Further, the occurrence of other infections and syndromes, till now unknown in patients with aids, has been observed . It is thought that these are caused by HAART-induced inflammation, a phenomenon due to immune enhancement following HAART . An important issue is whether primary and secondary prophylaxis against opportunistic infections can be discontinued after improvement of the immune system: indeed, there are reports that discontinuation is safe in patients with persistent CD4+ cell counts above the critical level for that particular infection while CD4+ cell counts are monitored carefully.

Ned Tijdschr Geneeskd, 1998 Oct 3, 142(40), 2177 - 9
{Fever in intensive care: keep medications in mind at all times}; Postema RR et al.; In two patients, men aged 35 and 69 years admitted postoperatively to the intensive care unit, fever of unknown origin developed . One had been admitted because aspiration was suspected . He had been treated immediately with amoxicillin and clavulanic acid . The other had undergone oesophageal excision and gastric reconstruction because of oesophageal carcinoma and had been subjected to antibiotic decontamination (amphotericin B, norfloxacine en fungizone) . No cause for the fever was detected, but it quickly subsided after discontinuation of the amoxicillin-clavulanic acid and the norfloxacine, respectively . When encountering fever of unknown origin in intensive care patients it is always important to think of drug fever.

Oncol Rep, 1999 Jan-Feb, 6(1), 55 - 8
Scrotal ulcer occurring in patients with acute promyelocytic leukemia during treatment with all-trans retinoic acid; Mori A et al.; Although all-trans retinoic acid (ATRA) has been shown to improve the outcome of patients with acute promyelocytic leukemia (APL) compared with chemotherapy alone, various adverse effects have been reported . We report here the development of scrotal ulcer in four patients with APL during ATRA treatment . ATRA 45 mg/m2 was administered orally to four patients with newly diagnosed APL, two of whom also received chemotherapy . Scrotal ulcers appeared in all four patients after a median of 22 days (range: 17-29 days) of ATRA treatment . ATRA was discontinued in only one patient, who was then treated with methylprednisolone pulse therapy . The fever resolved, and scrotal ulcer improved after this treatment . The other three patients were treated with steroid or antibiotic ointment for scrotal ulcers . ATRA was re-administered 2 years later in one patient who had relapse of APL . Ulcers appeared again on the scrotal and lower abdominal skin on day 27 of ATRA treatment . These findings strongly suggest that scrotal ulcer is a potential adverse effect of ATRA.

Infect Immun, 1999 Jan, 67(1), 36 - 42
Specificity of infection-induced immunity among Borrelia burgdorferi sensu lato species; Barthold SW; The specificity of infection-induced immunity in mice infected with cultured or host-adapted Borrelia burgdorferi sensu lato, the agent of Lyme disease, was examined . Sera obtained from mice following infection with high and low doses of cultured B . burgdorferi sensu stricto, transplantation of infected tissue (host-adapted spirochetes), or tick-borne inoculation all showed protective activity in passive immunization assays . Infection and disease were similar in mice infected with cultured spirochetes or by transplantation . Thus, the adaptive form of inoculated spirochetes did not influence the immune response during active infection . Mice infected with B . burgdorferi sensu stricto and then cured of infection with an antibiotic during early or late stages of infection were resistant to challenge with high doses of homologous cultured spirochetes for up to 1 year . In contrast, actively immune mice infected with different Borrelia species (B . burgdorferi sensu lato, B . burgdorferi sensu stricto cN40, Borrelia afzelii PKo, and Borrelia garinii PBi) and then treated with an antibiotic were resistant to challenge with cultured homologous but not heterologous spirochetes . Similar results were achieved for actively immune mice challenged by transplantation and by passive immunization with sera from mice infected with each of the Borrelia species and then challenged with cultured spirochetes . Arthritis and carditis in mice that had immunizing infections with B . afzelii and B . garinii and then challenged by transplantation with B . burgdorferi sensu stricto were equivalent in prevalence and severity to those in nonimmune recipient mice . These results indicate that protective immunity and disease-modulating immunity that develop during active infection are universal among species related to B . burgdorferi sensu lato but are species specific.

Zentralbl Bakteriol, 1998 Nov, 288(3), 361 - 72
Fibronectin and laminin binding of urogenital and oral prevotella species; Eiring P et al.; 88 strains of five Prevotella species--P . bivia, P . buccae, P . disiens, P . oralis, and P . oris--were examined for their fibronectin and laminin binding properties with the aid of latex particle agglutination assays . Beside single protein binding activities, all species showed strains that adhered to both fibronectin and laminin . The oral species, P . buccae, P . oralis, and P . oris were found to interact with laminin to a pronouncedly higher extent than with fibronectin . The urogenital species, P . bivia and P . disiens showed comparable activities of binding to fibronectin and laminin, with P . bivia exhibiting higher matrix protein binding rates than P . disiens . Within the oral species group, P . oralis showed a higher percentage of fibronectin and laminin reactive strains than did P . buccae and P . oris . The finding of species-related different binding properties may throw some light on the known differences in clinical relevance and pathogenicity of the urogenital species, P . bivia and P . disiens, but does so only in part concerning the oral species, P . buccae, P . oralis, and P . oris . Moreover, the observed differences in matrix protein binding of Prevotella species may have implications in chemotaxis and opsonization on the one hand and maintenance of colonization activities under antibiotic therapy on the other.

Plant Mol Biol, 1998 Nov, 38(5), 807 - 15
Isolation and characterization of an Arabidopsis thaliana C-8,7 sterol isomerase: functional and structural similarities to mammalian C-8,7 sterol isomerase/emopamil-binding protein; Grebenok RJ et al.; The yeast C-8,7 sterol isomerase contains a polyvalent high-affinity drug binding site similar to mammalian sigma receptors . Exogenously supplied sigma ligands inhibit sterol biosynthesis in yeast, demonstrating a pharmacological relationship between sigma ligand-binding and C-8,7 sterol isomerase activity . We report the isolation of an Arabidopsis thaliana C-8,7 sterol isomerase by functional complementation of the corresponding sterol mutant in yeast and its characterization by exposure to sigma ligands . The yeast erg2 mutant, which lacks the C-8,7 sterol isomerase gene and activity, was transformed with an Arabidopsis cDNA yeast expression library . Transformed colonies were selected for restoration of C-8,7 sterol isomerase activity (i.e . wild-type ergosterol production) by enhanced resistance to the antibiotic cycloheximide . Sterols produced in complemented lines were characterized by gas chromatography-mass spectroscopy (GC-MS) . The full-length A . thaliana cDNA (pA.t.SI1) that complemented the erg2 mutation contains an open reading frame encoding a 21 kDa protein that shares 68% similarity and 35% amino acid identity to the recently isolated mouse C-8,7 sterol isomerase . The sigma ligands, haloperidol, ifenprodil and verapamil inhibited the production of ergosterol in wild-type Saccharomyces cerevisiae and in the erg2 mutant complemented with pA.t.SI1 . Structural and biochemical similarities between the A . thaliana C-8,7 sterol isomerase and the mammalian emopamil-binding protein (EBP) are discussed.

J Biomol NMR, 1998 Nov, 12(4), 559 - 64
3D HCCH-COSY-TOCSY experiment for the assignment of ribose and amino acid side chains in 13C labeled RNA and protein; Hu W et al.; A new 3D HCCH-COSY-TOCSY experiment is presented for the assignment of RNA sugar and protein side chains . The experiment, which combines COSY and TOCSY units, is more powerful than the sum of individual HCCH-COSY and HCCH-TOCSY pulse sequences . The experiment was applied to a 13C, 15N-labeled 26 mer RNA complexed with the antibiotic tobramycin, and a 12 kDa 13C, 15N-labeled FKBP12 protein sample . The power of HCCH-COSY-TOCSY is demonstrated through complete spin system assignments of sugars in the 26 mer RNA sample, which could not be assigned using a combination of HCCH-COSY, HCCH-TOCSY and 13C-edited NOESY experiments.

Neurol Med Chir (Tokyo), 1998 Oct, 38(10), 657 - 60
Cerebral mycotic aneurysm treated with endovascular occlusion--case report; Watanabe A et al.; A 56-year-old male with two mycotic aneurysms associated with infective endocarditis was treated by endovascular surgery before mitral valve replacement . Angiography revealed a ruptured proximal aneurysm and an unruptured distal aneurysm on the right middle cerebral artery . The ruptured aneurysm was successfully treated with an interlocking detachable coil, and patency of the parent artery was preserved . The unruptured distal aneurysm disappeared as a result of antibiotic therapy . Endovascular surgery of the mycotic aneurysm is less invasive and more effective than craniotomy under general anesthesia for patients with infective endocarditis.

Nucl Med Commun, 1998 Nov, 19(11), 1037 - 45
Immunoscintigraphy (BW 250/183) in neonates and infants with fever of unknown origin; Gratz S et al.; Fever of unknown origin is defined as a temperature above 39.0 degrees C together with a white blood cell count > or = 15,000 mm-3, the duration of fever exceeding 2 weeks and a correct diagnosis not being obtained in the first week of hospitalization . In neonates and infants with fever of unknown origin, the localization of the infectious focus is often difficult and unsatisfactory . In this retrospective study, the clinical value of 99Tcm-labelled antigranulocyte antibodies for this group of patients was investigated . Thirty-two immunoscintigrams were performed using 185-259 MBq 99Tcm-labelled antigranulocyte antibodies (BW 250/183) in 30 neonates and infants (21 boys, 9 girls, mean age 29.4 +/- 2 months), who had fever of unknown origin . Immunoscintigraphy was carried out as whole-body images (n = 7) or single planar images (n = 25) 4 h and 24 h post-injection . In children with known cardiac failure, single photon emission tomography of the thorax was performed to diagnose endocarditis (n = 2) . For verification, the results of the immunoscintigrams were compared with radiology (conventional radiography = 14, MRI = 5, CT = 3), biopsy (n = 2), blood culture (n = 10) and clinical follow-up after specific therapy . In 11 of 30 children (36%), the diagnosis of an infective focus was possible with immunoscintigraphy . The sensitivity and specificity of diagnosing infective foci was 72% and 95% respectively (n = 11; colitis = 2, infection of the central permanent catheter tip = 2, middle ear infection = 1, spondylitis/discitis = 3, osteomyelitis = 2, umbilical infection = 1) . In vertebral body infections, all lesions were photopenic . In 18 children (60%), no infective focus was found on immunoscintigraphy . In this group of children, the main reason (n = 5) for fever of unknown origin was chronic juvenile rheumatoid arthritis . No uptake was seen in two infants with cardiac failure and suspected endocarditis on SPET . In 3 of the 18 patients (17%), localization of an infective focus was not possible with immunoscintigraphy or on other examinations . In these patients, the fever disappeared spontaneously after a few days of antibiotic therapy . In conclusion, we have shown that 99Tcm-anti-NCA-95 scanning is a safe method with a high sensitivity and specificity for detecting infectious foci in neonates and infants with fever of unknown origin . Furthermore, this method is easy to perform, since no withdrawal of blood is necessary.

Br J Anaesth, 1998 Sep, 81(3), 468 - 70
Adrenal failure in the critically ill; Duggan M et al.; Three critically ill patients suffered multiple organ failure secondary to sepsis . Despite adequate supportive therapy and appropriate antibiotic cover, they failed to improve and required inappropriate inotrope support . They had not been treated with steroids or other drugs known to suppress adrenal function . Adrenal insufficiency was suspected . A random cortisol concentration and a short synacthen test demonstrated concentrations below the range expected in all three cases . High-dose steroid therapy was commenced with marked improvement in the short-term . However, in each case sepsis eventually caused death.

Atherosclerosis, 1998 Oct, 140 Suppl 1, S31 - 5
Chlamydia pneumoniae: inflammation and instability of the atherosclerotic plaque; Gurfinkel E et al.; Coronary heart disease remains the most common cause of death in industrialized countries . Although atherosclerosis is generally asymptomatic in the early stages, progressive plaque development leads to arterial stenosis which is characterized by angina and may eventually lead to unstable angina, myocardial infarction and cardiac death . Evidence that the coagulation cascade is activated during acute coronary events has justified the use of antithrombotic agents such as aspirin, heparin and low molecular weight heparin (LMWH) in the standard management of acute coronary syndromes . The inflammatory process is also known to play a significant role in the pathogenesis of atherosclerosis, resulting in a cycle of continued inflammatory cell activation and ongoing cell recruitment . As the human leukocyte-associated antigen (HLA) system plays a key role in the regulation of the inflammatory process, the expression of HLA antigens in patients with symptomatic coronary heart disease has been investigated . These studies have demonstrated a relationship between the major histocompatibility complex (MHC) class II expression and the most severe pattern of angina refractory to conventional therapy, within the framework of a chronic infectious disease . A number of studies have documented an association between coronary heart disease and the presence of high titres of antibodies to Chlamydia pneumoniae, and this organism has been implicated in plaque instability . Such findings have stimulated interest in the role of C . pneumoniae in the pathogenesis of coronary heart disease, with a view to developing novel and effective treatment approaches . The ROXIS study showed a lower incidence of acute ischaemic events in patients with unstable angina treated with an antichlamydial antibiotic, roxithromycin.

Presse Med, 1998 Nov 28, 27(37), 1924 - 31
{Purulent pleurisy and empyema . With the exception of pleural tuberculosis}; Jebrak G et al.; CLINICAL SETTING: Purulent collections in the pleural cavity usually occur as complications of pneumonia in immunodeficient or socially underprivileged patients . PUNCTURE ASPIRATION: The key to diagnosis, pleural aspiration is indicated in case of sufficiently abundant collections, especially in patients with fever . Exploratory puncture is a therapeutic emergency, allowing optimal antibiotic therapy when a causal germ is isolated and drainage of the purulent collection . If there is the slightest doubt, imaging techniques should be used to guide the puncture . DRAINAGE: Drainage is essential and is indicated whenever the aspiration fluid is purulent, contains, germs or the chemistry suggests major bacterial colonisation (acid pH, low glucose, high lactic acid dehydrogenase) . Local injections of fibrinolytic agents improve drainage . PROGNOSIS: Complete recovery without sequellae is usually achieved . Physical therapy, provided early and for a prolonged period, helps improve the prognosis . Early care reduces the risk of recurrence of this potentially severe condition.

Gene, 1998 Nov 26, 223(1-2), 77 - 81
A new system to place single copies of genes, sites and lacZ fusions on the Escherichia coli chromosome; Yu D et al.; To place a single-copy lacZ fusion on the E . coli chromosome, a method was developed based on in vivo homologous DNA recombination through P1 transduction . The fusions, initially constructed on plasmids, are crossed to lambdalacZ fusion vectors which are then lysogenized at the chromosomal lambda att site . The features of the new system are: (1) lambda lysogens carrying the fusion are made without regard for copy number; (2) P1 transduction from the lysogenic strain into an appropriate recipient generates the single-copy fusion; (3) The lacZ fusion has no prophage associated with it; (4) the lacZ fusion can be transferred by P1 transduction to other strains, simply by selecting for an antibiotic marker; (5) the system can be widely applied to construct single copies of any gene or site placed between bla and lacZ on the standard lacZ fusion plasmid vectors; and (6) the single-copy construct flanked by prophage att sites can be excised by site-specific recombination to generate non-replicating circular DNA of the clone or a cell cured of the construct.

Mol Cell Biol, 1999 Jan, 19(1), 402 - 11
A trans-activation domain in yeast heat shock transcription factor is essential for cell cycle progression during stress; Morano KA et al.; Gene expression in response to heat shock is mediated by the heat shock transcription factor (HSF), which in yeast harbors both amino- and carboxyl-terminal transcriptional activation domains . Yeast cells bearing a truncated form of HSF in which the carboxyl-terminal transcriptional activation domain has been deleted {HSF(1-583)} are temperature sensitive for growth at 37 degreesC, demonstrating a requirement for this domain for sustained viability during thermal stress . Here we demonstrate that HSF(1-583) cells undergo reversible cell cycle arrest at 37 degreesC in the G2/M phase of the cell cycle and exhibit marked reduction in levels of the molecular chaperone Hsp90 . As in higher eukaryotes, yeast possesses two nearly identical isoforms of Hsp90: one constitutively expressed and one highly heat inducible . When expressed at physiological levels in HSF(1-583) cells, the inducible Hsp90 isoform encoded by HSP82 more efficiently suppressed the temperature sensitivity of this strain than the constitutively expressed gene HSC82, suggesting that different functional roles may exist for these chaperones . Consistent with a defect in Hsp90 production, HSF(1-583) cells also exhibited hypersensitivity to the Hsp90-binding ansamycin antibiotic geldanamycin . Depletion of Hsp90 from yeast cells wild type for HSF results in cell cycle arrest in both G1/S and G2/M phases, suggesting a complex requirement for chaperone function in mitotic division during stress.

Microbiol Immunol, 1998, 42(10), 683 - 8
Detection and long-term existence of Shiga toxin (Stx)-producing Escherichia coli in sheep; Asakura H et al.; The isolation and characterization of Shiga-like toxin (Stx)-producing Escherichia coli (STEC) from sheep are described . The distribution of stx genes in E . coli isolates was detected by PCR . When brain heart infusion (BHI) broth and novobiocin supplemented m-EC broth (N-mEC) were used as enrichment culture for the isolation of STEC, N-mEC, compared to BHI, showed clearly lower efficiency . Finally, 5 STEC isolates from 4 sheep were isolated and characterized by biochemical and genetical analysis . All of them were confirmed by ELISA and Vero cell cytotoxicity assay for the production of Stx . Moreover, some strains carried hemolysin and eaeA genes and harbored large plasmids . Based on their plasmid profiles, antibiotic patterns and PCR-based DNA fingerprinting analysis using random amplified polymorphic DNA (RAPD), all isolates were different from each other . Three of the isolates were identified to belong to serogroups O2, O153 and O165, respectively, and the STEC strains belonging to these serogroups had been isolated from STEC outbreaks in humans . Four months after the first isolation in July 1997, STEC from sheep #1 was isolated again . A new isolate, HI-11, was identified as STEC O2:Hnt . Simultaneously, 2 STEC, which were genetically and phenotypically different from each other, were isolated from the same sheep at intervals of 4 months . These results demonstrate that sheep may be an important animal for studying human STEC infections, and that further epidemiological surveys on STEC are necessary.

Pneumonol Alergol Pol, 1998, 66(3-4), 221 - 5
{Invasive pulmonary aspergillosis in the course of allergic pulmonary alveolitis}; Libura M et al.; 20 years old man with history of acute allergic alveolitis 7 years ago, was admitted to hospital because of dyspnea, fever and cough after massive exposition to organic dust . Corticosteroids were introduced . During 3-weeks treatment respiratory failure progressed . Chest x-ray showed massive bilateral nodular opacities . Antibiotic therapy was not effective . The autopsy revealed invasive pulmonary aspergillosis . Presence of precipitins to aspergillus fumigatus was confirmed postmortem . Diagnostic difficulties are discussed.

Ophthalmologe, 1998 Nov, 95(11), 748 - 54
{Depth of lamellar keratoplasty with the guided trephine system for transplantation of full-thickness donor sections}; Krumeich JH et al.; BACKGROUND: Despite the fact that deep lamellar keratoplasty (DLKP) is less invasive than to penetrating keratoplasty (PKP), this procedure is rarely performed . We therefore investigated whether or not the DLKP technique we employed can achieve stable improvement of visual acuity . MATERIALS AND METHODS: Thirty-three eyes underwent TLKP for treatment of superficial corneal pathology . The donor tissue transplanted was suitable for PKP . The donor lenticule was obtained on the artificial chamber of the guided trephine system (GTS) . The recipient cornea was trephined with the same trephine to a depth of 680 microns . Manual dissection was performed with a bevel-up blade . The donor lenticule with the endothelium peeled off was then sutured in with a 10 x 0 nylon double-running antitorque suture . Cortisone-antibiotic eye drops were administered postoperatively . RESULTS: Throughout the series no complications occurred . The mean best corrected visual acuity (BSCVA) over glasses was 0.29 (+/- 0.21) preoperatively, 0.1 (+/- 0.11) at 1 week, 0.33 (+/- 0.14) at 1 month, 0.5 (+/- 0.13) at 6 months, 0.61 (+/- 0.16) at 1 year and 0.63 (+/- 0.15) at 2 years . Clinically, we observed two subpopulations . In the first group of 87% of the cases, mean BSCVA was 0.67 (+/- 0.07) at 6 months . The remaining cases (BSCVA < or = 0.25 at 6 months) achieved a mean BSCVA of only 0.2 (+/- 0.04) at 1 year . Mean corneal astigmatism measured 2.93 D (+/- 1.62) preoperatively, 2.69 D (+/- 1.18) at 1 month, 2.09 D (+/- 1.07) at 1 year, and 2.22 D (+/- 1.11) at 2 years . We did not observe any graft rejection . CONCLUSION: The technique reported for DLKP provides excellent matching of donor lenticule and recipient bed . Separation of donor and recipient stroma prevents interface healing . DLKP appears to be a safe procedure for the surgical treatment of superficial corneal pathology and may offer a clinically applicable alternative to PKP.

Ned Tijdschr Geneeskd, 1998 Sep 12, 142(37), 2030 - 4
{The total knee prosthesis: indications and complications}; Hamelynck KJ; Severe pain, impaired movement, serious deformity and (or) instability of the knee due to osteoarthritis or another joint disease are indications for total knee replacement . Contraindications are a high surgical risk and poor function of the M . quadriceps femoris . The main problems immediately after the operation are: wound infection and prosthetic infection, palsy of the peroneal nerve and deep venous thrombosis . These occur in approximately 2% of the patients . After replacement and 3 months' rehabilitation the knee is usually free of pain and stable with a good range of movement . After 10 years, 93-98% of the operated knees are still satisfactory, and after 15 years, 85-95% . Reasons for revision are infection, mechanical loosening of components, wear of polyethylene and progressive instability.

Am J Obstet Gynecol, 1998 Dec, 179(6 Pt 1), 1599 - 604
Plasma ferritin, premature rupture of membranes, and pregnancy outcome; Goldenberg RL et al.; OBJECTIVE: The objective of this study was to determine whether plasma ferritin levels predict maternal or neonatal outcomes in women with preterm rupture of membranes at <32 weeks' gestation . METHODS: Plasma from 223 women with premature rupture of membranes at <32 weeks' gestation who had participated in a randomized antibiotic trial were analyzed for ferritin at random assignment and at delivery, and the results were compared with the development of clinical chorioamnionitis, latency until delivery, neonatal sepsis, and a composite adverse neonatal outcome variable . RESULTS: The mean plasma ferritin level rose from 19.2 +/- 29.1 microgram/L on admission to 38.3 +/- 54.3 microgram/L at delivery, with a mean latency of 9.3 +/- 14.6 days . Plasma ferritin levels were significantly higher at both times in mothers whose infants acquired sepsis than in those whose infants did not, especially at delivery (68.5 +/- 96.3 microgram/L vs 32.5 +/- 40.5 microgram/L, P =.01), and neonatal sepsis was 2 to 3 times more common among women with plasma ferritin levels above the median than among those with levels below the median . CONCLUSIONS: Among women with premature rupture of membranes at <32 weeks' gestation, plasma ferritin levels were significantly associated with neonatal sepsis . These data suggest that higher plasma ferritin levels may serve as a marker of infection among women with premature rupture of membranes; however, the clinical utility of plasma ferritin levels in predicting neonatal outcome appears limited.

Chirurgia (Bucur), 1998 Sep-Oct, 93(5), 285 - 90
{Laparoscopic cholecystectomy in acute cholecystitis}; Jitea N et al.; AIM: Results evaluation of laparoscopic cholecystectomy in acute cholecystitis . MATERIAL AND METHOD: Between 1994-1997 we performed 65 laparoscopic cholecystectomies for histopathologically proved acute lithiasic cholecystitis . We studied clinic and echographic diagnosis, operative moment, conversion rate, operative time, postoperative morbidity and hospitalization . The cholecystectomy was performed within 72 hours in 18 patients (trial I), 4 to 7 days in 25 patients (trial II) and over 7 days in 22 patients (trial III) . RESULTS: Diagnosis of acute lithiasic cholecystitis was always possible by clinical examination and ultrasonography . We performed 8 conversions in patients of trial II (2) and III (6) . The mean operative time was 68 min . Postoperative morbidity consisted in 4 bile leakages in the liver bed, 1 subhepatic abscess, 5 right pleural effusions . The mean hospitalization was 4.4 days . CONCLUSIONS: Urgent laparoscopic cholecystectomy is a beneficial act for acute lithiasic cholecystitis . The operative moment is the most important factor of influence on conversion rate, operative time and postoperative morbidity.

J Clin Microbiol, 1999 Jan, 37(1), 49 - 55
Mycobacterium species identification and rifampin resistance testing with high-density DNA probe arrays; Troesch A et al.; Species identification within the genus Mycobacterium and subsequent antibiotic susceptibility testing still rely on time-consuming, culture-based methods . Despite the recent development of DNA probes, which greatly reduce assay time, there is a need for a single platform assay capable of answering the multitude of diagnostic questions associated with this genus . We describe the use of a DNA probe array based on two sequence databases: one for the species identification of mycobacteria (82 unique 16S rRNA sequences corresponding to 54 phenotypical species) and the other for detecting Mycobacterium tuberculosis rifampin resistance (rpoB alleles) . Species identification or rifampin resistance was determined by hybridizing fluorescently labeled, amplified genetic material generated from bacterial colonies to the array . Seventy mycobacterial isolates from 27 different species and 15 rifampin-resistant M . tuberculosis strains were tested . A total of 26 of 27 species were correctly identified as well as all of the rpoB mutants . This parallel testing format opens new perspectives in terms of patient management for bacterial diseases by allowing a number of genetic tests to be simultaneously run.

South Med J, 1998 Dec, 91(12), 1107 - 14
Hidradenitis suppurativa; Brown TJ et al.; BACKGROUND: Hidradenitis suppurativa (HS) is a recurrent, suppurative disease manifested by abscesses, fistulas, and scarring . METHODS: We reviewed the literature to identify reliable information regarding epidemiology, pathogenesis, clinical manifestations, evaluation and differential diagnosis, treatment, complications, and prognosis . RESULTS: Hidradenitis suppurativa usually affects young women, with a prevalence of 0.3% to 4% in industrialized countries . Once considered to be "apocrine acne," HS is actually a defect of terminal follicular epithelium . Obesity, chemical irritants, or hyperandrogenism are not consistently associated; bacterial involvement is secondary . Hidradenitis suppurativa should be suspected in young adults with recurrent, deep furuncular lesions in flexural sites, especially when such lesions respond poorly to antibiotic therapy . Clindamycin and isotretinoin may be useful, though wide excision with healing by granulation is considered most efficacious . Anemia, arthropathy, and squamous cell carcinoma are potential complications . CONCLUSIONS: Since spontaneous resolution is rare and progressive disability the rule, early definitive surgical treatment of HS is advisable.

Cranio, 1998 Jul, 16(3), 143 - 53
Exogenous estrogen may exacerbate thrombophilia, impair bone healing and contribute to development of chronic facial pain; Glueck CJ et al.; A 32 year old white female, in apparently good health, failed to respond to conservative wound care for alveolar osteitis after a routine mandibular first molar extraction . Curettage and biopsy of necrotic alveolar bone from the #30 socket escalated her pain such that hospitalization was necessary for pain management with intravenous morphine . Twelve months prior to admission she had been placed on exogenous estrogen (Premarin, 0.625 mg/day) after a partial oophorectomy . While hospitalized, she was found to have resistance to activated protein C (APCR) . Premarin was discontinued . After discharge, weekly changes of an antibiotic impregnated dressing allowed for progressive regeneration of bone and epithelium with gradual reduction in her pain . She was found to be heterozygous for the mutant Factor V Leiden, a heritable factor for increased tendency to form thrombi, so-called thrombophilia . We speculate that the exogenous estrogen administration exacerbated the thrombophilia associated with the Factor V Leiden mutation by compounding the patient's resistance to activated protein C thereby contributing to her development of osteonecrosis and severe alveolar neuralgia.

Otolaryngol Head Neck Surg, 1998 Dec, 119(6), 581 - 7
Protection against aminoglycoside otic drop-induced ototoxicity by a spin trap: I . Acute effects; Hester TO et al.; Topical administration of aminoglycoside antibiotic drops containing neomycin and polymyxin B disrupts cochlear structure and function in rodents, possibly as a result of reactive oxygen species generation . This study investigated the ability of a spin trap, alpha-phenyl-tert-butyl-nitrone (PBN), to prevent acute aminoglycoside antibiotic drop-induced cochlear dysfunction . Guinea pigs were monitored for compound action potential thresholds and 1.0 microV root-mean-square cochlear microphonic isopotential curve values, then injected intraperitoneally with PBN (60 mg/kg) or saline solution . After 10 minutes, 50 microl of PBN (100 mmol/L) or artificial perilymph was applied to the round window membrane, followed after 10 minutes with artificial perilymph or aminoglycoside antibiotic drops (50 microl) . From 10 to 60 minutes after exposure, mean compound action potential thresholds progressively increased in the artificial perilymph-aminoglycoside antibiotic drop group, beginning with high frequencies and later including ever-lower frequencies . These threshold shifts in compound action potentials were significantly greater (p<0.05) than those seen in the artificial perilymph-artificial perilymph or PBN-aminoglycoside antibiotic drop groups . This finding indicates that PBN provided protection against acute aminoglycoside antibiotic drop-induced compound action potential threshold sensitivity loss . Mean cochlear microphonic shift values at 60 minutes in the artificial perilymph-aminoglycoside antibiotic drop group significantly exceeded those of the other groups only at the highest frequencies . These data suggest that acute aminoglycoside antibiotic drop-induced cochlear disruption primarily affects high frequency compound action potential function and may be partially reactive oxygen species-mediated and preventable.

J Biol Chem, 1998 Dec 18, 273(51), 34033 - 41
Evidence for the location of bicyclomycin binding to the Escherichia coli transcription termination factor Rho; Riba I et al.; The commercial antibiotic bicyclomycin (Bcm) has been shown to target the essential transcription termination factor Rho in Escherichia coli . Little is known about the Bcm binding domain in Rho . A recent structure-activity relationship study led us to evaluate the reductive amination probe, 5a-(3-formylanilino)dihydrobicyclomycin (FD-Bcm) . Biochemical studies showed that FD-Bcm possessed inhibitory activities comparable to Bcm in Rho-dependent ATPase and transcription termination assays . Incubation of Rho with FD-Bcm, ATP, and poly(C) followed by NaBH4 reduction and dialysis led to an appreciable loss of ATPase activity . Inclusion of Bcm with FD-Bcm in the reductive amination reaction protected Rho, indicating that Bcm and FD-Bcm competed for the same binding site in Rho . Incubation of Rho with FD-Bcm and poly(C) followed by NaBH4 reduction provided a sample with residual ATPase activity (12%) . Mass spectrometric analysis indicated the presence of two proteins in an approximate 1.2:1 ratio, whose masses corresponded to wild-type Rho (47,010 Da) and lysine-modified Rho (47,417 Da), respectively . Trypsin digestion of the Rho sample followed by high performance liquid chromatography separation and tandem mass spectrometry analysis identified the site of modification as Lys181 within the combined tryptic fragment, Gly-Leu-Ile-Val-Ala-Pro-Pro-Lys-Ala-Gly-Lys (residues 174-184) . Similar analysis of a lesser modified sample (following incubation with inclusion of ATP) showed that addition had again occurred at Lys181 . These findings provide the first structural information concerning the site of Bcm binding in Rho.

Mol Genet Metab, 1998 Nov, 65(3), 238 - 45
Plasma glutathione peroxidase and its relationship to renal proximal tubule function; Whitin JC et al.; Selenium-dependent extracellular glutathione peroxidase (E-GPx) is found in plasma and other extracellular fluids . Previous studies have indicated that patients with chronic renal failure on dialysis have low plasma GPx activity . In this study, dialysis patients had approximately 40% of control plasma GPx activity, while anephric individuals had lowest plasma GPx activities ranging from 2 to 22% of control . The residual plasma GPx activity in anephric individuals could be completely precipitated by anti-E-GPx antibodies, indicating that all plasma GPx activity can be attributed to E-GPx in both normal and anephric individuals . Plasma GPx activity rises rapidly following kidney transplantation, often reaching normal values within 10 days . The plasma GPx activity in some transplanted patients rises to levels higher than the normal range, followed by a return to the normal range . Since E-GPx in the kidney is primarily synthesized in the proximal tubules, we investigated whether nephrotoxic agents known to disrupt proximal tubule function also affected plasma GPx activity . The beta-lactam antibiotic cephaloglycin rapidly caused a decrease in plasma GPx activity in rabbits . In addition, the chemotherapeutic agent ifosfamide caused a decrease in plasma GPx activity in pediatric osteosarcoma patients . Fanconi syndrome associated with either ifosfamide therapy or valproic acid therapy also caused a decrease in plasma GPx activity . Thus plasma GPx activity is related to kidney function and is decreased in certain situations where nephrotoxic drugs are administered . Monitoring plasma GPx activity may have predictive value in evaluating the function of transplanted kidneys or in predicting those patients particularly at risk of nephrotoxic injury associated with certain medications .

J Laryngol Otol, 1998 Aug, 112(8), 800 - 1
Actinomycosis of the middle ear; Boor A et al.; Another case of actinomycosis of the ear is described in a nine-year-old boy, drawing attention to the increasing incidence of diseases of the ear considered to be rare . The patient presented with the clinical signs of chronic purulent otitis media, not responding to conservative treatment . After the diagnosis of actinomycosis was established the patient was treated by surgery and long-term antibiotic medication, responding favourably.

J Laryngol Otol, 1998 Aug, 112(8), 793 - 5
Mycotic aneurysm of the external carotid artery; Worley GA et al.; Mycotic aneurysms of the extracranial carotid arteries are extremely rare . A case is reported of a false aneurysm of the left external carotid artery . This developed secondary to cervical lymphadenitis which did not settle with high dose antibiotic therapy . The diagnosis was made on investigation with carotid doppler ultrasound and confirmed with computerized tomography . Digital subtraction angiography was performed to highlight the vascular anatomy . In addition percutaneous balloon catheter control of blood flow in the external carotid artery was used as an adjunct to surgical management.

Bone Marrow Transplant, 1998 Nov, 22(10), 965 - 9
A randomized trial of granulocyte colony-stimulating factor (Neupogen) starting day 1 vs day 7 post-autologous stem cell transplantation; Bence-Bruckler I et al.; The purpose of the study was to evaluate the effect of delayed granulocyte colony-stimulating factor (G-CSF) use on hematopoietic recovery post-autologous peripheral blood progenitor cell (PBPC) transplantation . Patients were randomized to begin G-CSF on day +1 or day +7 post transplantation . Thirty-seven patients with lymphoma or myeloma undergoing high-dose therapy and autologous PBPC rescue were randomized to daily subcutaneous G-CSF beginning on day +1 or day +7 post-transplant . Patients < or =70 kg received 300 microg/day and >70 kg 480 microg/day . All patients were reinfused with PBPCs with a CD34+ cell count >2.0 x 10(6)/kg . Baseline characteristics of age, sex and CD34+ cell count were similar between the two arms, the median CD34+ cell count being 5.87 x 10(6)/kg in the day +1 group and 7.70 x 10(6)/kg in the day +7 group (P=0.7) . The median time to reach a neutrophil count of >0.5 x 10(9)/l was 9 days in the day +1 arm and 10 days in the day +7 arm, a difference which was not statistically significant (P=0.68) . Similarly, there was no difference in median days to platelet recovery >20000 x 10(9)/l, which was 10 days in the day +1 arm and 11 days in the day +7 arm (P=0.83) . There was also no significant difference in the median duration of febrile neutropenia (4 vs 6 days; P=0.7), intravenous antibiotic use (7 vs 8 days; P=0.54) or median number of red blood cell transfusions (4 vs 7 units; P=0.82) between the two arms . Median length of hospital stay was 11 days post-PBPC reinfusion in both groups . The median number of G-CSF injections used was 8 in the day +1 group and 3 in the day +7 group (P < 0.0001) . There is no significant difference in time to neutrophil or platelet recovery when G-CSF is initiated on day +7 compared to day +1 post-autologous PBPC transplantation . There is also no difference in number of febrile neutropenic or antibiotic days, number of red blood cell transfusions or length of hospital stay . The number of doses of G-CSF used per transplant is significantly reduced with delayed initiation, resulting in a significant reduction in drug costs . For patients with an adequately mobilized PBPC graft, the initiation of G-CSF can be delayed until day +7 post-PBPC reinfusion.

Int J Pediatr Otorhinolaryngol, 1998 Oct 2, 45(2), 163 - 6
The silent epidural abscess as a complication of acute otitis media in children; Bizakis JG et al.; Acute otitis media with complications is a persistent problem in the modern antibiotic era with a relatively high mortality rate . Acute mastoiditis is a serious complication of acute otitis media with potentially grave consequences and the epidural abscess constitutes the commonest of all intracranial complications, arising from middle ear infections . We report two cases of children with acute mastoiditis without evidence of intracranial complication or subperiosteal abscess, in whom the early evaluation with computed tomography (CT) disclosed an unsuspected epidural abscess . Therefore, we stress the use of CT as a rule of thumb for every child with acute mastoiditis.

Jpn J Cancer Res, 1998 Oct, 89(10), 1055 - 60
In vivo efficacy and tumor-selective metabolism of amrubicin to its active metabolite; Noguchi T et al.; The tissue distribution of a novel antitumor anthracycline antibiotic, amrubicin, was studied using seven human tumor xenografts implanted into nude mice, in order to identify the principal factors determining its therapeutic efficacy . We found a good correlation between the level of the metabolite amrubicinol in the tumor and the in vivo efficacy . High metabolic activity of amrubicin to amrubicinol was detected in tumor tissue homogenates, especially in cell lines highly sensitive to amrubicin in vivo . In contrast to amrubicin, the administration of amrubicinol showed less tumor-selective toxicity in these human tumor xenograft models . These data indicate that the tumor-selective metabolism of amrubicin to amrubicinol resulted in a tumor-selective disposition of amrubicinol, leading to good efficacy in in vivo experimental therapeutic models.

Eur J Cancer, 1998 Jun, 34(7), 1063 - 9
An open-label, multicentre, randomised phase 2 study of recombinant human granulocyte colony-stimulating factor (filgrastim) as an adjunct to combination chemotherapy in paediatric patients with metastatic neuroblastoma; Michon JM et al.; Administration of combination chemotherapy to children with metastatic neuroblastoma induces profound myelosuppression resulting in chemotherapy treatment delays and febrile neutropenic episodes . The objective of this randomised multicentre study was to assess the incidence, duration and severity of neutropenia when filgrastim is added to induction chemotherapy administered to patients with metastatic neuroblastoma . In this study, 59 patients with metastatic neuroblastoma were randomised to receive chemotherapy (control group, n = 28) or chemotherapy plus filgrastim (filgrastim group, n = 31) . Chemotherapy consisted of four cycles of cyclophosphamide, vincristine and doxorubicin (CADO) alternating at 21-day intervals with cisplatin and etoposide (CDDP-VP16) . Filgrastim was administered subcutaneously at a dose of 5 micrograms/kg/day from day 7 for up to 14 days . The incidence of neutropenia (absolute neutrophil count {ANC} < 0.5 x 10(9)/l) in the filgrastim group was not reduced after the first CADO course . However, significant reductions were observed after courses 2, 3 and 4 . The duration of neutropenia and of intravenous antibiotic use were significantly reduced in the filgrastim group over the whole study period (9 days versus 26 days, P < 0.001; 12 days versus 20 days, P = 0.04, respectively) . However, the duration of hospitalisation and the incidence of febrile neutropenia were not significantly reduced . Compliance to treatment was good and the ability to administer chemotherapy without treatment delays was significantly better in the filgrastim group (P < 0.05) . Event-free survival was greater in the filgrastim than in the control group (2.4 years versus 1.3 years; P = 0.072) . Filgrastim is a beneficial adjunct to combination induction chemotherapy used in the treatment of metastatic neuroblastoma.

Ann R Coll Surg Engl, 1998 Sep, 80(5), 350 - 5
Current practice in primary total hip replacement: results from the National Hip Replacement Outcome Project; Best AJ et al.; As part of the National Study of Primary Hip Replacement Outcome, 402 consultant orthopaedic surgeons from three regions were contacted by postal questionnaire which covered all aspects of total hip replacement (THR) . There was a 70% response rate of which 71 did not perform hip surgery, a further 33 refused to take part, leaving 181 valid responses . Preoperative assessment clinics were used by 89% of surgeons, but anaesthetists and rehabilitation services were rarely involved at this stage . Of respondents, 99% used routine thromboprophylaxis, with 79% using a combination of mechanical and chemical methods . Of surgeons, 84% routinely used stockings, whereas 95.5% used chemical prophylaxis, 63% employed low molecular weight heparins . Theatre facilities were shared with other surgical specialties by 6% of surgeons and 18% regularly used body exhaust suits for THR . Antibiotic loaded cement was used by 69% of surgeons, the majority (65%) used a single brand of normal viscosity cement with 9% using reduced viscosity formulations . Modern cementing techniques were commonly used at least in part, 87% used a cement gun and 94% a cement restrictor for femoral cementing . On the acetabulum, 47% pressurised the cement . In all, 36 different femoral stems and 35 acetabular cups were in routine use, but the majority of surgeons (55%) used Charnley type prostheses . Of the surgeons, 57% performed only cemented THR, while 3% exclusively used uncemented THR . Of consultants, 21% followed up their patients to 5 years, the majority discharge patients within the first year . Of concern is a large proportion of surgeons using low molecular weight heparins despite a lack of evidence with regard to reducing fatal pulmonary embolism, and also the small number of surgeons using prostheses of unproven value . Third generation cementing techniques have yet to be fully adopted . The introduction of a national hip register could help to resolve some of these issues.

J Am Geriatr Soc, 1998 Dec, 46(12), 1538 - 44
Validation and application of the pneumonia prognosis index to nursing home residents with pneumonia; Mylotte JM et al.; OBJECTIVES: To evaluate the predictability of a pneumonia prognosis index in nursing home residents with pneumonia and to use the index to account for acute severity of pneumonia before comparing the short-term outcome of residents with pneumonia treated with intravenous antibiotic therapy in two different settings: an inpatient geriatrics unit and a nursing home DESIGN: A retrospective chart review of 158 episodes of nursing home-acquired pneumonia treated initially with intravenous antibiotics; 100 episodes were treated in an inpatient acute geriatrics service (AGS), and 58 were treated completely in a nursing home (Nursing Home group) SETTING: The AGS is a 20-bed unit within a 400-bed, public, university-affiliated hospital . The Nursing Home group consisted of residents of two nonproprietary nursing homes . PARTICIPANTS: Nursing home residents with radiographically proven pneumonia who had at least one of the following signs/symptoms: cough, fever, purulent sputum, respiratory rate > or = 25 per minute, localized auscultatory findings, or pleuritic pain . MEASUREMENTS: The pneumonia prognosis index was calculated for each resident at the time of diagnosis of pneumonia; the index has been validated as a predictor of hospital outcome in patients with community-acquired pneumonia and is also considered a measure of acute severity of pneumonia . Status (alive or dead) of each resident at 30 days after diagnosis was the major dependent variable RESULTS: Mean (+/-SD) duration of antibiotic therapy for the Nursing Home group (10.7+/-4.5 days) was not significantly different from that of the AGS group (9.6+/-3.4 days; P = .26) . The pneumonia prognosis index stratified the 158 episodes of pneumonia into low- and high-risk groups for 30-day mortality; the mortality rates in each risk strata were not significantly different from those reported in the original derivation and validation studies of the index . In addition, the distribution of episodes among the risk strata of the index was not significantly different for the two study groups, which was an indication that the two groups were similar in terms of acute severity of pneumonia . Thirty-day mortality was not significantly different between the two groups: AGS, 21% and Nursing Home, 24.1% (P = .66) . CONCLUSION: The pneumonia prognosis index seems to have the same capability for predicting the outcome in nursing home residents with pneumonia as in residents with community-acquired pneumonia . The index is also a measure of acute pneumonia severity . Nursing home residents with pneumonia, even those who are most acutely ill, can be treated successfully with intravenous therapy in the nursing home; their 30-day mortality was no different than that of those with the same acute severity of illness who were admitted to a hospital for treatment.

Am J Clin Nutr, 1998 Dec, 68(6 Suppl), 1369S - 1374S
Tyrosine kinase inhibitor effects on avian osteoclastic acid transport; Williams JP et al.; We found that tyrosine kinase pp60(c-src) coisolates with acid-transporting osteoclast membranes and hypothesized that this kinase regulates hydrochloric acid transport . We assayed the membrane acid transport and bone degradation effects of tyrosine kinase inhibitors in avian osteoclasts . Isoflavone, tyrphostin, and benzoquinonoid inhibitors were compared with inactive analogues to determine nonspecific effects . Acid-secreting membranes, isolated by nitrogen cavitation, were assayed as reconstituted vesicles by using acridine orange to indicate ATP-dependent hydrogen ion transport . The soy isoflavone genistein and the benzoquinonoid antibiotic herbimycin inhibited hydrochloric acid transport with 50% inhibition at approximately 10 and approximately 2 micromol/L, respectively; effects appeared in <2 min and were reversible . In membrane incubated with inhibitors, the herbimycin effect also inhibited Cl- transport by variable amounts, suggesting that this compound affects Cl- channel activity . However, genistein and tyrphostins did not produce chloride dependent effects . After 30 min with ATP, tyrphostin A47 irreversibly inhibited hydrochloric acid transport with 50% inhibition at approximately 10 micromol/L . Tyrphostin A25 and controls, tyrphostin A1 and daidzein (a genistein congener), were inactive despite preincubation . Osteoclastic bone resorption was more sensitive to the inhibitors over 3-5-d assays than was membrane acid transport, except for tyrphostins . Herbimycin and genistein inhibited bone resorption with half maximal effects at 0.5 and 10 micromol/L and complete inhibition at 3 d in 1 and 20 micromol/L, respectively . None of the tyrphostins, including A47, nor daidzein inhibited resorption to >20 micromol/L . We conclude that tyrosine kinase inhibition directly inhibits osteoclast membrane hydrochloric acid transport; differences among inhibitors may reflect chemical reactivity and permeability.

Aust N Z J Med, 1998 Oct, 28(5), 585 - 9
Seroprevalence of Helicobacter pylori in a longitudinal study of New Zealanders at ages 11 and 21; Fawcett JP et al.; BACKGROUND: Helicobacter pylori seroprevalence increases with age in adult life but spontaneous reversion may occur in childhood and adolescence . AIMS: To determine the seroprevalence of H . pylori in a longitudinal study of New Zealanders at ages 11 and 21 . METHODS: Serum from members of the Dunedin Multidisciplinary Health and Development Study (DMHDS) at age 11 (n = 561; 303 males, 258 females) and 21 (n = 785; 413 males, 372 females) was tested for H . pylori antibodies . A large proportion of those tested at age 11 was retested at age 21 (n = 465; 262 males, 203 females) . Serological status was examined in terms of gender, socioeconomic status (SES) and self-reported use of antibiotics . RESULTS: The seroprevalence of H . pylori decreased by 38% from 6.6% (37/561) at age 11 to 4.1% (32/785) at age 21 . Seroprevalence at age 11 was not associated with gender or SES . For those tested at both ages, the drop in seroprevalence from 6.7% to 4.1% was statistically significant (t = 2.57, p < 0.01, paired t-test) and was much greater in females (71%) than males (12%) . Of the 31 seropositive individuals at age 11, 17 (six males, 11 females) seroreverted and self-reported antibiotic use in the year preceeding age 21 was more common in females (eight/11) than males (zero/six) . Of the 434 seronegative individuals at age 11, only five (four males, one female) had seroconverted at age 21 . CONCLUSIONS: Seroprevalence in the DMHDS declined from age 11 to 21 predominantly in females . The decline involved a greater rate of seroreversion and lower rate of seroconversion in females than males.

Eur J Obstet Gynecol Reprod Biol, 1998 Oct, 80(2), 227 - 9
Genital tuberculosis in a HIV infected woman: a case report; Giannacopoulos KCh et al.; The incidence of HIV-associated tuberculosis is increasing worldwide, especially in developing countries . HIV infected patients rapidly develop clinically significant disease, respond poorly to complete treatment and present with extrapulmonary tuberculosis . Although a relative increase of genital tuberculosis would be expected, this has not been reported . Probably, tuberculous systemic disease is diagnosed earlier, before genital tuberculosis occur . The present study is a report of case of a young African female patient, who was admitted with symptoms of acute pelvic inflammatory disease due to genital tuberculosis and proved to be HIV infected . The patient was managed by intravenous antibiotic administration, but since no clinical or laboratory improvement was achieved, a laparotomy and salpingooophorectomy was performed . Histopathology revealed tuberculosis and after that the patient proved to be HIV infected . Further investigation did not reveal pulmonary or other extragenital manifestation of tuberculosis . The only manifestation of HIV infection and genital tuberculosis was the symptoms of an acute pelvic inflammatory disease, which is extremely rare.

Eur J Obstet Gynecol Reprod Biol, 1998 Oct, 80(2), 159 - 60
Delayed interval delivery and survival of the two fetuses after second trimester loss of one triplet; Matalliotakis IM et al.; Due to the implementation of assisted reproduction techniques, the incidence of multiple pregnancies associated with fetal and neonatal complications has significantly increased . A woman in the 24th week of a triplet pregnancy came to the hospital because of premature rupture of membranes of one amniotic sack and she had a miscarriage of one of the fetuses the same day . After confirmation of the viability of the two fetuses, she was kept under observation with antibiotic therapy only . The woman gave live birth to these remaining fetuses in her 32nd week of pregnancy . The outcome of this case demonstrates that watchful expectancy may be a feasible alternative to invasive intervention . The aim of this report is to add to the currently very limited literature of an expectant (conservative) policy with regard to pregnancy outcome after the early loss of a fetus from a multiple pregnancy.

Rev Chir Orthop Reparatrice Appar Mot, 1998 Oct, 84(6), 563 - 6
{Intra-thoracic costal sites of osteogenic exostoses in the child}; Cottalorda J et al.; PURPOSE OF THE STUDY: The authors report 2 cases of internal costal exostosis in children . OBSERVATIONS: Case 1: A 15-year-old boy with hereditary multiple exostosis presented for chest pain . Radiograph and CT scan showed an internal rib exostosis . It was removed by thoracotomy . Eighteen months later, the child was painfree . Case 2: An-11-year old boy presented with fever and a headache . A chest radiograph showed an image of pulmonary opacity interpreted as a pneumonia . The child was admitted for antibiotic therapy . Two months later, X-ray lesion persisted and a CT-scan was obtained . It showed a solitary costal internal exostosis which was removed by thoracotomy . At 12 months follow-up, he was asymptomatic . DISCUSSION: Internal costal exostosis can induce some complications such as hemothorax, diaphragmatic or pericardic wounds . In case of symptomatic exostosis, the authors recommend a surgical removal to avoid severe complications . If the exostosis is asymptomatic, abstention can be recommend . As a matter of fact, hemothorax, for instance, can occur even due to a round and smooth exostosis without any history of trauma.

J Vasc Surg, 1998 Dec, 28(6), 1082 - 93
Pharmacologic suppression of experimental abdominal aortic aneurysms: acomparison of doxycycline and four chemically modified tetracyclines; Curci JA et al.; BACKGROUND: Matrix metalloproteinases (MMPs) likely contribute to the degradation of medial elastin in abdominal aortic aneurysms (AAAs), and tetracycline antibiotics exhibit MMP-inhibiting properties . The purpose of this study was to compare the effects of doxycycline and several non-antibiotic chemically modified tetracyclines (CMTs) in a rat model of elastase-induced AAA . METHODS: Fifty-two male Wistar rats underwent intraluminal perfusion of the abdominal aorta with porcine pancreatic elastase . The rats then were treated for 7 days with subcutaneous injections of saline solution, different doses of doxycycline, or 1 of 4 different CMTs . The aortic diameters were measured with microcalipers, and the fixed tissues were examined by means of light microscopy . Gelatin zymography was used to assess the MMP activity in the aortic tissue extracts . RESULTS: The mean aortic diameter in the control group increased by 126% +/- 14% on day 7 (from 1.57 +/- 0.04 mm to 3.54 +/- 0.27 mm; P <.05), and 5 of 6 animals (83%) had AAAs . Doxycycline appeared to inhibit aortic dilatation in a dose-dependent manner, and AAAs did not develop in any animals . Half-maximal effects were observed at a dose of approximately 6 mg/kg/day, and maximal effects were noted at greater than 30 mg/kg/day . No AAAs were observed in the animals that were treated with CMTs at 15 mg/kg/day . Each of the following CMTs exhibited an efficacy that was similar to that of doxycycline (percent inhibition of aortic dilatation vs control; all P <.05): CMT-3 (47.6%), CMT-4 (38.9%), CMT-7 (47.6%), CMT-8 (54.0%), and doxycycline (51.6%) . Tissues from saline solution-treated controls exhibited a transmural inflammatory response and marked destruction of the medial elastic lamellae . Tetracycline derivatives limited the disruption of medial elastin without appearing to alter either the inflammatory response or the rat aortic wall production of metallogelatinases . CONCLUSION: Tetracycline derivatives suppress the development of AAAs after elastase-induced aortic injury in the rat . The aneurysm-suppressing effects of doxycycline appear to be dose-dependent and distinct from its antibiotic activities, and they coincide with the structural preservation of medial elastin fibers . Further studies are needed to explore the potential of MMP-inhibiting tetracyclines as a novel pharmacologic strategy for the suppression of aortic aneurysms.

J Indian Med Assoc, 1998 Apr, 96(4), 104 - 5, 108
Experience in running a Diarrhoeal Training cum Treatment Unit (DTTU) in a state teaching hospital in Calcutta; Sengupta B et al.; The performance of the Diarrhoeal Training cum Treatment Unit (DTTU) of NRS Medical College and Hospital, Calcutta, in a 2-year period was evaluated by record analysis . The study revealed that 73.6% cases out of a total 4349 could be successfully managed at the oral rehydration therapy (ORT) area and only 16.5% cases required indoor admission . Rest of the cases (9.9%) with "no dehydration" were sent home with advice . There were 84.7% cases out 3919 dehydration cases who could be successfully treated by ORT and only 15.3% required intravenous (i.v.) therapy . A definite decline was also evident in the proportion of diarrhoea cases requiring antibiotic therapy (13.5% in 1991 to 6.8% in 1992) . The case fatality rate due to diarrhoea was 1.7% in 1992 . Had all cases of diarrhoea with dehydration being admitted and treated with i.v . fluids and antibiotics, the estimated cost would have been Rs 14.2 lakhs, which with ORT, actually cost Rs 2.4 lakhs . Thus estimated total cost reduction was to the extent of Rs 11.8 lakhs in a 2-year periodPIP: The Diarrheal Training with Treatment Unit (DTTU) was established in the Department of Pediatrics, NRS Medical College and Hospital, in Calcutta, India, in 1990, to promote use of oral rehydration therapy (ORT) in diarrhea in children 0-5 years of age . To evaluate the success of this effort, a retrospective review was conducted of the 4349 child diarrhea cases presenting to DTTU in 1991-92 . 3919 children (90.1%) were dehydrated at admission; the nondehydrated cases received counseling only and were discharged . 3202 children (73.6%) with diarrhea-related dehydration were successfully treated with ORT; intravenous fluids were administered in 598 (15.3%) of these cases . 717 children (16.5%) required hospital admission; 83.4% of these children received intravenous fluids . The proportion of diarrhea cases requiring antibiotics decreased from 13.5% in 1991 to 6.8% in 1992 . Case fatality was 1.8% in 1991 and 1.7% in 1992 . The actual cost of treatment was Rs . 1,50,048 in 1991 and Rs . 91,178 in 1992 . These amounts represent savings of Rs . 6,00,912 and 5,77,867, respectively, over what would have been the costs if all cases had been treated on an inpatient basis with intravenous fluids and antibiotics . These findings confirm the effectiveness of DTTU's strategy of ORT management of children with diarrheal dehydration combined with proper training and motivation of both mothers and health workers .

Am J Physiol, 1998 Dec, 275(6 Pt 1), C1573 - 9
Endogenous expression of the renal high-affinity H+-peptide cotransporter in LLC-PK1 cells; Wenzel U et al.; The reabsorption of filtered di- and tripeptides as well as certain peptide mimetics from the tubular lumen into renal epithelial cells is mediated by an H+-coupled high-affinity transport process . Here we demonstrate for the first time H+-coupled uptake of dipeptides into the renal proximal tubule cell line LLC-PK1 . Transport was assessed 1) by uptake studies using the radiolabeled dipeptide D-{3H}Phe-L-Ala, 2) by cellular accumulation of the fluorescent dipeptide D-Ala-Lys-AMCA, and 3) by measurement of intracellular pH (pHi) changes as a consequence of H+-coupled dipeptide transport . Uptake of D-Phe-L-Ala increased linearly over 11 days postconfluency and showed all the characteristics of the kidney cortex high-affinity peptide transporter, e.g., a pH optimum for transport of D-Phe-L-Ala of 6.0, an apparent Km value for influx of 25.8 +/- 3 . 6 microM, and affinities of differently charged dipeptides or the beta-lactam antibiotic cefadroxil to the binding site in the range of 20-80 microM . pHi measurements established the peptide transporter to induce pronounced intracellular acidification in LLC-PK1 cells and confirm its postulated role as a cellular acid loader.

Biochemistry, 1998 Nov 10, 37(45), 15825 - 34
Evidence for differential binding of isoniazid by Mycobacterium tuberculosis KatG and the isoniazid-resistant mutant KatG(S315T); Wengenack NL et al.; Isoniazid is a mainstay of antibiotic therapy for the treatment of tuberculosis, but its molecular mechanism of action is unclear . Previous investigators have hypothesized that isoniazid is a prodrug that requires in vivo activation by KatG, the catalase-peroxidase of Mycobacterium tuberculosis, and that resistance to isoniazid strongly correlates with deletions or point mutations in KatG . One such mutation, KatG(S315T), is found in approximately 50% of clinical isolates exhibiting isoniazid resistance . In this work, 1H nuclear magnetic resonance T1 relaxation measurements indicate that KatG and KatG(S315T) each bind isoniazid at a position approximately 12 A from the active site heme iron . Electron paramagnetic resonance spectroscopy revealed heterogeneous populations of high-spin ferric heme in both wild-type KatG and KatG(S315T) with the ratios of each species differing between the two enzymes . Small changes in the proportions of these high-spin species upon addition of isoniazid support the finding that isoniazid binds near the heme periphery of both enzymes . Titration of wild-type KatG with isoniazid resulted in the appearance of a "type I" substrate-induced difference spectrum analogous to those seen upon substrate binding to the cytochromes P450 . The difference spectrum may result from an isoniazid-induced change in a portion of the KatG heme iron from 6- to 5-coordinate . Titration of KatG(S315T) with isoniazid failed to produce a measurable difference spectrum indicating an altered active site configuration . These results suggest that KatG(S315T) confers resistance to isoniazid through subtle changes in the isoniazid binding site.

Laryngorhinootologie, 1998 Oct, 77(10), 551 - 6
{Treatment of deep neck infections}; Constantinidis J et al.; BACKGROUND: The incidence of deep neck space infections has been significantly reduced by modern antibiotic therapy . These infections are relatively rare and yet the life-threatening complications merit special consideration by head and neck surgeons . PATIENTS: Seven cases of deep neck space infections as a consequence of purulent pharyngitis (3), peritonsillar abscess (2), retropharyngeal (1), and odontogenic (1) abscess are presented . Despite antibiotic therapy according to antibiogram all patients showed an increase in complaints with persisting febrile temperatures and rising inflammation parameters . Surgical intervention became necessary . In two cases the infection spread into the mediastinum . RESULTS: All patients were completely cured by means of early surgical intervention including extensive drainage of the primary focus, deep neck spaces and mediastinum, accompanied by intravenous antibiotic therapy . Tracheotomy was performed on one patient with increasing dyspnea . All patients had an uneventful recovery without major postoperative complications . CONCLUSIONS: The clinical course of the disease must be observed particularly closely even after starting antibiotic therapy and identification of the infectious focus . Antibiotic therapy may in some cases cover clinical symptoms . However, in the presence of abscess formation or necrotizing infections, antibiotics can prove to be ineffective . The optimum time for surgery is difficult to determine . Complete drainage of the neck spaces down to the mediastinum is a safe procedure to save the patients' life . This shortens the duration of the disease and prevents complications . The most common problems in the management of deep neck space infections are discussed.

Minerva Ginecol, 1998 Sep, 50(9), 391 - 5
{Modifications to the technic of cesarean section after Stark}; Corosu R et al.; BACKGROUND: As the operating births (caesarean section) increase, many surgical equipes have been compelled to revise operating techniques in order to reduce fetus extraction times and the whole expense of operation without renouncing, at the same time to beauty advantages . With Stark technique, that we have modified, we have obtained all these aims, improving at the same time patients' postoperative course as well succeeding to extract the fetus in about five minutes . In the '70 Cohen explained the utility of a transiliac incision allowing the access to abdominal cavity with rectus muscles unsticking in an area in which these muscles should present a less adhesiveness . METHODS: Since 1988 Stark has used Cohen's technique changing however uterus closing times, peritoneal membranes and abdominal walls . Our technique is different since we performed the incision according to Pfannestiel . RESULTS: The times are considerably reduced to 4.8 minutes for fetus extraction and in postoperative time the complications are drastically reduced too (infection, pain, hematoma, adhesions) . CONCLUSIONS: Therefore we can surely say that this kind of technique can be used with success in all gynaecological surgery, in extrauterine pregnancies and adnexial tumefactions (not malignant) . Personal opinion is that spinal anesthesia is the best analgesic technique.

FEMS Microbiol Lett, 1998 Oct 1, 167(1), 95 - 100
Enhancement of mycinamicin production by dotriacolide in Micromonospora griseorubida; Takenaka S et al.; Production of macrolide antibiotic mycinamicin was greatly increased by addition of sulfate ion into the culture medium of Micromonospora griseorubida . An O-sulfate ester compound, also produced by the strain, was shown to be dotriacolide . In an M . griseorubida dotriacolide non-producing strain, the production level of mycinamicin remained low, but increased to the level of dotriacolide producing strain by the addition of dotriacolide . Dotriacolide enhanced mycinamicin production in M . griseorubida by the formation of micelles with mycinamicin . As a result, dotriacolide played a critical role in mycinamicin production in M . griseorubida.

Semin Pediatr Surg, 1998 Nov, 7(4), 225 - 7
Current status of laparoscopic appendectomy in children; Blakely ML et al.; Appendectomy is the most common surgical emergency in children . Laparoscopic appendectomy (LA), first performed by Semm in 1983, has increased in popularity for both uncomplicated and ruptured appendicitis . The authors perform early laparoscopic appendectomy for acute uncomplicated appendicitis, but use aggressive antibiotic therapy for obvious ruptured appendicitis . Patients presenting with accessible abscesses have drainage using image guidance . Antibiotic therapy is continued at home until the fever has resolved and the white blood cell and differential counts have normalized . An interval appendectomy is performed 2 to 3 months later . Children with ruptured appendicitis for whom aggressive medical management had failed usually had a persistent pattern of small bowel obstruction noted 72 hours after initiation of treatment . The authors' preferred technique for laparoscopic appendectomy employs linear stapling of the mesoappendix and appendix . LA patients had a shorter hospital stay and a lower wound infection rate . The operating times for open and laparoscopic appendectomy were similar.

J Orthop Trauma, 1998 Nov-Dec, 12(8), 569 - 71
Office removal of tibial external fixators: an evaluation of cost savings and patient satisfaction; DiCicco JD et al.; OBJECTIVES: To evaluate the efficacy and patient satisfaction of office removal of tibial external fixators and to compare the cost of this procedure with the cost of removal of fixators in the operating room . DESIGN: A visual analog scale (VAS) and a questionnaire were answered by all patients after office external fixator removal . The treatment, complications, and costs were compared with those of patients having external fixator removal in the operating suite . SETTING: An urban orthopaedic trauma office with a Level I trauma center . PARTICIPANTS: Two similar groups of patients; thirty fixators removed in the office and twenty-nine fixators removed in the operating room . INTERVENTION: Office or operating room removal of tibial external fixators and application of a sterile dressing . A visual analog scale was answered by those patients who had office removal . MAIN OUTCOME MEASUREMENTS: Patient satisfaction and pain rating (VAS) with office removal of external fixators . Comparison of costs, infections, time in fixator, and surgical interventions between the office and operating room groups . RESULTS: Group I had thirty fixators (twenty-nine half-pin fixators) removed in the office . Group II had twenty-nine fixators removed in the operating room . Duration of time in the frame was not statistically different . Antibiotic usage during the fixator treatment period was 69 percent in both groups . On the visual analog scale, twenty-four members (80 percent) of the office fixator removal group rated the pain during removal as less than 25 percent of maximal, including nine (30 percent) who rated the removal as causing no pain . Cost analysis revealed an average cost of $248 for the office group versus $2,160 for the operating room group (p < 0.001) . CONCLUSIONS: Due to the cost savings and patient satisfaction, without compromising clinical care, the office is our preferred location for tibial half-pin external fixator removal.

Childs Nerv Syst, 1998 Oct, 14(10), 606 - 9
Nonoperative treatment of cerebellar abscesses . A case report and review of the literature; Spinnato S et al.; A case of a 5-year-old child presenting with a cerebellar abscess occupying the ponto-cerebellar region, who was treated with antibiotic therapy alone, is reported . Symptomatology, radiological findings, and antibiotic regimens are presented, and the literature is reviewed from the viewpoint of therapeutic management.

Appl Environ Microbiol, 1998 Dec, 64(12), 5061 - 3
Transfer of streptomycin biosynthesis gene clusters within streptomycetes isolated from soil; Egan S et al.; Streptomyces strains isolated from soil were found to possess various numbers of genes from the streptomycin biosynthesis cluster . The strains missing genes from the cluster also lacked the ability to produce streptomycin . Two of the isolates which contain only part of the cluster are apparently recipients of a gene transfer event . The implications for the role of gene transfer in antibiotic evolution are discussed.

J Gastroenterol Hepatol, 1998 Oct, 13(10), 1044 - 9
Metronidazole- and clarithromycin-resistant Helicobacter pylori in dyspeptic patients in western Sydney as determined by testing multiple isolates from different gastric sites; Xia HH et al.; It is unknown whether antibiotic susceptibility testing of antral isolates alone is representative of Helicobacter pylori susceptibility . We aimed to determine: (i) the prevalence of metronidazole- and clarithromycin-resistant strains in infected dyspeptic patients; and (ii) whether there is consistency in the susceptibility to metronidazole and clarithromycin among isolates cultured from different gastric sites . Antral, body and fundus biopsies were taken from 242 consecutive patients and cultured on blood agar under micro-aerophilic conditions for 5-7 days . Isolates from 66 patients (13 had one, 15 had two and 38 had three isolates) were tested for susceptibility to metronidazole and clarithromycin using previously validated disc diffusion tests . Of the 66 patients, 42 (64%) had strains resistant to metronidazole while four (6.1%) had clarithromycin-resistant strains . The prevalence of metronidazole resistance was not significantly different between men and women (65% vs 60%) or across different age groups . In five (9.4%) of the 53 patients with multiple isolates, discrepant results for metronidazole susceptibility were observed: susceptible antral and body isolates but resistant fundus isolates in two cases and susceptible antral isolates but resistant body and fundus isolates in the others . Clarithromycin susceptibilities were consistent among the isolates cultured from different gastric sites in all patients . It is concluded that metronidazole-resistant strains of H . pylori are common while clarithromycin-resistant strains are rare . Metronidazole susceptibility testing of antral isolates does not appear to be representative of isolates from the body and fundus in a subset of patients.

FEMS Microbiol Lett, 1998 Nov 15, 168(2), 221 - 6
Actinorhodin and undecylprodigiosin production in wild-type and relA mutant strains of Streptomyces coelicolor A3(2) grown in continuous culture; Kang SG et al.; The effects of growth rate and nutrient feed rate on the production of actinorhodin (Act) and undecylprodigiosin (Red) were determined in Streptomyces coelicolor A3(2) and in a congenic relA null-mutant known to be deficient in ppGpp synthesis and antibiotic production under conditions of nitrogen limitation . In the relA+ strain, Act production was inversely related to specific growth rate in continuous cultures limited by glucose, ammonium, or phosphate, while Red biosynthesis was optimal at 0.05 h-1 regardless of the specific nutrient limitation . Production of Act and Red in the relA mutant was lower than that of the parental strain, particularly under conditions of glucose- and ammonium-limitation, indicating an important and general role for ppGpp in determining the onset of the antibiotic biosynthesis under conditions of nutrient limitation . At constant growth rate, but with varying nutrient feed rates, the specific rate of Act production was adversely influenced by increasing levels of glucose, ammonium, and phosphate, with phosphate having the greatest inhibitory effect . Under the same conditions, the specific rate of Red production was stimulated by increasing glucose levels, but markedly decreased by increased levels of phosphate.

J Indian Med Assoc, 1998 Jun, 96(6), 181 - 2
A comparative study of various surgical treatments of hepatic hydatidosis with special reference to capitonnage; Joshi CP et al.; Nine patients treated by different modalities of surgical treatment were evaluated and the results were compared in terms of complications and total number of hospitalisation days . Most common complaint was pain abdomen and the commonest finding was an abdominal lump . After initial treatment of the cavity with a scolicidal agent the cyst was deroofed and the remaining cyst was dealt with in 3 different ways: (a) Three patients underwent simple drainage . (b) Marsupialisation was done in 3 cases . (c) Remaining 3 patients had capitonnage offered to them as the form of treatment . Complication rates in group (a) and (b) were 33% and 67% respectively and the average hospital stay was 13 and 20 days respectively while group (c) had no complication and the average hospital stay was 8.3 days.

Clin Radiol, 1998 Nov, 53(11), 816 - 9
Frequency of abdominal CT findings in AIDS patients with M . avium complex bacteraemia; Pantongrag-Brown L et al.; BACKGROUND: Use of blood culture studies for early diagnosis of Mycobacterium avium complex (MAC) infection has become important due to the recent development of effective antibiotic therapy for this condition . This study assessed the abdominal computed tomography (CT) findings in patients with AIDS who presented with bacteraemic MAC infection . METHODS: A retrospective analysis of abdominal CT scans was performed in 24 patients who presented with MAC-positive blood culture . CT images were reviewed specifically to evaluate for lymph node enlargement and attenuation, hepatomegaly, splenomegaly, bowel wall abnormality and for any other pathological changes . Comparison was made to prior reports of the CT findings in this disease process . RESULT: Enlarged intra-abdominal mesenteric and/or retroperitoneal lymph nodes were found in 10 patients (42%) . These nodes were characterized by homogeneous, soft-tissue attenuation in eight of the 10 patients . Hepatomegaly, splenomegaly and small bowel wall thickening were noted in 12 (50%), 11 (46%) and four (14%) patients, respectively . CT findings were evaluated as normal in six (25%) patients . CONCLUSIONS: Enlarged mesenteric and/or retroperitoneal lymph nodes in AIDS patients with bacteraemic MAC were observed much less frequently on CT than previously reported in AIDS patient populations . Normal abdominal CT findings do not exclude this diagnosis and may reflect a trend towards earlier detection of MAC disease.

Chirurg, 1998 Oct, 69(10), 1093 - 100; discussion 1100
{Comparative study of the cost-effectiveness of initial therapy with imipenem/cilastatin in secondary peritonitis}; Rodloff AC et al.; The total costs of the hospital treatment of patients with secondary peritonitis were investigated with a prospective, randomized, multicenter study . Moreover, the cost-effectiveness of an initial therapy with Imipenem/Cilastatin was compared to selected alternative antibiotic regimens . Altogether 154 patients (77 Imipenem/Cilastatin group, 77 alternative group) that displayed Mannheim Peritonitis Scores between 16 and 26 (average 20.8) were analyzed . The average total cost of treatment was DM 11,140 per patient (range DM 2794-45,526) . Patients receiving an initial therapy with Imipenem/Cilastatin incurred average costs of DM 10,455, while patients with alternative regimens caused average costs of DM 11,826 . The difference between the two treatment groups was statistically significant (P = 0.037).

Arch Mal Coeur Vaiss, 1998 Oct, 91(10), 1277 - 81
{Bartonella endocarditis on native valves . Apropos of 2 cases}; Berdague P et al.; The authors report two cases of Bartonella endocarditis in native valves . The first case was a 15 year old North African Girl who lived in poor social conditions and was admitted to hospital with pyrexia and congestive heart failure . Investigations revealed massive mitral regurgitation due to ruptured chordae tendinae, vegetations on the pulmonary valve with severe pulmonary hypertension due to persistent ductus arteriosus . After antibiotic therapy, the patient underwent surgery for mitral valve replacement, pulmonary valvuloplasty and closure of the patent ductus arteriosus . The second case was a 39 year old man with no fixed abode with a history of alcoholism who presented with a recurrent ischaemic stroke in a context of infection with a murmur of aortic regurgitation . Echocardiography showed a vegetation on the aortic valve with grade III/IV regurgitation requiring aortic valve replacement with a homograft after antibiotic therapy . The aetiological diagnosis was made a posteriori by the finding of high antibody titres and specific genetic amplification of Bartonella . In patients with negative blood cultures, Bartonella infection should be looked for systematically especially in those living under poor social conditions . The practical diagnostic investigation of endocarditis with negative blood cultures is reviewed.

J Thorac Cardiovasc Surg, 1998 Dec, 116(6), 943 - 8
Pleural space irrigation and modified Clagett procedure for the treatment of early postpneumonectomy empyema; Gharagozloo F et al.; OBJECTIVE: The incidence of postpneumonectomy empyema is 5% to 10% . Approximately half of postpneumonectomy empyemas occur within 4 weeks of pneumonectomy . A bronchopleural fistula is found in more than 80% of the patients . The classic treatment of postpneumonectomy empyema includes parenteral antibiotics, drainage of the pleural space, removal of necrotic tissue, and open pleural packing for many weeks followed by obliteration of the empyema space with antibiotic fluid or muscle . This approach results in prolonged hospitalization, repeated operations, and significant morbidity . As a possible means of decreasing morbidity with the classic treatment of postpneumonectomy empyema, we studied the use of pleural space irrigation in these patients . METHOD: In a 5-year period, we treated 22 patients with early postpneumonectomy empyema . All patients had a bronchopleural fistula . All patients underwent emergency drainage of the pleural space followed by thoracotomy, debridement of necrotic tissue, closure of the bronchial stump with absorbable monofilament suture, and pleural space irrigation . After a negative Gram stain from the pleural fluid, the pleural space was filled with 2 L of debridement antibiotic solution (DAB solution) (gentamicin 80 mg/L, neomycin 500 mg/L, and polymyxin B 100 mg/L), and the irrigation and drainage catheters were removed . RESULTS: Twenty patients had negative Gram stains on day 9, and 2 patients had a negative Gram stain on day 16 . The mean duration of hospitalization was 12.9 +/- 3 . 4 days . There was no recurrence of empyema or a bronchopleural fistula . CONCLUSIONS: Pleural space irrigation followed by obliteration of the pleural space with an antibiotic solution required one surgical procedure and resulted in significantly shorter hospitalization and decreased morbidity in patients with early postpneumonectomy empyema.

Pediatrics, 1998 Dec, 102(6), 1432 - 6
Characterization of the triage process in neonatal intensive care; Zupancic JA et al.; OBJECTIVE: Despite intense interest in allocation of resources to neonatal intensive care, no description exists of resource use by the large numbers of newborns admitted for triage, the process of short-term evaluation and management of infants after delivery . This study characterized the triage phase of neonatal care with respect to infant demographics, risk factors for illness, and the course of the hospital admission . We hypothesized that triage infants were responsible for a significant fraction of total intensive care resource utilization, and that patterns of use were predictable . DESIGN: Cross-sectional cost analysis of prospectively collected data . PARTICIPANTS: Data were collected prospectively on 2486 inborn infants admitted to two neonatal intensive care units (NICUs) for <24 hours and subsequently discharged to routine care . Over the 11-month study period, these two hospitals delivered 15 097 live births and admitted a further 1837 infants for nontriage NICU care . INTERVENTIONS: On a 50% random subsample, we calculated severity of illness using the Score for Neonatal Acute Physiology (SNAP) and applied a NICU resource checklist . Daily NICU workload was estimated according to the number and labor intensity of NICU admissions using Medicus and SNAP . Charges were obtained from patient-level item charge records and converted to costs using Medicare ratios of costs to charges . Length of stay (LOS) and costs for triage were correlated with diagnoses, perinatal descriptors, severity of illness, and markers of concurrent NICU workload using stepwise regression . RESULTS: Mean birth weight for triage infants was 3367 g (standard deviation, 600 g) and mean gestational age 39.1 weeks (standard deviation, 1.8 weeks) . The predominant reasons for evaluation were exclusion of sepsis (34%), birth complications including meconium aspiration, perinatal depression and trauma (24%), and transitional respiratory distress (23%) . Severity illness, as measured by SNAP, was minimal, with 70% having scores of 0, indicating no derangement . Only 6% experienced depressed 5-minute Apgar scores (<7), and 80% required no delivery room resuscitation . The most frequent forms of resource use were antibiotic administration (34%), placement of a peripheral intravenous line (40%), cardiac monitoring (53%) and external warming (26%) . Median LOS was 102 minutes, corresponding over the study period to 2% of total NICU hours but 7% of NICU days charged . Median cost was $870, with aggregate costs accounting for a total of 9.5% of total NICU costs . In the multivariate model, LOS was increased by respiratory diagnosis or hypoglycemia, severity of illness, lower gestational age, the need for intravenous placement, daytime shift, hospital, and lower acuity of concurrent NICU admissions (R2 = 0.24) . CONCLUSIONS: Neonatal triage is a low-acuity but time-intensive process that contributes significantly to total resource use by newborns because of the large numbers of infants involved . Both LOS and costs are affected not only by infant medical characteristics but also by nonmedical markers of unit structure, which may be amenable to change . This source of resource consumption should be recognized in future assessments of costs associated with neonatal intensive care.

Genetics, 1998 Dec, 150(4), 1459 - 66
Transfer of a supernumerary chromosome between vegetatively incompatible biotypes of the fungus Colletotrichum gloeosporioides; He C et al.; Two biotypes (A and B) of Colletotrichum gloeosporioides infect the tropical legumes Stylosanthes spp . in Australia . These biotypes are asexual and vegetatively incompatible . However, field isolates of biotype B carrying a supernumerary 2-Mb chromosome, thought to originate from biotype A, have been reported previously . We tested the hypothesis that the 2-Mb chromosome could be transferred from biotype A to biotype B under laboratory conditions . Selectable marker genes conferring resistance to hygromycin and phleomycin were introduced into isolates of biotypes A and B, respectively . A transformant of biotype A, with the hygromycin resistance gene integrated on the 2-Mb chromosome, was cocultivated with phleomycin-resistant transformants of biotype B . Double antibiotic-resistant colonies were obtained from conidia of these mixed cultures at a frequency of approximately 10(-7) . Molecular analysis using RFLPs, RAPDs, and electrophoretic karyotypes showed that these colonies contained the 2-Mb chromosome in a biotype B genetic background . In contrast, no double antibiotic colonies developed from conidia obtained from mixed cultures of phleomycin-resistant transformants of biotype B with biotype A transformants carrying the hygromycin resistance gene integrated in chromosomes >2 Mb in size . The results demonstrated that the 2-Mb chromosome was selectively transferred from biotype A to biotype B . The horizontal transfer of specific chromosomes across vegetative incompatibility barriers may explain the origin of supernumerary chromosomes in fungi.

Endothelium, 1998, 6(1), 23 - 32
Characterization of G protein-coupled receptors expressed by ECV304 human endothelial cells; Howl J et al.; The aims of this study were to characterize G protein-coupled receptors endogenously expressed by ECV304 human endothelial cells, and to determine the utility of this transformed cell line as a vehicle for the expression of cloned receptors . Cellular responses to a broad range of agonists were determined by measuring changes in the intracellular content of second messengers (inositol phosphates and cyclic adenosine monophosphate) . These studies identified H1 histamine receptors, P2U-purinoceptors and lysophosphatidic acid receptors which are functionally coupled to phosphoinositidase C . G protein-coupled receptors which bind adenosine (A2 receptor), calcitonin, and adrenaline (beta-adrenoceptor), and markedly stimulate adenylyl cyclase, are also endogenously expressed by ECV304 . Agonists which did not stimulate ECV304 cells are: angiotensin II, angiotensin1-7, bombesin, bradykinin, desArg9-bradykinin, carbachol, endothelin-1, neurotensin, serotonin, substance K, substance P, thrombin and vasopressin . The rat Via vasopressin receptor was expressed by lipofection in two antibiotic-resistant clonal lines and expression confirmed by measuring agonist-induced changes in inostol phosphate production . We conclude that the ECV304 cell line is a suitable in vitro system to study the signal transduction pathways of some endogenous G protein-coupled receptors known to modulate endothelial function in vivo . ECV304 is also appropriate for the expression and functional characterization of cloned receptor proteins.

J Clin Pharm Ther, 1998 Jun, 23(3), 203 - 11
A multidisciplinary approach to hospital-based drug cost containment; Pacey S et al.; OBJECTIVE: To develop and implement a range of strategies to control rising drug expenditure in a teaching hospital . METHOD: A multidisciplinary team was established to survey drug use and to identify areas where drug wastage was occurring . Once target areas were identified, strategies were developed and implemented and drug expenditure monitored prospectively . RESULTS: Communication and education about optimum drug use, efficient drug handling and therapeutic drug substitution were identified as areas for action . Antibiotic prescribing, outpatient prescribing and expenditure on new drugs were identified as target areas for cost savings . Compared to previous years, the rate of increase in drug expenditure on antibiotics was reduced by over 5000 pound sterling, from a baseline of 552 278 pound sterling over the study period compared to an increase of 65 984 pound sterling for the previous corresponding period . CONCLUSION: We believe that despite the short-coming of the study, which adopted an open design without a control group, it demonstrates that effective cost-containment strategies can be implemented by multidisciplinary teams if they are given sufficient support by senior management.

Am J Epidemiol, 1998 Nov 15, 148(10), 1018 - 26
Estimation of the incidence of Lyme disease; Campbell GL et al.; The incidence of Lyme disease in most endemic areas is unknown but will be an important factor in determining the cost-effectiveness of Lyme disease vaccines in those areas . The authors developed a deterministic model with nine components to estimate the frequency of Ixodes scapularis tick bites and the resulting incidence of Lyme disease in residents of endemic areas . For each component, best point estimates and plausible ranges of values were based on the published literature, unpublished data, expert opinion, or a combination of the above . By using the mean, crude, annual total of 3,827 Lyme disease cases reported from the endemic county of Westchester, New York, in 1991-1994, a mean of 178,889 I . scapularis bites (20.4 per 100 person-years) and a mean of 10,632 incident Lyme disease cases (1.2 per 100 person-years) were estimated to have occurred per year . Results of a sensitivity analysis that used two different methods suggested that this deterministic model is reasonably robust . In conclusion, according to this model, the incidence of Lyme disease in Westchester County is several-fold higher than suggested by the current passive reporting system.

Br J Haematol, 1998 Nov, 103(2), 422 - 4
Analysis of risk factors for over-anticoagulation in patients receiving long-term warfarin; Panneerselvam S et al.; A cohort of patients with an INR >7.0 were identified prospectively and compared with a group of patients with stable anticoagulant control . During the study 15,100 INR measurements were recorded and 31 (0.2%) were >7.0 . Odds ratios of patient characteristics were calculated as an estimate of relative risk for the development of a high INR . The highest risk factor was a target INR of 3.5 (OR 7.3, 95% CI 2.6-20.2) . The second highest risk factor was antibiotic therapy in the 4 weeks preceding the high INR (OR 6.2, 95% CI 1.4-27.7) . Bleeding was reported more frequently in the high INR group (OR 5.4, 95% CI 2.1-13.9) . Five major bleeds occurred in this group compared to none in the stable group . This analysis identifies risk factors for over-anticoagulation and hence when to intensify monitoring and when to consider pre-emptive warfarin dose reductions.

Am J Emerg Med, 1998 Nov, 16(7), 714 - 6
Subclavian mycotic aneurysm presenting as mediastinal abscess; Lee TY et al.; A 60-year-old man was admitted to a hospital for evaluation of intermittent fever, dysphagia, hoarseness, and general chest discomfort . Great vessel mycotic aneurysm was suspected when antibiotic trials failed and chest X-ray showed paraaortic mass with pleural effusion mimicking mediastinitis . Although the correct diagnosis of mycotic aneurysm of innominate artery was made thereafter and vigorous treatment was initiated immediately, this patient succumbed to overwhelming sepsis, probably due to a 2-week delay in another hospital . This case is reported to remind readers of the possibility of this unusual location of mycotic aneurysm . A high index of suspicion should be maintained to make an earlier diagnosis and obtain better prognosis . Computed tomography and 3D magnetic resonance angiography also significantly improve the diagnosis when mycotic aneurysm location is unusual and presentation is equivocal.

In Vivo, 1998 Sep-Oct, 12(5), 485 - 8
Evaluation of inhibitory effects of doxorubicin on collagenase using a bovine placentome model; Fecteau KA et al.; The chemotherapeutic antibiotic doxorubicin (Adriamycin) was reported to inhibit bacterial collagenase activity when tested on both a synthetic substrate and intact collagen . Our objective was to establish whether doxorubicin would inhibit bacterial collagenase activity on a bovine placentome model . Metabolically active, isolated bovine placentomes were infused, via umbilical vessels, with a mixture of bacterial collagenase and doxorubicin . Six experimental groups were used . Group (1) comprised of saline controls; (2), collagenase at 1,200 U/cc; (3, 4, and 5), collagenase (1,200 U/cc) plus doxorubicin at 0.04 mg/cc, 0.02 mg/cc, 0.01 mg/cc, respectively; (6), doxorubicin at 0.02 mg/cc . After 5 hrs of incubation (39 degrees C), manometric pressure (needed to separate caruncle and cotyledon), caruncle-cotyledon interface hydroxyproline (collagenolysis), and total protein (proteolysis) were determined . Results indicated no (P > 0.01) inhibition of collagenase by doxorubicin . We concluded that doxorubicin (at above dosages) is not an inhibitor for bacterial collagenase when tested on bovine placentomes.

Biochem Biophys Res Commun, 1998 Nov 18, 252(2), 472 - 5
Analysis of glutamines in catalysis in Cephalosporium acremonium isopenicillin N synthase by site-directed mutagenesis; Loke P et al.; Isopenicillin N synthase (IPNS), an important enzyme in the beta-lactam antibiotic biosynthetic pathway, is responsible for the catalytic conversion of delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine to isopenicillin N . Three catalytic ligands essential for IPNS activity have already been determined . Based on an Aspergillus nidulans IPNS crystal structure, the probable involvement of a fourth amino acid as a catalytic ligand was previously revealed . To continue the search for the fourth catalytic ligand, we report investigations on whether or not glutamines play a role in the catalytic action of Cephalosporium acremonium IPNS (cIPNS) . Three glutamine residues were targeted for modification based on the previous revelation of one (Q337) via crystal structure coordinates, the conservation of one (Q234) in isozyme alignment and the proximity of one (Q227) to the catalytic centre . Analysis of the biotransformed mutant enzymes showed retention of activity, thereby rejecting the involvement of a possible glutamine as a catalytic ligand in cIPNS catalysis .

Infect Immun, 1998 Dec, 66(12), 6054 - 7
Invasion of human oral epithelial cells by Prevotella intermedia; Dorn BR et al.; Invasion of oral epithelial cells by pathogenic oral bacteria may represent an important virulence factor in the progression of periodontal disease . Here we report that a clinical isolate of Prevotella intermedia, strain 17, was found to invade a human oral epithelial cell line (KB), whereas P . intermedia 27, another clinical isolate, and P . intermedia 25611, the type strain, were not found to invade the cell line . Invasion was quantified by the recovery of viable bacteria following a standard antibiotic protection assay and observed by electron microscopy . Cytochalasin D, cycloheximide, monodansylcadaverine, and low temperature (4 degreesC) inhibited the internalization of P . intermedia 17 . Antibodies raised against P . intermedia type C fimbriae and against whole cells inhibited invasion, but the anti-type-C-fimbria antibody inhibited invasion to a greater extent than the anti-whole-cell antibody . This work provides evidence that at least one strain of P . intermedia can invade an oral epithelial cell line and that the type C fimbriae and a cytoskeletal rearrangement are required for this invasion.

Eur J Pediatr Surg, 1998 Oct, 8(5), 278 - 81
Anaesthesia for liver transplantation in cystic fibrosis patients; Della Rocca G et al.; INTRODUCTION: Cystic fibrosis (CF) is a disease caused by an inherited genetic defect . While pulmonary and pancreatic abnormalities predominate the clinical spectrum, other organ involvement is common, including liver . The severity of liver disease does not appear to be related to the severity of exocrine pancreatic or lung function . We discuss anaesthesia in four CF patients undergoing liver transplantation . METHODS: We studied haemodynamic and oxygenation modifications during anaesthesia in four patients affected by CF with end-stage liver disease and mild to moderate pulmonary abnormalities . The patients received pancreatic enzyme prior to transplantation and two had insulin-dependent diabetes mellitus . All patients were treated with broad-spectrum antibiotic therapy . After a waiting time ranging one week to three months, all patients were successfully transplanted . General anaesthesia was induced with fentanyl, thiopental and pancuronium, and maintained with isoflurane supplemented by fentanyl in O2:air . Haemodynamic and oxygenation evaluations were made during the main phases of the transplant . After the intubation and at the end of the procedure all patients received a broncho-alveolar toilet through fiberoptic bronchoscopy . RESULTS: During anaesthesia for liver transplantation, PaO2 increased proportionally to the decreasing of Qs/Qt . In postoperative follow-up, Fev1 and FVC improved from preoperative time in all patients . In conclusion, even if cystic fibrosis is a multisystem disease, liver transplantation can be offered to CF patients with endstage liver disease and mild to moderate pulmonary function abnormalities . The four patients are still alive, enjoying good health . The improved respiratory function and quality of life of these children is remarkable.

FEBS Lett, 1998 Oct 23, 437(3), 197 - 200
The Pur10 protein encoded in the gene cluster for puromycin biosynthesis of Streptomyces alboniger is an NAD-dependent ATP dehydrogenase; Rubio MA et al.; The pur10 gene of the puromycin (pur) cluster of Streptomyces alboniger is essential for the biosynthesis of this antibiotic . Highly purified Pur10 protein, obtained in Escherichia coli as a recombinant protein fused to a histidine tail, had an NAD-dependent ATP dehydrogenase activity . The Km and Vmax values for ATP were 0.49 mM and 14.5 nmol/min and for NAD 0.53 mM and 15.2 nmol/min, respectively . The ATP-derived product of the reaction apparently decomposed producing a triphosphorylated compound plus an adenine derivative . These and previous results suggested that Pur10 carries out the first step of the puromycin biosynthetic pathway, namely, conversion of ATP into 3'-keto-3'-deoxyATP.

Int Endod J, 1998 Sep, 31(5), 343 - 7
Acute apical periodontitis: incidence of post-operative pain using two different root canal dressings; Fava LR; A clinical study using non-vital maxillary central incisors exhibiting acute apical periodontitis was carried out to evaluate the incidence of post-operative pain after biomechanical preparation and dressing with a calcium-hydroxide paste or a corticosteroid-antibiotic solution . Sixty teeth from 48 patients were prepared and dressed on the first visit and re-evaluated clinically 7 days later . No difference was observed in the incidence of post-operative pain between the two groups.

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