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