Antibiotics

Am J Surg, 1994 Jan, 167(1A), 31S - 36S
Diabetic foot ulcers; Laing P; Neuropathic and vascular changes in patients with diabetes mellitus put them at risk for developing chronic foot wounds after minor trauma or after pressure has caused a breakdown in the integrity of the skin . Accurate diagnosis of the underlying cause is the first step toward a successful treatment plan, and in patients with severe ischemia, vascular reconstruction may be needed . Neuropathic ulcers respond well to less-invasive procedures, particularly when combined with reducing the pressure that caused the ulcer . When pressure is relieved by means of total contact casting, necrotic materials are removed, and protection is secured with a hydrocolloid dressing, these wounds have been found to heal, on an outpatient basis, after approximately 6 weeks . All diabetic foot ulcers are contaminated with a variety of organisms, but antibiotic treatments are usually unnecessary . When signs of a clinical infection are present and/or bone is exposed, osteomyelitis should be suspected . In these patients, aggressive surgical debridement, systemic antibiotics, and meticulous wound care regimens to restore the body's own bacterial barrier will often prevent amputation, the most serious complication of these wounds.

Toxicol Pathol, 1994 Jan-Feb, 22(1), 15 - 22
Distribution of gentamicin to the cochlea of the chicken embryo; Fikes JD et al.; Aminoglycoside antibiotics are ototoxic in mammals and birds, including recently hatched chicks, but chicken embryos are insensitive to the ototoxicity of gentamicin, kanamycin, and streptomycin . To determine whether or not the insensitivity is due to a lack of antibiotic distribution to the avian cochlea, the distribution of gentamicin to the cochlea of the White Leghorn chicken embryo was compared to the distribution to the cochlea of the recently hatched White Leghorn chick . Fertile eggs were injected with a maximally tolerated dose of gentamicin sulfate (0.1 mg/egg/day) on incubation days 10-18, and the chicks were injected subcutaneously with either 5 mg (non-ototoxic) or 100 mg (ototoxic) gentamicin sulfate/kg body weight on days 1-9 after hatching . Gentamicin sulfate was histochemically detected within the basilar papilla (the avian equivalent of the organ of Corti) in all treated chicken embryos and chicks by 1 day after the first injection, and the staining was intense after 3 days of treatment . By ultrastructural immunocytochemistry, mild, diffuse labeling for gentamicin sulfate was detected within the endoplasmic reticulum of short and tall hair cells of chicken embryos by incubation day 17 . Moderate labeling of gentamicin sulfate was detected in the infracuticular region of lysosomes of hair cells in chicks receiving 5 treatments of gentamicin sulfate at 5.0 mg/kg body weight and after 1 treatment of gentamicin sulfate at 100 mg/kg body weight.(ABSTRACT TRUNCATED AT 250 WORDS)

Rev Med Chil, 1994 Jan, 122(1), 102 - 8
{Active epidemiologic surveillance of tuberculosis}; Medina E; With 5,000 new active cases each year, tuberculosis in Chile remains as the most important communicable disease in the country . Since the type of control programs are linked to the epidemiologic situation as far as infection, morbidity and mortality are concerned, an effective surveillance system is needed, with analysis of the general data and an active search for other evidences which show the advantages and problems of the control programs . The number of active cases shows a downward trend with 66 new cases per 100,000 population in 1982 and 37 in 1992 . nevertheless, in Santiago, comparing years 1991 and 1991, an increase of 4% in morbidity, 37% of mortality and 33% in the case fatality rate are observed . Morbidity rates are variable with highest numbers in the I Region of Tarapaca probably linked to the prevalent ethnic type of the population . One quarter out of total tuberculosis deaths depends on the late effects of the disease and three quarter are the consequences of recent active disease . People over 55 years of age represents 25% out of total new cases . Besides classical indicators it is important to consider the frequency and results of the practice of diagnostic laboratory tests; the antibiotic therapy resistance; the results of the treatment, analyzing cohorts of treated people; the importance of different infection factors; the evaluation of BCG immunization; the meaning of animal tuberculosis infection; the slowness in the beginning of treatment in new cases; the results of the screening of high risk population and the systematic analysis of each death due to tuberculosis.

J West Soc Periodontol Periodontal Abstr, 1994, 42(1), 5 - 8
Combination of tetracycline and metronidazole in the treatment and control of refractory periodontitis; Khatiblou FA; Nine patients with refractory periodontitis were selected for this study . Each patient had undergone surgery once or twice in the previous five years and had been on three-month recall for clinical examination and scaling . During the maintenance phase of therapy and despite regular scaling, each patient had additional pocket formation that was either localized or generalized . Pocket depths in each patient were recorded and scaling was carried out . Three months later the patients were examined, and again no improvement was observed in the pocket depths . This time all patients were scaled again, and 250 mg tetracycline every six hours for 20 days as well as 250 mg metronidazole every eight hours for seven days were systemically administered . After an additional three months, patients were again examined and pocket depths measured . The latter examination disclosed that the clinical condition of the gingiva, as shown by bleeding and exudate, had improved . The pocket depths had also been reduced . The scaling-alone mean pocket depths were 4.93 mm, whereas the scaling-plus-antibiotic measurements were reduced to 2.78 mm . The difference was significant (p = 0.01).

Arch Orthop Trauma Surg, 1994, 113(3), 167 - 9
Tissue concentrations of third-generation cephalosporins (ceftazidime and ceftriaxone) in lower extremity tissues using a tourniquet; Papaioannou N et al.; Prophylactic antibiotic administration for selected major orthopaedic procedures is feasible with wide-spectrum antibiotics that can achieve high tissue levels . We studied the influence of tourniquet on the in vivo concentrations of ceftazidime and ceftriaxone in soft tissue and bone . Our study group consisted of 47 patients undergoing reconstructive operations of lower extremities . The effect of different time intervals between antibiotic administration and tourniquet inflation was examined . Our data suggest that the time interval resulting in the highest tissue concentrations is approximately 20 min between administration and tourniquet inflation.

Scand J Gastroenterol Suppl, 1994, 201, 16 - 23
The role of acid inhibition in the treatment of Helicobacter pylori infection; Axon AT; The recognition that Helicobacter pylori is a causal factor in the development of most peptic ulcers (and may play a role in the pathogenesis of gastric cancer) has provided an impetus to the search for a suitable regimen that will eradicate the organism . Combinations of antibiotics with bismuth (triple therapy) eradicate the organism in around 90% of cases, but the regimens are complicated, and poor compliance and significant side effects are frequently seen . The observation that omeprazole in combination with a single antibiotic provides eradication rates of over 80% is an important advance, as this combination is a simple regimen and is well tolerated . In this article, the role of omeprazole in eradication therapy is discussed, the published data are reviewed and hypotheses relating to the mode of action of omeprazole are presented . Although the optimum therapy has yet to be identified, acceptable results should be obtained by using omeprazole, 40 mg twice daily, plus amoxycillin, 500 mg four times daily, for 2 weeks.

J Gynecol Obstet Biol Reprod (Paris), 1994, 23(2), 193 - 201
{Premature rupture of membranes . Prospective study of 218 cases}; Coste JP et al.; OBJECTIVES: To verify the importance of a wait-and-see attitude after premature rupture of the membranes before 34 weeks of amenorrhoea when allowed by the initial physical examination and of an intervening attitude after 34 weeks . STUDY: A prospective study included 218 cases of premature ruptures of the membranes divided into four groups according to the weeks of amenorrhoea: Group 1, before 32 weeks (n = 11); Group 2, between 32 and 34 weeks (n = 26); Group 3, between 34 and 37 weeks (n = 18); Group 4 after 37 weeks (n = 163) . RESULTS: Before 34 weeks of amenorrhoea, the frequency of premature rupture of the membranes was 0.72%, of germ-positive infants 8% and of infected infants, 11% . Perinatal mortality was 80% and 17.4% of the infants were delivered by cesarian section . Labour was induced in 100 cases (46%), when there was evidence of infection, after a 24-hour waiting period or at 34 weeks of amenorrhoea . When the aspect of the cervix was unfavourable, cervical maturation was induced by intravenous injection of prostaglandins in 75 cases (34%) . CONCLUSION: When the rupture occurred before 34 weeks of amenorrhoea and without signs of infection, tocolysis should be entertained . From 28 to 34 weeks and when a favourable outcome is expected, maturation by corticoids can be proposed . When chorio-amniotic infection is suspected and is not confirmed by the laboratory, antibiotic prophylaxy does not appear to improve fetal outcome . The beneficial effect of a conservative wait-and-see attitude before 34 weeks and of intervening thereafter can only be demonstrated with a large randomized study . Thus each case must be managed individually, making it difficult to establish a standard recommended attitude.

Vasa, 1994, 23(2), 159 - 62
{Autogenous reconstruction in mycotic inguinal aneurysm--long-term result}; Hegenscheid M et al.; A ruptured mycotic aneurysm of the left femoral artery in the groin area in a 44-year-old man had to be surgically treated in 1990 by an autogenous in-situ-repair consisting of aneurysmectomy including the femoral bifurcation, autologous vein interposition using medium-term absorbable suture material, and local application of an antibiotic bonded collagen . The infection could be checked in a short time . Three years after the operation the check-up gave evidence of an excellent local result with good arterial circulation in both legs . Autogenous in-situ-repair appears to be the most efficient procedure for treatment of an arterial infection or an infected graft . Especially in the area of bifurcations (i.e . inguinal and popliteal as well) this management is preferable to the aseptic extra-anatomic bypass procedure, since only this method can preserve the orthograde perfusion of the bifurcation branches.

Vox Sang, 1994, 66(3), 200 - 5
Relative importance of immune and non-immune causes of platelet refractoriness; Doughty HA et al.; In this prospective study, 26 consecutive patients being treated for haematological malignancies receiving standard (i.e . non-leucocyte-depleted) blood components were observed for the development of refractoriness to platelet transfusions . One hundred and sixteen of the 266 (44%) platelet transfusions failed to produce a satisfactory response . In 102/116 (88%), the poor response was in the presence of non-immune factors known to be associated with platelet refractoriness . Non-immune factors were present alone in 78/116 (67%), and in combination with immune factors in a further 24/116 (21%) . Immune factors (HLA and platelet-specific antibodies) were present during 29/116 (25%) of unsuccessful platelet transfusions . Statistical analysis confirmed that platelet refractoriness was significantly associated with the presence of non-immune factors . The non-immune factors associated with refractoriness were often multiple, most frequently a combination of fever, infection and antibiotic therapy . This study provides evidence that immune mechanisms were not the predominant cause of platelet refractoriness in the patient population studied . It also suggests that measures for the prevention of HLA alloimmunisation, such as leucocyte depletion, may have a limited impact in reducing the incidence of refractoriness to platelet transfusions.

Nat Toxins, 1994, 2(1), 4 - 13
Fusapyrone and deoxyfusapyrone, two antifungal alpha-pyrones from Fusarium semitectum; Evidente A et al.; A strain of Fusarium semitectum Berk . & Rav . from maize stalk rot in southern Italy produced bioactive metabolites when cultured on autoclaved rice kernels at room temperature for 4 weeks . The organic extracts of fungal culture showed a strong antibiotic activity towards Geotrichum candidum in disk diffusion assays, but they were not toxic to Artemia salina larvae . Two antifungal metabolites were isolated and characterized by chemical and spectroscopic methods as two 3-substituted-4-hydroxy-6-alkyl-2-pyrones, in particular, the 3-(4-deoxy-beta-xylo-hexopyranosyl)-4-hydroxy-6-{2-hydroxy-7-hydroxymeth yl- 1,1,5,9,11-pentamethyl-3,5,8-heptadecatrienyl}-2H-pyran-2-one and its 6-{2-hydroxy-1,1,5,7,9,11-hexamethyl} analog, which were named fusapyrone and deoxyfusapyrone, respectively.

Respir Med, 1994 Jan, 88(1), 49 - 53
Effect of addition of exercise to chest physiotherapy on sputum expectoration and lung function in adults with cystic fibrosis; Baldwin DR et al.; Promotion of sputum expectoration by chest physiotherapy is an essential part of cystic fibrosis management . The role of exercise in improving sputum expectoration and lung function in these patients is more contentious . We therefore investigated the effect of adding an exercise programme to conventional chest physiotherapy in eight adult subjects (four male) with cystic fibrosis . Subjects were treated on two non-consecutive days of the second week of a course of in-patient antibiotic therapy in a cross-over fashion . On the exercise and physiotherapy day, subjects exercised 60 min before physiotherapy . On the physiotherapy alone day, subjects rested for 60 min instead of exercising . Physiotherapy was administered on both study days (postural drainage, percussion, deep breathing, vibrations, forced expiratory technique and coughing) . Lung function tests were performed at baseline, after exercise or rest and again immediately and 30 min after physiotherapy . Sputum weights were measured in the 60 min of exercise or rest (period A) and for the 60 min physiotherapy period and 30 min after physiotherapy (period B) . Mean total sputum expectoration (period A and B) was 14 g on physiotherapy alone and 21.5 g (4.8) on exercise and physiotherapy (mean difference 7.5 g, 95% CI 1.4-13.6 g, P = 0.02) . Mean sputum weights during period A (i.e . rest vs . exercise) on physiotherapy alone and exercise and physiotherapy were 2.6 and 7 g respectively (mean difference 4.4 g, 95% CI-0.07-8.8 g, P = 0.053).(ABSTRACT TRUNCATED AT 250 WORDS)

Diagn Microbiol Infect Dis, 1994 Jan, 18(1), 7 - 12
Cultural studies on two isolates of "Mycobacterium genavense" from patients with acquired immunodeficiency syndrome; Tortoli E et al.; Two strains of the newly proposed species "Mycobacterium genavense" have been isolated, using the radiometric system (Bactec, Becton Dickinson), from the blood of two HIV-infected patients . Disseminated infections due to the new organism closely resemble those of the Mycobacterium avium complex, with prevalently intestinal symptomatology . We report here on the cultural behavior of the isolates, which are enhanced at pH 6, are inhibited by NAP, do not require supplements, and grow best at 37 degrees C . We also report on the antibiotic susceptibility of the isolates.

Clin Exp Obstet Gynecol, 1994, 21(1), 33 - 7
Ceftriaxone in prevention of complications after cesarean section and its influence on the newborn; Sulovic V et al.; The study included 303 patients subjected to elective cesarean section . Thirty two (11%) patients were classified in group A (with prophylactic ceftriaxone administration), 28 (87.5%) of whom had uneventful postoperative courses and 4 (12.5%) who had complications . Group B (with therapeutical application of ceftriaxone) was composed of 135 (45%) patents, 127 (94.1%) with uneventful postoperative courses and 8 (5.9%) with complications . Group C (in whom other antibiotics were used) consisted of 95 (31%) patients, 72 (75.8%) with uneventful postoperative courses and 23 (24.2%) with complications . Group D (no antibiotics used) was composed of 41 (13%) patients, 31 (75.6%) with uneventful postoperative courses and 10 (24.4%) with complications . Statistical analysis revealed highly significant differences in distribution of complications according to whether any, and which one of the antibiotics was used (X2 = 17.81, p < 0.005) . This difference mainly resulted from lower incidence of complications associated with ceftriaxone use than in patients with no antibiotic therapy (X2 = 11.66; p < 0.005) as well as in patients using other antibiotics (X2 = 15.95; p < 0.005) . Significant difference was also noted when patients given antibiotics other than ceftriaxone were compared with patients receiving no antibiotics other than ceftriaxone were compared with patients receiving no antibiotic therapy (X2 = 4.45; p < 0.05) . Group A of newborns included 17 (89.5%) with high Apgar score, while 2 children (10.5%) had the score below 8 . Group B had 2 children (11.7%) with Apgar score below 8, while 15 (88.3%) children had higher scores.(ABSTRACT TRUNCATED AT 250 WORDS)

Eye, 1994, 8 ( Pt 1), 35 - 40
The natural history and management of recurrent corneal erosion: a prospective randomised trial; Hykin PG et al.; One hundred and seventeen patients with a history of recurrent corneal erosion were recruited at initial hospital presentation . Seventy-five cases had a history of shallow corneal injury, 23 had epithelial basement membrane dystrophy (EBMD), 8 had both and 11 had neither . Mean age at presentation was 38 years and follow-up ranged from 6 to 16 months (mean 10.6 months) . Sixty-one patients presented with a first acute corneal erosion, 21 with a subsequent acute corneal erosion and 35 with chronic symptoms . Patients with EBMD or a trauma-related focal epithelial basement membrane abnormality were more likely to present with chronic recurrent symptoms than trauma-related cases with no abnormality on examination . Both EBMD and trauma-related cases typically recurred in the lower half of the cornea, frequently in the midline (z = 7.3, p < 0.0001), suggesting an intrinsic or acquired abnormality of the epithelial basement membrane at this site . Only four of 82 acute episodes did not resolve by 5 days with simple patching, cycloplegia and topical antibiotic ointment . In the vast majority of patients presenting with an acute erosion, simple management measures only are required . Of 117 cases started on prophylactic ointment at night, further therapy due to prophylaxis failure was required in only 5 . EBMD was a risk factor for failure (relative risk 10.77) . There was no difference in efficacy between once daily prophylactic paraffin and hypertonic saline ointments (p = 0.17), suggesting they both have only a lubricant action.

J Dent Hyg, 1994 Jan-Feb, 68(1), 30 - 4
A study of oral candidiasis in HIV-positive patients; Van Meter F et al.; PURPOSE . Candidiasis may occur as the first clinical sign or symptom of HIV disease . Oral candidiasis was studied with respect to immunological status, and response to antifungal therapy in a group of HIV-positive individuals with a history of recurrent oral candidal infections . METHODS . Yeast cultures were obtained from 16 HIV-positive patients and identified and quantitated on a weekly basis until the infection was controlled . Thereafter, cultures were taken monthly or when recurrences occurred for a minimum of three to a maximum of 15 months . Ketoconazole and fluconazole were administered to control clinical signs and symptoms, which were evaluated by appearance and location in the oral cavity . Culture smears were quantitated by colony-forming units (CFUs) on dextrose agar plates . Individual patient medical histories included current medications, the presence of xerostomia, smoking habits, and denture wear . Frequency data only are reported due to the small number of patients included in the study . RESULTS . The presence of clinical lesions coincided with increased colony-forming units, and a combination of pseudomembranous and erythematous lesions was the most prevalent . Frequently, a patient's lesions had the same clinical appearance as previous episodes involving the same oral sites . However, the presence of Candida cannot be accurately assessed by clinical signs alone since high CFU counts were found in patients demonstrating no clinical signs or symptoms . CONCLUSIONS . An increasing yeast burden in the oral flora may result from a combination of local factors such as smoking, xerostomia, antibiotic or antiviral medication, and decreasing cell mediated immunity leading to immune tolerance towards Candida . Negative cultures following antifungal treatment most likely reflect a diminished yeast population rather than eradication of Candida . Subclinical Candida in the oral flora warrants consideration in prophylactic treatment options for the HIV-positive patient.

DNA Seq, 1994, 4(4), 219 - 29
Cloning and nucleotide sequence of a region of the Kibdelosporangium aridum genome homologous to polyketide biosynthetic genes; Piecq M et al.; The actinomycete Kibdelosporangium aridum naturally produces ardacin, a new glycopeptide antibiotic, the biosynthetic pathway of which should involve the participation of a polyketide synthase (PKS) . A K . aridum 2.9 kb BamHI genomic fragment homologous to actI (a locus of the PKS cluster catalyzing polyketide chain assembly for actinorhodin biosynthesis in Streptomyces coelicolor) was isolated by shotgun cloning . This DNA fragment, called ardI, was sequenced and the deduced protein products were compared with those of other polyketide synthase genes, revealing similarities ranging from 50 to 80% . ardI was further used to probe a cosmid library of the K . aridum genome . Three hybridizing cosmids were obtained which contain overlapping inserts, together covering a 50 kb region, and including, 15 kb away from ardI, a fragment homologous to actIII, which codes for the ketoreductase of the actinorhodin PKS of S . coelicolor . All these findings indicate that at least part of a polyketide biosynthetic gene cluster has been isolated from the genome of the ardacin producer K . aridum.

Respiration, 1994, 61(4), 231 - 5
Efficacy of cefazolin in promoting ovine tracheal epithelial repair; Barrow RE et al.; Inhalation of toxic materials has been shown injurious to the upper airways . Because secondary infection can slow the repair process, we undertook this study to determine the efficacy of antibiotic therapy in promoting the healing process of acute tracheal wounds . In 18 anesthetized sheep, a portion of the cervical trachea was exposed to smoke from smoldering cotton cooled to 38 degrees C . Nine received the broad-spectrum antibiotic, cefazolin, while none received saline placebo . At 13 days after injury, nonciliated and ciliated cell counts were 75% and 33% respectively of noninjured trachea receiving placebo, while in those receiving cefazolin, nonciliated and ciliated cell counts increased to 93% and 114% of paired noninjured trachea, respectively . We suggest that cefazolin therapy allows cell proliferation and differentiation to proceed more rapidly than observed with placebo therapy and thus may be a helpful augmentor to the healing of an acute airway injury.

Nephrol Dial Transplant, 1994, 9(7), 797 - 9
Treatment of resistant peritonitis in continuous ambulatory peritoneal dialysis with intraperitoneal urokinase: a double-blind clinical trial; Innes A et al.; Resistant peritonitis in continuous ambulatory peritoneal dialysis (CAPD) is an indication for catheter removal, followed by interim haemodialysis and subsequent catheter replacement . This involves two surgical procedures using general anaesthetic and the availability of adequate hospital haemodialysis facilities . Urokinase is an alternative therapy but evidence of its effect is anecdotal and it has not been studied in a double-blind manner . Patients with resistant peritonitis (either no resolution of peritonitis within 4 days of appropriate antibiotic therapy or a third episode of peritonitis within 6 months) were randomized to receive intraperitoneal urokinase or placebo (saline) followed by 14 days of antibiotics in this double-blind prospective study . Treatment success was resolution of peritonitis within 4 days of giving urokinase/placebo (persistent infection) and no recurrence with the same organism for 6 months (recurrent infection) . Twelve patients received urokinase and 12 placebo . Treatment was successful in 8/12 in the urokinase group and 1/12 in the placebo group (Fisher's exact test; P = 0.0047) . Urokinase was successful in 8/12 patients with resistant peritonitis and significantly better than placebo . Urokinase is an effective and simple treatment that may avoid the need for catheter removal and interim haemodialysis in patients with resistant CAPD peritonitis.

Invest New Drugs, 1994, 12(1), 67 - 70
Phase II trial of menogaril in metastatic adenocarcinoma of the prostate . A Southwest Oncology Group study; Taylor SA et al.; Menogaril, a semisynthetic anthracycline antibiotic, was administered to patients with metastatic adenocarcinoma of the prostate . Forty-five patients with measurable disease and 45 patients with evaluable disease received 150-200 mg/m2 over 1 hour every 28 days . There were three partial responses (PR) among 87 patients evaluable for response . Myelosuppression was dose limiting . There were two deaths related to leukepenia . Other toxicities included phlebitis, alopecia, nausea and vomiting . One patient developed acute nonlymphocytic leukemia . Menogaril at these doses and schedule is toxic and has no significant antitumor activity in metastatic adenocarcinoma of the prostate.

Vet Res, 1994, 25(5), 489 - 94
Pharmacokinetics and distribution of thiamphenicol in sheep given repeated intramuscular doses; Abdennebi EH et al.; The pharmacokinetics of thiamphenicol and its distribution in various body fluids were studied after repeated intramuscular injection in clinically healthy adult Moroccan crossed Sardi-D'Man sheep . Thiamphenicol was rapidly absorbed from injection sites yielding peak plasma concentrations within 15-30 min . The elimination from the blood was also rapid, with a biological half-life of 1.51 +/- 0.51 h . The distribution pattern of thiamphenicol revealed that this antibiotic can penetrate many remote sites of the body . With the exception of the cerebrospinal fluid, concentrations of the drug in other body fluids were higher than the corresponding plasma concentrations.

Pediatr Neurosurg, 1994, 21(1), 45 - 9
Low-velocity penetrating craniocerebral injury in childhood; Domingo Z et al.; Fifty-four children with low-velocity penetrating injury of the skull and brain are described . The incidence of septic complications was 43%, which is significantly higher than that seen in adults . Nine percent of children developed vascular complications . Due to the high septic complication rate, a more aggressive management protocol consisting of craniectomy and dural repair under antibiotic cover is suggested.

Arch Virol, 1994, 137(3-4), 327 - 40
Replication of echo virus type 25 JV-4 reference strain and wild type strains in MRC5 cells compared with that of poliovirus type 1; Bailly JL et al.; In echo virus type 25/JV-4 the shut off of host cell protein synthesis took significantly longer and the kinetics of the synthesis of viral proteins and viral RNA occurred much later than in the poliovirus . However, these characteristics impaired neither polyprotein processing nor virus production in the JV-4 strain . In contrast the two wild strains M.1262 and Th.222 had a lower virus yield than strain JV-4 . The presence of a high Mr protein in the pattern of viral proteins of wild strains suggested that a defect in the polyprotein processing was responsible for the decreased virus yield . The infectious cycle of strain Th.222 differed from that of strains JV-4 and M.1262 in the rapid inhibition of host cell translation and the extent of viral protein synthesis . The sensitivity to actinomycin D was also investigated . Strain M.1262 was found to be insensitive . The virus yield of strains JV-4 and Th.222 was three- and fourfold lower respectively in the presence of actinomycin D . This sensitivity to the antibiotic was observed during viral RNA synthesis in strain JV-4 and during viral protein synthesis in strain Th.222 . These results suggest that cellular factors are involved in the replication of echo virus type 25 strains in MRC5 cells.

Zentralbl Gynakol, 1994, 116(8), 479 - 83
{Expectant management of premature rupture of fetal membranes before completion of the 35th week of pregnancy--retrospective analysis of 44 cases}; Muller H et al.; 44 cases of preterm premature rupture of fetal membranes (PPROM) before 35 completed weeks of gestation were analyzed retrospectively . Expectative management was based on infection diagnosis, vaginal disinfection and in case of signs of infection on systemic antibiotic therapy . Glucocorticoids for induction of lung maturity were generally administered . Perinatal mortality was 11.4%, after exclusion of one congenital anomaly 9.3% respectively . Lung immaturity was the main cause of neonatal death . Only 5 neonates developed clinical infection, with 4 of these showing prepartal maternal signs of infection . Maternal signs of infection are not a specific signal for later neonatal infection . Cerebral bleeding complications and pathological neurologic status occurred in 10/39 and 8/39 cases respectively . Cesarean section rate amounted to 15/44 (34%).

Scand J Infect Dis, 1994, 26(3), 339 - 47
Serological follow-up after treatment of Borrelia arthritis and acrodermatitis chronica atrophicans; Hammers-Berggren S et al.; To study the serological response to Borrelia burgdorferi after treatment of late Lyme borreliosis, consecutive serum samples from 20 patients with Borrelia arthritis and 21 with acrodermatitis chronica atrophicans were analysed with capture IgM ELISA and indirect IgG ELISA, both using B . burgdorferi flagella as antigen . Seven patients had positive IgM OD values, whereas all 41 had positive IgG OD values before therapy . In the majority, highly elevated IgG OD values were seen . All patients improved after antibiotic therapy, 32 recovering completely, while 9 had sequelae . At follow-up after 6 months to 5 years, 4/7 patients became negative IgM ELISA, whereas 3 still had slightly elevated IgM OD values 6 months, 1 year and 4.5 years, respectively, after therapy . Only one patient became negative in IgG ELISA during follow-up, although a significant decline in IgG OD values was seen in 22 of the remaining 40 initially IgG-positive patients . The serological response after successful treatment of Borrelia arthritis and acrodermatitis chronica atrophicans may persist for several years even with highly elevated IgG OD values in patients who have recovered completely.

J Med, 1994, 25(1-2), 65 - 89
Effects of S-adenosylmethionine (SAMe) on doxorubicin-induced cardiotoxicity in the rat; Russo S et al.; One of the most important factors that determine the therapeutic limits of doxorubicin (DXR), an anthracycline antibiotic, appears in acute and late cardiotoxicity . The aim of our investigations was to evaluate the effects of S-adenosylmethionine (SAMe), an important precursor of the organic sulfated compounds and a fundamental agent in physiologic transmethylation, on DXR-induced cardiotoxicity . For that purpose, normotensive Wistar rats were treated with DXR associated with or without SAMe . Pretreatment with SAMe significantly reduced DXR-induced electrocardiographic and morphologic changes, lethality, and body weight . The protective effect of SAMe may partly be due to its scavenger ability against free radicals and superoxides . In addition to its action as a fundamental precursor of the sulfated compounds, the principal agent in physiological transmethylations, and an increase of glutathione (GSH) synthesis.

Indian J Pediatr, 1994 Jan-Feb, 61(1), 63 - 9
Management of asymptomatic neonates with prolonged rupture of membranes; Teji JS et al.; Guidelines for management of asymptomatic term and preterm neonates born to mothers with prolonged rupture of membranes (PROM) have not been clearly established . A survey was conducted to identify current management practice of neonatologists in midwestern states and to find if there is consensus among physicians with regard to management of PROM without chorioamnionitis, with chorioamnionitis but without treatment prior to delivery, and with intrapartum maternal antibiotic therapy prior to delivery . One hundred thirty seven responses to the questionnaire were received . Management of asymptomatic at risk neonates varied in different clinical scenarios . Preterm neonates were screened (94% vs 82%, p < 0.001) and treated (64% vs 41%, p < 0.001) more often than term babies . In the absence of maternal symptoms of chorioamnionitis, term neonates were usually observed or treated based on screening test results . With maternal symptoms, 94% of physicians ordered screening test . Prematurity and perceived severity of maternal illness significantly influenced the decision to treat routinely irrespective of screening test results . Physicians favour routine treatment of infants born to mothers who had received intrapartum antibiotic therapy; opinion was divided about management of term asymptomatic infant born to mothers with chorioamnionitis without intrapartum antibiotic therapy . Lumbar punctures were not routinely done for term or preterm neonates prior to antibiotic therapy . Further studies are needed to answer questions regarding the benefits and risks of routine therapy of high risk neonates vs routine clinical observation and selective therapy of only infants who develop symptoms.

Magy Traumatol Ortop Kezseb Plasztikai Seb, 1994, 37(3), 245 - 9
{Experience with peflacine in the treatment of osteomyelitis}; Szucs G et al.; Authors report on the treatment of 20 chronic osteomyelitis patients in whom direct antibiotic therapy was performed using the preparation Peflacine . The infected area was exposed in every case, the bony focus was excised and the wound was drained . During the operation, as an induction 800 mg Peflacine in slow drop infusion was given . Oral preparation (2 x 400 mg/die) followed, and was continued for 30 days . The secretion of the wounds ceased in every case, after 3 weeks the latest . In 2 cases mild gastrointestinal symptoms as side effects were observed . Relapse the first time occurred 5-7 months after ending the treatment in 3 patients . These were again explored and after the excision more thorough than before the secretion ceased . According their experience and in conformity with the literature the Peflacine is held an effective medicament in the treatment of the acute exacerbation of chronic osteomyelitis, together with the excision of the focus.

Oncol Res, 1994, 6(1), 11 - 7
Inhibitory action of epiderstatin on EGF-stimulated growth of mouse epidermal . BALB/MK cells without direct effect on protein kinase activities; Osada H et al.; Epiderstatin, a distinctive glutarimide antibiotic isolated from Streptomyces pulveraceus subsp . epiderstagenes, has been revealed to be a potent inhibitor of the signal transduction of epidermal growth factor (EGF) . Epiderstatin inhibited the DNA synthesis induced by various peptide growth factors in a mouse epidermal cell line, BALB/MK, without inhibiting protein tyrosine kinase activity of EGF-receptor or serine/threonine kinase activity of protein kinase C . The 50% inhibitory concentration (IC50) value of epiderstatin for the EGF-stimulated incorporation of {3H}thymidine into BALB/MK cells was about 10 nM . When epiderstatin was added to the quiescent cells simultaneously with EGF-stimulation, the cells did not reenter into the growing cell cycle . The action of epiderstatin proceeded from the overexpression of c-fos and the suppression of c-myc transcription when EGF was added to quiescent BALB/MK cells.

Toxicol Appl Pharmacol, 1994 Jan, 124(1), 149 - 58
Avian embryonic brain reaggregate culture system . I . Characterization for organophosphorus compound toxicity studies; Funk KA et al.; An avian reaggregate culture system was characterized biochemically and morphologically for use in acute and chronic organophosphorus compound (OP) toxicity studies . Ten-day-old chick embryo brains were dissociated, reaggregated, and maintained in a chemically defined, serum- and antibiotic-free media . Acetylcholinesterase (ACHE), neuropathy target esterase (NTE), and 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP) were examined due to inhibition of these enzymes as a result of acute OP toxicity (ACHE) or delayed toxicity (NTE, CNP) . The selected enzymes also indicate reaggregate neuronal (ACHE, possibly NTE), oligodendroglial (CNP), and astrocytic (glutamine synthetase (GS)) activities . Enzyme activities were compared to those in age-matched chick embryo and hatched chick brains . Reaggregate ACHE specific activity was similar to or higher than that of chick embryo or hatched chick . Reaggregate NTE specific activity was initially similar to that of 10-day-old chick embryo, and then increased but subsequently averaged 7.8 nmol/min/mg protein . In chick brain, NTE peaked at hatching and averaged 28 nmol/min/mg protein thereafter . Reaggregate CNP specific activity ranged from 103 to 426 nmol/min/mg protein, whereas activity gradually increased in chick embryo brain to an average of 140 nmol/min/mg protein posthatching . The mean GS activity ranged from 0.15 (Culture Day 4) to 1.09 nmol/min/mg protein (Culture Day 62) . Mean protein values per flask ranged from 2.47 to 7.58 mg . Ultrastructurally, myelination was detected at Culture Day 7 and synapses at Day 6 . The biochemical and ultrastructural features demonstrate that this reaggregate culture is a practical and sensitive in vitro system for studying both the acute and the long-term neurotoxicological effects of organophosphorus compounds.

Yao Xue Xue Bao, 1994, 29(9), 656 - 61
{A fungus-derived novel nucleoside transport inhibitor potentiates the activity of antitumor drugs}; Su J et al.; Antibiotic C3368-B (CB), identified as 3,9-dihydroxy-1-methoxy-7-methylanthraquinone, is produced by a fungus strain, Chrysosporium verrucosum Tubaki, isolated from a soil sample collected from Antarctica . CB was found to be a highly-active nucleoside transport inhibitor . By radiolabelled nucleoside assay, CB was shown to markedly inhibit thymidine and uridine transport in Ehrlich carcinoma cells, with IC50 values of 7.5 and 9.6 mumol.L-1 respectively . CB showed fairly low cytotoxicity to tumor cells . The IC50 values for epidermoid cancer KB cells and hepatoma BEL-7402 cells in clonogenic assay was 77 and 69 mumol.L-1 . At relatively noncytotoxic concentrations, CB markedly enhanced the cytotoxicity of methotrexate, 5-fluorouracil, mitomycin C against KB cells and BEL-7402 cells . CB was also found to partly reverse the multi-drug resistance to vincristine and actinomycin D in leukemia L1210/MDR cells . The IC50 values were reduced by 4.9-fold (1.75 to 0.36 mumol.L-1) for vincristine and 3.3-fold (0.39 to 0.12 mumol.L-1) for actinomycin D . These results suggest that CB, as a newly-found nucleoside transport inhibitor, may be potentially useful in cancer chemotherapy.

Retina, 1994, 14(5), 425 - 9
Histopathologic study of epiretinal proliferations after vitrectomy with daunomycin and silicone oil; Mietz H et al.; PURPOSE: The cellular composition of primary and recurrent periretinal proliferations has been widely described . The use of daunomycin, an antiproliferative antibiotic, has been recommended to reduce these proliferations . Two recurrent membranes after intraoperative application of daunomycin were examined . METHODS: Two epiretinal membranes, which were removed 5 months and 20 months after vitrectomy with daunomycin, were examined by light and electron microscopy to determine the structure and cellular composition of these membranes . RESULTS: The matrix of the membranes consisted of new collagen with fiber diameters between 20 and 22 nm . Fibrocytes and macrophages were present in both specimens . Retinal pigment epithelial cells and fibrous astrocytes were present in only one specimen . CONCLUSION: Retinal pigment epithelial cells, which are consistently present in primary periretinal membranes, were found in only one of the two specimens examined . Myofibroblasts, also normally present, were not found . The other cells found are typically seen in primary periretinal proliferations.

Eur J Cardiothorac Surg, 1994, 8(11), 609 - 12
Cytoimmunological monitoring after homograft valve replacement; Schutz A et al.; Examination results concerning immunological reactions in cryopreserved allograft valves during the early postoperative course are so far not available . Cytoimmunological monitoring (CIM) is a well established method to prove rejection reaction after allograft transplantation and was used in this study . Allograft valves were harvested from patients who underwent heart transplantation, and did not require sterilizing in antibiotic solutions . The valves were dissected, conserved and subsequently frozen to -40 degrees C and stored in a freezing system at -196 degrees C . During the first 3 weeks following allograft implantation, CIM was performed daily . An activation index (AI) was determined from the cytological evaluation of the mononuclear concentrate in the peripheral blood . An increase of the AI > 1 was defined as an immunological reaction . As control we performed 98 CIM examinations in eight patients who underwent bioprosthetic valve replacement in the aortic position . Echocardiography (TTE and TEE) was used postoperatively as function control . Out of 16 patients who underwent cryopreserved aortic valve implantation in the aortic position, 336 CIM-results were obtained . An immunological reaction could be detected in all patients, starting on the 5th day on average . Comparing ABO-compatible (group I, n = 9) with ABO-incompatible (group II, n = 7) allografts, the AI-maximum in group I was 1.4 with a mean duration of 1.5 days . Group II was characterized by more intensive immunoreactions (mean = 2.3) which proved to be even more prolonged (mean = 3.3 days, P < 0.05) . Nevertheless it became apparent that all observed immunological events were completely reversible without the need for immunosuppressive drugs.(ABSTRACT TRUNCATED AT 250 WORDS)

Ann Urol (Paris), 1994, 28(6-7), 330 - 3
{Male urethritis}; Bohbot JM; The incidence of sexually transmitted diseases (STD) is decreasing, but often take on a more subacute form, which may be difficult to detect . Acute gonococcal urethritis, diagnosed by direct examination and culture (with antibiotic susceptibility testing) requires immediate single-dose treatment . Chlamydia trachomatis urethritis is frequent and insidious and may cause a wide range of complications (serological diagnosis with raised IgG) . It is sensitive to tetracyclines (for 15 days) . Other forms of urethritis are due to Mycoplasmas, Trichomonas and Herpes . The presence of urethritis is a good indicator of high-risk sexual behaviour and warrants proposal of HIV screening.

J Gastroenterol Hepatol, 1994, 9 Suppl 1, S109 - 11
The therapeutic strategy for peptic ulcer disease; Ivey KJ; Therapy of acid/peptic disease has evolved since the 1970s with development of: (i) more accurate endoscopes which permit precise examination and documentation of upper gastrointestinal lesions; and (ii) the histamine H2-receptor antagonists . As well, refined standards for clinical investigation have contributed to the clinical study of acid/peptide diseases . Initially, ulcer diseases were considered to be principally secondary to increased 'aggressive' factors (acid, pepsin) and the therapeutic focus was directed at antacids, the progressive evolution of additional histamine H2-receptor antagonists and recently the H+/K(+)-ATPase inhibitors . Later studies indicated efficacy of sucralfate, low dose antacids and prostaglandin analogues, drugs with either no or only modest antisecretory effect . This led to studies on the role of gastroduodenal mucosal defensive factors (mucus and bicarbonate secretion, blood flow, leucocyte adherence, cytokines, reactive oxygen radicals) . The prominent role played by aspirin and other non-steroidal anti-inflammatory drugs (NSAID) in initiating and causing recurrence of peptic ulcer disease has been increasingly realized . Recognition of those most at risk for NSAID-induced complication has led to newer approaches to treatment and prevention . Since 1983, Helicobacter pylori has been incriminated as a major factor in the pathogenesis of ulcer disease, particularly ulcer recurrences . Treatment of such ulcers now includes antibiotics and bismuth compounds in order to eradicate H . pylori . This therapeutic regimen is in a state of flux ('triple therapy' vs a H+/K(+)-ATPase inhibitor plus antibiotic) as is the question of how to work up and treat patients initially presenting with ulcer symptoms.

Eur J Clin Microbiol Infect Dis, 1994, 13 Suppl 2, S18 - 22
Role of granulocyte-macrophage colony-stimulating factor as adjuvant treatment in neutropenic patients with bacterial and fungal infection; Bodey GP et al.; The results are presented of two preliminary studies conducted to assess the role of GM-CSF as adjuvant treatment in neutropenic patients with bacterial or fungal infections . In the first study the effect of GM-CSF on the rate of response to antibiotics was assessed . Febrile neutropenic patients (n = 91) were randomized to receive ticarcillin-clavulanate plus netilmicin with or without GM-CSF (60 micrograms/m2) . Response rates were significantly higher in patients who received antibiotics plus GM-CSF (p = 0.05) . An increase in neutrophil count was seen in 89% of GM-CSF patients with initial low neutrophil counts (< 100/microliters) compared with 67% of control patients (p = 0.04) . In the second study the activity of GM-CSF in patients with fungal infections was assessed . Neutropenic patients with documented fungal infections received amphotericin B plus GM-CSF . Of the eight evaluable patients, six responded and four had a complete response to treatment . The neutrophil counts of the two non-responding patients did not increase substantially during GM-CSF treatment and both died of their fungal infection . The prognosis of neutropenic patients with fungal infections is usually poor and the results of this pilot study are therefore very encouraging . The two studies show that GM-CSF is able to stimulate neutrophil recovery in neutropenic patients and may improve the response to antibiotic and antifungal treatment.

Exp Clin Endocrinol, 1994, 102(5), 374 - 9
The effect of streptozotocin on the function of fetal porcine and rat pancreatic (pro-)islets; Liu X et al.; Streptozotocin (STZ) is a broad spectrum antibiotic with anti-tumor and diabetogenic properties . Although STZ has been studied for many years, the exact mechanism of its diabetogenic action has not yet been fully elucidated . The present study investigated the effect of STZ on both fetal porcine proislets (FPP) and fetal rat islets (FRI) in an attempt to elucidate the diabetogenic effect of STZ on fetal pancreatic beta cells . This study demonstrates that after in vitro exposure of both FPP and FRI for 30 min to 2.2 mM and 4.4 mM STZ, respectively, FPP showed microscopically an intact structure, a spherical shape and a translucent color, while, in contrast, most FRI were disrupted and showed a slight white color with dark centers . Based on these data, we first transplanted FPP and FRI beneath the renal capsules of nude mice . Three to four weeks later, a single dosage of streptozotocin (180 mg/kg) was intravenously administered . Six of the seven nude mice pretransplanted with FPP became diabetic (blood glucose, BG, 308.08 +/- 33.62 mg/dl) within 2-5 days and then gradually achieved normoglycemia 51.56 +/- 7.71 days after STZ injection . After removal of the grafts, all of the six diabetic mice with normoglycemia returned to hyperglycemia (BG > 300 mg/dl) . In contrast, all of the five nude mice pretransplanted with FRI persistently maintained hyperglycemia (BG > 300 mg/dl) and died 5 +/- 0.84 days after STZ injection.(ABSTRACT TRUNCATED AT 250 WORDS)

Arch Toxicol, 1994, 68(10), 643 - 7
Effect of gentamicin-induced nephrotoxicity on some carbohydrate metabolic pathways in the rat renal cortex; Abdel-Gayoum AA et al.; Rats were injected with gentamicin at doses of 20, 40 and 80 mg/kg per day for 6 consecutive days . The treatment caused nephrotoxicity as evidenced by dose-related increases in serum creatinine concentration and renal tubular necrosis . The nephrotoxicity was accompanied by reduced renal cortical and fasting blood glucose levels, and by increases in serum lactate concentrations . The activities of cortical malate dehydrogenase and alanine transaminase were significantly reduced by the three doses of gentamicin . On the other hand, aspartate transaminase activity was lowered only by the highest dose of antibiotic used . However, the activity of cortical glucose-6-phosphate dehydrogenase was altered by the 20 and 40 mg/kg doses of gentamicin, but not by the 80 mg/kg dose . The two lower doses reduced the lactate content of the cortex but activated lactate dehydrogenase . The activity of isocitrate dehydrogenase was not altered by any of the gentamicin doses used.

Wien Med Wochenschr, 1994, 144(10-11), 280 - 2
{Postpartum ovarian vein thrombophlebitis--case report}; Paulowitz HP et al.; Because of the low incidence and the lack of clinical symptomatology, puerperal ovarian vein thrombophlebitis has constituted a diagnostic problem now as ever, and diagnostic errors are frequent . With the help of US and CT, however, the chances of early detection have improved . On the 26-year old patient P . C . a section had to be performed in the 34th week of pregnancy because of premature rupture of the bag of waters . On the 7th postoperative day, the patient developed pyrexia inspite of antibiotic therapy . Sonographical examinated lead us to suspect a floating thrombus in the vena cava inferior . It was in the CT that the diagnosis of ovarian vein thrombosis was made for the first time . On the 13th day post partum a laparotomy and exstirpation of the v.ovarica dextra with removal of the thrombus plug from the v.cava inferior infrarenally was performed . Primarily, conservative treatment is given preference if the development is uncomplicated; operative sanitation is undertaken in case of difficulties only.

Neurosurg Rev, 1994, 17(3), 199 - 203
Pituitary abscesses . Report of three cases; Gokalp HZ et al.; Three cases of pituitary abscess are presented . In spite of improvements in radiological evaluation, preoperative diagnosis of pituitary abscess is quite difficult and definite preoperative diagnosis is rare in the literature . In our three cases, diagnosis was made postoperatively . Pituitary abscesses are associated with high mortality and morbidity . When first suspected, prompt antibiotic therapy should be considered . Early operative drainage seems to be an important factor in decreasing this high mortality and morbidity.

Microbios, 1994, 79(321), 231 - 9
Application of nuclear magnetic resonance spectrometry to measure the activity of bacterial macrolide esterase; O'Hara K; A new method of measuring the activity of macrolide antibiotic esterase in whole bacteria and in crude enzyme extracts was determined through the application of nuclear magnetic resonance spectrometry . The structure of the enzymatically esterolytic cleavage compound of oleandomycin was clearly shown to be the cyclic hemiacetal between the C-9 keto and the hydroxy group of C-13 in the open macrolide nucleus by physicochemical techniques.

Eye, 1994, 8 ( Pt 5), 555 - 63
Drug resistance and Acanthamoeba keratitis: the quest for alternative antiprotozoal chemotherapy; Hay J et al.; Trophozoites and cysts of 20 isolates of Acanthamoeba from the cornea and five from related samples were tested in vitro for sensitivity to ten drugs (three aromatic diamidines, two aminoglycosides, two macrolides, a polyene macrolide antibiotic, an organoarsenical and an antimetabolite) and two cationic antiseptics (chlorhexidine and polyhexamethylene biguanide, PHMB) . Only chlorhexidine and PHMB showed uniform amoebacidal activity . Aromatic diamidines (pentamidine isethionate, propamidine isethionate and diminazene aceturate) generally proved effective against both forms of the amoeba; only pentamidine gave synergy with the biguanide while propamidine gave an additive effect . Other drugs tested proved erratic or ineffective against different isolates . Chlorhexidine alone, or together with propamidine, was subsequently used in two patients with proven Acanthamoeba keratitis; the causative isolates were sensitive to the individual compounds and to the combination in vitro . The treatment provided resolution of the clinical disease; amoebae were shown to be nonviable by histology and culture . The combination of chlorhexidine and propamidine is recommended for treatment of proven Acanthamoeba keratitis.

Leuk Lymphoma, 1994, 14 Suppl 1, 121 - 5
The Scripps Clinic experience with 2-chlorodeoxyadenosine in the treatment of hairy cell leukemia; Piro LD et al.; Follow-up data is now available on 144 patients with hairy cell leukemia treated with 2-chlorodeoxyadenosine (2-CdA) at the Scripps Clinic . Of 144 patients followed for a median of 14.2 months, 123 (85%) obtained complete responses, 17 (12%) partial responses, 3 (2%) did not respond and 1 patients was unevaluable . So far, only 4 patients have relapsed at a median of 36 months . Fever was the major toxicity occurring in 43% of patients . Five patients resistant (3 patients) or intolerant (2 patients) to 2'-deoxycoformycin were also treated . Of these 5 patients, 4 obtained complete responses, including 2 patients resistant to 2'-deoxycoformycin, and 1 patient a partial response, suggesting a possible lack of cross-resistance between 2'-deoxycoformycin and 2-CdA in hairy-cell leukemia . More than 200 patients have been treated with 2-CdA worldwide with 82% obtaining complete remission and 12% partial remissions . Serial peripheral blood immunophenotypic analyses have documented the absence of circulating hairy cells . When bone marrow biopsies were examined using sensitive immunohistochemical staining techniques, residual hairy cells were detected in 25-50% of morphologic complete responders . Patients will need to be observed longitudinally to determine if this staining is predictive of relapse . A double-blind, placebo-controlled study of pentoxifylline, a modulator of tumor necrosis factor-alpha and other cytokines, was performed in 2-CdA-treated hairy cell leukemia patients to determine whether the incidence of neutropenic fever would be reduced . Although pentoxifylline resulted in less febrile, hospital and antibiotic therapy days than placebo, only the number of days in the hospitalized patients achieved statistical significance . 2-CdA is emerging as the treatment of choice for hairy cell leukemia given the high percentage of long-lasting, complete responses that follow a single course of therapy.

Zentralbl Neurochir, 1994, 55(3), 156 - 61
{Postoperative spondylodiscitis as the cause of failed-back syndrome--clinical aspects, diagnosis, therapy}; Trappe AE et al.; Postoperative lumbar spondylodiscitis can cause a failed back syndrome . With 0.1 to 3% according to the literature it belongs to the rarer complications following lumbar disc surgery . We present the characteristic clinical picture and typical findings (ESR, plain X-rays, MR) with suspected spondylodiscitis on 19 patients (= 0.2% of 9492 operative interventions for lumbar disc prolapse from 1980 to 1990) and show MR tomography to be the most sensitive investigation . Principles of therapy consist of lumbar immobilisation with a light cast orthesis for an average of 12 weeks and additional antibiotic therapy up to two weeks beyond normalisation of ESR . Finally results of therapy are presented with a satisfying outcome in 84.2% of cases.

Zentralbl Gynakol, 1994, 116(10), 555 - 60
{Puerperium after threatened premature labor--positive effects of infection screening by determination of CRP in pregnancy}; Winkler M et al.; Silent intrauterine infection as cause of preterm labour should be recognised early by measuring C-reactive protein (CRP) levels in the maternal serum . Ensuing antibiotic therapy may not only cause gestational prolongation, but also has a positive effect on pathology during the puerperal period . Consequently, we examined the rate of infectious puerperal complications of 181 patients who suffered from so-called idiopathic preterm labour . 84 patients showed normal CRP-levels at the onset of tocolysis (< 5 mg/l); an elevated level was found in 97 patients (> 5 mg/l) . Patients with elevated CRP-levels and supplemented antibiotic therapy during pregnancy (n = 51) showed significantly fewer symptoms of postpartal endometritis than women with similarly elevated CRP-levels but without antibiotics (n = 46) . This effect was not produced when preterm labour was associated with normal CRP-levels . Patients with premature contractions and elevated CRP-values at the onset of tocolysis seem to benefit from the antibiotic therapy during pregnancy because they show reduced infectious complications throughout the puerperal period.

Tsitologiia, 1994, 36(5), 427 - 36
{Na+ and K+ ion transport across the human erythrocyte membrane during the formation of nystatin channels under in-vitro conditions: the characteristics and an analysis of the processes}; Borisov IuA et al.; The kinetic properties (the spontaneous lysis velocity, the time of achievement, and the concentration level of the stationary stage) are shown to be strongly different, while the human erythrocytes are resuspended in various salt media . The analysis of Na+ and K+ concentrations, under the effect of a polyene antibiotic nistatin, on the human erythrocytes as an integral kinetic function of time is carried out . The processes engaged in this kinetic function are characterized.

Anaesthesiol Reanim, 1994, 19(5), 124 - 6
{Detection of Chlamydia pneumoniae in intrathoracic abscesses--a case report}; Schaffranietz L et al.; The case of a 52-year-old patient with intrathoracic abscesses following a traumatic fracture of the 11th thoracic vertebral body is described . The abscesses were resistant to conventional antibiotic therapy and attempts at local drainage under CT scan control remained unsuccessful . Finally, chlamydia pneumoniae was isolated using an immunofluorescence technique . Subsequent therapy with doxycycline caused complete resolution of the abscesses . We suggest that in cases of atypical pneumonias and abscesses, infection with chlamydia pneumoniae should be taken into consideration.

Vestn Otorinolaringol, 1994 Jan-Feb, (1), 22 - 6
{Clinical and biochemical aspects in the treatment of acute maxillary sinusitis with antioxidants}; Nikolaev MP et al.; A trial has been made of traditional versus antioxidant treatment of acute maxillary sinusitides . The patients were injected a mixture consisting of 4 ml emulsion of 10% dibunol liniment and 2 ml of 5% ascorbic acid made by dilution of 10 g dibunol in 30 ml sterile 0.5% novocaine solution . The mixture was introduced into the sinuses 2 times a day, in one of the study groups it was combined with 500,000 U of ampicillin in cases of purulent sinusitis . In catarrhal form the mixture was injected once a day without the antibiotic . Control groups received 4 ml dioxidine in a single dose after the sinus lavage in catarrhal sinusitis and 500,000 U ampicillin plus hydrocortisone emulsion (1 ml in 4 ml solution) 2 times a day in case of purulent sinusitis . All the patients received aevit (one capsule daily) . The mean number of manipulations for the study groups were 4.4 +/- 0.4 in catarrhal sinuses and 6.3 +/- 0.5 in purulent sinusitis; in control groups, respectively, 5.9 +/- 0.5 and 10.7 +/- 0.7 . Mean duration of treatment reached 5.3 +/- 0.4, 6.2 +/- 0.3 and 7.1 +/- 0.1 in the study groups and 8.5 +/- 0.2, 10.2 +/- 0.4 days in the control groups . Positive response to the treatment with antioxidants was confirmed by positive changes in blood levels of LPO products, activity of lysosomal hydrolases and antioxidant defense enzymes . The results obtained justify the inclusion of antioxidants in the schemes of acute sinusitis treatment.

Arch Tierernahr, 1994, 46(4), 321 - 5
{The effect of avilamycin and tylosin on the apparent digestibility of iron, zinc, copper, manganese and selenium in the beginning and ending performance of swine}; Kirchgessner M et al.; In two metabolism trials with growing and finishing pigs the effect of the antibiotic feed additives Avilamycin and Tylosin on the apparent digestibility of Fe, Zn, Cu, Mn and Se was investigated . The feed additives were supplied to the diet in levels of 40 ppm (growing pigs) and 20 ppm (finishing pigs) each . Dietary contents of Fe, Zn, Cu, Mn and Se covered the requirements of all treatment groups . Avilamycin and Tylosin increased the apparent digestibility by 4 (Fe), 4 (Zn), 5 (Cu), 2 (Mn) and 2 (Se) percentage units on an average.

Rev Elev Med Vet Pays Trop, 1994, 47(4), 379 - 80
Efficacy of chlortetracycline for controlling goat coccidiosis in Burundi; Dacasto M et al.; Eighteen cross-bred goats of Burundi naturally infected to varying degrees with multiple coccidia species of the genus Eimeria were orally administered 25 mg/kg body weight/day chlortetracycline . Effectiveness percentages more elevated than 99.0% were reached within the 9th day of treatment . No adverse reactions have ever been reported . Results demonstrate that the antibiotic is effective for the control of coccidiosis of goats naturally infected in Burundi.

Med Pregl, 1994 Jan-Feb, 47(1-2), 52 - 5
{Intravenous immunoglobulin in the treatment of infections in children with acute leukemias}; Gebauer E et al.; Infections are a common cause of complications in the course of applying highly aggressive combined cytotoxic therapy in children suffering from acute leukemias (ALL and ANLL) . The effect of adjuvant therapy of intravenous immunoglobulins (IVIG) was investigated in cases of infections of children with ALL and ANLL (24 with IVIG and 24 without this therapy) according to the system of matched pairs . The polyvalent functionally intact monomeric i.v . immunoglobulin "Endobulin" Immuno, 100 mg/kg was applied in infections--febrile episodes combined, if possible, with an aimed antibiotic therapy . It was established that children with the intravenous immunoglobulin therapy had had statistically significantly less febrile episodes (p < 0.01), as well as less febrile days (p < 0.05) . Although the acquired results speak in favor of this therapeutic possibility when applying this supportive therapy which is getting more and more important, authors made a conclusion that the final estimate of the value of this therapy remains open and requires further investigations.

Cell Biophys, 1994, 24-25, 119 - 26
Effect of a bifunctional monoclonal antibody directed against a tumor marker and doxorubicin on the growth of epidermoid vulvar carcinoma grafted in athymic mice; Morelli D et al.; Even though the first monoclonal antibodies (MAbs) directed against tumor cells were produced 15 yr ago, the therapeutic application of immunoconjugates is still at the beginning . This is principally because of the enormous work that is required for the development of completely new therapeutic tools . An alternative could be to only use MAbs to improve conventional treatment such as chemotherapy . To this aim, a MAb directed against doxorubicin (DXR) was produced . DXR is an anthracycline antibiotic of which the clinical usefulness in cancer chemotherapy is limited by serious side effects, such as cardiomyopathy, bone marrow depression, and gastrointestinal tract mucositis . This toxicity was found to be reduced by treatment with the antidrug MAb, as shown by reduction in body weight loss and mortality of experimental mice . To improve the DXR therapeutic index, a bifunctional hybrid MAb (DOXER2), capable of simultaneously recognizing DXR and the epidermal growth factor (EGF) receptor, was produced . This reagent was found in vitro to increase the drug toxicity on the epidermoid carcinoma cell line A431, which overexpresses the EGF-R and, at the same time, to reduce DXR cytotoxicity on EGF-R negative cells . The effect of DOXER2 on the DXR biodistribution in vivo was also investigated . In mice previously injected ip with the DOXER2, the uptake of the drug, in comparison to the control group, was found to be reduced in the intestine and in myocardial tissue, and significantly increased in the tumor.(ABSTRACT TRUNCATED AT 250 WORDS)

J Drug Target, 1994, 2(5), 363 - 71
Liposomes in the treatment of infections; Bakker-Woudenberg IA et al.; The use of liposomes in the treatment of severe infections is under investigation . Classical liposomes which localize in cells of the mononuclear phagocyte system (MPS) can be exploited in two ways . First for targeting of macrophage modulators such as muramyl peptides or IFN-gamma, to stimulate the cells of the MPS to maximal blood clearance capacity . This enhanced nonspecific anti-infectious resistance is important as in immunocompromised patients micro-organisms frequently appear in the blood from a local infection . Secondly, classical liposomes are successfully used as carriers of antibiotics in experimental intracellular parasitic-, viral-, fungal- or bacterial infections in MPS tissues . Based on these data extensive studies in patients with severe fungal infections have demonstrated successful treatment with liposomal or lipid-complexed amphotericin B . More recently, liposomal amphotericin B appeared to be effective in patients with drug-resistant visceral leishmaniasis . For the treatment of Mycobacterium avium complex infection in AIDS patients the efficacy of liposomal gentamicin is under investigation . With respect to infections in non-MPS tissues the applicability of Stealth liposomes characterized by long circulation half-lives is under investigation . Substantial localization of these liposomes in infected lung tissue of rats was demonstrated . Preliminary data in experimental bacterial lung infection showed superior efficacy of antibiotic encapsulated in Stealth liposomes.

Vestn Khir Im I I Grek, 1994 Jan-Feb, 152(1-2), 75 - 8
{The diagnosis and treatment of acute hematogenous osteomyelitis in children}; Neikov GN et al.; A clinical analysis of the diagnostics and treatment of 329 children with acute hematogenic osteomyelitis (AHO) has shown that the coloured liquid crystal thermography allows determination of the localization and spread of the inflammatory process in the bone, control of treatment efficiency, prognosis of the course and outcome of the disease . The use of the continuous-intermittent lavage of the bone with an enzyme-antibiotic mixture modified in the clinic in complex with a general treatment gives an improvement of the general condition 4-5 days earlier as compared with the traditional treatment, the disease taking the chronic form in 7.6% of the cases only.

Tsitologiia, 1994, 36(9-10), 1012 - 21
{Agents that act on chromatin structure affect the rate of intrachromosomal homologous DNA recombination in cultured cells}; Abramian DS et al.; A study was made of the influence of sodium butyrate and luminol on the rate of homologous recombination of aminoglycosidephosphotransferase gene copies, which contain non-overlapping deletions and are integrated in chromosomes of the Chinese hamster cells of line A238 . It is shown that treatment of cells of transformed clones with sodium butirate, which is known to stimulate DNA reparation and to loosen chromatin structure, inhibits intrachromosomal homologous recombination . Dexametazone, which is also capable of stimulating DNA reparation, displayed similar effect . In contrast, the treatment of cells with luminol, inhibiting DNA reparation and condensing chromatin structure, increased the efficiency of intrachromosomal homologous DNA recombination.

Acta Vet Scand, 1994, 35(4), 321 - 7
Comparison of two semen extenders in terms of in vitro development of bovine embryos following IVF; Lonergan P et al.; In order to conform with current EC standards with regard to antibiotic cover, the Norwegian Cattle Association is currently investigating the use of Biladyl as an alternative to the milk-based extender which has been traditionally used in Norway . A study was carried out to investigate the effect of using semen frozen with either milk extender or Biladyl on the outcome of in vitro fertilization and embryo culture . Semen from 6 Norwegian Red bulls was used . There was a significant difference p < 0.05 in terms of cleavage rate between the 2 extenders for 1 bull, 78.2% vs 94.9% for milk and Biladyl extenders, respectively, and for the overall total of 71.3% vs 76.1% for milk and Biladyl extenders, respectively . There were no significant differences in terms of blastocyst yield amongst any of the bulls . In conclusion, the results suggest that Biladyl can be used as a replacement for the traditional milk-based extender without any adverse effects on blastocyst yields following in vitro fertilization.

Biochem Soc Symp, 1994, 60, 173 - 82
Perception and transduction of an elicitor signal in cultured parsley cells; Nurnberger T et al.; Treatment of cultured parsley cells or protoplasts with a purified extracellular glycoprotein from Phytophthora megasperma f.sp . glycinea induces the transcription of the same set of defence-related genes as is activated in parsley leaves upon infection . Elicitor activity was shown to reside in a specific portion of the protein moiety which was isolated, sequenced and synthesized . Partial cDNAs encoding the entire mature protein as well as other related proteins have been isolated, indicating the presence of a small gene family . The elicitor-active oligopeptide is located in the C-terminal portion of the deduced amino acid sequence . Binding of the elicitor to target sites on the parsley plasma membrane appears to be the initial event in defence gene activation . The subsequent intracellular transduction of the elicitor signal was shown to involve rapid and transient influxes of Ca2+ and H+, as well as effluxes of K+ and Cl- . Inhibition of elicitor-induced ion fluxes by channel blockers also inhibited phytoalexin synthesis, while stimulation of similar ion fluxes by treatment of cells or protoplasts with the polyene antibiotic, amphotericin B, induced the production of phytoalexins and activated the complete set of defence-related genes in the absence of elicitor.

J Ultrasound Med, 1994 Jan, 13(1), 7 - 10
Infected renal cysts: sonographic diagnosis and management; Frishman E et al.; IRC are rare entities characterized by fever and unilateral flank pain resistant to antibiotic therapy . In our series of nine IRC in eight patients, the predominant sonographic finding was an abnormal echogenic texture of the cyst contents, in contrast to previous reports that stressed the frequency of wall thickening as a sign of infection . Sonographically guided cyst aspiration and drainage of eight cysts in seven patients provided diagnostic material and resulted in relief of symptoms . Although the cause of IRC is uncertain, these entities may be more common than previously suspected.

J Med Liban, 1994, 42(3), 117 - 22
{Infections in cancer patients with granulocytopenia . Retrospective studies of 59 febrile episodes with hospitalization}; Ghosn M et al.; A total of 59 febrile neutropenic episodes were retrospectively recorded at Hotel-Dieu de France Hospital between August 1st 1991 and December 31st 1992 . These episodes were recorded in 51 cancer patients . Median neutropenia was less than one week in 50% of the cases . The etiology of these fever was documented in 27 episodes (46%) and in 70% of the cases gram (-) rods were documented . B-Lactam and Aminoglycoside antibiotics were used in 34 episodes at the initial treatment of these patients . Success rate at this initial treatment or with a modification of the antibiotic therapy was recorded in 85% of the patients . Only 15% of the patients failed to this antibiotherapy, 2/3 of them had their disease in progression . The systemic use of Amphotericine E in those patients with prolonged febrile neutropenia and the concommitent use of growth factors in a sub-group of patients at high risk could lead to a higher success rate in these patients.

J Pathol, 1994 Jan, 172(1), 73 - 9
Whipple's disease: a histological, immunocytochemical, and electron microscopic study of the small intestinal epithelium; Ectors NL et al.; At endoscopy, the duodenum in Whipple's disease frequently appears abnormal and some clinical features such as gastrointestinal blood loss and anaemia suggest epithelial damage . However, the intestinal epithelial cells themselves appear to be normal on light and electron microscopy . The aims of this study were to analyse in detail the cytological changes in epithelial cells over time and in response to therapy in biopsies obtained from 20 patients, to investigate the functional repercussion on digestive enzymes such as lactase, and to assess the expression by the epithelial cells of MHC antigens . Cytological changes were minimal at both the light- and the electron-microscopic level and MHC class I expression was preserved . However, changes indicative of functional deficits were demonstrated . Lactase and MHC class II expression were reduced or even absent . Antibiotic therapy resulted in normalization within 3-6 months . These findings are consistent with the clinical evolution and are of interest with regard to the importance of the immune response in aetiopathogenesis.

Bone Marrow Transplant, 1994 Jan, 13(1), 37 - 41
Peripheral blood progenitors mobilised by G-CSF (filgrastim) and reinfused as unprocessed autologous whole blood shorten the pancytopenic period following high-dose melphalan in multiple myeloma; Ossenkoppele GJ et al.; Growth factor granulocyte colony-stimulating factor (G-CSF; filgrastim) is effective at progenitor release into the peripheral blood . After high-dose chemotherapy haematopoietic reconstitution occurs after reinfusion of these peripheral blood progenitor cells (PBPC) . However, the collection by leukapheresis and further processing of PBPC are very time consuming and expensive . We have studied the transplantation potential of a small volume of unprocessed autologous whole blood after G-CSF mobilisation . Six patients with plasma cell disorders received G-CSF 10 micrograms/kg sc during 6 days . Subsequently 11 of whole blood was collected by phlebotomy, kept unprocessed at room temperature and reinfused 24 h after high-dose melphalan 140 mg/m2 . CFU-GM content was 845 per ml blood (median, range 320-3472) and CD34+ cells rose to a median percentage of 0.9 (range 0.4-2.0) . Haematological recovery was significantly faster in the study group compared with the control group of 20 patients who received the same dose of melphalan without reinfusion of PBPC . The neutrophil count reached 0.5 x 10(9)/l at a median of 12.5 days after infusion of PBPC vs 38 days in the control group (p = 0.0003) . The platelet count reached 20 x 10(9)/l after a median of 23.5 days vs 38 days (p = 0.0218) . The shortened recovery was reflected by less transfusions, less antibiotic use and shortening of hospital stay (19 days vs 43 days, p = 0.0003) . We conclude that this easy technique of mobilisation and collection of PBPC is very effective for hastening haematologic recovery after high-dose chemotherapy.

Ann Oncol, 1994, 5 Suppl 2, 123 - 5
Cytokine efficiency in the treatment of high-grade malignant non-Hodgkin's lymphomas: results of a randomized double-blind placebo-controlled study with intensified COP-BLAM +/- rhGM-CSF; Engelhard M et al.; In high-grade malignant non-Hodgkin's lymphomas (hNHL) recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) was evaluated as support to chemotherapy . In a phase III trial, 172 patients (age 18-73 years, stage II-IV) were risk-stratified according to LDH levels and lymphoma size and randomized to receive rhGM-CSF (400 micrograms) (87 patients) or placebo (85 patients) subcutaneously days 8-14 of each cycle of an intensified COP-BLAM regimen . RhGM-CSF significantly reduced the length and nadir of neutropenia, the length of fever episodes, the frequency of all and of severe infections, and of hospitalization and antibiotic requirements . Complete response rates were 63% for all patients and 64% vs . 61% (n.s.) in the rhGM-CSF vs . the control group . Deviations from protocol in applied dosages of myelotoxic drugs and in cycle intervals maintained differed slightly in favor of the rhGM-CSF arm . However, there were no significant differences in overall survival between the GM-CSF treatment and control groups (21 vs . 23 months) . Early relapse rates were markedly lower than in the standard-dose COP-BLAM/IMVP-16 regimen . Thus, GM-CSF abates toxic side effects of chemotherapy and may help to maintain dose intensity in high-risk hNHL.

Nihon Kyobu Shikkan Gakkai Zasshi, 1994 Jan, 32(1), 55 - 61
{Pleuropulmonary aspergillosis with defective neutrophil functions--G-CSF effects on neutrophil functions}; Mineshita M et al.; A 66-year-old man was admitted to our hospital with productive cough and fever . Chest X-ray films showed pleural thickening of the right apex and calcification of the lung field . Antibiotic therapy was administered but no improvement was obtained . Chest CT scan revealed pleural thickening with effusion in the right apex . Needle aspiration biopsy was performed and Aspergillus fumigatus was isolated from pleural fluid . We began pleural drainage and intrapleural infusion of miconazole, with systemic administration of miconazole, amphotericin B and fluconazole . In spite of normal bone marrow findings, the neutrophil functions, NAP score and phagocytosis, of the patient were found to be subnormal . We commenced to treatment with granulocyte colony stimulating factor and his neutrophil functions improved (NAP score: 156-->309.5, phagocytosis: 64.9-->70.0%) . However, his fever persisted and he died following cardiopulmonary arrest . Autopsy revealed Aspergillus mycelia invading the visceral pleura . No intrapulmonary lesions caused by Aspergillus were found.

Khirurgiia (Sofiia), 1994, 47(6), 14 - 7
{Our experience with treating acute noncalculous cholecystitis}; Iarumov N et al.; Based on a comprehensive literature survey, personal experience with the management of 89 patients, presenting acute noncalculous cholecystitis, is shared . All patients are clinically observed in the acute phase of the disease . In 60 cases the latter becomes manifest with recurrent attacks, and in 29 there are no previous signs or symptoms of biliary diseases . Diagnosis is made on the ground of active echographic and clinical observation . Conservative therapy is effective in 28 cases . The remainder (61) are operated at 1 to 4-day intervals after the onset of the disease because of persisting symptomatology and/or deterioration of the patient's condition . During laparotomy the gallbladder presents marked enlargement with thickened, exudate-imbibed wall . Cholecystectomy is done in all 61 cases . In twelve of them, owing to dilatation of the common bile duct and minimal serum bilirubin increase, stenosing papillitis is diagnosed by intraoperative cholangiography, treated by external biliary drainage and endoscopic sphincterotomy, undertaken after improvement of the general condition . Acute inflammation, free of fibrosis, with isolated foci of gangrene and necrosis of the bladder wall are histologically documented . In four senile patients presenting serious concomitant diseases, with exceptionally high operative risk, echographic percutaneous transhepatic cholecystectomy is resorted to, followed by antibiotic bladder instillations with a very good outcome . The summed up results of acute noncalculous cholecystitis treatment are estimated as very good.

Khirurgiia (Sofiia), 1994, 47(6), 11 - 3
{Nonparasitic liver abscesses}; Stoianov G et al.; Abscess of the liver is a comparatively rate, but very serious disease, necessitating the undertaking of diagnostic and therapeutic measures on an emergency basis . The principal diagnostic method currently in use includes two imaging techniques--echography and CT . In therapeutic respect the target puncture under echographic or CT control has rather limited scope of application . Surgical therapeutic approach is the leading one--laparotomy, drainage of the abscess, and arbitrary use of a Kerr drainage for the choledochus and regional antibiotic therapy.

Biochem Biophys Res Commun, 1993 Dec 30, 197(3), 1203 - 8
The inhibition of the inositol 1,4,5-trisphosphate receptor from rat cerebellum by spermine and other polyamines; Sayers LG et al.; Inositol 1,4,5-trisphosphate-induced Ca2+ release from rat cerebellar microsomes can be inhibited by polyamines at mM concentrations . Spermine, one of the most abundant naturally occurring polyamines, inhibits InsP3-induced Ca2+ release with an IC50 of 1 mM . However, the antibiotic neomycin proved most efficacious at inhibiting InsP3-induced Ca2+ release (IC50 0.4mM) . The order of potency being neomycin > spermine > spermidine > putrescine . Although binding of {3H}InsP3 to cerebellar microsomes is also inhibited by polyamines, this may be due to InsP3 complexing with the polyamines under the binding conditions used . Under Ca2+ release conditions InsP3 binds weakly to spermine and therefore inhibition of InsP3-induced Ca2+ release is consistent with polyamines interacting with the InsP3 receptor.

FEBS Lett, 1993 Dec 28, 336(3), 496 - 500
Brefeldin A blocks protein glycosylation and RNA replication of vesicular stomatitis virus; Irurzun A et al.; Brefeldin A is a macrolide antibiotic that interferes with membrane traffic and blocks the growth of several animal viruses including vesicular stomatitis virus (VSV) . The inhibition of VSV by brefeldin A takes place at least at two different steps during the growth cycle: the glycosylation of VSV G protein and the replication of viral genomes . Our results indicate that interference with membrane traffic leads not only to inhibition of viral protein glycosylation, but also to the blockade of virus genome replication in several cytoplasmic RNA-containing viruses.

Schweiz Med Wochenschr, 1993 Dec 18, 123(50), 2370 - 7
{Brucellosis: case report and synopsis of 10 cases (1973-1992) in the Chur canton hospital}; Canova CR et al.; A 33-year-old patient from former Yugoslavia presented with low back pain and fever . Plain X-rays and myelography were normal, but a technetium-99m scan was suspect for vertebral osteomyelitis . Serology and blood cultures were positive for Brucella (melitensis) . Antibiotic therapy with tetracycline and rifampicine rapidly improved the signs and symptoms of the infection . A retrospective analysis of 11 cases of Brucellosis treated in the Kantonsspital, Chur, over the years 1973 to 1992 revealed that 9 patients were foreign workers from rural areas in the Mediterranean region (Spain, Portugal, Italy, Yugoslavia, Greece) . The majority had a history of consuming milk and dairy products from their own farm animals up to a few months before the onset of symptoms . Blood cultures were positive in 5 cases (B . melitensis) while the remaining 6 had high titers of agglutinating antibodies . A diagnostic delay of several weeks to months was typical . Because Brucellosis usually presents with unspecific often flu-like symptoms, with unspecific laboratory findings, and with a varying array of organ manifestations a high index of suspicion is essential for a timely diagnosis.

Blood, 1993 Dec 15, 82(12), 3770 - 7
Peripheral blood progenitor cell transplantation in lymphoma and leukemia using a single apheresis; Pettengell R et al.; Myeloablative treatment and peripheral blood progenitor cell (PBPC) transplantation are increasingly used for lymphomas and leukemias . We have sought to optimize conditions for priming, collection, and engraftment of the leukapheresis product . Fifty-four consecutive adult patients were eligible, 31 with high-grade non-Hodgkin's lymphoma of poor prognosis, 12 with Hodgkin's disease in chemosensitive relapse, and 11 with poor prognosis acute lymphoblastic leukemia . Filgrastim was administered after routine chemotherapy with VAPEC-B or HiCCOM to mobilize PBPC . A rapidly increasing white blood cell count was used to predict the time of peak PBPC release and plan leukapheresis . Forty-five patients underwent leukapheresis . A median of 14 L of blood was processed at a single apheresis . A median of 2.4 x 10(8)/kg mononuclear cells (MNCs), 1.04 x 10(6)/kg granulocyte-macrophage colony-forming cells (GM-CFCs), and 10.6 x 10(6)/kg CD34+ cells were obtained . Slightly fewer MNCs were obtained from the heavily pretreated Hodgkin's disease group . There were no other significant differences in the size or composition of the leukapheresis harvest in the three patient groups . Forty patients underwent high-dose therapy and PBPC transplantation . Filgrastim was administered by daily subcutaneous injection until the absolute neutrophil count was > or = 1 x 10(9)/L for 2 consecutive days . Rapid and sustained hematopoietic engraftment occurred in all patients . The median time to achieve a neutrophil count > or = 0.5 x 10(9)/L was 9 days (range, 8 to 16 days); to achieve a platelet count > or = 20 x 10(9)/L was 10 days (range, 6 to 88 days); and to achieve a platelet count > or = 50 x 10(9)/L was 15.5 days (range, 10 to 100 days) . Neutrophil recovery was faster than that of a historical control group treated with autologous bone marrow transplantation and filgrastim, but platelet recovery times were halved in the PBPC group . There was no secondary engraftment failure . Requirements for blood and platelet transfusions, antibiotic use, and parenteral nutrition were similar in the three patient groups . The median number of days in the hospital was 13 (range, 10 to 55) in the PBPC patients, compared with 19 (range, 14 to 51) in the historical controls . Leukapheresis yields (MNC, GM-CFC, and CD34+ cell numbers) were not useful for predicting the times to engraftment . We have shown that sufficient PBPC for transplantation can be obtained at a single leukapheresis after mobilization with routine chemotherapy and filgrastim in patients with non-Hodgkin's lymphoma, Hodgkin's disease, and acute lymphoblastic leukemia, even those heavily pretreated.(ABSTRACT TRUNCATED AT 400 WORDS)

Neuroreport, 1993 Dec 13, 5(3), 197 - 200
Effect of ketamine on stress protein immunoreactivities in rat olfactory mucosa; Carr VM et al.; Administration of 9 mg ketamine per 100 g b.wt . to rats leads to transient enhancement of immunoreactivity to monoclonal antibodies against two stress proteins, ubiquitin and human 70 kDa heat shock protein (HSP70), in the supranuclear region of supporting cells of the olfactory epithelium and in the Bowman's gland acinar cells in the subepithelial lamina propria . In the supporting cells the enhanced immunoreactivities are not caused by other drugs used in our surgical anesthetic/antibiotic regimen (xylazine, buprenorphine, and gentamicin), but in Bowman's glands they are . Results are discussed in terms of possible ketamine binding to phencyclidine receptors (either NMDA-associated or not) and possible direct stress-inducing interactions of ketamine or ketamine breakdown products with the inhalant detoxification or secretory systems in the reactive cells.

Pharmacoeconomics, 1994, 6 Suppl 2, 36 - 43
Economic analysis of lenograstim in the correction of neutropenia following chemotherapy for non-Hodgkin's lymphoma; Souetre E et al.; A prospective economic analysis of lenograstim and placebo was performed as part of a randomised double-blind trial in 162 patients receiving chemotherapy for non-Hodgkin's lymphoma (NHL) . The primary clinical end-point was the percentage of patients experiencing > or = 1 documented infection in each treatment group . The cost of hospitalisation and the cost of medical services used were the primary economic end-points . Economic analysis was based on the French Hospital perspective . Over the 56-day study period, patients in the placebo group received more days of inpatient intravenous (8.9 vs 5.3 days; p < 0.01) and oral (5.3 vs 4.2 days) antibiotic therapy than those in the lenograstim group . This difference was due to a higher rate of documented infection in the placebo group . Patients treated with placebo also spent more days in hospital for reasons other than administration of chemotherapy (18.5 vs 14.4; p < 0.05) . The number of days of chemotherapy was significantly greater in the lenograstim group than in the placebo group (19.4 vs 17.5; p < 0.001) because of shorter delays between chemotherapy cycles in the lenograstim group . The use of lenograstim to prevent chemotherapy-induced neutropenia in patients with NHL was associated with a reduction in total direct medical costs (excluding the cost of lenograstim) of FF7297 as a result of reduced patient morbidity . Furthermore, the higher rate of completion of chemotherapy in the lenograstim group may lead to better long term survival; this observation deserves further clinical investigation.

Pharmacoeconomics, 1994, 6 Suppl 2, 27 - 35
Economic evaluation of lenograstim (glycosylated rHuG-CSF) in the treatment of inflammatory breast cancer for Germany and Italy; Mapelli V et al.; Data from a French placebo-controlled double-blind trial in 120 female patients treated with high dose fluorouracil, epirubicin and cyclophosphamide (HD-FEC) chemotherapy for inflammatory breast cancer were used to assess the economic impact of adjunctive lenograstim therapy . The analysis compared direct costs of treatment, with or without lenograstim, with reference to the Social Security (Germany) or to the National Health Service (Italy) . Resource utilisation differed between the 2 treatment groups . The lenograstim group reported 32% fewer antibiotic therapy days (9.8 days vs 14.6; p = 0.01) and 24% fewer inpatient days for any reason other than chemotherapy (7.4 'excess' days vs 9.8) . By reducing infection-related morbidity associated with a high dose chemotherapy regimen, lenograstim decreased treatment costs by DM 1794 and ItL 1.2 million, excluding the cost of lenograstim itself . Since lenograstim patients reported fewer chemotherapy delays (16.4 vs 30.5%) and, hence, benefited from 1.2 (p = 0.04) more chemotherapy days, the related cost was DM 1519 and ItL 0.9 million higher than for the placebo group . This cost difference would be expected to be smaller if the placebo group patients had been followed until completion of their full chemotherapy regimen . Assuming that the costs of chemotherapy were the same for both groups, the direct cost saving for the lenograstim group would be 30% in Germany and 34% in Italy.

Int J Health Care Qual Assur, 1994, 7(3), 11 - 5
Comparative audit between hospitals: the example of appendectomy; Black NA et al.; How useful are routine, comparative audit systems? To attempt to answer this question, data from a system in North West Thames were used . A common procedure was selected (appendectomy) and data supplied by 17 surgeons between January and June 1990 were analysed . Aspects of the case-mix, clinical management, diagnostic accuracy and patient outcomes for the surgeons were compared . A total of 401 patients had been treated . All aspects of care varied between surgeons: mean age of patients (19-36 years), proportion of female patients (30-75 per cent), mean length of stay (2.1-7.1 days), prophylactic antibiotic use (0-85 per cent), diagnostic accuracy (40-100 per cent) and incidence of wound infections (0-4 per cent) . As a result of the small sample sizes (mean number of cases per surgeon was 23.6) few of these differences were statistically significant . In addition, there were some doubts about the accuracy of some of the data . If such methodological difficulties can be overcome, comparative audit systems offer a practical and useful way of uncovering unusual clinical practices and generating hypotheses for evaluative research.

Schweiz Rundsch Med Prax, 1993 Dec 7, 82(49), 1424 - 8
{Abdominal pain, fresh blood in the anus}; Bauer S et al.; A 60-year-old lady with type II diabetes, arterial hypertension and 'melancholia' was treated with Lithium, a neuroleptic (Leponex) and an ACE inhibitor (Reniten) . She was referred to our hospital because of abdominal pain, subfebrile temperatures, diarrhea and hematochezia . The radiological and sonographic examinations showed a thickened wall of the left hemicolon . Colonoscopy revealed a sharply delineated segment with pronounced inflammation in the descending colon and the proximal sigmoid colon, suggestive for an ischemic colitis . Histology of the inflamed colon was compatible with this diagnosis . Under suspended enteral feeding and antibiotic therapy the symptoms disappeared within two weeks, and a control colonoscopy six weeks later was completely normal . 1 1/2 years later the patient suffered from a second episode of ischemic colitis exactly a the same site . Again, complete cure was achieved by conservative treatment.

J Biol Chem, 1993 Dec 5, 268(34), 25385 - 8
Rapamycin-FKBP12 blocks proliferation, induces differentiation, and inhibits cdc2 kinase activity in a myogenic cell line; Jayaraman T et al.; Rapamycin is a potent immunosuppressant that binds to the cytosolic protein, FKBP12, and blocks T cell activation . Here we report that rapamycin also blocks myogenic proliferation and induces differentiation, associated with a decrease in p34cdc2 activity and cyclin A levels . In yeast and mammals, rapamycin blocks cell cycle progression by causing G1 arrest, arguing for a conserved signaling pathway governing the G1 to S transition . p34cdc2 has been shown to play a role in both the transition from G1 to S and from G2 to M in yeast . In higher eukaryotes the role of p34cdc2 in G1 to S transition is less clear . Rapamycin and the structurally related macrolide antibiotic FK506 both bind to a cytosolic protein, the FK506-binding protein (FKBP12) . We show that inhibition of myogenic proliferation is achieved at low doses of rapamycin (< 1 ng/ml) and is competed by a molar excess of FK506, indicating specificity for FKBP12 . The distinct FK506-calcineurin pathway did not affect myogenic proliferation, differentiation, or p34cdc2 kinase activity . Thus, the rapamycin-FKBP12 signaling pathway involves a specific and direct effect on p34cdc2 kinase activity at the G1 to S transition and identifies a regulatory step during myogenic differentiation.

J Hand Surg {Br}, 1993 Dec, 18(6), 783 - 9
Closed continuous irrigation as a treatment for infection in the hand; Nemoto K et al.; A method of closed irrigation has been devised to treat infections in the hand . After adequate debridement, two tubes are placed in the infected area, an inlet tube and an outlet tube . For a small infection, one tube serves both purposes . The wound is closed completely . Irrigation with saline and antibiotic solution is continued for 1 week, extended up to 3 weeks in cases of severe infection . This method has been applied in 31 cases including pyogenic tenosynovitis, tuberculous tenosynovitis, pyogenic arthritis, osteomyelitis, bite injury, crush injury and amputation stump infection . Infection healed primarily in 29 cases . Further surgery was needed in two cases which healed finally.

J Clin Microbiol, 1993 Dec, 31(12), 3090 - 5
Serodiagnosis in early Lyme disease; Aguero-Rosenfeld ME et al.; Using a commercially available enzyme-linked immunosorbent assay (ELISA) and an immunoblot assay (IB), we tested sera from 100 patients with erythema migrans (EM) seen in 1991 a the Westchester County Medical Center Lyme Disease Diagnostic Center . Convalescent-phase sera were available from 59 patients . Fifty-five patients had EM of < 7 days' duration, 31 had EM of 7 to 14 days' duration, and 14 had EM of > 14 days' duration . During the acute phase of infection, 35 patients had a positive ELISA result and 43 had a positive IB result by the recently published criteria of Dressler et al . (F . Dressler, J . A . Whalen, B . N . Reinhardt, and A . C . Steere, J . Infect . Dis . 167:392-400, 1993) for interpretation of IB in patients with Lyme disease . A greater sensitivity of IB was observed in patients with EM of < 7 days' duration, as follows: 14 of 55 (25%) for IB versus 7 of 55 (13%) for ELISA (P = 0.144) . Sera of all 14 patients with EM of > 14 days' duration were reactive by both tests, as follows: 13 positive and 1 equivocal by ELISA and 12 positive and 2 indeterminate by the IB . The band reactivity most frequently observed in the IB was to the 41- and 25-kDa antigens, the latter being the most frequent band observed in immunoglobulin M blots . Seroconversion was observed in 74 and 64% of evaluable patients by ELISA and IB, respectively, despite the use of antibiotic therapy.

Zhonghua Yi Xue Za Zhi (Taipei), 1993 Dec, 52(6), 408 - 12
Acute lobar nephronia: a case report; Chen SC et al.; Acute lobar nephronia (ALN), a term analogous to acute lobar pneumonia, refers to a renal mass caused by acute focal infection without liquefaction . An alternative term is acute focal bacterial nephritis (AFBN) . Fever, flank pain or back pain are the most frequently encountered clinical characteristics . Imaging modalities used to establish a definite diagnosis of acute lobar nephronia included sonography, computed tomography and nuclear medicine . Uroradiographic findings in this condition can mimic a renal abscess or neoplasm . Further distinction between acute lobar nephronia and other renal masses is aided by the appropriate use of renal sonography and computerized tomography is the most effective and least costly method in diagnosis . Serial sonograms can be used to monitor response to antibiotic therapy . Clinical and uroradiographic characteristics of a six year-old female patient with acute lobar nephronia are presented, along with a review of literature.

Pediatr Infect Dis J, 1993 Dec, 12(12 Suppl 3), S122 - 7
Comparative safety and efficacy of clarithromycin and amoxicillin/clavulanate in the treatment of acute otitis media in children; McCarty JM et al.; Clarithromycin is a new macrolide antibiotic with a wide spectrum of activity that includes the pathogens commonly causing pediatric otitis media . This randomized, investigator-blinded, multicenter trial compared the safety and efficacy of clarithromycin and amoxicillin/clavulanate in the treatment of acute otitis media in patients ages 6 months to 12 years . A total of 338 patients with acute otitis media diagnosed by otoscopy were randomized to receive clarithromycin 7.5 mg/kg twice daily, maximum 500 mg twice daily (n = 161), or amoxicillin/clavulanate 13.3 mg/kg three times daily, maximum 500 mg three times daily (n = 177), for 10 days . Treatment groups were comparable with respect to demographics, severity of infection and number of previous episodes . Efficacy was assessed by clinical examination performed within 48 hours of finishing study medication . A successful clinical response was seen in 90% (121 of 135) of evaluable clarithromycin patients vs . 92% (133 of 145) of evaluable amoxicillin/clavulanate patients (P = 0.681) . Clinical failure or relapse (Posttreatment Days 0 to 4) occurred in 10% (14 of 135) of clarithromycin-treated patients vs . 8% (12 of 145) of amoxicillin/clavulanate-treated patients . Gastrointestinal adverse events were the most commonly reported in both groups . Of these events diarrhea was the most frequent, occurring in 12% (19 of 161) of clarithromycin and 32% (57 of 177) of amoxicillin/clavulanate-treated patients (P < 0.001) . These results indicate that the efficacy of clarithromycin oral suspension was comparable with amoxicillin/clavulanate oral suspension in the treatment of acute otitis media in children . Clarithromycin was better tolerated than amoxicillin/clavulanate with a lower incidence of gastrointestinal side effects.

J Laryngol Otol, 1993 Dec, 107(12), 1113 - 8
Radical mastoidectomy: its place in otitic intracranial complications; Singh B et al.; Standard recommended treatment for patients with intracranial complications from otitis media, has been radical mastoidectomy, whether cholesteatoma is present or not . This was established in the pre-antibiotic era to improve survival . Over a six-year period, from January 1985 to December 1990, 268 patients were admitted with intracranial and extracranial complications of otitis media . The prospective treatment consisted of antibiotics and surgery . Surgery entailed mastoidectomy and drainage of intracranial collections of pus in all patients . However, prospectively in these patients the ear pathology and not the complication dictated the type of mastoidectomy performed . Cortical mastoidectomy was performed in non-cholesteatomatous ears and radical mastoidectomy in cholesteatomatous ears . Recurrence of intracranial complications occurred in only four patients (two per cent), a temporal lobe cerebritis in the non-cholesteatomatous ear group, and, a temporal lobe abscess, posterior fossa abscess and subdural empyema in the cholesteatomatous ear group . The temporal lobe cerebritis settled on intravenous antibiotics whilst the temporal lobe abscess, posterior fossa abscess and subdural empyema required redrainage . In none of these was the ear surgery revised . There were 15 deaths (eight per cent), all occurring in patients with intracranial complications, 12 associated with brain abscess, two with subdural empyema and one with meningitis . Eight were from the non-cholesteatomatous group and seven from the cholesteatomatous group . The mortality was directly related to the patients consciousness level on admission and not to the type of ear pathology . It can therefore be concluded that radical mastoidectomy is unwarranted in the non-cholesteatomatous ear, even with an otogenic intracranial complication.

Br J Oral Maxillofac Surg, 1993 Dec, 31(6), 360 - 5
The use of third molar surgery in clinical pharmacology; Meechan JG et al.; This review discusses the various sequelae that arise after third molar surgery and their use for assessing the efficacy of a variety of therapeutic measures . The surgical procedure provides an opportunity to investigate onset, depth, duration and possible systemic effects of local anaesthetic solutions . Also, the anxiety which often accompanies such surgery lends itself to the appraisal of different anxiolytic agents and sedation techniques . The immediate postoperative sequelae of pain, buccal swelling and trismus provides a useful clinical model for evaluating the efficacy of analgesics and anti-inflammatory drugs . Third molar tooth sockets are susceptible to infection and this propensity enables the assessment of different antibiotic regimens . A further advantage of the third molar model is its application for crossover studies, with the patient acting as their own control . Very few surgical procedures afford this facility, which further adds to the value of this model in clinical pharmacology.

Can J Surg, 1993 Dec, 36(6), 522 - 4
Acute abdominal emergencies in patients on long-term ambulatory peritoneal dialysis; Wellington JL et al.; OBJECTIVE: To review intercurrent abdominal emergencies in patients receiving long-term peritoneal dialysis on an ambulatory basis . DESIGN: A chart review . SETTING: Tertiary care referral centre . PATIENTS: Seven patients receiving long-term peritoneal dialysis, who suffered an acute abdominal emergency during a 7-year study period . INTERVENTIONS: Laparotomy with appropriate management depending on the findings . Antibiotic therapy and dialysate culture . RESULTS: In all patients the acute abdominal process involved the colon: five patients had perforated diverticulitis and two had ischemic colitis . The death rate overall was 57% . Peritonitis in these patients was difficult to differentiate from the peritonitis that occurs commonly in patients on long-term peritoneal dialysis . As a result there was a delay in the initiation of therapy ranging from 2 to 27 days . CONCLUSIONS: Coincidental abdominal emergency should be considered when patients receiving long-term peritoneal dialysis on an ambulatory basis present with peritonitis that does not respond to established antibiotic protocols and when culture results show evidence of multiple enteric organisms.

Plast Reconstr Surg, 1993 Dec, 92(7), 1342 - 9; discussion 1350-1
Diffusion versus iontophoresis in the transport of gentamicin in the burned rabbit ear model; Kaweski S et al.; This experimental study demonstrates that iontophoresis can be used to transport biologically active gentamicin into auricular cartilage . Fifty female New Zealand White rabbits were divided into three groups: live controls with unburned ears, live animals with burn-injured ears (deep or partial-thickness), and euthanized animals with unburned ears . Each group was then divided into subgroups that received gentamicin transported by iontophoresis or diffusion . In ears subjected to iontophoresis, adequate gentamicin activity could be demonstrated only in the cartilage of euthanized animals with unburned ears and live animals with full-thickness burned ears . Diffusion did not transport a detectable level of gentamicin in any instance . Diffusion is ineffective in the transport of gentamicin and should not be used as a primary method of treatment for ear chondritis . Iontophoresis did not transport active gentamicin across partial-thickness burns, presumably because the migrating antibiotic molecules were dispersed throughout the body by the circulation . However, if the circulation is destroyed, as in a full-thickness burn, iontophoresis can move the biologically active gentamicin into the cartilage.

J Bacteriol, 1993 Dec, 175(23), 7571 - 80
The tcmVI region of the tetracenomycin C biosynthetic gene cluster of Streptomyces glaucescens encodes the tetracenomycin F1 monooxygenase, tetracenomycin F2 cyclase, and, most likely, a second cyclase; Summers RG et al.; Certain mutations in the tcmVI region of the Streptomyces glaucescens chromosome affect formation of the D ring of the polyketide antibiotic tetracenomycin C (TCM C) . This region lies immediately upstream from the TCM C polyketide synthase genes (tcmKLM), and the nucleotide sequence reveals the presence of three small genes, tcmH, tcmI, and tcmJ . On the basis of the phenotypes of mutants and the effects of these genes, when coupled on a plasmid with the tcmKLMN177 genes (tcmN177 is a 3'-truncated version of tcmN), on the production of TCM intermediates in a TCM- mutant, the tcmH gene encodes the C-5 monooxygenase that converts TCM F1 to TCM D3, the tcmI gene encodes the D-ring cyclase that converts TCM F2 to TCM F1 (mutations in this gene are responsible for the type VI phenotype), and the tcmJ gene most likely encodes the B-ring cyclase that acts in the biosynthesis of TCM F2 . Furthermore, it appears that the N-terminal domain of the tcmN gene product (encoded by the tcmN177 gene) acts later in the biosynthesis of TCM F2 than the product of tcmJ, suggesting that the N-terminal domain of the TcmN protein is the C-ring cyclase.

Clin Orthop, 1993 Dec, (297), 238 - 41
Chronic septic arthritis caused by Borrelia burgdorferi; Battafarano DF et al.; Chronic arthritis occurs in 10% of Lyme disease patients . A patient had chronic septic Lyme arthritis of the knee for seven years despite multiple antibiotic trials and multiple arthroscopic and open synovectomies . Spirochetes were documented in synovium and synovial fluid (SF) . Polymerase chain reaction (PCR) analysis of the SF was consistent with Borrelia infection . Persistent infection should be excluded with silver stains and cultures in any patient with chronic monoarticular arthritis and a history of Lyme disease.

J S Afr Vet Assoc, 1993 Dec, 64(4), 162 - 4
Emphysematous cystitis in a non-diabetic cat; Davies NL et al.; Emphysematous cystitis in man and domestic animals is reviewed . A case of emphysematous cystitis occurring 5 d after standard therapy for urethral obstruction in a non-diabetic male Siamese-cross cat is described . Escherichia coli was isolated, and the cystitis resolved after antibiotic therapy.

Leuk Lymphoma, 1993 Dec, 12(1-2), 41 - 9
New insight into oncoprotein-targeted antitumor effect: herbimycin A as an antagonist of protein tyrosine kinase against Ph1-positive leukemia cells; Okabe M et al.; Herbimycin A, a benzoquinonoid anasamycin antibiotic, has been shown to reserve the oncogenic phenotypes of p60v-src transformed cells by the virtue of the inhibition of src protein tyrosine kinase . Furthermore, we previously demonstrated that herbimycin A displayed the antitumor activity on Ph1-positive leukemia cells and bcr/abl oncoprotein-associated transformed murine hematopoietic cells with the transfection of a retroviral vector expressing bcr/abl . Herbimycin A showed preferential inhibition on the in vitro growth of Ph1-positive leukemia cells and bcr/abl oncoprotein-associated murine hematopoietic cells through the inhibition of bcr/abl tyrosine kinase activity and the reduction of subsequent phosphotyrosyl proteins . Recently, from the view of investigating the oncogenic significance or of developing a future clinical application in malignancies, several developing agents targeted against oncoprotein have been tried . We reviewed the present progress in the mechanism of oncoprotein-targeted antitumor effects and focused on herbimycin A-induced antitumor activity on Ph1-positive leukemia cells.

J Otolaryngol, 1993 Dec, 22(6), 415 - 20
Septic internal jugular vein thrombosis; Tovi F et al.; Septic Internal Jugular Vein Thrombosis (SIJVT) is a rare but potentially life-threatening condition which necessitates early clinical recognition and rapid administration of appropriate therapy . Although termed by some authors a "forgotten disease" in the antibiotic era, this entity is still present but frequently overlooked . Deep neck infections, Lemierre syndrome, central venous catheterization and mastoiditis are the etiologies in this series . The diagnosis of SIJVT utilized CT and Doppler ultrasound imaging . The treatment included aggressive abscesses, necrotizing fasciitis, mastoiditis) . Anti-coagulant agents were used in order to reduce the risks of pulmonary embolism.

Comput Methods Programs Biomed, 1993 Dec, 41(2), 131 - 3
Microcomputer program for the assessment of one-way, two-way and factorial analysis of variance in pharmaceutical data; Abdullah ME et al.; A personal computer program in BASIC for the two-factor factorial analysis of variance has been developed . The factorial design is based on and combined with previous one-way and two-way ANOVA programs . The performance of the program is tested on data obtained from 3 months' consumption of three proprietary antibiotic products in four Saudi hospitals.

J Mol Endocrinol, 1993 Dec, 11(3), 335 - 41
Insulin delivery by somatic cell gene therapy; Stewart C et al.; The feasibility of somatic cell gene therapy as a method of insulin delivery has been studied in mice . Murine pituitary AtT20 cells were transfected with a human preproinsulin DNA in a plasmid containing a metallothionein promoter and a gene conferring resistance to the antibiotic G418 . The AtT20MtIns-1.4 clone of cells was selected because of its higher insulin-releasing activity compared with other clones . After culturing for 24 h in Dulbecco's medium containing 10 mM glucose, the AtT20MtIns-1.4 cells released human insulin at about 5 ng/10(6) cells per 24 h . Insulin release was not significantly altered by raised concentrations of glucose, potassium or calcium, but insulin release was increased by 20 mM arginine, 5 mM isomethylbutylxanthine and 90 microM zinc . AtT20MtIns-1.4 cells (2 x 10(6)) were implanted intraperitoneally into non-diabetic athymic nude (nu/nu) mice, and the mice were made diabetic by injection of streptozotocin after 7 days . Release of human insulin in vivo was assessed using a specific plasma human C-peptide assay . Human C-peptide concentrations were maintained at about 0.1 pmol/ml throughout the 29 days of the study . The development of streptozotocin-induced hyperglycaemia was delayed in recipients of the cells releasing human insulin, compared with a control group receiving an implant of non-transfected cells . At autopsy the implanted AtT20MtIns-1.4 cells in each recipient had formed a tumour-like aggregation, with an outer region of insulin-containing cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Minerva Pediatr, 1993 Dec, 45(12), 505 - 10
{The use of thymopentin in the prevention of recurrent infections of the respiratory system . Multicenter study}; Tovo PA et al.; Eighty children, between 1-12 years, suffering from recurrent respiratory infections were admitted to a multicentre study and treated with thymopentin, an immunomodulating compound that represents the active site of the natural thymic hormone thymopoietin . Thymopentin efficacy, measured as reduction in the number of infective episodes, and tolerability were assessed and, at the end of the study a global evaluation was made by each investigator . Moreover, the following factors were recorded: clinical course, duration of symptoms/signs, frequency of administration of antipyretic, antibiotic, anti-inflammatory and mucolytic therapy, school attendance and hospitalization . Thymopentin treatment resulted in a statistically significant decrease of infective recurrences . The use of symptomatic and antibiotic drugs was also reduced . Side effects were few and mild . The investigators' overall evaluation of thymopentin's efficacy and tolerability was favourable . In conclusion, thymopentin, administered subcutaneous for 5 weeks in winter, may be useful in the treatment of children with recurrent infections of the respiratory tract.

Minerva Pediatr, 1993 Dec, 45(12), 499 - 503
{Approach to acute gastroenteritis in children: comparison over the years}; Gaeta G et al.; Diagnostic and therapeutic approach to children admitted because of acute gastroenteritis has been retrospectively evaluated by auditing the hospital records in two periods respectively before (A: 103 patients) and after (B: 133 patients) the use of oral rehydration solution . Incomplete history taking was found out without differences between the two periods; in many cases the weight loss, one of the main criteria for hospitalization in acute diarrhoea, was not recorded at admission . In period B therapeutic behaviour was adequate to literature guidelines as regards both antibiotic prescription and use of oral rehydration solution . Nevertheless even if oral rehydration was carried out in more than 70% of patients, parenteral fluid administration was not significantly reduced in comparison with period A . Oral rehydration solution contributed to reduce the length of hospital stay in the more recent period . The study confirms the usefulness of medical audit to improve quality care.

J Trop Pediatr, 1993 Dec, 39(6), 346 - 9
Respiratory syncytial virus infection in young children hospitalized with respiratory illness in Riyadh; Jamjoom GA et al.; The occurrence of respiratory syncytial virus (RSV) infection among young children hospitalized with lower respiratory tract illness, at King Khalid University Hospital in Riyadh, was examined during the autumn-winter season between September 1991 and February 1992 . Sixty-nine cases were diagnosed by immunofluorescent antibody staining of viral antigen in nasopharyngeal aspirates from 127 children, constituting 54 per cent of these patients . Virus culture was attempted only in a few cases, yielding two isolates . Most children were < 1 year of age (median 2 months) . Bronchiolitis and bronchopneumonia were the major diagnoses on admission . Hospitalization was for an average of 5 days (range 1-36 days) . Treatment was supportive but most children received antibiotic therapy . There was no mortality . Few other bacterial or viral pathogens could be identified from RSV-positive or -negative patients . These results indicate that, during the season of infection, RSV may be the main pathogen of lower respiratory tract illness in hospitalized young children in this region.

Vet Parasitol, 1993 Dec, 51(1-2), 41 - 8
Concurrent infections of Giardia and Cryptosporidium on two Ohio farms with calf diarrhea; Xiao L et al.; Giardia and Cryptosporidium infections were diagnosed by immunofluorescence assay on two Ohio dairy farms with calf diarrhea problems . On the first farm, all nine diarrheic calves sampled once in June had Giardia cysts in their feces . On the second farm, all five diarrheic calves examined at the beginning of the diarrhea outbreak in March had Giardia infection . When resampled, the overall infection rate of normal and diarrheic calves was 82.4% in April, and 40.0% in August after the diarrhea subsided . Positive calves ranged from 11 to 164 days of age, and 22.2% of them were as young as 1 to 3 weeks of age . Eight of nine diarrheic calves (88.8%) on the first farm had Cryptosporidium infection . Lower infection rates (< 30%) were found on the second farm . Six of 10 positive calves were 11-22 days old, three were 164-177 days old, and one was 71 days old . Five of these 10 positive calves were also positive for Giardia infection . Five diarrheic calves on the northern Ohio farm and one diarrheic calf on the central Ohio farm were treated with metronidazole after failing to respond to antibiotic therapy . Clinical improvement was observed in all calves within 48 h after the start of treatment . The high Giardia infection rates and intensities in calves of a wide age range and the clinical response to metronidazole suggest that Giardia infection contributed to the outbreaks of diarrhea.

Ther Drug Monit, 1993 Dec, 15(6), 563 - 9
Mass spectrometric investigations of drug-receptor interactions; Henion J et al.; Mass spectrometric (MS) detection of biologically important noncovalent complexes is reviewed within the scope of on-going studies on this topic from this laboratory . The merits of ion spray MS and tandem MS are demonstrated in this area with examples that show systemic studies of several receptor-ligand, enzyme-substrate, and enzyme-product complexes associated with both an established well-characterized biological system (lysozyme hydrolysis of N-acetylglucosamine) and an important modern receptor-ligand complex (FKBP-FK-506 and FKBP-rapamycin) . These examples and recent applications of negative ion MS and MS/MS with DNA adducts, heme-globin complexes, and antibiotic-binding proteins suggest an exciting new area of applications for MS that have not been previously available to investigators.

Nihon Kyobu Shikkan Gakkai Zasshi, 1993 Dec, 31(12), 1606 - 11
{Acute exacerbation following bronchoalveolar lavage in idiopathic interstitial pneumonia}; Yoshitomi A et al.; We report two cases of idiopathic interstitial pneumonia (IIP) with acute deterioration after bronchoalveolar lavage (BAL) . Case 1 was a 54-year-old woman, and case 2 was a 75-year-old man . Both were diagnosed as having IIP, and hospitalized with complaints of high fever and dyspnea . After BAL, the degree of dyspnea increased . White blood cell count and lactate dehydrogenase were elevated, and PaO2 was decreased . Chest X-ray revealed consolidation of the upper lung fields and reticulo-granular shadows spreading through both lungs . BAL fluid examination showed an elevated neutrophil fraction (case 1: 6.5%, case 2: 35.2%), suggesting respiratory tract infection although bacteria could not be detected . Case 1 died of respiratory failure despite corticosteroid therapy . Autopsy revealed diffuse alveolar damage with focal pneumonia in the right S6 corresponding to the upper lobe consolidation . Case 2 improved after antibiotic therapy . These findings suggest that aspiration of infected fluid during BAL can cause acute exacerbation of IIP . It is important to recognize that the BAL procedure can induce an acute exacerbation of IIP.

J Chromatogr Sci, 1993 Dec, 31(12), 498 - 501
Characterization of three rifamycins via electrospray mass spectrometry and HPLC-thermospray mass spectrometry; Korfmacher WA et al.; Rifamycins are a class of antibiotic compounds of which rifampicin is the most commonly prescribed . Conventional electron-impact mass spectrometry of rifampicin has not been found to provide useful data . Thermospray and electrospray mass spectrometry are studied as potential tools for the analysis of rifampicin, rifamycin SV, and rifamycin B . Using thermospray and electrospray ionization, all three compounds provide significant ion intensity for either the {MH}+ or {MNa}+ ions . In addition, combined high-performance liquid chromatography-thermospray mass spectrometry provides useful analytical data for a mixture of the three rifamycins.

Trans R Soc Trop Med Hyg, 1993 Dec, 87 Suppl 3, 47 - 8
Diarrhoeal disease: current concepts and future challenges . Diarrhoeal disease--a military perspective; Kilpatrick ME; Diarrhoeal disease has always been a major medical problem during military operations . Lost personnel time has been significant, with over 50% of deployed forces being affected and unable to do their jobs for several days . During 'Operation Desert Shield' in Saudi Arabia in 1990, the US military took extensive precautions to prevent diarrhoeal disease . Surveys from 1% of the 200,000 US military personnel in Saudi Arabia indicated that 97% experienced diarrhoea, 22% sought medical care, and 19% were not able to perform their duties while affected . Medical evaluation of 452 individuals with diarrhoea determined a bacterial aetiology in 50% and a clear relationship with consumption of local fruits and raw vegetables . Prophylactic antibiotic administration was not a reasonable proposal and treatment was effective only when susceptibility patterns of local enteric agents were considered . Research efforts must continue for diagnostic tests to indicate which individuals with diarrhoeal disease would benefit from early antibiotic therapy and for development of vaccines effective against the common agents of diarrhoeal disease.

Jpn J Antibiot, 1993 Dec, 46(12), 1075 - 82
{Clinical evaluation of a new cephem S-1108 in infants and children}; Kino M et al.; A clinical study in children has been performed on S-1108, a newly developed cephem antibiotic . S-1108 was given orally to 30 patients, at doses between 8 and 12 mg/kg/day in 3 divided doses for 2 to 10 days . Clinical evaluations were made on 26 patients consisting of 12 patients of pharyngitis, 5 of tonsillitis and of impetigo, one each of bronchitis, cystitis, lymphadenitis and cellulitis . Overall clinical effects were excellent in 10, good in 15, fair in 1 with an efficacy rate of 96% . As to adverse reactions, mild diarrhea (2 patients) and transients elevation of transaminases (one patient) were observed . These data suggest that S-1108 is a useful oral antibiotic for the treatment of bacterial infections in children.

Ginekol Pol, 1993 Dec, 64(12), 587 - 90
{Personal experiences and effects of treatment in chronic, recurrent, aggravating inflammation of uterine adnexa}; Malarewicz A et al.; Authors presented the treatment of chronic, recurrent, aggravating inflammation of uterine adnexa currently used in their Ward and performed the task of evaluating the results of the carried out therapy . Material included 99 diseased women, at the age of 18-45, hospitalized at the Ward because of adnexitis chronica exacerbata . It was assumed that the criterion of recovery was regression of all clinical symptoms found by subjective and objective examination at the beginning of the treatment . Combined antibiotic-corticoid therapy was carried out complementary to resorptive treatment with lime and magnesium preparations, with ichthyol, dystreptase and a series of intravenous injection of chlormethine hydrochloride . Good results were achieved as far as regression of objective and subjective symptoms is concerned in 98% of the treated cases . Recurrence of the illness appeared in 6%.

Int J Artif Organs, 1993 Dec, 16 Suppl 5, 45 - 50
Survival after PBSC transplantation and comparison of engraftment speed with autologous and allogeneic marrow transplantation: results of a multicenter study; Iacone A et al.; We have analyzed the results of a multicenter study on peripheral blood stem cell transplantation (PBSCT) performed on 55 patients suffering from various neoplastic diseases . After myeloablative therapy, they received a median of 6.8 x 10(8)/kg MNC and 11.4 x 10(4)/kg CFU-GM harvested by a median of 9 apheresis after mobilization with chemotherapy alone . As of date, 34 of the 55 patients are alive and 28 of them are in continuous complete remission after a follow-up of 30 months . The probability of survival was related to the disease status at transplant, CR/PR vs . PD (p = 0.0001) and the bone marrow involvement, BM-vs . BM+ (P = 0.009) . Furthermore, a comparative study on speed of engraftment and clinical management was conducted on the 55 PBSCT patients as well as on 41 autoBMT and 52 alloBMT patients . Days to reach WBC > 1.0 x 10(9)/L, PMN > 0.5 x 10(9)/L and PLT > 50 x 10(9)/L was 12/14/33 for PBSCT, 17/20/23 for ABMT and 15/16.5/18 for BMT, respectively . Days with fever > 38 degrees C, systemic antibiotic therapy and length of hospitalization was 3/12/36 for PBSCT, 5/18.5/42 for ABMT and 9/25/46 for BMT respectively.

Proc Natl Acad Sci U S A, 1993 Dec 1, 90(23), 11122 - 6
Glyceraldehyde-3-phosphate dehydrogenase is required for the transport of nitric oxide in platelets; McDonald B et al.; Nitric oxide (NO) or NO-generating compounds like sodium nitroprusside (SNP) increase cellular levels of cGMP and produce S-nitrosylation of glyceraldehyde-3-phosphate dehydrogenase {GAPDH; D-glyceraldehyde-3-phosphate:NAD+ oxidoreductase (phosphorylating), EC 1.2.1.12} . In search of a reagent that could discriminate between these two effects, we used the sesquiterpene antibiotic koningic acid, which binds to GAPDH at the Cys-149 of the active site . Koningic acid inhibited basal and sodium nitroprusside-stimulated NAD-dependent covalent modification of purified rabbit muscle GAPDH in a dose-dependent manner . Furthermore, we tested the effect of koningic acid on human platelets . Approximately 90% of GAPDH is present in the cytosol of human platelets, and the exposure of platelet cytosol to koningic acid inhibited GAPDH activity, while the soluble guanylyl cyclase (basal and sodium nitroprusside-stimulated) activity remained unaltered . Pretreatment of intact platelets with koningic acid slowed the rate of aggregation induced by a submaximal concentration of thrombin . In addition, the antibiotic also inhibited the cGMP increases triggered by SNP, S-nitroso-N-acetylpenicillamine (SNAP), and 3-morpholinosyndomidine (SIN-1) but failed to prevent an increase in cGMP caused by nitrosylated albumin . Under the same conditions, koningic acid also inhibited basal and SNP- SNAP-, and SIN-1-stimulated NAD-dependent modification of GAPDH and its enzymatic activity . These results suggest that the mechanism of delivery of NO from SNP, SNAP, and SIN-1 to platelets may require the active form of GAPDH . When NO is delivered by nitrosylated albumin, active GAPDH was not necessary.

J Neurosurg, 1993 Dec, 79(6), 929 - 35
Subdural empyema of the cervical spine: clinicopathological correlates and magnetic resonance imaging . Report of three cases; Levy ML et al.; A paucity of formally described information is available in the scientific literature regarding spinal subdural empyema . Patients presenting with neurological deterioration associated with subdural empyema are rarely identified, and treatment is often based upon anecdotal cases . The authors contribute three cases of primary cervical spinal subdural empyema and review the seven found in the literature . All patients had clinical evidence of neurological compromise, cervical tenderness, cervical pain, and leukocytosis upon admission . Cervical involvement ranged from C-2 to C-7 . All patients underwent laminectomy with durotomy and drainage . The authors recommend prompt surgical decompressive laminectomy, copious irrigation, and drainage, followed with appropriate adjunctive antibiotic therapy for treatment of these patients.

Wiad Lek, 1993 Dec, 46(23-24), 941 - 3
{Abdominal actinomycosis imitating non-operable stage of cancer}; Madrzak D et al.; In a 44-year-old woman on the basis of short hospital medical observation and gynaecological consultations, malignancy of reproductive organs was preliminarily diagnosed . During the operation the gynaecological-surgical team confirmed the presence of generalized neoplastic process in the abdominal cavity . In the obtained surgical specimens actinomycosis was diagnosed by histological examination . Longterm antibiotic therapy caused an improvement of the patient's condition, increase of body weight, improvement of blood morphologic picture, regression of tumour-like changes in the liver . The case reminds the necessity of taking into account actinomycotic infection in the differential diagnosis of conditions suggesting a neoplastic process in the abdominal cavity.

Wiad Lek, 1993 Dec, 46(23-24), 929 - 32
{A case of coexisting allergic aspergillosis of the lungs with branchial candidiasis}; Sieminska A; A case is presented of allergic bronchopulmonary aspergillosis in a 36-year-old man . This disease was accompanied by bronchial candidiasis as the complication after longterm antibiotic therapy administered before the diagnosis was established . Diagnostic difficulties and outstanding effects of combined antifungal and corticoid treatment are described.

Afr J Med Med Sci, 1993 Dec, 22(4), 53 - 6
Hydrophobic response of Escherichia coli exposed to subminimal inhibitory concentrations of ampicillin and chloramphenicol; Salami JO et al.; Hydrophobicity generally increased as the cells passed from lag to exponential phases of growth and declined in the stationary phase . All concentrations of ampicillin used increased hydrophobicity, although still subject to effect of phase of growth . Chloramphenicol caused decline in hydrophobicity . Combination of the two antibiotics gave a concentration dependent balance of the two forces observed . Protein synthesis inhibition may render cells resistant to phagocytic uptake by lowering surface hydrophobicity . This phenomenon is probably involved in cases of therapeutic failures, persistent of recurrent infections . This is a further indication of the undesirability of antibiotic abuse.

Biochem Biophys Res Commun, 1993 Nov 30, 197(1), 85 - 91
Cytotoxic effect of free bleomycin A5-iron (II) complex and its conjugates with concanavalin A, insulin and calcitonin on mouse thymocytes; Matkhanov IE et al.; The possibility of using the antibiotic bleomycin as a part of a hybrid molecule consisting of a targeting fragment and a generator of reactive oxygen species has been investigated . The bleomycin-iron (II) complex was shown to destroy the plasma membrane of thymocytes by producing reactive oxygen species . Antioxidants protected the cells from destruction thus pointing to its free-radical mechanism . The protective effects of catalase and superoxide dismutase indicate that superoxide radical and hydrogen peroxide being formed during autooxidation of the complex are involved in cell damage . The covalent binding of bleomycin to targeting molecules (concanavalin A, insulin, and calcitonin) enhanced the ability of the bleomycin-iron (II) complex to destroy the plasma membrane of thymocytes.

Biochemistry, 1993 Nov 23, 32(46), 12279 - 82
Specific ammonium ion requirement for functional ribosomal RNA tertiary structure; Wang YX et al.; In compactly folded RNAs, coordination or hydrogen bonding of cations in specific sites is a potentially important aspect of the tertiary structure . NH4+ specifically stabilizes the tertiary structure of a conserved, 58-nt fragment of the large subunit ribosomal RNA, as judged in two ways: a melting transition associated with tertiary interactions is sharpened and stabilized more effectively by NH4+ than by any alkali metal cation, and the affinity of the RNA fragment for ribosomal protein L11 or the antibiotic thiostrepton is approximately 10-fold stronger when measured in NH4+ than in Na+ . The dependence of the melting temperature on NH4+ concentration shows that a single bound ion is responsible for these effects . The requirement of different ribosome functions for NH4+ suggests that other such sites exist in ribosomal RNAs.

Biochem Pharmacol, 1993 Nov 17, 46(10), 1819 - 24
NAD depletion after in vitro exposure of murine lung slices to bleomycin; Hoyt DG et al.; Bleomycin (BLM), a DNA-cleaving, antitumor antibiotic, causes pulmonary fibrosis . It also causes cell injury and activates the nuclear enzyme poly(ADP-ribose) polymerase (PAP; EC 2.4.2.30) in lung slices exposed to the drug in vitro . 3-Aminobenzamide (3-AB), a PAP inhibitor, prevents enzyme activation and cell injury . We have examined the potential role of ATP and NAD depletion in injury of BLM-sensitive C57B1/6N and -resistant BALB/cN murine lung slices treated with BLM or deprived of glucose, the major metabolic substrate of lung . Lung slices either were treated for 45 min with injurious concentrations of BLM (10-500 micrograms/mL) or were incubated without glucose, in the presence or absence of 2.5 mM 3-AB . Only the highest concentration of BLM, 500 micrograms/mL, caused any ATP depletion, and this 35% decrease was transient, occurring at 220 min in C57B1/6N slices . In contrast, glucose deprivation caused 50-70% ATP depletion in slices from both strains . BLM alone at 100 and 500 micrograms/mL caused a sustained 30-70% NAD depletion from 75 min through 400 min in C57B1/6N mouse lung slices . In the resistant BALB/cN lung slices, NAD depletion by BLM was only seen at 400 min . 3-AB almost completely antagonized NAD depletion in slices from both strains . In contrast to BLM, glucose deprivation did not decrease NAD levels unless 3-AB was present in C57B1/6N slices . Thus, ATP depletion may play a role in the injurious effects of glucose deprivation, but does not appear to be a major factor in pneumocyte injury caused by BLM . NAD depletion or other effects of PAP activation appear to account for the strain-selective, injurious effect of BLM on lung tissue.

Blood, 1993 Nov 15, 82(10), 3012 - 8
Combination protocols of cytokine therapy with interleukin-3 and granulocyte-macrophage colony-stimulating factor in a primate model of radiation-induced marrow aplasia; Farese AM et al.; Single cytokine therapy with granulocyte-macrophage colony-stimulating factor (GM-CSF) or interleukin-3 (IL-3) has been shown to be effective in decreasing the respective periods of neutropenia and thrombocytopenia following radiation- or drug-induced marrow aplasia . The combined administration of IL-3 and GM-CSF in normal primates suggested that a sequential protocol of IL-3 followed by GM-CSF would be more effective than that of GM-CSF alone in producing neutrophils (PMN) . We investigated the therapeutic efficacy of two combination protocols, the sequential and coadministration of recombinant human IL-3 and GM-CSF relative to respective single cytokine therapy, and delayed GM-CSF administration in sublethally irradiated rhesus monkeys . Monkeys irradiated with 450 cGy (mixed fission neutron:gamma radiation) received either IL-3, GM-CSF, human serum albumin (HSA), or IL-3 coadministered with GM-CSF for days 1 through 21 consecutively postexposure, or IL-3 or HSA for days 1 through 7 followed by GM-CSF for days 7 through 21 . All cytokines and HSA were injected subcutaneously at a total dose of 25 micrograms/kg/d, divided twice daily . Complete blood counts (CBC) and platelet (PLT) counts were monitored over 60 days postirradiation . The respiratory burst activity of the PMN was assessed flow cytometrically, by measuring hydrogen peroxide (H2O2) production . Coadministration of IL-3 and GM-CSF reduced the average 16-day period of neutropenia and antibiotic support in the control animals to 6 days (P = .006) . Similarly, the average 10-day period of severe thrombocytopenia, which necessitated PLT transfusion in the control animals, was reduced to 3 days when IL-3 and GM-CSF were coadministered (P = .004) . The sequential administration of IL-3 followed by GM-CSF had no greater effect on PMN production than GM-CSF alone and was less effective than IL-3 alone in reducing thrombocytopenia . PMN function was enhanced in all cytokine-treated animals.

Biochemistry, 1993 Nov 2, 32(43), 11669 - 75
Conformation-selective DNA strand breaks by dynemicin: a molecular wedge into flexible regions of DNA; Kusakabe T et al.; We present evidence that the enediyne antitumor antibiotic dynemicin recognizes and cleaves conformationally flexible regions of DNA . This is based on specific strand breaks at mismatches, bulges, and nicks as determined by high-resolution sequencing gels . On the basis of the weak association constant of dynemicin for DNA, it is expected that these more flexible regions would be preferred sites . In addition, the DNA unwinding behavior of dynemicin and the absorption spectrum of the dynemicin-DNA complex are strongly indicative of its intercalative binding with DNA . The results allow us to propose dynemicin as a molecular wedge that binds to the DNA by intercalating into the minor-groove side of conformationally flexible regions of DNA . Presumably, DNA local flexibility is able to create an open pocket in the minor groove, permits facile intercalation of dynemicin, and then increases the chances of its DNA damaging event . Implications for the biological action of dynemicin have also been discussed.

Can J Neurol Sci, 1993 Nov, 20(4), 319 - 23
The focal encephalopathies associated with mycoplasma pneumoniae; Sheth RD et al.; Five patients with evidence of focal encephalopathy are reported . In each case, evidence of mycoplasma pneumoniae infection was detected . No patient improved with conventional antibiotic therapy, but in three subjects, rapid and complete recovery did occur contemporaneously with the administration of high dose steroid therapy . It is suggested that focal as well as diffuse cerebral or cerebellar lesions may occur as manifestations of auto-immune disease complicating mycoplasmal infections in young people and that this illness may be designated as acute mycoplasma-associated encephalopathy.

J Adolesc Health, 1993 Nov, 14(7), 540 - 2
Adolescent knowledge of bacterial endocarditis prophylaxis; Cetta F et al.; OBJECTIVE: To determine if adolescents with congenital heart disease have adequate knowledge of bacterial endocarditis prophylaxis . DESIGN: Forty-eight adolescents attending a congenital heart disease summer camp were asked to complete an eight-question survey to assess their knowledge of heart disease, endocarditis, and endocarditis prophylaxis . RESULTS: Forty-five of 48 (94%) completed the questionnaire . Thirty-one (69%) knew the name of their heart disease . Two correctly defined endocarditis . None knew measures which could prevent endocarditis . Although 36 (80%) knew they needed to take "a medicine" prior to dental procedures, only 18 (40%) knew that an antibiotic was needed . There were significant gender differences for knowledge of antibiotics and for knowledge of current medications . However, patient gender and regular use of cardiac medications did not correlate significantly with knowledge of endocarditis or bacterial endocarditis prophylaxis . CONCLUSION: Whereas most adolescents know the names of their heart lesions and current medications, knowledge of endocarditis and bacterial endocarditis prevention and prophylaxis is inadequate.

J Rheumatol, 1993 Nov, 20(11), 1979 - 81
Fusobacterium septic arthritis of the sternoclavicular joint; Lau ES et al.; We describe a case of septic arthritis of the sternoclavicular joint caused by Fusobacterium in an otherwise healthy young man . The Fusobacterium had morphologic features most in keeping with Fusobacterium (F.) necrophorum, which was a common organism in sternoclavicular septic arthritis in the preantibiotic era . To our knowledge this is the first reported case of a fusobacterium sternoclavicular joint infection in the antibiotic era . This case should lead to heightened awareness of sternoclavicular joint infection and fusobacterium joint infection in the healthy host.

Int J Clin Pharmacol Ther Toxicol, 1993 Nov, 31(11), 557 - 60
Netilmicin kinetics in urology; Astobieta A et al.; Plasma kinetics of netilmicin, an aminoglycoside antibiotic was studied in 62 patients undergoing urologic surgery . Despite the use of a standard 100 mg-dose, no toxic levels were achieved except in one patient . A poor correlation was found between netilmicin plasma elimination constant and creatinine clearance (r = 0.34, p = NS) . We can conclude that the prediction of netilmicin plasma concentrations is not possible using only demographic patient's data . The monitoring of netilmicin levels should be performed in long-term treatments but not in 4-dose regimes such as in urologic prophylaxis.

Chem Pharm Bull (Tokyo), 1993 Nov, 41(11), 1955 - 9
Fungal metabolites . IX . Synthesis of a membrane-modifying peptide, hypelcin A-III, from Hypocrea peltata; Matsuura K et al.; A membrane-modifying peptide antibiotic having uncoupling activity on rat liver mitochondria, hypelcin A-III, has been synthesized by assembling five peptide fragments via the N,N'-dicyclohexylcarbodiimide method . The synthesized hypelcin A-III was identical with the natural product.

Eur J Clin Nutr, 1993 Nov, 47(11), 794 - 802
Diet and dental caries in preschool children; McMahon J et al.; A study was carried out in two New Zealand cities with a fluoridated water supply, to look at the dietary habits of preschool children and to investigate whether any dietary factors or other variables are associated with dental decay in the deciduous teeth of these children . From a final study of 355 (a 59% response rate), demographic data, a dental examination, a series of three 24 h recalls over a period of 1 year, and a food frequency questionnaire to cover the same 1 year interval were collected . The sample included 93 children with dental decay and 262 caries-free children, matched for age, sex and sociodemographic variables . The energy and nutrient intakes of the preschool children were sufficient to support normal growth . The main sources of dietary energy in the diets of this study group came from bakery and dairy products . Boys had slightly higher mean intakes of most nutrients than girls . No significant differences were found in the food patterns or intakes of macronutrients between the children of this study group with caries and those without . There was an inverse relationship between social background and dental health, with increasing social advantage being associated with decreasing dental health problems . Syrup medicines and, in particular, antibiotic syrups independently increased the risk that a child would have a number of carious lesions, especially if taken frequently.

Nippon Kyobu Geka Gakkai Zasshi, 1993 Nov, 41(11), 2266 - 9
{Extended tricuspid valve excision for active infective endocarditis associated with ventricular septal defect}; Tedoriya T et al.; We report a patient of ventricular septal defect associated with a vegetations on the tricuspid valve and a perforation of the aortic cusp caused by infective endocarditis . Antibiotics could not relieve the high fever of this patient, and disseminated intravascular coagulation caused by sepsis and two-sided heart failure developed . She underwent extended tricuspid valve excision, aortic valve replacement and VSD closure during the active stage . Post-operative antibiotic therapy was continued intravenously for 6 weeks, and orally for 3 more weeks . Although post-operative right ventriculography indicated tricuspid regurgitation and right atrium enlargement, pressure study of the right side of the heart revealed normal hemodynamics.

HNO, 1993 Nov, 41(11), 512 - 8
{The Wittmaack temporal bone collection and possibilities for cataloguing with electronic data processing}; Pau HW et al.; Karl Wittmaack, head of the otology department at Greifswald (1904-1908) and professor of otorhinolaryngology at the universities of Jena (1908-1925) und Hamburg (1926-1946) created a unique histological collection of human and animal temporal bones that is thought to be the largest of its kind in the world . The serial sections of more than 1700 human temporal bones still represent current otological problems--many of which are now rare but are still encountered--such as tuberculosis, lues or diphtheria of the ear . Complications following acute otitis--which were much more frequent and dangerous in the pre-antibiotic era--can be studied in detail . There are numerous cases of labyrinthitis, meningitis, sinus thrombosis, brain abscess etc.--complications which must always be borne in mind to this day . The same is true for tumors like acoustic neurinomas or even malignant tumors, metastases, or manifestations of leukemia . Differences in pneumatization or changes of the bone structure as in otosclerosis have been the subjects of studies dating from Wittmaack's time until very recently . In spite of its topicality, the true value of the collection has only be appreciated by a limited group of persons, which may be due in part to difficulties in orientation within this vast amount of material . Although there are catalogues, it may be difficult to find the appropriate preparations for particular questions . Searching for such specimens often requires rummaging through the whole collection, sometimes resulting in damage or loss of slides or handwritten notes.(ABSTRACT TRUNCATED AT 250 WORDS)

Mamm Genome, 1993 Nov, 4(11), 639 - 43
Insertional mutation of the hairless locus on mouse chromosome 14; Jones JM et al.; Crosses between heterozygous transgenic mice from line 5053 produced offspring with progressive irreversible hair loss beginning at day 19 . With increasing age, the skin of these animals became thicker and plicated in appearance . Histological analysis revealed the complete absence of normal hair follicles and numerous intradermic cystic structures, which enlarged with time and became filled with keratinaceous material . Test crosses demonstrated that the affected animals are homozygous for the transgene insertion . The clinical and histological phenotype of the new mutant closely resembles that of the rhino allele at the hairless locus on Chromosome (Chr) 14 . Complementation tests and linkage analysis indicate that the transgene has interrupted the hairless locus . It has been demonstrated previously that mutation at the hr locus is accompanied by a variety of immune deficiencies . Many of the older affected transgenic mice developed an impetigo-like skin eruption which responded to antibiotic ointment and which may reflect impaired immune function . The transgenic allele, hrTgN5053Mm, will be useful for identification of the transcription unit of the hairless locus.

J Gen Microbiol, 1993 Nov, 139 ( Pt 11), 2811 - 7
Periodic selection in longterm continuous-flow cultures of the filamentous fungus Fusarium graminearum; Wiebe MG et al.; By monitoring increases and decreases in the proportion of cycloheximide-resistant macroconidia, periodic selection was observed in populations of the filamentous fungus Fusarium graminearum, grown in glucose-limited chemostat cultures . The results indicated that periodic selection of advantageous mutants of F . graminearum occurred at intervals of about 124 h at both high (D = 0.19 h-1, approximately 34 generations) and low (D = 0.06 h-1, approximately 11 generations) dilution rates . Several 'adaptive' peaks (each indicating the appearance of an advantageous mutation) were observed before morphological (highly branched) mutants appeared in the populations; these mutants have previously been observed to have a selective advantage over the parental strain . At intervals, macroconidia harvested from the chemostat were used to inoculate plates of non-antibiotic-containing agar medium, and it was possible to monitor periodic selection in the original chemostat culture using second generation macroconidia harvested from these cultures . The proportion of cycloheximide-, potassium chlorate-, and p-fluoro-DL-phenylalanine-resistant macroconidia in these second generation macroconidia changed in a pattern similar to that observed when monitoring the proportion of cycloheximide-resistant macroconidia in the first generation population harvested directly from the chemostat . The experiments demonstrated that populations of filamentous fungi are heterogeneous and that much of this heterogeneity may already be present at the end of batch growth, i.e., before the onset of continuous cultivation.

Am J Perinatol, 1993 Nov, 10(6), 438 - 40
Association of clinical intra-amniotic infection and meconium; Wen TS et al.; The objective of this study was to determine the rate of intra-amniotic infection in patients with meconium-stained amniotic fluid compared to controls . With a retrospective case-controlled study design, we compared 100 pregnant women with meconium to 100 pregnant women without meconium for the development of intra-amniotic infection . Patients delivered between September 1 and December 31, 1990 . Exclusion criteria were active infection prior to labor or antibiotic use within the 7 days prior to delivery . We diagnosed clinical intra-amniotic infection in patients with ruptured membranes by a maternal temperature 100.4 degrees F or higher and any two of the following: maternal or fetal tachycardia, uterine tenderness, white blood cell count 10,500 mm3 or more, or foul-smelling amniotic fluid . Demographic variables, labor characteristics, maternal infectious morbidity, and neonatal outcome were analyzed using the Wilcoxin rank test, chi-square test, or Fisher's exact test as appropriate . The rate of clinical intra-amniotic infection was significantly higher in women with meconium-stained amniotic fluid (8%) compared with women with no meconium (2%) (p = 0.05).

Pediatr Infect Dis J, 1993 Nov, 12(11), 916 - 21
Fever and neutropenia in children with cancer: a therapeutic approach related to the underlying disease; Petrilli AS et al.; Antibiotic monotherapy is increasingly an option for the initial empiric treatment of febrile neutropenic cancer patients . We noted in a previous study that response to empiric therapy was related more to disease classification (solid tumors vs . leukemia) than to the regimen chosen . In the present study we based empiric monotherapy on the underlying disease in treating 240 episodes of fever and neutropenia in 145 children . Patients with leukemia or Stage III/IV non-Hodgkin's lymphoma (higher risk group) were treated with imipenem-cilastatin, whereas those with solid tumors or Stage I/II non-Hodgkin's lymphoma (lower risk group) received ceftriaxone . The regimens were modified in 15% of lower risk and 45% of higher risk episodes . Overall successful outcomes were obtained in 93.2% of the higher risk (n = 119) and 97.5% of the lower risk (n = 121) episodes . The two groups differed significantly in duration of neutropenia, frequency of positive blood cultures and superinfection and the need for modification of the monotherapy (P < 0.05) . Empiric monotherapy based on primary disease appears to be safe and effective for febrile neutropenic children with cancer at our Brazilian institution . Further studies will be needed before these findings can be generalized to patient populations in other settings.

Arch Dis Child, 1993 Nov, 69(5), 550 - 4
Remission death in acute lymphoblastic leukaemia: a changing pattern; Atra A et al.; The pattern of remission deaths was examined in 842 children with acute lymphoblastic leukaemia (ALL) treated at a single centre over 18 years . The mortality rate from leukaemia fell significantly during three consecutive time periods during which treatment became progressively more intensive and that during remission induction fell from 3.5% to under 1%, but the rate of death in remission stayed constant at 5-6% . The factors associated with an increased risk of remission death were: young age, a higher leucocyte count, bone marrow transplantation, and Down's syndrome . The pattern of remission deaths changed over the years; measles and herpes viruses decreased while deaths associated with periods of intensification and gut toxicity increased . Four children developed second neoplasms . Treatment of ALL is still associated with a significant risk of death in remission but the pattern of infective deaths has changed . Many should be avoidable by provision of adequate supportive care, close supervision after periods of intensive treatment, and appropriate antibiotic, antifungal, and cytokine therapy.

Transplantation, 1993 Nov, 56(5), 1137 - 42
The efficacy and toxicity of rapamycin in murine islet transplantation . In vitro and in vivo studies; Fabian MC et al.; We performed an in vivo and in vitro dose-response study of the novel immunosuppressive macrolide antibiotic rapamycin looking at murine islet allograft survival, impact on glucose homeostasis, and possible tissue toxicity . A total of 300 islets were isolated from CBA/J mice (H-2k) and transplanted beneath the renal capsule of streptozotocin-induced diabetic BALB/c (H-2d) recipients . Seven groups of allografted mice received intraperitoneally for 7 days post-transplant: no immunosuppression (n = 8); vehicle only (carboxymethyl-cellulose) (n = 6); or rapamycin at dosages of 0.05 (n = 8), 0.1 (n = 8), 0.3 (n = 8), 1.0 (n = 8), or 5.0 (n = 6) mg/kg/day . Blood glucose was monitored on alternate days, with graft failure defined by the first day of persistently high blood glucose (> 14 mmol/L) . The 0.1 and 0.3 mg/kg/day groups showed statistically significant prolongation of diet allograft survival (P < 0.01) when compared to the controls and vehicle-treated mice . Three mice in both the 0.1 and 0.3 mg/kg/day groups and one mouse in the 0.05 mg group reached 100 days normoglycemia and, following nephrectomy of the islet-bearing kidney, returned to hyperglycemia . The 0.05, 1.0, and 5.0 mg/kg/day groups showed no statistically significant prolongation of graft survival . In addition, the higher dosage (1.0 and 5.0 mg/kg/day) groups had erratic blood glucose control . Histologically, there was no evidence of toxicity seen in any of the multiple organ samples . In the in vitro analysis, BALB/c (H-2k) islets cultured in either 0, 10, 30, or 100 ng/ml rapamycin had no significant differences in insulin secretion following a 24-hr culture period; however, there was a significant deterioration in glucose stimulated insulin release after 72 hr culture at high rapamycin concentration (100 ng/ml) . Rapamycin significantly prolonged murine islet allograft survival . At doses 10 to 50 times the effective antirejection dosage, we demonstrated adverse impact on glucose homeostasis without histological evidence of end-organ toxicity . We also demonstrated an adverse impact on insulin release in vitro following prolonged culture (72 hr) in a high concentration of rapamycin.

Mol Pharmacol, 1993 Nov, 44(5), 1064 - 9
Antihelicase action of DNA-binding anticancer agents: relationship to guanosine-cytidine intercalator binding; Bachur NR et al.; DNA-binding antibiotics such as intercalators, narrow groove binders, and other substances modify duplex DNA, making it an altered substrate for DNA helicases . The intercalators daunorubicin, actinomycin D, echinomycin, and elsamicin, the narrow groove binders distamycin and mithramycin, and the plant toxin teniposide, each representing a different chemical class, block SV40 large T antigen DNA helicase action with IC50 values ranging from 4 x 10(-8) to 2 x 10(-6) M . A partially purified human HeLa cell DNA helicase is also potently blocked by daunorubicin, distamycin, and teniposide . Because eukaryotic cells contain helicases of varying abundance, specificity, and type, this site of action for DNA-binding antibiotics may help explain antibiotic potency and specificity for DNA or RNA inhibition . The antihelicase effect of the antibiotic-double-stranded DNA complex may be central to the anticancer activities of these substances . An additional interesting correlation is the antihelicase action of DNA-intercalating antibiotics and their DNA-binding preference for G-C base pair sites . The G-C base pair binding preference of the intercalating antibiotics may result from evolutionary selection because of the higher G-C binding stability, compared with A-T binding stability . The combination of the higher base pair stability at G-C regions and increased duplex DNA stability induced by intercalating antibiotic yields a total additive stability of the intercalator-G-C base pair complex that resists helicase action.

Vet Clin North Am Food Anim Pract, 1993 Nov, 9(3), 445 - 68
Procedures for mastitis diagnosis and control; Sears PM et al.; Procedures for mastitis diagnosis and control include culturing individual cow and bulk tank milk samples, antibiotic susceptibility testing, and evaluation of somatic cell count reports and clinical mastitis treatment records . Integrated use of such procedures is necessary for effective mastitis diagnosis and control.

Arthritis Rheum, 1993 Nov, 36(11), 1621 - 6
Persistence of Borrelia burgdorferi in ligamentous tissue from a patient with chronic Lyme borreliosis; Haupl T et al.; OBJECTIVE . To document the persistence of Borrelia burgdorferi in ligamentous tissue samples obtained from a woman with chronic Lyme borreliosis . METHODS . Spirochetes were isolated from samples of ligamentous tissue, and the spirochetes were characterized antigenetically and by molecular biology techniques . The ligamentous tissue was examined by electron microscopy . Humoral and cellular immune responses were analyzed . RESULTS . Choroiditis was the first recognized manifestation of Lyme disease in this patient . Despite antibiotic therapy, there was progression to a chronic stage, with multisystem manifestations . The initially significant immune system activation was followed by a loss of the specific humoral immune response and a decrease in the cellular immune response to B burgdorferi over the course of the disease . "Trigger finger" developed, and a portion of the flexor retinaculum obtained at surgery was cultured . Viable spirochetes were identified . Ultramorphologically, the spirochetes were situated between collagen fibers and along fibroblasts, some of which were deeply invaginated by these organisms . The cultured bacteria were identified as B burgdorferi by reactions with specific immune sera and monoclonal antibodies, and by polymerase chain reaction amplification and Southern blot hybridization techniques . CONCLUSION . To our knowledge, this is the first report of the isolation of B burgdorferi from ligamentous tissue . This suggests that tendon tissues serve as a specific site of spirochete residence in human hosts.

Arthritis Rheum, 1993 Nov, 36(11), 1493 - 500
"Chronic Lyme disease" as the incorrect diagnosis in patients with fibromyalgia; Hsu VM et al.; OBJECTIVE . To evaluate a large number of patients referred with persistent symptoms thought to represent chronic Lyme disease . METHODS . We retrospectively reviewed the charts of nearly 800 patients referred with persisting nonspecific musculoskeletal and/or neurologic symptoms thought to represent chronic Lyme disease . RESULTS . Seventy-seven patients were found to have fibromyalgia, not ongoing Lyme disease, as the explanation of their chronic symptoms . Many had received multiple courses of antibiotic therapy for symptoms of fibromyalgia mistakenly attributed to chronic Lyme disease . No patient reported permanent and/or total resolution of fibromyalgia symptoms following antibiotic therapy . Appropriate therapy for fibromyalgia in those who remained compliant, however, was often effective in improving some if not all of the chronic symptoms . CONCLUSION . Fibromyalgia is a treatable and potentially curable disorder, and should be considered in the evaluation of patients with "refractory Lyme disease."

Arch Surg, 1993 Nov, 128(11), 1253 - 9
Clinical diagnostic applications of the polymerase chain reaction . Infection and rejection; Rettinger SD et al.; In this review, we describe the power and sensitivity of the polymerase chain reaction and indicate areas of clinical medicine in which it is currently being applied . As this technology and automation improves and is simplified, its realm of application will expand, but its major impact will continue to be its facilitation of early, specific diagnoses in infectious disease, genetics, cancer, and transplantation . Polymerase chain reaction is currently most useful in the care of opportunistic infections in immunosuppressed hosts and in making the distinction between infection and rejection in transplant recipients . As the technique becomes more widely available and less costly, its application should minimize the need for broad-spectrum antibiotic therapy of infections, lower costs, and perhaps even shorten hospitalization . These potential beneficial effects of polymerase chain reaction will be particularly relevant in the current cost-conscious health-care environment.

Med J Aust, 1993 Nov 1, 159(9), 598 - 601
Typhoid in 1993; La Brooy JT; Typhoid remains a disease of major importance world-wide although improvements in public health have made it an exotic disease in developed countries like Australia . Effective antibiotic therapy with the advent of chloramphenicol, which was first used to treat typhoid in the 1940s, has also dramatically altered the natural course of the disease and reduced its mortality rate from around 25% to as low as 1% . The main areas of recent change include the emergence of resistance to previously effective antibiotics, more aggressive intervention in the management of severe typhoid and some of its complications such as perforation, and the development of an oral typhoid vaccine that may replace the equally effective but more unpleasant parenteral vaccination that has been widely used since World War.

J Bacteriol, 1993 Nov, 175(22), 7474 - 8
Identification of the gene encoding an N-acetylpuromycin N-acetylhydrolase in the puromycin biosynthetic gene cluster from Streptomyces alboniger; Lacalle RA et al.; The biologically inactive compound N-acetylpuromycin is the last intermediate of the puromycin antibiotic biosynthetic pathway in Streptomyces alboniger . Culture filtrates from either this organism or Streptomyces lividans transformants harboring the puromycin biosynthetic gene cluster cloned in low-copy-number cosmids contained an enzymic activity which hydrolyzes N-acetylpuromycin to produce the active antibiotic . A gene encoding the deacetylase enzyme was located at one end of this cluster, subcloned in a 2.5-kb DNA fragment, and expressed from a high-copy-number plasmid in S . lividans.

J Bacteriol, 1993 Nov, 175(21), 6932 - 8
Characterization of the Tn5 transposase and inhibitor proteins: a model for the inhibition of transposition; de la Cruz NB et al.; Tn5 is a composite transposon consisting of two IS50 sequences in inverted orientation with respect to a unique, central region encoding several antibiotic resistances . The IS50R element encodes two proteins in the same reading frame which regulate the transposition reaction: the transposase (Tnp), which is required for transposition, and an inhibitor of transposition (Inh) . The inhibitor is a naturally occurring deletion variant of Tnp which lacks the N-terminal 55 amino acids . In this report, we present the purification of both the Tnp and Inh proteins and an analysis of their DNA binding properties . Purified Tnp, but not Inh, was found to bind specifically to the outside end of Tn5 . Inh, however, stimulated the binding activity of Tnp to outside-end DNA and was shown to be present with Tnp in these bound complexes . Inh was also found to exist as a dimer in solution . These results indicate that the N-terminal 55 amino acids of Tnp are required for sequence-specific binding . They also suggest that Inh inhibits transposition by forming mixed oligomers with Tnp which still bind to the ends of the transposon but are defective for later stages of the transposition reaction.

J Bacteriol, 1993 Nov, 175(21), 6916 - 24
Precursor flux control through targeted chromosomal insertion of the lysine epsilon-aminotransferase (lat) gene in cephamycin C biosynthesis; Malmberg LH et al.; Targeted gene insertion methodology was used to study the effect of perturbing alpha-aminoadipic acid precursor flux on the overall production rate of beta-lactam biosynthesis in Streptomyces clavuligerus . A high-copy-number plasmid containing the lysine epsilon-aminotransferase gene (lat) was constructed and used to transform S . clavuligerus . The resulting recombinant strain (LHM100) contained an additional complete copy of lat located adjacent to the corresponding wild-type gene in the chromosome . Biological activity and production levels of beta-lactam antibiotics were two to five times greater than in wild-type S . clavuligerus . Although levels of lysine epsilon-aminotransferase were elevated fourfold in LHM100, the level of ACV synthetase, whose gene is located just downstream of lat, remained unchanged . These data strongly support the notion that direct perturbation of alpha-aminoadipic acid precursor flux resulted in increased antibiotic production . This strategy represents a successful application of metabolic engineering based on theoretical predictions of precursor flux in a secondary metabolic pathway.

Br J Cancer, 1993 Nov, 68(5), 856 - 61
A novel cell-based assay for the evaluation of anti-ras compounds; Jenkins DC et al.; In order to identify drugs active against mutated ras oncogenes we have developed an in vitro assay employing two clones of the human fibrosarcoma cell-line, HT1080 which carries an N-ras gene mutated at codon 61 . Clone, HT1080scc2, retains the transformed phenotype of the parental line, whilst the other, HT1081c, is a morphologically flat, non-tumourigenic, revertant with under-representation of the chromosome carrying the transforming N-ras allele . The clear implication of mutant ras in maintaining the transformed nature of HT1080scc2 was confirmed when these cells were microinjected with the pan ras neutralising antibody Y13-259, which resulted in the morphological detransformation of these cells to a phenotype resembling that of the HT10801c clone . A number of known anti-cancer drugs with modes of action unrelated to ras function were found to be equipotent against both clones . However, when compounds chosen on the grounds of their potential selective cytotoxic or differentiating activity were tested some interesting results were obtained . Thus 8-bromo cAMP affected some morphological detransformation of HT1080scc2 cells and reduced their colony forming potential . The IMP-dehydrogenase inhibitors, tiazafurin and mycophenolic acid also flattened the morphology of the transformed clone . Fumagillin, an antibiotic reported to exhibit selective activity against ras transformed cells showed very marked and selective cytostatic effects against HT1080scc2 cells with IC50 values as low as 1 x 10(-11) M.

Zhonghua Zhong Liu Za Zhi, 1993 Nov, 15(6), 423 - 6
{Modulation of mutagenic drug-induced unscheduled DNA synthesis (UDS) in primary rat hepatocytes by diallyl trisulfide}; Deng DJ; Most anticancer drugs are mutagenic/carcinogenic . A possible exception is diallyl trisulfide (DAT), a component of garlic, which inhibits growth of transplantable tumors in vitro and in vivo and mutagenicity and carcinogenicity of genotoxic agents . It is an antimutagenic anticancer chemical . Its modulating effect on induction of UDS by mutagenic mitomycin C (MMC), cyclophosphamide (CP), and cis-diamine dichloroplatin (DDP) was investigated with the assay in primary cultures of Wistar rat hepatocytes by autoradiographic technique . Results showed that MMC (1-10 mumol/L), CP (0.316-3.16mmol/L), and DDP(3.16-31.6mumol/L) resulted in a significant induction of dose-dependent UDS and that DAT (0.5-4.0 mumol/L) significantly enhanced induction of UDS by MMC, CP and DDP while DAT itself did not . A dose-response relation was also observed between the dosage of DAT and the enhancement of induction of UDS . Hepatocellular enzymes for metabolic activation of indirect mutagens may not be involved in the enhancement of UDS-induction since DAT also increased UDS level induced by direct mutagen DDP . DAT promotes UDS induction probably by increasing repair of damaged 4-DNA . DAT, an anti-infection antibiotic, may be used in cancer chemotherapy to alleviate the adverse side effects of chemotherapeutic agents with mutagenic/carcinogenic activities.

Pediatr Med Chir, 1993 Nov-Dec, 15(6), 631 - 4
{Liver abscess: is drug therapy only possible?}; Ciancio S et al.; We describe a case of liver abscess, whose favourable evolution, after the initial medical treatment, started when we didn't know the diagnosis, persuaded us to continue the begun treatment, based on localization of disease and on clinical improvement, instead of carrying out on evacuative puncture . At moment, according to our knowledge, this is the third case of liver abscess which has recovered by on antibiotic rational treatment without surgical punctures . Can we treat the liver abscess like the pneumonia according to features of localization and clinical history?

Trends Microbiol, 1993 Nov, 1(8), 310 - 4
Genetic transformation of mycobacteria; Hatfull GF; Recent advances in methods for introducing DNA into both fast- and slow-growing species of mycobacteria have stimulated the construction of a variety of cloning vectors and the development of a versatile genetic system . These tools will facilitate studies of mycobacterial pathogenicity, antibiotic action and drug resistance, and lead to more effective methods for diagnosis, prevention and treatment of mycobacterial diseases.

Minerva Chir, 1993 Nov, 48(21-22), 1361 - 6
{Office surgery: organization, legislative, and medico-legal problems . Personal experience}; Pepe N et al.; INTRODUCTION . The authors approach the subject of office surgery by underlining the advantages of this procedure . In particular, they focus attention on the anesthesiological and legislative problems . Depending on the setting used for surgery and the duration of hospitalisation, ambulatorial surgery can be divided into: day-hospital, office surgery, one-day surgery, short-stay surgery, same-day surgery, MATERIALS AND METHODS . The authors report their own experience relating to 103 cases with relative complications . A total of 103 operations of medium-to- major ambulatorial surgery were performed (100 females and 3 males, mean age 36.8) . One week prior to surgery all patients attended a medical out-patient examination in order to fill in medical records and be prescribed routine hematochemical tests, chest X-ray and ECG . The preoperative anesthesiological evaluation was made at the time of surgery . All patients received antibiotic prophylactic treatment . RESULTS . Postoperative complications were reported above all following neuroleptoanalgesia and amounted to a total of 5 cases: nausea (4 cases) associated with vomit (1 case), and postural hypotension (1 case) . No infective complications were observed . DISCUSSION AND CONCLUSIONS . The authors emphasise the importance of a careful preoperative selection of patients; an out-patient structure equipped with the appropriate instrument and machinery for surgery and the constant presence of anesthetists to ensure correct anesthesia (local, neuroleptoanalgesic, peridural general), reanimation and postoperative care . The aims of ambulatorial surgery are, in broad terms, the safety of procedures, convenience for the patient and organisational and economic savings for health structures . Ambulatorial surgery has an extremely high acceptance rate by patients . Lastly, the authors also report the juridical and bureaucratic problems faced by ambulatorial surgery and look forward to its wider diffusion . In the future office surgery might represent an important contribution to surgical therapeutic strategies, allowing, if well organised, an excellent compromise between safety, convenience and reduced costs for the patient.

Braz J Med Biol Res, 1993 Nov, 26(11), 1219 - 29
Differential effect of amphotericin B on the three evolutive stages of Trypanosoma cruzi and on the host cell-parasite interaction; de-Castro SL et al.; 1 . Amphotericin B (Am.B) was shown to have a direct effect on T . cruzi, with the three forms of the parasite presenting different susceptibilities to the drug in the following order: amastigotes > trypomastigotes > epimastigotes . These differences highlight the importance of using the vertebrate forms of the parasite in tests of new drugs . 2 . The treated parasites showed alterations of the plasma membrane, suggesting that, as in fungi, the primary effect of Am.B was probably via formation of complexes with membrane components . 3 . When exposed to filipin, another polyene antibiotic, the three parasite forms were observed to present a similar order of susceptibility, with comparable ultrastructural modifications . 4 . Higher concentrations of Am.B were required to damage the intracellular parasites in vitro, 2.3 micrograms/ml for parasites inside peritoneal macrophages and 7 micrograms/ml for parasites inside heart muscle cells . 5 . Am.B is effective against the parasite, but is also toxic to mammalian cells . Testing of Am.B for the control of Chagas' disease by blood transfusion may be useful, since bloodstream forms are lysed by lower concentrations of the drug than those required to affect intracellular parasites.

Mol Biochem Parasitol, 1993 Nov, 62(1), 37 - 44
Two more independent selectable markers for stable transfection of Leishmania; Freedman DJ et al.; Genetic transformation of Leishmania has relied upon two exogenous selectable markers, neo and hyg, encoding resistance to G418 and hygromycin B respectively . There is a need for multiple independent selectable markers, since Leishmania is diploid and experimental sexual crosses are not currently feasible . Here we report on the development of two additional markers: pac, conferring resistance to the glycopeptide antibiotic puromycin, and phleo, conferring resistance to the DNA-binding drug phleomycin . We constructed a set of four analogous shuttle vectors with these four markers, using DNA segments flanking the Leishmania major H region hmtxr gene to provide information required for expression . These constructs (pHM-NEO, pHM-HYG, pHM-PAC and pHM-PHLEO) were successfully transfected into L . major, mostly with efficiencies comparable to those observed with previous DHFR-TS-based neo and hyg-containing constructs . The exception was pHM-PHLEO, which transfected 30-fold less efficiently; this may be related to the nonenzymatic mechanism of resistance encoded by phleo . All four constructs were shown to replicate extra-chromosomally . Stable transfectants bearing all paired combinations of pHM constructs were obtained by a second round of transfection . These data show that the four markers are functionally independent and in conjunction with the Leishmania N-acetylglucosaminyl transferase gene, brings the number of selectable markers available in Leishmania to five.

Nutr Rev, 1993 Nov, 51(11), 327 - 32
The underprivileged, developing country child: environmental contamination and growth failure revisited; Solomons NW et al.; A major public health challenge to human populations in developing countries is poor linear growth and failure to maximize genetic potential in final adult stature . It is now clear that this process occurs in early life, and neither genetics nor dietary intake, or both, is the complete determinant . We suggest that a situation similar to the phenomenon of impaired growth of poultry and livestock reared under unsanitary conditions occurs in children from underprivileged countries . Recent advances in cell biology and immunology suggest that the intermittent or continuous activation of the acute-phase response with the consequent mediation of catabolic and antitrophic metabolic processes is responsible for the antibiotic-responsive growth impairment of chicks raised in unhygienic environments . Ongoing epidemiological studies in poor Third World children provide evidence for a prevalence of acute-phase response activation in the absence of overt clinical signs . The consequences of this immunostimulation of the growing infant or toddler could represent an important additional factor in the failure of children in developing countries to manifest adequate growth and to achieve their genetic potential for adult stature.

New Horiz, 1993 Nov, 1(4), 550 - 62
Diagnosis and treatment of pulmonary infections in adult respiratory distress syndrome; Leeper KV Jr; Nosocomial bacterial pneumonia, or the recently introduced term, "ventilator-associated pneumonia," is a common cause of infection in adult respiratory distress syndrome (ARDS) . The presence of ventilator-associated pneumonia in ARDS patients is associated with prolonged ventilatory support and increased mortality rates . Unfortunately, clinical and radiographic diagnoses of pneumonia are sensitive but nonspecific and, at best, select a patient population for which further diagnostic evaluation is warranted . The empiric use of broad-spectrum antibiotics in mechanically ventilated patients without pneumonia may be harmful by facilitating colonization and superinfection with virulent organisms . Recent techniques for sampling lower respiratory tract secretions (protected specimen brushing, bronchoalveolar lavage), via fiberoptic bronchoscopic and nonbronchoscopic guidance have been used to establish improved accuracy in the diagnosis of pneumonia . Although these methodologies are not in widespread use in the ICU setting, the results obtained, when properly performed and with carefully processed specimens, may direct the clinician to the appropriate antibiotic therapy and provide a method of assessing its effectiveness . Moreover, if pneumonia is not confirmed, then an aggressive reevaluation of fever and pulmonary infiltrates in the patient with ARDS is indicated.

J Med Assoc Thai, 1993 Nov, 76(11), 597 - 600
Ultrasound-guided liver biopsy: accuracy, safety and sonographic findings; Pongchairerks P; An experience of 97 liver biopsies performed under the guidance of a portable ultrasonographic procedure was reviewed . Of the 88 cases in which the results of biopsy were available, 73 malignant and 7 benign liver diseases were correctly diagnosed by the procedure, an accuracy of 90.9 per cent . There was no mortality . Significant complication was observed in 5 cases and consisted of 3 cases of intraperitoneal bleeding that required only blood transfusion, one case of upper gastrointestinal bleeding presumed to be hemobilia and one case of persistent fever of 38 degrees C that subsided after antibiotic administration . Ultrasound-guided liver biopsy can be an effective and safe outpatient procedure for pathological diagnosis of liver diseases . Analysis of sonographic and histologic correlation revealed that the types of sonographic appearance could not be significantly correlated to the histologic nature of the masses . Therefore, accurate prediction of pathology of liver masses from their sonograms is not possible.

Biotechnol Prog, 1993 Nov-Dec, 9(6), 555 - 72
Sustaining protein synthesis in the absence of rapid cell division: an investigation of plasmid-encoded protein expression in Escherichia coli during very slow growth; Flickinger MC et al.; The minimum growth rate capable of supporting plasmid-encoded gene expression is determined using continuous cultures of Escherichia coli MZ9387 at dilution rates (D) as low as 5% of the maximum specific growth rate . Expression from a low copy number plasmid, pMPR166, encoding cyanase under the control of P(lac) is investigated in order to study plasmid-encoded gene expression under conditions approaching starvation . Plasmid copy number was stabilized by selection in the presence of 500 micrograms/mL chloramphenicol by constitutive expression of chloramphenicol acetyl transferase (CAT) . Plasmid retention was determined by dot-blot hybridization and chloramphenicol resistance . The contribution of plasmid maintenance and cyanase expression to the maximum cell yield (Y'x/s) and the maintenance coefficient (ms) was determined for MZ9387 and MZ9387:pMPR166 under uninduced and IPTG-induced conditions . The values of Y'x/s and ms for non-plasmid-bearing cultures were 0.56 g of cell dry mass (DCM)/g of glucose and 0.26 g of glucose/g of DCM.h, respectively . The cell yield for plasmid-bearing cultures under uninduced conditions (Y 0'x/s) was 0.28 g of DCM/g of glucose, with m0s = 0.08 g of glucose/g of DCM.h . These values decreased following induction of cyanase expression . Glucose consumption in the presence of IPTG was linearly related to the growth rate at D < 0.28 h-1 but nonlinear at dilution rates greater than 50% of the maximum specific growth rate, indicating that cyanase expression alters metabolism and glucose consumption . The fraction of plasmid-free cells decreased with decreasing Damkohler number (Da) . These data confirm the usefulness of Da for predicting the relationship between plasmid-free and plasmid-bearing cells where plasmids are stabilized by concentrations of antibiotic greater than the minimum plasmid-free host cell growth inhibitory concentration . Specific cyanase expression increased as the dilution rate decreased to D = 0.15 h-1 . Between D = 0.15 h-1 and D = 0.14 h-1, expression decreased 7-fold . At very low dilution rates (D < or = 0.06 h-1), nonseptated filamentous cells appeared . The appearance of filamentous cells could be reversed by increasing the dilution rate . These data are evidence that when plasmid copy number is stabilized by chloramphenicol resistance, a minimum dilution rate exists below which stringent regulation of protein synthesis dramatically reduces gene expression.

Haematologica, 1993 Nov-Dec, 78(6), 383 - 8
Autologous transplantation of peripheral blood progenitor cells mobilized by chemotherapy with or without G-CSF (filgrastim) in resistant lymphoproliferative diseases: enhanced hemopoietic recovery with filgrastim primed progenitors; Sica S et al.; BACKGROUND AND METHODS . Bone marrow transplantation is increasingly used to overcome the bone marrow toxicity from myeloblative therapy . Peripheral blood progenitor cell transplantation (PBPCT) has been recognized as an alternative source of bone marrow for hemopoietic recovery after myeloblative therapy . In the steady state condition hemopoietic progenitors are scarce in peripheral blood; chemotherapy and growth factors are both able to increase PBPCs . Twenty-five patients affected by resistant lymphoproliferative diseases {4 multiple myeloma (MM), 19 non Hodgkin's lymphoma (NHL) and 2 Hodgkin's disease (HD)} were submitted to autologous peripheral blood progenitor cell transplantation (PBPCT) . PBPCs were collected after chemotherapy (CT) alone (8 patients) or plus filgrastim (17 patients) . Filgrastim was not administered after PBPCT in any case . RESULTS AND CONCLUSIONS . A statistically significant difference between the two groups was found for the following parameters: number of leukaphereses administered, amount of CFU-GM infused, time to hemopoietic recovery, amount of supportive care, number of days of antibiotic therapy, length of hospitalization . PBPCs primed with filgrastim CT appeared to be markedly superior to CT-recruited PBPCs in reducing the period of neutropenia and, surprisingly, of thrombocytopenia . Reduction in hematologic toxicity resulted in a decrease of transplantation-related toxicity and mortality, even in elderly and/or heavily pretreated patients.

Am J Otol, 1993 Nov, 14(6), 601 - 4
Effects of otitis media on child development; Baldwin RL; Otitis media is one of the most common diseases of childhood, and the broad continuum of this disease ranges from asymptomatic middle ear effusion to recurring or persistent infection . In spite of many modalities of successful treatment, there remains a large number of children with chronic otitis media after antibiotic management and even in some persistent cases after surgical management with ventilation and tube insertion . This report attempts to concisely review the studies on the effect of otitis media on childhood development.

Nurs N Z, 1993 Nov, 1(8), 19 - 22
Wound performance; Nicholls J; The purpose of this study was to collect information about wound management practices which would establish baseline wound healing data . This data would be used to make measurable comparisons with new wound management techniques . This study focuses on data collected from the surgical area of Auckland Hospital . All patients whose wounds were surgically acquired were included in the study . Data collection was started immediately post-operatively and continued at each dressing change until the patient was discharged . The data collection tool was developed from "nursing expectations" of wound healing performance . This previously undefined set of expectations is an aggregate of the result of nursing knowledge, nursing experience and individual patients' conditions . The tool was refined against actual wound recovery and became a standard to test the accuracy of expectations . The wounds involved in this study were categorised and allocated expected healing rates . This was linked with discharge planning . It was against the stated range of expectations that wounds were measured for performance, as--"better than (expected)," "average," or "less than." Patients were divided into three broad age groups that reflected a particular health status and pre-existing influences . The groups chosen were: "20 years and under," "20 to 70 years" and "70 years plus." These groups were used as indicators to determine risk for wound management . Wound healing was measured as to whether it met nursing expectations . Factors such as wound appearance, complications, solutions and induction antibiotic cover were also measured . Findings show the hospital has a minimal level of complications of surgically acquired wounds.(ABSTRACT TRUNCATED AT 250 WORDS)

Int J Immunopharmacol, 1993 Nov, 15(8), 853 - 63
The in vitro action of FK 565, bleomycin and cyclosporin A on different cell populations, with respect to the release of GM-CSF in the mouse; Blaney BA et al.; The experimental immunostimulatory tripeptide FK 565, the anti-tumor antibiotic Bleomycin and the immunosuppressive agent Cyclosporin A were examined for their in vitro effects on granulocyte-macrophage colony stimulating factor (GM-CSF) production utilizing different cell populations from three distinct murine stains . FK 565 produced an increase in GM-CSF release in all three experimental models used, providing evidence that FK 565 is among other things, a macrophage stimulating agent . Bleomycin increased GM-CSF release in the BALB/c and the 'Scid' mouse . Paradoxically with cells from the 'nude' mouse a significant decrease was observed, indicating that Bleomycin may induce a suppressive effect on B-cells . Cyclosporin A was found to inhibit the release of GM-CSF from BALB/c mice, however, no effect was observed in either 'nude' or 'Scid' mice.

Biochemistry, 1993 Oct 19, 32(41), 11149 - 54
Tetracenomycin F2 cyclase: intramolecular aldol condensation in the biosynthesis of tetracenomycin C in Streptomyces glaucescens; Shen B et al.; Tetracenomycin (Tcm) F2 cyclase, which catalyzes the cyclization of the anthrone Tcm F2 to the naphthacenone Tcm F1 in the biosynthesis of the anthracycline antibiotic Tcm C in Streptomyces glaucescens, has been purified to homogeneity and characterized . The N-terminal sequence of the enzyme establishes that it is encoded by the tcmI gene, whose deduced product has a molecular weight of 12,728 . SDS-PAGE analysis gave a single band with a molecular weight of 12,500, whereas gel-filtration chromatography yielded a molecular weight of 37,500, indicating that the Tcm F2 cyclase is a homotrimer in solution . Under pH > or = 8.0, the enzyme catalyzes the cyclization of Tcm F2 to Tcm F1 and has a Km of 121 +/- 18.2 microM and Vmax of 704 +/- 62.3 nmol.min-1.mg-1 . In contrast, under pH < or = 6.5, it catalyzes the cyclization of Tcm F2 to 9-decarboxy Tcm F1, a known shunt metabolite of the Tcm C biosynthetic pathway . Tcm F2 cyclase represents the first discrete enzyme for carbon-carbon bond formation via an intramolecular aldol condensation-dehydration mechanism, a key biochemical operation proposed in the early steps of the biosynthesis of all aromatic polyketides.

Am J Ophthalmol, 1993 Oct 15, 116(4), 424 - 30
Paresis of a vertical rectus muscle after cataract extraction; Esswein MB et al.; Nine patients had a permanent paresis of a vertical rectus muscle after cataract extraction . We sought to determine the common factors associated with and their contribution to vertical muscle paresis after cataract extraction . The study design included a survey that was conducted among the referring cataract surgeons and anesthesiologists with particular attention to surgical technique and anesthetic administered, as well as a medical history and examination and appropriate laboratory tests . Patients had a complete ophthalmic examination including prism cover testing in all nine diagnostic positions, forced-duction testing, and saccadic velocity and generated muscle force estimation . The results of the study demonstrate no correlation between the pareses and the use of a bridle suture, antibiotic or corticosteroid injection, systemic disease, or surgical technique . Peribulbar anesthesia was the most consistent feature in seven of the nine cases . In the other two, an atypical retrobulbar injection had been given . On the basis of the location of the injections, the needle type, and the concentration and quantity of the anesthetic injected, we conclude that permanent pareses of a vertical rectus muscle may be caused by a myotoxic effect of the local anesthetic.

J Mol Biol, 1993 Oct 5, 233(3), 488 - 97
A local alignment method for protein structure motifs; Orengo CA et al.; A method for the comparison of protein three-dimensional substructures was developed . The method employs the double dynamic programming method of Taylor & Orengo but identifies multiple local alignments rather than a single global alignment . A modification based on the Smith Waterman algorithm for sequence alignment enables the automatic identification and growth of the most structurally similar local alignments irrespective of length and composition . The method can also be used in a search mode to match substructures . Roughly five minutes is required to find all Greek-key motifs in a protein of 100 residues . Two novel globin folds have been detected using the method, the antibiotic protein colicin A and diphtheria toxin, neither of which have any functional relationship to the globins.

Toxicology, 1993 Oct 5, 82(1-3), 169 - 89
Biotransformation of methylxanthines in mammalian cell lines genetically engineered for expression of single cytochrome P450 isoforms . Allocation of metabolic pathways to isoforms and inhibitory effects of quinolones; Fuhr U et al.; V79 Chinese hamster cells genetically engineered for stable expression of single forms of rat cytochromes P450IA1, P450IA2, P450IIB1, human P450IA2, and rat liver epithelial cells expressing murine P450IA2 were used to allocate metabolic pathways of methylxanthines to specific isoforms and to test the suitability of such cell lines for investigations on drug interactions occurring at the cytochrome expressed . The cell lines were exposed to caffeine and/or theophylline and concentrations of metabolites formed in the medium were determined by HPLC . Caffeine was metabolized by human, rat and murine P450IA2, resulting in the formation of four primary demethylated and hydroxylated metabolites . However, there were differences in the relative amounts of the metabolites . The human and the mouse P450IA2 isoforms predominantly mediated 3-demethylation of caffeine . The rat cytochrome P450IA2 mediated both 3-demethylation and 1-demethylation of caffeine to a similar extent . The results support the hypothesis that caffeine plasma clearance is a specific in vivo probe for determining human P450IA2 activity . Addition of the quinolone antibiotic agents pipemidic acid or pefloxacin, both known to inhibit caffeine metabolism in vivo and in human liver microsomes, reduced formation rates of all metabolites of caffeine in cells expressing rat and human P450IA2 . Theophylline was mainly metabolized via 8-hydroxylation . All cell lines tested were able to carry out this reaction, with highest activities in cell lines expressing rat or human P450IA2, or rat P450IA1.

J Trauma, 1993 Oct, 35(4), 512 - 7
Diagnosing pneumonia in mechanically ventilated trauma patients: endotracheal aspirate versus bronchoalveolar lavage; Sauaia A et al.; We prospectively investigated the diagnostic value of semiquantitative (semiQC) and quantitative (QC) cultures of endotracheal aspirate (ETA) compared with QC of bronchoalveolar lavage (BAL) fluids in 18 mechanically ventilated trauma patients with clinical signs of pneumonia . The general agreement between QC of ETA and BAL was 89% when conventional cutoffs for the QC were used and 94% if the cutoffs were adjusted for previous antibiotic therapy . In all six patients whose clinical diagnoses of pneumonia were considered definite, both QC of ETA and QC of BAL were positive; however, standard semiQC of ETA showed comparable results in this group . On the contrary, in the 12 patients whose clinical diagnoses were uncertain, QC of BAL and ETA were negative in ten patients and in five (50%) of these, pneumonia was eventually excluded . Semiquantitative cultures of ETA were positive in all these patients . Five (28%) patients experienced a decrease in PaO2/FiO2 (> 15% of previous value) 2 hours after BAL, and in three (17%) this derangement persisted for 24 hours . These data suggest that BAL may be hazardous in mechanically ventilated trauma patients and that its use should be restricted to patients in whom the diagnosis is in doubt.

J Neurosurg, 1993 Oct, 79(4), 619 - 31
Neurosurgeon as innovator: William V . Cone (1897-1959); Preul MC et al.; Neurosurgeons are well known for being productive researchers and innovators . Few, however, have possessed the prolific ingenuity of William Cone . In 1934, he and William Penfield were cofounders of the Montreal Neurological Institute where, until 1959, he filled the twin roles of neurosurgeon-in-chief and neuropathologist . Because he did not find writing easy, many of his technical inventions and refinements remained unpublished . His numerous innovations included the extensive use of twist-drill technique for biopsy, drainage for subdural hematoma and cerebral abscess, and ventriculography . In the mid-1940's, he developed power tools driven by nitrogen that led to the modern, universally used air-driven tool systems . He had a special interest in the treatment of spinal dysfunction, for which he invented the Cone-Barton skull-traction tongs along with the Cone spinal operating table . He also devised operative procedures for vertebral fracture-dislocation and craniospinal anomalies . For the maintenance of muscle tone in the paralyzed bladder, he constructed a tidal drainage system . He introduced and popularized ventriculoperitoneal shunting techniques and carried out some of the earliest experimental trails to treat brain infections with sulphonamide and antibiotic drugs . He designed his own set of surgical suction devices, bone rongeurs, and a personal suction "air-conditioning" system for each surgeon . He had a keen early interest in intracranial tumors, and also demonstrated on monkeys how subdural mass lesions caused pupillary dilation and mesial temporal lobe damage due to cerebral compression . His work for the military during World War II on effects of altitude on brain pressure remained classified for many years . The first clipping and excision of an intracranial aneurysm is attributed to Cone . Although Penfield was known as "the Chief," Cone was referred to as "the Boss." His fervent dedication to provide total care to his patients was expressed in round-the-clock vigils; he did not separate "nursing" from "surgical" care . Ultimately, Cone's driving passion for perfection led in part to his tragic death . His accomplishments, inventions, and his example as teacher and physician have become part of neurosurgery's collective legacy.

Clin Orthop, 1993 Oct, (295), 8 - 12
Comparison of the clinical efficacy and tolerance of gentamicin PMMA beads on surgical wire versus combined and systemic therapy for osteomyelitis; Blaha JD et al.; These data do not prove a statistical superiority of conventional antibiotics or Septopal in the treatment of chronic osteomyelitis . This result, however, is complicated by the biased data set represented by the combined treatment . The data do suggest that cost of treatment is considerably less in patients who are treated with local antibiotics (i.e., Septopal) alone . The rate of adverse experiences was directly related to the use of parenteral antibiotics, with higher rates of adverse experiences in the conventional and combined treatment groups . Furthermore, the Cierny-Mader Physiologic Class had the best correlation with outcome, suggesting that host factors are probably of critical importance in inducing remission of chronic osteomyelitis . This protocol was not designed to test the role of debridement in the treatment of osteomyelitis: it was assumed that debridement would be the same in both groups . It is the investigators' strong opinion, however, that adequacy of debridement was an important determinant in quiescence or recurrence in the study patients . Similarly, there was no strict control for adequacy of soft-tissue coverage provided by local or distant tissue transfer . Again, the investigators believe that adequacy, including viability and durability, of soft-tissue covering was an important determinant for the end result in these patients . Other covariants such as smoking, history, nutritional status, and other measures of general health will be added to this model when data are available . This analysis will allow definition of the appropriate clinical situations in which use of Septopal alone or combined with parenteral antibiotic is indicated.

Clin Orthop, 1993 Oct, (295), 112 - 8
Septopal beads and autogenous bone grafting for bone defects in patients with chronic osteomyelitis; Patzakis MJ et al.; Thirty-five patients with chronic osteomyelitis were treated with autogenous bone grafts for bone defects . Of 35 patients, two were lost to follow-up evaluation . There were 27 men and six women . The age range was from 18 to 62 years (median age, 29 years) . The bones included 22 tibias, nine femurs, and two ulnas . The size of the bone defects ranged from 2.5 x 15 cm (median defect, 2.5 x 6 cm) . The length of infection ranged from two to 540 months (median, 31 months) . Twenty patients had nonunions and 19 patients required soft-tissue muscle transfers . Patients were treated with systemic antibiotics and/or gentamicin (Septopal) antibiotic beads . Twelve patients were treated with Septopal beads . The range of follow-up evaluation was 24 to 68 months (median, 47 months) . Thirty-one of 33 patients had one bone-graft procedure and two patients required two . The time from initial debridement and infection control to bone graft for patients not requiring soft-tissue muscle flaps was one to six weeks (median time, four weeks) . For patients requiring soft-tissue muscle transfer, the range was six to nine weeks (median, six weeks) . The median time to bone-graft incorporation was six months . All fractures united . Complications included two refractures from auto accidents in the immediate postoperative period, one partial muscle loss, one skin-graft loss, four pin tract draining sites, and two antibiotic-related skin rashes . There was one recurrent infection, and the infection arrest rate was 97%.(ABSTRACT TRUNCATED AT 250 WORDS)

Virology, 1993 Oct, 196(2), 458 - 74
Analysis of G418-selected Rat2 cells containing prototype, variant, mutant, and chimeric JC virus and SV40 genomes; Trowbridge PW et al.; The human polyomavirus JC virus (JCV) is highly tumorigenic in rodents, but transforms cells in culture inefficiently . To explore the basis for JCV's restricted transforming behavior, nonpermissive Rat2 cells were contransfected with pSV2-neo (encodes G418 resistance) and viral DNAs including prototype, variant, and mutant JCV genomes and two JCV-SV40 chimeras . By selecting cells displaying G418 resistance, lines were established that contain viral DNA and exhibit a wide range of transformed phenotypes . The G418-resistant lines were tested for their ability to grow under anchorage-independent conditions, to overgrow a monolayer of untransformed cells, and to form dense colonies on plastic . Expression of the viral T and t proteins and interaction of T protein with the cellular anti-oncoprotein p53 were measured . Also determined was the number of intact viral early coding regions integrated within the cellular DNA . The results of these studies suggested that most of the G418-resistant lines failed to express JCV T protein above a minimum threshold level required for their conversion to a fully transformed phenotype . In anchorage-independent growth assays, higher levels of a 17-kDa T-related peptide in JCV transformants appeared to compensate for decreased T antigen levels . Comparison of the T to p53 ratios in the cell lysates suggested that the quaternary structure of the JCV protein differed from that of its SV40 counterpart in the T-p53 complex . The presence of multiple vs single integrated copies of the viral genome in the cells did not correlate with elevated T antigen expression or an enhanced transformation status.

J Infect Dis, 1993 Oct, 168(4), 1042 - 5
Topical prophylaxis for Lyme disease after tick bite in a rodent model; Shih CM et al.; To determine whether infection with the Lyme disease spirochete (Borrelia burgdorferi) can be aborted by topical application of antibiotic to the site of tick attachment, individual infected nymphal deer ticks (Ixodes dammini) were permitted to feed on the ears of mice, and various antibiotics were applied to the feeding site at intervals after the replete infecting tick had detached . Infection in each mouse was determined by serology and by xenodiagnosis at 4 weeks after the bite of the infected tick . None of these mice became infected when antibiotic was topically applied to the site of tick attachment within 2 days after the spirochete-infected ticks had detached . In contrast, all nontreated and virtually all solvent-treated mice became persistently infected . Thus, persistent infection by the agent of Lyme disease can be aborted by appropriate topical application of antibiotic.

J Nat Prod, 1993 Oct, 56(10), 1799 - 804
Antifungal metabolites from Trichoderma harzianum; Ghisalberti EL et al.; A detailed examination of the metabolites produced in liquid cultures by a strain of Trichoderma harzianum, isolated from wheat roots, has resulted in the identification of a further five metabolites . Two of these, cyclonerodiol {5} and the octaketide keto diol 6, have previously been isolated from a strain of Trichoderma koningii . The structures of the three new octaketide-derived compounds 7, 8, and 10 have been deduced from spectroscopic and chemical studies . All newly isolated compounds show antibiotic activity towards the take-all fungus, Gaeumannomyces graminis var . tritici.

Aust N Z J Surg, 1993 Oct, 63(10), 811 - 4
Obturator foramen bypass in the management of infected prosthetic vascular grafts; Lai DT et al.; The obturator foramen bypass graft remains an excellent option for revascularizing the lower extremity when dealing with an infected prosthetic vascular graft in the groin . In this series, six obturator foramen bypass grafts were performed in five patients for infectious groin complications following vascular surgery . Conservative measures such as local antibiotic irrigation and abscess drainage designed to preserve the graft in situ had failed to eradicate the infection in all instances and was complicated by suture-line haemorrhage in three instances . An aggressive approach should be adopted, aimed at excision of the infected graft . The obturator foramen bypass graft remains a durable graft for limb salvage . Five out of six obturator foramen bypass grafts were patent after 11-26 months follow up.

Pharm Res, 1993 Oct, 10(10), 1516 - 20
Enhanced bioavailability of cefoxitin using palmitoylcarnitine . II . Use of directly compressed tablet formulations in the rat and dog; Sutton SC et al.; The performance of tablets containing the absorption enhancer palmitoylcarnitine chloride (PCC) and the antibiotic cefoxitin (CEF) was determined by direct placement of tablets in the rat stomach, small intestine, and colon . While the bioavailability (F) of tablets containing 12 mg CEF without PCC ranged from 0.6 to 3.9%, the addition of 24 mg PCC resulted in an enhanced CEF bioavailability in the rat colon (mean +/- SD: F = 57 +/- 19%) and rat jejunum (F = 71 +/- 16%) but not in the rat stomach . Following oral administration to dogs, tablets of 200 mg CEF without or with 600 mg PCC resulted in the same low bioavailabilities (7.0 +/- 10.3 and 7.0 +/- 3.6%, respectively) . However, when these tablets were enteric coated, PCC improved CEF bioavailability from 2.44 +/- 1.84 to 29.0 +/- 13.4% . Therefore, the use of enteric-coated direct compressed tablets containing PCC and direct compression excipients improved the peroral bioavailability of a poorly absorbed compound.

J Neurocytol, 1993 Oct, 22(10), 854 - 67
Freeze fracture analysis of apical membranes in cochlear cultures: differences between basal and apical-coil outer hair cells and effects of neomycin; Forge A et al.; Previous studies have shown that exposure of cochlear cultures to the ototoxic aminoglycoside antibiotic neomycin leads to the rapid formation of numerous membrane filled protrusions on the apical surface of the hair cells but not on the surrounding supporting cells, and that hair cells in basal-coil cultures are more sensitive to these effects of neomycin than those in the distal end of apical-coil cultures . Freeze-fracture has been used to examine and compare the apical surfaces of hair cells and supporting cells in basal and apical-coil cultures in order to look for features that may explain the differential sensitivity of the various cell types to neomycin, and to characterize the membrane type that forms in response to neomycin and compare it with the normal apical membrane of the hair cell . The apical surface of the highly responsive basal-coil outer hair cells differs significantly from the apical surfaces of apical-coil outer hair cells and supporting cells in both regions of the cochlea in both surface area and the number and density of endocytotic vesicles associated with this surface . Basal-coil hair cells have an average of 120 +/- 39 vesicles per cell surface and a density of 3.5 +/- 0.89 vesicles per microns 2, whereas apical-coil hair cells have 14.8 +/- 15.8 vesicles/cell surface and density of 0.73 +/- 0.72 vesicles per microns 2 . There are no significant differences in intramembrane particle (IMP) density on the apical surfaces of all the cell types examined, and qualitative observations of filipin-treated specimens indicate that cholesterol densities are also similar . The membrane that accumulates in response to neomycin treatment at the apical pole of the hair cell is IMP free, does not respond to filipin, and fractures in a manner that is indicative of a high content of unsaturated phospholipid in a fluid phase, and is therefore different in several respects from the normal apical surface of the hair cell . The results of this study suggest that apical surface associated endocytotic vesicle numbers may determine the differential sensitivity of apical and basal-coil hair cells to neomycin, and that neomycin may interfere with some aspect of phospholipid metabolism or membrane turnover in sensory hair cells.

Mol Cell Probes, 1993 Oct, 7(5), 357 - 60
Comparison of polymerase chain reaction and culture techniques for detection of Chlamydia trachomatis; Tabrizi SN et al.; The aim of this study was to compare culture and polymerase chain reaction techniques in detection of Chlamydia trachomatis in clinical specimens . Two hundred clinical specimens previously examined for C . trachomatis by culture were analysed blindly by polymerase chain reaction . A 144 bp fragment of DNA from the MOMP of C . trachomatis was amplified . In addition, a 250 bp segment of beta-globin gene was amplified as an internal control . In 27 culture negative specimens, the beta-globin amplicon was not detected . Of the 173 specimens assessable by PCR, 24 (13.8%) were positive by both methods . Four specimens were positive by PCR and negative by culture . Three were collected post-antibiotic treatment; two were from previous culture-proven chlamydia infection suggestive of the presence of DNA of non-viable organisms, and one case was toxic by culture . No specimen was positive by culture and negative by PCR . Overall PCR when compared to culture had a sensitivity of 100% and specificity of 97.3% with positive and negative predictive values of 85.7% and 100%, respectively . PCR is especially useful when culture results can not be confirmed due to toxicity, inadequate transport or insufficient specimen collected.

Pneumologie, 1993 Oct, 47(10), 593 - 6
{Extensive pulmonary tumor embolisms of anaplastic thyroid gland carcinoma as a rare cause of hemorrhagic pleural effusion in an 88-year-old patient}; Koppl H et al.; An 88 year old woman without substantial previous illness was admitted to hospital because of a rapidly developing dyspnea and thoracic pains . X-Ray, CT scan and ultra sound showed a subdivided pleural effusion of the left side . After a short time a pulmonary infiltrate as well as a contralateral pleural effusion developed . Neither tumor cells nor mycobacteria could be detected in repeated pleural punctions . The general condition of the patient was deteriorating continuously while an antibiotic therapy given in the meantime only led to a temporary recovery . Three weeks later the patient died under the picture of a cardio-respiratory failure . At autopsy the lungs showed parenchymal haemorrhages and multiple infarctions as well as pleural effusions . The above mentioned changes could be explained histologically by tumor embolism of small pulmonary arteries from an anaplastic thyroid carcinoma . The discussion gives a short survey about already published cases of tumor embolism in the lung . PMVC as the diagnostic method of choice is discussed.

Vet Hum Toxicol, 1993 Oct, 35(5), 414 - 8
Synergistic effects of monensin in combination with permethrin or neomycin on neuronal activity; Nation PN et al.; Drug combinations have the potential to produce novel and unpredictable responses on nervous tissue . This study was designed to test the hypothesis that the effects of combinations of monensin (an ionophore antibiotic) and either neomycin (an aminoglycoside antibiotic) or permethrin (synthetic pyrethroid) are synergistic . Effects of the drug combinations upon the electrical properties and membrane activities of an in vitro sensory neuron preparation were found to be greater than expected from addition of the effects of the same drugs acting individually, indicating synergism and thus supporting the hypothesis . It was concluded that drugs acting at different neuronal membrane sites and applied in combination produce unpredictable responses . Such drug combinations behave as if they were novel drugs.

Med Decis Making, 1993 Oct-Dec, 13(4), 293 - 301
Practice variation in the management of pharyngitis: the importance of variability in patients' clinical characteristics and in physicians' responses to them; Poses RM et al.; The objective of this study was to assess whether geographic differences in antibiotic-prescribing rates for patients with pharyngitis could be explained by intersite differences in patients' clinical characteristics and in how physicians responded to these clinical cues when making decisions . As part of the initial phase of a prospective controlled trial to improve physicians' diagnostic ability, the authors enrolled cohorts of consecutive patients seen at staff-model--HMO student health services in Pennsylvania and Nebraska . Physicians' decisions whether to prescribe antibiotics for 310 consecutive patients presenting with pharyngitis to the former and 214 such patients presenting to the latter at the time of the initial visit were examined . There was a large discrepancy between the antibiotic-prescribing rates at the student health services in Pennsylvania, 106/310, 32.4%, and Nebraska, 156/214, 72.9% . The clinical variables significantly independently associated with treatment at both sites in a logistic regression model were fever, adjusted odds ratio = 2.1 (95% CI = 1.1, 3.8); exudates, 5.4 (2.8, 10); palatine petechiae, 6.5 (1.5, 28); rhinorrhea, 0.46, (0.25, 0.85); and high risk of complications, 3.8 (1.04, 14) . There was a significant interaction between site and anterior cervical adenopathy, 5.5 (1.6, 19); and a borderline interaction between site and rhinorrhea, 2.4 (0.89, 6.7) . Site was not a significant independent predictor of treatment, 1.8 (0.45, 6.6.) . Practice variation was related to geographic differences in patients' clinical characteristics and in how physicians responded to these factors when prescribing antibiotics . How physicians weight patients' clinical characteristics when making decisions may be an important element of their "practice styles."

Am J Obstet Gynecol, 1993 Oct, 169(4), 970 - 6
Double-blind; placebo-controlled trial of piperacillin prophylaxis in preterm membrane rupture; Lockwood CJ et al.; OBJECTIVE: We attempted to test whether antibiotic therapy prolongs pregnancy in preterm premature rupture of membranes, because preterm premature rupture of membranes is frequently associated with chorionic-decidual infection . STUDY DESIGN: Women with preterm premature rupture of membranes and a singleton gestation at 24 to 34 completed weeks were randomized to receive either piperacillin 3 gm or placebo intravenously every 6 hours for 72 hours and were managed conservatively until spontaneous delivery, chorioamnionitis, or fetal distress . RESULTS: Between January 1987 and January 1992, a total of 75 patients were randomized to receive piperacillin (n = 38) or placebo (n = 37) . There were no differences between the piperacillin group and the placebo group in mean gestational age at randomization (30.2 +/- 3 vs 30.3 +/- 2.9 weeks) . However, a greater number of patients had pregnancy prolonged beyond 7 days (42.1% vs 10.8% p = 0.005) and the mean latency period was significantly prolonged (11.4 +/- 18.8 vs 6.1 +/- 13.6 days, p = 0.001) in the piperacillin group compared with the control groups . CONCLUSIONS: Use of intravenous piperacillin for 72 hours in preterm premature rupture of membranes significantly prolongs the latency period between membrane rupture and delivery.

Mov Disord, 1993 Oct, 8(4), 437 - 44
Increased striatal glucose consumption in Sydenham's chorea; Weindl A et al.; Positron emission tomography and 18F-fluorodeoxyglucose were used to measure the regional cerebral glucose consumption in a 15-year-old choreatic girl with classical Sydenham's chorea shortly after the onset of hyperkinetic movements and 5 months later after chorea had resolved and in a 74-year-old hemichoreatic woman with long-standing hyperkinesia as a residuum of Sydenham's chorea in adolescence . Whereas cerebellar, thalamic, and cortical glucose consumption was within normal limits in both patients, lentiform and caudate glucose consumption was significantly increased in both hemispheres of the 15-year-old patient and in the hemisphere contralateral to the chorea in the 74-year-old patient . In the younger patient, striatal glucose consumption returned to normal after her hyperkinesia had disappeared with antibiotic therapy . The observation of an increase in striatal glucose consumption in Sydenham's chorea, in contrast to the decrease of this variable encountered in the vast majority of other choreatic disorders, leads to questioning the pathophysiology of chorea in humans and suggests the use of emission tomographic measurement of variables related to cerebral energy metabolism for differential diagnosis in choreatic disorders.

Mol Gen Genet, 1993 Oct, 241(1-2), 73 - 80
Transient and stable gene expression in the fungal maize pathogen Cochliobolus heterostrophus after transformation with the beta-glucuronidase (GUS) gene; Monke E et al.; The bacterial GUS (beta-glucuronidase) gene has been used as a reporter gene in plants and bacteria and was recently expressed in filamentous fungi . Here, we report the application of GUS for the establishment of transient and stable gene expression systems in the phytopathogenic fungus Cochliobolus heterostrophus . The utility of the transient expression system is demonstrated in applications involving promoter analysis and in tests of various parameters of a transformation system, for comparing the rates of stable and transient transformation events using GUS as sole screening marker and for comparing different transformation systems using either GUS or a dominant selection marker . For these purposes two plasmids were constructed harbouring the GUS gene and the hph gene of Escherichia coli which confers resistance to the antibiotic hygromycin B (HygB), ligated either to the P1 or GPD1 (glyceraldehyde 3 phosphate dehydrogenase) promoter of C . heterostrophus . In transient expression studies the first appearance of GUS activity was observed within 2 h after transformation and maximal values were obtained after 7 or 10 h, depending on the promoter fused to the GUS gene . At peak activity, the GPD1 promoter was revealed to be five fold stronger than the P1 promoter . The same difference in promoter strength was observed when the vectors were stably integrated in the fungal genome . Using the GUS gene as a colour selection marker in plate assays, it was possible to detect transformants and monitor the process of transient gene expression visually . Blue transformants obtained by screening for the GUS phenotype were mitotically unstable . Transformants obtained by selecting for HygB resistance were mitotically stable and expressed the beta-glucuronidase gene constitutively.(ABSTRACT TRUNCATED AT 250 WORDS)

Kyobu Geka, 1993 Oct, 46(11), 937 - 40
{Extraction of infected pacemaker electrode using catheter and snare}; Mizuno A et al.; A 85-year-old man had undergone implantation of a transvenous pacemaker system in 1982 . Nine years later the generator was explanted and he was underwent implantation of a new generator and electrode . After one year of the second operation, infection of the old electrode had been noted and it was not cured in spite of partial explantation of the infected electrode and appropriate antibiotic therapy . We decided to remove the infected electrode and succeeded in extraction using catheter and snare . The patient's recovery was uneventful . We suggest catheter and snare is useful for explantation of chronic transvenous pacemaker electrodes.

Hematol Oncol Clin North Am, 1993 Oct, 7(5), 937 - 60
Management of the cancer patient with fever and prolonged neutropenia; Lee JW et al.; Cancer patients who suffer prolonged durations of fever and neutropenia are at high risk for developing serious infections . This article reviews the initial management of these fevers, subsequent modifications of the initial empirical regimens (both empirical changes in the antibiotic regimen and those changes directed at specific sites of infection that may become apparent during the course of prolonged neutropenia), and the potential impact of hematopoietic cytokines on future management of prolonged fever and neutropenia.

Hematol Oncol Clin North Am, 1993 Oct, 7(5), 919 - 35
Approach to treatment of the febrile cancer patient with low-risk neutropenia; Buchanan GR; All cancer patients who develop fever during a period of neutropenia are not at high risk of developing serious infection . Following hospitalization for empiric broad spectrum antibiotic therapy, certain low-risk patients can be identified and safely be discharged "early", prior to recovery of the absolute neutrophil count to 500 cells per mm3 . The medical, psychological, and financial benefits of early hospital discharge are immense . Careful examination for serial increases in components of the peripheral blood count herald marrow recovery and help identify the low-risk patient . It may also be possible to identify "low-risk" neutropenic patients upon development of fever in order to explore alternative management strategies (for example, outpatient oral or intravenous antibiotics) rather than routine hospitalization.

Biochem J, 1993 Oct 1, 295 ( Pt 1), 203 - 9
S-adenosyl-L-methionine decarboxylase of Acanthamoeba castellanii (Neff): purification and properties; Hugo ER et al.; S-Adenosyl-L-methionine decarboxylase (AdoMetDC) has been purified to near homogeneity from the Neff strain of Acanthamoeba castellanii . The holoenzyme molecular mass is 88.8 kDa, including two copies each of a 32.8 kDa alpha-subunit and a 10-15 kDa beta-subunit . The alpha-subunit contains the active site . It has an N-terminal pyruvoyl group, and the first 19 amino acids are 63 and 74% identical with comparable sequences from yeast and mammals, respectively . The apparent Km for S-adenosylmethionine (AdoMet) in the presence of 2 mM putrescine was 30.0 microM . The enzyme was stimulated 2-fold by putrescine, but was unaffected by spermidine . It was inhibited by the following anti-metabolites, listed with their Ki values: Berenil (0.17 microM), pentamidine (19.4 microM), propamidine (334 microM), hydroxystilbamidine (357 microM), methylglyoxal bis(guanylhydrazone) (604 microM) and ethidium bromide (1.3 mM) . Activity of the enzyme fell to undetectable levels during cell differentiation (encystment).

Am Surg, 1993 Oct, 59(10), 674 - 5
The Stamm gastrostomy: a sound procedure; Au FC; A review of 100 personal cases of open gastrostomy using a modified Stamm technique showed that the majority (82.7%) could be performed using local anesthesia with intravenous sedation . Only one patient suffered a wound infection, and there were no other technical complications . The use of a separate stab wound for the introduction of the tube and the routine use of antibiotic irrigation might have contributed to the reduction of wound complications . The overall mortality was 18 per cent, and all of the deaths were due to the patients underlying diseases . The Stamm procedure, which can be performed under local anesthesia without undue discomfort in the majority of patients, has a very low morbidity and no intrinsic mortality . It has a proper place in the armamentarium of nutritional support for these terminally ill patients.

Am J Med Sci, 1993 Oct, 306(4), 236 - 40
Case report: bacillary angiomatosis with massive visceral lymphadenopathy; Haught WH et al.; Bacillary angiomatosis is a newly characterized infectious disease occurring mainly in patients with AIDS . Most patients have cutaneous angiomatosis lesions resembling Kaposi's sarcoma or pyogenic granuloma . Although the disease may be life-threatening if not treated, it is curable with appropriate antibiotic therapy . A patient had a fever, nightsweats, abdominal pain, pleural effusions, and asymmetric peripheral lymphadenopathy . Computed tomography of the chest and abdomen revealed a unique pattern of enhancement of lymph nodes that, to this research team's knowledge, has not been reported previously with this condition . Appropriate antibiotic therapy resulted in a complete resolution of the disease . Included is a discussion of the clinical presentation, etiology, histology, and treatment of bacillary angiomatosis.

Am J Med, 1993 Oct, 95(4), 351 - 7
Ehrlichiosis presenting as a life-threatening illness with features of the toxic shock syndrome; Fichtenbaum CJ et al.; OBJECTIVE: To describe clinical and laboratory features of patients with severe ehrlichiosis, some of whom presented with toxic shock syndrome (TSS)-like illnesses, and to report, to our knowledge, the first documented fatal case of ehrlichiosis in a child . DESIGN: Case series . SETTING: Tertiary-care medical center . PATIENTS: All patients with documented ehrlichiosis during a 3-year period, August 1, 1989, to July 31, 1992 . RESULTS: Eight patients (age range: 2 to 46 years) met clinical and serologic diagnostic criteria for ehrlichiosis . The mean interval from first contact with a physician to initiation of appropriate antibiotic therapy was 4.6 days (range: 1 to 11 days) . All eight patients with ehrlichiosis had fever, chills, thrombocytopenia, and abnormal liver function test results . Most patients also had rash (seven), conjunctival hemorrhage or erythema (six), and leukopenia (six) . Four cases met diagnostic criteria for TSS with fever, hypotension, rash, and multiorgan dysfunction . Two patients required mechanical ventilation, and one of these, a 6 1/2-year-old boy, died of complications of the infection . A ninth patient with probable ehrlichiosis also met diagnostic criteria for TSS . CONCLUSIONS: Human ehrlichiosis can present as a severe, life-threatening illness that may resemble TSS . The diagnosis of ehrlichiosis was not considered by the physicians who first cared for these patients . Greater awareness of the potential severity of ehrlichiosis is needed to ensure that proper treatment is initiated early in the course of the disease.

Am Fam Physician, 1993 Oct, 48(5), 841 - 8
Outpatient management of chronic bronchitis in the elderly; Heath JM; Chronic bronchitis, one of the principal manifestations of obstructive lung disease, causes significant morbidity, especially among older patients . The "blue bloater" type of clinical presentation arises from hypoxemia and is characterized by breathlessness and functional impairments of communication and mobility . Acute infectious episodes often respond to antibiotic therapy, but the underlying problems of impaired airway immune responsiveness and hypersecretions cause chronic symptoms in many patients . Long-term management strategies are directed at optimizing immune defenses, improving airway patency through the use of anticholinergic and bronchodilating medications, correcting hypoxemia, providing supportive nutritional care and instituting measures to maximize the function of respiratory musculature.

Surg Gynecol Obstet, 1993 Oct, 177(4), 393 - 7
Acute appendicitis and the use of intraperitoneal cultures; McNamara MJ et al.; We reviewed the charts of 200 patients with a preoperative diagnosis of acute appendicitis (AA) to evaluate the influence and use of intraoperative culture results on patient management and antibiotic selection . Cultures were obtained in 66 percent of patients; 16 percent of the cultures in patients with AA yielded positive results versus 88 percent of cultures in patients with perforated or gangrenous appendicitis (complicated appendicitis {CA}) and in nine patients, positive cultures were used to adjust antibiotic therapy . Patients with CA who had antibiotic changes based on culture results had a complication rate of 25 percent versus a 29 percent rate for this group as a whole . We conclude that intraoperative cultures in patients with AA are rarely positive and do not influence antibiotic therapy or patient management . In CA, antibiotic changes based on culture results do not seem to alter patient outcome . Surgeons tend to rely on the proved efficacy of empiric antibiotic therapy and other basic surgical principles to afford the best outcome for their patients . The routine practice of obtaining peritoneal cultures in patients operated upon for AA and CA should be abandoned.

J Bioenerg Biomembr, 1993 Oct, 25(5), 537 - 45
Effects of equisetin on rat liver mitochondria: evidence for inhibition of substrate anion carriers of the inner membrane; Konig T et al.; The effect of equisetin, an antibiotic produced by Fusarium equiseti, has been studied on mitochondrial functions (respiration, ATPase, ion transport) . Equisetin inhibits the DNP-stimulated ATPase activity of rat liver mitochondria and mitoplasts in a concentration-dependent manner; 50% inhibition is caused by about 8 nmol equisetin/mg protein . The antibiotic is without effect either on the ATPase activity of submitochondrial particles or on the purified F1-ATPase . It inhibits both the ADP- or DNP-activated oxygen uptake by mitochondria in the presence of glutamate+malate or succinate as substrates, but only the ADP-stimulated respiration is inhibited if the electron donors are TMPD+ascorbate . It does not affect the NADH or succinate oxidation of submitochondrial particles . Equisetin inhibits in a concentration-dependent manner the active Ca(2+)-uptake of mitochondria energized both by ATP or succinate without affecting the Ca(2+)-uniporter itself . The antibiotic inhibits the ATP-uptake by mitochondria (50% inhibition at about 8 nmol equisetin/mg protein) and the Pi and dicarboxylate carrier . It does not lower the membrane potential at least up to 200 nmol/mg protein concentration . The data presented in this paper indicate that equisetin specifically inhibits the substrate anion carriers of the mitochondrial inner membrane.

Cir Pediatr, 1993 Oct, 6(4), 173 - 7
{Bone lengthening in children}; Vazquez Rueda F et al.; Since June 1987, were realized 45 limb lengthening (40 lower and 5 upper) in 34 children with between 3-15 years old . A dynamic axial fixator (DAF) system with telescoping capabilities, permits a slow distraction through a osteotomy and callotasis in 36 bones, and chondrodiatasis in 5 . Twenty-six unilateral lengthening were realized and 5 alineation-lengthening, 20 congenital and 11 acquired causes . 14 bilateral lengthening were done in 5 patients (4 achondroplastic and one Turner's syndrome) . The average increase in length was 5.5 cm . for limb and ranged from 4.3 to 8.0 cm . The healing index was 32.1 days for each centimeter of length gained in the femurs and 5.2 cm . with 28.2 days/cm . in the tibias . The complications were superficial pin tract infection (73%), that were not generally treated with antibiotic, 2 knee valve, 2 knee subluxation and one patella subluxation with knee flexion contracture.

J Chemother, 1993 Oct, 5(5), 317 - 24
Differential effect of human and murine polyclonal and monoclonal antisera on TNF-alpha production by human monocytes; Raponi G et al.; The capacity of human and murine polyclonal and monoclonal antibodies to inhibit lipopolysaccharide (LPS)-induced tumor necrosis factor-alpha (TNF-alpha) release from human monocytes was investigated . Human pooled immunoglobulin G (IVIG), human IgM monoclonal antibody (HA-1A) directed against the lipid A moiety of LPS, and murine IgG monoclonal antibody (MT-1F) raised in mice against antibiotic-treated Escherichia coli O6:K- were either added simultaneously with LPS to monocytes or preincubated for 1 h at 37 degrees C before being added to monocytes . TNF-alpha content in the monocyte supernatants was then tested . Simultaneous addition of increasing concentrations of IVIG (from 0.3 to 2.5 mg/ml) and 10 micrograms/ml of LPS to monocytes induced an enhanced release of TNF-alpha by monocytes in a dose dependent fashion . Preincubation of IVIG with LPS abolished the additive effect, but did not inhibit LPS-induced TNF-alpha release by monocytes . The simultaneous addition of LPS and HA-1A to monocytes had no additive effect nor did it inhibit TNF-alpha release . On the other hand, inhibition of TNF-alpha release was observed when HA-1A was preincubated with LPS before being added to monocytes . In all instances MT-1F inhibited TNF-alpha release when the monocytes were stimulated with smooth type LPS, but not with LPS isolated from rough mutants.

J Chemother, 1993 Oct, 5(5), 297 - 301
The effect of cefepime on some immune parameters in vitro: lack of interference with mitogen-induced lymphoproliferation, immunoglobulin synthesis, IFN-gamma and IL-2 secretion and IL-2 receptor expression; Di Marco R et al.; The possible interference of the novel antibiotic cefepime (CPE) with some functions of the immune system was investigated in vitro . Peripheral blood mononuclear cells (PBMC) cultured in the presence of drug concentrations ranging from 25 to 100 micrograms/ml normally maintained their responsiveness to polyclonal (PHA, Con A, PWM) mitogenic stimulation in regard to proliferative response, IgM and IgG synthesis and IFN-gamma and IL-2 secretory capacity . Moreover, PHA-induced expression of IL-2 receptors was comparable in PBMCs cultured in the presence or absence of CPE . Taken together, these data suggest that CPE does not interfere, at this specific level, with T- and B-cell mediated functions in vitro.

Cell Biol Toxicol, 1993 Oct-Dec, 9(4), 377 - 84
Effect of bacitracin on erythroid differentiation of MEL cells; Foresti M et al.; Bacitracin, an antibiotic widely utilized in clinical and veterinary use, was tested on murine erythroleukemia (MEL) cells . Tests were performed to evaluate the capacity of the drug to interfere with erythroid differentiation . Cells were exposed to a single treatment in S phase at sublethal doses of bacitracin . Two responses were found depending on the drug concentration . At higher concentrations (25 micrograms/ml and 250 ng/ml) a reduction in number of differentiating cells was observed but the kinetics of the process remained unchanged . At lower concentrations (from 2.5 ng/ml to 2.5 fg/ml) a dramatic alteration of the dynamic of differentiation was found . These two responses are related to different activities of the DNA repair mechanisms . Higher doses of bacitracin stimulate repair while lower concentrations are not able to active repair, as demonstrated by tests with hydroxyurea . The bacitracin-induced damage can be considered a stable genetic and/or epigenetic alteration, as demonstrated by the high frequency of mutant clones isolated from low-dose treated cells . The suitability of MEL cells system in evaluating genotoxicity of drugs for veterinary use is underlined.

J Hosp Infect, 1993 Oct, 25(2), 137 - 44
Surveillance and management of infection in a haematology unit: use of an in-house clinical database; Smyth ET et al.; An effective infection control surveillance programme is essential for the management of patients in a haematology unit . The programme can contribute to the production of antibiotic policies, the monitoring of current clinical practice and has potential in the cost analysis of infection . The use of a computerized database facilitates the management of such a programme . We describe an infection control database using dBASE IV software which runs on a personal computer . The system can accept data sets from other relevant databases and allows the generation of infection control data appropriate to the unit.

J Clin Invest, 1993 Oct, 92(4), 1812 - 8
Regulation of alveolar macrophage transforming growth factor-beta secretion by corticosteroids in bleomycin-induced pulmonary inflammation in the rat; Khalil N et al.; In a model of pulmonary inflammation and fibrosis induced by the antineoplastic antibiotic, bleomycin, we previously demonstrated that TGF-beta was markedly elevated within 7 d of bleomycin administration . At the time of maximal TGF-beta production, TGF-beta 1 was localized by immunohistochemistry to be present almost exclusively in alveolar macrophages . In this study, we have demonstrated that alveolar macrophages stimulated by bleomycin-induced injury secrete large quantities of biologically active TGF-beta 1 when explanted into tissue culture . However, alveolar macrophages from normal saline-treated rats secrete small quantities of biologically inactive TGF-beta . In contrast, splenic macrophages secrete large quantities of inactive TGF-beta and are unaffected by the intratracheal bleomycin treatment . High doses of the corticosteroid methylprednisolone given intramuscularly before and concomitantly with bleomycin administration prevented the influx of alveolar macrophages into the lungs, diminishing both the number of macrophages present in the alveoli and the total lung content of TGF-beta . However, the rate of secretion of TGF-beta by alveolar macrophages recovered from the alveoli was unchanged after corticosteroid treatment . When activated alveolar macrophages were cultured in the presence of several concentrations of dexamethasone that completely suppressed IL-1 secretion, little effect on TGF-beta secretion was observed . The findings in this study demonstrate that during bleomycin-induced injury, alveolar macrophages not only secrete large quantities of active TGF-beta 1, but are a predominant source of the enhanced TGF-beta response seen in this model . Furthermore, the alveolar macrophage secretion of TGF-beta is not inhibited by the presence of high concentrations of corticosteroids.

Braz J Med Biol Res, 1993 Oct, 26(10), 1105 - 10
Reduction of Sephadex-induced lung inflammation and bronchial hyperreactivity by rapamycin; Francischi JN et al.; Rapamycin is a macrolide antibiotic whose potent immunosuppressor activity was recently described in vivo and in vitro . The aim of the present work was to determine if rapamycin could affect an established inflammatory response . Conscious pathogen-free Dunkin-Hartley guinea pigs (300-400 g) were injected intravenously with Sephadex beads (G50, superfine, 10 to 40 microns, 24 mg/kg) to induce lung inflammation and bronchial hyperreactivity . Bronchoalveolar lavage (BAL) fluid was collected 2, 12 and 24 h after Sephadex administration and the cells were counted . Bronchial tissue was used to construct dose-response (contraction, g) curves to histamine and acetylcholine 24 h after the Sephadex injection, using a cascade system . Results are presented as area under the log dose-response curves . Test animals were injected with rapamycin (5 mg/kg) or its vehicle by the intramuscular route either 2 or 12 h after Sephadex injection and BAL fluid collected 24 h after Sephadex administration . Rapamycin administration 2 h after Sephadex reduced eosinophil and lymphocyte numbers in BAL by 52 and 55%, respectively, but not ex vivo bronchial hyperreactivity induced by Sephadex injection . However, rapamycin administration 12 h after Sephadex reduced BAL eosinophil and lymphocyte numbers (55 and 62%, respectively) and bronchial hyperreactivity . The increase in neutrophil numbers in BAL induced by Sephadex injection was not modified by rapamycin . Since lymphocyte numbers in BAL were significantly increased in Sephadex-treated animals at 12 h but not at 2 h after Sephadex injection, the present results suggest that the inhibition of bronchial hyperreactivity by rapamycin may be dependent on the presence of lymphocytes elicited into the airways by Sephadex injection.

FEBS Lett, 1993 Sep 20, 330(3), 334 - 8
Asparagine-135 of elongation factor Tu is a crucial residue for the folding of the guanine nucleotide binding pocket; Weijland A et al.; This work studies the structure-function relationships of Asn135, a residue situated in the GTP binding pocket of elongation factor Tu (EF-Tu) . For this purpose we constructed EF-TuN135D/D138N and assayed its reactivity towards various purine nucleotides . We found that EF-TuN135D/D138N had no functional effect with GTP, ATP, XTP and isoGTP . The lack of a productive interaction with isoGTP shows that the Asn135 side-chain does not recognize the exocyclic keto group of the guanine base . However, EF-TuN135D/D138N, whose native conformation is stabilized by either elongation factor Ts or kirromycin, was able to support the enzymatic binding of aa-tRNA to the ribosome in the absence of any nucleotide, when in complex with the antibiotic . Taken together, these results show that Asn135 is important for the correct folding of the nucleotide binding site and that EF-Tu.kirromycin can mediate the binding of aa-tRNA to the mRNA-programmed ribosomes independently of the native conformation of this site.

Biochim Biophys Acta, 1993 Sep 19, 1151(2), 237 - 45
H(+)-coupled dipeptide (glycylsarcosine) transport across apical and basal borders of human intestinal Caco-2 cell monolayers display distinctive characteristics; Thwaites DT et al.; Transepithelial transport and intracellular accumulation of the dipeptide glycylsarcosine (Gly-Sar) were studied using intact monolayers of the human intestinal epithelial cell line, Caco-2 . Gly-Sar transport was demonstrated in both absorptive (apical-to-basal) and secretory (basal-to-apical) directions . In both directions, transport and accumulation were enhanced in the presence of a pH gradient (pHo < pHi) . Under conditions similar to those found at the intestinal membrane in vivo (apical pH 6.0, basolateral pH 7.4), net absorption (145.2 pmol/cm2 per h) was observed, although experimental conditions could also be manipulated (apical pH 7.4, basolateral pH 6.0) so that net secretion was observed . Transport and accumulation (in both directions) were inhibited in the presence of either 20 mM (unlabelled) Gly-Sar or 20 mM cephalexin (an aminocephalosporin antibiotic) . When added to either the apical or basolateral surface of BCECF (2',7',-bis(2-carboxyethyl)-5(6)-carboxyfluorescein)-loaded Caco-2 cell monolayers Gly-Sar (20 mM), at pH 6.0, caused a marked intracellular acidification, demonstrating that dipeptide absorption is accompanied by H(+)-flow into the cells . Cephalexin (20 mM) had similar effects (as Gly-Sar) when presented at the apical surface but also caused a marked intracellular acidification when perfused into the basolateral chamber at pH 7.4 . In contrast, addition of Gly-Sar (20 mM) to the basolateral chamber (at pH 7.4) had no effect . Transepithelial absorption of dipeptides (Gly-Sar) and beta-lactam antibiotics (cephalexin) at low concentrations is predominately via a transcellular route mediated by carrier mechanisms located at both apical and basolateral membranes . Interestingly, Gly-Sar and cephalexin transport across the basolateral membrane (and, therefore, exit from the cell) display both common and distinct characteristics suggesting that more than one mechanism may be responsible for exit into the basolateral space.

Nucleic Acids Res, 1993 Sep 11, 21(18), 4281 - 7
(+)-CC-1065 as a structural probe of Mu transposase-induced bending of DNA: overcoming limitations of hydroxyl-radical footprinting; Ding ZM et al.; Phage Mu transposase (A-protein) is primarily responsible for transposition of the Mu genome . The protein binds to six att sites, three at each end of Mu DNA . At most att sites interaction of a protein monomer with DNA is seen to occur over three minor and two consecutive major grooves and to result in bending up to about 90 degrees . To probe the directionality and locus of these A-protein-induced bends, we have used the antitumor antibiotic (+)-CC-1065 as a structural probe . As a consequence of binding within the minor groove, (+)-CC-1065 is able to alkylate N3 of adenine in a sequence selective manner . This selectivity is partially determined by conformational flexibility of the DNA sequence, and the covalent adduct has a bent DNA structure in which narrowing of the minor groove has occurred . Using this drug in experiments in which either gel retardation or DNA strand breakage are used to monitor the stability of the A-protein--DNA complex or the (+)-CC-1065 alkylation sites on DNA (att site L3), we have demonstrated that of the three minor grooves implicated in the interaction with A-protein, the peripheral two are 'open' or accessible to drug bonding following protein binding . These drug-bonding sites very likely represent binding at at least two A-protein-induced bending sites . Significantly, the locus of bending at these sites is spaced approximately two helical turns apart, and the bending is proposed to occur by narrowing of the minor groove of DNA . The intervening minor groove between these two peripheral sites is protected from (+)-CC-1065 alkylation . The results are discussed in reference to a proposed model for overall DNA bending in the A-protein att L3 site complex . This study illustrates the utility of (+)-CC-1065 as a probe for protein-induced bending of DNA, as well as for interactions of minor groove DNA bending proteins with DNA which may be masked in hydroxyl radical footprinting experiments.

Biochemistry, 1993 Sep 7, 32(35), 9094 - 107
Footprinting titration studies on the binding of echinomycin to DNA incapable of forming Hoogsteen base pairs; Sayers EW et al.; In order to investigate the possible importance of Hoogsteen base pairing to the DNA-binding ability of echinomycin, quantitative DNase I footprinting has been performed . The substrate was the tyrT DNA restriction fragment, either "native" or substituted with one of the purine analogs 2'-deoxy-7-deazaadenosine and 2'-deoxy-7-deazaguanosine in both strands . The modified DNA species were prepared by PCR and selectively labeled at the 5' terminus of one strand (usually the upper "Watson" strand) with {32P}ATP and polynucleotide kinase . Proper incorporation of the analog nucleotides was verified by Maxam-Gilbert G- and C-sequencing reactions as well as exposure to osmium tetroxide and diethyl pyrocarbonate . OsO4 was found to react strongly with the 7-deaza nucleotides, providing a good check of faithful incorporation . The previously observed echinomycin-induced hyperreactivity of purines toward diethyl pyrocarbonate was eliminated by incorporating the appropriate 7-deazapurine . The DNase I footprinting titration studies greatly refined the existing knowledge of the DNA-binding characteristics of echinomycin, as they revealed five general types of concentration-dependent behavior at single-bond resolution . Estimates of microscopic binding constants at individual DNA binding sites were obtained by measuring the antibiotic concentration which produced a half-maximal effect on the concentration of a given DNase I cleavage product . All binding sites contained one or more CpG steps, and all CpG steps analyzed formed part of a binding site for echinomycin . No consistent differences in the estimated binding constants for these sites were observed by comparing normal and modified DNAs, indicating that the abolition of formal Hoogsteen pairs did not significantly alter the thermodynamics of echinomycin-DNA interaction . The lack of any detectable decrease in binding constants for critical sites in the 7-deazapurine-substituted DNAs argues against any anti-syn conformational transition of purine nucleosides occurring in association with the bis-intercalative complex formation.

Gene, 1993 Sep 6, 131(1), 145 - 50
Shuttle cosmid vectors for the trypanosomatid parasite Leishmania; Ryan KA et al.; We have developed two shuttle cosmid vectors for the trypanosomatid protozoan parasite Leishmania . Cosmids cLHYG and cLNEO contain hyg and neo markers, conferring resistance to hygromycin B and G418, respectively, replicate extrachromosomally after transfection into promastigotes, and bear a unique BamHI cloning site . To ensure the representation of telomeric sequences, which represent about 5% of the Leishmania genome, random insert DNAs were prepared by shearing followed by blunt-end ligation with BamHI adapters . Representative genomic libraries from Leishmania species representing the four major pathogenic complexes were prepared using cosmid cLHYG . The cosmid libraries were efficiently transfected into Leishmania, and individual cosmids were readily recovered by transformation back into Escherichia coli . The relatively small size of the Leishmania genome (50 Mb) combined with the capacity and transfection efficiency of these cosmid libraries (> 1000 Leishmania transfectants/plate) suggests the feasibility of functional genetic complementation in this parasite.

J Biol Chem, 1993 Sep 5, 268(25), 19092 - 100
Involvement of the vacuolar H(+)-ATPases in the secretory pathway of HepG2 cells; Yilla M et al.; The macrolide antibiotic concanamycin B is a highly selective inhibitor (IC50 = 5 nM) of the H(+)-ATPases of the vacuolar system . We have examined the effects of concanamycin B on the constitutive secretory pathway of the human hepatoma cell line, HepG2 . In cells exposed to 10 nM concanamycin B, transport from the endoplasmic reticulum to the Golgi occurs at normal rates, as determined by pulse-chase analysis of endoglycosidase H-sensitive product in conjunction with subcellular fractionation experiments . However, intra-Golgi trafficking or Golgi to plasma membrane delivery is significantly impaired . A delay in the onset of secretion of the major secretory proteins, albumin, alpha 1-antitrypsin and transferrin is observed . Processing of N-linked glycans by sialyltransferases is inhibited, resulting in secreted glycoproteins which are modified less extensively . In view of the acidic pH of the trans-Golgi and the trans-Golgi network, these studies suggest that acidification by vacuolar ATPases is critical to achieving timely secretion and correct N-linked glycan modifications of proteins which follow the constitutive secretory pathway.

Otolaryngol Head Neck Surg, 1993 Sep, 109(3 Pt 2), 606 - 10
Chronic sinusitis, steroid-dependent asthma, and IgG subclass and selective antibody deficiencies; Fadal RG; In the past 20 years considerable progress has been made in understanding the ways in which subtle immunologic defects can adversely affect health . Immunoglobulin G subclass deficiencies have been identified and are related to an increased susceptibility to respiratory tract infections in certain patients . To assess the immunocompetence of such patients, the quantity and quality of their antibody response must be evaluated . Immunologic evaluation is best performed by measuring selective antibodies before and after a specific challenge . Patients with mild immunodeficiency may benefit from prophylactic antibiotic therapy; those with profound immunodeficiency require antibody replacement therapy.

Cell Biochem Funct, 1993 Sep, 11(3), 193 - 200
Effect of diets containing adenosine, guanosine, inosine or xanthosine on the nucleotide content of Artemia . Influence of mycophenolic acid; Sillero A et al.; Artemia uses the stored diguanosine tetraphosphate as a source of adenine and guanine nucleotides during development from the encysted gastrula to the free swimming larva . Further development of the larvae depends on a dietary source of purine rings . We have investigated the growth of Artemia in axenic cultures supplemented with 0.6 mg ml-1 of adenosine, guanosine, inosine or xanthosine . The total protein and soluble nucleotide content of Artemia grown in the presence of adenosine, guanosine or inosine was very similar, around (2 A260 units and 500 mg protein) and (4 A260 units and 1000 mg protein) after 4 and 6 days of postlarval development, respectively . The nucleotide pattern of those extracts subjected to HPLC were almost identical, the major peaks corresponding to ATP, ADP and AMP . Other nucleotides, not well characterized, were also present in those extracts . Mycophenolic acid (10 micrograms ml-1) inhibited the growth of Artemia (as measured by their protein and soluble nucleotide content) in the presence of adenosine and inosine as the purine source, and had no appreciable effect in the presence of guanosine . A quantitative analysis of the chromatographic peaks obtained from Artemia grown in the presence of any of the three nucleosides +/- mycophenolic acid showed that the effect of the antibiotic on each one of the chromatographic peaks was very similar, suggesting that Artemia, and probably other organisms as well, tend to maintain a balance between all nucleotides and to adjust the overall level to the limiting step(s) in their rates of synthesis/interconversion . Xanthosine was not able to support the development of Artemia.

J Eukaryot Microbiol, 1993 Sep-Oct, 40(5), 581 - 9
Distribution of macromolecular methylations in promastigotes of Leishmania donovani and impact of sinefungin; Lawrence F et al.; Sinefungin, an antifungal and antiparasitic nucleoside antibiotic, is a very potent antileishmanial agent both in vitro and in vivo . This molecule, structurally related to S-adenosylmethionine, is a good competitive inhibitor of methyltransferases in vitro . The aim of this report is to analyze the impact of sinefungin on methylation pattern and the subcellular localisation of methyl groups and various methylases in promastigotes of Leishmania donovani . We have shown the presence of various methylated macromolecules in different subcellular fractions, with somewhat higher concentration in membrane fraction . In vitro, sinefungin inhibits the three main protein methylases, but in cells cultured in its presence the protein carboxylmethylations are specifically inhibited.

Dis Colon Rectum, 1993 Sep, 36(9), 862 - 5
Management of synergistic bacterial gangrene in severely immunocompromised patients . Report of four cases; Williamson M et al.; We present four cases of perianal synergistic gangrene in severely immunocompromised patients . In all patients, gangrene was controlled by radical surgery, including defunctioning colostomy in three patients, backed up by appropriate antibiotic therapy . Three of the patients survived and left the hospital; the fourth died in the intensive care unit of overwhelming sepsis from an unidentified source other than the anus . We review the literature and conclude that such infections in these patients are not inevitably fatal and that radical surgery can result in a cure.

Rofo, 1993 Sep, 159(3), 218 - 21
{Computed tomography in a case of pseudomembranous colitis}; Gaa J et al.; Pseudomembranous colitis (PMC) is an infectious colitis usually occurring as a complication of antibiotic therapy . The computed tomography (CT) findings of 10 patients with PMC are reviewed . All patients demonstrated an abnormal large bowel wall with an average thickness of 13 mm (range 7-31 mm) . Additional, but less frequent findings included mesenteric inflammation, ascites, pleural effusions, and dilatation of the large or small bowel . Pancolonic involvement was seen in 7 cases, while three patients had focal colitis . Although the CT appearance of PMC is not specific, the diagnosis may be suggested in the proper clinical setting.

Ann Surg, 1993 Sep, 218(3), 250 - 9; discussion 259-61
Anti-endotoxin monoclonal antibodies inhibit secretion of tumor necrosis factor-alpha by two distinct mechanisms; Burd RS et al.; OBJECTIVE: To determine whether monoclonal antibodies (mAbs) directed against lipopolysaccharide (LPS, endotoxin) act by promoting LPS neutralization, LPS uptake by macrophages, or both processes, the authors assessed the effects of these agents on LPS-induced cytokine secretion and cellular uptake of LPS . SUMMARY BACKGROUND DATA: MAbs directed against LPS have been shown to attenuate LPS-induced macrophage tumor necrosis factor-alpha (TNF-alpha) secretion, a process that may contribute to protective capacity . The mechanisms by which this process occurs have not been established . METHODS: MAbs directed against LPS were evaluated in vitro for their capacity to (1) inhibit TNF-alpha secretion, and (2) alter fluorescein isothiocyanate-labeled LPS uptake (employing flow cytometry analysis and fluorescence microscopy) by the macrophage-like cell line RAW 264.7 . RESULTS: MAb 8G9, an IgG3 directed against the O-antigen polysaccharide region of Escherichia coli 0111:B4 LPS, significantly reduced LPS-induced TNF-alpha secretion and promoted a more than 40-fold increase in LPS uptake by macrophages . The authors established that this was mediated by a Fc receptor-mediated process because 8G9 F(ab')2 fragments that lack the Fc portion of the IgG molecule were capable of inhibiting TNF-alpha secretion, but did not promote increased LPS uptake to the same degree . Cross-reactive, anti-deep core/lipid A mAb 1B6, an IgG2a, also promoted uptake of E . coli 0111:B4 LPS and O-antigen polysaccharide-deficient E . coli J5 LPS, but only inhibited TNF-alpha secretion induced by E . coli J5 LPS to which it binds most efficiently . MAb 3D10, an IgM also directed against the O-antigen polysaccharide region of E . coli 0111:B4 LPS, inhibited TNF-alpha secretion but did not increase cellular uptake of LPS, presumably acting solely due to LPS neutralization . Polymyxin B, an antibiotic that binds stoichiometrically to the lipid A portion of LPS, inhibited TNF-alpha secretion and prevented cellular LPS uptake . CONCLUSIONS: These results suggest that IgG and IgM anti-LPS mAbs exert protective capacity by extracellular neutralization of LPS, while IgG Fc receptor-mediated cellular uptake also may serve to bypass macrophage activation and TNF-alpha secretion by promoting internalization and intracellular neutralization.

Am J Obstet Gynecol, 1993 Sep, 169(3), 708 - 12
A rabbit model for ascending infection in pregnancy: intervention with indomethacin and delayed ampicillin-sulbactam therapy; Heddleston L et al.; OBJECTIVE: In a modified pregnant rabbit model using intracervical inoculation of Escherichia coli we investigated the effects of administration of delayed antibiotics and indomethacin on outcomes . STUDY DESIGN: We inoculated 10(5) colony-forming units of Escherichia coli or saline solution bilaterally in the cervix of New Zealand White rabbits at 70% of gestation and assigned animals to ampicillin-sulbactam therapy beginning at 0, 4, 8, 12, and 16 hours after inoculation with Escherichia coli or to no antibiotic therapy . We alternated indomethacin pretreatment in rabbits receiving no antibiotic therapy and rabbits starting ampicillin-sulbactam 4 hours after inoculation . RESULTS: Compared with saline solution inoculated control animals, those inoculated with Escherichia coli (and given no antibiotic therapy) had significant increases in fetal loss, fever, bleeding at 24 hours, and positive cultures (100%, 92%, 76%, 98% versus 0%, respectively, all p < 0.01) . In Escherichia coli-inoculated animals receiving no antibiotic therapy pretreatment with indomethacin significantly decreased bleeding and delivery within first 24 hours compared with those not treated with indomethacin (p < 0.05) but did not significantly improve fetal survival . Ampicillin-sulbactam treatment stated at 0, 4, 8, and 12 hours after inoculation resulted in improved fetal survival compared with the untreated group (100%, 56%, 50%, 50% versus 0%, respectively, all p < 0.05) . Treatment initiated at 16 hours resulted in outcomes similar to Escherichia coli-inoculated animals receiving no antibiotic therapy . CONCLUSION: Intracervical Escherichia coli inoculation produced infection in the uterus and uniform pregnancy loss . Pretreatment with indomethacin did not result in improved fetal survival . Ampicillin-sulbactam therapy, initiated as long as 12 hours after Escherichia coli inoculation, resulted in significant improvement in fetal survival compared with antibiotic therapy . We believe this model mimics ascending infection in pregnancy more closely than do previous animal models.

Proc Natl Acad Sci U S A, 1993 Sep 1, 90(17), 8009 - 12
Selective proteolytic activity of the antitumor agent kedarcidin; Zein N et al.; Kedarcidin is a potent antitumor antibiotic chromoprotein, composed of an enediyne-containing chromophore embedded in a highly acidic single chain polypeptide . The chromophore was shown to cleave duplex DNA site-specifically in a single-stranded manner . Herein, we report that in vitro, the kedarcidin apoprotein, which lacks any detectable chromophore, cleaves proteins selectively . Histones that are the most opposite in net charge to the apoprotein are cleaved most readily . Our findings imply that the potency of kedarcidin results from the combination of a DNA damaging-chromophore and a protease-like apoprotein.

Chest, 1993 Sep, 104(3), 973 - 5
Bronchopulmonary bacillary angiomatosis; Foltzer MA et al.; A man with prior AIDS developed acute febrile interstitial pneumonitis, hilar and paratracheal adenopathy, and bronchial polyps . The polyps were histologically typical for bacillary angiomatosis and complete symptomatic and radiographic response to oral clarithromycin was seen . The clinical presentation of bacillary angiomatosis includes pulmonary disease and in particular bronchial polyps; clarithromycin is an effective oral antibiotic.

Surg Gynecol Obstet, 1993 Sep, 177(3), 227 - 30
The significance of a positive test of morphine cholescintigraphy in hospitalized patients; Flancbaum L et al.; Morphine-augmented radionuclide cholescintigraphy (MC) is a useful adjunctive diagnostic tool for the identification of acute cholecystitis (AC) in patients who are hospitalized and critically ill with occult sepsis . The results of previous studies have demonstrated a reduction in false-positive rates, that is, nonvisualization, from 40 percent with standard radionuclide cholescintigraphy to 5 percent with MC in these high-risk patient groups, with an overall accuracy of 92 percent . This study was performed to determine the significance of a positive test result from MC in patients with occult sepsis . We reviewed the records of all 20 patients at high risk in whom MC was positive during the 35-month period ending 31 May 1992 . AC was confirmed by laparotomy in all 16 patients who underwent surgical treatment . There were two patients who recovered with antibiotic therapy alone (considered false-positives) and two additional patients who died without operation or a confirmed diagnosis of AC (excluded from analysis) . Thus, in this series, MC was associated with a positive predictive value of 0.89, confirming that it is a valuable adjunct in establishing the diagnosis of AC in patients who are seriously ill and hospitalized with occult sepsis.

Res Microbiol, 1993 Sep, 144(7), 565 - 74
Glycerol uptake in Escherichia coli is sensitive to membrane lipid composition; Truniger V et al.; In Escherichia coli, a functional GlpF protein is necessary for efficient uptake of glycerol at low concentrations . Here we show that GlpF-mediated glycerol uptake was sensitive to a variety of lipid alterations . Overproduction or mutation of the genes coding for enzymes involved in lipid biosynthesis resulted in changed membrane composition and fluidity . The strains with altered lipid composition had a substrate affinity for glycerol (Km) similar to that of wild-type cells, but the Vmax for glycerol uptake was affected . Experiments with glpF::lacZ and glpK::lacZ protein fusions showed that the expression of these two genes was not changed under these conditions . In addition, we observed that mutations in glpF were accompanied by reduced membrane permeability for compounds unrelated to glycerol . Passive diffusion across the membranes of glpF mutants for o-nitrophenyl galactoside was 5-fold slower than in glpF+ cells . The mutants were more resistant to the hydrophobic antibiotic tetracycline, as well as to the membrane perturbants ethanol and dimethylsulphoxide and to the stress of low-osmolarity medium.

J Emerg Med, 1993 Sep-Oct, 11(5), 555 - 64
Bacterial meningitis in infants and children: a review; Oliver LG et al.; Emergency physicians are often required to evaluate febrile infants and children with no obvious source of infection . Most have uncomplicated viral illnesses . It is imperative, however, to identify the child with potentially life-threatening bacterial meningitis . The clinical presentation of meningitis is variable and depends on many factors . These variables are discussed as well as the indications for lumbar puncture and guidelines for laboratory evaluation . Recommendations for antibiotic selection and dosages are provided . The clinical trials regarding the use of dexamethasone are also reviewed.

Infection, 1993 Sep-Oct, 21(5), 291 - 6
Diagnostic value of bronchoalveolar lavage in patients with opportunistic and nonopportunistic bacterial pneumonia; Dalhoff K et al.; In 29 patients with community-acquired pneumonia, 24 patients with hospital-acquired pneumonia and 35 patients with pneumonia in the immunocompromised host the diagnostic value of bronchoalveolar lavage (BAL) with quantitative bacterial and fungal cultures was studied; 32 patients with noninfectious pulmonary diseases and 14 healthy volunteers served as controls . An infectious etiology could be established in 81% of the pneumonia patients without differences between the three groups; significant infection was associated with colony counts of > or = 10(4) cfu/ml . Prior antibiotic therapy lowered the yield of BAL culture only in community-acquired pneumonia (94% vs 55% positive cultures in untreated vs pretreated patients, p < 0.02) . Furthermore the culture results were related to the radiographic extension of pulmonary infiltrates (92% positive cultures in multilobar vs 54% in lobar or segmental infiltrates, p < 0.001) . Therapeutic consequences of BAL were shown by resistance of the isolated organisms to predefined empiric treatment regimens in 41% community-acquired pneumonia, 43% pneumonia in the immunocompromised host and 67% hospital-acquired pneumonia patients.

Vopr Med Khim, 1993 Sep-Oct, 39(5), 10 - 3
{The effect of rolitetracycline on the level of nonesterified fatty acids, phospholipids, and triacylglycerols in ischemic damage to the myocardium}; Sedlakova A et al.; Myocardial ischemia developed in rabbits after ligation of coronary artery within 60 min . Single dose of rolytetracycline 40 mg/kg was administered intravenously before or after ligation . Alterations in content of unesterified fatty acids and phospholipids were studied in blood serum as well as of unesterified fatty acids, phospholipids and triacyl glycerols--in the myocardium . After ligation of coronary artery content of unesterified fatty acids and phospholipids was increased 2-fold in blood serum as compared with control values, while in the ischemic myocardium these substances were increased more than 2-fold and triacyl glycerol--about 7-fold . Administration of rolytetracycline before ligation of the artery led to a decrease in content of unesterified fatty acids and phospholipids in blood serum down to control values; the ligation-induced high content of triacyl glycerols and phospholipids in the myocardium was also decreased, while alterations in unesterified fatty acids content were not similar . Rolytetracycline administered after the artery ligation caused a decrease in content of unesterified fatty acids but triacyl glycerols were markedly increased . The antibiotic did not affect the lipid content in nonischemized tissues of myocardium.

J Cell Sci, 1993 Sep, 106 ( Pt 1), 153 - 66
The mouse brown (b) locus protein has dopachrome tautomerase activity and is located in lysosomes in transfected fibroblasts; Winder AJ et al.; Many genes mapping to pigmentation loci are involved in the regulation of melanin synthesis in the mouse . The brown (b) locus controls black/brown coat coloration, and its product has significant homology to the key melanogenic enzyme tyrosinase . This has led to suggestions that the b-protein is itself a melanogenic enzyme . In order to investigate its function, we have established lines of mouse fibroblasts stably expressing the b-protein by co-transfection of a b-protein expression vector and a plasmid conferring resistance to the antibiotic G418 . The b-protein synthesised by these cells has the expected molecular mass of 75 kDa and reacts with three different anti-b-protein antibodies . We were unable to confirm previous reports that the b-protein has tyrosinase or catalase activity, but detected stereospecific dopachrome tautomerase activity in b-protein-expressing fibroblasts . This dopachrome tautomerase binds to Concanavalin A-Sepharose, and the major product of its action on L-dopachrome is 5,6-dihydroxyindole-2-carboxylic acid . Since this activity is not present in untransfected cells we conclude that the b-protein has dopachrome tautomerase activity . Fibroblasts do not contain melanosomes, the specialised organelles in which the b-protein is located in melanocytes . Nevertheless, indirect immunofluorescence localisation of the b-protein in transfected fibroblasts produces a distinctive pattern of intense juxtanuclear staining combined with punctate cytoplasmic staining . Double-labelling shows co-localisation of the b-protein with the late endosomal/lysosomal markers beta-glucuronidase and LAMP-1, both in transfected fibroblasts and in mouse melanoma cells . These findings are consistent with the hypothesis that melanosomes are closely related to lysosomes.

J Antimicrob Chemother, 1993 Sep, 32(3), 393 - 400
Metronidazole uptake by sensitive and resistant isolates of Helicobacter pylori; Lacey SL et al.; The development of metronidazole resistance in Helicobacter pylori has become an important factor in the clinical use of this drug in the treatment of gastritis and peptic ulcers . The mechanism for the development of resistance is not known but may involve factors which influence metronidazole uptake and metabolism . In this study, a simple and reliable HPLC assay for metronidazole was developed and the uptake of the drug from broth cultures of both resistant and sensitive strains of H . pylori was investigated . Resistance to metronidazole was determined by the E test as well as plate and broth assays . In the presence of the antibiotic (approximately 10 mg/L), metronidazole-sensitive strains were killed within 24 h and there was a concomitant fall in the concentration of metronidazole in the broth . In contrast, the killing of resistant strains of H . pylori was associated with < 10% loss of antibiotic from broth . These differences in metronidazole uptake are ascribed to alterations in the mechanisms of action of the drug in sensitive and resistant strains.

Pharmacotherapy, 1993 Sep-Oct, 13(5), 494 - 9
Prevention of auditory sequelae in pediatric bacterial meningitis: a meta-analysis; Yurkowski PJ et al.; Meta-analysis methods were used to compare the effect of antibiotic regimens and corticosteroids on the development of auditory sequelae after pediatric bacterial meningitis . After a literature search of two major data bases, 11 studies met the criteria and were included in the analysis . Summary odds ratios, with 95% confidence intervals, were calculated that quantified the relative risk of developing auditory sequelae after specific therapies . No significant differences among antibiotics were identified in terms of reducing the risk of meningitis-related hearing impairment . However, corticosteroids significantly reduced the frequency of bilateral, moderate, or greater hearing loss . Patients receiving placebo versus dexamethasone were much more likely to develop auditory dysfunction (odds ratio 3.77; 95% CI 1.77-8.10) . The results of this study add quantitative evidence supporting the use of dexamethasone as adjunctive therapy in pediatric bacterial meningitis.

Drug Saf, 1993 Sep, 9(3), 156 - 84
Antiepileptic drugs . A review of clinically significant drug interactions; Patsalos PN et al.; Approximately 20 to 30% of patients with active intractable epilepsy are commonly treated with polytherapy antiepileptic drug regimens, and these patients may experience complicated drug interactions . Furthermore, because of the long term nature of treatment, the possibility of drug interactions with drugs used for the treatment of concomitant disease is high . Classically, clinically significant drug interactions, both pharmacokinetic and pharmacodynamic, have been considered to be detrimental to the patient, necessitating dosage adjustment . However, this need not always be the case . With the introduction of new drugs (e.g . vigabatrin and lamotrigine) with known mechanisms of action, the possibility exists that these can be used synergistically . The most commonly observed clinically significant pharmacokinetic interactions can be attributed to interactions at the metabolic and serum protein binding levels . The best known examples relate to induction (e.g . phenobarbital, phenytoin, carbamazepine and primidone) or inhibition {e.g . valproic acid (sodium valproate)} of hepatic monoxygenase enzymes . The extent and direction of interactions between the different antiepileptic drugs are varied and unpredictable . Interactions in which the metabolism of phenobarbital, phenytoin or carbamazepine is inhibited are particularly important since these are commonly associated with toxicity . Some inhibitory drugs include macrolide antibiotics, chloramphenicol, cimetidine, isoniazid and numerous sulphonamides . A reduction in efficacy of antibiotic, cardiovascular, corticosteroid, oral anticoagulant and oral contraceptive drugs occurs during combination therapy with enzyme-inducing antiepileptic drugs . Discontinuation of the enzyme inducer or inhibitor will influence the concentrations of the remaining drug(s) and may necessitate dosage readjustment.

Antimicrob Agents Chemother, 1993 Sep, 37(9), 1882 - 9
Adverse effects of pefloxacin in irradiated C3H/HeN mice: correction with glucan therapy; Patchen ML et al.; Opportunistic bacterial infections are the predominant cause of death following myelosuppressive radiation exposure . When used alone, a variety of immunomodulators and antibiotics have been reported to reduce radiation-induced death . In these studies, the combined therapeutic effects of the immunomodulator glucan and the quinolone antibiotic pefloxacin were evaluated for survival-enhancing effects in myelosuppressed C3H/HeN mice . Mice were exposed to 7.9 Gy of whole-body 60Co radiation and treated with saline, glucan (250 mg/kg of body weight intravenously, 1 h after irradiation), pefloxacin (64 mg/kg/day orally, days 3 to 24 after irradiation), or glucan plus pefloxacin . Survival 30 days after irradiation in mice receiving these respective treatments was 25, 48, 7, and 85% . Evaluation of granulocyte-macrophage progenitor cell (GM-CFC) recovery in mice receiving these treatments revealed that, compared with recovery in saline-treated mice, glucan stimulated GM-CFC recovery, pefloxacin suppressed GM-CFC recovery, and glucan administered in combination with pefloxacin could override pefloxacin's hemopoietic suppressive effect.

Anal Biochem, 1993 Sep, 213(2), 271 - 6
Derivative spectroscopy as a nonperturbative tool to detect the state of liposome-entrapped sulbactam; Maurizi G et al.; Sulbactam, a beta-lactam antibiotic, absorbs uv light at 273 nm when in alkaline media, whereas at neutral or acidic pH this peak disappears . Sulbactam-loaded liposomes, prepared by reverse-phase evaporation, were spectroscopically analyzed by the derivative mode measuring the peak-through amplitude between +258 and -285 nm, so that the spectral interference of the sample is eliminated . Taking advantage of this experimental approach, we could study the influence of different parameters on the dissociation state of the drug when entrapped in dipalmitoyl phosphatidylcholine liposomes . In particular, following the time course of sulbactam peak disappearance, we found that: (i) the effectiveness of protonating the sulbactam of the chosen buffers is acetate/acetic acid > succinate/succinic acid > citrate/citric acid; (ii) the rate of signal disappearance is influenced by the externally imposed pH and can be somewhat related to the dissociation state of the organic acids; (iii) as expected, the whole phenomenon is temperature dependent . The observations reported here might be the basis for quantitative permeation studies in synthetic and/or natural membranes using this methodology.

Anal Biochem, 1993 Sep, 213(2), 213 - 7
Quantitation of electrostatic and hydrophobic membrane interactions by equilibrium dialysis and reverse-phase HPLC; Wimley WC et al.; Equilibrium dialysis and reverse-phase HPLC have been used for the sensitive and precise quantitation of both electrostatic and hydrophobic interactions of peptides and small molecules with lipid bilayers . We show that hydrophobic solutes are rapidly and quantitatively released from lipid dispersions when loaded onto a C4 reverse-phase HPLC column equilibrated in water+0.1% trifluoroacetic acid and that the lipid molecules have no interfering effect on the chromatography . Peptides interacting electrostatically with bilayers are released quantitatively when a higher ionic strength buffer (water+2% ammonium acetate) is used . As little as 50 ng of solute can be accurately quantitated even in the presence of milligram amounts of lipid . We demonstrate the application of these methods to the hydrophobic interactions between indoles and lipid bilayers and to the electrostatic interaction between defensins, which are cationic antibiotic peptides, and anionic bilayers . The high sensitivity allows nondestructive quantitation of submicrogram amounts of precious solutes and the high precision allows the heat capacity change, an important thermodynamic parameter, to be obtained from the partitioning data.

J Pharm Sci, 1993 Sep, 82(9), 948 - 51
A thermodynamic approach to the binding mechanisms of cefotaxime to serum albumins; Fernandez GM et al.; The interaction between cefotaxime and the serum albumin of several mammalian species (swine, rabbits, and sheep) at the albumin concentration of 5 x 10(-5) M was studied . Ultrafiltration and spectrophotometric determination of the free antibiotic in the filtrate were used . Binding percentages were determined, and the binding constants and number of sites at various temperatures were calculated . An increase in binding constants, especially in sheep albumin, and an increase in the number of sites from two to three were observed when compared to the results obtained at the physiological albumin concentration . The thermodynamic parameters of interaction varied between the following values: change in Gibbs energy, between -5.7 and -6.4 kcal.mol-1; change in enthalpy, between -6.7 and -9.6 kcal.mol-1; and change in entropy, between -3.1 and -11.2 entropy units . The binding constants increased considerably as the ionic strength of the solution decreased although the number of binding sites remained unchanged . These results indicate the existence of ionic and hydrogen bonds . The possibility of a small contribution from hydrophobic bonds cannot be ruled out.

Nippon Jibiinkoka Gakkai Kaiho, 1993 Sep, 96(9), 1482 - 9
{Relationships between ototoxicities and chemical structures of ototoxic drugs}; Fujiwara Y; The relationships between degrees of ototoxicity and the chemical structures of ototoxic drugs were investigated using isolated bullfrog semicircular canals . Thirteen derivatives of tuberactinomycin (Tum), a peptide antibiotic with pharmacological characteristics similar to those of kanamycin, were prepared by replacing the R1 branch with various amino acids . The degrees of ototoxicity were measured in these derivatives as well as in different kinds of aminoglycoside (AGs) antibiotics (TOB, GM, NTL, ISP, AMK) . In order to measure the degree of ototoxicity, the ampullary nerve action potential of isolated bullfrog posterior semicircular canal, in response to mechanical endolymphatic flow, was recorded in Frog Ringer's solution and in the presence of different amounts of the various drugs . The degree of ototoxicity was determined by the amount of decrease in the maximal spike account . The degrees of ototoxicity of AGs were calculated to be in the order TOB > GM > ISP > AMK > NTL . This result was in agreement with those of previous morphological investigations . The derivatives of Tum with an R1 branch containing an acidic or a basic amino acid showed greater ototoxicities than those containing aliphatic side chains . The degree of ototoxicity of each drug tended to differ with each concentration, in both AG and Tum derivatives . Thus, the result indicate that chemical structure may be closely related to the degree of ototoxicity.

J Clin Pharmacol, 1993 Sep, 33(9), 861 - 5
Steady-state pharmacokinetics of theophylline in COPD patients treated with dirithromycin; Bachmann K et al.; Steady-state theophylline pharmacokinetic parameters were studied in a panel of 14 patients with chronic obstructive pulmonary disease (COPD) . Pharmacokinetic parameters were evaluated before, during, and after a 10-day regimen of the macrolide antibiotic, dirithromycin . The addition of dirithromycin (500 mg orally once daily at 7:00 AM) to a sustained-release theophylline dosing regimen (every 12 hours) elicited small changes in the steady-state pharmacokinetics of theophylline, which were not statistically significant . Mean steady-state plasma theophylline trough concentrations (Css,min) were invariant before, during, and after dirithromycin treatment . Mean average steady-state plasma theophylline concentrations (Cav) declined by 7% during dirithromycin treatment (NS), and mean peak plasma concentrations (Css,max) declined by 12% (NS) . Theophylline clearance (CL/F) also remained relatively unchanged during dirithromycin treatment exhibiting an increase of only 11% (NS) . Dirithromycin treatment does not significantly affect the steady-state pharmacokinetics of theophylline, and its use in COPD patients is not likely to modify treatment outcomes with theophylline.

J Antibiot (Tokyo), 1993 Sep, 46(9), 1439 - 46
Structure-antitumor activity relationship of semi-synthetic spicamycin analogues; Kamishohara M et al.; Spicamycin, a nucleoside antibiotic containing fatty acids with a variety of chain lengths (C12-C18), showed potent antitumor activity against human gastric cancer SC-9 and human breast cancer MX-1 in a xenograft model . We have made several semi-synthetic spicamycin analogues (SPMs) which differed in the chain length of the fatty acid moiety, and examined their structure-antitumor activity relationship . The cytotoxic activities of SPMs depended on the chain length of the fatty acid moiety, with dodecanoyl, tetradecanoyl, hexadecanoyl and icosanoyl analogues (SPM VIII, SPM X, SPM XII and SPM XVI) exhibiting the most potent cytotoxic activity against P388 murine leukemia cells . SPM VIII showed the most activity against SC-9 in the human tumor xenograft model with the highest therapeutic index among SPMs . The antitumor activity of SPM VIII was superior to that of mitomycin C.

Genetics, 1993 Sep, 135(1), 5 - 16
Gene conversions and crossing over during homologous and homeologous ectopic recombination in Saccharomyces cerevisiae; Harris S et al.; The pma1-105 mutation reduces the activity of the yeast plasma membrane H(+)-ATPase and causes cells to be both low pH and ammonium ion sensitive and resistant to the antibiotic hygromycin B . Revertants that can grow at pH 3.0 and on ammonium-containing plates frequently arise by ectopic recombination between pma1-105 and PMA2, a diverged gene that shares 85% DNA sequence identity with PMA1 . The gene conversion tracts of revertants of pma1-105 were determined by DNA sequencing the hybrid PMA1::PMA2 genes . Gene conversion tracts ranged from 18-774 bp . The boundaries of these replacements were short (3-26 bp) regions of sequences that were identical between PMA1 and PMA2 . These boundaries were not located at the regions of greatest shared identity between the two PMA genes . Similar results were obtained among low pH-resistant revertants of another mutation, pma1-147 . One gene conversion was obtained in which the resulting PMA1::PMA2 hybrid was low pH-resistant but still hygromycin B-resistant . This partially active gene differs from a wild-type revertant only by the presence of two PMA2-encoded amino acid substitutions . Thus, some regions of PMA2 are not fully interchangeable with PMA1 . We have also compared the efficiency of recombination between pma1-105 and either homeologous PMA2 sequence or homologous PMA1 donor sequences inserted at the same location . PMA2 x pma1-105 recombination occurred at a rate approximately 75-fold less than PMA1 x pma1-105 events . The difference in homology between the interacting sequences did not affect the proportion of gene conversion events associated with a cross-over, as in both cases approximately 5% of the Pma+ recombinants had undergone reciprocal translocations between the two chromosomes carrying pma1-105 and the donor PMA sequences . Reciprocal translocations were identified by a simple and generally useful nutritional test.

Clin Infect Dis, 1993 Sep, 17(3), 505 - 7
Nonfatal and fatal infections caused by Chromobacterium violaceum; Ti TY et al.; Human infection caused by Chromobacterium violaceum is rare, but when it occurs it is associated with a high mortality rate . We report the cases of two patients with infection due to Chromobacterium violaceum . One patient presented early in the course of disease and survived after receiving appropriate antibiotic therapy . The other patient presented late in the course of disease and died of fulminant sepsis with abscesses in multiple organs . We discuss the similarity between C . violaceum infection and the septicemic form of melioidosis.

Clin Infect Dis, 1993 Sep, 17(3), 420 - 5
An epidemic of infections due to Chlamydia pneumoniae in military conscripts; Ekman MR et al.; A prospective observational study of an epidemic of infection due to Chlamydia pneumoniae strain TWAR in Finnish military trainees provided new information on immunity following infection, the range of clinical syndromes and complications, and cell culture isolation . One-half of the trainees studied (43 of 86) had laboratory evidence of C . pneumoniae infection . The etiologic association of C . pneumoniae with disease was strengthened by the sharp increase in cases of pneumonia and in outpatient visits for acute respiratory disease along with the laboratory evidence of infection . The pattern of serological response suggested that 23 of the trainees had a primary TWAR infection and 20 had a reinfection . Evidence that prior infection modified the illness included the frequency of hospitalization (12 with primary infections vs . 1 with reinfection), the development of pneumonia (10 vs . 0), and the requirement for repeated courses of antibiotic therapy (13 courses vs . 0) . Isolation was more frequent in HL cells (n = 25) than in HeLa 229 cells (n = 10).

J Pharm Biomed Anal, 1993 Sep, 11(9), 823 - 7
HPLC analysis of salinomycin in human plasma using pre-column oxidation and automated heart cut column switching; Karnes HT et al.; Salinomycin is a polyether antibiotic used to promote growth in cattle and poultry . Workers may be exposed to salinomycin through handling of animal feeds that contain the drug and it is necessary to monitor plasma samples from these workers for salinomycin to ensure safety . A method for analysis of salinomycin in plasma samples was therefore developed . Salinomycin and the internal standard narasin are extracted into iso-octane then subjected to silica gel solid-phase extraction in which the sample is washed with methylene chloride-methanol (98.5:15) then eluted with a 90:10 proportion of the same mixture . Both salinomycin and narasin are oxidized with pyridinium dichromate to form a chromophore absorbing at 225 nm . The concentrated product was injected onto a C18 pre-column and heart cut from 1.85 to 3.65 min onto a C18 analytical column . The method was shown to be selective for salinomycin and narasin in six blank plasma samples . The method was linear over a range of 15-300 ng ml-1 with a detection limit of approximately 5 ng ml-1 . The mean absolute recovery was found to be 93.4 and 97.9% for salinomycin and narasin, respectively . The method was accurate to within 5% at all concentrations studied . Within-run and between-run precision were both less than 8% RSD at all concentrations studied and the method was suitable for the purpose of monitoring plasma from exposed agricultural workers.

Am J Physiol, 1993 Sep, 265(3 Pt 2), F435 - 9
Gentamicin-induced mobilization of iron from renal cortical mitochondria; Ueda N et al.; Iron, presumably by participating in generation of hydroxyl radical or other oxidant species or initiation of lipid peroxidation, has been shown to play an important role in several models of tissue injury, including acute renal failure induced by the antibiotic gentamicin . However, the sources of iron remain unknown . Rat renal mitochondria incubated at 37 degrees C with gentamicin resulted in a time- (15-60 min) and a dose-dependent (0.01-5 mM) iron release as measured by formation of iron-bathophenanthroline sulfonate complex FeII-(BPS)3 {at 60 min, control: 1.2 +/- 0.1 nmol/mg protein, n = 7; gentamicin (5 mM): 5.1 +/- 0.4 nmol/mg protein, n = 7} . No formation of FeII(BPS)3 complex was detected in the absence of mitochondria or when incubations were carried out at 0 degrees C . Similar results were obtained when 2,2'-dipyridyl, another iron chelator, was used for measurement of iron release . On the basis on our previous study that gentamicin enhances generation of hydrogen peroxide by renal cortical mitochondria, we examined whether effect of gentamicin on iron release is mediated by hydrogen peroxide . Catalase (which decomposes hydrogen peroxide), but not heat-inactivated catalase, as well as pyruvate, a potent scavenger of hydrogen peroxide, prevented gentamicin-induced iron mobilization . Superoxide dismutase, a scavenger of superoxide anion, or hydroxyl radical scavengers (dimethylthiourea or sodium benzoate) had no effect . Taken together, the data with scavengers indicate that gentamicin-induced iron mobilization from mitochondria is mediated by hydrogen peroxide.

Am J Physiol, 1993 Sep, 265(3 Pt 1), L250 - 9
Effect of tunicamycin on maturation of fetal mouse lung; Webster EH et al.; The mesodermal capsule of the fetal lung plays a role in differentiation of the respiratory region . It has been proposed for other epithelial organs that the mesodermal capsule influences development by modifying the basal lamina or the extended extracellular matrix . The effect could be on deposition or turnover of collagens, proteoglycans, and/or glycoproteins . This study tests the role of glycoproteins in differentiation of respiratory endings by inhibiting their synthesis with the antibiotic tunicamycin (TM) . Lungs at 16 and 18 days gestation and 3 days after birth were cultured with TM and examined for morphological and biochemical differences from normal controls . With TM, alveolar regions did not expand properly and formed fewer type I pneumocytes, although type II pneumocytes were unaffected . The epithelium of untreated respiratory regions showed greater incorporation of radioactive mannose than the airways region or mesenchyme . This incorporation was diminished in TM, but the pattern persisted . Comparison with the results obtained with beta-xyloside suggested that differentiation of type I and type II pneumocytes is under separate control.

Zhonghua Yan Ke Za Zhi, 1993 Sep, 29(5), 271 - 3
{Lyme disease in China and its ocular manifestations}; Liu AN; The authors report 30 chinese patients of ocular Lyme borreliosis, which is a tick-borne spirochaetal disease involving multiple organ systems . The ocular manifestations begin as conjunctivitis, and then as uveitis, choroidoretinitis, keratitis and vitritis . Diagnosis is based on case history and clinical and laboratory findings . Early cases may be cured by oral antibiotics while intravenous drip of large dosage is needed for advanced cases, with a relapsing rate of 16% . Prolonged systemic corticosteroids may predispose the patient to antibiotic failure; however, topical corticosteroids in combination with antibiotics may minimize ocular inflammation and complications.

Grud Serdechnososudistaia Khir, 1993 Sep-Oct, (5), 53 - 7
{Prosthesis of the aortic valve by a loose allograft}; Tsukerman GI et al.; A procedure has been developed to prepare live aortic allografts, which consists in taking a valve early after a donor's death, sterilizing it in antibiotics and freezing it to -190 degrees C in the presence of the cryoprotective agent dimethylsulfoxide . The preservation of valve tissue is evidenced by morphological studies . The first 3 operations for aortic valvular diseases were performed . In two cases, the indication for surgery was infectious endocarditis refractory to antibiotic therapy . Postimplantation complications were not seen . The competence of the allograft was confirmed by intraoperative transesophageal echocardiographical study . The patients examined 4 months postoperation developed no signs of aortic incompetence and infectious endocarditis . Thus, the creation of a bank of live valves allows this prosthesis to be implanted with appropriate indications, one of which is active infectious endocarditis of the aortic valve.

Arch Fam Med, 1993 Sep, 2(9), 997 - 1001
Chlamydia psittaci . An uncommon cause of community-acquired pneumonia; Kirchner JT et al.; Chlamydia psittaci is an uncommon cause of community-acquired pneumonia . Fewer than 200 cases of psittacosis are reported annually to the Centers for Disease Control and Prevention; however, many cases are believed to be unreported . Unrecognized cases not properly treated may result in significant morbidity and possibly have a fatal outcome . We describe a 42-year-old man with multilobar pneumonia and respiratory compromise secondary to infection with C psittaci . The patient also exhibited hepatic involvement and mild anemia as a result of systemic infection . Appropriate antibiotic therapy and respiratory support resulted in a good clinical outcome . The diagnosis of psittacosis requires serologic verification . All confirmed cases should be reported to local and state health departments and may require further investigation by the Centers for Disease Control and Prevention.

J ET Nurs, 1993 Sep-Oct, 20(5), 191 - 8
Diabetic foot ulcers: pathogenesis and management; Levin ME; Approximately 60,000 major lower extremity amputations annually are performed on diabetic patients in the United States . Diabetic foot ulcers are a major factor in 84% of these amputations . The ulcers develop as a result of minor trauma or callus breakdown in the insensate foot . Infection and vascular insufficiency lead to gangrene and amputation . Delay in treatment of these ulcers is a major factor leading to gangrene and amputation . The most important treatments of the ulcer are debridement to healthy bleeding tissue, proper culture and antibiotic therapy, identification of osteomyelitis, metabolic control, keeping weight off the foot, and (when indicated) peripheral arterial reconstruction to improve blood flow . Therapeutic shoes to prevent recurrence of the ulcer are extremely important in posttreatment of these ulcers . Because the management of ulcers is complicated, the team approach and consultation are frequently necessary . The most important step in prevention of foot ulcers in the diabetic is repeated patient education in foot care.

J Clin Neuroophthalmol, 1993 Sep, 13(3), 155 - 61; discussion 162
First isolation of Borrelia burgdorferi from an iris biopsy; Preac-Mursic V et al.; The persistence of Borrelia burgdorferi in six patients is described . Borrelia burgdorferi has been cultivated from iris biopsy, skin biopsy, and cerebrospinal fluid also after antibiotic therapy for Lyme borreliosis . Lyme Serology: IgG antibodies to B . burgdorferi were positive, IgM negative in four patients; in two patients both IgM and IgG were negative . Antibiotic therapy may abrogate the antibody response to the infection as shown by our results . Patients may have subclinical or clinical disease without diagnostic antibody titers . Persistence of B . burgdorferi cannot be excluded when the serum is negative for antibodies against it.

Mol Cell Biol, 1993 Sep, 13(9), 5175 - 85
Loss of transcriptional activation of three sterol-regulated genes in mutant hamster cells; Evans MJ et al.; Cholesterol biosynthesis and uptake are controlled by a classic end product-feedback mechanism whereby elevated cellular sterol levels suppress transcription of the genes encoding 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) synthase, HMG-CoA reductase, and the low-density lipoprotein receptor . The 5'-flanking region of each gene contains a common cis-acting element, designated the sterol regulatory element (SRE), that is required for transcriptional regulation . In this report, we describe mutant Chinese hamster ovary (CHO) cell lines that lack SRE-dependent transcription . Mutant cell lines were isolated on the basis of their ability to survive treatment with amphotericin B, a polyene antibiotic that kills cells by interacting with cholesterol in the plasma membrane . Four mutant lines (SRD-6A, -B, -C, and -D) were found to be cholesterol auxotrophs and demonstrated constitutively low levels of mRNA for all three sterol-regulated genes even under conditions of sterol deprivation . The mutant cell lines were found to be genetically recessive, and all four lines belonged to the same complementation group . When transfected with a plasmid containing a sterol-regulated promoter fused to a bacterial reporter gene, SRD-6B cells demonstrated constitutively low levels of transcription, in contrast to wild-type CHO cells, which increased transcription under conditions of sterol deprivation . Mutation of the SREs in this plasmid prior to transfection reduced the level of expression in wild-type CHO cells deprived of sterols to the level of expression found in SRD-6B cells . The defect in SRD-6 cells is limited to transcriptional regulation, since posttranscriptional mechanisms of sterol-mediated regulation were intact: the cells retained the ability to posttranscriptionally suppress HMG-CoA reductase activity and to stimulate acyl-CoA:cholesterol acyltransferase activity . These results suggest that SRD-6 cells lack a factor required for SRE-dependent transcriptional activation . We contrast these cells with a previously isolated oxysterol-resistant cell line (SRD-2) that lacks a factor required for SRE-dependent transcriptional suppression and propose a model for the role of these genetically defined factors in sterol-mediated transcriptional regulation.

Wiad Lek, 1993 Sep, 46(17-18), 718 - 20
{Neurologic complications of measles--clinical examples}; Franczak T et al.; Severe neurological complications are presented in the course of measles in three older children . In one child encephalomeningitis was diagnosed, and in two children encephalomeningingomyelitis was recognise . Favourable results were achieved after the use of hormonal therapy under antibiotic cover . The children were cured . In order to prevent effectively measles and itd complications, the prophylaxis should be intensified through rigorous programme of vaccination against this disease.

Ann Pharmacother, 1993 Sep, 27(9), 1052 - 4
Granulocyte-colony stimulating factor for sulfasalazine-induced agranulocytosis; Gales BJ et al.; OBJECTIVE: To report a case of sulfasalazine-induced agranulocytosis that was successfully treated with granulocyte-colony stimulating factor (G-CSF) . CASE SUMMARY: An 82-year-old woman developed agranulocytosis within two months of initiating sulfasalazine therapy . She was hospitalized, empiric antibiotic and antifungal agents were prescribed, and sulfasalazine therapy was stopped . The patient received G-CSF 600 micrograms/d subcutaneously for six consecutive days, starting on hospital day 5 . Agranulocytosis resolved on day 5 and leukopenia on day 6 of G-CSF therapy . No adverse reactions were attributed to administration of this agent and the patient was discharged on hospital day 13 . DISCUSSION: Numerous agents, including sulfasalazine, have been associated with agranulocytosis . Agranulocytic patients frequently experience life-threatening bacterial and fungal infections . Administration of colony stimulating factors may reduce the duration of agranulocytosis and incidence of life-threatening infections . CONCLUSIONS: G-CSF administration appears to have decreased the duration of this elderly patient's agranulocytosis and hospitalization.

Mutat Res, 1993 Sep, 319(1), 11 - 8
Sister-chromatid exchanges induced by chloramphenicol on bovine lymphocytes; Catalan J et al.; The induction of sister-chromatid exchanges (SCE) was studied in bovine lymphocyte cultures treated with chloramphenicol (CAP), an antibiotic agent in wide use in human and animal therapy . A total of six individuals, matched for sex, race, age and environmental conditions, were used for the analysis . Chloramphenicol was tested at four different concentrations (5, 10, 20 and 40 micrograms/ml) and acted for the last 24 h of the culture . Each experiment included two animals, each of which was exposed to all chloramphenicol doses, for a total of three repetitions . The results of the corresponding analysis of variance showed that this chemical had a small but statistically significant effect on the SCE frequency . In addition, the lymphocyte cultures responded strangely to this chemical: the highest SCE induction was produced by the lowest dose . However, the study of high frequency cells did not show the presence of this kind of cell which could explain this chloramphenicol response . In addition, chloramphenicol induced a high delay in the cell cycle.

J Bacteriol, 1993 Sep, 175(17), 5309 - 13
Peptidyl transferase inhibition by the nascent leader peptide of an inducible cat gene; Gu Z et al.; The site of ribosome stalling in the leader of cat transcripts is critical to induction of downstream translation . Site-specific stalling requires translation of the first five leader codons and the presence of chloramphenicol, a sequence-independent inhibitor of ribosome elongation . We demonstrate in this report that a synthetic peptide (the 5-mer) corresponding to the N-terminal five codons of the cat-86 leader inhibits peptidyl transferase in vitro . The N-terminal 2-, 3-, and 4-mers and the reverse 5-mer (reverse amino acid sequence of the 5-mer) are virtually without effect on peptidyl transferase . A missense mutation in the cat-86 leader that abolishes induction in vivo corresponds to an amino acid replacement in the 5-mer that completely relieves peptidyl transferase inhibition . In contrast, a missense mutation that does not interfere with in vivo induction corresponds to an amino acid replacement in the 5-mer that does not significantly alter peptidyl transferase inhibition . Our results suggest that peptidyl transferase inhibition by the nascent cat-86 5-mer peptide may be the primary determinant of the site of ribosome stalling in the leader . A model based on this concept can explain the site specificity of ribosome stalling as well as the response of induction to very low levels of the antibiotic inducer.

Biochim Biophys Acta, 1993 Aug 19, 1174(2), 162 - 70
Purification and characterization of nuclear scaffold proteins which bind to a highly repetitive bent DNA from rat liver; Hibino Y et al.; Our previous work (Hibino et al . (1992) Biochem . Biophys . Res . Commun . 184, 853-858) has shown that the binding affinities of a highly repetitive DNA component for rat nuclear scaffold proteins, P123 and P130, depend on the degree of sequence-directed bending of the helix axis . In the present experiment, these proteins have been purified and finally isolated by DNA-Sepharose column chromatography . The pI values of P123 and P130 were 7.2 and 8.1, respectively . The southwestern blotting revealed that a highly repetitive bent DNA (370-bp XmmI fragment) from rat liver binds readily to the isolated proteins under a hypotonic condition (50 mM NaCl) and that the level of the binding affinity for each protein was lowered with increasing NaCl concentration . The sedimentation analysis predicted that direct interaction between the XmnI fragment and P123 or P130 results in the formation of a complex which consists of two of the fragments and one molecule of the protein, alternatively, one of the fragment and three molecules of the proteins . Distamycin A, an antibiotic which binds specifically to AT-rich DNA, removed the bend in the XmnI fragment and inhibited binding of the fragment to P123 or P130, whereas neither removal of the bend nor binding inhibition was observed with chromomycin A3, an antibiotic specific for GC-rich sites in DNA . These results imply that AT-rich regions in a highly repetitive DNA component cause bending of the helix axis to be recognized by some of nuclear scaffold proteins.

J Biol Chem, 1993 Aug 15, 268(23), 17495 - 503
Single amino acid substitutions affecting the substrate specificity of the Escherichia coli K-12 nucleoside-specific Tsx channel; Fsihi H et al.; The Tsx protein from the Escherichia coli outer membrane is a channel-forming protein containing a nucleoside-specific binding site . The antibiotic albicidin enters the cell via this substrate-specific channel . Because albicidin is toxic for E . coli at a very low external substrate concentration, the Tsx channel is likely to contain a binding site for this antibiotic . To identify residues involved in the Tsx substrate-specific channel activity, we devised a selection scheme to isolate albicidin-resistant tsx mutants synthesizing Tsx proteins with defects in their nucleoside uptake function . We recovered seven distinct albicidin-resistant tsx alleles, six point mutations and a 39-base pair duplication . The mutants with a duplication of residues 21-33 of Tsx or with single amino acid substitutions of residue Gly28 (to Arg) and Ser217 (to Arg) are completely deficient in nucleoside uptake at a low substrate concentration . Substitutions of Phe27 to Leu, Gly28 to Glu, Gly239 to Asp, and Gly240 to Asp result in a Tsx protein partially defective in nucleoside transport . These mutant proteins still permit nonspecific diffusion of serine indicating that the mutations do not result in a block of the Tsx channel . Our results are discussed in terms of a model for the topological organization of the Tsx protein within the outer membrane of E . coli.

N Engl J Med, 1993 Aug 12, 329(7), 472 - 6
A randomized study of outpatient treatment with ceftriaxone for selected febrile children with sickle cell disease; Wilimas JA et al.; BACKGROUND . Because of their susceptibility to pneumococcal sepsis, children with sickle cell disease and fever are usually hospitalized for antibiotic therapy . Outpatient treatment may be a safe and less expensive alternative for selected patients . METHODS . After evaluation in the emergency room, children ranging from 6 months to 12 years of age who had sickle hemoglobinopathies and temperatures exceeding 38.5 degrees C were randomly assigned to treatment as either inpatients or outpatients . We excluded from randomization children at higher risk of sepsis (as defined by specific criteria, including temperature above 40 degrees C, white-cell count below 5000 per cubic millimeter or above 30,000 per cubic millimeter, and the presence of pulmonary infiltrates) or with complications of sickle cell disease (such as a hemoglobin level below 5 g per deciliter, dehydration, or severe pain); these children were treated as inpatients . All patients received an initial intravenous dose of ceftriaxone (50 mg per kilogram of body weight) . Those treated as outpatients returned 24 hours later for a second dose of ceftriaxone, whereas the in patients were treated as directed by their physicians . RESULTS . None of the 86 patients (with a total of 98 febrile episodes) in the randomized groups had sepsis, as compared with 6 of the 70 patients (7 of 86 episodes) excluded because of higher risk (P = 0.004) . Among the 44 children (50 episodes) assigned to outpatient treatment, there were 11 hospitalizations (22 percent of episodes) within two weeks after treatment (95 percent confidence interval, 12 to 36 percent), whereas after inpatient care only a single patient (2 percent of episodes) was rehospitalized . When the randomized groups were compared, outpatient treatment saved a mean of $1,195 per febrile episode . The median hospital stay was 3 days (range, 1 to 6) for the children randomly assigned to inpatient care and 4 days (range, 1 to 18) for the higher-risk children treated as inpatients (P < 0.001) . CONCLUSIONS . With the use of conservative eligibility criteria, at least half the febrile episodes in children with sickle cell disease can be treated safely on an outpatient basis, with substantial reductions in cost.

Pediatr Infect Dis J, 1993 Aug, 12(8), 659 - 63
Respiratory syncytial virus infections in hospitalized Canadian children: regional differences in patient populations and management practices . The Pediatric Investigators Collaborative Network on Infections in Canada; Law BJ et al.; Respiratory syncytial virus (RSV) is the most frequent cause of hospitalization for respiratory tract infection during the first 2 years of life . The optimal approach to management remains controversial . During the 1991 to 1992 RSV season RSV-infected children admitted to eight Canadian tertiary care pediatric centers were followed to: (1) assess the morbidity and mortality attributable to RSV infection among hospitalized patients with and without known risk factors for severe disease; and (2) assess regional variation in the management of RSV infection . Of 529 RSV-infected patients 69% (363) had one or more of the risk factors for severe disease and the remaining 31% (166) had none . There were significant differences (P < or = 0.01) between the high and low risk groups, respectively, for: intensive care unit admission (27%, 2%), assisted ventilation (14%, 0.6%), ribavirin therapy (20%, 2%), supplemental oxygen (75%, 34%), antibiotic therapy (69%, 58%) and length of hospital stay > or = 7 days (39%, 6%) . Among low risk patients, centers varied significantly (P < or = 0.01) in the use of systemic corticosteroids (from 3 to 69% of patients), supplemental oxygen (13 to 74%), bronchodilators (68 to 93%) and ribavirin (0 to 10%) . The observed regional variation in management of hospitalized children with RSV infection has implications for both the costs of hospital care and the conduct of multicenter trials of ribavirin and other therapies for RSV infection.

Int J Oral Maxillofac Surg, 1993 Aug, 22(4), 234 - 5
Myospherulosis of the lower lip . Report of a case; Horie N et al.; A 19-year-old man with myospherulosis of the lower lip is described . The lesion was probably caused by petrolatum-based antibiotic ointment.

FEMS Microbiol Lett, 1993 Aug 1, 111(2-3), 141 - 6
Characterization of three different lytic transglycosylases in Escherichia coli; Romeis T et al.; Two lytic transglycosylases, releasing 1,6-anhydromuropeptides from murein sacculi are present in a mutant deleted for the soluble lytic transglycosylase 70 (Slt70) . Thus, there are three different lytic transglycosylases in Escherichia coli . One of the remaining enzymes is soluble and one is a membrane protein that can be solubilized by 2% Triton X-100 in 0.5 M NaCl . Both enzymes are exo-muramidases . Only the membrane enzyme, but not the soluble ones, hydrolyses isolated murein glycan strands (poly-GlcNAc-MurNAc) . While the soluble enzymes are inhibited by the muropeptide TetraTriLysArg(dianhydro), the membrane enzyme is not . The antibiotic bulgecin that inhibits Slt70 does not inhibit the lytic transglycosylases present in the slt70 deletion mutant.

Clin Infect Dis, 1993 Aug, 17 Suppl 1, S58 - 62
Mycoplasmal pericarditis: evidence of invasive disease; Kenney RT et al.; Although the pathogenic mycoplasmas usually infect the respiratory and urogenital tracts, these organisms also can cause disease in remote sites . Such infections are difficult to diagnose because of both the fastidious nature of the mycoplasmas and the failure to consider their presence . Pericarditis is an uncommonly diagnosed and rarely confirmed example of invasive mycoplasmal infection . As part of a prospective study of large pericardial effusions, we discovered two cases with Mycoplasma pneumoniae infection . Subsequently, two cases of pericarditis due to Mycoplasma hominis and one due to Ureaplasma urealyticum were diagnosed . For all five patients, cultures of pericardial tissue and/or fluid were positive . In addition, four of the five patients either were immunocompromised or had undergone cardiac surgery previously . Appropriate antibiotic therapy was uniformly effective . We report here our experience with mycoplasmal pericarditis, provide evidence of an invasive pathogenesis for this syndrome, and suggest that pericardial disease caused by these organisms may not be an uncommon finding when sought in an aggressive manner.

Am J Med Sci . 1993 Aug;306(2):104.
Case report: oat cell cancer and renal failure; Andes WA; A 55-year-old woman on chronic hemodialysis was treated for small-cell lung cancer and associated symptoms of a paraneoplastic syndrome . Partial remission with an antineoplastic agent, an antineoplastic antibiotic, and vincristine was achieved . When the tumor advanced, carboplatin and etoposide resulted in a complete remission . Marked symptomatic improvement occurred with minimal side effects . Such examples indicate that carefully selected patients with renal failure may respond to chemotherapy and an improved quality of life.

Eur J Biochem, 1993 Aug 1, 215(3), 561 - 6
DNA-sequence binding preference of the GC-selective ligand mithramycin . Deoxyribonuclease-I/deoxyribonuclease-II and hydroxy-radical footprinting at CCCG, CCGC, CGGC, GCCC and GGGG flanked by (AT)n and An.Tn; Carpenter ML et al.; We have used hydroxy-radical and deoxyribonuclease-I footprinting to probe the interaction of mithramycin with DNA fragments containing the sequences (AT)10X(AT)10 (X = CCCG, CCGC or CGGC) and A14GCCCT15 . As expected the drug produces clear footprints located around the central four GC base pairs . The exact position of the footprint is different for the four sequences; the footprint with CCCG is displayed by two base pairs in the 5' direction relative to GCCC . These variations are explained by suggesting that mithramycin avoids the dinucleotide CG and binds better to GG/CC than GC . Although there is little change in deoxyribonuclease-I cleavage of the surrounding blocks of (AT)n, cleavage by deoxyribonuclease II is markedly enhanced and certain thymines on the 5' side of the ligand-binding site become hyperreactive to hydroxy-radical attack . Adjacent regions of An.Tn show enhanced rates of deoxyribonuclease-I cleavage in the presence of the antibiotic.

J Virol, 1993 Aug, 67(8), 4543 - 8
Entry of poliovirus into cells does not require a low-pH step; Perez L et al.; The requirement of a low-pH step during poliovirus entry was investigated by using the macrolide antibiotic bafilomycin A1, which is a powerful and selective inhibitor of the vacuolar proton-ATPases . Thus, viruses such as Semliki Forest virus and vesicular stomatitis virus that enter cells through endosomes and need their acidification, are potently inhibited by bafilomycin A1, whereas poliovirus infection is not affected by the antibiotic . The presence of lysosomotropic agents such as chloroquine, amantadine, dansylcadaverine, and monensin during poliovirus entry did not inhibit infection, further supporting the idea that poliovirus does not depend on a low-pH step to enter the cytoplasm . The effect of bafilomycin A1 on other members of the Picornaviridae family was also assayed . Encephalomyocarditis virus entry into HeLa cells was not affected by the macrolide antibiotic, whereas rhinovirus was sensitive . Coentry of toxins, such as alpha-sarcin, with viral particles was potently inhibited by bafilomycin A1, indicating that an active vacuolar proton-ATPase is necessary for the early membrane permeabilization (coentry of alpha-sarcin) induced by poliovirus to take place.

Monatsschr Kinderheilkd, 1993 Aug, 141(8), 645 - 7
{Life threatening late dislocation in chronic foreign body aspiration}; Czap C et al.; We report a case of a boy with a long-standing foreign body aspiration in the left main bronchus causing severe pneumonia of the left lung . During intravenous therapy with antibiotics there was a life-threatening event with acute dislocation of the foreign body into the right main bronchus, leading to acute respiratory insufficiency . We conclude that in chronic foreign body aspiration antibiotic therapy preceding bronchoscopy should only be performed in in-patients and with strict monitoring.

Fukuoka Igaku Zasshi, 1993 Aug, 84(8), 363 - 7
Enhancement of X-ray induced cytotoxicity by neocarzinostatin in asynchronous and synchronous rat 3Y1 fibroblasts; Nakamura K; A polypeptide antibiotic, neocarzinostatin (NCS), has recently been shown to fix potentially lethal damage and inhibit repair of sublethal damage . To extend these observations, the effects of NCS on X-ray induced cytotoxicity at different phases of the cell cycle and the induction of DNA double strand breaks (dsb) were examined using rat 3Y1 fibroblasts . Colony survival assays showed that postirradiation treatment with 0.019 micrograms/ml NCS for 20 min enhanced X-ray cell killing at all phases of the cell cycle . Neutral filter elution analyses showed that NCS increased DNA dsb induction after X-irradiation . Thus, NCS appears to enhance the radiosensitivity by increasing the initial level of radiation-induced DNA dsb.

Nippon Kyobu Geka Gakkai Zasshi, 1993 Aug, 41(8), 1335 - 40
{Cell viability assessment of cold-preserved (4 degrees C) and cryopreserved (-196 degrees C) allograft valves by flowcytometric analysis}; Niwaya K et al.; We introduced cryopreservation technique to store the allograft valve and subsequently commenced the use of the cryopreserved aortic allograft valve for aortic valve replacement . For the clinical use of the allograft valve, it is essential to evaluate the cell viability . We assessed cell viability of the allograft valve by flowcytometry (FCM), using a fluorescein diacetate (FDA)-propidium iodide (PI) stain . Pulmonary allograft valves were harvested from the cadavers with a consent . Of the 9 valves collected and sterilized in 4 degrees C antibiotic solution for 48 hours, 4 valves were stored under refrigeration (cold-preserved), and the remaining 5 valves were cryopreserved . The warm ischemic time from cardiac death to valve preservation was 7.3 +/- 5.4 hours . The cold-preserved valves were stored at 4 degrees C in the nutrient medium (TC-199, calf serum and HEPES buffer) . The cryopreserved valves were frozen by a programmable freezer to -80 degrees C in the same nutrient medium containing 10% dimethylsulfoxide (DMSO), and subsequently stored in liquid nitrogen (-196 degrees C) . We assessed the cell viability of the allograft valve leaflet, before storage and at 2 weeks, 1 month and 2 months after the storage . Suspensions of the valve leaflet fibroblasts were double-stained with FDA (1 micrograms/ml) and PI (1 microgram/ml) for flowcytometric analysis of the viable cells (cells showing a chromatic response to FDA but no response to PI) . In the cold-preserved group, percentage of the viable cell was 90.3 +/- 3.6% before storage, 62.0 +/- 3.0% after 1 month of storage, and 50.3 +/- 3.7% after 2 months of storage.(ABSTRACT TRUNCATED AT 250 WORDS)

Emerg Med Clin North Am, 1993 Aug, 11(3), 797 - 809
Emergency department treatment of hand burns; Drueck C 3rd; The hand burn, although small, can cause significant loss for the patient . Therefore, decisive attention to preserve the skin and the function of the fingers is required . This article reviews assessment of burn injuries, types of burn injuries, and treatment . Pain management information is provided along with recommended antibiotic regimens . Criteria on admission versus outpatient treatment, which is particularly relevant for the emergency physician, is also presented.

Burns, 1993 Aug, 19(4), 306 - 10
Topical phenytoin in the treatment of split-thickness skin autograft donor sites: a comparative study with polyurethane membrane drape and conventional dressing; Yadav JK et al.; The effectiveness of topical phenytoin as a wound healing agent was compared with that of OpSite (Smith & Nephew) and a conventional topical antibiotic dressing (Soframycin, Roussel) in a controlled study of 60 patients with partial-thickness skin autograft donor sites on the lower extremities . Mean time to complete healing (complete epithelialization) was 6.2 +/- 1.6 days in the phenytoin-treated group (30 patients), compared to 8.6 +/- 2.2 days with OpSite (15 patients), and 12.6 +/- 3.4 days in the 15 Soframycin-treated patients . The differences between the treatment groups were significant at P < 0.001 . Mean pain scores were also lower in the phenytoin-treated group, 0.40 +/- 0.55 vs . 0.66 +/- 0.60 with OpSite (P < 0.05) and 1.4 +/- 0.50 with the conventional dressing (P < 0.001) . Both phenytoin and OpSite were superior to the Soframycin dressing with respect to bacterial contamination and wound infection as measured by Gram stains of wound smears, swab and aspirate (OpSite) cultures, and clinical assessments (P < 0.001) carried out on the fifth day of treatment . No local or systemic adverse effects of the three agents used were noted . Phenytoin appears to be an effective, low-cost and safe method for the treatment of partial-thickness skin graft donor sites, comparing very favourably with, and in some aspects superior to, occlusive dressings . Further clinical use and evaluation of topical phenytoin are merited.

Arch Ital Urol Androl, 1993 Aug, 65(4), 391 - 6
{Transrectal echography in the evaluation of the effects of endocavitary laser therapy in patients with bacterial prostatitis}; Martino P et al.; 104 patients with acute bacterial prostatitis were randomized to an antibiotic therapy group (group I) and an antibiotic plus laser therapy group (group II) . Laser therapy was applied ever other day through a trans-rectally inserted fiberoptic probe . Resolution of the symptoms occurred in 87% of the patients in group I and 92% in group II (p < 0.001) . Transrectal ultrasound resulted in resolution of the peri-prostatic venous plexus congestion in 43.7% of the patients in group I and 89.7% in group II . In conclusion, the combination of laser therapy and antibiotics in bacterial prostatitis provides both a better resolution of the symptoms and a reduction or disappearance of the peri-prostatic venous congestion.

Br J Cancer, 1993 Aug, 68(2), 264 - 8
Structural and functional contributions to the G1 blocking action of the retinoblastoma protein . (the 1992 Gordon Hamilton Fairley Memorial Lecture); Livingston DM et al.; The retinoblastoma gene product (RB) contributes to normal cell growth control . One of its functions is manifest as a block to exit from G1, which is carried out by an RB subspecies which is un- or underphosphorylated . After RB phosphorylation, a process which occurs towards the end of G1 in cycling cells, the block is lifted allowing a cell to enter S . Here, we review a series of results which speak to the elements of RB structure which contribute to this activity . Included is its internal colinear protein receptor domain (i.e . the 'pocket').

J Trop Med Hyg, 1993 Aug, 96(4), 241 - 4
Ophthalmomyiasis in Kuwait: first report of infections due to the larvae of Oestrus ovis before and after the Gulf conflict; Hira PR et al.; We report for the first time four cases of ophthalmomyiasis due to the larvae of Oestrus ovis in Kuwait, before and after Operations Desert Shield and Desert Storm . The larvae were easily removed under local anaesthetic . The symptom complex of acute foreign body sensation, irritation, redness, lacrimation and photophobia resolved rapidly . Ophthalmic antibiotic and corticosteroid drops were also instilled and recovery was uneventful . The ophthalmomyiasis may not always be associated with contact with sheep-rearing per se . Medical personnel should therefore be aware that in cases of what might appear initially as acute, non-specific catarrhal conjunctivitis, patients with the persistent symptom complex should be re-examined to exclude ophthalmomyiasis due to the larvae of O . ovis in endemic areasPublication Types:

Case Reports

What Is Genome?, What is Food Microbiology?, What Is Salmonella?, What Is Prokaryote?, What Is Amino Acid?, e, Bacteriology, s, Bacterium, r, Microbe, i, Microbiology, i, Microbes, o, Micrococci, a, Staphylococcus aureus, o, Microbial, a, Escherichia coli, r, Escherichia coli, o, Escherichia coli, c, Propionibacteria, i, Microflora, r, Salmonella, i, Escherichia coli, n, Salmonella, c, Escherichia coli, i, Multidrug resistant, n, Shigella, r, Escherichia coli, c, Microbial, i, Antibiotic treatment, i, S. cerevisiae, o, Fermentations, a, Escherichia coli, o, Shigella

Scientific Publications - Work Done by Microbiology Reader Bioscreen C
Agricultural Microbiology Anaerobic Microbiology Antimicrobial Susceptibility Artificial Atmosphere Bioassay of Antibiotics Biofilm Microbiology Bioreactor Technology Biotechnology Cell Biology Clinical Microbiology Environmental Microbiology Experiments with Yeast	Fermentation Food Microbiology Functional Genomics Gene Technology Growth Media Development Growth Rate and Lag Time Industrial Microbiology Medical/Pharmaceutical Field Microbiological Assay Microbiological Research Microbiology of Cosmetics go to a specific theme...	Military Microbiology Molecular Microbiology Mutagenicity and Genotoxicity Oral Microbiology Patents Postantibiotic Studies Soil Microbiology Spore Microbiology Veterinary Microbiology Waste/Wastewater Treatment Water Microbiology Wine Microbiology

� 2005 Transgalactic Ltd (manufacturer of Bioscreen C software) | Privacy Statement | P.O. Box 1393, 00101 Helsinki, Finland, phone: +358 9 85172920, fax: +358 9 8749481, e-mail: microbiology@bionewsonline.com

Last modified: May 25, 2005