Antibiotics

Leuk Lymphoma, 1994 Dec, 16(1-2), 141 - 6
Delayed commencement of granulocyte colony-stimulating factor following autologous bone marrow transplantation accelerates neutrophil recovery and is cost-effective; Clark RE et al.; It is known that Granulocyte colony-stimulating factor (G-CSF) accelerates neutrophil recovery following bone marrow transplantation (BMT), though the optimal timing is not clear . We have undertaken a pilot study in 19 recipients of autologous BMT for non-myeloid malignancy, in which G-CSF was commenced 10 (13 cases) or 7 (6 cases) days after BM infusion . These patients were compared with 18 historical controls, who did not receive G-CSF . The median time to achieve both 0.5 and 1.0 x 10(9) neutrophils/Litre was significantly shorter in the treated group (18 and 21 days respectively) than the control group (20.5 and 29 days; p = 0.03 and 0.02 respectively) . No differences between the two groups were seen for the number of febrile days, days on antibiotics or the cost of the antibiotics . G-CSF-treated patients remained in hospital for significantly less time after marrow infusion (21 days compared to 29 days; p = 0.007) . The cost of the G-CSF therapy was offset by the decreased bed utilisation, so that the median combined antibiotic, G-CSF and hospitalisation cost was 754 pounds less for G-CSF treated patients . It is concluded that delaying the commencement of G-CSF after autologous BMT accelerates neutrophil recovery, and may allow earlier discharge from hospital, whilst not adversely affecting the cost of the procedure.

Clin Exp Immunol, 1994 Dec, 98(3), 494 - 502
Impact of 15-deoxyspergualin on effector cells in experimental autoimmune diseases of the nervous system in the Lewis rat; Jung S et al.; The influence of the immunosuppressive antibiotic agent 15-deoxyspergualin (DSG) on macrophages and autoreactive T helper lymphocytes from Lewis rats was analysed in vitro and in vivo . DSG did not inhibit antigen- or mitogen-induced proliferation of encephalitogenic or neuritogenic T helper cell lines in vitro . However, the presence of DSG during in vitro activation of the T cells strongly suppressed or completely abrogated their capacity to induce encephalitis (EAE) or neuritis (EAN) after adoptive transfer to naive rats, although expression of activation markers or adhesion molecules on the T line blasts was not down-regulated by DSG . Like activation-induced T cell proliferation, IL-2-dependent growth of CD4+ T line cells was not affected by DSG . Preincubation of CD4+ T line cells in DSG during IL-2-driven proliferation for 48 h, however, inhibited the subsequent antigen- but not mitogen-induced activation of these T cells, although neither density of T cell receptors nor other surface molecules involved in antigen recognition were lowered on the cells exposed to DSG . Similar to its effect in vitro, in vivo administration of DSG for 10 days even at a concentration with cumulative toxicity did not suppress in vitro proliferation of spleen cells induced by mitogen or a mitogenic combination of anti-CD2 antibodies . Furthermore, spleen cell and peripheral blood lymphocyte (PBL) surface antigens, particularly MHC molecules, were not altered by long-term treatment with DSG for 30 days . While there was a slight reduction in the number of polymorphonuclear cells in both populations, the proportion of the different leucocyte subpopulations remained unchanged . In contrast to the strong functional impact of DSG on autoreactive T helper cells, the drug did not inhibit the oxidative burst of macrophages or their MHC antigen expression . This study demonstrates a clear inhibitory effect of DSG on CD4+ T lymphocytes, but not macrophages . It provides an explanation for recent observations of a strong immunosuppressive in vivo effect of DSG on transplantation rejection and experimental autoimmune diseases, despite a normal mitogen response of T cells exposed to DSG in vivo and in vitro.

Toxicol Appl Pharmacol, 1994 Dec, 129(2), 214 - 22
Disruption of mitochondrial calcium homeostasis following chronic doxorubicin administration; Solem LE et al.; Doxorubicin (Adriamycin) is an anthracycline antibiotic with broad antineoplastic activity . However, the clinical success is limited by the incidence of cumulative cardiomyopathy . In vitro, doxorubicin elicits a cyclosporine A-sensitive release of calcium from cardiac mitochondria . It has been suggested that this leads to mitochondrial calcium cycling and depolarization of membrane potential, which may account for the inhibition of mitochondrial respiration and cytotoxicity observed with the drug . Implication of a similar mechanism in the manifestation of clinical doxorubicin toxicity requires evidence for a disruption of mitochondrial calcium homeostasis following chronic in vivo administration . Cardiac mitochondria isolated from doxorubicin-treated rats (2 mg/kg/week, s.c . x 13 weeks) had a lower RCR but no change in ADP/O compared to controls and exhibited an enhanced cyclosporine A-sensitive release of mitochondrial calcium . Associated with this was a calcium-induced depolarization of membrane potential, which was inhibited by either cyclosporine A or ruthenium red suggesting the induction of mitochondrial calcium cycling following chronic doxorubicin treatment . The persistence of these effects on mitochondrial calcium regulation 4-7 days after the last drug treatment is consistent with the cumulative cardiotoxicity associated with doxorubicin therapy . Cardiac mitochondria isolated from rats treated with iminodaunorubicin, a noncardiotoxic analog of doxorubicin, showed no differences from control suggesting that this disruption of mitochondrial calcium homeostasis in vivo may be an important determinant of the cardiomyopathy observed clinically with doxorubicin.

BMJ, 1994 Nov 19, 309(6965), 1329 - 32
Effect of homoeopathic medicines on daily burden of symptoms in children with recurrent upper respiratory tract infections; de Lange de Klerk ES et al.; OBJECTIVE--To investigate the intrinsic effects of individually prescribed homoeopathic medicines . DESIGN--Randomised double blind placebo controlled study . SETTING--Paediatric outpatient department of university hospital . PATIENTS--175 children with frequently recurring upper respiratory tract infections . Of the 170 children evaluable, 86 were randomised to homoeopathic medicines (47 boys, 39 girls; median age at start 4.2 years; median number of episodes in past year 4) and 84 to placebo (43 boys, 41 girls; median age at start 3.6 years; median number of episodes in past year 4) . MAIN OUTCOME MEASURES--Mean score for daily symptoms, number of antibiotic courses, and number of adenoidectomies and tonsillectomies over one year of follow up . RESULTS--The mean daily symptom score was 2.61 in the placebo group and 2.21 in the treatment group (difference 0.41; 95% confidence interval -0.02 to 0.83) . In both groups the use of antibiotics was greatly reduced compared with that in the year before entering the trial (from 73 to 33 in the treatment group and from 69 to 43 in the placebo group) . The proportion of children in the treatment group having adenoidectomies was lower in the treatment group (16%, 8/50) than in the placebo group (21%, 9/42) . The proportion having tonsillectomies was the same in both groups (5%) . CONCLUSION--Individually prescribed homoeopathic medicines seem to add little to careful counselling of children with recurrent upper respiratory tract infection in reducing the daily burden of symptoms, use of antibiotics, and need for adenoidectomy and tonsillectomy.

Virology, 1994 Nov 15, 205(1), 151 - 60
Mutational analysis of the translational signal in the human cytomegalovirus gpUL4 (gp48) transcript leader by retroviral infection; Cao J et al.; A short upstream open reading frame (uORF2) in the human cytomegalovirus (CMV) gpUL4 (gp48) transcript leader is conserved among CMV strains and inhibits translation of a downstream cistron . Remarkably, this inhibitory effect depends on the amino acid coding information of uORF2, at least in transient transfection assays in diploid human fibroblasts . Using retroviral vectors, we now report that the gp48 leader inhibits downstream translation in multiple additional cell types, even when expressed from a stably integrated gene, and on a transcript containing an additional kilobase of complex leader sequences . The magnitude of inhibition can be augmented approximately 3- to 10-fold by replacing the context of nucleotides flanking the wild-type initiation codon of uORF2 with an optimal context, suggesting that leaky scanning past the wild-type AUG codon accounts for translation of the downstream cistron . Using an in vivo mutagenesis protocol that relies on reverse transcriptase infidelity, we isolated mutants in which the inhibitory effect of the gp48 leader was inactivated as a result of alterations in the coding information of uORF2 . These studies demonstrate that, independent of the cell type or expression system used, CMV gp48 uORF2 is a potent translational inhibitory element.

Gene, 1994 Nov 4, 149(1), 165 - 72
Binding of Sp1 to the 21-bp repeat region of SV40 DNA: effect of intrinsic and drug-induced DNA bending between GC boxes; Sun D et al.; The effect of the antitumor antibiotic (+)-CC-1065 on the binding of Sp1 to the 21-bp repeats of SV40 DNA has been investigated . (+)-CC-1065 alkylates N3 of adenine in DNA and resides in the minor groove . As a consequence of alkylation of the two 5'-AGTTA* sequences (* indicates covalent modification site), which reside between GC boxes III and IV, and boxes V and VI, protein binding to the 3' sites is completely abolished and there is a significant decrease in Sp1 binding to the other regions . The effect of substituting A5 tracts for the (+)-CC-1065-bonding sequence was intermediate between the unmodified 5'-AGTTA* and the drug-modified sequences . It is proposed that a structural distortion of DNA associated with stiffening of the helix induced by the drug-adduct formation is primarily responsible for the inhibition of binding of Sp1 molecules to 21-bp repeats, rather than steric hindrance due to the occupancy by drug molecules of the minor groove within that region.

Del Med J, 1994 Nov, 66(11), 603 - 6, 609-13
The epidemiology of Lyme disease in Delaware 1989-1992; Wolfe D et al.; OBJECTIVES: The study was conducted to describe the temporal, geographic, demographic and treatment characteristics of Lyme disease in Delaware and to assist health planners in developing and implementing control strategies . METHODS: All physician-submitted Centers for Disease Control and Prevention (CDC) follow-up Lyme disease report forms from 1989 through 1992 were reviewed for completeness . Data were gathered from completed forms only . All cases were classified according to the 1990 CDC surveillance case definition . Cases were further subdivided into two groups . Antibiotic usage patterns were then identified for each group . Data on the percentage of infected ticks by county were obtained from a 1988 study conducted by the University of Delaware; Delaware Health and Social Services, Division of Public Health; and the Department of Natural Resources and Environmental Control . RESULTS: Reported cases of Lyme disease increased 246 percent between 1989 and 1992 . The 1992 statewide incidence rate was 12.6 cases per 100,000 population . Whites were four times more likely to contract Lyme disease than were blacks . The majority of cases were reported between June and October . The number of patients being treated with oral antibiotics for localized disease for three weeks or longer increased from 52 percent in 1991 to 94 percent in 1992 . Ixodid ticks infected with Borrelia burgdorferi were found in all three counties . CONCLUSION: The Delaware State Board of Health made Lyme disease reportable in September 1989 . This requirement increased the quality of Lyme disease surveillance; however, the disease is probably under-reported since Delaware does not actively solicit Lyme disease reports . Delaware's case data reflect national data which indicate an increase in reported cases . A trend toward longer duration of treatment for localized Lyme disease is evident.

Am Surg, 1994 Nov, 60(11), 872 - 80
Management of exposed inguinofemoral arterial conduits by skeletal muscular rotational flaps; Thomas WO 3rd et al.; Peripheral vascular reconstructions are common operations for the treatment of occlusive atherosclerosis, and the vast majority are uncomplicated . However, despite all precautionary measures, a small percentage of patients will manifest wound infection and graft exposure that may evolve to loss of limb and/or life . Treatment has traditionally consisted of systemic administration of antibiotic medication(s), graft extirpation, and extra-anatomic arterial bypass; yet despite use of these more radical modalities, morbidity and mortality have remained high . An additional meritorious adjunct for the treatment of exposed prosthetic or autogenous saphenous vein arterial bypass grafts is the use of local/regional autogenous skeletal muscular rotational flaps . Reported herein are the results of this technique applied to the inguinofemoral regions of eight patients . Rectus abdominis (1 patient), rectus femoris (4), and sartorius (4) skeletal muscular rotational flaps were employed . Seven of eight (88%) patients convalesced well at mean duration of follow-up measuring 24 months, although one patient subsequently required major amputation due to progression of occlusive atherosclerosis . One of eight (12%) patients succumbed secondary to irreversible sepsis, despite radical amputation . The data suggest that use of local/regional skeletal muscular rotational flaps is a useful adjunct for the treatment of patients with exposed arterial conduits.

South Med J, 1994 Nov, 87(11), 1147 - 50
Gastrospirillum hominis in acute gastric erosion; al-Himyary AJ et al.; Gastrospirillum hominis is a spirochete that has been described in association with chronic gastritis and duodenal ulcers . We report the case of a patient having acute gastric erosion in whom biopsy showed abundant organisms . The erosion resolved while the patient was receiving sucralfate and omeprazole therapy . We discuss the histopathology and mode of transmission of G hominis, along with the role of antibiotic therapy.

Radiol Clin North Am, 1994 Nov, 32(6), 1259 - 74
Duodenal ulcer; Glick SN; Duodenal ulcer constitutes one component of the clinical-pathologic complex of peptic disease of the duodenum . Recent evidence suggests that this chronic process may be cured with antibiotic therapy . Radiologic evaluation provides a cost-effective approach to the selection of patients for such management . Emphasis upon meticulous technique is essential for maximum patient benefit.

Mol Pharmacol, 1994 Nov, 46(5), 1009 - 14
New aspects of the kinetics of inhibition by lincomycin of peptide bond formation; Kallia-Raftopoulos S et al.; We have investigated the inhibition of peptide bond formation by the antibiotic lincomycin, at 150 mM NH4Cl . We have used an in vitro system in which a ribosomal ternary complex, the acetyl{3H} phenylalanine-tRNA-70 S ribosome-poly(U) complex (complex C), reacts with puromycin, forming peptide bonds . Complex C can be considered an analog of the elongating ribosomal complex and puromycin an analog of aminoacyl-tRNA . In a previous study we reported on the kinetics of inhibition by lincomycin at 100 mM NH4Cl . In the present investigation, we find that an increase of the ammonium ion concentration to 150 mM causes profound changes in the kinetic behavior of the system, which can be summarized as follows . First, the association rate for complex C and lincomycin is increased . At a lincomycin concentration of 10 microM the apparent equilibration rate constant is 4.3 min-1 at 100 mM NH4Cl, whereas it becomes 6.7 min-1 at 150 mM . Second, at 150 mM NH4Cl, with increasing concentrations of lincomycin, there is a transition from competitive to mixed-noncompetitive inhibition . The prevailing notion is that lincomycin acts at the ribosomal A-site, a mechanism that agrees only with competitive kinetics (mutually exclusive binding between puromycin and lincomycin) . At the molecular level, the change in the kinetics of inhibition that we observe may mean that the mutually exclusive binding between aminoacyl-tRNA and lincomycin is converted to simultaneous binding, as a result of conformational changes occurring in the elongating ribosomal complex.

Leuk Res, 1994 Nov, 18(11), 867 - 73
In vivo antitumor activity of herbimycin A, a tyrosine kinase inhibitor, targeted against BCR/ABL oncoprotein in mice bearing BCR/ABL-transfected cells; Okabe M et al.; Herbimycin A, a benzoquinoid ansamycin antibiotic, has been shown to reverse the oncogenic phenotype of p60v-src transformed cells because of the inhibition of src protein tyrosine kinase . We previously demonstrated that herbimycin A displayed antitumor activity on the in vitro growth of Philadelphia chromosome-positive leukemia cells and BCR/ABL-transfected murine hematopoietic FDC-P2 cells through the inhibition of BCR/ABL protein tyrosine kinase . In this study, the transformed FDC-P2 cells were demonstrated to be tumorigenic in syngeneic DBA/2 mice . The intraperitoneal (i.p.) injection of the transformed tumor cells into DBA/2 mice induced infiltrations of abdominal organs, and then all of the mice died within time periods proportional to the cell numbers of inoculation . In mice that received an i.p . inoculation with greater than 1 x 10(5) cells, in vivo administration of herbimycin A by i.p . injection inhibited tumor formation and significantly prolonged survival time, and further, in mice inoculated with 1 x 10(4) cells, herbimycin A completely suppressed the in vivo growth of transformant FDC-P2 cells and brought about a complete remission . The present study revealed the in vivo efficacy of herbimycin A in mice bearing BCR/ABL-transfected cells.

J Clin Oncol, 1994 Nov, 12(11), 2471 - 508
American Society of Clinical Oncology . Recommendations for the use of hematopoietic colony-stimulating factors: evidence-based, clinical practice guidelines; Managing otitis media with effusion in young children . American Academy of Pediatrics The Otitis Media Guideline Panel; This reference guide contains highlights from the Clinical Practice Guideline, Otitis Media with Effusion in Young Children . The Otitis Media Guideline Panel, a private-sector panel of health care providers, developed the Guideline after comprehensively analyzing the research literature and current scientific knowledge of the development, diagnosis, and treatment of otitis media with effusion in young children . Specific recommendations are given for the management of otitis media with effusion in young children age 1 through 3 years with no craniofacial or neurologic abnormalities or sensory deficits . The natural history of otitis media with effusion, the functional impairments that may result from otitis media with effusion, and the difficulty of measuring the effects of medical and surgical interventions on long-term outcomes are included . The medical interventions studied involve antibiotic, steroid, and antihistamine/decongestant therapies . The surgical interventions studied involve myringotomy with insertion of tympanostomy tubes, adenoidectomy, and tonsillectomy . Short-term outcomes addressed are resolution of effusion and restoration of hearing.

Pediatrics, 1994 Nov, 94(5), 719 - 23
Pulmonary hemorrhage risk in infants with a clinically diagnosed patent ductus arteriosus: a retrospective cohort study; Garland J et al.; OBJECTIVE . To determine if an early, clinically detectable patent ductus arteriosus (PDA) was associated with pulmonary hemorrhage (PH) in infants who received rescue artificial surfactant therapy . METHODS . This retrospective cohort study of 233 low birth weight infants (< or = 1700 g) who received artificial surfactant therapy for respiratory distress syndrome compared antenatal and postnatal characteristics of infants with PH and without PH . Pulmonary hemorrhage was defined by an onset of bright red blood from the endotracheal tube in quantities that resulted in increased ventilatory support and a new infiltrate on a chest radiograph . RESULTS . Pulmonary hemorrhage occurred in 6% (15/233) of the infants . Thirty-three percent (5/15) of the infants with PH died within 14 days of the hemorrhage . Of the 15 PH, 73% occurred within 48 hours of the first surfactant dose . Pulmonary hemorrhage was more common in male infants and infants of mothers who received antibiotic therapy during labor (P < or = .04) . Infants with PH received surfactant earlier than those without PH (P = .04) . Nursery events or therapies occurring following surfactant therapy that were associated with PH included: little improvement in ventilatory efficiency index (P = .01), dopamine infusion (P = .04), and the presence of a clinically detectable PDA before, or at the time of, the PH {60% (9/15) vs 33% (71/217), P = .03} . After adjusting for severity of illness before surfactant therapy, risk of PH remained greater in infants who developed symptoms of a PDA . Dopamine support appeared to modify the association between PDA and PH . CONCLUSIONS . In this retrospective cohort study, pulmonary hemorrhage, was associated with the presence of a clinically detectable patent ductus arteriosus before, or at the time of, pulmonary hemorrhage.

Clin Investig, 1994 Nov, 72(11), 850 - 2
Successful treatment of meningoencephalitis caused by Mycobacterium avium intracellulare in AIDS; Malessa R et al.; A wide variety of pathologies afflicting the CNS is see in patients infected with the human immunodeficiency virus . We report the case of relapsing meningoencephalitis caused by Mycobacterium avium intracellulare (MAI) in a homosexual male with the acquired immunodeficiency syndrome in whom repeated use of polymerase chain reaction was required to detect MAI-specific DNA in the cerebrospinal fluid . Successful responses to early empirical antibiotic combination treatment, including the drugs clarithromycin and rifabutin, were demonstrated by clinical, EEG, and CSF improvement during an 8-month period . To our knowledge, this study presents the first known patient with the acquired immunodeficiency syndrome effectively treated for MAI meningoencephalitis and suggests that modern antimycobacterial combination therapy may improve the poor prognosis of CNS infections with nontuberculous mycobacteria.

Clin Infect Dis, 1994 Nov, 19(5), 902 - 9
Information management in infectious diseases: survival of the fittest; Classen DC; Like all physicians, infectious disease practitioners are concerned and uncertain about their future role as the United States undergoes a major reform of its health care system . Managed care has become the dominant type of health care provided to most patients in the United States, and specialists are increasingly threatened as patient referrals decrease, reimbursements decline, and health care organizations preferentially recruit primary care physicians over specialists . These changes may represent a potential shift in responsibilities and duties for many infectious disease practitioners . The primary role of the infectious disease physician has traditionally been consultative, although many practitioners have organized programs in infection control, hospital epidemiology, and antibiotic management . These programs have become more important as managed care organizations understand the implications of their potential cost savings . The value of these programs will also be significantly enhanced by the ongoing revolution in medical information management that is being driven by computerization . This paper outlines the enlarging role of computerized information management in clinical patient care and its impact on infectious disease practitioners who are increasingly involved in infection control, hospital epidemiology, and antibiotic management programs, as well as in the development of computerized clinical information systems.

Equine Vet J, 1994 Nov, 26(6), 448 - 53
Histological findings in corneal stromal abscesses of 11 horses: correlation with cultures and cytology; Hamilton HI et al.; Histopathology was compared to culture results and cytology from horses with corneal stromal abscess at the Auburn University and the Ohio State University Veterinary Teaching Hospitals . Significant bacteria were not isolated in culture or seen on histopathology in any of the horses . Although most bacteria infecting equine corneas can be isolated with blood and MacConkey's agars, failure to detect bacterial growth may not rule out infection because anaerobic or intracellular bacteria would not be isolated . The inability to visualise bacterial organisms on histological sections did not rule out their presence in the tissue, because there is often destruction of bacteria by neutrophils, macrophages and antibiotic therapy greatly reducing their numbers . Fungal keratitis was diagnosed by histopathology in 4 of 11 eyes (36%) and keratitis with no aetiological agent in 7 of 11 eyes (64%) . Nine of 11 horses (82%) had a prominent neutrophilic stromal infiltrate and 2 (18%) had a predominantly pyogranulomatous reaction . Two of the 4 lesions that showed histological evidence of fungal infection were positive for identifiable fungi on culture and cytology . Fungal cultures of the other 2 cases with histological evidence of mycotic keratitis were negative or grew unidentifiable fungi which were considered pathogenic because, on histopathological sections, fungal hyphae were found deep in the corneal stroma surrounded by an inflammatory reaction . In 3 of 6 cases where fungi were recovered on culture, they were considered contaminants based on lack of evidence of organisms in histopathological sections . Histopathology and the use of special stains were important in the interpretation of culture and cytology results.

Pharmacotherapy, 1994 Nov-Dec, 14(6), 734 - 9
Ampicillin-sulbactam versus cefoxitin for prophylaxis in high-risk patients undergoing abdominal surgery; Paladino JA et al.; This double-blind study compared ampicillin-sulbactam 3 g versus cefoxitin 2 g in 136 adult patients at risk for developing an infection after abdominal surgery . Separate randomization schedules were used for colorectal, upper gastrointestinal/biliary, and other abdominal procedures . Study antibiotics were administered within 30 minutes before incision and repeated 6 hours later . Patients having colorectal surgery received a third dose of antibiotic 6 hours after the second . Efficacy evaluations were made on 123 patients, 62 in the ampicillin-sulbactam group and 61 in the cefoxitin group . The overall postoperative infection rates were 12.9% for ampicillin-sulbactam and 9.8% for cefoxitin (p > 0.05); one wound infection occurred in each group . Adverse events were experienced by 13.2% of the ampicillin-sulbactam and 19.1% of the cefoxitin recipients (p > 0.05) . Cost-minimization analysis revealed that ampicillin-sulbactam was a cost-effective alternative to cefoxitin for the prevention of infection after abdominal surgery.

Mol Biol (Mosk), 1994 Nov-Dec, 28(6), 1383 - 99
{Design of de novo specific DNA-binding peptides, using the motif beta-chain-turn-beta-chain for recognizing a nucleotide sequence in DNA}; Surovaia AN et al.; De novo design and synthesis by a solid phase technique of linear and cyclic 26-residues peptides are reported . The peptides use beta-strand-turn-beta -strand motif for sequence recognition on DNA . Amino acid sequences in the two peptides are identical, but the structure of the cyclic peptide is constrained by S-S bridge between two cysteine residues . A 28-residue peptide containing at the N-terminus a copper-chelating peptide Gly-Gly-His is also synthesized which can be used as a potential DNA-cleaving reagent . Binding of these peptides to various natural and synthetic DNAs and DNA fragment with a known base pair sequence has been studied by CD spectroscopy, fluorescence methods and DNAse I footprinting technique . By means of CD spectroscopy it is shown that 26-residue linear and cyclic peptides are partially in disordered and beta-conformations in aqueous solution in absence and in presence of 20% trifluoroethanol (TFE), but assume partially an alpha-helix conformation in the presence of 50% TFE . It is shown that linear and cyclic peptides bind to DNA . The binding approaches saturation level when one peptide molecule is bound approximately per three or four DNA base pairs . We found that antibiotic distamycin A, binding in the minor DNA groove, competes effectively with the 26-residue linear and cyclic peptides for binding to poly(dA).poly (dT) . According to the CD spectroscopy data the linear and cyclic peptides undergo conformation changes upon binding to DNA, whereas the DNA structure is not markedly altered . Difference CD spectra obtained by subtracting the spectrum of the free DNA from the spectrum of the peptide-DNA mixture differ from the spectrum of the free peptide . The shapes of difference CD spectra are consistent with a conformation transition from a disordered conformation into a beta-like conformation upon binding of peptide to DNA . DNAase I footprinting diagrams show that there is a specific protection by linear and cyclic peptides of the nucleotide sequences on two ends of operators OR1, OR2 and OR3 and pseudooperators within the cro gene of 434 phage.

J Heart Lung Transplant, 1994 Nov-Dec, 13(6), 958 - 62
Monitoring of acute lung rejection and infection by bronchoalveolar lavage and plasma levels of hyaluronic acid in clinical lung transplantation; Rao PN et al.; Local immunological injury caused by acute lung rejection leads to fibroblast proliferation . Hyaluronate is a product of activated fibroblasts and possibly an indicator of fibroblast proliferation . One hundred thirty-six bronchoalveolar lavage and plasma hyaluronate assays were performed in 57 lung transplant recipients . Pulmonary endothelial cell function was assessed by measuring bronchoalveolar lavage levels of purine nucleoside phosphorylase . Presence of acute cellular rejection was monitored by transbronchial biopsy histologic evaluation and was classified as minimal to mild (acute rejection I, II) and moderate to severe (acute rejection III, IV) . Infection was confirmed by bronchoalveolar lavage culture and antibiotic sensitivity . Bronchoalveolar lavage hyaluronate levels in clinically stable recipients were 33.5 +/- 4.69 micrograms/L and were significantly higher than with clinically stable recipients (p = 0.0001), infection (p = 0.008), or mild rejection (p = 0.001) . Levels were highest in recipients with diffuse alveolar damage (392.4 +/- 60.6 micrograms/L) . Diffuse alveolar damage also resulted in significant elevations of plasma HA as compared with stable recipients (p = 0.001) and mild rejection . We conclude that clinically significant injury to the allograft from rejection or diffuse alveolar damage can be assessed by bronchoalveolar lavage hyaluronate assays and suggest that the source of hyaluronate in these instances are activated fibroblasts.

Support Care Cancer, 1994 Nov, 2(6), 369 - 73
Outpatient management of febrile episodes in neutropenic cancer patients; Rubenstein EB et al.; Febrile neutropenic patients have traditionally received hospital-based parenteral antibiotic therapy because of the risk of serious complications and associated mortality . Recently a low-risk subset among febrile neutropenic patients has been identified . Several alternatives to hospital-based therapy have been evaluated in such patients . These include early discharge to home antibiotic therapy after initial stabilization in the hospital, or treatment of the entire febrile episode with intravenous and/or oral antibiotics in an ambulatory setting . A multidisciplinary approach involving the physician and other health-care providers, the patients, and their families, ensures the success of this therapeutic modality . Careful patient selection, daily follow-up, close monitoring for the development of complications and/or adverse reactions, and informed consent along with detailed instructions to patients, minimize the risk of the development of serious complications . Outpatient antibiotic therapy for febrile episodes in low-risk neutropenic patients should now be considered an acceptable alternative to hospital-based therapy.

Recenti Prog Med, 1994 Nov, 85(11), 526 - 36
{Intestinal mycobacterial infections in AIDS . Clinical course and treatment of infections caused by Mycobacterium avium, Mycobacterium kansasii, Mycobacterium genavense}; Dionisio D et al.; Digestive apparatus is a common target of atypical mycobacteriosis in AIDS patients (at least 50% of patients with CD4+ lymphocytes < 50/mm3) . We describe the clinical-histological features of two cases of Whipple-like syndrome likely caused by Mycobacterium avium (MAI) (study performed by light and electron microscopy), of one case of infection caused by two morphological variants of a MAI strain with a different sensitivity to antibiotics, of one case of M . kansasii infection and of two cases of M . genavense infection accompanied by sensitivity tests to antibiotics (as far as we know, these are the first described quantitative sensitivity tests of M . genavense to antibiotics) . In conclusion, we discuss the present therapeutical outlines for M . kansasii and avium, together with the teramporary pharmacological options for M . genavense as suggested by antibiotic sensitivity tests performed on the strains isolated from the studied patients.

J Clin Microbiol, 1994 Nov, 32(11), 2791 - 800
Use of an ATP bioluminescent assay to evaluate viability of Pneumocystis carinii from rats; Chen F et al.; A bioluminescent assay which employs the luciferin-luciferase ATP-dependent reaction was used to evaluate the viability of populations of Pneumocystis carinii derived from infected rat lungs . Contamination with host cells was reduced by a purification method which involved a combination of low- and high-speed centrifugations resulting in a 1,000-fold reduction of the rat cells while enriching for the trophic form of P . carinii . A linear correlation for the number of P . carinii nuclei versus the amount of ATP was observed . The ATP content of the organism populations could be maintained at inoculum levels for one week, although the number of organisms did not increase . Addition of respiratory chain inhibitors dramatically decreased the ATP content of the P . carinii after 24 h of incubation, with the exception of the antibiotic oligomycin B . Low concentrations of trimethoprim-sulfamethoxazole and pentamidine isethionate reduced the organism ATP content by over 50% after 24 h of exposure, while no effect was observed with 100-fold greater concentrations of ampicillin . The bioluminescent assay was found to be a more sensitive indicator of viability than a dual fluorescent staining technique . This assay does not require replication of P . carinii and should be a useful method for in vitro drug screening and viability assessment of P . carinii populations.

PDA J Pharm Sci Technol, 1994 Nov-Dec, 48(6), 318 - 29
Prediction of lyophile collapse temperature by dielectric analysis; Morris KR et al.; A new method for predicting lyophile collapse temperatures based upon dielectric analysis (DEA) of frozen two component systems is presented . The method, called the take off frequency model (TOF), relies both on the inherent ability of DEA to detect molecular motion and on the abrupt change in viscosity experienced by a frozen sample undergoing a glass-liquid transition . Collapse temperatures for binary glass forming systems (an antibiotic, sucrose, trehalose, or sorbitol, with water) were in good agreement with the values reported in the literature . DEA was easily able to detect glass transitions poorly defined by differential scanning calorimetry (DSC) . Conservative lyophilization cycles for simple systems can be quickly determined on the basis of the TOF model.

J Am Board Fam Pract, 1994 Nov-Dec, 7(6), 465 - 71
Cervical inflammation and preterm delivery in pregnant women with a history of preterm delivery; Blake RL Jr et al.; BACKGROUND: A previous preterm delivery is a risk factor for preterm delivery in a subsequent pregnancy . We tested the hypothesis that evidence of inflammation on a Papanicolaou smear obtained during pregnancy is a risk factor for preterm delivery for women with a history of preterm delivery . METHODS: We studied women who had two singleton deliveries at a university hospital during an 8-year period . Women eligible for our study were those whose first delivery was preterm (< 37 weeks of gestation) and for whom a Papanicolaou smear was obtained during the second pregnancy . These smears were examined for evidence of inflammation by a cytopathologist . Information about the second pregnancy was obtained by chart review . RESULTS: The cytopathologist reviewed Papanicolaou smears from 92 study pregnancies and found evidence of cervical inflammation on 34 smears (37 percent) . Preterm delivery ended 24 (26.1 percent) of the second pregnancies . The incidence of preterm delivery in women with inflammation on Papanicolaou smear was 41.2 percent compared with an incidence of 17.2 percent in women without inflammation (relative risk of 2.40 with a 95 percent confidence interval of 1.19 to 4.83) . This association remained significant after controlling for potential confounding variables . A stratified analysis found that the association of cervical inflammation with preterm delivery was limited to women who had systemic exposure to an antibiotic during pregnancy . CONCLUSION: Among pregnant women with a history of preterm delivery, evidence of inflammation on Papanicolaou smear was associated with an increased risk of preterm delivery . If replicated in other studies, this finding might have implications for the management of pregnancies in women with a history of preterm delivery.

Radiologe, 1994 Nov, 34(11), 671 - 3
{Intracerebral abscess 48 years after grenade splinter injury}; Wegner-Kempf L et al.; The case report of a 54-year-old patient with a right frontal intracerebral abscess 48 years after a missile injury is presented . Treatment included surgical evacuation and antibiotic therapy . The patient was discharged without neurological deficit.

Nutr Hosp, 1994 Nov-Dec, 9(6), 375 - 84
{Bacterial translocation: the effect of supplements with dietary fiber in enteral diets in an experimental model of methotrexate-induced enterocolitis}; Gil Sanchez MD et al.; Bacterial translocation, described by 1979 by Berg and Garlington as the movement of viable bacteria through anatomically intact intestinal mucosa to the mesenteric ganglia, is suspected of playing an important role in the development of sepsis with no apparent focus, fundamentally in polytraumatized and sever surgical patients: even now, with the wide range of antibiotic and chemotherapy agents available for treatment, this sepsis represents a high rate of hospital morbid-mortality . To assess the function as barrier of the intestinal mucosa and the influence of dietary fiber thereon, we studied bacterial translocation measured as positive cultures of the mesenteric lymphatic ganglia in an experiment model of enterocolitis induced by the intraperitoneal injection of 20 mg/kg of Methotrexate (MTX), using 72 male S-D rats, half of which were used as control group . These animals were sub-divided into four series according to the diet they were to receive . In addition to bacterial translocation, we examined the intestinal mucous parameters (mucosa weight, protein and DNA content, and number of mitoses) to quantify the potential trophic effect of dietary fiber on the intestinal mucosa . In the group subject to enterocolitis, there were no significant differences in the bacterial translocation with the series fed with defined-formula diets supplemented or otherwise with dietary fiber . Only the series receiving standard feed showed a significant reduction of bacterial translocation . pectin improved all mucous parameters when compared with the other diets studied . In the control group, the bacterial translocation rate was zero in all dietary series.

Nippon Ika Daigaku Zasshi, 1994 Nov, 61(6), 556 - 62
{Flow cytometry studies on the long-term effect of adriamycin on cell cycles}; Kokuma M; Little is known today about the long-term influence of the anti-cancer antibiotic . Adriamycin (ADR), on the cell cycle . With this in mind, the author used flow cytometry (FCM) to observe the changes with time in the cell cycle . The changes were examined every 24 hours for 14 days . Prior to this HeLa S3 cancer cells were cultured in three ADR concentrations--0.01 micrograms/ml, 0.1 micrograms/ml, 1.0 micrograms/ml-- . In the cell group exposed to the low ADR concentration of 0.01 microgram/ml for one hour, no noteworthy effect on the cell cycle was noted, and the cell count was slightly depressed as compared with the control group . In the group exposed to the moderate ADR concentration of 0.1 micrograms/ml for one hour, the G2 phase cells increased in number after 24 hours, but decreased on and after ten days, though there was an increase in the number of G1 phase cells . In addition, the cell count, which had shown no growth till the eight day, began to increase on and after the ninth day . In the cell group exposed to the high ADR concentration of 1.0 micrograms/ml for one hour, complete G2 block was observed on and after the 24th hour, with no subsequent change . The cell count also continued to decrease . The previous assumption that once G2 block has been caused by ADR, the cell group dies, was again shown to be valid.2+ e

G Ital Cardiol, 1994 Nov, 24(11), 1407 - 12
{Value of transesophageal echocardiography in the diagnosis of paravalvular aortic abscess}; Caso P et al.; Paravalvular abscesses are a serious complication of aortic endocarditis . Echocardiography is the method of choice for the visualization of the valve-attached vegetations, however the detection of endocarditis-associated abscesses by transthoracic approach is extremely difficult . Recently transesophageal echocardiography has been proved as an excellent tool to correctly detect these lesions . We report on two patients with endocarditis-associated abscesses in whom transesophageal echocardiography allowed us to diagnose paravalvular abscesses not recognized by transthoracic echocardiography; furthermore in the first patient, performing two successive transesophageal examinations before and after antibiotic therapy, we could follow the evaluation of aortic abscess which became a fistula draining into the left ventricular outflow tract . In conclusion these two cases suggest that transesophageal echocardiography should be always performed in patients suspected or known to have endocarditis and that a following examination is indicated to assess any evolving echocardiographic finding.

Eur J Vasc Surg, 1994 Nov, 8(6), 694 - 702
Arterial autografts and PTFE vascular microprostheses: similarities in the healing process; Bellon JM et al.; A comparative study has been carried out dealing with the vascular healing process in two experimental vascular graft models to determine the differences or similarities between the two . One of the models consisted of the use of arterial autografts and the other of the implantation of vascular microprostheses of polytetrafluoroethylene (PTFE) . The common iliac artery of female Sprague-Dawley rats was used . The length of the grafts in both models was 5 mm . A microsurgical technique was employed, and anticoagulant and antibiotic therapies were not used . The results were studied using light microscopy, transmission and scanning electron microscopies, autoradiography, and immunohistochemistry . A patency of 100% was obtained in the arterial autografts, and 87.6% in the PTFE implants . The histopathological findings were as follows: a) the mechanisms of immediate postgrafting response were similar, with marked presence of fibrin and platelet deposition in the form of a nonthrombogenic monolayer; b) a "neoadventitia" formed over the implant in both models; c) the endothelialisation was complete in both types of grafts 2 to 3 weeks after implantation; d) an intimal hyperplastic response appeared in both, although at different times (in the first week in the autografts and at one month with the PTFE); e) white cell accumulation was significantly greater on the PTFE luminal surface than on the autograft . The intimal hyperplasia was formed mainly by secretory myocytes in the autografts, while in the PTFE implants, fibrosis predominated.

Hautarzt, 1994 Nov, 45(11), 769 - 71
{Pregnancy after drug therapy of severe andrological disorder}; Jung A et al.; Initial examination of an andrological patient revealed high-grade oligoasthenoteratozoospermia and ureaplasma infection . An elevated FSH level and significantly reduced testicular size were indicative of severely damaged testicular parenchyma . The presence of macrophages in the sperm smear was interpreted as a sign of chronic epididymitis . Antibiotic couple therapy with doxycycline, followed by a 3-month recovery period with combined treatment with vitamin C and E and zinc, resulted in a significantly improved spermiogram . After another 2 months intrauterine insemination resulted in pregnancy, and the birth of a healthy daughter followed . Preparation of the ejaculate was done by glasswool filtration . At that time, the patient had only mild teratozoospermia.

Diabetes Care, 1994 Nov, 17(11), 1348 - 53
Rhinocerebral mucormycosis in IDDM . Sequential magnetic resonance imaging of long-term survival with intensive therapy; Moll GW Jr et al.; OBJECTIVE--To describe the clinical course and the utility of computerized tomography (CT) and magnetic resonance imaging (MRI) in the successful management of an often fatal fungal infection in a 12-year-old patient with insulin-dependent diabetes mellitus (IDDM) . CASE--The patient was admitted to The University of Mississippi Medical Center (UMC) for the purpose of diabetic ketoacidosis (DKA) management and subsequent intensive therapy for mucormycosis according to nationally accepted standards of care . Strict diabetic control was instituted with frequent monitoring of blood glucose levels and interval assessment of HbA1c . Sequential MRI studies were obtained according to approved patient standards; the clinical and MRI course of the infection was charted . RESULTS--The patient's DKA resolved within 12 h on intravenous fluid repletion and insulin therapy . His sinusitis/rhinitis noted on admission did not respond to intravenous antibiotic therapy and progressed with obvious left orbital involvement and left cranial nerve palsies by 72 h of hospitalization . CT and MRI were invaluable aids to the early diagnosis and design of appropriate surgical and antifungal management of this patient, who survived with minimal left cranial nerve palsies . CONCLUSIONS--Our patient is among the youngest of IDDM patients reported to have survived rhinocerebral mucormycosis . His survival is attributed to early recognition of possible mucormycosis with diagnostic support of CT and MRI, surgical debridement and antifungal therapy, and intensive blood glucose control . Sequential MRI is invaluable to the design of therapy for this type of patient and shows the nearly 3-year recovery from mucormycosis.

J Clin Ultrasound, 1994 Nov-Dec, 22(9), 525 - 9
Ultrasound evaluation of hepatic and splenic microabscesses in the immunocompromised patient: sonographic patterns, differential diagnosis, and follow-up; Gorg C et al.; High-dose chemotherapy, especially for bone marrow transplantation, causes a great degree of immunosuppression, and thus carries the risk for invasive fungal infections . Although hepatic and splenic involvement in disseminated candidiasis is frequent, involvement of these organs is rarely appreciated antemortem . During the last decade, focal hepatosplenic candidiasis has been recognized increasingly by ultrasound . We report the sonographic and clinical findings of 6 patients: 3 AML (acute myeloid leukemia), 2 NHL (non-Hodgkin's lymphoma), and 1 HD (Hodgkin's disease) who demonstrated multiple, small-nodule, hypoechoic lesions in spleen and/or liver after high-dose chemotherapy . All patients were in complete hematologic remission when the study was performed . Septic fever was unresponsive to antibiotic therapy . Granulocytopenia (< or = 1000/mm3) was seen for at least 10 days . However, the manifestation of hepatolienal microabscesses became apparent by ultrasound only after the neutrophil count returned to normal in all but 1 patient . Microabscesses decreased or disappeared on follow-up examination after antifungal treatment . Systemic candida infection was confirmed serologically . Sonographic-guided abscess biopsy (n = 3) revealed necrosis/abscess . Structural inhomogeneity of parenchymal organs was seen for several months after therapy.

Ir J Med Sci, 1994 Nov, 163(11), 494 - 5
Isolated pulmonary valve endocarditis: a rare or an underdiagnosed disease?
Cherukuri AK, Maloney M, O'Briain DS, Weir DG.
A 48 year old patient with resistant coeliac disease developed prolonged unexplained pyrexia after surgery for small bowel volvulus . Despite extensive investigations and intensive antibiotic therapy, he deteriorated and died eight weeks postoperatively and significant isolated pulmonary valve endocarditis was discovered at autopsy . This diagnosis should be considered in all critically ill patients with unexplained pyrexia even in the absence of clinical features of endocarditis and transoesophageal echocardiography performed to exclude or confirm this lesion.

Arch Fam Med, 1994 Nov, 3(11), 961 - 6
Patients' interpretation of qualitative probability statements; Woloshin KK et al.; BACKGROUND: Physicians often use qualitative probability statements to compare treatment options or describe risks of treatment, especially if exact numerical information is not readily available . OBJECTIVES: To determine (1) the effect of context, experience, age, gender, race, occupation, and education on patients' numerical interpretation of probability terms and (2) patient preferences for information about side effects (qualitative or numerical) . DESIGN: Cross-sectional survey . SETTING: A university-based family practice in Ann Arbor, Mich . PARTICIPANTS: Patients 18 years of age and older and parents of patients younger than 18 years of age seen during January and February 1993 for any reason except complete physical examination . METHODS: A questionnaire presented scenarios of minor and major complications related to four different medical conditions . Participants were asked to estimate how many people of 100 would have a complication if their physician described the risk for the complication in each scenario as unlikely . Participants were then asked whether they preferred receiving information from their physician about the risk for complications in words or numbers . RESULTS: Of 345 questionnaires distributed, 307 patients (89%) completed them . The rates assigned to the minor complications were significantly higher than the rates assigned to the major complications (P = .0001) . Participants who had experienced the described complication reported significantly higher rates for the minor complications of vaccination and surgery (P = .0001 and P = .0235, respectively) . Education had a significant effect only on the rates assigned to vaccination complications (P = .0069) . Occupation had a significant effect only on the rates assigned to antibiotic side effects (P = .0090) . CONCLUSIONS: When a physician uses qualitative probability statements, he or she must be sensitive to the patient's previous experience with that procedure or medication . Also, if one wants to convey the same potential rate of occurrence for major and minor side effects, then one needs to use different words for each.

Minerva Anestesiol, 1994 Nov, 60(11), 663 - 8
{Results of early external ventricular diversion in posthemorrhagic ventricular dilatation in the newborn}; Massone ML et al.; OBJECTIVE AND DESIGN . The authors report the outcome of early treatment with long-term external ventricular drainage (EVD) of progressive post-hemorrhagic ventricular dilatation (PPHVD), following peri-intraventricular hemorrhage (PIVH) in a population of preterm newborns . SETTING . Neonatal Intensive Care Unit (NICU) of a Children's Hospital . PATIENTS . Twenty-one preterms of 29.6 +/- 2.4 weeks of gestational age, weighing at birth 1443 +/- 445 g, mechanically ventilated, submitted to early EVD because of PPHVD following PIVH of III (n 11) e IV (n 10) grade . METHODS . PPHVD was diagnosed on the basis of US and TC findings . An external liquoral drainage suitable, for its technical characteristics, to be maintained for a long period of time and peculiar anesthesiologic, intra and postoperative treatments were utilized . RESULTS . EVD was placed at 21 +/- 5.8 days of life and maintained for 40 +/- 16 days . In all cases reduction of ventricular size was observed . One case (5%) developed liquoral infection and recovered with antibiotic therapy . No obstruction or dislocation of the ventricular catheter occurred . During EVD 3 patients (14%) died because of respiratory complications . After the normalization of cerebrospinal fluid (CSF), a "permeability test" was performed to assess the canalization of the liquoral system . Seven patients (33.5%) underwent ventriculo-peritoneal shunt (VPS) and 11 (52.5%) became shunt-free . CONCLUSIONS . Our results indicate that long-term use of EVD has a low risk of complications, avoids the need for transcutaneous tips and allows monitoring of CSF characteristics . Furthermore EVD protects the brain from liquoral hypertension, while waiting for a possible recurrence of natural CSF circulation, and is associated with a low number of definitive VPS.

Bioorg Med Chem, 1994 Nov, 2(11), 1251 - 9
Use of triethylene glycol to mimic oligosaccharides: design and synthesis of a ligand based on chromomycin A3; Silva DJ et al.; Chromomycin A3 (CRA3) is an antitumor antibiotic that binds to DNA . It contains an acac-like metal binding site and forms a 2:1 complex with Mg2+ . Interestingly, acac ligands similar to CRA3 form 1:1 complexes with Mg2+ . We have previously shown that the unusual stability of the 2:1 CRA3-Mg2+ complex is related to a favorable intermolecular interaction between the CDE trisaccharide of one CRA3 molecule and the chromophore of the other . We have used this knowledge to design and synthesize a very simple molecule in which a triethylene glycol chain mimics the CDE trisaccharide of CRA3 . This minimalist ligand behaves like CRA3 with respect to dimer formation . This result sheds light on how the CRA3 sugars function to stabilize the dimer . At the same time, the work provides a starting point for investigating the relationship between dimer formation and DNA binding . Starting from these relatively simple metal complexes, it should be possible to develop a better understanding of the structural requirements for DNA binding by CRA3 and related molecules.

Br J Gen Pract, 1994 Nov, 44(388), 515 - 8
Reported management of patients with sore throat in Australian general practice; Carr NF et al.; BACKGROUND . Sore throat is one of the commonest presenting symptoms in general practice in Australia, and results in the prescription of an antibiotic in 50-90% of cases, despite the finding of bacterial throat infection in around 30% of cases or fewer . AIM . This study set out to examine whether inaccurate knowledge about the pathophysiological features and management of sore throat helps to explain the high level of inappropriate antibiotic prescribing for sore throat by general practitioners . METHOD . A questionnaire with four case vignettes of sore throat presentations was sent to 400 randomly selected general practitioners, practising in Victoria, Australia . Of 367 eligible respondents, 284 responded (77%) . RESULTS . Of the respondents 97% reported that they would prescribe an antibiotic for the case of tonsillitis, 70% for the case of possible glandular fever, 29% for the child with probable viral sore throat and 9% for the adult with probable viral infection . There were no differences in prescribing rates between general practitioners of different sex, practice location, practice type or qualification . Overall, 25% of the antibiotics which formed the respondents' first choice were inappropriate broad-spectrum antibiotics . CONCLUSION . General practitioners are generally accurate in their assessment of the features of sore throats, but less accurate in their knowledge of appropriate antibiotics.

Ann Acad Med Singapore, 1994 Nov, 23(6), 819 - 22
Randomised study comparing imipenem/cilastatin to ceftriaxone plus gentamicin in cancer chemotherapy-induced neutropenic fever; Au E et al.; Prompt initiation of empiric antibiotic therapy is the cornerstone in the therapy of chemotherapy-induced neutropenic sepsis in cancer patients . Ceftriaxone plus gentamicin (ceftriaxone/gentamicin) is the most widely used combination of empiric antibiotics in the Department of Medical Oncology, Singapore General Hospital . However, imipenem/cilastatin has been shown to be a practical alternative . To compare the efficacy and cost effectiveness of monotherapy with our usual combination antibiotic therapy, 50 evaluable neutropenic cancer patients admitted for fever were randomised to empiric imipenem/cilastatin or ceftriaxone/gentamicin . Ceftriaxone/gentamicin was started in 24 patients . The initial clinical response rate to ceftriaxone/gentamicin was 62.5% and 84.6% to imipenem/cilastatin (P = 0.075) . The average cost of antibiotics per patient started on ceftriaxone/gentamicin including cost of change of antibiotics was S$63 per day of antibiotic use and for imipenem/cilastatin it was S$252 (P < 0.02) . In conclusion, although more patients receiving imipenem/cilastatin had an initial clinical response than those receiving ceftriaxone/gentamicin, this difference was not statistically significant . It would appear that imipenem/cilastatin is equivalent to ceftriaxone/gentamicin for the treatment of neutropenic sepsis . However, ceftriaxone/gentamicin was more cost effective.

J Refract Corneal Surg, 1994 Nov-Dec, 10(6), 640 - 6
Treatment of corneal abrasions with soft contact lenses and topical diclofenac; Salz JJ et al.; BACKGROUND: Treatment of corneal abrasions often involves antibiotic ointment and pressure patching . The corneal abrasions following excimer laser photorefractive keratectomy have been managed with disposable soft contact lenses and diclofenac (Voltaren) eye drops . METHODS: We report 13 patients with corneal abrasions from trauma or recurrent corneal erosions treated with application of a disposable soft contact lens and instillation of diclofenac and antibiotic eye drops . RESULTS: All 13 patients reported significant pain relief and all abrasions healed within 3 days (most within 24 hours) . Two of the recurrent erosion patients suffered subsequent spontaneous abrasions and one of the traumatic abrasion patients developed a possible infectious keratitis which cleared without visual loss . CONCLUSIONS: In this small series, the combination of a disposable soft contact lens and the instillation of diclofenac drops provided significant pain relief while the abrasion healed and allowed the patients to function with binocular vision . This treatment regimen offers an alternative to pressure patching in the treatment of corneal abrasions.

Hokkaido Igaku Zasshi, 1994 Nov, 69(6), 1443 - 54
Suppression of tumorigenicity and induction of senescence on human endometrial carcinoma cell lines by transfer of normal human chromosomes; Yamada H; The author examined the ability of human chromosomes derived from normal fibroblast cells to suppress the tumorigenicity of HHUA and Ishikawa cells, human endometrial carcinoma cell lines . Using DNA transfection, the human chromosome tagged with a selectable marker (the pSV2neo gene, which encodes resistance to the antibiotic, G418) was transferred to mouse A9 cells by cell hybridization and microcell fusion techniques . Thus, a library of mouse A9 clones containing individually a different human chromosome tagged with the pSV2neo plasmid DNA was constructed . Transfer by microcell fusion of either chromosome 1, 6, 9, 11 or 19 into the HHUA and Ishikawa cell lines was performed, and the abilities of the microcell hybrids to form tumors in nude mice were examined . The introduction of chromosome 19 had no effect on the tumorigenicity, whereas microcell hybrid clones with an introduced chromosome 1, 6 and 9 completely suppressed the tumorigenicity of the both lines . A decrease in tumor-take incidence in some but not all clones of HHUA cells was observed following the introduction of a chromosome 11 . The nontumorigenic microcell hybrids with an introduced chromosome 1 differed from the nontumorigenic microcell hybrids with an introduced chromosome 6, 9, or 11 . A large percentage of hybrids with chromosome 1 sensed and/or showed alterations in cellular morphology and transformed growth properties in vitro on the both cell lines . These results indicate that more than one chromosome carries a tumor suppressor gene(s) for human endometrial carcinoma cell lines, and indicate that normal human chromosome 1 carries gene(s) which suppresses the immortalization . This supports the hypothesis that multiple tumor suppressor gene(s) control the various tumorigenic phenotypes at the different step during process of neoplastic development.

Biol Pharm Bull, 1994 Nov, 17(11), 1496 - 500
Improvement of the rectal bioavailability of latamoxef sodium by adjuvants following administration of a suppository; Nakanishi K et al.; The absorption of an antibiotic, latamoxef sodium (LMOX), following the rectal administration of a suppository containing adjuvants was investigated . A lipophilic base (Witepsol H15) was used . The rectal absorption of LMOX following the administration of a suppository without adjuvants was very low . Diclofenac sodium (DF) was used as an absorption promoter; it enhances rectal membrane permeability . The blood level of LMOX following the addition of DF(10 mg) to the base was increased only about 1.3-fold compared with that achieved with LMOX alone (difference not significant); even with a higher dose of DF, the absorption of LMOX was not sufficient . The release rate of LMOX from the base was slow . When Tween 80, a non-ionic surfactant, was added to improve the release rate of LMOX, the rate was sufficiently increased . The rectal absorption of LMOX on the addition of both Tween 80 and DF was markedly increased compared to that achieved with LMOX alone or with DF . These results indicate that the rectal absorption of LMOX after administration by a suppository was sufficiently improved by enhancing both the release rate from the base and the membrane permeability of the rectum . Lymphatic uptake and blood levels of LMOX were also investigated after the rectal administration of the LMOX preparation containing both Tween 80 and DF; the lymphatic uptake of LMOX was significantly enhanced compared with the LMOX preparation in which only DF was used as an adjuvant . The mechanism whereby adjuvants lead to the absorption of a non-absorbable drug, and the subsequent drug transportation routes through the membrane are discussed.

Circ Shock, 1994 Nov, 44(3), 138 - 47
Effect of cardiogenic shock on pharmacokinetics and tissue distribution of ampicillin-sulbactam; Arden WA et al.; A reversible cardiogenic shock model in pigs investigated shock-induced changes in the pharmacokinetics and tissue distribution of ampicillin-sulbactam and the efficacy of this antibiotic regimen in eliminating enteric bacterial translocation . Sixteen pigs were randomly allocated to 3 groups: group I (shock, ampicillin-sulbactam, n = 6), group II (no shock, ampicillin-sulbactam, n = 6), and group III (shock, no ampicillin-sulbactam, n = 4) . Nalidixic acid-resistant E . coli (60 x 10(6) CFU) were instilled into a jejunal loop created in each pig, and bacterial cultures were taken from thoracic duct lymph, periportal, and mesenteric lymph nodes . Ampicillin-sulbactam was administered intravenously at a standard dose of 3 g . Results showed that 1) ampicillin and sulbactam concentrations generally increase during cardiogenic shock; 2) cardiogenic shock does not increase ampicillin concentrations in jejunum and liver; 3) during resuscitation, thoracic duct lymph ampicillin concentrations decrease; and 4) during and immediately after cardiogenic shock, standard doses of ampicillin-sulbactam appear efficacious in eliminating translocated bacteria.

Immunopharmacol Immunotoxicol, 1994 Nov, 16(4), 473 - 96
Effect of anticancer drugs on the release of TGF-beta in vitro; Kassem SM et al.; Some conventional and experimental anticancer drugs were tested for their effect on Concanavalin A (Con A)-induced Transforming Growth Factor-beta (TGF-beta) release from BALB/c splenocytes, lipopolysaccharide (LPS)-induced TGF-beta release from Nude mouse splenocytes and BALB/c peritoneal exudate cells stimulated by LPS in vitro . When 5 x 10(6) BALB/c and Nude mouse splenocytes/ml stimulated with 1 microgram/ml Con A, 50ng/ml LPS respectively, and 5 x 10(6)/ml peritoneal exudate cells stimulated with 50ng/ml LPS were incubated with various non-cytotoxic concentrations of the vinca alkaloid Vincristine, there was an inhibition of the release of TGF-beta in culture supernatants of both BALB/c splenocytes and peritoneal exudate cells . But, in Nude mouse Vincristine did not alter the release of TGF-beta . The antitumour antibiotic Bleomycin, the immunoactive peptide FK565 and the immunosuppressive agent Cyclosporin A (CsA) were found to have no effect on the release of TGF-beta from all culture supernatants.

J Cardiovasc Pharmacol, 1994 Nov, 24(5), 813 - 7
Effect of rapamycin on rat aortic ring vasomotion; Corbin F et al.; Rapamycin (RAPA) is an antifungal antibiotic with interesting new immunosuppressive properties . We evaluated RAPA's effects in vitro on basal and stimulated tension of isolated intact or denuded rat aortic rings . Rings were prepared in an organ chamber and contracted with 40 mM KCl (reference 100%) . Some rings were treated with either RAPA's polysorbate/polyethylene glycol-based (PEG) vehicle (0.8% vol/vol) or with different concentrations of RAPA (10, 100, and 1,000 ng/ml) diluted in PEG; untreated rings were used as controls . Variation in tension with time (2 h) and the dose-response to thromboxane A2 analogue (U46619) and phenylephrine (PE) were measured in controls and treated rings . PEG potentiated the increase in basal tension in rings with endothelium after 2-h treatment (44.66 +/- 3.59 vs . 14.82 +/- 2.43% for controls, p < 0.05, n = 10) . RAPA antagonized the contraction induced by its own vehicle dose dependently . At 1,000 ng/ml, RAPA caused relaxation of intact rings below the control level (4.29 +/- 2.20 vs . 14.82 +/- 2.43%, p < 0.05, n = 10), but not in rings without endothelium . RAPA did not modify the response to PE or U46619 in rings with endothelium . RAPA relaxed the vessels by an endothelium-dependent mechanism, and this effect can be modulated by its vasoconstrictive PEG vehicle.

Drugs, 1994 Nov, 48(5), 731 - 60
Filgrastim . A review of its pharmacological properties and therapeutic efficacy in neutropenia; Frampton JE et al.; Filgrastim, a recombinant human granulocyte colony-stimulating factor (G-CSF), has identical biological activity to that of endogenous human G-CSF, but differs in that it contains an N-terminal methionine residue and is not glycosylated . It principally stimulates activation, proliferation and differentiation of neutrophil progenitor cells and has been evaluated in the treatment of patients with various neutropenic conditions, both iatrogenic and disease-related . Two comparative studies have demonstrated that prophylactic administration of filgrastim 230 micrograms/m2/day significantly reduces the incidence, duration and severity of neutropenia in patients with previously untreated small-cell lung cancer receiving standard-dose chemotherapy with CDE (cyclophosphamide, doxorubicin plus etoposide) . Concomitant with the amelioration of neutropenia, the incidence of febrile neutropenia was significantly reduced by 50% and there were 35 and 50% decreases in hospitalisation rates and intravenous antibiotic requirements . Since not all patients receiving standard-dose chemotherapy are at risk of infectious complications, prophylactic filgrastim use may be reserved for those patients who have developed febrile neutropenia during a previous cycle of the same regimen . This strategy may prove less costly, although potential savings must be weighed against a greater risk of patient morbidity and reduced quality of life . When combined with standard intravenous antibiotic therapy, filgrastim further decreases morbidity in patients with established febrile neutropenia and may have a positive impact on overall treatment costs by shortening the length of hospitalisation . Attention is focused on the use of haematopoietic growth factors to support dose-intensification of chemotherapy with a view to improving treatment outcomes in patients with chemo-responsive tumours . Filgrastim, used alone, permits modest increases in dose-intensity and/or dose-escalation of some standard-dose chemotherapy regimens . Moreover, the drug has proven useful as an adjunct to myeloablative chemotherapy followed by stem cell rescue with autologous bone marrow transplantation and/or peripheral blood progenitor cells . However, the impact of these dose-intensification approaches on survival remains to be determined in well-controlled clinical studies . Filgrastim is effective in increasing the neutrophil count and decreasing morbidity in patients with severe chronic neutropenia, including Kostmann's syndrome, and in idiopathic and cyclic neutropenia . In addition, filgrastim has accelerated neutrophil recovery in patients with idiosyncratic drug-induced agranulocytosis . Available data indicate that filgrastim is generally well tolerated . The most frequent adverse reaction is mild to moderate medullary bone pain, reported by approximately 20% of patients, although this can generally be controlled using simple analgesics without the need to discontinue treatment.(ABSTRACT TRUNCATED AT 400 WORDS)

Am J Respir Crit Care Med, 1994 Nov, 150(5 Pt 1), 1391 - 401
Dexamethasone and oxytetracycline reverse the potentiation of neurogenic inflammation in airways of rats with Mycoplasma pulmonis infection; Bowden JJ et al.; Mycoplasma pulmonis infection in rats causes a chronic inflammatory airway disease . Along with extensive remodeling of the airway mucosa, lymphocytic infiltrates, angiogenesis, and mucosal thickening, there is an abnormal sensitivity of the blood vessels to mediators that evoke "neurogenic inflammation" . As a result, substance P, a peptide released from sensory nerves, produces an unusually large amount of plasma leakage . These changes can be prevented or reduced by prophylactic treatment with antibiotics, but it is unknown whether the extensive remodeling of the airway mucosa and potentiation of neurogenic inflammation can be reversed once they are established . We addressed this issue in F344 rats that were infected with M . pulmonis at 8 wk of age . Six weeks later, the rats were treated daily with an antibiotic (oxytetracycline, 20 mg/kg intramuscularly), to reduce the number of infecting organisms, or with an antiinflammatory steroid (dexamethasone, 0.5 mg/kg intraperitoneally), to reduce the inflammatory and immunologic response to the infection . Sham-treated infected rats received daily injections of 0.9% NaCl . After 1, 2, or 4 wk of treatment the rats were anesthetized and then challenged with substance P (5 micrograms/kg intravenously) . The sham-treated rats had pathologic changes in their airways typical of severe M . pulmonis infection, and had as much as a threefold increase in substance P-induced plasma leakage . By comparison, after 4 wk of treatment with oxytetracycline or dexamethasone, the chronic inflammation was nearly resolved and the response to substance P was in the normal range . Unexpectedly, dexamethasone, like oxytetracycline, reduced the number of infecting organisms.(ABSTRACT TRUNCATED AT 250 WORDS)

Br J Cancer, 1994 Nov, 70(5), 943 - 5
Filgrastim fails to improve haemopoietic reconstitution following myeloablative chemotherapy and peripheral blood stem cell rescue; Dunlop DJ et al.; The morbidity of high-dose chemotherapy has been considerably reduced by the use of autologous peripheral blood progenitor cell reinfusion . Most studies have used myeloid colony-stimulating factors after stem cell reinfusion, making it difficult to determine the relative contribution of each of these variables to the early recovery of blood cells . The financial implications of colony-stimulating factor use are an area of concern as dose intensification in chemosensitive malignancies is increasingly employed . We have studied 19 consecutive patients receiving high-dose chemotherapy with and without filgrastim (Amgen, granulocyte colony-stimulating factor, G-CSF) after stem cell infusion to examine its effect on the kinetics of blood cell recovery, the complications of myelosuppression and the associated costs . Analysis of the two treatment groups reveals that administration of filgrastim 10 micrograms kg-1 day-1 following stem cell reinfusion does not further accelerate haemopoietic recovery, fails to reduce the incidence of neutropenic fever or antibiotic usage and significantly increases the cost of the procedure . The results of this study do not support the routine use of filgrastim after high-dose chemotherapy and peripheral blood stem cell reinfusion.

Mutat Res, 1994 Nov, 325(2-3), 91 - 8
Adriamycin induces large deletions as a major type of mutation in CHO cells; Yu Y et al.; Adriamycin (ADR), a commonly used cancer chemotherapy antibiotic, exhibits a variety of genotoxicities . In this study, we have examined the mutagenicity of ADR at the hypoxanthine-guanine phosphoribosyltransferase gene (hprt) in Chinese hamster ovary (CHO) cells and the xanthine-guanine phosphoribosyltransferase locus (gpt) in a pSV2gpt-transformed CHO cell line, AS52 . Although ADR induced a dose-dependent increase of mutant frequency at both loci, it was more mutagenic to the gpt gene than to the hprt locus . Multiplex PCR analysis revealed that 35% of the 103 independent ADR-induced HPRT-deficient mutants carried large deletions . Among these deletion mutants, 33% were total gene deletions, 22% affected multiple exons, and 42% involved a single exon, of which most (9/15) were exon 1 . The majority (63%) of ADR-induced AS52 mutants had a total deletion of the gpt gene . These observations indicate that ADR induces large deletions as a major type of gene mutation in mammalian cells, suggesting the involvement of reactive oxygen species as one mutagenic pathway in the mutagenesis of ADR.

Exp Hematol, 1994 Nov, 22(12), 1197 - 202
Effects of rhG-CSF (filgrastim) on the recovery of hematopoiesis after high-dose chemotherapy and autologous peripheral blood stem cell transplantation in children: a report from the Children's Cancer and Leukemia Study Group of Japan; Suzue T et al.; In a nonrandomized study, hematopoietic recovery kinetics were evaluated in 98 consecutive patients who underwent high-dose chemotherapy without total body irradiation (TBI) and autologous peripheral blood stem cell transplantation (PBSCT) . Fifty-three patients received recombinant human granulocyte colony-stimulating factor (rhG-CSF) (filgrastim) therapy after PBSCT, and the data were compared by actuarial analysis to those of 45 historic controls . The number of days required to achieve a white blood cell count (WBC) of 1 x 10(9)/L, an absolute granulocyte count (AGC) of 5 x 10(8)/L, and a platelet count (PLT) of 5 x 10(10)/L were, respectively, 12.8 +/- 6.4 (mean +/- standard deviation {SD}), 13.4 +/- 6.4, and 49.2 +/- 78.2 in treated patients vs . 12.8 +/- 4.6, 14.4 +/- 10.3, and 31.4 +/- 38.8 days in historic controls, with no significant differences . There was no significant difference between the average number of days with fever in the treated group (6.0 +/- 6.6) and that in the control group (4.0 +/- 2.8) . All febrile episodes responded promptly and successfully to parenteral antibiotic therapy . Thus, the data may suggest the possibility that therapy with filgrastim has only a limited ability to enhance hematopoietic recovery after PBSCT . To confirm this notion, we initiated a prospective randomized trial by recruiting a larger number of patients.

EMBO J, 1994 Oct 17, 13(20), 4877 - 85
The structural and functional basis for the kirromycin resistance of mutant EF-Tu species in Escherichia coli; Mesters JR et al.; A structural and functional understanding of resistance to the antibiotic kirromycin in Escherichia coli has been sought in order to shed new light on the functioning of the bacterial elongation factor Tu (EF-Tu), in particular its ability to act as a molecular switch . The mutant EF-Tu species G316D, A375T, A375V and Q124K, isolated by M13mp phage-mediated targeted mutagenesis, were studied . In this order the mutant EF-Tu species showed increasing resistance to the antibiotic as measured by poly(U)-directed poly(Phe) synthesis and intrinsic GTPase activities . The K'd values for kirromycin binding to mutant EF-Tu.GTP and EF-Tu.GDP increased in the same order . All mutation sites cluster in the interface of domains 1 and 3 of EF-Tu.GTP, not in that of EF-Tu.GDP . Evidence is presented that kirromycin binds to this interface of wild-type EF-Tu.GTP, thereby jamming the conformational switch of EF-Tu upon GTP hydrolysis . We conclude that the mutations result in two separate mechanisms of resistance to kirromycin . The first inhibits access of the antibiotic to its binding site on EF-Tu.GTP . A second mechanism exists on the ribosome, when mutant EF-Tu species release kirromycin and polypeptide chain elongation continues.

Am J Cardiol, 1994 Oct 15, 74(8), 807 - 9
Bacterial pericarditis in infancy and childhood; Dupuis C et al.; The authors report on a cooperative study of 43 cases of bacterial pericarditis observed in children . This disorder was suspected in patients with septicemia who developed symptoms and signs of pericarditis (precordial pain, muffled heart sounds, pericardial friction rub, cardiomegaly) . Early diagnosis of this condition is now facilitated by echocardiography . A combination of medical and surgical treatments (appropriate antibiotic therapy after culture and sensitivity tests and early pericardial drainage) led to complete recovery in almost all of the cases (42 of 43) . After long-term follow-up, no cases of constrictive pericarditis were observed.

Eur J Biochem, 1994 Oct 15, 225(2), 755 - 64
Enzymology of FK-506 biosynthesis . Purification and characterization of 31-O-desmethylFK-506 O:methyltransferase from Streptomyces sp . MA6858; Shafiee A et al.; FK-506 is a macrolide antibiotic with immunosuppressant activity . Structurally, this compound contains three methylated hydroxyl groups at C13, C15 and C31 . Previous biosynthetic studies using stable isotope-feeding experiments have established methionine as the source of the methyl for these methylated hydroxyl groups . Based on this information and also the availability of the 31-O-desmethylFK-506, a metabolic precursor for the biosynthesis of FK-506, a S-adenosyl-L-methionine-dependent enzyme assay was developed and the enzyme 31-O-desmethylFK-506 O:methyl-transferase was isolated from an extract of Streptomyces sp . MA 6858 and purified to near homogeneity . 31-O-DesmethylFK-506 O:methyltransferase is a monomeric protein with an apparent molecular mass of 30,000 Da and a pI of 4.4 . The first 38 N-terminal amino acids have been sequenced and are H2N-SDVVETLRLPNGATVAHVNAGEAQFLYREIFTDRXYLRH . Functionally, This enzyme has a requirement for Mg2+ with an optimum temperature of 34 degrees C and a pH of 7.4 for full activity . Moreover, it catalyses the methylation of 31-O-desmethylimmunomycin as efficiently as its own natural substrate, 31-O-desmethylFK-506 . Additionally, FKMT catalyzes the C31 transmethylation reaction of 13,31-O-bis-desmethyl-, 15,31-O-bisdesmethyl-, 13,15,31-O-trisdesmethyl- and 31-O-19,22-cyclic-hemiketalimmunomycins, which are all structural analogues of FK-506 . The reaction is, however, completely blocked if the vicinal hydroxyl which is present at the C-32 position of the 31-O-desmethylFK-506 structure is replaced with azide, phosphate or other substituents . Finally, evidence is presented indicating the close similarity of FKMT and DIMT, a 31-O-desmethyl-immunomycin: O methyltransferase, previously isolated from a cell-free extract of Streptomyces hygroscopicus var ascomyceticus, an immunomycin (ascomycin/FK-520) producer.

Biochem Biophys Res Commun, 1994 Oct 14, 204(1), 76 - 83
Rifampicin prevents the aggregation and neurotoxicity of amyloid beta protein in vitro; Tomiyama T et al.; The aggregation and cerebral deposition of amyloid beta protein (A beta), which is a major component of senile plaques in Alzheimer's disease (AD) brains, is believed to be involved in the pathogenesis of AD . Inhibition of A beta aggregation would seem to be a promising strategy for the treatment of AD . Here, we show that rifampicin, which is an antibiotic widely used in the treatment of tuberculosis and leprosy, inhibited the aggregation and fibril formation of synthetic A beta 1-40 peptide in a dose-dependent manner at reasonable concentrations . Furthermore, rifampicin was found to prevent A beta 1-40-induced neurotoxicity on rat pheochromocytoma PC12 cells . Rifampicin may have therapeutic potential as an agent for inhibiting the initial step of amyloid formation in AD.

Nucleic Acids Res, 1994 Oct 11, 22(20), 4268 - 75
Patterns of intracellular compartmentalization, trafficking and acidification of 5'-fluorescein labeled phosphodiester and phosphorothioate oligodeoxynucleotides in HL60 cells; Tonkinson JL et al.; We have examined the intracellular compartmentalization and trafficking of fluorescein labeled (F) phosphodiester (PO) and phosphorothioate (PS) oligodeoxynucleotides (oligos) in HL60 cells . A series of F-oligos (PO and PS) were incubated for 6 hrs . with HL60 cells and the mean intracellular fluorescence determined by flow cytometry . The F signal was normalized by the addition of the ionophore monensin . An increase in signal intensity following addition of monensin indicated that the oligo was resident in an acidic intracellular environment . F-PS, but not F-PO oligos were found to reside in an acidic environment . An exception was a PO homopolymer of 15 cytidine bases (FOdC15) which was acidified . Using two different methods, the average resident intracellular pH of F-PS oligos and F-OdC15 was shown to be approximately 1 pH unit lower than that of F-PO oligos . Acidification of F-PS oligos could be blocked by the antibiotic bafilomycin, indicating that acidification was occurring in endosomes or vacuoles . F-PO and F-PS oligos were effluxed from HL60 cells from two intracellular compartments . However, approximately 60% of internalized F-PO oligo resided in a 'shallow' compartment that was turned over rapidly (t1/2 = 5-10 min.) whereas only 20% of F-PS oligo resided in this compartment . Conversely, approximately 80% of the internalized F-PS oligo but only 40% of F-PO oligo resided in a 'deep' compartment that turned over with t1/2 = 2-5 hrs . This report is the first quantitative demonstration that PO and PS oligos, and PO oligos of different sequences are trafficked differently by HL60 cells.

Pharmacoeconomics, 1994 Nov, 6(5), 464 - 77
Economic evaluation of immunoprophylaxis in children with recurrent ear, nose and throat infections; Banz K et al.; This study compares the costs of immunoprophylaxis versus no immunoprophylaxis in children with recurrent ear, nose and throat (ENT) infections (otitis media and rhinopharyngitis) using ribosomal immunotherapy ('Ribomunyl') . The per-patient cost of ribosomal immunotherapy (FF297) is offset by direct savings garnered through the prevention of many acute infectious episodes . The net 6-month per-patient savings associated with immunoprophylaxis range from FF272 to FF1704, depending on the indication and the type of treatment-cost estimate . Saved healthcare resources include physician consultations and visits, laboratory tests, medicotechnical services (audiometric tests) and antibiotic therapy . Sensitivity analysis of efficacy and treatment-cost estimates enabled threshold ranges of incremental efficacy to be identified . Cost-equivalence between the 2 treatment options was found to exist when the incremental efficacy of immunoprophylaxis lay between 7.4 and 17.5% (recurrent otitis media), and between 8.9 and 26.1% (recurrent rhinopharyngitis) . Thus, even when clearly lower incremental efficacy rates than those reported in controlled clinical trials (approximately 40 to 60%) are assumed, ribosomal immunotherapy can still be expected to be cost effective . An analysis of the perspectives of the various payers in the French healthcare system demonstrated that net savings occurred for all payers involved . However, social security insurance would gain most from an immunoprophylaxis programme . Based on the evidence presented here for France, physicians and payers should give increased attention to this treatment option.

Ulster Med J, 1994 Oct, 63(2), 144 - 50
Complications associated with central venous catheters in a haematology unit; Sharpe PC et al.; The use of central venous catheters in patients suffering from haematological disorders has brought enormous benefits, but has been associated with an increase in septicaemia . We have reviewed septic and other complications in 43 patients who received one of three different forms of central venous catheters (type A-Hickman, type B-Portacath, type C-Pasport) during 1991 . All complications were reviewed up to 18 months following insertion . The total complication rate was 31% (0.97 per 100 catheter days), and the total sepsis complication rate was 18.8% (0.49 per 100 catheter days) . Type A catheters had the greatest sepsis complication rate of 29.5% (0.84 per 100 catheter days), with type B 15% (0.39 per 100 catheter days) and type C 9.9% (0.32 per 100 catheter days) . Prophylactic antibiotics on the day of catheter insertion did not reduce the sepsis rate or prolong catheter survival.

Br J Anaesth, 1994 Oct, 73(4), 545 - 7
Meningitis after combined spinal-extradural anaesthesia in obstetrics; Harding SA et al.; We report two cases of meningitis which developed after combined spinal-extradural procedures for obstetric analgesia . The first case was thought to be caused by aseptic or chemical meningitis and the second was a case of bacterial meningitis in a patient who also received an extradural blood patch . It is important that meningitis is considered as a differential diagnosis in patients who present with headache after spinal anaesthesia and that antibiotic therapy is selected to cover unusual organisms.

Compendium . 1994 Oct;15(10):1228, 1230, 1232 passim; quiz 1244.
Drug interactions in dental practice: a summary of facts and controversies; Becker DE; The potential for drug interactions is a concern to all dentists . The issue is made even more imposing by the amount of scientific information published each month . It is not only important for dentists to be aware of interactions that have been established, but also those that are no longer tenable . Of particular concern are continued misconceptions about the antibiotic-oral contraceptive and the vasopressor-antidepressant interactions . This article will clarify these issues as well as highlight established interactions associated with those drug classes used most frequently in dental practices.

Arch Surg, 1994 Oct, 129(10), 1031 - 41; discussion 1042
Effect of interferon gamma on infection-related death in patients with severe injuries . A randomized, double-blind, placebo-controlled trial; Dries DJ et al.; OBJECTIVE: To assess the efficacy of interferon gamma in reducing infection and death in patients sustaining severe injury . DESIGN: Multicenter, randomized, double-blind, placebo-controlled trial with observation for 60 days and until discharge for patients with major infection on day 60 . SETTING: Nine university-affiliated level 1 trauma centers . PATIENTS: Four hundred sixteen patients with severe injuries, assessed by Injury Severity Score and degree of contamination . INTERVENTION: Recombinant human interferon gamma, 100 micrograms, was administered subcutaneously once daily for 21 days (or until patient discharge if prior to 21 days) as an adjunct to standard antibiotic and supportive therapy . MAIN OUTCOME MEASURES: Incidence of major infection, death related to infection, and death . RESULTS: Infection rates were similar in both treatment groups; however, patients treated with interferon gamma experienced fewer deaths related to infection (seven {3%} vs 18 {9%}; P = .008) and fewer overall deaths (21 {10%} vs 30 {14%}; P = .17) . While 12 early deaths (days 1 through 7) occurred in each treatment group, late death occurred in 18 placebo-treated patients and nine in interferon gamma-treated patients . The results were dominated by findings at one center, which had the highest enrollment and higher infection and death rates . Statistical analysis did not eliminate the possibility of an unidentified imbalance between arms as an explanation for the results . CONCLUSION: Further evaluation is required to determine the validity of the observed reduction in infection-related deaths in patients treated with interferon gamma.

J Gen Virol, 1994 Oct, 75 ( Pt 10), 2595 - 606
Involvement of the vacuolar H(+)-ATPase in animal virus entry; Perez L et al.; Semliki Forest virus (SFV) enters cells by receptor-mediated endocytosis, followed by acidification of endosomes by the action of the vacuolar H(+)-ATPase . Fusion of the viral and the endosomal membrane delivers the viral genome to the cytoplasm . Direct blockade of the vacuolar H(+)-ATPase by the selective inhibitor bafilomycin A1 (BFLA1) prevented the infection of cells by SFV, if the compound was present during the first minutes of infection . Attachment and penetration of virus particles were not the targets of the antibiotic . BFLA1 and the ionophore monensin potently blocked SFV infection even at low pH, indicating that acidic pH is not sufficient for SFV to deliver its genome to the cytoplasm, but the proper functioning of the H(+)-ATPase pump is necessary . Other enveloped RNA-containing viruses, such as vesicular stomatitis virus or influenza virus were also blocked by BFLA1, whereas no effect was observed with Sendai virus, which enters into cells by direct fusion with the plasma membrane . Enveloped DNA-containing viruses, such as herpes-viruses and vaccinia virus, infected the cells even when the vacuolar H(+)-ATPase was inhibited by BFLA1; similar behaviour was observed with poliovirus and adenovirus . Animal virus particles promote the internalization of proteins and other macromolecules during entry . BFLA1 blocked co-entry of the toxin alpha-sarcin when induced by SFV, but not when induced by Sendai virus . The inhibition of the enzyme responsible for acidification of endosomes by means of the potent inhibitor BFLA1 constitutes a selective and powerful tool to analyse the low-pH dependent mechanism(s) during virus entry and will aid in understanding the mechanisms and routes of entry of animal viruses into cells.

J Bacteriol, 1994 Oct, 176(20), 6270 - 80
Isolation and sequence analysis of polyketide synthase genes from the daunomycin-producing Streptomyces sp . strain C5; Ye J et al.; A contiguous region of about 30 kbp of DNA putatively encoding reactions in daunomycin biosynthesis was isolated from Streptomyces sp . strain C5 DNA . The DNA sequence of an 8.1-kbp EcoRI fragment, which hybridized with actI polyketide synthase (PKS) and actIII polyketide reductase (PKR) gene probes, was determined, revealing seven complete open reading frames (ORFs), two in one cluster and five in a divergently transcribed cluster . The former two genes are likely to encode PKR and a bifunctional cyclase/dehydrase . The five latter genes encode: (i) a homolog of TcmH, an oxygenase of the tetracenomycin biosynthesis pathway; (ii) a PKS Orf1 homolog; (iii) a PKS Orf2 homolog (chain length factor); (iv) a product having moderate sequence identity with Escherichia coli beta-ketoacyl acyl carrier protein synthase III but lacking the conserved active site; and (v) a protein highly similar to several acyltransferases . The DNA within the 8.1-kbp EcoRI fragment restored daunomycin production to two dauA non-daunomycin-producing mutants of Streptomyces sp . strain C5 and restored wild-type antibiotic production to Streptomyces coelicolor B40 (act VII; nonfunctional cyclase/dehydrase), and to S . coelicolor B41 (actIII) and Streptomyces galilaeus ATCC 31671, strains defective in PKR activity.

J Bacteriol, 1994 Oct, 176(19), 6045 - 9
Genetic transformation of the Lyme disease agent Borrelia burgdorferi with coumarin-resistant gyrB; Samuels DS et al.; No useful method to genetically manipulate Borrelia burgdorferi, the causative agent of Lyme disease, has been developed previously . We have used resistance to the coumarin antibiotic coumermycin A1, an inhibitor of DNA gyrase, as a genetic marker to monitor the transformation of B . burgdorferi by electroporation . Introduction of site-directed mutations into the gyrB gene demonstrated that transformation was successful, provided evidence that homologous recombination occurs on the chromosome, and established that mutations at Arg-133 of DNA gyrase B confer coumermycin A1 resistance in B . burgdorferi . The coumermycin A1-resistant gyrB marker and genetic transformation can now be applied toward dissecting the physiology and pathogenesis of the Lyme disease agent on a molecular genetic level.

Infect Immun, 1994 Oct, 62(10), 4101 - 6
C9-mediated killing of bacterial cells by transferred C5b-8 complexes: transferred C5b-9 complexes are nonbactericidal; Blanchard KP et al.; The formation of the C5b-9 complex on the outer membrane of complement-sensitive cells of Escherichia coli results in inhibition of inner membrane function and the death of the cell . Cells bearing a precursor of the C5b-9 site, the C5b-8 complex, suffer no loss in viability . Antibiotic-sensitive, complement-sensitive donor cells bearing precursor C5b-8 complexes were incubated with equal numbers of antibiotic-resistant, complement-sensitive acceptor cells that had not been exposed to a complement source . This cell mixture was incubated with 5 mM EDTA for 5 min and then with calcium chloride (20 mM) for various times . The excess calcium ion concentration was effectively reduced with additional EDTA, and the cell mixture was washed and resuspended in buffer . The viability of the acceptor cells was assayed by plating on antibiotic-containing media . C9 was added to the mixture, and the mixture was incubated for 10 min at 37 degrees C and then plated as described above . It was found that the acceptor cells were killed by the addition of purified C9 only after incubation with donor cells bearing C5b-8 sites during the transfer procedure . This indicates that precursor C5b-8 sites that support C9-mediated killing could be transferred between cells . No loss in viability was detected for acceptor cells subjected to the procedure described above in the presence of donor cells bearing complete C5b-9 complexes, formed prior to mixing with acceptor cells for the transfer procedure.

Clin Orthop, 1994 Oct, (307), 174 - 81
Staged arthrodesis for salvage of the septic hallux metatarsophalangeal joint; Myerson MS et al.; Failed surgery at the hallux metatarsophalangeal joint may present substantial difficulties in treatment, especially when complicated by infection . This retrospective study reviews the staged treatment of 5 patients with complications of hallux valgus surgery associated with sepsis of the metatarsophalangeal joint . The initial salvage treatment included debridement with placement of an antibiotic cement spacer and either an intramedullary Kirschner wire (4 patients) or an external fixator (1 patient) . At the second stage procedure, the spacer and fixation were removed, and an autogenous tricortical iliac crest graft was inserted into the joint . All patients had clinical control of joint sepsis . Pseudoarthrosis occurred at the proximal end of the tricortical graft in 2 patients . Patients were evaluated at an average of 28 months after the fusion . Staged arthrodesis appears to be a satisfactory approach to postoperative sepsis of the hallux metatarsophalangeal joint.

Br J Cancer, 1994 Oct, 70(4), 631 - 5
Deleterious effect of serum proteins on the amphotericin B-induced potentiation of cisplatin in human colon cancer cells; Assem M et al.; Inherent resistance of colon cancer cells to cis-diamminedichloroplatinum(II) (CDDP) is partly attributed to reduced drug penetration through plasma membrane . Amphotericin B (AmB), a polyene antifungal antibiotic, has been shown to increase CDDP penetration and cytotoxicity on several non-digestive cancer cell lines . We demonstrated here that AmB dramatically increases the penetration of CDDP, and to a lesser extent that of carboplatin (Carbo-P) and oxaloplatin (L-OHP), in the primary resistant HT 29 human colon cancer cells when drug incubation is performed in serum-free medium . The cytotoxicity of CDDP but not that of Carbo-P and L-OHP was increased by AmB . However, AmB-induced potentiation of CDDP penetration and toxicity was almost completely abolished when cell incubation was performed in presence of human serum . We investigated whether the dilution of human serum by a high osmotic power gelatine solution (Lomol) could restore the positive effect of AmB on CDDP accumulation in HT 29 cells . Incubation of cells with CDDP and AmB in pure Lomol resulted in a 6-fold increase in platinum cellular content . However, addition of serum (25%) in Lomol solution reduced to only 2-fold the increase in platinum cellular content provoked by AmB . These disappointing results show that AmB is probably uninteresting as a modulator of CDDP resistance in clinical practice . The use of haemodilution to restore the positive AmB effect on platinum cellular accumulation cannot be warranted.

Arch Histol Cytol, 1994 Oct, 57(4), 395 - 403
Fine structural aspects on auditory hair cell degeneration in the budgerigar, Melopsittacus undulatus, as induced by kanamycin; Umemoto M et al.; The effects of kanamycin, an antibiotic of the aminoglycoside group, on the auditory sensory epithelium of the budgerigar, Melopsittacus undulatus, were examined using both scanning and transmission electron microscopes . Results show that the threshold of the auditory brainstem response increased in birds treated with kanamycin 200 mg/kg for 49 days . While the auditory sensory epithelium of the normal budgerigar consists of short and tall hair cells, and supporting cells, following kanamycin administration, the middle to proximal region of the epithelium of the inner ear showed degenerative changes, with the other parts remaining apparently intact . In the damaged region, the short hair cells were flattened, and the tall ones became heterogeneous in shape . Both types of cells contained many dense bodies in their cytoplasm; they were rounded in shape and homogeneously dense . Severely degenerated tall hair cells also contained many large vacuoles with heterogeneous contents . Because the dense bodies and large vacuoles were positive for acid phosphatase reaction, they were respectively judged to be primary lysosomes and secondary lysosomes containing degenerating cell debris . Most supporting cells in the impaired region were lower in cytoplasmic electron density, and their apical surface became enlarged in area . Some flattened short hair cells were situated on the apical part of the swollen supporting cells . This finding suggests that the short hair cells are pressed toward the scala media by the supporting cells.

Endosc Surg Allied Technol, 1994 Oct, 2(5), 265 - 8
Technique and results using the glass-rectoscope for tumour resection; Seifart W; The glass-rectoscope, developed by P . Dewey is a cylinder speculum with a closed end and a working window at the side . This is a cheap instrument and method for transanal approach to the lower rectum . After preparation of the patient by saline lavage the day before operation and one dose antibiotic preoperatively, the operation is performed under general or epidural anesthesia . The digital slow dilatation of the anal sphincter is followed by introduction of the instrument, of which several versions are available . After focusing the lesion in the working window, diathermy-excision of the mucosa or of the total rectal wall is performed . Bleeding is controlled by electrocoagulation or by continuous suture of the resulting defect in the rectal wall . In 34 patients treated by transanal tumour resection, there was one local infection and four postoperative haemorrhages required operative revision by resuture . The method is suitable for removing lesions of the lower rectum up to the diameter of 2 cm and for stage T1N0 malignant lesions.

J Endourol, 1994 Oct, 8(5), 365 - 9
Role of laparoscopic pelvic lymph node dissection in the management of patients with penile cancer and inguinal adenopathy; Assimos DG et al.; Patients with invasive squamous cell carcinoma of the penis and tumor involvement of the inguinal nodes are at risk for pelvic lymph node metastases . When this spread occurs, the chance for patient survival is limited . Because the sensitivity of CT in detecting pelvic lymph node metastases is low, open surgical pelvic lymphadenectomy is frequently performed . We have utilized laparoscopic pelvic lymphadenectomy as a minimally invasive alternative to this open approach in three patients with Stage T3 (UICC staging system) squamous cell carcinoma of the penis who had persistent inguinal adenopathy after a standard course of postpenectomy antiobiotic therapy . There were no intraoperative or postoperative complications, and all patients were discharged within 24 hours after surgery . The mean number of nodes removed was eight, and all specimens were free of tumor . Laparoscopic pelvic lymphadenectomy should be considered in patients with persistent inguinal adenopathy after antibiotic therapy before proceeding with inguinal lymph node dissection.

J Vet Diagn Invest, 1994 Oct, 6(4), 423 - 7
Mycoplasma infection in a commercial goat dairy caused by Mycoplasma agalactiae and Mycoplasma mycoides subsp . mycoides (caprine biotype); Kinde H et al.; A commercial dairy goat herd of 600 animals experienced sudden onset of arthritis/polyarthritis, clinical mastitis, and sudden death in does . The offending infectious agents were Mycoplasma agalactiae and M . mycoides subsp . mycoides (caprine biotype) . The disease syndrome began approximately 4 weeks following the 1) introduction into the herd of a lactating doe with no apparent clinical signs and 2) a breakdown of proper hygienic conditions in the milking parlor . Over a period of 3 weeks, 90 does (15%) either died or were culled because of arthritis/polyarthritis and mastitis . A management decision resulted in only the does affected with M . mycoides subsp . mycoides being submitted for necropsy; those affected with M . agalactiae, which were in a different "string," were not submitted for evaluation . Gross necropsy of the does affected with M . mycoides subsp . mycoides showed purulent discharges from the udders, enlarged supramammary lymph nodes, enlarged and firm spleens, and swollen livers . Microscopic findings were characterized by a loss of vascular integrity and diffuse fluid leakage in multiple organs . Antibiotic therapy with tylosin was attempted but was not successful . The outbreak was terminated following the removal or segregation of affected does and implementation of hygienic conditions in the milking parlor.

J Vet Pharmacol Ther, 1994 Oct, 17(5), 365 - 8
Thiamphenicol pharmacokinetics in beef and dairy cattle; Abdennebi EH et al.; The pharmacokinetics of thiamphenicol were investigated in 10 calves and six lactating cows . It was found that this drug is rapidly absorbed (15 min) following intramuscular injection with an absorption rate constant and a bioavailability of 8.7 h-1 and 84%, respectively . The drug appears to be widely distributed into various body fluids, yielding a volume of distribution (Vd(area) of approximately 0.9 l/kg . The micro-rate constants indicated that the antibiotic rapidly diffuses into the peripheral compartment (k12 > k21) . Elimination from plasma is relatively rapid, with a biological half-life of about 1.75 h . Thiamphenicol appears shortly in milk (15 min) after its intravenous administration, and gives milk to plasma concentration ratios greater than one between 4 and 12 h.

Nihon Kyobu Shikkan Gakkai Zasshi, 1994 Oct, 32(10), 1032 - 7
{Two cases of invasive pulmonary aspergillosis in non-immunocompromised hosts}; Sugimura S et al.; Invasive pulmonary aspergillosis generally occurs in immunocompromised hosts such as patients with leukemia, and other malignancies, who are receiving anti-cancer chemotherapy . In this report, two non-immunocompromised patients who developed invasive pulmonary aspergillosis are presented . Case 1: A 63-year-old man complained of productive cough and fever . He received antibiotic therapy from his personal physician . This symptoms did not respond, however, and dyspnea developed . He was then transferred to our hospital, about one month after the onset . The chest X-ray showed a meniscus shadow suggesting an aspergilloma in the right upper lung field and an infiltrative shadow in the remaining right lung field . Case 2: A 78-year-old man was admitted because of dyspnea, productive cough and appetite loss over the previous three months . The chest X-ray showed a meniscus shadow in the left upper field, an infiltrative shadow in the left lower field and a right pleural effusion sign was also observed . Both cases were diagnosed as having aspergillosis, early in their illness, by the detection of aspergillus antigen in their sera and histopathological and cultural studies of specimens obtained by TBLB . Both improved with intravenous amphotericin B (30 mg/day) and intravenous ulinastatin (200000 IU/day) administration . On the examinations conducted during hospitalization, there was no evidence of any immunosuppressive diseases or immunoincompetent conditions such as leukemia, and other malignancies human immunodeficiency virus infection, diabetes or alcoholism.

Endod Dent Traumatol, 1994 Oct, 10(5), 233 - 8
Reaction of inflamed periapical tissue to intracanal medicaments and root canal sealers; Tepel J et al.; The effects of different intracanal medicaments and zinc oxide-eugenol based root canal sealers on an experimentally induced apical periodontitis were studied histologically in mesial roots of lower molars of Wistar rats . After root canal instrumentation each canal was filled either with an intracanal medicament twice for 3 days each time or with a sealer for 21 days . The intracanal medicament chlorophenol caused periapical tissue damage . P-chloroxylenol-camphor lead to periapical improvement as did 5% sodium-hypochlorite . 12% sodium-hypochlorite gave tissue damage . After intracanal medication with an aqueous suspension of calcium hydroxide periapical repair was clearly visible . A combination of a corticoid and an antibiotic appeared to induce damage of the periapical tissues . The root canal sealers Endomethasone and N2 essentially impaired periapical repair . The results were acceptable for Aptal-Zink-Harz root canal fillings after 21 days as well as after 56 days.

Med Vet Entomol, 1994 Oct, 8(4), 381 - 5
Protein hydrolysates and associated bacterial contaminants as oviposition attractants for the mosquito Culex quinquefasciatus; Beehler JW et al.; Six protein or protein hydrolysate solutions were tested for activity as attractants for ovipositing Culex quinquefasciatus mosquitoes in the laboratory . Four of these solutions (egg albumin, lactalbumin hydrolysate, casein hydrolysate and yeast hydrolysate) were attractive to ovipositing females at varying concentrations, when compared to distilled water controls . Soy hydrolysate was repellent at 1%, but not significantly attractive or repellent at lower concentrations . 'Nulure', a tephritid fly bait containing protein hydrolysate, also had no significant effect on oviposition behaviour . Gravid females mostly oviposited within the first 4 h of the scotophase, regardless of the presence or absence of an oviposition attractant . Lactalbumin hydrolysate 1% solution, with or without 0.1% neomycin antibiotic, was attractive to Cx quinquefasciatus . This effect was reduced by the presence of neomycin which, alone, had no effect on oviposition . Hence both lactalbumin hydrolysate and bacterial contaminants were shown to be attractive to gravid Cx quinquefasciatus.

J Obstet Gynecol Neonatal Nurs, 1994 Oct, 23(8), 675 - 81
Home infusion therapies for obstetric patients; Romeo CC et al.; This article focuses on current indications for home intravenous therapy for the high-risk obstetric patient . Therapeutic indications and clinical care for obstetric patients in need of hydration/total parenteral nutrition, heparin infusion, terbutaline pump, and antibiotic therapies are presented.

J Community Health, 1994 Oct, 19(5), 307 - 18
Quality of care problems among Medicare and Medicaid patients; Nenner RP et al.; The purpose of this study was to characterize quality of care problems among Medicare and Medicaid inpatients in New York State . The patients selected for this study comprised 1991 and 1992 Medicare and all 1992 Medicaid inpatients in whom quality of care problems with actual or potential adverse effects were found . The patients in this study were drawn from public, proprietary, voluntary and teaching hospitals . A total of 1000 quality of care problems with either actual or potential adverse effects were found in 706 Medicare patients . Two hundred and seventy-five (275) quality of care problems with actual or potential adverse effects were found in 154 Medicaid patients . Premature death occurred in 53 (7.4%) of the 706 Medicare and in 42 (27.2%) of the 154 Medicaid patients . Treatment problems and monitoring failures accounted for the majority of quality of care problems with actual or potential adverse effects for both Medicare (63.0%) and Medicaid (75.7%) patients . Among Medicare patients, the treatment of infections and antibiotic use, fluid and electrolyte management, and inappropriate drug use were among the leading causes of quality of care problems . Attending physicians were associated with the majority of Medicare quality of care problems while house staff and attending physicians were associated with the majority of those among Medicaid patients . The results of this study indicate that there are several leading causes of quality of care problems among Medicare and Medicaid patients . Treatment problems and monitoring failures together comprise the majority of such problems . Among Medicare patients, it was found that most quality of care problems were associated with the treatment of infections and antibiotic use, fluid and electrolyte management, and inappropriate drug use . Most quality of care problems among Medicaid patients were associated with these categories as well as with labor and delivery problems, and poor discharge planning . The results of this study reflect the peer-review process in which providers are given an opportunity to respond to physician-reviewer decisions about the presence of actual or potential adverse effects . Such a process, which permits the presentation of additional data and information by providers, produces fewer final adverse outcome determinations than a process uniquely based on chart review . The quality of care problems observed in this study are amenable to focused educational interventions . Such remedial interventions could yield significant improvements in the quality of care for all patients.

Neurosurg Clin N Am, 1994 Oct, 5(4), 741 - 54
Infections in the neurosurgical intensive care unit; Kim YS et al.; The sources of fever and infection in neurosurgical patients in the intensive care unit are varied and complex . Benign postoperative fever due to atelectasis of the lungs or from central nervous system sources are difficult to define . Distinguishing between these "benign" sources and true nosocomial bacterial infections can be a difficult clinical process . Empiric antibiotic regimens are outlined, and some guidelines are proposed for the management of infected catheters.

Harefuah, 1994 Oct, 127(7-8), 236 - 42, 287
{Our experience with diagnosis, evaluation and treatment of poststernotomy sternal wound infections}; Gur E et al.; During 1984-1992 162 patients with post-sternotomy sternal wound infections were treated . Between 0.4-5% of these undergoing sternotomy suffer from this complication which carries a mortality of about 50% when treated by conventional, nonsurgical methods . 80% of our patients had undergone aortocoronary bypass surgery and 11% valve replacement . Major risk factors identified for postoperative infection were prolonged mechanical ventilation, prolonged extracorporeal bypass, smoking, diabetes, obesity and chronic lung disease . Of 152 patients who underwent surgery, 35 had recurrent infections, especially during the first years of the study . 10 were managed by conservative methods . Reconstruction of the chest wall was performed in 125, using pectoralis major flaps (74 cases), rectus abdominis muscle flaps (53), myocutaneous flaps (5) and omental flap (1) . Our series demonstrates the importance of a comprehensive, multi-disciplinary approach in evaluating and stabilizing these often critically ill patients . Computed tomography together with sinography have proven to be of major importance in diagnosing the location and extent of sternal wound infections . Strict adherence to antibiotic protocols, radical debridement of infected bone and soft tissues and subsequent reconstruction with muscle flaps has enabled us to reduce recurrent infection and improve morbidity and mortality rates.

Unfallchirurg, 1994 Oct, 97(10), 545 - 6
Perforation of the small intestine caused by fixation plate penetration into the abdomen; Smrkolj V et al.; The authors report a case of intestinal loop penetration and peritonitis caused by penetration of the tip of the fixation into the abdominal cavity after internal fixation of an unstable intertrochanteric fracture . Complete regression of acute infection was achieved by suturing the intestinal wound, removing the internal fixation device and administering systemic and local antibiotic therapy.

Neth J Med, 1994 Oct, 45(4), 170 - 3
Acute thyroiditis caused by Moraxella nonliquefaciens; Sudar JM et al.; A 43-year-old woman presented with thyroiditis caused by Moraxella nonliquefaciens . Antibiotic therapy resulted in complete recovery . The literature on M . nonliquefaciens and acute bacterial thyroiditis is reviewed . This is the first documented case of a thyroiditis caused by M . nonliquefaciens.

J Trop Pediatr, 1994 Oct, 40(5), 279 - 84
Acute respiratory infections in Nigerian children: prospective cohort study of incidence and case management; Fagbule D et al.; A community-based prospective surveillance and case management study of acute respiratory infection (ARI) in children aged 2-60 months of age was carried out over a 12-month period in Pakata, a semi-urban community in Ilorin, Kwara State, Nigeria . A cohort of 481 children was followed by trained community health assistants with thrice weekly home visits to record all symptoms and signs of ARI, and institute treatment based on WHO recommendations . There were three episodes of mild, moderate, or severe ARI per child per year, including 1.3 pneumonia episodes per child per year . The peak of infection corresponded to the rainy season (July-November), and a smaller peak to the dry season (February-April) . Most of the health worker decisions were considered appropriate, although there was a tendency toward over-treatment with antibiotic drugs . An effective referral system was established from the community to a tertiary centre . There were no ARI-related deaths during the study period . These data indicate that a system of case management using trained community health workers can improve case management of ARI and may prevent severe ARI-related disease and deaths.

J Clin Periodontol, 1994 Oct, 21(9), 628 - 37
Treatment of subjects with refractory periodontal disease; Magnusson I et al.; The aim of the present study was to evaluate the effect of non-surgical periodontal therapy with the adjunct of a selected antibiotic in subjects diagnosed with refractory periodontal disease . 21 subjects were selected for the study; all had a history of periodontal surgery, tetracycline therapy, and regular maintenance by a periodontist . When disease activity was detected, a bacterial sample was taken and a whole plaque susceptibility test was performed . Before the outcome of the susceptibility test the subjects were assigned to either antibiotic or placebo therapy . All subjects received scaling and rootplaning prior to antibiotic or placebo therapy . Based on the susceptibility test, subjects in the antibiotic group were treated either with Augmentin or clindamycin . The results demonstrated that in subjects with refractory periodontal disease there was no significant difference (N.S.) in the proportion of sites losing attachment before and after treatment (11.3% and 12.4%, respectively) over a 2-year post therapy observation period . However, the proportion of sites showing gain of attachment increased from 0.9% before therapy to 5.1% (p = 0.029) following selective antibiotic therapy when combined with scaling and rootplaning . The remainder of sites showed no change between pre- and post-therapy monitoring periods . The progression of attachment loss in the active sites could not be completely stopped over the entire 2-year period . After 12-15 months following therapy, there was a tendency towards new loss of attachment and an increase of pocket depth . However, all 4 subjects treated with placebo drug demonstrated continuous deterioration and had to be retreated . Although the proportion of sites losing attachment decreased from 5.1% to 2.3% (N.S.), the proportion of sites gaining attachment also decreased from 2.0% to 1.0% (N.S.) . The results suggest that scaling and rootplaning together with selected antibiotic therapy repeated every 12-15 months may be beneficial for these subjects although it may not completely stop progressive attachment loss.

J La State Med Soc, 1994 Oct, 146(10), 448 - 52
Ceftazidime as monotherapy for fever and neutropenia: experience in a community hospital; Bizette GA et al.; Fever and neutropenia is occurring in a wider variety of clinical settings, and the proper antibiotic therapy for its treatment is an area of debate . Our study is a retrospective analysis of the experience of the Oncology Division of the Medical Center of Baton Rouge, which used ceftazidime as monotherapy in the empiric treatment of fever and neutropenia . A total of 53 episodes in 38 patients were studied . Using ceftazidime as monotherapy in our study population was associated with an 8% mortality rate, indicating that monotherapy is a viable option for the treatment of fever and neutropenia.

Biosci Biotechnol Biochem, 1994 Oct, 58(10), 1914 - 7
An extracellular quinoprotein oxidase that catalyzes conversion of enacyloxin IVa to enacyloxin IIa; Oyama R et al.; A new extracellular quinoprotein oxidase named enacyloxin oxidase (ENX oxidase), which is involved in biosynthesis of ENX IIa, a congener of ENX, was found in the culture supernatant of Frateuria sp . W-315 and purified as a homogeneous protein on SDS-PAGE . ENX oxidase was shown to have a molecular mass of 73 kDa by SDS-PAGE and 79 kDa by gel filtration . The enzyme was inhibited by various carbonyl reagents and the activity was stimulated by addition of PQQ . This is the first report on a quinoprotein oxidase that is secreted into the culture medium in the logarithmic growth phase, and acts for biosynthesis of the antibiotic.

Zhongguo Yi Xue Ke Xue Yuan Xue Bao, 1994 Oct, 16(5), 328 - 33
{Biodistribution of monoclonal antibody and Fab fragment and antitumor effect of their conjugates on hepatoma xenografts}; Li J et al.; McAb 3A5, a rat monoclonal antibody directed against human hepatoma cells, and its Fab fragment were compared on their biodistribution and the therapeutic effects of their conjugates linked to C1027, a highly potent antitumor antibiotic, on the growth of human hepatoma xenografts in nude mice . Biodistribution study with 125I-labeled McAb 3A5 and its Fab fragment in hepatoma-bearing nude mice revealed that ID%/g values of McAb 3A5 were higher than those of the Fab fragment in tumor, liver, spleen and kidney; however, the T/NT ratios of Fab were higher than those of McAb 3A5 . Imaging study with 131I-3A5 and 131I Fab showed that clear images of the tumor emerged 12h after injection of Fab and 40 h after that of McAb 3A5 . IC50 values for McAb-C1027 and Fab-C1027 were 4.2 x 10(-14) mol/L, 8.6 x 10(-16) mol/L, respectively . Fab-C1027 conjugate was 49-fold more potent than McAb-C1027 . Therapeutic effect of the conjugates was evaluated with hepatoma xenograft in nude mice . When treatment started 3 days after sc transplantation of the tumor with equivalent dose of C1027, 0.15 mg/kg, i.v., x3, tumor inhibition rates for McAb-C1027 and Fab-C1027 conjugates were 68% and 66%, respectively . When the treatment started on day 10 after transplantation with 0.10 mg/kg, i.v., x6, tumor inhibition rates for McAb-C1027 and Fab-C1027 conjugates were 24% and 54%, respectively . The results showed that compared with the intact McAb, Fab fragment displays higher specificity in biodistribution and exerts stronger inhibitory effect on the growth of established tumor xenografts.

Z Geburtshilfe Perinatol, 1994 Oct-Dec, 198(5-6), 215 - 8
{Infection and uterine contraction}; Winkler M; A great number of studies on women as well as experiments on animals support the association of silent intrauterine infection with the initiation of preterm labour . However, the success of antibiotic therapy in reducing bacteria-induced labour in animals could only be confirmed in few reports concerning women in preterm labour . Disregarding direct effects of bacterial products such as Phospholipase-A2 and endotoxins evidence suggests that immunological effects (release of Cytokines) may enhance the synthesis of prostaglandins in the uterus, placenta and fetal membranes . New therapeutical approaches are in discussion, but only time will tell whether a reduced rate of women with failed tocolysis will be the result.

Chir Organi Mov, 1994 Oct-Dec, 79(4), 425 - 8
Reimplantation or resection arthroplasty for septic loosening; Morscher E; Resection arthroplasty should nowadays be considered as obsolete for the following reasons: the removal of the implant and adequate antibiotic therapy can clear the infection . From this point of view the reimplantation of an endoprosthesis is possible . "Deficient bone stock" is not a contraindication to the reimplantation since there are surgical means available to replace bone stock . The results of revision arthroplasty (reimplantation) are incomparably better today that they were years ago (cement-free technique, bone replacement, supports of the acetabulum, special revision prostheses etc.

Chir Organi Mov, 1994 Oct-Dec, 79(4), 341 - 6
Infection therapy in cementless T.H.A; Marchetti PG et al.; Reimplantation (when possible) represents today the method of choice when dealing with and attempting to resolve cases of deep infection in total hip arthroplasty . In recent years we have, however, had the chance to treat some cases of infection in cementless arthroplasty (without loosening) by conservative treatment: surgical debridement and specific antibiotic therapy (2 cases), or medical therapy alone (1 case), both associated with immobilization in a plaster cast for 2-3 weeks . The long-term results proved to be quite encouraging: none of the 3 patients treated conservatively showed (after 5-6 years) clinical-radiographic signs of recurrence of the infection.

G E N, 1994 Oct-Dec, 48(4), 209 - 18
{Gastrointestinal fistulas . Treatment with a somatostatin analogue (SMS 201-995)}; Gerardo Perez D et al.; Post surgical gastrointestinal fistulas are a frequent problem around the world . We present our experience with a synthetic analog of somatostatin (SMS 201-955) used in 19 patients with gastrointestinal fistulas between January 1992 {corrected} and November 1993 . We compare them with 50 patients with gastrointestinal fistulas randomized selected between 1980 . The fistulas were classified according to their topographic location in five groups and to their flow in two groups: high and low fistulas . All patients were treated with nutritional support, antibiotic and octreotide (SMS 201-995) . In the first 24 hours the fistulas flow where reduced in 51.63% and 72 hours later the reduction was of 70.62% . In 13 patients the fistulas where closed between 36.7 + 0 - 13.94 days (p < 0.01) . This difference represent a cost reduction of 1,220,673.96 Bs . for each patient or 45,581.55 Bs . for each day . Two patients died in the study (10.52%) and two patients stop the drug because of adverse reaction . The octreotide reduced the fistulas flow and reduced the time needed to close.

Mayo Clin Proc, 1994 Oct, 69(10), 949 - 54
Vancouver hybrid: preliminary experience in the treatment of Hodgkin's disease in childhood and adolescence; Khan SP et al.; OBJECTIVE: To describe our preliminary experience with 19 young patients with newly diagnosed Hodgkin's disease who received the Vancouver hybrid chemotherapeutic regimen . DESIGN: We summarized the characteristics of our 19 study patients, the treatment administered (between June 1988 and June 1992), and the outcome . RESULTS: The Vancouver hybrid, which consists of mechlorethamine, vincristine sulfate (Oncovin), procarbazine hydrochloride, prednisone, doxorubicin hydrochloride (Adriamycin), bleomycin, and vinblastine sulfate (MOPP/ABV), was based on the hypothesis of preventing drug resistance by early introduction and alternation of all active agents and was aimed at decreasing the severity and frequency of treatment-related complications . Of our 19 patients with Hodgkin's disease (age range, 6 to 20 years) treated with this regimen, 2 had clinical stage I disease, 10 had stage II, 6 had stage III, and 1 had stage IV . Only two patients had systemic symptoms, and nodular sclerosis was the most common histologic feature . Patients were given four to eight cycles of chemotherapy, depending on the clinical stage of disease . In addition, 10 patients received irradiation, including 6 of 9 patients with bulky disease . In all patients, complete remission was achieved . After a median follow-up of 3.3 years, only two patients had had a relapse; both underwent autologous bone marrow transplantation and were alive and well with no evidence of disease at last follow-up . The treatment was well tolerated, and delivery of treatment was excellent . The only severe toxicity was myelosuppression; 8 patients experienced a total of 15 episodes of fever and neutropenia that necessitated hospitalization and antibiotic therapy, but no systemic infections were confirmed during 104 cycles of therapy . CONCLUSION: The MOPP/ABV hybrid is an effective and well-tolerated therapy in most young patients with Hodgkin's disease . Long-term monitoring is needed to evaluate late effects.

Ann Intern Med, 1994 Oct 1, 121(7), 492 - 501
Filgrastim in patients with chemotherapy-induced febrile neutropenia . A double-blind, placebo-controlled trial; Maher DW et al.; OBJECTIVE: To determine if filgrastim (recombinant human methionyl granulocyte colony-stimulating factor) used in addition to standard inpatient antibiotic therapy accelerated recovery from infection associated with chemotherapy-induced neutropenia . DESIGN: Randomized, double-blind, placebo-controlled trial . SETTING: Hematology and oncology wards of four teaching hospitals . PATIENTS: 218 patients with cancer who had fever (temperature > 38.2 degrees C) and neutropenia (neutrophil count < 1.0 x 10(9)/L) after chemotherapy . INTERVENTION: Patients were randomly assigned to receive filgrastim (12 micrograms/kg of body weight per day) (n = 109) or placebo (n = 107) beginning within 12 hours of empiric therapy with tobramycin and piperacillin . Patients received treatment and remained in the study until the neutrophil count was greater than 0.5 x 10(9)/L and until 4 days without fever (temperature < 37.5 degrees C) had elapsed . MEASUREMENTS: Days of neutropenia and fever and days in the study (hospitalization); time to resolution of fever and febrile neutropenia; and frequency of the use of alternative antibiotics . RESULTS: Compared with placebo, filgrastim reduced the median number of days of neutropenia (3.0 compared with 4.0 days of a neutrophil count of < 0.5 x 10(9)/L; P = 0.005) and the time to resolution of febrile neutropenia (5.0 compared with 6.0 days; P = 0.01) but not days of fever (3.0 days for both groups) . The frequency of the use of alternative antibiotics was similar in the two groups (46% compared with 41%; P = 0.48) . The median number of days patients were hospitalized while on study was the same (8.0 days; P = 0.09); however, filgrastim decreased the risk for prolonged hospitalization (> 11 days, 4th quartile) by half (relative risk, 2.1 {95% CI, 1.1 to 4.1}; P = 0.02) . In exploratory subset analyses, filgrastim appeared to provide the greatest benefit in patients with documented infection and in patients presenting with neutrophil counts of less than 0.1 x 10(9)/L . CONCLUSIONS: Filgrastim treatment used with antibiotics at the onset of febrile neutropenia in patients with cancer who have received chemotherapy accelerated neutrophil recovery and shortened the duration of febrile neutropenia.

Wiad Lek, 1994 Oct, 47(19-20), 763 - 5
{Assessment of gentamicin dosage in patients before planned surgical operation}; Andrys I et al.; The study included 18 patients, whom before planned surgical operation administered preventively gentamicin in the dose 3 x 80 mg/24 h i.m . After 24 hours the venous blood was taken before administration of the next dose of the drug and the concentration of gentamicin was determined by FPIA method . The subtherapeutic level of the drug was found in 15 patients (83%), therapeutic level - in 2 patients (11%) and toxic level in 1 patient (6%) . It seems, that in patients after surgical operation, in whom after the prophylactic administration the treatment of gentamicin is continued, it is necessary the monitoring of the concentration of this antibiotic.

Biochem Biophys Res Commun, 1994 Sep 30, 203(3), 1821 - 7
Stable expression of the neuronal BI (class A) calcium channel in baby hamster kidney cells; Niidome T et al.; Plasmids containing the BI (alpha 1) cDNA with the dihydrofolate reductase (DHFR) gene, skeletal muscle alpha 2-subunit cDNA with the neo marker gene, and beta-subunit cDNA were co-transfected into baby hamster kidney (BHK) cells . BHK cells lack endogenous calcium channel activity . Twenty percent of the methotrexate (MTX) and G418 resistant clones were found to express calcium channel activity using the patch-clamp technique . A single clone, BHKBI147, demonstrated stable electrophysiological characteristics over 20 passages . Ca2+ currents of the BI channel in BHKBI147 cells were largely blocked by a specific P-type blocker, omega-AgaIVA, with an IC50 of 150 nM . Unlike the BI channel, Ca2+ currents of cardiac L-type channels expressed in BHK cells were completely blocked by the L-type antagonist, nifedipine, with an IC50 of 56 nM.

Biochemistry, 1994 Sep 27, 33(38), 11493 - 500
Binding of actinomycin D to the T(G)nT motif of double-stranded DNA: determination of the guanine requirement in nonclassical, non-GpC binding sites; Bailey SA et al.; Strong binding of the antitumor antibiotic actinomycin D to the sequence 5'-TGGGT-3' in double-stranded DNA was recently established by equilibrium binding studies (Bailey et al., 1993) . Actinomycin D binding to this -TGGGT- containing sequence was shown to be comparable to that of an -XGCY- containing oligonucleotide (Ka approximately 10(6) M-1) . Investigation of -TGGGT- as a high-affinity binding site for actinomycin D follows from our 1989 sequencing study (Rill et al., 1989) in which the photoaffinity analog of actinomycin D (7-azidoactinomycin D) was used to determine DNA base sequence specificities and neighboring base effects . The studies presented here examine the guanine requirements for actinomycin D binding to such nonclassical (non-dGpC) sites by varying the number of central guanine residues in a series of selected duplex oligonucleotides . The central -T(G)nT- motif varies from n equals 1 to 4 . Actinomycin D binding to each of these undecamers is characterized and correlated with binding to oligonucleotides of identical length and similar sequences that contain classical dGpC binding sites . Binding affinities of actinomycin D to this series of oligonucleotide duplexes (10 degrees C) can be summarized as -TGGGT- > -TGGT- > TGGGGT- > -TGT . The kinetics of SDS-induced dissociation of actinomycin D from these oligonucleotides reveal single-exponential decays with duration dependent on the sequence at the binding site . With the exception of the -TGGGT- containing oligomer, dissociation times for the T(G)nT duplexes were drastically different and much shorter than times obtained for the dissociation of actinomycin D from oligonucleotides having classical dGpC sites.(ABSTRACT TRUNCATED AT 250 WORDS)

Biochemistry, 1994 Sep 27, 33(38), 11438 - 52
Sequential 1H, 13C, and 15N NMR assignments and solution conformation of apokedarcidin; Constantine KL et al.; Kedarcidin is a recently discovered antitumor antibiotic chromoprotein . The solution conformation of the kedarcidin apoprotein (114 residues) has been characterized by heteronuclear multidimensional NMR spectroscopy . Sequence-specific backbone atom resonance assignments were obtained for a uniformly 13C/15N-enriched sample of apokedarcidin via a semiautomated analysis of 3D HNCACB, 3D CBCA-(CO)NH, 4D HNCAHA, 4D HN(CO)CAHA, 3D HBHA(CO)NH, and 3D HNHA(Gly) spectra . Side-chain assignments were subsequently obtained by analysis of (primarily) 3D HCCH-TOCSY and HCCH-COSY spectra . A qualitative analysis of the secondary structure is presented on the basis of 3J alpha NH coupling constants, deviations of 13C alpha and 13C beta chemical shifts from random coil values, and NOEs observed in 3D 15N- and 13C-edited NOESY-HSQC spectra . This analysis revealed a four-stranded antiparallel beta-sheet, a three-stranded antiparallel beta-sheet, and two two-standed antiparallel beta-sheets . The assignments of cross-peaks in the 3D NOESY spectra were assisted by reference to a preliminary model of apokedarcidin built using the program CONGEN starting from the X-ray structure of the homologous protein aponeocarzinostatin . An ensemble of 15 apokedarcidin solution structures has been generated by variable target function minimization (DIANA program) and refined by simulated annealing (X-PLOR program) . The average backbone atom root-mean-square difference between the individual structures and the mean coordinates is 0.68 +/- 0.08 A . The overall fold of apokedarcidin is well-defined; it is composed of an immunoglobulin-like seven-stranded antiparallel beta-barrel and a subdomain containing two antiparallel beta-ribbons . Highly similar tertiary structures have been previously reported for the related proteins neocarzinostatin, macromomycin, and actinoxanthin . Important structural features are revealed, including the dimensions of the chromophore-binding pocket and the locations of side chains that are likely to be involved in chromophore stabilization.

FEBS Lett, 1994 Sep 26, 352(2), 118 - 22
Mutations to kirromycin resistance occur in the interface of domains I and III of EF-Tu.GTP; Abdulkarim F et al.; The antibiotic kirromycin inhibits protein synthesis by binding to EF-Tu and preventing its release from the ribosome after GTP hydrolysis . We have isolated and sequenced a collection of kirromycin resistant tuf mutations and identified thirteen single amino acid substitutions at seven different sites in EF-Tu . These have been mapped onto the 3D structures of EF-Tu.GTP and EF-Tu.GDP . In the active GTP form of EF-Tu the mutations cluster on each side of the interface between domains I and III . We propose that this domain interface is the binding site for kirromycin.

JAMA, 1994 Sep 21, 272(11), 867 - 70
Use of cell culture and a rapid diagnostic assay for Chlamydia trachomatis screening; Hook EW 3rd et al.; OBJECTIVE--To compare a rapid, office-based test with standard cell culture for screening of women for Chlamydia trachomatis infections . DESIGN AND SETTINGS--An 8-month prospective crossover trial used alternating screening protocols in two Baltimore (Md) sexually transmitted disease clinics from January 2 through August 14, 1991 . PARTICIPANTS--Consecutive women attending the two clinics who had no indication for administration of antichlamydial antibiotic therapy (eg, history of recent sexual contact with a partner with a sexually transmitted disease, mucopurulent cervicitis, pelvic inflammatory disease, known gonorrhea, or previously diagnosed Chlamydia infections) . INTERVENTIONS--Chlamydia screening was offered according to one of two protocols . Use of the two screening protocols was alternated between clinics each month . In the "rapid test clinic," eligible women were screened with both a 30-minute enzyme immunoassay test and tissue culture . Patients screened with the rapid test were asked to remain in the clinic until their rapid assay results were available so that, if positive, the patients could be treated . In the "routine screening clinic," eligible women were screened for Chlamydia by cell culture . Women identified as being infected with Chlamydia by screening culture were later confidentially notified of their test results by health department disease intervention specialists and referred for therapy . MAIN OUTCOME MEASURES--Performance of screening tests for bringing infected patients to therapy; time intervals between initial clinic visits and therapy; and pelvic inflammatory disease occurring between initial visits and therapy . RESULTS--Chlamydia cultures were positive in 100 (6.6%) of 1526 women screened with the solid-phase immunoassay, 47 of which were detected and treated on the basis of rapid test results . In contrast, 93 (74%) of 126 women with positive screening cultures returned to the clinic and received therapy . The median interval between testing and therapy for women with positive screening cultures was 14 days, and three (3.2%) developed pelvic inflammatory disease in the interval between testing and return for therapy . CONCLUSIONS--Neither cell culture nor a rapid diagnostic test performed well for ensuring therapy of women with Chlamydia infections . The sensitivity of the rapid diagnostic test was low, and nearly one fourth of the women with positive screening cultures did not return for therapy . Evaluation of screening for Chlamydia should consider the utility of strategies for bringing patients to treatment, as well as the more usual measures of test performance, such as sensitivity, specificity, and predictive values.

Blood, 1994 Sep 15, 84(6), 1703 - 21
Biologic effects of leukocytes present in transfused cellular blood products; Bordin JO et al.; A considerable literature has accumulated over the past decade indicating that leukocytes present in allogeneic cellular blood components, intended for transfusion, are associated with adverse effects to the recipient . These include the development of febrile transfusion reactions, graft-versus-host disease, alloimmunization to leukocyte antigens, and the immunomodulatory effects that might influence the prognosis of patients with a malignancy . Moreover, it has become evident that such leukocytes may be the vector of infectious agents such as CMV, HTLV-I/II, and EBV as well as other viruses . An interesting development that has occurred coincidentally in transfusion medicine is that agencies responsible for the provision of blood products are being designated manufacturers of biologicals . The trend among manufacturers of biologicals is to try to produce pure products to provide for the specific therapeutic need of patients . Thus, with the realization that allogeneic leukocytes and their products may have adverse biologic activities, there is increasing pressure from various sources for the reduction of the leukocyte content in allogeneic blood components to minimize the occurrence of their adverse effects . Although the threshold leukocyte number below which these effects might no longer occur is still to be determined, a 2 to 3 log10 leukocyte reduction, provided by the currently available commercial leukocyte filters, has been shown to reduce the frequency of many of such reactions . On the other hand, the immunosuppressive effects produced by the infusion of allogeneic leukocytes might be beneficial for some patients, ie, for the maintenance of kidney allografts, in possibly reducing the relapse rate in patients with inflammatory bowel diseases, and in ameliorating recurrent spontaneous abortion . Moreover, therapeutic granulocyte transfusions may be of benefit in certain well-defined categories of patients infected with bacteria, yeast, and/or fungi . These include neonates with bacterial sepsis associated with bone marrow failure as well as severely neutropenic leukemic patients with an infection unresponsive to appropriate and specific antibiotic therapy . Many of the results obtained with the use of leukocyte depletion filters are tantalizing, but the actual clinical benefit of leukodepletion has not been established in most instances, because much of the available data are retrospective or from uncontrolled clinical trials . Moreover, issues of cost-effectiveness and quality control have not been considered adequately . Properly designed prospective clinical trials are essential to provide data with which to answer such questions and also to help define the optimal conditions required for the preparation of blood components ultimately destined for clinical use . Only with the availability of such data can sound decisions be made about the clinical value of leukodepletion.

Cancer Lett, 1994 Sep 15, 84(2), 149 - 54
The pH-dependent reduction of Adriamycin catalysed by NADH:cytochrome b5 reductase; Hodnick WF et al.; Adriamycin is a redox active antineoplastic antibiotic that upon reduction can, in the presence of oxygen, redox cycle to form reactive oxygen species, while in anaerobiosis can generate a reactive quinone methide . NADH:cytochrome b5 reductase catalysed the reduction of adriamycin at pH 6.6 with an apparent Km of 1.8 microM; at pH 7.6, no measurable reduction of adriamycin occurred . Aerobically, in the presence of enzyme and NADH, adriamycin stimulated oxygen consumption and concomitant accumulation of hydrogen peroxide . At pH 7.6, no discernible oxygen consumption nor detectable hydrogen peroxide generation was observed . The findings demonstrate that NADH:cytochrome b5 reductase is capable of reducing adriamycin, in a pH-dependent manner, to species that can redox cycle in the presence of oxygen to form reactive oxygen molecules and thus may contribute to the generation of oxidative stress, a phenomenon suggested to be involved in both the toxicity and the antineoplastic activity of adriamycin.

Thromb Res, 1994 Sep 15, 75(6), 643 - 51
Inhibition of plasminogen activation by polymerized ampicillin; al-Roof Higazi A et al.; The polymerized beta-lactam antibiotic ampicillin inhibits the proteolytic activity of human plasmin upon 125I-labeled fibrin clots . The inhibition is dose-dependent, with half-maximal inhibition occurring at 1.25 mM of the polymerized antibiotic . Polymerized ampicillin also inhibits binding of plasmin to fibrin, and 38% inhibition of binding occurs at 10 mM of the antibiotic . Furthermore, polymerized ampicillin inhibits the activation of plasminogen by either urokinase-like plasminogen activator (uPA) or tissue type-plasminogen activator (tPA) . At 7.5 mM of polymerized ampicillin, the uPA-mediated plasminogen activation is suppressed by 94%, and half-maximal inhibition is obtained at 0.66 mM . The direct activity of uPA on the chromogenic substrate L-pyroglutamyl-glycyl-L-arginine p-nitroanilide hydrochloride (S-2444) is unaffected by polymerized ampicillin levels of up to 10 mM . The inhibitory effects of the polymerized antibiotic on the activation of plasminogen by both uPA and tPA is totally abolished in presence of fibrin . These interactions may serve as a novel model for ligands that enhance the clot-specificity of thrombolytic agents.

J Biol Chem, 1994 Sep 9, 269(36), 22875 - 81
Prosomatostatin processing in permeabilized cells . Endoproteolytic cleavage is mediated by a vacuolar ATPase that generates an acidic pH in the trans-Golgi network; Xu H et al.; To investigate the relationship between prohormone processing and sorting of mature polypeptides into nascent secretory vesicles, we recently developed a permeabilized cell system that supports both these reactions (Xu, H., and Shields, D . (1993) J . Cell Biol . 122, 1169-1184) . Rat anterior pituitary GH3 cells expressing high levels of prosomatostatin (proSRIF) were incubated at 20 degrees C; this temperature prevented exit from the trans-Golgi network and inhibited proSRIF processing . Following the 20 degrees C block, the cells were mechanically permeabilized and incubated at 37 degrees C, and proSRIF processing was determined . Cleavage of proSRIF to the mature hormone required ATP hydrolysis and was inhibited by chloroquine, a weak base, or carbonyl cyanide m-chlorophenylhydrazone, a protonophore . This suggested that a proton gradient and/or an acidic pH facilitated by a vacuolar H(+)-ATPase was required for prohormone processing . We have now utilized the permeabilized cell system in conjunction with the antibiotic bafilomycin A1, a specific inhibitor of vacuolar H(+)-ATPases, to elucidate the role of acidic pH in prohormone processing . Here we report that (i) proSRIF processing was inhibited in vivo and in vitro by low concentrations of bafilomycin A1, confirming the involvement of a vacuolar type ATPase in prohormone processing; (ii) the ATP requirement for processing could be circumvented in vitro by incubating permeabilized cells at acidic pH in the presence of protonophores, indicating that an acidic pH rather than a H+ gradient is necessary for processing; and (iii) a pH of between 6 and 6.2 in the trans-Golgi network was optimal for proSRIF cleavage . We also demonstrate that prohormone convertase 2 exhibited temperature-dependent activity in which proSRIF processing was inhibited at 20 degrees C in vitro . This result explains our previous observation that prohormone processing is inhibited when intact cells are incubated at 20 degrees C.

Curr Opin Ophthalmol, 1994 Oct, 5(5), 45 - 52
Thyroid ophthalmopathy; Faktorich EG et al.; Thyroid ophthalmopathy, idiopathic orbital inflammation, and orbital infection can occasionally demonstrate overlapping clinical features . It is essential to distinguish between these processes because appropriate treatments are distinct in each case . In the past year, the pathophysiology of thyroid ophthalmopathy has been the topic of many reports . Orbital inflammation, particularly the fibrotic form, has been recognized to represent a distinct disease entity that may require more specifically directed treatment . In some cases cytotoxic therapies may be indicated . Orbital infection, particularly in the setting of orbital abscess, may be treated conservatively with antibiotic therapy and observation or more aggressively with surgical drainage procedures . In several recent studies, appropriate management of such infectious processes appears to be related to patient age, as well as to the specific clinical pattern of presentation.

South Med J, 1994 Sep, 87(9), 884 - 8
Therapeutic approach to hepatic abscesses; Moulds-Merritt C et al.; Thirty-five patients with hepatic abscesses were treated at our institution during an 8-year period . Twenty-nine patients had bacterial abscesses, and six patients had amoebic abscesses . The patients were admitted with fever (95%), right upper quadrant pain (63%), and nausea and vomiting (40%) as the most common symptoms . Eleven patients had some inciting cause for the abscess formation; the remaining 18 bacterial abscesses were cryptogenic . The primary abnormal test results were leukocytosis (91%) and liver enzyme elevations (80%) . All patients with amoebic abscesses were serologically positive for amoebic infection . Computed tomography (CT) was the most effective imaging modality for diagnosis . Twenty patients were treated with open surgical drainage, 11 with percutaneous drainage, and 4 with antibiotics alone . Three of the four latter patients had amoebic abscesses . Abscesses in two patients initially treated with percutaneous drainage did not resolve, and the patients ultimately required surgery . The remaining indications for surgery were concomitant conditions requiring surgical intervention or inaccessibility of the abscess to percutaneous drainage . Antibiotics were given to all patients, with treatment duration from 10 to 60 days . The hospital mortality was 6% due to sepsis and a postoperative myocardial infarction in one patient, and perioperative myocardial infarction in another; overall morbidity was 20% . At a mean follow-up of 13 months, all surviving patients had resolution of the abscess shown by either CT (11 patients) or clinical examination (22 patients) . We conclude that effective drainage, whether it be surgical or percutaneous, and appropriate antibiotic coverage are the mainstays of therapy for hepatic abscesses.

Isr J Med Sci, 1994 Sep, 30(9), 684 - 9
Cefuroxime efficacy in pneumonia: sequential short-course i.v./oral suspension therapy; Shalit I et al.; For children with acute respiratory infections in hospital, it is desirable to transfer from parenteral to oral therapy at the earliest opportunity . The introduction of a pediatric suspension of cefuroxime axetil provides a continuous course of one antibiotic with transition from injectable to oral therapy . This open study was designed to investigate the efficacy of cefuroxime in pediatric patients aged 3 months to 5 years with community-acquired pneumonia . Children had evidence of lobar pneumonia on chest X-ray, a white blood cell count of > 15,000/mm3 and a rectal temperature of > or = 38.5 degrees C on enrollment . Cefuroxime was given by i.v . injection at 75 mg/kg per day in three divided doses for 48-72 h followed by oral cefuroxime suspension at 30 mg/kg per day in two divided doses . Of 84 evaluable patients 82 (97.6%) were cured or improved post-treatment, and of 74 evaluable children who returned for follow-up assessment 73 (98.6%) remained well . Oral therapy with twice daily cefuroxime axetil suspension following 2-3 days of i.v . cefuroxime administration was confirmed as effective and safe treatment for lobar pneumonia in children under 5 years of age.

Gynecol Oncol, 1994 Sep, 54(3), 372 - 6
Metastatic cervical cancer and pelvic inflammatory disease in an AIDS patient; Singh GS et al.; The Center for Disease Control (CDC) recently added invasive cervical cancer to its list of surveillance case-defining diseases, and also included cervical dysplasia, carcinoma in situ, and pelvic inflammatory disease (PID) in the classification system . There are several reported cases of cervical cancer in AIDS patients that behaved in an unusually aggressive fashion and responded poorly to therapy . In light of the above-reported cases, it may be expected that cervical cancer may manifest itself in unusual ways in HIV-positive women . A case of aggressive cervical cancer in an AIDS patient with PID is reported . She was admitted with PID and newly diagnosed cervical cancer with recurrent fever spikes despite adequate antibiotic coverage . An aspiration of a presumed psoas abscess revealed metastatic squamous cell carcinoma . These data suggest that not only are HIV-infected women at risk for aggressive and unusual presentations of cervical cancer, but also that coexistent pelvic infection may contribute to development and spread of the disease . Immunosuppression from the virus may increase the incidence and severity of neoplasia . Data suggest that cervical cancer in HIV-infected women is often of advanced stage and responds poorly to treatment . Unique treatment approaches may need to be developed as conventional strategies do not seem to be adequate . More research is required to determine what these strategies should be . Lastly, universal HIV screening of women with either PID or cervical cancer seems prudent.

Radiol Clin North Am, 1994 Sep, 32(5), 1023 - 43
The acute abdomen in individuals with AIDS; Wyatt SH et al.; Both AIDS-related infections and neoplasms of the gastrointestinal tract may be manifest by a clinical picture of acute abdominal disease . Severe abdominal pain may be seen in this population even in the absence of true surgical complications such as perforation, abscess formation, or obstruction . Localizing signs and symptoms are frequently misleading due to underlying immunosuppression, debilitation, and prior or current antibiotic use . CT assumes a critical role in evaluation of the symptomatic AIDS patient, providing evaluation of the entire abdomen and pelvis including lymph nodes, solid viscera, and the bowel itself . CT is thus the modality of choice for characterization of AIDS-related abdominal disease and for direction of appropriate therapy.

J Bacteriol, 1994 Sep, 176(18), 5857 - 60
Nikkomycin Z is a specific inhibitor of Saccharomyces cerevisiae chitin synthase isozyme Chs3 in vitro and in vivo; Gaughran JP et al.; Nikkomycin Z inhibits chitin synthase in vitro but does not exhibit antifungal activity against many pathogens . Assays of chitin synthase isozymes and growth assays with isozyme mutants were used to demonstrate that nikkomycin Z is a selective inhibitor of chitin synthase 3 . The resistance of chitin synthase 2 to nikkomycin Z in vitro is likely responsible for the poor activity of this antibiotic against Saccharomyces cerevisiae.

Med Clin North Am, 1994 Sep, 78(5), 967 - 85
New pathogens in pneumonia; Guerra LG et al.; It appears that many commonly recognized syndromes such as the ARDS may well be caused by agents that have only recently emerged as respiratory pathogens . HPS represents one such entity . It appears likely that the increasing pressure of antibiotic use as well as the reemergence of certain pathogens will continue to challenge the clinician . Paramount to the identification and treatment of unusual pneumonias will be the degree with which an effort is made to make an etiologic diagnosis through sputum examination, transtracheal aspirate, bronchoscopy, or lung biopsy . Although pneumococcal pneumonia is the most common community-acquired pneumonia seen by practicing physicians, in all likelihood from time to time a physician will encounter pneumonia caused by one of the unusual pathogens described in this article or else by an altogether new pathogen.

J Gen Virol, 1994 Sep, 75 ( Pt 9), 2197 - 203
Action of brefeldin A on translation in Semliki Forest virus-infected HeLa cells and cells doubly infected with poliovirus; Perez L et al.; Brefeldin A (BFA) is a macrolide antibiotic that blocks membrane traffic through the vesicular system and affects the glycosylation of viral glycoproteins . Treatment of HeLa cells infected with Semliki Forest virus (SFV) with BFA enhances the synthesis of late viral proteins . Proteolytic cleavage of p107 is partially blocked and viral glycoproteins accumulate in BFA-treated cells . This enhanced synthesis of late SFV proteins is due, at least in part, to an increase in the formation of the subgenomic SFV 26S mRNA . Since BFA blocks the replication of poliovirus genomes without affecting the cleavage of the translation initiation factor p220, protein synthesis was analysed in doubly infected cells . HeLa cells infected with SFV and poliovirus at the same multiplicity predominantly synthesize poliovirus proteins . But if these cells are treated with BFA they synthesize significant amounts of SFV capsid protein C for several hours, despite the fact that p220 has been degraded.

Urology, 1994 Sep, 44(3), 311 - 8
Prospective development of a cost-efficient program for radical retropubic prostatectomy; Koch MO et al.; OBJECTIVES . We designed and implemented a broad-based program to decrease costs while maintaining quality of care in patients undergoing radical retropubic prostatectomy . METHODS . This program initially involved identification of factors that contribute to patient costs after radical prostatectomy and elimination or control of items that were deemed unnecessary . Patient care was standardized with a collaborative care pathway coordinated by a clinical nurse specialist and that served as a goal for each case . RESULTS . Length of total hospital stay was reduced from a mean of 5.7 days to 3.6 days after full implementation of the program (p < 0.0001) . A reduction in operating room time, material utilization, antibiotic use, routine laboratory studies, and refinements in postoperative pain management contributed significantly to cost savings . Overall, the average adjusted total hospital charges were reduced from $13,783 to $7741 (p < 0.0001) by the implementation of this program, with no discernible adverse effect on morbidity rates . CONCLUSIONS . Careful analysis of the critical components of medical care and implementation of a standardized pathway with emphasis on a collaborative approach can substantially increase the cost efficiency of medical care.

Postgrad Med, 1994 Sep 1, 96(3), 30 - 2, 35-8, 43 passim
Acute and chronic diarrhea . How to keep laboratory testing to a minimum; Talal AH et al.; Diagnosing a cause of diarrhea is a challenging undertaking but can be accomplished if a systematic approach is used for evaluation . Pathophysiologic mechanisms of acute diarrhea (eg, Giardia lamblia infection, antibiotic use) are different from those of chronic diarrhea (eg, secretory dysfunction from thyrotoxicosis, lactose or fructose intolerance), so adequate history taking and physical examination are essential in narrowing the diagnosis . Laboratory investigation can then be directed using the information obtained, and the cause of the diarrhea can be established without subjecting the patient to extensive and expensive testing . Undoubtedly, some functional entities that contribute to diarrhea await discovery.

Clin Orthop, 1994 Sep, (306), 175 - 82
Semiopen cancellous bone grafting . A 2 step method for closing small infected tibial bone defects; Ueng WN et al.; Thirteen infected small tibial bone defects with overlying skin loss were treated with a 2 stage procedure . In the 1st stage, antibiotic impregnated polymethylmethacrylate bead chains were used to obliterate the debrided osseous cavity and a meshed porcine skin graft was used for temporary wound coverage . In the 2nd stage, the bead chains were replaced with autogenous cancellous bone graft, and the wound was again covered with a meshed porcine skin graft . All wounds and bone grafts healed without the need for an additional autogenous skin or bone graft . The patients were hospitalized an average of 23 days . The length of time to the completion of secondary epithelialization of the wound ranged from 2 to 5 months (average, 3 months) . The length of time to bone union ranged from 5 to 8 months (average, 6.4 months) . An additional application of porcine skin graft was required in 3 patients . Minor pin tract infections were seen in 2 patients . There was no recurrence of osteomyelitis during an average followup of 37 months (range, 24-54 months) . This method was helpful in securing the closure of infected tibial bone defects with small skin losses and avoided both prolonged hospitalization and the morbidity usually accompanying free tissue transfer or the Papineau method of open cancellous bone grafting.

Clin Chem, 1994 Sep, 40(9), 1800 - 4
Microfabrication in silicon microphysiometry; Baxter GT et al.; Over the past 5 years, microphysiometry has proved an effective means for detecting physiological changes in cultured cells, particularly as a functional assay for the activation of many cellular receptors . To demonstrate the clinical relevance of this method, we have used it to detect bacterial antibiotic sensitivity and to discriminate between bacteriostatic and bacteriocidal concentrations . The light-addressable potentiometric sensor, upon which microphysiometry is based, is well suited for structural manipulations based on photolithography and micromachining, and we have begun to take advantage of this capability . We present results from a research instrument with eight separate assay channels on a 5-cm2 chip . We discuss the planned evolution of the technology toward high-through-put instruments and instruments capable of performing single-cell measurements.

Blood, 1994 Sep 1, 84(5), 1553 - 8
Structural elements influencing von Willebrand factor (vWF) binding affinity for platelet glycoprotein Ib within a dispase-digested vWF fragment; Miura S et al.; We investigated the structural elements in human von Willebrand factor (vWF) that influence binding affinity for platelet glycoprotein (GP) Ib using a dispase-digested vWF fragment as a prototype (residues Leu480/Val481-Gly718 of the vWF subunit; Andrews et al, Biochemistry 28:8326, 1989) . The major structural features of this fragment are a large A1-loop formed by an intrachain disulfide bond between Cys509 and Cys695 and six O-linked sugar chains . The fragment was chemically modified by (1) reduction and S-carboxyamido-methylation (R/A), (2) desialylation (DS), or (3) a combination of both (R/A-DS) . The GPIb binding affinity of these fragments was basically evaluated by competitive binding assay with anti-GPIb monoclonal antibody (LJ-Ib1), a receptor blocker for vWF (Sugimoto et al, Biochemistry 30:5202, 1991) . Both the prototype and the R/A fragments were also assessed for their function in shear-induced platelet aggregation . Results unambiguously demonstrated that the presence of a disulfide bridge (Cys509-Cys695) within this domain downregulates the affinity of vWF to GPIb . In addition, it was also demonstrated that the terminal sialic acids attached to six o-linked sugar chains within this domain contribute to optimal functional modulation by the antibiotic ristocetin, but not by snake venom botrocetin.

Infect Immun, 1994 Sep, 62(9), 3766 - 72
A carAB mutant of avian pathogenic Escherichia coli serogroup O2 is attenuated and effective as a live oral vaccine against colibacillosis in turkeys; Kwaga JK et al.; Colibacillosis is a serious and economically important disease of the respiratory tract of chickens and turkeys . The serogroups of Escherichia coli commonly associated with colibacillosis in poultry are O1, O2, and O78 . Although previous attempts to develop a vaccine have not been very successful, vaccination is still considered the most effective way of controlling the disease . Therefore, our laboratory has been involved in the development of an attenuated live vaccine that will be effective in the prevention of colibacillosis . The carAB operon coding for carbamoyl-phosphate synthetase, an essential enzyme in arginine and pyrimidine metabolism, was selected for study . Generalized transduction was used to transfer a Tn10-generated mutation from a laboratory strain to virulent avian field isolates of E . coli . Molecular techniques were used to determine the point of Tn10 insertion within the carAB operon . The insertion mutants were then cured of the tetracycline resistance gene of the transposon to select for antibiotic-sensitive and stable carAB mutants . The degree of attenuation obtained by the mutation was determined in day-old chickens . Typically, when 100-fold the 50% lethal dose (for the wild type) was given, no more than 50% mortality in the day-old chickens was observed . The deletion mutant of serotype O2 was also found to be avirulent in turkeys rendered susceptible to infection with hemorrhagic enteritis virus A . Turkey poults vaccinated orally at 4 weeks old with either the wild-type E . coli EC317 strain or its carAB mutant EC751 were completely protected from infection following challenge with the homologous wild-type strain . Our data indicate that carAB mutants of virulent avian strains of E . coli will be effective and safe as live oral vaccines for prevention of colibacillosis in poultry.

J Heart Valve Dis, 1994 Sep, 3(5), 473 - 5
Homograft mitral valve replacement--a case report; Kumar AS et al.; This case report describes a 25-year-old patient with calcific rheumatic mitral restenosis who underwent mitral valve replacement using a fresh, antibiotic preserved mitral homograft . The technical details of the implantation are described.

J Heart Valve Dis, 1994 Sep, 3(5), 470 - 2
Double mitral homograft for recurrent bacterial endocarditis of the mitral and tricuspid valves; Acar C et al.; A young patient suffering from acute bacterial endocarditis underwent reconstructive surgery of the mitral and tricuspid valves . One year later a recurrent endocarditis occurred that could not be controlled with antibiotic therapy . Two separate mitral homografts were used to replace both the mitral and the tricuspid valves . The homografts' papillary muscles were sutured side to side to the recipient's and a circumferential suture of the leaflet tissue was accomplished . Homograft implantation was associated with Carpentier ring annuloplasty of the atrioventricular valves . In the right sided position, the mitral homograft was oriented in an anti-anatomical manner and an inverted semi-rigid prosthetic ring of the mitral type was inserted . Clinical and echocardiographic follow up at four months was excellent.

Klin Monatsbl Augenheilkd, 1994 Sep, 205(3), 161 - 6
{Corneal ulcer in chronic graft-versus-host disease: treatment with collagen shields}; Spraul CW et al.; BACKGROUND: After bone marrow transplantation various ocular diseases have been described . Ocular involvement is very common in patients with chronic Graft-versus-Host Disease (GvHD) . These patients show clinical and histological evidence of a dry-eye condition in 60-100 per cent . A severe complication is the development of a corneal ulcer with possible corneal perforation . Two patients with a severe dry-eye condition and development of corneal stroma ulceration are described . The corneal ulcers healed after treatment with collagen-shield . HISTORY AND SIGNS: In a 13-year-old boy an allogeneic bone marrow transplantation was performed in April 1989 because of Fanconi's anemia . In November 1989 a severe dry-eye condition occurred due to GvHD with skin, liver, and gastrointestinal tract manifestation . In April 1991 he presented with corneal stroma ulceration of the right eye . In a 24-year-old patient an allogeneic bone marrow transplantation was performed because of chronic myeloid leukemia in August 1989 . In December 1989 he developed dry-eye condition due to GvHD with skin, mucosa and liver involvement . In December 1991 a corneal ulcer of the left eye occurred . THERAPY AND OUTCOME: Repeated conjunctival and corneal smears were negative . Local antibiotic and antiviral treatment showed no effect . Corneal ulcers deteriorated progressively with corneal thinning . Both patients were therefore treated with daily collagen-shields and hourly polyvinyl-pyrrolidon eye-drops resulting in healing of the corneal ulcer within 3 and 2 weeks respectively . CONCLUSION: Treatment of corneal stromal ulceration in dry eye condition caused by chronic GvHD is difficult . In noninfectious ulcers daily application of collagen-shields and hourly artificial tears may prevent severe ocular complications like corneal perforation.

Mol Biol (Mosk), 1994 Sep-Oct, 28(5), 1137 - 48
{Synthesis and interaction of two peptides, modeling the DNA-binding domain of the v-jun transcription activator, with DNA}; Grokhovskii SL et al.; Synthesis and DNA-binding activities of the two synthetic 26-residue peptides, containing in two copies a part of the DNA-binding region of the transcription activator v-Jun, are reported . Aminoacid sequences of the two peptides are identical, but in one of them the structure of the DNA-binding region is stabilized by S-S-bond between the two cysteine residues . Using CD spectroscopy, it is shown that the two peptides exist in a random coil conformation in aqueous solution, but assume partially an alpha-helical conformation in the presence of 20% trifluoroethanol . The percentage of alpha-helix is increased in the presence of 40% trifluoroethanol up to approximately 65% and 40% in the absence and presence of S-S-bond between the two cysteine residues, respectively . Evidently, formation of S-S-bond prevents a coil to alpha-helix transition in one of the two DNA-binding regions of the peptide, whereas the formation of alpha-helix in another DNA-binding region is allowed . It is shown that the two peptides bind to DNA . We found that the DNA minor groove-binding antibiotic distamycin A competes with the two peptides for binding to poly(dA).poly(dT) . The binding of the two peptides to DNA is accompanied by conformational transitions in the peptide molecules, whereas the structure of DNA does not undergo a marked change . The difference CD spectrum obtained by subtracting the spectrum of DNA from the spectrum of a peptide-DNA mixture differs from the CD spectrum of the free peptide . The shapes of the difference CD spectra are consistent with alpha-beta and coil-beta transitions induced upon binding of the two peptides to DNA . DNase I footprinting diagrams show that peptides mediated cleavage protection of DNA takes place at regions containing 5'-TGA-3' and 5'-TGC-3' nucleotide sequences.

Mol Biol (Mosk), 1994 Sep-Oct, 28(5), 1128 - 36
{Interaction of a synthetic peptide, containing a part of the DNA-binding domain of the v-jun transcription activator, with DNA}; Grokhovskii SL et al.; Synthesis and DNA-binding activity of the synthetic 26-residue peptide, containing in two copies a part of the DNA-binding domain of the transcription activator v-Jun, are reported . Using CD spectroscopy, it has been shown that the peptide exists in a random coil conformation in aqueous solution, but assumes partially an alpha-helical conformation in the presence of 20% trifluoroethanol . The percentage of alpha-helix is increased in the presence of 40% trifluoroethanol up to approximately 80% . It has been shown that the peptide forms two types of complexes with DNA . The first type of complexes saturates when one peptide molecule occupies six base pairs . At further increase of molar peptide to DNA ratio the binding became a cooperative process . The binding approaches saturation when one peptide molecule is bound approximately to four DNA base pairs . The binding constant of the monomer peptide complex with DNA has been estimated to be approximately 1.10(5) M-1 in the presence of 0.2 M NaCl . The peptide binds more strongly to poly(dG).poly(dC) and poly(dA).poly(dT) than to poly{d(GC)}.poly{d(GC)} . We found that the DNA minor groove-binding antibiotic distamycin A competes effectively with the peptide for binding to poly(dA).poly(dT).

Ann Plast Surg, 1994 Sep, 33(3), 330 - 2
Blastomycosis infection of the hand; Bergman BA et al.; Blastomycosis is an uncommon cause of infection in the hand . Fungal infection should be suspected in any case when expected improvement does not occur with appropriate antibiotic therapy and wound care . We describe a rare case of primary blastomycosis of the hand that progressed to severe soft tissue destruction and significant loss of hand function.

Clin Chest Med, 1994 Sep, 15(3), 581 - 602
Life-threatening pneumonia; Gleeson K et al.; Severe pneumonia can be acquired by previously healthy patients, those with pre-existing illness, or those hospitalized for an unrelated illness . Because diagnosis is frequently difficult or delayed, treatment is usually empirically tailored to the most probable offending organisms and the patient's condition . This article reviews the pathogenesis of community- and hospital-acquired pneumonia, clinical features, and diagnostic techniques . An approach to selecting an antibiotic regimen is suggested.

Urologe A, 1994 Sep, 33(5), 370 - 6
{New immunosuppressive therapies in kidney transplantation}; Pomer S; New approaches to successful prevention and management of transplant rejection include the use of biological immunosuppressants, such as monoclonal antibodies targeting the CD3 and CD4 molecules on native T cells, the interleukin 2 receptor on activated T cells, monocytes and B cells, and adhesion molecules . Several new drugs have been found to be effective immunosuppressive agents: FK 506, a macrolid antibiotic inhibiting lymphokine gene transcription, lymphokine production and secretion, rapamycin, which blocks effects of lymphokine-induced signal transduction, and RS 61443, brequinar and mizoribine, which inhibit DNA/RNA synthesis and lymphocyte proliferation . Initial experience with these drugs clinical protocols currently in use and already devised for use in the near future to test these and other emerging immunosuppressants are reviewed.

Parasitology, 1994 Sep, 109 ( Pt 3), 281 - 9
Septata intestinalis frequently isolated from stool of AIDS patients with a new cultivation method; van Gool T et al.; Two species of microsporidia, Enterocytozoon bieneusi and Septata intestinalis have been reported as intestinal parasites of AIDS patients . In attempts to establish E . bieneusi in vitro, spores were concentrated from stool samples from 4 AIDS patients with biopsy-proven E . bieneusi infections . After sterilization of the concentrate in antibiotic solution, the spores were added to monolayers of RK13 cells grown on the membranes of Transwells . Cultures were established from 7 stool samples from the 4 patients but in every case the species established was S . intestinalis not E . bieneusi . On retrospective examination of the stools, a very small number of spores of a size comparable to that of S . intestinalis was found but this species was not detected in biopsies . Typical septate vacuoles containing Type I tubules were observed in vitro but in contrast to the original description, meronts were intravacuolar and sporogony was mainly disporoblastic . The cultivation system, used for the first time for microsporidia, revealed the presence of unsuspected S . intestinalis infections and indicates that this species may be much more common than hitherto suspected . S . intestinalis has not previously been cultured.

Leber Magen Darm, 1994 Sep, 24(5), 203 - 9
{Helicobacter pylori therapy with omeprazole and clarithromycin: current status}; Labenz J; Clarithromycin and its 14-OH-metabolite are highly effective against Helicobacter pylori in vitro . This drug is acid stable and soluble and reaches considerable concentrations in the gastric mucosa and the mucus layer after oral administration . Several studies have meanwhile demonstrated that combined treatment with omeprazole and clarithromycin may eradicate . H . pylori infection in a remarkable proportion of treated patients . On the basis of the results of a recently published randomized doubleblind multicenter trial, at two-week therapy course comprising omeprazole 40 mg once in the morning and clarithromycin 500 mg thrice daily can be recommended for routine practice . One-week low dose triple therapy regimens combining omeprazole, clarithromycin and tinidazole or metronidazole might be a valuable alternative to omeprazole enhanced antibiotic monotherapy in the future, but the encouraging results of three pilot studies (H . pylori cure rates: 90%-100%) have to be confirmed in randomized and controlled trials.

Thorax, 1994 Sep, 49(9), 856 - 9
Intrapleural streptokinase in the management of empyema; Taylor RF et al.; BACKGROUND--Significant morbidity and mortality result from the ineffective evacuation of empyema . Failure of conventional first line treatment with closed intercostal tube drainage and antibiotic therapy may result in fibrin deposition and loculated empyema . Enzymatic debridement using intrapleural instillation of streptokinase is a non-invasive therapeutic option which may obviate the need for surgical intervention . METHODS--Eleven adults with multiloculated post-pneumonic empyemas who had failed to respond satisfactorily to intercostal tube drainage and antibiotic therapy were treated with intrapleural streptokinase between November 1992 and January 1994 . A small catheter was inserted under ultrasound guidance into a loculation within the pleural space . Aliquots of 250,000 units of streptokinase in 100 ml normal saline were instilled into the pleural cavity and the tube clamped for four hours . Response was assessed by clinical outcome, measurement of drain output after unclamping, and subsequent pleural ultrasound, chest radiography, or both . RESULTS--Streptokinase enhanced drainage in all patients . Complete resolution of the empyema with re-expansion of the underlying lung was effected in eight patients, all of whom remain well . Further resolution of minimal pleural thickening was shown on subsequent chest radiographs . Two patients with considerably thickened visceral pleura following empyema drainage underwent successful decortication . The other, with myocarditis and a pyopneumothorax, underwent surgery for non-resolution of the pneumothorax but died perioperatively from cardiac failure . The number of streptokinase instillations per patient ranged from two to six (median three), and the volume of empyema fluid drained per patient ranged from 100 ml to 4870 ml (median 900 ml) . Streptokinase was well tolerated in all patients . CONCLUSIONS--Intrapleural streptokinase is an effective adjunct in the management of complicated empyema and may reduce the need for surgery.

FEMS Microbiol Lett, 1994 Sep 1, 121(3), 275 - 9
Influence of iron on microcin 25 production; Salomon RA et al.; The effect of the iron content of the medium on the yield of the peptide antibiotic microcin 25 was examined; synthesis was optimal in minimal media and was reduced by adding iron . Escherichia coli AY25, the wild-type producer of the antibiotic, showed a 95% decrease in microcin yield when grown in minimal medium containing 10 microM iron (high iron) as compared to 0.2 microM (low iron) . Addition of chelators to Luria broth elicited microcin production, and there was a complete reversal of the effect of the chelators by adding iron . Studies with Escherichia coli mutants deficient in iron-regulated proteins (fur) suggested that factors other than Fur could mediate iron regulation of microcin synthesis.

J Biomol NMR, 1994 Sep, 4(5), 689 - 702
Assignment of the protonated 13C resonances of apo-neocarzinostatin by 2D heteronuclear NMR spectroscopy at natural abundance; Lefevre C et al.; Nearly complete assignment of the protonated carbon resonances of apo-neocarzinostatin, a 113-amino acid antitumor antibiotic carrier protein, has been achieved at natural 13C abundance using heteronuclear 2D experiments . Most of the cross peaks in the proton-carbon correlation map were identified by the combined use of HMQC, HMQC-RELAY and HMQC-NOESY spectra, using already published proton chemical shifts . However, double-DEPT and triple-quantum experiments had to be performed for the edition of CH and CH2 side-chain groups, respectively, which were hardly visible on HMQC-type maps . The triple-quantum pulse sequence was adapted from its original scheme to be applicable to a natural abundance sample . The correlation between carbon chemical shifts and the apo-neocarzinostatin structure is discussed . In particular, 13C alpha secondary shifts correlate well with the backbone conformation . These shifts also yield information about the main-chain flexibility of the protein . Assignments reported herein will be used further for interpretation of carbon relaxation times in a study of the internal dynamics of apo-neocarzinostatin.

Jpn J Pharmacol, 1994 Sep, 66(1), 1 - 6
Preventive effect of betamipron on nephrotoxicity and uptake of carbapenems in rabbit renal cortex; Hirouchi Y et al.; The preventive effect of betamipron (N-benzoyl-3-propionic acid: BP) on the renal uptake and nephrotoxicity of carbapenems (panipenem and imipenem) was studied in rabbits . Panipenem, a new carbapenem antibiotic, induced nephrotoxicity at a dose of 200 mg/kg, i.v., but this was less severe than that caused by a single dose of imipenem or cephaloridine . Along with the significant reduction of nephrotoxicity, the uptake of these carbapenems in the renal cortex was remarkably inhibited by simultaneous treatment with BP (200 mg/kg, i.v.) . These results suggest that BP reduces the nephrotoxicity of carbapenems through inhibiting the active transport of carbapenems in the renal cortex . Because of the low toxicity of BP (LD50 in the rat, more than 3,000 mg/kg, i.v.), it was concluded that BP might be a good candidate for reducing the nephrotoxicity induced by panipenem or imipenem.

Orthop Nurs, 1994 Sep-Oct, 13(5), 41 - 52; quiz 53
Patients with long-term vascular access devices: care and complications; Hagle ME et al.; Orthopaedic nurses will be dealing with more long-term vascular access devices, such as tunneled catheters, implanted ports, and peripherally inserted central catheters as antibiotic and other supportive intravenous therapy is administered over longer periods . Caring for patients with these devices requires an understanding of the purpose and design of the device, use and maintenance of the catheter or port, and actions to take if complications arise . Knowing the cause and response to the most common clinical problems, such as infection, occlusion, and thrombosis, will help in problem solving and support a variety of teaching strategies for patients . Nurses who are familiar with these central venous devices will be able to provide safe and effective care for patients in the hospital and at home.

Clin Exp Rheumatol, 1994 Sep-Oct, 12(5), 535 - 7
Cutaneous infection with rapidly growing mycobacteria in patients with systemic rheumatic disease; Pablos JL et al.; We report two patients with systemic rheumatic disease being treated with steroids whose cases were complicated by subcutaneous nodules . In both, clinical and histological features suggested cutaneous infection and M . chelonae was isolated from skin specimens . Antibiotic therapy in both and surgery in one led to healing after a prolonged course . A review of the literature and our experience with these two patients suggest that rheumatic patients on steroid therapy are at risk of infection with these unusual pathogens . Knowledge of the risk factors and the distinctive picture of cutaneous mycobacteriosis should improve its diagnosis and therapy.

Biol Chem Hoppe Seyler, 1994 Sep, 375(9), 629 - 33
Chemical reactivity of the toxin oosponol from Gloeophyllum abietinum with nucleophilic agents; Dietrich J et al.; It is shown that contrary to most isocoumarins the antibiotic compound oosponol from the fungus Gloeophyllum abietinum reacts instantaneously with nucleophilic agents like thiol compounds . The reason for this high reactivity is due to the vinylogous acid anhydride character of the compound which is produced by a single oxidation step of the non toxic biological precursor oospoglycol . One must assume that reactions of oosponol with HS-groups of polypeptides form the basis for its toxicity . The ring-opening reactions were studied in detail with the synthetic analogue 4-acetyl-isocoumarin . The structures of some reaction products have been analysed mainly with H-1 and C-13 NMR spectroscopy.

Gen Pharmacol, 1994 Sep, 25(5), 957 - 61
Pertussis toxin prevents neomycin-induced calcium-dependent electrophysiological effects in rat hippocampal slices; Frank C et al.; 1 . The influence of pertussis toxin has been studied on the effects of neomycin on CA1 field potentials in rat hippocampal slices in order to determine a role played by G protein in the modulation of synaptic transmission by the drug . 2 . Neomycin (500 microM), within 30 min significantly (P < 0.01) decreased the magnitude of the somatic CA1 excitatory postsynaptic potentials (EPSP) and population spike (PS) in control hippocampal slices . 3 . Neomycin (500 microM), within 30 min failed to significantly affect the magnitude of the somatic CA1 EPSP and PS in slices obtained from animals treated intracerebroventricularly (ICV) with 1-2 micrograms of pertussis toxin 3 days before . 4 . The results demonstrated that pertussis toxin prevents some electrophysiological effects of neomycin, suggesting a role of G protein in the modulation of the aminoglycoside antibiotic on central synaptic transmission.

Hum Gene Ther, 1994 Sep, 5(9), 1115 - 20
Transfer of an anti-HIV-1 ribozyme gene into primary human lymphocytes; Leavitt MC et al.; We reported previously that human CD4+ T cell lines stably expressing a hairpin ribozyme targeted to the human immunodeficiency virus type 1 (HIV-1) U5 leader sequence were resistant to challenge with diverse HIV-1 viral clones and clinical isolates (Yamada et al., 1994) . To simulate more closely the in vivo infection process for investigations of anti-HIV-1 ribozyme gene therapy, we developed a system to transfer this ribozyme gene into freshly isolated human peripheral blood lymphocytes (PBLs) using a murine retrovirus vector . Following transduction and G418 selection, human PBLs from multiple donors expressed the ribozyme and resisted challenge by HIV-1 viral clones and clinical isolates, while control vector-transduced PBLs remained fully permissive for HIV-1 infection . No inhibition of an HIV-2 clone lacking the target was seen in ribozyme-expressing PBLs . Ribozyme expression had no effect on viability or proliferation kinetics of the primary lymphocytes . This study is the first demonstration in primary human T cells of resistance to HIV-1 infection conferred by gene transfer . A human clinical trial is in development to test further the safety and efficacy of this ribozyme in PBLs of HIV-1-infected patients in vivo.

J Pharm Sci, 1994 Sep, 83(9), 1294 - 9
Comparison of quantitative whole-body autoradiographic and tissue dissection techniques in the evaluation of the tissue distribution of {14C}daptomycin in rats; Chay SH et al.; Quantitative whole-body autoradiography (QWBA) was evaluated and compared to tissue dissection/liquid scintillation counting (TD/LSC) techniques by determining the tissue distribution of radiocarbon in rats following iv administration of the antibiotic {14C}daptomycin (LY146032) . QWBA, using computer-assisted video-image analysis, was initially evaluated by characterizing and calibrating commercial standards to blood and brain, kidney, liver, and lung homogenates . Frozen (carboxymethyl)cellulose blocks containing tissue homogenates spiked with {14C}glucose (370-37,000 Bq/g or 10-1000 nCi/g) were sectioned and optical densities (OD) measured . Characterization of QWBA included repeated measures data analysis to determine the significance of tissue type and intra- and inter-section and block variability . Regression models relating OD to radiocarbon concentration were also used to calibrate commercial standards for use in QWBA analyses . Results indicated that there were no substantial differences between OD readings from different tissues; however, the greatest source of variation in OD reading was section thickness . Because quantitative variations were largely attributed to section thickness, an internal standard (IS), consisting of liver homogenates spiked with {14C}glucose, was evaluated as a correction factor . Tissue concentrations of radiocarbon in male Fischer 344 rats were evaluated by QWBA and TD/LSC techniques 0.25 h following a single iv 10 mg/kg dose of {14C}daptomycin . Results indicated that tissue concentrations of radiocarbon obtained by QWBA, normalized using an IS, were comparable to those obtained by TD/LSC.

Psychiatr Clin North Am, 1994 Sep, 17(3), 541 - 58
Mad, homeless, and unwanted . A history of the care of the chronic mentally ill in America; Grob GN; The history of the care and treatment of the mentally ill in America for nearly four centuries offers a sobering example of a cyclical pattern that alternated between enthusiastic optimism and fatalistic pessimism . In the nineteenth century an affinity for institutional solutions led to the creation of the mental hospital, an institution designed to promote recovery and to enable the individual to return to the community . No institution ever lives up to the claims of its promoters, and the mental hospital was no exception . Plagued by a variety of problems, its reputation and image were slowly tarnished . When it became clear that hospitals were caring for large numbers of chronic patients, the stage was set for an attack on its legitimacy after World War II . Its detractors insisted that a community-based policy could succeed where an institutional policy had failed, and that it was possible to identify mental illnesses in the early stages, at which time treatment would prevent the advent of chronicity . Between the 1940s and 1960s, there was a sustained attack on institutional care that finally succeeded when Congress enacted and the president signed a piece of legislation that shifted the locus of care and treatment back to the community . The community mental health policy proved no less problematic than its institutional predecessor . Indeed, the emergence of a new group of young chronic mentally ill persons in the 1970s and 1980s created entirely new problems, for the individuals who constituted this group proved difficult to treat and to care for under any circumstances . Each of these stages was marked by unrealistic expectations and rhetorical claims that had little basis in fact . In their quest to build public support and legitimate their cherished policy, psychiatric activists invariably insisted that they possessed the means to prevent and to cure severe mental disorders . When such expectations proved unrealistic, they placed the blame either upon callous governments, an uninformed public, or an obsolete system that failed to incorporate the findings of medical science . If American society is to deal effectively, compassionately, and humanely with the seriously mentally ill, several elements must be taken into account . First, the seriously mentally ill include individuals with quite different disorders, prognoses, and needs . Secondly, outcomes vary considerably over time . Some schizophrenics, for example, have reasonably good outcomes; others lapse into chronicity and become progressively more disabled . Finally, serious mental disorders are often exacerbated by poverty, racism, and substance abuse . Although psychiatric therapies can alleviate symptoms and permit individuals to live in the community, there is no "magic bullet" that will cure all cases of serious mental illnesses in the same way that antibiotic drugs are effective against acute infectious diseases.(ABSTRACT TRUNCATED AT 400 WORDS)

Clin Infect Dis, 1994 Sep, 19(3), 463 - 79
Mechanisms of brain injury in bacterial meningitis: workshop summary; Pfister HW et al.; Morbidity and mortality associated with bacterial meningitis remain high, although antibiotic therapy has improved during recent decades . The major intracranial complications of bacterial meningitis are cerebrovascular arterial and venous involvement, brain edema, and hydrocephalus with a subsequent increase of intracranial pressure . Experiments in animal models and cell culture systems have focused on the pathogenesis and pathophysiology of bacterial meningitis in an attempt to identify the bacterial and/or host factors responsible for brain injury during the course of infection . An international workshop entitled "Bacterial Meningitis: Mechanisms of Brain Injury" was organized by the Department of Neurology at the University of Munich and was held in Eibsee, Germany, in June 1993 . This conference provided a forum for the exchange of current information on bacterial meningitis, including data on the clinical spectrum of complications, the associated morphological alterations, the role of soluble inflammatory mediators (in particular cytokines) and of leukocyte-endothelial cell interactions in tissue injury, and the molecular mechanisms of neuronal injury, with potential mediators such as reactive oxygen species, reactive nitrogen species, and excitatory amino acids . It is hoped that a better understanding of the pathophysiological events that take place during bacterial meningitis will lead to the development of new therapeutic regimens.

Antimicrob Agents Chemother, 1994 Sep, 38(9), 2221 - 3
Penetration of cefotetan into suction skin blister fluid and tissue homogenates in patients undergoing abdominal surgery; Mazzei T et al.; The penetration of cefotetan (2-g intravenous bolus) into the suction blister fluid and tissue homogenates of 11 patients was investigated . Mean concentrations in tissue were significantly lower than contemporary suction blister fluid levels . These data show that the determination of beta-lactam concentrations by the tissue homogenate method may seriously underestimate the actual antibiotic levels in extracellular fluid.

J Pediatr Surg, 1994 Sep, 29(9), 1242 - 4
Total anomalous pulmonary venous return complicating portoenterostomy for biliary atresia; Lallier M et al.; Cardiovascular anomalies such as absent inferior vena cava and preduodenal portal vein are reported in cases of biliary atresia and make hepatic portoenterostomy a technical challenge . The authors present the case of a severe cardiac anomaly that significantly altered the functional outcome of a Kasai procedure . Baby M., an 8-week-old boy born with total anomalous pulmonary venous return (TAPVR), underwent hepatic portoenterostomy for biliary atresia . Over the next 3 months he remained icteric and febrile, and failed to gain weight . After multiple antibiotic treatments for suspected cholangitis, he underwent reexploration of the portoenterostomy, with no improvement in his overall condition . His prognosis was considered dismal because correction of the cardiac anomaly is associated with a high mortality rate (> 90%) . The cardiac surgeon agreed to attempt a cure of the TAPVR, provided liver transplantation is contemplated if the patient survived . Within 48 hours postoperatively, his hepatic function had improved drastically . He became afebrile, had an improved appetite and weight gain, and was finally discharged 203 days after admission . One year later, he is thriving and remains anicteric . The exact reason for this drastic improvement is not well understood, but the right-sided cardiac failure caused by the TAPVR had a significant effect on the functional outcome of the portoenterostomy.

J Lipid Res, 1994 Sep, 35(9), 1524 - 34
The ansamycins: hypolipidemic agents stimulating cholesterol removal by nonclassical mechanisms; Gibson JC et al.; The ansamycins CGP 43371 and CGS 24565 are derivatives of the antibiotic rifamycin that reduce plasma cholesterol levels in both primate and nonprimate species . In vivo, a striking accumulation of macrophage cholesteryl ester was seen in ansamycin-treated rats and hamsters, but carbon clearance studies and reticuloendothelial system blockade by gadolinium chloride indicated that phagocytosis was not involved . Simple addition of an ansamycin to macrophages or monocytes in vitro failed to stimulate radiolabeled lipoprotein cholesteryl ester association or mass accumulation . In contrast to mononuclear cells, however, the ansamycins did enhance radiolabeled lipoprotein cholesteryl ester association by liver cells in vitro . Primary hepatocyte cultures prepared from rats treated with radiolabeled CGP 43371 secreted CGP 43371 over an 18-h period in a fraction floating at d < 1.02 g/ml after density gradient ultracentrifugation that was relatively enriched in apoA-I . The medium containing this secreted {14C}GP 43371-labeled lipoprotein was capable of enhancing the cholesteryl ester content of macrophages in vitro, suggesting that ansamycin-induced liver modification of lipoproteins might be involved . These drugs may serve as valuable tools for studying mechanisms of lipoprotein uptake.

J Infect, 1994 Sep, 29(2), 195 - 202
Infection in immunocompromised patients with malignant blood disorders in a district general hospital; Flanagan NG et al.; The pattern and management of infection in immunocompromised patients over a period of 3 years in a district general hospital has been studied . A total of 222 positive cultures was obtained in 607 episodes of suspected infection all involving patients with malignant blood disorders . Febrile episodes requiring intravenous antibiotics occurred in 248 instances involving 107 patients . The pattern of organisms cultured and the responses to various antibiotic regimes are reported . The costs of antibiotic therapy are considered in the light of the overall response . Of the patients studied, 54 died, infection having a likely causative or contributory part in 21 of them (less than 10% of infective episodes) . We conclude that the infective complications of these disorders, particularly in older patients, can be efficiently managed in a district general hospital when full supportive facilities are available.

J Accid Emerg Med, 1994 Sep, 11(3), 195 - 7
Non-penetrating corneal foreign body injuries: factors affecting delay in rehabilitation of patients; Jayamanne DG et al.; A review of 783 patients with non-penetrating, superficial corneal foreign bodies (FBs), indicated that delay in rehabilitation was related to two factors: (1) the size of the abrasion following removal of the FB, larger abrasions requiring longer duration of antibiotic ointment, and (2) inadequate removal of corneal rust . Allergy to chloramphenicol 1% ointment (5.5 in 1000), commonly used in the management of corneal abrasions, is unpredictable and can also impair rapid rehabilitation.

Hinyokika Kiyo, 1994 Sep, 40(9), 853 - 60
{Evaluation of clinical efficacy and safety of cefpodoxime proxetil (CPDX-PR) in acute uncomplicated cystitis}; Furusawa T et al.; One hundred and fifty female patients with acute uncomplicated cystitis were given 200 mg of CPDX-PR twice daily for 3-7 days to evaluate both its overall clinical efficacy and its adverse effects . In 82 cases (Group I) in which it was administered for 3 days, the overall clinical efficacy, evaluated by the criteria proposed by the Japanese UTI committee, was excellent in 64 cases, moderate in 17 and poor in one, with the effective rate being 98.8% . In 35 cases (Group II) in which it was administered for 4-7 days, the overall clinical efficacy was excellent in 18 cases, moderate in 15 and poor in 2, with the effective rate being 94.3% . The overall clinical evaluation was not performed in another 33 cases because they were given CPDX-PR for more than 8 days or 300 mg/day . Subjective adverse effects such as hoarseness and lingual inflammation were observed in only one of the 150 cases, but they disappeared spontaneously after the cessation of administration of CPDX-PR . These findings suggest that CPDX-PR is one of the most effective and safe antibiotic in the treatment of acute uncomplicated cystitis.

Int J Qual Health Care, 1994 Sep, 6(3), 219 - 30
Concerted action programme on quality assurance in hospitals 1990-1993 (COMAC/HSR/QA) . Global results of the evaluation; Klazinga N; This article describes the global results of the evaluation of a concerted action programme on quality assurance in hospitals that was executed between 1990 and 1993 in a total of 262 hospitals in 15 European countries . The programme aimed to introduce quality assurance notions into European hospitals and focused on four specific topics; record keeping, prophylactic antibiotic use in surgery, preoperative assessment and the prevention of bedsores . Evaluation took place on a national level (descriptive country reports), hospital level (questionnaire) and topic level (questionnaire and results of QA studies performed in the participating hospitals) . Different situational and operational factors on national, hospital and topic level, that seem to influence the effectiveness of strategies for the implementation of quality assurance, are identified . The relative importance of these factors is discussed and supported with empirical evidence . Part of the analysis is based on quantitative data based on comparing the situation in 113 hospitals in 1990 and 1993, before and after the intervention.

Biosci Biotechnol Biochem, 1994 Sep, 58(9), 1579 - 83
Action of FR901228, a novel antitumor bicyclic depsipeptide produced by Chromobacterium violaceum no . 968, on Ha-ras transformed NIH3T3 cells; Ueda H et al.; FR901228, a novel antitumor antibiotic, reversed the transformed morphology of the Ha-ras transformants, Ras-1 cells, and inhibited their growth . The reduction of c-myc expression was observed in FR901228-treated Ras-1 cells by RNA dot-blot hybridization . This reduction of c-myc expression and morphological reversion of the transformed cells to normal were correlated with growth inhibition (G0/G1 arrest in cell cycle).

Minerva Stomatol, 1994 Sep, 43(9 Suppl 1), 1 - 4
{Clarithromycin in the treatment of oral infections}; Cali G et al.; The authors show the results of a clinical study to test the efficacy and the tolerance of clarithromycin when used in the treatment of odontological infections . Forty-one subjects were selected for the study . All the subjects were affected by odontological infections and needed antibiotic therapy . The results obtained are satisfactory and demonstrate the effectiveness of the use of clarithromycin in the treatment of odontological infections.

Eksp Klin Farmakol, 1994 Sep-Oct, 57(5), 29 - 32
{The transplacental transit and action of ceftazidime on the fetus in an experiment on animals at different times of the pregnancy}; Kasabulatov NM et al.; The experiments were conducted on pregnant albino rats to study the transplacental transit of ceftazidime (Fortum) to the fetus on days 14 and 21 of pregnancy after a single intramuscular injection of 100 mg/kg . The antibiotic transition was 5.23, and 51.94% on days 14 and 21, respectively . The total toxic and embryotoxic effects of ceftazidime were studied in pregnant albino rats given intramuscular injections of 100 and 500 mg/kg/day on days 9-20 of pregnancy . Ceftazidime was found to have neither negative effects on the maternal body and nor embryotoxic and teratogenic properties.

Lancet, 1994 Aug 27, 344(8922), 581 - 2
Randomised trial of prevention of biliary stent occlusion by ursodeoxycholic acid plus norfloxacin; Barrioz T et al.; Biliary stents are liable to clog . We investigated whether a choleretic plus an antibiotic could delay clogging . 20 consecutive patients with a malignant biliary stricture were randomised after endoscopic insertion of a polyethylene stent to receive ursodeoxycholic acid plus norfloxacin (13-15 mg/kg and 400 mg, daily) or conservative treatment . The drug combination was associated with: a longer median patency of first (49 vs 6 weeks) and all stents (38 vs 7 weeks); a prolonged median survival (67 vs 18 weeks); and a shorter mean hospital stay (0.2 vs 1.0 days per week of survival) . Thus ursodeoxycholic acid plus norfloxacin may prevent stent clogging.

Arch Intern Med, 1994 Aug 22, 154(16), 1793 - 802
Outpatient treatment of community-acquired pneumonia in adults; Pomilla PV et al.; Most adults with community-acquired pneumonia are treated as outpatients . Despite this, the majority of studies regarding community-acquired pneumonia have been in hospitalized patients only and may not be applicable to an ambulatory population . This review critically examines the literature regarding the diagnosis, cause, appropriate patient selection, and treatment of nonhospitalized adults with community-acquired pneumonia, including human immunodeficiency virus-infected individuals . English-language articles on oral antibiotic trials for community-acquired pneumonia, obtained from a MEDLINE search from 1966 to the present, are reviewed . Etiologic diagnosis is helpful in determining appropriate outpatient treatment for community-acquired pneumonia, and usually requires only sputum Gram's stain analysis . Viral, mycoplasmal, and chlamydial agents are among the most common pathogens encountered in individuals treated as outpatients, although much variability exists . Many oral antibiotic trials for community-acquired pneumonia have been published, but shortcomings in study design limit their clinical applicability . A treatment algorithm is offered, using the best available data.

Science, 1994 Aug 19, 265(5175), 1098 - 101
Generation of lymphohematopoietic cells from embryonic stem cells in culture; Nakano T et al.; An efficient system was developed that induced the differentiation of embryonic stem (ES) cells into blood cells of erythroid, myeloid, and B cell lineages by coculture with the stromal cell line OP9 . This cell line does not express functional macrophage colony-stimulating factor (M-CSF) . The presence of M-CSF had inhibitory effects on the differentiation of ES cells to blood cells other than macrophages . Embryoid body formation or addition of exogenous growth factors was not required, and differentiation was highly reproducible even after the selection of ES cells with the antibiotic G418 . Combined with the ability to genetically manipulate ES cells, this system will facilitate the study of molecular mechanisms involved in development and differentiation of hematopoietic cells.

J Biol Chem, 1994 Aug 19, 269(33), 21177 - 83
Yeast bleomycin hydrolase is a DNA-binding cysteine protease . Identification, purification, biochemical characterization; Xu HE et al.; Bleomycin (BLM) is a DNA binding and damaging antibiotic produced by Streptomyces verticillus that has been used as an anti-tumor drug for various human cancers . The mammalian BLM hydrolase is a cysteine protease that inactivates BLM to relieve the toxicity of BLM to normal and tumor cells . The normal physiological function of BLM hydrolase is not known, but its activity limits the use of BLM in cancer chemotherapy . We have discovered a DNA binding activity for the yeast homolog of the mammalian BLM hydrolase in the course of studying the interaction of GAL4, a DNA-binding transcription factor, with its DNA recognition sites . Using gel mobility shift assays, we have purified a protein from yeast that binds specifically to the GAL4 DNA-binding sites . The purified protein is a tetramer of a 48-kDa polypeptide . The gene encoding the 48-kDa polypeptide was cloned and has a high homology to rabbit BLM hydrolase . The purified protein was confirmed to have a cysteine protease activity that can hydrolyze and inactivate BLM in vitro . We have established the optimal conditions for the protease activity of this protein and biochemically characterized its DNA binding activity . This protein binds both single- and double-stranded forms of the GAL4 DNA-binding sites with high affinity (10 nM to single strand and 1 microM to double strand) . Its DNA binding activity is heat stable and resistant to various detergents . This protein may represent the first example of a eukaryotic DNA-binding protease . The discovery of a DNA binding activity for BLM hydrolase suggests an in vivo interaction between it and BLM on DNA.

Am J Med, 1994 Aug 15, 97(2A), 50 - 5
Reducing costs and hospital stay for pneumonia with home intravenous cefotaxime treatment: results with a computerized ambulatory drug delivery system; Williams DN; Studies have documented the efficacy and safety of antibiotic infusion in the home as a cost-effective alternative to in-hospital infusion . The present analysis focuses on home treatment of pneumonia with cefotaxime delivered via an ambulatory infusion pump and the potential of this therapy to reduce the length of hospital stay . Data presented here and in previously published studies of a variety of serious infections show that admitting patients into home intravenous antibiotic therapy programs can significantly reduce, and sometimes eliminate, hospital stay, while providing efficacy and safety comparable to that expected from hospital treatment . Analysis of hospitalization patterns for pneumonia patients placed on cefotaxime therapy delivered via portable infusion pump revealed that length of stay was only 10% of that for the reference diagnosis-related group . Despite the great potential cost savings, there are reimbursement barriers to the use of home infusion antibiotics . However, healthcare reform may promote greater acceptance, use, and support of home infusion technology.

Blood, 1994 Aug 15, 84(4), 1333 - 41
Ganciclovir treatment of herpes simplex thymidine kinase-transduced primary T lymphocytes: an approach for specific in vivo donor T-cell depletion after bone marrow transplantation?
Tiberghien P, Reynolds CW, Keller J, Spence S, Deschaseaux M, Certoux JM, Contassot E, Murphy WJ, Lyons R, Chiang Y, et al.
Allogeneic bone marrow transplantation (BMT) is associated with a severe complication--graft-versus-host disease (GVHD) . Although effectively preventing GVHD, ex vivo T-lymphocyte marrow depletion unfortunately increases graft rejection and reduces the graft-versus-leukemia (GVL) effect . The ex vivo transfer of the herpes simplex thymidine kinase (HS-tk) suicide gene into T cells before their infusion with hematopoietic stem cells could allow for selective in vivo depletion of these T cells with ganciclovir (GCV) if subsequent GVHD was to occur . Thus, one could preserve the beneficial effects of the T cells on engraftment and tumor control in patients not experiencing severe GVHD . To obtain T cells specifically depleted by GCV, we transduced primary T cells with a retroviral vector containing the HS-tk and neomycin resistance (NeoR) genes . Gene transfer was performed by coculturing PHA +/- CD3- or alloantigen-stimulated purified T cells on an irradiated retroviral vector producer cell line or by incubating the T cells in supernatant from the producer . Subsequent culture in G418 for 1 week allowed for the selection of transduced cells . GCV treatment of interleukin-2-responding transduced and selected cells resulted in greater than 80% growth inhibition, whereas GCV treatment of control cells had no effect . Similarly, the allogeneic reactivity of HS-tk-transduced cells was specifically inhibited by GCV . Combining transduced and nontransduced T cells did not show a bystander effect, thus implying that all of the cells inhibited by GCV were indeed transduced . Lastly, studies involving the transduction of the HUT-78 (T-lymphoma) cell line suggest that stable expression of HS-tk can be maintained over 3 months in vitro in the absence of G418 . In summary, we have established the feasibility of generating HS-tk-transduced T cells for subsequent in vivo transfer with hematopoietic stem cells and, if GVHD occurs, specific in vivo GCV-induced T-cell depletion in allogeneic BMT recipients.

FEBS Lett, 1994 Aug 8, 349(3), 327 - 30
Concanamycin A blocks influenza virus entry into cells under acidic conditions; Guinea R et al.; The selective inhibitor of the vacuolar proton-ATPase, concanamycin A, powerfully blocks influenza virus entry into cells, if present during the initial times of virus infection . Attachment of virus particles to cells is not prevented by concanamycin A, rather the exit of influenza virus from endosomes is the step blocked by this macrolide antibiotic . Inhibition of influenza virus entry into cells by concanamycin A or by nigericin takes place under acidic conditions . Moreover, if the pH gradient is abolished by pre-incubation of cells in acidic pH, influenza virus entry does not occur even in the absence of any inhibitors . These results indicate that acidic conditions per se are not sufficient to promote virus entry into cells; rather this step of virus infection requires a pH gradient.

Pharmacoeconomics, 1994 Sep, 6(3), 233 - 9
The costs of treating febrile neutropenia in patients with malignant blood disorders; Leese B et al.; Retrospective data were collected over a 1-year period from the medical records of patients admitted to a district general hospital, either with febrile neutropenia or who developed this complication whilst receiving inpatient chemotherapy . Costs were calculated for inpatient stay, drug treatment and diagnostic tests . The median total costs for 46 episodes of febrile neutropenia were 2068.35 pounds and the median total cost per day was 139.41 pounds . Inpatient bed-days accounted for 57.8% of total costs, followed by drug treatment at 25.8% and diagnostic tests at 16.4% . The costs of blood products were excluded since they are frequently administered irrespective of the neutropenia . This study serves as a useful pointer to the expenditure in measurable antibiotic costs and investigations in patients with malignant blood disorders who develop febrile neutropenia.

N Engl J Med, 1994 Aug 4, 331(5), 310 - 4
Septic abortion; Stubblefield PG et al.; PIP: Abortion-related deaths, which account for 47% of total maternal mortality in the world, result primarily from sepsis and are widespread in developing countries where abortion is illegal or inaccessible . Septic abortion offers opportunities for prevention on the primary, secondary, and tertiary level of medial care . Primary prevention of septic abortion encompasses the provision of effective contraception, provision of safe and legal abortion in cases of contraceptive failure, and appropriate medical management of abortion . Secondary prevention involves the prompt diagnosis of endometriosis and effective treatment to avert more serious infection . The diagnosis of septic abortion should be considered when women of reproductive age present to health facilities with vaginal bleeding, lower abdominal pain, and fever . Tertiary prevention is aimed at avoiding the serious complications of postabortal infection, including hysterectomy and death . Women with high fever, pelvic peritonitis, and tachycardia should undergo uterine evacuation and parental antibiotic therapy . Supportive care for cardiovascular system and other organs may be essential . The medical technology needed to avert serious complications and deaths from septic abortion is available . Lacking is a political commitment on the part of many governments and health care agencies to address this avoidable contributor to maternal morbidity and mortality .

Biochim Biophys Acta, 1994 Aug 3, 1193(2), 287 - 92
Lasalocid and biomimetic membranes: insertion in Langmuir films of lipids; Hasmonay H et al.; The interfacial properties at the water surface of dipalmitoylphosphatidylcholine (DPPC) in monomolecular films containing various concentrations of lasalocid sodium salt (LAS) have been studied in the range from r = 0.005 to 0.1 (r = molar ratio LAS:DPPC) . The data from which the results have been expressed were obtained from the following compression isotherms at constant temperature (22 degrees C): of mixed films, of pure DPPC and of pure LAS . The incorporation of LAS resulted in pressure and concentration dependent molecular area increase, between 0 and 16 mN m-1 . The observed effect has been expressed as the area SA* occupied by each antibiotic molecule in the mixed films . The variations of SA* have been discussed at two levels of constant surface pressure, at 8 mN m-1 which is situated in the phase transition region of the DPPC isotherm and at 4 mN m-1 in the liquid expanded state . In both cases, the SA* values decreased as r increased . They have been related to the molar areas SA of LAS, obtained from the compression isotherm of the pure antibiotic and expressed as SA*/SA . This ratio was considerably greater than unity in the phase transition region within the studied concentration range and close to unity in the liquid expanded state . Using the method of Goodrich, the excess free energy of mixing GXS has been calculated . The values were positive above r = 0.01 and they increased with increasing concentrations . The results indicate non miscibility and strong repulsion between the two kinds of molecules in the mixed films . Two different mechanisms of insertion have been suggested.

Eur J Haematol, 1994 Aug, 53(2), 114 - 8
Treatment of hypogammaglobulinaemia in chronic lymphocytic leukaemia by low-dose intravenous gammaglobulin; Jurlander J et al.; Intravenous immunoglobulin replacement therapy reduces the number of bacterial infections in B-cell chronic lymphocytic leukaemia (B-CLL) patients . However, due to the complexity of immunodeficiency in B-CLL and the cost-effectiveness of replacement therapy, it is important to identify patients who are likely to benefit from the treatment and to investigate which dose should be used . 15 patients with hypogammaglobulinaemia and a history of recurrent infections received a fixed dose of 10 grams of gammaglobulin intravenously every 3 weeks . Serum IgG levels were significantly higher after three doses (p = 0.0002), and stabilized just above lower reference value after 11 doses . The total number of infection-related events during 168 months before therapy was compared to the total number of infection-related events in 169 months during therapy . The number of antibiotic prescriptions was reduced from 78 to 54 (N.S.), the number of admissions to hospital due to infections was reduced from 16 to 5 (p = 0.047) and the number of febrile episodes was reduced from 63 to 31 (p = 0.004) . We conclude that a fixed low dose of gammaglobulin intravenously can restore normal serum IgG levels in hypogammaglobulinaemic B-CLL patients, and leads to a decreased number of febrile episodes and admissions to hospital due infections.

Can Fam Physician, 1994 Aug, 40, 1407 - 13
Nipple candidiasis among breastfeeding mothers . Case-control study of predisposing factors; Tanguay KE et al.; OBJECTIVE: To investigate factors that predispose breastfeeding mothers to nipple candidiasis . DESIGN: A retrospective case-control study of women attending the Calgary Breastfeeding Clinic . SETTING: Ambulatory breastfeeding referral centre . PARTICIPANTS: All women (105) who attended the clinic during a 3.5-month study period . All were referred for problems with breastfeeding; 27 (the case group) had positive diagnostic criteria for nipple candidiasis . The other 78 formed a control group . MAIN OUTCOME MEASURE: A patient information sheet, completed while taking a medical history, recorded the presence or absence of four possible predisposing factors . Two infant variables were also noted on physical examination . Patients were diagnosed as having or not having nipple candidiasis on the basis of specific clinical criteria, and statistics on other variables were compared for those with positive and with negative diagnoses . RESULTS: A statistically significant correlation (P < 0.05) was found between nipple candidiasis and three factors: vaginal candidiasis (P = 0.001), previous antibiotic use (P = 0.036), and nipple trauma (P = 0.001) . CONCLUSIONS: Further research is required to establish clear causality . However, we recommend that physicians be suspicious of nipple candidiasis; avoid antibiotics or use the shortest effective course; treat yeast vaginitis during the third trimester and after delivery aggressively; and treat mothers for nipple yeast if babies have oral or diaper candidiasis . Breastfeeding mothers can also be counseled in preventive measures.

J Egypt Soc Parasitol, 1994 Aug, 24(2), 239 - 46
Aminosidine sulphate in experimental cryptosporidiosis; Youssef MM et al.; The present study aimed at investigating the efficiency of a recent antibiotic Aminosidine sulphate (Gabbroral) in experimental cryptosporidiosis . The course of infection was studied when the drug was given early before the infection, and late during the infection both parasitologically and histopathologically . When the drug was given early, the results were satisfactory, with a significant reduction of size, number and pathological changes of the parasites in the stool and in ileal sections of infected mice . However, the drug had no effect when given late during the infection.

Am J Physiol, 1994 Aug, 267(2 Pt 2), H734 - 41
Furazolidone increases thapsigargin-sensitive Ca(2+)-ATPase in chick cardiac myocytes; Lax D et al.; Furazolidone is a nitrofuran antibiotic that causes dilated cardiomyopathy in turkeys and chicks and serves as an important model of human dilated cardiomyopathy . The mechanism by which furazolidone produces cardiac injury remains unknown . We investigated the hypothesis that furazolidone alters Ca2+ homeostasis in cardiac muscle cells . Myocytes harvested from 7-day-old chick embryos were treated with furazolidone (0.02, 0.1, and 1 mM) for 24-52 h and then coloaded with seminaphthorhodafluor-1 (SNARF 1) and fura 2 to measure simultaneously intracellular pH (pHi) and intracellular Ca2+ concentration ({Ca2+}i), respectively . Furazolidone did not affect steady-state {Ca2+}i levels in cardiac myocytes . Na+ removal was associated with a rapid increase in {Ca2+}i due to the Na+/Ca2+ exchanger, which was similar in control and furazolidone-treated cells . The rate of {Ca2+}i recovery after Na+ removal was significantly increased in the furazolidone-treated cells compared with controls . In most cells, recovery from Ca2+ load is accomplished by the activity of Ca(2+)-adenosinetriphosphatases (ATPases) . Thapsigargin, inhibitor of sarcoplasmic reticulum Ca(2+)-ATPase, prevented the furazolidone-induced changes . These results demonstrate that furazolidone increases the activity of thapsigargin-sensitive Ca(2+)-ATPase without affecting Na+/Ca2+ exchange . These data enhance our understanding of the mechanism of furazolidone-induced injury in cardiac myocytes and may be useful in determining mechanisms of injury in dilated cardiomyopathy.

J Trauma, 1994 Aug, 37(2), 171 - 4; discussion 174-5
Evaluation of pulmonary infections in patients with extremity fractures and blunt chest trauma; D'Alise MD et al.; The use of preventive antibiotics has become the standard of care in the management of patients with multiple trauma who have injuries at risk for infection . In many areas of surgical practice, preventive antibiotic utilization has been restricted to the perioperative period only . In this study we reviewed a series of trauma patients with combined blunt chest injuries and extremity fractures to determine whether the duration of postoperative antibiotic administration would have adverse effects upon nosocomial pneumonia rates and severity.

Am J Hematol, 1994 Aug, 46(4), 363 - 6
Hemolytic anemia and acute renal failure associated with temafloxacin-dependent antibodies; Maguire RB et al.; Quinine-ingestion has been associated with immune-mediated recurrent pancytopenia, hemolysis, and renal failure . The structure of fluoroquinolone antibiotics is similar to the structure of quinine . Over a 3 month period, three patients at our institution developed hemolysis and renal failure following ingestion of the fluoroquinolone antibiotic temafloxacin . Two of the three patients required hemodialysis . Following withdrawal from the drug, the hemolysis resolved and the renal function eventually returned to normal in all three patients . One patient also had a transient mild thrombocytopenia . Sera from all three patients were tested for drug-dependent antibodies to red blood cells, platelets, and neutrophils . Temafloxacin-dependent red cell antibodies were detected in one patient, and temafloxacin-dependent red cell and neutrophil antibodies were detected in a second patient . No temafloxacin-dependent antibodies were detected in the third patient . Sera from all three patients were also tested for quinine and quinidine-dependent antibodies to red cells, platelets, and neutrophils . Sera from the patient without temafloxacin-dependent red cell antibodies reacted with red cells in the presence of quinine . These results suggest that, at least in some patients, the toxicities associated with temafloxacin are immune mediated.

Curr Genet, 1994 Aug, 26(2), 95 - 9
Mistranslation of human phosphoglycerate kinase in yeast in the presence of paromomycin; Grant CM et al.; Missense errors in the translation of mRNAs in Saccharomyces cerevisiae were screened by looking for charge heterogeneity of proteins on two-dimensional gels resulting from the substitution of charged and neutral amino acids . No such mistranslation was detected in wild-type yeast strains grown in the presence of the translational error-inducing antibiotic paromomycin . However, paromomycin-induced mistranslation of a heterologous mRNA, encoding human phosphoglycerate kinase expressed in yeast, was seen . We suggest that the combination of error-prone translation of a heterologous mRNA, and growth in the presence of paromomycin, leads to an accumulation of mistranslated proteins that can be detected by two-dimensional gel electrophoresis.

Mol Mar Biol Biotechnol, 1994 Aug, 3(4), 217 - 27
Parasexual crosses and hybrid selection with a near haploid variant of the epithelioma papulosum cyprini, cell line EPC: a tissue culture model for the analyses of dominance, recessiveness, and complementation of mutant phenotypes; Li ZF et al.; We describe techniques for insertional mutagenesis of tissue-cultured piscine cells in which we use transfection with G418 and hygromycin B resistance-conferring plasmids, cell matings by electrofusion, and positive selections of fusion hybrids by dual challenge with the antibiotics G418 and hygromycin B . These techniques are designed to facilitate genetic and molecular analyses of tissue-cultured cells . The experiments were conducted with EPC-1, a new variant of the carp epithelioma cyprini cell line . EPC, with a near haploid number of chromosomes, EPC-1 retains cell morphology and growth characteristics of EPC, including anchorage independence, but shows a higher degree of contact inhibition . The number of metaphase chromosomes of EPC-1 is 53, as opposed to 96 reported for EPC.

Vet Hum Toxicol, 1994 Aug, 36(4), 306 - 8
Human exposures to tilmicosin (MICOTIL); McGuigan MA; Tilmicosin is a new veterinary antibiotic that has significant cardiovascular toxicity when administered in large doses . Over 30 mo, the Ontario Regional Poison Information Centre at The Hospital for Sick Children in Toronto collected 36 cases of accidental human exposure to tilmicosin . Analysis of the cases revealed that 75% of the patients were exposed to probably less than 1 mL of tilmicosin, that 72% of exposures resulted from needle punctures, and that local symptoms predominated . Based on the information gathered, it is recommended that patients with accidental exposures of less than 1 mL of tilmicosin be treated symptomatically and do not need to be evaluated in a hospital setting.

Pharm Res, 1994 Aug, 11(8), 1148 - 54
Effect of medium-chain glycerides on physiological properties of rabbit intestinal epithelium in vitro; Yeh PY et al.; Medium chain glycerides (MCGs) have been reported to enhance intestinal absorption of hydrophilic drugs . However, the mechanisms involved in absorption enhancement are not well understood . The effects of MCGs (CapMul MCM) on physiological properties of rabbit ileum and distal colon, including active ion transport, transepithelial resistance (Rt) and passive permeability, have been investigated in vitro . CapMul MCM inhibited active ion transport (measured as a decrease in short-circuit current, Isc) in both intestinal segments in a concentration-dependent manner . The inhibition of Isc was rapidly reversible (within 100 min) upon removal of CapMul MCM . The data indicate that CapMul MCM preferentially affected ion transport by villus cells in the ileum and surface cells in the distal colon . Ion transport in crypt cells in both segments was not significantly altered . Rt of the ileum was not significantly affected by 5% CapMul MCM, while mannitol transport was 6 fold enhanced . Treatment of distal colon with 1% CapMul MCM reduced Rt by 95%, while mannitol transport was 100 fold enhanced . In a parallel experiment, mucosal(m)-to-serosal(s) transport of cephalexin, a beta-lactam antibiotic, in the ileum was about 40% reduced in the presence of 5% CapMul MCM, whereas transport in the s-to-m direction was 2.5 fold enhanced . Treatment of the distal colon with 1% CapMul MCM resulted in 25 fold enhancement of cephalexin transport in either direction . These results suggest that absorption enhancement by MCGs results from an increased permeability of the intestine confined to the villus or surface epithelium.

Neurosurgery, 1994 Aug, 35(2), 307 - 9; discussion 309
Management of infected laminectomy wounds; Shektman A et al.; Wound infection after lumbar, thoracic, or cervical laminectomies is a rare but potentially devastating complication . It can range in severity from superficial wound infection to an extensive wound dehiscence . The usual treatment of these wounds consists of intensive local care, debridement, and appropriate antibiotic therapy . Secondary healing can result in chronic, painful wounds that are difficult to manage and can create the potential for osteomyelitis . Seven cases of infected dehiscent laminectomy wounds are presented . Either critical structures were exposed, or the patients did not heal after secondary or delayed primary closures . In each case, full healing was attained by means of reconstruction with a regional muscle flap . We propose that muscle flap reconstruction offers an excellent alternative for the reconstruction of difficult postlaminectomy wounds.

J Pediatr Surg, 1994 Aug, 29(8), 1130 - 3; discussion 1133-4
Management of perforated appendicitis in children: a decade of aggressive treatment; Lund DP et al.; Perforated appendicitis in children continues to be associated with significant morbidity . In 1976, a treatment algorithm was begun at the authors' institution, which included immediate appendectomy, antibiotic irrigation of the peritoneal cavity, transperitoneal drainage through the wound, and 10-day treatment with intravenous ampicillin, clindamycin, and gentamicin . Initial results with this scheme in 143 patients demonstrated a 7.7% incidence of major complications and no deaths . From 1981 through 1991, the authors continued to use this treatment plan in all patients with perforated appendicitis . Three hundred seventy-three patients with perforated appendicitis were treated, and the rate of major complications was 6.4% . Infectious complications occurred in 18 patients (4.8%) and included intraabdominal abscesses (5 patients, 1.3%), phlegmon treated with an extended course of antibiotics (6 patients, 1.6%), wound infections (5 patients, 1.3%), and enterocutaneous fistula requiring further operations (2 patients, 0.5%) . There were six cases of small bowel obstruction (1.6%), which required operative intervention . There were no deaths . The average length of stay for all patients was 11.4 days (range, 8 to 66 days) . Utilization of transperitoneal drainage and choice of antibiotic therapy continue to be sources of controversy in the surgical literature . However, the treatment plan used in the present study resulted in the lowest complication rate reported to date, and the authors conclude that this scheme is truly the "gold standard" for treatment of perforated appendicitis . New treatment plans using laparoscopic appendectomy, different or shorter courses of antibiotics, or not using drains should have complication rates that are as low as, or lower than this one to be considered as useful alternatives.

Brain Res, 1994 Aug 1, 652(2), 243 - 8
Rapid, reversible elimination of medial olivocochlear efferent function following single injections of gentamicin in the guinea pig; Smith DW et al.; Measurements were made of the ability of nonsimultaneous, contralaterally presented broadband noise maskers to suppress ipsilaterally-evoked compound action potentials (CAPs) of the auditory nerve to 8-kHz tone pips in guinea pigs . Contralateral acoustic stimuli have been shown to suppress responses to ipsilateral stimuli through the action of the medial olivocochlear efferent bundle . In this study, maximum suppression across subjects ranged from 2-6 dB . The ability of the contralateral noise to suppress ipsilateral CAPs was rapidly reduced beginning within minutes of a single intramuscular injection of the aminoglycoside antibiotic gentamicin (150 mg/kg), and, in general, was completely abolished by 1.5-2 h . Changes in suppression were presumably produced by gentamicin-induced blockade of presynaptic calcium channels on the medial olivocochlear efferents and closely follow the pharmacokinetics of gentamicin in perilymph . Reductions in efferent-mediated suppression were observed in the absence of any measurable change in either CAP thresholds to different frequencies or CAP input/output . Suppression was partially restored in some animals after 24 h, and was fully recovered in all subjects within 96 h postinjection . The present studies suggest that measures of efferent function might form the rational basis for an objective means to assess aminoglycoside insult on the cochlea in the absence of hair cell damage . These results also indicate that single injections of gentamicin offer a reversible, non-invasive model in which medial efferent function can be studied in behavioral animals.

Chest Surg Clin N Am, 1994 Aug, 4(3), 593 - 615
Thoracoplasty; Barker WL; Langston and Sampson point out that the sine qua non of empyema management is early, adequate, and dependent drainage . Diagnostic thoracentesis followed by closed tube thoracostomy and conversion to open drainage, either by a large-bore tube or a rib-resection with a pleurocutaneous fistula, are initial procedures that may be continued for an extended period to control infection, obliterate loculations, and heal co-apted pleural surfaces secondarily . Clagett and Geraci have noted that postpneumonectomy empyema spaces can be "sterilized" and the initial drainage site can be closed after antibiotic instillation . Miller, however, reports success rates for this procedure only in the range of 25% to 33% . Our results are somewhat higher . Obliteration of the persistent space after control of infection by drainage can be accomplished by interposition of muscle flaps with closure of any bronchopleural fistulas and/or by thoracoplasty . As stated previously, myoplastic techniques to obliterate empyemas and close bronchial fistulas in tuberculous disease have a success rate of approximately 75% . Such techniques, however, not only assist in limiting the extent of thoracoplasty, but also may avoid the procedure entirely in some cases . Virkkula has emphasized that use of pedicled myoplasty does not necessarily obviate the need for thoracoplasty . Pairolero and colleagues reported that the use of selected thoracoplasty combined with muscle transposition afforded a 73% success rate for postpneumonectomy empyema and a 64% success rate for closure of persistent bronchopleural fistulas and precludes protracted drainage and/or extended thoracoplasty . Young and Ungerleider concluded that (1) thoracoplasty is more successful if it is applied for patients with parapneumonic rather than postresectional empyemas; (2) concomitant tailoring thoracoplasty has a higher rate of failure; (3) preliminary drainage followed by thoracoplasty has a higher success rate in eliminating the empyema than thoracoplasty alone; (4) first rib resection is indicated for apical collapse only; (5) preoperative preparation is important to control and manage underlying suppurative processes; and (6) thoracoplasty of any type should not be used as a desperation modality of therapy in which uncontrolled sepsis and inadequate drainage are present or in which cancer or unidentified sites of hemorrhage exist . Sequential management of the residual infected space can proceed along several pathways . Many patients with empyema are well-controlled with simple open drainage and with underlying lung reexpansion, either spontaneously or in association with decortication, and may never need thoracoplasty . Drainage and thoracoplasty alone may be effective not only in obliterating an empyema space but also in sealing a bronchopleural fistula.(ABSTRACT TRUNCATED AT 400 WORDS)

Chest Surg Clin N Am, 1994 Aug, 4(3), 561 - 82
Parapneumonic and post-traumatic pleural space infections; Magovern CJ et al.; Thoracic empyema, an accumulation of pus in the pleural space, was first described by Hippocrates . Today, parapneumonic and post-traumatic empyemas account for two thirds of all pleural space infections . Although modern antibiotic therapy has significantly reduced the incidence of thoracic empyemas, it remains a problem that thoracic surgeons will encounter and should feel comfortable about recognizing and treating . The successful management of thoracic empyemas centers on adequate and timely drainage, the use of appropriate antibiotics, the selective use of decortication, and the proper treatment of underlying pulmonary parenchymal disease.

Cardiovasc Surg, 1994 Aug, 2(4), 478 - 83
Vein harvest ischemia: a peripheral vascular complication of coronary artery bypass grafting; Gandhi RH et al.; Lower-extremity ischemia can lead to impaired healing of saphenous vein excision sites in patients with significant peripheral vascular disease (PVD) . Five patients who required infrainguinal revascularization for wound necrosis of the harvest site after coronary artery bypass grafting are described . The male/female ratio was 2:3 with a mean age of 67 (range 45-87) years . The most commonly associated problems were insulin-dependent diabetes mellitus (80%) and congestive heart failure (60%) . The saphenous vein was harvested from the thigh and leg in three patients and exclusively from the leg in the others . Manifestations of ischemia ranged from persistent ulceration to complete wound disruption threatening limb loss . Impaired healing was isolated to infragenicular wounds in all patients . Pedal pulses were not detected in any of the affected extremities . Determination of the ankle/brachial pressure indices (ABI) revealed values of < 0.5 in three affected limbs . Non-compressible vessels resulted in falsely raised ABI of > 1.0 in the remaining two limbs; however, Doppler waveform analysis in these patients demonstrated significant PVD . Aggressive wound care and antibiotic therapy were continued for mean of 9 weeks before operative intervention . Infrainguinal reconstruction included femoropopliteal (two), femorotibial (two) and popliteal-tibial bypass (one) . Autologous arm and saphenous veins in addition to expanded polytetrafluoroethylene grafts were used effectively . Limb salvage and wound healing were achieved in 100% of the patients without untoward sequelae . It is concluded that unrecognized PVD in patients undergoing coronary artery bypass grafting can lead to significant morbidity . Patients at risk may be identified with a combination of history, physical examination and non-invasive testing.(ABSTRACT TRUNCATED AT 250 WORDS)

Aust Dent J, 1994 Aug, 39(4), 203 - 5
Donovanosis of the oral cavity . Case report; Doddridge M et al.; Donovanosis (Granuloma inguinale) is an infectious disease, the effects of which are usually confined to the genital region . Various extragenital manifestations of the disease have been described . This report describes a case where the condition represented in the oral cavity some time after the apparently successful treatment of the genital lesion . Members of both the medical and dental profession serving the northern parts of Australia and adjacent tropical regions should be aware of the possibility of encountering this disease . Delay in its diagnosis may result in extensive tissue destruction and a potentially fatal outcome . Intensive antibiotic therapy followed by long-term follow-up is usually curative.

Oral Surg Oral Med Oral Pathol, 1994 Aug, 78(2), 163 - 74
Oral manifestations of HIV infection in homosexual men and intravenous drug users . Study design and relationship of epidemiologic, clinical, and immunologic parameters to oral lesions; Lamster IB et al.; This article describes the baseline findings from a study designed to compare the oral manifestations of HIV infection in homosexual men and intravenous drug users . Both seropositive and seronegative persons were studied . A standard examination instrument was developed to record indexes of oral disease as well as to record the presence of oral lesions . The two groups differed in terms of education, race, socioeconomic status, employment status, housing, and smoking experience . The prevalence and type of oral lesions differed in the two seropositive groups . In seropositive homosexual men, white lesions on the tongue (28.4%) predominated; whereas for the seropositive intravenous drug users, oral candidiasis (43.0%) and gingival marginal erythema (33.3%) were most often detected . We also observed that seronegative intravenous drug users displayed a greater number of oral lesions than seronegative homosexual men . For seropositive homosexual men, lesion presence was significantly associated with decreased levels of CD4; positive associations were seen with current smoking, antiviral drug use, and antibiotic use, and a negative association was observed with current employment . In contrast, only exposure to antiviral drugs was significantly correlated with lesion presence for seropositive intravenous drug users . This baseline analysis from our longitudinal study suggests clear differences in oral manifestations of HIV infection between seropositive homosexual men and intravenous drug users and between seronegative homosexual men and intravenous drug users . Among other parameters, it is apparent that lifestyle, access to health care, and the condition of the oral cavity before infection influence the development of oral lesions in persons with HIV infection.

Oral Surg Oral Med Oral Pathol, 1994 Aug, 78(2), 156 - 62
Chronic recurrent multifocal osteomyelitis involving the mandible; Suei Y et al.; A patient with chronic recurrent multifocal osteomyelitis is presented for the first time in the dental literature . On the basis of the initial diagnosis of diffuse sclerosing osteomyelitis of the mandible, the clinical course was protracted and refractory to surgical and antibiotic therapies . The literature is reviewed to evaluate the relationship between chronic recurrent multifocal osteomyelitis and diffuse sclerosing osteomyelitis . Distinguishing features between the two entities could not be found . It is recommended that a skeletal survey be performed when the diagnosis of diffuse sclerosing osteomyelitis is established.

Jpn J Antibiot, 1994 Aug, 47(8), 1071 - 6
{Serum and tissue levels of cefodizime in the pediatric patients}; Matsuura K et al.; We administrated cefodizime (40 mg/kg) to 13 patients with simple herniorrhaphy in the pediatric field and determined its concentrations in tissues and serums . The mean serum and tissue levels of cefodizime after administration were 43.1 +/- 13.3 micrograms/ml, and 23.1 +/- 6.4 micrograms/g, respectively, at 3 hours . Cefodizime concentrations of the tissue and serum were maintained at relatively high levels for many hours . The ratio of cefodizime concentrations in tissue to serum became high at 3 hours after administration, and this suggests that tissue concentrations decreased more slowly than serum levels, and cefodizime concentrations in tissue were maintained at fairly high levels over a long period . No side effects caused by cefodizime were observed . From pharmacokinetic and clinical observations, cefodizime appears to be a safe and effective injectable antibiotic for the treatment of infections in children.

Jpn J Antibiot, 1994 Aug, 47(8), 1065 - 70
{Empiric therapy with fluconazole in granulocytopenic patients with carcinoma or leukemia}; Fukuda M et al.; We performed a randomized clinical trial in granulocytopenic patients with carcinoma or leukemia . Patients with persistent fever for more than 2 days despite antibiotic therapy were randomized to antibiotic plus fluconazole therapy group (FLCZ group) or antibiotic therapy only group (antibiotic group) by the envelope method . It was possible to evaluate clinical efficacies in 62 patients (37 patients in FLCZ group and 25 patients in antibiotics group) . In patients whose neutrophil counts were less than 100/microliters on the initial day of therapy, clinical efficacy rates were 72.0% (18/25) in FLCZ group and 57.1% (8/14) in antibiotics group . In patients whose neutrophil counts continued to be less than 100/microliters during therapy, clinical efficacy rates were 64.3% (9/14) and 50.0% (3/6), respectively . Further, in patients whose neutrophil counts continued to be less than 500/microliters during therapy, they were 76.9% (20/26) and 53.3% (8/15), respectively . No severe side effects nor severe case of abnormal change in laboratory test values due to fluconazole were observed in this trial . These data suggest that empiric antifungal therapy with fluconazole is effective for fungal infections in granulocytopenic patients with carcinoma and leukemia.

Can J Microbiol, 1994 Aug, 40(8), 672 - 6
Relationship between valine, fatty acids, and spiramycin biosynthesis in Streptomyces ambofaciens; Laakel M et al.; Spiramycin biosynthesis in Streptomyces ambofaciens was stimulated in the presence of valine or by sequential addition of some short-chain fatty acids to a culture medium containing an ammonium salt as source of nitrogen . Acetate kinase and acetyl-CoA carboxylase, enzymes that catalysed the formation of precursors of spiramycin biosynthesis (acetyl-CoA and malonyl-CoA), were detected during the active growth and antibiotic production phases . In this latter phase a higher level of acetyl-CoA carboxylase activity was observed with valine (1.02 mumol.min-1.mg protein-1) than with ammonium (0.05 mumol.min-1.mg protein-1) as nitrogen source, while the evolution and the level of acetate kinase activity were the same in both media . Successive addition of acetate and isobutyrate stimulated highly and weakly the acetyl-CoA carboxylase and acetate kinase activity, respectively.

J Biomol Struct Dyn, 1994 Aug, 12(1), 111 - 29
Binding of echinomycin to d(GCGC)2 and d(CCGG)2: distinct stacking interactions dictate the sequence-dependent formation of Hoogsteen base pairs; Gallego J et al.; Molecular dynamics simulations have been used to explore the behavior of the complexes of echinomycin with the DNA tetramers d(GCGC)2 and d(CCGG)2 in which the terminal bases have been paired according to either a Hoogsteen or a Watson-Crick hydrogen bonding scheme . The energy of the four resulting complexes has been monitored along the dynamics trajectories and the interaction energy between echinomycin and DNA has been decomposed into contributions arising from the planar aromatic systems and the depsipeptide part of the antibiotic . Our calculations predict a large increase in overall stabilization upon protonation of the terminal cytosines and subsequent Hoogsteen pair formation in the complex of echinomycin with d(GCGC)2 but not with d(CCGG)2, in agreement with the experimental evidence {Gao and Patel, Quart . Rev . Biophys . 22, 93-138 (1989)} . The conformational preferences appear to arise mainly from differential stacking interactions in which the electrostatic component is shown to play a dominant role . Differences in hydrogen bonding patterns are also found among the complexes and these are compared in relation to available crystal structures . The binding of echinomycin to DNA appears as a complex process involving many interrelated variables.

J Bioenerg Biomembr, 1994 Aug, 26(4), 421 - 33
Hormone- and growth factor-stimulated NADH oxidase; Morre DJ; An NADH oxidase activity of animal and plant plasma membrane is described that is stimulated by hormones and growth factors . In plasma membranes of cancer cells and tissues, the activity appears to be constitutively activated and no longer hormone responsive . With drugs that inhibit the activity, cells are unable to grow although growth inhibition may be more related to a failure of the cells to enlarge than to a direct inhibition of mitosis . The hormone-stimulated activity in plasma membranes of plants and the constitutively activated NADH oxidase in tumor cell plasma membranes is inhibited by thiol reagents whereas the basal activity is not . These findings point to a thiol involvement in the action of the activated form of the oxidase . NADH oxidase oxidation by Golgi apparatus of rat liver is inhibited by brefeldin A plus GDP . Brefeldin A is a macrolide antibiotic inhibitor of membrane trafficking . A model is presented where the NADH oxidase functions as a thiol-disulfide oxidoreductase activity involved in the formation and breakage of disulfide bonds . The thiol-disulfide interchange is postulated as being associated with physical membrane displacement as encountered in cell enlargement or in vesicle budding . The model, although speculative, does provide a basis for further experimentation to probe a potential function for this enzyme system which, under certain conditions, exhibits a hormone- and growth factor-stimulated oxidation of NADH.

Matrix Biol, 1994 Aug, 14(4), 329 - 35
Characterization of primary cultures of chondrocytes from type II collagen/beta-galactosidase transgenic mice; Lefebvre V et al.; Studies on the function of extracellular matrix components of cartilages and on chondrocyte-specific regulatory mechanisms will benefit from approaches in which transgenic mice and cell cultures will complement each other . We therefore established and extensively characterized primary cultures of mouse chondrocytes isolated from rib growth plates of newborn mice harboring a transgene in which type II collagen gene regulatory sequences were driving expression of an E . coli beta-galactosidase reporter gene . Primary chondrocytes expressed a fully differentiated phenotype in monolayer culture, producing mRNAs for the collagen types II, IX and X, and for the transgene . Transgenic cells also synthesized high levels of E . coli beta-galactosidase, easily quantifiable and also detectable in individual cells by X-gal staining . When chondrocytes were isolated from transgenic mice in which beta-galactosidase was fused to the product of the neomycin resistance gene, they displayed resistance to G418 . After one to two weeks in culture, chondrocytes progressively lost expression of the transgenes, in parallel with that of cartilage-specific genes, and started expressing high levels of type I collagen RNA . The use of transgenic chondrocytes allowed us to easily score phenotypic changes by assaying beta-galactosidase activity and neomycin resistance . Cultures of mouse chondrocytes, such as those reported here, should also help characterize biochemically the phenotypes of other transgenic mice in studies of genetic diseases of cartilages and of mechanisms involved in chondrogenesis.

Chest, 1994 Aug, 106(2), 458 - 61
Roxithromycin reduces the degree of bronchial hyperresponsiveness in children with asthma; Shimizu T et al.; We evaluated the effects of a new semisynthetic macrolide antibiotic, roxithromycin, on the bronchial hyperresponsiveness to histamine in children with asthma . Twelve hospitalized asthmatic children, aged 11 to 15 years (mean age, 12.9 years), were enrolled in this study . They were treated with 150 mg of roxithromycin once a day orally for 8 weeks without any side effects . The PC20 value 4 or 8 weeks after the administration of roxithromycin increased significantly over the initial values (p < 0.05, p < 0.01, respectively) . No significant change was observed in serum theophylline concentrations during this study . Serum cortisol level in the morning did not change after the administration of roxithromycin for 4 weeks . These results suggest that administration of roxithromycin may act favorably in the treatment of childhood asthma.

Wiad Lek, 1994 Aug, 47(15-16), 619 - 24
{Infection as a risk factor in biliary system surgery}; Cybulski Z et al.; Infection of the biliary system in which one of the signs is the presence of bacteria in bile is connected with an increase of incidence of postoperative complications especially in elderly people . Therefore, early diagnosis of infections and their prophylaxis and treatment are an important aspect of surgical management which is particularly significant in view of large number of patients with acute and chronic cholangitis . Proper selection of the operation time and the use of antibiotic therapy with adequate utilization of even broader spectrum of antibiotics may be of decisive importance for effective treatment.

Antibiot Khimioter, 1994 Aug, 39(8), 27 - 9
{An in vivo experiment on the antitumor action of bleomycin bound to an ion exchange carrier}; Tikhomirov GA et al.; Bleomycetin, an antitumor antibiotic of the domestic origin, is component A5 of the bleomycin complex . Design of new drug delivery systems especially for local application is an important problem of antitumor chemotherapy . Bleomycetin immobilized on ion exchange medical gauze was studied with this purpose in an in vivo experimental model of murine lympholeukemia NK/Ly . Subcutaneous implantation of the new dosage form of bleomycetin with prolonged action provided a significant antitumor systemic effect evident from an increase in the mouse life-span . In vitro determination of the bleomycetin contents in the gauze revealed that the antibiotic was completely absorbed from the carrier within 72 hours . The bleomycetin half-life in the plasma after the antibiotic administration in the bound form on the ion exchange gauze was twice as long as that after the antibiotic injection with NaCl isotonic solution.

Hinyokika Kiyo, 1994 Aug, 40(8), 699 - 702
Pyogenic psoas muscle abscess: report of three cases; Takagi S et al.; We report three cases of primary psoas muscle abscess . Two of these cases were treated by open drainage through a lumbar incision and the other was by ultrasonography (USG)-guided percutaneous aspiration of the abscess . Antibiotic therapy was also instituted in all cases . Post-operatively, the patients recovered well with no sign of recurrence . USG-guided percutaneous drainage combined with appropriate antibiotic therapy appears to be the first choice procedure for treatment of the primary psoas abscess if correct diagnosis is promptly made and the procedure can be performed.

Schweiz Med Wochenschr, 1994 Jul 30, 124(30), 1334 - 8
{Hypersensitivity myocarditis . A case of myocarditis following drug administration}; Jaup T et al.; Based upon the findings of eosinophilia and concomitant ECG changes, hypersensitivity myocarditis was diagnosed in a patient who had been given longstanding antibiotic therapy . With cessation of drug treatment the disease resolved spontaneously.

Biochemistry, 1994 Jul 26, 33(29), 8719 - 27
Time-resolved fluorescence studies of tomaymycin bonding to DNA; Chen Q et al.; Tomaymycin is an antibiotic that reacts at guanine N2 in the minor groove of the DNA helix . The number and type of tomaymycin-DNA adducts present on natural sequence DNA were identified using time-resolved fluorescence spectroscopy . At low bonding density, only two discrete species were observed with lifetimes of 4.3 and 7.1 ns and relative amplitudes of 40% and 60% . These two lifetime species are proposed to represent either R5' or S5' and S3' binding modes at the preferred bonding sequence 5'-AGA . R and S denote the configuration at C11 of tomaymycin, and 5' and 3' describe the orientation of the aromatic ring on the covalently modified strand . These two species were present over a range of solution conditions, including pH, nucleotide to drug ratio, DNA concentration, and DNA size . They have the same emission spectra, but slightly shifted absorption spectra . The weak temperature dependence of the fluorescence lifetimes presumably is due to the excited-state proton-transfer reaction that quenches tomaymycin fluorescence . The rate of formation of the longer lifetime species of DNA adduct is about twice as fast as that of the shorter lifetime species . Under saturating conditions, the fluorescence decay shows a bimodal lifetime distribution whether analyzed by least-squares assuming a Gaussian distribution model or by the maximum entropy method . The two groups of lifetimes are centered around 2-3 and 6-6.6 ns, reflecting multiple species on different bonding sequences.

FEBS Lett, 1994 Jul 25, 349(1), 117 - 9
A fatty-acid-binding protein from wheat kernels; Castagnaro A et al.; A protein of about 7 kDa (W-FABP) has been isolated from mature wheat kernels by H2O extraction and gel filtration of the extract, followed by two steps of high-performance liquid chromatography . The N-terminal amino acid-sequence has been determined up to the 28th residue and found to be identical (except for positions 4 and 5) to that deduced from a barley cDNA (EMBL X15257), which had been improperly classified as a non-specific lipid transfer protein (LTP2) . Similarly with LTPs, W-FABP does bind fatty acids, but in contrast, it is not significantly homologous to LTPs, it is not recognized by LTP antibodies, it has a more acidic isoelectric point (pH < 6.8 vs . pH > 9.6), and it does not show antibiotic properties.

Carbohydr Res, 1994 Jul 16, 260(2), 219 - 32
One-pot-synthesis of alpha-linked deoxy sugar trisaccharides; Kopper S et al.; Various alpha-linked 2,6-dideoxy-ribo-trisaccharides, models for part of the antibiotic kijanimicin, were synthesised by the N-iodosuccinimide method employing different pathways . The efficiency of a sequential synthesis suffered from side reactions of the axial HO-3, which are typical of digitoxosides . These problems did not arise in a straightforward polymerisation, performed as a one-pot-procedure . It afforded the trisaccharide directly from the monosaccharide precursor in 30% yield . A combination of the oligomerisation pathway and the sequential synthesis led to trisaccharides with different protecting group patterns . In these reactions different glycal and alcohol components were used and allowed to define the optimal partners in a sequential synthesis: the two components should ideally be of comparable reactivity.

J Biol Chem, 1994 Jul 15, 269(28), 18315 - 9
Analysis of the puromycin binding site in the 70 S ribosome of Escherichia coli at the peptide level; Bischof O et al.; Photoinduced cross-linking of Escherichia coli 70 S ribosomes with {3H}puromycin has led to the labeling of ribosomal proteins S7, S14, S18, L18, and L29 . Proteolytic fragmentation of these proteins and separation of the peptide mixtures by C18 reversed-phase high performance liquid chromatography resulted in six puromycin-labeled peptides which were applied to sequence analysis . The following peptides were found labeled: Pro1-Lys10 of S7, Ala28-Lys46 and Ala7-Lys11 of S14, Asp24-Lys29 of S18, Tyr64-Lys68 of L18, and Thr55-Lys60 of L29 . For the first time the molecular environment of an antibiotic in the procaryotic ribosome is presented at the peptide level.

Clin Diagn Lab Immunol, 1994 Jul, 1(4), 373 - 8
Sustained cellular immune responses to Borrelia burgdorferi: lack of correlation with clinical presentation and serology; Horowitz HW et al.; Fifty-one patients with erythema migrans were followed up prospectively with serial clinical evaluations, serologic determinations for antiborrelial antibodies, and lymphocyte stimulation responses to Borrelia burgdorferi antigens to determine (i) the factors associated with sustained cellular immune responses and (ii) whether lymphocyte stimulation is a good indicator of prior exposure to B . burgdorferi in patients treated early after erythema migrans . Positive lymphocyte stimulation responses ( > 2 standard deviations above normal control values) were found in 15 (29%) of 51 patients 3 months after treatment for erythema migrans and in 8 (18%) of 44 patients 1 year posttreatment . Heightened lymphocyte responses were not associated with the number or duration of erythema migrans lesions prior to treatment, the mean size of the largest erythema migrans lesion, or the number of symptoms at the time of presentation . The development of Jarisch-Herxheimer reaction, choice of antibiotic, and clinical outcome also were not associated with a positive lymphoproliferation assay result . Changes in the lymphocyte stimulation indices between the two time points assessed (3 months and 1 year posttreatment) also did not correlate with the above variables . When serologic results and lymphoproliferative responses were evaluated as categorical or continuous variables, there were no correlations between values . One year after treatment for early Lyme disease, lymphocyte reactivity is not a good indicator of prior infection with B . burgdorferi.

ASAIO J, 1994 Jul-Sep, 40(3), M406 - 11
Anti-infection treatment of a transcutaneous device by a collagen-rifampicine composite; Suh H et al.; The polyurethane surface of a transcutaneous energy transmitter, which is implanted into a subcutaneous pouch for a total artificial heart, was coated with a Type I atelocollagen and rifampicine composite to prevent the infection that frequently occurs in the interfacial space between the tissue and the device . The specimen obtained after 7 weeks from a transcutaneous energy transmitter placed in a dorsal subcutaneous pouch of a dog revealed noninfected but well-attached dermal tissue without specific epithelial down-growth around the transcutaneous energy transmitter surface at the pouch-orifice area . The transcutaneous energy transmitter implanted in the pouch adhered well to the subcutaneous tissues . The collagen matrix seemed to have provided a favorable environment for the regenerating dermal tissue to obstruct the interfacial space . The coated collagen-antibiotic composite was degraded.

J Dermatol, 1994 Jul, 21(7), 497 - 500
Primary actinomycosis of the breast: a clinical review and a case report; Jain BK et al.; An uncommon situation of primary actinomycosis of the breast is reported in a 40-year-old woman who presented with a lump, clinically simulating malignancy, in the right breast . Diagnosis of actinomycosis was established by incision biopsy . Resolution of infection, while conserving the breast, was achieved by timely diagnosis, limited surgery, and effective antibiotic therapy . Diagnostic failures leading to avoidable mastectomies have not been uncommon in cases previously reported in the literature . It is, therefore, imperative that this condition be considered in the differential diagnosis of intractable breast abscess and malignancy.

Chemotherapy, 1994 Jul-Aug, 40(4), 239 - 44
In vitro sensitivity of medically significant Fusarium species to various antimycotics; Sekhon AS et al.; Sixteen isolates belonging to Fusarium chlamydosporum (n = 4), Fusarium equiseti (n = 1), Fusarium moniliforme (n = 2), Fusarium oxysporum (n = 3), Fusarium proliferatum (n = 1), and Fusarium solani (n = 5) were tested against amphotericin B, 5-fluorocytosine, fluconazole, itraconazole, ketoconazole, JAI-amphotericin B (water-soluble compound), hamycin and amphotericin B combined with 5-fluorocytosine, using antibiotic medium M3, high-resolution broth (pH 7.1), Sabouraud's dextrose, and yeast-nitrogen broth media (1 ml/tube) . The minimal inhibitory and minimal fungicidal concentrations of 5-fluorocytosine and fluconazole for all species were > 100 micrograms/ml . All Fusarium isolates, except F . equiseti (3.125 micrograms), gave minimal inhibitory concentrations of 12.5-100 micrograms/ml for hamycin . The values for amphotericin B, itraconazole, ketoconazole, JAI-amphotericin B, and amphotericin B combined with 5-fluorocytosine were 1.56-100, 0.78-50, 3.125-100,50-100, and 1.56 to > 100 micrograms/ml, respectively . Although a wide range of minimal inhibitory concentrations was recorded for most of the isolates studied, it appears that some--F . solani, F . oxysporum, F . chlamydosporum, F . equiseti, and F . moliniforme--were more susceptible to amphotericin B, itraconazole, ketoconazole, hamycin, and amphotericin B in the presence of 5-fluorocytosine . All isolates showed resistance to 5-fluorocytosine and fluconazole . The minimal fungicidal concentrations were either the same or several times higher than the minimal inhibitory concentrations.

Recenti Prog Med, 1994 Jul-Aug, 85(7-8), 391 - 6
{Infective pneumopathies in old age}; Leonardi R et al.; The present paper focuses main and different aspects of pneumonia in the elderly, in relation to our recent experience in this field . Presentation, clinical features, cause and therapeutic aspects in geriatric age have important peculiarities (increased incidence of infection and non infection complications, and mortality) . In the elderly patient pneumonia with slow resolution is a frequent occurrence . For a correct therapy is essential to distinguish between nosocomial and community acquired pneumonia . In our experience supportive measures seems important as much effective antibiotic therapy that can be carried out with different drugs: cephalosporins, macrolides, penicillines plus beta-lactamasi inhibitors; in case of nosocomial pneumonia and of 'difficult' germs, is more rationale to use antibiotic associations (also with aminoglycosides and/or chinolonics).

Microbiology, 1994 Jul, 140 ( Pt 7), 1737 - 44
Altered amino acid metabolism in lrp mutants of Escherichia coli K12 and their derivatives; Ambartsoumian G et al.; An Escherichia coli lrp mutant, lacking the leucine-responsive regulatory protein and the global response it controls, is deregulated in the expression of many genes, but is nevertheless able to grow in glucose-minimal medium at 37 degrees C . In the presence of isoleucine and valine, the growth rate of the lrp mutant at 37 degrees C is significantly increased by exogenous L-serine or L-leucine (or both), suggesting that synthesis of these amino acids is limiting . In the absence of isoleucine and valine, however, growth is severely inhibited by both L-serine and L-leucine . A shift to 42 degrees C or to anaerobiosis makes the lrp mutant auxotrophic for L-serine . Three double mutants carrying lrp and another known mutation, acquire new auxotrophies: lrp relA, lacking the stringent response to amino acid limitation, requires leucine; lrp ssd with numerous metabolic perturbations and antibiotic resistances, requires serine and leucine; and lrp pnt, lacking pyridine nucleotide transhydrogenase, requires glutamate or aspartate (or the corresponding amides) . The lrp mutant, although able to achieve balanced growth in some conditions, is clearly on the edge of a metabolic precipice, unable to tolerate many physiological and genetic perturbations which are inocuous to wild-type E . coli.

Abdom Imaging, 1994 Jul-Aug, 19(4), 376 - 8
Pseudodiverticulosis: unusual appearance for metastases to the ureter; Wasserman NF; A rare pseudodiverticular pattern of metastatic malignancy to the ureter is reported along with pathologic findings at postmortem examination in three patients . There was no clinical or pathological obstruction . This pattern is due to malignancy-induced edema in the subepithelial connective tissues and muscularis propria causing displacement of these layers into the ureteral lumen resulting in an undulating epithelial surface . The epithelium itself is normal . Metastases to the ureter is uncommon in life unless associated with ureteral obstruction . Ureteral pseudodiverticulosis found in vivo in a nonobstructed patient with known metastatic malignancy is likely due to inflammatory causes and usually reversible with antibiotic and medical therapy . A patient with widespread malignancy showing nonreversibility of the ureteral pseudodiverticular pattern, even in the absence of obstruction, should be considered a candidate for impending obstruction and followed closely for ureteral stent placement.

J Antibiot (Tokyo), 1994 Jul, 47(7), 799 - 805
Tricholin, a new antifungal agent from Trichoderma viride, and its action in biological control of Rhizoctonia solani; Lin A et al.; Tricholin, a ribosome-inactivating protein isolated from the culture broth of Trichoderma viride, has been shown to exert fungicidal effects on Rhizoctonia solani through a multi-hit kinetic interaction . Tricholin causes a parallel cessation of growth, uptake of amino acids, and protein biosynthesis . The in vivo mode of action of tricholin on protein synthesis and cell growth appears to be attributed to the diminishing of the polysome formation in R . solani through damage to large ribosomal subunits . These results concur with previous data and prove that tricholin is an effective inhibitor of protein synthesis . The efficacy of tricholin as an antibiotic agent was estimated to have a duration of approximately 42 hours.

J Antibiot (Tokyo), 1994 Jul, 47(7), 787 - 91
Monoclonal antibody raised against apoprotein of C-1027: effect on biochemical and biological activities of the holoantibiotic; S-Tsuchiya K et al.; A monoclonal antibody raised against C-1027 apoprotein recognized not only the apoprotein, but also the holoantibiotic (Antibiotic C-1027) almost equally . Among the biochemical and biological activities of the holoantibiotic, the antibody inhibited the aminopeptidase activity and the cytotoxicity to Ehrlich carcinoma cells in cultures, but not the DNA-cleaving activity in vitro . The immunohistogram, using this antibody, of Ehrlich carcinoma cells that had been exposed to the holoantibiotic suggested penetration of the holoantibiotic into target cells.

Curr Opin Rheumatol, 1994 Jul, 6(4), 415 - 22
Lyme disease; Evans J; In the United States, Lyme disease is the most common arthropod-borne infection . The majority of cases occur in the Northeast, the Midwest, and California, which are areas with established foci of Borrelia burgdorferi . Phenotypic and genotypic diversity of B . burgdorferi has resulted in its classification into three separate genospecies and may account for differences in disease expression . Clinical features of Lyme disease have expanded to include a flulike illness without erythema migrans and the persistence of intrathecal antibody responses after successful antibiotic therapy in neuroborreliosis . Better understanding of the pathogenic mechanisms of Lyme arthritis will help guide future treatment decisions, and recent progress made in assessing the risk of infection from tick bites and vaccine development may help calm public anxiety about Lyme disease.

Curr Opin Rheumatol, 1994 Jul, 6(4), 401 - 7
Osteomyelitis; Laughlin RT et al.; Osteomyelitis can be difficult to treat . Current trends emphasize early diagnosis and aggressive treatment . Imaging has improved with nuclear scans and magnetic resonance imaging, and recent modifications in technique have enhanced the specificity . Treatment depends on debridement of necrotic bone and tissue, obtaining accurate cultures, and administration of culture- and sensitivity-directed antibiotics . Antibiotic delivery has expanded to include effective oral agents and local agents mixed with polymethylmethacrylate or a biodegradable substance . Success rates in treating this disease have improved with a systematic approach, making outcome more predictable.

J Cell Biol, 1994 Jul, 126(2), 475 - 83
v-src transformation of rat embryo fibroblasts . Inefficient conversion to anchorage-independent growth involves heterogeneity of primary cultures; Tavoloni N et al.; To clarify whether a single oncogene can transform primary cells in culture, we compared the transforming effect of a recombinant retrovirus (ZSV) containing the v-src gene in rat embryo fibroblasts (REFs) to that in the rat cell line 3Y1 . In the focus assay, REFs exhibited resistance to transformation as only six foci were observed in the primary cultures as opposed to 98 in 3Y1 cells . After G418 selection, efficiency of transformation was again somewhat lower with REFs compared to that with 3Y1 cells, but the number of G418-resistant REF colonies was much greater than the number of foci in REF cultures . Furthermore, while 98% of G418-resistant colonies of ZSV-infected REFs were morphologically transformed, only 25% were converted to anchorage-independent growth, as opposed to 100% conversion seen in ZSV-infected 3Y1 cells . The poor susceptibility of REFs to anchorage-independent transformation did not involve differences in expression and subcellular distribution of p60v-src, or its kinase activity in vitro and in vivo . It rather reflected a property of the primary cultures, as cloning of REFs before ZSV infection demonstrated that only 2 out of 6 REF clones tested were permissive for anchorage-independent growth . The nonpermissive phenotype was dominant over the permissive one in somatic hybrid cells, and associated with organized actin filament bundles and a lower growth rate, both before and after ZSV infection . These results indicate that the poor susceptibility of REFs to anchorage-independent transformation by p60v-src reflects the heterogeneity of the primary cultures . REFs can be morphologically transformed by p60v-src with high efficiency but only a small fraction is convertible to anchorage-independent growth . REF resistance seems to involve the presence of a suppressor factor which may emerge from REF differentiation during embryonic development.

J Bone Joint Surg Br, 1994 Jul, 76(4), 636 - 40
Primary semiconstrained total elbow arthroplasty . Survival analysis of 113 consecutive cases; Kraay MJ et al.; We used survival analysis to evaluate 113 consecutive semiconstrained total elbow arthroplasties (TEAs) in 95 patients at a maximum follow-up of 99 months . Our criteria for failure were mechanical malfunction, revision for any reason, and deep infection . The primary diagnosis was inflammatory arthritis in 86 elbows, post-traumatic arthritis in 6, supracondylar nonunion or fracture in 12, osteoarthritis in 2 and other causes in 3 . Seven failures were due to deep infection, and five of these had a primary diagnosis of inflammatory arthritis . Eight failures were revised or had revision recommended for aseptic loosening, and six of these were in patients with post-traumatic arthritis or supracondylar nonunion . The cumulative survival for TEAs performed for post-traumatic arthritis, fractures or supracondylar nonunion was 73% at three years and 53% at five years, significantly worse than the cumulative three- and five-year survivals of 92% and 90%, respectively, for patients with inflammatory arthritis . TEA with a semiconstrained prosthesis appears to have a satisfactory survival in selected patients with arthritic disorders . The incidence of deep infection was reduced by improvements in surgical technique and postoperative management, and the routine use of antibiotic-impregnated cement . The incidence of aseptic loosening was low, except in patients with supracondylar nonunion or post-traumatic arthritis.

Clin Pract Guidel Quick Ref Guide Clin, 1994 Jul, (12), 1 - 13
Managing otitis media with effusion in young children . Agency for Health Care Policy and Research; Reduction of central nervous system reperfusion injury in rabbits using doxycycline treatment; Department of Neurology, Oregon Health Sciences University, Portland 97201BACKGROUND AND PURPOSE: Activated leukocytes appear to potentiate central nervous system reperfusion injury, and agents that block leukocyte adhesion have shown neuroprotective efficacy in experimental models . Doxycycline, a tetracycline antibiotic, inhibits leukocyte function in vitro, presumably through divalent cation binding . We used a model of focal central nervous system reperfusion injury to determine the efficacy of doxycycline treatment in preserving neurological function . METHODS: Rabbits randomly received 10 mg/kg i.v . doxycycline 30 minutes before ischemia (pretreatment group) or 45 minutes after ischemia (posttreatment group) or received phosphate-buffered saline vehicle (control group) followed by 10 mg/kg q 8 hours times two . The average length of reversible spinal cord ischemia required to produce paraplegia (P50) at 18 hours was calculated for each group . RESULTS: For the control group (n = 13), the P50 was 22.8 +/- 2.2 minutes; for the pretreatment group (n = 14), 35.5 +/- 2.4 minutes (P < .01; t = 3.8); and for the posttreatment group (n = 13), 31.4 +/- 4.2 minutes (not significant; t = 1.6) . Doxycycline also attenuated postischemic decreases in vivo leukocyte counts and inhibited in vitro leukocyte adhesion . Therapeutic doxycycline levels at 24 hours were confirmed in the plasma and spinal cord . CONCLUSIONS: This significant protective effect suggests that doxycycline, a safe and readily available agent, may play a role in reducing clinical central nervous system reperfusion injury.

South Med J, 1994 Jul, 87(7), 762 - 3
Fever and leukocytosis related to terconazole vaginal suppository; Hyder SS et al.; We describe a 22-year-old woman who developed fever, shaking chills, and leukocytosis after insertion of a terconazole (80 mg) vaginal suppository for mild vaginal candidiasis . The patient became afebrile and asymptomatic 24 hours after hospital admission without antibiotic therapy . More experience with terconazole is needed before it can be considered as safe as other imidazole derivatives that have been available for more than 15 years.

Anesth Analg, 1994 Jul, 79(1), 35 - 9
Comparison of pH-adjusted bupivacaine 0.75% and a mixture of bupivacaine 0.75% and lidocaine 2%, both with hyaluronidase, in day-case cataract surgery under regional anesthesia; Sarvela PJ et al.; Alkalinized bupivacaine 0.75% (pH 6.8) and a mixture (1:1) of bupivacaine 0.75% and lidocaine 2%, both with hyaluronidase, were compared in regional ophthalmic anesthesia for day-case cataract surgery . Eighty-two patients were randomized into two groups (n = 39 and 43) to receive one of the two solutions in a double-blind manner . Two intraorbital injections were administered initially: an inferolateral intraconal injection (3 mL) and a medial extraconal injection (3.5 mL) . The progress of lid and globe akinesia was examined every 2.5 min up to 25 min and postoperatively . The block was supplemented at 10 and 20 min, if needed . Significantly better globe akinesia was achieved with the bupivacaine-lidocaine mixture; the patients who had received alkalinized bupivacaine needed additional injections significantly more often at 10 and 20 min . In lid akinesia, the onset time and recovery were similar in the two groups . One patient in the alkalinized bupivacaine group felt intraoperative pain, and eight patients in the bupivacaine-lidocaine group and seven in the alkalinized bupivacaine group sensed pain postoperatively from corticosteroid and antibiotic injections . Seventy percent of the pH-adjusted bupivacaine group and 8% of the lidocaine-bupivacaine group had diplopia the day after surgery . Of the two local anesthetic mixtures studied, lidocaine (2%) with bupivacaine (0.75%) provided regional ophthalmic anesthesia of better quality.

Cancer, 1994 Jul 1, 74(1), 189 - 96
Safety and cost effectiveness of early hospital discharge of lower risk children with cancer admitted for fever and neutropenia; Bash RO et al.; BACKGROUND . Standard treatment for fever during periods of chemotherapy-induced neutropenia includes hospitalization and administration of intravenous antibiotics until the patient is afebrile and no longer neutropenic . This study prospectively evaluates the safety and cost-effectiveness of early discharge of selected low risk children before recovery from neutropenia . METHODS . We studied 74 children with cancer during 131 consecutive admissions for fever during a period of neutropenia . All patients initially were hospitalized and received broad-spectrum antibiotics . Intravenous antibiotic therapy was discontinued, and the patients promptly were discharged even if they had an absolute neutrophil count (ANC) of less than 500 cells/mm3 as long as they were afebrile, appeared clinically well, had negative cultures, exhibited control of local infection, and showed hematologic evidence of bone marrow recovery . RESULTS . Intravenous antibiotics were discontinued in 82 cases (63%) before recovery of the ANC to more than 500 cells/mm3, and 78 patients were discharged immediately . None of 70 patients discharged while neutropenic but exhibiting a rising ANC at the time of discharge developed recurrent fever and required readmission . Thirty of these children had an improving localized infection when intravenous antibiotics were discontinued and completed a course of oral antibiotics at home . The estimated mean savings in hospital charges due to early discharge was $5058 per patient . CONCLUSIONS . Low risk children with cancer who are hospitalized and treated for fever and neutropenia but appear clinically well may have intravenous antibiotics discontinued and be discharged safely irrespective of the ANC, as long as their granulocyte count is rising . This approach shortens hospital stays and results in considerable cost savings.

Pathology, 1994 Jul, 26(3), 257 - 60
Actinomycin D associated hepatic veno-occlusive disease--a report of 2 cases; Barclay KL et al.; Until recently, actinomycin D (AMD), a cytotoxic antibiotic, was considered to cause little or no liver damage . There are now reports of liver failure following treatment of childhood cancers with AMD . This report describes the pathological changes in liver biopsy samples taken from 2 children who developed liver failure after combined chemotherapy for Wilms' tumor . The changes were those of nodular hyperplasia, sclerosis of terminal hepatic venules with associated zone 3 hemorrhagic necrosis, and sinusoidal fibrosis . These features were initially ascribed to the veno-occlusive disease caused by pyrrolizidine alkaloids, radiotherapy and some therapeutic drugs but have not been described in detail as a complication of AMD therapy . An additional feature peculiar to these 2 cases was the presence of unexplained extramedullary hematopoiesis.

Biochem Mol Biol Int, 1994 Jul, 33(4), 633 - 42
Protective effect of exogenous coenzyme Q against damage by adriamycin in perfused rat liver; Valls V et al.; We have investigated the effect of rat liver perfusion with adriamycin on mitochondrial activities . Although the perfusion treatment per se induces some decline of respiratory activities, adriamycin strongly potentiates this effect; moreover the coenzyme Q9 content of the mitochondrial membrane is significantly lowered by the antibiotic . Coaddition of coenzyme Q10 in the perfusate significantly protects the mitochondria, not only from loss of respiratory activities but also of the endogenous CoQ9 content . Exogenous CoQ10 fails to enhance respiratory activities in control rats, not treated with adriamycin, even though CoQ concentration has been proven not to be kinetically saturating in the respiratory chain under physiological conditions . Thus, the beneficial effect of CoQ10 in the perfusate does not appear to be the result of its role in the respiratory chain but is a consequence of its antioxidant action.

J Pharm Biomed Anal, 1994 Jul, 12(7), 875 - 81
Spectrofluorimetric analysis of cefuroxime in pharmaceutical dosage forms; Murillo JA et al.; A fluorimetric method has been developed for the quantitative analysis of cefuroxime, based upon the formation of a fluorescent derivative formed by alkaline hydrolysis with 1.0 M sodium hydroxide and heating at 100 degrees C for 60 min . The fluorescent product gave excitation and emission maxima at 380 and 436 nm, respectively . The method was performed in aqueous solution adjusted to pH 10.5 by addition of phosphate buffer solution . The calibration curve was found to be linear in the range of concentrations 0.050-1.70 micrograms ml-1 . The lower limit of detection was 1.0 x 10(-2) micrograms ml-1 . The method was applied to authentic pharmaceutical preparations containing cefuroxime sodium or cefuroxime axetil, the 1-(acetyloxy) ethyl ester of the drug, and was found to be satisfactory . Cefuroxime sodium was also determined in physiological solutions used to prepare intravenous infusions of this antibiotic.

Acta Derm Venereol, 1994 Jul, 74(4), 307 - 9
Vein surgery with or without skin grafting versus conservative treatment for leg ulcers . A randomized prospective study; Warburg FE et al.; In order for us to evaluate the efficiency of perforator vein surgery and skin grafting in leg ulcer patients, 47 patients were randomized into 3 treatment groups (group A: surgery for incompetent perforators, group B: surgery for incompetent perforators and ulcer excision followed by grafting, group C: control group) . All the patients were treated with a compression bandage . When cellulitis was observed, a systemic antibiotic was given; eczema was treated with a steroid ointment . Fourty patients were evaluated regularly during one year after entry . There were no differences between the 3 treatment groups considering base-line characteristics, median ulcer size at entry and after one year . According to a review of the initial phlebograms, the occurrence of post-thrombotic changes in the deep veins were recorded in the majority of the legs . Our results suggest that ligation of incompetent perforators and skin grafting, as used in the present study, may not offer an additional advantage for venous ulcer patients with insufficiency of the deep veins when compared to conservative treatment . However, the removal of insufficient superficial veins was not studied.

Pediatr Pulmonol, 1994 Jul, 18(1), 21 - 7
Plasma interleukin-1 alpha and beta, tumor necrosis factor-alpha, and lipopolysaccharide concentrations during pulmonary exacerbations of cystic fibrosis; Wilmott RW et al.; Earlier studies have reported the presence of interleukin-1 (IL-1) and tumor necrosis factor (TNF) in the plasma of patients with cystic fibrosis (CF), but the results have been inconsistent . To investigate the relationships among plasma IL-1 alpha, IL-1 beta, TNF, lipopolysaccharide (LPS), and clinical status, measurements were made before and after 14 days of intravenous antibiotic therapy in 13 patients with CF . In addition, whole blood cytokine production rates were measured in 18 hr cultures stimulated with 10 micrograms/mL LPS or sterile saline (control) . On admission, patients with CF had significantly greater plasma levels of LPS and IL-1 alpha compared with 20 healthy adult controls . In response to antibiotic therapy, the patients had statistically significant increases in weight, oxygen saturation, chest radiograph score, and forced expiratory volume in 1 second . They had significant decreases in pulse rate, residual volume/total lung capacity ratio, white blood count, neutrophil count, LPS concentration, and resting energy expenditure per kg body weight . There were no significant changes in the plasma concentrations of IL-1 alpha, IL-1 beta, or TNF and no significant changes in the basal or stimulated whole blood production rates of IL-1 alpha, IL-1 beta, or TNF . The immunological variables did not correlate significantly with clinical measurements of severity or the presence of fever . It is likely that in CF local pulmonary effects of cytokines are of more pathophysiologic significance than systemic effects.

Lab Anim, 1994 Jul, 28(3), 270 - 3
Helminthic infestation complicated by intussusception in baboons (Papio hamadryas); Hennessy A et al.; Two juvenile baboons presented with diarrhoea, which did not resolve completely following antibiotic therapy . Ileal intussusception was identified at autopsy in both cases . Trichuris was the only gastrointestinal pathogen for which evidence could be found . This helminth is well-recognized as a cause of intussusception in human infants, but the complication has not been reported previously in non-human primates . It is likely to be fatal if undiagnosed.

Eur J Nucl Med, 1994 Jul, 21(7), 666 - 74
Scintigraphic detection of inflammatory heart disease; Morguet AJ et al.; Inflammatory diseases of the heart encompass myocarditis, endocarditis and pericarditis . This paper discusses the diagnostic potential of scintigraphy in these entities . In myocarditis, indium-111 antimyosin Fab imaging can visualize active myocyte damage and thus contribute substantially to the diagnosis . Antimyosin uptake is also seen in a large subset of patients with dilated cardiomyopathy, indicating ongoing myocyte injury in these cases . In endocarditis, immunoscintigraphy using monoclonal technetium-99m-labelled antigranulocyte antibodies provides useful diagnostic information in patients with equivocal echocardiographic findings . Immunoscintigraphy seems to indicate the floridity of the inflammatory process in endocarditis and may be used to monitor antibiotic therapy . In pericarditis, the clinical value of scintigraphy has not been convincingly demonstrated.

Zhongguo Zhong Xi Yi Jie He Za Zhi, 1994 Jul, 14(7), 429 - 31
{Study on effect of emodin on the isolated intestinal smooth muscle of guinea-pigs}; Jin ZH et al.; Emodin is an active principle of Rheum palmatum . It is reported that emodin possesses antibiotic and antineoplastic functions . The effect of emodin action on the isolated intestinal smooth muscle of guinea-pigs were dose dependent . When the dose of emodin was less than 29.6 mumol/L, the contraction effect enhanced obviously with increasing dosage; but whenever the dose increased to more than 29.6 mumol/L, on the contrary, the effect decreased gradually and ceased finally . Emodin with appropriate concentration (14.8 mumol/L) strengthened the effect of acetylcholine (Ach) on the isolated ileum and large intestine of guinea-pigs (P < 0.05 and P < 0.01) . But high concentration of emodin could reduce even completely antagonize the effect of Ach . Under such condition, CaCl2 could restore the effect of Ach on the smooth muscle . It is suggested that emodin has biphasic regulatory effect on the intestinal smooth muscle, and its effect is related to calcium ion.

Z Naturforsch {C}, 1994 Jul-Aug, 49(7-8), 483 - 8
In vitro and in vivo binding of epirubicin to red blood cells and human plasma proteins; Bandak S et al.; In this study, the in vitro interaction of epirubicin (EPR), a cytostatic antibiotic, with plasma proteins (PP), namely alpha-HSA, gamma-HSG, alpha+beta-HSG and with isolated human red blood cells (RBCs) was investigated and further correlated with the in vivo pharmacokinetics and binding of EPR and two of its metabolites, 13-dihydroepirubicin and 7-deoxydoxorubicinone to RBCs . The in vitro encapsulation rate in isolated erythrocytes amounts to 52.9 +/- 2.8% and remains constant within the range of studied concentrations (2.5-20 micrograms/ml) . EPR was found to bind differently to the various PP in vitro . Binding to alpha-HSA amounted up to 51.0 +/- 7.10%, to alpha+beta-HSG 79.45 +/- 2.7%, to gamma-HSG 57.1 +/- 2.8% . The in vivo-binding rate of EPR, dihydroepirubicin and deoxydoxorubicinone to RBCs after 5 min of injection was 32 +/- 6.96%, 11.6 +/- 3.1% and 10.05 +/- 3.5% respectively, their availability in serum was 42.6 +/- 11.8%, 2.4 +/- 0.4% and 1.2 +/- 0.67% respectively.

Arch Esp Urol, 1994 Jul-Aug, 47(6), 553 - 6
{Epididymo-testicular abscess}; Granados Loarca EA et al.; We reviewed the records of 34 patients with epididymal and/or testicular abscess that were treated at our institution . The mean age of the patients was 48.6 years . The most common clinical manifestation was scrotal pain . The diagnosis was made on the clinical and/or scrotal ultrasound findings . E . coli was isolated in 84.6% of the cases . Chronic and acute orchitis with abscess formation were the most common histological findings . Twenty-nine cases required antibiotic therapy plus surgery and five cases required antibiotics alone.

J Cataract Refract Surg, 1994 Jul, 20(4), 373 - 7
Intraocular gentamicin sulfate and postcataract anterior chamber aspirate cultures; Dickey JB et al.; We cultured anterior chamber aspirates of 28 patients who had uncomplicated cataract surgery . Fourteen patients had received 80 micrograms/ml of gentamicin in balanced salt solution through irrigation of the anterior chamber throughout cataract extraction, and 14 patients had received 8 micrograms/ml of gentamicin . Cultures of anterior chamber fluid obtained at the end of surgery from all 28 patients had no growth on two nonselective media . There was no clinical evidence of ocular toxicity . This study demonstrates that antibiotic in the intraocular irrigation fluid can reduce or eliminate the expected intraocular bacterial load after cataract surgery.

J Clin Microbiol, 1994 Jul, 32(7), 1644 - 9
Reisolation of Ehrlichia canis from blood and tissues of dogs after doxycycline treatment; Iqbal Z et al.; We present evidence that supports the carrier status of dogs experimentally infected with Ehrlichia canis after treatment with doxycycline . Canine ehrlichiosis was induced in five dogs by intravenous inoculation with E . canis-infected DH82 cells . All animals developed mild clinical signs of transient fever, body weight loss, thrombocytopenia, and increased gamma globulin levels in plasma . An indirect fluorescent-antibody test (IFA) revealed that all dogs had seroconverted (titer, 5,120) by day 10 postinoculation (p.i.) . E . canis was reisolated from blood samples collected at intervals throughout the 2-month period p.i . Doxycycline was administered orally once daily at 10 mg/kg of body weight per day for 1 week starting at 2 months p.i . Following treatment, gamma globulin levels in plasma were decreased . At necropsy on days 54 to 59 after the start of treatment, spleen, liver, kidney, and lymph nodes were collected for E . canis culture and histopathologic examination . Although the dogs did not show significant clinical signs during or after treatment with the antibiotic, E . canis was reisolated from the blood and tissue samples of three of five dogs . A 16-fold reduction in IFA titer was noted in two dogs which were negative for E . canis reisolation at day 49 after the start of treatment, whereas a zero- to fourfold reduction in IFA titer was seen in the remaining three dogs . Western immunoblot reactions to higher-molecular-size E . canis antigens in the sera of two dogs which were negative for E . canis on blood culture decreased, whereas they remained continuously high or only transiently decreased for the duration of the study for antigens in the sera of three dogs from which E . canis was reisolated . Histopathologically, prominent plasmacytosis in the kidney cortex was present in three dogs from which E . canis was reisolated, whereas the kidney cortices of two dogs had moderate to minor plasmacytosis . These findings pose questions regarding the efficacy, dosage and duration of doxycycline treatment in dogs with E . canis infection . In addition, it was shown that IFA and Western immunoblotting may aid in assessing the efficacy of antibiotic therapy when definitive reisolation procedures are not readily available.

Arch Biochem Biophys, 1994 Jul, 312(1), 1 - 13
Human cytoplasmic 3-hydroxy-3-methylglutaryl coenzyme A synthase: expression, purification, and characterization of recombinant wild-type and Cys129 mutant enzymes; Rokosz LL et al.; A cDNA for the human cytoplasmic 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) synthase (EC 4.1.3.5) was subcloned and expressed from a T7-based vector in Escherichia coli . The over-produced enzyme was purified using a three-step protocol that generated 20 to 30 mg protein/liter cell culture . The physical and catalytic properties of the recombinant synthase are similar to those reported for the nonrecombinant enzymes from chicken liver {Clinkenbeard et al . (1975a) J . Biol . Chem . 250, 3124-3135} and rat liver {Mehrabian et al . (1986) J . Biol . Chem . 261, 16249-16255} . Mutation of Cys129 to serine or alanine destroys HMG-CoA synthase activity by disrupting the first catalytic step in HMG-CoA synthesis, enzyme acetylation by acetyl coenzyme A . Furthermore, unlike the wild-type enzyme, neither mutant was capable of covalent modification by the beta-lactone inhibitor, L-659,699 {Greenspan et al . (1987) Proc . Natl . Acad . Sci . USA 84, 7488-7492} . Kinetic analysis of the inhibition by L-659,699 revealed that this compound is a potent inhibitor of the recombinant human synthase, with an inhibition constant of 53.7 nM and an inactivation rate constant of 1.06 min-1.

Avian Dis, 1994 Jul-Sep, 38(3), 630 - 4
Proventriculitis and ventriculitis associated with zygomycosis in ostrich chicks; Jeffrey JS et al.; This report describes eight cases of proventriculitis and ventriculitis in ostrich chicks less than 2 months old . Clinical signs included acute onset of lethargy and anorexia in three cases, and chronic weight loss with lethargy and anorexia in four cases; no history was available in one case . There was limited antibiotic therapy in two cases; a third case was treated for giardiasis . Concurrent bacterial, yeast, and viral infections were common . Lymphoid depletion and/or necrosis of bursa, thymus, and spleen suggested severe immune challenge or immunosuppression in many cases . Histologically, there was severe ulcerative proventriculitis and ventriculitis with intralesional fungal hyphae . In two chicks with granulomatous pneumonia, similar fungal hyphae were also observed in the lung . Fungal hyphae were rarely septate, with irregular, non-parallel walls, and ranged in diameter from 7 to 20 microns . Occasional globoid distentions of the hyphae were present . Fungi were identified morphologically as species in the Zygomycetes class; in one case a Mucor sp . was cultured . Zygomycetes appear to be potentially serious opportunistic pathogens of ostrich chicks.

Shock, 1994 Jul, 2(1), 29 - 33
Bacterial translocation and lipopolysaccharide-induced mortality in genetically macrophage-deficient op/op mice; Feltis BA et al.; Genetically macrophage-deficient op/op mice have a total absence of macrophage colony-stimulating factor (also known as colony-stimulating factor 1 or CSF-1), and therefore an absence of a population of macrophages dependent on CSF-1 . op/op mice also have profound secondary deficiencies in certain cytokines secreted by this macrophage population, such as tumor necrosis factor, interleukin-1, and granulocyte colony-stimulating factor . In the present study, op/op mice were used to clarify the role of the macrophage in two clinical processes: (a) bacterial translocation in response to antibiotic-induced intestinal overgrowth, and (b) endotoxin-induced bacterial translocation, morbidity, and mortality . The results were unexpected, in that bacterial translocation and endotoxin-induced morbidity and mortality were similar in op/op mice and their functionally normal littermates . These data indicated either that a specific macrophage population and its cytokines (including tumor necrosis factor and interleukin 1) might not play pivotal roles in the pathogenesis of bacterial translocation and endotoxin-induced septic shock, or alternatively, as yet unknown redundancies in vivo might compensate for the genetic deficiencies associated with the op/op mutation.

J Dermatol Sci, 1994 Jul, 7 Suppl, S47 - 54
Hair growth-stimulating effects of cyclosporin A and FK506, potent immunosuppressants; Yamamoto S et al.; Cyclosporin A (CsA), a cyclic endecapeptide, is a T cell-specific immunosuppressant and is successfully used in the field of organ transplantation . Another T cell-specific immunosuppressant, FK506, a more recently discovered macrolide antibiotic, is effective against graft rejection at much lower doses than CsA . Although totally different in structure, both compounds inhibit T cell activation by interfering with the production of interleukin-2 (IL-2) by inhibiting IL-2 gene expression, probably through the inhibition of calcineurin, a Ca2+/calmodulin-dependent phosphatase . Clinical studies have revealed that FK506 induces a variety of side effects in common with CsA . One of the most common side effects of CsA is hypertrichosis . The hair growth stimulating effect of CsA is observed not only in normal but also in pathological conditions of hair growth, i.e . in patients with alopecia areata and also in some patients with male-pattern alopecia . Although hypertrichosis is induced by both topical and oral administration of CsA, there has been no report showing that FK506 induces hypertrichosis . Recently we have found that topical application of FK506 to skins of mice, rats and hamsters markedly stimulates hair growth . This hair growth stimulating effect of FK506 is observed when applied topically but not by oral administration, even with a dose which causes marked immunosuppression . The hair growth stimulating effect of FK506 in normal animals may apparently be unrelated to its immunosuppressive effect . In vitro studies revealed that FK506 directly stimulates hair follicles . Mechanisms of hair growth stimulating effects of FK506 and CsA remain to be elucidated.(ABSTRACT TRUNCATED AT 250 WORDS)

Prikl Biokhim Mikrobiol, 1994 Jul-Oct, 30(4-5), 657 - 61
{Membranolytic activity of gradex}; Petrykina ZM et al.; The membranolytic activity of gradex towards bacterial protoplasts and human erythrocytes has been demonstrated . Dextran shows no such activity . The lytic activity of gradex towards protoplasts is much lower as compared to gramicidin S . The increase in gramicidin S content from 2 to 5% caused no significant changes in the lytic activity of gradex towards protoplasts . The reduced form of gradex nad no hemolytic effect on human erythrocytes up to a concentration of 300 micrograms/ml . However, the non-reduced form of gradex af a concentration of 500 micrograms/ml lysed from 31 to 48% of erythrocytes depending on the antibiotic content in the polymeric matrix.

Drugs, 1994 Jul, 48(1), 59 - 70
Acne . A review of optimum treatment; Sykes NL Jr et al.; Acne vulgaris is a disease of the pilosebaceous unit of the skin . It may have profound psychological sequelae . The lesions are due to abnormally adherent keratinocytes causing plugging of the follicular duct followed by accumulation of sebum and keratinous debris . This results in the formation of the primary lesion of acne, the comedo . Inflammation of comedones produces papules, pustules and nodules, which often prompt patients to seek treatment . Various effective treatments include topical anti-inflammatory, antibiotic and peeling agents, oral antibiotics, topical and oral retinoids, and hormonal agonists and antagonists . Useful combination regimens are discussed, and treatment approaches suggested . Mild cases of comedonal acne may respond to a topical retinoid or benzoyl peroxide, while inflammatory lesions benefit from topical antibiotics . More severe inflammatory acne is treated with systemic antibiotics . Recalcitrant cases often require oral isotretinoin or hormonal manipulation.

Clin Endocrinol (Oxf), 1994 Jul, 41(1), 31 - 9
Effect of FK-506 on xenografted human Graves' thyroid tissue is severe combined immunodeficient mice; Yoshikawa N et al.; OBJECTIVE: We studied the macrolide antibiotic FK-506, an immunosuppressive agent, in an attempt to ameliorate the lesion of autoimmune thyroid disease in human thyroid tissue xenografted into severe combined immunodeficient (SCID) mice . It was not felt appropriate to employ this agent directly in patients with autoimmune thyroid disease because adequate therapeutic modalities are available and the introduction of new, experimental agents could not be justified . Moreover, the study of the tissue before and after treatment could not have been undertaken directly in patients . DESIGN: Human thyroid xenografts from four patients with Graves' disease and two normal persons were xenografted into SCID mice . Two weeks after xenografting, human immunoglobulin G (IgG) was detectable in all SCID mice xenografted with Graves' thyroid tissue . Mice were divided into two groups with human IgG levels similar to each other . Mice in the first group were treated with FK-506 daily for 6 weeks; mice in the second (similar) group were given phosphate-buffered saline (PBS) only (control group) . MEASUREMENTS: Blood samples were taken every 2 weeks from the tail veins for human IgG, thyroid stimulating antibody, thyroperoxidase antibodies, thyroglobulin antibodies, and interferon-gamma (IFN-gamma) . After 8 weeks treatment, animals were sacrificed; thyroid tissue was examined histologically and for thyrocyte HLA-DR expression . FK-506 was also added to thyrocytes in in-vitro tissue culture conditions . RESULTS: After 4-6 weeks of FK-506 therapy, human IgG, all thyroid antibodies and IFN-gamma were suppressed, while the levels remained elevated in the control group . Lymphocytic infiltration virtually disappeared in the human thyroid tissue of the FK-506-treated mice and thyrocyte HLA-DR expression markedly declined; in the control mice, lymphocytic infiltration remained heavy and HLA-DR expression remained high . On the other hand, FK-506 added directly to thyrocytes in vitro (without lymphocytes) did not reduce thyrocyte HLA-DR expression . CONCLUSIONS: FK-506 appears to suppress the activation of intrathyroidal lymphocytes, but not thyrocytes . From these observations, it is concluded that this agent, by its action on intrathyroidal lymphocytes, is able to ameliorate the immunologically mediated histological and serological disturbance in human autoimmune thyroid disease, at least under these circumstances.

Radiology, 1994 Jul, 192(1), 241 - 6
Malignant biliary obstruction: preliminary results of palliative treatment with hepaticogastrostomy under fluoroscopic, endoscopic, and laparoscopic guidance; Soulez G et al.; PURPOSE: To report a technique of peripheral biliary decompression by means of anastomosis of a bile duct in segment II of the liver to the lesser curvature of the stomach . MATERIALS AND METHODS: Seven patients with unresectable biliary neoplasm were treated . After transhepatic catheterization of a segment II bile duct, the left lobe of the liver and the lesser curvature of the stomach were perforated under fluoroscopic and laparoscopic guidance . Anastomosis between the biliary tree and the stomach was maintained with a gastrostomy tube placed across the tract . After 2 weeks, the tube was removed and patency of the tract was preserved with a metallic stent . RESULTS: Three patients died, at 3, 6, and 9 months, respectively, without reocclusion; the other four were alive at 5 months without jaundice . One patient had an episode of cholangitis, which was resolved with antibiotic therapy . CONCLUSION: This method yields a good patency rate with few problems . Further investigation is required to evaluate long-term patency and the necessity of laparoscopic guidance.

Biochem Biophys Res Commun, 1994 Jun 30, 201(3), 1270 - 8
Concanamycin A: a powerful inhibitor of enveloped animal-virus entry into cells; Guinea R et al.; Concanamycin A, a selective inhibitor of the vacuolar proton ATPase, blocks the infection of animal cells by vesicular stomatitis virus, Semliki Forest virus and influenza virus even when the drug is present at the low concentration of 5 nM . Nevertheless the antibiotic prevents neither the attachment, to cells, of Semliki Forest virus nor its subsequent internalization . Under certain conditions, described in this communication, virus entry is prevented even when the pH of the medium is low, thus suggesting that a pH gradient, rather than low pH per se, is required to drive the entry, into cells, of these enveloped animal viruses.

Mol Cell Biochem, 1994 Jun 29, 135(2), 159 - 69
Brefeldin A down-regulates the transferrin receptor in K562 cells; Schonhorn JE et al.; The fungal metabolite brefeldin A (BFA) induces profound alterations in the morphology of intracellular organelles . Although BFA promotes the formation of extensive tubular endosomal domains, our understanding of the effects of the antibiotic on vesicle traffic events associated with endocytosis is limited . Thus, alterations in the transferrin (Tf) receptor's endocytic/recycling pathway upon treatment of human erythroleukemia K562 cells with BFA were studied as a pharmacological response . Treatment of K562 cells with BFA caused a down-regulation in the number of cell surface Tf receptors . This effect is highly reminiscent of the well-known action of phorbol 12-myristate 13-acetate (PMA) on Tf receptor traffic in K562 cells . However, our results demonstrate that these two agents down-regulate the Tf receptor via different mechanisms . The effects of BFA and PMA were additive when K562 cells were incubated with both together . Using the In/Sur method, the endocytic rate constant for Tf internalization was determined and PMA was found to greatly enhance ke, from 0.28 min-1 to 0.43 min-1, while BFA had little effect (Ke = 0.20 min-1) . In contrast, BFA-treatment alters the exocytic rate constant for return of internalized receptors to the cell surface, with the largest effect exerted on a 'slow-release', monensin-sensitive, compartment . The sum of the endocytic and exocytic kinetic data support a model in which BFA and PMA down-regulate the Tf receptor in K562 cells by mechanistically distinct actions, with BFA targeting exocytic monensin-sensitive intracellular compartments and PMA acting to exert a profound influence on elements of receptor internalization.

Transplantation, 1994 Jun 27, 57(12), 1786 - 94
Prevention of the humoral response induced by an anti-CD3 monoclonal antibody by deoxyspergualin in a murine model; Alegre ML et al.; Multiple treatments with the potent immunosuppressant murine antihuman CD3 mAb OKT3 is sometimes precluded by the onset of a neutralizing humoral response mostly consisting of anti-idiotypic antibodies . A hamster antimurine CD3 monoclonal Ab, 145-2C11, shares many properties with OKT3, in particular the ability to induce a strong Ab response in mice . Deoxyspergulain (DSG), a metabolite of the antibiotic spergualin, has been shown to reduce Ab production triggered by pathogens in a variety of infectious models and against common antigens . In this study, we examined the ability of DSG to inhibit the humoral response induced by 145-2C11 . DSG prevented the Ab production triggered by the anti-CD3 mAb in an Ag-specific manner and significantly reduced the Ab production in mice previously primed with 145-2C11 . We showed that DSG had a long-term effect on B cells and a transient effect on T cells . In effect, DSG was found to induce a prolonged Ag-specific unresponsiveness of B lymphocytes, and to transiently reduce the capacity of T lymphocytes to deliver help to B cells, in part by reducing IL-4 production . DSG did not reduce the immunosuppressive properties of the anti-CD3 mAb . In fact, the combination of DSG with 145-2C11 prolonged the survival of allogeneic skin grafts when compared with the administration of 145-2C11 or DSG alone . Thus, the coadministration of DSG with OKT3 may be of clinical interest to reduce the humoral response triggered by the mAb.

N Z Med J, 1994 Jun 22, 107(980), 240 - 2
A comparison of the respiratory care given to asthmatic and nonasthmatic children in a general practice; Kljakovic M; AIM . To compare the management of respiratory problems in asthmatic and nonasthmatic children . METHOD . A comparison of recorded morbidity in clinical records with parental replies to questionnaires for random matched samples of 5 to 9 year old asthmatic and nonasthmatic children from a suburban middle class general practice over the 1990 year . RESULTS . Eighty six percent of parents of asthmatic children and 75% of parents of nonasthmatic children responded . 11% of asthmatic children left the practice without giving a forwarding address . Asthmatic children consulted more often, saw more general practitioners, and were prescribed more antibiotic and asthma related drug items than nonasthmatic children . Asthmatic children were no more likely than nonasthmatic children to have their respiratory system examined at the general practice when well and no more likely to use secondary services . Fifty seven percent of asthmatic children had an asthma drug related prescription written and 22% of asthmatic children had a peak flow recording . Disagreement between records and parental report: 31% of nonasthmatic children were reported by parents to have asthma related symptoms . 31% of these children did not see a general practitioner, 31% were seen for other problems, and 38% were treated for respiratory problems but not diagnosed as asthmatic . Forty nine percent of asthmatic children were reported to be taking daily asthma medication but 38% of these children had not been prescribed their medication in the practice . Fifty one percent of asthmatic children were reported not to be taking daily asthma medication but 50% of these children had been prescribed an asthma drug in the practice . CONCLUSION . Asthmatic and nonasthmatic children have nearly all their respiratory illnesses managed in general practice . In the general practice management of asthma the issues of workload, continuity of care, acute management, practice population based management, and communication need more research.

Semin Arthroplasty, 1994 Jul, 5(3), 142 - 6
Two-stage reimplantation of the infected hip; Garvin KL; To determine the diagnosis of patients with infection after total hip replacement may be very difficult, and successful reimplantation is even more challenging . Surgical debridement, removal of all foreign material, and the prosthesis followed by antibiotic therapy are essential for successful eradication of the infection . Reimplantation of the hip allows for functional recovery of the patient . The optimal time for reimplantation of the prosthesis and the role of antibiotic impregnated cement is less clear . A review of the literature strongly favors a two-stage reimplantation with local antibiotic delivery with successful results of approximately 93%.

FEBS Lett, 1994 Jun 6, 346(1), 59 - 64
Energy-coupled transport through the outer membrane of Escherichia coli small deletions in the gating loop convert the FhuA transport protein into a diffusion channel; Braun V et al.; Active transport of Fe3+ as ferrichrome complex through the outer membrane of Escherichia coli is mediated by the FhuA outer membrane protein and the TonB-ExbB-ExbD protein complex in the cytoplasmic membrane . The required energy is provided by the electrochemical potential of the cytoplasmic membrane which is assumed to induce a conformation of the TonB protein that causes a conformational change in FhuA so that bound ferrichrome is released into the periplasmic space located between the outer and the cytoplasmic membrane . Excision of segments as small as 12 amino acids in the largest surface loop of FhuA converted FhuA into an open channel through which ferrichrome and antibiotics diffused independent of TonB-ExbB-ExbD . It is proposed that FhuA forms a closed channel which is opened by movement of the gating loop through a kind of allosteric interaction with TonB . The gating loop is also involved in binding of all FhuA ligands which in addition to ferrichrome are the phages T1, T5, phi 80, colicin M and the antibiotic albomycin.

Otolaryngol Head Neck Surg, 1994 Jun, 110(6), 505 - 9
Functional endoscopic sinus surgery in patients with normal computed tomography scans; Cook PR et al.; Eighteen patients were operated on by functional endoscopic sinus surgery who had no ostiomeatal unit obstruction on computed tomography scan and had unremarkable paranasal sinuses . These patients also had no apparent ostiomeatal unit obstruction on diagnostic nasal endoscopy . Data were collected on these patients regarding the impact of very limited functional endoscopic sinus surgery on their principal complaint of recurrent sinusitis with facial pain/headache thought to be of sinogenic origin . Sixteen patients (88.9%) had a reduction in the number of sinus infections requiring antibiotic therapy . This reduction was significant at p < 0.0001 . Twelve of 14 patients whose facial pain/headache was believed to be of sinogenic origin had a significant reduction in severity (95% confidence interval, 49.2% to 95.3%) . We discuss the role of reversible nasal mucosal disease in the pathophysiology of recurrent rhinosinusitis in this patient population . This was a very small, select group of patients who had specific complaints and had had medical treatment failures . This therapy is not recommended for every patient, but only a select few with classic complaints of sinus headaches or recurrent sinusitis and negative computed tomography scans.

Leuk Res, 1994 Jun, 18(6), 415 - 21
Serum concentrations of tumour necrosis factor-alpha during chemotherapy-induced leukopenia in patients with acute leukaemia and bacterial infections; Bruserud O et al.; Serum concentrations of tumour necrosis factor-alpha (TNF-alpha) increase during septicaemia in previously healthy individuals . To investigate whether a similar increase in TNF-alpha can be seen in severely immunocompromised patients with acute leukaemia and chemotherapy-induced leukopenia, serum TNF-alpha was analysed in leukopenic patients with bacterial infections . Pretherapy serum levels of TNF-alpha were decreased in leukaemia patients compared with healthy controls, and serum TNF-alpha levels showed a further decrease when patients developed chemotherapy-induced leukopenia . When leukopenic patients developed bacterial infections, serum concentrations of TNF-alpha increased . Serum levels of TNF-alpha decreased when clinical signs of infection resolved during antibiotic therapy, but an increase occurred later in parallel with haematopoietic reconstitution.

Am Fam Physician, 1994 Jun, 49(8), 1815 - 20
Anaerobic lung infections; Vincent MT et al.; Aspiration is the leading cause of anaerobic lung infections . Risk factors for these infections include a depressed level of consciousness, a history of seizure, general anesthesia, central nervous system or neuromuscular disease, cerebrovascular accident, impaired swallowing and use of a tracheal or nasogastric tube . Clinical presentation includes fever, weight loss, malaise and cough productive of foul-smelling sputum . Diagnosis is based on radiographic findings, clinical features and a characteristic morphology of mixed flora on Gram stain of uncontaminated pulmonary specimens . The diagnosis is confirmed by isolation of organisms, usually polymicrobial, on culture . Treatment includes proper drainage, debridement of necrotic tissue and an antibiotic regimen (often initially empiric) with an agent active against anaerobic and aerobic organisms.

Can J Surg, 1994 Jun, 37(3), 209 - 13
Infected tibial nonunion; Shahcheraghi GH et al.; OBJECTIVE: To compare three methods of surgical treatment for infected nonunion of tibial fractures . DESIGN: Chart review . SETTING: Two teaching hospitals of Shiraz University Medical School in Iran . PATIENTS: Fifty-eight patients with infected nonunion of tibial fractures treated between 1976 and 1989 . All patients had received antibiotic therapy before treatment for nonunion . INTERVENTIONS: Bone grafting with cast immobilization (group 1), bone grafting with insertion of compression plates (group 2) and bone grafting with intramedullary rod fixation (group 3) . MAIN OUTCOME MEASURES: A clinical scoring system based on functional ability, range of knee and ankle motion, shortening, infection and pain . RESULTS: After the first operation union was achieved in 75% of group 1 patients, 84% of group 2 and 100% of group 3; 41% of patients had excellent or good results and 47% had fair or poor results . Twelve percent of patients had nonunion (failure) . Union in fractures treated with intramedullary rod fixation (group 3) occurred faster, and patients in this group had a higher number of good or excellent results than those in the other groups . Treatment without fixation (group 1) resulted in fair or poor results in over 50% of cases . CONCLUSION: In terms of union and function, the best surgical treatment for infected nonunion of tibial fractures in this series was bone grafting and intramedullary rod fixation, after adequate debridement and antibiotic therapy.

Am J Cardiol, 1994 Jun 1, 73(15), 1089 - 91
Clinical impact of transesophageal echocardiography in the diagnosis and management of infective endocarditis; Lowry RW et al.; Transesophageal echocardiography (TEE) has assumed a prominent role in the diagnosis and management of infective endocarditis (IE) . The impact of negative TEE findings on the management of patients suspected of having IE is not clear . To better understand how a negative TEE examination would influence patient management, the medical records of 93 consecutive patients undergoing TEE to evaluate for IE were examined . The influence of TEE was assessed based on changes in diagnosis, antibiotic therapy, or the need for surgical intervention during hospitalization . The negative predictive value of TEE was found to be 100% in native valves and 90% in prosthetic valves . The overall impact of negative TEE findings was significant in terms of final diagnosis and duration of antibiotic therapy (a negative TEE resulted in 60% reduction in antibiotic duration, p = 0.0001) . These findings suggest that in patients with native heart valves, a negative TEE examination virtually excludes IE . In patients with prosthetic valves, a negative TEE significantly decreases the likelihood of IE but does not completely exclude the diagnosis; therefore, in this setting, a negative finding should be closely correlated with the clinical course.

Surg Clin North Am, 1994 Jun, 74(3), 591 - 607
Necrotizing soft-tissue infections; Sutherland ME et al.; In the realm of clinical practice, this disease entity defies applicability to any classification scheme . Of paramount importance is the early identification of all necrotizing soft-tissue infections . This requires a high index of suspicion, aided by recognition of various risk factors and organ system dysfunction out of proportion to the extent of local signs and symptoms . Expedient, aggressive surgical therapy is imperative: resuscitation, wide debridement, and antibiotic therapy . Once the infection has been controlled, continued supportive care, reconstruction, and rehabilitation can proceed.

Surg Clin North Am, 1994 Jun, 74(3), 557 - 70
Intravenous and central catheter infections; Garrison RN et al.; Catheter-associated infections are quite common in hospitalized patients and account for significant morbidity and mortality . Multiple causative factors are present in everyday clinical practice to account for these infections . A high index of suspicion for these infections is needed in any evaluation of a patient who has a febrile illness . Removal of the catheter and quantitative culture are necessary initial steps in treatment, and systemic antibiotic therapy, based on specific culture results, is indicated in any patient whose systemic signs of infection do not resolve promptly . In the absence of such a response, other sources of infection should be sought; however, one must maintain a high index of suspicion for the local site of catheter insertion, and repeated examination of all insertion sites is indicated until the fever resolves.

J Parasitol, 1994 Jun, 80(3), 380 - 3
Evaluation of different medium supplements for in vitro cultivation of Brugia malayi third-stage larvae; Smillie CL et al.; Growth and development of Brugia malayi (Nematoda: Filarioidea) third-stage larvae (L3) were compared in 5 medium supplements . The basic culture medium (NI) consisted of a 1:1 (v/v) mixture of NCTC-135 and Iscove's modified Dulbecco's medium, an antibiotic/antimycotic mixture, and 1 of the following 5 supplements: 25 mg/ml bovine albumin fraction-V (BAF), 10% fetal bovine serum (FBS), 10% commercially obtained human serum (CHS), 10-15% pooled human serum from hospital patients (PHS), and 10-15% human serum from a single individual (SHS) . Cultures were maintained at 37 C in an atmosphere of 5% CO2 in air . NI-BAF and NI-CHS did not support molting of L3 to fourth-stage larvae (L4), whereas NI-FBS, NI-PHS, and NI-SHS did support molting of L3 to L4 but only the larvae in NI-SHS attempted the fourth molt . Growth and development of in vitro larvae in NI-PHS and NI-SHS were comparable to that observed in jirds for the first 28 days, after which the in vitro larvae lagged behind in vivo larvae . Optimal growth and development may be dependent on certain as yet unidentified components of specific human serum.

Blood, 1994 Jun 1, 83(11), 3132 - 7
Amifostine (WR-2721) shortens the engraftment period of 4-hydroperoxycyclophosphamide-purged bone marrow in breast cancer patients receiving high-dose chemotherapy with autologous bone marrow support; Shpall EJ et al.; 4-Hydroperoxycyclophosphamide (4-HC), a commonly used marrow-purging agent, is active against many tumors, but is also toxic to normal marrow progenitors . Amifostine (WR-2721) is a sulfhydryl compound with chemoprotectant activity . Preclinical studies using suspensions of bone marrow and breast cancer cells demonstrated that ex vivo treatment with amifostine followed by 4-HC resulted in protection of marrow progenitors, with no compromise in the antitumor effect of 4-HC . This fact stimulated the development of a clinical trial . Bone marrow was harvested from 15 poor-prognosis breast cancer patients and randomly assigned to ex vivo treatment with amifostine followed by 4-HC (amifostine + 4-HC), or treatment with 4-HC alone . High-dose chemotherapy was then administered followed by infusion of the purged autologous bone marrow support (ABMS) . Leukocyte engraftment, defined as a white blood cell count > or = 1 x 10(9)/L, was achieved in an average of 26 days for patients whose marrow was purged with amifostine + 4-HC versus 36 days for patients whose marrow was purged with 4-HC alone (P = .032) . The average number of platelet transfusions (12 v 29; P = .017) and days of antibiotic therapy (28 v 40; P = .012) were significantly less for patients whose marrow was exposed to amifostine + 4-HC, compared with 4-HC alone . Unpurged backup marrow fractions were infused into three patients whose marrow was purged with 4-HC alone, because of inadequate marrow recovery . None of the patients who received amifostine + 4-HC-purged marrow required a backup marrow fraction . Complete remissions were achieved in 83% of patients with measurable disease, with no difference between the two cohorts . Forty-three percent of patients remained alive and progression-free at a mean of 13 months posttransplant . There was no significant difference in the rate or pattern of relapse for patients whose marrow was purged with amifostine + 4-HC compared with those whose marrow was purged with 4-HC alone . Ex vivo treatment of marrow with amifostine significantly shortens the time to marrow recovery, thereby reducing the risk of myelosuppressive complications in breast cancer patients receiving high-dose chemotherapy and 4-HC-purged ABMS . Since supportive care requirements are also significantly decreased, amifostine may reduce the cost of such therapy.

Unfallchirurgie, 1994 Jun, 20(3), 157 - 61
{Optimal timing of wound closure in severe open fractures with temporary coverage by skin substitute}; Ostermann PA et al.; In a consecutive series of 1085 open fractures treated at the University of Louisville Level I Trauma Center from May 1983 to July 1992, 381 severe compound fractures in 335 patients were managed with the antibiotic bead pouch technique . There were 27 grade I (marked swelling, compartment syndrome), 115 grade II and 239 grade III open fractures (94 type IIIA, 114 type IIIB and 31 type IIIC) . These fractures were managed with early administration of broad spectrum antibiotics, copious wound irrigation, serial debridements and external skeletal stabilization . Tobramycin-PMMA-beads were placed in the wound and porous plastic film (Opsite) covered the soft tissue defect . This dressing was changed every 48 to 72 hours until wound coverage/closure could be obtained . Infection rate either on an acute or chronic basis was 2.6% in grade II open fractures and 8.4% in grade III compound fractures . There was no infected wound or bone in the grade I category . Those fractures which did not develop an infection were closed at a mean time of 7.6 days; those which developed an infection were closed at a mean time of 17.9 days . The difference was statistically highly significant (p < 0.001) . When severe open fractures are managed with the antibiotic bead pouch technique, wound closure should be obtained within one week to prevent infectious complications.

Microbiology, 1994 Jun, 140 ( Pt 6), 1359 - 65
Isolation and characterization of aclacinomycin A-non-producing Streptomyces galilaeus (ATCC 31615) mutants; Ylihonko K et al.; Twelve mutants of Streptomyces galilaeus (ATCC 31615) blocked in the production of aclacinomycin A, an anthracycline antibiotic with significant antitumour activity, accumulated intermediates of the biosynthesis of aclacinomycins and several anthracyclines with variant sugar moieties . Three of these aklavinone glycosides have not been described before . Mutant strains H028, H061 and H036 were blocked before the formation of aklavinone, a common intermediate for most anthracyclines . Strain H039 accumulated aklavinone and H026, H035, H038 and H054 had mutations that changed glycosylation of aklavinone . Characterization of the mutants and their products is described.

Can J Anaesth, 1994 Jun, 41(6), 523 - 6
Anaesthetic management of an asthmatic child for appendicectomy; Kuwahara B et al.; A 13-yr-old boy was scheduled for emergency appendicectomy because of abdominal pain . His preoperative medical history was complicated by a recent hospital admission for management of asthma . He had presented to hospital seven days earlier because of dyspnoea, tachypnoea and oxygen desaturation to 77% on room air . Following admission, he required intensive nonventilatory management of his asthma, including intravenous salbutamol, methylprednisolone, and aminophylline, as well as use of an ipratroprium bromide inhaler and 100% oxygen by mask . He was discharged to the ward, and continued on prednisone (delta-cortisone), beclomethasone inhaler, ipratroprium inhaler, and salbutamol inhaler . During his ICU stay, he complained of nonspecific abdominal pain, interpreted as gastro-oesophageal reflux . After four days, he was discharged to the ward . On his sixth hospital day, he began to experience right-sided lower abdominal pain and right shoulder pain . A surgeon was consulted, and the patient was found to have a very tender right lower quadrant with guarding and rebound pain . He was therefore scheduled for appendicectomy; antibiotic therapy with ampicillin, gentamicin, and metronidazole was initiated.

Curr Opin Pediatr, 1994 Jun, 6(3), 272 - 9
Pulmonary complications of tissue transplantation in children; Stokes DC; Pediatric bone marrow transplantation and transplantation of solid organs rapidly expanded during the 1980s . Antibiotic therapy for bacterial pneumonias, improved transplant preparative regimens, and improvements in prevention and therapy of graft-versus-host disease have made possible significant improvements in overall bone marrow transplant survival . Despite these advances, pulmonary complications of transplantation remain major causes of morbidity and mortality in pediatric transplant patients . Fungal and cytomegalovirus infections have emerged as the major posttransplant pulmonary infections whereas idiopathic interstitial pneumonias and bronchiolitis obliterans are the major noninfectious pulmonary problems . Recent developments in antiviral therapy for cytomegalovirus pneumonia offer hope that the dismal prognosis of cytomegalovirus pneumonia in transplant patients can be improved . New early detection methods for cytomegalovirus using polymerase chain reaction may also help identify patients for prophylactic therapy and prevent development of cytomegalovirus pneumonitis . Early diagnosis and treatment for fungal pneumonias and other opportunistic pathogens remain significant challenges in immunocompromised transplant patients.

Acta Chem Scand, 1994 Jun, 48(6), 498 - 505
Synthesis and antiviral activity of three pyrazole analogues of distamycin A; Ding L et al.; The synthesis of three new monopyrazole analogues of the antiviral compound distamycin A is reported . Suitably protected 4-amino-1-methylpyrrole-2-carboxylic acid and 3-amino-1-methylpyrazole-5-carboxylic acid derivatives were chosen as starting materials . The construction of the trimeric polyamide framework was accomplished by assembly of the monomeric precursors under condensing conditions by analogy with our previous methodology, although with significant improvements in some pivotal steps . After chromatographic purification and spectroscopic characterisation, the analogues were assayed for antiviral activity . Compounds 7a-c inhibited vaccinia virus at a concentration similar to or lower than distamycin A and the related antibiotic netropsin . Analogues 7b and 7c exhibited an antiviral effect comparable to those of distamycin A and netropsin against HSV-1 and HSV-2, whereas their antiviral activity against several other viruses including HIV-1 and HIV-2 was somewhat lower . The cellular toxicity of 7a-c toward different host cell types proved to be of similar magnitude or lower than those of distamycin A and netropsin.

Ryumachi, 1994 Jun, 34(3), 651 - 5
{A case of rheumatoid arthritis associated with agranulocytosis during bucillamine treatment}; Negishi M et al.; Bucillamine has been reported to have beneficial effects in rheumatoid arthritis . This report concerns a case of RA in which agranulocytosis developed while on a course of bucillamine . A 52-year-old female with RA developed a rapid fall in white blood cell count after 4 weeks of bucillamine treatment at daily dose of 50 mg . Agranulocytosis was diagnosed (WBC 1300/mm3, granulocytes 5%) . The administration of bucillamine was halted and she was treated with only prophylactic antibiotic regime . The peripheral granulocyte count result rapidly reversed within 3 days after discontinuation of the bucilamine treatment . Anti-leukocyte antibody was detected by the leukocyte lysis phenomenon method during the period of agranulocytosis . And high intrinsic G-CSF activities were detected in the patient serum before the recovery period of agranulocytosis . Agranulocytosis is a rare side effect of bucillamine but it is potentially more harmful than other side effects . In treatment with bucillamine, therefore, the drug should be carefully administered and regular blood examinations carried out to prevent the occurrence of this side effectPublication Types:

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