J Dairy Sci, 1995 Nov, 78(11), 2584 - 9 Commercial utilization of minor milk components in the health and food industries; Horton BS; Whey has gained a great deal of respectability in the US during the past 5 to 10 yr as an ingredient in many food and dairy products . However, its value as a resource for many medically active components is not recognized in this country as it is in Japan and Europe . This paper reviews the minor components in whey and the potential for commercial application . Individual whey components of significance include alpha-lactalbumin, beta-lactoglobulin, bovine serum albumin, immunoglobulins, lactoferrin, and lactoperoxidase . Whey is also a good resource for lactose and lactose derivatives such as lactulose, lactitol, and oligosaccharides . Other minor milk components of biological significance include milk salts and components related to casein . Many of these components exhibit biological activity that is valuable in nutraceuticals or antimicrobials . Commercial utilization in the US is compared with that of other countries. Therapie, 1995 Nov-Dec, 50(6), 575 - 86 {Pharmacokinetics of antibiotics in burn patients}; Lesne-Hulin A et al.; The pathophysiology associated with major burns is complex and subject to a state of flux (coexistence of pain, infectious diseases, multiple trauma, disturbances of metabolism and acid-base status, etc) which could affect the disposition and the pharmacokinetic behaviour of drugs . In current clinical practice, practitioners often use powerful antimicrobial agents; however, few pharmacokinetic studies are available in burns patients (of the order of 30 studies) . Furthermore, the methods used are sometimes questionable . After dealing with the ethical and physiological context in which such research is undertaken, the authors report a review of the pharmacokinetic studies done during the last 15 years . Concerning both aminoglycosides and glycopeptides, no therapeutic recommendations are available (therapeutic schedules) . However, in this case, therapeutic monitoring is available and represents a suitable tool to better master their use . In the case of beta-lactam antibiotics and quinolones, more data are available . Some investigations have shown the possibility of translesional diffusion of certain agents in burns (such as gentamicin, piperacillin/tazobactam combination, or fosfomycin) . This phenomenon could be a co-factor of success in treatment . Considering the relatively meager pharmacokinetic and pharmacodynamic data available in burns, it is important in the future to refine our knowledge of the distribution and metabolism of drugs in burns patients in order to better master their use . Finally, ethical and methodological considerations need to be taken in account. Rev Assoc Med Bras, 1995 Nov-Dec, 41(6), 379 - 85 {Analysis of the program of control of the use of antimicrobials at the Hospital São Paulo--Escola Paulista de Medicina}; Pereira CA et al.; BACKGROUND AND OBJECTIVE: Antimicrobial agents represent a group of drugs that are frequently used in hospitals . Approximately, 50% of hospitalized patients receive at least one antimicrobial drug during the hospitalization period . However, half of these drugs are prescribed incorrectly . The objective of this paper was to analyse the antimicrobial control program that has been used at Escola Paulista de Medicina since 1989 . CASUISTIC & METHODS: The prescription of eleven controlled antibiotics should be done in a special form . Any requisition of a controlled antibiotic was evaluated, within 24 hours, by an infection diseases specialist who was hired exclusively for this function . RESULTS: During 1989, 5,573 controlled antimicrobials were requested by the hospital staff, and 17.6% of them were considered inadequate and were refused . Such a percentage was high considering that our institution is a university hospital where the antibiotic usage should be more precise and adequate . We also should take into account that the indication of only 11 antimicrobial drugs were evaluated . CONCLUSION: The results allow us to conclude that each hospital should have not only a policy on antimicrobial usage but also an effective program of control of these drugs. Rinsho Shinkeigaku, 1995 Nov, 35(11), 1235 - 40 {Meningeal seeding of spinal cord glioblastoma multiforme without any signs of myelopathy}; Chida K et al.; An autopsy case of meningeal spreading of glioblastoma multiforme (GBM) probably originating in the cervical cord was reported . In contrast to autopsy findings, main symptoms were similar to subacute meningitis, and any signs of myelopathy could not be detected during the clinical course . The patient was a 22-year-old man who was hospitalized because of a 2-week history of progressive headache following cough and slight fever . Vomiting and somnolence, developing 5 days before admission, were improved the day after a lumbar puncture performed at another hospital . On admission, meningeal signs, mild right abducens palsy, and depressed deep tendon reflexes were detected . There was no muscle weakness, sensory loss, or Babinski sign . Lumbar puncture yielded CSF with an opening pressure of 280 mmH2O, 21 mononuclear cells/mm3, a protein level of 645 mg/dl, and a glucose level of 7 mg/dl . Cytology for malignancy and multiple cultures were negative . Brain CT scan showed mild hydrocephalus and swelling of the brainstem and cerebellum . Intravenous administration of antimicrobial drugs was started and ventriculoperitoneal shunt surgery was performed . During the third hospital week, however, meningeal signs progressed and somnolence reappeared, followed by progressive multiple cranial neuropathy and polyradiculopathy characterized by flaccid tetraparesis, muscle atrophy, and sensory impairment without a level . Babinski sign could not be detected . MRI revealed an intramedullary lesion in the lower cervical cord, swelling of the brainstem, cerebellum, spinal cord and nerve roots, and a diffuse or nodular thickning of leptomeninges . Repeated CSF cytology disclosed atypical cells . Examinations for extraneural malignancies were negative . During the 9th hospital week, flaccid tetraplegia progressed and stupor developed, and the patient died 2 weeks later . The pathological study was limited to the brain . The brain showed a diffuse opalescent thickening of the leptomeninges, especially over the ventral aspect of the brainstem and cerebellum, where the blood vesseles and cranial nerves were obscured . Histological examination revealed the appearance of GBM . The malignant cells filled the subarachnoid space, and to a variable extent penetrated the brainstem and cerebellum along perivascular spaces . Hypertrophied optic tracts and trigeminal nerves were also infiltrated by the cells . However, there were no mass lesions assumed to be primary ones anywhere in the cerebral parenchyma . Therefore, it was thought that GBM primarily growing in cervical cord metastasized to intracranial subarachnoid space by way of the cerebrospinal fluid pathway . Spinal cord GBM usually presents signs of myelopathy from the early stage . The present case was characterized by no signs of myelopathy during the clinical course . It is speculated that the intramedullary GBM, originating near the surface of cervical cord, had been rapidly disseminated into the subarachnoid space up to the intracranial cavity before myelopathy appeared, and caused cranial and spinal nerve roots dysfunction, which covered signs of myelopathy . Cord GBM should be always considered as a differential diagnesis in a case of subacute meningitis. J Intraven Nurs, 1995 Nov-Dec, 18(6 Suppl), S17 - 21 Intravenous modalities in the treatment of bloodborne pathogen illnesses: antibiotics, antifungals, and antivirals; Corbett S; A variety of intravenous antimicrobial agents are used to treat infections with bloodborne pathogens . In using these agents to manage our patients, as well as any accidental employee exposure, it is important to understand how these agents work, and in which settings they are appropriate . This article will briefly review the historic development of antimicrobial agents and examine the agents according to the five basic mechanisms of action . Resistance to antimicrobial agents also will be discussed, as will the clinical and other factors that can positively or negatively affect the outcome of therapy. J Intraven Nurs, 1995 Nov-Dec, 18(6), 297 - 300 Emerging problems in antimicrobial resistance; Tenover FC; The ability of many different species of bacteria to resist the inhibitory action of antimicrobial agents has become a global problem . As the magnitude of the problem continues to increase, it is imperative that healthcare professionals, particularly nurses who administer antimicrobial agents on a daily basis, become familiar with the causes of antibiotic resistance and the ways in which the emergence of resistance can be prevented or minimized . It also is important that the proper use of antimicrobial agents and the problems associated with misuse be conveyed to patients receiving intravenous therapy, particularly those receiving therapy outside of traditional healthcare settings . This article will highlight some of the factors leading to the development of resistance in bacteria and the problems facing the medical community and the public regarding the spread of resistant bacteria in hospital and community settings. Kekkaku, 1995 Nov, 70(11), 615 - 9 {In vitro antimicrobial activity of a new quinolone, levofloxacin, against atypical mycobacteria}; Oya S et al.; We measured th in vitro antimicrobial activity of a new quinolone, levofloxacin (LVFX) against seven clinically isolated species of atypical mycobacteria, including 30 strains of M . avium complex . 8 of M . fortuitum, 4 of M . scrofulaceum, 2 of M . kansasii, 2 of M . gordonae, and 1 of M . chelonae (subsp chelonae) . LVFX showed a potent antimicrobial activity against M . kansasii, M . gordonae and M . chelonae (subsp chelonae) . In addition, it was suggested that LVFX may be effective for the treatment of infections caused by M . avium complex, since satisfactory antimicrobial activity was displayed against some strains of M . avium complex . Considering the fact that LVFX shows good concentration levers in sputum, this drug could be used in the chemotherapy against the infection with M . avium complex. Immunopharmacology, 1995 Nov, 31(1), 31 - 41 Effect of bismuth salts on systemic and mucosal immune responses to orally administered cholera toxin; Horowitz NS et al.; While the antimicrobial and antisecretory effects of bismuth salts are well documented, little is known regarding their effects on immune responses to enterotoxins such as that of V . cholerae or to orally administered vaccine antigens . To evaluate the effects of Pepto Bismol (PB) on the induction of systemic and mucosal immune responses to cholera toxin (CT), C57BL/6 mice were orally administered 10 micrograms CT and PB, or mice were pretreated with PB 30 min prior to CT administration . When co-administered with CT, PB attenuated serum IgG1, IgG2a, IgG2b and IgG3 anti-CT responses in a dose-dependent manner and also reduced levels of circulating anti-CT IgA and total serum IgE . Similarly, anti-CT intestinal IgA responses were also decreased . However, when administered 30 min prior to CT, PB had little to no effect on serum or intestinal anti-CT immunoglobulin responses . Administration of bismuth subsalicylate (BSS), the active component of PB, or sodium salicylate did not reduce immune responses to CT, suggesting that the combination of BSS plus other constituents contained within PB contributed to the decreased immune response to CT . Moreover, bismuth subgallate alone inhibited antibody responses to CT . Our data are consistent with the hypothesis that, when administered orally with CT, PB and bismuth subgallate create a physical barrier to antigen uptake. Infection, 1995 Nov-Dec, 23(6), 349 - 55 A randomized study of imipenem compared to cefotaxime plus piperacillin as initial therapy of infections in granulocytopenic patients; Bohme A et al.; The objective of the presented, randomized study was to compare the efficacy of antimicrobial monotherapy with imipenem (3 x 0.5g/d) to a combination therapy with cefotaxime (3 x 2g/d) plus piperacillin (3 x 4g/d) for empirical treatment of infections in neutropenic patients . In 165 patients, 237 infectious episodes were evaluable . The overall response rate of patients treated with cefotaxime plus piperacillin was 67/115 (58%), of those treated with imipenem 66/122 (54%) . In patients not responding to the initial therapy regimen within 2 or 3 days, the antimicrobial therapy was modified . After therapy modification 85/100 patients were cured . Fever of unknown origin (FUO) showed the most favourable course compared to other infection types, with a response in 46/59 (78%) and in 35/50 (70%) cases, respectively . In comparison, pneumonias were successfully treated in only 3/21 (14%) and 7/37 (19%) cases . Even including patients with modified therapy, only 66% (21/32) of pneumonia episodes responded . The unfavourable results in pneumonias is mainly due to the high rate of 13 systemic mycoses in this group (22%) . Overall, a similar response was observed in patients treated with cefotaxime plus piperacillin in comparison with imipenem . In primary bacteremias however, an advantage was observed in patients treated with imipenem (20/27; 74%) compared with cefotaxime plus piperacillin (11/23; 48%). Todays OR Nurse, 1995 Nov-Dec, 17(6), 5 - 12 Management of infected hip arthroplasty; Morscher E et al.; 1 . Infected hip arthroplasties can be successfully managed with the appropriate surgical treatment and a long-term antimicrobial therapy . 2 . The type of surgical treatment must be based on considerations of various prognostic indications such as the infective agent, the duration of the infection, the stability of the implant component, and the quality of the bone stock and the soft tissue . 3 . The majority of infections in artificial hip joints occur by direct inoculation during surgery or by contamination of a local hematoma that arose after surgery. J Antimicrob Chemother, 1995 Nov, 36(5), 773 - 80 Antimicrobial prescribing in patients on haemofiltration; Cotterill S; Continuous haemo(dia)filtration techniques as a means of extracorporeal renal replacement therapy are being used more and more, especially on intensive care units . The effect of intermittent haemodialysis on the pharmacokinetics of systemic antibiotics is well documented and advice is provided in the drug data sheets regarding dosage, timing and additional doses (post haemodialysis) . Continuous haemofiltration significantly alters the handling of these same antibiotics compared with haemodialysis, such that if the advice given for 'haemodialysis' is used for patients on haemofiltration, under-dosing the patient may lead to sub-therapeutic antibiotic levels . The reasons for these differences are discussed and suggested dosage modifications are given for commonly used antimicrobials based on available published data. Clin Rheumatol, 1995 Nov, 14(6), 695 - 700 Sacroiliitis in sarcoidosis: case reports and review of the literature; Kotter I et al.; We report the occurrence of bilateral sacroiliitis in 2 cases of biopsy-proven sarcoidosis . Tuberculosis was excluded by tuberculin testing and bronchoalveolar lavage in both cases . In the literature, 5 cases of sacroiliitis and sarcoidosis have thus far been described, but in all tuberculosis was not excluded (tuberculin testing was not performed or revealed a positive test result) . In 1 of these cases tuberculosis was even simultaneously suspected to be present . In all previous cases, antituberculous or other antimicrobial agents were given . Previously reported cases of sacroiliitis in sarcoidosis are briefly reviewed, and possible relations between seronegative spondylarthropathies, slow bacterial infections, sarcoidosis and other granulomatous diseases are discussed. Infect Control Hosp Epidemiol, 1995 Nov, 16(11), 638 - 41 The need for surveillance for antimicrobial resistance; Lorian V; Currently, collection of bacterial susceptibility data is very incomplete; national or international susceptibility data simply do not exist . The large volume of scientific publications on this subject contributes to the perception that bacterial resistance to antimicrobials is extensive and growing . However, only a very few papers address the epidemiology of bacterial resistance . Those papers that do report quantitatively on this topic are from hospitals that are systematically different from hospitals that do not publish . No one can deny the existence and the importance of drug resistance, but the sensational reports from the media are grossly untrue . Multidrug-resistant bacteria affect an extremely small proportion of patients . Most antibiotics still are highly effective and cure the majority of infections . It is proposed that medical microbiology laboratories report their susceptibility data on eight common species that constitute 68.5% of all isolates . Such reports could be analyzed and published yearly. Andrologia, 1995 Nov-Dec, 27(6), 335 - 9 Immunohistochemical study of secretory IgA in the human male reproductive tract; Sirigu P et al.; Male human genital tract was treated for the immunohistochemical demonstration of secretory IgA in order to verify its own possible antimicrobial properties . An intensely positive immunoreaction for sIgA in the epithelial cells of prostate and urethral glands was observed; in the same organs the presence of immunoreactive cell clusters in the subepithelial layers was noted . Immunostaining in the epithelia of deferent duct, seminal vesicle, deferential ampulla, ejaculatory duct and bulbourethral glands was absent . The findings suggest that a local immune response sIgA-mediated is present in the lower male genital tract. J Nat Prod, 1995 Nov, 58(11), 1776 - 80 Cacospongionolide B, a new sesterterpene from the sponge Fasciospongia cavernosa; De Rosa S et al.; Cacospongionolide B {2a}, a new cacospongionolide-related sesterterpene, has been isolated from the Adriatic sponge Fasciospongia cavernosa . The structure was elucidated by spectral and chemical means . The antimicrobial activity and brine shrimp and fish lethalities of 2a are reported. Farmaco, 1995 Nov, 50(11), 779 - 82 Synthesis and antimicrobial properties of N-substituted halides of (E)-azastilbenols; Prukala W et al.; The synthesis of 15 new N-benzyl substituted derivatives of (E)-gamma-azastilbenols-2'(3' and 4') and their antimicrobial activity are reported . In particular, compounds 1a-c, 1h and 2a-b showed good antibacterial activity against Staphlococcus aureus. Baillieres Clin Rheumatol, 1995 Nov, 9(4), 759 - 69 Antimicrobial therapy for rheumatoid arthritis; Kloppenburg M et al.; New interest in the use of antibiotics in the treatment of arthritis was stimulated by two factors: (1) observations that, in some forms of chronic arthritis, microbial antigens persist in the synovial membrane, and (2) the increasing knowledge of the anti-inflammatory and immunosuppressive effects of antibiotics . Recently, several published controlled studies reported a beneficial effect of tetracyclines on RA and reactive arthritis . Whether the anti-arthritic activity of the tetracyclines investigated is mediated by the antimicrobial, anti-inflammatory or immunomodulatory properties remains to be determined . It may be concluded from these studies that tetracyclines have a beneficial effect on RA, especially when laboratory parameters are considered . The effect on the clinical parameters is not unequivocal . The adverse effects seem to be mild but the long-term efficacy and safety of tetracyclines as disease-modifying antirheumatic drugs remain to be demonstrated. J Hosp Infect, 1995 Nov, 31(3), 169 - 76 Do 'chlorine covers' exert a sustained bactericidal effect on the bacterial hand flora? Koller W, Rotter ML, Gottardi W. Treatment of skin with chlorine generates 'chlorine covers' which, in a previous study, exerted significant sustained bactericidal effects against transient skin flora on the upper arm and forearm . In this investigation, this effect was studied on both the transient and resident flora of the hands using test models for the evaluation of hand disinfectants as agreed upon in Austria and Germany . Chlorine covers were generated by bathing hands in a solution of 2% sodium tosylchloramide for 1 min . Subsequently, this cover was destroyed on one, randomly selected, hand by bathing it in a solution of 0.5% sodium thiosulphate for 15 s . The amount of chlorine on the fingertips of chlorinated hands was 2.2 +/- 0.4 micrograms/cm2; that on subsequently dechlorinated hands was 0.2 +/- 0.1 microgram/cm2 . In experiments with artificially contaminated hands (Escherichia coli), the kinetics of bacterial die-off were the same on both hands . Also, in experiments with resident flora, the kinetics of bacterial die-off did not suggest bacterial reductions that increase with the duration of contact with the chlorine cover . It was concluded that with the test models used, a significant sustained antimicrobial effect of the chlorine cover could not be demonstrated on hands. Pediatr Infect Dis J, 1995 Nov, 14(11), 959 - 65 A randomized trial of chloramphenicol vs . trimethoprim-sulfamethoxazole for the treatment of malnourished children with community-acquired pneumonia; Mulholland EK et al.; Children in developing countries who present with malnutrition often have infections, particularly pneumonia, at the time of presentation . We evaluated the initial antibiotic management of 144 Gambian children who presented for the first time with malnutrition and who had clinical or radiologic evidence of pneumonia . They were enrolled in a double blind trial of trimethoprim-sulfamethoxazole vs . chloramphenicol . Most children in the study underwent detailed investigations of bacterial and viral etiology as part of another study . The study drug was administered for a week along with oral metronidazole, vitamins and standardized nutritional therapy . Treatment failure was defined as the need for change to parenteral antibiotics during treatment, failure to respond to a week of treatment with the study drug or relapse during the following 2 weeks . There were no differences between the treatment groups in the clinical indicators of severity, etiology or radiologic findings . Thirty-three children were excluded from the analysis because of tuberculosis, inappropriate enrollment or inadequate follow-up . Of the 111 children remaining, 32 (16 in each arm of the study) failed treatment . Clinical failure was not related to in vitro antimicrobial resistance in the 20 cases in which invasive bacterial isolates were obtained . Those who failed treatment were more likely to have had lower chest wall indrawing and positive bacterial cultures than those who were successfully treated . In an area with infrequent antimicrobial resistance of common respiratory pathogens, oral chloramphenicol and trimethoprim-sulfamethoxazole were equally effective in the initial management of malnourished children with community-acquired pneumonia. J Neurol Sci, 1995 Nov, 133(1-2), 112 - 8 Quinolinic acid in tumors, hemorrhage and bacterial infections of the central nervous system in children; Heyes MP et al.; A potential mechanism that may contribute to neurological deficits following central nervous system infection in children was investigated . Quinolinic acid (QUIN) is a neurotoxic metabolite of the kynurenine pathway that accumulates within the central nervous system following immune activation . The present study determined whether the levels of QUIN are increased in the cerebrospinal fluid of children with infections of the CNS, hydrocephalus, tumors or hemorrhage . Extremely high QUIN concentrations were found in patients with bacterial infections or the CNS, despite treatment with antimicrobial agents . CSF QUIN levels were also elevated to a lesser degree in patients with hydrocephalus or tumors . CSF L-kynurenine levels increased in parallel to the accumulations in QUIN, which is consistent with increased activity of the first enzyme of the kynurenine pathway, indoleamine-2,3-dioxygenase . The CSF levels of neopterin, a marker of immune and macrophage activation, were also increase in patients with infections . The cytokines tumor necrosis factor-alpha and interleukin-6 were also detected in some patients' samples, and were highest in patients with infection . These results suggest that QUIN is a sensitive marker of the presence of immune activation within the CNS . Further studies of QUIN as a potential contributor to neurologic dysfunction and neurodegeneration in children with CNS inflammation are warranted. Biophys J, 1995 Nov, 69(5), 1964 - 71 Leakage of membrane vesicle contents: determination of mechanism using fluorescence requenching; Ladokhin AS et al.; Agents such as antimicrobial peptides and toxins can permeabilize membrane vesicles to cause leakage of entrapped contents in either a graded or an all-or-none fashion . Determination of which mode of leakage is induced is an important step in understanding the molecular mechanism of membrane permeabilization . Wimley et al . (1994, Protein Sci . 3:1362-1378) have developed a fluorescence method for distinguishing the two modes that makes use of the dye/quencher pair 8-aminonapthalene-1,3,6 trisulfonic acid (ANTS)/p-xylene-bis-pyridinium bromide (DPX) without the usual need for the physical separation of vesicles from released contents . Their "requenching" method establishes the mode of release through the fluorescence changes that occur when DPX is added externally to a solution of vesicles that have released some fraction of their contents . However, the requenching method as originally stated ignored the possibility of preferential release of dye or quencher . Here we extend the theory of the method to take into account preferential release and the effects of graded leakage . The ratio of the rates of release of the cationic quencher DPX and anionic dye 8-aminonapthalene-1,3,6 trisulfonic acid can be estimated by means of the theory . For graded leakage, we show that the release of the markers does not coincide with the fluorescence changes observed in the standard leakage assay . This is true for self-quenching dyes as well and means that 1) the amount of released material will be overestimated and 2) the kinetics will be nonexponential and have artificially high apparent rates.(ABSTRACT TRUNCATED AT 250 WORDS) J Clin Microbiol, 1995 Nov, 33(11), 2940 - 7 Genotypic and phenotypic characterization of Helicobacter cinaedi and Helicobacter fennelliae strains isolated from humans and animals; Kiehlbauch JA et al.; By DNA-DNA hybridization, we classified 26 human strains, 4 dog and cat strains, and 4 hamster strains putatively identified as Helicobacter cinaedi as well as 2 human strains and 2 animal strains of Helicobacter fennelliae . All but one human strain belonged to the same hybridization group as the type strain of H . cinaedi . The animal strains also appeared to belong to this hybridization group . Both human strains of H . fennelliae were shown to be H . fennelliae by DNA-DNA hybridization, but both animal strains were less than 15% related to the type strain . All strains were also characterized by plasmid profiles and ribotyping . Plasmids were found in 23% of the human strains, 100% of the hamster strains, and 33% of the dog and cat strains . Human strains were essentially identical by ribotyping, but were clearly differentiated from the hamster and dog and cat strains . Some strains may be difficult to culture on primary isolation; we found that our strains grew well on anaerobic CDC agar, brucella agar, and tryptic soy agar II . Our H . cinaedi and H . fennelliae strains differed from those previously described because some were resistant to cephalothin: some H . cinaedi strains were also resistant to nalidixic acid . All isolates were also characterized by antimicrobial susceptibility testing . We found that human strains of H . cinaedi were more resistant to clindamycin and erythromycin than were animal isolates; 19% of the human strains were resistant to ciprofloxacin . Therefore, we recommend that antimicrobial susceptibility results be obtained before initiating therapy for H . cinaedi and H . fennelliae infections. Am J Otol, 1995 Nov, 16(6), 722 - 4 Safety of silver oxide-impregnated silastic tympanostomy tubes; Chole RA et al.; Otorrhea occurs after the insertion of tympanostomy tubes in as many as 50% of ears . Although topical antibiotic solutions minimize otorrhea in the immediate postoperative period, recurrent otorrhea is sometimes a clinical problem . The antimicrobial effects of silver oxide when impregnated into a tympanostomy tube may decrease the incidence of recurrent otorrhea . This study demonstrates that silver oxide-impregnated silicone elastomer is well tolerated within the middle ear of gerbils when implanted for 1 year, and the tissue reaction is no more than silicon elastomer without silver oxide . When applied directly to the round window of guinea pigs, there was no evidence of ototoxicity of silver oxide as measured by electrocochleography (N-1 thresholds) and cytocochleography (hair cell counts) . These animal studies indicate that silver oxide-impregnated silicone elastomeric tympanostomy tubes may be used safely in clinical trials to determine efficacy. Respir Med, 1995 Nov, 89(10), 677 - 84 Additive effect of continuous low-dose ofloxacin on erythromycin therapy for sinobronchial syndrome; Ishiura Y et al.; It has been established that long-term low-dose erythromycin therapy (EM therapy) is very effective for sinobronchial syndrome, a common condition in Japan characterized by chronic upper and lower airway inflammation . The effect does not result from its bacteriocidal activity and the detailed mechanisms are not known . It takes 3-6 months for EM therapy to improve the symptoms . This study was designed to evaluate the additive effect of continuous low dosage or intermittent usual dosage of ofloxacin (OFLX) on EM therapy in patients with sinobronchial syndrome . Patients with sinobronchial syndrome were randomly allocated to receive one of the following four regimens . Patients in Group A received both low-dose OFLX and EM therapy daily for 6 months . Patients in Group B received EM therapy and intermittent treatment of OFLX for 6 months . Patients in Group C underwent EM therapy for 6 months . Patients in Group D received neither OFLX nor EM therapy . All patients were given carbocystein for more than 2 months before starting each treatment and during the study period . In patients receiving OFLX and/or EM therapy, these antimicrobial agents were well-tolerated during the treatment period . Amount of sputum in the morning was significantly less in Group C than in Group D after 3-6 months, and decreased significantly in Group A as compared with Group B after 2 weeks, Group C after 2 weeks to 2 months, and Group D after 2 weeks to 6 months . Other symptoms such as number of expectorations, difficulty of expectoration and severity of cough also improved rapidly in Group A . These findings suggest that it is useful to add low-dose OFLX to EM therapy for sinobronchial syndrome, especially within 1-2 months from starting treatment, and it may be cost-effective as this combination therapy can shorten the treatment period of EM therapy. Fundam Appl Toxicol, 1995 Nov, 28(1), 59 - 64 Quinolone-induced arthropathy in the neonatal mouse . Morphological analysis of articular lesions produced by pipemidic acid and ciprofloxacin; Linseman DA et al.; Quinolone antibiotics are extensively utilized in antimicrobial chemotherapy . However, quinolone treatment in developing adolescents of several animal species is associated with acute arthropathy of the weight-bearing joints . Although arthropathy has rarely been observed following quinolone therapy in man, the toxicity observed in immature animals has resulted in restricted use of these drugs in children and pregnant women . Therefore, identification of novel quinolone antibiotics which do not cause arthropathy is highly desirable . This task would be facilitated by a bioassay of cartilage toxicity which utilizes small quantities of test material and has greater sensitivity than current toxicity assays . This study evaluated the utility of neonatal mice as a potential bioassay of quinolone-induced joint toxicity . Seven-day-old CF-1 mice (8-10/dose group) were treated subcutaneously with either pipemidic acid (50, 400, or 3150 mg/kg/day) for 7 or 14 days or ciprofloxacin (50 or 200 mg/kg/day) for 5, 7, or 14 days . Lameness was observed only after high-dose pipemidic acid treatment for 2-7 days . Histopathological assessment of the principal weight-bearing joints (knee, elbow, and multiple articulations in the fore- and hind-feet) revealed a lesion characterized by chondrocyte loss, matrix degeneration, and erosion of the articular cartilage in mice treated with pipemidic acid at 400 or 3150 mg/kg/day for 7 days or ciprofloxacin at 200 mg/kg/day for 5 days . Mice treated for 14 days with 400 mg/kg/day pipemidic acid demonstrated a lower incidence of lesions than mice treated for 7 days, suggesting the potential for reversibility during ongoing treatment . The results suggest that neonatal mice are sensitive to quinolone-induced arthropathy, but less so than previously reported for adolescent dogs . It is concluded that the neonatal mouse may be an appropriate screening system for identifying novel quinolones devoid of cartilage toxicity; however, follow-up studies with select compounds in a more sensitive species, such as the dog, are encouraged. J Periodontol, 1995 Nov, 66(11), 925 - 32 Clinical significance of bacterial resistance to tetracyclines in the treatment of periodontal diseases; Greenstein G; Tetracyclines are frequently employed during the treatment of clinical infections in medicine and dentistry, however, emergence of resistant bacterial strains has decreased the utility of these drugs . Accordingly, there is concern that indiscriminant administration of tetracyclines during periodontal therapy will further contribute to the development of additional resistant microorganisms which can complicate infectious disease therapy . This review paper briefly discusses the utility of tetracyclines as an antimicrobial agent in the treatment of periodontal diseases . It then focuses on the clinical significance of bacterial resistance to tetracyclines . Patterns of resistance that may be associated with the following scenarios are addressed: short- and long-term antibiotic therapy, individuals with a history of prior tetracycline therapy, patients with refractory periodontitis, and following controlled local drug delivery . It appears that selection and development of bacterial resistant strains is an inevitable consequence of antibiotic therapy . Nevertheless, prudent administration of tetracyclines may help delay or prevent the emergence of resistant microorganisms. J Clin Periodontol, 1995 Nov, 22(11), 830 - 4 The effect of a commercially available triclosan-containing toothpaste compared to a sodium-fluoride-containing toothpaste and a chlorhexidine rinse on 4-day plaque regrowth; Binney A et al.; Many compounds could be added to toothpaste to assist plaque inhibition, but ionic interactions can cause formulation difficulties . Moreover, the actual chemical action of a plaque inhibitory agent added to a toothpaste is difficult to assess when the product is used in the conventional manner, i.e., in addition to toothbrushing . The non-ionic antimicrobial triclosan has been incorporated in toothpastes and shown to have variable plaque inhibitory activity both alone and in conjunction with certain polymers or metal ions . Little is known of the efficacy of triclosan toothpastes compared to conventional fluoride toothpastes . The aim of this study was to compare a commercially available toothpaste containing 0.3% triclosan/co-polymer with a sodium fluoride toothpaste for chemical plaque inhibitory effects over a 4-day period . The study was designed to stratify the relative efficacy plaque inhibitory action of the products, comparisons were made with a positive control, chlorhexidine rinse and a negative control, saline . The study design was a randomised single blind crossover design balanced for first-order carryover . A total of 18 healthy, dentate volunteers participated in the study . On day 1 of each period the volunteers suspended toothcleaning and rinsed 2 x daily with the allocated mouthrinse or toothpaste slurry . On day 5, the plaque on the teeth was disclosed and scored by index and area . Increasing plaque scores were in the order chlorhexidine, triclosan toothpaste, fluoride toothpaste, and saline . Chlorhexidine was significantly more effective than all the other agents tested, and both toothpaste preparations were significantly better than the saline rinse . There was no significant difference between the two toothpaste rinses . Consistent with other studies the triclosan toothpaste offers only moderate plaque inhibitory properties when compared to a conventional toothpaste. J Clin Pathol, 1995 Nov, 48(11), 1067 - 8 Do blood cultures need continuous monitoring so that clinical action can be taken outside normal working hours? Murdoch DA, Koerner RJ, Speirs GE, MacGowan AP, Reeves DS. Many automated blood culture reading systems monitor bacterial growth 24 hours a day but it is unclear if reacting to prompts indicating bacterial growth outside normal laboratory hours is of clinical benefit . An analysis of 50 blood cultures from 43 patients which had organisms seen on Gram films and had triggered positive out-of-hours showed that examination of the Gram film altered management of seven patients and the results of culture or sensitivity testing altered that of a further four . However, after review, it was felt the clinical outcome would not have been influenced by earlier intervention in any of these patients . We therefore consider that an out-of-hours service for dealing with positive blood cultures is not justified in our hospital . This conclusion may not apply universally, especially in hospitals where potential pathogens show less predictable antimicrobial sensitivity patterns. Immunopharmacol Immunotoxicol, 1995 Nov, 17(4), 775 - 81 Effect of short-term therapy with ceftizoxime and ceftriaxone on human peripheral WBC, serum immunoglobulins and lymphocyte subpopulations; Karakaya A et al.; Serum immunoglobulins, peripheral white blood cells and lymphocyte subpopulation counts of twenty patients who received ceftizoxime and ceftriaxone for antimicrobial prophilaxis in surgery were examined in order to obtain a profile of the effects of these drugs on humoral and cellular immune system of human . No differences in the serum concentrations of IgG, IgM, IgA, peripheral blood lymphocytes and lymphocyte subpopulations 24 h and 48 h following the last dose of these two drugs were observed. J Exp Med, 1995 Nov 1, 182(5), 1469 - 79 Nitric oxide potentiates hydrogen peroxide-induced killing of Escherichia coli; Pacelli R et al.; Previously, we reported that nitric oxide (NO) provides significant protection to mammalian cells from the cytotoxic effects of hydrogen peroxide (H2O2) . Murine neutrophils and activated macrophages, however, produce NO, H2O2, and other reactive oxygen species to kill microorganisms, which suggests a paradox . In this study, we treated bacteria (Escherichia coli) with NO and H2O2 for 30 min and found that exposure to NO resulted in minimal toxicity, but greatly potentiated (up to 1,000-fold) H2O2-mediated killing, as evaluated by a clonogenic assay . The combination of NO/H2O2 induced DNA double strand breaks in the bacterial genome, as shown by field-inverted gel electrophoresis, and this increased DNA damage may correlate with cell killing . NO was also shown to alter cellular respiration and decrease the concentration of the antioxidant glutathione to a residual level of 15-20% in bacterial cells . The iron chelator desferrioxamine did not stop the action of NO on respiration and glutathione decrease, yet it prevented the NO/H2O2 synergistic cytotoxicity, implicating metal ions as critical participants in the NO/H2O2 cytocidal mechanism . Our results suggest a possible mechanism of modulation of H2O2-mediated toxicity, and we propose a new key role in the antimicrobial macrophagic response for NO. J Immunol, 1995 Nov 1, 155(9), 4476 - 84 Rat neutrophil defensins . Precursor structures and expression during neutrophilic myelopoiesis; Yount NY et al.; Defensins constitute a family of 3- to 4-kDa antimicrobial peptides that are stored in the cytoplasmic granules of neutrophils, some macrophages, and intestinal Paneth cells . We have assessed defensin gene expression during myeloid differentiation by first characterizing cDNAs for each of the four known rat neutrophil defensins (RatNP 1-4) . The cDNA sequences revealed that the peptides are synthesized as 87-94 amino acid precursors, each containing signal, pro-, and mature peptide segments . RatNP-3 and -4 mRNAs, but not those for RatNP-1 and -2 or other myeloid defensins, contained unique polypurine tracts located close to the termination codon in the 3' untranslated region . By using cDNA probes and/or riboprobes, we evaluated defensin transcript levels in a variety of tissues and in the full spectrum of neutrophil precursors . By in situ hybridization, defensin mRNAs were localized to neutrophil precursors in the bone marrow, with the highest mRNA levels occurring in promyelocytes and somewhat lower signals occurring in myeloblasts and myelocytes . Defensin mRNAs were not detectable in bands or mature neutrophils, nor at significant levels in tissues other than bone marrow . The accumulation of defensin protein in bone marrow cells was assessed by immunohistochemical staining with anti-RatNP-1 Ab . RatNP 1-4 mRNAs and protein levels were then correlated for each stage of neutrophilic differentiation to reveal the maturational profile of myeloid defensin gene expression in the rat. Chest, 1995 Nov, 108(5), 1326 - 32 Tracheal aspirates in long-term mechanically ventilated patients . A human model of gram-negative infection and airway inflammation; Palmer LB et al.; It is well known that patients requiring long-term mechanical ventilation and tracheostomy have nearly universal airway colonization with Gram-negative organisms . However, useful parameters to objectively describe the airway inflammation associated with airway instrumentation and colonization have not been well define . In our respiratory care unit, patients who are medically stable except for ventilator dependence are readily available for longitudinal assessment of airway secretions and therefore provide a unique population for studying airway inflammation and infection . To quantitate production of respiratory secretions, we instituted a uniform protocol of suctioning over a 6-h period . Further, we devised a method of dilution and homogenization of tracheal aspirates that permits reproducible intrasample total cell counts (coefficient of variation, 4.6%) . With these techniques, patients were then studied serially over a 4- to 7-week period . Total cell count, inflammatory cell differential, and two indices of airway inflammation, human neutrophil elastase (HLE) and soluble-intercellular adhesion molecule-1 (sICAM-1) studied in the sol phase of secretions were monitored . The mean total cell count was 42.2 x 10(6) cells per gram of secretions when patients were clinically stable and not receiving antibiotics . The average differential was neutrophils 69.9%, macrophages 26.9%, and lymphocytes 2.8% . Mean active HLE was 35.6 micrograms/mL and mean sICAM-1 was 83 ng/mL . Six patients during the period of observation received intravenous oral or aerosolized antibiotics for tracheobronchitis . A threefold drop in volume of secretions was measured (p < 0.018) . The total cell count and percent neutrophils decreased from 76.4 x 10(6)/g of sputum to 54.9 x 10(6) and 72.2 to 54.9%, respectively . While these changes were not statistically significant, the absolute number of airway neutrophils over the 6 h decreased sevenfold (p < 0.014) . Similarly sICAM-1 burden (micrograms per 6-h period) also decreased significantly (p < 0.034) . These patients provide a unique human model for future studies specifically designed to assess the effect of novel modalities of anti-inflammatory and antimicrobial agents on respiratory secretions. Immunity, 1995 Nov, 3(5), 657 - 66 Tissue-specific targeting of cytokine unresponsiveness in transgenic mice; Dighe AS et al.; The ubiquitous cellular distribution of certain cytokine receptors has hampered attempts to define the physiologically important cell-specific functions of cytokines in vivo . Herein, we report the generation of transgenic mice that express a dominant-negative IFN gamma receptor alpha chain mutant under the control of either the human lysozyme promoter or the murine lck proximal promoter, which display tissue-specific unresponsiveness in the macrophage or T cell compartments, respectively, to the pleiotropic cytokine, IFN gamma . We utilize these mice to identify previously undefined cellular targets of IFN gamma action in the development of a murine antimicrobial response and the mixed lymphocyte reaction . Moreover, we identify the macrophage as a critical responsive cell in manifesting the effects of IFN gamma in regulating CD4+ T helper subset development . These studies thus represent a novel approach to studying the cell-specific actions of an endogenously produced pleiotropic cytokine in vivo. CMAJ, 1995 Nov 1, 153(9), 1293 - 6 Mycobacterium abscessus infection of a Norplant contraceptive implant site; Alfa MJ et al.; The authors report a case of Mycobacterium abscessus infection of a subdermal levonogestrel implant (Norplant) site . The infection lasted 12 weeks and was indolent, skin manifestations were low grade and difficult to detect . Culture of exudate samples showed that M . abscessus was the only causative agent . After the implant was removed the patient's arm healed uneventfully without antimycobacterial therapy . The authors recommend that if Gram staining of apparently infected material from an implant site does not reveal a causative organism, then cultures should be done for mycobacteria and fungi . Kinyoun staining for acid-fast bacteria and calcoflour-white staining for fungi should also be performed . The implant should be removed and the patient given antimicrobial therapy as indicated . The authors emphasize the need to be aware of the potential for M . abscessus infection of implant sites and stress that appropriate microbiologic culture procedures are essential for accurate diagnosis. Am J Gastroenterol, 1995 Nov, 90(11), 1969 - 73 Prevalence of Helicobacter pylori infection in patients with large gastric folds: evaluation and follow-up with endoscopic ultrasound before and after antimicrobial therapy; Avunduk C et al.; OBJECTIVES: Large gastric folds may result from infectious, inflammatory, neoplastic, vascular, and infiltrative disorders involving a part or the entire gastric wall . Helicobacter pylori infection of the gastric mucosa is associated with an active gastritis characterized by infiltration of the mucosa and submucosa with neutrophils, eosinophils, macrophages, and lymphocytes . The purposes of the study were: 1) to study patients with large gastric folds noted on computed tomography, upper gastrointestinal series, or endoscopy, with endoscopy and biopsies and endoscopic ultrasound to determine the prevalence of H . pylori infection and the location of the thickening within the gastric wall; 2) to reexamine H . pylori-infected patients with EUS after antimicrobial therapy to determine whether resolution of the wall thickening accompanied eradication of H . pylori and improvement of histological gastritis . METHODS: Thirty-two patients with thickened gastric folds were studied . Eighteen patients had H . pylori infection and were treated with amoxicillin 1 g b.i.d . and omeprazole 40 mg b.i.d . x 14 days . One month after antimicrobial therapy, patients were reexamined by EUS, and gastric biopsies were obtained . RESULTS: Eighteen of 32 patients had H . pylori infection and gastritis . In the H . pylori-infected patients with gastritis, EUS demonstrated diffuse thickening of the inner three layers (mucosa-lumen interface, deep mucosa, submucosa) without thickening of the 4th and 5th layers of the gastric wall . After antimicrobial therapy and resolution of gastritis, EUS demonstrated concomitant resolution of this thickening and normalization of layers 1-3 . CONCLUSIONS: H . pylori gastritis is a common cause of gastric wall thickening . EUS allows intrinsic localization of the gastric wall thickening in patients with large gastric folds and H . pylori infection and documents the resolution of this wall thickening upon eradication of H . pylori and resolution of gastritis. Am J Gastroenterol, 1995 Nov, 90(11), 1962 - 4 Confirmation of successful therapy of Helicobacter pylori infection: number and site of biopsies or a rapid urease test; el-Zimaity HM et al.; BACKGROUND: Although a number of tests have been described to detect the presence of Helicobacter pylori in biopsy specimens, studies of positive and negative value have largely been performed on untreated patients; testing the reliability of posttherapy has not been done . METHODS: We examined the value of the number and site of biopsies performed and the method used for specimen evaluation posttherapy . For postantimicrobial therapy of 141 patients with previously confirmed H . pylori infection, three biopsies were taken, two from the antrum and one from the corpus . Individual slides were coded, randomized, and interpreted blindly by two pathologists . Furthermore, in 143 patients, a biopsy specimen was taken from the antrum and was immediately inserted into the gel of the rapid urease test, and the results were compared with those obtained from histopathology obtained at the same time . RESULTS: In 71 patients, H . pylori therapy was unsuccessful; in 61 (86%), all three sites were positive . The highest yield with a single large cup biopsy specimen was 94%; the lowest was 91% . Two antral biopsies were negative in 4% {95% confidence interval (CI) = 1-12%} . The combination of a biopsy from the angulus incisura and one from the greater curvature of the corpus correctly identified all treatment failures (95% CI = 95-100%) . The rapid urease test was false-negative in 5% (95% CI = 1-13%); there were no false-positives . CONCLUSION: Use of either the rapid urease test or two antral biopsies for evaluation of success of antimicrobial therapy for H . pylori infection will result in a false declaration of cure in at least 5% of cases . Three large cup gastric mucosal biopsies for histology are recommended for evaluation of the success of anti-H . pylori therapy. Postgrad Med, 1995 Nov, 98(5), 46 - 8, 54, 57-8 passim Inflammatory diseases of the colon . Narrowing a wide field of symptoms and possible causes; Tooson JD et al.; Symptoms and physical findings may indicate the severity of inflammatory disease of the colon, but detailed history taking is needed to limit the wide spectrum of possible causes . Infectious causes should be ruled out before other disease is assumed to be present . No single test is sufficient to diagnose ulcerative colitis or Crohn's disease . Laboratory testing, histologic assessment, endoscopy, radiology, and bowel studies are often necessary in differential diagnosis . Because of the systemic nature of colitis, manifestations in the musculoskeletal, ocular, dermatologic, hepatobiliary, and other systems may occur and provide clues . Treatment depends on the type and severity of disease . Sulfasalazine (Azulfidine), sulfa-free 5-aminosalicylic acid compounds, and corticosteroids are mainstays of treatment of ulcerative colitis and Crohn's disease . Supportive care and judicious use of antimicrobial therapy are usually effective in colitis due to bacterial, parasitic, and sexually transmitted infections and are useful for symptoms caused by colonic ischemia and vasculitis . Colitis resulting from radiation therapy may present several years after the procedure and can be difficult to diagnose and treat . In many cases of inflammatory colon disease, especially chronic conditions, consultation with a gastroenterologist is highly recommended. FEBS Lett, 1995 Oct 23, 374(1), 1 - 5 Cathelicidins: a novel protein family with a common proregion and a variable C-terminal antimicrobial domain; Zanetti M et al.; A novel protein family, showing a conserved proregion and a variable C-terminal antimicrobial domain, and named cathelicidin, has been identified in mammalian myeloid cells . The conserved proregion shows sequence similarity to members of the cystatin superfamily of cysteine proteinase inhibitors . Cathelicidins are stored in the cytoplasmic granules of neutrophil leukocytes and release the antimicrobial peptides upon leukocyte activation . Some of these peptides can assume an alpha-helical conformation, others contain one or two disulfide bonds, still others are Pro- and Arg-rich, or Trp-rich . In addition to bacterial killing, some of these peptides exert additional functions related to host defense such as LPS-neutralization and promotion of wound healing. Chem Biol Interact, 1995 Oct 20, 98(1), 1 - 13 Determination of structure-activity relationships of Annonaceous acetogenins by inhibition of oxygen uptake in rat liver mitochondria; Landolt JL et al.; A new group of natural compounds, the Annonaceous acetogenins, have recently been determined to inhibit ATP production at a similar site of action and higher levels of potency as rotenone, i.e., at NADH-ubiquinone oxido-reductase, complex I of the mitochondrial electron-transport chain . The acetogenins had earlier been determined to be pesticidal, antimalarial, antimicrobial, anti-parasitic, cytotoxic, and in vivo active as potentially new antitumor agents . In order to determine structural activity relationships (SARs) among these compounds, at the subcellular level, several available acetogenins have been tested . Data obtained, from the inhibition of oxygen consumption by rat liver mitochondria, demonstrated that all of the twenty acetogenins tested are active with IC50 values in the range of 15-800 nM/mg protein . The IC50 value of rotenone was 17 nM/mg protein . The bis-adjacent THF ring acetogenins and the bis-nonadjacent THF ring compounds are about ten times more active than the mono-THF ring acetogenins . Overall, 30-OH and 31-OH-bullatacinone were the most active and were slightly more active than rotenone . The least active were the 4-deoxy bis-adjacent THF ring compounds followed by the mono-THF ring group . There was some variation between the groups, e.g., within the bis-adjacent and mono-THF ring groups, the alpha, beta-unsaturated-gamma-lactones were less active than the keto-lactones, but this observation was reversed for one of the pairs of bis-nonadjacent THF ring acetogenins . Additional hydroxylations, to a maximum of three, seemed to increase activity within all of the groups . Before final decisions on SARs can be made, additional comparisons of the results of this subcellular assay (as an in vitro assay) with the results of in vivo assays should be made . Also, future investigations into the exact site of action within complex I and other possible sites of action (such as the NADH oxidase of plasma membranes) need to be conducted for a more . complete understanding of the utility and potential of this new group of very potent compounds. Biochim Biophys Acta, 1995 Oct 17, 1264(1), 23 - 5 Molecular cloning of cDNAs encoding precursors of frog skin antimicrobial peptides from Rana rugosa; Park JM et al.; Gaegurins, a family of peptide antibiotics with sizes ranging from 24 to 37 amino acids, have recently been purified from Rana rugosa skin (Park, J.M., Jung, J.-E . and Lee, B.J . (1994) Biochem . Biophys . Res . Commun . 205, 948-954) . Two complete cDNAs encoding gaegurins 4 and 5 were isolated from a library constructed with the frog skin mRNAs . Each clone contained a single open reading frame that encodes a gaegurin precursor polypeptide . The deduced amino acid sequences revealed that the precursors have a unique tripartite structure: a putative signal sequence at the NH2-terminus followed by an acidic spacer region rich in glutamic and aspartic acids, and a mature gaegurin peptide at the COOH-terminus . Similar modes of organization were also found in antimicrobial or opioid peptide precursors of other frog species, although their mature peptides show little sequence homology . The family of peptides with this characteristic now expands . Northern analysis revealed that gaegurins are extensively expressed in the skin tissue, but not in liver and muscle. Biochemistry, 1995 Oct 17, 34(41), 13663 - 71 Solution structure of bovine neutrophil beta-defensin-12: the peptide fold of the beta-defensins is identical to that of the classical defensins; Zimmermann GR et al.; The solution structure is reported for bovine neutrophil beta-defensin-12 (BNBD-12), a member of the beta-defensin family of antimicrobial peptides . Structural constraints in the form of proton-proton distances, dihedral angles, and hydrogen bond constraints were derived from two-dimensional, homonuclear magnetic resonance spectroscopy experiments . The three-dimensional structure of BNBD-12 was calculated using distance geometry and restrained molecular dynamics . An ensemble of structures with low NOE constraint violation energies revealed a precisely defined triple-stranded, antiparallel beta-sheet as the structural core of the peptide . The N-terminal beta-strand and three locally well-defined tight turns form a hydrophobic face . Conserved isoleucine and glycine residues form a beta-bulge structure which initiates a beta-hairpin secondary structure motif composed of the second and C-terminal beta-strands . The beta-hairpin contains numerous charged residues and forms the cationic face of BNBD-12 . The N-terminal residues were found to be disordered, due to an absence of tertiary NOEs . The triple-stranded beta-sheet, the beta-bulge preceding the hairpin, and the cationic/hydrophobic amphiphilic character are definitive features of all defensin structures determined to date . Further, we predict that the tracheal antimicrobial peptide (TAP) and the recently described gallinacins will have tertiary structures similar to that of BNBD-12. Eur J Biochem, 1995 Oct 15, 233(2), 694 - 700 Metchnikowin, a novel immune-inducible proline-rich peptide from Drosophila with antibacterial and antifungal properties; Levashina EA et al.; One of the characteristics of the host defense of higher insects is the rapid and transient synthesis of a variety of potent antimicrobial peptides . To date, several distinct inducible antimicrobial peptides or peptide families have been totally or partially characterized . We present here the isolation and characterization of a novel 26-residue proline-rich immune-inducible peptide from Drosophila, which exhibits both antibacterial (Gram-positive) and antifungal activities . Peptide sequencing and cDNA cloning indicate the presense of two isoforms in our Drosophila Oregon strain, which differ by one residue (His compared to Arg) as a consequence of a single nucleotide change . The gene, which maps in position 52A1-2 on the right arm of the second chromosome, is expressed in the fat body after immune challenge . The novel peptide, which we propose to name metchnikowin, is a member of a family of proline-rich peptides, and we discuss the possible evolutionary relationships within this family. N Engl J Med, 1995 Oct 12, 333(15), 984 - 91 The treatment of Helicobacter pylori infection in the management of peptic ulcer disease; Walsh JH et al.; Antimicrobial therapy against H . pylori is indicated for all patients with documented peptic ulcer disease who have evidence of the infection . The regimen of first choice, selected on the basis of available studies, is triple therapy with bismuth, metronidazole, and tetracycline (Table 1) . For patients who are known to have taken metronidazole previously, clarithromycin may be substituted for metronidazole . For patients with active, symptomatic peptic ulcers we also recommend an antisecretory drug to promote healing and relieve symptoms . Second-choice regimens consist of combinations of two antimicrobial drugs--metronidazole, amoxicillin, or clarithromycin--with an antisecretory agent, preferably an H+/K+-ATPase antagonist such as omeprazole . The combination of a single antimicrobial drug (especially amoxicillin) with omeprazole is less efficacious and cannot be recommended . Regardless of the antimicrobial regimen used, successful eradication of H . pylori infection markedly reduces the risk of recurrent peptic ulcers . If this therapeutic approach is taken with all patients with peptic ulcers, the recurrence of ulcers should become a rarity in medical practice. Echocardiography, 1995 Nov, 12(6), 651 - 61 Echocardiographic assessment of vegetations in patients with infective endocarditis: prognostic implications; Mugge A et al.; Today, echocardiography is the most important technique next to clinical findings and blood cultures in the diagnosis of infective endocarditis . The sensitivity of echocardiography, particularly the transesophageal approach, for detection of vegetations and endocarditis related valvular destructions is high . In addition, echocardiographic findings may have some prognostic implications . The size and mobility of vegetations stratifies endocarditis patients into a high risk group for arterial embolism . In particular, mobile vegetations attached to the mitral valve with a maximal diameter > 10 mm may be prone to embolic events . Furthermore, increase in size of vegetations during antimicrobial treatment may identify patients with no, or at least a prolonged, healing process . Also, a lack of increase in the echo density of vegetations under adequate antibiotic treatment may indicate a poor healing process and may necessitate more aggressive management . The demonstration of paravalvular abscesses by echocardiography, particularly by transesophageal echocardiography, identifies a subgroup of patients who will need urgent cardiac surgery before widespread tissue destruction has occurred. Biochemistry, 1995 Oct 3, 34(39), 12553 - 9 Kinetics of pore formation by an antimicrobial peptide, magainin 2, in phospholipid bilayers; Matsuzaki K et al.; The kinetics of the pore formation by magainin 2, an antimicrobial peptide from Xenopus laevis, in lipid vesicles was investigated . The pore formation was estimated by the efflux of a fluorescent dye, calcein, from large unilamellar vesicles composed of egg yolk phosphatidylglycerol . The time courses of the dye release were well-described by a novel model in which the peptide molecules translocate from the outer to the inner monolayer by forming a pore . The concentration dependence of the leakage rate suggested that the pore consists of pentameric magainin . The obtained kinetic parameters estimate that, at a lipid-to-peptide molar ratio of 117, 9 pores with a lifetime of 40 microseconds open per second per vesicle in the initial phase . The apparent deactivation of the pore with increasing time can be ascribed to the reduced peptide density in the outer leaflet due to the translocation . Incorporation of phosphatidylcholine destabilized the pore, indicating the importance of anionic lipids in the stable pore formation. Microb Drug Resist, 1995 Fall, 1(3), 273 - 83 Survey of antimicrobial resistance in bacterial isolates from diseased cattle in France; Martel JL et al.; Since 1982, a national veterinary network has been involved in the monitoring of resistance to antimicrobial agents in the main pathogenic bacteria isolated from diseased cattle in France . It is based on 40 regional veterinary diagnostic laboratories and managed by a central reference laboratory (CNEVA Lyon) . Highly standardized methods are used in the diagnostic laboratories . This network collects up-to-date information on antimicrobial resistance in veterinary isolates and gathers strains for specific studies on fastidious bacteria and for the analysis of mechanisms of resistance to antibiotics . Such a permanent survey is essential to establish a rational veterinary antibiotic policy . It could be connected to other compatible systems developed in other fields such as human medicine, food, and environment, to evaluate the importance of resistance and R-factors spread for public health . The limits and perspectives of this surveillance system are discussed. Am J Health Syst Pharm, 1995 Oct 1, 52(19 Suppl 4), S11 - 4 Cost-effectiveness of autologous bone marrow transplantation; Lawless GD; The impact of filgrastim on the use of health care resources during recovery from autologous bone marrow transplantation (ABMT) was studied . The charts for patients with metastatic breast cancer treated with ABMT at a general hospital between November 1989 and July 1993 were reviewed by Blue Cross of Western Pennsylvania . The 58 patients were divided into five groups: group 1-bone marrow purged, no filgrastim therapy; group 2-bone marrow not purged, no filgrastim therapy; group 3-bone marrow purged, filgrastim therapy after ABMT; group 4-bone marrow not purged, filgrastim therapy after ABMT; and group 5-peripheral blood stem cells (PBSCs) given, followed by filgrastim therapy . The groups were compared for total length of stay (LOS), number of days the absolute neutrophil count (ANC) was < 500/cu mm, total number of days of filgrastim therapy, and total number of cumulative unit days of antimicrobial use . Total LOS was shorter for patients who received filgrastim (groups 3-5) than for patients who did not . Filgrastim was associated with fewer days of ANC < 500/cu mm in groups 4 and 5 . The total number of cumulative unit days of antimicrobial use was lower in filgrastim recipients . Patients who received PBSCs needed fewer days of filgrastim therapy than the other filgrastim recipients . The health insurance company determined that, as a result of filgrastim therapy and PBSC transplantation, ABMT costs to the company have dropped by more than 50% since 1990 . Patients now have available an alternative to conventional therapy for metastatic breast cancer without prejudice or penalty from their payer. Clin Infect Dis, 1995 Oct, 21 Suppl 2, S174 - 7 Reducing the risk of Chlamydia trachomatis genital tract infection by evaluating the prophylactic potential of vaginally applied chemicals; Lyons JM et al.; The need to provide women with a partner-independent method of prophylaxis against sexually transmitted disease (STD) against, including Chlamydia trachomatis, has led to a direct effort to develop a vaginally applied, broad-spectrum antimicrobial preparation that is both safe and effective . Using a murine model of C . trachomatis lower genital tract infection, we tested the ability of various vaginally applied chemicals to alter the course of infection in female mice challenged with infectious doses ranging from 10(3) to 10(6) inclusion forming units of an oculogenital serovar of C . trachomatis . When administered in a methylcellulose/propylene glycol-base gel 15 minutes prior to challenge, four widely used topical antimicrobials (benzalkonium chloride, chlorhexidine, nonoxynol-9, and polymyxin B) were shown to protect against infection . These results support the possibility that this type of interventional method may be a clinically relevant means of prophylaxis against sexually transmitted infection with C . trachomatis, the most common bacterial STD agent. Clin Infect Dis, 1995 Oct, 21 Suppl 2, S162 - 5 NO inhibitions: antimicrobial properties of nitric oxide; De Groote MA et al.; The past decade has witnessed a veritable explosion of interest in the simple molecule nitric oxide (NO) as a vasodilator, neurotransmitter, and antimicrobial agent . NO and other reactive nitrogen intermediates exhibit cytostatic or cytocidal activity against a remarkable breadth of pathogenic microorganisms . Mammalian cells, including human cells, produce nitric oxide both constitutively and inducibly in response to inflammatory stimuli . This review will provide a brief overview of current knowledge regarding the antimicrobial activity of NO and the possible importance of this activity in infection, particularly with regard to intracellular pathogens. Clin Infect Dis, 1995 Oct, 21 Suppl 2, S152 - 7 Nitric oxide and infection: another view; Schoedon G et al.; Nitric oxide (NO) has been nicknamed "murderer" and "mediator" because it has toxic and signaling properties . We review these two aspects of NO synthesis from the perspective of the clinical infectious disease specialist by considering the potential of NO as an endothelium-derived relaxing factor (EDRF) in inflammation and sepsis and its potential as an antimicrobial system . We deviate from observations in recent authoritative reviews and point to important species differences that make it unlikely that NO serves as an EDRF mediating inflammatory vasodilatation in humans or that NO synthesized by humans phagocytes has an antimicrobial function . We propose that in humans, No synthesis is more confined and compartmentalized than in certain other animal species, and therefore, unwelcome toxicity, vasodilatation, or disturbance of paracrine signaling mechanisms (i.e., modulation of phagocytic cell functions) are avoidable during inflammation. Dermatol Clin, 1995 Oct, 13(4), 909 - 13 Antimicrobial treatment of psoriasis; Skinner RB Jr et al.; At the Problem Psoriasis Clinic at the University of Tennessee, Memphis, we use an antimicrobial approach for the treatment of psoriasis . This method is described for patient history, physical examination, and laboratory tests as well as treatment. Int J Immunopharmacol, 1995 Oct, 17(10), 849 - 56 The pro-oxidative riminophenazine B669 neutralizes the inhibitory effects of Mycobacterium tuberculosis on phagocyte antimicrobial activity; Wadee AA et al.; The effects of clofazimine, a riminophenazine antimicrobial agent, and its analogue B669 on phagocyte functions have been investigated . Clofazimine, at concentrations attainable in vivo, and B669, in particular, increased the intracellular killing ability of phagocytes following appropriate cell stimulation . Similarly, nitro blue tetrazolium reduction, hydrogen peroxide production, lysosyme release and hexose monophosphate shunt activity were all increased by treating phagocytes with the riminophenazines . It has previously been shown that a 25 kDa glycolipoprotein derived from Mycobacterium tuberculosis inhibits phagocyte functions associated with phagocyte antimicrobial activity . The present study confirms these observations . A further aspect of the study examined the ability of riminophenazines to reverse the inhibition of phagocyte functions by the 25 kDa mycobacterial fraction . Whilst both riminophenazines were capable of partially but significantly reversing the inhibition due to the mycobacterial fraction, the restorative capacity of B669 was greater than that of clofazimine. Clin Microbiol Rev, 1995 Oct, 8(4), 496 - 514 Antimicrobial agent resistance in mycobacteria: molecular genetic insights; Musser JM; The primary theme emerging from molecular genetic work conducted with Mycobacterium tuberculosis and several other mycobacterial species is that resistance is commonly associated with simple nucleotide alterations in target chromosomal genes rather than with acquisition of new genetic elements encoding antibiotic-altering enzymes . Mutations in an 81-bp region of the gene (rpoB) encoding the beta subunit of RNA polymerase account for rifampin resistance in 96% of M . tuberculosis and many Mycobacterium leprae isolates . Streptomycin resistance in about one-half of M . tuberculosis isolates is associated with missense mutations in the rpsL gene coding for ribosomal protein S12 or nucleotide substitutions in the 16S rRNA gene (rrs) . Mutations in the katG gene resulting in catalase-peroxidase amino acid alterations nad nucleotide substitutions in the presumed regulatory region of the inhA locus are repeatedly associated with isoniazid-resistant M . tuberculosis isolates . A majority of fluoroquinolone-resistant M . tuberculosis isolates have amino acid substitutions in a region of the DNA gyrase A subunit homologous to a conserved fluoroquinolone resistance-determining region . Multidrug-resistant isolates of M . tuberculosis arise as a consequence of sequential accumulation of mutations conferring resistance to single therapeutic agents . Molecular strategies show considerable promise for rapid detection of mutations associated with antimicrobial resistance . These approaches are now amenable to utilization in an appropriately equipped clinical microbiology laboratory. J Antimicrob Chemother, 1995 Oct, 36 Suppl B, 119 - 33 Bone marrow transplantation: current situation, complications and prevention; Hunter AE et al.; The number of patients undergoing BMT is rising steadily . The increase is due to a broadening of the indications for transplantation and an increase in the donor pool . There has been a progressive improvement in outcome particularly due to a fall in transplant-related mortality . Methotrexate and cyclosporin are the mainstay of graft versus host disease (GVHD) prophylaxis, but acute GVHD remains a major problem in the unrelated donor recipient . Infections remain an important cause of death and emphasise the crucial role of antimicrobial prophylaxis; death from Gram-negative sepsis has been significantly reduced by the use of prophylactic antibiotics . Fungal infections carry a high mortality, especially in allogenic transplant recipients . Fluconazole is used to protect patients in the neutropenic period and beyond in higher risk individuals . Viral infections, which may occur late, are emerging as a significant cause of morbidity and mortality in the allogeneic, particularly unrelated transplantation setting . A long term susceptibility to encapsulated bacteria suggests delayed immune reconstitution; revaccination policies are standard in most units . The longer term effects of transplantation are increasingly important with improving survival and include chronic GVHD, endocrine, cardiorespiratory and other systemic abnormalities . The increased risk of secondary malignancies is also of concern. J Chemother, 1995 Oct, 7(5), 420 - 3 Effects of lomefloxacin and sparfloxacin on human platelet aggregation; Losasso C et al.; Platelet aggregation is inhibited by high concentrations of most antibiotics . For this reason it is important to evaluate the effects of new antimicrobial agents on platelet aggregation . Lomefloxacin and sparfloxacin are new difluorinated quinolone antimicrobial agents . The aim of this work was to evaluate in vitro the effects of lomefloxacin and sparfloxacin on adenosinediphosphate (ADP) and collagen-induced human platelet aggregation . Our data showed that both antibiotics (lomefloxacin and sparfloxacin) at therapeutic doses did not inhibit in vitro human platelet aggregation . Lomefloxacin, only at the highest tested concentration (1 mg/ml), which is far higher than the clinically achievable one, significantly (P < 0.05) inhibited collagen-induced platelet aggregation . Sparfloxacin also caused inhibition of collagen and ADP-induced human platelet aggregation only at the highest tested concentration (0.01 mg/ml), which is higher than that reached in vivo . These findings suggest that therapeutic doses of lomefloxacin and sparfloxacin do not affect human platelet aggregation. J Chemother, 1995 Oct, 7(5), 414 - 6 Susceptibility of Capnocytophaga to antimicrobial agents; Kolokotronis A; A total of 22 clinically isolated Capnocytophaga strains were tested for their susceptibility to antimicrobial agents frequently used in dental practice . All strains were susceptible to penicillin, ampicillin, cefaclor, cefuroxime, erythromycin, clindamycin and tetracycline . Metronidazole had poor activity against most strains. Arzneimittelforschung, 1995 Oct, 45(10), 1074 - 8 Synthesis and pharmacological evaluation of some novel 5-(pyrazol-3-yl)thiadiazole and oxadiazole derivatives as potential hypoglycemic agents; Hanna MA et al.; Four series of 5-(pyrazol-3-yl)thiadiazole and oxadiazole derivatives (Va-c, VIa-c, VIIIa-c, IXa-c) have been synthesized from 5-arylazo-3-carbethoxy-4-methoxy-1-phenylpyrazole (Ia-c) with a view to investigate their pharmacological activity . The structure of the synthesized products was inferred from elemental and spectral data . The hypoglycemic effect, antimicrobial activity and toxicity of these potential chemotherapeutic agents were evaluated . Nineteen of these products were effective, when administered at an oral dose of 100 mg/kg body weight in inducing a marked reduction in blood glucose level. Farmaco, 1995 Oct, 50(10), 713 - 8 Synthesis and antimicrobial activity of 7 beta-{N-(arylmethyloxyimino) acetamido}cephalosporanic acid derivatives; Macchia M et al.; Some cephalosporanic acid derivatives substituted on the C(7) amino nitrogen with (arylmethyloxyimino)acetyl moieties were synthesized and tested in vitro for their antimicrobial activity against Gram positive and Gram negative bacteria . The new compounds showed a modest activity directed only against Gram positive microorganisms. J Vet Pharmacol Ther, 1995 Oct, 18(5), 357 - 62 Pharmacokinetics of enrofloxacin after single intravenous, intramuscular and subcutaneous injections in lactating cows; Kaartinen L et al.; Five Ayrshire cows were given enrofloxacin (5 mg/kg body weight) intravenously (i.v.), intramuscularly (i.m.) and subcutaneously (s.c.) . The antimicrobial activity was measured in milk and serum samples using the agar-diffusion technique . High-performance liquid chromatography (HPLC) assay was used to study the extent of metabolism of enrofloxacin to ciprofloxacin . Analysis of the serum concentration-time data was based on statistical moment theory . Mean t1/2 beta of antimicrobial activity in serum was 1.7, 5.9 and 5.6 h after i.v., i.m . and s.c . administration, respectively . Both i.m . and s.c . routes were associated with a marked flip-flop phenomenon . Based on HPLC analysis of serum samples, the half-lives of enrofloxacin and ciprofloxacin were approximately the same . A marked proportion of enrofloxacin was metabolized to ciprofloxacin . The enrofloxacin fraction bound in vitro to serum proteins was 36-45% . About 0.2% of the total enrofloxacin dose was found in milk during the first 24 h and the amount transferred did not depend on the route of administration . Based on the HPLC data, enrofloxacin concentration in milk was parallel to that in serum, while ciprofloxacin was concentrated in milk . After i.v . injection, the peak concentration of enrofloxacin in milk was reached between 0.7 and 1.3 h but occurred much later for ciprofloxacin (tmax 5-8 h) . After i.m . and s.c . administration the concentration-time curves for both enrofloxacin and ciprofloxacin in milk were shallow and there were no obvious peaks. Pediatr Infect Dis J, 1995 Oct, 14(10), 885 - 90 Comparison of the response to antimicrobial therapy of penicillin-resistant and penicillin-susceptible pneumococcal disease; Friedland IR; The continued spread of penicillin-resistant pneumococci raises therapeutic concerns . Optimal therapy for resistant infections is unknown and it is not clear whether the efficacy of penicillin or equally active beta-lactam agents is compromised in non-meningeal-resistant infections . A prospective nonintervention study was undertaken to compare the clinical response in penicillin-resistant vs . penicillin-susceptible bacteremic pneumococcal infections, excluding meningitis . Of 108 children enrolled, 35 (32%) had penicillin-resistant (one highly resistant) isolates . Seventy-eight children had pneumonia, 21 had occult bacteremia (sepsis) and 9 had peritonitis . Children with resistant infections were more likely to have underlying disorders, especially human immunodeficiency virus infection, and to have received antimicrobial therapy in the previous month . After 48 hours of therapy 64% of penicillin-susceptible infections showed improvement vs . 60% of penicillin-resistant infections (odds ratio, 1.2; 95% confidence intervals, 0.5 to 3.0) . In children with pneumonia treated with ampicillin or an equivalent beta-lactam agent, 93% with penicillin-susceptible infections had improved by Day 7 of therapy compared with 88% with resistant infections (odds ratio, 1.9; 95% confidence interval 0.3 to 15.9) . The durations of respiratory distress, fever and oxygen requirement were similar in penicillin-susceptible and -resistant infections . These results suggest that intermediate penicillin resistance is of little significance in pneumococcal pneumonia or sepsis and that standard beta-lactam therapy is still highly effective . Further studies of highly penicillin-resistant infections are necessary. Nutr Rev, 1995 Oct, 53(10), 271 - 82 Drug-nutrient interactions; Thomas JA; Nutrition status plays a significant role in a drug's pharmacodynamics . Some disease states and other special conditions affect nutrient status and a drug's therapeutic efficacy . Many classes of drugs, including antimicrobials, hypoglycemics, and hypocholesterolemic agents, can be affected by the presence of food, with the geriatric patient particularly at risk . While a drug's pharmacokinetic profile can usually be predicted, it can be modified by nutrients and by certain pathophysiologic conditions, including aging, hepatic dysfunction, and micronutrients. J Clin Microbiol, 1995 Oct, 33(10), 2686 - 91 Detection and identification of Mycobacterium tuberculosis directly from sputum sediments by Amplicor PCR; Moore DF et al.; Sputum specimens received for the diagnosis of tuberculosis or other mycobacterial infections were tested by a PCR-based assay and culture techniques . Results of the PCR assay (Amplicor Mycobacterium tuberculosis Test) were compared with results of standard culture techniques with cultures held for 6 weeks . One thousand nine specimens were included: 301 retrospective specimens (frozen at -70 degrees C and later tested by PCR) and 708 prospective specimens (tested within 1 day of processing) . One hundred sixty-two (16%) of the specimens were culture positive for M . tuberculosis; 83 (51%) of these were also fluorochrome stain positive . The sensitivity and specificity of the Amplicor PCR compared with those of culture were 83% (134 of 162 specimens) and 97% (800 of 827 specimens), respectively . The sensitivity for fluorochrome stain-positive specimens was 99%, and that for fluorochrome stain-negative specimens was 66% . The great majority of the 28 PCR-negative, culture-positive specimens were low positives; 27 were smear negative and 19 contained < 100 CFU of M . tuberculosis per ml . The 27 PCR-positive, culture-negative specimens included 24 that were positive by repeat testing by alternate primer PCR and were from patients with tuberculosis on antimicrobial therapy . With these considered culture misses, the final sensitivities of PCR and culture were 85, and 87%, respectively, while the specificities were 99.6 and 100%, respectively . After normal laboratory processing of sputum specimens, the Amplicor PCR assay can be completed in 8 h . Thus, it is possible to have results available within 10 h of specimen submission. Trends Microbiol, 1995 Oct, 3(10), 405 - 7 Are bacterial proteinases pathogenic factors? Travis J, Potempa J, Maeda H. Evidence is rapidly accumulating that suggests that the growth and proliferation of pathogenic bacteria depend on proteolytic enzymes of the invading organism and of the host . Proteinase inhibitors targeting bacterial proteinases may be useful antimicrobial agents. Vet Microbiol, 1995 Oct, 46(4), 347 - 60 Swine dysentery: more unknown than known; ter Huurne AA et al.; Swine dysentery (SD) is an economically important disease . It is caused by the spirochete Serpulina hyodysenteriae . In order to minimize the economic damage of SD, several methods to control this disease are recommended . Whereas hygienic measures and use of antimicrobials are actually practised for prevention, detection and exclusion of carriers of S . hyodysenteriae and vaccination against the disease still needs further attention . The last two methods require reliable and sensitive diagnostic tests and understanding of the pathogenesis of and immune development against SD . At present the detection of all individual carriers of S . hyodysenteriae is not yet assured, since the tests for screening individual animals are not satisfactorily evaluated as far as sensitivity and/or specificity are concerned . Studies on the pathogenesis of SD have been performed to develop a vaccine . Besides hemolysin/cytotoxin production, no other virulence factors have been identified with certainty for S . hyodysenteriae . Recently however, further indications for a role of motility in the pathogenesis of SD have been obtained . In this manuscript we summarize the most relevant recent findings. Otolaryngol Clin North Am, 1995 Oct, 28(5), 1081 - 91 Choice of wound dressings and ointments; Brown CD et al.; Over the last several decades, methods for wound dressing have dramatically changed . This article reviews the effects of wound dressing, antiseptics, and antimicrobials on the process of wound healing and on the incidence of wound infection . A set of guidelines is provided to help the surgeon decide what to apply topically to wounds and which dressing to select to achieve the best possible outcome in wound healing. Monaldi Arch Chest Dis, 1995 Oct, 50(5), 383 - 7 Antileucoprotease in the airways and emphysema; Dijkman JH; Antileucoprotease (ALP) is a natural occurring anti-elastase, and is produced in the epithelium of the conducting airways . It is a small protein, consisting of 107 amino-acids arranged in 2 domains . The second domain carries the antiproteolytic active site, the first is responsible for antimicrobial activity . In hamsters, intratracheal installation of ALP prevents the development of emphysema after administration of elastase . The daily production of ALP is remarkably constant, even during exacerbations of COPD . In the human lung a positive correlation was found between the number of ALP-producing bronchiolar cells and small airway's disease and emphysema . ALP is able to penetrate the alveolar-capillary membrane and has a tendency to associate with elastic fibers. Ann Med, 1995 Oct, 27(5), 605 - 7 Antibody titres in Helicobacter pylori infection: implications in the follow-up of antimicrobial therapy; Kosunen TU; Regular presence and persistence of specific serum antibodies in Helicobacter pylori infection gives an excellent tool for diagnostic work . Eradication of the infection leads to gradual disappearance of the gastritis and decrease of specific serum antibodies . The fall of IgG and IgA antibody titres can be followed with quantititative enzyme immunoassays . Success in eradication is reflected in 40-50% decrease of antibody titres within 5-6 months . The decrease continues and most patients have normal titres within 2 years . Serology offers a cheap and convenient way to follow the treated patients and makes most follow-up endoscopies unnecessary. Ann Med, 1995 Oct, 27(5), 601 - 4 New options in eradication of Helicobacter pylori; Seppala K et al.; Better treatment options to eradicate Helicobacter pylori are needed, while we await a possible effective vaccine against the world's most common infection . The goals of therapy for H . pylori infection should be an effective and low-cost therapy with a low frequency of side-effects . The currently available eradication regimens are cumbersome, which can lead to a reduction of compliance and a lower efficacy . More recent studies have shown, however, that the duration of antimicrobial treatment may be shortened, which also makes the treatment more cost-effective and more tolerable . At this point it seems relevant to treat H . pylori infection first with some antisecretory modification of triple therapy, while the therapeutic failures can be treated with other more relevant and suitable alternatives . Metronidazole is still a cornerstone of triple therapy and the more expensive clarithromycin is an alternative second-line treatment . Time will show the effectiveness and suitability of the latest topical 1-day treatments. Naunyn Schmiedebergs Arch Pharmacol, 1995 Oct, 352(4), 351 - 64 Nitric oxide synthase: expression and expressional control of the three isoforms; Forstermann U et al.; Three isozymes of nitric oxide synthase (NOS) have been identified . Their cDNA- and protein structures as well as their genomic DNA structures have been described . NOS I (ncNOS, originally discovered in neurons) and NOS III (ecNOS, originally discovered in endothelial cells) are low output, Ca(2+)-activated enzymes whose physiological function is signal transduction . NOS II (iNOS, originally discovered in cytokine-induced macrophages) is a high output enzyme which produces toxic amounts of NO that represent an important component of the antimicrobial, antiparasitic and antineoplastic activity of these cells . Depending on the species, NOS II activity is largely (human) or completely (mouse and rat) Ca(2+)-independent . In the human species, the NOS isoforms I, II and III are encoded by three different genes located on chromosomes 12, 17 and 7, respectively . The amino acid sequences of the three human isozymes (deduced from the cloned cDNAs) show less than 59% identity . Across species, amino acid sequences are more than 90% conserved for NOS I and III, and greater 80% identical for NOS II . All NOS produce NO by oxidizing a guanidino nitrogen of L-arginine utilizing molecular oxygen and NADPH as co-substrates . All isoforms contain FAD, FMN and heme iron as prosthetic groups and require the cofactor BH4 . NOS I and III are constitutively expressed in various cells . Nevertheless, expression of these isoforms is subject to regulation . Expression is enhanced by e.g . estrogens (for NOS I and III), shear stress, TGF-beta 1, and (in certain endothelial cells) high glucose (for NOS III) . TNF-alpha reduces the expression of NOS III by a post-transcriptional mechanism destabilizing the mRNA . The regulation of the NOS I expression seems to be very complex as reflected by at least 8 different promoters transcribing 8 different exon 1 sequences which are expressed differently in different cell types . Expression of NOS II is mainly regulated at the transcriptional level and can be induced in many cell types with suitable agents such as LPS, cytokines, and other compounds . Whether some cells can express NOS II constitutively is still under debate . Pathways resulting in the induction of the NOS II promoter may vary in different cells . Activation of transcription factor NF-kappa B seems to be an essential step for NOS II induction in most cells . The induction of NOS II can be inhibited by a wide variety of immunomodulatory compounds acting at the transcriptional levels and/or post-transcriptionally. Rinsho Byori, 1995 Oct, 43(10), 1066 - 70 {Identification of Capnocytophaga species by microplate hybridization method, and its restriction endonuclease digestion patterns}; Fujita S et al.; Because differentiation of Capnocytophaga on a species level has been reportedly proved impossible, we used a microplate hybridization method to identify three Capnocytophaga species . Photobiotin labeled DNAs from clinical isolates were added to the wells of a microdilution plate in which reference DNA had been immobilized . After 2 h of hybridization at 40 degrees C, hybridized DNAs were quantitatively detected with peroxidase-conjugated streptavidin and the substrate, tetramethylbenzidine . Of the 22 strains of Capnocytophaga species, 6 strains were identified as C . sputigena, 8 strains as C . gingivalis, and 8 strains as C . ochracea . Genomic DNAs from 25 strains of Capnocytophaga were treated with restriction endonuclease of HindIII, HaeIII, and HinfI . Nine strains of C . gingivalis showed no bands by the conventional electrophoresis of digested DNA . However, twelve strains (6 strains of C . sputigena and 6 strains of C . ochracea) revealed bands by the electrophoresis of HinfI-digested DNA, and ten isolates had its own digestion patterns, indicating the presence of genetic variation . On the other hand, two strains of beta-lactamase-producing C . ochracea, one from blood and one from throat swabs obtained from a patient with acute leukemia, were classified as the same isolate by the identical digestion pattern and by the antimicrobial susceptibility test results, which strongly suggested that the oral lesion is the portal of entry into the blood. Rinsho Byori, 1995 Oct, 43(10), 1005 - 9 {Hospital management and the role of clinical microbiology laboratory for preventing nosocomial infection}; Ichiyama S; Nosocomial infection is a serious issue in the hospital management . Countermeasures for this issue have been discussed from various points including clinical and laboratory medicine, nursing as well as hospital administration . This issue is of great importance to those of us medical practitioners, who engage in diagnosis and treatment of infectious diseases . The role of clinical microbiology laboratories for prevention of nosocomial infection includes performing epidemiological survey, giving information and education, and training and instruction to medical staff . In order to instruct and inspect the countermeasures against nosocomial infection, it is necessary to have a dedicated team in the hospital . We have organized an infection control team(ICT) to collect information and offer training and instruction regarding nosocomial infection . The ICT activities include 1) inspecting if the nosocomial infection control manual is followed correctly, 2) reporting the results of epidemiological survey regarding nosocomial infection, 3) offering the information regarding antimicrobial agents and disinfectants, 4) offering the information regarding the isolation of microorganisms in the hospital and their antimicrobial sensitivities, 5) cost calculation for nosocomial infection control. Immun Infekt, 1995 Oct, 23(5), 185 - 6 {Nosocomial transmission of pneumococcus}; Dallugge-Tamm H et al.; Increasing resistance of pneumococci against antimicrobial agents in several parts of the world is reported . We observed a probably nosocomial transmission of a pneumococcal strain with reduced susceptibility to penicillin (capsular type 6A) . Recommendations for diagnostic procedures in the laboratory and therapy are given. Boll Chim Farm, 1995 Oct, 134(9), 503 - 8 Potentially active antimicrobial agents from 2-benzenesulfonyloxyphenyl-3,1-benzoxazine-4-one derivative; Habib OM et al.; Fourteen of nitrogeneous heterocyclic compounds that accommodate the sulfonate-ester moiety were synthesized through interaction of 2-benzenesulfonylo xyphenyl-3,1-benzoxazine-4-one with some nucleophilic reagents . The assigned structures for the prepared new compounds were confirmed on the basis of elemental and spectral data . Evaluation of the antimicrobial activity of these products, relative to standard antibiotics was tested and discussed. J Pediatr Gastroenterol Nutr, 1995 Oct, 21(3), 288 - 96 Human milk kappa-casein and inhibition of Helicobacter pylori adhesion to human gastric mucosa; Stromqvist M et al.; Readily digested caseins, which account for almost half of the protein content in human milk, are important as nutritional protein for breast-fed infants . It has also been advocated that part of the antimicrobial activity of human milk resides in the caseins, most likely the glycosyated K-casein . Top explore this possibility, we purified K-casein from human milk to homogeneity by a two-step size-exclusion chromatography procedure . Purified human K-casein, in contrast to K-casein purified from bovine milk, effectively inhibited the cell lineage-specific adhesion of fluoroisothiocyanate-labeled Helicobacter pylori to human gastric surface mucous cells . The inhibitory activity was abolished by metaperiodate oxidation and considerably reduced by preincubation with alpha-L-fucosidase but not with alpha-N-acetylneuraminidase or endo-beta-galactosidase . These results strongly support the view that fucose containing carbohydrate moieties of human K-casein are important for inhibition of H . pylori adhesion and, thus, infection . They also suggest that breastfeeding may protect from infection by H . pylori during early life and that species-specific glycosylation patterns, as illustrated by human bovine K-casein, partly determine both the narrow host spectrum of this human gastric pathogen and the capacity to resist infection. Ir J Med Sci, 1995 Oct-Dec, 164(4), 285 - 8 Acute haematogenous osteomyelitis--evaluation of management in the 1990s; Lane-O'Kelly A et al.; There are three main areas of debate in the management of acute haematogenous osteomyelitis: The value of early operative intervention, the duration and route of antibiotic treatment and the choice of antibiotic therapy . The aim of this study is to evaluate the management protocol of acute haematogenous osteomyelitis as used in The Childrens' Hospital, Temple Street . The protocol can be recommended . Absence of pyrexia and a normal Erythrocyte Sedimentation Rate do not exclude acute haematogenous osteomyelitis . Current thoughts on antimicrobial therapy are presented. Ir J Med Sci, 1995 Oct-Dec, 164(4), 271 - 3 Comparative antimicrobial activity and spectrum of CP-99,219, a novel fluoroquinolone, tested against ciprofloxacin-resistant clinical isolates; Murphy SP et al.; The fluoroquinolones have an established role in treatment of infection with aerobic gram negative rods . The increased importance of gram positive nosocomial infection and of acquired fluoroquinolone resistance has stimulated a search for new compounds with enhanced potency and spectrum . CP-99,219 is a novel compound in this class with enhanced activity against gram positive organisms . We have studied the activity of CP-99,219 relative to ciprofloxacin, fleroxacin, ofloxacin, and sparfloxacin using test panels of organisms with a high proportion of ciprofloxacin resistance . CP-99,219 is more potent than any of the other four compounds against both gram positive and gram negative bacteria . The activity of CP-99,219 against many bacteria resistant to the established agents, warrants further in vitro and clinical studies. J Am Acad Dermatol, 1995 Oct, 33(4), 597 - 602 Results of evaluation of 203 patients for photosensitivity in a 7.3-year period; Fotiades J et al.; BACKGROUND: Although photosensitivity disorders have been well described, their incidence in a referral institution had not been studied . OBJECTIVE: The purpose of this study was to evaluate the incidence of photosensitivity disorders, including photocontact dermatitis, in an academic medical center . METHODS: The results of the assessment of 203 consecutive patients, all of whom had phototests, referred for the evaluation of photosensitivity disorders during a 7.3-year period were reviewed . RESULTS: The mean age was 50 years, and 63% of the patients were women . The most frequent diagnoses were polymorphous light eruption (26% of the total patient population), chronic actinic dermatitis (17%), photoallergic contact dermatitis (8%), systemic phototoxicity to therapeutic agents (7%), and solar urticaria (4%) . Positive photopatch reactions, patch test reactions, or both were observed in 40 (29%) of the 138 tested patients . The frequencies of the positive photopatch test reactions were sunscreens (57%), fragrances (18%), and antimicrobial agents (13%) . Of the positive patch test responses, fragrances elicited 47% of the total positive reactions, followed by sunscreens (39%) and antimicrobial agents (7%) . CONCLUSION: Polymorphous light eruption, chronic actinic dermatitis, and photoallergic contact dermatitis were the most frequently made diagnoses . Sunscreens, fragrances, and antimicrobial agents were the most common clinically relevant photoallergens and allergens. J Am Acad Dermatol, 1995 Oct, 33(4), 551 - 73; quiz 574-6 Cutaneous photosensitivity diseases induced by exogenous agents; Gould JW et al.; Cutaneous photosensitivity diseases may be idiopathic, produced by endogenous photosensitizers, or associated with exogenous photosensitizers . Those caused by exogenous agents include phototoxicity, photoallergy, and the exacerbation or induction of systemic disorders in which photosensitivity is a prominent clinical manifestation . Phototoxic disorders have a high incidence, whereas photoallergic reactions are much less frequent . The action spectra for most phototoxins and photoallergens lie in the UVA range . Phototoxic and photoallergic reactions can be distinguished on the basis of pathogenesis, clinical characteristics, diagnosis, and management . Drugs capable of causing phototoxic reactions include psoralens, porphyrins, coal tar, antibiotics, and nonsteroidal antiinflammatory agents . Drugs capable of causing photoallergic reactions include topical antimicrobial agents, fragrances, sunscreens, nonsteroidal antiinflammatory agents, plants, and psychiatric medications . Drug-induced systemic diseases in which photosensitivity is a prominent component include drug-induced lupus erythematosus, porphyria, and pellagra. Isr J Med Sci, 1995 Oct, 31(10), 611 - 5 A survey of current Israeli practices and approach to partially treated meningitis in children; Meshulach-Netzer I et al.; Children with partially treated (PT) meningitis present diagnostic and therapeutic dilemmas . Since the approach to these children is not uniform, both in the literature and in daily practice, we conducted a survey among leading Israeli pediatricians from various hospitals to learn about their opinions and practices relating to this problem . Twenty-eight of 30 senior pediatricians responded to a questionnaire encompassing the various aspects of PT meningitis . The results of the survey highlighted the confusion and lack of clear policy regarding the definition, diagnostic approach and treatment of these children . Fifty percent of the pediatricians stated that even one dose of an antimicrobial agent, regardless of the type of drug, is sufficient for the definition of PT meningitis; 43% of the responders did not require any threshold parameter in CSF findings for the definition of probable bacterial meningitis among PT children and 52% did not think that a second lumbar puncture was useful as a diagnostic aid in PT meningitis . Epidemiological circumstances played a role in the diagnostic and therapeutic approach of infectious disease specialists mainly, but less so in the other groups of pediatricians . Finally, more than half the responders did not use throat cultures to identify potential carriers among PT meningitis patients and did not consider the use of prophylactic treatment in close contacts . These data clearly indicate the need for guidelines regarding the various aspects of PT meningitis. Am Ind Hyg Assoc J, 1995 Oct, 56(10), 993 - 1001 Exposure while applying industrial antimicrobial pesticides; Popendorf W et al.; Forty-three assessments were made of dermal and/or inhalation chemical exposure while applying industrial antimicrobial pesticide products, either by manually pouring or pumping liquids or by pouring a solid (powder or flake) product . Inhalation exposure was assessed via a personal air sample but was usually below the chemical limit of detection . Dermal exposure outside work clothing and dermal deposition inside the clothing was assessed via dermal gauze dosimeters . While dosimeters at discrete body locations often received exposures below the limit of detection, one or more dosimeters on individual applicators almost always showed measurable exposure . The median measured dose was between 30% and 70% of the maximum credible summed dose calculated by assuming that each dosimeter showed either the level of measurable deposition or one-half of the detection limit at locations where the chemical was unmeasurable . Because of differences in settings and the low level of control implicit in these application processes, measurable dermal doses were highly variable . Mean measurable dose rates were near 3, 8, and 10 mg product/hr, and daily total deposited doses were 2, 3.5, and 5 mg of product for pouring and pumping liquids and for pouring solids, respectively . Although the effect of gloves cannot be directly determined, wearers of gloves had geometric mean hand total doses 155- to 290-fold less than those not wearing gloves . Similar to the statistics for agricultural pesticides, the dermal route of exposure for these industrial pesticides exceeds the inhalation route by 5X to 100X, depending on assumptions regarding nondetectable values. Pediatrics, 1995 Oct, 96(4 Pt 1), 712 - 5 Managing otitis media: a time for change; Paradise JL; Given the increasing prevalence of multiply resistant pneumococcal infection and the heightened risks associated with antimicrobial usage, antimicrobial treatment of otitis media in children should be restricted generally to the extent possible without compromising individual children's well-being and without subjecting them to risks potentially greater than the risks associated with antimicrobial usage . Not infrequently the decisions required will be difficult and matters of judgment . However, in most cases the indications for initiating or prolonging antimicrobial treatment will be either straightforward, calling for a decision to proceed, or marginal, in which case the decision not to proceed should be clear. J Fam Pract, 1995 Oct, 41(4), 345 - 51 Treatment of Chlamydia pneumoniae infection in adult asthma: a before-after trial; Hahn DL; BACKGROUND . Some diseases previously believed to be noninfectious, eg, peptic ulcer disease, are now known to be caused by chronic infection . Recently, chronic Chlamydia pneumoniae infection has been suggested as a cause for adult-onset asthma . The purpose of this study was to determine whether antichlamydial treatment would affect the natural history of this disease . METHODS . An open-label, before-after treatment trial was performed in a community-based, primary care office . Forty-six patients (mean age 47.7 years; range 17 to 78) with moderate to moderately severe, stable, chronic asthma were treated a median of 4 weeks (range 3 to 9) with oral doxycycline (100 mg twice daily), azithromycin (1000 mg once weekly), or erythromycin (1000 mg daily) . Post-treatment pulmonary function and asthma symptoms were compared with baseline values . Follow-up was an average of 6 months (range 1.5 to 36) post-treatment . RESULTS . Four patients with C pneumoniae respiratory tract infection developed chronic asthma, which disappeared after treatment in each case . Of the remaining 42 seroreactive patients who were treated a mean of 6 years after the development of chronic asthma, one half had either complete remission or major clinical improvement (3 and 18 patients, respectively) . This improvement was significantly more likely to occur in patients with early disease (P = .01) and before the development of fixed obstruction (P < .01) . CONCLUSIONS . Antimicrobial therapy appeared to "cure" or significantly improve asthma in approximately one half of treated adults, and the response pattern was consistent with chlamydial pathogenesis . C pneumoniae infection in asthma may be clinically important and should be investigated further. J Infect Dis, 1995 Oct, 172(4), 1149 - 52 Mycobacterium avium complex in macaques with AIDS is associated with a specific strain of simian immunodeficiency virus and prolonged survival after primary infection; Mansfield KG et al.; Mycobacterium avium complex (MAC) in simian immunodeficiency virus (SIV)-infected macaques is a frequent opportunistic infection that shares many features with the condition in human AIDS patients . A retrospective analysis of necropsies on 135 macaques with SIV-induced simian AIDS that received neither antiretroviral nor antimicrobial therapy revealed that 17% (23/135) were infected with MAC . MAC developed in 31.3% (21/67) of the animals inoculated with uncloned SIVmac251 versus 1.9% (1/53) and 6.7% (1/15) of the animals inoculated with the molecular clones SIVmac239 and SIVmac239/316EM, respectively (P = .001) . This is the first example in which the risk of infection with a specific opportunistic organism was affected by the infecting strain of immunodeficiency virus . In addition, animals with MAC had a longer mean survival after primary infection and lower CD4 cell counts at death than animals that did not develop this opportunistic infection . The SIV-inoculated macaque is a valuable model in which to study the pathogenesis of MAC in the immunocompromised host. Chest, 1995 Oct, 108(4), 1036 - 40 Effect of previous antimicrobial therapy on the accuracy of the main procedures used to diagnose nosocomial pneumonia in patients who are using ventilation; Timsit JF et al.; We evaluated the effect of antibiotic treatment received before the suspicion of pneumonia on the diagnostic yield of protected specimen brush (PSB), direct examination (BAL D) and culture (BAL C) of lavage fluid on consecutive mechanically ventilated patients with suspected nosocomial pneumonia . Bronchoscopy was always performed before any treatment for suspected pneumonia . One hundred and sixty-one patients with suspected pneumonia underwent PSB and BAL before any institution or change in antibiotic therapy (AB) . Sixty-five patients received AB for an earlier septic episode (ON AB group) and 96 patients did not (OFF AB group) . All but two strains recovered were highly resistant to previous AB . Sensitivity and specificity of each test were not different between the ON AB and OFF AB groups as well as the percentage of complete agreement between the 3 procedures, 74 and 67% respectively . We conclude that previous AB received to treat an earlier septic episode unrelated to suspected pneumonia do not affect the diagnostic yield of PSB and BAL. Trends Biotechnol, 1995 Oct, 13(10), 438 - 45 Recent developments in retro peptides and proteins--an ongoing topochemical exploration; Chorev M et al.; Main-chain peptidomimetics