Antibiotics

FEBS Lett, 1995 Mar 6, 360(3), 231 - 4
The observation of a hedamycin-d(CACGTG)2 covalent adduct by electrospray mass spectrometry; Wickham G et al.; Covalent binding of the antitumour antibiotic hedamycin to the self-complementary hexadeoxyribonucleotide 5'-CACGTG-3' has been investigated by electrospray ionization mass spectrometry (ESI-MS) . Ions due to double-stranded forms of the free 5'-CACGTG-3' and the hedamycin-5'- CACGTG-3' adduct have been observed in ESI mass spectra and their identity has been confirmed by resolution of individual charge states in ESI-MS spectra . Clear evidence that specific base-paired associations are being observed in ESI-MS is provided by the results of a titration experiment involving alkylated and non-alkylated complementary strands . This work demonstrates the potential of this powerful new tool for studying ligand-DNA binding.

Vet Rec, 1995 Mar 4, 136(9), 217 - 20
Severe post-dipping dermatitis and subcutaneous fluid swellings associated with two outbreaks of sheep scab (Psoroptes ovis infestation)
Sargison ND, Scott PR, Clarke CJ, Penny CD, Pirie RS.
Large subcutaneous fluid swellings developed on some of the sheep in two flocks infested with Psoroptes ovis during the two weeks after they had been plunge-dipped in phenol-based solutions . The swellings contained between 1 and 10 litres of exudate and affected 4 per cent of the sheep in each flock . The sheep with subcutaneous fluid swellings or exudative dermatitis had significantly lower serum albumin concentrations than the unaffected sheep (P < 0.05) . In most cases secondary bacterial infections of the exudate occurred and these necessitated intensive antibiotic therapy . The severity of the skin lesions posed a serious welfare problem.

Presse Med, 1995 Mar 4, 24(9), 454 - 8
{Infection from arterial prostheses}; Goeau-Brissonniere O; Infection is a rare complication after implantation of arterial prostheses but the consequences can be particularly severe, both in terms of functional outcome and mortality . Due to this double risk, experimental models have been developed to better understand the pathophysiological mechanisms involved and elaborate preventive and curative strategies . Arterial allografts for in situ replacement constitute a major advance for the prevention of infection . An antibiotic-impregnated protein network fixed to the prosthesis is another promising approach, both for the prevention and the treatment of infected prostheses.

Southeast Asian J Trop Med Public Health, 1995 Mar, 26(1), 188 - 92
Vaginal scrub prophylaxis in abdominal hysterectomy; Vinkomin V; This study was aimed at reducing postoperative infection after abdominal hysterectomy in Chon Buri Hospital . Thirty patients scheduled for total abdominal hysterectomy were randomly divided equally into two groups of 15 patients each and received different preoperative preparation procedures . Group I patients received the procedure routinely used at Chon Buri Hospital comprising vaginal scrubbing in the evening before the operation day followed by abdominal scrubbing in operating room, whereas group II patients received the same treatment as Group I with additional vaginal scrubbing with 10% povidone-iodine immediately prior to the operation . All patients were given routinely antibiotics prophylaxis . After removal of the uterus, the discharge from the vaginal cuff was taken before and after closing the vaginal stump for aerobic and anaerobic cultures . Only 3 of group II patients (20%) were culture-positive before closure of vaginal cuff compared with 11 (73%) of group I patients (p < 0.01) . After closure of the vaginal cuff, the positive bacterial culture declined to 5 (33%) in group I and 2 (13%) in group II (p > 0.05) . Most of isolated organisms were vaginal normal flora . Postoperative infection with E . coli occurred in 2 patients of group I and none of group II (p > 0.05) . Our results suggested that additional prophylactic vaginal scrubbing reduced postoperative bacterial infections, but this observed reduction did not reach a statistically significant level . Thus a larger sample size is needed to substantiate whether vaginal scrubbing could be advocated in a routine practice.

Am J Physiol, 1995 Mar, 268(3 Pt 2), F391 - 7
H(+)-peptide cotransport in Madin-Darby canine kidney cells: expression and calmodulin-dependent regulation; Brandsch M et al.; The transport of the dipeptide glycylsarcosine was studied in the kidney cell lines OK, LLC-PK1, and Madin-Darby canine kidney (MDCK), grown as confluent monolayers on impermeable plastic supports . Uptake of the dipeptide in OK and LLC-PK1 cells was slow, was not inhibited by other peptides, and was not influenced by an inwardly directed H+ gradient, indicating lack of expression of the H(+)-peptide cotransport system in these cells under our conditions . In contrast, uptake of the dipeptide in MDCK cells was rapid and was found to be stimulated by an inwardly directed H+ gradient . This stimulation was markedly reduced by the protonophore carbonyl cyanide p-trifluoromethoxy-phenylhydrazone . The H+ gradient-dependent uptake of glycylsarcosine was inhibited by dipeptides and tripeptides and by the beta-lactam antibiotic cephalexin but not by the amino acids glycine and leucine . The uptake was saturable and apparently occurred via a single transport system . The Michaelis-Menten constant for the system was 1.3 +/- 0.1 mM, and the maximal velocity was 13.3 +/- 0.7 nmol.30.min-1.mg protein-1 . Treatment of MDCK cells with the calmodulin antagonists N-(6-aminohexyl)-5-chloro-1-napthalenesulfonamide (W-7), CGS-9343B, or calmidazolium inhibited the glycylsarcosine uptake by 40-50% in a time- and dose-dependent manner . In contrast, the uptake of alanine, leucine, glucose, and taurine was found to be stimulated by treatment with W-7 . Kinetic analysis revealed that the inhibition of the peptide transport activity was mainly associated with a decrease of the maximal velocity of the system.(ABSTRACT TRUNCATED AT 250 WORDS)

Medicine (Baltimore), 1995 Mar, 74(2), 107 - 8
AIDS in India; Bartlett JG; PIP: The first case of AIDS in India was reported in 1986 . It is now estimated, however, that more than 1.5 million people in the country are infected with HIV, with current projections indicating that India will have more cases of AIDS than any other country in the world by the year 2000 . The HIV epidemic in India is similar in many ways to the epidemics in sub-Saharan Africa and Thailand . Heterosexual intercourse is the main mode of viral transmission, with prostitution and an high prevalence of genital ulcer diseases appearing to be the major contributing factors . Wasting is especially common and Pneumocystis carinii appears to be rare . Tuberculosis is the most dominant opportunistic pathogen among people with HIV in India . The high rates of antibiotic use and abuse, however, suggest the development of multi-drug resistance now or in the near future . The serious nature of the HIV epidemic in India reflects the lack of public health efforts and public education . For example, there is no standardized national program to report cases, the illegal status of homosexuality and prostitution make it difficult to get reliable data on risk factors in official reports, much of the blood supply is not screened, and HIV education is extremely limited . One survey found 40% of physicians unaware that HIV causes AIDS, and 25% believing that AIDS can be transmitted through causal contact . Reprehensible conditions, indeed, ten years into the epidemic .

Am Fam Physician, 1995 Mar, 51(4), 821 - 6
Screening for Chlamydia trachomatis infection; Skolnik NS; Infection with Chlamydia trachomatis can be either symptomatic or asymptomatic . In adults, complications include infertility, chronic pelvic pain and ectopic pregnancy . Complications in newborns include conjunctivitis and pneumonia . Screening of asymptomatic women at high risk for the disease can identify candidates for antibiotic therapy . Until recently, chlamydia cell culture was the only diagnostic test and it was not widely available . Because the specificity of cell culture is 100 percent, it remains the standard against which other tests are measured . The recent development of nonculture tests makes it feasible for most laboratories and physicians' offices to offer testing . The main disadvantage of nonculture tests is low specificity . A positive screening test in a woman at low risk should be confirmed by a second test . Routine screening and treatment of patients who are at high risk can decrease the incidence, complications and transmission of chlamydial infection.

Am J Respir Crit Care Med, 1995 Mar, 151(3 Pt 2), S70 - 4
Aerosolized dornase alfa (rhDNase) for therapy of cystic fibrosis; Hodson ME; The major causes of morbidity and mortality in cystic fibrosis (CF) are the obstruction and damaged airways that result from the accumulation of viscid and infected secretions . Dornase alfa, also called recombinant human DNase I (rhDNase), cleaves extracellular DNA, which is present in inordinately high concentrations in purulent CF airway secretions . Dornase alfa has been found to increase the pourability and reduce the viscoelasticity of CF sputum in vitro and, in an animal model, to increase its mucociliary transportability . Short-term (10-day) Phase I and II clinical trials showed dornase alfa to be safe and effective in improving pulmonary function in clinically stable CF patients with mild to moderate pulmonary disease (FVC > or = 40% of predicted value) . A long-term (24-week) Phase IIB clinical trial demonstrated the importance of administering dornase alfa daily to maintain its efficacy . A large-scale, long-term, Phase III clinical trial, consisting of a 24-week double-blind period and a 24-week open-label extension, confirmed these findings and further demonstrated that dornase alfa reduces the incidence of respiratory tract infectious exacerbations requiring parenteral antibiotic therapy . Dornase alfa also decreased the rate of hospitalizations, the number of days missed from work or school, and the frequency of CF-related symptoms . Adverse events were limited to upper airway irritation (i.e., voice alteration, laryngitis, pharyngitis), rash, chest pain, and conjunctivitis . These manifestations generally were mild and transient, and they did not limit the use of dornase alfa . A small proportion (2 to 4%) of patients developed serum antibodies to dornase alfa, but no patient developed anaphylaxis.(ABSTRACT TRUNCATED AT 250 WORDS)

Am J Surg, 1995 Mar, 169(3), 320 - 3
The surgical implications of chronic granulomatous disease; Eckert JW et al.; BACKGROUND: Chronic granulomatous disease (CGD) of childhood is a rare congenital abnormality of the phagocyte NADPH oxidase system . Affected neutrophils and macrophages have an ineffective respiratory burst and cannot destroy certain phagocytized bacteria and fungi . CGD patients usually present with recurrent pyogenic and fungal infections . Catalase-positive bacteria are frequently involved, since they metabolize the hydrogen peroxide they produce, making it unavailable for augmentation of microbicidal activity in CGD neutrophils . Afflicted patients also have a tendency to form granulomas, which can lead to obstruction of the gastrointestinal and genitourinary tracts . METHODS: Charts of 10 patients with CGD were reviewed for age at diagnosis, surgical procedures, complications of these procedures, and medical treatment . RESULTS: Eight of the 10 children were male . The average age at first presentation was 18 months (range 2 days to 9.8 years) . Each child developed a mean of 9.9 infections and an average of 1.4 infections per year . All required surgical procedures, with an average of 2.9 procedures each . Five children had operative procedures for infections that preceded the diagnosis of CGD . The procedures performed most frequently were incision and drainage of soft-tissue abcesses (7) or perirectal abscess (3), thoracentesis (3), and bronchoscopy (3) . Three children had poor wound healing following surgery . Two developed partial gastric outlet obstruction which resolved with antibiotic therapy . One developed granulomatous cystitis with obstruction which responded to antibiotics . CONCLUSIONS: Since patients with undiagnosed CGD may present with surgical problems, surgeons need to be familiar with this condition . The diagnosis should be suspected in children who have recurrent or unusual infections or unexplained problems with wound healing.

Hepatology, 1995 Mar, 21(3), 674 - 9
Two different dosages of cefotaxime in the treatment of spontaneous bacterial peritonitis in cirrhosis: results of a prospective, randomized, multicenter study; Rimola A et al.; Cefotaxime (CTX) is considered one of the first-choice antibiotics in the therapy of spontaneous bacterial peritonitis (SBP) in cirrhosis . Because CTX is largely metabolized in the liver, this drug may also be effective in SBP by administering lower doses than those habitually used . To investigate this possibility, a prospective, randomized, multicenter study was performed to compare the therapeutic efficacy of two different dosages of CTX in 143 patients with SBP: 71 (group I) were allocated to receive a high dose (2 g every 6 hours, which is one of the most frequently recommended doses in this infection), and 72 (group II) were allocated to receive a low dose (2 g every 12 hours) . At inclusion, both groups were similar in relation to clinical and laboratory data, with the exception of a higher incidence of positive ascitic fluid culture in group I than in group II (59% vs . 40%; P = .029) . The rate of infection resolution was similar for both groups (77% vs . 79%) . Hospital survival was also similar in both groups (69% vs . 79%) . No difference was observed between patients with positive or negative ascitic fluid cultures with regard to infection resolution and patient survival . The duration of antibiotic therapy was similar in both groups (9.0 +/- 3.3 days in group I vs . 8.8 +/- 3.1 days in group II) . In a subset of 13 patients from group I and 11 patients from group II CTX levels were determined in serum (peak and trough) and ascitic fluid (concomitantly with trough serum) . Peak serum levels were similar in patients from both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

J Bacteriol, 1995 Mar, 177(5), 1216 - 24
Regulation of daunorubicin production in Streptomyces peucetius by the dnrR2 locus; Otten SL et al.; Sequence analysis of the dnrR2 locus from the cluster of daunorubicin biosynthesis genes in Streptomyces peucetius ATCC 29050 has revealed the presence of two divergently transcribed open reading frames, dnrN and dnrO . The dnrN gene appears to encode a response regulator protein on the basis of conservation of the deduced amino acid sequence relative to those of known response regulators and the properties of the dnrN::aphII mutant . Surprisingly, amino acid substitutions (glutamate and asparagine) at the putative site of phosphorylation (aspartate 55) resulted in a reduction rather than a complete loss of DnrN activity . The deduced DnrO protein was found to be similar to the Streptomyces glaucescens tetracenomycin C resistance gene repressor (TcmR) and to two Escherichia coli repressors, the biotin operon repressor (BirA) and the tetracycline resistance gene repressor (TetR) . The dnrN::aphII mutation was suppressed by introduction of the dnrI gene on a plasmid . Since the introduction of dnrN failed to restore antibiotic production to a dnrI::aphII mutant, these data suggest the presence of a regulatory cascade in which dnrN activates the transcription of dnrI, which in turn activates transcription of the daunorubicin biosynthesis genes.

Pediatrics, 1995 Mar, 95(3), 373 - 7
The diagnostic utility of bronchoalveolar lavage in immunocompetent children with unexplained infiltrates on chest radiograph; Rock MJ; OBJECTIVE . To assess the diagnostic utility of bronchoalveolar lavage (BAL) in a heterogeneous group of immunocompetent children with unexplained infiltrates on chest radiograph . DESIGN . This was a retrospective case series . SETTING . The setting was a tertiary care referral center in an urban children's hospital . PATIENTS . Twenty-five consecutive children, median age 4 years 6 months, had flexible bronchoscopy with BAL . Preprocedure diagnoses were right middle-lobe syndrome (3 patients), granulomatous lung disease (3 patients), adult respiratory distress syndrome (3 patients), and persistent infiltrate on chest x-ray (16 patients) . The majority of patients were receiving parenteral antibiotics before bronchoscopy . BAL fluid was sent for bacterial, viral, fungal, and, if indicated, mycobacterial cultures . RESULTS . Twenty-seven procedures were performed in 25 patients . A specific diagnosis was made in eight (30%) of the procedures . Four patients had viral infections, two had fungal infections, one had a bacterial infection, and one had a mixed fungal and bacterial infection . CONCLUSION . Submitting BAL fluid for bacterial, viral, and fungal culture can be helpful in diagnosing infection in immunocompetent children . Empiric antibiotic therapy remains the standard treatment for pneumonia in children . Bronchoalveolar lavage may yield a diagnosis in patients unresponsive to empiric antibiotics . Careful selection of patients, a bronchoscopist skilled in the procedure, and the risk/benefit ratio all must be considered.

JAMA, 1995 Mar 1, 273(9), 712 - 20
Foot infections in diabetic patients . Decision and cost-effectiveness analyses; Eckman MH et al.; OBJECTIVE--To examine the cost-effectiveness of approaches to the diagnosis and treatment of patients with type II (non-insulin-dependent) diabetes mellitus (NIDDM) who have foot infections and suspected osteomyelitis . DESIGN--Decision and cost-effectiveness analyses were performed using a Markov model . We examined the prevalence of osteomyelitis, the major complications and efficacies of long-term antibiotic therapy and surgery, and the performance characteristics of four diagnostic tests (roentgenography, technetium Tc 99m bone scanning, indium in 111-labeled white blood cell scanning, and magnetic resonance imaging) . Data were drawn from the English-language literature using MEDLINE searches and bibliographies from selected articles . SETTING--Primary care . PATIENTS--Patients with NIDDM who had foot infections and suspected osteomyelitis but no signs of systemic toxicity . INTERVENTIONS--Following hospitalization for surgical debridement and intravenous antibiotic therapy: (1) treatment for presumed soft-tissue infection, (2) culture-guided empiric treatment for presumed osteomyelitis, (3) 71 combinations of diagnostic tests preceding antibiotic therapy for osteomyelitis, (4) 71 combinations of tests preceding amputation, and (5) immediate amputation . MAIN OUTCOME MEASURES--Quality-adjusted life expectancy, average costs . RESULTS--Culture-guided empiric treatment for osteomyelitis with 10 weeks of oral antibiotic therapy has similar effectiveness to testing followed by a long course of antibiotic therapy if any test result is positive . However, empiric treatment is the least expensive strategy . CONCLUSIONS--Noninvasive testing adds significant expense to the treatment of patients with NIDDM in whom pedal osteomyelitis is suspected, and such testing may result in little improvement in health outcomes . In patients without systemic toxicity, a 10-week course of culture-guided oral antibiotic therapy following surgical debridement may be as effective as and less costly than other approaches.

Reprod Toxicol, 1995 Mar-Apr, 9(2), 159 - 64
Teratogenic effects of DA-125, a new anthracycline anticancer agent, in rats; Chung MK et al.; DA-125 is a new anthracycline antitumor antibiotic derived from adriamycin . Preclinical studies suggest that it may have greater activity and less cardiac toxicity than adriamycin . The potential of DA-125 to induce embryotoxicity was investigated in the Sprague-Dawley rat . One hundred twenty mated SD rats (sperm in vaginal lavage = day 0) were distributed among three treated groups and a control group . DA-125 was given at dose levels of 0, 0.1, 0.3, and 1.0 mg/kg/day administered intravenously to pregnant rats from days 7 to 17 of gestation . All dams were subjected to caesarean section on day 20 of gestation . At 1 mg/kg/day, reduced food intake, reduced body weight, and decreased spleen weight were observed in dams . An increase in the resorption rate and a reduction in the fetal weight were also found . In addition, various types of external, visceral, and skeletal malformations occurred at an incidence of 11.9, 41.8, and 14.5%, respectively . Characteristic malformations included exencephaly, gastroschisis, cleft lip, dilatation of lateral and third ventricles, and fused ribs, among others . There were no signs of maternal toxicity or embryotoxicity at 0.1 and 0.3 mg/kg . The results show that DA-125 is teratogenic at a minimally maternally toxic dose in rats.

Vopr Med Khim, 1995 Mar-Apr, 41(2), 8 - 11
{Production and some properties of covalent conjugates of total histone and kanamycin}; Matiushichev VB et al.; A complex containing total histone and antibiotic kanamycin was produced under optimal conditions using glutaric aldehyde . The obtained water-soluble covalently bound conjugates of these substances were identified by means of enzyme labelled immunoassay and their molecular mass estimated . The validity of new class of highly effective drugs, which may be produced basing on the principles studied, was substantiated considering that histones exhibit the transport properties and are able to augment hematoencephalic barrier permeability.

Eur Respir J, 1995 Mar, 8(3), 467 - 9
Occupational asthma, rhinitis and urticaria due to piperacillin sodium in a pharmaceutical worker; Moscato G et al.; A 28 year old man with no history of atopy was referred to our hospital for possible work-related asthma . He had been employed in the production section of a pharmaceutical company for 2 yrs, and in the last 2 months he had complained of dyspnoea, wheezing, chest tightness, symptoms of rhinitis and a cutaneous rash when exposed to powdered antibiotics . Symptoms disappeared after being transferred to the packaging section . When the subject was admitted to our department he was asymptomatic . Basal lung function tests were in the normal range . Bronchial challenges with methacholine and with ultrasonically-nebulized distilled water were negative . Skin-prick test with piperacillin sodium gave a strong positive response at a very low concentration . Specific inhalation challenge with piperacillin sodium resulted in an immediate asthmatic reaction, and also reproduced rhinitis symptoms and the cutaneous rash . A control challenge with lactose, and the specific challenge test with cefuroxime sodium (another antibiotic to which the patient was exposed at the workplace) were negative . We conclude that piperacillin sodium is an agent that can cause occupational asthma.

Stem Cells, 1995 Mar, 13(2), 94 - 100
Hematopoietic growth factors for the treatment of severe chronic neutropenia; Dale DC; Severe chronic neutropenia (SCN) is a rare but important cause of recurrent fevers, oropharyngeal ulcerations and severe infections . In three forms of SCN, i.e., congenital neutropenia (Kostmann's syndrome and related syndromes), idiopathic neutropenia (both childhood and adult), and cyclic neutropenia, it is now established that long-term treatment with the hematopoietic growth factor, recombinant human granulocyte colony stimulating factor (rHuG-CSF or Filgrastim), can elevate blood neutrophil counts to the normal range in most patients, with a concomitant reduction in infection-related events including fever, oral ulcerations, antibiotic use and symptoms of inflammation . Treatment with this growth factor causes an increase in the number and maturity of marrow cells of the neutrophilic series; other cell lines are largely unaffected . Marrow stimulation and expansion are reflected by the occurrence of bone pain early in therapy, as well as some increase in spleen size in most cases . Adverse effects of therapy are infrequent in both children and adults, and long-term treatment with daily or every-other-day s.c . injections of rHuG-CSF are well accepted . Because of the risk that some patients with chronic neutropenia may have or develop myelodysplasia and/or leukemia, careful pretreatment evaluations (blood, bone marrow and cytogenetics) and long-term observations are extremely important . An international registry for patients with SCN has been established to maintain records and further investigate these conditions.

J Child Neurol, 1995 Mar, 10(2), 105 - 9
Does iron deficiency raise the seizure threshold?
Kobrinsky NL, Yager JY, Cheang MS, Yatscoff RW, Tenenbein M.
To determine the effect of iron status on the seizure threshold, measures of iron sufficiency were prospectively evaluated in 51 children presenting to a pediatric emergency department with a febrile illness with (26) or without (25) an associated febrile seizure . A higher proportion of children from the febrile seizure group had a family history of mental retardation (5/26 versus 0/25, P = .02) or of previous febrile seizures (10/26 versus 2/23, P = .01) . The two groups were otherwise comparable for age, sex, race, family history of afebrile seizures, temperature at presentation, white blood cell count, differential, and vitamin and antibiotic use . Patients with febrile seizures were less frequently iron deficient as defined by a free erythrocyte protoporphyrin level above 0.80 ng/L (2/23 versus 10/25, P < .01), hemoglobin concentration less than 110 g/L (1/26 versus 6/25, P < .03), hematocrit less than 0.30 L/L (0/22 versus 4/25, P < .02), mean corpuscular hemoglobin less than 20 pg (0/25 versus 3/24, P < .04), mean corpuscular volume less than 65 fL (0/26 versus 4/24, P < .02), and platelet count higher than 550 x 10(9)/L (0/26 versus 3/25, P < .04) . This association was even stronger when adjusted for differences in family history . None of the patients in the febrile seizure group was being treated for iron deficiency at presentation, whereas three of 25 controls used an iron supplement (P < .04) . Iron deficiency may protect against the development of febrile seizures.

Childs Nerv Syst, 1995 Mar, 11(3), 129 - 32
Timing of surgery in patients with infected spinal dermal sinuses: report of two cases; Calvit MF et al.; In the past, if infection was present at the time a spinal dermal sinus was discovered, the sinus opening and cerebrospinal fluid were sterilized with a course of appropriate antibiotic therapy prior to the surgical intervention . The cases of two children with an infected spinal dermal sinus are reported here . One patient developed acute paraplegia during the initial stage of antibiotic therapy, and the second patient, who was admitted only with signs of fever and irritability, experienced after antibiotic therapy a complete myelographic blockade secondary to a large infected intradural dermoid tumor . The authors stress the importance of early neuroradiological and neurosurgical management of these lesions, even when an infection is present.

Neurol Med Chir (Tokyo), 1995 Mar, 35(3), 160 - 4
Diagnosis and treatment of brainstem abscess using magnetic resonance imaging and microsurgical aspiration--case report; Imai H et al.; A 6-year-old boy presented with a pontine abscess initially misdiagnosed as brainstem glioma, but he deteriorated rapidly and developed new symptoms of respiratory distress . Magnetic resonance (MR) imaging revealed a rapidly growing mass lesion in the pons . Microsurgical evacuation of the abscess via a suboccipital retromastoid approach resulted in neurological improvement and resolution of the lesion on MR images . Brainstem abscess can be successfully treated with early, accurate diagnosis based on MR imaging and appropriate microsurgical and antibiotic management.

J Clin Gastroenterol, 1995 Mar, 20(2), 154 - 6
D-lactic acidosis in a patient with jejunoileal bypass; Kadakia SC; D-Lactic acidosis is an unique complication of jejunoileal bypass occurring because of alteration of colonic bacterial flora with selective proliferation of D-lactate-producing bacteria . The D-lactate accumulation in the serum is associated with encephalopathy, which responds to oral antibiotic drugs in most patients . Because gastroenterologists may encounter such patients for some time to come, we report a new case and review the literature.

Vnitr Lek, 1995 Mar, 41(3), 179 - 81
{Drugs affecting gastric acidity in the therapy of ulcer disease}; Jirasek V; The most substantial factor in the pathogenesis of peptic ulcers of the gastroduodenum is a preserved HCl secretion (frequently hypersecretion) and the presence of Helicobacter pylori . In some of the ulcers a part is played by non-steroid antirheumatic drugs . In the treatment inhibition of acid secretion by antagonists of H2 receptors proved useful as they heal approximately 80% ulcers in the course of four weeks . Drugs of this group however, do not resolve the main problem of anti-ulcerous treatment, i.e . the liability of ulcers to relapse . 70-80% of the patients develop a relapse within one to two years . Moreover, in 5-10% of the patients the ulcers are resistant to treatment with H2 receptor antagonists . An obvious advance in treatment are inhibitors of the proton pump which intensely inhibit HCl secretion independently on the type of stimulation . At present in clinical practice omeprazole, lansoprazole and pantoprazole are used, all being derivates of benzimidazole . They are the drugs of choice in ulcers resistant to H2 receptor antagonists, in severe forms of reflux oesophagitis in Zollinger-Ellison's syndrome, in ulcers induced by non-steroid antirheumatics . The most substantial fact is that in combination with amoxacillin (or another suitable antibiotic) in 70-80% of cases they eradicate also Helicobacter pylori and heal in a large percentage (70-80%) the ulcerous defect within two weeks.

Res Vet Sci, 1995 Mar, 58(2), 123 - 7
Disposition of antimony and aminosidine in dogs after administration separately and together: implications for therapy of leishmaniasis; Belloli C et al.; The pharmacokinetic behaviour of aminosidine (15 mg kg-1) and antimony (25.65 mg kg-1 as N-methylglucamine antimoniate), administered subcutaneously either separately or together was studied on four dogs . The results demonstrated that antimony (Sb) did not significantly modify the kinetics of aminosidine (AM) but that the kinetic behaviour of the metal was markedly influenced by the antibiotic, as shown by the differences in mean residence time (MRT), elimination rate constant (Kel) and area under the curve (AUC) with and without the antibiotic (MRT{Sb} = 243.8 +/- 29.5 minutes, MRT{Sb+AM} = 1067.9 +/- 199.2 minutes; Kel{Sb} = 0.008 +/- 0.001 min-1, Kel{Sb+AM} = 0.0015 +/- 0.0003 min-1; AUC{Sb} = 21,024.6 +/- 4448.5 micrograms min ml-1, AUC{Sb+AM} = 130,478.5 +/- 30,481.7 micrograms min ml-1) . The persistence of high serum concentrations of antimony when it was administered with aminosidine suggests that the therapeutic doses commonly used should be reduced and that the interval between administration should be increased to avoid the metal reaching toxic concentrations.

HNO, 1995 Mar, 43(3), 188 - 90
{Unilateral recurrent nerve paralysis in suspected Lyme borreliosis}; Neuschaefer-Rube C et al.; Cranial nerve palsy can often be observed in Borrelia burgdorferi infection . A dysphonic patient with a long lasting left-sided recurrent nerve palsy was treated with ceftriaxone, an antibiotic drug for the therapy of Lyme borreliosis . On the 7th day of application the paretic vocal fold showed recovering movements up to regular vocal fold function and normal stroboscopic results . Clinical and serologic constellations and their therapeutical implications are discussed.

Z Orthop Ihre Grenzgeb, 1995 Mar-Apr, 133(2), 166 - 75
{The use of massive allograft in reconstruction following resection of bone tumors of the extremities}; Wuisman P et al.; Reported are indications, techniques and clinical outcome of 45 patients with resection of a primary malignant or aggressive benign tumor of the extremities, reconstructed with an allograft . The goal of this procedure is to achieve a wide resection of the tumor and to reconstruct the defect saving the limb . Bridging the osseous defect, we used an osteochondral allograft (14), intercalary allograft (16), allograft arthrodesis (14) and composite reconstruction (1) . There were 3 deep infections, 3 superficial infections, 2 pseudarthrosis and 1 rejection found as complications . After local revision of the infections by allograft explantation and temporary implantation of antibiotic-loaded chains, another allograft could be implanted with success . Using different, individual adapted operative methods and allografts, a broad spectrum of bone defects after resection of bone tumors and, if necessary revisions, can be treated.

Med J Malaysia, 1995 Mar, 50(1), 42 - 51
Outcome of inborn compared with outborn very low birth weight infants admitted to level 3 Malaysian nurseries . Neonatal Data Collection Group; Therapeutic lamellar keratectomy in the management of nontuberculous Mycobacterium keratitis refractory to medical treatments; Department of Ophthalmology, National Cheng Kung University Hospital, Tainan, Taiwan, R.O.CNontuberculous Mycobacterium keratitis is characterized by its indolent course and poor response to antibiotic drugs . Between November 1989 and September 1993, 10 eyes diagnosed to have nontuberculous Mycobacterium keratitis underwent therapeutic lamellar keratectomy in conjunction with fortified topical medications . Nine operated eyes (90%) recovered with a shortened course and healed with an inactive scar . Six patients (60%) achieved a visual acuity of 20/40 or better postoperatively . For recalcitrant nontuberculous Mycobacterium keratitis, therapeutic lamellar keratectomy is highly recommendable for patients with intractable paracentral or peripheral ulcer, for uncompliant patients, for patients who cannot tolerate drug-induced ocular toxicity, or when penetrating keratoplasty is to be reserved for late rehabilitation of the eye.

Eur J Gastroenterol Hepatol, 1995 Mar, 7(3), 283 - 6
Primary pulmonary hypertension developing 11 years after a splenorenal shunt for portal hypertension in hepatic cirrhosis; Shah HA et al.; OBJECTIVE: To describe a patient with pulmonary and portal hypertension and to review the pathogenesis and management of this condition . PATIENT: A 22-year-old woman with portal hypertension and liver cirrhosis who later developed pulmonary hypertension . INTERVENTIONS: The patient received antibiotic therapy and underwent a splenectomy and proximal splenorenal shunt for portal hypertension . She later received hydralazine, digoxin and warfarin for pulmonary hypertension . MAIN OUTCOME MEASURES: After undergoing a splenorenal shunt the patient made a good recovery . However, she later developed pulmonary hypertension and died after undergoing a hysterectomy and a bilateral salpingo-oophorectomy . CONCLUSIONS: The concomitant development of portal and pulmonary hypertension in the same patient has a poor prognosis . The treatment available for patients with these conditions is unsatisfactory and most patients eventually die as a result of cardiovascular disease . Cardiopulmonary and liver transplantation should be considered in suitable patients.

Nippon Jibiinkoka Gakkai Kaiho, 1995 Mar, 98(3), 368 - 79
{Distortion-product otoacoustic emissions in kanamycin-treated guinea pig cochlea}; Kumagai S; Measurement of distortion-product otoacoustic emissions (DPOAE) is widely accepted as one of the most valuable tools for evaluating the frequency of specific cochlear pathology . Previous studies have revealed that distortion-product levels in the ear canal are definitely correlated with degree of damage in the cochlea . However, there seem to be no clear data of help in predicting the distribution and grade of damage in the cochlea quantitatively on the basis of the results of this non-invasive test . The present study is designed to assess correlations between degree of outer hair cell (OHC) damage by a potent ototoxic antibiotic, kanamycin, and DPOAE levels at the characteristic frequency at the site . Guinea pigs were used after daily intramuscular administration of kanamycin for 7 or 10 days . DPOAE levels were measured using a system (CUBDIS: Etymotic Research) with 78 frequency combinations of iso-intensity primaries from 0.5kHz to 16kHz of f2 . The frequency ratio (f2/f1) was set at 1.2 . Distortion-product level plots versus f2 (DP-grams) were constructed . The integrity of the OHC system was evaluated histologically by the succinic dehydrogenase (SDH) method under a light microscope . Cochleograms were constructed by calculating percentages of intact OHCs along the basilar membrane in 1-mm blocks . The DP-grams and the histopathological cochleograms showed essentially identical patterns in the kanamycin-damaged guinea pig cochlea . The results suggest that: 1) The generation of DPOAE requires functioning OHCs . 2) DPOAE measurement provides information allowing prediction of OHC damage distribution in the cochlea without histological investigations . 3) Careful setting of primary levels and other parameters is necessary to reliably predict the pathology . 4) Attempts to detect of minimal OHC damage could fail . 5) DPOAE seem very useful for monitoring cochlear function in clinically.

J Clin Pathol, 1995 Mar, 48(3), 223 - 5
Iron metabolism and fungal infections in patients with haematological malignancies; Iglesias-Osma C et al.; AIM--To determine whether iron metabolism influences the incidence of systemic fungal infection in patients with haematological malignancies . METHODS--The study population comprised 74 patients who had undergone myeloablative chemotherapy . Systemic fungal infections were classified as confirmed (histological confirmation or characteristic septate hyphae) or possible (antibiotic resistant fever which resolved following administration of intravenous amphotericin B, together with either typical radiographic lesions or massive oropharyngeal candidiasis) . Parameters of iron metabolism included serum iron concentrations, total iron binding capacity, serum transferrin, and ferritin concentrations and transferrin saturation values . RESULTS--Patients who developed a fungal infection had substantially increased transferrin saturation values and ferritin concentrations at diagnosis together with low serum transferrin and high serum iron concentrations . This profile was present in patients with a fungal infection regardless of the underlying haematological disorder . CONCLUSION--Increased transferrin saturation values and high ferritin concentrations may be additional risk factors for the development of systemic fungal infection in patients with haematological malignancies.

Toxicol Lett, 1995 Mar, 76(2), 127 - 34
Gentamicin-induced kidney damage and lipid peroxidation in rats; Fauconneau B et al.; Although it has been reported that injections of gentamicin induces lipid peroxidation in rat renal cortex (Ramsammy et al . (1985) Biochem . Pharmacol . 34, 3895-3900), our results showed no modification of thiobarbituric-reagent substances (TBARS) or in analysis of the polyunsaturated fatty acid profile . Moreover, endogenous vitamin E and glutathione were not consumed . In in vitro systems, gentamicin incubated with microsomes, homogenates and kidney slices from the normal rat failed to induce lipid peroxidation . We show that the increase in TBARS in vivo detected by Ramsammy et al . was wrongly attributed to the oxidant power of gentamicin . As this antibiotic does react positively to thiobarbituric acid in the presence of a system generating free radicals, it is possible that these authors accidentally introduced such a system into their experiments.

Aust Fam Physician, 1995 Mar, 24(3), 379 - 85
The management of male subfertility by in vitro fertilisation techniques; Kovacs G et al.; Although IVF was developed for the treatment of tubal infertility, it is clear that it has a significant application in treatment of couples where the problem is one of male subfertility . This is particularly relevant because, despite the developments in reproductive medicine, in most males there is no identifiable cause for the poor semen quality . Therefore, for these men there is no efficacious method of treatment . Varicocele ligation and the use of agents such as clomiphene citrate, mesterolone empirical antibiotic therapy, and anabolic steroids have not been show to be beneficial when subject to controlled trials . The concept of improving the chance of fertilisation by taking the oocytes to the sperm in vitro is therefore the first feasible therapeutic option available to these subfertile couples . However, these possibilities should not obviate the need for a thorough assessment of the subfertile male and continuing research into the basis of male infertility . During the past decade new methods of sperm preparation, modified methods of insemination, and the use of microinjection have been developed . IVF is now a realistic option for couples if the male is subfertile . It has been suggested by some critics of these techniques that the brunt of the discomfort and risk has to be borne by the women where the problem appears to be solely with the male partner . Nevertheless, as having children is a 'couple' decision, prospective couples need to consider whether such procedures are acceptable to them.(ABSTRACT TRUNCATED AT 250 WORDS)

J Intraven Nurs, 1995 Mar-Apr, 18(2), 92 - 6
Peripherally inserted central catheter exchange using a breakaway sheath: a new approach; Fabian B; There is an increasing demand for the use of peripherally inserted central catheters (PICC) . In hospitals, clinics, nursing homes, skilled care centers, hospices, alternative care centers, and homes, more PICC lines are being inserted . Therapies are complex and involve lengthy protocols to combat multiple diseases and antibiotic-resistant infections.

Minerva Anestesiol, 1995 Mar, 61(3), 71 - 5
{Long-term results of a hearing screening in critically ill patients dismissed from an intensive care unit}; Cavaliere F et al.; AIM . To evaluate the auditive function of a group of critical patients after discharge from an ICU . DESIGN . An audiological screening was carried out 90-120 days after discharge . PATIENTS . Eighteen patients, that had been admitted to a polyvalent ICU for head injury, stroke or complicated neurosurgical procedures . They had all been in a coma . INTERVENTIONS: all the patients had undergone orotracheal intubation and mechanical ventilation lasting more than a week as well as ototoxic drugs (aminoglycosides and furosemide) administration . Antibiotic plasma levels had been monitored . MEASUREMENTS AND RESULTS . At examination, only 7 subjects were aware of being hypoacusic; no other symptom was reported . However audiometry and impedentiometry revealed the presence of mono or bilateral middle ear effusion in 11 subjects (61%) and high frequency neurosensorial hypoacusia in 2 cases (11%) . Human voice frequencies were poorly affected by both transmissive and neurosensorial damages so that subjects did not report any hearing loss . CONCLUSIONS . Neurosensorial hypoacusia was probably caused by amynoglycoside toxicity in spite of blood level monitoring; ABR could be effective in preventing toxic damage by detecting early hearing impairment . Middle ear effusion occurrence is difficult to be prevented but appropriate medical therapy is usually effective after the recovery from coma.

J Diarrhoeal Dis Res, 1995 Mar, 13(1), 39 - 43
Genetic analysis of tetracycline-resistant plasmids in enteropathogenic Escherichia coli isolated from patients in Nigeria; Daini OA et al.; Genetic analysis of antibiotic-resistant plasmids from 102 serologically defined strains of enteropathogenic Escherichia coli from Nigeria was carried out . All the isolates were screened for susceptibility to antibiotics, and 47 were found resistant to tetracycline . A total of 138 plasmids was isolated by agarose gel electrophoresis . Transformation and conjugation experiments showed that 57.4% of the resistant strains carried R-plasmids ranging in sizes from 2 to 46 x 10(6) daltons . Plasmid-determined resistance to tetracycline, ampicillin and streptomycin was found . Restriction endonuclease analysis of three of the commonest plasmids: p1679, p529 and p1479 revealed relatedness with respect to function and structure . The DNA segment on which TcR gene is located on each of them was identified by cloning into the vector plasmid pGL101 . The recombinant plasmids pOADI and pOAD2 gave full expression of TcR gene when transformed into E . coli DHI . Furthermore, the tetracycline-resistant strains were examined for their phenotypic behaviour with respect to tetracycline and its lipophilic analogs.

Bull Cancer, 1995 Mar, 82(3), 202 - 7
{Combination of mitoxantrone-vinorelbine as first-line chemotherapy for metastatic breast carcinoma}; Ferrero JM et al.; A phase II trial was performed to assess the efficacy and toxicity of the combination mitoxantrone (MXN) and vinorelbine (VNR) as first-line chemotherapy for metastatic breast cancer . Forty-one patients with metastatic disease or local relapse recruited between March 1991 and April 1993 received a first-line chemotherapy treatment consisting in 12 mg/m2 intravenous (IV) bolus of MXN on day 1 followed by a 20-minute perfusion of 25 mg/m2 of VNR on days 1 and 8 . Cycles were repeated every 21 days until evidence of disease progression or of severe toxicity . Thirty-seven patients were evaluable for response and all 41 for toxicity . An objective response was observed in 19 patients (51%; 95% confidence interval, 45 to 74%) . The response was complete in a further 11 (30%) . Median time to treatment failure was 9 months . Median survival was 14 months . There were no treatment-related deaths . Limiting toxicity was myelosuppression . Leukopenia occurred in 29 patients (71%) and was grade 3 or 4 in nine of these (15%) . Grade 2 or 3 anemia was encountered in six patients (15%), grade 1 thrombocytopenia in one, neurotoxicity (constipation) in two, and grade 2 or 3 alopecia in 12 (29%) . Nausea/vomiting requiring antiemetic treatment was experienced by only two patients (5%) . There were two cases of septicemia treated by antibiotic therapy in hospital.

JPEN J Parenter Enteral Nutr, 1995 Mar-Apr, 19(2), 133 - 6
Peripherally inserted central catheters: a report of 2506 catheter days; Loughran SC et al.; BACKGROUND: The establishment of reliable central venous access is essential in the management of patients with major complications, including pneumothorax and hemopneumothorax . Although peripherally inserted central catheters (PICCs) offer advantages over traditional central venous approaches, PICC lines are associated with a number of insertion and maintenance problems, including clotting and catheter fracture . These complications often result in catheter removal before completion of prescribed therapy . METHODS: We conducted a retrospective descriptive study in a convenience sample of 322 consecutively placed PICC lines . Study variables included size of catheter, tip placement, infused solutions, patient diagnosis, and unit of line placement . The rationale for line discontinuance as well as for complication rates is described . RESULTS: Complication rates for infection and central venous thrombosis were less than 1% . Phlebitis occurred in 9.7% of patients, and catheter fracture occurred in 9.7% of patients . Two distinct clusters of phlebitis, early and late development, were observed . Early phlebitis is attributable to the mechanics of insertion, and late phlebitis is attributable to chemical and patient-specific causes . Catheter fractures were primarily related to tearing of the catheter during insertion or traction on the catheter-hub junction (51.6%) . CONCLUSIONS: The majority of published data about PICC lines is in the area of chemotherapy or antibiotic infusion . Our study supports the use of PICC lines in patients receiving a variety of solutions, primarily parenteral nutrition . With an experienced, team approach to catheter placement and maintenance, PICC lines provide reliable, cost-effective venous access and reduce many of the complications of central venous access in a variety of clinical settings.

Comp Biochem Physiol C Pharmacol Toxicol Endocrinol, 1995 Mar, 110(3), 321 - 7
Inhibitory effect of sodium ursodeoxycholate on basal and stimulated short-circuit current across the isolated toad skin; Alonso CE et al.; The effect of sodium ursodeoxycholate (U) on short-circuit current (SCC), an index of basal and stimulated net ion transport across isolated skins of Bufo arenarum toads, was tested . U inhibited basal SCC when added to the epidermal side of the skins . The inhibitory effect was reversible after rinsing the preparation during 60 min . U also inhibited the natriferic response to oxytocin, db-cAMP and theophylline by 82%, 49% and 47%, respectively . Inhibition of SCC by exposure to U was reversed by the polyene antibiotic nystatin . In turn, SCC induced by nystatin in the amiloride-treated skin was insensitive to U and blocked by ouabain, a Na+, K(+)-ATPase inhibitor . These results strongly suggest that the effect of U is exerted at the apical membrane of sodium transporting cells, and rule out the existence of an additional site of inhibitory action of U.

Bone Marrow Transplant, 1995 Mar, 15(3), 479 - 81
Pulmonary nocardiosis in a patient with a bone marrow transplant . Bone Marrow Transplantation Team; Shearer C et al.; Infection with nocardia is rare in BMT patients . We described the first reported case of pulmonary nocardiosis in an allogeneic marrow recipient with graft-versus-host disease . The patient developed nocardial infection while receiving trimethoprim-sulfamethoxazole as prophylaxis against Pneumocystis . The salient clinical presentation was right lower lung consolidation; the diagnosis was established by prolonged incubation of an open lung biopsy specimen . Antibiotic therapy included timentin and later, imipenem . However, the patient died with uncontrolled infection . Necropsy revealed nocardial lung abscesses and disseminated infection from cytomegalovirus.

Biofizika, 1995 Mar-Apr, 40(2), 317 - 22
{Intensification of the ionophoric effect of polymyxin M by free fatty acids . Dependence of the length of the fatty acid chain}; Podgaets ER et al.; Mechanisms of potentiation of ionophoric effect of polymyxin M by free fatty acids was studied using measurement of electrical properties of bilayer lipid membranes . Among used unsaturated fatty acids the palmitic acid appeared to be the most effective . The obtained dependence of ionophoric effect of membrane antibiotic on the chain length of the fatty acid may be explained by the existence of the complex of special size appropriate to the membrane thickness . We suppose that free fatty acid and polymyxin M form the ion-conducting structure in lipid bilayer.

Antibiot Khimioter, 1995 Mar, 40(3), 16 - 21
{Multifactor analysis of the action of norfloxacin on the humoral immune response}; Iordanova AI et al.; Multifactor analysis of the norfloxacin action on the primary immune response to the bacterial antigen (EV vaccine fraction 1) and cellular antigen (sheep erythrocytes) in mice was carried out with using a wide variety of the doses and administration times . In the doses corresponding to the average therapeutic ones norfloxacin was shown to have no effect on the humoral immune response to the bacterial and cellular antigens . In the subtherapeutic doses norfloxacin increased it thus mainly stimulating the synthesis of the IgM antibodies . In the doses exceeding the therapeutic ones the antibiotic lowered the antibody content . The diverse type immunoregulatory action of norfloxacin on the content of the IgG and IGM antibodies could be useful in the rational choice of fluoroquinolones for the treatment of patients with selective deficiency of immunoglobulins of various classes.

In Vivo, 1995 Mar-Apr, 9(2), 113 - 5
The effects of roxatidine on neuromuscular transmission; Bossa R et al.; We have investigated the effects of the H2 receptor antagonist roxatidine on the neuromuscular transmission by using the sciatic nerve-gastrocnemius muscle preparation of the rat in vivo . Roxatidine, administered by i.v . injection, potentiates the neuromuscular blockade induced by d-tubocurarine, pancuronium and aminoglycoside antibiotic, kanamycin . Moreover, the drug alone is capable of producing a blockade on the preparation stimulated at high frequency . The neuromuscular blockade induced by roxatidine is partially reversed by 4-aminopyridine but not by dimaprit.

Biol Chem Hoppe Seyler, 1995 Mar, 376(3), 179 - 85
Nitric oxide generation during cellular metabolization of the diabetogenic N-methyl-N-nitroso-urea streptozotozin contributes to islet cell DNA damage; Kroncke KD et al.; The N-methyl-N-nitroso-urea streptozotocin is an antibiotic with diabetogenic, carcinogenic and antitumor activity thought to act via alkylation of DNA and proteins . Evidence points to a release of bioactive nitric oxide (NO) from streptozotocin as an additional cytotoxic activity of this drug . Here we show by EPR spectroscopy, that NO is not generated during spontaneous decay of streptozotocin but that its metabolization in rat hepatocytes and pancreatic islet cells yields NO . This NO formation is not due to a NO synthase (NOS) activity since NO formation in hepatocytes in the presence of streptozotocin is not blocked by the NOS inhibitor NG-methyl-L-arginine . By iNOS-specific RT-PCR no positive signal for specific mRNA presence was obtained in streptozotocin-treated cells, proving that iNOS activity was not induced during cell isolation procedures and did not account for the NO release . Furthermore, early DNA-strand breaks induced either by SZ or by the NO donor nitroprusside were both significantly reduced in the presence of an intracellular NO scavenger . In contrast, DNA damage found after incubation with the purely alkylating agent methylmethanesulfonate was not inhibited by the NO trap . These results prove that intracellular formation of NO occurs during degradation of SZ within cells . This NO appears to contribute significantly to streptozotocin-induced cytotoxicity.

Bone Marrow Transplant, 1995 Mar, 15(3), 349 - 51
G-CSF after autologous bone marrow transplantation for malignant diseases in children . Spanish Working Party for Bone Marrow Transplantation in Children; Madero L et al.; The use of recombinant human granulocyte-stimulating factor (G-CSF) has been shown to effectively accelerate granulocytic recovery after autologous bone marrow transplantation (BMT) in adults . The experience, however, is limited in children . We evaluated the hematopoietic reconstitution in 41 consecutive children undergoing autologous BMT for hematologic malignancies (21 acute lymphoblastic leukemia, five non-Hodgkin's lymphoma) and solid tumours (seven neuroblastoma, two brain tumor, three Ewing's sarcoma, two Wilms' tumor, one rhabdomyosarcoma) . Their ages ranged from 2 to 16 years (mean 7.2 years) . rhG-CSF was given at a dose of 10 micrograms/kg/day i.v . in a 2h infusion from day +1 until +28 or until the absolute neutrophil count (ANC) was > 1 x 10(9)/L . These patients were compared with a similar historical control group of 38 children who did not receive rhG-CSF after autologous BMT . The number of cells infused was similar in both groups . At the dose and schedule used in the present study, rhG-CSF was well tolerated and no side-effects were observed . The number of cell infused was similar in both groups . At the dose and schedule used in the present study, rhG-CSF was well tolerated and no side-effects were observed . Our data show that rhG-CSF accelerates engraftment and reduces the number of febrile days and antibiotic use . Furthermore, patients who were treated had less infections.

J Membr Biol, 1995 Mar, 144(2), 131 - 45
Ion selectivity of colicin E1: III . Anion permeability; Bullock JO et al.; The antibiotic protein colicin E1 forms ion channels in planar lipid bilayers that are capable of conducting monovalent organic cations having mean diameters of at least 9 A . Polyvalent organic cations appear to be completely impermeant, regardless of size . All permeant ions, whether large or small, positively or negatively charged, are conducted by this channel at very slow rates . We have examined the permeability of colicin E1 channels to anionic probes having a variety of sizes, shapes, and charge distributions . In contrast to the behavior of cations, polyvalent as well as monovalent organic anions were found to permeate the colicin E1 channel . Inorganic sulfate was able to permeate the channel only when the pH was 4 or less, conditions under which the colicin E1 protein is predominantly in an anion-preferring conformational state . The less selective state(s) of the colicin E1 channel, observed when the pH was 5 or greater, was not permeable to inorganic sulfate . The sulfate salt of the impermeant cation Bis-T6 (N,N,N',N'-tetramethyl-1,6-hexanediamine) had no effect on the single channel conductance of colicin E1 channels exposed to solutions containing 1 M NaCl at pH 5 . The complete lack of blocking activity by either of these two impermeant ions indicates that both are excluded from the channel lumen . These results are consistent with our hypothesis that there is but a single location in the lumen of the colicin E1 channel where positively charged groups can be effectively hydrated . This site may coincide with the location of the energetic barrier which impedes the movement of anions.

Curr Eye Res, 1995 Mar, 14(3), 209 - 14
Effects of topical FK506 on endotoxin-induced uveitis (EIU) in the Lewis rat; Hikita N et al.; FK506 is a macrolide antibiotic and a potent immunosuppressant . To investigate the effect of topical FK506 on acute ocular inflammation, we evaluated its action on the development of endotoxin-induced uveitis (EIU) . At two different concentrations of 0.05% and 0.3%, topical FK506 was applied to Lewis rats with EIU . In aqueous, the mean number of inflammatory cells per microliter +/- SEM was 2,389 +/- 1,277, 1,571 +/- 1,562, 898 +/- 882, and 69 +/- 152 for rats treated with vehicle alone, 0.05%, 0.3% FK506, and 1% prednisolone acetate . The median of histological grades was 2, 1.5, 0.8, and 0.5 for animals treated with these 4 different regimens respectively . Analysis of aqueous protein showed a small reduction in FK506-treated animals . Mean blood levels of FK506 were low in rats treated with topical FK506 (0.05%, 0.84 ng/ml; 0.3%, 2.0 ng/ml) suggesting that its therapeutic effect was not secondary to the systemic absorption of the drug . Although FK506 is not as effective as prednisolone, 0.3% FK506 produced significant decreases in the mean aqueous inflammatory cell number and histological inflammatory score as compared to control vehicle alone . We conclude that topical FK506 can suppress EIU in a dose-dependent fashion and may be an alternative medication for patients with anterior uveitis and contra-indication to topical steroid.

J Neurosci Methods, 1995 Mar, 57(1), 27 - 35
Perforated-patch recording with gramicidin avoids artifactual changes in intracellular chloride concentration; Kyrozis A et al.; The antibiotic gramicidin, when incorporated into lipid membranes, forms pores that are exclusively permeable to monovalent cations and small unchanged molecules . We report the use of gramicidin for perforated patch-clamp recordings in the whole-cell mode . Recordings were performed in cultured rat spinal cord dorsal horn neurons . Cells had stable resting potentials and series resistances for times routinely exceeding 60 min . To test if intracellular chloride concentration ({Cl}i) remains stable with this technique, we measured responses to agonists of glycine and GABAA receptors, both of which gate chloride conductances . The driving force for these responses remained stable at values that differed significantly from values that would be expected if {Cl-}i were biased towards pipette {Cl-} . We conclude that gramicidin perforated-patch recording, in addition to other properties of the perforated-patch recording technique, has the advantage of not altering {Cl-}i . It is, therefore, an electrophysiological method particularly suitable for studies of anionic channels when {Cl-}i is a variable of interest, as well as for studies of homeostatic {Cl-}i regulation.

Leuk Lymphoma, 1995 Mar, 17(1-2), 139 - 45
Economic analysis of prophylactic G-CSF after mini-BEAM salvage chemotherapy for Hodgkin's and non-Hodgkin's lymphoma; Dranitsaris G et al.; The objectives of this study were to compare the costs of managing lymphoma patients who underwent mini-BEAM salvage chemotherapy with G-CSF prophylactic support against a group of similar patients without growth factors . Methods used included: 1) A retrospective chart review was conducted to estimate the average length of hospitalization and resource consumption for the management of fever and neutropenia in the two groups of patients and 2) An economic analysis was then performed from a hospital perspective which considered only institutional resource utilization . Costs of antibiotic support and monitoring, lab tests as well as G-CSF were calculated . Results demonstrated that overall, patients who received prophylactic G-CSF after chemotherapy required 2 fewer hospital days compared to controls . The administration of G-CSF resulted in a savings of approximately $1580/patient relative to control . When the initial G-CSF expenditure was included in the analysis, the total net cost/patient was similar between the two groups . In conclusion, the results of the current study support the routine use of G-CSF in patients receiving salvage chemotherapy with mini-BEAM . The initial G-CSF expenditure would be offset by reduced hospitalization.

Bioorg Khim, 1995 Mar, 21(3), 188 - 96
{Cleavage of a double-stranded DNA target by bleomycin derivatives of oligonucleotides, forming a ternary complex}; Sergeev DS et al.; Hexadecathymidylate derivatives, containing covalently-bound antitumor antibiotic bleomycin A5, were shown to form a triple-helix complex with double-strand 30-bp DNA-target and to carry out within this complex complementary-addressed DNA modification . Fivefold excess of reagent in relation to target leads to non-specific cleavage mainly of pyrimidine-rich DNA strand . Total degrees of the target-strand cleavage by 5'- and 3'-bleomycin derivatives of hexadecathymidylate were 25 and 35% for purine-rich strand and 47 and 36% for pyrimidine-rich strand . Degrees of non-specific cleavage by 5'-bleomycin derivative of hexadecanucleotide that does not form triple-helix were 6 and 16% for purine- and pyrimidine-rich strands, respectively . Comparison of these data has shown that site-specific cleavage prevailed nonspecific one . Triplex of 5'-bleomycin derivative with DNA melted by 5 degrees C lower (m.p . 40 degrees C) than the similar triplex of hexadecathymidylate . Temperature lowering from 50 to 20 degrees C increases the DNA-cleavage degree according to the increase in the part of target molecules involved in triple-helix formation.

Mov Disord, 1995 Mar, 10(2), 195 - 200
Oculofacial-skeletal myorhythmia in central nervous system Whipple's disease: additional case and review of the literature; Simpson DA et al.; A case of oculofacial-skeletal myorhythmia associated with cerebral Whipple's disease is presented . This peculiar abnormal movement disorder consists of a convergent-divergent pendular nystagmus associated with a synchronous, rhythmic movement of the mouth, jaw, and extremities . The movements in previous cases have responded inconsistently to a variety of broad-spectrum antibiotic drugs, and antiepileptic, muscle relaxant, antispastic, and psychotropic drugs . The current patient's mental status improved after starting intravenous ceftriaxone but improvement of the abnormal movements occurred only after the addition of oral valproate . Current treatment consists of intravenous trimethoprim-sulfamethoxazole for 2 weeks followed by oral trimethoprim-sulfamethoxazole twice daily for 1 year . Presented here is an alternative treatment of intravenous ceftriazone followed by oral trimethoprim-sulfamethoxazole in combination with valproate for abnormal movements not responsive to antibiotic drugs alone.

J Clin Oncol, 1995 Mar, 13(3), 652 - 9
Can cytotoxic dose-intensity be increased by using granulocyte colony-stimulating factor? A randomized controlled trial of lenograstim in small-cell lung cancer; Woll PJ et al.; PURPOSE: The use of granulocyte colony-stimulating factor (G-CSF) to increase cytotoxic dose-intensity was assessed in a randomized trial in better-prognosis small-cell lung cancer (SCLC) . Both control and G-CSF arms were subject to the same dose-intensification strategy . PATIENTS AND METHODS: Patients with newly diagnosed SCLC and either no or one adverse prognostic factor were randomized to receive vincristine, ifosfamide, carboplatin, and etoposide (VICE) alone or with recombinant human (rHu)G-CSF (lenograstim) 5 micrograms/kg/d between cycles . Six chemotherapy cycles were given, with prophylactic cranial irradiation after cycle 1 and thoracic irradiation after cycle 3 . There was no fixed dose interval . In both arms, patients were eligible for re-treatment when the WBC count was > or = 3 x 10(9)/L and platelet count was > or = 100 x 10(9)/L . No dose reductions were permitted . Dose-intensity was expressed relative to standard every-4-weeks VICE . RESULTS: Sixty-five consecutive patients in one institution were randomized to control (n = 31) or G-CSF (n = 34) . WBC and neutrophil counts were consistently higher in G-CSF patients than in the control group, but there were no significant differences in the incidence of febrile neutropenia, antibiotic or transfusion requirements, or days in hospital . In both treatment arms, the median dose-intensity was greater than one for each cycle (control group, P = .0009; G-CSF group, P = .0001) . The G-CSF group received a significantly higher dose-intensity than the control group, with the greatest difference in the first three cycles (1.34 v 1.17, P = .001) . There were more chemotherapy-related deaths in the G-CSF group than in the control group (six v one), but this group had a better 2-year survival rate (32% with G-CSF, 95% confidence interval {CI}, 16 to 48; 15% with controls, 95% CI, 2 to 27) . CONCLUSION: The dose-intensity of VICE chemotherapy was increased in both groups . Patients randomized to receive G-CSF achieved a significantly higher dose-intensity than controls . Despite early toxicity, they had a better 2-year survival rate.

Am J Gastroenterol, 1995 Mar, 90(3), 455 - 9
Tacrolimus (FK 506), a treatment for primary sclerosing cholangitis: results of an open-label preliminary trial; Van Thiel DH et al.; Primary sclerosing cholangitis (PSC) is a chronic inflammatory disease of the liver that is characterized by progressive cholestasis and the development of secondary biliary cirrhosis . There is no widely recognized therapy for this disease, although anti-inflammatory agents (steroids), immunosuppressive agents (methotrexate), anti-fibrotics (colchicine), and choleretic agents (ursodeoxycholic acid) have been used in various small series . In the present study, Tacrolimus (FK 506), a new and powerful immunosuppressive macrolide antibiotic, has been used to treat 10 patients with PSC . Each subject had a liver biopsy, ERCP with visualization of the intra- and extrahepatic biliary tree, and a panel of hematological, serological, and biochemical laboratory tests before the initiation of the FK 506 therapy . The FK 506 was administered orally at 12-h intervals and was monitored by serial plasma FK 506 trough levels . After 360 days of treatment, the median serum bilirubin level was reduced by 75%, and the serum alkaline phosphatase was reduced by 70% . Moreover, the serum ALT and AST levels were reduced by 80 and 86%, respectively . No change in the serum level of BUN and creatinine levels occurred as a consequence of the FK 506 treatment . These data demonstrate that: 1) FK 506 can be used to treat PSC; 2) the response to FK 506 by patients with PSC is rapid; and, 3) no adverse effect on the serum BUN and creatinine levels was observed . It is anticipated that FK 506 will become an important agent for the treatment of patients with PSC because of its powerful immunosuppressive activity.

Circ Res, 1995 Mar, 76(3), 412 - 7
Rapamycin-FKBP inhibits cell cycle regulators of proliferation in vascular smooth muscle cells; Marx SO et al.; Multiple growth factors can stimulate quiescent vascular smooth muscle cells to exit from G0 and reenter the cell cycle . The macrolide antibiotic rapamycin, bound to its cytosolic receptor FKBP, is an immunosuppressant and a potent inhibitor of cellular proliferation . In the present study, the antiproliferative effects of rapamycin on human and rat vascular smooth muscle cells were examined and compared with the effects of a related immunosuppressant, FK520 . In vascular smooth muscle cells, rapamycin, at concentrations as low as 1 ng/mL, inhibited DNA synthesis and cell growth . FK520, an analogue of the immunosuppressant FK506, is structurally related to rapamycin and binds to FKBP but did not inhibit vascular smooth muscle cell growth . Molar excesses of FK520 blocked the antiproliferative effects of rapamycin, indicating that the effects of rapamycin required binding to FKBP . Rapamycin-FKBP inhibited retinoblastoma protein phosphorylation at the G1/S transition . This inhibition of retinoblastoma protein phosphorylation was associated with a decrease in p33cdk2 kinase activity . These observations suggest that rapamycin, but not FK520, inhibits vascular smooth muscle cell proliferation by reducing cell-cycle kinase activity.

RNA, 1995 Mar, 1(1), 95 - 101
Inhibition of the hammerhead ribozyme by neomycin; Stage TK et al.; A series of antibiotics was tested for stimulation or inhibition of the hammerhead ribozyme cleavage reaction . Neomycin was found to be a potent inhibitor of the reaction with a Kl of 13.5 microM . Two hammerheads with well-characterized kinetics were used to determine which steps in the reaction mechanism were inhibited by neomycin . The data suggest that neomycin interacts preferentially with the enzyme-substrate complex and that this interaction leads to a reduction in the cleavage rate by stabilizing the ground state of the complex and destabilizing the transition state of the cleavage step . A comparison of neomycin with other aminoglycosides and inhibitors of hammerhead cleavage implies that the ammonium ions of neomycin are important for the antibiotic-hammerhead interaction.

Biochemistry, 1995 Feb 21, 34(7), 2267 - 75
Specific binding of the biradical analog of neocarzinostatin chromophore to bulged DNA: implications for thiol-independent cleavage; Yang CF et al.; The enediyne anticancer antibiotic neocarzinostatin chromophore generates a single, site-specific break at a bulge in DNA in a thiol-independent reaction, involving intramolecular drug activation under general base catalysis {Kappen, L . S., & Goldberg, I . H . (1993) Biochemistry 32, 13138-13145} . As part of an effort to elucidate the three-dimensional structure of the active complex formed between the labile drug and bulged DNA, we have studied the binding of stable drug products generated in the course of the cleavage reaction with oligodeoxynucleotides containing the bulged structure . By use of fluorescence quenching, we have found that one drug product, which is also formed in the absence of bulged DNA and most closely resembles the biradical intermediate in the cleavage reaction, specifically binds bulged DNA with a Kd in the low micromolar range and competitively inhibits the cleavage reaction . Other drug products, including one formed only in the presence of bulged DNA, fail to bind to the bulged DNA . Implications of these results for the proposed mechanism of bulge-specific cleavage and for the role of the DNA bulge in generating a unique drug product are discussed.

Biochim Biophys Acta, 1995 Feb 15, 1233(2), 145 - 52
Target size analysis of the peptide/H(+)-symporter in kidney brush-border membranes; Boll M et al.; The apparent functional molecular mass of the kidney peptide/H(+)-symporter was determined by radiation inactivation in brush-border membrane vesicles (BBMV) of rat kidney cortex . Purified BBMV were irradiated at low temperatures with high energy electrons generated by a 10-MeV linear accelerator at doses from 0 to 30 megarads . Uptake studies were performed with {3H}cefadroxil, a beta-lactam antibiotic which serves as a substrate for the kidney peptide/H(+)-symporter . Inhibition of influx of {3H}cefadroxil into BBMV was used to determine the functional molecular mass of the transporter . Additionally, direct photoaffinity labeling of the transport- and/or binding proteins for {3H}cefadroxil in control and irradiated BBMV was performed to determine the molecular mass of the putative transporter by SDS-polyacrylamide gel electrophoresis . Initial rates of pH-gradient dependent uptake of {3H}cefadroxil decreased progressively as a function of radiation dose . The apparent radiation inactivation size (RIS) of the transport function was found to be 414 +/- 16 kDa . Direct photoaffinity labeling yielded labeled membrane proteins with apparent molecular masses of 130 kDa and 105 kDa, respectively . The proteins displayed different labeling characteristics with respect to incubation time, specificity and the response to irradiation . It appears that only a 105 kDa protein is directly involved in transport function since (a) only it showed a specific pH gradient dependent labeling pattern and (b) the covalent incorporation of {3H}cefadroxil into this protein decreased parallel to the loss of transport function in irradiated BBMV . The peptide/H(+)-symporter in kidney brush-border membranes therefore appears to have a monomer mass of 105 kDa and may function in an oligomeric arrangement.

Blood, 1995 Feb 15, 85(4), 1095 - 103
The pro region of human neutrophil defensin contains a motif that is essential for normal subcellular sorting; Liu L et al.; Human defensins (human neutrophil peptides) HNP 1-3 are 29-30 amino acid antibiotic and cytotoxic peptides highly abundant in the cytoplasmic granules of polymorphonuclear leukocytes . The peptides are produced from 94 amino acid (aa) prepropeptides by proteolytic cleavage of the signal sequence and stepwise removal of the 44-45 aa anionic propiece . To study the role of the propiece, we constructed five in-frame deletions in preproHNP-1 cDNA between the signal peptidase site and the amino-terminus of the mature defensin region (aa 21-64) . The wild type HNP-1 cDNA and the deletion mutants were ligated into the pBabe-Neo retroviral vector, expressed in GP+E86 packaging derivative of NIH 3T3 cells, then transduced into the 32D cl3 granulocytic cell line . For each construction and both cell lines, we measured the accumulation of the various defensin forms in cells and media by 24-hour labeling or pulse-chase with 35S-cysteine- and immunoprecipitation/sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) . Deletions in the amino-terminal two-fifths of the propiece, delta 21-28 and delta 21-38, had only minor effects on defensin biosynthesis in both cell lines and did not interfere with the accumulation of mature defensin in the granules of 32D cl3 cells . Deletions in the carboxyterminal three-fifths of the propiece (delta 21-51 and delta 21-64) diminished net defensin synthesis, blocked constitutive secretion of prodefensin in both cell lines, and interfered with defensin accumulation in cytoplasmic granules of 32D cl3 cells . These effects were reproduced by the smaller deletion delta 40-51, which contains highly conserved secondary structure . The propiece segment 40-51 appears to be essential for the subcellular trafficking and sorting of HNP-1 defensin.

Rev Prat, 1995 Feb 15, 45(4), 461 - 4
{Eyelid and lacrimal abscesses}; Fayet B et al.; Nonspecific eyelid abscesses are rare, whereas periorbital infections occur more frequently . Localisation of a maximum number of inflammatory signs is essential for diagnosis . A superior external localisation suggest dacryoadenitis or infection of a dermal cyst and the end of the eyebrow . An internal canthal localisation would reflect lacrimal disorder . In the adult, the main cause of infection is acute dacryocystitis . After antibiotic and anti-inflammatory drug treatment, dacryocystorhinotomy is necessary to preclude recurrence . In the newborn, bilateral forms of dilatation of the lacrimal sacs can lead to respiratory distress . The treatment of choice is resection of the endonasal pouches.

J Mol Biol, 1995 Feb 10, 246(1), 164 - 79
Solution structure of a quinomycin bisintercalator-DNA complex; Chen H et al.; The quinomycin antibiotic UK-63052 (designated QN) exhibits a chemical structure related to the antibiotic echinomycin which is known to bisintercalate into DNA . Common features among these antibiotics include two heterocyclic aromatic ring systems propagating from a cross-bridged cyclic octadepsipeptide scaffold . We report on the solution structure of the QN-d(A1-C2-A3-C4-G5-T6-G7-T8) complex (one QN molecule per duplex) based on a combined NMR-molecular dynamics study including intensity-based refinement . The 3-hydroxy quinaldic acid rings bisintercalate into the duplex at (A3-C4).(G5-T6) steps and stack with flanking Watson-Crick A3.T6 and C4.G5 base-pairs . The intercalation sites at (A3-C4).(G5-T6) steps are wedge-shaped and unwound, with significant unwinding also observed at the (C4-C5).(C4-G5) step bracketed between the intercalation sites . The cross-bridged cyclic octadepsipeptide is positioned in the minor groove with the methyl groups on its Ala and NMe-MCp residues directed towards and making van der Waals contacts with the minor groove edge of the duplex . A pair of adjacent intermolecular hydrogen bonds between the Ala backbone atoms and the G5 minor groove edge (Ala-NH to G5-N(3) and G5-NH2e to Ala-CO) account for the sequence specificity associated with complex formation . The solution structure of the QN-DNA oligomer complex, which contains only Watson-Crick base-pairs flanking the bisintercalation site, is compared with the crystal structure of the related echinomycin-DNA oligomer complex, which contains Hoogsteen base-pairs on either side of the bisintercalation site.

FEMS Microbiol Lett, 1995 Feb 1, 126(1), 55 - 61
Physiological factors affecting streptomycin production by Streptomyces griseus ATCC 12475 in batch and continuous culture; Reza Fazeli M et al.; Conditions of growth are described for the production of streptomycin by Streptomyces griseus ATCC 12475 using chemically defined minimal medium and complex medium . It was found using batch cultures that early synthesis of the antibiotic occurred during growth in minimal medium but was delayed until the onset of stationary phase in complex medium . This effect was independent of whether spores or vegetative cells were used as inoculum . Stability of streptomycin biosynthesis in continuous culture was dependent on dilution rate and medium employed . Cultures were highly unstable when grown on complex medium but could be maintained in steady states in continuous culture using minimal medium when the dilution rate was increased in a stepwise manner, starting at a dilution rate of 0.02 h-1 (15% of mumax) . The effect of changing dilution rate on growth, streptomycin production and the level of streptomycin phosphotransferase was examined using this technique.

Mol Pharmacol, 1995 Feb, 47(2), 307 - 13
Characterization of two affinity states of adenosine A2a receptors with a new radioligand, 2-{2-(4-amino-3-{125I}iodophenyl)ethylamino}adenosine; Luthin DR et al.; Adenosine analogs substituted in the 2-position with arylamino groups have been found to have high affinity and selectivity for A2a adenosine receptors . Two such compounds, 2-{2-(4-aminophenyl)ethylamino}adenosine and 2-{2-4-amino-3-iodophenyl)ethylamino}adenosine (I-APE), were synthesized and found to be potent coronary vasodilators (ED50 < 3 nm) . These compounds bind weakly to A1 adenosine receptors of rat cortex (Ki > 150 nM) . 125I-APE was synthesized and the new radioligand was found to bind to two affinity states of rat striatal A2a adenosine receptors (Kd = 1.3 +/- 0.1 nM and 19 +/- 4.5 nM) . The high affinity site represents a previously unrecognized small (15-20%) fraction of A2a adenosine receptors coupled to G proteins . Guanosine 5'-O-(3-thio)triphosphate (GTP gamma S) reduces specific binding of 125I-APE half-maximally at a concentration of 45 +/- 2 nM . {3H}CGS21680 also binds to two affinity states of A2a receptors on striatal membranes (Kd = 3.9 +/- 0.9 and 51 +/- 5.5 nM), although in previous studies single Kd values ranging from 5 to 15 nM have been reported . This high affinity site is substantiated by the finding that the IC50 of CGS21680 in competition with 125I-APE binding to striatal membranes is shifted leftward in membranes diluted for 4 min before filtration, to selectively dissociate radioligand from low affinity receptors . Assuming that agonist radioligands bind to both coupled and uncoupled forms of striatal A2a adenosine receptors, we could simulate with the computer the finding that the decrease in specific binding induced by GTP gamma S (100 microM) is variable and depends on radioligand concentration, ranging from 20 to 90% . Unlike 125I-APE, {3H}CGS21680 is charged at physiological pH, and treatment of membranes with the pore-forming antibiotic alamethicin uncovers cryptic {3H}CGS21680 but not 125I-APE binding sites . We conclude that the GTP gamma S-sensitive high affinity form of the A2a adenosine receptor can be preferentially labeled by 125I-APE, due to both its high specific activity and its physicochemical properties . Possible functional manifestations of poor coupling of A2a adenosine receptors to G proteins are discussed.

J Nutr, 1995 Feb, 125(2), 183 - 8
Investigations into the actions of glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1(7-36)amide on lipoprotein lipase activity in explants of rat adipose tissue; Knapper JM et al.; The direct actions of glucose-dependent insulinotropic polypeptide, glucagon-like peptide-1(7-36)amide and insulin on lipoprotein lipase activity in explants of rat epididymal adipose tissues were investigated . Lipoprotein lipase was extracted into the incubation medium by heparin release of lipoprotein lipase and measured by fatty acid release from a glyceroltriolein emulsion . Insulin and glucose-dependent insulinotropic polypeptide caused a significant stimulation of lipoprotein lipase activity over a dose range of 0.25-4 nmol/L and 4-8 nmol/L, respectively . Explants incubated in the presence of both insulin and glucose-dependent insulinotropic polypeptide (at 0.5 and 4 nmol/L, respectively) showed levels of lipoprotein lipase activity significantly greater than that seen with either hormone alone . Neither insulin- nor glucose-dependent insulinotropic polypeptide-stimulated lipoprotein lipase was modified by the presence of the antibiotic actinomycin-D in the incubation medium, indicating that these two hormones exert their actions on the pre-existing cellular pool of lipoprotein lipase . Glucagon-like polypeptide-1(7-36)amide, over a dose range of 1-8 nmol/L, did not stimulate lipoprotein lipase activity . This study indicates that glucose-dependent insulinotropic polypeptide, in addition to stimulating insulin secretion, has a direct biological action on adipose tissue and in vivo, together with insulin, may promote lipoprotein lipase activity postprandially.

J Pharmacol Exp Ther, 1995 Feb, 272(2), 511 - 8
Comparison of A4 and A2a binding sites in striatum and COS cells transfected with adenosine A2a receptors; Luthin DR et al.; A putative A4 adenosine receptor is characterized by a distinct structure activity profile of compounds in competition for {3H}2-phenylaminoadenosine ({3H}CV 1808) binding sites on rat brain membranes assayed at 4 degrees C . We now confirm that A4 binding sites can be demonstrated on ice-cold membranes of rat striatum and demonstrate a similar binding site on COS cells transfected with rat A2a adenosine receptors (COS/A2a) . The characteristic A4 potency order is: CV 1808 > {1R-(1 alpha, 2 alpha, 3 beta, 5 beta)}-3-(2,6-diamino-N2-(3-carbethoxyphenyl)-9 H-purin-9-yl)-5'-(N-ethylcarbamoyl)-1,2-cyclopentanediol (CGS 22988) >> 5'-N-ethylcarboxamidoadenosine (NECA) > or = 2-{4-(2- carboxyethyl)phenylethylamino}-5'-N-ethylcarboxamidoadenosine (CGS 21680); 9-chloro-2-(2-furyl){1,2,4}-triaolo{1,5-c}-quinazolin-5-a min e (CGS 15943) only partially inhibits binding at 1 microM . If {3H}CGS 21680 is used for ice-cold assays, or if either {3H}CV 1808 or {3H}CGS 21680 are used for assays at 21 degrees C, the potency order of competing compounds changes markedly and becomes characteristic of A2a adenosine receptor binding sites; CGS 15943 > or = CGS 21680 congruent to NECA > CGS 22988 > or = CV 1808 . Binding of {3H}CGS 21680, but not {3H}CV 1808, is significantly enhanced by the pore-forming antibiotic, alamethicin . Guanosine 5'-O-(3-thiotriphosphate) decreases the binding of both radioligands to striatal membranes at 21 degrees C significantly more than to membranes on ice.(ABSTRACT TRUNCATED AT 250 WORDS)

Tijdschr Diergeneeskd, 1995 Feb 1, 120(3), 75 - 7
{Discospondylitis and immune-mediated polyarthritis in a Bernese mountain-dog}; van der Wel TJ et al.; In this case report we describe the clinical picture and treatment of a Bernese mountain dog with discospondylitis and a presumably reactive immune-mediated polyarthritis . The clinical signs consisted of apathy, fever, anorexia, and a stiff gait . The diagnosis was based on the typical radiographic signs of discospondylitis and the cytology of the synovial fluid . The dog was treated with a broad-spectrum antibiotic for 6 weeks and thereafter with a synthetic glucocorticoid for the polyarthritis . Five months after cessation of therapy, the dog was free from the initial signs.

J Pediatr, 1995 Feb, 126(2), 313 - 6
Short-term use of amoxicillin-clavulanate during upper respiratory tract infection for prevention of acute otitis media; Heikkinen T et al.; We performed a randomized, double-blind, placebo-controlled study to determine whether acute otitis media could be prevented by antibiotic therapy initiated promptly after the appearance of symptoms of upper respiratory tract infection . One hundred four children aged 1 to 4 years received a 7-day course of either amoxicillin-clavulanate or placebo . Acute otitis media developed in 9 (18%) of the 50 children receiving amoxicillin clavulanate and in 12 (22%) of the 54 children receiving placebo (p = 0.59).

J Infect Dis, 1995 Feb, 171(2), 356 - 61
Biliary complications in the treatment of unsubstantiated Lyme disease; Ettestad PJ et al.; Treatment of unsubstantiated Lyme disease has led to serious complications in some cases . Two case-control studies, based on information in clinical records of patients discharged with a diagnosis of Lyme disease during 1990-1992, were conducted at a central New Jersey hospital . Twenty-five patients with biliary disease were identified, and 52 controls were selected from 1352 patients with suspected Lyme disease . Only 3% of 71 evaluatable subjects met the study criteria for disseminated Lyme disease . Patients with biliary disease were more likely than were antibiotic controls to have received ceftriaxone and more likely than ceftriaxone controls to have received a daily ceftriaxone dose > or = 40 mg/kg and to be < or = 18 years old . Fourteen of 25 biliary case-patients underwent cholecystectomy; all had histopathologic evidence of cholecystitis and 12 had gallstones . Thus, treatment of unsubstantiated diagnoses of Lyme disease is associated with biliary complications.

Am J Respir Crit Care Med, 1995 Feb, 151(2 Pt 1), 353 - 9
Asthma self-management education program by home monitoring of peak expiratory flow; Ignacio-Garcia JM et al.; A prospective controlled trial of home monitoring of peak expiratory flow rate (PEFR) was conducted to determine the usefulness of an objective measure of lung function in association with an education program and a medication self-management plan in reducing morbidity in adult patients with asthma . Thirty-five patients managed themselves, using peak flow readings as the basis for the therapeutic plan coupled with educational intervention, whereas 35 control patients used symptoms and spirometric data for following physicians' treatment plans . After a 6-mo study period, patients in the experimental group showed statistically significant improvements in morbidity parameters (days lost from work, acute asthma attacks, days on antibiotic therapy, physician consultations, and emergency room admissions for asthma), increases in FVC, FEV1, and FEV1/FVC, mean PEFR and mean morning PEFR, decrease in percentage of the mean PEFR amplitude, and a reduction in the use of inhaled beta-agonists, oral theophylline, and oral prednisone . Although improvements in some of these parameters were also found in the control group, they did not reach the levels of significance obtained in the experimental group . The personal use of an objective measure of lung function in association with a medication self-management plan leads to improvement in the patient's condition.

J Am Acad Dermatol, 1995 Feb, 32(2 Pt 1), 192 - 8
Pustular vasculitis of the hands; Strutton G et al.; BACKGROUND: Several patients were observed with a peculiar cutaneous eruption limited to the dorsa of the hands and fingers . Clinically the lesions had some resemblance to those seen in Sweet's syndrome, but biopsy specimens showed severe leukocytoclastic vasculitis . OBJECTIVE: Our purpose was to characterize this eruption clinically and histologically and compare it with previously described diseases . METHODS: Six patients observed since 1977 are described . Skin biopsy specimens were obtained . RESULTS: In six women (age, 41 to 79 years) a symmetric eruption of papules and plaques limited to the dorsa of the radial sides of the hands and first three digits developed . The lesions resembled those of Sweet's syndrome and were associated with fever, sterile culture, blood neutrophil leukocytosis, nonresponse to antibiotic therapy, and rapid response to prednisone . Biopsy specimens showed a severe leukocytoclastic vasculitis . CONCLUSION: These patients appear to have a distinct entity that we have termed pustular vasculitis of the hands.

Thromb Haemost, 1995 Feb, 73(2), 180 - 5
Urokinase therapy in neonates with catheter related central venous thrombosis; Wever ML et al.; The results of fibrinolytic therapy with urokinase were evaluated in 26 neonates with catheter related central venous thrombosis . Complete thrombolysis could be achieved in 13 patients (50%), partial thrombolysis in 3 patients (12%) . No effect was seen in 10 patients (38%) . Therapy success was influenced by age, size and location of the thrombus . Coincidence of infection occurred in 16 patients (62%) . Mild hemorrhagic complications were seen in 2 patients (8%), no other significant side effects were observed . Nine patients with residual thrombosis were treated with oral anticoagulants following urokinase resulting in resolution of the thrombus in 6 patients within 3 months (67%) . The incidence of asymptomatic recurrent thrombosis was high (28%) . Urokinase might be an effective and safe treatment for central venous thrombosis in neonates . Prophylactic antibiotic therapy during the infusion of urokinase and long-term treatment with oral anticoagulants after thrombosis are advisable . Early detection of thrombosis might enhance the success rate of fibrinolytic therapy . Therefore, we strongly recommend routine echocardiographic screening of central venous catheters.

Diagn Cytopathol, 1995 Feb, 12(1), 76 - 80
Sialadenitis with crystalloid formation: a report of six cases diagnosed by fine-needle aspiration; Johnson FB et al.; Six cases of sialadenitis diagnosed by fine-needle aspiration contained large numbers of crystalloids . Light microscopy, ultrastructure, and chemical analysis suggest that the crystalloids represent crystallized salivary alpha-amylase . The inflammatory swelling may mimic benign and/or malignant neoplasms of the salivary glands . Drainage and/or antibiotic therapy may allow surgery to be avoided in these patients.

J Vet Med Sci, 1995 Feb, 57(1), 173 - 6
Effect of terdecamycin on experimentally induced swine dysentery in pigs; Ueda Y et al.; The authors evaluated the effect of terdecamycin, a novel antibiotic, on experimentally induced Serpulina (S.) hyodysenteriae infection in pigs . In a prophylactic test, feed containing terdecamycin was fed to pigs for 7 days before inoculation and 21 days after inoculation . Dysenteric diarrhea, development of lesions in the large intestinal mucosa and colonization of S . hyodysenteriae in colonic mucosa were completely inhibited by treatment with 5 ppm or 10 ppm terdecamycin . In the therapeutic test, an unmedicated feed was fed to pigs inoculated with S . hyodysenteriae, until the typical mucohemorrhagic diarrhea appeared after inoculation, and was then changed to the medicated feed for 10 days . By treating with 20 ppm terdecamycin, the clinical signs in the pigs were improved and S . hyodysenteriae was completely eradicated.

Acta Paediatr Jpn, 1995 Feb, 37(1), 12 - 6
Helicobacter pylori colonization in children with peptic ulcer disease . III . Diagnostic value of the 13C-urea breath test to detect gastric H . pylori colonization; Yamashiro Y et al.; The efficiency of the 13C-Urea Breath Test (13C-UBT) for the detection of Helicobacter pylori colonization in gastric mucosa was evaluated . The 13C-UBT was performed in five pediatric and six adult subjects who had had upper gastrointestinal endoscopy within 2 weeks . H . pylori colonization was confirmed in two pediatric and three adult subjects with peptic ulcer combined with antral gastritis, by histological examination of antral biopsy specimens . When an individual with H . pylori colonization ingested a solution containing 13C-urea, a significant amount of 13CO2 appeared in the respiratory CO2 within 10 min . The mean cumulative percentage dose of 13C recovered in the breath over 30 min in the cases with H . pylori colonization was significantly higher than that in those who were not colonized (4.91 vs 0.41, P < 0.001) . In addition, the effect of antibiotic on the eradication of H . pylori from gastric mucosa was monitored by 13C-UBT in two cases . The values of cumulative percentage dose of 13C over 30 min fell to the same levels as those observed in H . pylori negative subjects after just 2 weeks treatment with amoxicillin; however, positive results were obtained again 1 month after the withdrawal of amoxicillin . In summary, 13C-UBT is a simple, reliable, non-invasive method in the diagnosis of gastric H . pylori colonization especially for pediatric patients.

Br J Surg, 1995 Feb, 82(2), 170 - 1
Primary anastomosis with transverse colostomy as an alternative to Hartmann's procedure; Maddern GJ et al.; Hartmann's procedure remains the favoured option in patients with acute left colonic and sigmoid disease, despite the well documented morbidity and mortality associated with reversal . In 40 patients with left colonic pathology, primary anastomosis was performed; 32 had a covering transverse colostomy . There were six hospital deaths, five in the transverse colostomy group . Closure was not attempted in seven of the 27 patients surviving with a colostomy (three refused, four had disseminated malignancy) . In the 20 undergoing closure, there was no morbidity or mortality . With advances in intensive care, antibiotic therapy and anaesthesia, it is reasonable to consider alternatives to Hartmann's procedure, particularly when subsequent reconstruction is envisaged.

J Dairy Sci, 1995 Feb, 78(2), 412 - 20
Effects of a colostrum substitute and of dietary brewer's yeast on the health and performance of dairy calves; Seymour WM et al.; We tested the effects of substituting a whey protein concentrate for dam's colostrum at first feeding and of 1% brewer's yeast in dry feed on calf health and performance . Eighty-four calves were assigned to four preweaning and eight postweaning treatments based on feeding either dam's colostrum or a whey protein concentrate at birth and either yeast or no yeast in the dry feed both before and after weaning . After the first feeding, all calves were fed colostrum through 4 d of age and an all milk protein milk replacer from d 5 to 46 of age . Daily feed intakes, health measurements, and weekly BW were recorded . Calves fed whey protein concentrate at birth had similar health parameters and greater feed efficiency than calves fed colostrum over the preweaning period . Addition of 1% brewer's yeast to the dry feed apparently reduced the incidence of fever and the number of associated antibiotic treatments during the preweaning period, but had no effects thereafter . Under the conditions of this study, whey protein concentrate was an effective substitute for dam's colostrum at first feeding, and 1% brewer's yeast fed in dry feed may reduce susceptibility to infection prior to weaning.

J Pharm Sci, 1995 Feb, 84(2), 226 - 7
Comparison of the crystallinity of imipenem samples by X-ray diffraction of amorphous material; Crocker LS et al.; The intensity of X-rays diffracted by amorphous material in samples of the beta-lactam antibiotic imipenem {(5R,6S)-3-{{2-(formimidoyl-amino)ethyl}thio}-6-{(R)-1- hydroxyethyl}-7-oxo-1-azabicyclo{3.2.0}hept-2-ene-2-carboxylic acid} was used to compare the crystallinity of the samples . The method makes use of the intensity in the X-ray powder diffraction (XRPD) pattern at a diffraction angle of 28 degrees (2 theta), at which no crystalline peaks are observed . A linear relationship (R2 = 0.9999) exists between amorphous intensity and crystallinity for synthetic mixtures of amorphous and crystalline imipenem . Sample preparation techniques ordinarily used in XRPD experiments were utilized.

Arch Pediatr, 1995 Feb, 2(2), 147 - 9
{Tuberculous dacryocystitis}; Cotton JB et al.; BACKGROUND--Acute infection and inflammation of the nasolacrimal sac may complicate congenital obstruction of the nasolacrimal duct . Acute dacryocystitis is uncommon later and tuberculosis is exceptionally responsible for it . CASE REPORT--A 4 1/2 year-old boy was admitted because he suffered from acute left dacryocystitis with fever and cervical adenitis . Involvement of both lacrymal gland and lymph node persisted despite antibiotic and corticosteroid therapy . Needle biopsy of the lymph node showed presence of Mycobacterium tuberculosis and excision revealed caseating granulomas . The tuberculin skin test was positive while pulmonary tuberculosis was discovered in the patient's father . The patient was successfully given izoniazid, rifampin for 9 months and pyrazinamide for 2 . Drainage of the sac area was necessary after 1 month of treatment followed by dacryocystorhinostomy . CONCLUSION--This rare case of tuberculous dacryocystitis permits to delineate the difficulties of ophthalmologic therapy.

Nihon Kyobu Shikkan Gakkai Zasshi, 1995 Feb, 33(2), 202 - 8
{A case of hypersensitivity pneumonitis probably caused by a humidifier in winter}; Nakagawa A et al.; A 64-year-old man was admitted complaining of cough, hemoptysis, dyspnea, and fever . His chest X-ray film on admission showed reticulo-granular shadows in both lung fields . Ausculation of his chest revealed fine crackles in both lower zones . After admission, he was treated with antibiotics, but his chest-radiographic appearance worsened temporarily, and sputum cytology results were repeatedly positive . Diagnosis was difficult . Differential cell count of the bronchoalveolar lavage fluid showed lymphocytosis, with a high CD 4/8 ratio . Transbronchial lung biopsy specimens revealed Masson bodies and alveolitis . With antibiotic therapy alone, his condition improved, and he was discharged . Five and a half hours later, his symptoms worsened and he was readmitted . His chest X-ray film on the second admission was almost the same as that on the first admission . His symptoms became less severe, and his condition improved without treatment . Hypersensitivity pneumonitis was diagnosed . Because the onset was in February, this was not considered to be a case of so-called summer type hypersensitivity pneumonitis a provocation test was done with water from the humidifier he had been using at home . The white blood cell count increased and PaO2 decreased significantly, so the result of the provocation test was thought to be positive . Therefore, so-called humidifier lung was strongly suspected . The results of sputum cytology on the first admission were probably falsely positive.

J Pharmacol Toxicol Methods, 1995 Feb, 33(1), 35 - 45
Combination of computerized morphonuclear and multivariate analyses to characterize in vitro the antineoplastic effect of alkylating agents; Pauwels O et al.; The influence of 13 anticancer alkylating agents on cell proliferation, cell cycle parameters, and morphonuclear characteristics was monitored in vitro on three neoplastic cell lines . This monitoring was carried out by means of the digital cell image analysis of Feulgen-stained nuclei . This computer-assisted microscope analysis of chromatin texture made it possible to assess 15 morphonuclear parameters . These 15 parameters were submitted to multivariate analyses, that is, principal-components analyses followed by the canonical transformation of the data . The 13 alkylating agents included four nitrogen mustards (chlormethine, chlorambucil, melphalan, and cyclophosphamide), two nitrosoureas (carmustine and lomustine), two platinum analogues (cisplatine and carboplatine), two ethyleneimine derivatives (thiotepa and investigational PE1001), one antibiotic (mitomycin C), one alkylsulfonate (busulfan), and one triazene (dacarbazine) . The mouse MXT mammary and the human J82 and T24 bladder tumor cell lines were used in this study . The results show that these alkylating agents induced specific modifications to the chromatin pattern according to the subclass to which they belong . In other words, the multivariate statistical analyses of the 15 parameters made it possible to identify, at least partly, distinct subclasses of alkylating agents according to their mechanisms of action . As a validation of the methodology, the results also show that most of the alkylating agents induced an increase in the percentage of cells in the G2 phase, while some sometimes induced an increase in the percentage of cells in the S phase of the cell cycle.

Postgrad Med J, 1995 Feb, 71(832), 98 - 101
Descending necrotising mediastinitis; Alsoub H et al.; Descending necrotising mediastinitis is a rare but serious complication of oropharyngeal infections with high mortality . Diagnosis is frequently delayed, contributing to this high mortality, but awareness of such a complication and early diagnosis using computed tomographic scanning leads to prompt surgical drainage, proper antibiotic therapy, and survival.

Ophthalmologe, 1995 Feb, 92(1), 31 - 4
{Monotherapy vs combination therapy with topical prednisolone and indomethacin}; Hessemer V et al.; The anti-inflammatory effects of topical steroids and nonsteroidal anti-inflammatory drugs (NSAID) are claimed to be additive, according to fluorophotometric measurements . This finding was reevaluated using laser flare-cell photometry . PATIENTS AND METHODS: Thirty patients (61-79 years of age) without pre-existing deficiencies of the blood-aqueous barrier were investigated preoperatively as well as on day 1 and 3 after ECCE with IOL implantation . The laser flare-cell photometer (model FC-1000; Kowa Company) which was used for examination enables sensitive and exact in vivo determination of aqueous flare . The patients were randomly assigned to one of the following three treatment groups: group A, monotherapy with prednisolone 1% eyedrops (Inflanefran forte); group B, monotherapy with indomethacin 1% eyedrops (Chibro Amuno); group C, combination therapy with prednisolone 1% + indomethacin 1% eyedrops . One drop of either drug was administered five times per day to each patient, beginning immediately after completion of surgery . In addition, all patients received antibiotic therapy with gentamicin . Parabulbar or oral steroids were not administered . RESULTS: Under monotherapy with prednisolone, the flare (photon counts/ms) on days 1 and 3 postoperatively averaged 30.9 and 27.8, respectively . Under indomethacin monotherapy, the flare values were similar (no significant differences) . Under combination therapy with prednisolone+indomethacin, however, the flare values were significantly lower both on day 1 (24.2) and on day 3 (20.6) . CONCLUSIONS: Combination therapy with topical prednisolone+indomethacin thus seems superior to monotherapy with either of these agents . This confirms the previous fluorophotometric finding that the anti-inflammatory effects of topical steroids and NSAID are additive, a phenomenon attributable to different pharmacological sites of action.

Tuber Lung Dis, 1995 Feb, 76(1), 4 - 10
Acute respiratory infections in children: a community-based study comparing a primary health center and a pediatric unit, Republic of Guinea; Sow O et al.; OBJECTIVE: A community-based study was carried out in the Republic of Guinea in order to evaluate the frequency of occurrence, severity of illness, risk factors and the results of planned treatment of acute respiratory infections (ARI) in children under the age of 15 years . DESIGN: The study was performed over a 1-year period in 2 distinct areas, 1 rural and 1 urban . A total of 2622 ARI were identified among children under 15 years of age . In the rural area, data were collected by primary health-care workers and by 2 physicians who were trained to supervise the study . RESULTS: Among the rural population, 1422 ARI were identified . In the city center, Conakry, 1200 ARI were identified in one children's hospital . The child population under 5 years of age was significantly greater in the rural area (95.2%) than in the city center (83.2%) (P < 0.0001) . Malnutrition affected 10.6% of all the children . There were discrepancies in symptoms and signs affecting the 2 groups but the severity scores, including children under 5 years of age, were not significantly different: including children under 5 years of age, were not significantly different: 10-11% of the children were considered to have severe disease and 6.2% required urgent referral to hospital . Upper and lower respiratory infections (URI and LRI) were equally represented (49.9% and 50.1% respectively) . Distribution of each type of ARI was significantly different in the 2 groups: there were significantly more URI in the city center, especially tonsillitis . Bronchitis and bronchopneumonia occurred significantly more often in the rural area . Pneumonia and bronchopneumonia represented 9.8% of all ARI . Use of antibiotic therapy was known in 2557 patients: 1268 URI and 1289 LRI . In children with URI, 69.7% did not receive antibiotic therapy, 29.9% received 1 antibiotic and 0.03% received 2 antibiotics successively . Children from the city center received significantly more antibiotics than in the rural health center . In children with LRI, 17.8% did not receive antibiotic therapy, 81.7% received 1 antibiotic and 0.05% received 2 antibiotics successively . There was no significant difference between the 2 centers in antibiotic prescription . Clinical outcome showed that 93% of children were considered to be cured at day 7 and 99.4% at day 14 . 14 children with severe pneumonia died . The infection cost (antibiotics plus other drugs prescribed as supportive care) was 0.45 US$ per child in the rural area and 9.7 US$ in the children's hospital . CONCLUSION: This supervised study constitutes the first large longitudinal study concerning respiratory infections in West Africa . It demonstrates that simple guidelines are valid in order to prevent mortality and complications . Care appropriate to population requirements in term of infectious diseases can be delivered with low cost and low technology.

J Clin Microbiol, 1995 Feb, 33(2), 428 - 31
Isolation of Coxiella burnetii from heart valves of patients treated for Q fever endocarditis; Muhlemann K et al.; Coxiella burnetii was isolated from the valve material of two patients who underwent valvectomy because of progressive congestive heart failure due to endocarditis . In each case antibiotic therapy was administered for several months prior to valvectomy . Classical histopathological examination of the valves did not reveal an etiology . However, coxiella-like organisms were demonstrated in valvular material with Koster, Stamp, and Giemsa stains, and the organisms were grown in cell culture . Antibody titers were consistent with the diagnosis of chronic C . burnetii infection . This report illustrates the advantage of simple and fast staining techniques and cell culture for the demonstration and isolation of C . burnetii in the heart valve tissue of patients with Q fever endocarditis.

J Clin Microbiol, 1995 Feb, 33(2), 419 - 27
Immunoblot interpretation criteria for serodiagnosis of early Lyme disease; Engstrom SM et al.; We monitored the antibody responses of 55 treated patients with early Lyme disease and physician-documented erythema migrans . Six sequential serum samples were obtained from patients before, during, and until one year after antibiotic therapy and analyzed by in-house enzyme-linked immunosorbent (ELISA) and immunoblot assays . An immunoblot procedure utilizing a gradient gel and an image analysis system was developed . A relational database management system was used to analyze the results and provide criteria for early disease immunoblot interpretation . Recommended criteria for the immunoglobulin M (IgM) immunoblot are the recognition of two of three proteins (24, 39, and 41 kDa) . The recommended criteria for a positive IgG immunoblot are the recognition of two of five proteins (20, 24 {> 19 intensity units}, 35, 39, and 88 kDa) . Alternatively, if band intensity cannot be measured, the 22-kDa protein can be substituted for the 24-kDa protein with only a small decrease in sensitivity . Monoclonal antibodies were used to identify all these proteins except the 35-kDa protein . With the proposed immunoblot interpretations, the sequential serum samples were examined . At visit 1, the day of diagnosis and initiation of treatment, 54.5% of the serum samples were either IgM or IgG positive . The peak antibody response, with 80% of the serum samples positive, occurred at visit 2, 8 to 12 days into treatment . The sensitivities of the IgM and IgG immunoblot for detecting patients that were seropositive into the study period were 58.5 and 54.6%, respectively, at visit 1 and 100% at visit 2 . Twenty percent of the patients remained seronegative throughout the study . The specificities of the IgM and IgG immunoblots were 92 to 94% and 93 to 96%, respectively . The IgM immunoblot and ELISA were similar in sensitivities, whereas the IgG immunoblot had greater sensitivity than the IgG ELISA (P = 0.006).

J Korean Med Sci, 1995 Feb, 10(1), 62 - 5
A case of shunt nephritis; Lee HS et al.; Nephritis associated with a chronically infected ventriculoatrial shunt is known as shunt nephritis . A 6-year-old girl with prior history of a ventriculoatrial shunt presented complaining of fever and gross hematuria . Serum complement levels were decreased and a coagulase-negative S . epidermidis was cultured from her blood . The renal biopsy specimen showed features of membranoproliferative glomerulonephritis type I . Hydrocephalus was so severe that shunt removal was impossible . With antibiotic therapy, clinical symptoms and laboratory findings include complement levels were normalized although microscopic hematuria persisted . To our knowledge, this is the first case of shunt nephritis in Korea . In addition to the case report, a brief review of shunt nephritis has been added.

Biochemistry, 1995 Jan 31, 34(4), 1376 - 85
Role of magnesium ion in mithramycin-DNA interaction: binding of mithramycin-Mg2+ complexes with DNA; Aich P et al.; Mithramycin is an anticancer drug that blocks macromolecular synthesis via reversible interaction with the DNA template in the presence of bivalent metal ions such as Mg2+ . The role of Mg2+ in this antibiotic-DNA interaction is not clear . We approached the problem in two steps via studies on the interactions between (i) mithramycin and Mg2+ and (ii) mithramycin-Mg2+ complex(es) and DNA . Spectroscopic techniques such as absorption, fluorescence, and CD were employed for the purpose . From equilibrium and kinetic studies, we earlier reported that MTR forms two different types of complexes with Mg2+ {Aich, P., & Dasgupta, D . (1990) Biochem . Biophys . Res . Commun . 173, 689} . The two complexes are referred to as complex I (with 1:1 stoichiometry in terms of mithramycin: Mg2+) and complex II (with 2:1 stoichiometry in terms of mithramycin: Mg2+) . In this report, we have further characterized these complexes by fluorescence spectroscopy . Interactions of these complexes with calf thymus DNA were examined to elucidate their binding . Evaluation of binding parameters (intrinsic binding constant and stoichiometry) from spectrophotometric and fluorimetric titrations suggests that the complexes bind differently to the same DNA . Measurement of van't Hoff enthalpies for the interaction of the two ligands and DNA shows that the complex I-DNA interaction is exothermic, in contrast to the endothermic nature of the complex II-DNA interaction . This could originate from a difference in the molecular nature of the interactions between the complexes and calf thymus DNA . Our studies to detect the nature of the groove via which these complexes bind to DNA suggest that both complexes approach via the minor groove of the DNA.(ABSTRACT TRUNCATED AT 250 WORDS)

Int J Cancer, 1995 Jan 17, 60(2), 280 - 4
Experimental local therapy of human melanoma with lytic magainin peptides; Soballe PW et al.; Magainin peptides and model amphipathic peptides exhibit antibiotic activity and are also cytolytic for transformed human cells . Here we demonstrate in vitro that MSI-511 (an all-D amino-acid model magainin peptide) and MSI-130 (a margainin analogue) were more lytic for 17 human melanomas than for normal melanocytes . Melanomas established s.c . in athymic nude mice and then injected once with the peptide MSI-511 completely disappeared in 6 out of 9 animals, whereas a control peptide had no effect . Murine skin at the tumor injection site was initially affected, but healed within 2 weeks with minimal scarring . Similarly, accelerated healing was seen in human skin grafted to SCID mice and injected with MSI-511 . Our results indicate that lytic magainin peptides can be used for local tumor therapy with minimal long-term damage to normal tissues.

Biochemistry, 1995 Jan 17, 34(2), 583 - 92
Effects of the enediyne C-1027 on intracellular DNA targets; Cobuzzi RJ Jr et al.; We examined DNA damage induced by the enediyne-containing antitumor antibiotic C-1027 in intracellular nuclear and mitochondrial DNA targets using the episome-containing cell line 935.1 . Strand-scission activity of the C-1027 holoantibiotic was measured by the topological forms conversion assay in episomal and mitochondrial DNA, as well as in cell-free plasmid DNA . Genomic DNA damage was quantitated by filter elution analysis . Comparisons were made to the well-characterized enediyne neocarzinostatin . From these studies, mixed single- and double-strand breaks were observed not only in cell-free, plasmid DNA but also in intracellular episomal, mitochondrial, and genomic DNA at low nanomolar concentrations . C-1027 cleaved DNA 285-fold more efficiently in cells than in a cell-free environment, and displayed preference for intracellular DNA species in the following rank order: episome > mitochondrial DNA >> genomic . NCS also damaged the non-histone-associated mitochondrial DNA, but not the episome . Cleavage of the 935.1 cell episome by C-1027 occurred at specific sites including the BPV origin of replication and E6/E7 open reading frame regions, as well as the MMTV LTR promoter region.

Eur J Pharmacol, 1995 Jan 16, 288(2), 187 - 92
Interaction of pristinamycin IA with P-glycoprotein in human intestinal epithelial cells; Phung-Ba V et al.; Pristinamycin IA is a cyclo-peptidic macrolactone antibiotic belonging to the streptogramin family . In the present work, the interaction of pristinamycin IA with the multidrug transporter P-glycoprotein was investigated in the differentiated human intestinal epithelial cell line Caco-2 . Pristinamycin IA specifically inhibited the efflux of the P-glycoprotein substrate {3H}vinblastine, thus increasing the cellular accumulation of the drug . Pristinamycin IA also reduced by 70% the basolateral to apical secretion of {3H}vinblastine across Caco-2 cell monolayers . The cellular accumulation of {14C}pristinamycin IA was very low and was increased by P-glycoprotein inhibitors (verapamil, chlorpromazine and reserpine) . The basolateral to apical transport of {14C}pristinamycin IA was 100-fold higher than apical to basolateral passage . This polarized transport was inhibited by verapamil and by ATP depletion . The results suggest that pristinamycin IA is a substrate for the P-glycoprotein, a finding which may have important consequences for the pharmacokinetics of this drug.

Brain Res, 1995 Jan 16, 669(2), 234 - 44
Relation of {Ca2+}i to dopamine release in striatal synaptosomes: role of Ca2+ channels; Carvalho CM et al.; We compared the effects of KCl and 4-aminopyridine (4-AP) stimulation on the coupling of Ca2+ channel activation to {3H}dopamine ({3H}DA) release in rat striatal synaptosomes and used specific Ca2+ channel blockers to discriminate between the different VSCC's activated by the two stimulatory agents . We found that whereas {3H}DA release is strictly Ca(2+)-dependent in the case of KCl depolarization, 4-AP, at concentrations above 100 microM, progressively causes a large Ca(2+)-independent release of {3H}DA . Thus, at 1 to 3 mM 4-AP, as much as 80-95% of the {3H}DA release is Ca(2+)-independent and can be partially blocked by nomifensine, indicating that some {3H}DA release is occurring through reversal of the DA carrier . Therefore, in the studies relating {Ca2+}i to {3H}DA release we selected 4-AP concentrations lower than 100 microM and corrected for the Ca(2+)-independent release . Under these conditions, we determined that: (1) Ca2+ entry through N-type VSCC's is involved in {3H}DA release both in the case of KCl depolarization (35% inhibition by omega-CgTx) and in 4-AP stimulation (23% inhibition by omega-CgTx); (2) Ca2+ entering through P-type and/or Q-type VSCC's is also involved in {3H}DA release due to 4-AP stimulation (26% inhibition by 200 nM omega-Aga IVA); (3) Neomycin (0.35 mM) inhibited the {3H}DA release due to 4-AP stimulation by about 20% and decreased the KCl induced {3H}DA release by 55%; the effects of neomycin (0.35 mM) and omega-CgTx were additive in both cases, indicating that, at this concentration, the antibiotic does not affect significantly N-type Ca2+ channels; (4) When applied together, omega-CgTx and omega-Aga IVA inhibited the 4-AP stimulated {3H}DA release by about 40-50%, suggesting that the remaining large fraction of the VSCC's activated by 4-AP stimulation are non-N, non-P VSCC's and are coupled to Ca(2+)-dependent {3H}DA release; (5) The contribution of L-type VSCC's is uncertain, since there seemed to be a small contribution in the case of KCl depolarization, but not in the case of 4-AP stimulation . On the whole, the results suggest that the release of {3H}DA in the rat striatal nerve terminals depends on Ca2+ entry through N-, P-, possibly Q-, and other non-N-, non-P-type VSCC's when either KCl or 4-AP stimulation is utilized.

Eur J Biochem, 1995 Jan 15, 227(1-2), 428 - 32
Interaction studies between elongation factor Tu and anthraniloyl-fluorescent analogues of guanyl nucleotides; Giovane A et al.; A fluorescent analogue of GDP, the 3'-O-anthraniloyl-GDP (anl-GDP) was demonstrated to bind to the elongation factor Tu (EF-Tu) with an affinity even higher than that of the parent nucleotide . As a consequence of the binding, an increase in fluorescence anisotropy and an emission band arising from non-radiative energy transfer among the protein intrinsic fluorophores and the labelled nucleotide were observed . Therefore, it was possible to study the exchange kinetics and the equilibrium between the protein-bound labelled GDP and the natural nucleotide through modifications, occurring during the course of the reaction, of fluorescence anisotropy and non-radiative energy transfer . In this way, it was also easily proven that, in the presence of aurodox (N-methylkirromycin), an antibiotic impairing EF-Tu biological function, the exchange kinetics between the protein-bound labeled GDP and the natural nucleotide was faster . Moreover, it was also found that the labelled nucleotide is recognized as a substrate by pyruvate kinase, being converted by this enzyme, in the presence of phosphoenolpyruvate, into anl-GTP . Pyruvate kinase is also able to convert, in the presence of phosphoenolpyruvate, the complex EF-Tu.anl-GDP into the complex EF-Tu.anl-GTP . The fluorescence properties of the 3'-O-anthraniloyl-labeled guanyl nucleotides and their feature as excellent acceptors of fluorescence arising from protein intrinsic fluorophores, may make these compounds useful for structural and binding studies on guanosine-nucleotide-binding proteins.

Curr Opin Ophthalmol, 1995 Feb, 6(1), 31 - 5
Anesthesia, preoperative, and postoperative medications; Gills JP et al.; Retrobulbar and peribulbar anesthesia remain the principle means of ophthalmic anesthesia . Methods, needles, and medications continue to vary in the search for what works best, and that is a very individual preference as is seen by the literature over the past year . The increased role of nonsteroidal anti-inflammatory drugs is discussed, along with prophylactic antibiotic use.

J Biol Chem, 1995 Jan 6, 270(1), 431 - 6
Isolation and molecular cloning of a novel bone phosphoprotein related in sequence to the cystatin family of thiol protease inhibitors; Hu B et al.; We describe here the isolation of a novel non-collagenous protein from the acid demineralization extract of bovine cortical bone . This 24-kDa protein is multiply phosphorylated at serine residues in Ser-X-Glu/Ser(P) sequences, a recognition motif for phosphorylation by the secretory pathway protein kinase, and we have termed this protein secreted phosphoprotein 24 (spp24) . The cDNA structure of spp24 was determined by sequencing cDNA fragments obtained by reverse transcription-polymerase chain reaction, 3'-rapid amplification of cDNA ends, and screening a lambda gt11 cDNA library . This cDNA sequence predicts a 200-residue initial translation product which consists of a 20-residue signal sequence and the 180-residue mature spp24 . Northern blot analysis using the spp24 cDNA showed that spp24 mRNA is in liver and bone but not in heart, lung, kidney, or spleen . A search of existing protein sequences revealed that the N-terminal 107 residues of mature spp24 are related in sequence to the cystatin family of thiol protease inhibitors, which suggests that spp24 could function to modulate the thiol protease activities that are known to be involved in bone turnover . Several of the proteins in the cystatin family that are most closely related to spp24 are not only thiol protease inhibitors but are also precursors to peptides with potent biological activity, peptides such as bradykinin and the neutrophil antibiotic peptides . It is therefore possible that the intact form of spp24 found in bone could also be a precursor to a biologically active peptide, a peptide which could coordinate an aspect of bone turnover.

Nucleic Acids Symp Ser, 1995, (34), 47 - 8
Efficient guanine alkylation through cooperative heterodimeric formation of duocarmycin A and distamycin A; Isomura M et al.; Antitumor antibiotic Duocarmycin A alkylates adenines at the 3 end of sequences of three or more consecutive A or T base pairs through binding to the minor groove of DNA . In the presence of distamycin A, duocarmycin A was found to alkylate guanine residue in G-C rich sequences, which are not alkylated by duocarmycin A alone . Efficient guanine alkylation through cooperatively binding of a heterodimer in the minor groove of DNA will be discussed.

Ann Chir, 1995, 49(10), 936 - 40
{Voluminous inguinal hernias can also be treated under local anesthesia}; Chiotasso P et al.; In patients with a large inguinal hernia, surgeons are usually reluctant to use a local anesthesia as described in the Shouldice technique . The purpose of this study was to appreciate the efficiency of such a technique . Routine local anesthesia used 200 cc of 0.5% lidocaine injected subcutaneously in the groin area and more deeply, near the anterior superior iliac spine in order to achieve a nerve block of the genital branches of the ilioinguinal and genitofemoral nerves . If necessary, the peritoneal sac is injected with lidocaine: it is usually not opened, just pushed back into the abdomen . At the end of the procedure, the estimated size of the peritoneal sac, the presence of pain, the necessity of converting the local anesthetic technique into an other procedure and the use of a prosthesis were recorded in the patient's charts . From January 1986 to December 1992, all patients with an inguinal hernia more than 6 cm in diameter, were included in the study . 111 consecutive patients were defined as having a large hernia and were operated by one of the authors . 3 patients were excluded, following general anesthesia as the first approach, males leaving 108 cases . The mean age was 59.8 years (range: 21 to 92) . There were 103 males and 5 females, 60 right hernias, 37 left and 11 bilateral of which 4 were bilateral and large, giving a total of 112 large hernias . The mean diameter of the sac was 8.6 cm (range: 6 to 30) . 7 patients were operated for recurrent large hernia . During the procedure, 9 patients reported pain which necessitated repeated injections of local anesthetic . The local procedure never had to be converted into general anesthesia . All patients had a Shouldice repair and none required the use of a prosthesis . Patients were reviewed after a mean of 36 months of postoperative course (from 5 to 79 months) . No hernia recurrence was observed, five patients had "residual" pain.

Rocz Akad Med Bialymst, 1995, 40(3), 619 - 24
The assessment of the therapeutic effectiveness of IRS-19 in allergic children with recurrent or chronic respiratory infections; Maciorkowska E et al.; The subject of the clinical-laboratory examinations was a group of 36 children aged 1 4/12 - 17 years with recurrent upper (94%) and lower (63%) airway infections, whose condition did not improve after antibiotic therapy, elimination diet and anti-histaminic treatment . In 83% of the examined patients respiratory tract symptoms co-existed with skin (61%), gastrointestinal tract (44%) and OUN (16%) diseases . 75% of examined children, with humoral and/or cellular response disorders, were given an IRS-19 vaccine, which resulted in the regression of the respiratory tract symptoms in 78% of patients . Due to side-effects in the form of high temperature, the treatment was terminated in 14% of children . The obtained therapeutic effects and convenience of administration of the vaccine, justify IRS-19 treatment in children with recurrent lower and upper airway infections, after complex immunological examination.

J Clin Gastroenterol, 1995, 21 Suppl 1, S140 - 5
Nonulcer dyspepsia: association with chronic Helicobacter pylori infection-related gastritis?
Ching CK, Lam SK.
Nonulcer dyspepsia (NUD) is a highly prevalent yet poorly understood condition . Although Helicobacter pylori infection and its associated chronic gastritis are very common in patients with NUD, there is no convincing evidence to support their etiologic role in this condition on the basis of current literature review, nor is there any evidence that H . pylori-induced chronic atrophic (type B) gastritis causes the symptoms observed in NUD . Most studies that attempted to correlate H . pylori and NUD, by epidemiologic or therapeutic intervention studies, were flawed by the lack of appropriately matched controls . Despite significant improvement observed in most therapeutic studies in histologic gastritis after treatment with bismuth-containing compounds, with or without antibiotic(s), there is conflicting evidence about whether treatment confers any clinical benefits on NUD symptomatology . A validated, universally accepted objective scoring system is desperately needed so that future controlled studies can adopt the same or a similar system to evaluate the results observed in different centers and populations . Until a definitive, positive association between H . pylori infection and NUD, such as H . pylori infection and peptic ulcer disease, has been established, it would be futile to routinely look for evidence of H . pylori infection and/or to treat the infection with eradication therapy.

Ann Oncol, 1995, 6 Suppl 4, 13 - 6
New strategies for the application of high-dose chemotherapy with haematopoietic support in paediatric solid tumours; Hartmann O; Because paediatric solid tumours are usually highly chemosensitive, conventional-dose adjuvant chemotherapy has improved survival rates for the majority of paediatric patients . However, high-dose regimens are being explored for the treatment of tumours not curable by, or resistant to, conventional treatment . The use of high-dose melphalan and the BACT regime have produced encouraging results in neuroblastoma and Ewing's sarcoma, and non-Hodgkin's lymphoma respectively . Haematopoietic growth factors have also emerged as useful adjuncts both to conventional therapy and in megatherapy with bone marrow transplantation (BMT) . Thus, granulocyte colony-stimulating factor (G-CSF) (filgrastim) given to children with disseminated neuroblastoma receiving intensive chemotherapy significantly reduced the duration of febrile neutropenia and led to significantly fewer cycles of chemotherapy requiring antibiotic support . Studies are currently underway to compare the use of autologous BMT with that of peripheral blood progenitor cell (PBPC) rescue in children with solid tumours receiving high-dose chemotherapy . The studies will explore the reduction in thrombocytopenia achievable with PBPC and also the effect of filgrastim on the duration of neutropenia and fever . It seems that haematopoietic growth factors have an important supportive role to play in the treatment of paediatric solid tumours.

Acta Otolaryngol Suppl, 1995, 520 Pt 1, 181 - 3
In vitro electrogenic K secretion in the frog semicircular canal: absence of effect of streptomycin; Ferrary E et al.; In vitro, the frog semicircular canal secretes an endolymph-like fluid, i.e . a K-rich, positively polarized fluid . This electrogenic K secretion involved basolateral Na+, K(+)-ATPase and Na-K-Cl co-transporter and a luminal protein possessing sulfhydryl groups blocked by N-ethylmaleimide . Streptomycin, an ototoxic antibiotic, is known to block the non-specific mechano-dependent channels in the sensory cells of the ampulla of the semicircular canal . The aim of the present study was to investigate the possible effect of streptomycin on the K fluxes in the ampulla of the semicircular canal . The posterior frog semicircular canal was isolated and the lumen was filled with perilymph-like solution containing or not containing 0.5 mM streptomycin . The luminal K concentration and the transepithelial potential were measured and the unidirectional K fluxes calculated . The K influxes (into the lumen, pmoles/min/mm2) were 114 +/- 25.9 and 111 +/- 3.2 (mean +/- SE, n = 3) in the absence and presence of streptomycin, respectively . The transepithelial potential was not altered (4.0 +/- 1.08 mV versus 3.4 +/- 1.03 mV, n = 3) . When ouabain (10(-3)M) was added to the basolateral solution together with luminal streptomycin, no further alteration occurred as compared with the effect of ouabain alone . These results suggest that in these conditions, the sensory organ does not have a major role in the endolymphatic K secretion in the ampulla of the frog semicircular canal.

Acta Neurochir (Wien), 1995, 137(1-2), 54 - 7
Are intra- and suprasellar masses detected by CT and MR really tumours?
Toth S, Miko L, Kollar J, Sikula J, Varallyay G.
The difficulties of differential diagnosis between intra- and suprasellar tumours resp . inflammatory processes are discussed, based on three personal cases . In all three computed tomography (CT) and magnetic resonance imaging (MR) had demonstrated a tumour, but the clinical signs with discrepancies between radiological and clinical findings were pointing to an inflammatory process . The correct diagnosis of an inflammation was achieved by co-operation between neurologist, neurosurgeon, otologist and ophthalmologist . An unnecessary neurosurgical operation was avoided and the patients were cured by otological intervention and antibiotic therapy.

Acta Neurochir (Wien), 1995, 136(1-2), 1 - 7
Risk of infection after cerebrospinal fluid shunt: an analysis of 884 first-time shunts; Borgbjerg BM et al.; Postoperative infections are major complications of cerebrospinal fluid (CSF) shunting in the treatment of hydrocephalus and other conditions with obstructed CSF circulation . In a retrospective study 884 first-time shunted patients with hydrocephalus operated on in the years 1958-1989 were investigated with special reference to the infection rate and to the influence of the following variables: time period, age of the patient, education of the neurosurgeon, length and time of the operation and the exact placement of the distal drain . The overall infection rate for all implanted CSF shunts was 7.4% (5.7-9.3%) and the acute rate of infection was 6.2% (4.6-7.9%) . The rate of infection was virtually constant for all variables with the exception of the education of the neurosurgeon . Neurosurgical trainees particularly had a significantly higher rate of infection . Shunt infection is still a major complication . The infection rate has not declined in recent decades . It is not possible to relate any main cause to the infection rate . The literature recommends removal of the infected shunt combined with antibiotics . The use of prophylactic antibiotics is still controversial . No prospective, double-blind studies, including a sufficiently large number of patients to evaluate this issue, exist today.

Microsurgery, 1995, 16(9), 606 - 11
Refinements in the one-stage procedure for management of chronic osteomyelitis; Guelinckx PJ et al.; Posttraumatic osteomyelitis remains a frequent problem and requires aggressive surgical treatment to be cured . Radical debridement of all involved soft and hard tissues, obliteration of dead space, and neovascularization of the involved area are obligatory for successful management of the disease . Microvascular free tissue transfer provides the necessary tissue bulk and neovascularization to reconstruct the resulting defect . The transplanted muscle can be optimally mobilized and adjusted in size to obliterate the dead space in contrast to local transposition flaps . This is facilitated by smoothening the bony cavity using a rotating drill system . With an optimal interface between the muscle and the wall of the cavity, small foci of infection can be eliminated . Moreover after free muscle transfer, the optimal environment for secondary bone reconstruction is created . These principles of radical debridement combined with muscle transfer for dead space obliteration, are generally accepted in literature . Nevertheless to achieve this goal several different treatment schedules of repetitive debridements, prolonged antibiotic regimes, and finally various flap transfers have been advocated . We present 16 patients with chronic osteomyelitis treated with radical debridement and immediate free muscle transfer using the latissimus dorsi muscle preferably . Postoperatively an antibiotic course of only 12 days was given . With a mean follow-up of 2 years all patients remained symptom free . Therefore, our results indicate that this long-term problem can be solved by a one-stage procedure using a free flap combined with a short course of antibiotics . However definite conclusions should be reserved for 20 years.

Microsurgery, 1995, 16(10), 704 - 12
One-stage treatment of infected bone defects of the tibia with skin loss by free vascularized osteocutaneous grafts; Doi K et al.; Twenty-six patients who had an infected nonunion or segmental defect of the tibia with skin loss were treated in one stage with debridement and a free vascularized osteocutaneous fibula or iliac graft . Successful control of infection, closure of skin defects, and incorporation of bone union were achieved in all patients except one . In an average follow-up of 39 months, no recurrence of infection was seen . There were four stress fractures of the grafted fibula; these healed within 2 months with cast immobilization . Graft hypertrophy was common in the fibula grafts, but it took 1 1/2 years for hypertrophy of the graft to be strong enough to remove external supports without stress fracture or an additional cancellous bone graft . The use of a one-stage free vascularized osteocutaneous graft for the management of infected bone defects of the tibia with skin loss is effective because extensive debridement can remove all devitalized and infected tissue and can increase vascularity in the region of infection and osseous defect to enhance antibiotic delivery.

Blood Cells Mol Dis, 1995, 21(3), 239 - 47
Safety and effectiveness of long-term interferon gamma therapy in patients with chronic granulomatous disease; Bemiller LS et al.; In chronic granulomatous disease (CGD), diminished or absent neutrophil NADPH oxidase function leads to recurrent pyogenic infections and granuloma formation . In a recent randomized, placebo-controlled trail, short-term prophylactic use of recombinant human interferon gamma (rIFN-gamma 1b) reduced the risk of serious infection in CGD patients by 67%, The current study evaluated the safety and effectiveness of long-term rIFN-gamma therapy in CGD patients . Patients were treated three times weekly with rIFN-gamma and evaluated semiannually . Serious infections (requiring hospitalization and parenteral antibiotic therapy), adverse clinical events, and measures of growth and development were noted . Thirty patients were evaluated for 12 months . The total average duration of rIFN-gamma therapy was 2.5 years . Three patients developed a total of four serious infections (0.13 infections per patient year) . This rate compare favorably with rates of 1.10 and 0.38 infections per patient year found in the placebo and rIFN-gamma groups, respectively, during a previous study . Common adverse events were fever (23%), diarrhea (13%), and flu-like illness (13%) . No serious adverse event was attributable to rIFN-gamma therapy and no obvious effects on growth and development were observed . rIFN-gamma is a safe and effective adjunctive therapy for reducing the frequency and severity of serious infections in CGD patients.

Kurume Med J, 1995, 42(4), 221 - 9
Pancreatojejunal sutural insufficiency occurring after pancreatoduodenectomy and countermeasures; Kinoshita H et al.; Pancreatojejunal sutural insufficiency occurring after pancreatoduodenectomy and countermeasures are discussed . In the Department of Surgery at Kurume University School of Medicine, 318 patients underwent pancreatoduodenectomies . The present study includes 15 of these patients, all of whom had pancreatojejunal sutural insufficiency . The frequency of sutural insufficiency was 4.7% . Five patients had bile duct cancer, 5 had cancer of the papilla of Vater, 2 had a carcinoma of the pancreatic head, 1 each had gallbladder cancer, chronic pancreatitis, and papillitis . Six (40%) of the 15 patients died during hospitalization . The presence or absence of sutural insufficiency was confirmed mainly by radiography and determining the properties and amylase levels of the drainage fluid . There was no significant difference due to the method of anastomosis . End-to-side anastomosis had a rate of 5 (5.9%) of 85 patients, while end-to-end had 10 (4.3%) of 233 patients . The sutural insufficiency was manifested as a major leakage in 6 patients and a minor leakage in 9 . The degree of lymph node dissection was D0 in 6.1%, D1 in 1.4%, D2 in 4.8% and D3 in 10.8%, with a high incidence of sutural insufficiency in D3 patients . The pancreatic duct diameter was smaller than 4 mm in 10, 5-7 mm in 4 and over 8 mm in 1 patient . The intraoperative pancreatic findings were a soft pancreas in 8, slightly hard in 3, and hard in 4 patients . Fibrosis of the pancreas was normal to slight in 11 and moderate in 4 patients . Drainage by relaparotomy was performed in 4 of the 6 patients with major leakages to control sutural insufficiency, and the other 2 underwent continuous aspiration with an intraperitoneal drain inserted during the operation . The 9 patients with minor leakage underwent conservative treatment including continuous aspiration via an intraperitoneal drain inserted during surgery, fasting, intravenous hyperalimentation, and antibiotic administration . All of the patients with major leakage died from an associated occurrence of hepatic insufficiency, renal insufficiency, intraperitoneal hemorrhage or diffuse peritonitis during hospitalization . However, 8 of the 9 patients with minor leakage had some healing, and the 1 remaining patient developed a pancreatic fistula . The frequency of pancreatojejunal sutural insufficiency was high in patients with minimal pancreatic fibrosis, with soft pancreatic tissue without dilatation of the pancreatic duct, and with relatively good pancreatic function.

Scand J Infect Dis, 1995, 27(4), 405 - 7
Progressive intractable actinomycosis in patients with AIDS; Manfredi R et al.; Two rare cases of progressive oropharyngeal actinomycosis, characterized by a subacute and invasive course despite seemingly appropriate antibiotic and surgical treatment, have been observed in patients with AIDS . A brief review of previously reported cases of actinomycosis in HIV-infected patients is presented . Clinical, diagnostic and therapeutic problems dealing with actinomycosis in the immunocompromised host are discussed.

Arch Inst Pasteur Madagascar, 1995, 62(1), 52 - 8
{Evolution of the Mycobacteria Laboratory of the Pasteur Institute of Madagascar from 1991 to 1994}; Menard D et al.; In 1991, the Laboratory of Mycobacteria was a small laboratory, part of the Clinical Biology Centre (CBC) of the Institut Pasteur de Madagascar: 656 pathological samples have been analysed for the account of the CBC and the National Control Programme activities . Within 4 years, the number of samples tested increased by more than threefold and the technical ability has evolved in an important way, specially for the identification and the antibiotic sensitivity testing . The scientific equipment have been modernized and the rooms surface increased by fourfold . In 1995, this laboratory was officially designated as the National Reference Laboratory for the culture, the identification and antibiogramme for the account of the National Control programme and for the private clinicians . It also participates to the tuberculosis research programmes of Institut Pasteur de Madagascar . It is associated to the Laboratory of Mycobacteria in the Institut d'Hygiene Sociale of Antananarivo which is the National Reference Laboratory for the bacilloscopy, the teaching and the supervision of the peripheral laboratories.

Scand J Thorac Cardiovasc Surg, 1995, 29(3), 125 - 9
Early decortication for postpneumonic empyema in children . Effect on pulmonary perfusion; Eren N et al.; Early pulmonary decortication was performed on 66 of 137 children with postpneumonic empyema, while 71 received conventional treatment . The mean age of the 66 patients with decortication was 5.5 years (range 6 months-14 years) . The empyema was left-sided in 34 and right-sided in 32 . Decortication was performed when lung expansion was not obtained after 10-12 days of intercostal tube drainage, antibiotic therapy (guided by sensitivity tests of pleural fluid) and pleural irrigation . Scintigraphy showed loss of pulmonary perfusion on the side of empyema to be 65% +/- SD 20 (25-98)% before decortication in the 23 tested patients . In ten of them the test was repeated after surgery and showed significant (p < 0.001) diminution of the perfusion defect, from 57 +/- 6.8 (25-84)% to 4 +/- 2.6 (0-8)% . The hospital stay was significantly (p < 0.001) shorter for the surgically treated than for the classically managed patients, viz . 19.5 +/- 4 (13-36) days vs 73.6 +/- 14 (34-110) days . Early decortication thus had beneficial effects on pulmonary perfusion and hospital stay.

Arch Tierernahr, 1995, 48(4), 357 - 66
Influence of lasalocid, cationomycin and feeding frequency on the postprandial kinetics of some plasma parameters in the rumen vein, portal vein and mesenteric artery of sheep; Gomez L et al.; Two adult sheep, A and B, received successively during three experimental periods a forage-based pelleted feed, then the same diet supplemented with 33 mg/kg of lasalocid (L) or cationomycin (C) . The feed was given in either eight (sheep A) or two (sheep B) daily meals . After four weeks of adaptation, 11 blood samples were taken through catheters in the rumen vein (RVA) and the mesenteric artery (MAA) in sheep A and in the rumen vein (RVB) and portal vein (PVB) in sheep B over a 5-hour period after the morning meal . Because of a blockage in the catheter it was not possible to measure the effect of C in MAA . Food intake had no immediate effect on the plasma levels measured: the distribution of eight daily meals stabilized plasma levels and made it easier to determine the effect of the ionophores . This effect varied according to the sampling site, the animal and the antibiotic, sometimes contradictorily . All the plasma parameters monitored in RVA were significantly modified by either one of the ionophores . A decrease in plasma albumin concentration (P < 0.05) was observed with L in MAA and with C in RVA and MAA . Aceto-acetate concentration decreased (P < 0.05) with L in MAA but increased with L and C in RVB . A decrease in glycaemia and uraemia (P < 0.05) was observed with L in MAA, RVA and RVB and with C in RVA . Total amino acid concentration decreased (P < 0.05) with C in RVA or increased (P < 0.05) with L in PVB and RVB . These variations in results may be due to different mechanisms of action of L and C on digestion, particularly in the rumen . While the changes undergone by the ketone bodies in the blood suggested a decrease in hepatic ketogenesis with L, there was no evidence that the ionophores had a direct postprandial effect.

J Enzyme Inhib, 1995, 9(2), 123 - 33
Amide and ester derivatives of N3-trans-epoxysuccinoyl-L-2,3-diaminopropanoic acid: inhibitors of glucosamine-6-phosphate synthase; Andruszkiewicz R et al.; Several analogs 5, 6, 7, 8, 10 and 11 of the C-terminal fragment of a peptide antibiotic Sch 37137 were designed and tested as inhibitors of glucosamine-6-phosphate synthase from Saccharomyces cerevisiae . From IC50 values and kinetic parameters of inhibition of glucosamine-6-phosphate synthase by compounds 5-11 it has been found that the inhibitory potency of these compounds follows the order: 6 > 5 > 8 > 9 > 7, 10, 11 . This suggests that an inhibitor with a primary amido group binds better to the active site of the enzyme than other inhibitors . The order of reactivity of compounds 5-11 may be attributed to a steric inability of the inhibitor to fit into the active site of the enzyme and also indicates the importance of the chirality of trans-epoxysuccinic acid on the inhibitory properties of the synthesized compounds.

J Clin Apheresis, 1995, 10(3), 124 - 7
Clinical perspectives of platelet transfusions: defining the optimal dose; Strauss RG; To halt bleeding in patients with severe thrombocytopenia due to bone marrow failure, it is desirable to achieve a post-transfusion blood platelet count of 40 x 10(9)/L by platelet transfusions . Based on calculations of corrected count increments, each 1 x 10(11) platelets transfused will increase the blood platelet count approximately 10 x 10(9)/L per each square meter of patient body surface area . Thus, the post-transfusion blood platelet count will be approximately 20 x 10(9)/L following transfusion of 3 x 10(11) platelets to a 5 foot, 8 inch patient weighing 170 pounds (2.0 m2), who is bleeding because of a pre-transfusion platelet count of 5 x 10(9)/L . The post-transfusion platelet count likely will be even lower in sick patients (sepsis, amphotericin B plus antibiotic therapy, splenomegaly, graft-vs.-host disease, etc.) or if platelets are lost from the unit by leukofiltration before transfusion . Although a dose of 3 x 10(11) platelets is acceptable, in a regulatory sense for product quality, it is inadequate to control bleeding in most thrombocytopenic adult patients . Adjusting dose for body size, bleeding patients with pre-transfusion blood platelet of < 10 x 10(9)/L and weighing > 120 pounds should receive approximately 6 x 10(11) platelets, those weighing 30 to 120 pounds should receive 3 x 10(11) platelets, and infants weighing < 30 pounds (15 kg) should receive 5-10 ml/kg of platelet concentrate.

Scand J Gastroenterol Suppl, 1995, 210, 89 - 91
Sucralfate in Helicobacter pylori eradication strategies; Lam SK et al.; BACKGROUND: Sucralfate monotherapy has been shown to suppress but not eradicate Helicobacter pylori . The combination of sucralfate with antibiotic(s) has been evaluated recently in the treatment of H . pylori-positive duodenal ulcer . The aim of this article is to review the efficacy of sucralfate-containing duotherapy and triple therapy in duodenal ulcer healing and H . pylori eradication rates . METHODS: Reports on duotherapy and triple therapy including sucralfate as the mediating agent were analysed to assess the duodenal ulcer healing and H . pylori eradication rates . RESULTS: One study on duotherapy with sucralfate and amoxycillin achieved an ulcer healing rate of 86% and H . pylori eradication rate of 40%, which compared favourably with sucralfate monotherapy that resulted in duodenal ulcer healing and H . pylori eradication rates of 65% and 0% respectively . A total of six studies have examined triple therapy using sucralfate with two antibiotics . The duodenal ulcer healing rates were generally over 90% and the H . pylori eradication rates about 80% (range 59% to 100%) . In one comparative study, the 4-week duodenal ulcer healing and H . pylori eradication rates of sucralfate-containing triple therapy were not distinguishable from those of omeprazole-containing triple therapy . CONCLUSIONS: It is concluded that sucralfate is an effective mediating agent for the eradication of H . pylori in patients with duodenal ulcer.

Scand J Gastroenterol Suppl, 1995, 210, 1 - 5
To repair the fault or end the acid reign?
Modlin IM.
BACKGROUND: Despite the vast effort and expense devoted to the elucidation of the cause of esophagogastro-duodenal ulcer disease, relatively minimal progress has been made towards the understanding of causation . Since earliest times, it has been recognized that milk, chalk powder, or charcoal ameliorate the disease process and its symptoms . In addition, the avoidance of acidic or spicy foods provides some relief . Thus ulcer disease has been ascribed to acid or the consequences of hyperacidity . Reams of data and countless meetings have purported to confirm and support this viewpoint . Surprisingly, the co-secretion in the stomach of the powerful proteolytic enzyme pepsin has been virtually ignored as a pathogenetic agent . Marshalling distant antipodean resources, a novel bacteria, H . pylori, was identified as a significant causative agent in ulcer disease . To the amazement of nobody but gastroenterologists, it became apparent that there might be more than one cause for ulcer disease . Subsequently, both corporations and physicians seized the reins of multi-variant antibiotic therapy as a panacea for the third millennium treatment of peptic ulcer disease . Only a brave few have raised the issues of possible abnormalities in intrinsic mucosal function which might generate a locus minoris resistentiae . Defective mucosal repair mechanisms have barely been evaluated, since the regulation of normal mucosal healing is so poorly understood . Nevertheless, consideration of the therapeutic potential of mucosal protection has found support at both an intellectual and a clinical level . The more exciting recent possibility of the local delivery of growth factors which might promote healing has provided a unique opportunity for further therapeutic advance . CONCLUSIONS: Indeed in the future the exogenous regulation of mucosal repair may provide a milieu conductive to the resolution of an old but ill-understood problem . It is certainly apparent that processes beyond parietal cell proton secretion are critical and require both delineation and management . The acid reign may be in decline but the site of the fault and its repair remain to be defined.

Yao Xue Xue Bao, 1995, 30(8), 583 - 7
{Effect of the conjugate composed of a human monoclonal antibody and pingyangmycin on mammary cancer}; Wang WG et al.; To avoid or reduce the induction of human anti-mouse antibody reaction, it is important to use human antibody for the preparation of therapeutic immunoconjugate . CM1, a human monoclonal antibody directed against mammary cancer, was linked to pingyangmycin (PYM), an antitumor antibiotic identical to bleomycin A5 currently in clinical use, employing Dextran T-40 as an intermediate agent . As determined by clonogenic assay with mammary cancer CAMA cells, the IC50 values for CM1-PYM conjugate and free PYM were 0.35 mumol.L-1 and 4.0 mumol.L-1, respectively . Mammary cancer CAMA was transplanted sc in nude mice . Peritumoral injection of CM1-PYM conjugate at doses of 1.25 mg.kg-1 and 2.5 mg.kg-1 inhibited the growth of CAMA xenograft by 86% and 95% (P < 0.01), whereas the injection of equivalent doses of free PYM inhibited CAMA xenograft by 49% and 58% (P < 0.05), respectively . CM1-PYM conjugate showed remarkable suppression on CAMA xenograft and the inhibitory effect of CM1-PYM conjugate was much higher than that of free PYM . By histo-pathological examination, no toxic changes were found in the heart, lung, liver, intestines, kidney, spleen and bone marrow of the CM1-PYM- or PYM-treated animals . These results suggest that local administration of the immunoconjugate composed of a human monoclonal antibody and pingyangmycin is highly effective and the conjugate may be useful in therapy for human breast cancer.

Int J Colorectal Dis, 1995, 10(4), 197 - 9
Closure of rectal stump after colectomy for acute colitis; Wojdemann M et al.; In a retrospective study complications, mortality and morbidity following acute colectomy for severe colitis with intra-abdominal closure of the rectal stump were reviewed in 147 consecutive patients (71 women and 76 men, median age of 40 years, range 18-95 years) . Five patients (3%) died within 30 days postoperatively; none of the deaths were related to the rectal stump . Three patients (2%) had a pelvic abscess due to leakage of the rectal closure, all were treated successfully with percutaneous drainage, guided by ultrasonography . No difficulties in locating the rectal stump or performing intended subsequent surgery were reported . The overall complications and mortality rate in this study are low and comparable to the best results reported from centers using the mucous fistula . Closure of the rectal stump is a safe procedure, and has the advantage of not leaving the patient with a second stoma.

Rev Chir Orthop Reparatrice Appar Mot, 1995, 81(6), 553 - 6
{Multifocal bone tuberculosis: apropos of a case}; Moujtahid M et al.; INTRODUCTION: Tuberculosis of bone is rare (10 to 20 per cent of all skeletal tuberculosis) . The multifocal form is exceptional even in endemic countries of tuberculosis . It constitutes less than 5 per cent of all osseous tuberculosis . CASE REPORT: O.H . 34 year-old, Moroccan woman of black race not vaccinated against tuberculosis, with a contagion, complained for a year from scapular pain and weight loss . She noticed that two masses had appeared six months ago . The patient was feverish (38 degrees) . The physical exam showed a non inflammatory mass 10 cm wide located in front of the left sacroiliac joint and seeming to be a cold abscess . The radiologic assessment showed a lytic image of the humerus upper extremity, the right iliopubis branch, the left ischium and the left iliac wing . The surgical biopsy of the humerus showed an evolutive caseo-follicular tuberculosis . The nuclear scan of bone found two other localizations in the fourth lumbar vertebra and the ninth left rib . We concluded to a multifocal bone tuberculosis with seven localizations: The upper extremity of both humerus Right pubis Left ischium Left iliac wing 4th lumbar vertebra 9th left rib . The treatment consisted in a specific antibiotic therapy for 6 months associated to the evacuation of the cold abscess . DISCUSSION: Multifocal bone tuberculosis is more frequent in young adults of black race . The beginning of the disease is progressive and the fistulas are the main reason of consultation . The radiologic lesions are not specific and have a geodic shape rimmed with an osteocondensation . Multifocal bone tuberculosis in black african predominate in flat bones . Otherwise in the white race it is located in the long bones extremities . The diagnosis of certitude is based on histologic findings of the peripheric bone lesion . The specific antibiotic therapy leads to the recovery if given early . Short protocols (9 or 6 months) are recently more used with success.

Exp Brain Res, 1995, 106(1), 57 - 68
Intrinsic burst generation of preinspiratory neurons in the medulla of brainstem-spinal cord preparations isolated from newborn rats; Onimaru H et al.; In brainstem-spinal cord preparations isolated from newborn rats, intrinsic burst-generating properties of preinspiratory (Pre-I) neurons in the rostral ventrolateral medulla, which have been suggested to be primary respiratory rhythm-generating neurons, were studied by "perforated" whole-cell recordings using the antibiotic nystatin . Nystatin causes small pores to be formed in the cells, through which pass small monovalent ions . For blockade of chemical synaptic transmission, perfusate Ca2+ concentration was lowered to 0.2 mM and the Mg2+ concentration was increased to 5 mM . In low-Ca2+, high-Mg2+ solution (referred to here as "low Ca"), 10 of 55 Pre-I neurons generated rhythmic bursts (burst type), 14 fired tonically (tonic type), and 31 were silent (silent type) . Burst-type neurons showed periodic depolarization of 5-12 mV in low Ca, at a rate of 12 +/- 6.5/min . Hyperpolarization of the membrane caused decrease in or disappearance of the periodic depolarization and prolongation of the cycle period . Thus, the burst generations were voltage dependent . The firing frequency of tonic-type neurons was 2.3 +/- 1.6 Hz and was decreased by hyperpolarization . In 6 of these neurons, the firing patterns changed to burst patterns during continuous hyperpolarization . Membrane depolarization by continuous outward current injection into some silent-type neurons (3 of 11 tested) induced bursting activity . Activity of C4 and Pre-I neurons was completely silent with 0.1-1 microM tetrodotoxin (TTX) added to the standard perfusate . In low Ca, burst-type neurons (n = 3) were also silent with 1 microM TTX perfusion . Inspiratory neurons either became silent (n = 4) or fired tonically (n = 1) in low Ca . The present study by "perforated" whole-cell recordings confirmed that some Pre-I neurons possess intrinsic burst-generating properties, which were not attributable to phasic synaptic inputs.

J Orthop Trauma, 1995, 9(5), 401 - 6
Bone toxicity of locally applied aminoglycosides; Miclau T et al.; The effect of tobramycin on osteoblasts was studied . Osteoblast-like cells from the MG-63 human osteosarcoma cell line were grown in antibiotic-free media and exposed to concentrations of tobramycin: first at order of magnitude intervals between 0 and 10,000 micrograms/ml, and then at closer intervals between 100 and 1,000 micrograms/ml to more accurately define toxic levels . Cell number and 3H-thymidine incorporation at 0, 24 and 72 h were determined . Similarly, primary cultures of rat osteoblasts were exposed to the same concentrations of tobramycin to confirm the validity of the MG-63 cell line as a model for nontransformed cells . The results of this study demonstrate that local levels of tobramycin of < or = 200 micrograms/ml have little or no effect on osteoblast replication . Concentrations of 400 micrograms/ml significantly decreased cell replication, and concentrations of 10,000 micrograms/ml caused cell death . Results obtained with primary rat osteoblast cultures were similar to those obtained from the MG-63 cultures at the tested tobramycin concentrations.

Infection, 1995, 23 Suppl 2, S70 - 3
Acute otitis media in childhood: a study of 20,532 cases; Del Castillo F et al.; We present a study of acute otitis media among 20,532 Spanish children during a 6-month period from January through June 1991 . The study was done by distributing a questionnaire to all Spanish pediatricians . Of the patients 51.7% were girls and 48.3% boys; 68.7% of all children were younger than 5 years . The most frequent symptoms were otalgia or irritability, 92.7%; fever, 63.5%; otorrhea, 24.9%; vomiting, 21.4%; and another concomitant upper respiratory tract infection, 65.5% . Otitis was bilateral in 45.6% of the cases . The most frequently used antibiotic was cefixime (38%), followed by amoxicillin-clavulanate (22.2%), amoxicillin (15.3%), 2nd-generation cephalosporins (13.5%) and macrolides (8.8%) . In 11.8% of the patients, a change in the initial antibiotic therapy was required due to adverse effects . Resolution of symptoms occurred in 77.8% of the patients.

Urol Int, 1995, 55(2), 101 - 4
Sequential changes in the prostatic fluid level of latamoxef in patients with acute bacterial prostatitis; Itoh M et al.; The sequential expressed prostatic secretion (EPS) levels of latamoxef (LMOX) were measured in 14 patients with acute bacterial prostatitis to evaluate the diffusion of this antibiotic from the plasma into the prostatic fluid . All patients received 2 g of LMOX on the 1st, 4th, and 7th days of hospitalization . The mean LMOX level in EPS and the EPS/serum ratio were 16.4 micrograms/ml and 0.24 on the 1st day, 5.5 micrograms/ml and 0.08 on the 4th day, and 3.5 micrograms/ml and 0.04 on the 7th day, respectively . The mean value of prostatic fluid was 7.7, 7.8, and 7.8, respectively . Thus, both the EPS level of LMOX and the EPS/serum ratio decreased along with the recovery from acute bacterial prostatitis and did not correlate with the pH gradient between prostatic fluid and plasma.

Khirurgiia (Sofiia), 1995, 48(2), 28 - 9
{Economic surgical interventions on the foot in diabetic gangrene}; Petkov R et al.; Primary surgical toilet is the main stage of surgical management of diabetic gangrene, usually associated with amputation of isolated toes, or varying in type transmetatarsal amputations . Elimination of the basic tissue decomposition and wide exposure of all purulent cavities contribute greatly to restrict the purulent gangrenous process in course . Simultaneously, adequate insulin and antibiotic therapy is conducted . If necessary, at a second stage plastic reconstructive operations are performed with a view to improve the biomechanics of the foot.

Rapid Commun Mass Spectrom, 1995, 9(13), 1297 - 301
Analysis of tilmicosin in swine liver extracts by liquid chromatography/atmospheric pressure chemical ionization mass spectrometry; Kiehl DE et al.; Tilmicosin is a semisynthetic macrolide antibiotic used in the treatment of respiratory disease in cattle and swine . The technique of liquid chromatography/atmospheric pressure chemical ionization mass spectrometry (LC/APCI-MS) was employed in an on-line capacity for the analysis of tilmicosin in extracts from spiked swine liver . Increasing the potential in the cone/skimmer region of the ion source resulted in an increased abundance of unique structurally indicating fragment ions of tilmicosin . Three ions, {M+H}+ and two diagnostic fragment ions were chosen for confirmation of the presence of tilmicosin in swine liver tissue extracts using the mass spectrometer in selected-ion monitoring mode . The ion abundance ratios arising from any given combination of ions in data acquired from extracts of swine liver tissue spiked with tilmicosin at 5 and 10 ppm were within +/- 10% of the corresponding mean standard abundance ratio, and duplicate sample analyses exhibited < 10% relative standard deviation . These results suggest the potential for the application of LC/APCI-MS as a confirmatory technique for tilmicosin in swine liver.

Annu Rev Nutr, 1995, 15, 399 - 417
The importance of menaquinones in human nutrition; Suttie JW; Bacterially produced menaquinones, 2-methyl-1,4-naphthoquinones with an unsaturated polyisoprenoid chain at the 3-position, are biologically active forms of vitamin K that are present in high concentrations in the human lower bowel . Menaquinones are found in human liver and circulate in human plasma at much higher concentrations than previously thought . Numerous case reports of antibiotic-induced, vitamin K-responsive hypothrombinemias have been taken as evidence that menaquinones contribute importantly to satisfying the human vitamin K requirement . However, more recent production of symptoms of vitamin K insufficiency in normal human subjects by dietary restriction of vitamin K argues against their nutritional significance . Current data support the view that menaquinones may partially satisfy the human requirement but that their contribution is much less than previously thought.

Arch Toxicol, 1995, 69(7), 472 - 9
Development of a suspension organ culture of the fetal rat palate; al-Obaidi N et al.; On the basis of an already established suspension organ culture system of mouse palate anlagen, we developed a corresponding culture system for rat palate anlagen . In order to optimize the culture results we systematically studied the influence of main "culture conditions" such as dissection technique, rotation speed, gassing schedule, and developmental stage at the onset of culture for mice and rat palate anlagen . This system allows culturing rat palate anlagen from day 15 of gestation to day 18 + 8 h (80 h) under serum- and antibiotic-free conditions using a chemically defined medium, resulting in 90% fused palates . The explants, containing the maxillary vault and the palatal shelves, were cultured in siliconized culture flasks at a rotation speed of 12 rpm and a temperature of 37 degrees C (Table 1).

J Bacteriol, 1995 Jan, 177(1), 152 - 5
Purification and characterization of a novel extracellular Streptomyces lividans 66 enzyme inactivating fusidic acid; von der Haar B et al.; The wild-type strain Streptomyces lividans 66 is resistant against the steroid-like antibiotic fusidic acid . Comparative studies of the wild-type strain and a fusidic acid-sensitive mutant allowed the identification of an extracellular enzyme which inactivates fusidic acid . With the help of a combination of ultrafiltration and chromatographies with Phenyl-Sepharose and an anion exchanger, the enzyme was highly purified . Its apparent molecular mass is 48 kDa, its optimal activity ranges between 45 and 55 degrees C, and its optimal pH is 6.0 to 9.0 . It is stimulated by neither monovalent nor divalent ions . The enzyme acts as a specific esterase which removes the acetyl group at C-16 from fusidic acid . The resulting intermediate is unstable, and spontaneous lactonization between C-21 and C-16 occurs rapidly.

J Am Coll Surg, 1995 Jan, 180(1), 10 - 5
Interposed jejunal segment with nipple valve to prevent reflux in biliary reconstruction; Shamberger RC et al.; BACKGROUND: Resection is the accepted management of a choledochal cyst . However, the debate continues regarding the optimal method of biliary reconstruction . The Roux-en-Y limb is used most frequently, but concerns have been raised about this method due to associated peptic ulcer disease, cholangitis, and poor growth . A method of reconstruction using an interposed segment of jejunum with a nipple valve placed between the common bile duct and the duodenum has been proposed . STUDY DESIGN: We have reviewed a series of 12 children requiring biliary reconstruction for choledochal cyst (11 children) and biliary stricture (one child) . All had reconstruction with a nipple valve, and ten had an interposed segment of jejunum . RESULTS: All of the children are alive and have had follow-up evaluation from six months to 8.5 years (median of three years) . Sequential examinations with ultrasound and biliary excretion scans have shown no evidence of obstruction, and liver function tests have remained normal . Three children have had cholangitis . One child had a brief episode in the perioperative period . The second child had cholangitis 16 months postoperatively, and the third child had multiple episodes of cholangitis . These latter two children were unique . One had Alonso-Lej type IV choledochal cyst with intrahepatic dilatation, which persisted after reconstruction . The other had a prior diversion with a Roux-en-Y limb from the gallbladder after resection of a choledochal cyst and had multiple episodes of cholangitis before reconstruction . These episodes are now controlled with chronic antibiotic suppression . Postoperative complications were limited to two episodes of obstruction of the small bowel requiring lysis of adhesions . No child has had peptic ulcer disease . These children have grown well after reconstruction, except for three with multiple anomalies or chronic pancreatitis . CONCLUSIONS: Biliary reconstruction with a jejunal interposition containing a nipple valve can be performed safely with a low incidence of complications . It offers a more physiologic method of reconstruction and a low incidence of postoperative cholangitis.

AJR Am J Roentgenol, 1995 Jan, 164(1), 57 - 61
Bronchogenic carcinoma in HIV-positive patients: findings on chest radiographs and CT scans; Fishman JE et al.; OBJECTIVE . The radiographic manifestations of bronchogenic carcinoma in HIV-positive individuals may resemble or accompany changes of inflammatory disease . To provide information that is useful in the differential diagnosis, we studied the findings on plain radiographs and chest CT scans in 30 HIV-positive patients with proven bronchogenic carcinoma and correlated the radiographic features with the presence or absence of thoracic opportunistic infection . SUBJECTS AND METHODS . Thirty HIV-positive individuals had bronchogenic carcinoma diagnosed at our institution between 1986 and 1993 . Fourteen (47%) of the 30 had AIDS at the time of cancer diagnosis . All but one of the patients were men, and the median age at diagnosis was 48 years (range, 32-66 years) . Most (90%) had a history of smoking . Eighteen (60%) of the 30 had a history of pulmonary tuberculosis, Pneumocystis carinii pneumonia, or both . We retrospectively reviewed all available chest radiographs (n = 27) and chest CT scans (n = 25) for tumor size and location, adenopathy, pleural disease, and pulmonary infiltrates . RESULTS . Eighteen tumors (60%) were peripheral, 11 (37%) were central (hilar or mediastinal), and one manifested as a metastatic pleural mass . Of the peripheral tumors, 17 (94%) were in the upper lobes . All the central tumors showed obstructive consolidation of lung in the distribution of the affected airway . Adenopathy was present in 63% of the patients, and pleural effusions or masses were seen in 33% . A history of tuberculosis or Pneumocystis carinii pneumonia was present in 83% of the patients with peripheral tumors but only 27% of the patients with central lesions (p = .005) . Superimposed infiltrates were present in six patients (20%) . Three (17%) of 18 peripheral tumors were obscured by or mistaken for inflammatory disease, delaying the diagnosis of cancer . CONCLUSION . Bronchogenic carcinoma usually manifests as a peripheral upper lobe mass in HIV-positive patients with a history of tuberculosis or Pneumocystis carinii pneumonia, whereas central masses are more common in patients without a history of thoracic opportunistic infection . Carcinoma should be suspected in patients with peripheral lesions that persist despite appropriate antibiotic therapy.

AJR Am J Roentgenol, 1995 Jan, 164(1), 201 - 6
Treatment of pelvic abscesses: value of one-step sonographically guided transrectal needle aspiration and lavage; Kuligowska E et al.; OBJECTIVE . The percutaneous treatment of pelvic abscesses has traditionally involved the placement of drainage catheters via a transgluteal, transrectal, or transvaginal route . These procedures are painful and prolonged . The goal of this study was to demonstrate the effectiveness of a one-step, single-puncture method for draining pelvic abscesses by use of a transrectal sonographically guided needle for aspiration and lavage instead of a two-step Seldinger technique for catheter placement . SUBJECTS AND METHODS . Thirty-three pelvic abscesses in 24 patients were drained by use of transrectal ultrasound guidance . All abscesses were initially seen on transrectal sonograms or CT scans and ranged from 2 to 11 cm in diameter . Abscesses were located in the prostate (n = five), seminal vesicles (n = five), pouch of Douglas (n = 21), and interloop (between bowel loops) (n = two) . Causes of pouch of Douglas (cul-de-sac) abscesses included appendicitis (n = two), Crohn's disease (n = two), diverticulitis (n = three), trauma (n = six), HIV infection (n = two), complications of sigmoidectomy (n = one), complications of colectomy (n = one), pelvic inflammatory disease (n = two), and severe prostatitis (n = two) . Interloop abscesses were attributable to HIV infection (n = one) and lymphoma (n = one) . The procedure was performed without a cleansing enema or local anesthesia and required less than 30 min . An 18-gauge needle was inserted transrectally into the abscess cavity under transrectally guided sonography . The fluid collection was completely aspirated, and the cavity was lavaged with saline . Administration of antibiotics for 7-21 days, rather than prolonged catheter drainage, was used to treat residual infection . Resolution was documented after 7 days by sonography or CT examination . RESULTS . Transrectal aspiration was successful in treating 28 (85%) of the 33 pelvic abscesses in 21 (88%) of the 24 patients . Failure occurred in three patients, two with multiple abscesses and one with an enteric fistula for whom surgical drainage was subsequently required . The volume of aspirates ranged from 5 to 220 ml . There were no complications . CONCLUSION . Transrectal sonographically guided needle aspiration-lavage offers a one-step method for treating pelvic abscesses that does not require catheter placement or prolonged drainage . The procedure produces minimal discomfort and essentially no complications . Our results show that transrectal sonographically guided needle aspiration combined with antibiotic therapy is an effective treatment for pelvic abscesses.

Digestion, 1995, 56(1), 14 - 20
High-dose omeprazole plus amoxicillin or clarithromycin cures Helicobacter pylori infection in duodenal ulcer disease; Labenz J et al.; Treatment with omeprazole plus amoxicillin or clarithromycin resulted in encouraging Helicobacter pylori cure rates in pilot and controlled studies . The present prospective, randomized study was designed to compared the efficacy and safety of amoxicillin and clarithromycin as constituents of omeprazole-enhanced antibiotic therapy of H . pylori infection . Fifty patients with active duodenal ulcer disease and histologically and/or culturally confirmed H . pylori colonization of the gastric mucosa were treated with omeprazole (day 1-14: 40 mg twice daily, day 15-42: 20 mg once in the morning) . The patients were randomly assigned to receive either amoxicillin (1 g twice daily; group I: n = 25) or clarithromycin (500 mg twice daily; group II: n = 25) during the first 2 weeks of treatment . The patients of group I and II had comparable demographic and clinical characteristics . One patient of group I was lost to follow-up . H . pylori infection was cured in 87.5% of group I and 84.0% of group II (p = 1.00) . All ulcers had healed after 6 weeks of omeprazole treatment . Pain relief occurred within the first day of treatment in the majority of patients of both groups (p = 0.89) . Minor side effects were recorded in 6 patients of group I and in 4 patients of group II (25 vs . 16%; p = 0.50) . In 1 female patient amoxicillin had to be withdrawn after 3 days because of nausea and emesis . In conclusion, 2 weeks of treatment with omeprazole plus amoxicillin or clarithromycin are highly and equally effective regimens to cure H . pylori infection in patients with duodenal ulcer disease.

Wien Klin Wochenschr, 1995, 107(3), 95 - 100
{Idiopathic CD4+ T-lymphocytopenia in 2 patients without indications for HIV infection}; Pohl W et al.; We report on two patients with idiopathic CD4+ T cell depletion . A 26 year-old woman presented to us with acute respiratory failure requiring mechanical ventilation . Despite combined antibiotic therapy parenterally the opacities increased in the chest X-ray . An open lung biopsy was performed and led to the histological diagnosis of bronchiolitis obliterans organizing pneumonia (BOOP) . Respiratory function was improved impressively by high dose parenteral cortisone administration . This patient showed a general lymphocytopenia with severe CD4+ T cell depletion (60(37%)/mm3 blood) . The CT4+ T cell concentration increased during a follow up period of 14 months, but did not reach normal values . The second patient was a 33 year-old homosexual . He was admitted with a mucocutaneous fungal infection which was successfully treated by antifungal drugs . This patient demonstrated a transient CD4+ T cell depletion (350(32%)/mm3 blood) . In both patients HIV type 1 and 2 infections were excluded by antibody- and p 24-antigen testing, polymerase chain reaction and virus culture . CONCLUSION . Idiopathic CD4+ T lymphocytopenia differs from HIV infection in immunological profile, in the tendency to reversal of the CD4+ T cell depletion over time and in its better prognosis . It is unclear if this is a new syndrome and whether a transmissible agent, or possibly a genetically-determined reaction to noxious agents is responsible.

J Clin Epidemiol, 1995 Jan, 48(1), 149 - 57
The practice of meta-analysis; Bailar JC 3rd; Meta-analysis seems to have a potentially useful role in carefully selected situations where the primary literature is of good quality, heterogeneity in the response to treatment of the tested population is small and well-understood, interest centers on estimation of a specific, critical parameter of outcome, and the meta-analyst is deeply expert in the subject matter . Other uses can produce, and have produced, results that may be seriously misleading . Five short case studies are presented (diethylstilbestrol and outcome of pregnancy, chlorination of drinking water and cancer, cisplatin and cancer of the ovary, antibiotic therapy for otitis media with effusion, and beta-agonists and asthma).

J Chromatogr Sci, 1995 Jan, 33(1), 49 - 54
Factors that influence the determination of residual solvents in pharmaceuticals by automated static headspace sampling coupled to capillary GC-MS; Mulligan KJ et al.; The impact of several experimental parameters on static headspace sampling for volatile impurities is discussed . Figures of merit are provided for some common organic solvents dissolved in dimethylacetamide . The performance is compound specific, but in the best case, detectability is about 0.2 mg/L with the mass spectrometer operating in the scanning mode . Sensitivity improves by about a factor of 50 when single ion monitoring is used . Linearity extends for about 4 orders of magnitude . This system is used to determine acetone as a residual solvent in the sulfonamide antibiotic, sulfamethazine, at levels of 1 to 15 mg/kg with precision of 3 to 5%.

Orthop Clin North Am, 1995 Jan, 26(1), 123 - 31
Management of civilian gunshot injuries to the hip; Long WT et al.; The orthopedic surgeon at a civilian trauma center is likely to encounter a gunshot injury to the hip . The nonmilitary literature regarding this injury gives few guidelines regarding an appropriate diagnostic evaluation or the indication for arthrotomy . We found that the best diagnostic test to detect joint penetration was hip aspiration followed by an arthrogram . Selected cases can be treated successfully with antibiotic therapy without an arthrotomy . These cases involve a low-velocity missile that passes through the joint, causes minimal bone disruption, and is free of bowel contaminants . If an arthrotomy is not performed, the physician must follow the patient with repeated physical examinations, complete blood counts, and a hip aspiration whenever infection is suspected . All transbdominal hip injuries require an immediate arthrotomy . In this series, bullets left in contact with joint fluid resulted in joint destruction or infection . Each patient with a displaced femoral neck fracture had a poor outcome with internal fixation . Hip arthroplasty or fusion should be considered as elective procedures for definitive management of these injuries.

Isr J Med Sci, 1995 Jan, 31(1), 59 - 61
Oral fluoroquinolone use in the community; Elhanan G et al.; The use of oral fluoroquinolone in the community was evaluated in the Jezreel Valley area in northern Israel over an 8-month period . A total of 1,136 prescriptions for oral quinolones were prescribed for a population of 300,000 people . The findings of the study show that 70% of the prescriptions were initiated by outpatient clinic specialists or at hospital discharge, and that 70% of all prescriptions were justified and properly prescribed . No significant difference was found whether the initiating physician was a specialist or family practitioner or when the drug was recommended on hospital discharge . Moreover, the manner in which the different antibiotics were internally divided indicated the prescribing physicians' understanding of the properties of each drug . The results demonstrate that oral fluoroquinolones have been used in the Jezreel Valley area sparingly, judiciously, and according to each drug's properties . The high degree of justified use may reflect successful antibiotic control within the medical center serving that area.

Neurology, 1995 Jan, 45(1), 6 - 10
Idiopathic intracranial hypertension associated with tetracycline use in fraternal twins: case reports and review; Gardner K et al.; Fraternal twin sisters developed idiopathic intracranial hypertension (IIH) shortly after beginning tetracycline for treatment of acne . We reviewed from the literature 19 familial cases of IIH and 37 cases of IIH associated with tetracycline usage . Among the 37 combined adult and pediatric cases, 26 of 37 had resolution of signs or symptoms of IIH within hours to days of stopping the antibiotic, and rapid recurrence with reinitiation of drug occurred in 4 of 37 . We suggest that these cases may be tetracycline-induced, may be related to an underlying genetic susceptibility, and support the notion of multifactorial etiologies for IIH.

Food Chem Toxicol, 1995 Jan, 33(1), 57 - 68
Effects of contact sensitizers neomycin sulfate, benzocaine and 2,4-dinitrobenzene 1-sulfonate, sodium salt on viability, membrane integrity and IL-1 alpha mRNA expression of cultured normal human keratinocytes; Pastore S et al.; The toxic effect of three potential contact sensitization chemicals {the aminoglycosidic antibiotic neomycin sulfate, the local anaesthetic benzocaine and the primary sensitizer 2,4-dinitrobenzene 1-sulfonate, sodium salt (DNBS)}, on cultured human keratinocytes was examined . The three chemicals were compared with respect to their cytotoxic potential (determined by crystal violet staining assay), their membrane disruptive potential ({3H}arachidonic acid release assay), and their effects on interleukin 1 alpha (IL-1 alpha) mRNA expression {reverse transcription-polymerase chain reaction (RT-PCR)} . At the concentrations used, neomycin sulfate (0.004-0.32%) and benzocaine (0.0165-0.165%) did not show relevant cytotoxicity or membrane perturbation . On the other hand, DNBS (0.001-1%) caused a significant dose-dependent cytotoxic response at concentrations higher than 0.1%, while the {3H}arachidonic acid release assay indicated absence of membrane perturbation activity in all the range of DNBS concentrations examined . The effects of the three sensitizers on IL-1 alpha mRNA expression were varied; neomycin sulfate caused a dose-dependent induction of IL-1 alpha mRNA, benzocaine did not significantly affect its signal, and DNBS suppressed IL-1 alpha gene expression.

Hum Genet, 1995 Jan, 95(1), 49 - 55
High resolution mid-prophase human chromosomes induced by echinomycin and ethidium bromide; Sawyer JR; The antitumor antibiotic echinomycin (EM) was used in combination with ethidium bromide (EB) to induce high resolution mid-prophase chromosomes from amethopterin synchronized blood lymphocytes . With this combination of drugs, trypsin G-banded chromosomes showed over 1200 bands per haploid set in cells having a mid-prophase length of decondensation.

Dis Colon Rectum, 1995 Jan, 38(1), 4 - 6
Operative repair of anovaginal and rectovaginal fistulas; Mazier WP et al.; PURPOSE: Operative repair of low rectovaginal fistulas should be tailored to the specific anatomic defect . Endoanal flap repair frequently provides successful fistula closure; however, if substantial injury to the perineal body, anal sphincter, or rectovaginal septum exists, a more extensive repair is required . We present our experience with 95 consecutive patients, operated for rectovaginal fistulas via septal repair after conversion to a fourth degree perineal laceration, endoanal flap, or anoperineorrhaphy . METHODS: A retrospective chart review was performed . Data collected included etiology, location, size, repair type, and degree of anal continence . All patients received standard mechanical and antibiotic bowel preparation and parenteral antibiotics . No covering stomas were used . RESULTS: Fistula etiology included obstetric injury (N = 77), perianal cryptoglandular infection (N = 15), and other (N = 3) . Thirty-one patients had previous unsuccessful repairs . Types of repairs were fourth degree perineal laceration (38), endoanal flap (19), and anoperineorrhaphy (38) . Excellent or good functional results occurred in 92 patients (97 percent) . Similar success occurred in patients with previous failed repairs (90 percent excellent or good) . The recurrence rate was 3 percent . There were no outcome differences between techniques . CONCLUSION: We believe that all three types of repair for rectovaginal fistulas result in a high cure rate, thereby allowing operative technique to be tailored to the anatomic defects present . This approach should allow for optimal functional outcome.

Chest, 1995 Jan, 107(1), 96 - 100
Influence of three factors on the diagnostic effectiveness of transthoracic needle aspiration in pneumonia; Zalacain R et al.; Prior antibiotic therapy, size of the infiltrate, and the person who performed the technique were the three factors that we studied to assess their influence on the effectiveness of transthoracic needle aspiration (TNA) . Ninety-one patients with a diagnosis of severe bacterial pneumonia, who underwent TNA, have been included in the study . The technique was carried out with an ultrathin needle gauge 25 and without fluoroscopic control . A univariate (UA) and a multivariate statistical analysis were made . The sensitivity of TNA was 34.1% . Fifty-seven of 91 (62.6%) had received antibiotic therapy prior to TNA; sensitivity was higher in nontreated patients than in treated patients (p = 0.0033; UA) . There were 34 patients with an infiltrate that was smaller than a lobe (MINLOB); 39 cases affected a complete lobe (LOB) and 18 more than one lobe (MAJLOB) . The TNA sensitivity was higher in LOB cases than in MINLOB cases (p = 0.0004; UA) while when comparing LOB cases and MAJLOB cases, sensitivity was higher in the former (p = NS; UA) . In 28 of 91 cases (30.8%), the TNA was performed by A (a trained physician who regularly carries out the technique) and in 63 of 91 cases (69.2%) by B (other physicians, 10 in our study, who sporadically perform the technique) . The TNA sensitivity was higher when the technique was performed by A, although this difference was not significant; if we add negative TNA with leukocytes present in Gram stains (which would indicate that aspiration was done in the correct area) to positive TNA, the difference between A and B was higher (p = 0.0248) . The multivariate statistical analysis confirmed that there are two variables that are independently connected to a positive TNA (prior antibiotic therapy and size of the infiltrate) . As regards the variable "person who carries out the technique," a significant association with a positive TNA was not established, although the estimations we obtained show a possible clinical relevance.

Chest, 1995 Jan, 107(1), 85 - 95
Decision making in nosocomial pneumonia . An analytic approach to the interpretation of quantitative bronchoscopic cultures; Baker AM et al.; Quantitative cultures of specimens obtained at fiberoptic bronchoscopy have been used to diagnose nosocomial pneumonia in research settings, but their clinical role remains controversial . We reviewed the literature comparing these culture techniques with other accepted methods to diagnose pneumonia in mechanically ventilated patients and extracted data to describe the receiver operator characteristics (ROC) of quantitative cultures of protected specimen brush (PSB) and bronchoalveolar lavage (BAL) samples . Analysis of ROCs reveals that these tests have a discriminating power comparable or superior to that of many widely accepted routinely used tests . Current data do not suggest that either culture technique offers an advantage over the other . Since benefits of antibiotic therapy of pneumonia and risks of treatment of noninfected critically ill patients are not well quantified, universally applicable recommendations for appropriate values to define an abnormal test result cannot logically be made . Multiple decision analytic tools show that values lower than those previously recommended are more appropriate in patients suspected of having pneumonia unless the risk of antibiotic therapy is judged to be extreme . On the basis of these findings, we suggest guidelines for clinicians' interpretation of PSB and BAL quantitative culture results.

Mayo Clin Proc, 1995 Jan, 70(1), 50 - 4
Adults with congenital heart disease: patient knowledge of endocarditis prophylaxis; Cetta F et al.; OBJECTIVE: To determine whether adults with congenital heart disease have adequate knowledge of infective endocarditis and endocarditis prophylaxis and to ascertain whether an educational program effectively improves patient knowledge and compliance . MATERIAL AND METHODS: We asked 102 consecutive patients to complete a 12-question survey to assess their knowledge of heart disease, infective endocarditis, and endocarditis prophylaxis . RESULTS: Of 102 patients, 100 (98%) completed the questionnaire . Sixty-eight patients knew the name of their heart disease . Fifty patients correctly defined endocarditis, but only 43 knew hygiene measures that could prevent endocarditis . Ninety-six patients knew that they needed to take "a medicine" before dental procedures, and 76 of those patients (79%) knew that an antibiotic was necessary . Patient use of cardiac medications and a history of endocarditis correlated significantly with knowledge of endocarditis . Patients who had been to the Adult Congenital Heart Disease Clinic at least once knew endocarditis prevention measures and the importance of regular dental and cardiology follow-up significantly more frequently than did first-time attendees . Despite educational counseling, however, patient recall of endocarditis and its prevention is disappointing . CONCLUSION: Many adults with congenital heart disease have inadequate knowledge of their cardiac lesion, endocarditis, and endocarditis prophylaxis . Educational efforts for adults with congenital heart disease need to be updated and reinforced regularly.

Circulation, 1995 Jan 1, 91(1), 10 - 5
Probucol protects against adriamycin cardiomyopathy without interfering with its antitumor effect; Siveski-Iliskovic N et al.; BACKGROUND: The usefulness of adriamycin (ADR), a potent antitumor antibiotic, is limited by the development of life-threatening cardiomyopathy and congestive heart failure . Subcellular changes leading to heart failure are suggested to be mediated by a drug-induced increase in free radicals and lipid peroxidation . In an earlier study, concurrent treatment with probucol (PROB), a lipid-lowering drug with strong antioxidant properties, was shown to offer only partial protection against ADR cardiomyopathy . The present study had two aims: to determine whether this protective effect can be improved further by extended treatment with PROB, and to determine whether PROB affects the antitumor properties of ADR . METHODS AND RESULTS: ADR (cumulative dose, 15 mg/kg body wt) was administered in rats in six equal injections (IP) over a period of 2 weeks . Three weeks after the end treatment, cardiomyopathy and congestive heart failure were characterized by ascites, congested liver, depressed cardiac function, elevated left ventricular end-diastolic pressure, and myocardial cell damage . Myocardial glutathione peroxidase (GSHPx) activity was decreased and lipid peroxidation was increased . Administration of PROB (cumulative dose, 120 mg/kg body wt) in 12 equal injections (IP), before and concurrent with ADR, completely prevented these cardiomyopathic changes, normalized left ventricular function, lowered mortality, and eliminated ascites . Treatment with PROB was also accompanied by an increase in myocardial GSHPx and superoxide dismutase activities with a concomitant decrease in lipid peroxidation . Tumor regression in syngeneic DBA/2 mice inoculated with L5178Y-F9 lymphoma cells in the ADR+PROB group was significant and comparable to the ADR group . CONCLUSIONS: These data show for the first time that PROB can provide complete protection against ADR cardiomyopathy without interfering with antitumor properties of the drug . This protective effect of PROB may be related to the maintenance of the antioxidant status of the heart.

Eur Neurol, 1995, 35(2), 113 - 7
Seronegative chronic relapsing neuroborreliosis; Lawrence C et al.; We report an unusual patient with evidence of Borrelia burgdorferi infection who experienced repeated neurologic relapses despite aggressive antibiotic therapy . Each course of therapy was associated with a Jarisch-Herxheimer-like reaction . Although the patient never had detectable free antibodies to B . burgdorferi in serum or spinal fluid, the CSF was positive on multiple occasions for complexed anti-B . burgdorferi antibodies, B . burgdorferi nucleic acids and free antigen.

Int J STD AIDS, 1995 Jan-Feb, 6(1), 31 - 4
The role of Chlamydia trachomatis in urethritis and urethral symptoms in women; Horner PJ et al.; One hundred and fifty women who attended a genitourinary medicine clinic and who required a speculum examination were investigated to determine the association between Chlamydia trachomatis and urethral symptoms and signs . Those who had taken antibiotics with anti-chlamydial activity within 3 months or those who were menstruating, pregnant or using an intrauterine contraceptive device were excluded . C . trachomatis infection of the urethra, or infection of the urethra and cervix together, combined with each separately, were strongly associated with > = 5 polymorphonuclear (PMN) leucocytes per high-power field (x 1000) in a Gram-stained urethral smear (P < 0.00005 and P < 0.0005, respectively) . This appeared not to arise from leucocyte contamination from the lower genital tract . However, C . trachomatis infection of the urethra was not associated with symptoms of dysuria or frequency . In conclusion, it seems likely that C . trachomatis infection of the urethra in women probably causes urethritis which is usually asymptomatic . Women who have objective evidence of urethritis might best be managed by appropriate antibiotic therapy and counselling, and advice that partners should attend for review.

Environ Mol Mutagen, 1995, 25 Suppl 26, 102 - 14
Influence of heredity on human sensitivity to environmental chemicals; Weber WW; Hereditary peculiarities in individual responses to environmental chemicals are a common occurrence in human populations . Genetic variation in glutathione S-transferase, CYP1A2, N-acetyltransferase, and paraoxonase exemplify the relationship of metabolic variation to individual susceptibility to cancer and other toxicants of environmental origin . Heritable receptor protein variants, a subset of proteins of enormous pharmacogenetic potential that have not thus far been extensively explored from the pharmacogenetic standpoint, are also considered . Examples of interest that are considered include receptor variants associated with retinoic acid resistance in acute promyelocytic leukemia, with paradoxical responses to antiandrogens in prostate cancer, and with retinitis pigmentosa . Additional heritable protein variants of pharmacogenetic interest that result in antibiotic-induced deafness, glucocorticoid-remediable aldosteronism and hypertension, the long-QT syndrome, and beryllium-induced lung disease are also discussed . These traits demonstrate how knowledge of the molecular basis and mechanism of the variant response may contribute to its prevention in sensitive persons as well as to improved therapy for genetically conditioned disorders that arise from environmental chemicals.

Tex Heart Inst J, 1995, 22(1), 81 - 5
Scopulariopsis endocarditis associated with Duran ring valvuloplasty; Gentry LO et al.; Fungal endocarditis is rare and is usually caused by Aspergillus and Candida species . We present a patient with endocarditis caused by Scopulariopsis brevicaulis . The patient had a history of mitral valve disease and, 1 year earlier, had undergone valvuloplasty with the placement of a prosthetic Duran ring in the mitral valve position . S . brevicaulis was cultured from samples of a large vegetation on the mitral valve apparatus . The mitral valve was replaced with a St . Jude mechanical prosthesis . The patient was treated with amphotericin B but was later switched to oral itraconazole when antibiotic tests indicated susceptibility to that agent . We believe this is the 1st reported case of endocarditis caused by Scopulariopsis.

Eur J Cardiothorac Surg, 1995, 9(3), 163 - 5
Pyoderma gangrenosum as a complication of coronary artery bypass grafting; Koss-Harnes D et al.; A 60-year-old male patient developed progressive wound ulcerations, simulating wound sepsis after coronary bypass operation . The condition did not respond to intensive antibiotic therapy . Based on clinical signs and biopsy, the diagnosis of pyoderma gangrenosum was made and successfully treated with cyclosporin A . Pyoderma gangrenosum, although extremely rare, must be considered as a possible diagnosis in wound complications unresponsive to traditional therapy.

Akush Ginekol (Mosk), 1995, (2), 17 - 9
{The transplacental passage and distribution of ceftazidime in the fetal and maternal organs in a 2nd-trimester abortion}; Kulakov VI et al.; Transplacental passage of ceftazidime was studied in 17 women with second-trimester pregnancy which had to be discontinued for medical causes . A single intramuscular injection of the antibiotic resulted in creation of therapeutically active concentrations in fetal blood and organs, amniotic fluid, and placenta . Transplacental passage of ceftazidime from the mother to the fetus was 19.12%, diffusions to the amniotic fluid 14.46%, diffusion to the placenta 48.46% . Ceftazidime may be effective for the prevention and therapy of fetal intrauterine infection and chorioamnionitis.

Infection, 1995, 23 Suppl 1, S15 - 20
Roxithromycin 150 mg b.i.d . versus amoxycillin 500 mg/clavulanic acid 125 mg t.i.d . for the treatment of lower respiratory tract infections in general practice; Karalus NC et al.; Two hundred and forty-two patients over 16 years of age with community-acquired lower respiratory tract infection (LRTI), matched for age and sex, were randomised to receive either roxithromycin 150 mg b.i.d . or amoxycillin 500 mg/clavulanic acid 125 mg t.i.d . for 7 days, with a further 7 days if insufficient response was seen . Clinical efficacy at 7 days was 69% for roxithromycin and 56% for amoxycillin/clavulanic acid (p = 0.05) and at study end it was 91% for both antibiotics . There were fewer second treatment courses in the roxithromycin group (26% vs . 38%, p = 0.04) and a shorter treatment duration (8.29 days vs . 9.34 days, p > 0.05) . Twelve patients (9.8%) treated with roxithromycin and 19 (17.1%) treated with amoxycillin/clavulanic acid had adverse effects possibly, or probably, related to the antibiotic . Roxithromycin appears to be a more appropriate choice than amoxycillin/clavulanic acid for the treatment of LRTI in the community given its more appropriate in vitro spectrum, efficacy against most common and atypical pathogens, greater cost-effectiveness, more convenient dosage regimen (b.i.d.), and superior tolerability profile.

Cancer Chemother Pharmacol, 1995, 36(3), 233 - 8
A limited sampling strategy for the study of pirarubicin pharmacokinetics in humans; Marchiset-Leca D et al.; Pirarubicin (4'-O-tetrahydropyranyldoxorubicin, THP-Adriamycin) is a new anthracycline antibiotic that has recently been developed because its reduced cardiac toxicity is associated with an antitumour efficacy similar to that of doxorubicin . Pirarubicin is characterised by strong haematological toxicity, which has been shown to be correlated with pharmacokinetic parameters, especially the area under the time-concentration curve . To obtain routine pharmacokinetic evaluations of pirarubicin for dose monitoring we developed a limited sampling strategy relying on three blood samples taken at the end of the infusion and at 12 and 24 h post-infusion . The characteristics of interindividual variability were assessed on the first courses of treatment performed in 18 patients; the model was then validated on 10 independent first courses of treatment performed in 10 other patients . The main pharmacokinetic parameters (half-lives, total volume of distribution, total plasma clearance) were estimated in the test group by maximum-likelihood estimation using all samples and by Bayesian estimation using three samples . The concordance between the two estimates was correct (the bias and precision for clearance were 2.3% and 12.1%, respectively), which shows that this limited sampling strategy can be used in routine drug monitoring.

Scand J Gastroenterol Suppl, 1995, 208, 47 - 52
The current role of Helicobacter pylori eradication in clinical practice; Hunt RH et al.; Helicobacter pylori is probably the commonest bacterial infection worldwide and is now accepted as the cause of chronic active type B gastritis . It is increasingly accepted as having a critical role in duodenal ulcer, where the prevalence of infection is 90 to 100% . More important is the dramatic reduction in duodenal ulcer recurrence after successful eradication of the organism to about 4% in a year compared to recurrences of up to 80% in those whose ulcers have been healed but in whom the infection persists . There is increasing evidence that what is now clear for duodenal ulcers may also hold true for patients with a gastric ulcer who are infected with H . pylori . Moreover, evidence is accumulating that the risk of a duodenal ulcer complication, such as, bleeding, is reduced following successful eradication of H . pylori . The treatment of duodenal ulcer patients with H . pylori eradication treatment has been advocated by an international working party who met first in Sydney at the 1990 World Congress and subsequently in Athens during the First European Gastroenterology Week . The most recent recommendation suggests that the infection should be treated in any duodenal ulcer patient after the first recurrence, and that a triple therapy regimen or a proton pump inhibitor combined with either amoxicillin or clarithromycin may be prescribed . The combination of a proton pump inhibitor and an antibiotic can eradicate H . pylori in over 80% of cases and simultaneously offers the advantage of rapid symptom relief and the highest rates of duodenal ulcer healing.(ABSTRACT TRUNCATED AT 250 WORDS)

Eur J Obstet Gynecol Reprod Biol, 1995 Jan, 58(1), 47 - 51
Culture and wet smear microscopy in the diagnosis of low-symptomatic vulvovaginal candidosis; Zdolsek B et al.; OBJECTIVES: To compare the clinical usefulness of culture and wet smear microscopy in low-symptomatic vulvovaginal candidosis (VVC) diagnosis . STUDY DESIGN: Women attending for contraceptive advice were screened for vaginal yeast fungi by culture and wet smear microscopy . A positive culture was found in 130 (13.2%) of the 983 women studied, while a positive wet smear was found in 133 (13.9%) . In 40 (30%) of these women both the culture and wet smear was positive . RESULTS: The methods were equally sensitive in predicting symptoms of VVC, such as pruritus, smarting and burning pain, as well as for dyspareunia (35% vs . 36%), but wet smear microscopy was more sensitive in predicting signs of VVC, such as erythema and abnormal discharge (52% vs . 34%) . The highest sensitivity was reached when both methods were positive (60% for symptoms, 75% for signs) . There was no quantitative correlation between number of Candida colonies on culture on the one hand and symptoms, signs or a positive wet smear on the other hand . Using four parameters as a diagnostic battery for VVC, the two methods complemented each other . The correlation between symptoms and/or signs for wet smear was high than for culture . CONCLUSION: Wet smear microscopy of vaginal secretion, along with signs found at examination, should be the first-line test in the diagnosis of VVC . Culture must, however, be used when there is a clinical suspicion of VVC and a negative wet smear, or when speciation or antibiotic susceptibility tests of isolates are required.

Clin Ther, 1995 Jan-Feb, 17(1), 126 - 35
Pharmacoeconomics of piperacillin/tazobactam and imipenem/cilastatin in the treatment of patients with intra-abdominal infections; Jhee SS et al.; Costs involved in using piperacillin 4 g/tazobactam 500 mg, given as intermittent intravenous infusions every 8 hours, were compared with those for imipenem/cilastatin 500 mg, given as intermittent intravenous infusions every 6 hours, for the treatment of patients with gangrenous or perforated appendicitis . A total of 88 patients were included in our cost analyses: 42 patients in the piperacillin/tazobactam group and 46 patients in the imipenem/cilastatin group . Durations (mean +/- SD) of antibiotic therapies were 7.8 +/- 3.3 days and 7.1 +/- 2.6 days for the piperacillin/tazobactam and imipenem/cilastatin groups, respectively . No statistical significance was found for the difference in duration of therapy (P = 0.376) . Total drug treatment costs were $538.83 +/- $385.33 for the piperacillin/tazobactam group and $687.66 +/- $345.37 for the imipenem/cilastatin group . This difference in treatment cost was statistically significant (P = 0.0001) . The need for laboratory tests and the use of other medications were not different between the two groups . Total hospital-days charges were higher for the piperacillin/tazobactam group ($18,339.76 +/- $6090.38) compared with the imipenem/cilastatin group ($16,150.00 +/- $5088.60) (P = 0.052) . These findings suggest that length of hospital stay should be the economic focus of antibiotic therapy.

Plasmid, 1995 Jan, 33(1), 51 - 7
In vivo and in vitro stability of the broad-host-range cloning vector pBBR1MCS in six Brucella species; Elzer PH et al.; Previous studies have shown that the broad-host-range plasmid pBBR1MCS can be used for genetic complementation in Brucella abortus . To extend these observations, the in vivo and in vitro stability of pBBR1MCS was evaluated in the six currently recognized species of the genus Brucella . pBBR1MCS was readily introduced into all of the strains tested by electroporation and was stably maintained in broth cultures without antibiotic selection during five serial passages over a 10-day period . Furthermore, isolates of all six Brucella strains containing pBBR1MCS obtained from the spleens of BALB/c mice 1 week postinfection maintained the plasmid . Although pBBR1MCS maintains the mobilization locus present in the parental plasmid pBBR1CM, attempts to detect transfer of pBBR1MCS between Brucella strains by conjugation were unsuccessful . These results demonstrate the in vitro and in vivo stability of pBBR1MCS in Brucella spp . and reinforce the usefulness of this cloning vector for the genetic analysis of these organisms.

Nat Toxins, 1995, 3(1), 32 - 40
Lung tumor induction in A/J mice and clastogenic effects in CD-1 mice of the sequence-selective DNA alkylating agents (+)-CC-1065 and (-)-CC-1065; Linseman DA et al.; The in vivo genotoxic effects of the antitumor antibiotic, (+)-CC-1065, and its unnatural enantiomer, (-)-CC-1065, were investigated in two mouse models . These two compounds alkylate AT-rich regions of double stranded DNA with distinct sequence selectivities . (+)-CC-1065 dose-dependently increased the chromosomal aberration frequency in bone marrow cells of CD-1 mice from 1.2 +/- 0.8% in vehicle control animals to 5.0 +/- 1.2%, 11.4 +/- 3.9%, and 20.6 +/- 2.3% 24 hours following single intravenous doses of 2, 4, and 8 micrograms/kg, respectively . (-)-CC-1065 was significantly less potent with a maximal response at 8 micrograms/kg approximately one-third of that observed for (+)-CC-1065 . (+)-CC-1065 induced a significant (P < or = 0.05), three-fold increase in the number of lung tumors/mouse in strain A/J mice from 0.27 +/- 0.15 for vehicle control animals to 0.83 +/- 0.15 24 weeks following a single intravenous dose of 8 micrograms/kg . This effect was paralleled by corresponding threefold increases in the percentage of mice with tumors and the percentage of mice with multiple tumors, compared to vehicle controls . (-)-CC-1065 at 8 micrograms/kg induced 0.67 +/- 0.15 tumors/mouse and resulted in slightly smaller increases in the tumor incidence and multiple tumor incidence, compared to (+)-CC-1065 . The above results demonstrate that single intravenous doses of (+)- CC-1065 and (-)-CC-1065 which cause chromosomal damage in CD-1 mice also induce an increased incidence of lung tumors in A/J mice.(ABSTRACT TRUNCATED AT 250 WORDS)

Hum Exp Toxicol, 1995 Jan, 14(1), 13 - 7
The effect of thyroxine or carbimazole treatment on gentamicin nephrotoxicity in rats; Ali BH et al.; 1 . This study examines the effect of treating rats with gentamicin (80 mg kg-1 day-1 intramuscularly (i.m.), for 6 days) alone or with either L-thyroxine or the anti-thyroid drug carbimazole . 2 . Gentamicin produced significant increases in serum creatinine and urea concentrations, and significantly reduced the activity of Na+,K+ATPase in renal cortex . The concentration of serum triiodothyronine (T3) was unaffected by graded doses (20, 40 and 80 mg kg-1) of the antibiotic . Histopathologically, gentamicin produced necrosis of proximal tubules in the renal cortical tissues of treated rats . 3 . Treatment of rats with either L-thyroxine or carbimazole alone did not significantly affect any of the biochemical variables investigated . Carbimazole alone produced only mild tubular necrosis . 4 . Treatment of rats with either L-thyroxine (100 micrograms kg-1 day-1, subcutaneously) for 10 days, and gentamicin (80 mg kg-1, i.m . daily during the last 6 days of treatment significantly reduced the gentamicin-induced increases in serum creatinine and urea concentrations, and increased the activity of cortical N+,K+ATPase to control levels . Histopathologically, the severity of gentamicin-induced tubular necrosis was reduced by L-thyroxine treatment . 5 . Carbimazole (12 mg ml-1 in drinking water for 21 days) and gentamicin (80 mg kg-1 i.m.) daily during the last 6 days of treatment, stimulated the increase in serum urea concentration produced by gentamicin, but did not significantly affect the gentamicin-induced changes in serum creatinine or cortical N+,K+ATPase.

Clin Plast Surg, 1995 Jan, 22(1), 167 - 85
Reconstruction of posterior trunk defects; Ramasastry SS et al.; A high rate of success can be expected in the management of posterior trunk defects with muscle flaps . The surgeon has to adhere closely to the basic reconstructive principles of adequate debridement of all necrotic or devitalized tissues; management of infection with local wound care and appropriate antibiotic therapy; and coverage with well-vascularized tissue to obliterate any residual dead space and to cover bone grafts, orthopedic hardware, and vital structures such as the dura and spinal cord . Flap selection is also of paramount importance for success, and only muscles with appropriate arc of rotation, vascularity (vascular pedicles outside the field of radiation injury, or intact vascularity following previous procedures) and bulk should be used . Adequate flap mobilization to obtain a tension-free closure and judicious use of drains and perioperative antibiotic agents are essential . Occasionally, microvascular free-tissue transfer may be necessary if local flaps are unavailable . The complications of flap reconstruction include partial flap loss, persistent dead space for lack of adequate muscle bulk, and persistent infection . Debridement and re-advancement of the flap is adequate in most cases . If there is significant or total flap loss, however, a second flap reconstruction is often necessary to obliterate the dead space and protect vital structures.

J Heart Valve Dis, 1995 Jan, 4(1), 49 - 55
Comparative assessment of bioprosthesis durability in the aortic position; Grunkemeier GL et al.; Published durability results of porcine and pericardial bioprostheses in the aortic position have been reviewed for the purpose of a qualitative comparison between these valve types, and also with previously reviewed series of homograft valves . Porcine bioprostheses exhibit a wide range of failure curves, with a characteristic Weibull-shaped pattern . Patient characteristics must account for the majority of differences seen among the series . Newer series generally contain older patients and have better results . A second generation pericardial valve has distinctly better durability than a previously discontinued pericardial model, and appears to be as durable as that of the best porcine valve series . Homograft valves using cold antibiotic storage have durability results approximately equal to porcine valves, but with younger patients on the average . The results with cryopreserved valves may be comparable, but insufficient long term information is available . To make these qualitative comparisons quantitative would require a formal analysis which takes age and other patient-related characteristics into account.

Rev Pneumol Clin, 1995, 51(1), 36 - 40
{Interstitial pneumonia and mitomycin C . Apropos of a case with analysis of the bronchoalveolar lavage}; Coetmeur D et al.; Mitomycin C is an antibiotic used for its alkylizing effect in the treatment of broncogenic cancer . Haematologic, renal or pulmonary complications are sometimes severe . We report a case in a patient with poorly differentiated epidermoid bronchogenic carcinoma who developed clinical and radiological signs of bilateral infiltrating pneumonia due to mitomycine . This observation emphasizes the importance of bronchoalveolar lavage which implicated the immunological toxicity of mitomycine and explained the efficacity of corticosteroid treatment . Pulmonary lesions due to mitomycine were discussed.

Crit Care Clin, 1995 Jan, 11(1), 79 - 96
Bronchial hygiene therapy; Peruzzi WT et al.; Bronchial hygiene therapy is useful and effective in the presence of careful patient evaluation, clear definition of therapeutic goals, and application of appropriate modalities . This article defines the variable bronchial hygiene modalities and discusses their indications, contraindications, and applications . Prophylactic and therapeutic bronchial hygiene modalities, diagnostic methods associated with bronchial hygiene therapy, inhaled antibiotic therapy, and therapist driven protocols are also addressed.

Acta Paediatr, 1995 Jan, 84(1), 10 - 3
The usefulness of serial C-reactive protein measurement in managing neonatal infection; Kawamura M et al.; Recent advances in laboratory technology have enabled us to measure C-reactive protein with a higher sensitivity in a short period using a minimal amount of blood . Thus C-reactive protein can be measured easily several times a day . In this study, serial changes in C-reactive protein values were evaluated in 108 term and 240 preterm newborn infants with suspicion of infection, and the changing patterns of C-reactive protein values were compared with clinical outcome . For a diagnosis of infection, the negative predictive values in term and preterm infants were 99.0% and 97.8%, respectively, although the sensitivities were 61.5% and 75.0%, respectively . Antibiotic therapy was started at birth and discontinued when the changing pattern of C-reactive protein and clinical findings did not suggest infection . As a result, mean durations of administration of antibiotics in the term and preterm infants were 3 and 4 days, respectively . Recognition of the changing pattern of C-reactive protein was very useful in excluding infection and minimizing unnecessary antibiotic therapy in managing neonatal infection.

Acta Otorrinolaringol Esp, 1995 Jan-Feb, 46(1), 31 - 4
{Nasal endoscopic surgery in complicated ethmoiditis}; Llorente Pendas JL et al.; Spread of infection from paranasal sinuses is uncommon but, when it occurs may lead to serious ocular or intracranial complications . In this article we present four patients, three of them with orbital complications and one with an intracranial abscess, who were successfully treated with endoscopic surgery of the sinuses and antibiotic therapy . We describe some potential advantages of this approach.

Eur J Clin Microbiol Infect Dis, 1995 Jan, 14(1), 1 - 5
Polymerase chain reaction for detection of Borrelia burgdorferi DNA in skin lesions of early and late Lyme borreliosis; von Stedingk LV et al.; The aim of this study was to evaluate the polymerase chain reaction (PCR) as a diagnostic tool for Lyme borreliosis on large numbers of samples from clinically well-defined cases of early and late cutaneous borreliosis . Skin biopsy specimens from patients with erythema migrans and acrodermatitis chronica atrophicans were analysed blindly together with an equal number of control biopsies . Using two different dilutions of each DNA specimen increased the number of total positives detected . All of the 76 control biopsies were PCR negative . Biopsy specimens from 18 of 26 (69%) erythema migrans lesions and from 22 of 36 (61%) acrodermatitis chronica atrophicans lesions were PCR positive . Fourteen post-therapy biopsies from patients with acrodermatitis chronica atrophicans were all negative, supporting the opinion that antibiotic therapy is successful in this chronic manifestation of Lyme borreliosis.

Arch Gynecol Obstet, 1995, 256(1), 35 - 8
Necrotizing fasciitis following postpartum tubal ligation . A case report and review of the literature; Piper JM et al.; Necrotizing fasciitis is a rare, but devastating subcutaneous bacterial infection which occurs following breaks in skin integrity, either natural, post traumatic or post surgical . Although it has been described following many surgical procedures, necrotizing fasciitis has not been previously described following postpartum tubal ligation . Necrotizing fasciitis was diagnosed four days after an uncomplicated postpartum tubal ligation via an infraumbilical incision . Rapid surgical debridement with broad spectrum antibiotic coverage provided successful therapy . Postpartum tubal ligation is one of the most common surgical procedures in obstetrics and gynecology, thus reports of complications resulting from this procedure are quite relevant to clinical practice . We present here the first reported case of necrotizing fasciitis following postpartum tubal ligation through an infraumbilical incisionPIP: Necrotizing fasciitis, a fulminant polymicrobial infection of the subcutaneous tissues following a break in the integrity of the skin barrier, has been reported following a variety of injuries and surgical procedures . This article presents the first reported case of necrotizing fasciitis after postpartum tubal ligation performed through an infraumbilical incision . The patient, a 43-year-old Hispanic woman from Texas (US), had routine bilateral tubal ligation performed on the first postpartum day . 4 days after the procedure, the patient presented with fever, chills, and a profuse, foul-smelling, watery discharge from the infraumbilical incision . At surgical debridement, necrotic fascia and subcutaneous fat were identified extending inferiorly from the original incision . After a 5-day course of intravenous antibiotics, wound closure was performed and recovery was complete . The keys to successful management of this potentially life-threatening complication are rapid recognition, immediate surgical excision of necrotic tissue, and broad spectrum antibiotic therapy . The clinical diagnosis of necrotizing fasciitis is usually quite clear based on the rapid progression, cutaneous anesthesia, and preferential involvement of the fascial plane .

Mol Biol (Mosk), 1995 Jan-Feb, 29(1), 180 - 91
{Liquid crystals and liquid crystal dispersions of DNA-daunomycin complexes}; Evdokimov IuM et al.; The X-ray and optical properties as well as the textures of liquid crystals formed of DNA molecules bound in complex with an anthracycline antibiotic daunomycin were investigated . It was shown that DNA.daunomycin complexes, depending on the extent of alteration of the DNA secondary structure by daunomycin, could yield two types of cholesterics differing in the direction of their spatial twisting as well as nematics . Liquid-crystalline dispersions of DNA.daunomycin complexes have CD spectra with "mirror" bands depending on daunomycin concentration . "Testing" of the orientation of daunomycin molecules on the DNA in liquid-crystalline particles suggested two types of binding.

Exp Toxicol Pathol, 1995 Jan, 47(1), 1 - 9
Overview of toxicological data on rifabutin; Brughera M et al.; Rifabutin is a wide spectrum antibiotic particularly active on atypical and rifampicin-resistant mycobacteria . Rifabutin is more potent than rifampicin on Mycobacterium tuberculosis in vitro . Its mode of action is characterized by a high intracellular penetration in treated individuals . Clinical trials have proven the therapeutic value of rifabutin especially in AIDS patients with concomitant MAC . The preclinical safety evaluation of this compound included single and repeated dose toxicity studies of up to one year in rodents and non-rodents, reproduction and carcinogenicity studies and mutagenicity tests . During toxicological studies the most significant finding after repeated administration of rifabutin was the presence of multinucleated hepatocytes (MNH) in rats . This is a species specific finding which did not affect the life span of the hepatocytes . As shown in carcinogenicity studies, there was no tendency to further proliferative changes . Another specific histological feature among the species studied was the presence of a lipofuscin-like brown pigment, which was seen in many organs . This is a common finding with amphipilic compounds, such as rifabutin, which bind lipids and proteins, forming membrane-bound complexes . Even in carcinogenicity studies this change did not constitute a stimulus to cell proliferation and did not cause any secondary changes . In rodents, there was a mild hemolytic anemia at doses higher than 10 mg/kg/day . At doses ranging from 160-200 mg/kg/day rifabutin inhibited the functions of the male gonads in rats . This effect was reflected in a reduction of implantations observed in the fertility studies . Doses of 40 mg/kg/day did not induce any embryotoxic effects or changes in reproductive performance.(ABSTRACT TRUNCATED AT 250 WORDS)

Intern Med, 1995 Jan, 34(1), 42 - 5
Septic pulmonary emboli secondary to pyogenic liver abscess in a diabetic patient; Zenda T et al.; A 70-year-old woman with poorly controlled diabetes mellitus was admitted because of persistent remittent fever . Soon a liver abscess was detected as the cause of the fever by ultrasonography, and antibiotic therapy was started . However, suddenly serious dyspnea with chest and back pain developed . The morbid condition was definitely diagnosed as septic pulmonary emboli (SPE) with pulmonary perfusion scan . It should be recognized that liver abscess can be a latent focus of systemic metastatic complications such as SPE, and not only early detection but also prompt appropriate drainage of liver abscesses is essential.

An Otorrinolaringol Ibero Am, 1995, 22(1), 67 - 73
{Kikuchi-Fujimoto's syndrome in ENT: a case report}; Fernandez Perez A et al.; Kikuchi-Fujimoto disease (KFD) is a rare entity of uncertain cause which commonly presents as a lymphoadenopathy unresponsive to antibiotic therapy . Although usually it follows a benign self-limited course KFD has been repeatedly misdiagnosed as lymphoma . With this new case data about the etiology and clinical trend of KFD are added . Review of the literature.

Postgrad Med J, 1995 Jan, 71(831), 24 - 7
Chronic suppurative lung disease with associated vasculitis; Bruce IN et al.; We report a patient with chronic bronchiectasis who developed systemic vasculitis . The patient was initially treated with immunosuppression; however, the addition of antibiotic therapy improved control of her vasculitis and the need for immunosuppression was reduced . Chronic bronchial suppuration may have an aetiological role in the pathogenesis of this condition.

Vet Surg, 1995 Jan-Feb, 24(1), 25 - 31
Effects of cephalothin, cefazolin, and cefmetazole on the hemostatic mechanism in normal dogs: implications for the surgical patient; Wilkens B et al.; Twenty-six female beagles were used to evaluate the effects of intravenous and long-term subcutaneous administration of cephalothin, cefazolin, and cefmetazole on platelet function and the coagulation cascade . Platelet aggregation in response to an adenosine diphosphate (ADP) agonist, bleeding time, platelet count, platelet size, prothrombin time (PT), and activated partial thromboplastin times (aPTT) were evaluated before and 90 minutes after two intravenous doses (22 mg/kg) of cephalothin, cefazolin, and cefmetazole given at 90-minute intervals . Dogs given saline injections were used as controls . Platelet count, platelet size, PT, and aPTT were evaluated after 7 days of subcutaneous administration of saline, cefazolin, and cefmetazole (22 mg/kg every 8 hours) . A significant decrease in platelet aggregation in response to ADP was detected 90 minutes after intravenous administration of cephalothin . Bleeding time was increased significantly 90 minutes after intravenous administration of cefmetazole . Platelet size was decreased significantly 24 hours after onset of the study in all animals, including controls . No significant changes in platelet count, platelet size, PT, or aPTT were detected after 7 days of subcutaneous administration . Cefazolin had no adverse effects on platelet aggregation in response to ADP, bleeding time, platelet count, platelet size, PT, or aPTT . Therefore, cefazolin should be considered as a perioperative antibiotic in dogs with conditions predisposing to hemostatic complications.

Nephrologie, 1995, 16(1), 33 - 6
{Access of the abdominal cavity for treatment by continuous peritoneal dialysis}; Chanard J et al.; Anatomical and functional characteristics of the peritoneal cavity have to be evaluated prior to catheter implantation for continuous ambulatory peritoneal dialysis (CAPD) . This review summarizes the constraints that may be encountered and the few technical certitudes that have been validated . The American Registry for CAPD is the unique source of validated data, indicating that the early risk for peritonitis following catheter implantation is significantly lessened with a two-cuff catheter used by a surgeon . Catheter shape as well as per-operative antibiotic prophylaxy have no effect on prognosis.

Biopolymers, 1995 Jan, 35(1), 21 - 9
A nonhelical, multiple beta-turn conformation in a glycine-rich heptapeptide fragment of trichogin A IV containing a single central alpha-aminoisobutyric acid residue; Gurunath R et al.; The conformational properties of the protected seven-residue C-terminal fragment of the lipopeptaibol antibiotic Trichogin A IV (Boc-Gly-Gly-Leu-Aib-Gly-Ile-Leu-OMe) has been examined in CDCl3 and (CD3)2SO by 1H-nmr . Evidence for a multiple beta-turn conformation {type I' at Gly(1)-Gly(2), type II at Leu(3)-Aib(4), and a type I' at Aib(4)-Gly(5)} suggests that Leu(3) has preferred an extended or semiextended conformation over a helical conformation in CDCl3 . This structure is thus in contrast to earlier observations of seven-residue peptides containing a single central Aib preferring helical conformations in both solution and crystalline states . A structural transition to a frayed right-handed helix is observed in (CD3)2SO . These results suggest that nonhelical conformations may be important in Gly-rich peptides containing Aib . Further, the presence of amino acids with contradictory influences on backbone conformational freedom can lead to well-defined conformational transitions even in small peptides.

Antimicrob Agents Chemother, 1995 Jan, 39(1), 94 - 8
Comparison of concentrations of two doses of clavulanic acid (200 and 400 milligrams) administered with amoxicillin (2,000 milligrams) in tissues of patients undergoing colorectal surgery; Martin C et al.; The concentrations of clavulanic acid and amoxicillin were determined in sera and different abdominal tissues of 17 patients who underwent elective colorectal surgery . Patients were randomly allocated to two groups . At the time of induction of anesthesia, patients in group 1 were given 200 mg of clavulanic acid with 2,000 mg of amoxicillin and patients in group 2 received 400 mg of clavulanic acid with 2,000 mg of amoxicillin . In both groups, the initial dose was administered again after 2 h . Blood samples were collected to determine peak and trough antibiotic levels . Serial blood samples were also collected at predetermined periods (opening and closure of the abdominal cavity and surgical anastomosis) . Abdominal wall fat, epiploic fat, and colonic wall tissue samples were collected simultaneously . Antibiotic concentrations were determined by high-performance liquid chromatography . Increasing the dose of clavulanic acid to 400 mg resulted in significantly higher peak and trough levels in serum (P < 0.03) . Following the injection of 400 mg, mean concentrations of clavulanic acid in the fatty tissues were significantly increased at the time of opening (P < 0.02) . The concentrations of clavulanic acid and amoxicillin in fatty tissues were 17 to 52% and 12 to 23% of the levels in sera, respectively . In the colonic wall, the concentrations of clavulanic acid and amoxicillin were 52 to 63% and 49 and 27% of the levels in sera, respectively . In sera, clavulanic acid given at a dose of 200 or 400 mg reached or exceeded the concentrations found to be effective in vitro to reduce the MICs of amoxicillin from the resistant to the susceptible category for 90% of the potential pathogens . In most of the tissues investigated, increased the dose of clavulanic acid to 400 mg resulted in a significantly higher number of samples with concentrations found to be effective in vitro (72 versus 11%; P < 0.05) . In conclusion, increasing the dose of clavulanic acid to 400 mg resulted in higher levels in sera and improved penetration into the abdominal tissues in patients undergoing colorectal surgery.

Antimicrob Agents Chemother, 1995 Jan, 39(1), 75 - 8
Chemoprophylaxis of Cryptosporidium parvum infection with paromomycin in kids and immunological study; Mancassola R et al.; The anticryptosporidial activity of paromomycin, a natural antibiotic weakly absorbed when administered per os, was assessed in goat kids experimentally infected once via the oral route with 10(6) Cryptosporidium parvum oocysts . Paromomycin used prophylactically at a dose of 100 mg/kg of body weight per day from day-1 to day 10 (day 0 was the inoculation day) prevented infection during the period of drug administration . A delayed low infection was suggested by an antibody rise, but the infection developed below the microscopic detection limits . This low parasite development induced a partial immunity in kids, which reacted immunologically to a challenge on day 21 without symptoms or detectable oocyst shedding . So, paromomycin is a good candidate for field trials because it is prophylactically effective against experimental C . parvum infection and well tolerated by animals . This drug would be useful in an adapted form as an anticryptosporidial agent for neonatal ruminants.

Antimicrob Agents Chemother, 1995 Jan, 39(1), 15 - 9
Effects of macro- and microcirculatory functions on ceftriaxone concentrations in tissues of patients with stage IV peripheral arterial occlusive disease; Hirschl M et al.; The objective of the study was to determine the ceftriaxone levels achievable within lesions (toe or forefoot area) in patients with septic gangrene and to investigate the relationship between macro- and microcirculatory parameters and antibiotic concentration . Fifteen patients with severe chronic peripheral occlusive disease received an intravenous injection of 2 g of ceftriaxone . Antibiotic levels in venous and capillary blood and in an exudative part of the lesion were measured . Macrocirculatory functions were assessed by Doppler sonography, plethysmography, and angiography; microcirculatory functions were assessed by quantitative capillaroscopy and fluorescence video microscopy . The mean antibiotic concentrations measured between 4 and 8 h after injection were 92 +/- 26 micrograms/ml in venous blood and 84 +/- 46 micrograms/ml in capillary blood . The concentration in tissue reached its maximum 4 h after injection; the average concentration at between 2 and 8 h was 95 +/- 55 micrograms/ml . Only dynamic capillary parameters showed significant (P < 0.01) correlations to antibiotic levels in tissue . Significantly (P < 0.01) higher levels in tissue were observed in patients with adequate microcirculatory functions (138 +/- 48 micrograms/ml) than in patients with poor microcirculatory function (51 +/- 26 micrograms/ml) . Microcirculatory dysfunction appears to be the limiting factor for tissue antibiotic levels . However, even those patients with poor microcirculatory function showed tissue antibiotic levels that were above the MICs for the pathogens most frequently isolated from gangrenous lesions . Therefore, intravenous application was found to be adequate and additional measures such as intra-arterial therapy or Bier's occlusion are basically unnecessary . Our finding that microcirculatory function is the limiting factor for the tissue antibiotic concentration is corroborated by computations based on a three-compartment model.

Ann Pharm Fr, 1995, 53(3), 97 - 110
{Expression of intercellular adhesion molecule 1 (ICAM-1) on human alveolar macrophages}; Fattal-German M et al.; Modulation of intercellular adhesion molecule 1 (ICAM-1) expression on alveolar macrophages (AM) may be one of the the basic mechanisms by which AM regulate the course of inflammatory response during pulmonary allograft rejection and infectious processes by mediating macrophage-lymphocyte interactions . As a model for studying anti-inflammatory activity of drugs on AM, we have investigated the effect of fusafungine, a local antibiotic which displays also anti-inflammatory properties, on the regulation of ICAM-1 membrane expression induced in vitro by stimulating AM from lung-transplant recipients . We have studied ICAM-1 membrane expression by immunocytofluorometric analysis using the anti-CD54 monoclonal antibody . The ICAM-1 molecule was expressed on 10 to 47% of freshly isolated AM, depending on the clinical status of the patients . After 24 hr cultivation with 250 U/ml gamma-IFN, the percentage of ICAM-1+ AM s increased to more than 90% . When added with the stimulating agent, fusafungine could inhibit the induction of ICAM-1 membrane expression, up to 90% of inhibition at 8 microgram/ml . However, once ICAM-1 was induced after 24 hr cultivation upon stimulation, fusafungine could not afford any reversion . On going investigations on mRNA for ICAM-1 should indicate whether fusafungine acts at the transcriptional level . These results clearly demonstrate the capacity of fusafungine to down-regulate ICAM-1 expression on AM upon activation . This approach could represent a useful tool for in vitro study of drug efficacy upon inflammatory processes of the respiratory mucasa.

J Clin Gastroenterol, 1995, 20 Suppl 1, S28 - 31
Adjuvant therapy for Helicobacter pylori eradication: role of lansoprazole in clinical studies; Lamouliatte H; Helicobacter pylori (Hp) eradication can lead to cure of duodenal ulcer . Eradication of Hp was first attempted with bismuth salts alone or in combination with one or two antibiotics . In 1990, triple therapy with bismuth, tetracycline or amoxicillin, and metronidazole or tinidazole was standard . Proton pump inhibitors are active in vitro against Hp and have therefore been tested in monotherapy, dual therapy, and triple therapy . When lansoprazole was used as monotherapy, the mean Hp eradication was 6% in four studies . When lansoprazole was used in dual therapy with amoxicillin, pooled data from four trials employing various dosage schedules showed Hp eradication in 38.9% of patients . When lansoprazole was used in dual therapy with clarithromycin, the eradication rate was about 47.7% with lansoprazole 30 mg daily and 69.1% with lansoprazole 30 mg twice daily . When lansoprazole was used in triple therapy, Hp eradication rates ranged from 80% to 96%, with the best results obtained with a combination of lansoprazole, amoxicillin, and clarithromycin . Lansoprazole together with one or preferably two antibiotics is effective in Hp eradication . With the new macrolides, which have a lower rate of Hp resistance than metronidazole or tinidazole, we can expect to achieve eradication of Hp in all patients who are compliant with antibiotic therapy and infected with sensitive strains.

J Clin Gastroenterol, 1995, 20 Suppl 1, S1 - 6
Suppression of acid secretion in peptic ulcer disease; Feldman M; Until recently, suppression of gastric acid secretion in patients with peptic ulcer was empirical and of unproven value . Anticholinergic drugs had only modest inhibitory effects on acid secretion, many side effects, and uncertain efficacy . Controlled trials using antacids demonstrated the value of reducing gastric acidity for healing duodenal ulcer . The discovery of histamine-2 (H2) receptor antagonists in the 1970s and the introduction of H+,K(+)-ATPase inhibitors in the 1980s made reduction of acid secretion the first-choice modality for healing and preventing recurrences of duodenal and gastric ulcers . The demonstration in the late 1980s and early 1990s that Helicobacter pylori (Hp) was a major risk factor for duodenal and gastric ulcer recurrences suggested that peptic ulcer could be cured by eradicating this organism from the stomach . However, antibiotic eradication of Hp can be difficult, often requiring simultaneous administration of a drug that suppresses acid secretion . Therefore, H2 and proton pump inhibitors continue to play a role in the management of duodenal and gastric ulcers associated with Hp and also play a primary role in the therapy of other acid-related disorders, such as gastroesophageal reflux diseases, stress ulcers, ulcers associated with nonsteroidal anti-inflammatory drugs, and gastrinoma (Zollinger-Ellison syndrome) and other acid hypersecretory states.

Annu Rev Biophys Biomol Struct, 1995, 24, 185 - 208
Structure and mechanism of DNA topoisomerases; Wigley DB; DNA topoisomerases are ubiquitous enzymes that control the level of supercoiling of DNA in cells . There are several classes, each with distinct properties, which are briefly discussed in this review . High-resolution X-ray crystallographic structures have been obtained for fragments of two classes of these enzymes, which when combined with biochemical data, reveal a great deal about the gymnastics that the enzymes undergo during catalysis and provide fascinating snapshots of their mechanisms . These mechanisms are discussed in detail . Finally, the first structure of a topoisomerase in a complex with an antibiotic was recently solved . This structure is briefly discussed with regard to the biochemical activity of the compound.

Dermatology, 1995, 190(4), 284 - 7
Current indications for isotretinoin as a treatment for acne vulgaris; Goulden V et al.; BACKGROUND: There is at present little published information on the current indications for isotretinoin as a treatment of acne vulgaris . OBJECTIVES: To investigate the factors which influence our current prescribing of isotretinoin: acne severity, response to previous therapy, scarring and psychological effect . METHODS: Data on the factors influencing treatment of 200 patients with isotretinoin between January 1993 and May 1994 were examined . RESULTS: 41% of patients were prescribed isotretinoin for partial response to previous therapy, 26% for partial therapy and scarring and 17% for partial response to treatment and psychological disturbance . Only 16 patients received isotretinoin for severe acne . CONCLUSION: Patients who show only partial response to conventional antibiotic therapy should be prescribed isotretinoin in order to minimize scarring and significant psychological disturbance, independently of the severity of the acne.

Surg Today, 1995, 25(3), 207 - 10
Peritoneal lavage versus drainage for perforated appendicitis in children; Toki A et al.; A total of 231 children with acute appendicitis were treated at our hospitals during the 10 years between 1984 and 1993, 53 of whom had a perforated appendix . These 53 patients were randomly assigned to two groups at the time of surgery according to the different procedures performed . Thus, 29 children were managed by appendectomy followed by peritoneal lavage using a large amount of saline, and intravenous antibiotic therapy consisting of aminoglycoside and cephem (lavage group), while the other 24 children were treated by appendectomy with silicon tube drainage and the same systemic antibiotic therapy (drainage group) . The mean length of hospitalization, and the mean durations of fever and the need for fasting after laparotomy in the lavage group were significantly less than those in the drainage group: 10.1 versus 18.8 days, 2.8 versus 7.7 days, and 1.8 versus 3.5 days, respectively . The operation wounds healed well in the lavage group due to the fact that there was no drain . Wound infections occurred in two children from the lavage group and six from the drainage group . Intra-abdominal abscesses occurred in two children from the drainage group . Accordingly, peritoneal lavage appears to be superior to intraperitoneal tube drainage for the management of perforated appendicitis in children.

Eur Biophys J, 1995, 24(1), 23 - 30
Nystatin-, mycoheptin- and levorin-induced conductance in the membrane of frog skeletal muscle fibres; Shvinka NE et al.; The effects of the polyene antibiotics nystatin (2 x 10(-5)-10(-4) mol/l), mycoheptin (1.3 x 10(-6)-10(-5) mol/l) and levorin (10(-8)-5 x 10(-5) mol/l) on isolated frog skeletal muscle fibres and whole sartorius muscles of the frog have been investigated . Cation conductance was measured under current clamp conditions using a double sucrose-gap technique . Cation effluxes were studied by means of flame emission photometry . All three antibiotics increased the cation conductance and efflux rates; however, differences between the polyenes were found in the steady state values of induced cation transport at a given concentration . The values of both induced conductance gA infinity and efflux rate constants KA formed the following sequence: levorin > mycoheptin > nystatin, demonstrating a correlation with the order of antifungal activities . The dose-response curves of lg polyene-induced cation transport against lg of antibiotic concentration in our experiments had slope values which were much lower than those in bilayers: 1.7 and 1.3 for nystatin and mycoheptin, respectively, whereas the aromatic heptaene levorin had an even smaller concentration dependence . The decline in the equilibrium conductance caused by nystatin- and mycoheptin removal was very fast (during the first minute tau = 0.74 and 2.39 min, respectively) . In contrast, levorin-induced conductance was irreversible . It is proposed that the processes which limit the rate of channel formation are different in biological and model membranes.

Cancer Chemother Pharmacol, 1995, 36(4), 305 - 15
Preclinical pharmacologic evaluation of geldanamycin as an antitumor agent; Supko JG et al.; The plasma pharmacokinetics of the anti-tumor antibiotic geldanamycin (GM: NSC 122750), a naturally occurring benzoquinoid ansamycin, was characterized in mice and a beagle dog . Concentrations of GM well above 0.1 microgram/ml, which was typically effective against neoplastic cell lines responsive to the drug in vitro, were achieved in the plasma of the mice and the dog treated by i.v . injection . However, the systemic duration of the drug was relatively short . Plasma levels decayed below 0.1 microgram/ml within 3-4 h after administration of the apparent maximum tolerated doses, which were approximately 20 mg/kg for the mice and 4 mg/kg for the dog . The drug exhibited linear pharmacokinetic behavior within the dose ranges studied . However, there were significant interspecies differences in its disposition . Whereas the mean biological half-life of GM was slightly longer in the mice (77.7 min) than in the dog (57.9 min), its mean residence time in the dog (46.6 min) was more than twofold greater than that observed in the mice (20.7 min) . Nevertheless, the drug was cleared from plasma much faster by the dog (49.4 ml/min per kg) than by the mice (30.5 ml/min per kg) . These apparent anomalies were principally associated with differences in the relative significance of the terminal phase upon overall drug disposition . The liver appeared to be the principal target organ of acute drug toxicity in the dog . Doses of 2.0 and 4.2 mg/kg both produced elevations in serum levels of the transaminases and other indicators of liver function characteristic of acute hepatic necrosis . Additional effects included symptoms of minor gastrointestinal toxicity and alterations in serum chemistry parameters consistent with less severe nephrotoxicity . Drug-related toxicity appeared to be reversible . In consideration of the potential for acute hepatotoxic reactions to GM, as well as to the other benzoquinoid ansamycins based upon structural analogy, additional pharmacological and therapeutic information is required to ascertain whether these compounds are viable candidates for clinical development.

J Med Assoc Thai, 1995 Jan, 78(1), 37 - 41
Ten year review of brain abscess in Children's Hospital Bangkok, Thailand; Ratanasiri B; Brain abscesses are the most common form of intracranial suppurative process in children . In ten years, 54 cases of brain abscess in the Children's Hospital, Bangkok were diagnosed mostly on the basis of clinical features, roentgenogram, CT scanning and basic laboratory findings . The age distribution of brain abscess was from 3 months to 14 years . Evidence of signs of increased ICP was frequently present . Almost half of the patients had associated congenital heart disease particularly Tetralogy of Fallot . CT scanning was very useful in the advantage of rapid diagnosis, early management and short and long-term follow-up, by decreasing the mortality of the patients . Definite diagnosis must be established by obtaining pus or infected ncrotic brain for culture . Brain abscess bacteria can be recovered from properly performed culture . In our series, anaerobic peptostreptococci was the organism most frequently encountered . In the present series, the mortality rates for antibiotic alone and for antibiotic plus aspiration or followed by excision showed no significant difference . Most of deaths were due to brain herniation . It is concluded that with earlier diagnosis, with CT scanning technology, with appropriate antibiotics and with the use of proper surgical methods, the mortality rate from brain abscess should be zero and neurological deficit should be reduced as well.

Probl Tuberk, 1995, (3), 53 - 4
{Lymphogenic introduction into lesser circulation of orally administered rifampicin in standard and liposomal forms}; Petrenko TI et al.; Pharmacokinetics of water and liposomal suspensions of lipophilic antibiotic rifampicin introduced intragastrically through a tube was studied in experiments on Wistar rats . After administration of water suspension rifampicin concentration reached its peak in all the tissues in 3 hours, lung concentration being 1.6 and 1.9 times higher than blood one . After liposomal suspension administration lymphatic rifampicin concentrations were maximal in 3 hours, while in the lungs and blood they were the highest in 6 hours . It is concluded that oral liposoluble drug enter primarily chyle vessels and via thoracic lymphatic duct directly lesser circulation . Liposomal inclusion of the drug warrants its high concentration in lymphatic system and lung tissue.

Adv Ren Replace Ther, 1995 Jan, 2(1), 60 - 9
Extracorporeal techniques of endotoxin removal: a review of the art and science; Malchesky PS et al.; The incidence of sepsis in the United States has risen in the past few years, and mortality from sepsis has risen over the past several decades . These increases have occurred despite the progress made in antibiotic therapy . The high mortality rate may not be related to the bacteria themselves but rather to the host's response . Of particular concern is the bacterial release of endotoxins, the development of endotoxic shock, and the resulting multiorgan failure, which has a high fatality rate and is the leading cause of death in patients admitted to intensive care units . Removing or neutralizing endotoxins are the two major therapeutic approaches to treating sepsis . To date, pharmacological methods have not been successful . Extracorporeal techniques are based on filtration, sorption, or both . Results with hemofiltration have not been definitive, in part because endotoxin levels have not been measured . Sorption devices, based on polymyxin B and anion exchange matrices, do remove endotoxins . Clinical studies in Japan on septic shock or multiorgan failure with polymyxin-B-bound fibers in direct hemoperfusion continue to suggest the utility of extracorporeal techniques for endotoxin removal . Continued effort is required and warranted to assess the clinical efficacy of these techniques.

Wien Med Wochenschr, 1995, 145(7-8), 195 - 6
{AV-block II and arthritis as manifestations of Lyme borreliosis}; Aringer M et al.; A 23-year old patient suffered from transient oligoarthritis and second degree AV block . The diagnosis of stage II systemic Lyme borreliosis was supported by a history of tick bites and the detection of both IgG and IgM borrelia antibodies in the patient's serum . The ECG-findings (bradyarrhythmia and AV block II) were detected several weeks after the onset of arthritis, whilst the patient reported no cardiac symptoms . Treatment was started with ceftriaxone and then continued with doxycycline because of an allergic reaction to the first antibiotic.

Wien Med Wochenschr, 1995, 145(7-8), 186 - 8
{ALS-like sequelae in chronic neuroborreliosis}; Hansel Y et al.; CSF investigation in a 61-year old female patient with clinical picture of motoneuron disease gave evidence for chronic infection with Borrelia burgdorferi . Improvement of clinical and CSF findings could be observed after antibiotic therapy . The diagnosis of amyotrophic lateral sclerosis which was initially suspected had to be revised and the disorder was interpreted as chronic neuroborreliosis.

Tohoku J Exp Med, 1995 Jan, 175(1), 43 - 53
Alteration of ammonia and carnitine levels in short-term treatment with pivalic acid-containing prodrug; Ito T et al.; We investigated the influence on mitochondrial functions in carnitine deficiency caused by short-term treatment of cefteram-pivoxil (CFTM-PI) which is one of pivaloyloxymethyl-esterified antibiotics in adult volunteers and diseased children . Administration of CFTM-PI caused hypocarnitinemia in all cases, and we observed a significant elevation of blood ammonia levels compared with those after its withdrawal in diseased children . A significant negative correlation was found between the levels of serum free carnitine and blood ammonia, and a positive correlation was observed between serum carnitine and blood glutamine levels in all adult samples and samples during administration in diseased children . Our data suggest that these antibiotic medications affect the mitochondrial function even in a short-term treatment and that L-carnitine supplementation would be necessary for patients treated with CFTM-PI.

Int Urol Nephrol, 1995, 27(2), 137 - 9
Acute renal failure due to acute pyelonephritis; Soylemezoglu O et al.; We report a case of acute renal failure due to acute pyelonephritis with microabscess formation . Despite antibiotic therapy renal function deteriorated, necessitating peritoneal dialysis . Although rare, acute pyelonephritis is an important consideration in the differential diagnosis of acute renal failure, and prompt antibiotic therapy is crucial to insure a favourable outcome.

Braz J Med Biol Res, 1995 Jan, 28(1), 39 - 50
Effects of dietary protein, angiotensin I converting enzyme inhibition and mesangial overload on the progression of adriamycin-induced nephropathy; Barretti P et al.; Adriamycin, a commonly used antineoplastic antibiotic, induces glomerular lesions in rats, resulting in persistent proteinuria and glomerulosclerosis . We studied the effects of dietary protein and of an angiotensin I converting enzyme inhibitor on the progression of this nephropathy and the evolution of the histological lesions, as well as mesangial macromolecule flow . Adriamycin nephropathy was induced by injecting a single iv dose of adriamycin (3 mg/kg body weight) into the tail vein of male Wistar rats (weight, 180-200 g) . In Experiment I animals with adriamycin-induced nephropathy were fed diets containing 6% (Low-Protein Diet Group = LPDG), 20% (Normal-Protein Diet Group = NPDG) and 40% (High-Protein Diet Group = HPDG) protein and were observed for 30 weeks . In Experiment II the rats with adriamycin nephropathy were divided into 2 groups: ADR, that received adriamycin alone, and ADR-ENA, that received adriamycin plus enalapril, an angiotensin I converting enzyme inhibitor . The animals were sacrificed after a 24-week observation period . Six hours before sacrifice the animals were injected with 131I-ferritin and the amount of 131I-ferritin in the glomeruli was measured . In Experiment III, renal histology was performed 4, 8 and 16 weeks after adriamycin injection . At the end of Experiment I the tubulointerstitial lesion index was 2 for LPDG, 8 for NPDG, and 7.5 for HPDG (P < 0.05); the frequency of glomerulosclerosis was 19 +/- 6.1% in LPDG, 42.6 +/- 6% in NPDG, and 54 +/- 9% in HPDG (P < 0.05); and proteinuria was 61.1 +/- 25 mg/24 h in LPDG, 218.7 +/- 27.5 mg/24 h in NPDG, and 324.5 +/- 64.8 mg/24 h in HPDG (P < 0.05) . In Experiment II, at sacrifice, 24-h proteinuria was 189 +/- 16.1 mg in ADR, and 216 +/- 26.1 mg in ADR-ENA (P > 0.05); the tubulointerstitial lesion index was 5 for ADR, and 5 for ADR-ENA (P > 0.05); the frequency of glomerulosclerosis was 40 +/- 5.2% in ADR and 44 +/- 6% in ADR-ENA (P > 0.05); the amount of 131I-ferritin in the mesangium was 214.26 +/- 22.71 cpm/mg protein in ADR and 253.77 +/- 69.72 cpm/mg protein in ADR-ENA (P > 0.05) . In Experiment III, sequential histological analysis revealed an acute tubulointerstitial cellular infiltrate at week 4, which was decreased at week 8 . Tubular casts and dilatation were first seen at week 8 and increased at week 16 when few glomerular lesions were found.(ABSTRACT TRUNCATED AT 400 WORDS)

Antisense Res Dev, 1995 Summer, 5(2), 149 - 54
Helix-stabilizing agent, CC-1065, enhances suppression of translation by an antisense oligodeoxynucleotide; Kim DY et al.; The antitumor antibiotic CC-1065 is known to bind at selected sequences in the minor groove of duplex nucleic acids and to hyperstabilize the duplexes against thermal melting . These properties suggested that CC-1065 may enhance translation inhibition by antisense oligonucleotides directed against a specific mRNA . A 585 bp mRNA transcript containing the equine infectious anemia virus (EIAV) S2 gene and a portion of the env gene was prepared . Also, a complementary 20 mer antisense oligodeoxynucleotide (5'-TGTTGGGTAATAGG-GGTTGA-3') was prepared against a target sequence in the mRNA located near the translational initiation sites of the overlapping S2 and env genes . The center of the target sequence had an expected CC-1065 recognition sequence (5'-UAUUA-3') . Translation in the presence of CC-1065 and antisense was markedly suppressed compared with that of antisense alone . Addition of a sense 20 mer strand, with or without CC-1065, had little or no effect on translation . CC-1065 and related compounds may be useful as ligands for enhancing the stability of sense-antisense duplexes and for promoting the inhibition of translation by antisense oligonucleotides.

Rev Laryngol Otol Rhinol (Bord), 1995, 116(2), 85 - 7
Pediatric cochlear implants . Surgical aspects: the Nottingham pediatric cochlear implant programme; Lloyd RV et al.; The implantation of young children is widely accepted as a means of rehabilitating profoundly/totally deaf children . This paper will review the surgical aspects of implanting young children based on the first 50 children implanted in the Nottingham paediatric cochlear implant programme . Having thoroughly counselled the children's parents, the child is operated on under prophylactic antibiotic cover . The incision (extended endaural) is made directly down to bone and a full-thickness flap is elevated . Meticulous attention is paid to haemostasis . The steps involved in posterior tympanotomy, cochleostomy and implant insertion, often in the presence of osteogenesis, will be described . Electrophysiological testing is done systematically peroperatively . Surgical complications were few . There was no cases of facial weakness, haematoma, implant extrusion or infection . One patient, whose implant was laid in an extracochlear gutter, developed pain on electrical stimulation and was explanted . Another patient developed a retraction pocket cholesteatoma . These few complications are far outweighed by the overwhelming benefits accrued from implantation.

Mycopathologia, 1995, 129(3), 183 - 90
Chemical and physiological characterization of taxa in the Fusarium sambucinum complex; Thrane U et al.; Forty-one isolates of Fusarium sambucinum sensu lato were screened for production of secondary metabolites in agar cultures . Of 16 strains of F . sambucinum sensu stricto all but two strains produced diacetoxyscirpenol and two unidentified metabolites, TB1 and TB2 respectively . The two remaining F . sambucinum strains produced T-2 toxin, TB1 and TB2 . Fusarium venenotum (6 strains) produced diacetoxyscirpenol and an unidentified metabolite BB . Fusarium torulosum (8 strains) produced wortmannin and antibiotic Y . The three species could be differentiated by their pattern of identified and unidentified metabolites detected by agar plug TLC combined with chemical data from HPLC-diode array detection of fungal extracts, and data on growth rates on potato sucrose agar and tannin sucrose agar.

Med Pregl, 1995, 48(5-6), 175 - 7
{Prediction of progression of suppurative meningitis based on clinical characteristics and cerebrospinal fluid findings at the onset of the disease}; Canak G et al.; Some factors (sex, age, the way of onset, previous antibiotic therapy, instant of hospitalization in relation to the appearance of initial symptoms) associated with the course of suppurative meningitis prior to the hospitalization have been analyzed and a trial has been made to locate them in the prognosis of the disease progression . At the Clinic of Infective Diseases in Novi Sad during 10 years (1977 to 1987, except 1983) 162 patients with a diagnosed purulent meningitis had been treated . The patients were classified into two groups: a group of 62 patients with complications and a group of 100 patients with an expected progression of the disease . Statistical data were analyzed using the x2 test and t test . In the period considered in this investigation the sickness passed with complications in 38.24% cases, 32.10% of them being of neurological nature, while 6.14% of complications appeared in other organs and systems . The statistical analysis shows that sex, age, the way of onset (data from history of the disease), previous antibiotic therapy, time of hospitalization in relation to appearance of initial symptoms, can not be used as reliable parameters in predicting the further course of suppurative meningitis . Complications have been registered in patients having more than 2.16g/l proteins and less than 1.12mmol/l sugar in the liquor at the beginning of the disease . These values can be used as a reference for predicting the further course of the disease.

Med Trop (Mars), 1995, 55(2), 160 - 4
{Role of hysterosalpingography in the evaluation of infertility in Black Africa}; De Muylder X; Infertility affects a great number of women in Black Africa and tubal obstruction seems to be common . Because of this high incidence, an accurate test for tubal patency is needed and several examinations have been proposed . Recent reports indicate that the method of choice is hysterosalpingography since it is simple, quick, and reliable . Concordance with laparoscopy, the gold standard, is 85% for assessment of tubal patency and 75% for detection of tubal abnormalities . Due to the lack of radiological facilities in most hospitals in Black Africa, a simplified examination is proposed and seems to be useful as an initial screening test . This simplified test consists of obtaining a delayed anteroposterior image after a brief walk . The most severe complication of hysterosalpingography is pelvic infection which occurs in 2 to 4% of cases and requires prophylactic antibiotic therapy . Interestingly an increase in pregnancy rate has been observed in the months after hysterosalpingography . Recent reports concerning infertility workups in developing countries confirm that the method of choice for assessment of tubal function is hysterosalpingography provided that the risk of infection can be controlled.

Curr Med Res Opin, 1995, 13(5), 274 - 81
Rifaximin in the treatment of chronic hepatic encephalopathy; Puxeddu A et al.; A study was performed to assess the efficacy and tolerability of rifaximin in the treatment of encephalopathy during cirrhosis of the liver . Fifty-five patients suffering from grade 1, 2 and 3 portosystemic encephalopathy, with a mean age of 58.9 years (range 30 to 86 years) were evaluated . The patients were treated for 15 consecutive days with rifaximin, an antibiotic which is not absorbed by the intestinal wall, at a dosage of 1200 mg/day in association with sufficient lactulose to induce 2 or 3 evacuations per day . Combined use of the 2 drugs proved an efficient means of controlling the majority of signs and symptoms . After just a few days, an improvement in the signs of encephalopathy was noted in all patients . The treatment was well tolerated and the patients completed the trial without any drug-related side-effects . The results of our trial, although in the context of an open assessment, confirm the clinical efficacy of rifaximin in association with a non-absorbable disaccharide such as lactulose . The 2 compounds have a synergetic effect in reducing ammonia-producing flora . Its efficacy and good tolerability make rifaximin a valid alternative to the use of aminoglycoside antibiotics associated with disaccharides in the treatment of patients with liver disease, particularly in the case of prolonged therapy.

Parasitol Res, 1995, 81(1), 26 - 31
Stage-dependent effects of analogs of gramicidin A on the growth of Plasmodium falciparum in vitro; Otten-Kuipers MA et al.; Tryptophan-N-formylated gramicidin A, a nonhemolytic derivative of the toxic peptide antibiotic gramicidin A, has previously been shown to induce potassium leakage from Plasmodium falciparum-infected erythrocytes in vitro and to inhibit the growth of the parasite . In the present study the antimalarial activities of two other nonhemolytic derivatives of gramicidin A, viz., acylated gramicidin A and desformylated gramicidin A, were tested and compared with those of gramicidin A and tryptophan-N-formylated gramicidin A . The 50% growth-inhibitory concentrations (IC50 values) of the four compounds varied from 0.3 to 18.3 nM, and complete growth inhibition was detected within one parasitic growth cycle . Using highly synchronized cultures of P . falciparum, it was furthermore shown that the gramicidin analogs are inhibitory to all developmental stages of the parasite, although their efficiency in accomplishing growth inhibition was found, as expected, to be clearly stage-dependent and to increase with the age of the parasite.

Chest, 1995 Jan, 107(1), 276 - 8
Impairment in gas exchange after granulocyte colony stimulating factor (G-CSF) in a patient with the adult respiratory distress syndrome; Schilero GJ et al.; We describe the previously unreported finding of reproducible arterial d desaturation after successive injections of granulocyte colony stimulating factor in a orthotopic liver transplant recipient with the adult respiratory distress syndrome and antibiotic-induced neutropenia.

Am J Nephrol, 1995, 15(5), 379 - 85
Pathobiology and functional status of long-term hemodialysis patients; Ifudu O et al.; There may be cumulative 'metabolic scars' after a decade or more of long-term hemodialysis . We studied 39 patients who have been on maintenance hemodialysis for 10-24 years to determine their functional status and pathobiology . The 39 long-term (> or = 10 years) patients were compared with a control cohort of 37 age-, gender-, race-, and renal-diagnosis-matched patients on hemodialysis for < or = 3 years . The functional status was measured using a modified Karnofsky scale, and the employment status was noted as well . Details of hospitalizations and intercurrent infections requiring outpatient oral or intravenous antibiotic therapy during the preceding year were obtained . Comorbid medical conditions were documented, and basic laboratory tests were performed . The mean age of the long-term patients was 51.8 +/- (SE) 1.9 years, and the mean age of the control group was 51.5 +/- 2.4 years (p = 0.92) . Three times weekly hemodialysis prescriptions were similar in both groups (long-term: 3.5 +/- 0.02 h, control: 3.4 +/- 0.02 h; p = 0.27) . The mean modified Karnofsky scores were equivalent in both groups . The rate of hospitalization during the preceding year was higher among the long-term patients (0.92 +/- 0.19/patient year) than in the control patients (0.51 +/- 0.15/patient year; p = 0.09) . The long-term patients had more intercurrent infections (1.23 +/- 0.21) than the controls (0.68 +/- 0.16; p = 0.04) . (ABSTRACT TRUNCATED AT 250 WORDS)

Parasitol Res, 1995, 81(5), 421 - 5
Ribosomes of Leishmania are a target for the aminoglycosides; Maarouf M et al.; Ribosomes of Leishmania, a parasitic protozoan (member of the order of Kinetoplastidae), were purified on a sucrose density gradient . Two different types of ribosomes were isolated from the promastigotes: cytoplasmic (88S and 91S from L . tropica and L . donovani, respectively) and mitochondrial (75S in both species) . Both types of ribosome dissociated into their subunits at low Mg2+ concentration (1-2 mM) as follows: 67S and 49S for the 91S cytoplasmic ribosomes of L . donovani and 61S and 43S for the 88S cytoplasmic ribosome of L . tropica; 55S and 34S for L . tropica and 60S and 39S for L . donovani mitochondrial ribosomes, respectively . Paromomycin (aminosidine), an aminoglycoside aminocyclitol antibiotic, interacted with the ribosomes to promote the association of the subunits . Under similar experimental conditions, spermidine and pentamidine were inactive.

Acta Oncol, 1995, 34(7), 919 - 24
Effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) on hematologic toxicity induced by high-dose chemotherapy in patients with metastatic breast cancer; Hansen F et al.; Twenty patients with recurrent metastatic breast cancer treated with high-dose myelosuppressive antineoplastic drugs (cyclophosphamide 2.5 g/m2 or epirubicin 130 mg/m2, both every 3 weeks) as first or second line chemotherapy were randomized in a prospective study to GM-CSF 5 micrograms/kg per day (n = 11) or control (n = 9) . Significant reduction in granulocyte nadir duration (2 days with GM-CSF vs . 7 days) and severity (0.4 x 10(9)/l with GM-CSF vs . 0.2 x 10(9)/l) was found . No difference in frequency of neutropenic fever or antibiotic use could be observed . Even though the patients treated with GM-CSF at random were more heavily pretreated with chemotherapy, there was a surprisingly higher response rate in these patients as compared to the control-arm, namely 64% vs . 28.5% . However, this difference was not statistically significant . No severe side-effects were seen, but presumably due to GM-CSF one patient developed an allergic type 1 reaction and one patient a possible pericardial exudation . Both were fully reversible after cessation of the cytokine treatment.

An Otorrinolaringol Ibero Am, 1995, 22(5), 467 - 78
{Sudden bilateral deafness as allergic manifestation}; Vallejo Valdezate LA et al.; The paper reports the case of a young woman who presented with a serious bilateral sudden deafness, after the ingestion of a betalactam antibiotic (known as allergic for her) in association with a mucolytic . Account of the course of the clinical events noticed, which are compared with the findings observed in other scarce publications on sudden deafness linked with allergic reactions . Finally the AA . outline a pathogenetic hypothesis in order to explain these cases of deafness involved with digestive allergic reactions.

Rev Med Interne, 1995, 16(9), 687 - 90
{Uveitis: late complication of undiagnosed Whipple disease}; Wechsler B et al.; We report a case of severe chronic bilateral uveitis in a 60-year-old white man without neurological manifestations . Spondylarthritis and isolated malabsorption suggested the diagnosis of Whipple's disease . A normal duodenal biopsy delated the diagnosis, who was secondarily demonstrated an adenopathy biopsy and macrophage study on vitrectomy sample (macrophage distended by periodic acid-Schiff positive material) . With 1 year follow-up the uveitis was rapidly and completely cured by an antibiotic association (rifampicin and trimethoprim-sulfamethoxazol) . The characteristics of ocular involvement in Whipple's disease and treatment of the disease are discussed.

Rev Med Interne, 1995, 16(9), 658 - 61
{Is the indomethacin test able to indicate the etiological diagnosis of isolated fever?}; Barrier J et al.; The aim of this study was to determine if evolution of fever after administration of indomethacin to febrile patients could separate those with fever of infectious origin from those with non-infectious origin . All patients with a rectal body temperature superior than 38 degrees C for at last 5 days and without any antibiotic or antipyretic therapy for more than 48 hours, were included in a 1 year prospective study . Each patient received one time 50 mg of indomethacin and rectal body temperature was obtained every 3 hours for 12 hours . Forty-five patients were included, 20 in group I (fever of infectious origin) and 25 in group II (fever of non-infectious origin) . The mean age and mean initial body temperature were similar in the two groups . After administration of indomethacin, mean duration and mean amplitude of abatement of fever were similar in the two groups . Hypothermia was observed more frequently in group II (28%) than in group I (10%) (p < 0,05) and was preferentially associated to a malignant lymphoma . Also, diagnostic procedure with indomethacin is of little interest to separate fever of infectious origin from other, but hypothermia would suggest a fever due to a malignant lymphoma.

Nephrol Dial Transplant, 1995, 10(7), 1194 - 7
Pneumocystis carinii pneumonia in renal transplant recipients; Branten AJ et al.; In 1991 and 1992 Pneumocystis carinii pneumonia (PCP) was diagnosed in 28 renal transplant recipients . The incidence of PCP in our renal transplant centre was remarkably increased from 1.1% before 1991 to 11.5% in 1991-1992 . We compared 28 PCP patients with a control group of 27 renal transplant recipients, matched for transplantation day and without an episode of PCP . The mean age was significantly higher in the PCP group (50 +/- 13 versus 38 +/- 13 years) . We observed no differences in basic immunosuppressive and rejection treatment nor in antibiotic consumption, number of hospitalization days, and incidence of CMV infection . In March 1993 we introduced PCP prophylaxis . More than 140 renal transplant recipients received co-trimoxazole, starting 1 day after transplantation and continued for a period of 4 months . To the time of writing no one in this group had developed PCP.

Tumori, 1994 Dec 31, 80(6), 453 - 8
The role of granulocyte colony-stimulating factor (filgrastim) in maintaining dose intensity during conventional-dose chemotherapy with ABVD in Hodgkin's disease; Silvestri F et al.; BACKGROUND: The aim of the study was to evaluate the role and potential benefit of granulocyte colony-stimulating factor (G-CSF, Filgrastim), administered following cytotoxic chemotherapy with the ABVD regimen in Hodgkin's disease, in maintaining cycle schedule and dose intensity and in decreasing neutropenia and number of infections . PATIENTS AND METHODS: Twenty-two patients affected by high-risk Hodgkin's disease (14 localized and 8 diffuse), aged 15 to 69 years (median, 34), were given ABVD chemotherapy for a total of 6 courses (for the purpose of this study, each single course of chemotherapy was considered as two 15-day periods) . No patient was given G-CSF after the first cycle . After each cycle, G-CSF was administered only for: 1)absolute neutrophil count < 1 x 10(9)/L between cycles; 2) delay in cycle schedule due to an absolute neutrophil count < 1 x 10(9)/L on the planned day of treatment; or 3) fever or a documented infection, regardless the absolute neutrophil count . Once administered, G-CSF was maintained in the subsequent cycles . RESULTS: Seventeen of 22 patients (77%) required the administration of G-CSF (5 micrograms/kg b.w.; a median of 5 doses/cycle); most of them (13/17) before the 5th dose of chemotherapy . The main reason for introducing G-CSF into therapy was neutropenia during the interval between courses (n = 4) or on the planned day of treatment (n = 11) . Comparing 112 courses where G-CSF was not administered with 124 where it was, in the latter group we observed: 1) a significantly lower (P = 0.0002) incidence of cycle delays (0 vs 13), with a median delay of 7 days (5 to 11) . The main reason for cycle delay was neutropenia (n = 13); 2) a greater dose intensity delivered to the patients while on G-CSF (100% vs 95.2 +/- 8.8%; P = 0.0001); 3) an absolute neutrophil count significantly higher at day 8 (P < 0.0001) and day 15 (P < 0.0001); 4) a significantly lower (P = 0.0003) incidence of neutropenia (2 vs . 17) . No difference in the incidence of infections was observed between the two groups of cycles (P = 0.5889), but the duration and severity of the same were greater during chemotherapy without G-CSF, requiring antibiotic therapy and causing cycle delay . CONCLUSIONS: In conclusion, our data suggest the use of Filgrastim in Hodgkin's disease also during conventional-dose chemotherapy with ABVD . It is not required from the first dose of therapy, but as soon as neutropenia appears between cycles or on the planned day of treatment . Then, its use allows maintenance of the chemotherapy schedule and dose intensity . It also decreases frequency, duration and severity of neutropenia and its sequelae.

Gene, 1994 Dec 30, 151(1-2), 17 - 21
Gene organization in the bleomycin-resistance region of the producer organism Streptomyces verticillus; Calcutt MJ et al.; A nucleotide sequence of 7 kb is reported, encompassing two bleomycin-resistance (BmR-encoding) genes and five other open reading frames (ORFs) from the Bm-producing organism Streptomyces verticillus ATCC 15003 . The deduced ORFs, in sequence order, encode for (i) a protein homologous to an amino-acid dioxygenase; (ii) BlmA, the BmR-binding protein described by Sugiyama et al . {Gene 151 (1994) 11-16}; (iii) a product containing three copies of a sequence homologous to the ankyrin repeat; (iv) a product lacking homology to any of the sequences in the Protein Identification Resource database (PIR), release 37; (v) BlmB, the BmR acetyltransferase described by Sugiyama et al . (1994); (vi) an unidentified protein which augmented resistance determined by ORF2 (BlmA); (vii) a member of the ATP-binding cassette (ABC) family of transport protein . Predicted translational frameshifts in the -1 frame occur at the junctions between ORF3 and ORF4, ORF4 and ORF5, and ORF6 and ORF7 . Sequences homologous to ORF2 and ORF3 were identified in the genome of the producer organism for the related antibiotic phleomycin.

Ned Tijdschr Geneeskd, 1994 Dec 24, 138(52), 2584 - 7
{Spondylodiscitis cause by Brucella suis}; Kant GD et al.; In a 72-year-old Dutchman Brucellae suis spondylodiscitis TXII-LI was diagnosed, complicated by a paraspinal abscess, for which surgical drainage was carried out . The patient failed to recover after the combined antibiotic regimen of doxycycline, rifampicin and trimethoprim-sulfamethoxazole . There was good clinical improvement after a course of doxycycline and streptomycin, however . After a symptom-free period of 9 weeks a relapse occurred . The patient refused treatment and died 6 weeks later at home . The infection had probably been contracted after handling wild boar carcasses from eastern Europe.

Biochem Biophys Res Commun, 1994 Dec 15, 205(2), 1358 - 65
Destruxin B, a specific and readily reversible inhibitor of vacuolar-type H(+)-translocating ATPase; Muroi M et al.; Destruxin B, a peptide antibiotic, inhibits vacuolar-type ATPase (V-ATPase) specifically and dose-dependently among ATPases examined . Acidification of intracellular organelles is also blocked by destruxin B at comparable concentrations when assessed by accumulation of acridine orange . The inhibitory activity of destruxin B is weaker than that of bafilomycin A1 and folimycin, well known macrolide inhibitors of V-ATPase, when compared at the same molar concentration . Unlike the macrolide antibiotics, however, the inhibitory activity of destruxin B is readily reversible . This novel feature of destruxin B should make it a useful probe in the analysis of V-ATPase function in cell physiology.

FEBS Lett, 1994 Dec 12, 356(1), 1 - 4
Import of phosphatidylinositol and phosphatidylcholine into mitochondria of the yeast, Saccharomyces cerevisiae; Lampl M et al.; An in vitro assay was designed to study the import of 3H-labeled phosphatidylinositol and phosphatidylcholine, respectively, from unilamellar vesicles into isolated mitochondria of the yeast, Saccharomyces cerevisiae . Both phospholipids reached the inner mitochondrial membrane . During import they were detected in contact sites between the outer and the inner mitochondrial membrane, supporting the notion that these zones are sites of intramitochondrial phospholipid transport . The uncoupler CCCP, the antibiotic adriamycin, and energy depletion caused by oligomycin and apyrase did not inhibit the transport of phosphatidylinositol and phosphatidylcholine into mitochondria.

Nucleic Acids Res, 1994 Dec 11, 22(24), 5241 - 6
Daunomycin modifies the sequence-selective recognition of DNA by actinomycin; Ridge GS et al.; The antitumour antibiotic actinomycin D normally binds to DNA by intercalation at sequences containing the CpG step, but in the presence of daunomycin it has been reported to interact with poly(dA-dT) . This observation has neither been confirmed nor explained . Here we have used a photoreactive 7-azido derivative of actinomycin to study the effect of daunomycin on its binding to three DNA fragments . Daunomycin did indeed alter the binding of actinomycin to the DNA, such that the antibiotic was displaced from its primary GpC sites onto secondary sites in the DNA, though not to AT regions especially . These findings suggest a possible scientific explanation for the increased toxicity seen during combination chemotherapy with these two drugs.

Med Clin (Barc), 1994 Dec 10, 103(20), 761 - 5
{Intravenous amphotericin B as prevention of deep mycoses in allogeneic bone marrow transplantation}; Carreras E et al.; BACKGROUND: To evaluate the efficacy of i.v . amphotericin B (AmB) as prophylaxis of deep mycosis (DM) in allogenic bone marrow transplantation (BMT) . METHODS: From July 1991 to May 1993, 45 consecutive patients treated by allogenic BMT with no previous history of systemic mycosis and with normal renal function were administered prophylactic AmB at a dose of 0.5 mg/kg/48 h from day + 1 BMT until hemoperipheral recovery (group A) . These were compared with an historic control group made up of 45 consecutive patients submitted to BMT from January 1990 to June 1991 who did not receive prophylactic AmB (group B) . During the neutropenic phase all the patients remained in isolation units with laminar flow of filtered air and were administered oral non absorbable antibiotic therapy and diet of low bacterial content . The incidence of DM and the dose of AmB administered during the first 120 days post BMT were evaluated . RESULTS: In the first 30 days following BMT 3 (7%) cases of DM were observed in group A and 3 (7%) in group B . Four (9%) additional cases were found from days 30 to 120 in group A and 3 (7%) in group B . In 3 (7%) patients of the group which received prophylaxis and in 4 (9%) of the control group Candida spp . was isolated . In 3 (7%) patients from group A and 1 (2%) patient from group B the infection was due to Aspergillus . Although the patients from group A received therapeutic AmB less frequently (78% vs 91%) and later (13 {SD +/- 5.9} vs 9.2 {SD +/- 4.6} days) than those of group B (p < 0.002) the mean dose of AmB per patient treated was similar in both groups (11.3 {SD +/- 8.8} vs 11.8 {SD +/- 7} mg/kg) . CONCLUSIONS: The prophylactic use of systemic amphotericin during the neutropenic phase of bone marrow transplantation does not reduce either the incidence of deep mycosis or the mean dose of amphotericin administered.

Schweiz Med Wochenschr, 1994 Dec 10, 124(49), 2220 - 5
{Ethics of antibiotherapy in geriatric medicine}; Michel JP et al.; The high frequency of infections in the elderly, at home as well as in institutions, raises the question of the place antibiotic therapy should occupy . Too often, unfortunately, antibiotic therapy is prescribed indiscriminately in cases of infection . Between therapeutic abstention and overtreatment there is room for a more rational and adapted medical decision which is the outcome of a clinical process integrating a rigorous biomedical approach, taking due account of the environment, the functionality and the quality of life of the elderly patient . The importance of human, ecological, pharmacological and economic constraints should lead to deeper consideration of the appropriateness of antibiotic therapy in geriatric practice.

Top Hosp Pharm Manage, 1995 Jan, 14(4), 68 - 77
Use of total quality management techniques to improve compliance with a medication use indicator; Woster PS et al.; Total quality management techniques were used to lay the groundwork for and to implement procedural changes designed to improve compliance with the Joint Commission on Accreditation of Healthcare Organizations' medication use indicator for ordering and administering presurgical antibiotics . The effect of these procedural changes on patient outcomes (i.e., postsurgical infection rates and length of hospitalization) is described . In a study to assess compliance, 57 (30 percent) of 40 control patients received a presurgical antibiotic within 1 hour of incision compared with 65 (52 percent) of 126 study group patients, and 83 (44 percent) of the control group received a presurgical antibiotic within 2 hours of incision compared with 88 (70 percent) of 126 study group patients . Postsurgical infection rates and length of hospitalization were not significantly different (p = .407 and p = .885, respectively).

Ophthalmology, 1994 Dec, 101(12), 1935 - 40
Impression debridement of corneal lesions; Arora I et al.; PURPOSE: The technique of impression cytology using cellulose acetate filter paper as a debriding agent was evaluated . METHODS: Lesions were assessed using a slit-lamp biomicroscope before and after the impressions were taken and appropriate antibiotic therapy was started . The filter paper impressions were stained with hematoxylin-eosin and examined by light microscopy . The 72 corneal ulcers and three cases of suture infiltration around exposed corneoscleral cataract-related sutures were effectively debrided . Five of the six foreign bodies and all of the filaments in the six filamentary keratitis cases were removed with minimal damage to the surrounding cornea . RESULTS: Results of microscopic examination showed that the cells that were transferred to the filter paper were primarily the affected cells . In corneal ulcers, the degenerated epithelial cells, inflammatory cells, and organisms were removed . The inflammatory cells superimposed on affected epithelial cells in suture infiltration and the filaments of filamentary keratitis were removed . In cases of superficial corneal foreign bodies, the foreign bodies overlying a sheet of degenerated epithelial cells were lifted up . CONCLUSION: "Impression debridement" improves the quality and efficiency of debridement for most of these conditions, with much less risk to the surrounding tissue than the conventional techniques . Besides being an adjunct to therapy, it simultaneously provides replicas of the lesions that give accurate histologic details after microscopic evaluation.

J Trauma, 1994 Dec, 37(6), 938 - 40
The management of open fractures associated with arterial injury requiring vascular repair; Seligson D et al.; Seventy-two open fractures associated with arterial injury requiring vascular repair (Gustilo type IIIC injuries) were treated at the University of Louisville from May 1983 and through 1992 . The involved anatomic areas were the humerus (four), forearm (ten), femur (eight), tibia (31), ankle (ten), and foot (nine) . Fracture management consisted of careful debridement, wound irrigation, fasciotomy, and fracture stabilization . Additionally, 40 wounds (55.6%) were treated with the supplemental use of local antibiotics (tobramycin-PMMA bead chains) . Twenty-three patients (32.1%) underwent primary amputation, and 49 (67.99%) of the injured vessels were repaired . There were seven secondary amputations because of infection or poor revascularization, resulting in an overall amputation rate of 41.6% . The wound infection rate was 13.9% (10 of 72) and the rate for osteomyelitis was 4.2% (3 of 72) . The local use of the antibiotic bead chains was of significant benefit in lowering infectious complications . Primary coverage of soft-tissue defects with free tissue transfer had an infection rate of 66%; temporary wound coverage with the "antibiotic bead pouch" technique until wound closure can be obtained in a sterile and viable environment appears to be a better option.

J Am Coll Surg, 1994 Dec, 179(6), 727 - 32
Prognostic factors for pyogenic abscess of the liver; Chou FF et al.; BACKGROUND: Percutaneous drainage and antibiotics for pyogenic abscess are well established therapeutic modalities . However, the mortality rate for hepatic abscess of liver remains high . STUDY DESIGN: Three hundred fifty-two cases of pyogenic hepatic abscesses were studied to evaluate prognostic factors . RESULTS: Using univariate analysis, the following factors were associated with a high mortality rate: patient age, gas-forming abscess, rupture of abscess, bilobe involvement, clinical sepsis, bilirubin (more than 2 mg per dL), blood urea nitrogen (more than 20 mg per dL), serum creatinine (more than 2 mg per dL), aspartate aminotransferase (more than 100 U per L), and albumin (less than 2.5 gm per dL) . Using multivariate analysis, the following were independent significant factors in predicting mortality: patient age (more than 60 years), blood urea nitrogen (greater than 20 mg per dL), serum creatinine (greater than 2 mg per dL), total bilirubin (greater than 2 mg per dL), and albumin (less than 2.5 gm per dL) . CONCLUSIONS: Systemic effects of hepatic abscess with sepsis and multiple organ failure were significant factors in predicting mortality . Local findings, such as rupture of the abscesses, multiple abscesses, and gas-forming abscesses, were not independent factors . Percutaneous drainage is always considered if the condition of the patient can not be improved with antibiotic therapy . Operative treatment is indicated if the patient is unresponsive to medical treatment and percutaneous drainage or if the patient has complications of biliary tract stone or rupture of the abscess.

Spine, 1994 Dec 1, 19(23), 2614 - 8
Gentamicin penetration into normal rabbit nucleus pulposus; Currier BL et al.; STUDY DESIGN . Radioactively labeled gentamicin was administered to 24 rabbits to assess the concentration of antibiotic in the nucleus pulposus . OBJECTIVES . The purpose of the study was to investigate the pharmacokinetics of gentamicin penetration into normal rabbit nucleus pulposus . SUMMARY OF BACKGROUND DATA . Disc space infection is a complication of spinal surgery that can be prevented by prophylactic antibiotics . Gentamicin can be used in conjunction with other antibiotics as a prophylactic agent . One previous study demonstrated that a similar antibiotic, tobramycin, penetrates the disc, but no data have been reported on the pharmacokinetics of disc penetration . METHODS . Twenty-four rabbits were given an intravenous injection of gentamicin labeled with iodine 125 . Four rabbits were killed at hourly intervals 1 to 6 hours after injection . Specimens of nucleus pulposus, blood, whole liver, and saline-perfused liver were obtained and prepared . The radioactivity in the specimens was measured . RESULTS . The gentamicin concentration in the nucleus pulposus peaked at 2 hours and remained at this level for the duration of the experiment . Twenty percent of the gentamicin recovered from the nucleus pulposus was tissue bound . CONCLUSIONS . Gentamicin concentration in the rabbit nucleus pulposus does not peak until 2 hours after an intravenous bolus of drug . If gentamicin penetrates human nucleus pulposus in a similar fashion, this study could have implications for the timing of administration of this agent for prophylaxis.

Orthopedics, 1994 Dec, 17(12), 1155 - 8
Conversion of resection arthroplasty to total hip replacement; Berman AT et al.; Conversion of Girdlestone arthroplasty is a demanding procedure dependent on adequate debridement at time of resection and appropriate long-term antibiotic therapy . Patients must be followed closely for persistent sepsis through ESR, aspiration, and physical examination . Pre-reconstruction, existing bone stock should be assessed and revision techniques utilized where appropriate . Our experience is that conversion of Girdlestone pseudoarthrosis to THR can yield good functional results and restore independence.

Microbiology, 1994 Dec, 140 ( Pt 12), 3233 - 40
Transposon mutagenesis of Nostoc sp . strain ATCC 29133, a filamentous cyanobacterium with multiple cellular differentiation alternatives; Cohen MF et al.; Nostoc sp . strain ATCC 29133 (PCC 73102; Nostoc 29133) is a symbiotically-competent, facultatively heterotrophic, diazotrophic cyanobacterium with the capacity to differentiate specialized cells such as heterocysts, akinetes and hormogonial filaments . We have optimized several methods for physiological and molecular genetic analysis of Nostoc 29133 . By use of a Tn5 derivative, Tn5-1063 (Km(r)Bm(r)Sm(r)), delivered by conjugation from Escherichia coli, antibiotic-resistant mutants of Nostoc 29133 were generated at a frequency of approximately 1 x 10(-6), 0.4% of which expressed a nitrogen fixation (heterocyst) defective phenotype . Mutant strain UCD 328 was isolated after co-culture of 86 Nostoc 29133::Tn5-1063 clones with the symbiotic plant partner, Anthoceros punctatus; strain UCD 328 expressed a symbiotic phenotype of increased frequency of hormogonia-dependent infection . The transposon and flanking genomic DNA was recovered from strain UCD 328, the mutation and phenotype reconstructed by homologous recombination in Nostoc 29133, and the transposition site identified from a Nostoc 29133 genomic library . Transposon mutagenesis has thus provided the means for isolation and identification of developmental and symbiotic-specific genes of Nostoc 29133.

Analyst, 1994 Dec, 119(12), 2761 - 4
Novel approach to the 'on-site' testing for sulfamethazine in pork carcasses; Shearan P et al.; Rapid 'on-site' methods are required by the pork industry to screen for the presence of antibiotic residues in meat and meat products . There are few rapid and easy-to-use methods suitable for application in non-analytical laboratories . This paper describes a novel approach for the screening of sulfamethazine in pork muscle using matrix solid phase dispersion, a microcolumn preconcentration step and thin-layer chromatographic detection . The characteristics of the method are reported allowing for the detection of residues at the maximum residue limit of 100 ppb . Results from the industrial evaluation of the complete method are also presented.

Kansenshogaku Zasshi, 1994 Dec, 68(12), 1543 - 7
{A child with iritis due to Chlamydia pneumoniae infection}; Yamada S et al.; A case of uncommon iritis due to Chlamydia pneumoniae (C . pneumoniae) is reported . The patient was a 9-year-old boy who had suffered from cough, pharyngeal pain, and low grade fever . The symptoms persisted for more than 1 month in spite of an oral cephem antibiotic . Ophthalmalgia, congestion around the iris and cough had lasted with alleviation and exacerbation . A diagnosis of C . pneumoniae infection was made by specific polymerase chain reaction (PCR) method and microimmunofluorescence test (MIF) . The symptoms subsided with administration of clarithromycin (CAM: 300 mg/day) for 2 weeks . Because of the simultaneous alleviation of iritis, C . pneumoniae infection was considered to introduce the iritis . Much remains to be clarified about this pathogenesis of iritis and more detailed evaluations are required.

J Clin Gastroenterol, 1994 Dec, 19(4), 306 - 9
Cytomegalovirus as an exacerbating factor in ulcerative colitis; Loftus EV Jr et al.; Cytomegalovirus (CMV) colitis has been reported infrequently in patients with underlying inflammatory bowel disease, and usually in those who are taking long-term corticosteroid drugs and who are potentially immunosuppressed . We report a 39-year-old man with long-standing ulcerative colitis, taking only sulfasalazine, who developed a viral prodrome followed by bloody diarrhea . Severe colitis was noted on endoscopy . He worsened with intravenous steroid and antibiotic drugs . Flexible sigmoidoscopy with biopsy before a contemplated colectomy revealed a moderately active colitis with large cells containing intranuclear inclusions scattered throughout the biopsies, characteristic of CMV colitis . Serologic and immunologic studies suggested recent CMV infection . The patient improved with intravenous ganciclovir and a steroid taper, and colectomy was avoided . CMV colitis is a potentially treatable cause of fulminant colitis.

Ophthal Plast Reconstr Surg, 1994 Dec, 10(4), 260 - 1
Bilateral nasolacrimal duct obstruction associated with Crohn's disease successfully treated with dacryocystorhinostomy; Mauriello JA Jr et al.; A 41-year-old woman developed epiphora due to bilateral nasolacrimal duct obstruction 1 year after a definitive diagnosis of Crohn's disease . Treatment with systemic and topical antibiotic therapy resulted in resolution of the left-sided obstruction but epiphora persisted on the right side . The patient underwent standard dacryocystorhinostomy with insertion of silicone tubes . Six months after surgery, she remains free of symptoms . To our knowledge, this is the first report of bilateral nasolacrimal duct obstruction that occurred in a patient with active Crohn's disease.

Arch Esp Urol, 1994 Dec, 47(10), 1019 - 21
{Renal infarction following pulmonary surgery in a 13-year-old boy}; Borrego Hernando J et al.; We report a case of renal polar infarction in a 13-year old boy following surgical excision of contralateral congenital lobar emphysema . Patient history was unremarkable and yielded no data suggestive of any other underlying pathology or systemic disease . The diagnosis was made on the CT, arteriography and DMSA scan findings . The etiology could not be determined . The patient was treated conservatively with prophylactic antibiotic therapy and followed closely . There were no complications; the patient was asymptomatic one month after the episode . The control IVP showed residual segmental atrophy and ultrasound evaluation disclosed cortical atrophy . The most common cause of this condition, the diagnostic algorithm, treatments and their indications are discussed . Renal graft infarction, which may be associated with acute rejection or venous and/or arterial thrombosis, warrants special attention . The treatment and clinical course are significantly different, although the diagnosis is made using the same methods.

Arzneimittelforschung, 1994 Dec, 44(12A), 1516 - 20
Pidotimod activity against chronic bronchitis exacerbations; Ciaccia A; The efficacy of pidotimod ((R)-3-{(S)-(5-oxo-2-pyrrolidinyl) carbonyl}-thiazolidine-4-carboxylic acid, PGT/1A, CAS 121808-62-6) in the management of infectious exacerbations of chronic bronchitis was evaluated in a double-blind, placebo-controlled study in parallel groups over 5 months (60 days of treatment and 90 days of follow-up) . The study enrolled 580 patients, of whom 514 could be evaluated . The pidotimod group had fewer and shorter infectious episodes, fewer days of antibiotic therapy and fewer days unable to undertake normal activities . The difference vs . placebo was significant during the follow-up period and, in those subjects with a less severe history, during the treatment period also . Pidotimod was well tolerated.

Zhonghua Yi Xue Za Zhi (Taipei), 1994 Dec, 54(6), 442 - 6
Bowel perforation--a fatal complication following renal transplantation: a report of two cases; Lin HS et al.; From May 1983 to January 1993, 162 patients received renal transplantation at Taichung Veterans General Hospital . Two patients developed bowel perforation after this surgery . One was proved at 21 days and another, at 13 days after renal transplantation . Both patients died as a direct result of the perforation . From a review of literature, the average incidence is 2.7%, and the average mortality rate is 56.5% . Because of this high mortality rate, a high clinical suspicion, prompt and adequate surgical intervention, reduction of immunosuppressive agents and effective antibiotic coverage should contribute to a decline in mortality.

Br J Oral Maxillofac Surg, 1994 Dec, 32(6), 380 - 3
Symptoms from impacted wisdom teeth; Samsudin AR et al.; A study of patients referred for wisdom teeth removal was carried out, to investigate symptoms prior to consultation and during the period on the waiting list for surgery . The reasons for treatment of asymptomatic wisdom teeth were investigated . Pain was the main indication for surgery in 73.7% of patients waiting for consultation . 168 patients waiting for consultation consumed a total of 271 courses of antibiotics, averaging 1.6 courses of antibiotics per patient . The antibiotic consumption increased to an average of 2.5 courses per patient in 94 patients waiting for operation . 67 out of 423 patients had an average of three lost working days due to symptoms from wisdom teeth . The long waiting list for consultation and treatment added further to the discomfort . The extent of symptoms from wisdom teeth may be underestimated.

J Antibiot (Tokyo), 1994 Dec, 47(12), 1447 - 55
Isolation and characterization of linear plasmids from lankacidin-producing Streptomyces species; Kinashi H et al.; Streptomyces rochei 7434AN4, a producer of lankacidin and lankamycin contains three large linear plasmids, pSLA2-L (200 kb), M (100 kb), and S (17 kb) . Studies on the mutants of 7434AN4 having a different plasmid profile showed a parallel relationship between the presence of pSLA2-L and the production of both lankacidin and lankamycin . When pSLA2-L was transferred by protoplast fusion to S . rochei 2-39, a non-antibiotic-producing mutant of 7434AN4 which contained no detectable plasmid, the fusants gained the capacity to produce both antibiotics . From the physical maps of pSLA2-L and pSLA2-L1, a deletion plasmid (160 kb) of pSLA2-L, the latter plasmid was determined to contain a symmetrical linear repeat composed of the right 80-kb part of pSLA2-L . Four other lankacidin-producing Streptomyces strains were also found to have distinctive large linear plasmids which hybridized with the pSLA2-L probe . These results support the involvement of pSLA2-L in the production of lankacidin and lankamycin in S . rochei 7434AN4.

J Can Dent Assoc, 1994 Dec, 60(12), 1066 - 70
Technology assessment in dentistry; Leake JL et al.; Technology, in the context of dental health care, is a term that can encompass systems such as water fluoridation, clinical procedures such as sealants, or clinical protocols such as antibiotic coverage of patients with a history of heart surgery . Similarly, the term technology assessment (TA) describes a multidisciplinary, scientific process established to guide policy on the adoption and distribution of health technologies . While this process is already well established in medicine, it is just beginning in dentistry . As such, TA is still evolving in dental care in terms of methods and process . TA is required to guide the content of curriculum and standards of practice in a rapidly changing dental environment . It should precede the adoption or deletion of both technologies and of writing practice guidelines . TA makes it possible to shed inappropriate technologies or the inappropriate application of existing technologies, which may free resources to pay for improvements in the dental care we offer.

J Appl Bacteriol, 1994 Dec, 77(6), 689 - 93
Survival of genetically-engineered and wild-type strains of the yeast Saccharomyces cerevisiae under simulated environmental conditions: a contribution on risk assessment; Fujimura H et al.; A genetically-engineered strain of Saccharomyces cerevisiae employed for the industrial production of the human coagulation Factor XIIIa (rhFXIIIa) was used for a survival study under simulated environmental conditions . The homologous strain devoid of the recombinant plasmid and the homologous strain bearing the 2 microns-based vector plasmid without the rhFXIIIa-encoding DNA insert were compared . The strains were introduced into natural soil/water suspension, into soil/medium suspension and into waste water . After intervals, samples of cell suspensions were taken and viable cell numbers were determined by plating on antibiotic-containing medium . In addition, a non-radioactive technique involving enhanced chemiluminescence was employed to detect plasmid-bearing yeast cells . The rhFXIIIa expression plasmid showed a high stability during the simulated environmental condition . No differences in survival rates, however, could be detected for the plasmid-bearing and plasmid-less strains under the three conditions tested, suggesting that the presence of plasmid does not confer selective advantages on the survival of the yeast cells . It is concluded that, even after accidental release of the engineered yeast cells into the environment, elimination rates would be comparable to those for non-recombinant yeast strains.

Br J Ophthalmol, 1994 Dec, 78(12), 888 - 91
Factors affecting the success rate of open lacrimal surgery; Walland MJ et al.; Postoperative soft tissue infection may predispose to failure of open lacrimal surgical procedures . Using a retrospective analysis of 413 cases, the failure rates for primary and repeat surgery were 12.0% and 8.9% respectively (0.25 < p < 0.5) . Postoperative soft tissue infection is associated with an increased risk of failure (p < 0.005); antibiotics decrease the rate of postoperative infection and may thus decrease the failure rate . Furthermore, antibiotic therapy decreases the rate of failure in cases after previous facial trauma . Curative antibiotic therapy for established postoperative infection is less effective than preventative therapy at improving the success rate after surgery . Previous trauma is also associated with a greater rate of failure (p < 0.02), possibly owing to the frequent canalicular problems in such patients . Silicone tubes appear to increase neither the rate of infection nor failure (p > 0.5) . Trauma, acute dacryocystitis, and silicone tubes appear to act on outcome independently of each other.

Am J Trop Med Hyg, 1994 Dec, 51(6), 791 - 6
Filariasis testing in a jird model: new drug leads from some old standbys; Kinnamon KE et al.; A total of 65 compounds, most of which were from chemical classes having members known to be active against one or more parasitic organisms, were evaluated against Brugia pahangi and Acanthocheilonema viteae for macrofilaricidal activity in male Mongolian jirds (Meriones unguiculatus) . Sixteen of the 65 compounds tested suppressed the number of parasites . Of these 16, three were suppressive for B . pahangi, 10 for A . viteae, and three for both parasites . The antibiotic nigericin and the antihistaminic isothipendyl were found to be most active.

Am J Trop Med Hyg, 1994 Dec, 51(6), 758 - 66
Paromomycin resistance in Leishmania tropica: lack of correlation with mutation in the small subunit ribosomal RNA gene; Fong D et al.; The aminoglycoside antibiotic paromomycin is a potentially useful anti-leishmanial chemotherapeutic agent . Resistance to this antibiotic was studied using Leishmania tropica . Promastigotes resistant to 210 micrograms/ml of paromomycin were selected by exposing them to gradual increments of this drug . Previous work in Escherichia coli, Tetrahymena, and yeast mitochondrial mutants has demonstrated mutations in the E . coli small subunit ribosomal RNA at the 1409:1491 basepair position, or equivalent positions in other organisms, resulting in basepair disruption . When the nucleotide sequence at both the DNA and RNA levels of the resistant L . tropica promastigotes cultured in the presence of paromomycin was compared with those of the drug-sensitive parent, there was no sequence change at the putative mutation site . Paromomycin resistance in L . tropica is apparently due to other mechanisms.

Am J Obstet Gynecol, 1994 Dec, 171(6), 1588 - 93
Antiendotoxin antibody is protective against tubal damage in an Escherichia coli rabbit salpingitis model; Pearlman MD et al.; OBJECTIVE: This study was designed to determine whether pretreatment with an endotoxin antibody reduces tubal damage and tumor necrosis factor-alpha production in an Escherichia coli rabbit salpingitis model . STUDY DESIGN: Twenty New Zealand White rabbits underwent laparotomy with direct inoculation of Escherichia coli into the fallopian tube . The animals were given either antibody and antibiotic, antibiotic alone, or no treatment . At 7 days the degree of tubal damage was measured by gross observation, light microscopy, and electron microscopy . Serum tumor necrosis factor-alpha levels were also assayed at 0, 2, 4, and 36 hours . RESULTS: Animals pretreated with antiendotoxin antibody demonstrated significantly less damage on the basis of gross observation and electron microscopy compared with both antibiotic alone and untreated animals . Tumor necrosis factor-alpha levels were also significantly reduced at 2 and 4 hours in the antibody-treated group . CONCLUSIONS: Endotoxin plays a direct role in tubal damage in this Escherichia coli salpingitis model, and damage can be blocked, in part, by pretreatment with antiendotoxin antibody . Tumor necrosis factor-alpha appears to play a significant role in mediating tubal damage resulting from endotoxin.

J Fam Pract, 1994 Dec, 39(6), 589 - 91
Suspected trimethoprim/sulfamethoxazole-induced hypoprothrombinemia; Cook DE et al.; The following report illustrates a case of trimethoprim/sulfamethoxazole-induced hypoprothrombinemia in a patient receiving ongoing warfarin therapy for atrial fibrillation and aortic valve replacement . He was treated with trimethoprim/sulfamethoxazole (TMP/SMX) for sinusitis . During this time, the patient's prothrombin time international normalized ratio (INR) increased 3.5 times higher than the baseline value . The INR values decreased when the antibiotic was discontinued . If a patient is on warfarin and TMP/SMX is added, INR values should be monitored closely.

Arch Mal Coeur Vaiss, 1994 Dec, 87(12), 1735 - 8
{Spondylodiscitis disclosing endocarditis on the endocavitary electrodes of cardiac pacemakers}; Bonal J et al.; Permanent pacemaker electrode infection is rare but can be fatal . The authors report two cases presenting with spondylodiscitis, a previously described mode of presentation of valve endocarditis but not previously reported in this context . In one case, recurrent courses of antibiotics did not prevent repeated episodes of bacteraemia . In the second, the relapse of infection occurred at different sites of the vertebral column until surgical removal of the electrodes: the usual features of this pathology were observed: frequent but not constant infection at the site of the pacemaker implantation, making the diagnosis more difficult; delayed signs of spondylodiscitis after implantation of the pacemaker; recurrence of infection when antibiotic therapy alone was prescribed and, therefore, the need for surgical ablation of all implanted material . The authors underline the diagnostic value of transoesophageal echocardiography.

J Cardiovasc Surg (Torino), 1994 Dec, 35(6 Suppl 1), 207 - 9
Transvenous implantable cardiovascular defibrillator lead system: experience in 28 patients; Matsa M et al.; Morbidity and mortality following Automatic Implantable Cardioverter Defibrillation (AICD) is mostly related to thoracotomy performed during placement of epicardial leads . From July 1991 to January 1994, a transvenous lead system (TLS) (Endotak C; CPI) was implanted in 28 patients (24 males, 4 females, age 15-76 years) who suffered from life threatening ventricular tachyarrhythmias . Twenty four patients had a previous MI, mean LVEF was 26% (14-65%), two had mitral valve prolapse (one with prolonged QT), one had hypertrophic and another had dilated cardiomyopathy . The implantation procedure was performed in the operating room (n = 26) or in the Cath lab . (n = 2) . Nineteen (out of the 28) patients were treated with Amiodarome before implantation (5 out of 7 had LVEF < 30%) . A satisfactory defibrillation threshold (DFT) was achieved using Endotak lead alone in 22 (79%) patients . These patients had LVEF between 10% to 65% (less than 30% in three patients) . In six patients the DFT was measured as lower than 20 J, and a subcutaneous patch was added (LVEF 12-38%, 4 patients with Amiodarome therapy) . The implanted devices were all from CPI: 1600 (n = 5), PRX (n = 7), P2 (n = 15), PRX II (n = 1) . During a 1-32 months of follow-up one patient died from severe CHF . The implanted device operated in 9/28 patients . The only complication related to implantation was infection at the pocket site (n = 2), which responded to antibiotic therapy in one patient, but required device explantation in another patient . The device was reimplanted in that patient three month later, with no further complications.(ABSTRACT TRUNCATED AT 250 WORDS)

J Anim Sci, 1994 Dec, 72(12), 3169 - 76
Effect of dietary chlortetracycline during breeding and(or) farrowing and lactation on reproductive performance of sows: a cooperative study . S-145 Committee on Nutritional Systems for Swine to Increase Reproductive Efficiency; Maxwell CV et al.; A cooperative regional study involving 850 litters was conducted at five experiment stations (Arizona, Florida, Oklahoma, Texas, and Virginia) to assess the effects of feeding 220 mg/kg of chlortetracycline (CTC) from 1 wk before to the initiation of the breeding season to 15 d after the breeding season and(or) from 110 d of gestation through lactation on reproductive performance of sows (2 x 2 factorial) . Sows were fed 1.82 kg/d (2.27 kg during December, January, and February) during the breeding period and before farrowing . Feed was consumed on an ad libitum basis during lactation . Feeding CTC during the breeding season increased litter size at birth (10.8 vs 10.3; P < .05) and decreased feed consumption (5.4 vs 5.5 kg/d; P < .05) in the subsequent lactation period . Feeding CTC during lactation reduced lactation weight loss in sows (4.3 vs 6.1 kg; P < .07) . Feeding the antibiotic at breeding had no effect on conception rate; however, feeding the antibiotic during lactation improved subsequent conception rate at the first service (80 vs 73%; P < .10) and overall conception rate (89 vs 84%; P < .05) . This indicates that some carryover effect of feeding CTC during lactation occurred during the subsequent breeding period . Station x treatment interactions were observed for survival rate to 21 d (P < .05) and to weaning (P < .06) . Overall, survival rates were not greatly affected by antibiotic feeding . No treatment interaction was observed for any trait measured, indicating that the effects of CTC during the breeding and lactation periods were independent.(ABSTRACT TRUNCATED AT 250 WORDS)

Eur J Gastroenterol Hepatol, 1994 Dec, 6 Suppl 1, S113 - 9
Eradication of Helicobacter pylori; O'Connor HJ; PURPOSE: To critically review current indications and therapies for Helicobacter pylori eradication . DATA IDENTIFICATION: Studies selected for this review were identified from Medline and a manual search of the literature . RESULTS OF DATA ANALYSIS: The clearest indication for H . pylori eradication is in the treatment of H . pylori-positive duodenal and gastric ulcer since eradication of the infection prevents ulcer relapse, effectively curing the disease . The use of anti-H . pylori therapy in non-ulcer dyspepsia remains controversial and further studies are required . Despite strong circumstantial evidence linking H . pylori and gastric cancer, it is premature to advocate H . pylori therapy for primary prevention of neoplasia . Triple therapy (bismuth, metronidazole, tetracycline) can eradicate H . pylori in over 90% of cases but this multidrug regimen is not ideal because of side effects, possible non-compliance and doubtful efficacy against metronidazole-resistant infection . Proton-pump inhibitor-antibiotic combinations are a promising alternative to triple therapy with few side effects and good compliance, but there is uncertainty about the most effective combination . H . pylori reinfection after successful eradication is unusual (< 1% per year) . CONCLUSIONS: H . pylori eradication is now the treatment of choice in H . pylori-positive peptic ulcer disease . The search continues for the ideal H . pylori treatment regimen which will combine high efficacy, safety and patient acceptability, with low cost.

Antibiot Khimioter, 1994 Dec, 39(12), 23 - 6
{Preclinical pharmacokinetics of pefloxacin}; Manuilov KK et al.; The substance and tablets of pefloxacin mesilate manufactured by the Urals Polytechnical University and the National Research Centre of Antibiotics were studied on rats and dogs with the drug oral administration in single and multiple doses equivalent to the human ones . The bioavailability of the drug was good and its blood levels were efficient for a prolonged period (at least 24 hours) after a single oral administration . No cumulation of the antibiotic after its repeated use was observed . The pefloxacin mesilate tablets proved to be fully equivalent to the drug manufactured by Rhone-Poulenc-Rorer (France).

J Biomol Struct Dyn, 1994 Dec, 12(3), 625 - 36
Fluorescence polarization studies of the binding of BMS 181176 to DNA; Krishnan BS et al.; The DNA binding of BMS 181176, an antitumor antibiotic derivative of rebeccamycin was characterized by DNA unwinding assays, as well as by fluorescence emission and polarization spectroscopic techniques . Unwinding and rewinding of supercoiled DNA was interpreted in terms of intercalation of BMS 181176 into DNA . BMS 181176 shows an enhanced fluorescence emission upon binding to the AT sequence and no enhancement upon binding to the GC sequence . BMS 181176 appears to be a weaker binder to poly(dAdT).poly(dAdT) compared to doxorubicin and ethidium bromide . When bound to DNA, the rotational motion of BMS 181176 is substantially decreased as evident from the increase in fluorescence polarization . BMS 181176 exhibits a range of binding strengths depending on the DNA . This is demonstrated by the Acridine Orange displacement assay using fluorescence polarization.

Hepatogastroenterology, 1994 Dec, 41(6), 554 - 8
Enteral and parenteral anti-endotoxin treatment in experimental colitis; Gardiner KR et al.; Systemic endotoxemia has been described in ulcerative colitis and Crohn's disease and shown to correlate positively with disease activity and the extent of intestinal ulceration . This study evaluated the efficacy of antibiotic and anti-endotoxic treatment in reducing systemic endotoxemia in a hapten-induced rat model of colitis . Enteral administration of paromomycin was associated with a significant reduction in systemic endotoxin concentrations (7.4 +/- 1.2 pg/ml) when compared with controls (39.8 +/- 12.6 pg/ml; p = 0.032) . Intravenous injection of taurolidine was also found to significantly reduce systemic endotoxemia (3.1 +/- 1.3 pg/ml) in comparison with controls receiving saline injection (17.5 +/- 4.2 pg/ml; p = 0.008) . Enteral neomycin, parenteral polymyxin or metronidazole and cefuroxime were ineffective anti-endotoxin treatments in this model . Enteral paromomycin or parenteral tauro-lidine therapy are potential methods of preventing and treating systemic endotoxemia in patients with inflammatory bowel disease.

Gen Pharmacol, 1994 Dec, 25(8), 1719 - 22
Effects of gentamicin on rat submandibulary gland functions; Dehpour AR et al.; 1 . Submandibular saliva was collected from anesthetized gentamicin-treated and control rats using carbachol, isoproterenol and pilocarpine as secretagogue . 2 . Intraperitoneal injection of a large single dose (80 mg/kg) of gentamicin caused marked changes in saliva flow rate, protein and electrolyte concentrations in the presence of parasympathetic or sympathetic agents used as stimulants . 3 . The secretion of N-acetyl-beta-D-glucosaminidase in saliva was determined and there was a marked increase in the enzyme activity of saliva of gentamicin-treated rats in comparison to that of controls . 4 . The results of this study suggest that gentamicin as an aminoglycoside antibiotic at the dose employed, can influence the secretory mechanisms of rat submandibular glands.

Clin Ter, 1994 Dec, 145(12), 481 - 92
{Pertussis}; Melino C et al.; A synthesis concerning whooping cough is presented with the object of taking stock of the situation regarding the pediatric disease which, in spite of developments in antibiotic therapy and vaccine prophylaxis is still a cause for series concern in view of its all but rare complications, especially in infants of less than one year, and of the uncertainties surrounding the validity of specific vaccines . An up-date on this is certainly not superfluous, especially now when we are at a true turning point in prophylaxis with the use of acellular vaccines obtained by genetic enegenering . This is particularly interesting for the practitioner who is in direct contact with the actual situation.

Mol Microbiol, 1994 Dec, 14(5), 975 - 88
The site-specific recombination system regulating expression of the type 1 fimbrial subunit gene of Escherichia coli is sensitive to changes in DNA supercoiling; Dove SL et al.; We have studied the effect of altering the in vivo level of DNA supercoiling on the phase-variable expression of the Escherichia coli fimA gene . Transcription from the fimA promoter was unaffected by changes in DNA supercoiling whether caused by the introduction of a topA::Tn10 mutation or by inhibition of DNA gyrase with the antibiotic novobiocin . However, inversion of the fimA promoter fragment was altered in response to perturbation of DNA supercoiling . Specifically, inactivation of topA reduced the rate of promoter fragment inversion in both the ON-to-OFF and the OFF-to-ON directions . This effect correlated with the loss of functional topA and not with the global level of DNA supercoiling . Inhibition of DNA gyrase introduced a bias in favour of the OFF-to-ON inversion; the ON-to-OFF inversion was affected only slightly . Changes in expression of fimB, the gene coding for the recombinase that catalyses fimA promoter fragment inversion in the strains used in this study, did not correlate with effects on fimA phase variation: we found that transcription of fimB was inhibited by loss of functional topA and was enhanced by inhibition of DNA gyrase in a manner that correlated well with the global level of in vivo DNA supercoiling . A model is presented to account for the effects of lost topoisomerase function on fimA gene expression.

Bone Marrow Transplant, 1994 Dec, 14(6), 989 - 90
Neutropenic fever in patients after high-dose chemotherapy followed by autologous haematopoietic progenitor cell transplantation and human recombinant granulocyte-macrophage colony stimulating factor; Gluck S et al.; Neutropenic fever has been one of the most difficult complications in the recovery period following high-dose chemotherapy and autologous haematopoietic progenitor cell transplantation . The differentiation between human recombinant GM-CSF (sargramostim)-related fever and active infection can be difficult during this observation time . In 7 of 17 patients treated for metastatic breast cancer with HDCT and PBPC within 6 consecutive months, neutropenic fever without signs of infection was observed, which may be sargramostim-related fever . The typical presentation must fulfil the following criteria: cyclical elevation in body temperature that happens at the predicted time after sargramostim administration; absence of other signs or symptoms of infections; quick resolution of the fever after onset acetaminophen administration . Having met these criteria, none of these patients has been treated with intravenous antibiotics for active infections . At the time of haematological recovery (at a median time of 13 days from PBPC reinfusion to absolute neutrophil counts of > or = 0.5/nl) the febrile episode gradually resolved . No serious complications or other side-effects were observed . No toxic deaths occurred . Only if specific symptoms or signs of infection develop, would intravenous empiric antibiotic therapy be started.

Bone Marrow Transplant, 1994 Dec, 14(6), 903 - 6
Fatal pneumococcal infections following allogeneic bone marrow transplant; Rege K et al.; Six cases of fatal pneumococcal sepsis are described, occurring in the post-allograft setting, between 3 and 39 months after transplantation . Five of the six patients were suffering from chronic graft-versus-host disease and were receiving immunosuppressive therapy . Most were receiving prophylactic antibiotic therapy . This represents approximately 2% of the allograft population treated during the study period who survived for > 3 months after transplant . Pneumococcal sepsis is thus still a significant cause of death after allogeneic BMT and approaches to minimise its occurrence are discussed.

Tokai J Exp Clin Med, 1994 Dec, 19(3-6), 109 - 13
Nephrotic syndrome associated with subacute bacterial endocarditis (SBE): a case report; Yamauchi F et al.; We experienced a female nephrotic patient associated with subacute bacterial endocarditis . Her proteinuria was completely normalized after antibiotic therapy and valve replacement . Immunofluorescence and an electron microscopic study of a renal biopsy specimen showed little evidence of immune complex in the glomeruli . Marked deposition of properdin in the glomeruli and the reduced level of serum complement may indicate involvement of the complement system in the pathogenic mechanism of massive proteinuria in this case.

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