Antibiotics

Biochimie, 1987 Feb, 69(2), 131 - 6
Does streptomycin cause an error catastrophe?
Fast R, Eberhard TH, Ruusala T, Kurland CG.
We have examined the interpretation that streptomycin kills a bacterial culture by initiating the so-called error catastrophe . In particular, we asked whether the increased translational error rate induced by the antibiotic gives rise to an autocatalytic loss of functional fidelity of the devices responsible for gene expression, which ultimately causes the death of the culture . We have analyzed the performance characteristics of one of these devices, namely the ribosome in streptomycin-treated bacteria . We find that, although the treated ribosomes are constructed from error-containing proteins, they are not significantly different in elongation rate and fidelity from those ribosomes taken from untreated bacteria . We conclude that the bacteriocidal effect of streptomycin is not due to the initiation of an error catastrophe.

Ann Surg, 1987 Feb, 205(2), 111 - 8
Proximal bile duct cancer . Quality of survival; Lai EC et al.; A retrospective study of 97 patients with proximal bile duct cancer treated at the University of California, Los Angeles Medical Center was conducted to determine the benefits of different operative treatments . Eighty-nine patients were divided into three treatment groups: Group I, curative resection (29 patients); Group II, palliative resection (13 patients) and bypasses (8 patients); and Group III, operative intubation (39 patients) . Two patients died before operation and six patients were treated without operation by percutaneous biliary decompression . High morbidity rate (53.8%) and mortality rate (69.2%) were encountered in 13 patients who had hepatic resection . Survival rates of the three treatment groups were comparable . For the 64 patients closely monitored after discharge, quality of survival was assessed according to six parameters: frequency of hospitalization for cholangitis; catheter-related problems; the percentage of days hospitalized; duration of jaundice; antibiotic requirements; and analgesic needs . Group I patients had the best qualitative survival, whereas Group II patients had the worst result when compared with either Group I (p less than 0.001) or Group III (p less than 0.005) . Curative resection is recommended when it can be done without a concomitant hepatic resection . When noncurable disease is found on examination, operative intubation after dilatation is the preferred palliative measure.

Biochemistry, 1987 Jan 27, 26(2), 438 - 45
Biosynthesis of lasalocid A: biochemical mechanism for assembly of the carbon framework; Sherman MM et al.; Labeling experiments on the biosynthesis of the polyether antibiotic lasalocid A (1) using carboxylic acid precursors bearing 13C, 2H, and 3H labels at various positions established the following: (1) 2H or 3H at C-2 of propionate or 2H at C-2 of butyrate was partially retained at C-12 and C-14 of 1, respectively . (2) 2H at C-2 of propionate or at C-2 and C-3 of succinate did not label C-10 . These and earlier data {Hutchinson, C . R., Sherman, M . M., Vederas, J . C., & Nakashima, T . T . (1981) J . Am . Chem . Soc . 103, 5953; Hutchinson, C . R., Sherman, M . M., McInnes, A . G., Walter, J . A., & Vederas, J . C . (1981) J . Am . Chem . Soc . 103, 5956} are consistent with a hypothesis for the stereochemical control of lasalocid A biosynthesis, whose main tenets are that the configuration of C-12 and C-14 is determined by the stereoselectivity of the carbon chain forming condensation between acyl thio ester and 2-carboxyacyl thio ester intermediates and that the configuration of C-11 and C-15 results from the reduction of 2-keto thio ester intermediates with opposing stereospecificities.

Science, 1987 Jan 16, 235(4786), 350 - 2
Epithelial wound healing enhanced by transforming growth factor-alpha and vaccinia growth factor; Schultz GS et al.; Epidermal regeneration following middermal injuries to skin requires both proliferation and migration of keratinocytes . Epidermal growth factor (EGF) stimulates the proliferation of keratinocytes in culture, and topical administration of EGF accelerates epidermal regeneration of partial thickness burns or split-thickness incisions in vivo . Transforming growth factor-alpha (TGF-alpha) and vaccinia growth factor (VGF) have substantial sequence homology with EGF, and all appear to bind to the same receptor protein . Whether TGF-alpha or VGF can affect epidermal wound healing in vivo is not known . The present studies show that topical administration of TGF-alpha or VGF in antibiotic cream to partial thickness burns (second degree) accelerated epidermal regeneration in comparison with untreated or vehicle-treated burns . Low levels of both TGF-alpha and VGF (0.1 microgram per milliliter) appeared to be more effective than EGF in stimulating epidermal regeneration . Regenerated epithelium from burns treated with TGF-alpha or VGF appeared normal histologically . This finding suggests that topical application of selected growth factors may be useful in accelerating healing of partial thickness injuries.

Cancer, 1987 Jan 15, 59(2), 259 - 65
Concurrent radiotherapy and chemotherapy with cisplatin in inoperable squamous cell carcinoma of the head and neck . An RTOG Study; Al-Sarraf M et al.; In patients who have locally advanced and inoperable head and neck cancer, the achievement of initial local control (complete response) of the disease with initial definitive treatment with radiotherapy (RT) with or without chemotherapy, is an important prognostic factor for overall survival . Cisplatin 100 mg/M2-intravenously (IV) with hydration and mannitol diuresis was given every 3 weeks for three doses concurrently with definitive radiotherapy (followed by salvage surgery {if possible} for persistent disease) was activated by the Radiation Therapy Oncology Group (RTOG) in 1981 . One hundred thirty-four patients were initially registered and 124 were eligible and analyzed for this report . Eighty-two percent of the patients had Stage IV disease and greater than 50% of the primary sites were in oropharynx (39%), nasopharynx (22%), and oral cavity (18%) . Eighty-seven percent of the patients are known to have finished the planned RT greater than 6450 cGy and 60% received three courses of cisplatin . Overall, 60% finished the planned combined treatment . Complete response to initial treatment occurred in 69% and an additional one patient (1%) was rendered disease-free after radical node dissection . Severe toxicities were as follows: leukopenia, 11%; anemia, 8%; nausea and vomiting, 6%; stomatitis, 31%; and renal, 6% . One toxic death occurred when a nephrotoxic antibiotic was administered at the same time . All patients were evaluated for total disease and survival regardless of compliance to the treatment or the cause of death . At 1 year, an estimated 51% of the patients had their disease totally controlled and an estimated 66% were alive . Incidence of initial complete response by various patient characteristics also were analyzed . The authors concluded that the combination of cisplatin and radiotherapy is an effective and safe treatment in patients with advanced head and neck cancer and needs to be tested against radiotherapy alone.

Hosp Formul, 1987 Feb, 22(2), 182 - 6
Altering aminoglycoside selection in a community hospital; Mioduch HJ et al.; The aminoglycoside antibiotics make up a large part of the pharmacy budget . A method developed by the pharmacy department in conjunction with the P & T Committee for implementing usage guidelines at a community hospital is presented . The program was designed to promote cost-effective therapy while maintaining safety and efficacy . After the program was implemented, both aminoglycoside use and expenditures were altered . The data indicate that by incorporating current medical information into an institution-specific program, it is possible to bring about a decrease in the cost of antibiotic therapy . This study suggests that interventions may be effective in community hospitals as well as in large teaching institutions.

Klin Wochenschr, 1987 Jan 5, 65(1), 40 - 7
{Amphotericin B and flucytosine therapy of Aspergillus pneumonia and acute renal failure}; Staib F et al.; Kidney failure and pneumonia by Aspergillus flavus and A . fumigatus were found in a 56-year-old woman who had received antibiotic and corticoid treatment to control high fever . Her bloody tracheal secretion was a suspension of granule-like spore-free colonies of both Aspergillus species . Hemorrhages in mucous membranes and skin suggested a hematogenous dissemination of the fungi . Aspergillus spores in the soil of ornamental plants were assumed to be responsible for the inhalatory infection . The kidney function normalized rapidly under treatment by amphotericin B plus flucytosine and hemodialysis performed eight times . After 29 days of antimycotic treatment (amphotericin B 463 mg, flucytosine 150 g), besides normalization of the kidney function, healing of the pneumonia and bleeding from skin and mucal membranes took place . One and a half years later kidney function and blood parameters were found to be normal . In cases of Aspergillus pneumonia and kidney failure, a combined treatment by hemodialysis and amphotericin B plus flucytosine is recommended . In addition, there is discussion of the general importance of uremia and its influence on the mycotic infection.

No To Shinkei, 1987 Jan, 39(1), 65 - 70
{Intracranial hemorrhage in infancy due to vitamin K deficiency: report of a case with multiple intracerebral hematomas with ring-like high density figures}; Nishio T et al.; It is well known that vitamin K deficiency is an important cause of the spontaneous intracranial hemorrhage in infancy . A 60-day-old male infant with spontaneous intracerebral hematomas due to vitamin K deficiency was presented . He was breast-fed . He had been medicated oral antibiotic agent for diarrhea and fever . Three days later he developed petechien, vomiting and twitching, and became drowsy . The blood studies showed anemia, and advance of ESR . He was administered of vitamin K immediately . CT scan was showed four intracerebral hematomas with niveau, which were surrounded by high-density rings . The ring-like figures were unique for this case . The reason may be next, we think . Under the states in which blood can separate easily with advance of ESR, blood clot would adhere to the wall of the hematomas . So these hematomas showed ring-like figures and had niveau in them . CT scan of this case was also interesting because there was little deviation in spite of the big hematomas . The reason of this may be that the brain of infancy is incomplete in myelination and contains much water, and that the possibility of bleeding due to vitamin K occurs slowly . We examined 84 cases of intracranial hemorrhage due to vitamin K deficiency from literatures, and they were all identified for the hemorrhage sites by CT scan . Subarachnoidal hemorrhage was in 72 cases (85.7%), subdural hemorrhage was in 41 cases (48.8%), intracerebral hematomas was in 36 cases (42.9%) and intraventricular hemorrhage was in 9 cases (10.7%) . In 52 cases the CT findings were described.(ABSTRACT TRUNCATED AT 250 WORDS)

Acta Anat (Basel), 1987, 128(1), 76 - 9
Increase in cholesterol in the apical plasma membrane of uterine epithelial cells during early pregnancy in the rat; Murphy CR et al.; Freeze-fracture cytochemistry with the cholesterol-binding antibiotic filipin has been used to examine the plasma membrane of uterine epithelial cells at different stages of pregnancy in the rat . We find many more filipin-induced lesions on day 6 of pregnancy than on day 1 and suggest that this indicates a higher cholesterol content at this time . Since day 6 of pregnancy is the time at which blastocysts implant in the rat uterus, we consider the possible significance of an increased cholesterol content for implantation.

Rev Infect Dis, 1987 Jan-Feb, 9(1), 88 - 96
Esophagitis in the immunocompromised host: role of esophagoscopy in diagnosis; Wheeler RR et al.; Thirty episodes of presumed infectious esophagitis in immunocompromised patients were investigated by means of esophagoscopy . Indications for esophagoscopy included dysphagia, odynophagia, and retrosternal pain . Factors potentially predisposing patients to esophagitis included previous exposure to radiation, recent cytotoxic chemotherapy, recent antibiotic therapy, corticosteroid therapy, and neutropenia . Sixteen of the 18 barium esophagograms done before esophagoscopy was performed revealed abnormalities; in 14 cases the results were consistent with infectious esophagitis . Abnormalities were noted during 27 of 30 esophagoscopy procedures . Visual findings were consistent with candidal esophagitis in 18 cases, with viral esophagitis in four, and with both in one . Specific infectious diagnoses were established by culture or histology in 17 episodes: 12 of candidal esophagitis, two of herpes simplex esophagitis, two of concomitant candidal and herpetic esophagitis, and one of enteroviral esophagitis . Specific noninfectious diagnoses were made in two episodes, and the esophagus was found to be normal in three . No specific diagnosis was made in eight episodes although visual examination indicated the presence of esophagitis . The only postesophagoscopy complications recorded were isolated episodes of spiking fever in three patients . In this compromised-host population with presumed infectious esophagitis, esophagoscopy resulted in a rapid and specific infectious diagnosis in 57% of episodes.

Folia Microbiol (Praha), 1987, 32(1), 1 - 5
Production of quinomycin A in Streptomyces lasaliensis; Steinerova N et al.; In addition to lasalocid, an oligoether coccidiostatic compound, other compounds are synthesized by Streptomyces lasaliensis . Mutants producing either of two antibiotics, lasalocid A or quinomycin A (an antibiotic of quinoxaline character), were obtained by natural selection and by mutagenesis . Methods of isolation, purification and estimation of both compounds were established.

J Int Med Res, 1987 Jan-Feb, 15(1), 49 - 56
Rifaximin, a rifamycin derivative for use in the treatment of intestinal bacterial infections in seriously disabled patients; Alvisi V et al.; This study reports the results of an evaluation of the effectiveness and tolerability of rifaximin, an intestinal topical antibiotic . It was administered using a nasogastric tube in patients with severe enterocolitis and bacterial superinfections causing intestinal inflammatory diseases and portosystemic encephalopathy . The drug proved highly effective clinically and produced neither local nor systemic side-effects.

Can J Surg, 1987 Jan, 30(1), 42 - 4
The epidural opioid internalized system; Miller BJ et al.; For several years opioids have been given epidurally with success to control chronic intractable pain . The authors report their 2-year experience with internalization of the epidural catheter and injection port in 18 patients at University Hospital, Saskatoon . In all, 21 devices were used . All patients had metastatic cancer; 16 are now dead . The need for other medications was eliminated with 9 and reduced with 12 devices . In the patients who died, the devices were effective for 82% of their remaining life-span . They were able to spend 46% of this time at home . Blockage of the epidural end of the device was the most common mechanical problem, followed by leakage from the port . One patient suffered meningitis after 11 days as a result of subarachnoid placement of the catheter but responded to removal of the device and antibiotic therapy . The authors have been impressed with the excellent pain relief afforded to many of these patients, and their ability to enjoy life free of the sedative effects of other methods of narcotic administration.

J Clin Oncol, 1987 Jan, 5(1), 75 - 82
High-dose cytosine arabinoside as the initial treatment of poor-risk patients with acute nonlymphocytic leukemia: a Leukemia Intergroup Study; Preisler HD et al.; Sixty-seven patients with newly diagnosed acute nonlymphocytic leukemia (ANLL) who were considered to be poor candidates for treatment with cytosine arabinoside (ara-C)/anthracycline antibiotic therapy were treated with high-dose ara-C (HDara-C) remission induction therapy . Thirty-four of the 67 patients had a hematologic disorder before developing acute leukemia or had a history of exposure to marrow toxins, 23 patients were greater than 70 years old, and 10 patients had medical problems that were felt to be a contraindication to therapy with an anthracycline antibiotic . Forty-two percent of patients entered complete remission (CR), whereas 22% failed to enter remission because of persistent leukemia . Treatment was associated with substantial toxicity varying from nausea and vomiting to irreversible cerebellar toxicity . Thirty-four percent of patients died during therapy . Poor performance status, a low serum albumin, and a low platelet count were associated with death during remission induction therapy, whereas a high pretherapy leukemic cell mass and a large number of residual leukemic cells in the marrow after six days of therapy were associated with treatment failure due to persistent leukemia.

Am J Surg, 1987 Jan, 153(1), 125 - 9
Percutaneous cholecystostomy for acute cholecystitis in high-risk patients; Klimberg S et al.; Seventeen high-risk critically ill patients with suspected cholecystitis underwent percutaneous transhepatic cholecystostomy between 1981 and 1986 using Hawkins' needle guide system for gallbladder intubation . Acute cholecystitis was documented in 15 patients, including 1 with common bile duct obstruction . Two other patients had common bile duct obstruction secondary to metastatic cancer (one patient) and chronic pancreatic fibrosis (one patient) . There was rapid resolution of the signs and symptoms of cholecystitis, sepsis, or both in 16 of the 17 patients . One critically ill patient with positive findings on blood culture and an organism resistant to triple antibiotic therapy died soon after percutaneous cholecystostomy . In the entire group of 17 patients, there was no evidence of bile leaks or other catheter complications . Six patients subsequently underwent successful cholecystectomy and two underwent common bile duct exploration without complications . One patient underwent cholecystojejunostomy, and in three patients, the catheter was removed with no sequelae of cholecystitis . Two remaining patients had the catheter in place and were awaiting operation at last follow-up . Three of four patients who died within 30 days of percutaneous transhepatic cholangiographic cholecystostomy died either from the terminal malignant condition (two patients) or from arrhythmia (one patient with cirrhosis) . This review suggests that percutaneous cholecystostomy is a safe and effective procedure for resolving acute cholecystitis in high-risk patients . In addition, the technique of percutaneous transhepatic cholangiographic cholecystostomy appears well suited for percutaneous dissolution of stones, sclerosis of the gallbladder, or both in selected high-risk critically ill patients.

J Vasc Surg, 1987 Jan, 5(1), 160 - 9
The impact of multiple operations on the importance of arterial wall cultures; Durham JR et al.; The present study reviewed arterial culture data from 172 patients undergoing major vascular reconstructions between July 1, 1977, and Dec . 31, 1984 . Prosthetic graft infection was documented in 0 of 97 cases (0%) with negative arterial cultures but in six of 75 cases (8%) with positive arterial cultures (chi 2 = 5.84; 0.01 less than p less than 0.025) . The data were reanalyzed after the patients were subdivided into two groups on the basis of the numbers of operations: group I (132 patients)--a culture obtained at initial vascular reconstruction--and group II (40 patients)--a culture obtained at a subsequent vascular reconstruction . Positive arterial cultures had no predictive value for graft infection among patients in group I (1 of 57 cases vs . 0 of 75 cases; chi 2 = 0.019), whereas the presence of positive arterial cultures was associated with a significant increase in the incidence of graft infection in group II patients (5 of 18 cases vs . 0 of 22 cases; chi 2 = 4.68; 0.025 less than p less than 0.05) . For group I patients, we believe that neither routine arterial culture nor long-term antibiotic therapy for patients with positive arterial cultures is indicated . For group II patients we recommend that routine arterial cultures should be obtained; perioperative antibiotics should be continued until definitive arterial culture information is available; and positive arterial cultures should be treated with a short course of high-dose intravenous antibiotics . Thereafter, long-term treatment of positive arterial cultures with oral antibiotics, although not statistically validated, is probably appropriate.

J Fam Pract, 1987 Jan, 24(1), 35 - 8
An association between acute bronchitis and asthma; Williamson HA Jr et al.; The relationship between the common acute bronchitis syndrome and atopic disease was examined using a retrospective, case-control method . The charts of 116 acute bronchitis patients and of a control group of 60 patients with irritable colon syndrome were reviewed for evidence of previous and subsequent atopic disease or asthma . Bronchitis patients were more likely to have a previous history of asthma, a personal history or diagnosis of atopic disease, and more previous and subsequent visits for acute bronchitis . The main finding of the study was a tenfold increase in the subsequent visit rate for asthma in the acute bronchitis group . Thirty percent of patients with acute bronchitis made return visits for unresolved cough despite an 83 percent rate of antibiotic use . These findings challenge the common belief that the symptoms of acute bronchitis are solely infectious in origin and suggest the involvement of occult bronchospasm.

Infection, 1987, 15(5), 378 - 80
Clinical course of an exacerbated pulmonary infection in a girl with cystic fibrosis (CF); Dockter G; The treatment of severe pulmonary infection in young CF-adults depends on age, clinical course, bacterial colonization of the lung, susceptibility pattern and state of nutrition . Besides specific antibiotic therapy, enzyme replacement and physiotherapy, high caloric nutrition, continuous oxygen insufflation and early mobilisation are the main tools in the treatment of an exacerbated pulmonary infection with respiratory insufficiency.

Clin Neurol Neurosurg, 1987, 89(4), 269 - 70
Rapidly growing head circumference as an isolated presenting symptom of brain abscesses in an infant; Lahat E et al.; A rapid and excessive enlargement in occipito frontal circumference (OFC) as the only manifestation of multiple cerebral abscesses in infancy is extremely rare . A 2-month-old asymptomatic infant presenting with increasing OFC is described . Surgical drainage of the cerebral abscesses followed by prolonged antibiotic therapy resulted in complete recovery.

Ann Chir Gynaecol, 1987, 76(3), 139 - 44
Early endocarditis following open-heart surgery--importance of surgical treatment; Verkkala K et al.; Nine cases of proven early form of endocarditis occurred after open-heart surgery . Eight of these occurred after valve surgery with an incidence 0.7% while one complicated correction of Fallot's tetralogy . Sternal wound infection preceeded endocarditis in two cases and respiratory tract infection in one case . In these three patients, the infection was caused by the same bacteria as the subsequent postoperative endocarditis . In only one patient were there no signs of infection during the immediate postoperative course . A new cardiac murmur suggesting prosthetic malfunction was a clear indication for early reoperation in five patients; four of them survived . In one patient with a paravalvular leakage the decision to operate was delayed with fatal outcome . Generally, in patients without signs of prosthetic valve malfunction or other prosthetic complication the indication and timing of surgery is problematic . In our series the antibiotic therapy was continued over two months in three patients . Two of them died while the third patient was operated on successfully.

Vet Med Nauki, 1987, 24(7), 32 - 6
{Pharmacological research on ophthalmic drug lamellae containing gentamycin sulfate in laboratory and agricultural animals}; Vangelov S et al.; The in vitro and in vivo solubility of ocular drug lamellae, containing 1.5 and 3 mg gentamycin sulphate, was followed up . It was found that those that contained lower amount of the antibiotic disintegrated in the eyes of rabbits, lambs, and sheep for 30-40 minutes, while lamellae having 3 mg gentamycin disintegrated for 45-50 minutes . It is stated that such ocular lamellae are well tolerated by the conjunctiva of the animal species referred to . With the application of one lamella with 3 mg gentamycin sulphate therapeutic concentrations of the antibiotic in the lacrimal secretion are found up to the 24 th hour with cows, sheep, and lambs, and up to the 48h hour with rabbits.

Intensive Care Med, 1987, 13(6), 419 - 21
Psittacosis: diagnosis and management of severe pneumonia and multi organ failure; Wainwright AP et al.; Two patients were admitted directly to our Intensive Care Unit in acute respiratory failure due to pneumonia with septicaemic shock, renal and hepatic impairment . Sputum and blood cultures failed to grow any organisms and despite broad spectrum antibiotic therapy for 7 days, neither patient improved . Diagnosis of the rare pneumonic form of psittacosis was made following a raised titre . After treatment with tetracyclines, both patients made a rapid recovery . Retrospective direct questioning revealed that they had close contact with psitacine birds.

Antonie Van Leeuwenhoek, 1987, 53(3), 191 - 6
In vitro tetracycline susceptibility of Chlamydia trachomatis in clinical specimens; Hsu AH et al.; A novel approach to determine the tetracycline susceptibility of Chlamydia trachomatis directly from specimens without cell culture propagation and adaptation has been explored . Out of a total of 1290 genital specimens from a sexually transmitted disease clinic, 211 (16.4%) were positive for C . trachomatis . A tetracycline concentration of 0.032 microgram/ml completely inhibited the appearance of inclusions in all of the 211 positive specimens . Of the positive specimens, 120 (56.9%) and 18 (8.5%) respectively showed the presence of 1 to 9 and 100 or more inclusions per microtiter well in antibiotic free medium . Other antibiotics are being tested in the same manner.

Acta Obstet Gynecol Scand, 1987, 66(3), 201 - 4
Early complications after induced first-trimester abortion; Heisterberg L et al.; Complications subsequent to 5,851 consecutively induced first-trimester abortions during the period 1980-85 were analysed . Three hundred and fifty-six abortions (6.1%) led to complications requiring hospital admission . According to bivariable analysis, women below 25 years of age, women with parity 0, women with no spontaneous and with no induced abortions, and women in gestational week 8 had significantly higher postabortal complication rates than women 25 years of age and older (p less than 0.001), women with previous births (p less than 0.0001), women with spontaneous abortions (p less than 0.005), women with induced abortions (p less than 0.005), and women in other gestational age groups (p less than 0.0005) . The mean stay in hospital per complicated abortion was 5.3 days . It was discussed whether the administration of prophylactic antibiotics to women with a history of pelvic inflammatory disease and young women completing their first pregnancy could reduce the complication ratePIP: The number of complications subsequent to 1st trimester abortion performed during the past 6 years at the Department of Gynecology and Obstetrics, University Hospital, Copenhagen, at Hvidovre, were evaluated . The associations between the women's age, obstetric history, gestational age, and the rate of early postabortal complications were analyzed . The number of hospital days spent because of such complications was calculated . All 1st trimester abortions performed at University Hospital during the January 1980 to November 1985 period were included . All procedures were performed under general anesthesia by dilatation with Hegars dilators and vacuum aspiration after cleansing of the perineum and vagina . Following aspiration, blunt curettage was performed to ensure that the uterine cavity was empty . Intravenous doses of methylergometrin 0.2 mg were administered . 85% of the women were discharged the same day and 15%, mostly for social reasons, on the following day . 5851 1st trimester abortions were performed . 356 abortions (6.1%) were complicated by 1 or several of the following complications: pathologic bleeding with or without recurettage; temperature; pelvic inflammatory disease (PID) requiring antibiotic therapy; uterine perforation; cervical injury requiring suture; continued pregnancy; and readmission without therapy . The distribution of complications in the 356 women showed significantly more complications in women in the age groups younger than 19 and 20-24 years than in other women . For 353 women, the distribution showed significantly more complications in women with parity 0 vis-a-vis parity greater than 1 . In 353 and 354 women, respectively, there were significantly more complications in women with no previous spontaneous or induced abortion than in women with 1 or more spontaneous or induced abortions . In 356 women the distribution showed significantly more complications in women in gestational week 8 than in other women . Only 1 woman required blood transfusion because of perioperative bleeding . 1889 hospital days were registered following 356 complicated abortions . The total complication rate of 6.1% compares favorably with the results of recent large investigations of abortion populations .

Intensive Care Med, 1987, 13(5), 342 - 6
Early onset pneumonia: a multicenter study in intensive care units; Langer M et al.; A prospective multicenter study concerning the incidence, onset time, risk factors and mortality of pneumonia was carried out by the Intensive Care Units Collaborative Group for Infection Control in Lombardy, Northern Italy . Out of 1304 patients admitted over 3 months in 16 intensive care units (ICUs), 441 met the criteria for the protocol (no previous pulmonary infection or irreversible terminal illness, ICU stay greater than 48 h) . The incidence of acquired pneumonia was 21.3% (94/441), with 54.2% of cases diagnosed within 4 days of admission (early onset pneumonia) . Impairment of airway reflexes on admission and more than 24 h respiratory assistance were shown as significant risk factors (RR) for early onset pneumonia (respectively RR = 12.4, with 95% confidence interval (CI) = 5.3-28.9 and RR = 3.3, with 95% CI = 1.8-5.9) . A suggested pathogenetic mechanism is aspiration of oropharyngeal contents at the onset of acute illness, due to depression of protective reflexes with delayed clearance of bacterial contamination . No protection was offered by routinely applied prophylactic antibiotic therapy.

Vet Med Nauki, 1987, 24(1), 64 - 71
{Apramycin blood concentrations and distribution in the body of calves after different methods of administration}; Shikha I; The serum concentrations of apramycin in calves were studied after i/v application at the rate of 20 mg/kg body mass, after i/m injection at 20-40 mg/kg b . m., and after oral administration (with milk) at 40 mg/kg b . m . in terms of establishing certain pharmacokinetic parameters . It was found that at i/v route of application the concentrations of the antibiotic ranged above 2 micrograms/cm3 within the interval from the 15th min up to the 8h hour . The time of half-distribution (t1/2 alpha) was 0.28 h, while the biologic half-life of half-elimination (t1/2 beta) was 2.31 h . After muscular application of apramycin at 20 and 40 mg/kg it was rapidly adsorbed at the site of injection; the maximum concentrations were 99 micrograms/cm3 and 202 micrograms/cm3, resp., from the first to the second hour . Levels above 2 micrograms/cm3 were found in the blood serum in the course of 8 to 10 hours when the antibiotic was applied at 20 mg/kg b . m., and they have persisted for more than 12 hours when it was administered at the rate of 40 mg/kg . The biologic half-life (t1/2 beta) was 1.63 h and 1.97 h, respectively . Following the oral administration of the antibiotic at 40 mg/kg subtherapeutic levels were established up to the 24 th hour, with the exception of the interval of the 6 th to 8 th when the concentrations were below the minimum therapeutic one (2 micrograms/cm3).(ABSTRACT TRUNCATED AT 250 WORDS)

Vet Med Nauki, 1987, 24(1), 57 - 63
{Changes in amoxicillin pharmacokinetics in white rats with experimentally damaged kidneys and liver}; Lashev L et al.; The blood level and the basic pharmacokinetic parameters (kel, Cop, T 1/2, AUC) of amoxicillin trihydrate were studied following its oral application to albino rats with experimentally injured kidneys (potassium chromate) and liver (tetrachloromethane) . It was found that the impairment of these organs changed the extent of absorption, distribution, and excretion of the antibiotic.

Rev Neurol (Paris), 1987, 143(3), 182 - 8
{Meningoradiculitis after a tick bite . Study of 31 cases}; Hirsch E et al.; A retrospective study covering a period of 20 years identified reports on 31 cases of meningoradiculitis of the Garin-Bujadoux-Bannwarth type (MRGBB) . Clinical, biological, electromyographic characteristics and course of the disease were studied . The most recent cases (n = 8) in 1984 and 1985 had serological tests for Borrelia Burgdorferi and half of the cases had negative results . Conversely, in some patients with meningoradiculitis, even in the absence of a tick bite or of migrating chronic erythema, serology was positive for Borrelia Burgdorferi antigen . The efficacy of antibiotic therapy against pain and on the quality and time of functional recovery justifies the use of this therapy under these two circumstances.

Arch Orthop Trauma Surg, 1987, 106(3), 144 - 51
Chronic sclerosing osteomyelitis of the clavicle . A manifestation of chronic recurrent multifocal osteomyelitis; Jurik AG et al.; The cases of five children/adolescents and two young adults with unilateral chronic osteomyelitis of the clavicle are reported . The clinical course was prolonged and characterized by intermittent periods of exacerbation followed by improvement . Extensive investigations revealed no causative organisms and the disease seemed resistant to antibiotic therapy . The only laboratory abnormality was elevated ESR, present in five cases . Osteomyelitis of other bones was detected in four cases and pustulosis palmoplantaris in two, suggesting that the disease is a manifestation of chronic recurrent multifocal osteomyelitis.

Soc Sci Med, 1987, 24(8), 689 - 95
Why we seek treatment here: retail pharmacy and clinical practice in Maiduguri, Nigeria; Igun UA; This study based on interviews with 418 persons treated for various health problems at two retail pharmacies in Maiduguri, Nigeria, sought to know why the population uses the retail pharmacies as outpatient clinics . The most frequent reasons given by the respondents for their use is 'expeditious action in consultation and treatment' . This is followed by 'efficacy of treatment given' and 'convenience' (nearest source) . There was no significant relationship between the reasons given and demographic background factors except age . The single most important advantage of retail pharmacy treatment over hospital treatment cited by respondents is 'expeditious treatment' . This is followed by 'availability of unadulterated drugs at all times' . The majority of respondents were in the habit of using retail pharmacies whenever they have illness episodes . Relatives and friends constituted the social network of significant influence over the decision to seek treatment at the particular retail pharmacy . The range of health problems reported for treatment was very wide with malaria as the most frequently reported . But the most frequent treatment given is antibiotic chemotherapy by injection or orally.

Jpn J Antibiot, 1987 Jan, 40(1), 145 - 69
{General pharmacological studies on isepamicin sulfate (HAPA-B)}; Shibata K et al.; General pharmacological properties of isepamicin sulfate (HAPA-B), a new aminoglycoside antibiotic, were studied in animals and the results obtained were summarized below . Intramuscular injections of HAPA-B at doses of 500 mg/kg inhibited the writing response induced by acetic acid, and at doses of 1,000 mg/kg, caused muscle relaxation, respiratory depression, suppression of spontaneous motor activity and prolongation of thiopental anesthesia . Anticonvulsive action and the effect on the rectal temperature were not observed . Intravenous Intravenous HAPA-B showed no significant effect on the general behavior and the function of the central nervous system at doses of 100 mg/kg . Intravenous injections of HAPA-B to anesthetized dogs resulted increases in the femoral arterial blood flow at doses of 12.5 mg/kg, decrease in the blood pressure and increase in the respiratory rate at doses of 25 mg/kg, and increase in the carotid arterial blood flow at doses of 50 mg/kg . Apparent changes were not recognized in the heart rate and electrocardiograms . In conscious rabbits, intravenous HAPA-B produced increases in the heart rate without significant changes of the blood pressure and electrocardiograms at doses of 100 mg/kg . Spontaneous beatings of isolated atria were depressed by HAPA-B in concentrations of 3 X 10(-4) to 10(-3) g/ml . The HAPA-B inhibited the gastric secretion at intramuscular doses of 500 mg/kg or intravenous doses of 100 mg/kg, and depressed charcoal transport through small intestine and the spontaneous movement of isolated ileum at intramuscular doses of 1,000 mg/kg and at concentrations of 3 X 10(-4) to 10(-3) g/ml, respectively . No irritative effect was found on the gastric mucous membrane . Intravenous HAPA-B inhibited the response of nictitating membrane to pre and post ganglionic stimulations of cervical sympathetic nerve at doses of 100 mg/kg . In in vitro test, HAPA-B inhibited nonspecifically the constrictive responses of trachea, aorta, stomach, ileum and vas deferens to various agonists in concentrations of 3 X 10(-4) to 10(-3) g/ml . Spontaneous movements of uteri of estrous or pregnant animals were depressed by HAPA-B at intravenous doses of 50 to 100 mg/kg and in in vitro at concentrations of 10(-4) to 3 X 10(-4) g/ml . Antidiuretic effect was also observed at intramuscular doses of 250 mg/kg . HAPA-B increased the length of the whole blood clotting time and raised the plasma glucose level at intramuscular doses of 1,000 mg/kg and inhibited the platelet aggregation induced by ADP in vitro at concentrations of 10(-3) g/ml.(ABSTRACT TRUNCATED AT 400 WORDS)

Int J Clin Pharmacol Res, 1987, 7(1), 51 - 8
Study on pulmonary, prostatic and renal (medulla and cortex) distribution of sagamicin at different time intervals; Fraschini F et al.; In order to assess the therapeutic activity of an antibiotic, not only its serum kinetics but also its kinetics in the peripheral tissues must be determined, thus evaluating the specific power of penetration of the drug . Sagamicin is an aminoglycosidic basic antibiotic closely related to gentamicin and its penetration rate into lungs, kidney and prostate, together with its serum concentrations time-course, were investigated . The findings obtained showed that this antibiotic attained a good distribution in the peripheral tissues, where it easily reached therapeutic levels.

Int J Clin Pharmacol Res, 1987, 7(1), 33 - 7
Digitoxin elimination in healthy subjects taking ampicillin; Lucena MI et al.; The present study was carried out to evaluate the changes in digitoxin kinetics during ampicillin administration . Subjects were informed of the nature of the study and the treatment was applied to those who gave their written consent . Six healthy volunteers received a single oral dose of 1.0 mg of digitoxin . Three days later, they were given orally ampicillin trihydrate, 500 mg four times daily, for five consecutive days . Blood samples were taken at 24, 36, 48, 60, 72, 96, 120, 144, 168 and 192 hours after digitoxin . Compliance with ampicillin regimen was verified by fluorimetric measurement of serum ampicillin . Concentrations of serum digitoxin were determined by radioimmunoassay . The mean digitoxin elimination half-life changed from 162.8 +/- 12.9 h before to 181.3 +/- 10.1 h (mean +/- s.e . mean) after ampicillin . These differences were not significant . No consistent evidence of a kinetic interaction between digitoxin and the broad-spectrum antibiotic ampicillin was found.

Chemotherapy, 1987, 33(2), 85 - 92
Multiple-dose pharmacokinetics in serum and sputum of sagamicin administered intramuscularly to patients; Fraschini F et al.; Sagamicin is an aminoglycosidic antibiotic produced by Micromonospora sagamiensis, chemically related with gentamicin . Single- and multiple-dose pharmacokinetics have been investigated in patients affected by bronchopulmonary infections treated with 60 mg sagamicin i.m . every 12 h . The two concentration-time curves for sputum and serum are parallel; while there is no evidence of accumulation in the serum at the 7th day of treatment, sagamicin concentrations in the sputum are significantly higher on the 7th day, and this is also confirmed by a remarkable difference between the two AUC values . The good penetration power of sagamicin into sputum makes this antibiotic useful for the treatment of infections of the respiratory tract.

Antibiot Med Biotekhnol, 1987 Jan, 32(1), 15 - 20
{Polymorphism of a culture of Streptomyces olivocinereus, the producer of heliomycin}; Sokolova ZG et al.; Polymorphism of the heliomycin-producing organism S . olivocinereus was studied and not less than 5 stable spontaneous variants differing in their differentiation levels were detected . Variant I (the main type) had the most developed cultural and morphological features characteristic of the whole population: abundant aerial mycelium with all specific subsequent stages of the development terminated by heavy sporulation and formation of long spiral spore chains . The other variants markedly differed from variant I . In variant III grey aerial mycelium (the final stage of differentiation) formed only at the colony margin . In variant IV it formed with a significant delay as a thin layer . In variant II it was very scanty and in variant V it differed by its pigmentation . Sporulation in variants II, III, IV and V was scanty and the character of the spore chains differed from that of the main type . Capacity for heliomycin production in the variants correlated with the level of morphological differentiation: the antibiotic activity of the highly differentiated variant I was the highest, while the low differentiated variant II was practically inactive.

Neurochirurgie, 1987, 33(1), 71 - 3
{Lumbar extradural Brucella abscess without spondylitis . Apropos of a case}; Scuccimarra A et al.; One case of lumbar extradural abscess of brucellar etiology without spondylodiscitis is described . The recovery was obtained only with antibiotic therapy.

J Antibiot (Tokyo), 1987 Jan, 40(1), 73 - 6
Biological effects of acetomycin . I . Activity against tumor cells in vitro and in vivo; Mamber SW et al.; The antibiotic acetomycin was active in vitro against HCT-8 human colon adenocarcinoma cells (IC50, 1.5 microgram/ml) and L1210 murine leukemia cells (IC50, 2.2 micrograms/ml) . Acetomycin also had marked activity in the human tumor stem cell assay, with a 33% overall response rate (less than or equal to 30% survival) against 49 primary tumors . However, acetomycin was inactive in four in vivo tumor assay systems (L1210 and P388 leukemias, B16 melanoma and the MX-1 mammary xenograft system) . This lack of in vivo activity may result from metabolic inactivation of acetomycin.

Drugs Exp Clin Res, 1987, 13(2), 105 - 14
Ceftazidime: experimental and clinical evaluation of biliary elimination; Brogard JM et al.; During a 3-h perfusion of five isolated rabbit liver preparations, 1.4% of 10 mg of ceftazidime added to the circulating blood was eliminated in the bile and 0.9% was metabolized or inactivated in the liver . Five normal subjects were given 2 g of ceftazidime intravenously; antibiotic concentration in the aspirated duodenal fluid rose progressively during the 4 h of the investigational period to a maximal mean level of 21.3 +/- s.e.m . 9.2 micrograms/ml and 0.05% of the dose given was recovered during this period . The same dose was given to 12 cholecystectomized patients fitted with a Kehr drain . An average peak value of 36.3 +/- 4.0 micrograms/ml was reached in the collected bile during the second hour after drug administration . The 12-h biliary recovery was 0.21% of the dose given . Ceftazidime concentrations in choledochal and gallbladder bile sampled peroperatively in 10 patients 1 h after intravenous administration of 2 g of ceftazidime were 78.3 +/- 12.0 and 17.9 +/- 7.5 micrograms/ml respectively . These data compare favourably with the results of the authors' studies on the biliary elimination of 15 other beta-lactams and are consistent with a possible beneficial effect of ceftazidime in the treatment of biliary tract infections.

Radiologe, 1987 Jan, 27(1), 20 - 4
{Microabscesses of the spleen in patients with acute leukemia}; Schmidt H et al.; Eight patients with acute myelogenous leukemia in complete remission after induction chemotherapy developed septic fever . Fever was unresponsive to broad-spectrum antibiotic therapy . Ultrasonography showed multiple 0.5-2 cm in diameter, anechoic densities and some 1-3 cm "target" appearances in spleen and liver . Computed tomography demonstrated multiple, round, 0.5-2 cm areas of diminished attenuation in spleen and liver, which did not enhance like the surrounding parenchyma . These microabscesses increased in size and number without equivalent antifungal therapy and decreased or disappeared after specific treatment . Candida-infection was confirmed by histologically from liver specimens in four patients, fungal organisms were seen microscopically an liver-biopsy in one patient and at autopsy one patient was found to have candida disseminated to the spleen, liver, kidneys, lung and CNS.

Radiat Res, 1987 Jan, 109(1), 47 - 57
Bile loss in the acute intestinal radiation syndrome in rats; Geraci JP et al.; The effects of bile duct ligation (BDL), choledochostomy, bile acid sequestering within the intestinal lumen by cholestyramine, and fluid and electrolyte replacement on survival time and development of diarrhea after whole-body exposure to doses of ionizing radiation that result in death from acute intestinal injury were studied . BDL significantly prolonged survival and delayed the onset of diarrhea after exposure to 137Cs gamma rays, fission neutrons, or cyclotron-produced neutrons in the range of doses that produce intestinal death or death from a combination of intestinal and hematopoietic injuries . Cannulation of the bile duct with exteriorized bile flow (choledochostomy) to protect the irradiated intestine from the mucolytic action of bile salts did not duplicate the effect of BDL in increasing survival time . Choledochostomy without fluid replacement eliminated the occurrence of diarrhea in 15.4 Gy irradiated rats . Diarrhea did occur in irradiated animals with choledochostomy if they received duodenal injections of fluid and electrolytes to replace the fluid lost as a result of bile drainage . Duodenal injection of fluid and electrolytes, however, had no significant effect on survival time in irradiated rats . In contrast, injection of fluid and electrolytes into the peritoneal cavity of irradiated rats resulted in an increase in survival time that was comparable to that observed after BDL . Addition of antibiotics to the peritoneally injected fluid and electrolytes further increased survival time (up to 9 days) . This survival time approached that seen in animals receiving the same radiation dose but which had the intestine exteriorized and shielded to minimize radiation injury to the intestine . Postmortem histological examinations of the irradiated small intestine showed mucosal regeneration in these long-term survivors receiving fluid and antibiotic therapy . In contrast, duodenal injection of cholestyramine post irradiation to bind bile acids had no effect on survival time or diarrhea incidence . The conclusions from these experiments are that BDL prolongs survival and postpones the onset of diarrhea in irradiated rats dying from acute intestinal injury primarily by slowing down the loss of fluid and electrolytes and that bile acids play no significant role.

Surgery, 1987 Jan, 101(1), 15 - 9
Moxalactam as single-agent prophylaxis in the prevention of wound infection following colon surgery; Hinchey EJ et al.; A single agent systemic antibiotic (moxalactam) when used prophylactically in patients undergoing colon surgery was associated with a wound infection rate comparable to that achieved by a combination of oral neomycin and intravenous metronidazole . The data obtained demonstrated that the reduced infection rate was not the result of a reduction in the bacterial content of the colon alone but due to the prophylactic agents used for elective colon surgery.

G Batteriol Virol Immunol, 1987 Jan-Dec, 80(1-12), 225 - 30
{Cefonicid toxicity . I . Effects on the reactivity of the specific immune system}; Gariglio M et al.; The degree of toxicity of the antibiotic Cefonicid on the cellular reactivity of the immune system was evaluated . The effects on some lymphokine (IL-2 and IFN-gamma) production and the degree of proliferation of splenic lymphocytes following mitogen stimulation have been considered . Our results show that Cefonicid does not impair the immune response, except at very high doses (500 micrograms/ml).

J Microencapsul, 1987 Jan-Mar, 4(1), 39 - 46
Streptomycin sulphate microspheres: dissolution rate studies and release kinetics . I; Gurkan H et al.; Targeting of drugs by microspheres, nanoparticles and liposomes is intended to increase the selective targeting to specific organs and to reduce their side effects . Streptomycin sulphate, a tuberculostatic antibiotic, is used as the active principle in this study . The aim is to accumulate the loaded microspheres in the lungs . The release of drugs associated with microsphere carriers has been found to be dependent on a number of factors . The aim of the investigation was to study the influence of the extent and nature of cross-linking, the type and the amount of the matrix material on the release characteristics of streptomycin sulphate microspheres . Human serum albumin and gelatin (Type B) were used as two different matrix materials . The crosslinking agents used were 2,3-butanedione and formaldehyde at different concentrations, and variable duration times . The in vitro release of streptomycin sulphate from microspheres is characteristically biphasic, with an initial fast release (the 'burst effect'), followed by a much slower release . Alteration in the characteristics of drug-loaded microspheres result in significant changes in the second (slow) phase of release . The release profiles of the different formulations has been studied and evaluated kinetically.

J Ocul Pharmacol, 1987 Fall, 3(3), 191 - 7
The suppression of acute corneal inflammation by Bredinin; Carter JM et al.; This study tested the effect of Bredinin, a nucleoside antibiotic of fungal origin, on experimentally induced acute inflammation of the rabbit cornea . Inflammation was produced by abrasive removal of a 9 mm disk of corneal epithelium . In the dose-response experiments, one eye of each rabbit was treated topically with Bredinin, and the other eye with vehicle immediately after deepithelialization . The acute inflammatory leukocytes in tear film samples were counted at various times and the corneas were examined histologically at the end of the study . A paired t-test revealed that the numbers of acute inflammatory leukocytes after 5 hours were significantly less in the Bredinin-treated eyes, compared with the untreated eyes . The timing of drug-treatment was important; Bredinin was most effective in suppressing acute ocular inflammation when administered at, or within, one hour of the inflammatory stimulus . Histologic analysis demonstrated fewer acute inflammatory leukocytes on the ocular surface and in the stroma of the Bredinin-treated eyes, compared with the untreated eyes . No obvious corneal toxicity was noted, and the drug-treated eyes appeared less inflamed than the control eyes . The results of this study demonstrate the capacity of Bredinin to suppress the entry of inflammatory leukocytes into the tear film and suggest that this drug may have potential for use as a topical anti-inflammatory agent.

Zentralbl Chir, 1987, 112(24), 1538 - 44
{Emergency interventions in complicated colonic diverticulosis}; Wehrli H et al.; An account is given in this paper of 480 patients who had been hospitalised for colonic diverticulosis or diverticulitis in the surgical department of the Municipal Waid Hospital of Zurich, between 1970 and 1986 . Laparotomy had to be performed on 219 of them (45.6 per cent), among them 84 emergency interventions . The average age of these patients was 70.7 years . Indications for emergency surgery included diffuse or locally delimited peritonitis with abscess development in 72 patients, ileus in ten cases, and massive colon haemorrhage in two . The latter two cases were handled with good success by subtotal colectomy with ileorectostomy and, one of them with the source of bleeding known, by colotomy and suturing of that source of bleeding . Sigmaincontinence resection according to Hartmann has been considered the optional approach since 1977 to diffuse peritonitis and to many cases of ileus (n = 39) . In more recent time, anastomosis has been used as primary approach to some patients who survived fibrinous abdominal peritonitis (n = 4) . The mortality rate associated with drainage operations according to expectation, has been clearly higher than that following resection, the comparable figures being 32.3 and 17.2 per cent . That has been attributable to non-removal of the septic focus . After all, nowadays combined antibiotic therapy is commonly used for seven to ten days for simultaneous control of both aerobic and anaerobic pathogens . This has become routine practice and involves aminoglycoside, metronidazole, and ampicillin . Overall mortality associated with emergency interventions is clearly higher than that after planned operations, the figures being 22.6 and 4.4 per cent.(ABSTRACT TRUNCATED AT 250 WORDS)

Drug Chem Toxicol, 1987, 10(3-4), 237 - 56
Comparative vestibular toxicity study with 3-O-demethylfortimicin A disulfate and gentamicin sulfate in cats; Yang CL et al.; 3-O-demethylfortimicin A disulfate (ODMF), a novel aminocyclitol antibiotic, was administered subcutaneously for three months to groups of male and female cats at 15, 30 or 60 mg base/kg/day . Gentamicin sulfate (GS) at doses of 6 and 13 mg base/kg/day served as a reference compound . Signs of vestibular toxicity were considered to include persistent unsteady gait and stance, impaired righting reflex and abnormally diminished postrotatory vestibular nystagmus . Renal toxicities produced by ODMF and GS were also determined and compared . ODMF at 15 and 30 mg base/kg/day produced no signs of vestibular toxicity, while a dosage of 60 mg base/kg/day of ODMF produced vestibular toxicity in 7/10 cats . Three affected male cats died or were killed in moribund condition between study days 49 and 64 . Vestibular toxicity was observed in 10/10 cats treated with GS at 13 mg base/kg/day and in 3/10 cats at 6 mg base/kg/day . All ten cats treated with GS at 13 mg base/kg/day died or were killed in moribund condition between study days 30 and 81 . The deaths and moribundity in cats treated with ODMF or GS were attributed to renal toxicity . The vestibular toxicity and nephrotoxicity produced by ODMF and GS were more severe in male cats than in females . In conclusion, ODMF given at doses up to 60 mg base/kg/day for three months induced comparatively less vestibular toxicity and renal pathology than did GS at a dose of 13 mg base/kg/day.

Jpn J Ophthalmol, 1987, 31(2), 218 - 29
Immunosuppressive effects of polynactins (tetranactin, trinactin and dinactin) on experimental autoimmune uveoretinitis in rats; Tanouchi Y et al.; Macrotetrolide antibiotic polynactins {dinactin, trinactin and tetranactin (1:4:5)} are hydrophobic cyclic esters produced by Streptomyces aureus . Polynactins (PN) and their major component tetranactin (TN) delayed or suppressed the onset of S-antigen-induced experimental autoimmune uveoretinitis (EAU) in Lewis rats . Termination of treatment with PN or TN before day 14 of immunization resulted in a delayed onset of EAU in many animals . Thus, the immunosuppressive effect of PN and TN was not lasting . PN and TN suppressed anti-S-antigen antibody formation . Skin hypersensitivity tests indicated suppression by PN of the delayed-type rather than Arthus type hypersensitivity to S-antigen . PN, TN and trinactin all inhibited 3H-thymidine incorporation into concanavalin A-treated lymphocytes at the early stage of cell activation . For each drug, 50% inhibition was obtained at about 0.1 ng/ml . Under the incubation condition that the cells were exposed to TN for 21 hours, cell viability remained unchanged up to 100 ng/ml of TN . It is evident that PN and TN suppress T-lymphocyte proliferation without cell injury . These results suggest that PN and TN inhibit the onset of EAU primarily through the suppression of cell-mediated immunity but also by affecting humoral immunity.

Eur J Drug Metab Pharmacokinet, 1987 Jan-Mar, 12(1), 50 - 7
Troleandomycin effects on methylprednisolone and methylprednisone interconversion and disposition in the rabbit; Ebling WF et al.; A study of the effects of troleandomycin (TAO) on the disposition of intravenous methylprednisolone in rabbits was performed in order to develop an animal model to further evaluate the mechanism of TAO/steroid beneficial effects in severe asthma . The plasma concentration-time profiles of methylprednisolone and methylprednisone were determined in the presence and absence of single and multiple dose TAO regimens . Pharmacokinetic analysis revealed a significant decrease in total plasma clearance of methylprednisolone in the presence of multiple dose TAO . Alterations in the disposition of the reversible metabolite, methylprednisone, were also observed . The TAO-methylprednisolone interaction may involve decreasing the degree of interconversion between the steroid and its reversible metabolite . TAO also decreases metabolite turnover more than three-fold . The antibiotic does not cause marked deviation from linear biexponential elimination of methylprednisolone as observed in man . The rabbit may serve as a useful animal model for further studies of the TAO/methylprednisolone interaction.

Eur J Clin Pharmacol, 1987, 31(6), 701 - 4
Effect of miocamycin on theophylline kinetics in children; Principi N et al.; The interaction between a new macrolide antibiotic, miocamycin, and theophylline was evaluated in a single cross-over study in 5 asthmatic children . Each patient received a single dose of theophylline (4.3 mg/kg) delivered in 15 min using a constant-rate infusion pump, immediately before and after a 10 day course of miocamycin 17.5 mg/kg b.d . The pharmacokinetics of theophylline were calculated for each phase of the study . The elimination rate constant (3.92 vs 3.74 h-1), the mean total body clearance (1.71 vs 1.8 ml X min X kg-1) and the mean apparent volume of distribution (0.57 vs 0.581 X kg-1) did not differ . The result can be explained by the inability of the antibiotic to form inactive cytochrome P-450 metabolite complexes which can interfere with the metabolism of theophylline . Thus, miocamycin can safely be administered to asthmatic children requiring theophylline treatment, when they have an infection due to susceptible pathogens.

Am J Med, 1987 Jan, 82(1), 73 - 8
Pneumocystis carinii pneumonia . Review of 53 cases; Peters SG et al.; Between 1976 and 1983, 53 cases of Pneumocystis carinii pneumonia were documented at the Mayo Clinic . Underlying diseases included leukemia in 15 patients, lymphoma in nine, nonhematologic malignancies in five, acquired immune deficiency syndrome in two, an various inflammatory diseases treated by corticosteroids in 16 patients . Cytotoxic drugs with corticosteroids were used in 68 percent of patients, whereas 23 percent received corticosteroids alone . Clinical features consisted of progressive dyspnea (74 percent), cough (55 percent), and fever (62 percent), with normal findings on examination (43 percent), or crackles (53 percent) . Arterial oxygen tension and oxygen saturation were 48.6 +/- 12.8 mm Hg and 81.2 +/- 6.5 percent, respectively . Chest roentgenographs exhibited diffuse alveolar and interstitial infiltrates with predominantly perihilar distribution . The diagnostic rates for open lung biopsy and bronchoscopy were 97 percent and 62 percent, respectively . Clinical improvement and survival following appropriate therapy were noted in 22 patients (41.5 percent), whereas the remaining 31 patients died within four weeks of hospitalization . When survivors were compared with nonsurvivors, there was no difference in mean age, leukocyte counts, arterial oxygen tension, or duration of symptoms before treatment . A coexisting pulmonary infection was identified more frequently in nonsurvivors (51.6 percent) than in survivors (22.7 percent, p = 0.01) . The mortality from P . carinii pneumonia alone was 47 percent, whereas 76 percent of those with coexisting infection died . Despite antibiotic therapy and potentially effective chemoprophylaxis, P . carinii pneumonia remains a significant and life-threatening complication of diseases or treatments associated with immune suppression.

Scand J Infect Dis Suppl, 1987, 52, 40 - 5
Pharmacokinetic and clinical evaluation of imipenem/cilastatin in children and neonates; Begue PC et al.; Imipenem, a new carbapenem (thienamycin) beta-lactam antibiotic which is clinically used in a 1:1 combination with cilastatin, an inhibitor of renal metabolism of imipenem, was evaluated in 25 patients; 11 children and 14 neonates . A mean daily dose of 60 mg/kg was given to children and the dose in neonates was 50 mg/kg . Clinically, 21 patients were cured, two failed to respond to treatment and two were not evaluable . Pharmacokinetic studies were performed in the 11 children and in 10 of the neonates . The mean elimination half-life of imipenem was 0.87 h in children and 2.1 h in neonates . The mean cilastatin elimination half-life was 0.73 h in children and 5.1 h in neonates . This difference in half-life between children and neonates is similar to the one noted between healthy adults and adults with renal insufficiency . No accumulation of imipenem was seen in neonates studied on the first and fifth days of treatment.

Scand J Infect Dis Suppl, 1987, 52, 15 - 9
Imipenem/cilastatin treatment of lower extremity skin and soft tissue infections in diabetics; Calandra GB et al.; The efficacy and safety profile of imipenem/cilastatin was investigated in 94 patients with diabetes mellitus with infections of the lower extremity . Ninety-eight percent of the pathogens were susceptible to imipenem; this was higher than to other antibiotics tested . Ninety-two percent of the patients were cured (47%) or improved (45%) . Bacterial eradication was achieved for 79% of the pathogens . Adverse experiences were similar to those reported previously . Imipenem-cilastatin proved to be a very effective antibiotic with a good safety profile for use in diabetic patients with lower extremity infections.

Clin Ther, 1987, 10 Suppl A, 59 - 65
Measurement of C-reactive protein to compare ceftizoxime versus cefoxitin/doxycycline therapy for septic pelvis: a preliminary report; Mercer LJ et al.; C-reactive protein (CRP), a biological marker of inflammation, may be a useful indicator of therapeutic response in patients with septic pelvis . In a study comparing ceftizoxime and cefoxitin/doxycycline in patients with septic pelvis, quantitative CRP levels were closely correlated with the responses and failures of therapy . The results of this study showed the two antibiotic regimens to be equally effective, with 23 of 25 patients in each treatment group achieving a satisfactory response . The fact that ceftizoxime was effective in four of five patients with Chlamydia trachomatis in cervical isolates suggests that intravenous therapy for the acute infection can be accomplished without the addition of an antichlamydial agent . Upon discharge from the hospital, patients can continue therapy with an oral drug that is specifically active against Chlamydia.

Invest New Drugs, 1987, 5(2), 171 - 6
Phase I and pharmacokinetic study of high volume intraperitoneal aclacinomycin-A (Aclarubicin); Kerr IG et al.; Aclacinomycin-A (Aclarubicin) is a relatively new anthracycline antibiotic with potential activity against ovarian cancer . Eight patients with various malignancies (4 ovary, 1 breast and ovary, 1 breast, 1 colon, 1 leiomyosarcoma) and intraperitoneal disease were treated in a Phase I trial with escalating doses of intraperitoneal Aclacinomycin . Drug treatments were administered through a peritoneal catheter in a 2 liter fluid volume (1.5% Dianeal) . Seventeen cycles were administered with doses ranging from 25 to 75 mg of Aclacinomycin . Pharmacokinetic studies were carried out in 7 patients . Although high concentrations of Aclacinomycin could be obtained in the peritoneal cavity no drug was detected in the plasma . The major dose-limiting toxicity was chemical peritonitis . Two patients had reduction in the amount of ascites . The recommended dose for Phase II trials is Aclacinomycin 50 mg in 2 liters given every 2 weeks.

Chemotherapy, 1987, 33(4), 291 - 6
Effect of prophylactic intravenous ceftriaxone in maxillofacial surgery; Stoll P; Cephalosporins are commonly used in maxillofacial surgery because they achieve high concentrations in bone . Prophylactic antibiotic therapy was given to 65 patients undergoing diverse surgical procedures . 20 patients received cefotiam in 2 doses of 2 g for 5 days; 15 patients received cefotiam in 2 doses of 2 g only perioperatively . No difference was found between these two groups with respect to prophylactic protection against infection . A further 15 patients received ceftriaxone in a single dose of 2 g preoperatively . Since we found that local infection and febrile morbidity was not significantly different even in the 'one-shot' group, we investigated the effect of 'low-dose' prophylaxis with only 1 g ceftriaxone preoperatively in another 15 patients . We found that this dose was sufficient to prevent infection in patients.

Postgrad Med, 1987 Jan, 81(1), 131 - 2, 135-6
Nosocomial and nursing home-acquired pneumonia . Recent therapeutic advances; Roselle GA; In recent years, new broad-spectrum antibiotics have become available for the treatment of complex pneumonia . Used with care, these agents may allow effective monotherapy of difficult-to-treat pulmonary infections, with the added benefit of decreased toxicity in comparison with the more traditional multiple-drug combinations . The newer antibiotics are relatively expensive, but cost of their use can be justified by their reduced toxicity (in comparison with some antibiotic combinations) and by the avoidance of additional laboratory fees for routine drug monitoring . It is hoped that the major benefits that can accrue with proper use of the newer agents will not be outweighed by problems resulting from their indiscriminate use, such as increased bacterial resistance and exorbitant healthcare costs.

J Am Dent Assoc, 1987 Jan, 114(1), 65 - 8
Severe infections of the head and neck resulting from gas-forming organisms: report of case; Schroeder DC et al.; A case of severe infection of the head and neck associated with gas-forming organisms in a patient with fractures of the mandible is presented . Selected aspects of antibiotic therapy are discussed.

J Cell Physiol, 1987 Jan, 130(1), 51 - 7
Mouse Balb/c3T3 cell mutant with low epidermal growth factor receptor activity: induction of stable anchorage-independent growth by transforming growth factor beta; Kuratomi Y et al.; A mutant clone (MO-5) was originally isolated as a clone resistant to Na+/K+ ionophoric antibiotic monensin from mouse Balb/c3T3 cells . MO-5 was found to show low receptor-endocytosis activity for epidermal growth factor (EGF): binding activity for EGF in MO-5 was less than one tenth of that in Balb/c3T3 . Anchorage-independent growth of MO-5 was compared to that of Balb/c3T3 when assayed by colony formation capacity in soft agar . Coadministration of EGF and TGF-beta efficiently enhanced anchorage-independent growth of normal rat kidney (NRK) cells, but neither factor alone was competent to promote the anchorage-independent growth . The frequency of colonies appearing in soft agar of MO-5 or Balb/c3T3 was significantly enhanced by TGF-beta while EGF did not further enhance that of MO-5 or Balb/c3T3 . Colonies of Balb/c3T3 formed in soft agar in the presence of TGF-beta showed low colony formation capacity in soft agar in the absence of TGF-beta . Colonies of MO-5 formed by TGF-beta in soft agar, however, showed high colony formation capacity in soft agar in the absence of TGF-beta . Pretreatment of MO-5 with TGF-beta induced secretion of TGF-beta-like activity from the cells, while the treatment of Balb/c3T3 did not induce the secretion of a significant amount of TGF-beta-like activity . The loss of EGF-receptor activity in the stable expression and maintenance of the "transformed" phenotype in MO-5 is discussed.

J Basic Microbiol, 1987, 27(8), 449 - 55
Development of a plasmid-cloning system for Streptomyces viridochromogenes Tü494; Strauch E et al.; A plasmid-cloning system was developed for Streptomyces viridochromogenes Tu494, a producer of the tripeptide antibiotic phosphinothricyl-alanyl-alanine (PTT) . Parameters affecting protoplast formation and transformability of S . viridochromogenes were investigated in detail . A procedure giving rise to transformation efficiencies of 10(4)-10(5) transformants per microgram DNA was worked out . Several Streptomyces plasmid vectors such as pIJ350, pIJ61, pEB2, pGM4 and pSW2 were tested in S . viridochromogenes . Some of these vectors (pGM4, pEB2) showed a high copy number, whereas the copy number of others (pIJ350, pIJ61 and pSW2) was markedly lower . Under non-selective conditions some of the vectors (pIJ350, pEB2) were not stably maintained, in contrast to the vectors pGM4 and pSW2 which did not require any selection pressure for stable maintenance . Therefore, the plasmid vectors pGM4 and pSW2 derived from endogenous replicons of Streptomyces ghanaensis strains represent appropriate plasmid vehicles for cloning experiments in S . viridochromogenes.

Acta Biochim Pol, 1987, 34(4), 369 - 76
Pleiotropic effect of anticapsin on HeLa S3 cells; Woynarowska B et al.; Anticapsin, the terminal epoxyaminoacid moiety of tetaine, inhibits irreversibly growth of HeLa S3 cells . The antibiotic decreases to a similar extent incorporation of 3H-labelled precursors into nucleic acids and protein in intact cells: inhibition of protein synthesis prevails on prolonged incubation . Also incorporation of {3H}dTTP and {3H}UTP is inhibited in the presence of anticapsin into permeabilized cells . These effects, however, are not due to the interference with DNA or RNA polymerases since anticapsin only slightly suppresses RNA polymerase activity and has no effect on DNA polymerase in the cell-free systems . The results indicate that the mechanism of antiproliferative action of anticapsin in HeLa S3 cells differs from that of tetaine and imply that inhibition of protein synthesis might be the primary effect of anticapsin.

Vet Med Nauki, 1987, 24(10), 28 - 35
{Pharmacokinetic research and the ultrastructural changes in the lungs of white rats after aerosol administration of a high dose of kanamycin sulfate}; Feodorov V et al.; Studied is kanamycin sulphate "Pharmachem", substance with activity 750 UI/mg, applied on albino rats in the form of water aerosol . The experiments are carried out in aerosol camera of flow-dynamic type with capacity 450 l at exchange of the air 60 l/min with aerosol apparatus of pneumatic type, for 10 min and staying in the aerosol cloud another 10 min . It is established that the kanamycin sulphate, after aerosol application on albino rats in dose of 50000 UI/m3, passes in the blood and is found out in the serum yet in the first hour (1.75 +/- 0.23 mg/cm3 serum) . The maximal quantities of antibiotic are established in the first hour in the lungs (52.1 +/- 11.4 micrograms/g) and the antibiotic is detained in therapeutical concentrations for 240 h (0.1 +/- 0.03 micrograms/g) . The content of the kanamycin in the kidneys is in the limits from 0.1 +/- 0.02 to 1.69 +/- 0.17 micrograms/g . At the electronic-microscopic tests of the lungs is observed hyperemia and destruction of the lamella corpuscles, which processes up to the 120th hour gradually calmed down.

Drugs Exp Clin Res, 1987, 13(12), 737 - 9
Toxic effects on rabbit kidney cell cultures of a new aminoglycoside; Viano I et al.; In this study the cellular toxicity of two aminoglycosides (gentamicin and dactimicin) have been evaluated using rabbit kidney cell cultures . The correlation between toxic effect and antibiotic concentration, and between toxic effect and the period of contact have been evaluated . The toxic effect was measured in rabbit kidney cell cultures by means of the release of N-acetyl-beta-glucosaminidase . This enzyme was chosen in order to establish a correlation between in vitro and in vivo results . Gentamicin clearly shows in both tests a non-linear correlation between cellular toxicity and concentration or period of contact . Dactimicin, a new aminoglycoside probably less toxic than others, also shows in both tests a non-linear correlation between cellular toxicity and concentration or period of contact, but the release of enzyme was significantly reduced during the treatment of the cell cultures with this aminoglycoside.

Eye, 1987, 1 ( Pt 5), 581 - 4
Day case strabismus surgery without post-operative ocular medication . A masked randomised study; Hagan MC et al.; A masked, randomised study was designed to test the hypothesis that day case strabismus surgery and the absence of post-operative topical medication is a plan of management that does not compare unfavourably with discharge from hospital on the day after surgery with topical antibiotic and anti-inflammatory therapy for 14 days . The results indicate that patients who have day case surgery do not have more complications than overnight stay patients and that their inflammation and discomfort settle just as quickly without topical therapy . Medical, social and financial benefits of day case surgery are noted.

Ann Otolaryngol Chir Cervicofac, 1987, 104(8), 625 - 31
{Laryngeal dyspnea of infectious origin in the adult . Apropos of 54 cases}; Perrin A et al.; Principal etiologies in 54 patients with acute laryngeal dyspnea of infectious origin were epiglottitis (35 cases), glotto-subglottal laryngitis (8 cases) and adjacent infections (9 cases) . These cases are reviewed together with the relevant published literature and various conclusions drawn . The affection is serious (35 deaths out of 425 cases in the literature), and requires careful examination, immediate treatment and routine hospital care under surveillance . Apart from cases where the condition of the patient necessitates urgent intubation, those cases with rapidly evolving signs over 24 hours must be admitted to intensive care since worsening of dyspnea can lead to delayed decompensation . Wide spectrum antibiotic therapy is necessary for patients with epiglottitis and adjacent infective ulcerations since many germs may be implicated, while for the always benign glotto-subglottal laryngitis Amoxicillin + clavulinic acid is sufficient.

Vet Med Nauki, 1987, 24(9), 52 - 5
{Treatment of puerperal endometritis in cows by the intra-arterial injection of drugs}; Venev S; Cured were 59 cows, affected by puerperal catarrhal suppurative endometritis, by intra-aortic and uterine infusion of procaine and antibiotic solutions . A good curative and biological effect was reached . The aortic-treated animals were fertilized at average independence and service periods--accordingly 43.52 and 57.31 days, for the uterine treatment--accordingly 51.67 and 78 days.

Vet Med Nauki, 1987, 24(8), 64 - 8
{Embryotoxic and teratogenic effects of Pharmachim's lincomycin hydrochloride}; Chakurov R et al.; Tested was the teratogenic and embryotoxic action of linkomycin hydrochloride with both placental and nonplacental animals . It was found that when applied twice, orally, to albino rats on the 4th day of pregnancy at the rate of 250 mg/kg body mass (=5 ED50), and once to chick embryos at 50 mg per egg the antibiotic raised the percent of pre- and postimplantation loss of embryos . In a series of applications (oral) from the 3rd up to the 19th day at 50 mg/kg body mass to rats as well as in a single application to chick embryos at 10, 20, and 50 mg per egg linkomycin showed no teratogenic effects.

Vet Med Nauki, 1987, 24(8), 55 - 63
{Toxicological and pharmacokinetic research on lincomycin hydrochloride in broiler chickens and layer hens}; Chaleva E et al.; Tested was the activity of linkomycin hydrochloride at the rate of 820 IU/mg . The LD50 of the preparation was found to exceed 12.0 g/kg body mass at intracrop application to broiler birds . When offered with the drinking water or the feed in amounts that were 3 to 5 times higher than the therapeutic ones for broilers in the course of 45 days it did not cause mortality nor induced changes in the white and red blood cell counts, in the total protein, and in the levels of urea, blood sugar, AlT, and AcT . Neither were there any structural changes in the internal organs . Upon the single intracrop treatment of broilers with linkomycin at 50 and 100 mg/kg most of the amount introduced was established in the blood serum at the second hour and up to the 6th and 8th hour, respectively . Studies on the effect of age on the serum concentrations at this route of introduction revealed that the preparation was absorbed at higher rates in the broilers than in the layers, while with the persistence of the levels there were no essential differences . At the single oral administration with broilers in amounts of 100 mg/kg linkomycin was chiefly retained in the kidneys, liver, and lungs as well in the content of the small and large intestines . At intracrop application to layers in doses of 100 mg/kg in the course of 7 days the antibiotic was excreted with the eggs at the time of treatment and in the course of 4 days later in bacteriostatic concentrations of 0.6-5.9 micrograms/cm3.

Chromosoma, 1987, 96(1), 26 - 32
Regional assignment of the gene for diphtheria toxin sensitivity using subchromosomal fragments in microcell hybrids; Hayes H et al.; Human x mouse microcell hybrids resistant to G418 were constructed between mouse hepatoma cells and human x mouse whole cell hybrids containing only intact human chromosome 5 and 22 with an integrated neor-gene . Among these, microcell hybrid BG15 produced four subclones, BG15-4, BG15-6, BG15-7 and BG15-9, which contained variously sized complements of human chromosome 5 . BG15-6 contained an intact human chromosome 5, BG15-7 a deleted human chromosome 5 (5pter-q22) and BG15-4 and BG15-9 a translocation between parts of human chromosome 5 (pter-qter? and pter-q23, respectively) and a mouse chromosome . Southern DNA blot analysis showed that the human dihydrofolate reductase (DHFR) gene was present in all four subclones, whereas the human homolog of the v-fms gene was present in BG15-4 and 15-6, but absent from BG15-7 and 15-9 . BG15-4, 15-6 and 15-9 were sensitive to diphtheria toxin, and only BG15-7 was resistant to the toxin . We used these microcell hybrids to restrict further the regional location of the gene for diphtheria toxin sensitivity to the q23 region of human chromosome 5.

Arch Gynecol Obstet, 1987, 241(3), 177 - 82
Serum CRP in the diagnosis and treatment of pelvic inflammatory disease; Hemila M et al.; The usefulness of serum C-reactive protein (CRP) measurement was studied in a population of 152 patients admitted to a gynaecological emergency unit . Fifty-one of 55 patients with PID had raised (over 10 mg/l) (13-270 mg/l) CRP levels with a mean of 76.1 mg/l . CRP was elevated (12-40 mg/l) in 2 of 18 patients with threatened abortion with successful outcome, in 8 of 28 patients with incomplete abortion, and in 2 of 16 patients with ectopic pregnancy . Furthermore, 6 of 35 patients with noninfectious disorders (ovarian cyst, uterine fibroid, unexplained pelvic pains) had slightly elevated (12-59 mg/l) CRP levels . Thus, in this series a CRP greater than 10 mg/l had good sensitivity (93%) and specificity (83%) in the diagnosis of PID . Furthermore, CRP levels became normal much sooner than did erythrocyte sedimentation rate following effective antibiotic therapy, suggesting that it is useful in monitoring therapeutic response.

Vutr Boles, 1987, 26(5), 105 - 8
{Risk factors and the prevention of status asthmaticus in bronchial asthma patients}; Petrov D et al.; For a 10 year period 1005 patients with bronchial asthma were treated . 203 (20.19%) of these patients, from 17 up to 71 years of age (mean age 44.2 years) and duration of the disease from 2 up to 28 years, had been in asthmatic state . For this 10 year period 72 (35.46%) of these 203 patients had been in asthmatic state from 2 to 7 times with an interval of 1.5 to 3.5 years . The asthmatic state is a frequent and severe complication of bronchial asthma sometimes with lethal outcome . As risk factors for the development of asthmatic state in asthmatic patients can be pointed out the insufficient treatment of the asthmatic attacks before admittance to the hospital, ill founded corticosteroid treatment and late search for medical help . The antibiotic therapy in patients with an asthmatic attack due to pulmonary infection influences favourably the bronchial obstructive syndrome and is the best prophylaxis of asthmatic state parallel with founded corticosteroid treatment, well organized prophylactic medical care and improvement of the medical knowledge of asthmatic patients.

Pharmacotherapy, 1987, 7(5), 188 - 90
Spiramycin in the treatment of cryptosporidiosis; Pilla AM et al.; Spiramycin, a macrolide antibiotic, has been advocated for the treatment of cryptosporidiosis . The disease most commonly occurs in patients with AIDS and can be debilitating, as diarrhea and malnutrition may be contributing factors in the death of these patients . Until recently, treatment for cryptosporidiosis has been largely symptomatic . Response rates with drug therapy such as metronidazole, quinidine-clindamycin, and pentamidine have been extremely poor . Although response to spiramycin has appeared promising, there have been several reported cases of treatment failure . Further investigation with the agent is advocated to determine its role in the treatment of cryptosporidiosis.

Drugs Exp Clin Res, 1987, 13(9), 539 - 46
Concentration and time dependence of amphotericin B-induced permeability changes across plasma membrane vesicles from Leishmania sp; Cohen BE et al.; The main purpose of this paper is to show that the polyene antibiotic amphotericin B may form two types of channels in plasma membrane vesicles from Leishmania sp.: ionic and aqueous . The experimental design was to follow the light scattering changes of a suspension of membrane vesicles under an osmotic shock . The results show that a low concentration of amphotericin B(0.2 to 0.8 microM) led to an enhancement of urea and salt permeability without affecting the total osmotic response of Leishmania vesicles . Such an increment of solute permeability induced by low concentrations of amphotericin B was 100% blocked by tetraethylammonium . Low concentrations of amphotericin B were also able to induce an enhancement of glucose permeability but only after Leishmania membrane vesicles were incubated for 15 min with the antibiotic, previous to mixing . On the other hand, high amphotericin B concentrations (greater than 0.8 microM) induced a decrease in the total extent of shrinkage of membrane vesicles immediately after its mixing with urea solutions . At this high concentration of amphotericin B the blocking of tetraethylammonium was reduced by 50% . These results support the authors' previous conclusion (1) that in ergosterol-containing membranes, amphotericin B may form two different types of channels differing in internal diameter.

Allerg Immunol (Paris), 1987 Jan, 19(1), 13 - 7
The viral factor in childhood asthma; Oehling A et al.; Independently of the important role the infections bacterial factor plays in childhood asthma, many authors have considered the virus the primary triggering factor of bronchospasm . This latter factor has been so exaggerated that some authors have even conceded it the maximum importance . In studies carried out with a more numerous population than in those works presented so far, controlling the presence of antibodies during the crisis and a week later in serum from asthmatic children, the authors found that only 13.5% presented specific antibodies against one or two of the sixteen viral antigens studied . These children at the same time developed a bacterial infection which remitted with antibiotic therapy, with the consequent disappearance of the asthma . In etiopathological studies realized in 700 children it was equally confirmed that the bacterial factor was involved in 90% of the cases, in the sense of a sinopulmonary syndrome . More profound studies are needed to clarify this point which is held in little consideration by many clinicians.

Arq Gastroenterol, 1987 Jan-Mar, 24(1), 30 - 5
{Acute emphysematous cholecystitis . Report of a case and review of the literature}; Waisberg J et al.; The authors report a case of acute emphysematous cholecystitis (AEC) operated on at the University Hospital of ABC Medical School (Sao Paulo), with a review of the literature . The infrequency of this finding and the participation of local ischemic factors, associated with secondary infection by gas forming bacteria are pointed out . The authors emphasize the importance of considering this entity potentially more severe than acute non-emphysematous cholecystitis (AnEC) because in AEC gallbladder gangrene is 30 times higher and perforation occurs 5 times more frequently than in AnEC . Besides, the patient with AEC may shows no clinical signs of severity, as in the case reported, where gallbladder gangrene was seen at surgery . In AEC, diagnosis is established usually when the plain abdominal X-ray shows gas within the gallbladder or in its walls . The best results are obtained with cholecystectomy and antibiotic therapy.

Adv Exp Med Biol, 1987, 224, 93 - 115
Pathogenesis and significance of urogenital mycoplasmal infections; Cassell GH et al.; U . urealyticum and M . hominis can no longer be considered as harmless commensals of the lower genitourinary tract . Both can produce disease in humans . Diagnosis and management of infections due to these organisms must be based upon isolation of the organisms from the affected site and preferably the number of organisms present . Due to the frequent resistance of both organisms to tetracycline, treatment must be based upon appropriate antibiotic sensitivities . For a more detailed description of the basic biology of these organisms and isolation and identification and treatment, the reader is referred to several recent reviews.

Curr Genet, 1987, 12(5), 305 - 10
Phenotypic suppression and nuclear accommodation of the mit- oxi1-V25 mutation in isolated yeast mitochondria; Zagorski W et al.; Phenotypic suppression by the antibiotic, paromomycin, of the mitochondrial oxi1- -V25 mutation, a mutation which arrests by premature ochre codon the synthesis of the cox II subunit, was studied in isolated yeast mitochondria competent in translation . This antibiotic is known to suppress the mutation in vivo (Dujardin et al . 1984) and allowed in vitro, at concentrations of 20-1100 micrograms per ml . the synthesis of the cox II subunit . This strongly suggests that phenotypic suppression of mit- mutations is due to the direct action of paromomycin on mitochondrial ribosomes . The effect of paromomycin bears a resemblance to the function of the omnipotent nuclear suppressor mutation R705 . The nuclear suppression was expressed in isolated mitochondria; suppressor mutation influenced the structure of the mitoribosome . Therefore, it appears that mitoribosomes are indeed the common target in the phenotypical and genetic nuclear suppression of the oxi1-V25 mutation.

Ciba Found Symp, 1987, 130, 229 - 46
Gene therapy: efforts at developing large animal models for autologous bone marrow transplant and gene transfer with retroviral vectors; Eglitis MA et al.; Two new large animal models, non-human primates and fetal sheep, have been developed in an effort to determine the feasibility of using retroviruses for gene therapy . The retroviral vectors N2 and SAX have been used to introduce the genes for neomycin phosphotransferase (neoR, conferring resistance to the antibiotic G418) and human adenosine deaminase (ADA; EC 3.5.4.17), respectively . Varying levels of human ADA activity have been detected in six of the eight SAX-treated monkeys analysed . In the monkey with the greatest activity, human ADA levels approximately 0.5% of endogenous monkey ADA levels were detected . By in situ hybridization, roughly one in 100 bone marrow cells were found to express vector DNA . Sheep have been used for studies of the infectability of fetal blood progenitors in vivo . Blood cells were treated with the N2 vector at the 96th day of gestation, and marrow cells were assayed for the presence of G418-resistant haematopoietic progenitors, starting from one week after birth (62 days after treatment) . Up to 33% of colony-forming progenitors were drug resistant initially and, although the proportion of resistant colony-forming units declined, a level of 10% has been found 153 days after transplantation . Human bone marrow has also been treated with the N2 vector, resulting in 1-2% G418-resistant progenitors.

Acta Anaesthesiol Belg, 1987, 38(4), 333 - 9
Complications of splenectomy; Shatney CH; During the last three decades it has become clear that removal of the spleen, for any reason, is not a benign procedure . In both adults and children splenectomy places the patient at significantly higher risk of overwhelming infection, compared to the normal population . The risk of the post-splenectomy septic syndrome is lifelong and is not eliminated by the administration of polyvalent pneumococcal vaccine . Thus far, the reported rate of overwhelming sepsis in asplenic individuals has ranged from 2.5-13.5% . As more long-term follow-up data become available, it is likely that the true incidence will be 5-10% . In addition to this late complication, splenectomy increases the frequency of adverse events, including death, in the immediate postoperative period . Infections, particularly pulmonary and abdominal sepsis, constitute the majority of the complications . The mortality rate from postoperative sepsis is substantial . Atelectasis, pancreatitis/fistula, pulmonary embolism and bleeding at the operative site are also relatively common occurrences following splenic removal . These alarming statistics have spurred surgeons to change their attitudes concerning splenectomy for trauma, both accidental and iatrogenic . Nonoperative management of hemodynamically stable patients with isolated splenic injury and splenorrhaphy in patients requiring laparotomy are now firmly entrenched in the surgical armamentarium . Patients in whom splenectomy is necessary are given polyvalent pneumococcal vaccine and are instructed to seek early medical attention for febrile illnesses . Splenic autotransplantation and lifelong prophylactic antibiotic therapy have been used in some centers, but their clinical value remains to be proven.

Ann Biol Clin (Paris), 1987, 45(6), 673 - 9
{Current role of amphotericin B in the treatment of deep mycoses}; Dei-Cas E et al.; Amphotericin B (Am . B), a polyene heptaene, is an antifungal antibiotic substance produced by Streptomyces nodosus, a telluric actinomycetal from Venezuela . Although it is a very toxic substance and its pharmacokinetic is not completely known, Am . B is yet the former antifungal substance utilised against number of pathogenic agents of systemic mycoses . Am . B binds irreversibly to sterols of fungal cytoplasmic membranes causing a leak of potassium and other impairments leading the fungal cell to death . Further, Am . B might to induce an enhancement of humoral and cellular immunity . After intravenous perfusion, 95 per cent of Am . B binds to plasma lipoproteins . Only a low proportion of the Am . B serum level is detected in the CSF . Distribution of Am . B to extravascular inflammatory fluids and secretions might be letter . Am . B might be eliminated essentially by biliary way . Am . B toxic effects are very frequent . Generalized reactions are observed to the earlier doses . Toxic visceral, above all, nephrotoxic manifestations, appearing later . Recent results, from experimental and human infections suggest that Am . B encapsulated in liposomal vesicles is more active, less toxic and more easily administered.

Clin Ther, 1987, 10 Suppl A, 66 - 71
Treatment of nosocomial aspiration pneumonia and soft-tissue infections in diabetic patients; Venezio FR; Nosocomial aspiration pneumonia and infections of soft tissue are most often caused by mixed aerobic and anaerobic pathogens . Single-agent therapy with a beta-lactam antibiotic is tending to replace combination therapy because it is as effective and less toxic . Important considerations in choosing among the beta-lactam antibiotics include a long pharmacologic half-life, permitting less frequent administration, and cost per gram.

Biomed Pharmacother, 1987, 41(5), 233 - 7
Clinical studies of aclacinomycin A (ACM); Majima H et al.; Aclacinomycin A (ACM) is a new anthracycline antibiotic, isolated from Streptomyces galilaeus . This agent is presenting major chemical differences from the conventional anthracycline DNR and ADM, as a class II anthracyclines which inhibit more RNA than DNA . In clinical studies, good CR responses ranging about 30% in AML patients depend upon their background . Toxicities consisted of mainly upper GI tract and bone marrow . Cardiac toxicities, especially late cumulative effects are not reported . Some responses noted in malignant lymphomas and breast carcinoma, but needed further studies, including possibility of cross resistance and differentiation effects.

Drugs Exp Clin Res, 1987, 13(6), 345 - 51
Antitumor activity of new N-substituted daunorubicin derivatives; Mazerska Z et al.; The biological properties of two new structural groups of modification products of daunorubicin, the N-glycosyl and enamino derivatives, were investigated . The activities of the compounds were characterized in vitro (yeasts and leukaemia cells) and in vivo (L1210 leukaemia in mice) . Among the compounds studied DR-19, N-(1-carboethoxypropen-1-yl)daunorubicin, exhibited activity comparable with that of the parent antibiotic . The correlation coefficients calculated showed good correlation between in vitro tests . In vitro activity and potency (reciprocal of optimal dose) in mice leukaemia were also correlated . However, no correlation between the in vitro activity and activity in mice leukaemia (increase of life span) was observed.

Arkh Patol, 1987, 49(4), 3 - 9
{Role of opportunistic fungi in human pathological anatomy}; Khmel'nitskii OK et al.; The role of opportunistic fungi (OF) in modern human pathology is discussed in connection with the increased incidence of mycotic infections caused by these organisms . Due to a complex of biological properties, OF are able to survive both in the environment and in human body, exhibiting their pathogenic potential when the body defenses are compromised . The highest frequency of infections caused by OF is encountered in the presence of risk factors (immunodeficiencies, endocrinopathies, oncological and hematological diseases, organ transplantation, antibiotic and corticosteroid therapy, infancy and pregnancy) . The spectrum of lesions caused by OF encompasses practically all organs and systems . Being a secondary process, mycotic infection may either have no influence on the primary process, or aggravate it . In most severe cases it may overbalance the importance of the underlying disease . Cytohistological methods play a special role in the diagnosis of mycotic infections, as they are able to reveal the invasive process, evaluate its extent and the characteristics of host defense responses.

Respiration, 1987, 51 Suppl 1, 42 - 51
Ambroxol for the prevention of chronic bronchitis exacerbations: long-term multicenter trial . Protective effect of ambroxol against winter semester exacerbations: a double-blind study versus placebo; Olivieri D et al.; In a 6-month, double-blind multicenter trial conducted over the winter, the effects of daily administration of ambroxol retard (75 mg) were compared with those of placebo in preventing exacerbations and improving symptoms and clinical signs in chronic bronchitis patients . The trial was completed by 110 patients in the ambroxol group and by 104 in the placebo group . Initially, there were no significant differences between the groups . By the end of the 2nd month of treatment, 67.2% of the ambroxol group had had no exacerbations compared to 50.4% in the placebo group . At the end of the 6-month trial, 45.5% of the treatment group had had no exacerbations, compared to only 14.4% of the control group . These differences were statistically significant . Patients in the treatment group lost significantly fewer days through illness (442) and had fewer days when they needed antibiotic therapy (371) compared to the placebo group patients (837 and 781) . Ambroxol also produced statistically significant symptomatic improvement, measured as difficulty in expectoration, coughing, presence of dyspnea and the auscultatory signs as compared to controls . Since ambroxol was well tolerated and compliance was good, it appears like a drug of choice for pharmacological prophylaxis of chronic bronchitis.

J Chronic Dis, 1987, 40(7), 651 - 60
Prescription drug use among diabetics--a population study; Isacson D et al.; Diabetes mellitus is a multifaceted disease which intervenes in the personal lives of those afflicted in many different ways . In this study prescription drug use among diabetics was analyzed in order to shed light on the characteristics of diabetic morbidity . Prescription drug use among diabetics and non-diabetics in a total population of 21,000 inhabitants in a defined geographic area were studied . The diabetic population was categorized according to the type of treatment received: insulin treatment, oral anti-diabetic treatment or dietary treatment or dietary treatment only . The pattern of prescription drug use differed between diabetics and non-diabetics and important differences were observed also between diabetics according to type of treatment . Drug use among those treated with insulin and those treated orally was substantially higher than among non-diabetics while the difference between diabetics on dietary regimen and non-diabetics was much smaller . All three treatment groups had considerably higher consumption of cardiovascular drugs than non-diabetics . Additional findings include more frequent antibiotic use among diabetics treated orally and on diet only than among non-diabetics . The use of these drugs was also common among insulin treated diabetics but did not differ significantly from among non-diabetics . Use of psychotropics was more common among diabetics treated with insulin and orally than among non-diabetics.

Br J Neurosurg, 1987, 1(3), 343 - 51
Experience with 'open evacuation of pus' in the treatment of intracerebral abscess; Maurice-Williams RS; Twenty-seven of 29 consecutive patients with brain abscess were treated by 'open evacuation of pus' . This technique involves wide exposure of the brain so that the abscess capsule may be incised and cleared of pus under direct vision . The empty capsule is left in situ after antibiotic irrigation and the wound is closed without drainage . Of the 27 patients, one died (3.7%), two were partly disabled and 24 (88.9%) were left with no neurological disability caused by the abscess . In only one case was a further operation required to remove pus which had reformed after an adequate primary clearance . There were no cases of wound sepsis or of late recurrence of the abscess . The author believes that 'open evacuation of pus' is the most satisfactory surgical technique for an intracerebral abscess.

Ophthal Plast Reconstr Surg, 1987, 3(1), 1 - 7
Orbital cellulitis with periosteal elevation; Lemke BN et al.; Computerized tomography scan evidence of periosteal elevation in patients with orbital cellulitis is interpreted in the current medical literature as an indication of subperiosteal abscess . We present three such cases in which surgical drainage yielded clear fluid or granulation tissue rather than pus . A fourth case resolved on antibiotic therapy alone . Cases of periosteal elevation that resolve without surgery may represent inflammatory effusion, infections of lesser virulence, or propagation of granulation tissue rather than true abscesses . We suggest that periosteal elevation seen in patients with orbital cellulitis should represent a relative rather than an absolute indication for drainage surgery.

Arch Immunol Ther Exp (Warsz), 1987, 35(5), 699 - 724
Biosynthesis of benzylpenicillin by Penicillium chrysogenum and its Golgi apparatus; Kurylowicz W et al.; The fine structure of high and low-yield mutants of Penicillium chrysogenum producing 10,000 and 100 units of benzylpenicillin was compared . The cells of both mutants showed typical eukaryotic ultrastructure . The Golgi vesicles, present in largest number in cells of high-yield mutant, fuse with the cell membrane and play an important role in the transport of benzylpenicillin from the cytoplasm to the cell environment . Benzylpenicillin was localized in cells of the high-yield mutant by means of enzymatical and immunological methods . The results indicate that benzylpenicillin is stored in the vesicles of the Golgi apparatus . The Golgi vesicles isolated from the protoplasts of high-yield mutant showed activities of enzymes of the pathway of benzylpenicillin biosynthesis i.e., delta-/L-alpha-aminoadipyl/-L-cysteinyl-D-valine synthetase, isopenicillin N synthetase, phenylacetyl: coenzyme A ligase, and acyl-exchange activity . Cell-free biosynthesis of antibiotic by the native Golgi vesicles was investigated in a well-defined reaction mixture . The native Golgi vesicles produced antibiotic in amount corresponding to 320 nmol.mg protein-1.h-1 . The activity yield of the calcium alginate immobilized Golgi vesicles was 44% . Moreover, a hypothetical scheme for localization of the enzymes of pathway of benzylpenicillin biosynthesis in the cells of high-yield mutant is presented.

Clin Ther, 1987, 9(5), 512 - 22
Efficacy of a new intravenous immunoglobulin preparation in primary immunodeficient patients; Ochs HD et al.; The safety and efficacy of a new second-generation intravenous immunoglobulin manufactured using ion-exchange chromatographic methods was studied in 17 patients with primary immunodeficiency . In assessing safety, the incidence of adverse reactions during the first 48 hours after each infusion and long-term changes in laboratory values were considered . Efficacy was determined by the number of acute and new chronic infections as well as by the number of prescriptions filled for antibiotics . These results were compared with those reported for similar preparations . Results showed a low (4.4%) incidence of acute adverse reactions, and no serious reactions or significant changes were noted in any of the laboratory test results . The incidences of infection and antibiotic usage were as low as or lower than those reported with other preparations . Thus we conclude that this new intravenous immunoglobulin product is a safe, effective prophylactic treatment for patients who have primary immunodeficiency.

Eur J Nucl Med, 1987, 13(3), 121 - 4
Intestinal accumulation of 111In-granulocytes in patients studied because of occult infection; Syrjala MT et al.; 111In-granulocyte scintigraphy was performed on 245 patients in whom a localized infection was suspected . In 123 patients scintigraphy was positive and of these 35 (28%) had intestinal accumulations of 111In-granulocytes . Specific local causes for the intestinal uptake of radioactivity were antibiotic associated colitis (eight patients), local pyogenic bowel infection (four patients), systemic disease (two patients), bowel necrosis (two patients), colonic cancer (one patient) and Stevens-Johnson's syndrome (one patient) . Nonspecific mechanisms of bowel accumulation were desquamation of labelled granulocytes (12 patients) and bleeding (two patients) . In three cases the mechanism of colonic accumulation of granulocytes was not revealed . These results show that unexpected accumulations of labelled granulocytes in the gut is not a rare phenomenon and is often due to clinically significant intestinal inflammation or other disease, especially in patients who do not have signs of respiratory, pancreatic or oesophageal inflammation causing desquamated granulocytes to accumulate in the gut.

C R Acad Sci III, 1987, 304(12), 325 - 9
{A statistical model for interpreting the antibiogram}; Scavizzi M et al.; Up to now, to interpret antibiotic susceptibility tests, the common practice has been to use: first, breakpoints without any quantitative justification, secondly, concordance curves between the different measurement techniques; these are not well adapted to the heterogeneous character of bacterial populations . We hereby propose another method: it is based on a global data analysis for each bacterial species, each antibiotic family and each measurement technique . So, we have drawn up a new model for the interpretation, both global and data-processed; it is based on qualifying classes, which are obtained and interpreted by hierarchical ascendent classification, principal components analysis, and comparison with pharmacological data . It can be used by any biologist . What is more, justified breakpoints with a numerical risk and quality control are defined . There are also some additional uses: evaluation of the effect of new antibiotics, standardization of new measurement techniques, detection of the emergence of new bacterial resistance in patients, guidance for research into unknown resistance mechanisms and characters.

Eksp Onkol, 1987, 9(1), 37 - 40
{Cytotoxic factors of neutrophils in rats with 7,12-dimethylbenz{a}anthracene-induced sarcoma}; Cherdyntseva NV; A study of intraleukocyte cytotoxic system and phagocytic function of granulocytes was carried out in rats with 7,12-dimethylbenz(a)anthracene-induced sarcoma . There were no distinctive alterations of microbicidal factors of polymorphonuclear neutrophils (PMN) at the initial stage of the tumour growth . The inhibition of some antibiotic neutrophil factors at later stages of the tumour growth in rats was compensated by preferential activity of others . The essential impairments of both the oxygen-dependent and oxygen-independent mechanism of cytotoxicity of PMN at the terminal stage of sarcoma growth were detected . At the same time the phagocytic activity of neutrophils was depressed.

Aviat Space Environ Med, 1987 Jan, 58(1), 83 - 5
Implications of emerging isoniazid resistance in Mycobacterium tuberculosis in Korea; Berliner DS et al.; In 1981, the Korean National Institute of Health (KNIH) reported that 17% of all tuberculosis patients had primary resistance to isoniazid while an additional 17% acquired isoniazid resistance during chemotherapy . This 34% isoniazid resistance rate in the Republic of Korea, where an estimated 6-8% of the total population have active tuberculosis, poses significant concerns regarding management of U.S . military health care beneficiaries who develop tuberculosis or have tuberculosis skin test conversion while residing in or after departure from Korea . To address this issue, the prevalence of Korean acquired isoniazid resistance was estimated in U.S . beneficiaries by performing antibiotic sensitivities on all positive cultures from October 1981 through December 1982 . Of 42 patient isolates, six were isoniazid resistant (14.3%) . When the data was analyzed further, it was determined that as many as 9.5% of those U.S . beneficiaries infected had primary isoniazid resistance . This is higher than the most recent U.S . population-based drug resistance study, in which 6.9% of tuberculosis patients had primary drug resistance . This data comparison points toward the need for judicious management of Korean acquired infections and skin test conversions . Emphasis is on criteria necessary to warrant use of chemotherapeutic agents other than isoniazid to prevent further introduction of resistant organisms into locales where isoniazid resistance is not as prevalent as reported in Korea.

Gene, 1987, 54(1), 73 - 81
Selectable genes for transformation of the fungal plant pathogen Glomerella cingulata f . sp . phaseoli (Colletotrichum lindemuthianum); Rodriguez RJ et al.; Glomerella cingulata f . sp . phaseoli (Gcp) was transformed using either of two selectable markers: the amdS + gene of Aspergillus nidulans, which encodes acetamidase and permits growth on acetamide as the sole nitrogen source and the hygBR gene of Escherichia coli which encodes hygromycin B (Hy) phosphotransferase and permits growth in the presence of the antibiotic Hy . The amdS+ gene functioned in Gcp under control of A . nidulans regulatory signals and hygBR was expressed after fusion to a promoter from Cochliobolus heterostrophus, another filamentous ascomycete . Protoplasts to be transformed were generated with the digestive enzyme complex Novozym 234 and then were exposed to plasmid DNA in the presence of 10 mM CaCl2 and polyethylene glycol . Transformation occurred by integration of single or multiple copies of either the amdS+ or hygBR plasmid into the fungal genome . There was no evidence of autonomous plasmid replication . Transformants were mitotically stable on selective and nonselective media . However, transforming DNA in hygBR transformants was observed to occasionally rearrange during nonselective growth, resulting in fewer copies of the plasmid per genome . These transformants were capable of infecting bean (Phaseolus vulgaris), the Gcp host plant, and after recovery from infected tissue were found to have retained both the transforming DNA unrearranged in their genomes and the Hy resistance phenotype . All single-conidial cultures derived from both amdS+ and hygBR transformants had the transplanted phenotype, suggesting that transformants were homokaryons.

Chemotherapy, 1987, 33(4), 272 - 7
Cytostatic and antiherpesvirus type 1 and 2 activities of 1-beta-D-arabinofuranosylthymine (ara T) prodrugs; Allen LB et al.; A series of derivatives of the antibiotic 1-beta-D-arabinofuranosylthymine (ara T) was synthesized by esterification of the hydroxy group in the 5'-position of the arabinose moiety of the nucleoside with straight-chain and branched-chain carboxylic acids: acetyl-ara T, butyryl-ara T, valeroyl-ara T, pivaloyl-ara T and palmitoyl-ara T . These ara T prodrugs were evaluated for their effect on growth of L5178y mouse lymphoma cells and noninfected BHK-21 cells as well as for their antiviral activity in Herpes simplex virus type 1 and 2 infected BHK-21 cells . All compounds exhibited a marked antiherpes virus activity, whereas the cytostatic activity of two of them, the pivaleric ester and the palmitic ester, was extremely weak . The relative antiviral indices of the 5'-pivaloyl-ara T and 5'-palmitoyl-ara T were found to be much better than the index of ara T itself.

Arch Dermatol Res, 1987, 279(3), 147 - 50
Topical treatment of psoriasis with the topoisomerase inhibitors novobiocin and nalidixic acid: a pilot study; Bohr VA et al.; Our studies in human epidermal keratinocytes as a model system have suggested that the antibiotic topoisomerase II inhibitors, novobiocin and nalidixic acid, may be of value for the treatment of hyperproliferative skin disorders . We have therefore conducted a pilot study of the clinical efficacy of these compounds for the treatment of psoriasis . The compounds were administered topically to psoriatic plaques in seven healthy patients over a period of 6 weeks . Nalidixic acid (2%) or novobiocin (2% or 5%) in methylcellulose were applied twice daily under occlusion, and methylcellulose alone was used as a control . In six of the seven patients, one or both compounds effected somewhat greater improvement than in the control within 3 weeks of treatment.

Somat Cell Mol Genet, 1987 Jan, 13(1), 47 - 56
Analysis of spontaneous mutations in a chromosomally located HSV-1 thymidine kinase (TK) gene in a human cell line; Goring DR et al.; We have developed a system for studying spontaneous mutations at a chromosomally located single-copy HSV-1 thymidine kinase (TK) gene in the human 143 TK- cell line . The neo gene, which confers resistance to the antibiotic G418, was placed next to the TK gene for the purpose of screening out gross chromosomal alterations . TK- mutations were selected using the anti-TK nucleotide analogs trifluorothymidine, acyclovir, and DHPG 9-(1,3 dihydroxy-2-propoxymethyl)-guanine either separately, or in combination to eliminate leaky mutations . Analysis of the TK- mutations by Southern blotting revealed that the majority had undetectable alterations of less than 50 base pairs . The results using the methylation-sensitive enzymes HpaII, AvaI, and SmaI suggest that the inactivation of the TK gene was not due to extensive methylation, although specific methylation of a limited number of MspI sites cannot be ruled out . Reversion studies, however, showed that of 16 mutants analyzed, about half had a very high reversion frequency (approximately 10(-2) . This suggests that inactivation of the TK gene may have occurred by a variety of mutational events.

Eur J Clin Pharmacol, 1987, 33(2), 191 - 5
Binding of teicoplanin to human serum albumin; Assandri A et al.; The interaction between the main components of the new glycopeptide antibiotic teicoplanin, A2-2, A2-3, A2-4, A2-5 and A3-1, and human serum albumin has been studied in vitro by equilibrium dialysis (pH 7.4, 37 degrees C) . From Scatchard analysis of the data, the calculated association constants (Ka) were: A2-2, 2.47 X 10(4), A2-3, 2.86 X 10(4), A2-4, 2.95 X 10(4) and A2-5, 3.87 X 10(4) mol.l-1 . The number of binding sites per albumin molecule ranged between 1.23 to 1.31 . A3-1 had a lower affinity with a Ka of about 5 X 10(3) mol.l-1 . Extrapolated to the in vivo situation, the data suggested that about 90-95% of A2 components will be bound to serum albumin, and about 68-72% of A3-1 . The in vitro findings were confirmed by a pharmacokinetic study in volunteers given {14C} teicoplanin i.v., in whom the fraction of teicoplanin bound to serum protein ranged between 87.6 and 90.8%.

Int J Tissue React, 1987, 9(5), 443 - 6
Low-dose isotretinoin in severe acne; Bellosta M et al.; A selected group of 60 patients who had been resistant to previous systemic antibiotic therapy was treated with low-dose isotretinoin (0.5 mg/kg/day in two doses) for 12 to 20 weeks . The results confirmed the efficacy of the drug on pustular, nodular and cystic acne even with low-dose treatment . In only one case was it necessary to suspend the treatment because of an increase in serum cholesterol and triglycerides . The authors therefore advise the use of low dosage and that treatment should be restricted to cases of severe acne.

Free Radic Biol Med, 1987, 3(1), 41 - 54
Free radical mechanisms in neocarzinostatin-induced DNA damage; Goldberg IH; The molecular mechanisms by which the antitumor protein antibiotic, neocarzinostatin, interacts with DNA and causes DNA sugar damage is discussed . Physical binding of the nonprotein chromophore of neocarzinostatin to DNA, involving an intercalative process and dependent on the microheterogeneity of DNA structure, is followed by thiol activation of the drug to a probable radical species . The latter attacks the deoxyribose, especially at thymidylate residues, by abstracting a hydrogen atom from C-5' to generate a carbon-centered radical on the DNA . This nascent form of DNA damage either reacts with dioxygen to form a peroxyl radical derivative, which eventuates in a strand break with a nucleoside 5'-aldehyde at the 5'-end or reacts with the bound drug to form a novel drug-deoxyribose covalent adduct . Nitroaromatic radiation sensitizers can substitute for dioxygen, but the DNA damage products are different . Similarities between the various biological effects of neocarzinostatin and ionizing radiation are reviewed.

Pediatr Neurosci, 1987, 13(5), 251 - 4
Subdural empyemas in children; Pattisapu JV et al.; Subdural empyema is a neurosurgical emergency which is rapidly fatal if not recognized and managed promptly . Most series report a 30-40% mortality, and recommend a craniotomy along with aggressive medical therapy . Between 1978 and 1986, 8 children (2 months to 13 years) with subdural empyemas were diagnosed and treated at our institution, and form the basis for this study . Burr hole and catheter drainage was the treatment of choice in 5 children, while craniotomy was required in 1 case of sinusitis with osteomyelitis . Three infants received multiple subdural taps via the anterior fontanel . All patients responded to surgical intervention and antibiotic therapy . The average follow-up period was 29 months, and 5 children had no developmental delay, decrease in school performance, or impairment of intellectual function . There were no deaths in our series . Although the surgical management of subdural empyemas remains controversial, it appears that burr hole and catheter drainage is sufficient in most cases . With earlier diagnosis, aggressive antibiotic therapy, and timely surgical intervention, the morbidity and mortality of subdural empyemas have significantly diminished in recent years.

Folia Microbiol (Praha), 1987, 32(5), 388 - 401
Physiology of a wild strain and high yielding mutants of Streptomyces rimosus, producing oxytetracycline; Al-Jawadi M et al.; A wild-type Streptomyces strain, yielding 1 g/L of oxytetracycline was compared with mutants giving up to 7 g/L, using complex media in stirred and shaken culture . Increased production of oxytetracycline was associated with high specific production rates and a longer production period . The superiority of the mutants was associated with changes in morphological behaviour during growth in submerged culture, and in their patterns of growth and respiration, coupled with increased resistance to the product . The productivity of the mutants was sensitive to the rate of stirring, the type of calcium carbonate used in the medium and the type of inoculum . Careful control of these factors was necessary to obtain high yields of oxytetracycline . With the exception of acetyl-CoA carboxylase, the levels of enzymes measured and of amounts of adenylates in the mycelium did not appear to be related to the degree of antibiotic production.

Oncogene, 1987, 1(4), 337 - 45
Transformation of differentiated neonatal rat hepatocytes in primary culture by polyoma virus early region sequences; Hohne M et al.; Neonatal rat hepatocytes (NRH) in primary cultures were transformed upon transfection with plasmid pSV 5-neo containing polyoma virus (Py) early region sequences . Clones of cells (Py-NRH) resistant to the antibiotic G418 were obtained after selection in arginine-deficient medium with serum, epidermal growth factor (EGF), transferrin and insulin . They did not undergo senescence during serial subcultivation . One clone (Py-NRH Cl A) harbored a single integrated copy of Py early region sequences and expressed transforming Py genes, hepatocyte-specific transcripts, including albumin, alpha-fetoprotein (AFP) and tyrosine aminotransferase (TAT) mRNAs . Subclones isolated after about 45 cell doublings still contained albumin and AFP, but no TAT mRNAs, indicating that long-term stabilization of liver functions is not necessarily permanent unless selected for (e.g . arginine synthesis) . Cells grew unrestricted in medium containing insulin and no longer required EGF . Cells grew in agar, secreted a beta-transforming growth factor-like activity into the medium and were tumorigenic in nude mice . Hybridization studies using v-erbB DNA as a probe showed that Py-NRH, unlike neonatal hepatocytes in primary culture, express the EGF receptor gene at low or undetectable levels . Py-NRH Cl A and a subclone (5A) derived from it, however, contained elevated levels of rat c-neu oncogene-related RNA, whereas levels in another subclone (3A) were low or undetectable . These findings demonstrate that a proto-oncogene was activated after transfection of hepatocytes with DNA tumor virus transforming genes . However, the expression of c-neu oncogene is not related to the maintenance of the transformed state.

Surg Endosc, 1987, 1(2), 99 - 102
Endoscopic sealing of infected bronchus stump fistulae with fibrin following lung resections . Experimental and clinical experience; Waclawiczek HW et al.; Bronchus stump insufficiency following lung resection, with an average incidence of 4%, is a serious complication which carries a mortality of up to 90% . Operative transthoracic approaches have been largely unsatisfactory because of the high operative risk and rapidly spreading infection . In an experimental study on 18 pigs, endoscopic occlusion of infected bronchus stump fistulae was achieved with fibrin sealant (1 ml, 500 units/ml thrombin, 3500 units/ml aprotinin) applied via a flexible bronchoscope . During autopsy, all bronchus stump fistulae were found to have healed after the second postoperative week . Transitory local abscesses of the pleura could be prevented by high-dose systemic antibiotic therapy for 5 postoperative days but not by antibiotics added to the fibrin sealant . This endoscopic method has already been performed successfully in 3 clinical cases; additional sclerotherapy with (2-3 ml Ethoxysclerol applied around the fistula orifice was carried out before fibrin sealing to stimulate fibrosis . Endoscopic controls demonstrated fistula closure by granulation tissue after 2 weeks . This procedure could become the method of choice for infected postoperative fistulae of the bronchus stump and should be attempted in any case before operative approaches are considered.

Acta Physiol Pharmacol Bulg, 1987, 13(4), 55 - 9
Changes in the antitumour effect of some cytostatic agents applied under conditions of morphine-induced hyperthermia; Ovtcharov R et al.; The effect of the cytostatic agents bleomycetin, vincristine and methotrexate on the growth of the Lewis lung carcinoma was investigated under conditions of normothermia and morphine-induced hyperthermia . Morphine was administered 1, 3, 5, 7, 9 and 11 days after the tumour transplantation (in a single of 20 mg/kg), 75 min prior to the administration of bleomycetin (in a single dose of 2 mg/kg), vincristine (in a single dose of 0.3 mg/kg) and methotrexate (in a single dose of 5 mg/kg) . The therapeutic effect was assessed on the 24th hour after the end of the treatment through determining the tumour growth inhibition . The administration of morphine to mice was found to be accompanied by the development of a hyperthermal reaction, with a maximum between the 90th and 120th min after the treatment, the change in the rectal temperature of the animals being of the order of 2.2 +/- 0.14 degrees C . Hyperthermia potentiates the effect of the antitumour antibiotic bleomycetin which, unlike bleomycin, does not manifest a threshold effect of interaction with the hyperthermia . Temperatures of the order of 40 degrees C are found to result in sensitization of the relatively resistant cells of the Lewis lung carcinoma to the antitumour effect of vincristine . Hyperthermia did not affect the activity of methotrexate . The analysis of the data obtained suggests that morphine-induced hyperthermia is a convenient model in mice for testing the behaviour of the cytostatic agents under conditions of increased temperature.

Cancer Chemother Pharmacol, 1987, 20(4), 277 - 84
Comparative effects of adriamycin and DNA-non-binding analogues on DNA, RNA, and protein synthesis in vitro; Israel M et al.; Drug-DNA binding is claimed to be the basis by which the antitumor antibiotic adriamycin (doxorubicin) inhibits DNA and RNA synthesis in vitro . However, in preliminary studies the DNA-non-binding adriamycin analogue N-trifluoroacetyladriamycin-14-valerate (AD 32) showed somewhat greater inhibition of DNA and RNA synthesis than adriamycin under identical conditions . The kinetics of macromolecule synthesis inhibition induced by adriamycin and AD 32, and the two principal DNA-non-binding metabolites of AD 32, N-trifluoroacetyladriamycin (AD 41) and N-trifluoroacetyladriamycinol (AD 92), have now been subjected to comparative study in cultured CEM (human leukemic lymphoblastic) cells . At equimolar concentrations (10 microM), or at concentrations related to their 50% growth-inhibitory values vs CEM cells, AD 32 was consistently found to be more inhibitory than adriamycin of DNA and RNA synthesis, as measured by the incorporation of tritiated thymidine and uridine, respectively, into acid-precipitable fractions relative to untreated controls . Marked inhibitory activity was apparent with 10 microM AD 32 even at the earliest sampling time (15 min); with adriamycin at the same concentration the maximal effect was not achieved until 3 h . AD 32 at 4.8 microM concentration continued to show strong inhibition of nucleic acid synthesis, whereas adriamycin at 1.0 microM was essentially inactive . Like AD 32, AD 41 and AD 92 showed greater inhibition than adriamycin of DNA and RNA synthesis at the early sampling times, although in all instances the effects of AD 32 were more profound . AD 32 at 10 microM concentration produced a moderate but significant inhibition of the incorporation of tritiated methionine into protein compared with adriamycin, which at this concentration was not active . Parallel HPLC analytical studies with similar drug-treated cultures indicated that, while small amounts of adriamycin were found in cells treated with 10 microM AD 32, the amount of adriamycin present at 15 min was only a small fraction (less than 5%) of the amount of adriamycin achieved at 3 h in cultures treated with 1.0 microM adriamycin, a concentration already shown to be only slightly inhibitory of nucleic acid synthesis under the culture conditions . The present study thus confirms the marked DNA and RNA synthesis-inhibitory effects of AD 32, and establishes that this inhibitory activity is not due to conversion of AD 32 into adriamycin . These findings accordingly call into question the validity of the drug-DNA binding mechanism as the explanation for the nucleic acid synthesis inhibitory effects seen with ADR.

J Gen Virol, 1987 Jan, 68 ( Pt 1), 219 - 23
Amphotericin B delays the incubation period of scrapie in intracerebrally inoculated hamsters; Pocchiari M et al.; The scrapie-infected hamster has been considered an excellent model for the study of slow virus diseases of man (Creutzfeldt-Jakob disease) and animals . At the moment no therapy is available for the cure of these fatal central nervous system diseases, although several drugs have been tested . We found that amphotericin B (AmB), a polyene antibiotic, increased the incubation time of scrapie disease in animals infected by either the intraperitoneal or intracerebral route . Hamsters inoculated with a 10% brain suspension of the 263K strain of scrapie showed clinical signs of disease in 54.6 +/- 4.7 days . Under AmB treatment (1 mg/kg for 6 days a week) the incubation time increased with the length of treatment, up to a maximum delay of 45 days . AmB may interact with the scrapie agent on cell plasma membranes and may thereby decrease the rate of scrapie replication . However, AmB did not have any effect when administered after the clinical onset of scrapie disease.

Biochemistry, 1986 Dec 30, 25(26), 8430 - 6
Construction and characterization of a site-directed CC-1065-N3-adenine adduct within a 117 base pair DNA restriction fragment; Needham-VanDevanter DR et al.; The design, construction, and characterization of a site-directed CC-1065-N3-adenine adduct in a 117 base pair segment of M13mpI DNA are described . CC-1065 is an extremely potent antitumor antibiotic produced by Streptomyces zelensis . Previous studies have demonstrated that the cyclopropyl ring of CC-1065 reacts quite specifically with N3 of adenine in double-stranded DNA to form a CC-1065-DNA adduct . Following alkylation, the drug molecule lies snugly within the minor groove of DNA, overlapping with five base pairs for which a marked sequence preference exists {Hurley, L . H., Reynolds, V . R., Swenson, D . H., Petzold, G . L., & Scahill, T . A . (1984) Science (Washington, D.C.) 226, 843-844} . On the basis of the unique characteristics of the reaction of CC-1065 with DNA and the structure of the resulting DNA adduct, we have designed a general strategy to construct a site-directed CC-1065-DNA adduct in a restriction fragment . The presence of unique AluI and HaeIII restriction enzymes sites on each side of a high-affinity CC-1065 binding sequence (5'-GATTA) permitted the preparation of a partial duplex DNA molecule containing the CC-1065 binding sequence in the duplex DNA region . Since CC-1065 only binds to duplex DNA, potential CC-1065 binding sequences in the long single-stranded regions were protected from drug binding during the construction process.(ABSTRACT TRUNCATED AT 250 WORDS)

Biochemistry, 1986 Dec 16, 25(25), 8330 - 6
Aminoacyl-tRNA-elongation factor Tu-ribosome interaction leading to hydrolysis of guanosine 5'-triphosphate; Takahashi K et al.; We investigated the elongation factor Tu (EF-Tu) dependent binding of Phe-tRNA and Phe-tRNAs with the nicks at positions 46, 37, and 17 to the Escherichia coli 70S ribosome-poly(U)-tRNAPhe complex . Binding of Phe-tRNA1-45 + 47-76, Phe-tRNA1-36 + 38-76, or Phe-tRNA1-16 + 17-76 to the 70S ribosome has been found to be poly(U) X tRNA dependent and, similar to that of intact Phe-tRNA, is inhibited by the antibiotic thiostrepton . We have further found that, contrary to a previous report {Modolell, J., Cabrer, B., Parmeggiani, A., & Vazquez, D . (1971) Proc . Natl . Acad . Sci . U.S.A . 68, 1796}, the EF-Tu-ribosome GTPase mediated by Phe-tRNA is not inhibited by thiostrepton; rather, the drug stimulates the endogenous GTPase of the EF-Tu X 70S ribosome . Phe-tRNA fragments 47-76, 38-76, and 17-76 all promote the EF-Tu X GTPase reaction in the presence of 70S ribosome-poly(U)-tRNAPhe yeast . Moreover, since the GTPase-promoting activities of both the short and long fragments are similar, it appears that the most important aminoacyl transfer ribonucleic acid (aa-tRNA) interaction with EF-Tu occurs alongside its 3' quarter . Thiostrepton slightly stimulates the GTPase activity of these Phe-tRNA fragments . Although the Phe-tRNA1-36 + 38-76 cannot bind to poly(U) during its binding to 70S ribosomes, its binding at high Mg2+ concentration occurs at the A site . Thus, most of the bound modified Phe-tRNA functions as the acceptor in the peptidyltransferase reaction.(ABSTRACT TRUNCATED AT 250 WORDS)

Thromb Res, 1986 Dec 15, 44(6), 793 - 806
Characterization of a potent inhibitor of platelet aggregation and release reaction isolated from allium sativum (garlic); Mohammad SF et al.; When added to platelet-rich plasma, aqueous extracts of garlic inhibited platelet aggregation and the release reaction . Subsequent experiments designed to characterize the inhibitory component revealed that the inhibitory activity was i) associated with small molecular-weight components, ii) the inhibitory component possessed the typical garlic odor and contained an abundance of sulfur, iii) the inhibitory activity could be extracted with organic solvents, and iv) temperatures above 56 degrees C and alkaline pH above 8.5 quickly destroyed the inhibitory activity . The Rf value of the major inhibitory component after thin-layer chromatographic separation was similar to that of allicin, an unique thiosulfinate in garlic previously shown to possess strong antibiotic and antifungal properties . Allicin was synthesized . On thin-layer chromatographic plates, allicin co-migrated with the inhibitory component in garlic . At 10 microM concentration, allicin inhibited completely platelet aggregation and the release reaction . Comparative studies suggest that the major platelet aggregation and release inhibitor in garlic may be allicin.

Eur J Biochem, 1986 Dec 15, 161(3), 647 - 53
Characterization of the elongation factors from calf brain . 2 . Functional properties of EF-1 alpha, the action of physiological ligands and kirromycin; Crechet JB et al.; The properties of EF-1 alpha from calf brain have been investigated and compared with those of EF-Tu . EF-1 alpha binds GDP and GTP in a 1:1 stoichiometry, showing the same affinity for both nucleotides (K'd = 2-4 microM) . EF-1 beta strongly enhances the dissociation rate of the EF-1 alpha X GDP complex and to a lesser extent of the EF-1 alpha X GTP complex . Aminoacyl-tRNA (aa-tRNA) stabilized EF-1 alpha X GTP much less efficiently than the EF-Tu X GTP complex . Unlike EF-Tu, EF-1 alpha sustains the binding of aa-tRNA to the ribosome also in the presence of GDP or in the absence of any nucleotide, though to a lesser degree than with GTP . Kirromycin enhances the dissociation rate of both EF-1 alpha X GTP and EF-1 alpha X GDP but especially that of the latter . This effect results in an increase of the exchange rate of the EF-1 alpha-bound nucleotide with free nucleotides . Although in this regard the effect of kirromycin mimics that of EF-1 beta, the antibiotic is incapable of increasing the EF-1 alpha X GDP/GTP exchange rate when aa-tRNA and ribosomes are present . Therefore, unlike EF-1 beta, kirromycin cannot enhance the rate of poly(Phe) synthesis . On the other hand, the failure of kirromycin to induce a GTP-like conformation of EF-1 alpha X GDP, as in the case of EF-Tu X GDP, explains its inability to inhibit peptide bond formation in the eukaryotic system.

J Biol Chem, 1986 Dec 15, 261(35), 16584 - 90
Selective inhibition by ionophore A23187 of the enzyme isomerization in the catalytic cycle of sarcoplasmic reticulum Ca2+-ATPase; Hara H et al.; The effect of a lipophilic antibiotic, ionophore A23187, on the purified Ca2+-ATPase from sarcoplasmic reticulum was investigated . When the enzyme was pretreated with A23187 in the presence and absence of Ca2+, the Ca2+-dependent ATPase activity was inhibited almost completely, but the activity of the contaminating Mg2+-ATPase was unaffected . The steady state level of the phosphoenzyme (EP) from ATP or Pi was not substantially altered . When the pretreatment was performed in the presence of Ca2+, EP formation from ATP was only slightly retarded, but EP decomposition was strongly inhibited . Under these conditions, the accumulated EP was ADP-sensitive . EP formation from Pi after chelating of Ca2+ was quite slow, whereas EP once formed was in rapid equilibrium with Pi of the medium . On the other hand, when the pretreatment was performed in the absence of Ca2+, EP formation from ATP was extremely slow, but EP once formed was in rapid dynamic equilibrium with ATP of the medium . EP formation from Pi was very fast, and this EP was in rapid equilibrium with Pi of the medium . These results demonstrate that A23187 selectively inhibits isomerization of the enzyme between the high Ca2+-affinity form and the low Ca2+-affinity form in the catalytic cycle, whether or not the enzyme is phosphorylated . This suggests that interactions between the enzyme protein and the surrounding lipids could play a crucial role in this isomerization.

J Biol Chem, 1986 Dec 5, 261(34), 15854 - 62
Expression of platelet glycoprotein Ib alpha in HEL cells; Kieffer N et al.; We have previously shown that platelet glycoprotein Ib is expressed in a minority of cells of the human leukemic cell line HEL (Tabilio, A., Rosa, J . P., Testa, U., Kieffer, N., Nurden, A . T., Del Canizo, M . C., Breton-Gorius, J., and Vainchenker, W . (1984) EMBO J . 3, 453-459) . In this report, we have selected a stable HEL subclone with increased expression of glycoprotein (GP) Ib as assessed by 6 different monoclonal antibodies in order to investigate the biochemical characteristics of this glycoprotein . A single polypeptide chain of apparent Mr = 60,000 was precipitated under reducing and nonreducing conditions by a specific polyclonal anti-platelet glycocalicin antibody and two anti-GPIb alpha monoclonal antibodies (AN51 and AP1), both from surface-labeled and metabolically labeled HEL cells . We were unable to demonstrate the presence of a polypeptide corresponding to the beta subunit of GPIb or GPIX which is closely associated with GPIb . Competitive immunoprecipitation performed in the presence of an excess amount of cold platelet glycocalicin completely displaced the Mr = 60,000 polypeptide . Synthesis of N-linked oligosaccharide chains on this Mr = 60,000 polypeptide was inhibited by the antibiotic tunicamycin, and a shift of the apparent Mr from 60,000 to 48,000 was observed . O-Linked oligosaccharide chains identical to platelet GPIb hexasaccharides were deficient or incomplete since no peanut agglutinin binding to the Mr = 60,000 polypeptide was observed after neuraminidase treatment of HEL cells . Thus, our results provide evidence that the Mr = 60,000 polypeptide expressed on the surface membrane of HEL cells is closely related to platelet GPIb and corresponds to an incompletely or abnormally O-glycosylated GPIb alpha subunit.

Drug Intell Clin Pharm, 1986 Dec, 20(12), 953 - 4
Serum sickness associated with cefoxitin and pentoxifylline therapy; Panwalker AP et al.; Human serum sickness is a syndrome characterized by fever, malaise, skin rashes, arthralgias, gastrointestinal disturbances, and lymphadenopathy . It is believed to be mediated by circulating immune complexes composed of a foreign antigen and host antibody . Several cephalosporins have been associated with serum sickness . We report the occurrence of serum sickness in a patient who received cefoxitin, a commonly used cephamycin antibiotic, and pentoxifylline, a xanthine derivative that improves the flow properties of blood by decreasing its viscosity . Serum sickness has not been previously reported with the use of cefoxitin or pentoxifylline.

Antimicrob Agents Chemother, 1986 Dec, 30(6), 888 - 91
Continuous sampling for determination of pharmacokinetics in rat cerebrospinal fluid; Meulemans A et al.; A method for determining drug concentration relationships between plasma and cerebrospinal fluid (CSF) in rats is described . Continuous CSF samples were collected directly from the third anterior ventricle with an indwelling cannula inserted through the bregma point, and drug concentrations were determined by high-pressure liquid chromatography and radioimmunoassay micromethods . Three antibiotics with different abilities to cross the blood-CSF barrier (chloramphenicol, piperacillin, and gentamicin) were tested . This method was found to be reproducible for each drug even if the antibiotic levels were low and the sample volumes very small . Peak CSF concentrations occurred between 0.75 and 1.25 h after injection for all three antibiotics . Percent penetration values at 1 h were 50, 1.2, and 5.4% for chloramphenicol, piperacillin, and gentamicin, respectively.

Chem Biol Interact, 1986 Dec, 60(3), 275 - 85
Inhibition of acetyl-coenzyme A dependent activation of N-hydroxyarylamines by phenolic compounds, pentachlorophenol and 1-nitro-2-naphthol; Shinohara A et al.; Pentachlorophenol (PCP) and 1-nitro-2-naphthol were found to be potent inhibitors of enzymatic acetyl-CoA dependent activation, which is suggested as proceeding through direct O-acetylation, of N-hydroxyarylamines to tRNA binding by liver cytosolic enzymes from hamsters and rats . IC50 values of PCP for the activation of 2-hydroxyamino-6-methyldipyrido{1,2-a:3',2'-d}imidazole (N-OH-Glu-P-1), 3-hydroxyamino-1-methyl-5H-pyrido{4,3-b}indole (N-OH-Trp-P-2) and N-hydroxy-2-aminofluorene (N-OH-AF) were 20, 25 and 17 microM, respectively, in hamster cytosol system . Similar inhibition was observed with rat liver cytosol (IC50 values of PCP and 1-nitro-2-naphthol were 13 and 12 microM, respectively, for the binding of N-OH-Glu-P-1) . PCP is known as an inhibitor of sulfotransferase; however, another potent inhibitor of sulfotransferase, 2,6-dichloro-4-nitrophenol, did not inhibit the acetyl-CoA dependent binding . Antibiotic thiolactomycin, which inhibits bacterial O-acetyltransferase, did not affect the activation by hamster and rat cytosol, indicating the difference in property between bacterial and mammalian enzymes . The kinetic data obtained with hamster cytosol suggested the competitive inhibition of PCP with substrate, N-OH-Glu-P-1, and non-competitive inhibition with acetyl-CoA . In addition to the O-acetylation, PCP and 1-nitro-2-naphthol also inhibited N-acetylation of arylamines and N,O-acetyltransfer reaction of N-hydroxy-2-acetylaminofluorene (N-OH-AAF) by hamster cytosol . IC50 values for these two types of acetyltransfer reactions, however, were slightly higher than those observed for acetyl-CoA dependent activations of N-hydroxyarylamines.

Postgrad Med, 1986 Dec, 80(8), 100, 105 - 7
Acute suppurative thyroiditis in a 3-year-old boy; Smeal WE et al.; A previously healthy 3-year-old boy was referred because of persistent fever and anterior neck swelling and pain . The diagnosis of a mixed bacterial abscess of the thyroid gland was made . Incision and drainage were performed, and fever abated immediately . Antibiotic therapy was given in the hospital and for ten days after discharge . Acute suppurative thyroiditis is a rarely encountered infection . The majority of cases reported in the recent literature are from Japan . The case presented here, from the United States, demonstrates the difficulty that can be encountered in diagnosing this type of thyroiditis.

J Vasc Surg, 1986 Dec, 4(6), 563 - 6
Septic deep vein thrombosis; Ang AK et al.; Anticoagulation is the cornerstone in the treatment of deep vein thrombosis . However, the treatment of septic deep vein thrombosis is controversial . Unlike septic superficial vein thrombosis, venous excision is often associated with limb-threatening or even life-threatening complications . Some authors have suggested thrombectomy as the only means of resolving the sepsis . We reviewed our experience with seven patients who had septic deep vein thrombosis . Phlebography or noninvasive studies documented deep vein thrombosis and blood cultures were positive in all patients . The mean age was 31.5 years with a male/female ratio of 5:2 . All patients were treated with anticoagulants and intravenous antibiotics . One patient required surgical exploration for associated abscess of the groin . The patients became afebrile with normal white blood cell counts from 3 to 18 days after therapy was begun . No cases of recurrent sepsis occurred . We conclude that antibiotic therapy and anticoagulation are adequate treatment and therefore consider venous thrombectomy unnecessary.

J Med Chem, 1986 Dec, 29(12), 2484 - 92
Molecular mechanics simulations on covalent complexes between anthramycin and B DNA; Rao SN et al.; We present molecular mechanics simulation of the covalent interactions of the potent antitumor antibiotic belonging to the pyrrolo{1,4}benzodiazepine class, anthramycin, with six deoxydecanucleotides, d(GCGCGCGCGC)2, d(G10) X d(C10), d(GCGCGTGCGC) X d(GCGCACGCGC), d(GCGCGAGCGC) X d(GCGCTCGCGC), d(GGGGGAGGGG) X d(CCCCTCCCCC), and d(GGGGGTGGGG) X d(CCCCACCCCC), in their minor grooves . The complexes are characterized by both a network of hydrogen bonds between the drug and the polynucleotide and good packing interactions . The DNA double helix in these complexes shows very minimal distortion, and interactions of the drug with the decanucleotides seem to be not very sensitive to the sequence variation around the site of complex formation . The conformational features in the complexes obtained are generally consistent with the experimentally derived conclusions by recent NMR and 2-D NOE studies.

Cancer Res, 1986 Dec, 46(12 Pt 1), 6322 - 6
Relationship between expression of tumor-specific transplantation antigens and neoplastic transformation in an ultraviolet radiation-induced murine skin cancer; Ananthaswamy HN; Ultraviolet radiation-induced murine skin cancers often express highly immunogenic tumor-specific transplantation antigens (TSTA) . The relationship between expression of TSTA and neoplastic transformation is not clear . I have used DNA transfection techniques to determine whether expression of TSTA and the transformed phenotype are associated at the genetic level . C3H mouse embryo fibroblast 10T1/2 clone 8 cells were transfected with high-molecular-weight genomic DNA from a highly antigenic ultraviolet radiation-induced 2240 tumor cell line . A cotransfection protocol using pSV2-neo DNA, which confers resistance to the antibiotic G418, was used to select cells that had taken up foreign DNA . Morphologically transformed, G418-resistant colonies were isolated and tested for expression of 2240 tumor-specific antigens by means of a cytotoxic T-lymphocyte assay . None of the 12 morphologically transformed colonies tested expressed 2240 tumor-specific antigens on their cell surface as revealed by their inability to be killed by 2240 tumor-specific cytotoxic T-lymphocytes . In addition, the morphologically transformed cells did not inhibit the killing of 51Cr-labeled 2240 cells by 2240 tumor-specific cytotoxic T-lymphocytes in a cold-target inhibition assay . Cell surface expression of Class I major histocompatibility antigens was not significantly altered in 2240 DNA transformants . These results demonstrate that, in ultraviolet radiation-induced murine skin tumors, there is not coordinate expression of TSTA and the transformed phenotype, even though most ultraviolet radiation-induced skin tumors exhibit both characteristics . This finding suggests that the two phenotypes are controlled by separate genes.

Surg Neurol, 1986 Dec, 26(6), 577 - 80
Persistence of a mycotic aneurysm of the intracavernous carotid artery; Isaacs BA et al.; Mycotic aneurysms of the intracavernous portion of the carotid artery are rare, especially in children . In reported cases, treatment has been by antibiotics alone, or by some form of carotid surgery . In the present case only antibiotic therapy was used . Subsequent angiography showed spontaneous thrombosis of the internal carotid artery, but persistence of the mycotic aneurysm . The implications of these findings are discussed with regard to the management of the condition.

J Urol, 1986 Dec, 136(6), 1318 - 9
Prostatic abscess: computerized tomography scanning as an aid to diagnosis and treatment; Vaccaro JA et al.; In the antibiotic era prostatic abscesses are rare and the clinical picture often can be confusing . In 2 recent cases computerized tomography scanning not only proved the diagnosis easily but it also simplified greatly the definitive surgical procedure.

Arch Otolaryngol Head Neck Surg, 1986 Dec, 112(12), 1274 - 9
Deep-neck space infections . Diagnosis and management; Stiernberg CM; Deep-neck space infections, which affect soft tissues and fascial compartments of the head and neck, can lead to lethal complications . Eight cases treated over a two-year period were reviewed, and the experience was used to formulate management guidelines . Specific clinical variables analyzed included patient presentation, work-up, treatment, complications, and length of hospital stay . Seven of eight cases required surgery for treatment, one of which was complicated by airway obstruction . Treatment of deep-neck space infections requires knowledge of the natural history of the disease and a detailed understanding of anatomy . Management guidelines include hospitalization, culture and sensitivity tests, antibiotic therapy, diagnostic radiographic procedures, and surgical intervention.

Antibiot Med Biotekhnol, 1986 Dec, 31(12), 897 - 9
{Physicochemical properties of octamycin}; Lysenkova LN et al.; Octamycin, an original polyenic antibiotic was developed . The antibiotic is of an amphoteric character . The number and nature of the functional groups were determined by potentiometric titration . It was shown that the antibiotic contained the neutral sugar galactose . The equivalent weight of the antibiotic (990) was measured by potentiometric titration and the content of the sugar in the molecule . With high performance liquid chromatography it was demonstrated that the antibiotic consisted of 2 components at a ratio of 1:2 . The molecular weights of the components were evaluated with mass spectrometry.

Jpn J Antibiot, 1986 Dec, 39(12), 3311 - 28
{Effect of isepamicin (HAPA-B) on reproduction . IV . Peri- and post-natal study in rats (intramuscular administration)}; Kubota H et al.; Peri- and post-natal effect of HAPA-B, a new aminoglycoside antibiotic, was studied in Jcl: Wistar rats . The antibiotic was given intramuscularly to dams at doses of 25, 100 and 200 mg/kg from day 17 of gestation to 21 days after delivery and throughout lactation . Influences of the drug on dams and their offspring were studied . A decrease in food intake and an increase in water intake were observed in the 200 mg/kg treated group . At autopsy of dams after weaning, pale discoloration and hypertrophy of the kidney were observed in 100 and 200 mg/kg groups . All other observations including delivery and nursing performance of dams, postnatal development of offspring, behavior and reproduction performance of the offspring were normal . The no effect dose level of HAPA-B found in this study was 25 mg/kg on rat dams and 100 mg/kg on the offspring.

Jpn J Antibiot, 1986 Dec, 39(12), 3291 - 310
{Effect of isepamicin (HAPA-B) on reproduction . II . Teratological study in rats (intramuscular administration)}; Sasaki M et al.; Teratological study of isepamicin (HAPA-B), a new aminoglycoside antibiotic, was performed in Jcl: Wistar rat . The drug was given intramuscularly to dams at doses of 25, 100 and 200 mg/kg from day 7 to 17 after mating . The influence on dams, their fetuses and offspring was studied . A decrease in food intake and a development of pale color of the kidney of dams at a dose level of 200 mg/kg were observed in the prenatal study . The HAPA-B did not show any influence on prenatal development of fetuses . In the postnatal study, no effect of HAPA-B on parturition and lactation of dams was seen except that a discoloration of the kidney was observed at autopsy . However, some differences were observed between the control and treatment groups in postnatal development, behavior and reproduction performance of offspring . Dose-response effects of HAPA-B on offspring were not observed in the postnatal study . No effect dose levels of HAPA-B established in this study on rat fetuses and offspring were 200 mg/kg and 100 mg/kg on pregnant rat, respectively.

Jpn J Antibiot, 1986 Dec, 39(12), 3283 - 90
{Effect of isepamicin (HAPA-B) on reproduction . I . Fertility study in rats (intramuscular administration)}; Sasaki M et al.; Effect of isepamicin (HAPA-B), a new aminoglycoside antibiotic, on fertility and reproductive performance in Wistar rats was studied . The drug was injected intramuscularly to rats at a daily dose of 25, 100 or 200 mg/kg . Male rats were treated for 63 days before mating and during the mating period, and female rats were treated for 2 weeks and through the mating period to the 7th day after mating . In male rats, an inhibition of body weight gain and a development of a pale color and hypertrophy of the kidney were observed in 100 and 200 mg/kg dose-groups . In female rats, inhibition of body weight gain was observed in 100 and 200 mg/kg dose-groups and a pale color of the kidney was seen in the 200 mg/kg group . No significant differences were observed in mating and fertility performance of male and female rats between the control and treated groups . Numbers of corpora lutea, implantation sites and living fetuses in the 200 mg/kg group decreased significantly . No external, visceral and skeletal anomalies due to the treatment of HAPA-B were observed in the live fetuses . No effect dose levels of HAPA-B found in this study were 25 mg/kg on parent rats and 100 mg/kg on reproduction ability and their fetuses.

Orthopedics, 1986 Dec, 9(12), 1657 - 60
Comparison of ceforanide and cephalothin prophylaxis in patients undergoing total joint arthroplasty; Soave R et al.; One hundred one patients undergoing total hip and knee arthroplasty were randomly assigned to receive either two 1 gm doses of ceforanide or five doses of cephalothin perioperatively . Simultaneous plasma and cancellous bone specimens were obtained intraoperatively and assayed for antibiotic concentration . Ceforanide plasma and bone levels remained sustained over six hours . Cephalothin plasma and bone levels obtained three to four hours post administration were 91% lower than levels obtained one hour post-dose . Patients were examined for infection for up to 18 months following surgery . None of the patients developed an infected implant . The sustained plasma and bone levels achieved with ceforanide obviate the need for intraoperative dosing necessary with other agents.

Int J Clin Pharmacol Ther Toxicol, 1986 Dec, 24(12), 677 - 9
Use of ceftazidime in the treatment of osteomyelitis and osteoarthritis; De Bastiani G et al.; The authors report the results obtained with the use of ceftazidime, administered by various methods, in 18 cases of orthopedic infections (osteomyelitis, arthritis) . The results, which are regarded as good, are stable over time . The antibiotic therapy proves particularly efficacious in those cases subjected to appropriate surgical treatment.

J Chir (Paris), 1986 Dec, 123(12), 709 - 12
{Value of short prophylactic antibiotherapy in thoracic and vascular surgery . Comparative randomized double-blind study of 3 and 8 injections of cefamandole}; Kitzis M et al.; The subject of whether an optimal duration of prophylactic antibiotic therapy exists was evaluated by comparing results of short and medium-term treatment in aseptic surgery during a double-blind, randomized, prospective trial in 507 patients undergoing vascular or thoracic operations . Patients were randomly allocated to receive either 3 injections of cefamandole: at induction of anesthesia and after 4 and 10 hours (251 cases) or 8 injections of the same antibiotic: at induction of anesthesia, after 4 hours and then every 6 hours up to 40 hours (256 cases) . Evaluation on discharge showed that among the 251 patients receiving 3 injections, 21 (8.33%) were infected while in the group treated with 8 injections (256 cases) 25 (9.8%) were infected . The X2 was 0.25 and there is a lack of statistically significant difference between treatments . Duration of prophylactic antibiotic therapy can be shortened, without loss of efficacy in thoracic or vascular aseptic surgery, to reduce selection of resistant germs and to lower costs.

J Bacteriol, 1986 Dec, 168(3), 1484 - 6
Inhibition of biosynthesis of Saccharomyces cerevisiae sugar transport system by tunicamycin; Lagunas R et al.; Tunicamycin apparently inhibited the biosynthesis of glucose, galactose, and maltose transport systems in Saccharomyces cerevisiae . Under the conditions used, the antibiotic also blocked the biosynthesis of invertase, a well-known yeast glycoprotein, as well as the glycosylation of a marker mannoprotein of the yeast cell wall . However, the antibiotic did not affect certain proteins which did not contain carbohydrate . It seems, therefore, that these sugar carriers are glycoproteins.

J Bacteriol, 1986 Dec, 168(3), 1384 - 91
Cloning and mapping of the genetic determinants for microcin C7 production and immunity; Novoa MA et al.; Microcin C7, a peptide antibiotic inhibitor of protein synthesis, is produced by Escherichia coli K-12 strains that carry the 43-kilobase low-copy-number plasmid pMccC7 . Microcin C7 production and immunity determinants of this plasmid have been cloned into the vectors pBR322 and pACYC184 . The resulting plasmids overproduce microcin C7 and express immunity against the microcin . Mcc- and Mcc- Imm- mutants have been isolated on recombinant plasmids by inserting transposable elements . Physical and phenotypic characterization of these mutants shows that a DNA region of 5 kilobases is required to produce microcin C7, and that two small regions located inside the producing region are also required to express immunity . Analysis of plasmids carrying mcc-lacZ gene fusions indicates that all microcin DNA is transcribed in the same direction . The results suggest that a structure like a polycistronic operon is responsible for microcin C7 production and immunity.

Chest, 1986 Dec, 90(6), 852 - 6
The prognostic value of loculations in parapneumonic pleural effusions; Himelman RB et al.; Forty-eight patients with pleural effusions who had sonographically directed thoracocentesis were evaluated retrospectively for radiologic findings, pleural fluid chemistries, and outcome . Loculation was found to be a radiologic marker of diagnostic and prognostic significance . The presence of loculations correlated with exudative pleural fluid chemistries, but no radiologic finding was specific for empyema . "Extreme" pleural fluid chemistries were associated with loculation, but not with empyema . Patients with loculated effusions had larger effusions, longer hospitalizations, and more frequent tube thoracostomy procedures than patients with nonloculated effusions . Light's criteria for tube thoracostomy were found to be unreliable in patients with loculated parapneumonic effusions or in patients treated with prolonged antibiotic therapy prior to thoracocentesis.

Blood, 1986 Dec, 68(6), 1348 - 54
Stromal cells in myeloid and lymphoid long-term bone marrow cultures can support multiple hemopoietic lineages and modulate their production of hemopoietic growth factors; Johnson A et al.; Hemopoiesis in long-term bone marrow cultures (LTBMC) is dependent on adherent stromal cells that form an in vitro hemopoietic microenvironment . Myeloid bone marrow cultures (MBMC) are optimal for myelopoiesis, while lymphoid bone marrow cultures (LBMC) only support B lymphopoiesis . The experiments reported here have made a comparative analysis of the two cultures to determine whether the stromal cells that establish in vitro are restricted to the support of myelopoiesis or lymphopoiesis, respectively, and to examine how the different culture conditions affect stromal cell physiology . In order to facilitate this analysis, purified populations of MBMC and LBMC stroma were prepared by treating the LTBMC with the antibiotic mycophenolic acid; this results in the elimination of hemopoietic cells while retaining purified populations of functional stroma . Stromal cell cultures prepared and maintained under MBMC conditions secreted myeloid growth factors that stimulated the growth of granulocyte-macrophage colonies, while no such activity was detected from purified LBMC stromal cultures . However, this was not due to the inability of LBMC stroma to mediate this function . Transfer of LBMC stromal cultures to MBMC conditions resulted in an induction of myeloid growth factor secretion . When seeded under these conditions with stromal cell-depleted populations of hemopoietic cells, obtained by passing marrow through nylon wool columns, the LBMC stromal cells could support long-term myelopoiesis . Conversely, transfer of MBMC stroma to LBMC conditions resulted in a cessation of myeloid growth factor secretion; on seeding these cultures with nylon wool-passed marrow, B lymphopoiesis, but not myelopoiesis, initiated . These findings indicate that the stroma in the different LTBMC are not restricted in their hemopoietic support capacity but are sensitive to culture conditions in a manner that may affect the type of microenvironment formed.

Cancer Treat Rep, 1986 Dec, 70(12), 1439 - 40
Idarubicin in advanced breast cancer: a phase II study; Lionetto R et al.; Twenty-nine patients with metastatic breast cancer were treated orally with idarubicin (15 mg/m2 X 3 days every 3-4 weeks) . Objective response was seen in 31% of all patients . Toxicity was acceptable . There should be further clinical trials of new anthracycline antibiotic.

J Gen Microbiol, 1986 Dec, 132 ( Pt 12), 3253 - 9
Microcin-E492-insensitive mutants of Escherichia coli K12; Pugsley AP et al.; Mutations in three Escherichia coli K12 genes, tonB, exbB and the newly discovered semA, reduce sensitivity to the low Mr polypeptide antibiotic microcin E492 . The products of the tonB and exbB genes were previously shown to be involved in the uptake of siderophore-complexed iron and in the action of a number of colicins . Strains mutated at or close to semA (collectively referred to as sem mutations) remained fully sensitive to these colicins, and grew as well as wild-type strains under conditions of iron starvation . Expression of a number of sem-lacZ operon fusions was not affected by iron limitation, and sem mutations did not affect the production of iron-regulated outer membrane proteins which are known or thought to be involved in iron uptake . Hfr conjugation and P1 phage transduction experiments indicated that semA is located close to pabB at 40 min on the E . coli K12 chromosome . This places semA close to the mng locus, wherein mutations result in decreased manganese sensitivity . However, strains carrying the semA mutation exhibited increased manganese sensitivity.

J Virol, 1986 Dec, 60(3), 868 - 73
Rat embryo fibroblast cells expressing human papillomavirus 1a genes exhibit altered growth properties and tumorigenicity; Green M et al.; Human papillomavirus 1a (HPV1a) induces benign tumors (papillomas or warts) in humans under natural conditions of infection but has not been found to replicate significantly in cell culture or in experimental animals . To establish model systems to study the oncogenic properties and expression of HPV genes, we established cell lines by cotransfecting the 3Y1 rat fibroblast cell line with HPV1a DNA constructs containing an intact early gene region and the Tn5 neomycin resistance gene . Most cell lines selected for expression of the neomycin resistance gene by treatment with the antibiotic G-418 contained viral DNA in a high-molecular-weight form . The growth characteristics of several cell lines containing high copy numbers of HPV1a DNA were studied further . They were shown to differ from the parental cell line and from G-418-resistant cell lines that did not incorporate viral DNA in the following properties: morphological alteration, increased cell density at confluence, growth in 0.5% serum, efficient anchorage-independent growth in soft agar, and rapid formation of tumors in nude mice . Those cell lines that possessed altered growth properties and tumorigenicity were found to express abundant quantities of polyadenylated virus-specific RNA species in the cytoplasm.

Spine, 1986 Dec, 11(10), 1013 - 9
Lumbar spine osteolysis: an entity caused by spinal instability; Bradford DS et al.; Presented is a new entity in the spectrum of complications following spinal decompression . It occurs in patients with spinal instability after decompression . Thereafter, instability accelerates, leading to a rapid clinical and radiologic deterioration . The presenting symptoms are back pain and lower extremity weakness, resembling spinal stenosis . Erythrocyte sedimentation rate and temperature remain normal . Radiologically, a distinct form of progressing osteolysis is present . This entity may present a difficult diagnostic problem and is usually diagnosed erroneously as a destructive osteomyelitis . Craig needle biopsy results are normal . Treatment consists of stabilization rather than antibiotic therapy and debridement . It is apparent that patients with spinal instability are to be considered "at risk" as further decompression may accelerate the instability, resulting in progressive osteolysis.

J Pediatr Surg, 1986 Dec, 21(12), 1195 - 7
Zipper closure of the abdominal wall in the treatment of recurrent intra-abdominal abscesses; Doody DP et al.; Diffuse retroperitoneal soilage following rectal laceration with a blunt object resulted in significant morbidity despite prompt recognition, parenteral antibiotic administration, and early surgical intervention . A septic postoperative course was complicated by perforation of the third portion of the duodenum and a diffuse suppurative peritonitis with multiple intra-abdominal abscesses . Closure of the incision at reexploration was facilitated by sewing Marlex to the fascia while a centrally located nylon zipper allowed access to the peritoneal cavity for further explorations and eventual ablation of the septic process.

Acta Trop, 1986 Dec, 43(4), 307 - 17
Freeze-fracture studies on the surface membranes of pleomorphic bloodstream and in vitro transformed procyclic Trypanosoma brucei; Tetley L; The surface membranes of bloodstream long slender, short stumpy and culture procyclic stages of Trypanosoma brucei brucei were compared with respect to freeze-fracture electron microscopy, intramembrane particle (IMP) distribution and beta-hydroxysterol content as shown by the characteristic intramembrane lesions induced by the polyene antibiotic, filipin . Little difference was observed between IMP density of long slender and short stumpy form body membranes: IMP's were more abundant on the protoplasmic face (PF) than on the exoplasmic face (EF) . The procyclic culture form body membrane showed an increased density of PF IMPs and a decreased density of EF IMPs over their bloodstream short stumpy form predecessors . Flagellar membrane fracture faces displayed higher IMP densities than body membrane fracture faces of the same trypanosome . The numbers of filipin-induced lesions (FIL) indicated an increased level of beta-hydroxysterols in the short stumpy forms relative to the level in the long slender bloodforms . FIL density was further increased in the body membrane of the procyclic culture form . FIL density was higher in the flagellar membrane than in the corresponding body membrane and FIL were excluded from flagellum to body attachment zones of the flagellar membrane of all stages . The polarity of the FIL in the surface membranes was reversed on transforming from bloodstream to culture procyclic stages . These observations indicate qualitative differences between the surface membranes of the three stages, independent of the presence or absence of the surface coat.

Obstet Gynecol, 1986 Dec, 68(6), 842 - 6
Neutropenia and fever in patients undergoing combination chemotherapy for malignant germ cell tumors of the ovary; Chambers SK et al.; Fifteen neutropenic febrile episodes occurred in 29 patients undergoing chemotherapy for malignant germ cell tumors of the ovary . Vincristine, actinomycin-D, and cyclophosphamide were used in 24 patients; cis-diamminedichloroplatinum, vinblastine, and bleomycin in three; and both regimens in two . All 15 patients were treated with antibiotic combinations (gentamicin and clindamycin in 12 cases), usually until neutropenia resolved . The mean nadir total granulocyte count was 123/mm3 . There was no septicemia or drug-related deaths . With reduction in chemotherapy dosage, 87% of patients tolerated subsequent courses . The survival rates in this disease are excellent, although toxicity is substantial from both regimens . These neutropenic febrile episodes can be managed successfully without interrupting chemotherapy.

Vet Rec, 1986 Nov 29, 119(22), 551 - 3
An assessment of the economic benefits of a mastitis control scheme; Blowey RW; Over a six-year period from 1979 to 1985 the incidence of mastitis among dairy herds being recorded in a veterinary practice in Gloucestershire decreased from 26.5 per cent to 19.6 per cent of cows affected each year and from 51.0 to 31.7 cases per 100 cows per year . Over the same period the rolling mean herd milk cell count fell from 346,000/ml to 243,000/ml and the usage of intramammary antibiotic tubes fell from 2.6 to 2.1 per lactating cow per year . The proportion of cases needing repeat treatments in a 12-month period also fell from 25 per cent to 10.6 per cent . Possible causes for the decrease in the incidence of mastitis are given . The cost of an average case of mastitis was estimated to be 40 pounds, and on this basis the farms involved reduced their losses from mastitis by 772 pounds per 100 cows per year, a more than 12-fold return on their investment in veterinary services.

Biochemistry, 1986 Nov 18, 25(23), 7408 - 16
Molecular recognition between oligopeptides and nucleic acids: novel imidazole-containing oligopeptides related to netropsin that exhibit altered DNA sequence specificity; Lown JW et al.; Oligopeptides have been synthesized that are structurally related to the antiviral antitumor antibiotic netropsin, but in which each of the pyrrole units is successively replaced by an imidazole moiety, as well as their di- and triimidazole-containing counterparts . These compounds bind to duplex DNA with constants in the range (1.06-1.98) X 10(6) M-1 but not to single-stranded DNA . Since they bind to T4 DNA, it is inferred that, like the parent antibiotic netropsin, they are also minor groove selective . This series of compounds exhibits a progressively decreasing preference for AT sites in binding studies with both native DNAs and synthetic oligonucleotides and a corresponding increasing acceptance of GC base pairs . Footprinting experiments utilizing a 139 base pair HindIII/NciI restriction fragment from pBR 322 DNA revealed that these lexitropsins, or information-reading oligopeptides, recognize more sites than the parent netropsin . In addition, some regions of enhanced nuclease action as the result of drug binding to the fragment were identified . The diimidazole compound in particular recognizes GC-rich sites, implying the formation of new hydrogen bonds between G-C(2)NH2 in the minor groove and the additional N3 imidazole nitrogens . It is clear however that, since the lexitropsins appear to tolerate the original (AT)4 site, an N-methylimidazole group on the ligand will permit either a GC or AT base pair in the binding sequence . Another factor that may be significant in molecular recognition is the high negative electrostatic potential of A X T regions of the minor groove, which is likely to strongly influence binding of these cationic species to DNA.(ABSTRACT TRUNCATED AT 250 WORDS)

Biochemistry, 1986 Nov 18, 25(23), 7401 - 8
Nuclease activity of 1,10-phenanthroline-copper ion: reaction with CGCGAATTCGCG and its complexes with netropsin and EcoRI; Kuwabara M et al.; The self-complementing dodecamer 5'-CGCGAATTCGCG-3' and its complexes with the antibiotic netropsin and the restriction endonuclease EcoRI provide substrates of known three-dimensional structure to study the stereochemistry and mechanism of the artificial nuclease of 1,10-phenanthroline-copper ion {(OP)2Cu+} . Analysis of the reaction products with the 5'-32P dodecamer on 20% sequencing gels has demonstrated the presence of 3'-phosphoglycolate ends in addition to 3'-phosphomonoester ends expected from previous studies . A reaction intermediate, which is a precursor to 3'-phosphomonoester termini, has been trapped; in contrast, no comparable species for the 5'-phosphomonoester termini can be detected when 3'-labeled DNAs are utilized as substrates . The reactive oxidative species formed by the coreactants (OP)2Cu+ and hydrogen peroxide is distinguishable in its chemistry from the hydroxyl radicals produced by cobalt-60 gamma-irradiation . The freely diffusible hydroxyl radicals generated by cobalt-60 irradiation produce equivalent amounts of 3'-phosphomonoester and 3'-phosphoglycolate termini whereas the 3'-phosphomonoesters are the preferred product of (OP)2Cu+ and H2O2 . On the basis of the structures of the products obtained, the principal site of attack of the coordination complex is on the C-1 of the deoxyribose within the minor groove . This conclusion is supported by the footprinting of netropsin binding to the dodecamer . Crystallographic results have demonstrated that netropsin binds to the minor groove at the central AATT residue . A clear protection of attack by the coordination complex at the deoxyriboses associated with A-5, T-6, T-7, and C-9 is fully consistent with attack from the minor groove without intercalation during the course of the cleavage reaction.(ABSTRACT TRUNCATED AT 250 WORDS)

Postgrad Med, 1986 Nov 15, 80(7), 74 - 84
Surgical infections--the general surgeon's perspective . Defining the problem, seeking solutions; Luke WP; Infection has been historically the greatest threat to patients undergoing surgery, but with effective surveillance programs, the risk of surgical infection can be markedly reduced . An effective approach to infection control involves attention to the triad complex of infection--asepsis (keeping bacteria below the "critical inoculum"), antisepsis (disciplined use of antibiotics), and host defense mechanisms (altering factors that reduce immunity) . Several large studies indicate a national trend toward decreased wound infection rates . This trend is probably attributable to a wide acceptance of surveillance programs, shorter length of hospitalization, and better use of antibiotic therapy.

Anal Biochem, 1986 Nov 15, 159(1), 210 - 6
The preparation of tritiated tunicamycin; Hunnicutt RE et al.; A relatively simple and inexpensive procedure was devised for the radiolabeling of the glycoprotein biosynthesis inhibitor, tunicamycin . The procedure is based on hydrogen exchange in alkaline solutions of tritiated water . It was noted that the antibiotic was much more alkali labile than model compounds such as uridine . The alkali stability of the inhibitor was studied to determine conditions for optimum labeling and yield . The effects of alkaline incubation on the inhibitory properties of the antibiotic were also investigated and it was found that the breakdown products are not effective inhibitors of the reaction that transfers N-acetylglucosamine-1-phosphate to dolichyl phosphate . The isolated radioactive tunicamycin homologs, however, retained all their inhibitory action . Incubation of tunicamycin in the presence of deuterated water and mass spectral analysis showed that under the conditions used for the tritiation of tunicamycin the major product exchanged six hydrogen atoms . The position of the tritium atoms in labeled tunicamycin was not determined . The radioactive label in these compounds was shown to be stable under physiological conditions and should be useful for investigations involving the action of these antibiotics.

Mech Ageing Dev, 1986 Nov 14, 36(3), 259 - 67
Autofluorescence and ageing: changes in ribosome accuracy and lysosome {corrected} function; Buchanan JH et al.; Autofluorescence increased with decreasing proliferative capacity of fibroblast cultures . It also increased rapidly when cultures were treated with the aminoglycosides, streptomycin, paromomycin and G418, as well as with ammonium chloride . All these compounds are known to accumulate in lysosomes . Paromomycin is known to reduce proliferative capacity and G418 was found to have a similar effect . As these aminoglycosides accumulate in the lysosomes, promote errors in protein synthesis and reduce proliferative capacity this has led us to suggest that such compounds may cause a loss of homeostasis between erroneous protein synthesis and lysosome function . The increase in autofluorescence may be a consequence of reduced lysosome function arising from lack of control of the intralysosomal pH.

Antibiot Med Biotekhnol, 1986 Nov, 31(11), 871 - 4
{Pharmacokinetics of cefazolin during hemosorption and hemodialysis}; Firsov AA et al.; The influence of hemosorption and hemodialysis on the pharmacokinetics of cefazolin was studied in 20 patients with chronic and acute renal insufficiency . The integral mean value of the antibiotic extraction coefficient in hemosorption was approximately 2 times higher than that in hemodialysis . In the first case the value of this parameter systematically lowered with time (the constant of the process rate amounted to 0.89 h-1), while in the second case it was constant.

Antibiot Med Biotekhnol, 1986 Nov, 31(11), 866 - 70
{Antitumor activity of doxorubicin in respect to solid tumors in mice}; Ul'ianova LA et al.; Antitumor activity of doxorubicin, an antibiotic prepared in the USSR was studied with respect to 4 solid tumors of mice: lymphosarcoma LIO-1, sarcoma 180, pregastric cancer OZh5 and melanoma B-16 . Doxorubicin showed high antitumor activity against lymphosarcoma and sarcoma 180 . However, it was somewhat lower than that of rubomycin and carminomycin . By selective antitumor activity against mouse pregastric cancer doxorubicin was superior to rubomycin and carminomycin . Estimation of antitumor activity of doxorubicin revealed its advantages in inhibition of melanoma B-16 growth, while carminomycin was superior in prolonging the animal life-span.

Ophthalmology, 1986 Nov, 93(11), 1413 - 7
Management of rhegmatogenous retinal detachment with macula detached . Steroids, choroidal detachment, and acuity; Valone J Jr et al.; One hundred thirty-four consecutive eyes with rhegmatogenous retinal detachment involving the macula were evaluated with reference to the effectiveness of systemic steroids in preventing choroidal detachment after scleral buckling surgery and in facilitating both anatomic and functional success . The occurrence of postoperative choroidal detachment was inversely related to the routine intravenous administration of steroids under antibiotic coverage beginning in the recovery room (P = 0.014) . Eyes so treated were free of both clinically significant infection and extrusion . The infrequent but worrisome complication of angle closure sufficient to require choroidal tap did not occur among treated eyes . Routine steroid use may have been associated with increased preservation of acuity at the level of 20/200 or better (P = 0.043).

Handchir Mikrochir Plast Chir, 1986 Nov, 18(6), 336 - 8
{Therapy of enchondroma with a plaster implant--renaissance of a treatment principle}; Geldmacher J; The treatment of tuberculous osteitis, osteomyelitis or bone tumors by filling the cavity with plaster of Paris implants after complete removal of the focus or tumor tissue by curettage is a method, nearly 100 years old, practised successfully again and again but little noted . Finally Richter et al . gave an account of 25 cases of tuberculous osteitis, osteomyelitis and bone tumors treated by this method . We have practised this method since 1984 in the treatment of enchondroma . Careful scraping-out with a sharp curette, milling the sclerosed wall and rinsing the cavity with dehydrated alcohol is followed by immediate reconstruction, filling the cavity with a gamma-ray-sterilized CaSO4-paste mixed with the local antibiotic Nebacetin siccum . As observed by other authors, this implant clearly stimulates osteogenesis . It is not necessary to take spongiosa fragments out of the iliac crest and we need no general anaesthesia . There were no complications and no tumor recurrences thus far.

Farmaco {Sci}, 1986 Nov, 41(11), 881 - 91
New N-amino acid derivatives of daunorubicin; Dzieduszycka M et al.; New N-amino acid derivatives of daunorubicin have been obtained by acylation of daunorubicin amino group with alpha, beta, and gamma amino acids and their N,N-dibenzyl derivatives . The results of the antitumor activity determination have evidenced that the change of the amino function position in the daunorubicin derivatives, in relation to that of the parent antibiotic, causes the loss of activity.

Pediatr Infect Dis, 1986 Nov-Dec, 5(6 Suppl), S236 - 8
Ureaplasma urealyticum in the immunocompromised host; Taylor-Robinson D et al.; The lack of antibody in hypogammaglobulinemic patients probably results in failure of mycoplasmas to be "neutralized" and accounts for the diminished ability of the patients to cope with these organisms escaping hematogenously from the respiratory and urogenital tracts . Furthermore Ureaplasma urealyticum and other mycoplasmas are ingested by neutrophils in the absence of opsonins, indicated by the fact that they are able to trigger the release of chemiluminescence from these cells; ureaplasmas are not killed during this process and it is possible that carriage occurs within phagocytes to various sites . Several mycoplasmal species have localized in joints and U . urealyticum organisms are no exception . They have been isolated from the purulent synovial fluids of at least three hypogammaglobulinemic patients in Canada, England and the United States, respectively, the arthritides responding to appropriate antibiotic therapy . In one male patient, however, repeated and prolonged episodes of arthritis over several years, associated with antibiotic-resistant ureaplasmas, responded only to the administration of specific hyperimmune serum . Apart from joint involvement subcutaneous abscesses have been seen, and in the latter patient persistent urethritis was caused by ureaplasmas, these being the only organisms recovered from the urethra . Chronic urethrocystitis/cystitis in hypogammaglobulinemic patients has been associated also with ureaplasmal infection . In addition polyarthritis with recovery of both ureaplasmas and Mycoplasma hominis from the joints has been seen in a kidney allograft patient on an immunosuppressive regimen . However, further evidence that ureaplasmas cause a problem in immunosuppressed patients or in those with the acquired immunodeficiency syndrome is lacking.

J Infect, 1986 Nov, 13(3), 293 - 6
The rise and fall of Legionnaires' disease in Nottingham; Woodhead MA et al.; The annual number of confirmed cases of Legionnaires' disease in both Nottingham, and England and Wales, reached a peak in 1980 and has since declined . Legionella infection is a rare cause of community-acquired pneumonia managed at home (accounting for less than 1% of cases), more common in those admitted to hospital (5-15%) and more common still in patients with severe pneumonia as seen on an intensive care unit (up to 30% of cases) . Antibiotic therapy for any patient with moderate or severe pneumonia of uncertain aetiology should cover legionella infection.

Chem Biol Interact, 1986 Nov, 60(2), 201 - 6
Inhibition of microtubule assembly by actinomycin D, an anti-tumour drug; Rajagopalan R et al.; Effect of actinomycin D, an antibiotic, was investigated on the biological function of tubulin from bovine brain . The microtubule assembly was inhibited nearly completely when an equal molar ratio of actinomycin D and tubulin was used . The depolymerisation of the same, however, was not altered under the same conditions . The competence of tubulin to bind colchicine and GTP was also not affected . Chromatographic and the spectrophotometric studies showed that 0.94 mol of actinomycin D binds per mole of tubulin.

Am J Kidney Dis, 1986 Nov, 8(5), 304 - 7
Renal cortical uptake kinetics of gentamicin in rats with impaired renal function; Verpooten GA et al.; The renal cortical uptake kinetics of the aminoglycoside antibiotic gentamicin was determined in the remnant kidney model . Renal failure was induced by partial ablation of the right kidney followed by left nephrectomy in female Wistar rats . The animals received a six-hour gentamicin infusion at a constant rate yielding steady-state serum concentrations ranging from 0.5 to 150 micrograms/mL . The renal cortical gentamicin concentrations were determined and related to the serum concentrations achieved . This relationship was nonlinear and followed Michaelis-Menten kinetics . Gentamicin cortical uptake rate, however, did not show clear saturation in the range of gentamicin serum levels studied as was observed in rats with normal renal function . The Michaelis-Menten parameters determined by nonlinear regression were Km = 15.0, 73.9, and 135.7 micrograms/mL; and Vmax = 149.9, 213.7, and 239.2 micrograms/g cortex/h, respectively, for controls, rats with serum creatinine levels between 0.9 and 1.2 mg/dL, and those with levels between 1.3 and 1.8 mg/dL . It is concluded that at serum levels below 100 micrograms/mL, the gentamicin renal cortical uptake is diminished in rats with renal failure . This decrease in renal cortical uptake is more pronounced in the group of rats with more severe renal failure.

Toxicol Appl Pharmacol, 1986 Nov, 86(2), 271 - 85
Impairment of lysosome-pinocytic vesicle fusion in rat kidney proximal tubules after treatment with gentamicin at low doses; Giurgea-Marion L et al.; Gentamicin, an aminoglycoside antibiotic, is known to accumulate within the kidney cortex and to elicit nephrotoxic reactions due to the necrosis of proximal tubules . Female Sprague-Dawley rats, treated for 9 days with gentamicin at a low dose (10 mg/kg ip, once a day), were used to determine the fate of the antibiotic within the proximal tubular cells and its effects on the functional properties of the lysosomes . The analysis of the lysosomes by isopyknic equilibration in sucrose gradient (density 1.10-1.24 g/ml) revealed that gentamicin remains associated with these organelles (marker enzymes sulfatase B and cathepsin B) throughout the treatment duration . Gentamicin treatment markedly decreased the buoyant density of the lysosomes . As was shown by electron microscopic examination of the subcellular fractions collected from the sucrose gradient, the shift of the lysosomes toward lower densities was a result of overloading with undegraded phospholipids (myelin-like figures) . The effect of gentamicin on the functional properties of the lysosomes was examined by using horseradish peroxidase (HRP) as a marker of endocytic activity and of the processing by tubular cells of exogenous proteins . Treatment with gentamicin did not significantly modify the intracortical accumulation of HRP, which was estimated to be 2.2% of the amount injected . HRP was shown by isopyknic equilibration to be mostly associated with the lysosomes . This was confirmed by electron microscopic examination of proximal tubular cells after cytochemical demonstration of HRP with diaminobenzidine and H2O2 . In rats not exposed to gentamicin, more than half of the lysosomes contained HRP activity . In animals treated with gentamicin, one-third of the lysosomes that retained a normal appearance exhibited HRP activity . In contrast, lysosomes overloaded with phospholipids (identified by the presence of myelin-like figures) were very seldom labeled with HRP activity . Taken altogether, the present observations suggest that the alterations induced by gentamicin treatment impair their ability to fuse with incoming endocytic vesicles.

Radiat Res, 1986 Nov, 108(2), 146 - 57
Transfection of a human gene for the repair of X-ray- and EMS-induced DNA damage; Spiro IJ et al.; EM9 cells are a line of Chinese hamster ovary cells that are sensitive to killing by ethylmethanesulfonate (EMS) and X ray, since they are unable to repair the DNA damage inflicted by these agents . Through DNA-mediated gene transfer, human DNA and a selectable marker gene, pSV2neo, were transfected into EM9 cells . Resistant clones of transfected cells were selected for by growth in EMS and G418 (an antibiotic lethal to mammalian cells not containing the transfected neo gene) . One primary clone (APEX1) and one secondary clone (TEMS2) were shown to contain both marker and human DNA sequences by Southern blot . In cell survival studies, APEX1 was shown to be as resistant to EMS and X ray as the parental cell type AA8 (CHO cells) . TEMS2 cells were found to be partially resistant to EMS and X ray, displaying an intermediate phenotype more sensitive than AA8 cells but more resistant than EM9 cells . Alkaline elution was used to assess the DNA strand-break rejoining ability of these cells at 23 degrees C . APEX1 cells showed DNA repair capacity equal to that of AA8 cells; 75% of the strand breaks were repaired with a rejoining T 1/2 of 3 min . TEMS2 showed similar levels of repair but a T 1/2 for repair of 9 min . EM9 cells repaired only 25% of the breaks and showed a T 1/2 for repair of 16 min . The DNA repair data are consistent with the survival data in that the more resistant cell lines showed a greater capacity for DNA repair . The data support the conclusion that APEX1 and TEMS2 cells contain a human DNA repair gene.

Am J Surg, 1986 Nov, 152(5), 513 - 6
Single dose prophylaxis in elective cholecystectomy . A prospective, double-blind randomized study; Kaufman Z et al.; We tested the effectiveness of a single dose of prophylactic antibiotic (gentamicin) in elective cholecystectomy in a double-blind, controlled randomized study . All patients recognized preoperatively as being at risk were excluded . The treatment group comprised of 102 patients received a single dose of gentamicin and the 74 patients in the control group received a placebo . Of the patients who received gentamicin, wound infection developed in 4.9 percent versus 13.5 percent in the control group . Among 45 patients who had positive bile cultures, the wound infection rate for those in the treatment group was 14 percent versus 44 percent for those in the control group . Of 17 patients who underwent unexpected exploration of the choledochus, none of those in the treatment group had development of wound infection . The rate of wound infection in the control group was 50 percent . As 30 percent of the patients undergoing elective cholecystectomy were found to have risk factors for the development of wound infection which could not be identified preoperatively, we recommend single dose prophylaxis for all patients undergoing cholecystectomy.

Am J Surg, 1986 Nov, 152(5), 510 - 2
Managing the granulocytopenic patient with acute perianal inflammatory disease; Shaked AA et al.; Acute perianal inflammation concomitant with a decrease in the number of circulating granulocytes developed in 15 patients with various hematologic disorders . The treatment included antibiotic coverage alone (11 patients) or combined with surgical drainage of the inflamed area (7 patients) . Our study shows that surgical drainage during agranulocytosis resulted in slow healing of the wound, prolonged hospitalization, and a higher mortality rate, when compared with the group that received antibiotics alone (28 percent versus 18 percent) . The preferred treatment for these patients is the administration of broad spectrum antibiotics without attempting drainage of the infected area.

J Pediatr, 1986 Nov, 109(5), 753 - 8
Childhood Lyme arthritis: experience in an endemic area; Eichenfield AH et al.; We report 25 children with oligoarticular arthritis associated with Lyme disease . There were 16 boys (male/female ratio 1.8:1); ages ranged from 2 to 15 years . Thirteen (52%) children had no history of erythema chronicum migrans or other rash . Thirteen had temperatures as high as 41 degrees C for up to 2 months before the onset of arthritis . Twelve recalled definite tick bites . Ten (40%) children, of whom seven had no history of rash, were hospitalized for presumed septic arthritis . Another four had diagnoses of pauciarticular juvenile rheumatoid arthritis for as long as 3 years . Seven patients had less acute, recurrent episodes of synovitis . Two children had seventh nerve palsies 2 months before onset of arthritis . All patients had antibodies to the Lyme spirochete . In 14 patients, synovial fluid white blood cell counts ranged from 180 to 97,700/mm3 (greater than or equal to 76% polymorphonuclear leukocytes) . Antibiotic therapy was effective in all patients; in 13, orally administered therapy alone resulted in elimination of synovitis and recurrent attacks . Lyme arthritis may be confused with acute bacterial septic arthritis or recurrent "pauciarticular juvenile rheumatoid arthritis," particularly when there is no history of erythema chronicum migrans.

Geriatrics, 1986 Nov, 41(11), 67 - 9, 74-7, 80
Management of common infections in the elderly outpatient; Nagami P; Bacteriuria is not thought to cause progressive renal damage in the asymptomatic adult . Therefore, in the elderly patient with relapsing asymptomatic bacteriuria, further antibiotic therapy may be withheld, and the patient instructed to return in the event of symptomatic exacerbations . Postherpetic neuralgia is particularly frequent and severe in the elderly, occurring in 25 to 40% of patients over age 60 with herpes zoster . When the patient is seen within the first week, a 3-week regimen of oral corticosteroid therapy may shorten the duration of neuralgia.

Clin Orthop, 1986 Nov, (212), 182 - 91
Infection following intramedullary nailing of long bones . Diagnosis and management; Patzakis MJ et al.; In 30 patients (23 femurs and 7 tibias) with infection of long bone fractures following intramedullary (IM) nailing, the follow-up study ranged from eight to 84 months (mean, 20 months) . Six patients retained active infection at the time of follow-up examination . Ununited fractures were present in four and sequestra in two patients . Stabilization for fracture healing after irrigation and debridement with appropriate systemic antibiotic therapy was the critical factor in the orthopedic management of this series of patients.

Cancer Res, 1986 Nov, 46(11), 5518 - 23
Reduced toxicity and enhanced antitumor effects in mice of the ionophoric drug valinomycin when incorporated in liposomes; Daoud SS et al.; Valinomycin (NSC 122023) is a cyclic depsipeptide antibiotic with potassium selective ionophoric activity . This drug has been reported to display antitumor effects but its utilization has been limited by its extreme toxicity . Here we report that the incorporation of valinomycin into multilamellar liposomes composed of dimyristoyl phosphatidyl choline:cholesterol:phosphatidyl serine (10:4:1 M ratio) results in a profound reduction in toxicity with maintainence of antitumor efficacy . Thus the median lethal dose (LD50) for i.p . administered valinomycin (VM) in C57BL/6 X DBA/2 mice is 1.7 mg/kg whereas the LD50 for liposome incorporated valinomycin (MVL-VM) is in excess of 50 mg/kg . In like manner, the LD50 for i.v . administered VM is 0.18 mg/kg where the LD50 for MLV-VM preparations passed through a 0.6-micron filter is greater than 10 mg/kg . The antitumor efficacies of i.p . administered VM or MLV-VM against i.p . P388 mouse leukemia were similar in multiple dose formats using doses below the maximal tolerated dose for VM . However, since MLV-VM was substantially less toxic than VM, the liposomal drug also produced significant (170% median survival time of treated mice/median survival time of untreated control) antitumor effects when administered as a single dose at levels above the maximal tolerated dose for free VM; single doses of free VM at the maximal tolerated dose were ineffective in this context . In experiments with i.v . inoculated P388 leukemia, MLV-VM but not free VM, displayed antitumor activity (144% median survival time of treated mice/median survival time of untreated control) when administered i.v . at equitoxic doses . Thus the use of a lipid vesicle drug carrier system permits a reduction in the toxicity of valinomycin with maintainence or enhancement of antitumor activity against i.p . or i.v . P388 leukemia.

J Nat Prod, 1986 Nov-Dec, 49(6), 988 - 94
Molecular genetics of Red biosynthesis in Streptomyces; Feitelson JS et al.; We have studied the molecular biology of undecylprodigiosin (Red) biosynthesis by Streptomyces coelicolor as a model system for understanding the genetic regulation of antibiotic biosynthesis . A collection of new red mutants was obtained using a directed screen . Regions of DNA involved in the transcriptional regulation of red gene expression were also isolated.

Mikrobiologiia, 1986 Nov-Dec, 55(6), 905 - 9
{Relation between the transport of glutamic acid and Escherichia coli resistance to tetracyclines}; Plakunov VK et al.; The rate of glutamate uptake was shown to decrease while the rate of glutamate export from preloaded cells increased after the resistance to tetracyclines had been induced in the cells of plasmid-bearing Escherichia coli strains . Similar results were obtained with membrane vesicles prepared from the cells induced by the antibiotic and from the non-induced cells . These data imply that the transport channel formed after the induction in the membranes of resistant cells can also function as a mechanism which mediates the active export of glutamate from the cells.

Rev Infect Dis, 1986 Nov-Dec, 8(6), 841 - 9
Pathogenesis and treatment of acute hematogenous osteomyelitis: evaluation of current views with reference to an animal model; Emslie KR et al.; Antibiotic therapy and surgical drainage of the bone are the most commonly accepted forms of therapy for acute hematogenous osteomyelitis; the efficacy of these two treatment modalities, however, has not been fully established . Treatment regimens remain empiric and open to much controversy . Many contentious issues concerning the management of this disease have arisen because the natural history of the untreated condition has not been properly understood, because therapeutic regimens alternative to those empirically initiated and perpetuated have not been adequately tested, and because most follow-up studies have dealt with small numbers of patients over relatively short periods . A highly reproducible animal model of acute hematogenous osteomyelitis was developed and utilized in a reexamination of issues regarding the natural history and pathology of the disease and the influence of appropriate treatment.

Pediatr Infect Dis, 1986 Nov-Dec, 5(6 Suppl), S262 - 5
Evaluation of the role of Ureaplasma urealyticum in infertility; Taylor-Robinson D; The involvement of Ureaplasma urealyticum in male infertility has been suggested in 10 studies in which strains were found more often in the semen of infertile than fertile men and/or were associated with poor motility or other abnormalities . In contrast these findings have not been supported by those of an equal number of other studies . Ureaplasmas adhere to sperm and therefore have an opportunity to affect them . The numbers of organisms present in semen samples suggest that such a direct effect is unlikely but the question of whether metabolic byproducts affect sperm and whether ureaplasmas cause structural damage to the male genital tract remains unanswered . Ureaplasmas have been isolated from the genital tracts of women of infertile couples more often than from those of women of fertile couples by some but not all investigators and antibiotic therapy has also provided conflicting results . Two groups of workers have reported improvements in sperm motility and quality and increased conception rates in couples rendered Ureaplasma-negative by tetracycline administration . Such observations are provocative but have to be viewed against the failure of other investigators to note similar improvements in conception rates in studies where some attention was paid to controlling them . It should be noted, however, that the beneficial effect of an antibiotic may not be seen clearly if ureaplasmas are responsible for only a small subset of infertility cases.

Am J Vet Res, 1986 Nov, 47(11), 2468 - 76
Methylprednisolone and gentamicin effects on hepatosplanchnic blood flow and carbohydrate metabolism in endotoxemic Yucatan miniature pigs; Fettman MJ et al.; Conjoint therapy of a glucocorticoid and aminoglycoside antibiotic have been recommended for septic shock . These studies examined the hemodynamic and metabolic effects of methylprednisolone sodium succinate (MPSS) with and without gentamicin sulfate in a nonanesthetized model of nonseptic endotoxemia in Yucatan miniature pigs . Methylprednisolone sodium succinate alone had no effect on endotoxin-induced systemic hypotension . Endotoxemic pigs treated with MPSS in combination with gentamicin sulfate had lower mean arterial pressures than did MPSS-treated and nontreated endotoxemic pigs . Methylprednisolone sodium succinate alone and with gentamicin sulfate improved portal and hepatic venous blood flows moderately . Net hepatic lactate extraction, glucose production, and whole body {6-3H}glucose-derived rates of glucose appearance were also improved, but {6-3H}glucose-derived rates of glucose disappearance and blood lactate concentrations were increased, leading to no improvement in plasma glucose concentration . Pancreatic insulin secretion was higher in treated groups, which may have contributed to greater glucose utilization rates . Hepatic oxygen extraction efficiency was not affected by treatment, but increased in all groups to maintain hepatic oxygenation at base-line values . Although a calcium-antagonistic activity of gentamicin has been reported to synergize with endotoxin, thereby adversely affecting cardiovascular function, such effects did not complicate the metabolic response to steroid in the present studies.

Ann Vasc Surg, 1986 Nov, 1(3), 382 - 5
Intervertebral disk space infection following translumbar aortography; Fieve G et al.; After 1,748 translumbar aortograms three cases of intervertebral disk space infection were observed over a five-year period, for an incidence of 0.15% . Cultures suggested that the intervertebral disk had been inoculated with digestive tract organisms by the needle used to puncture the aorta . Diagnosis of this complication can be made early by retrieval of the responsible organisms from the intervertebral disk under CT control . Treatment consists of prolonged immobilization associated with appropriate antibiotic therapy for at least three months.

Rev Infect Dis, 1986 Nov-Dec, 8 Suppl 5, S609 - 11
Penetration of sulbactam into cerebrospinal fluid of patients with viral meningitis or without meningitis; Hanninen P et al.; In a study designed to determine the penetration of sulbactam into the central nervous system, a single intramuscular dose of 0.5-1.0 g was given to 19 patients: nine with viral meningitis and 10 with normal cerebrospinal fluid (CSF) . Drug levels in CSF were first detectable 2 hr after administration in patients with viral meningitis and 4 hr after administration in patients with normal CSF . The sulbactam levels were low (0-3.7 mg/ml), and no significant differences were found between levels in the two groups of patients . For the achievement of therapeutic concentrations of sulbactam in CSF, doses larger than those administered in this study should be used in conjunction with a beta-lactam antibiotic.

J Virol, 1986 Nov, 60(2), 674 - 82
Construction and properties of a cell line constitutively expressing the herpes simplex virus glycoprotein B dependent on functional alpha 4 protein synthesis; Arsenakis M et al.; We report the construction of a cell line constitutively expressing the glycoprotein B (gB) of herpes simplex virus (HSV) 1 . The cell line was constructed in two steps . In the first, a baby hamster kidney cell line was transfected with the DNA of a plasmid containing the neomycin phosphotransferase gene that confers resistance to the antibiotic G418 and the gene specifying a temperature-sensitive (ts-) alpha 4 protein of HSV-1, the major viral regulatory protein . A clonal cell line, alpha 4/c113, selected for resistance to the antibiotic G418, expressed high levels of alpha 4 protein constitutively . Superinfection of these cells with HSV-2 resulted in twofold induction of the resident HSV-1 alpha 4 gene . In the second step, alpha 4/c113 cells were transfected with the DNA of a plasmid carrying the gB gene and the mouse methotrexate resistance dihydrofolate reductase gene . A clonal cell line, alpha 4/c113/gB, selected for methotrexate resistance expressed gB constitutively . Expression of both gB and alpha 4 continued unabated for at least 32 serial passages . Cells passaged serially in medium containing both methotrexate and G418 after passage 10 contained a higher copy number of the alpha 4 gene and produced larger amounts of both gB and alpha 4 proteins than did cells maintained in medium containing methotrexate alone . Expression of gB was dependent on the presence of functional alpha 4 protein inasmuch as expression of gB ceased on shift up to nonpermissive temperatures, when shifted to permissive temperatures, the cell line reinitiated expression of gB after a delay commensurate with the length of incubation at the nonpermissive temperature, and the cell-resident HSV-1 gB gene was expressed at the nonpermissive temperature in cells infected with a recombinant expressing a ts+ alpha 4 protein and an HSV-2 gB . The properties of the alpha 4/c113 cell line suggest that it may express other viral genes induced by alpha 4 protein constitutively, provided that the product is not toxic to the cells.

Int J Fertil, 1986 Nov-Dec, 31(5), 356 - 9
Mycoplasma, chlamydia, Epstein-Barr, herpes I and II, and AIDS infections among 100 consecutive infertile female patients and husbands: diagnosis, treatment, and results; Kundsin RB et al.; One hundred consecutive infertile patients were studied to determine the incidence of sexually transmitted diseases (STDs) among middle and upper income patients, most of whom were referred as longstanding failures by other physicians . There were no cases of syphilis, gonorrhea, or AIDS found among these patients . One patient was pregnant when first seen, and was eliminated . Genital mycoplasmas were cultured from 64 wives . Antibodies for past or recent infection with Chlamydia were present in only 23 . Antibodies to Epstein-Barr virus and to herpes II were found in 92 and 65, respectively . If only the mycoplasmas, Chlamydia, and herpes II are considered possible causes of human infertility, only 7 of the 99 couples showed no evidence of ever having had any of these three infections . Edometrial histology was positive for the changes associated with Mycoplasma infection in 47 of the 86 patients biopsied . Of the 39 with negative biopsies, 24 yielded positive cultures for Mycoplasma . Hence, only 15 of the 99 patients were negative for Mycoplasma by both culture and/or endometrial histology . Treatment with the antibiotic of choice, as indicated by sensitivity testing of all Mycoplasma-positive cultures, was an important factor in producing 43 pregnancies during the first year of study . Two of these were ectopic; 11 were spontaneous abortions, with one of these women now pregnant again and in mid-trimester; 28 have delivered healthy babies; and two are still pregnant and doing well.

J Am Vet Med Assoc, 1986 Oct 15, 189(8), 916 - 7
Uveitis associated with Ehrlichia platys infection in a dog; Glaze MB et al.; Bilateral anterior uveitis, nonregenerative anemia, and thrombocytopenia were found in a 9-month-old Chow Chow infected with Ehrlichia platys . Diagnosis was based on the finding of basophilic inclusions in platelets and an E platys antibody titer . The dog was treated orally with tetracycline, topically with antibiotic/corticosteroid, and topically with a mydriatic.

Biochem J, 1986 Oct 15, 239(2), 317 - 23
Selective action of mycobacillin on the uptake of releasable cell materials by Aspergillus niger; Das SK et al.; The uptake of normally releasable (i.e . releasable in the absence of the antibiotic) cell constituents (namely lysine, proline, ATP, Pi, Na+, K+ and Ca2+) by sensitive cells of Aspergillus niger that occurs in the absence of mycobacillin is gradually enhanced with increase in concentration of the antibiotic until the uptake attains the maximum . With still higher concentrations the uptake decreases until it becomes the same as in the control without mycobacillin . Uptake follows saturation kinetics both in the absence and in the presence of the antibiotic . Mycobacillin significantly increases Vmax . for uptake with any effect on Km, Mycobacillin has no action on the uptake of non-releasable materials.

Virology, 1986 Oct 15, 154(1), 41 - 55
A transforming plasmid from HSV-2 transformed cells contains rat DNA homologous to the HSV-1 and HSV-2 genomes; Bejcek B et al.; Morphologically transformed rat (3Y1) cell lines were established following transfection with HSV-2 mtrII DNA sequences (0.585 to 0.601 map units) . The mtrII sequences were cloned in plasmids containing the neor gene . Cells resistant to the antibiotic G-418 were passed into soft agarose, and clonal lines were established from individual colonies . The DNAs from two cell lines examined by Southern blot hybridization were shown to contain the original transfected viral DNA sequences in a fashion consistent with a multiple and complex pattern of integration . From one cell line, an approximately 20-kbp plasmid was isolated after transformation of bacteria with Hirt supernatant DNA . This plasmid was capable of rapidly transforming rat cells at a greater than 1000-fold higher frequency than the mtrII DNA . This plasmid consists mainly of unique sequence rat DNA with two copies of the HSV-2 mtrII region DNA (HSV-2 genomic map unit location of ca . 0.595) present at sites distant from each other . The rat DNA in the rescued plasmid is homologous to the putative focus-forming sequences present in the HSV-2 mtrIII (0.53 to 0.58 map units) and the colinear HSV-1 DNA . The genomic copy of these rat sequences in four HSV-2 mtrII transformed cell lines appears to have undergone rearrangement . These data provide evidence that the HSV-2 mtrII sequences are involved in transformation, and that the HSV-2 mtrII region may affect transformation by rearranging the cellular sequences that are homologous to mtrIII.

Respir Care, 1986 Nov, 31(11), 1086 - 91
Contamination of a multiple-use suction catheter in a closed-circuit system compared to contamination of a disposable, single-use suction catheter; Ritz R et al.; Multiple-use (M-U) closed-system endotracheal suction catheters are effective in preventing arterial oxygen desaturation in patients on positive end-expiratory pressure (PEEP) and may lessen the frequency of bradycardia and hypotension in unstable patients who are prone to these complications of suctioning . However, because M-U catheters remain attached to the ventilator circuit and are reintroduced repeatedly into the patient's airway over 24 hours or longer, they could become heavily contaminated with pathogens . We hypothesized a risk of autocontamination to the patient by re-inoculation of the respiratory tract with organisms that flourished on the M-U catheter while it was isolated from the patient's immune defenses or antibiotic therapy . Methods: We tested this hypothesis in 30 mechanically ventilated adult patients with positive sputum cultures . We measured and compared the amount of bacteria present on an M-U catheter at the end of a 24-hour use period, the amount of bacteria present in the patient's sputum at that time, and the amount of bacteria present on a single-use (S-U) catheter at that time, after it had made one pass into the patient's airway . Organisms recovered and colony counts were also compared to results of a sputum culture obtained before the study began . Results: Fourteen different pathogens or potential pathogens were recovered, in numbers of 2 x 10(1) to 2 x 10(7)colony-forming units . The greatest number of colonies was most often recovered from the sputum specimen, and statistical analysis showed no differences in rate or magnitude of contamination between M-U and S-U catheters.(ABSTRACT TRUNCATED AT 250 WORDS)

Biochemistry, 1986 Oct 7, 25(20), 5929 - 32
Depletion of nicotinamide adenine dinucleotide in normal and xeroderma pigmentosum fibroblast cells by the antitumor drug CC-1065; Jacobson MK et al.; CC-1065 is an extremely potent antitumor antibiotic that forms a well-defined adduct with DNA in which the molecule lies within the minor groove and is covalently attached through N3 of adenine . Addition of CC-1065 to human fibroblast cells produced a prolonged depletion of the nicotinamide adenine dinucleotide (NAD) pool even at extremely low drug concentrations (0.01 microgram/mL) . The depletion of NAD by CC-1065 was blocked by 3-aminobenzamide, which is consistent with a NAD depletion mechanism involving poly-(ADP-ribose) synthesis in response to a repair-induced DNA strand breakage event . Significantly, similar extents of NAD depletion were also evident in xeroderma pigmentosum cells of complementation groups A and D following exposure to CC-1065 . Since this NAD depletion is presumably associated with repair-induced incision, the repair of CC-1065-DNA adducts can probably take place by a pathway distinct from that involved in repair of more conventional bulky DNA adducts . The prolonged depletion of NAD, even at low doses of drug, suggests that CC-1065 causes DNA damage that results in a delay or block in DNA excision repair between the excision and ligation steps.

Vet Rec, 1986 Oct 4, 119(14), 350 - 1
Mycoplasma californicum mastitis in the dry dairy cow; Mackie DP et al.; Mastitis in 85 of 140 dry cows and 16 of 101 milking animals on one farm was shown to be caused by Mycoplasma californicum . The infection was eradicated from the herd over a five month period by a combined programme of identification, segregation and culling of infected animals . Some dry cows produced a self-cure, but the majority calved with nonfunctional quarters which produced very little colostrum and resulted in a high incidence of calf mortality . The source of the infection could not be established, but it was probably spread in the dry cows by the unhygienic application of long acting intramammary antibiotic therapy.

Jpn J Antibiot, 1986 Oct, 39(10), 2754 - 60
{Clinical studies on te concentration of cefaclor in sera and lung tissues of patients with respiratory diseases}; Imaizumi M et al.; A 500 mg dose of cefaclor (CCL) was administered orally before surgery to each of patients with respiratory diseases and in fasting . Average concentrations of CCL in sera were 4.04 micrograms/ml at 1.5 hours, 3.03 micrograms/ml at 2 hours, 1.68 microgram/ml at 3 hours and 0.45 microgram/ml at 5 hours after administration . Average concentrations in lung tissues during operation were 0.120 microgram/g at 3 hours, 0.272 microgram/g at 4 hours and 0.297 microgram/g at 5 hours after administration . Ratios of concentrations of CCL in lung tissues to that in sera were from 7.1 to 66.0 percent . The CCL was considered to be a useful antibiotic for the treatment of patients with respiratory diseases.

Antibiot Med Biotekhnol, 1986 Oct, 31(10), 768 - 74
{Effect of doxorubicin on animals in multiple intravenous administration}; Shepelevtseva NG et al.; Toxicity of doxorubicin prepared with an original chemical method from rubomycin (daunomycin) was studied on albino rats and dogs . The antibiotic was administered intravenously in multiple doses . A significant loss of the body weight, a decrease in the relative weight of the spleen, thymus and ovary and an increase in the relative weight of the heart, kidneys and adrenal gland were observed in the rats after daily administration of doxorubicin in various doses 5 times . In a dose of 0.5 mg/kg doxorubicin was lethal for the dogs after 5, 7 and 10 administrations . Multiple administration of the antibiotic in doses of 0.25 and 0.125 mg/kg did not result in death of the dogs . There were areas of alopecia on the belly and joints, ulcers, body weight loss, increased urea levels in serum and diarrhea before death . The faeces contained significant admixtures of blood . Doxorubicin had an inhibitory effect on hemopoiesis of the albino rats and dogs . Before death bone marrow aplasia was recorded . After discontinuation of doxorubicin administration the inhibitory effect of the antibiotic on hemopoiesis persisted for 2-3 days . Histological examination of the organs and tissues of the animals killed at different periods after multiple intravenous administration of doxorubicin in various doses showed that doxorubicin had mainly the damaging effect on the gastrointestinal epithelium, heart muscle, epithelium of the proximal tubuli of the kidneys, lymphoid organs and testis . The damage depended on the dose of doxorubicin and duration of its use . By the character of the toxic effect and the size of the doses inducing certain effects doxorubicin made in the USSR did not differ from the analogous foreign drug.

Int J Clin Pharmacol Ther Toxicol, 1986 Oct, 24(10), 555 - 8
Pharmacokinetics of gentamicin in children with nephrotic syndrome; Gonzalez-Martin G et al.; The disposition of gentamicin was studied in five children with nephrotic syndrome and five control children to observe the effect of nephrotic syndrome on the distribution and elimination of the antibiotic . After a single intravenous dose of gentamicin (2.0 mg/kg body wt.) administered to each child, blood samples were drawn at frequent intervals during a 4-h period and then analyzed by homogeneous enzyme immunoassay (EMIT) . Time-concentrations drug profiles were characterized by means of a two-compartment open model . The mean half-life of gentamicin in nephrotic children (96.4 +/- 16.8 min) was significantly longer than in the control group (62.5 +/- 7.1 min) . The distribution volume of the central compartment was similar in both groups studied, but the distribution volume at steady-state was increased in children with nephrotic syndrome . Total plasma clearance was found decreased in nephrotic (2.8 +/- 0.5 ml/min/kg) in comparison with controls (3.7 +/- 0.7 ml/min/kg) . From our findings, it could be concluded that serum level of children with nephrotic syndrome treated with gentamicin should be carefully monitored in order to avoid the toxic effects of the antibiotic.

Mol Biochem Parasitol, 1986 Oct, 21(1), 47 - 54
Protein methylation and protein methylases in Leishmania donovani and Leishmania tropica promastigotes; Paolantonacci P et al.; We studied the content of acid-stable methylated amino acids of soluble proteins in promastigotes of Leishmania donovani and L . tropica . epsilon-N-Trimethyllysine and NG,NG-dimethylarginine were found in both Leishmania species after culture in the presence of {methyl-14C}methionine . In addition, 3-N-methylhistidine was found only in L . tropica and epsilon-N-dimethyllysine only in proteins of L . donovani . As sinefungin, an antileishmanial nucleoside antibiotic, is a known transmethylase inhibitor, its effect on protein methylation was studied, in whole cells and in vitro . In the first case the drug had no effect on the content of methylated amino acid residues of soluble proteins . In vitro, histone methylation by crude extracts was studied at pH 7.2 and 9.0, known in other organisms as optimum pH values for arginine and lysine methylation, respectively . Surprisingly, arginine methylation by extracts of L . donovani was the same at both pH values while lysine residues were more efficiently methylated at pH 7.2 than at pH 9 by the extracts of the two species . These results indicate that the properties of protein methylases I and III of these parasites are different from those of other organisms hitherto studied . The inhibition constants of sinefungin for the leishmanial protein methylases were weak in comparison with those for enzymes from other sources, with the exception of the constant of L . donovani enzyme at pH 9.

Int J Cardiol, 1986 Oct, 13(1), 88 - 92
Detection of infection of a cardiac xenograft by gallium-67 scan; Bahar RH et al.; We describe a case complicated by infection of a xenograft conduit with subsequent septic emboli to the left kidney in the setting of pulmonary atresia with ventricular septal defect which was positively imaged using radioactive gallium-67 . Confirmation was provided by cross-sectional echocardiography and positive blood culture . The patient improved with antibiotic therapy.

Drug Intell Clin Pharm, 1986 Oct, 20(10), 796 - 8
Management of pediatric patients with bacterial meningitis in the emergency department; Nahata MC et al.; The pattern and appropriateness of the use of antibiotics, fluids, and laboratory data in the emergency department were evaluated in 50 pediatric patients with meningitis due to Hemophilus influenzae, type b . Results indicate that the quality of care in emergency departments for patients with bacterial meningitis can be improved by administering appropriate antibiotic doses; minimizing the delay in administration of antibiotics; and avoiding the excess fluid administration to decrease the potential for hyponatremia and cerebral edema.

Drug Intell Clin Pharm, 1986 Oct, 20(10), 752 - 6
Drug use in a surgical intensive care unit; Dasta JF; A retrospective review of drug usage in 180 patients admitted to a surgical intensive care unit was conducted . The average stay was three days and the total and daily number of drugs averaged 7.6 and 5.6, respectively . The most common drug class used was antibiotics, with cefazolin being the most commonly used antibiotic . Other commonly used drugs include analgesics, diuretics, H2-antagonists, vasoactive drugs and inotropes, antacids, and antiarrhythmics . This study indicates that patients admitted to a surgical intensive care unit are exposed to a variety of potent drugs, often given in combination over a short time period . Although further studies are needed to delineate specific aspects of drug use and patient characteristics, this study suggests that there is a need for close monitoring of drug therapy in these patients with special attention to reduction of drug costs.

Clin Orthop, 1986 Oct, (211), 108 - 15
Revision of infected total hip arthroplasty; Weber FA et al.; Extension of infection down the medulla of the femur to the supracondylar region may occur in cases of chronic infected total hip arthroplasty . Because this cannot always be identified before operation, the femur should be reamed and flushed proximally from the lateral condyle in all cases where there is suspicion of infection around the femoral component . Where infection is unequivocal and extensive, a period of irrigation and suction drainage is advisable before final total hip arthroplasty . After the prosthesis has been inserted in either one or two stages, it is wise not to rely on antibiotic cement mixtures alone but to monitor the bacterial flora and prescribe local antibiotic therapy accordingly.

Arch Dermatol, 1986 Oct, 122(10), 1180 - 2
Primary lymphocutaneous Nocardia brasiliensis infection; Moeller CA et al.; We report a rare case of primary lymphocutaneous Nocardia brasiliensis infection occurring in an elderly diabetic man maintained on long-term therapy with prednisone . The mode of inoculation was that of a puncture wound caused by a contaminated needle that occurred one month prior to the development of the clinically apparent infection . The course of this patient's infection was protracted and required two surgical procedures and several months of antibiotic therapy . A review of 15 previously reported cases is presented as well as a discussion of appropriate medical therapy.

Postgrad Med, 1986 Oct, 80(5), 213 - 6, 219, 222-3
Pleural effusions caused by infection; Varkey B; Diagnostic thoracentesis is imperative when pneumonia is accompanied by an effusion (parapneumonic effusion) . Examination of the pleural fluid is the only way to differentiate empyema and complicated parapneumonic effusions from uncomplicated parapneumonic effusions, and this differentiation is vital in deciding whether chest tube drainage is needed . If the aspirated pleural fluid contains pus or bacteria, closed chest tube drainage and antibiotic therapy should be started promptly . The same management approach is indicated if the pleural fluid pH is less than 7.00 or the glucose level is less than 40 mg/ml, since these effusions almost invariably are complicated parapneumonic effusions that do not resolve without fluid drainage . If the pleural fluid pH is greater than 7.20 and glucose level is more than 40 mg/ml, antibiotic therapy alone will suffice . Management of parapneumonic effusions with a pH of 7.00 to 7.20 should be based on serial observations of clinical status and pleural fluid findings.

Obstet Gynecol, 1986 Oct, 68(4), 473 - 8
Randomized comparison of five irrigation solutions at cesarean section; Dashow EE et al.; A randomized double-blind study was undertaken to determine which irrigation solution might be best at cesarean section . A saline placebo was compared with ampicillin sodium and one each of three generations of cephalosporins: cephapirin sodium, cefamandole nafate, and moxalactam disodium . A total of 360 cesarean sections were studied, and comparisons made between antibiotic and control groups relative to demographics, possible risk factors, and multiple measures of postoperative morbidity . The total group was further divided into high- and low-risk labor and repeat cesarean groups . Post-cesarean endometritis was diagnosed in the following frequencies for the group as a whole: placebo (24.6%), ampicillin sodium (8.5%), cephapirin sodium (11.4%), cefamandole nafate (4.6%), and moxalactam disodium (16.4%) . Cefamandole nafate consistently demonstrated significant decreases in endometritis and other morbidity measures versus placebo both in laboring patients and the group as a whole.

J Thorac Imaging, 1986 Oct, 1(4), 25 - 33
Nosocomial pulmonary infections in children; Fisher MC; Nosocomial infections prolong hospitalization and increase morbidity, mortality, and costs . Unfortunately only 50% of hospital-acquired infections are preventable . Factors that increase the risk for infection include use of monitoring devices, performance of invasive diagnostic and therapeutic procedures, prolonged duration of hospitalization, and impairment of host defense . Diagnosing nosocomial pulmonary infections is challenging . Radiographic studies must be combined with other diagnostic techniques to confirm diagnoses . Aggressive pursuit of a definitive diagnosis is important in evaluation of the compromised host . Specific therapy is preferred over empiric therapy . Outcome is related to the infecting agent and the patient's underlying condition . Preventive measures include hand-washing, isolation of infected patients, and careful attention to aseptic technique when inserting and manipulating catheters . In general, antibiotic therapy will not prevent infection but will alter the patient's flora and increase the likelihood of infection by resistant pathogens.

Hinyokika Kiyo, 1986 Oct, 32(10), 1443 - 8
The treatment of bladder cancer by neothramycin; Tsugaya M et al.; Neothramycin (NTM), an anthramycin-group anticancer antibiotic, was used in the treatment of superficial carcinoma of the bladder . NTM was instilled into the bladder in the following dosages . Ten mg NTM in 20 ml of sterile distilled water was given first, and increased to 40 mg in 20 ml . This procedure was performed every second week to twice a day . Recently, in 2 patients, the treatment has been combined with 20 mg NTM intravenous administration . In 4 of the 11 patients (36%) the tumors disappeared completely, while in 6 patients (55%) there was partial disappearance of more than 50% and in one patient (9%) there was no effect . Three of the patients had irritable bladder symptom (temporarily) . NTM was concluded to be effective for superficial carcinoma of the bladder.

J Antimicrob Chemother, 1986 Oct, 18 Suppl C, 133 - 9
Resistant bacteria in the normal human flora; Hawkey PM; The occurrence of antibiotic-resistant bacteria in the normal human flora has been documented by many groups over the last 20 years . These studies are surveyed and the reasons for the occurrence of resistant bacteria in the normal flora are discussed . The need for surveys in the 1980s using modern molecular techniques to characterize mechanisms of resistance is suggested.

Mol Gen Genet, 1986 Oct, 205(1), 186 - 8
Mutant EF-Tu increases missense error in vitro; Tapio S et al.; We have studied the consequences of mutational alteration in the structure of EF-Tu on the missense errors and proofreading activity of bacterial ribosomes in vitro . Our data show that the EF-Tu Bo mutant form of EF-Tu (van der Meide et al . 1983a) is inactive in polypeptide synthesis on the ribosome, even though it binds aminoacyl-tRNA . A second mutant form, EF-Tu Ar (van der Meide et al . 1983a), is active in polypeptide synthesis but supports a much higher messense incorporation with either leucine isoacceptor 2 or leucine isoacceptor 4 in the in vitro system . Further analysis of the kinetic basis of this enhanced missense frequency revealed that the mutation responsible for the alteration in EF-Tu Ar increases the errors at both the proofreading step and the initial selection . In this respect the effect of this particular mutation is similar to the mode of action of the antibiotic kanamycin (Jelenc and Kurland 1984).

J Clin Periodontol, 1986 Oct, 13(9), 841 - 4
Concentration of doxycycline in human gingival fluid; Pascale D et al.; Doxycycline is a synthetic tetracycline compound whose main advantages over tetracycline hydrochloride are increased oral absorption, prolonged serum half-life and decreased gastrointestinal side-effects . The purpose of this study was to measure the concentration of doxycycline in gingival fluid and blood after oral administration . 4 volunteers were given doses of 100 mg doxycycline every 12 h on the first day of antibiotic administration followed by a maintenance dose of 100 mg per day for an additional 4 days . 3 of these volunteers were also given tetracycline hydrochloride every 6 h for 5 days either 1 month before or after doxycycline administration to compare gingival fluid levels of these 2 tetracycline compounds . Gingival fluid was sampled from 4 gingival sites in each volunteer at hourly intervals from hours 0 to 6, 9, 24, 27, 48 to 54, 57, 72, 75, 96 to 102 and 105 . Blood was sampled by finger puncture at hours 0, 3, 6, 24, 48, 54, 72, 96 and 102 . Antibiotic levels in gingival fluid and blood were measured using an agar diffusion assay method . The results demonstrated that doxycycline achieved much higher levels in the gingival fluid than in blood and yielded comparable gingival fluid levels to those achieved by tetracycline hydrochloride . Doxycycline levels in gingival fluid ranged between 1.2 micrograms/ml and 8.1 micrograms/ml in the first 24 h and generally achieved 3-10 micrograms/ml after 48 h . Blood levels after 48 h ranged between 2.1 micrograms/ml and 2.9 micrograms/ml . Tetracycline hydrochloride in gingival fluid after 48 h was generally in the range of 4 micrograms/ml-10 micrograms/ml with blood levels between 2.2 micrograms/ml and 3.4 micrograms/ml.(ABSTRACT TRUNCATED AT 250 WORDS)

J Clin Microbiol, 1986 Oct, 24(4), 507 - 11
Effect of medium composition on results of macrobroth dilution antifungal susceptibility testing of yeasts; Doern GV et al.; A total of 62 different clinical yeast isolates were examined for susceptibility to four antifungal agents, amphotericin B, 5-fluorocytosine (5-FC), ketoconazole, and miconazole, using synthetic amino acid medium-fungi (SAAM-F), buffered yeast nitrogen broth (BYNB), Kimmig broth, casein-yeast-glucose broth (CYG), antibiotic medium 3-FDA (ANTI-3), and tryptic soy broth (TSB) . A macrobroth dilution format was used with MICs determined after incubation for 24 and 48 h . All analyses were performed in duplicate . In general, MICs were more reproducible after 48 h of incubation . Furthermore, with certain medium-antifungal agent combinations, MICs determined after incubation for 48 h were significantly higher than those determined after 24 h . For instance, with 5-FC irrespective of the medium used, greater than 25% of all 48-h MICs were more than one twofold dilution higher than the corresponding MICs determined after incubation for 24 h . Similar observations were made with amphotericin B when tested with BYNB and CYG and with the imidazoles when tested in all of the media except CYG . The actual MICs obtained with the different antifungal agents were clearly influenced by the test medium used . The rank order of amphotericin B MICs according to test medium was as follows: BYNB greater than SAAM-F = Kimmig = CYG = ANTI-3 = TSB . With 5-FC, the following pattern was observed: Kimmig = ANTI-3 greater than SAAM-F = CYG = TSB greater than BYNB . For both imidazoles, ketoconazole and miconazole, the rank order of MICs according to test medium was BYNB = Kimmig = CYG = ANTI-3 = TSB greater than SAAM-F . The results of this investigation suggested that broth dilution susceptibility testing of yeasts is best performed with an incubation period of 48 h . Furthermore, medium composition can significantly influence the results of such testing.

Gan To Kagaku Ryoho, 1986 Oct, 13(10), 3034 - 9
{Mitoxantrone-containing combination chemotherapy in patients with non-Hodgkin's lymphoma}; Kimura I et al.; Thirty-one patients with advanced non-Hodgkin's lymphoma were entered in a trial of a four-drug combination of mitoxantrone, cyclophosphamide, vincristine, and prednisolone (MCOP) . This trial was intended to test the efficacy of substituting mitoxantrone for adriamycin in the CHOP combination, and to evaluate tumor response in patients who had received anthracycline antibiotic therapy . Of 31 patients, 25 were fully evaluated for tumor response and toxicity . There were 7 responses (4 complete, 3 partial) among 9 patients who had received radiation alone or chemotherapy not containing anthracycline antibiotics, whereas there were 7 responses (3 complete, 4 partial) in 16 patients who had been given anthracycline-containing chemotherapy . Median duration of response was 11+ weeks (range; 5 to 43+ weeks) . The major toxicity was myelosuppression, although patients tolerated this well . This study suggested that mitoxantrone is not fully cross-resistant with anthracycline antibiotics and that MCOP is an effective regimen in patients with previously treated non-Hodgkin's lymphoma . However, when salvage chemotherapy for CHOP-failure is intended, cyclophosphamide and vincristine in MCOP should be further substituted by other agents such as etoposide and cis-platinum.

Proc Natl Acad Sci U S A, 1986 Oct, 83(19), 7344 - 7
Transformation of Phycomyces blakesleeanus to G-418 resistance by an autonomously replicating plasmid; Revuelta JL et al.; The fungus, Phycomyces blakesleeanus, shows many well-defined responses to a number of external stimuli . Genetic analysis shows that at least eight genes are involved in Phycomyces sensory transduction . As a first step toward the molecular analysis of these genes and their products, we have developed a transformation protocol for Phycomyces by using a plasmid containing the kanamycin-resistance gene from Tn903 and a Phycomyces DNA fragment capable of supporting autonomous replication in yeast (ARS) . Our results demonstrate that the Tn903 gene is expressed in Phycomyces and that the ARS fragment selected in yeast supports autonomous replication in Phycomyces as well.

J Urol, 1986 Oct, 136(4), 889 - 91
Vesicocalicostomy as ultimate solution for recurrent urological complications after cadaveric renal transplantation in a patient with poor bladder function; van Son WJ et al.; We report a case of a neurogenic bladder in which hydronephrosis recurred early after renal transplantation . After 2 unsuccessful attempts at ureteroneovesicostomy of the donor ureter a vesicocalicostomy was performed, since reconstruction with the donor pelvis or ureter was impossible owing to the extended fibrosis and scar formation around the renal hilus and ureter . During the 23 months of followup renal function has been good without serious infectious sequela with a regimen of self-catheterization and no antibiotic maintenance therapy.

J Immunol, 1986 Oct 1, 137(7), 2156 - 61
B cell triggering properties of a nontoxic derivative of amphotericin B; Sarthou P et al.; The immunomodulating properties of amphotericin B (AMB), an antifungal polyene antibiotic, have been reported in multiple studies . However, many findings on the subject are conflicting, and the precise mechanism of AMB action on the immune system is yet unknown . Because toxicity and limited solubility of AMB are likely to be responsible for these discrepancies, we synthesized a nontoxic derivative of AMB (AMBSH), and we investigated its immune modulating effects on murine B cells . Our results show that AMBSH induces a strong proliferative response under conditions where AMB is weakly efficient or toxic, and that AMBSH supports maturation to Ig secretion . When suboptimal doses of LPS (or BCGF) are present together with AMBSH, a synergistic effect on B cell proliferation occurs . Frequency analyses reveal that, although only a limited number of B cells respond to AMBSH alone, a large population of B cells will respond to subthreshold doses of LPS in the presence of this polyene . Finally, we show that incubation of spleen cells with AMBSH results in an increase in Ia expression . These results are discussed in terms of the membrane disorganizing properties of polyene antibiotics.

Otolaryngol Head Neck Surg, 1986 Oct, 95(3 Pt 1), 333 - 43
Complicated frontal sinusitis: evaluation and management; Gardiner LJ; The diagnosis and management of complicated cases of frontal sinusitis are challenging problems . Unacceptable mortality and morbidity from delay in diagnosis and treatment must be weighed against the early performance of deforming surgical procedures . Many of these patients require prolonged hospitalization for intravenous antibiotic therapy . The assessment of the optimal time course for such therapy has been difficult . Six illustrative cases of frontal sinusitis, complicated by intracranial suppuration, osteomyelitis, and/or bone erosion, are presented . The use of CT, bone, and gallium scans in the diagnosis of complications--and in the timing of antibiotic therapy and surgical intervention--are discussed . Guidelines are formulated for the evaluation and treatment of complicated frontal sinusitis.

J Antimicrob Chemother, 1986 Oct, 18 Suppl C, 25 - 34
Molecular biology of transposable elements; Schmitt R; Transposable elements play an essential part in the epidemic spread of antibiotic resistances among bacterial populations . Their ubiquity and their role in the molecular evolution of genomes and organisms has captured the interest of molecular biologists, who investigate the genetic structure and novel mechanisms of recombination underlying transposition . This article, after introducing the general structure of mobile genetic elements and basic mechanistic concepts of transposition in bacteria, uses the well-studied Tn3 family as paradigm for gene organization, gene function and gene regulation . Finally, new applications of transposons in genetic engineering will be described.

J Gen Microbiol, 1986 Oct, 132 ( Pt 10), 2685 - 92
R-plasmid-mediated chromosome mobilization in Bordetella pertussis; Smith CJ et al.; Antibiotic-resistant and auxotrophic mutants of Bordetella pertussis were isolated . These were used as recipients for the uptake from Escherichia coli of broad-host-range R plasmids R68.45, RP1, and RP1 and RP4 carrying transposons Tn501 and Tn7 respectively . B . pertussis transconjugants from these crosses were used as donors to mobilize StrR, NalR, thr+ and gly+ chromosomal markers to B . pertussis or to B . parapertussis recipient strains . The frequency of plasmid transfer varied and depended on the donor and recipient strains used . Differences in chromosome mobilization frequencies of individual markers were observed and appeared to depend on the presence or absence of transposons Tn501 and Tn7 on the plasmid . Linkage was detected between the gly+ and NalR markers.

Exp Cell Res, 1986 Oct, 166(2), 391 - 8
Maintenance of expression of differentiated function of kidney cells following transformation by SV40 early region DNA; Scott DM et al.; This study describes the isolation and characterization of epithelial cell lines that maintain their differentiated phenotype following the stable integration of SV40 genes . Epithelial cells were derived from a defined location of rabbit kidney, the thick ascending limb of Henle's loop, and were co-transfected with genes from the early region of SV40 together with pSV2-neo DNA (which confers resistance to the antibiotic G418) . These cells were shown to be resistant to G418, express SV40 large T-antigen and continued to express differentiated characteristics typical of cells of their origin . Such characteristics include the expression of high levels of activity of both Na,K-ATPase and the functionally important Na,K,Cl-co-transport system, the synthesis of Tamm-Horsfall glycoprotein and the presence of a barium-sensitive K+ channel on the apical membrane surface.

Biochim Biophys Acta, 1986 Sep 25, 861(1), 141 - 51
Thermodynamic analysis of incorporation and aggregation in a membrane: application to the pore-forming peptide alamethicin; Schwarz G et al.; Interaction of the pore-forming antibiotic alamethicin with small unilamellar vesicles of dioleoylphosphatidylcholine has been studied by means of circular dichroism . The data strongly suggest that alamethicin does not bind to the surface of the vesicles but incorporates into the lipid phase to a fairly large extent . Furthermore, aggregation of the peptide in the membrane is apparent from the existence of a 'critical concentration' . Quantitative evaluation and interpretation of the data rest on a quite generally applicable thermodynamic analysis . The underlying phenomenon is treated in terms of a partition equilibrium between the aqueous and lipid media . In the bilayer phase non-ideal interactions (described by appropriate activity coefficients) as well as aggregate formation are considered . Using this approach the relevant parameters of the alamethicin-lipid system have been determined (yielding, in particular, a partition coefficient of 1.3 X 10(3) for the monomeric peptide and a critical aqueous concentration of 2.5 microM) . Finally, the possible relevance of these results for the voltage-dependent gating of alamethicin is briefly pointed out.

Biochim Biophys Acta, 1986 Sep 25, 861(1), 83 - 94
Mechanism of inhibition of mitochondrial enzymatic complex I-III by adriamycin derivatives; Goormaghtigh E et al.; We demonstrate here that complex I-III of bovine heart mitochondrial membrane is inhibited by adriamycin derivatives . This inhibition is a cardiolipin-dependent process . This lipid, specific to the inner mitochondrial membrane, has been shown previously to interact specifically with adriamycin in model membranes (Goormaghtigh, E., Chatelain, P., Caspers, J . and Ruysschaert, J.-M . (1980) Biochim . Biophys . Acta 597, 1-14) and in mitochondrial membranes (Cheneval, D., Muller, M., Toni, R., Ruetz, S . and Carafoli, E . (1985) J . Biol . Chem . 260, 13003-13007) . The differential scanning calorimetry data indicate that, in multilamellar liposomes, the formation of antibiotic-cardiolipin complexes induces a clustering of cardiolipin molecules . Conformational analysis of the antibiotic-cardiolipin complexes suggests that plane-plane interactions between the antibiotics aromatic moieties stabilize this complex formation . Possible mechanisms of inactivation of complex I-III by adriamycin are proposed.

Biochemistry, 1986 Sep 23, 25(19), 5533 - 9
Magnetic resonance studies of fredericamycin A: evidence for O2-dependent free-radical formation; Hilton BD et al.; Fredericamycin A, a newly described potent antitumor antibiotic, exhibits unusual spectroscopic and physical properties . The drug shows a striking color change from red to blue on exposure to O2, with the appearance of an optical absorption band at 675 nm; on addition of acid these changes are readily reversed . 1H and 13C NMR spectra of fredericamycin A show that the resonances from the quininoid half of the molecule disappear after exposure to O2 but reappear on acidification in parallel with the observed optical spectral shift . These unusual NMR data are explained by electron spin resonance studies which demonstrate that fredericamycin A spontaneously forms an oxidized free radical with electron transfer to O2 . The observed hyperfine structure of this radical is consistent with one-electron oxidation of the quininoid group . After fredericamycin A is exposed to O2, an EPR signal is observed with axial symmetry with temperature and power saturation behavior suggestive of .O2- . Spin-trapping EPR studies demonstrate that the drug reduces O2 to .O2- and H2O2 to .OH . This spontaneous mechanism of O2 reduction with the generation of oxidized drug free radicals and reduced oxygen free radicals is unprecedented among anticancer drugs, suggesting that fredericamycin A could be the forerunner of a new class of anticancer drug.

Nucleic Acids Res, 1986 Sep 11, 14(17), 6785 - 801
Echinomycin and distamycin induce rotation of nucleosome core DNA; Low CM et al.; When nucleosome cores reconstituted from chicken erythrocyte histones and a 160 bp DNA molecule are exposed to echinomycin, a bis-intercalating antitumour antibiotic, the DNA appears to rotate with respect to the histone octamer by about half a turn . New bands appear in patterns of DNAase I digestion at positions approximately mid-way between those characteristic of control core samples, while the control pattern is largely suppressed . Similar (but not identical) changes are produced when nucleosome cores are exposed to distamycin, a non-intercalating DNA-binding antibiotic . The effects of both ligands can be explained in terms of a change in rotational orientation of the core DNA, so as to place antibiotic binding sites on the inward-facing (concave) surface of the DNA supercoil . Presumably this serves to optimise non-bonded contacts with the polynucleotide backbone . These results establish that the positioning of DNA about the histone octamer is not absolutely determined by its nucleotide sequence, but may be modified by the binding of such relatively small molecules as antibiotics.

Biochim Biophys Acta, 1986 Sep 11, 860(3), 608 - 19
Mode of action of gramicidin S on Escherichia coli membrane; Katsu T et al.; The action of a cationic antibiotic gramicidin S on the outer and cytoplasmic membranes of Escherichia coli was studied . It was found that gramicidin S disrupted the permeability barrier of the outer membrane, permitting the permeation of an antibiotic ionophore, this being similar to the action of the dimer in compound 48/80 (Katsu, T., Shibata, M . and Fujita, Y . (1985) Biochim . Biophys . Acta 818, 61-66) . However, differently from the dimer, gramicidin S further stimulated the efflux of K+ through the cytoplasmic membrane of E . coli . The time course of K+ permeability change accorded well with that of change in the viability of E . coli cells . These changes occurred at temperatures above the phase transition of the cytoplasmic membrane . This temperature range differed greatly from the case of polymyxin B, a polycationic antibiotic acting at temperatures above the phase transition of the outer membrane . We discuss the mode of gramicidin S action on the cytoplasmic membrane of E . coli, in comparison with the results on red blood cells and liposomes.

Brain Res, 1986 Sep 3, 381(2), 397 - 400
Reversal of organophosphate-induced muscle block by neomycin; Bradley RJ; The organophosphate, diisopropyl fluorophosphate, and the aminoglycoside antibiotic, neomycin, both independently block neuromuscular transmission . At the neuromuscular junction, neomycin reduces the presynaptic release of acetylcholine, whereas diisopropyl fluorophosphate irreversibly inhibits acetylcholinesterase, thereby increasing the acetylcholine concentration . In the rat diaphragm preparation, the block in neuromuscular transmission caused by diisopropyl fluorophosphate could be reversed by adding neomycin.

J Gen Microbiol, 1986 Sep, 132 ( Pt 9), 2621 - 31
Occurrence of the stringent response in Streptomyces sp . and its significance for the initiation of morphological and physiological differentiation; Ochi K; Streptomyces sp . MA406-A-1 produced formycin (a nucleoside antibiotic) in parallel with cell growth in a synthetic medium . When the synthetic medium was supplemented with 1% (w/v) Casamino acids, however, formycin was produced only after the end of exponential growth . The intracellular ppGpp pool increased gradually towards the end of exponential growth and was maximal at the beginning of formycin production . After shift down from Casamino acids medium to synthetic medium, the ppGpp pool increased immediately, while the GTP pool decreased; under such conditions, the ability to produce formycin increased eightfold . Relaxed (rel) mutants, the first isolated for a Streptomyces species, were found at high incidence (10%) among spontaneous thiopeptin-resistant isolates and had severely reduced abilities to accumulate ppGpp . These rel mutants also failed to produce formycin under the usual culture conditions and exhibited numerous pleiotropic effects such as an inability to produce melanin and an extended delay of aerial mycelium formation . Thus Streptomyces sp . exhibited a typical stringent response, and the response initiated (or was needed for) the induction of secondary metabolism . The response may have also participated in the initiation of aerial mycelium formation by decreasing the intracellular GTP pool.

J Antibiot (Tokyo), 1986 Sep, 39(9), 1263 - 9
Biosynthesis of valanimycin; Yamato M et al.; In the biosynthesis of valanimycin, valine is mostly incorporated into the isobutyl moiety of the antibiotic . The alpha-substituted acrylic moiety of valanimycin is derived from alanine . However, a part of alanine is metabolized into valine, thus incorporated also into the isobutyl moiety . Anaerobic conditions and some reducing agents strongly inhibit the biosynthesis.

Eur J Respir Dis, 1986 Sep, 69(3), 160 - 8
Choice of nebulisers and compressors for delivery of carbenicillin aerosol; Newman SP et al.; Although aerosol antibiotics have been used successfully to treat respiratory tract infection in patients with cystic fibrosis, little information exists concerning the correct nebulisation technique for antibiotic solutions . We have measured aerosol output, droplet size and nebulisation time for 1 g carbenicillin (Pyopen, Beechams) diluted with 3 ml or 4 ml water for injection and delivered from six brands of jet nebuliser (Cirrus, DeVilbiss, Inspiron, Turret, Unicorn and Upmist) . Three relatively weak compressors (Medix Traveller, Medic-Aid PortaNeb 50 and Inspiron) and three more powerful compressors (Medix WOBL, Medix Maxi mark I and Gast) were used as driving sources . Maxi and Gast compressors increased the quantity of "respirable" (less than 5 micron diameter) carbenicillin aerosol, and reduced nebulisation times; with the weaker compressors, nebulisation times (up to 50 min) were unacceptably long . The Turret nebuliser proved to be the most efficient, but several other brands would also be acceptable if used with a powerful compressor.

Antibiot Med Biotekhnol, 1986 Sep, 31(9), 695 - 8
{Assessment of the reproductive function of white rats exposed to cephalexin by inhalation}; Anufrieva RG et al.; The embryotoxic and teratogenic effects of cefalexin were studied on Wistar albino rats subjected to inhalations of the antibiotic within the whole gravidity term . It was shown that in a concentration of 1.29 mg/m3 cefalexin did not increase the rate of fetus intrauterine death, had no unfavourable effect on the fetus and placenta development and did not induce anomalies in development of the fetus internal organs . The frequency of sensitization in the gravid and nongravid animals was the same . No signs of sensitization were detected in the litter of the rats treated with cefalexin inhalations.

Antibiot Med Biotekhnol, 1986 Sep, 31(9), 684 - 7
{Pharmaceutical aspects of creating an effective drug form of carfecillin}; Berezovskaia LN et al.; Physical and technological parameters of carfecillin powder and carfecillin with auxiliary substances in the form of the powder mixture and granulate were studied comparatively . Possible preparation of carfecillin capsules characterized by high levels of the antibiotic dissolution was shown.

Mol Biol (Mosk), 1986 Sep-Oct, 20(5), 1313 - 20
{X-ray diffraction and infrared circular dichroism of DNA-violamycin B1 complexes}; Riaim T et al.; X-ray diffraction and infrared linear dichroism of oriented samples of DNA-violamycin B1 complexes have been studied at different antibiotic/DNA phosphate ratios (r) as a function of relative humidity . Violamycin B1 binds to DNA according to the intercalation as well as to the outside binding model . At low r values, where the intercalation predominates the unwinding angle of DNA helix is between 6 degrees and 12 degrees per intercalation site as followed from the dependence of the pitch of helix versus r . At r greater than or equal to 0.17 the intercalation sites are saturated and the outside binding becomes prevalent; however the violamycin B1 chromophore is still oriented in the plane of DNA bases . Conformational mobility of DNA in the violamycin B1 complexes is largely inhibited compared with pure DNA, but it is higher than that of the daunomycin complexes . At least 30% of DNA in violamycin complexes has A conformation at the medium humidities as followed by IR linear dichroism . In the case of x-ray diffraction the A conformation was not detected . The distance between DNA molecules in the complex is found to be 23.2 A, that is 2 A less than in pure DNA at the same conditions and it does not depend upon r.

Arch Phys Med Rehabil, 1986 Sep, 67(9), 595 - 7
Spine fractures in ankylosing spondylitis; Fast A et al.; Patients with ankylosing spondylitis are susceptible to spine fracture, usually in the cervical spine . Less frequently, the thoracic and lumbar spine is affected . The fracture line may involve anterior and posterior elements . Frequently, it extends through the entire width of the spine . As a result the fracture tends to be unstable and may cause neurologic damage . Prompt immobilization and reduction of the dislocated spine followed by stabilization may prevent neurologic damage . We report a 45-year-old man who fell and sustained a fracture dislocation of L2 vertebra . The patient was operated and stabilized with Harrington rods . A deep wound infection developed, which did not respond to antibiotic therapy and led to removal of the rods . In spite of bed immobilization with a body jacket the fracture remained unstable and dislocated . As a result the patient sustained severe neurologic damage . Many fractures in patients with ankylosing spondylitis occur following minor trauma . We feel that a very important aspect of ankylosing spondylitis management is prevention of these fractures . Alerting patients of their spine fragility and teaching then how to evade situations leading to spinal trauma may help in avoiding this situation.

Am J Vet Res, 1986 Sep, 47(9), 1924 - 7
Resistance of preimplantation bovine embryos to infection with Brucella abortus; Stringfellow DA et al.; Preimplantation bovine embryos were exposed in vitro to Brucella abortus to determine if the bacteria would adhere to zona pellucida (ZP)-intact embryos or adhere to or infect ZP-free embryos . Brucella abortus was not isolated from ZP-intact or ZP-free groups of embryos after 10 sequential antibiotic-free washings . Brucella abortus was isolated from all groups containing ZP-defective embryos after the exposure period and washing . Detrimental effects on healthy in vitro development of embryos were not observed.

Drug Intell Clin Pharm, 1986 Sep, 20(9), 694 - 7
Evaluation of tetracycline on theophylline disposition in patients with chronic obstructive airways disease; Gotz VP et al.; Theophylline is a commonly used bronchodilator in the treatment of chronic obstructive airways disease (COAD) with a narrow therapeutic range of 10 to 20 micrograms/ml . Patients with COAD frequently receive concomitant antibiotic therapy for respiratory infections . This study evaluated the effect of tetracycline therapy on theophylline disposition in adults with COAD . Six males (five nonsmokers) with obstructive ventilatory defects were studied in two phases: control, after receiving sustained-release theophylline in the same dosage regimen for four days, and treatment, after receiving tetracycline 250 mg po qid for five days in addition to theophylline . During each phase, 10 blood samples were obtained over one dosing interval and analyzed for theophylline content . The following pharmacokinetic parameters were calculated: Cmin, Cmax, Css, percentage fluctuation and Cl . Differences for each value were tested as paired data with Student's two-tailed t-test . When all patients were evaluated, the only statistically significant difference was for Cmax . However, when the five nonsmokers were evaluated separately, differences were observed for Css (micrograms/ml; mean +/- SD) 9.3 +/- 3.0, control, and 10.6 +/- 3.8, treatment (p = 0.041); and for Cl {( ml/h}/kg; mean +/- SD) 49.0 +/- 11.1, control, and 43.6 +/- 10.2, treatment (p = 0.019) . This study demonstrates that tetracycline may weakly inhibit theophylline clearance in nonsmoking adults with COAD.

Gan To Kagaku Ryoho, 1986 Sep, 13(9), 2800 - 6
{A phase II study of mitoxantrone in refractory and relapsed malignant lymphomas . Cooperative Study Group of Mitoxantrone in Malignant Lymphomas}; Kimura I et al.; A phase II clinical trial of mitoxantrone in refractory or relapsed malignant lymphomas was conducted by a cooperative study involving 17 institutions . Of 46 patients entered, 33 were evaluable for responses and toxicity . Thirty-one of the 33 had been previously exposed to adriamycin at a median dose of 220 mg/m2 (range 21-489 mg/m2), and two additional patients had each been given THP-adriamycin at a dose of 80 mg/m2 or 4'-epi adriamycin at a dose of 69 mg/m2 . Mitoxantrone was administered in 3 different schedules: 8-12 mg/m2, every 3-4 weeks in 23 patients; 4-6 mg/m2, weekly, in 3 patients; and 2-4 mg/m2, for 5 days, in 7 patients . Summarizing the responses obtained in the 3 schedules, there were 2 partial responders among 5 with Hodgkin's disease, while there were 8 complete responders and 4 partial responders among 28 with non-Hodgkin's lymphoma . The overall response rate for all the evaluable patients was 42% with a complete response rate of 24% . The median response duration was 7+ weeks (range 4-27+ weeks) for complete responders and 7 weeks (range 4-46+ weeks) for partial responders . The major toxicity was myelosuppression: leukocytopenia less than 3,000/microliter occurred in 79% of patients, and thrombocytopenia less than 75,000/microliter in 35% . Other toxic effects were minimal, mild nausea and/or vomiting occurred in 39%, and diarrhea in 3% . Possible drug-related liver and renal dysfunctions were observed in 19% and 10%, respectively . The favorable response to mitoxantrone in patients with prior anthracycline antibiotic therapy suggests that the drug is not fully cross-resistant with anthracycline antibiotics, and that this drug is of value in combination with other drugs as a salvage therapy for patients with refractory or relapsed malignant lymphomas.

Laryngoscope, 1986 Sep, 96(9 Pt 1), 948 - 58
Amelioration of cisplatin-induced ototoxicity by fosfomycin; Schweitzer VG et al.; The continued chemotherapeutic application of cisplatin (cis-diamminedichloroplatinum {II}) necessitates reduction of its dose-limiting toxicity without decreasing its tumoricidal effect . This research project evaluated the efficacy of fosfomycin, a phosphonic acid antibiotic, in decreasing or ameliorating the ototoxicity (high frequency sensorineural hearing loss) and nephrotoxicity (renal tubular necrosis and interstitial nephritis) of cisplatin . Experimentally, fosfomycin effectively inhibits aminoglycoside-induced ototoxicity and nephrotoxicity in animals and humans . The efficacy of fosfomycin in blocking platinum-induced toxicity in the guinea pig was evaluated histologically and functionally using cytocochleography and light microscopy of the organ of Corti and the auditory brain stem evoked response (ABR), and light microscopy of renal corticomedullary tissues, small bowel, liver, lung, and peripheral nerve . The results demonstrate that fosfomycin ameliorates the acute renal tubular necrosis and interstitial nephritis and markedly inhibits the elevation of ABR thresholds and simultaneous outer hair cell loss that can result from cisplatinum administration . Fosfomycin should be considered a potential antidote for the dose-limiting ototoxicity and nephrotoxicity of cisplatin chemotherapy.

Clin Chem, 1986 Sep, 32(9), 1648 - 54
Quantification of analyte and interferent by multipoint analysis; Czervionke RL et al.; We have investigated the application of multipoint kinetic curve-fitting methods to the determination of an analyte in the presence of a single interferent . Our model system for the analyte-interferent was creatinine-acetoacetate as determined with the kinetic Jaffe method . We examined the utility of the following multipoint approaches: simultaneous equations, multivariable linear regression, and iterative multivariable nonlinear regression . With appropriate restrictions, all approaches could detect acetoacetate interference and quantify both creatinine and acetoacetate . A two-stage linear regression approach was both versatile and computationally simple . Interferent was detected in the first stage, and both analyte and interferent were quantified in the second stage if the interferent was assumed known and an adequate fit of the model to the data was obtained . Using the two-stage linear regression model, we obtained results for 10 ketotic patients that correlated well with results by enzymatic methods for creatinine (r = 0.976) and acetoacetate (r = 0.995); we also demonstrated that creatinine could be quantified in the presence of the antibiotic cefoxitin.

J Foot Surg, 1986 Sep-Oct, 25(5), 404 - 6
Bone grafts in the management of osteomyelitis; Isaac MR et al.; Chronic osteomyelitis is a condition that requires aggressive surgical treatment in combination with adequate antibiotic therapy . The use of autogenous cancellous bone grafts to fill the defect created by radical sequestrectomy is an effective way of returning function and stability to the involved part and should, therefore, be considered a viable treatment modality by podiatric surgeons who deal with this type of problem.

Vet Clin North Am Small Anim Pract, 1986 Sep, 16(5), 835 - 49
Periodontal disease . Therapy and prevention; Hawkins BJ; Success in veterinary dentistry lies in good home care and regular, thorough dental prophylaxis . The removal of supragingival and subgingival calculus must be accomplished before periodontal disease can be controlled . When gingival sulcus depths exceed 4 or 5 mm, the gingivae must be excised or reflected to allow proper treatment of the pocket area . Antibiotic therapy should be instituted in the extensively involved veterinary dental patient.

J Vet Pharmacol Ther, 1986 Sep, 9(3), 273 - 9
An evaluation of apramycin soluble powder for the treatment of naturally acquired Escherichia coli infections in broilers; Cracknell VC et al.; During 1983, a series of trials was carried out in Greece, Italy and Jordan, to test the efficacy of the aminocyclitol antibiotic apramycin as a treatment for naturally acquired Escherichia coli infections in broilers . The trials involved a total of 40,389 broilers, 27-39 days of age, in twelve houses at eight different production sites . Three levels of apramycin medication were evaluated: 125, 250 and 500 mg activity/litre drinking water, administered for five consecutive days . Treatment was only initiated after disease had been confirmed by laboratory examination of dead birds . Not all treatments were evaluated in every house . However, each house contained a group of unmedicated birds as controls, while the remaining birds were allocated to one or more apramycin treatment groups . There was a reduction in mortality and an improvement in the final weight and the economic feed conversion ratio in all three treatment groups . The data presented provide support for the use of apramycin sulphate administered in the drinking water for the treatment of E . coli infections in broilers.

Hinyokika Kiyo, 1986 Sep, 32(9), 1359 - 69
{Cooperative phase II study of epirubicin (EPI) in bladder cancer, renal pelvic and ureteral tumors--Urological Cooperative Study Group of EPI}; Niijima T et al.; A phase II study of a new anthracycline anti-cancer antibiotics, epirubicin (EPI), was undertaken in 71 patients with urothelial malignancies; 40 with advanced urothelial malignancies and 31 with superficial bladder cancer . Out of them 32 patients with advanced stage of urothelial cancer were evaluated for the systemic use of EPI, while 30 patients with superficial bladder cancer for intravesical use . Intravenous administration of this new anticancer antibiotic, at a dosage of 60 mg/m2 every three weeks, showed the response rate of 20.0% for advanced bladder cancer and 14.3% for renal pelvic and ureteral tumors . In cases of superficial bladder cancer, at a dosage of 60 mg/30 ml X 3 day every week in principal, the response rate was 66.7% . Eight out of 30 patients showed complete disappearance of the tumor . Twelve patients also showed more than 50% tumor regression . As for adverse effects no serious cardiotoxicity was demonstrated . Anorexia and other gastrointestinal side effects, such as nausea and vomiting, were also seen . Alopecia and myelosuppression were the major adverse effects among patients with systemic EPI administration . With intravesical use of EPI, cystitis syndrome was the major toxicity . However, no systemic side effects were noted in these cases . In conclusion, EPI was assumed to be effective for the treatment of advanced urothelial tumors and superficial bladder cancer.

Jpn J Antibiot, 1986 Sep, 39(9), 2525 - 33
{Pharmacokinetic and clinical studies of cefotiam in the perinatal period}; Yamamoto T et al.; Pharmacokinetic and clinical studies on cefotiam (CTM) in the perinatal period were performed and results obtained are summarized below . Concentrations of CTM in maternal serum, umbilical cord serum and amniotic fluid were examined after a bolus intravenous administration at a dose of 1 g . Data were analyzed using simulation curves drawn by the two- or three-compartment open model . The peak level of CTM in maternal serum was 86.6 micrograms/ml and the half-life of the beta-phase was 0.91 hour . Peak levels of CTM in umbilical cord serum and amniotic fluid were 20.8 micrograms/ml at 0.1 hour and 9.2 micrograms/ml at 3.2 hours after the administration, respectively . The concentration of CTM in amniotic fluid decreased after reaching the peak, but it was still as high as 1.6 micrograms/ml even at 12.0 hours after the administration . These results clearly demonstrated that the transfer of CTM to umbilical cord serum and to amniotic fluid was efficient in protection of perinatal infections . In a clinical trial, CTM was given to 11 patients with perinatal infections . Clinical efficacies were evaluated as excellent in 2 patients, good in 8 patients and poor in 1 patient . No adverse effects were observed in any of the patients studied . In conclusion, CTM was useful and safe antibiotic for the treatment of infections in the perinatal period.

Jpn J Antibiot, 1986 Sep, 39(9), 2488 - 96
{Pharmacokinetic and clinical studies of cefotiam in the perinatal period}; Cho N et al.; Pharmacokinetic studies and clinical evaluations of cefotiam (CTM) were carried out in perinatal mothers and infants and following results were obtained . The drug was promptly absorbed after intravenous injection or intravenous drip infusion in pregnant women, producing dose-related peak serum levels . Placental transfer to the fetus was effective . After intravenous injection or intravenous drip infusion of 1-2 g of CTM, drug concentration of the umbilical cord blood, amniotic fluid and fetal blood exceeded MICs of the drug against main pathogenic organisms . By administration of the dose of 1-2 g twice a day, therefore, perinatal infections should be successfully prevented or treated . Clinically, CTM was effective in the treatment of perinatal infections . Moreover, newborn infants delivered from mothers receiving CTM treatment had drug concentrations higher than MICs of CTM against main pathogenic organisms . Blood CTM concentrations in infants, however, did not remain high very long after birth, and these infants did not exhibit any abnormalities in laboratory tests . Penetration of CTM into mother's milk was ineffective, thus the transfer of CTM from milk to newborn infants was negligible . These results demonstrated that CTM is a clinically useful antibiotic for the prophylaxis and the treatment of perinatal infections.

Oral Surg Oral Med Oral Pathol, 1986 Sep, 62(3), 276 - 9
Analysis of the American Heart Association's recommendations for the prevention of infective endocarditis; Tzukert AA et al.; A probabilistic model analyzes the American Heart Association's (AHA) recommendations for the prevention of infective endocarditis (IE) of dental origin . The model, presented in the form of a flow chart, combines available data elements with the AHA recommendations; mortality serves as the sole valued outcome and payoff measure . The analysis shows that an annual death rate of 1.36 per million population is attributable to the antibiotics administered in an attempt to prevent IE, whereas not more than 0.26 annual deaths per million are traceable to IE of dental origin . Sensitivity and threshold analyses were conducted to determine the conditions under which the recommended prophylactic policy will prove beneficial . The model suggests that the standard AHA antibiotic regimen should be exploited only in IE susceptible patients belonging to the high risk categories and that its value in moderate, low, and negligible risk patients is doubtful . When the use of antibiotics is unavoidable, oral administration is the preferable route.

Proc Natl Acad Sci U S A, 1986 Sep, 83(18), 6702 - 6
Reaction of DNA with chemically or enzymatically activated mitomycin C: isolation and structure of the major covalent adduct; Tomasz M et al.; The antitumor antibiotic mitomycin C is shown to form a covalent complex with calf thymus DNA under anaerobic conditions in the presence of either NADPH cytochrome c reductase/NADPH, xanthine oxidase/NADH, or the chemical reducing system H2/PtO2 . Digestion of the complex with DNase I/snake venom diesterase/alkaline phosphatase yields a single mitomycin deoxyguanosine adduct as the major DNA alkylation product, identified as N2-(2'' beta,7''-diaminomitosen-1'' alpha-yl) 2'-deoxyguanosine (Structure 2) . Two minor adducts, 2-5% each of the total adduct pool, are isolated and identified as the 1'' beta stereoisomer of 2 (Structure 3), and 10''-decarbamoyl-2 (Structure 7) . The same results were obtained with M13 DNA and poly(dG-dC).poly(dG-dC); however, in the latter case, a minor adduct apparently possessing two deoxyguanosine and one mitomycin unit is isolated . Digestion of the covalent mitomycin-calf thymus DNA complex with nuclease P1 yields four dinucleotide adducts, all of which consist of 2 linked at its 3' end to each of the four possible 5' nucleotides (A, T, G, and C) . Upon treatment of each dinucleotide adduct with snake venom diesterase/alkaline phosphatase, 2 is released along with the corresponding free nucleoside . In apparent conflict with the present results, previous reports from another laboratory have indicated that modification of calf thymus DNA by mitomycin C under conditions identical to those described here result in the isolation of three mitomycin C mononucleotide adducts possessing linkages of the drug to N2 and O6 of guanine and N6 of adenine . Evidence is shown suggesting that the latter adducts are actually three of the above four dinucleotide derivatives of 2 obtained independently by us and, thus, all of them in fact possess an identical N2-mitosenylguanine adduct moiety . Model-building studies indicate an excellent fit of the guanine N2-linked drug molecule inside the minor groove of B-DNA with no appreciable distortion of the DNA structure.

J Bacteriol, 1986 Sep, 167(3), 1058 - 65
Growth phase and ompR regulation of transcription of microcin B17 genes; Hernandez-Chico C et al.; The synthesis of the peptide antibiotic microcin B17 was shown to occur as the cells entered the stationary phase of growth . This type of growth phase regulation is commonly observed in the production of a number of different bacterial products such as toxins and antibiotics . Microcin B17 synthesis is also dependent on the product of the ompR gene . To determine the role of transcription in this double regulation of microcin B17 production, operon fusions with Mu d1 (Ap lac) were constructed . Insertions were obtained in all four plasmid genes involved in production of microcin B17 (mcbA-D) and in the immunity region . Three classes of fusions were obtained . Fusions into mcbA, mcbB, and mcbC (first class) exhibited an increase in their transcription as the cells approached the stationary phase . These increases as well as basal levels of transcription were dependent on OmpR . Expression of fusions in mcbD and in the immunity region (second class) was also dependent on OmpR, but their expression remained constant throughout growth . One fusion in mcbC (third class) was obtained which was transcribed in the opposite direction than the others . It showed no growth phase regulation and no OmpR dependence . The implications of these results in terms of the transcriptional organization of the mbc genes are discussed.

J Virol, 1986 Sep, 59(3), 746 - 50
Large T antigens of simian virus 40 and polyomavirus efficiently establish primary fibroblasts; Jat PS et al.; Recombinant retroviruses that transduce the simian virus 40 (SV40) large T antigen or the polyomavirus large T antigen as well as encoding resistance to antibiotic G418 were used to investigate whether these genes alone were sufficient for immortalization of primary cells . The results provided definitive evidence that either viral gene can efficiently establish primary fibroblasts . The capability of the SV40 large T antigen to establish primary fibroblasts was undiminished by a mutation that alters its binding to sequences within the origin of replication . Surprisingly, most of the primary cells established by the expression of the SV40 large T antigen did not have a transformed phenotype . This suggests that transformation by SV40 is not simply due to a high level of expression of the SV40 large T antigen and stabilization of cellular p53.

Int J Zoonoses, 1986 Sep, 13(3), 206 - 9
Human amoebiasis: cultivation and experimental transmission in animals; Akinboade OA et al.; In vitro cultivation was carried out on an initial strain of Entamoeba histolytica from human source . Dysphasic medium was used and concentrations of horse serum and antibiotic varied in response to developments . Experimental infection of dogs, rabbits and mice was carried . Except for the controls, all animals were orally infected and monitored until the experiment was terminated . Parasitaemia became evident as from the 6th day in dogs experimentally infected and until about the 20th day when lower parasitaemia were obtained . Characteristic erosions were observed at autopsy . The tests in rabbits and mice showed that the strain used in this experiment was virulent . This paper highlights both the virulent nature of this parasite on other animals and its zoonotic potential.

Trop Med Parasitol, 1986 Sep, 37(3), 255 - 7
Evaluation of sinefungin for the treatment of Trypanosoma (Nannomonas) congolense infections in goats; Zweygarth E et al.; Caprine Trypanosoma (N.) congolense infections were treated with sinefungin, an antifungal antibiotic nucleoside . Single doses from 10 to 20 mg/kg bodyweight given intramuscularly were not curative for goats; single doses of 25 and 50 mg/kg were toxic, and caused death . Five and 7.5 mg/kg administered twice daily over a three-day period, resulted in a cure in 2 animals, while 2 others relapsed . All animals relapsed when given a single daily dose of 5 or 7.5 mg/kg for 4 consecutive days . When such doses were given twice a day, they caused death in 50% of the goats and the remainder were cured . Raised serum urea levels indicated the severe nephrotoxic side-effects of sinefungin even at subcurative levels . Histopathological examinations revealed an acute tubulonephrosis.

Mutagenesis, 1986 Sep, 1(5), 339 - 41
Tallysomycin-induced mitotic aneuploidy and point mutations in Aspergillus nidulans; Demopoulos NA et al.; Tallysomycin is an antibiotic compound structurally related to bleomycin, and like bleomycins and phleomycins also shows antitumour activity . We have investigated the genetic activity of tallysomycin in the ascomycete Aspergillus nidulans for malsegregation of chromosomes at mitosis and for point mutations . We found that the antibiotic at very low concentrations from 0.025 to 0.2 micrograms/ml had an inhibitory effect on colonial growth of up to 50% and it increased the number of mitotic malsegregants from 311% to 607% over the control value . Tallysomycin at concentrations between 2 and 16 micrograms/ml (which inhibited the germination of conidia from 30 to 90%) also increased the number of methionine suppressor revertants from 59 to 368 per 10(6) conidia . With regard to the mechanism for induced mitotic segregation it was shown that this may involve non-disjunction of chromosomes which through the intermediate formation of unstable aneuploids resulted in formation of stable haploid and diploid segregants.

Schweiz Med Wochenschr, 1986 Aug 30, 116(35), 1166 - 72
{Pyogenic liver abscess}; Vogtlin J et al.; 27 patients who presented with pyogenic liver abscess from 1957 to 1984 are analyzed retrospectively and compared with the literature . Diagnosis and start of therapy were frequently delayed because of the unspecificity of symptoms . Symptoms included fever, abdominal pain, weakness, and loss of weight . In 50% of all patients, the abscess was found by chance at laparotomy or autopsy . The most frequent causes of abscess formation were cholestasis due to extrahepatic obstruction and intraabdominal infections . Frequently a predisposing condition such as carcinoma, diabetes mellitus or alcohol abuse was found . The overall mortality was 25%, and was higher in patients with multiple abscesses of the liver (36%) than in patients with solitary abscesses (10%) . With the introduction of new imaging procedures (ultrasound, computer tomography), the abscesses can be punctured under view and the antibiotic therapy can be based on bacterial analysis . The causative bacterial organism could be identified by cultures of the abscess fluid and blood in up to 90% . The bacteria identified usually were identical to the intestinal flora . Using specific antibiotic therapy, surgical treatment is often unnecessary and can be reserved for abscesses resistant to conservative treatment and for those due to correction of the original source of abscess formation.

J Biol Chem, 1986 Aug 25, 261(24), 11328 - 33
Transfer of fatty acids from the 1-position of phosphatidylethanolamine to the major outer membrane lipoprotein of Escherichia coli; Jackowski S et al.; The utilization of exogenous fatty acids for phospholipid synthesis via the sn-glycerol-3-phosphate acyltransferase was blocked in Escherichia coli mutants lacking acyl-CoA synthetase activity (fadD) resulting in the selective esterification of the 1-position of phosphatidylethanolamine by extracellular fatty acids (Rock, C . O., and Jackowski, S . (1985) J . Biol . Chem . 260, 12720-12724) . The incorporation of exogenous {1-14C}palmitate into phosphatidylethanolamine in fadD mutants was inhibited by chloramphenicol and was depressed by preventing the acylation of the amino terminus of the lipoproteins with the antibiotic globomycin . Lipoprotein acylation was directly examined in fadD mutants harboring hybrid plasmids containing either the major outer membrane lipoprotein gene or a lipoprotein-beta-lactamase gene fusion transcriptionally regulated by the lacUV5 promoter-operator region . Induction of lipoprotein synthesis in the presence of extracellular {1-14C}palmitate increased the amount of radioactivity entering the 1-position of phosphatidylethanolamine and efficiently labeled lipoprotein acyl moieties . Labeling of the 1-position of phosphatidylethanolamine prior to the induction of lipoprotein biosynthesis resulted in the transfer of fatty acid from phosphatidylethanolamine to the lipoprotein . Lipoprotein fatty acids derived from the 1-position of phosphatidylethanolamine were resistant to hydroxylamine hydrolysis, and globomycin reduced the incorporation of exogenous {1-14C}palmitate into lipoproteins by 80% suggesting that this fatty acid is primarily attached to the amino terminus of the lipoprotein . These data illustrate that fatty acid turnover in phosphatidylethanolamine is initiated by the transfer of 1-position acyl moieties to the major outer membrane lipoprotein.

J Biol Chem, 1986 Aug 25, 261(24), 11398 - 403
Novel blockade by brefeldin A of intracellular transport of secretory proteins in cultured rat hepatocytes; Misumi Y et al.; We examined the effect of brefeldin A, an antiviral antibiotic, on protein synthesis, intracellular processing, and secretion in primary culture of rat hepatocytes . The secretion was strongly blocked by the drug at 1 microgram/ml and higher concentrations, while the protein synthesis was maintained fairly well . Pulse-chase experiments with {35S}methionine demonstrated that brefeldin A completely blocked the proteolytic conversion of proalbumin to serum albumin up to 60 min of chase, although its conversion was observed as early as 20 min in the control cells . The drug also inhibited the terminal glycosylation of oligosaccharide chains of alpha 1-protease inhibitor and haptoglobin . These two modifications have been shown to occur at the trans region of the Golgi complex . The drug, however, had no effect on the proteolytic processing of the haptoglobin proform which takes place within the endoplasmic reticulum . Such an effect by brefeldin A is very similar with that induced by the carboxylic ionophore monensin . However, in contrast to evidence that monensin causes a delayed secretion of the unprocessed forms of these proteins, brefeldin A allowed the completely processed forms to be secreted after a prolonged accumulation of the unprocessed forms . Morphological observations demonstrated that the endoplasmic reticulum was markedly dilated by treatment with the drug at 10 micrograms/ml which continuously blocked the secretion . On the other hand, brefeldin A caused no inhibitory effect on the endocytic pathway as judged by cellular uptake and degradation of 125I-asialofetuin . These results indicate that brefeldin A is a unique agent which primarily impedes protein transport from the endoplasmic reticulum to the Golgi complex by a mechanism different from those considered for other secretion-blocking agents so far reported.

Med J Aust, 1986 Aug 4-18, 145(3-4), 158 - 60
Alveolar proteinosis treated with a single bronchial lavage; Wilson JW et al.; An acute febrile illness with respiratory failure and pulmonary infiltrates is a recognized accompaniment of many infective and inflammatory diseases . We report a case of pulmonary alveolar proteinosis, with secondary bacterial infection, that responded to a single pulmonary lavage and the elimination of occupational exposure to dust . In contrast to other interstitial lung diseases, therapy with corticosteroid or antibiotic agents alone was not appropriate . This report underlines the need for early, active intervention in diffuse lung diseases, and emphasizes the importance of obtaining a specific diagnosis in directing subsequent therapy.

Aust Vet J, 1986 Aug, 63(8), 262 - 4
Granulocytopaenia and thrombocytopaenia in dairy cattle--a suspected mycotoxicosis; Jeffers M et al.; During a 6-week period, 22 Dairy Shorthorn cows and heifers died with granulocytopaenia and thrombocytopaenia . Clinical signs observed in the affected animals included increased salivation, pyrexia, depression, rumenal stasis, bilateral epistaxis, melaena, increased bleeding after removal of retained foetal membranes and rapid weight loss . Despite intensive antibiotic and vitamin K therapy and blood transfusions, all affected animals died . The aetiological agent, thought to be a fungal toxin, could not be isolated from post mortem specimens or pasture samples.

J Pharmacobiodyn, 1986 Aug, 9(8), 631 - 7
In vivo evaluation of ethyl cellulose microcapsules containing ampicillin using rabbits, beagle dogs and humans; Uchida T et al.; Ampicillin, an orally administered antibiotic, was microencapsulated with different viscosity grades of ethyl cellulose (10, 50 and 100 cps EC) and was orally administered to rabbits, beagle dogs and humans . A significant sustained release pattern was observed in rabbits . While a significant decrease in the area under the plasma concentration curve occurred, and the sustained release pattern was not obtained in beagle dogs . In humans, the extent of the sustained release was intermediate between the pattern observed in beagle dogs and rabbits . The treatment of data by log-log plots yielded a linear relation between half lives of dissolution of ampicillin from microcapsules in vitro (T50) and the ratios of pharmacokinetic parameters of microcapsules to those of powder . In order to explain the difference in the sustained release pattern of rabbits, beagle dogs and humans, a pharmacokinetic model, considering gastric-emptying and intestinal-transit rates of drug formulations, was established and the pharmacokinetic consideration was done on the basis of the model . It seems that success in sustained release of a drug depended on the magnitude of the gastric-emptying and intestinal-transit rate constant (kgi) of microcapsules, in the case of a drug with a small absorption rate constant (ka) as observed with ampicillin . The magnitude of kgi was thought to be in the order of beagle dogs, humans and finally rabbits.

Chemioterapia, 1986 Aug, 5(4), 263 - 7
Acute, subacute, chronic toxicity and mutagenicity studies of rifaximin (L/105) in rats; Borelli G et al.; Acute, subacute and chronic toxicity-mutagenicity studies of rifaximin (L/105), a new semisynthetic rifamycin SV antibiotic, were conducted in rats . The oral LD50 value for this species was greater than 2000 mg/kg . Rifaximin given orally to rats up to 6 months produced no evident adverse effects up to 100 mg/kg . The moderate effects noted were probably due to the topical action of the drug . Rifaximin did not show any mutagenic activity when compared with mutagenic standards.

Antibiot Med Biotekhnol, 1986 Aug, 31(8), 603 - 6
{Microcalorimetric study of the parameters of dicloxacillin binding with human serum albumin at different temperatures}; Markovich MN et al.; The thermodynamic parameters of human serum albumin (HSA) binding with dicloxacillin, an antibiotic widely used in clinical practice, were determined with the method of differential flow microcalorimetry at 18, 25, 30, 37 and 45 degrees C . The experiments were performed at two ionic strengths: 0.02 and 0.15 . Two hypothetic models of interaction in the HSA-drug system were considered in processing the data for the curves of calorimetric titration . The first model implies the presence of independent homogeneous active sites on the protein . In accordance with the second model there are one primary and secondary independent homogeneous active sites on the biopolymer molecule . It is shown that dicloxacillin association with HSA proceeds according to the mechanism suggesting the presence of one primary and one secondary active sites on the protein molecule . The binding process in the system studied is exothermic, the enthalpy increasing at the temperature change from 18 to 45 degrees C . At the same time the binding constant and enthropy of the system decrease . The influence of the solution ionic strength on the binding process was practically lacking . On the basis of the analysis of the thermodynamic data it is concluded that the character of the binding in the HSA-dicloxacillin system at 18-30 degrees C is hydrophobic . With an increase in the temperature the hydrophoby level decreases.

Virus Res, 1986 Aug, 5(2-3), 265 - 76
The effect of cerulenin on Moloney murine leukemia virus morphogenesis; Katoh I et al.; Cerulenin is an antibiotic that interferes with fatty acid synthesis in eukaryotic cells . It had been shown by Schultz and Oroszlan (1983), that murine leukemia virus (MuLV) Pr65gag, the polyprotein precursor to the virion core proteins contains the fatty acid myristate at its NH2 terminus . We showed that when 20 micrograms/ml of cerulenin is added for 3 h to mouse fibroblasts chronically infected with Moloney (M)-MuLV it causes a greater than 4-fold decrease in virus production . This is accompanied by an accumulation of uncleaved Pr65gag in the infected cells . Further, thin-section electron micrographs of cerulenin-treated cells show a 2-fold increase in the number of nascent-budding forms, as well as the appearance of aberrant viral forms at the cell membrane . This suggests that the failure to add myristic acid to Pr65gag prevents their proper assembly into viral particles.

J Antibiot (Tokyo), 1986 Aug, 39(8), 1144 - 7
Cyclization of phenylacetyl-L-cysteinyl-D-valine to benzylpenicillin using cell-free extracts of Streptomyces clavuligerus; Luengo JM et al.; Benzylpenicillin, a typical antibiotic produced by some species of fungi, was obtained by direct cyclization of the heteropeptide phenylacetyl-L-cysteinyl-D-valine using cell-free extracts of Streptomyces clavuligerus . This is the first description of evidence of the synthesis of benzylpenicillin from a non natural molecule using a bacterial enzyme.

J Antibiot (Tokyo), 1986 Aug, 39(8), 1086 - 91
PD 113,618 and PD 118,309, new pactamycin analogs; Hurley TR et al.; Two antibiotics were isolated from culture broths of a Streptomyces sp . and identified as 8"-hydroxypactamycin and 7-deoxypactamycin . The latter antibiotic was shown to be identical to cranomycin . An additional compound, 8"-hydroxypactamycate, was also isolated.

Fundam Appl Toxicol, 1986 Aug, 7(2), 272 - 86
Association between adverse maternal and embryo-fetal effects in norfloxacin-treated and food-deprived rabbits; Clark RL et al.; Norfloxacin is a new antibiotic which caused embryo-fetal toxicity in association with maternotoxicity when given orally to rabbits at 100 mg/kg/day . The intestinal flora of rabbits is unusually sensitive to many antibiotics and it was suspected that the maternotoxicity and embryo-fetal toxicity caused by oral norfloxacin were secondary to an effect on the intestinal flora . To test this idea, a teratologic study was conducted in which rabbits were dosed on Days 6 to 18 of gestation with norfloxacin given orally at 100 mg/kg/day or subcutaneously at 20 mg/kg/day . The oral treatment caused decreased food consumption (to less than 15 g/day in some animals), body weight loss, an increased resorption rate, and decreased fetal weight . Among the females in the orally dosed group, there was a significant correlation (p less than or equal to 0.005) between the effects on maternal body weight and the resorption rate . The subcutaneous treatment caused little intestinal exposure (biliary excretion = only 2-4% of dose) and no maternotoxicity or embryo-fetal toxicity, even though blood levels of drug were at least as high as those in the oral group . Since the maternotoxicity and embryo-fetal toxicity were specific to the oral route and not correlated with the level of systemic exposure, the maternotoxicity may have been secondary to an effect on the intestinal flora and the embryo-fetal toxicity may have been secondary to the maternotoxicity . The decreased food consumption observed in the oral group may have contributed to the embryo-fetal toxicity since, in a separate study, it was found that lowering the amount of food provided to rabbits on Days 6 to 18 of gestation from 150 g/day to 50 or 15 g/day also caused adverse maternal and fetal effects including, at 15 g/day, fetal malformations.

J Neurol, 1986 Aug, 233(4), 237 - 41
Polymorphonuclear pleocytosis in the cerebrospinal fluid during chemotherapy for tuberculous meningitis; Teoh R et al.; Five patients on chemotherapy for tuberculous meningitis developed sudden and unexpected cerebrospinal fluid pleocytosis consisting predominantly of polymorphonuclear leucocytes . The cellular changes, which developed 4-108 days after starting treatment, were not accompanied by an alteration in the clinical state and disappeared within a week whether or not an additional antibiotic was prescribed . Through the cause is uncertain, possible mechanisms are discussed . We are prompted to report these cases because the cytological changes are not well recognised and may cause difficulties in management.

Br J Obstet Gynaecol, 1986 Aug, 93(8), 843 - 51
Evaluation of colposcopy in the postmenopausal woman; Toplis PJ et al.; Cytology, colposcopy and histology findings in 121 postmenopausal and 120 premenopausal women referred to the Oxford colposcopy clinic were compared; 88% of postmenopausal and 69% of premenopausal women were referred by their general practitioners . Cervical smear reports, within the preceding 5 years, were available for 21% of the postmenopausal and 54% of the premenopausal women . Colposcopic assessment was technically unsatisfactory in 53% of the postmenopausal women because the transformation zone was not completely visible, this contributed to a cone biopsy rate of 71% in this group . Only 17% of postmenopausal women with cervical intraepithelial neoplasia (CIN) were managed with local ablative techniques compared with their use in 61% premenopausal patients overall and in over 70% of the women under 35 years . Local ablation was used in 10 of 14 women using hormone replacement therapy . The cytological false negative rate for postmenopausal Papanicolaou class III, IV and V smears was 9% but for persistent class II inflammatory smears it was 43% . Nine of 23 postmenopausal women with persistent inflammatory dyskariosis despite antibiotic or antifungal treatment were found to have colposcopic appearances of CIN and four had microinvasion or invasion . Colposcopy revealed probable microinvasive or invasive disease in 17 postmenopausal women, seven of whom had class II or III cytology.

J Bacteriol, 1986 Aug, 167(2), 575 - 80
Isolation of tetracenomycin C-nonproducing Streptomyces glaucescens mutants; Motamedi H et al.; We analyzed the properties of tetracenomycin C (TcmC)-nonproducing mutants of Streptomyces glaucescens to establish the nature of pathway intermediates and to provide some information about the genetics of antitumor anthracycline antibiotic production . Using cosynthesis properties and metabolite accumulation data, we classified a collection of 34 TcmC-nonproducing strains into seven different groups . From this information, we deduced the positions of the tcm mutations in relation to a hypothetical TcmC biosynthetic pathway and suggest which pathway enzymes are affected by the different mutations.

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