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| Surg Neurol, 1999 Nov, 52(5), 445 - 8 Successful treatment of brainstem abscess with stereotactic aspiration; Nakajima H et al.; BACKGROUND: Brainstem abscess is an uncommon condition associated with a high mortality . We report a case of brainstem abscess in a 51-year-old female with a pulmonary arteriovenous fistula that was cured after appropriate antibiotic therapy following stereotactic aspiration . The value of stereotactic aspiration in the management of brainstem abscess is documented with a review of the relevant literature . CASE REPORT: A 51-year-old female with a pulmonary arteriovenous fistula suffered fever, diplopia and weakness on the right side . Magnetic resonance (MR) imaging of the brain showed a large cystic mass with ring-like enhancement in the brainstem . A diagnosis of brainstem abscess as a complication of pulmonary arteriovenous fistula was made . MR imaging-guided stereotactic exploration was carried out via the suboccipital transcerebellar approach and the pathogen of the brainstem abscess was identified . The brainstem abscess was cured after treatment employing antibiotics to which the pathogen was sensitive . CONCLUSIONS: Stereotactic aspiration is an effective procedure for brainstem abscesses . This procedure is less invasive than open surgery and can be performed even in patients in poor general condition. Int J Antimicrob Agents, 1999 Oct, 13(2), 117 - 25 The MYSTIC (meropenem yearly susceptibility test information collection) programme; Turner PJ et al.; The primary objective of the MYSTIC study is to monitor the performance of meropenem over a period of at least 3 years during which this carbapenem is prescribed in different hospital units thus allowing profiles to be established within individual hospitals . Monitoring is being carried out by assessing the antibiotic susceptibility of bacterial pathogens isolated from patients with a predominate problem of intraabdominal infections (IAI) and/or lower respiratory tract infections (LRTI), treated in specialist centres (haematology wards, the Intensive Care Unit {ICU}, cystic fibrosis units) and non-specialised centres . Samples will be collected over each year and tested against meropenem and a set of comparators . The data obtained from the first year of the study (1997) come from 33 centres spread mainly throughout Europe but also in Israel and Mexico . The results shows that meropenem retains its broad spectrum and potency whilst there is evidence that the activity of comparator antibiotics is being eroded by a variety of resistance mechanisms . Data from subsequent years of the programme will determine whether these trends continue and will allow a series of individual centre profiles to be compiled and presented. Am J Contact Dermat, 1999 Dec, 10(4), 226 - 7 Allergic contact dermatitis to polyethylene glycol and nitrofurazone; Guijarro SC et al.; We report a case of worsening dermatitis after the application of an antibiotic ointment (Furacin) containing furazone and polyethylene glycol . Patch tests to nickel sulfate, potassium dischromate, chloride cobalt, Furacin, nitrofurazone 1% petrolatum, polyethylene glycol mix 4% petrolatum, polyethylene glycol (PEG) 300 4% petrolatum, and PEG 400 as is (ai) were positive . The use of topical agents containing nitrofurazone or polyethylene glycol on damaged skin may predispose to contact allergy . We discuss the sensitizing properties of nitrofurazone and polyethylene glycol. Pediatr Res, 1999 Nov, 46(5), 566 - 75 Maternal infection, fetal inflammatory response, and brain damage in very low birth weight infants . Developmental Epidemiology Network Investigators; Leviton A et al.; Echolucent images (EL) of cerebral white matter, seen on cranial ultrasonographic scans of very low birth weight newborns, predict motor and cognitive limitations . We tested the hypothesis that markers of maternal and feto-placental infection were associated with risks of both early (diagnosed at a median age of 7 d) and late (median age = 21 d) EL in a multi-center cohort of 1078 infants <1500 x g . Maternal infection was indicated by fever, leukocytosis, and receipt of antibiotic; fetoplacental inflammation was indicated by the presence of fetal vasculitis (i.e . of the placental chorionic plate or the umbilical cord) . The effect of membrane inflammation was also assessed . All analyses were performed separately in infants born within 1 h of membrane rupture (n = 537), or after a longer interval (n = 541), to determine whether infection markers have different effects in infants who are unlikely to have experienced ascending amniotic sac infection as a consequence of membrane rupture . Placental membrane inflammation by itself was not associated with risk of EL at any time . The risks of both early and late EL were substantially increased in infants with fetal vasculitis, but the association with early EL was found only in infants born > or =1 after membrane rupture and who had membrane inflammation (adjusted OR not calculable), whereas the association of fetal vasculitis with late EL was seen only in infants born <1 h after membrane rupture (OR = 10.8; p = 0.05) . Maternal receipt of antibiotic in the 24 h just before delivery was associated with late EL only if delivery occurred <1 h after membrane rupture (OR = 6.9; p = 0.01) . Indicators of maternal infection and of a fetal inflammatory response are strongly and independently associated with EL, particularly late EL. Br J Orthod, 1999 Dec, 26(4), 295 - 8 Orthodontics and infective endocarditis; Khurana M et al.; Infective endocarditis associated with orthodontics is a rare occurrence . Unfortunately, many orthodontic practitioners do not treat patients potentially at risk of developing endocarditis due to the lack of practical guidelines and fear of precipitating the infection . Additionally, many patients that undergo orthodontic treatment are inappropriately prescribed antibiotic cover for procedures that have a minimal bacteraemic risk . In this paper the literature linking orthodontic treatment and infective endocarditis is examined . Recommendations are made for the appropriate management of patients at risk of infective endocarditis for orthodontic procedures . Refereed Paper ASAIO J, 1999 Nov-Dec, 45(6), 531 - 4 A novel percutaneous barrier device that permits safe subcutaneous access; Yu C et al.; Successful subcutaneous access is important for optimal management of internal artificial organs and treatment of many diseases . However, skin downgrowth and tissue infection are still significant problems in the use of devices that require long-term subcutaneous access . The authors developed a new percutaneous device that provides a unique biologic boundary with surrounding connective tissue while minimizing the risk of complications . This new percutaneous device is made of a circumferential, strong, thin, and flexible mesh collar with millimeter size holes for connecting the structure . It has two distinct functional portions: a connecting zone and a sealing line . The most important features of the structure are: 1) Connective tissue grows through the millimeter size pores of the connecting zone to form a strong bond between the device and healthy tissue . 2) The millimeter size pores of the connecting zone allow capillaries to grow through its entire surface, ensuring sufficient blood supply . 3) The tissue of the connecting zone and the device surface form a biosealed junction (sealing line) . This sealing line is protected by the connecting zone and is free from external forces acting on local skin . 4) The device is generally functional immediately after surgical implantation . The subcutaneous perimeter of the functional dome contains extruded rigid rings of millimeter size holes permitting growth of subcutaneous tissue through the device . This functions as the minor connecting structure of the device . Four of five implanted rabbits have remained healthy 8 months postimplantation without antibiotic administration . The fifth rabbit died 4 months postimplantation for reasons unrelated to the device . Gross or histopathologic inspection revealed no signs of tissue injury or inflammation . Growth of healthy connective tissue was clearly observed . These results indicate this percutaneous device can provide a strong, stable, and effective connection to internal organs without bioboundary damage, skin downgrowth, or tissue infection. J Radiol, 1999 Nov, 80(11), 1569 - 71 {US-guided percutaneous drainage of an infected epidermoid cyst of the spleen in a child}; Blondel C et al.; Epidermoid cyst of the spleen is a rare entity (2.5% of all splenic cysts) and rarely becomes complicated by hemorrhage, rupture or infection . Classically, management consisted of total or partial splenectomy . We report the case of an 8-year-old boy presenting with a splenic abscess complicating an epidermoid cyst . Percutaneous drainage of the abscess was performed under sonographic guidance and completed by intravenous antibiotic therapy . Six weeks later, laparoscopic surgery was performed and the splenic parenchyma could be preserved. Cancer Invest, 1999, 17(8), 586 - 93 A dose-escalation phase II clinical trial of infusional mitomycin C for 7 days in patients with advanced measurable colorectal cancer refractory or resistant to 5-fluorouracil; Anderson N et al.; Chemotherapy for 5-fluorouracil (5-FU)-resistant colorectal cancer is largely ineffective with new and innovative therapeutic strategies needed to benefit patients developing progressive disease while receiving 5-FU or 5-FU-based programs . The tumor antibiotic mitomycin C is an alkylating agent with a broad range of clinical activity in a variety of gastrointestinal malignancies and is therefore a reasonable agent to test for clinical activity in the setting of 5-FU-resistant or -refractory colorectal cancer . The principal goal of this study is to investigate the logistical feasibility and clinical efficacy of a 7-day infusion of mitomycin C, delivering an equitoxic dose to the standard bolus delivery in patients with progressive disease while receiving 5-FU-based chemotherapy . Twenty-five patients with advanced measurable colorectal cancer, resistant or refractory to 5-FU-based chemotherapy, were treated with a 7-day intravenous infusion of mitomycin C . Doses ranged between 1.5 and 3.0 mg/M2/day for total cumulative mitomycin C, ranging between 10.5 and 21.0 mg/M2 per chemotherapy cycle . Forty-four courses of infusional mitomycin C were delivered to 25 patients via surgically implanted venous access devices . The median age of all patients was 63 years (range, 27-83); there were 11 men and 14 women . Eleven patients had received two or more prior chemotherapy combinations, with the average number of prior therapies before mitomycin C being 1.6 . The median number of cycles of mitomycin C administered was two (range, one to six) . Thirty-seven of 44 cycles were administered at the dose range of 2.0-3.0 mg/M2/day . Hematologic toxicity was mild, with only three courses associated with grade III thrombocytopenia and one course with grade III neutropenia . No extrahematologic toxicities were observed . No patient had a complete response; two patients (8%) showed partial responses that lasted for 145 and 190 days . One patient had stable disease for 180 days . Twenty-two of 25 patients (88%) developed progressive disease during mitomycin C administration . Infusional mitomycin C for 7 days, cycled every 42 days, is logistically feasible and associated with minimal clinical toxicity . Used on this schedule and with these doses in 5-FU-resistant/refractory colorectal cancer, however, there is no meaningful clinical activity for this agent, and it cannot be recommended as a salvage or second-line therapy in the treatment of metastatic colorectal cancer. Dermatology, 1999, 199(3), 268 - 70 Skin invasion of Hodgkin's disease mimicking scrofuloderma; Takagawa S et al.; We report a case of direct skin invasion by Hodgkin's disease from a left supraclavicular lymph node . Clinical and pathological presentations mimicked infectious disease such as scrofuloderma . The nodule later developed a fistula following a biopsy that never healed despite numerous antibiotic treatments . Ten months later, other nodules with spontaneous fistula formation appeared on the anterior neck . A diagnosis of Hodgkin's disease was then made . Subsequent COPP cytostatic therapy remarkably improved the skin lesions and lymph nodes achieving complete remission. Eur J Pediatr, 1999 Dec, 158(12), 975 - 7 Ceftriaxone-associated nephrolithiasis and biliary pseudolithiasis; de Moor RA et al.; Biliary pseudolithiasis has been reported in patients who received ceftriaxone therapy . In addition to biliary sludge formation occasional reports of ceftriaxone-induced nephrolithiasis have been published . In general, these adverse effects will develop after seven to ten days of treatment . We report on a seven-year-old boy with ceftriaxone-associated biliary pseudolithiasis and nephrolithiasis four days after initiation of treatment . Patients receiving a high dose of ceftriaxone and developing colicky abdominal pain should be considered for ultrasound and a change in antibiotic therapy if appropriate. Pathologe, 1999 Nov, 20(6), 351 - 4 {Malakoplakia of the colon}; Kruger S et al.; We report on a 62-year-old female patient with melena in which polypoid lesions of the cecum were discovered endoscopically . Histological examination of mucosal biopsies revealed an inflammatory process with lots of histiocytes and so-called Michaelis-Gutmann bodies, leading to the diagnosis of a malakoplakia of the colon . No other organs were found affected . In the course of an antibiotic therapy, there was no melena detectable over a period of six months . Malakoplakia, an inflammation usually affecting the urogenital tract, is rarely found in the colon, with only 35 cases published until now . It is frequently associated with other diseases like neoplastic or inflammatory disorders, immune defect syndromes or heroin abuse . This spectrum is expanded by our report in which a long-standing alcohol abuse was found as an attendant disease. Laryngoscope, 1999 Dec, 109(12), 1924 - 7 Role of aerating mastoidectomy in noncholesteatomatous chronic otitis media; Ruhl CM et al.; OBJECTIVE: To assess the success rate of revision tympanoplasty with aerating mastoidectomy in patients with noncholesteatomatous chronic otitis media who had failed at least one prior tympanoplasty . STUDY DESIGN: Retrospective chart review . METHODS: Data were analyzed from 135 patients available for clinical and audiometric studies with a minimum of 18 months' follow-up . All patients had failed at least one prior tympanoplasty and presented with: 1) a persistent tympanic membrane perforation with intermittent drainage, or 2) a wet draining ear, unresponsive to systemic antibiotic and topical management . All patients underwent 1.5-mm, high-density, bone window computed tomography (CT) scanning to assess middle ear, epitympanic, and mastoid air cell pneumatization . All patients underwent revision tympanoplasty with aerating mastoidectomy via a postauricular approach . Patient charts were reviewed for information regarding preoperative radiographic findings, mucosal and ossicular findings at the time of surgery, and success or failure of revision tympanomastoidectomy . RESULTS: The tympanic membrane graft take rate for the entire group of 135 patients was 90.4% (13 grafts failed) . A majority of the patients were found to have radiographic and intraoperative evidence of middle ear/mastoid disease . CONCLUSION: For patients with noncholesteatomatous chronic otitis media who have failed prior tympanoplastic reconstruction, an aerating mastoidectomy may be indicated and may improve the success rate of the surgery. J Antimicrob Chemother, 1999 Dec, 44(6), 735 - 42 Mechanisms involved in the development of resistance to fluoroquinolones in Escherichia coli isolates; Tavio MM et al.; Eighteen quinolone-resistant isolates of Escherichia coli were selected by exposing ten clinical isolates to increasing concentrations of norfloxacin and lomefloxacin . The mutant isolates showed a multiple-antibiotic-resistance phenotype . All of them contained single mutations in gyrA consisting of the substitution of Ser-83-->Leu (n = 14), Val (n = 1) or Ala (n = 1) and the substitution of Asp-87-->Asn (n = 2) . Only one concomitant mutation in parC (Ser-80-->Arg) was detected . Four parent isolates exhibited a single mutation in gyrA which required < or = 12 mg/L of norfloxacin to be inhibited . Fluoroquinolone resistance, in the 18 quinolone-resistant mutants, was a result of mutations affecting DNA gyrase plus decreased fluoroquinolone uptake . This latter mechanism of resistance was a combined effect of an absence of OmpF and an increase in active efflux in eight isolates, or an increased active efflux alone in the remaining ten selected mutants. Biophys J, 1999 Dec, 77(6), 3152 - 5 Orientation of cecropin A helices in phospholipid bilayers determined by solid-state NMR spectroscopy; Marassi FM et al.; The orientation of the insect antibiotic peptide cecropin A (CecA) in the phospholipid bilayer membrane was determined using (15)N solid-state NMR spectroscopy . Two peptide samples, each specifically labeled with (15)N at Val(11) or Ala(27), were synthesized by solid phase techniques . The peptides were incorporated into phospholipid bilayers, prepared from a mixture of dimyristoylphosphatidylcholine and dimyristoylphosphatidylglycerol, and oriented on glass slides . The (15)N chemical shift solid-state NMR spectra from these uniaxially oriented samples display a single (15)N chemical shift frequency for each labeled residue . Both frequencies are near the upfield end of the (15)N chemical shift powder pattern, as expected for an alpha-helix with its long axis in the plane of the membrane and the NH bonds perpendicular to the direction of the magnetic field . These results support a mechanism of action in which CecA binds to and covers the membrane surface, thereby causing a general destabilization and leakiness of the lipid bilayer membrane . The data are discussed in relation to a proposed mechanism of membrane lysis and bacterial killing via an ion channel activity of CecA. Urol Clin North Am, 1999 Nov, 26(4), 829 - 39, x Management of prosthesis infections in urologic surgery; Carson CC 3rd; Prosthetic devices are a cornerstone of urologic surgical care . The most disastrous complication of these surgical procedures is infection . The prevention, identification, and management of infections are critical to maintaining functional urologic prosthetic devices . Although the incidence is low, rapid identification of infections once they occur and proper management with antibiotics, surgical intervention, irrigation, and salvage procedures can maintain the function of urologic prosthetic devices despite clinical infection. Mol Biochem Parasitol, 1999 Oct 25, 104(1), 39 - 53 Expression of foreign proteins in Trypanosoma congolense; Downey N et al.; An expression vector was constructed to express foreign genes in Trypanosoma congolense . The foreign gene and a neomycin phosphotransferase (NPT) gene are flanked by glutamate and alanine rich protein (GARP) gene processing signals and their expression is driven by a ribosomal RNA gene promoter . The plasmid is not maintained as an episome in T . congolense, but the NPT gene permits selection of cells in which the plasmid has integrated into the genome . We used this plasmid to express luciferase, green fluorescent protein and a surface protein of Trypanosoma brucei, glycine-proline-glutamate glutamate threonine procyclic acidic repetitive protein (GPEET PARP) . The plasmid-derived GPEET PARP is expressed on the surface of procyclic T . congolense and comigrates on a polyacrylamide gel with native GPEET PARP from T . brucei procyclic cells . We also attempted to use the plasmid to overexpress a previously identified T . congolense cysteine protease . The plasmid-derived cysteine protease mRNA species occurs in the transfected cells, but we were unable to detect increased levels of protein or protease activity. J Clin Periodontol, 1999 Nov, 26(11), 757 - 63 GCF levels of MMP-3 and MMP-8 following placement of bioresorbable membranes; Said S et al.; Matrix metalloproteinases (MMPs) are responsible for remodeling and degrading extracellular matrix and basement membrane components . MMP-3 and -8 levels were assessed in this study during the early healing phase following a guided tissue regeneration (GTR) procedure . 32 patients, having 2 or 3 walled intrabony defects of PD > or =6 mm, were stratified into 2 groups on the basis of age, sex, smoking status and disease severity . All intrabony defects were treated using the resorbable Guidor membrane but only 1 group of patients was given a pre-operative dosage of antibiotic (3 g amoxycillin) . GCF samples for the quantification of MMP-3 and -8 levels were obtained from the intrabony site where a membrane was placed (membrane site), from the non-adjacent site on the adjacent tooth which was involved in the surgical flap (surgical control site), and from a healthy site (healthy) on the contralateral side . The GCF samples taken at baseline, 1 week, 4 weeks and 3 months after surgery were analyzed using an enzyme linked immunoabsorbent essay (ELISA) for MMP-3 and using a time-resolved immunofluorescence assay (IFMA) for MMP-8 . MMP-3 was detected in a very low % of sites at baseline while relatively high levels of MMP-8 were detected at all 3 types of sites at baseline . MMP-8 levels increased for all sites at week 1, and this was statistically significant for the membrane site, but at week 4, the levels decreased for both the membrane and the surgical sites . There was no statistically significant difference between the levels of MMP-3 and -8 in the antibiotic and non-antibiotic group . Collagen remodelling occurs during the early wound healing period following surgical and regenerative procedures . The levels of MMP-3 and -8 in GCF appear to reflect these processes . Interestingly, the presence of the membranes appeared to increase the levels of MMP-3 and -8 and may relate to the resorption of the resorbable membrane by host systems. J AOAC Int, 1999 Nov-Dec, 82(6), 1316 - 20 Determination of sulfamethazine in milk by biosensor immunoassay; Gaudin V et al.; A biosensor based on surface plasmon resonance (SPR) measurement was developed for use in an immunoassay for detection of sulfamethazine (SMZ) in milk . The biospecific surface was a carboxymethyl dextran-modified gold-surface sensor chip to which SMZ was covalently bound . The assay was based on inhibition of the binding of polyclonal antibodies to immobilized SMZ by SMZ in the sample . The SPR response changed inversely in relation to the antibiotic concentration in the sample . Calibration curves were constructed for SMZ in buffer and in milk at a concentration which included the maximum residue limit (0 to 200 micrograms/kg) . The analysis time per sample varied from 8 to 30 min . Different flow rates and antibodies were modified alternatively during the study to assess their influence on the performance of the assay . The active antibody concentration was calculated at approximately 1880 and 180 nM for the antibody anti-SMZ 1 and the antibody anti-SMZ 2, respectively . No cross-reactivity of antibodies with other antibiotics was found . Under optimal conditions, the detection limits in milk for SMZ were 8 and 1.7 micrograms/kg, respectively, for antibody 1 and antibody 2, at a flow rate of 20 microL/min. Vet Clin North Am Equine Pract, 1999 Dec, 15(3), 623 - 46 Equine infectious keratitis; Hamor RE et al.; Corneal ulcers are one of the most common ocular disease presentations in the horse . With the use of correct diagnostic techniques and selection of an appropriate treatment regimen, most cases result in a satisfactory outcome . The eye does not respond well to inflammation, and in complicated ulcers, this should be managed aggressively using systemic NSAIDs with a high priority assigned to removing the infectious agent . Care needs to be taken to avoid topical or systemic corticosteroid use for the treatment of equine ocular disease, however, unless the clinician is completely sure that the corneal disease is not caused by an infectious process . The use of combination corticosteroid-antibiotic ophthalmic preparations without an appropriate treatment rationale can result in doing more harm than good . It is important to have a treatment plan and to monitor the elected treatment regimen . The clinician should decide on some objective criteria at initiation of treatment so that any changes are made rationally . This approach should also include consideration of early referral of the eye's care to a veterinary ophthalmologist. Arch Esp Urol, 1999 Oct, 52(8), 892 - 5 {Bladder malacoplakia: 14-year follow-up of a case}; Collado Serra A et al.; OBJECTIVE: To describe the clinical findings, treatment and results of long-term follow-up of a case of malacoplakia of the bladder . METHODS/RESULTS: After diagnostic endoscopic evaluation, transurethral resection of the lesion was performed and antibiotic therapy was administered . The same treatment was repeated 4 years later . During the following 10 years, the patient had a yearly endoscopic evaluation that showed no recurrence of the lesion . CONCLUSIONS: Transurethral resection combined with antibiotic therapy is effective in the treatment of malacoplakia of the bladder . The importance of long-term follow-up of the patient is emphasized. J Allergy Clin Immunol, 1999 Dec, 104(6), 1265 - 72 Sensitization to Aspergillus species in the congenital neutrophil disorders chronic granulomatous disease and hyper-IgE syndrome; Eppinger TM et al.; BACKGROUND: Hyper-IgE syndrome (HIE) and chronic granulomatous disease (CGD) are congenital immunodeficiency diseases with increased susceptibility to bacterial and fungal infections . Both carry significant morbidity and mortality rates because of invasive infections by Aspergillus species . We encountered 2 patients, one with HIE and one with CGD, in whom detection of sensitization to Aspergillus species preceded the diagnosis of immunodeficiency . With high-dose systemic corticosteroids for allergic bronchopulmonary aspergillosis (ABPA), an inflammatory disorder caused by sensitization to Aspergillus species, pulmonary abscesses developed in the patient with HIE, and the patient with CGD succumbed to an overwhelming Aspergillus species-induced pneumonia . OBJECTIVE: We sought to assess the prevalence of sensitization to Aspergillus fumigatus and the presence of diagnostic criteria for ABPA in patients with CGD and HIE . METHODS: We measured A fumigatus-specific serum IgE, IgG, and precipitating antibodies as indicators for A fumigatus sensitization in the sera of 18 patients with neutrophil disorders (7 with HIE and 11 with CGD) . Hospital records were reviewed for the presence of other diagnostic criteria for ABPA (asthma, elevated total serum IgE concentration, and radiographic abnormalities) . RESULTS: Twelve (67%) of 18 patients were sensitized to A fumigatus, as evidenced by precipitating A fumigatus-specific antibodies . Six (33%) of 18 patients had serologic evidence of ABPA . Five of those 6 patients had radiologic abnormalities consistent with a diagnosis of ABPA . One patient with HIE also had asthma, thus fulfilling minimal essential criteria for concurrent ABPA . CONCLUSIONS: Patients with HIE syndrome and CGD have a high incidence of sensitization to Aspergillus species . A clinical picture indistinguishable from ABPA may coexist or emerge in patients with CGD or HIE and create a major management dilemma because systemic corticosteroids may accelerate tissue damage and invasive fungal infections . It is important to distinguish individuals with congenital neutrophil disorders from uncomplicated classic ABPA. Pediatr Transplant, 1999, 3 Suppl 1, 45 - 51 Can we make some general recommendations regarding immune recovery after hematopoietic reconstitution preceded by ablative therapy? Trigg ME. Children undergoing marrow transplantation have compromised immune systems for variable periods of time after transplant . A number of methods have been utilized to assess recovery of the immune system . Four recommendations are made in regards to the testing that should be done, when the testing should be done, when immunizations should be provided and when antibiotic and other infection prophylaxis can be reduced. J Vet Intern Med, 1999 Nov-Dec, 13(6), 507 - 15 Gastric function in dogs with naturally acquired gastric Helicobacter spp . infection; Simpson KW et al.; The association of Helicobacter pylori with gastritis, peptic ulcers, and gastric neoplasia has led to fundamental changes in the understanding of gastric disease in humans . The relationship of Helicobacter spp . infection to gastric disease in dogs is unclear . The objective of this study was to determine if Helicobacter infection affects the gastric secretory axis of dogs . Eight Beagle dogs with naturally acquired Helicobacter spp . infection were studied before and after (4 and 29 days) the attempted eradication of Helicobacter spp . with a combination of amoxicillin, metronidazole, and famotidine (AMF) . Six specific-pathogen-free, Helicobacter-free Beagle dogs served as controls . The electron microscopic appearance of spiral organisms in infected dogs indicated coinfection with Helicobacter felis- and H bizzozeronii-like organisms . Unstimulated gastric pH and fasting, postprandial, and bombesin-stimulated plasma gastrin were similar in both infected and uninfected dogs, although a trend (P = .09) toward higher meal-stimulated gastrin was observed in infected dogs at 60 minutes . Pentagastrin-stimulated maximal acid output (mmol HCI/kg0.75/hour) and titratable acidity (mmol HCl/mL) were similar in both infected and uninfected dogs, but gastric pH during maximal acid output was lower (P < .01) in uninfected dogs . Mild gastric inflammation was present in both infected and uninfected dogs . Gastric spiral organisms were undetectable in 6/8 infected dogs 4 days after AMF but had recurred in 8/8 dogs 29 days after AMF . Analysis of gastric DNA with Helicobacter-specific primers indicated persistence of Helicobacter DNA at 4 and 29 days after antibiotic therapy . Acid secretion, plasma gastrin, and mucosal inflammation were not affected by the transient suppression of Helicobacter spp . by AMF . These findings suggest that gastric secretory function in dogs is not markedly perturbed by naturally acquired Helicobacter spp . infection and that treatment with amoxicillin, metronidazole, and famotidine causes suppression rather than eradication of gastric Helicobacter spp . in dogs. Ren Fail, 1999 Nov, 21(6), 635 - 45 Co-administration of co-trimoxazole does not augment tacrolimus-induced impairment in kidney function in rats; Agarwala S et al.; Co-trimoxazole is an antibiotic that is frequently used in organ transplant patients . Our objective was to determine the effect of co-trimoxazole on tacrolimus-mediated functional impairment of the kidney in rats . Sprague Dawley rats were divided into three groups . Group 1 (dextrose) received 5% dextrose and Group 2 (tacrolimus) received tacrolimus (1 mg/kg/day) as a continuous intravenous infusion for seven days . Group 3 (combination) received tacrolimus as above and co-trimoxazole (30 mg/kg/day trimethoprim and 150 mg/kg/day sulfamethoxazole) intraperitoneally for six or seven days . Biochemical and functional parameters were measured pre- and post-drug infusion . On day 7, glomerular filtration rate (GFR) was evaluated using 3H-inulin while the effective renal plasma flow (ERPF)/cationic tubular secretion was assessed using 14C-tetraethylammoniumbromide(TEA) . GFR (mL/min/kg) as measured by inulin clearance was higher (p < or = 0.05) in the dextrose (12.0 +/- 1.4) group as compared to tacrolimus group (6.0 +/- 1.3) and combination group (6.4 +/- 1.6), but there was no difference between the tacrolimus and combination group . ERPF/cationic tubular secretion (mL/min/kg) was also significantly higher in the dextrose group (62.6 +/- 10.3) as compared to the other two groups . ERPF/cationic tubular secretion was not different between the combination (33.3 +/- 5.9) and the tacrolimus (35.1 +/- 6.7) groups when there was no co-trimoxazole in the body . However, in the presence of co-trimoxazole ERPF/cationic tubular secretion was significantly reduced in the combination (23.1 +/- 3.5) group as compared to the tacrolimus group (35.1 +/- 6.7) . These results indicate that co-trimoxazole does not further potentiate tacrolimus induced impairment in kidney function but is likely to further inhibit cationic tubular secretion in patients on tacrolimus therapy. Ann Thorac Surg, 1999 Nov, 68(5), 1648 - 51 Adjuvant treatment of deep sternal wound infection with collagenous gentamycin; Leyh RG et al.; BACKGROUND: The treatment of deep sternal wound infections remains controversial . Currently advocated procedures carry the risk of reinfections . The significance of local antibiotic-releasing systems as an adjuvant therapy to avoid reinfections is the subject of the presented study . METHODS: Forty-two patients with deep sternal wound complication were treated with radical wound debridement, sternal refixation, retrosternal suction drainage, bilateral pectoralis major muscle flaps, and placement of collagenous drug carrier loaded with gentamycin (Sulmycin Implant) underneath, above, and between the sternal edges . RESULTS: No treatment failure and death were observed in our patients . Side effects after adjuvant treatment with collagenous gentamycin were not detected . CONCLUSIONS: The preliminary results of adjuvant therapy with collagenous gentamycin in combination with surgical debridement leads to excellent results in the treatment of early deep sternal wound infections with no death and no primary treatment failures . This technique is easy to perform, reliable, and safe . For final judgment controlled randomized trials are mandatory. Spectrochim Acta A Mol Biomol Spectrosc, 1999 Oct, 55A(12), 2547 - 58 NMR study of pradimicin derivative BMY-28864 and its interaction with calcium ions in D2O; Hu M et al.; The dynamic structure of the antifungal antibiotic pradimicin BMY-28864 in D2O and its interaction with calcium ions were analyzed using one- and two-dimensional 1H nuclear magnetic resonance (NMR) . Spectra indicate extensive self-association of molecules in the solution . Two-component spectra were observed simultaneously in a very dilute solution, suggesting equilibrium of two aggregative states . The addition of CaCl2 caused a number of changes in NMR spectra . Therefore we concluded that pradimicin BMY-28864 could form a complex with the Ca2+ ion, causing a movement of the equilibrium . The position of the bound calcium ion is determined indirectly by observing how the NMR shift affects protons that are close to the binding site . The stoichiometry of Ca2+ ion to the Pradimicin molecule for the Ca(2+)-saturated complex is verified to be 1:2 . Signal broadening and changes in chemical shift in the 1H NMR spectroscopy of BMY-28864 are assumed to be related to changes in the molecular aggregate conformation. Hum Reprod Update, 1999 Sep-Oct, 5(5), 421 - 32 Relevance of male accessory gland infection for subsequent fertility with special focus on prostatitis; Weidner W et al.; Infections of the male genitourinary tract may contribute to infertility to a various extent depending on the site of inflammation . Especially in prostatitis, the exact classification of the infection contributes to its impact on changes in the ejaculate . Similarly, in urethritis, epididymitis and orchitis, only a clear clinical diagnosis allows a rational approach to altered sperm parameters . Several inflammatory and reactive alterations of sperm quality seem to be proven; nevertheless, the impact of these findings on male fertility remains in many cases unclear . Even therapeutic trials do not provide more insights into the association of male genital infections and impaired fertility, although the efficacy of antibiotic trials seems to be proven . For the future, it may be decisive to evaluate inflammatory changes in the ejaculate not only on the basis of standard but also on functional parameters, thus providing new definitions of the interactions between male urogenital tract infection and disturbances of male fertility. Vestn Oftalmol, 1999 Sep-Oct, 115(5), 14 - 7 {The prevention and treatment of recurrences after dacryorhinostomies}; Beloglazov VG et al.; A total of 1206 dacryorhinostomies carried out from January, 1991 to December, 1997 at Institute of Ocular Diseases of the Russian Academy of Medical Sciences are analyzed . The main causes of relapses were underevaluation of the data of examinations and improper choice of operative access and method of surgery, errors in the technique of operation, and wrong postoperative treatment . For improving the efficacy of surgery, the authors developed a comprehensive method for preventing and treating relapses . X-ray and rhinological data are decisive for the choice of the access and method of operation . Unfavorable rhinogenic factors are removed and measured aimed at suppression of the cicatricial process at the site of anastomosis are carried out in primary dacryorhinostomy . For this purpose the authors for the first time in Russia applied a cytostatic antibiotic mitomycin C to the site of dacryostoma (44 cases) and a polymeric film Diplen with hemostatic and wound-healing effects (87 cases) with good results . Thorough follow-up after surgery detected a threatened relapse sufficiently early to carry out adequate treatment promoting cure. Complement Ther Med, 1999 Sep, 7(3), 132 - 5 A randomized comparison of homoeopathic and standard care for the treatment of glue ear in children; Harrison H et al.; OBJECTIVE: To pilot a model for determining whether homoeopathic treatment of children suffering from glue ear is more effective than standard GP care at producing a return to normal hearing (a hearing loss of less than 20 dB) within 12 months . DESIGN: Non-blind, randomized controlled trial . SETTING: General practice in two locations in southern England . SUBJECTS: Thirty-three children aged 18 months to 8 years with otitis media with effusion, hearing loss > 20 dB and an abnormal tympanogram . OUTCOME MEASURES: Hearing loss, tympanogram, referrals to specialists and number of courses of antibiotics at 12 month follow-up . RESULTS: A higher proportion of children receiving homoeopathic care had a hearing loss less then 20 dB at follow-up (64 vs 56%), though this difference did not reach statistical significance (95% confidence interval for the difference between means of -25 and 42%) . More homoeopathy patients than controls had a normal tympanogram (75 vs 31%, P = 0.015) . Referrals to specialists and antibiotic consumption was lower in the homoeopathy group, though differences between groups did not reach statistical significance . CONCLUSION: Further research comparing homoeopathy to standard care is warranted . Assuming recovery rates of 50 and 30% in homoeopathy and standard care groups respectively, 270 patients would be needed for a definitive trial. Microbios, 1999, 100(396), 117 - 27 Correlation of actinomycin X2 to the lipid profile in static and shaken cultures of Streptomyces nasri strain YG62; el-Naggar MY et al.; Streptomyces nasri strain YG62 produces a broad-spectrum antibiotic designated actinomycin X2 . The influence of static and shaken incubation on the production of actinomycin X2 and lipid profiles of S . nasri strain YG62 was investigated . It was found that shaken incubation was superior to the static process for both actinomycin X2 (2-fold) and total lipids (1.6-fold) . Triglyceride and phospholipid levels paralleled the actinomycin X2 production with an increase in the triglyceride (2.8-fold) and phospholipid (1.2-fold) concentrations in the shaken culture over the static incubation . Analysis of fatty acid patterns revealed the occurrence of a wide range of fatty acids (C10-C22) . The mean percentage of total saturated fatty acids in shaken culture was higher than those of the static culture . The mean percentage of mono-unsaturated fatty acids was almost the same in both cultures . The mean percentage of the total polyunsaturated fatty acids in the static culture was slightly higher than that of the shaken culture . The polyunsaturated/saturated fatty acid ratio (P/S) was higher in the static culture compared with the shaken culture . A positive correlation was recorded between triglycerides, phospholipids and actinomycin X2 . A negative correlation on the other hand, was found between fatty acids and actinomycin X2. J Antibiot (Tokyo), 1999 Aug, 52(8), 721 - 9 Melithiazols, new beta-methoxyacrylate inhibitors of the respiratory chain isolated from myxobacteria . Production, isolation, physico-chemical and biological properties; Sasse F et al.; New antibiotic compounds, melithiazols, were isolated from the culture broth of strains of the myxobacteria Melittangium lichenicola, Archangium gephyra, and Myxococcus stipitatus . The compounds belong to the group of beta-methoxyacrylate (MOA) inhibitors and are related to the myxothiazols . The melithiazols show high antifungal activity, but are less toxic than myxothiazol A and its methyl ester in a growth inhibition assay with mouse cell cultures . The melithiazols inhibit NADH oxidation by submitochondrial particles from beef heart . Melithiazol A blocks the electron transport within the bc1-segment (complex III) and causes a red shift in the reduced spectrum of cytochrome b. Cell Calcium, 1999 Jun, 25(6), 429 - 38 Functional characterization of thapsigargin and agonist-insensitive acidic Ca2+ stores in Drosophila melanogaster S2 cell lines; Yagodin S et al.; The role of acidic intracellular calcium stores in calcium homeostasis was investigated in the Drosophila Schneider cell line 2 (S2) by means of free cytosolic calcium ({Ca2+}i) and intracellular pH (pHi) imaging together with measurements of total calcium concentrations within intracellular compartments . Both a weak base (NH4Cl, 15 mM) and a Na+/H+ ionophore (monensin, 10 microM) evoked cytosolic alkalinization followed by Ca2+ release from acidic intracellular Ca2+ stores . Pretreatment of S2 cells with either thapsigargin (1 microM), an inhibitor of endoplasmic reticulum Ca(2+)-ATPases, or with the Ca2+ ionophore ionomycin (10 microM) was without effect on the amplitude of Ca2+ release evoked by alkalinization . Application of the cholinergic agonist carbamylcholine (100 microM) to transfected S2-DM1 cells expressing a Drosophila muscarinic acetylcholine receptor (DM1) emptied the InsP3-sensitive Ca2+ store but failed to affect the amplitude of alkalinization-evoked Ca2+ release . Glycyl-L-phenylalanine-beta-naphthylamide (200 microM), a weak hydrophobic base known to permeabilize lysosomes by osmotic swelling, triggered Ca2+ release from internal stores, while application of brefeldin A (10 microM), an antibiotic which disperses the Golgi complex, resulted in a smaller increase in {Ca2+}i . These results suggest that the alkali-evoked calcium release is largely attributable to lysosomes, a conclusion that was confirmed by direct measurements of total calcium content of S2 organelles . Lysosomes and endoplasmic reticulum were the only organelles found to have concentrations of total calcium significantly higher than the cytosol . However, NH4Cl (15 mM) reduced the level of total calcium only in lysosomes . Depletion of acidic Ca2+ stores did not elicit depletion-operated Ca2+ entry . They were refilled upon re-exposure of cells to normal saline ({Ca2+}o = 2 mM), but not by thapsigargin-induced {Ca2+}i elevation in Ca(2+)-free saline. J Otolaryngol, 1999 Oct, 28(5), 260 - 5 New method for packing the external auditory canal, middle ear space, and mastoid cavities after otologic surgery; Wiesenthal AA et al.; Since its introduction in 1945, an absorbable gelatin sponge, Gelfoam, has long been a staple used for packing in otologic surgery . The present method commonly employed at the University of Manitoba teaching hospitals requires that operating room nurses carefully prepare extremely small pieces of both compressed and noncompressed Gelfoam . These pieces are then selectively soaked in an antibiotic solution and carefully placed, one by one, into the appropriate position . We describe a new paste preparation of Gelfoam powder, Thrombostat, acetic acid, and Bacitracin ointment, which can very quickly be injected from a syringe into the operated cavity . Our preliminary study indicates that this preparation reduces operating time, while making the process of packing easier for the surgeon . In addition, it ensures a more evenly packed cavity while still fulfilling the requirements of middle ear packing . Postoperatively, it was found to be easier to debride from the operative cavity in the office, decreasing patient discomfort and procedure time . Reported below is a preliminary clinical patient series report comparing this new method to the old method. Bone Marrow Transplant, 1999 Nov, 24(10), 1089 - 93 Itraconazole oral solution as antifungal prophylaxis in children undergoing stem cell transplantation or intensive chemotherapy for haematological disorders; Foot AB et al.; This was an open study of oral antifungal prophylaxis in 103 neutropenic children aged 0-14 (median 5) years . Most (90%) were undergoing transplantation for haematological conditions (77% allogeneic BMT, 7% autologous BMT, 6% PBSC transplants and 10% chemotherapy alone) . They received 5.0 mg/kg itraconazole/day (in 10 mg/ml cyclodextrin solution) . Where possible, prophylaxis was started at least 7 days before the onset of neutropenia and continued until neutrophil recovery . Of the 103 who entered the study, 47 completed the course of prophylaxis, 27 withdrew because of poor compliance, 19 because of adverse events and 10 for other reasons . Two patients died during the study and another five died within the subsequent 30 days . No proven systemic fungal infections occurred, but 26 patients received i.v . amphotericin for antibiotic-unresponsive pyrexia . One patient received amphotericin for mycologically confirmed oesophageal candidosis . Three patients developed suspected oral candidosis but none was mycologically proven and no treatment was given . Serious adverse events (other than death) occurred in 21 patients, including convulsions (7), suspected drug interactions (6), abdominal pain (4) and constipation (4) . The most common adverse events considered definitely or possibly related to itraconazole were vomiting (12), abnormal liver function (5) and abdominal pain (3) . Tolerability of study medication at end-point was rated as good (55%), moderate (11%), poor (17%) or unacceptable (17%) . Some patients had poor oral intakes due to mucositis . No unexpected problems of safety or tolerability were encountered . We conclude that itraconazole oral solution may be used as antifungal prophylaxis for neutropenic children. Ann Intern Med, 1999 Nov 2, 131(9), 668 - 72 Reversal of iron deficiency anemia after Helicobacter pylori eradication in patients with asymptomatic gastritis; Annibale B et al.; BACKGROUND: Iron deficiency anemia is the most common form of anemia worldwide . Recent studies have suggested an association between Helicobacter pylori infection and iron deficiency . OBJECTIVE: To investigate the effects of eradicating H . pylori with combination antibiotic therapy on iron deficiency anemia in patients with H . pylori-associated gastritis . DESIGN: Case series . SETTING: University hospital . PATIENTS: 30 patients with a long history of iron deficiency anemia in whom H . pylori-associated gastritis was the only pathologic gastrointestinal finding detected . INTERVENTION: Eradication therapy with two antibiotics and discontinuation of iron replacement therapy . MEASUREMENTS: Complete blood count, ferritin levels, and gastroscopy with biopsy to evaluate H . pylori status . RESULTS: At 6 months, 75% of patients had recovered from anemia (P<0.001), ferritin values increased from 5.7+/-0.7 microg/L to 24.5+/-5.2 microg/L (95% CI, 8.85 to 29.97) . After 12 months, 91.7% of patients had recovered from anemia . CONCLUSIONS: Cure of H . pylori infection is associated with reversal of iron dependence and recovery from iron deficiency anemia. Int J Pediatr Otorhinolaryngol, 1999 Oct 5, 49 Suppl 1, S173 - 8 Otitis media in Australian Aboriginal children: an overview; Leach AJ; Remote and rural Australian Aboriginal children achieve lower standards of numeracy and literacy than their non-Aboriginal peers . The reasons are complex, but extraordinarily high rates of conductive hearing loss (> 50%) are, in part, responsible for poor classroom success . In addition to the burden of acute bacterial respiratory illness (highest rates of invasive pneumococcal disease in the literature), chronic disease affects virtually every young child . In the Aboriginal community studied, otitis media commenced within 3 months of birth for all infants, progressed to chronic suppurative otitis media in 60% and did not resolve throughout early childhood . Our findings, supported by mathematical modelling, show that the vicious cycle of endemic chronic otitis media is perpetuated by high carriage rates of multiple species and multiple types of respiratory bacterial pathogens, by high cross-infection rates and thus, by early age of pathogen acquisition and prolonged carriage . Long-term damage to respiratory mucosa, possibly linked to later chronic bronchitis and bronchiectasis, follows a constant series of infections by each of the concurrently held pathogens, without periods of recovery . Overcrowding and poor hygiene promote this vicious cycle . Medical and social options for intervention are limited by poor resources, low expectations for health and a complex biology that includes antibiotic resistant pneumococci. Arch Esp Urol, 1999 Sep, 52(7), 792 - 4 {Squamous carcinoma of the male urethra, its presentation as a scrotal abscess}; Medina Perez M et al.; OBJECTIVE: To report a case of urethral carcinoma presenting as scrotal abscess . METHODS: A 53-year-old man presented with swelling, redness and pain in the scrotum . He had a history of urethral stricture and multiple scrotal abscesses . Incision and drainage were performed and the patient was treated with antibiotics without improvement . Incision and drainage were repeated and a biopsy of the tissue edges of the abscess were performed . RESULTS: Histopathological analysis disclosed a squamous cell carcinoma arising from the urethra . CONCLUSION: Patients with a history of urethral stricture should be followed closely . A scrotal biopsy should be performed in patients who do not improve with antibiotic therapy. Can Fam Physician, 1999 Oct, 45, 2397 - 404 Diagnosing and treating asymptomatic tuberculosis infection; Wang CT; OBJECTIVE: To summarize relevant parts of the guidelines recommended by the Canadian and American Thoracic Societies for diagnosis and management of asymptomatic tuberculosis (TB) infection . QUALITY OF EVIDENCE: The latest guidelines published by the Canadian and American Thoracic Societies were reviewed . Unfortunately, neither of these guidelines state explicitly how recommendations were derived . The references accompanying each set of guidelines, however, suggest that they were developed by extensive literature review of the subject and consensus among expert panels . MAIN MESSAGE: Only higher-risk patients should receive a TB screening test (Mantoux test) to minimize the possibility of false-positive test results . The cutoff points for positive tests vary to reflect the pretest likelihood of TB infection . An induration 5 mm or greater is considered positive in patients at highest risk of TB infection, that is, HIV-infected patients, close contacts of active TB cases, and patients with chest x-ray abnormalities suggestive of previous untreated TB . All other patients are considered positive if they have induration greater than 10 mm according to the Canadian guideline . A 15-mm cutoff point, however, is used for patients without risk factors in the American guideline . All patients with positive Mantoux test results should be considered infected with TB . Infected patients should be offered 6 to 12 months of isoniazid prophylaxis if they have HIV infection, if they have medical conditions that increase the risk of TB activation, or if they are younger than 35 years . CONCLUSIONS: Prophylactic treatment of infected individuals effectively prevents the spread of TB infection . Family physicians, who most often see patients in the asymptomatic stage of TB infection, are uniquely situated to prevent secondary cases of TB by offering appropriate patients prophylactic treatment . Patients should be counseled about the risk and benefit of prophylactic treatment so they give informed consent for it. Hepatogastroenterology, 1999 Sep-Oct, 46(29), 2986 - 90 Severe acute pancreatitis associated with hyperlipidemia: report of two cases and review of the literature in Japan; Ohmoto K et al.; Two cases of severe acute pancreatitis associated with type V hyperlipoproteinemia are reported . A 39-year-old obese woman was hospitalized with continuous severe abdominal pain . The diagnosis was made on the day of admission to our hospital, and treatment using continuous regional arterial infusion of a protease inhibitor and an antibiotic was performed with good results . The other patient was a 35 year-old woman in the 35th week of pregnancy, and a diagnosis of gestational hyperlipidemic pancreatitis was made on the day of onset . She was treated supportively using intravenous hyperalimentation, protease inhibitors, and antibiotics . She recovered from the acute pancreatitis and delivered a healthy term infant . It is difficult to diagnose acute pancreatitis in patients with type V hyperlipoproteinemia, because even when serum amylase levels are high, the value is reduced by high serum triglycerides . Early diagnosis was achieved in both of the present cases, and early intensive therapy was performed, which may be of the utmost importance in saving the life of a patient. Scand J Infect Dis, 1999, 31(5), 475 - 80 Helicobacter pylori infection in Ethiopian children: a cohort study; Lindkvist P et al.; Risk factors for infection with Helicobacter pylori (HP) were investigated in a cohort study of 121 seronegative children in Ethiopia aged 2-4 y, who had previously participated in a case-control study . Blood samples were drawn at inclusion in the cohort study and again after 12 and 30 months . At 12 months the parents were also interviewed about putative risk factors for infection, using a structured questionnaire . Analyses were made by comparing risk factors in seropositive and seronegative children . The seroconversion rate during the first year was 31% (27/87) and during the following 18 months 34% (17/50; corresponding to an annual incidence of 24%) . After a period of 30 months, 58% (14/24) of the children who were 24-29 months old at inclusion in the study had seroconverted, compared with 40% (4/10) of those who were 30-35 months old, 73% (22/30) of those who were 36-41 months old and 31% (4/13) of those who were 42 months old or more . These results indicate that peak age for HP infection is below 6 y in this cohort in Ethiopia, and might also reflect a pattern of repeated seroconversion and sero-reversion in early childhood . Independent predictors of HP-seroconversion were the variables 'drinking-water', comparing water from a well with water from rivers or pipes (RR = 1.46, 95% CI 1.0-2.15) and 'antibiotic treatment' (RR = 1.84, 95% CI 1.16-2.92). An Esp Pediatr, 1999 Sep, 51(3), 235 - 40 {Neutropenia as early manifestation of X-linked agammaglobulinemia . Report on 4 patients}; Plo Rodriguez F et al.; OBJECTIVE: The aim of this study was to determine the frequency of neutropenia associated to X-linked agammaglobulinemia (XLA) and to describe the clinical characteristics of the children diagnosed in our unit . PATIENTS AND METHODS: A revision of the medical records registered in our unit during a 28 year period (1970-1998) according to the diagnostic criteria of XLA was performed . We included in the study group those patients that expressed a neutropenia . Immunological studies by standard techniques were performed . RESULTS: Of the 37 patients fulfilling the diagnostic criteria of XLA, 4 cases had experienced episodes of neutropenia (10.81%) . The frequency of neutropenia within the group without familiar antecedents was 15% and within the group with familiar antecedents 5.88% . In all cases, the neutropenia was present during a serious acute infectious disease . The neutropenia was transient and resolved promptly after the onset of antibiotic therapy in all patients . None of the patients experienced neutropenia while under therapy with intravenous gammaglobulin . CONCLUSIONS: The association of XLA and neutropenia seems to be sufficiently frequent as to include it in the differential diagnosis of neutropenia during infancy . It is important to consider a primary immunodeficiency diagnosis when a child presents neutropenia and a serious acute infectious disease . Quantification of serum immunoglobulin levels and enumeration of lymphocyte subpopulations can lead to an early diagnosis. Rev Chir Orthop Reparatrice Appar Mot, 1999 Oct, 85(6), 640 - 5 {Traction-mobilization in 2-stage treatment of infected total knee prosthesis . Apropos of 12 cases}; Lecuire F et al.; INTRODUCTION: A two stages reimplantation is advised by most authors in salvage of infected total knee arthroplasty . This treatment is more difficult, but seems more successful in controlling infection . It set the problem of the attitude between the two operative stages: an antibiotic cement spacer is usually used, but articular mobilization is not possible, except with an articulating spacer . MATERIAL AND METHODS: Since 1989, we use traction-mobilisation between the two operative stages, with mobilization under traction up to 50 degrees, and on edge of bed up to 70-90 degrees, till the reimplantation . We used this method on 12 cases of chronic infection in total knee arthroplasty . The reimplantation was done 34 to 47 days later . The reimplantation was more easy and more comfortable in approach and exposition, and post operative mobilisation easier . RESULTS: We did not have any recurrence of infection in this patients, but the follow up is too short for some of them . One prosthesis was removed for mechanical failure . The mean range of motion is 86 degrees at two months, 96 degrees at one year . DISCUSSION: The antibiotic cement spacer presents the disadvantage of leaving material in a potentially infected environment . It does not allow mobilisation, except using an articulating spacer . Traction-mobilisation keep articular flexion, allows mobilization, and does not leave any material in articulation . But this method has the disadvantage of requiring an hospital care between the two stages: that is reasonable if the delay is short . CONCLUSION: Traction mobilization seems to be an alternative to cement spacer . It makes the reimplantation easier, facilitates post operative recovery of mobility, and does not seem to increase recurrence of infection. Nutrition, 1999 Nov-Dec, 15(11-12), 968 - 71 The Second International Scientific Symposium on Tea & Human Health, September 14th, 1998; Phipps RP; It is fascinating to reflect that tea, the world's most widely consumed beverage next to water, began in Chinese antiquity not as a beverage but as a medicine . Several millennia later, modern scientific research is confirming that such ancient intuition has relevance to contemporary health concerns including cancer, heart disease, and antibiotic-resistant bacteria . The timeliness of this message as the 20th century concludes could not be better . The importance of a balanced diet has been recognized and studied throughout this century . The concept that we are what we eat has become a part of popular culture . If tea's health message, which future scientific research will continue to articulate, is creatively presented and embraces the romantic image that tea affords the industry, there is every reason to expect a rebirth and reinvigoration of this ancient beverage as a new millennium commences. Structure Fold Des, 1999 Nov 15, 7(11), 1365 - 72 Crystal structure of colicin E3 immunity protein: an inhibitor of a ribosome-inactivating RNase; Li C et al.; BACKGROUND: Colicins are antibiotic-like proteins of Escherichia coli that kill related strains . Colicin E3 acts as an RNase that specifically cleaves 16S rRNA, thereby inactivating the ribosomes in the infected cell . The producing organism is protected against colicin E3 by a specific inhibitor, the immunity protein Im3, which forms a tight 1:1 complex with colicin E3 and renders it inactive . Crystallographic studies on colicin E3 and Im3 have been undertaken to unravel the structural basis for the ribonucleolytic activity and its inhibition . RESULTS: The crystal structure of Im3 has been determined to a resolution of 1.8 A . The structure consists of a four-standard antiparallel beta sheet flanked by three alpha helices on one side of the sheet . Thr7, Phe9, Phe16 and Phe74 form a hydrophobic cluster on the surface of the protein in the vicinity of Cys47 . This cluster is part of a putative binding pocket which also includes nine polar residues . CONCLUSIONS: The putative binding pocket of Im3 is the probable site of interaction with colicin E3 . The six acidic residues in the pocket may interact with some of the numerous basic residues of colicin E3 . The involvement of hydrophobic moieties in the binding is consistent with the observation that the tight complex can only be dissociated by denaturation . The structure of Im3 resembles those of certain nucleic acid binding proteins, in particular domain II of topoisomerase I and RNA-binding proteins that contain the ribonucleoprotein (RNP) sequence motif . This observation suggests that Im3 has a nucleic acid binding function in addition to binding colicin E3. JPEN J Parenter Enteral Nutr, 1999 Nov-Dec, 23(6), 363 - 5 Tunneled right atrial catheter infection presenting as renal failure; Yared G et al.; We report two cases of progressive renal failure secondary to membranoproliferative glomerulonephritis associated with subclinical septicemia from a tunneled right atrial catheter used for home parenteral nutrition administration . Although the occurrence of line infection and septicemia is a common complication of central venous catheters, a review of the literature reveals only one case report of renal failure secondary to an infected implanted central venous device . Both patients presented with azotemia and had biopsy-proven membranoproliferative glomerulonephritis, accompanied by leukocytoclastic vasculitis . In both cases, removal of the right atrial catheter and prolonged antibiotic therapy was effective in resolving the ongoing infection and resulted in marked improvement in renal function . A high index of suspicion for catheter sepsis should be maintained in patients with tunneled right atrial catheters presenting with subacute renal failure. J Chromatogr B Biomed Sci Appl, 1999 Oct 29, 734(1), 7 - 14 Determination of flumequine and doxycycline in milk by a simple thin-layer chromatographic method; Choma I et al.; Tetracycline and quinolone antibiotics have for many years served as important classes of veterinary drugs . Two representatives of both classes: doxycycline from tetracyclines and flumequine from quinolones are often administered together . When the withdrawal periods are not obeyed, the antibiotic residues may be present in edible products, e.g., in meat, eggs or milk . In the present paper a simple thin-layer chromatography (TLC) screening method is established for determining these drugs in milk . Only two developments of the plate with concentrating zone are needed: one as a clean-up procedure, the other as a proper analysis . The spots were detected both by UV lamp with dual wavelength (254 and 366 nm) and by densitometry. Rev Med Interne, 1999 Oct, 20(10), 869 - 74 {Systemic reaction induced my minocycline treatment: a report of four patients and a review of the literature}; Piette AM et al.; We report four cases of the side effects of minocycline seen during the last two years in our department . There was one case of drug-related lupus and three cases of hypersensitivity reactions, including one eosinophilic pneumopathy with pericarditis, one nephropathy and one severe, pseudo-infectious episode of high fever, rash, lympadenopathy, hepatitis and eosinophilia . Minocycline is a tetracycline agent widely used for acne therapy in France and all over the world . During the last few years, there has been an increasing number of reports concerning systemic adverse reactions to minocycline, with on the one hand auto-immune disorders (lupus, autoimmune hepatitis, vascularitis with ANCA), occurring after a prolonged course of therapy and reported recently in the last few years, and on the other hand, hypersensitivity reactions (eosinophilic pneumopathies, hepatitis, nephropathies, myocarditis, serum sickness or pseudo-infectious reactions), occurring precociously in the course of therapy, and potentially severe . Although these side effects are uncommon in the context of the high number of patients who have been prescribed the drug, the first-line antibiotic therapy in acne must probably be reconsidered. Dig Dis Sci, 1999 Nov, 44(11), 2295 - 302 H . pylori-negative duodenal ulcer prevalence and causes in 774 patients; Gisbert JP et al.; The prevalence of H . pylori infection has been reported to be very high in duodenal ulcer (DU) disease, but the precise frequency and causes of H . pylori-negative DU are not well known . In some geographical regions, however, a relatively low prevalence of the infection has been described . Our aim was to study the frequency and causes of H . pylori-negative DU and to evaluate whether empirical H . pylori eradication therapy without confirmation of the infection is justified . In all 774 consecutive patients with an endoscopic diagnosis of DU were studied prospectively . Exclusion criteria were associated diseases and previous gastric surgery . The use of NSAIDs, antibiotics (during the last month), and proton pump inhibitors (during the last month) was evaluated by means of a specific questionnaire . At endoscopy, two biopsies from both antrum and corpus were obtained in all 774 patients for histologic study (H&E stain) . One sample from the antrum for rapid urease test, one sample each from the antrum and corpus for culture, and two duodenal biopsies for histologic study were also obtained in the first 307 patients . A {13C} urea breath test was carried out in the remaining 467 patients . Patients were considered infected if any of the diagnostic tests were positive and noninfected when all tests performed were negative . Age (mean +/- SD) was 46+/-12 years, 70% were males . NSAID, antibiotic, and proton pump inhibitor use was described, respectively, in 8.9%, 5.8%, and 6.3% of the cases . H . pylori infection was demonstrated, overall, in 95.3% (95% CI: 93.6-96.6%) of the patients . H . pylori prevalence increased up to 99.1% (98.1-99.6%) if patients taking NSAIDs and/or antibiotics were excluded . Among the 36 H . pylori-negative patients, 20 (55%) were taking NSAIDs, 9 (25%) were taking antibiotics, and 1 (3%) both of them . Therefore, in only 6/774 patients (0.8%) could DU disease be considered truly "idiopathic." Differences were demonstrated between H . pylori-positive and -negative patients (univariate study; chi2) with regard to NSAID intake (7% vs 58%; P < 0.0001) and previous antibiotic use (5% vs 28%; P < 0.0001) . In the multivariate analysis (logistic regression), NSAID use (OR: 0.06; CI: 0.03-0.13; P < 0.001) and antibiotic use (OR: 0.23; CI: 0.09-0.59; P < 0.01) were the only variables that correlated with H . pylori infection . The most important factors associated with H . pylori-negative DU are NSAIDs and prior antibiotic use, and if these agents are excluded, the prevalence of infection in our area is as high as 99% . Therefore, in DU patients not taking NSAIDs and living in areas where previous studies have shown the prevalence of the infection in DU disease to be very close to 100%, empirical H . pylori eradication therapy without confirmation of the infection may be justified. Int J Pharm, 1999 Dec 1, 192(1), 63 - 75 The use of MTDSC to assess the amorphous phase content of a micronized drug substance; Guinot S et al.; Mechanical treatments such as grinding, milling or micronization applied to crystalline drug substances may induce changes such as the occurrence of crystal defects and/or amorphous regions . These changes are likely to affect the chemical and physical properties of the material as well as the corresponding drug product performances . Various analytical techniques such as standard differential scanning calorimetry, isothermal and solution microcalorimetry as well as dynamic vapour sorption can be used to characterise and possibly quantify the amorphous phase content of these materials . These techniques have been applied for the development of analytical methods based on temperature- or solvent-induced (including water) recrystallization of the amorphous phase in semi-crystalline drug substances and excipients and have sometimes allowed for detecting low amounts of amorphous phase . We have developed an alternative MTDSC method for the quantitation of the amorphous content in samples of a micronized drug substance co-crystal (form A), an antibiotic drug substance which does not recrystallize even when exposed to temperature or solvent vapours . This is performed through measurement of the heat capacity jump associated with the amorphous phase glass transition . The MTDSC parameters and experimental conditions were optimised for this system . The amorphous content calibration curve was established using pure crystalline and amorphous drug substance samples and their known mixtures . Limits of detection and quantification of 0.9 and 3.0% (w/w) respectively were obtained for specimen mass less than 5 mg. Nippon Geka Gakkai Zasshi, 1999 Oct, 100(10), 683 - 8 {Shock and acute organ dysfunction}; Murata A et al.; Multiple trauma, hemorrhage, and sepsis may produce various kinds of shock, and such a host as shock could not be controlled and may easily fall into multiple organ dysfunction . Although those mechanisms on the pathogenesis of these sequential inflammatory responses have been clarified recently, the clinical outcome of such patients suffering from severe sepsis and multiple organ dysfunction is still very low . This inflammatory response against the insult shows a sequential manner; cardiovascular system failure, renal system failure, respiratory system failure, central nervous system failure, and finally, hepatic failure . However, the host response to the insult is a kind of defense against the invasion, and the clinical goal might be to stabilize hemodynamic system, metabolic system, and immunologic system . To achieve hemodynamic homeostasis, we use catecholamines and blood transfusion to improve the oxygen supply to important organs and enhance tissue repair . For metabolic homeostasis, early administration of hyperalimentation may be needed, either parenterally or enterally . Enteral feeding may also provided a route for bacterial translocation . To achieve immunologic homeostasis, prophylactic antibiotic administration and metabolic support may be required and should also protect against infection as a secondary invasion . This review explains these mechanisms in terms of the relationship between shock and organ dysfunction and the general features of clinical management. Australas J Dermatol, 1999 Nov, 40(4), 204 - 7 Pustular vasculitis of the hands; Hall AP et al.; A case of pustular vasculitis of the hands with evidence of systemic involvement is described . A 64-year-old woman presented with a 2-day history of large, tense bullae arranged symmetrically over the dorsum of the three radial digits and extending on to the radial aspect of the dorsum of each hand . The bullae caused some discomfort and prevented normal use of her hands . There was no response to antibiotic therapy initiated prior to referral to hospital . Initial investigations revealed a raised white cell count with a neutrophilia, a raised erythrocyte sedimentation rate and a raised C-reactive protein . Abnormalities of liver function were detected . Aspirates from the bullae and blood cultures were sterile . The histology of debrided tissue demonstrated a florid neutrophilic dermal infiltrate with many blood vessels associated with prominent fibrin . A diagnosis of pustular vasculitis of the hands was made . The bullae were surgically debrided and treatment with oral corticosteroids was started . Two days after commencement of oral prednisolone, a crusted pustule appeared on her upper cutaneous lip . There was rapid resolution of both the vasculitis of the hands and the pustule on her upper lip following an increase in the dose of oral prednisolone . The patient was discharged on the seventeenth day following admission. Mol Pharmacol, 1999 Dec, 56(6), 1329 - 39 The orphan human pregnane X receptor mediates the transcriptional activation of CYP3A4 by rifampicin through a distal enhancer module; Goodwin B et al.; Cytochrome P-450 3A4 (CYP3A4), the predominant cytochrome P-450 expressed in adult human liver, is subject to transcriptional induction by a variety of structurally unrelated xenobiotics, including the antibiotic rifampicin . The molecular mechanisms underlying this phenomenon are poorly understood . We transfected a human liver-derived cell line (HepG2) with various CYP3A4-luciferase reporter gene constructs containing a nested set of 5'-deletions of the CYP3A4 5'-flanking region . Rifampicin-inducible transcription of the reporter gene was observed only with the longest construct, which encompassed bases -13000 to +53 of CYP3A4 (3-fold induction) . The responsive region was functional regardless of its position or orientation relative to the proximal promoter of CYP3A4 and was capable of conferring rifampicin-inducible expression on a heterologous promoter . Further deletion mutants localized the induction to bases -7836 to -7607 . In vitro DNase I footprint analysis of this region revealed four protected sites (FP1, FP2, FP3, and FP4) . Two of these sites, FP3 (bases -7738 to -7715) and FP4 (bases -7698 to -7682), overlapped binding motifs for the orphan human pregnane X receptor (hPXR) . Cotransfection of responsive constructs with a hPXR expression vector substantially increased the rifampicin-inducibility to approximately 50-fold . In addition, the rifampicin-responsive constructs were strongly activated by a range of CYP3A inducers . Finally, we demonstrate cooperativity between elements within the distal enhancer region and cis-acting elements in the proximal promoter of CYP3A4 . Our results provide evidence for the existence of a potent enhancer module, 8 kb distal to the transcription start point, which mediates the transcriptional induction of CYP3A4 by activators of hPXR. Infect Immun, 1999 Dec, 67(12), 6583 - 90 Escherichia coli msbB gene as a virulence factor and a therapeutic target; Somerville JE Jr et al.; A mutation in the msbB gene of Escherichia coli results in the synthesis of E . coli lipopolysaccharide (LPS) that lacks the myristic acid moiety of lipid A . Although such mutant E . coli cells and their purified LPS have a greatly reduced ability to stimulate human immune cells, a minor reduction in the mouse inflammatory response is observed . When the msbB mutation is transferred into a clinical isolate of E . coli, there is a significant loss in virulence, as assessed by lethality in BALB/c mice . When a cloned msbB gene is provided to functionally complement the msbB mutant, virulence returns, providing direct evidence that the msbB gene product is an important virulence factor in a murine model of E . coli pathogenicity . In the genetic background of the clinical E . coli isolate, the msbB mutation also results in filamentation of the cells at 37 degrees C but not at 30 degrees C, a reduction in the level of the K1 capsule, an increase in the level of complement C3 deposition, and an increase in both opsonic and nonopsonic phagocytosis of the msbB mutant, phenotypes that can help to explain the loss in virulence . The demonstration that the inhibition of msbB gene function reduces the virulence of E . coli in a mouse infection model warrants further investigation of the msbB gene product as a novel target for antibiotic therapy. Dig Surg, 1999, 16(5), 420 - 4 Complicated diverticulitis of the sigmoid: a prospective study concerning primary resection with secure primary anastomosis; Hoemke M et al.; BACKGROUND: The Hartmann procedure remains the standard concerning the surgical treatment of acute complicated sigmoid diverticulitis . The aim of this study was to prove the possibility of performing a secure primary anastomosis without colostomy in patients with complicated acute diverticulitis . METHODS: From June 1988 to October 1996, 113 patients suffering from acute complicated sigmoid diverticulitis were included in this prospective study . Within 24-48 h of hospital admission, when symptoms of the illness persisted despite the use of antibiotic therapy, the patients underwent primary resection of the sigmoid . In all patients primary anastomosis was performed, using CEEA staplers, avoiding colostomy and intraoperative colon irrigation . RESULTS: During the observation period of 19 days, there was no anastomotic leakage found either by radiological methods or clinical parameters . Two patients died of early septic complications, 1 of therapy-resistant endocarditis . CONCLUSION: The results of this study demonstrate the safety of primary anastomosis after primary resection of the sigmoid under antibiotic conditions, avoiding the disadvantages associated with two-stage procedures . Copyright Arch Dermatol, 1999 Nov, 135(11), 1317 - 26 Solitary erythema migrans in Georgia and South Carolina; Felz MW et al.; OBJECTIVE: To evaluate the incidence of Borrelia burgdorferi infection in humans with erythema migrans (EM) in 2 southeastern states . DESIGN: Prospective case series . SETTING: Family medicine practice at academic center . PATIENTS: Twenty-three patients with solitary EM lesions meeting Centers for Disease Control and Prevention (CDC) criteria for Lyme disease . INTERVENTIONS: Patients underwent clinical and serologic evaluation for evidence of B burgdorferi infection . All lesions underwent photography, biopsy, culture and histopathologic and polymerase chain reaction analysis for B burgdorferi infection . Patients were treated with doxycycline hyclate and followed up clinically and serologically . MAIN OUTCOME MEASURES: Disappearance of EM lesions and associated clinical symptoms in response to antibiotic therapy; short-term and follow-up serologic assays for diagnostic antibody; growth of spirochetes from tissue biopsy specimens in Barbour-Stoenner-Kelly II media; special histopathologic stains of tissue for spirochetes; and polymerase chain reaction assays of tissue biopsy specimens for established DNA sequences of B burgdorferi . RESULTS: The EM lesions ranged from 5 to 20 cm (average, 9.6 cm) . Five patients (22%) had mild systemic symptoms . All lesions and associated symptoms resolved with antibiotic therapy . Overall, 7 patients (30%) had some evidence of B burgdorferi infection . Cultures from 1 patient (4%) yielded spirochetes, characterized as Borrelia garinii, a European strain not known to occur in the United States; 3 patients (13%) demonstrated spirochetallike forms on special histologic stains; 5 patients (22%) had positive polymerase chain reaction findings with primers for flagellin DNA sequences; and 2 patients (9%) were seropositive for B burgdorferi infection using recommended 2-step CDC methods . No late clinical sequelae were observed after treatment . CONCLUSIONS: The EM lesions we observed are consistent with early Lyme disease occurring elsewhere, but laboratory confirmation of B burgdorferi infection is lacking in at least 16 cases (70%) analyzed using available methods . Genetically variable strains of B burgdorferi, alternative Borrelia species, or novel, uncharacterized infectious agents may account for most of the observed EM lesions. J Biol Chem, 1999 Nov 26, 274(48), 34072 - 82 Regulation of the biosynthesis of N-acetylglucosaminylpyrophosphoryldolichol, feedback and product inhibition; Kean EL et al.; The assembly of the core oligosaccharide region of asparagine-linked glycoproteins proceeds by means of the dolichol pathway . The first step of this pathway, the reaction of dolichol phosphate with UDP-GlcNAc to form N-acetylglucosaminylpyrophosphoryldolichol (GlcNAc-P-P-dolichol), is under investigation as a possible site of metabolic regulation . This report describes feedback inhibition of this reaction by the second intermediate of the pathway, N-acetylglucosaminyl-N-acetylglucosaminylpyrophosphoryldolichol (GlcNAc-GlcNAc-P-P-dolichol), and product inhibition by GlcNAc-P-P-dolichol itself . These influences were revealed when the reactions were carried out in the presence of showdomycin, a nucleoside antibiotic, present at concentrations that block the de novo formation of GlcNAc-GlcNAc-P-P-dolichol but not that of GlcNAc-P-P-dolichol . The apparent K(i) values for GlcNAc-P-P-dolichol and GlcNAc-GlcNAc-P-P-dolichol under basal conditions were 4.4 and 2.8 microM, respectively . Inhibition was also observed under conditions where mannosyl-P-dolichol (Man-P-dol) stimulated the biosynthesis of GlcNAc-P-P-dolichol; the apparent K(i) values for GlcNAc-P-P-dolichol and GlcNAc-GlcNAc-P-P-dolichol were 2.2 and 11 microM, respectively . Kinetic analysis of the types of inhibition indicated competitive inhibition by GlcNAc-P-P-dolichol toward the substrate UDP-GlcNAc and non-competitive inhibition toward dolichol phosphate . Inhibition by GlcNAc-GlcNAc-P-P-dolichol was uncompetitive toward UDP-GlcNAc and competitive toward dolichol phosphate . A model is presented for the kinetic mechanism of the synthesis of GlcNAc-P-P-dolichol . GlcNAc-P-P-dolichol also exerts a stimulatory effect on the biosynthesis of Man-P-dol, i.e . a reciprocal relationship to that previously observed between these two intermediates of the dolichol pathway . This network of inhibitory and stimulatory influences may be aspects of metabolic control of the pathway and thus of glycoprotein biosynthesis in general. Am J Gastroenterol, 1999 Nov, 94(11), 3181 - 3 Successful recovery of H . pylori from rapid urease tests (CLO tests); Windsor HM et al.; OBJECTIVE: Culture of Helicobacter pylori (H . pylori) and the determination of its antibiotic susceptibility is of increasing importance with the rise in numbers of antibiotic-resistant strains . The aim of this study was to determine whether H . pylori could be successfully isolated from antral biopsies used in Rapid Urease Tests (CLOtests) in clinical practice . METHODS: Antral biopsies from patients undergoing endoscopy were inserted into the gel of CLOtests to determine the H . pylori status of the patients . If the CLOtest was positive at the end of the endoscopy session, it was kept at ambient temperature until processed . In the laboratory, biopsies were removed from the gel and cultured on selective and nonselective media . In an attempt to enhance the recovery rate of H . pylori, a subset of positive CLOtests were kept at 4 degrees C from the time that the color change was noted until the removal of the biopsy . RESULTS: One hundred and forty-one positive CLOtests were studied at times between 1 h and 6 h postendoscopy . Culture success was 93% in the 1st hour but fell off sharply after 2 h (p < 0.001) . Isolation was also improved if positive CLOtests were stored at 4 degrees C and plated out within 4 h (p < 0.001) . CONCLUSIONS: H . pylori can be successfully cultured from biopsies in CLOtests kept at room temperature within 2 h or within 4 h if kept at 4 degrees C . Thus the antral biopsy in the CLOtest can be usefully retrieved when, in the light of the CLOtest result, the physician wishes to obtain both culture and antibiotic sensitivity results. Proc AMIA Symp . 1999;:696-700. Development of a Web-based clinical information system for surveillance of multiresistant organisms and nosocomial infections; Bouam S et al.; To optimize the surveillance and control of infections at our hospital, we have developed a clinical information system (CIS) linked to a server providing three kinds of patient-oriented data reports: 1/an automated alert for multiresistant bacteria from a data-driven mechanism; 2/the relevant data for surveillance of hospital-acquired infections; 3/some clinical and educational data for antibiotic prescribing . The new CIS is a Web-based one and now integrated to the Hospital Information System (HIS) . In a close collaboration with the experts, we have, first, specified the relevant information for each report . Then, we have linked the system to those HIS DBs containing this information . Finally we have developed a well-secured intranet Web site, on which the concerned practitioners can instantaneously review the latest alerts and/or the summarized/detailed reports . The preliminary results shows that the system is reliable in medical practice and the response time is satisfying. Ann Ital Med Int, 1999 Jul-Sep, 14(3), 202 - 4 Acute cholecystitis and pancreatitis in a patient with biliary sludge associated with the use of ceftriaxone: a rare but potentially severe complication; Famularo G et al.; Ceftriaxone may precipitate in the bile leading to the formation of biliary sludge . Biliary complications, even serious ones, have rarely been described in patients treated with this antibiotic . A 71-year-old woman presented to the emergency room with biliary sludge complicated by acute cholecystitis and pancreatitis after 10 days of treatment with ceftriaxone (2 g, 40 mg/kg per day) . There had been no evidence of sludge or gallstones on a transabdominal ultrasonography performed 6 months earlier . The patient underwent open cholecystectomy and recovered fully . Ceftriaxone should be kept in mind as a potential cause of biliary sludge . In most cases, resolution of sludge occurs after interruption of ceftriaxone . Young subjects, patients receiving a prolonged course and a daily dose > or = 40 mg/kg, and subjects with impaired gallbladder emptying have a greater risk of ceftriaxone-associated sludge . Cholecystectomy is the definitive therapy for severe complications. J Clin Microbiol, 1999 Dec, 37(12), 4048 - 50 Comparison of a nonradiometric liquid-medium method (MB REDOX) with the BACTEC system for growth and identification of mycobacteria in clinical specimens; Liu YC et al.; Early identification of tuberculosis in the clinical setting is of great importance in order for specific therapy to be swiftly initiated . MB REDOX (Heipha Diagnostika), a growth-based medium without radioactive materials, was evaluated and was compared to the BACTEC system for detection of mycobacteria, including the Mycobacterium tuberculosis complex and atypical mycobacteria . MB REDOX consists of a Kirchner medium enriched with growth-promoting additives, antibiotic compounds, and a redox indicator which can be monitored to detect growth of mycobacteria with the naked eye . MB REDOX only detects growth and cannot differentiate the M . tuberculosis complex (M . tuberculosis, M . bovis, and M . africanum) from other species of Mycobacterium . Therefore, PCR-restriction fragment length polymorphism analysis (PRA) was used in this investigation to identify to the species level organisms showing positive growth with MB REDOX . Our data demonstrate the usefulness of MB REDOX for the detection of mycobacteria in clinical specimens . The rate of detection of M . tuberculosis complex with MB REDOX (84 . 3%) was higher than that with the BACTEC system (68.6%) . When combined with PRA for species identification, MB REDOX is easy to perform and is suited to most clinical laboratory settings for the detection and identification of mycobacteria. J Clin Microbiol, 1999 Dec, 37(12), 3946 - 51 Microdilution susceptibility testing of amphotericin B, itraconazole, and voriconazole against clinical isolates of Aspergillus and Fusarium species; Arikan S et al.; We compared the activities of amphotericin B, itraconazole, and voriconazole against clinical Aspergillus (n = 82) and Fusarium (n = 22) isolates by a microdilution method adopted from the National Committee for Clinical Laboratory Standards (NCCLS-M27A) . RPMI 1640 (RPMI), RPMI 1640 supplemented to 2% glucose (RPMI-2), and antibiotic medium 3 supplemented to 2% glucose (AM3) were used as test media . MICs were determined after 24, 48, and 72 h . A narrow range of amphotericin B MICs was observed for Aspergillus isolates, with minor variations among species . MICs for Fusarium isolates were higher than those for Aspergillus isolates . MICs of itraconazole were prominently high for two previously defined itraconazole-resistant Aspergillus fumigatus isolates and Fusarium solani . Voriconazole showed good in vitro activity against itraconazole-resistant isolates, but the MICs of voriconazole for F . solani were high . RPMI was the most efficient medium for detection of itraconazole-resistant isolates, followed by RPMI-2 . While the significance remains unclear, AM3 lowered the MICs, particularly those of amphotericin B. Mikrobiol Z, 1999 Jul-Aug, 61(4), 22 - 7 {The isolation and characteristics of mutant Streptomyces globisporus 1912 defective for landomycin E biosynthesis}; Matseliukh BP et al.; Mutants defective in the synthesis of antitumor angucycline antibiotic landomycin E were obtained from the asporogenic and initial sporulating strains of Streptomyces globisporus 1912 by means of nitrosoguanidine treatment and UV-irradiation of the mycelium fragments and protoplasts . The frequency of induction of LanE mutants in the protoplasts of strain 3-1 was 3 times higher (0.55%) as compared to mycelium fragments (0.17%) . After mutagenic treatment of spores the yield of such mutants was lower (0.044-0.071%) . It was shown, that izoflavon daidzein was an effective and necessary regulator of the landomycin E synthesis . The collection of 53 landomycin defective mutants was divided into three groups on the basis of their ability to produce antibiotic and regulator: 1) mutants LanE-Dai+ (45 strains), which did not synthesize landomycin E, but produced daidzein; 2) mutants LanE+Dai- (4 strains), which could restore landomycin E synthesis after adding exogenic daidzein to the medium and 3) mutants LanE- Dai- which did not synthesize landomycin E in the presence of daidzein. Int J Antimicrob Agents, 1999 Sep, 13(1), 41 - 6 Effects of aztreonam on natural immunity in mice; Ortega E et al.; The influence of the dose and the duration of treatment with aztreonam, a monocyclic beta-lactam antibiotic, on the natural immune response of mice has been investigated . The results show the effects induced by the antibiotic on several immune parameters were affected by the duration of treatment . Thus, treatment with 28 mg/kg per day of aztreonam over 14 days increased every immune parameter tested, while treatment with 57 mg/kg per day of aztreonam for 7 days only enhanced the natural killer (NK) activity of splenocytes . Since aztreonam does not apparently impair the innate immune response, it might be a suitable therapy for the treatment of patients who are immunosuppressed. Vet Clin North Am Small Anim Pract, 1999 Nov, 29(6), 1291 - 301 Mycobacterial dermatitis; Lemarie SL; Mycobacterial skin disease in cats associated with atypical mycobacteria is an uncommon disease in small animal practice, and the disease is rarely encountered in dogs . A mycobacterial etiology should be considered in cases of chronic nodular dermatitis, draining tracts, and panniculitis . Cats and dogs affected with atypical mycobacterial infections are usually otherwise healthy, and systemic illness is unusual . In most cases, a diagnosis is made based on histopathological findings and growth of a causative organism . Group IV atypical mycobacteria can usually be grown following submission of affected tissue . Treatment should be based on antibiotic sensitivity test results . Treatment is prolonged and is unsuccessful in many cases . In cases of feline leprosy and canine leproid granuloma syndrome, organisms are difficult if not impossible to grow, and clinical and histopathological findings should be used to make a diagnosis . Spontaneous resolution of disease has been reported in atypical mycobacteriosis, feline leprosy, and canine leproid granuloma syndrome. Vet Clin North Am Small Anim Pract, 1999 Nov, 29(6), 1281 - 90 Feline herpesvirus 1-associated facial and nasal dermatitis and stomatitis in domestic cats; Hargis AM et al.; Feline herpesvirus-associated dermatitis has rarely been reported . Recently we documented a unique ulcerative and often persistent facial dermatitis or stomatitis syndrome associated with feline herpesvirus 1 . We believe this syndrome is relatively common, with the 10 cases in our series diagnosed between 1996 and 1997 . The syndrome is associated with epithelial cell necrosis, eosinophilic inflammation, and intraepithelial herpesvirus inclusion bodies . The prevalence of eosinophilic inflammation and low number of inclusion bodies may lead to the misdiagnosis of allergic dermatitis or a lesion within the eosinophilic granuloma complex group of disorders . Feline herpesvirus 1 can be identified in lesional tissue by PCR methodology . Most of our cases developed under circumstances suggesting reactivation of latent herpesvirus infection, and previous glucocorticoid therapy or stress from overcrowding may have played a role in lesion development . Cats with ulcerative dermatitis, especially of the face and nose, and cats with stomatitis should be evaluated for the presence of feline herpesvirus . Treatment options include surgical excision, topical or systemic antibiotic therapy to treat secondary bacterial infection, and oral alpha interferon. Nurs Manage, 1999 Jun, 30(6), 44 - 9; quiz 50 VRE & MRSA . Putting bad bugs out of business; Sheff B; Are you unwittingly contributing to the spread of these dangerous antibiotic-resistant organisms? Learn to protect your patients--and yourself--from out-of-control infections. Ann Acad Med Singapore, 1999 Jul, 28(4), 476 - 80 A prospective study of infections with atypical pneumonia organisms in acute exacerbations of chronic bronchitis; Goh SK et al.; The objective of this paper was to study the incidence of 6 atypical pneumonia pathogens or atypical organisms in local patients admitted for acute exacerbation of chronic bronchitis . This is a prospective observational study . Over a period of 3 years (1995 to 1997), 90 patients admitted to a large general hospital in Singapore for acute exacerbation of chronic bronchitis were tested for the following infections: Legionella, Mycoplasma, Chlamydia, influenza A, influenza B and parainfluenza viruses, using paired serological examination . The antibiotic prescribing pattern by the attending physicians in these cases were also examined . Positive serologies were found in 31 patients (34%), of whom 26 patients (28%) had viral infections . The most common organism was influenza A with 18 positive serologies (20%) . Five patients were tested positive for Legionella . There was no evidence of acute infections by Mycoplasma pneumoniae or chlamydia using serological tests. J Clin Oncol . 1999 Apr;17(4):1227. Effect of CD34(+) cell dose on resource utilization in patients after high-dose chemotherapy with peripheral-blood stem-cell support; Schulman KA et al.; PURPOSE: The mean time to neutrophil and platelet recovery for patients receiving high-dose chemotherapy (HDC) supported with peripheral-blood stem cells (PBSCs) is related to the dose of CD34(+) cells infused . The effect of cell dose on resource utilization after transplantation has not been previously reported . MATERIALS AND METHODS: We assessed CD34(+) cell dose and resource utilization for 1,317 patients undergoing transplantation with PBSCs from April 1991 to June 1997 . PBSCs were collected after mobilization with chemotherapy and recombinant human granulocyte colony-stimulating factor (rhG-CSF) . Daily measurement of the CD34(+) content of the PBSC collection was performed by a central laboratory using a single CD34(+) analysis technique . Resource utilization included engraftment parameters, length of stay, and transfusion requirements for 100 days posttransplantation . Analysis included descriptive statistics and multiple regression . RESULTS: Mean patient age was 47 years, and 86% of patients were female . Median cell dose was 3.6 x 10(6)/kg and 13.2 x 10(6)/kg for patients receiving less than 5.0 x 10(6) CD34(+) cells/kg and 5.0 x 10(6) or more CD34(+) cells/kg, respectively . Patients receiving less than 5 . 0 x 10(6) CD34(+) cells/kg were more likely to have metastatic breast cancer or non-Hodgkin's lymphoma and required more platelet and RBC transfusions, 3.3 more hospital days, and increased antibiotic and antifungal use . In univariate analysis, the cost of care was $41,516 (+/-$20,876 SD) and $32,382 (+/-$16,353 SD) for patients with less than 5.0 x 10(6) CD34(+) cells/kg and 5.0 x 10(6) or more CD34(+) cells/kg, respectively . In multivariate analysis, patients with less than 5.0 x 10(6) CD34(+) cells/kg had an increase in costs of $5,062 (+/- $1,262 SE) . CONCLUSION: Infusion of more than 5.0 x 10(6) CD34(+) cells/kg was associated with a reduction in resource utilization . Achieving a target of 5.0 x 10(6) CD34(+) cells/kg should have important clinical and economic benefits for patients. Sex Transm Dis, 1999 Nov, 26(10), 556 - 63 Evaluation of the use of calendar blister packaging on patient compliance with STD syndromic treatment regimens; Wright JM et al.; BACKGROUND: Good compliance with antibiotic therapy is critical for successful management of sexually transmitted diseases (STDs) . GOAL OF THIS STUDY: To evaluate the use of user-friendly drug packaging as a means of improving patient compliance with STD therapy and the acceptability of the packaging . STUDY DESIGN: Compliance of patients with STDs with treatment regimens for three different STD syndromes, using antibiotics packed in standard medicine packaging (SP), was compared to that of patients using calendar blister packaged drugs . Compliance was measured by counting the remaining pills at two return visits . Questionnaires were used to evaluate acceptability of the packs . RESULTS: Compliance was significantly better among patients using the calendar blister packs than among those using standard packs, irrespective of dosing frequency . The degree of poor compliance increased with increasing dosing frequency . There was a high level of satisfaction with the blister pack among patients and health care workers . CONCLUSION: Compliance can be improved by the introduction of user-friendly drug packaging, especially for more complex dosing regimens. Mycopathologia, 1999, 145(1), 43 - 56 Production of mycotoxins on artificially and naturally infested building materials; Nielsen KF et al.; In this study, the ability to produce mycotoxins during growth on artificially infested building materials was investigated for Penicillium chrysogenum, Pen . polonicum, Pen . brevicompactum, Chaetomium spp., Aspergillus ustus, Asp . niger, Ulocladium spp., Alternaria spp., and Paecilomyces spp., all isolated from water-damaged building materials . Spores from the different isolates of the above mentioned species were inoculated on gypsum board with and without wallpaper and on chipboard with and without wallpaper . Fungal material was scraped off the materials, extracted, and analyzed using high performance liquid chromatography-diode array detection and thin layer chromatography . All six isolates of C . globosum produced the toxic chaetoglobosins A and C, at levels of up to 50 and 7 microg/cm2 respectively . The quantities of secondary metabolites produced by Penicillia were generally low, and no toxin production was detected from any of the five isolates of Pen . chrysogenum . Both isolates of Pen . polonicum produced 3-methoxy-viridicatin, verrucosidin, and verrucofortine . Two of five isolates of Pen . brevicompactum produced mycophenolic acid . From five out of six isolates of Alternaria spp., altenariol and alternariol monomethyl ether were detected . From Ulocladium spp., Paecilomyces spp., and Asp . ustus no known mycotoxins were detected, although the latter two are known mycotoxin producers . Asp . niger produced several naphtho-gamma-pyrones and tetra-cyclic compounds . All investigated species, especially Asp . ustus and Asp . niger produced many unknown secondary metabolites on the building materials . Analyses of wallpaper and glass-fibre wallpaper naturally infested with Asp . versicolor revealed sterigmatocystin and 5-methoxysterigmatocystin . Analyses of naturally infested wallpaper showed that C . globosum produced the chaetoglobosins A and C, and Pen . chrysogenum produced the antibiotic meleagrin. J Bacteriol, 1999 Nov, 181(22), 7131 - 5 Inactivation of the tricarboxylic acid cycle aconitase gene from Streptomyces viridochromogenes Tü494 impairs morphological and physiological differentiation; Schwartz D et al.; The tricarboxylic acid (TCA) cycle aconitase gene acnA from Streptomyces viridochromogenes Tu494 was cloned and analyzed . AcnA catalyzes the isomerization of citrate to isocitrate in the TCA cycle, as indicated by the ability of acnA to complement the aconitase-deficient Escherichia coli mutant JRG3259 . An acnA mutant was unable to develop aerial mycelium and to sporulate, resulting in a bald phenotype . Furthermore, the mutant did not produce the antibiotic phosphinothricin tripeptide, demonstrating that AcnA also affects physiological differentiation. Fed Regist . 1999 May 17;64(94):26657. Conforming regulations regarding removal of section 507 of the Federal Food, Drug, and Cosmetic Act; confirmation of effective date . Food and Drug Administration, HHS . Direct final rule; confirmation of effective date; "Guidance for Industry: On the Content and Format of Chemistry et al.; The Food and Drug Administration (FDA) is announcing the availability of a document entitled "Guidance for Industry: On the Content and Format of Chemistry, Manufacturing and Controls Information and Establishment Description Information for an Allergenic Extract or Allergen Patch Test." The guidance document is intended to provide guidance to applicants on the content and format of the chemistry, manufacturing and controls (CMC) and establishment description sections of the "Application to Market a New Drug, Biologic, or an Antibiotic Drug for Human Use" (revised Form FDA 356h) for an allergenic extract or allergen patch test . This action is part of FDA's continuing effort to achieve the objectives of the President's "Reinventing Government" initiatives and the FDA Modernization Act of 1997, and is intended to reduce unnecessary burdens for industry without diminishing public health protection. Fed Regist, 1999 Mar 8, 64(44), 11023 - 4 "Guidance for industry: content and format of chemistry, manufacturing and controls information and establishment description information for a biological in vitro diagnostic product;" availability . Food and Drug Administration, HHS . Notice; Effect of surgical adhesion reduction devices on the propagation of experimental intra-abdominal infection; Channing Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass 02115, USA . atzianabos@channing.harvard.edu HYPOTHESIS: The use of certain surgical adhesion reduction devices where there is a risk of concomitant bacterial contamination potentiates intra-abdominal infection . DESIGN: Evaluation of adhesion reduction devices in an experimental model of intra-abdominal infection . SETTING: Experimental animal model . INTERVENTIONS: Adhesion reduction devices were administered at the time of bacterial challenge . MAIN OUTCOME MEASURES: Animal mortality rate, abscess formation, and bacterial counts in peritoneal fluid and blood cultures . RESULTS: The use of bioresorbable membrane adhesion reduction devices in the presence or absence of antibiotic therapy did not alter the disease process as compared with appropriate control groups . However, adhesion reduction gels prepared from sodium hyaluronate and carboxymethylcellulose chemically modified with carbodiimide or ferric ion complexed sodium hyaluronate increased the incidence of peritonitis in treated animals . Gel formulations containing diimide-modified carboxymethylcellulose did not have this effect . CONCLUSIONS: The use of certain adhesion reduction devices resulted in the propagation of intra-abdominal infection in an experimental rat model . This outcome was dependent on the composition of the device employed . The use of adhesion reduction devices should be tested in appropriate models of infection where there is the risk of concomitant bacterial contamination. Curr Opin Pediatr, 1999 Oct, 11(5), 447 - 56 Minocycline and autoimmunity; Eichenfield AH; Minocycline is the most widely prescribed systemic antibiotic for the management of acne . In the past several years, increasing attention has been paid to the drug, both for its potential use as a disease-modifying antirheumatic agent and for its propensity to engender untoward autoimmune reactions, including serum sickness-like disease, drug-induced lupus, and autoimmune hepatitis . This paper reviews the evidence for minocycline as an anti-inflammatory and immunomodulatory agent, its utility in the treatment of rheumatoid arthritis, and the spectrum of adverse reactions that have been ascribed to the drug in the past 5 years. Eur J Cardiothorac Surg, 1999 Sep, 16(3), 362 - 3 Do not snog the dog: infective endocarditis due to Capnocytophaga canimorsus; Ngaage DL et al.; We present a case of prosthetic valve endocarditis and paravalvular abscess caused by the canine bacteria Capnocytophaga canimorsus in a 63-year-old man, who made a habit of snogging his pet dog . Capnocytophaga canimorsus can cause culture-negative endocarditis, therefore a high level of clinical awareness and the appropriate isolation techniques are important for making the diagnosis . Antibiotic therapy and properly timed excision of the infected focus are recommended. Hautarzt, 1999 Oct, 50(10), 739 - 42 {Periorbital lipogranuloma following endonasal sinus surgery}; Weidmann E et al.; A 60-year-old woman developed a periorbital lipogranuloma after endonasal surgery on her paranasal sinuses . The granulomatous inflammation was caused by nonabsorbable lipids introduced by the postoperative nasal tamponade which was soaked in antibiotic ointment . These lipids were transported into the periorbital tissue by the postoperative hemorrhage . Since the course of the inflammatory process is chronic, surgical removal is the best treatment. J Biol Chem, 1999 Nov 12, 274(46), 32829 - 34 Disruption of an aromatase/cyclase from the oxytetracycline gene cluster of Streptomyces rimosus results in production of novel polyketides with shorter chain lengths; Petkovic H et al.; Oxytetracycline is a polyketide antibiotic made by Streptomyces rimosus . From DNA sequencing, the gene product of otcD1 is deduced to function as a bifunctional cyclase/aromatase involved in ring closure of the polyketide backbone . Although otcD1 is contiguous with the ketoreductase gene, they are located an unusually large distance from the genes encoding the "minimal polyketide synthase" of the oxytetracycline gene cluster . A recombinant, disrupted in the genomic copy of otcD1, made four novel polyketides, all of shorter chain length (by up to 10 carbons) than oxytetracycline . All four novel structures contained the unusual carboxamido group, typical of oxytetracycline . This implies that the carboxamido group is present at the start of biosynthesis of oxytetracycline, a topic that has been debated in the literature . Loss of the cyclase protein has a profound influence on the length of polyketide chain assembled, implying that OtcD1 plays a greater role in the overall integrity of the quaternary structure of the polyketide complex than hitherto imagined. J Hosp Infect, 1999 Oct, 43(2), 85 - 100 Mopping up hospital infection; Dancer SJ; Hospital cleaning is a neglected component of infection control . In the UK, financial constraints have forced managers to re-evaluate domestic services and general cleaning has been reduced to the bare minimum . Services have been contracted out in some hospitals, which has further lowered standards of hygiene . Control of infection personnel believe that cleaning is important in preventing hospital-acquired infections but they do not manage domestic budgets and have failed to stop their erosion . It is difficult to defend high levels of hygiene when there is little scientific evidence to support cleaning practices . This review examines the common micro-organisms associated with hospital-acquired infection and their ability to survive in the hospital environment . It also describes studies which suggest that comprehensive cleaning disrupts the chain of infection between these organisms and patients . It is likely that restoring hygienic standards in hospitals would be a cost-effective method of controlling hospital-acquired infection . Furthermore, good cleaning is achievable whereas the enforcement of hand washing and good antibiotic prescribing are not. Nutr Hosp, 1999 May, 14 Suppl 2, 129S - 140S {Drug-food interactions}; Cardona Pera D; Pharmacological interaction is identified among other aspects when the effects of a drug are significantly altered clinically by the presence of food . The most important clinical significance in the history of drug-food interactions occurred in the fifties, the vitamin B6 deficiency when administering the tuberculostatic isoniazide, but there is no doubt that the interaction in the sixties between drugs that were inhibitors of the enzyme mono-amine oxidase and the biogenic amines tyramine and histamine had an important clinical significance due to the increase in hypertension and deaths due to cerebro-vascular accidents . In the seventies the types of interactions were due to the chelation between tetracyclines and the calcium of milk products, influencing the bioavailability of the antibiotic, and from this point on, studies explore in depth the interaction of foods with the different steps in the pharmacokinetics of the drugs (absorption, distribution, metabolization, and excretion), and these have helped to explain the metabolization interactions of drugs like the clinical significance between grapefruit juice whose naringenine flavonoid is a powerful inhibitor of cytochrome 450, particularly the CYP3A4 family, and terfenadine (antihistamine), with an increase in the plasma levels of the drug and patient death due to ventricular arrhythmia . In the USA the Joint Commission on Accreditation of Health Care Organization (JCAHO) has recommended monitoring of the possible drug and food interactions since 1985, and recommends that patients be informed of this . Despite the recommendations of the JCAHO, few American hospitals have protocolized these interactions and even fewer comply with these, and according to some authors, this is due to the lack of motivation caused by the lack of clinical significance . In this chapter we will study the effect of foods on drugs in two aspects: at the pharamcokinetic level with the possible alterations in absorption, distribution, metabolization, and excretion, and at the pharamcodynamic level, by alterations in the action of the drug . Also, based on a study by Delgado, which we have changed somewhat, we will report how the drugs should be taken to avoid interactions with foods . As a conclusion, it is difficult to establish which are the relevant drug-food interactions, unless they have given clinical problems . The following are important: a) drugs with a narrow therapeutic margin in which an absorption problem or a metabolization problem may disrupt the plasma levels and the patient needs (digoxin, teophylline, cyclosporin, etc) . And b) the drugs like some antibiotics that, because of their action mechanisms, need to maintain adequate plasma concentrations. J Ultrasound Med, 1999 Nov, 18(11), 729 - 34; quiz 735-6 Color Doppler ultrasonographic evaluation of osteomyelitis in children; Chao HC et al.; We investigated the capability of color Doppler sonography in evaluating acute osteomyelitis in children . Twelve children suspected of having osteomyelitis were evaluated with color Doppler ultrasonography at admission and at regular intervals to observe the inflammatory process of osteomyelitis, determine the response of antibiotic therapy, and predict the need of surgery in these patients . At admission, color Doppler flow within or around the infected periosteum was found in patients with symptoms for 4 days or longer, whereas those with symptoms for less than 4 days showed no color Doppler flow within and around the periosteum . During sonographic follow-up, six cases were found to have increased color Doppler vascular flow within and around the affected periosteum, and two of them had periosteal abscess . They eventually required surgical treatment . Persistent or increased color Doppler flow during follow-up examination correlated with elevated serum levels of C-reactive protein as well . Our study indicated that color Doppler vascular flow within or around the infected periosteum correlated with advanced acute osteomyelitis, and surgery usually was required in these patients . Those with early stage acute osteomyelitis usually showed no vascular flow within or around the infected periosteum . Thus, color Doppler sonography allowed detection of advanced osteomyelitis and revealed the progression of inflammation during antibiotic therapy . Color Doppler ultrasonography might be valuable in determining the efficacy of antibiotic therapy and justifying the need for operation. Retina, 1999, 19(5), 442 - 6 Ocular toxicity of intravitreal clarithromycin; Unal M et al.; OBJECTIVE: To investigate the ocular toxicity and clearance of intravitreal clarithromycin lactobionate (Klaricid) and to determine the highest nontoxic dose . MATERIALS AND METHODS: To evaluate toxicity, 24 New Zealand white rabbits were divided into six groups (four rabbits each) . Rabbits were examined preoperatively and electroretinography (ERG) was performed . The left eyes of the animals served as controls and received intravitreal injection of 0.1 mL sterile water . Klaricid (0.1 mL) was injected into the midvitreous cavity of the right eyes at concentrations of 25 microg, 250 microg, 500 microg, 1.0 mg, 2.0 mg, and 4.0 mg/0.1 mL . The animals were followed up to 15 days postinjection by clinical examination and ERG . The animals were killed and the eyes were enucleated and processed for light microscopy . Ten New Zealand rabbits were used for the vitreous clearance study as drug test rabbits and two additional rabbits were used to generate control retina and vitreous . The highest nontoxic dose (1 mg) was injected into the vitreous and the concentration of clarithromycin in the vitreous was determined using high-performance liquid chromatography at various time intervals after injection . RESULTS: Cataract occurred after intravitreal doses of 2.0 and 4.0 mg . Electroretinography showed decreasing b-wave amplitude with both dark- and light-adapted stimulus in the 4.0-mg group; it was normal in other groups . Histopathologic sections showed localized retinal necrosis and disorganization with the 2.0 and 4.0 mg dosage . No histologic changes were found in the other groups . The half-life of intravitreal clarithromycin was found to be 2 hours . No metabolites of clarithromycin were observed in the vitreous samples . CONCLUSION: Intravitreal clarithromycin lactobionate is nontoxic to rabbit eyes up to a dose of 1.0 mg . Because of its broad-spectrum antibiotic effect and appropriate half-life in the vitreous, it may be a good choice for intravitreal treatment of susceptible organisms. AIDS, 1999 Oct 22, 13(15), 2069 - 74 Effectiveness of isoniazid chemoprophylaxis for HIV-infected drug users at high risk for active tuberculosis; Gourevitch MN et al.; OBJECTIVE: To define the effectiveness of chemoprophylaxis, outside of a clinical trial setting, in preventing tuberculosis among tuberculin-reactive and anergic HIV-infected drug users at high risk of developing active tuberculosis . DESIGN: An observational cohort study . SETTING: Methadone maintenance treatment program with on-site primary care . PARTICIPANTS: Current or former drug users enrolled in methadone treatment . INTERVENTIONS: Annual skin testing for tuberculosis infection and anergy was performed, and eligible patients were offered daily isoniazid for 12 months and followed prospectively . MAIN OUTCOME MEASURE: The development of active tuberculosis . RESULTS: A total of 155 persons commenced chemoprophylaxis . Among tuberculin reactors, tuberculosis rates were 0.51 and 2.07/100 person-years in those completing 12 months versus those not taking prophylaxis {rate ratio 0.25, 95% confidence interval (CI) 0.06-1.01} . Among anergic individuals, comparable rates were 0 and 1.44/100 person-years . Lower tuberculosis rates among completers were not attributable to differences in immune status between the treated and untreated groups . CONCLUSION: The completion of isoniazid chemoprophylaxis was associated with a marked reduction in tuberculosis risk among tuberculin reactors and anergic persons in this high-risk population . These data support aggressive efforts to provide a complete course of preventative therapy to HIV-infected tuberculin reactors, and lend weight to the findings of others that isoniazid can reduce the rate of tuberculosis in high-risk anergic HIV-infected persons. Clin Orthop, 1999 Oct, (367), 238 - 42 Blood management in two-stage revision knee arthroplasty for deep prosthetic infection; Pagnano M et al.; Treatment of infected total knee arthroplasty requires aggressive management to treat the infection and restore joint function . For patients with infected knee arthroplasties, a two-stage procedure is used that involves resection of the joint and placement of an antibiotic impregnated cement spacer followed by implantation of a new prosthetic 6 weeks later . Patients undergoing the two-stage procedure typically endure high allogeneic blood transfusion rates (82% to 88%) and progressive anemia because the two surgeries are spaced closely and because the infection precludes the use of alternatives to allogeneic blood . Records were reviewed of 75 patients who underwent two-stage total knee arthroplasty to characterize perioperative hemoglobin levels and blood transfusion needs in this patient group . Although transfusions were administered only when warranted by clinical symptoms and were not based on predetermined hematologic values, 62 (82%) patients received a mean of 2.3 units of blood at first-stage surgery, and 60 (80%) patients received a mean of 2.1 units of blood at the second stage . Overall, only 12% of patients did not have allogeneic blood transfusion . At the first stage before resection, mean hemoglobin concentration was 11.6 g/dL and reached a mean nadir of 8.6 g/dL 3 days after surgery . At the second stage before reimplantation, hemoglobin concentration averaged 11.1 g/dL and reached a mean nadir of 8.2 g/dL 3 days after surgery . After the first stage, allogeneic blood transfusion failed to improve postoperative hemoglobin levels enough to prevent transfusions associated with the second-stage . Patients undergoing two-stage total knee arthroplasty have anemia, and a substantial proportion of these patients require allogeneic blood transfusion at both stages . Thus, novel blood management practices are required to improve hemoglobin levels and reduce allogeneic transfusion rates in this patient population. Pediatrics, 1999 Nov, 104(5 Pt 2), 1192 - 7 The influence of having an assigned Medicaid primary care physician on utilization of otitis media-related services; Berman S et al.; OBJECTIVE: This study documents the influence of having an assigned Medicaid primary care physician (PCP) on the utilization of otitis media-related services . DESIGN/METHODS: This is a retrospective study using the 1991 Colorado Medicaid administrative database that followed 28 844 children <13 years who had at least 1 visit for otitis media . RESULTS: Children continuously enrolled in Medicaid throughout the entire year were >4 times (odds ratio: 4.2 and 4.89, respectively) as likely to always or sometimes have a PCP compared with children who were discontinuously enrolled . The likelihood of ever using the emergency department for an otitis media-related visit was increased by 26% and 50%, respectively, when a child sometimes or never had a PCP compared with always having a PCP . The likelihood of ever filling an antibiotic for otitis media was reduced by 23% and 34%, respectively, when a child sometimes or never had a PCP compared with always having a PCP . The likelihood of ever having otitis media-related surgery was not affected by PCP status, but young children, 13 to 18 months of age, had higher referral rates when they had an assigned PCP . CONCLUSIONS: These findings suggest that having an assigned Medicaid PCP influences the utilization patterns of some otitis media-related medical services. Appl Environ Microbiol, 1999 Nov, 65(11), 5028 - 34 Isolation, oxygen sensitivity, and virulence of NADH oxidase mutants of the anaerobic spirochete Brachyspira (Serpulina) hyodysenteriae, etiologic agent of swine dysentery; Stanton TB et al.; Brachyspira (Serpulina) hyodysenteriae, the etiologic agent of swine dysentery, uses the enzyme NADH oxidase to consume oxygen . To investigate possible roles for NADH oxidase in the growth and virulence of this anaerobic spirochete, mutant strains deficient in oxidase activity were isolated and characterized . The cloned NADH oxidase gene (nox; GenBank accession no . U19610) on plasmid pER218 was inactivated by replacing 321 bp of coding sequence with either a gene for chloramphenicol resistance (cat) or a gene for kanamycin resistance (kan) . The resulting plasmids, respectively, pCmDeltaNOX and pKmDeltaNOX, were used to transform wild-type B . hyodysenteriae B204 cells and generate the antibiotic-resistant strains Nox-Cm and Nox-Km . PCR and Southern hybridization analyses indicated that the chromosomal wild-type nox genes in these strains had been replaced, through allelic exchange, by the inactivated nox gene containing cat or kan . Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western immunoblot analysis revealed that both nox mutant cell lysates were missing the 48-kDa Nox protein . Soluble NADH oxidase activity levels in cell lysates of Nox-Cm and Nox-Km were reduced 92 to 96% compared to the activity level in parent strain B204 . In an aerotolerance test, cells of both nox mutants were at least 100-fold more sensitive to oxygen exposure than were cells of the wild-type parent strain B204 . In swine experimental infections, both nox mutants were less virulent than strain B204 in that fewer animals were colonized by the mutant cells and infected animals displayed mild, transient signs of disease, with no deaths . These results provide evidence that NADH oxidase serves to protect B . hyodysenteriae cells against oxygen toxicity and that the enzyme, in that role, contributes to the pathogenic ability of the spirochete. Cutis, 1999 Oct, 64(4), 253 - 8 SAPHO syndrome: report of three cases and review of the literature; Gmyrek R et al.; SAPHO (synovitis, acne, pustulosis, hyperostosis, and osteitis) is an acronym that describes a seronegative syndrome of bone and joint lesions, frequently localized to the anterior chest wall, associated with variable dermatologic manifestations . Dermatologists should be aware of this entity, as early diagnosis can prevent unnecessary surgery and avoid prolonged ineffective antibiotic therapy . We report three new cases and review the literature. Hematol Cell Ther, 1999 Aug, 41(4), 171 - 7 Evaluation of hematopoietic progenitors in hematopoietic progenitor cell transplants . CD34+ dose effect in marrow recovery . Retrospective analysis in 38 patients; Gabus R et al.; Our main goal was to evaluate the CD34+ dose in patients undergoing haemotopoietic stem celltransplantation and its results in terms of recovery of neutrophile and platelet counts, transfusion requirements, days of fever, antibiotic requirements and length of hospital stay . We studied 38 consecutive patients with haematological malignancies transplanted at our Department, from Feb . 96 through Sept . 98 . The CD34+ cell quantification technique was standardized, using a modification of the ISAGHE 96 protocol . Patients were sorted into three groups according to the CD34+ count administered: a) between 3 and 5 x 10(6) cells/kg; b) between 5 and 10 x 10(6) cells/kg; c) > 10 x 10(6) CD34+ cells/kg . As a secondary end point, results were assessed according to the number of aphereses required to arrive at the target count of CD34+, separating those patients that required only 1 or 2 aphereses versus those requiring 3 or more . Finally, an analysis was made of the results of transplantation comparing the different sources of stem cells (PBSC versus PBSC + B.M.) . The best results were obtained in the group with cells between 3 and 5 x 10(6) CD34+ . No statistically significant advantages were found in the group with cells over 5 . The supra-optimal dose of more 10 x 10(6) would yield no additional beneficial results, while they can imply a greater infusion of residual tumor cells . The number of aphereses had no impact on engraftment . Results obtained with PBSC transplants were better than those with BM+PBSC in terms of neutrophile and platelet recovery . The number of CD34+ cells remains the main element in stem cell transplantation to evaluate the haematopoietic recovery after engraftment . Minimum and optimum yields remain unclear . Centers should establish their own optimal dose based on local methodologies and outcomes, maximizing costs and benefits. Ann Allergy Asthma Immunol, 1999 Oct, 83(4), 271 - 88, 291; quiz 291-2 Chlamydia pneumoniae, asthma, and COPD: what is the evidence? Hahn DL. LEARNING OBJECTIVES: Reading this article will familiarize the reader with (1) the unique chlamydial intracellular life cycle and the propensity for human chlamydial infections to become persistent and to result in immunopathologic (inflammatory) damage in target organs and (2) current evidence linking Chlamydia pneumoniae (Cpn) infection to obstructive lung diseases (asthma and chronic obstructive pulmonary disease, COPD) . Potential therapeutic implications of the Cpn-asthma association are also discussed . DATA SOURCES: All Medline articles (January 1985 to March 1999) that cross-referenced the exploded MESH headings "lung diseases, obstructive" and "Chlamydia pneumoniae" (N = 76) . Additional referenced articles, published abstracts, book chapters, and conference proceedings were also utilized . STUDY SELECTION: (1) Case reports and case series that identified Cpn infection in asthma and/or COPD and (2) epidemiologic studies of markers for Cpn infection in asthma and/or COPD that included one or more control groups . RESULTS: Of 18 controlled epidemiologic studies (over 4000 cases/controls), 15 found significant associations between Cpn infection and asthma using organism detection (polymerase chain reaction (PCR) testing (n = 2 studies) or fluorescent antigen testing (n = 1)), Cpn-specific secretory IgA (sIgA) antibody testing (n = 1), and/or specific serum IgE (n = 2), IgA (n = 4), IgG (n = 3) or other antibody criteria (n = 7) . Eight case reports and 13 case series of Cpn infection in asthma (over 100 patients) also include descriptions of improvement or complete disappearance of asthma symptoms after prolonged antibiotic therapy directed against Cpn . Significant associations with COPD (over 1000 cases/controls) were reported in 5 of 6 studies . Results of treating chronic chlamydial infections in COPD patients have not been reported . CONCLUSIONS: Although the full clinical significance of these Cpn-obstructive lung disease associations remains to be established, reports of asthma improvement after treatment of Cpn infection deserve further investigation . Clinicians who manage asthma should be aware of this information since it may help to manage difficult cases . The hypothesis that Cpn infection in COPD can amplify smoking-associated inflammation and worsen fixed obstruction also deserves further study. Clin Radiol, 1999 Oct, 54(10), 636 - 9 The value of ultrasound and aspiration in differentiating vaso-occlusive crisis and osteomyelitis in sickle cell disease patients; Booz MM et al.; We have studied 50 patients with sickle cell disease who presented with musculoskeletal pain over a 2-year period to assess the use of ultrasound in differentiating infection from infarction . All the patients were evaluated by ultrasound . Five had soft tissue oedema and no fluid collection adjacent to the bone . Forty-five had a subperiosteal fluid collection . Twelve patients whose collections were not aspirated were diagnosed according to clinical evaluation . The remaining 33 patients underwent aspiration under ultrasound guidance to distinguish between an infection and infarction . Twenty-three of these were diagnosed as osteomyelitis and 10 as vaso-occlusive crises . In 21 out of the 23 infected cases, the fluid collection was greater than 10 mm at its thickest point perpendicular to the bone surface and all those with infarction had fluid less than 10 mm thickness . Aspiration under ultrasound guidance is a useful method to differentiate the two clinical entities . In patients suffering from osteomyelitis, identification of the organisms guides antibiotic administration . Needle decompression can help to relieve pain in osteomyelitis and vaso-occlusive crisis. Adv Ther, 1999 Mar-Apr, 16(2), 103 - 11 Efficacy and safety of a fixed-combination homeopathic therapy for sinusitis; Adler M; The efficacy and safety of a fixed-combination homeopathic medication (Sinusitis PMD) consisting of Lobaria pulmonaria, Luffa operculata, and potassium dichromate were investigated in an open-label practice-based study of 119 male and female patients, 12 to 57 years of age, with clinical signs of acute sinusitis not previously treated . At the first visit, after a mean of 4.1 days of treatment, secretolysis had increased significantly and typical sinusitis symptoms, such as headache, pressure pain at nerve exit points, and irritating cough, were reduced . Ninety-nine patients received only the test medication . Twenty patients were able to discontinue concomitant medication at the first visit . Only one patient needed an antibiotic . The average treatment duration was 2 weeks . At the end of treatment, 81.5% of patients described themselves as symptom free or significantly improved . Adverse drug effects were not reported. Adv Ther, 1999 Jan-Feb, 16(1), 51 - 70 Efficacy and mode of action of an immunomodulator herbal preparation containing Echinacea, wild indigo, and white cedar; Wustenberg P et al.; Using the example of an allopathic herbal combined preparation containing Echinacea root, wild indigo root, and white cedar leaf tips (Echinaceae radix + Baptisiae tinctoriae radix + Thujae occidentalis herba = Esberitox N), the efficacy and mode of action of a phytoimmunomodulator, or immune system enhancer, is described . Efficacy of the immunomodulator has been demonstrated in studies of acute viral respiratory tract infections and infections requiring antibiotic therapy . In a recent study compliant to GCP, the therapeutic superiority of the herbal immunomodulator over placebo was confirmed as statistically significant and clinically relevant . The present overview describes a model of the antigen-independent mode of action of phytoimmunomodulation ("immunobalancing"). Proc Natl Acad Sci U S A, 1999 Oct 26, 96(22), 12400 - 5 Isolation of a Chinese hamster ovary cell mutant defective in intramitochondrial transport of phosphatidylserine; Emoto K et al.; A CHO-K1 cell mutant with a specific decrease in cellular phosphatidylethanolamine (PE) level was isolated as a variant resistant to Ro09-0198, a PE-directed antibiotic peptide . The mutant was defective in the phosphatidylserine (PS) decarboxylation pathway for PE formation, in which PS produced in the endoplasmic reticulum is transported to mitochondria and then decarboxylated by an inner mitochondrial membrane enzyme, PS decarboxylase . Neither PS formation nor PS decarboxylase activity was reduced in the mutant, implying that the mutant is defective in some step of PS transport . The transport processes of phospholipids between the outer and inner mitochondrial membrane were analyzed by use of isolated mitochondria and two fluorescence-labeled phospholipid analogs, 1-palmitoyl-2-{N-{6(7-nitrobenz-2-oxa-1, 3-diazol-4-yl)amino}caproyl}-PS (C6-NBD-PS) and C6-NBD-phosphatidylcholine (C6-NBD-PC) . On incubation with the CHO-K1 mitochondria, C6-NBD-PS was readily decarboxylated to C6-NBD-PE, suggesting that the PS analog was partitioned into the outer leaflet of mitochondria and then translocated to the inner mitochondrial membrane . The rate of decarboxylation of C6-NBD-PS in the mutant mitochondria was reduced to approximately 40% of that in the CHO-K1 mitochondria . The quantity of phospholipid analogs translocated from the outer leaflet of mitochondria into inner mitochondrial membranes was further examined by selective extraction of the analogs from the outer leaflet of mitochondria . In the mutant mitochondria, the translocation of C6-NBD-PS was significantly reduced, whereas the translocation of C6-NBD-PC was not affected . These results indicate that the mutant is defective in PS transport between the outer and inner mitochondrial membrane and provide genetic evidence for the existence of a specific mechanism for intramitochondrial transport of PS. J Bone Joint Surg Am, 1999 Oct, 81(10), 1434 - 45 Infection after total knee arthroplasty . A retrospective study of the treatment of eighty-one infections; Segawa H et al.; BACKGROUND: The clinical presentation of an infection at the site of a total knee arthroplasty can be used as a guide to treatment, including the decision as to whether the prosthesis should be retained or removed . We reviewed the results of treatment of infection after total knee arthroplasty to evaluate the effectiveness of four treatment protocols based on the clinical setting of the infection . METHODS: We retrospectively evaluated the results of treatment of eighty-one infections in seventy-six consecutive patients who either had an infection after a total knee arthroplasty or had multiple positive intraoperative cultures of specimens of periprosthetic tissue obtained during a revision total knee arthroplasty performed because of presumed aseptic loosening . The patients were managed according to one of four protocols . Five infections in five patients who had positive intraoperative cultures were treated with antibiotic therapy alone . Twenty-three early postoperative infections in twenty-one patients were treated with debridement, antibiotic therapy, and retention of the prosthesis . Twenty-nine late chronic infections in twenty-eight patients were treated with a delayed-exchange arthroplasty after a course of antibiotics . Seven acute hematogenous infections in six patients were treated with debridement, antibiotic therapy, and retention of the prosthesis . Seventeen infections in seventeen patients were not treated according to one of the four protocols . Sixteen late chronic infections were treated either with an arthrodesis (five infections) or with debridement, antibiotic therapy, and retention of the prosthesis (eleven infections) . One acute hematogenous infection was treated with resection arthroplasty because of life-threatening sepsis . RESULTS: The mean duration of follow-up was 4.0 years (range, 0.3 to 14.0 years) . Eleven patients who had an arthrodesis, a resection arthroplasty, or an above-the-knee amputation after less than two years of follow-up were included in the study as individuals who had a failure of treatment . In the group of patients who were managed according to protocol, the initial course of treatment was successful for all five infections that were diagnosed on the basis of positive intraoperative cultures, five of the ten deep early infections, all thirteen superficial early infections, twenty-four of the twenty-nine late chronic infections, and five of the seven acute hematogenous infections . Only one of eleven prostheses in patients who had a late chronic infection that was not treated according to protocol was successfully retained after debridement . CONCLUSIONS: Our treatment protocols, which were based on the clinical setting of the infection, were successful for most patients . A major factor associated with treatment failure was a compromised immune status . Bone loss and necrosis of the soft tissues around the joint also complicated the treatment of these infections. J Gastroenterol Hepatol, 1999 Sep, 14(9), 931 - 4 Case report: Percutaneous drainage of the pancreatic head hydatid cyst with obstructive jaundice; Yattoo GN et al.; We report a rare case of a patient with a primary hydatid cyst in the head of the pancreas who presented with obstructive jaundice caused by extrinsic compression of the intrapancreatic portion of the bile duct . The patient was treated successfully by ultrasound-guided percutaneous drainage of the cyst using hypertonic (20%) saline as the scolicidal agent and albendazole chemoprophylaxis before and after the drainage . The cyst was not visible on ultrasonography at 6 months follow up . Clinical, sonographic and serological follow up to 35 months showed no evidence of cyst recurrence or dissemination . In endemic areas of hydatid disease, hydatid cyst should be a differential diagnosis in cystic lesions of the pancreas in patients presenting with obstructive jaundice. Ann Pharmacother, 1999 Oct, 33(10), 1060 - 2 Oxacillin-induced tissue necrosis; Fromm LA et al.; OBJECTIVE: To report a case of oxacillin-induced tissue necrosis in which recommended concentration guidelines for dilution and administration were used . Oxacillin concentration data, potential risk factors, and treatment options for extravasation injuries are also briefly reviewed . CASE SUMMARY: Oxacillin was infused peripherally by infusion pump in a 79-year-old white woman as prophylactic antibiotic coverage for permanent pacemaker placement . Oxacillin extravasation occurred after the second postoperative dose . A dime-sized area of necrosis was noted at the heparin-lock insertion site . DISCUSSION: Only one case of oxacillin-induced necrosis has been reported . The degree of damage and concentration of drug used were not specifically described . Concentration may play a role in the appearance or absence of tissue damage after an antibiotic extravasation and should be taken into consideration when evaluating a drug's tissue toxicity potential . CONCLUSIONS: The potential exists for oxacillin 50 mg/mL to cause tissue damage in humans if an extravasation occurs . This reaction may be avoided with use of a less-concentrated preparation, avoidance of infusion pump administration, and identification of high-risk patients. Zhonghua Yi Xue Za Zhi (Taipei), 1999 Oct, 62(10), 690 - 4 Surgical treatment of bronchiectasis: 10 years' experience; Chiang TC et al.; BACKGROUND: Since antibiotic therapy and vaccination have been widely used in medical practice, the incidence of bronchiectasis has decreased steadily . The principal role of surgery associated with this disease is for the treatment of complications . We present an analysis of surgical results during a 10-year period . METHODS: The medical records of bronchiectasis patients who were surgically treated were retrospectively reviewed from July, 1987, to March, 1998 . The surgical indications, complications and recurrences of bronchiectasis were evaluated . RESULTS: A total of 41 bronchiectasis patients underwent surgical treatment from 1987 to 1998 at our hospital . There were 18 males (mean age, 37.8 +/- 15.3 years; range, 16-73 years), and 23 females (mean age, 33 +/- 7.1 years; range, 21-46 years) . The indications for surgery were hemoptysis in 30, failed medical treatment in eight, suspected neoplasm in two and retention of a foreign body in one patient . Anatomic resections of the diseased sites were carried out more frequently on the left lower lobes of the lungs . In total, there were 20 left lower lobes, five right lower lobes, 10 left lingular lobes, five right middle lobes, four left upper lobes and one right upper lobe that required surgery . Surgical complications included hemorrhage in one patient, bronchopleural fistula in one and galactorrhea in one patient . The follow-up intervals were from two to 131 months (mean, 72.5 +/- 37.6 months; median, 74 months) . There were two cases of recurrent symptoms and six cases of recurrent hemoptysis; all were easily controlled by medication . There were no mortalities . CONCLUSIONS: Surgical treatment of bronchiectasis yields immediate resolution of symptoms, better quality of life and no mortalities . Cessation of smoking, avoiding air pollution and careful medical follow-up are mandatory. Chem Phys Lipids, 1999 Sep, 101(2), 223 - 35 Binding of nystatin and amphotericin B with sterol-free L-dilauroylphosphatidylcholine bilayers resulting in the formation of dichroic lipid superstructures; Milhaud J et al.; Interactions of multilamellar vesicles (MLV) of dilauroylphosphatidylcholine (DLPC) with the polyene antibiotics, amphotericin B (AmB) and nystatin (Ny), were followed by circular dichroism (CD) . These interactions proceed with both antibiotics through a slow association with high {DLPC}/{antibiotic} stoichiometric molar ratios (> or = 130), at room temperature for which DLPC membranes are in a fluid state . Microscopic investigations of the spatial distributions of the antibiotic and the MLV in the mixtures revealed that MLV form clusters inside which the antibiotic is strongly concentrated and lipid superstructures appear . Concomitantly with the appearance of these superstructures a DLPC dichroic signal emerges . This observation indicates that the chiral properties of antibiotic oligomers can induce a chirality of the DLPC molecules which are bound to them . These results support the hypothesis of a recent molecular modeling of AmB oligomers which postulates that their chiral properties result from a chiral assemblage of antibiotic molecules (Millie et al., J . Phys . Chem . B, in press). Pediatr Emerg Care, 1999 Oct, 15(5), 341 - 3 Descending suppurative mediastinitis: nonsurgical approach to this unusual complication of retropharyngeal abscesses in childhood; Sztajnbok J et al.; OBJECTIVE: To alert the pediatric emergency physician about suppurative mediastinitis as an unusual, life-threatening complication of retropharyngeal abscesses in children and to report an alternative therapeutic option for these cases . METHODS: We describe a case of suppurative mediastinitis secondary to a retropharyngeal abscess in a 19-month-old girl and discuss the pathophysiology, diagnosis, and treatment of this disease . RESULTS: Prompt diagnosis, based on clinical, radiographic, and CT findings, followed by immediate retropharyngeal drainage and appropriate antibiotic therapy, allowed conservative management of the mediastinal abscess, without the need for surgery . The child presented a good outcome and was discharged on hospital day 14 . CONCLUSIONS: When evaluating a retropharyngeal abscess, the pediatric emergency physician should be aware of its complications . A chest radiograph should be prescribed for each patient presenting with an indolent course . Widening of the mediastinum should be considered as strong evidence of a mediastinal abscess for which the best therapeutic option is aggressive surgical drainage . In the rare cases in which marked improvement is achieved after retropharyngeal drainage, a nonsurgical approach to the mediastinal abscess could be attempted . CT scan and a simple chest radiograph have proved to be useful for diagnosis and follow-up. Vopr Onkol, 1999, 45(4), 374 - 9 {Detrimental effects of Daunorubicin and Doxorubicin on human erythrocytes in vitro}; Skorokhod AA et al.; In isotonic medium, daunorubicin in the concentration range of 0.5-5.0 mg/ml of cells and doxorubicin in the concentration range of 0.2-1.0 mg/ml of cells caused hemoglobin (Hb) and K+ to efflux from red blood cells (RBC), to increase RBC size and to lower their deformability . Hb and K+ efflux rates were proportional to the antibiotic concentrations and remained stable for a few hours . Hb efflux did not change significantly in the 4-21 degrees C range (exempt at an experimental concentration of daunorubicin of 5.0 mg/ml of cells) but soared sharply at 37 degrees C . At the daunorubicin and doxorubicin concentration of 0.2 mg/ml of cells, Hb and K+ efflux virtually did not differ from control values . At the antibiotic concentration of 1.0 mg/ml of cells, 37 degrees C, Hb efflux rate was 0.34-5.6%, while that of K+(-) 1.0-8.2%, per hour, of possible maximum value . For the daunorubicin level of 5.0 mg/ml of cells, the respective values were 10 and 17% . At the daunorubicin concentration of 5.0 mg/ml, at 4 degrees C, Hb efflux from RBC was significantly higher than at 21 degrees C . RBC malleability, which was determined as their ability to pass through membrane filters having 3 mm dia pores, did not differ significantly from control values for a few hours antibiotic concentrations not exceeding 0.3 mg/ml of cells . At the antibiotic concentration of 1.0 mg/ml and higher RBC deformability dropped to zero within 10 min . ATP level in RBC practically remained identical to control values during incubation with the antibiotics for several hours. J Bone Joint Surg Br, 1999 Sep, 81(5), 893 - 4 Pyoderma gangrenosum . A diagnosis not to be missed; Armstrong PM et al.; We describe a case of pyoderma gangrenosum which presented with severe wound breakdown after elective hip replacement . The patient was treated successfully with minimal wound debridement and steroids . This diagnosis should always be considered when confronted with an enlarging painful skin lesion which does not grow organisms when cultured and fails to respond to antibiotic therapy, especially if there are similar lesions in other sites . In patients who have a past history of pyoderma gangrenosum, prophylactic steroids may be indicated at the time of surgery or may be required early in the postoperative period. Clin Infect Dis, 1999 Sep, 29(3), 670 - 2 Corticosteroids as adjunctive therapy for severe Pneumocystis carinii pneumonia in non-human immunodeficiency virus-infected patients: retrospective study of 31 patients; Delclaux C et al.; The aim of this retrospective study was to assess whether corticosteroid adjunctive therapy (CAT) could prevent death in immunocompromised patients with severe Pneumocystis carinii pneumonia (PCP) who do not have human immunodeficiency virus (HIV) infection, similarly to what has been demonstrated for HIV-infected patients . The charts of all non-HIV-infected patients who were admitted to two medical intensive care units between 1988 and 1996 because of severe PCP, defined by an arterial oxygen pressure (determined while the patient was breathing room air) of <70 mm Hg, and who were treated with trimethoprim-sulfamethoxazole were analyzed retrospectively . Thirty-one patients met the study criteria, of whom 23 received CAT (within 72 hours of antibiotic therapy) and eight did not receive CAT . The need for mechanical ventilation (10 {43%} of 23 vs . 4 {50%} of 8) and the mortality rate (9 {39%} of 23 vs . 4 {50%} of 8) were similar for the two groups . Although this small study does not have a statistical power high enough to rule out the possibility of a difference, the results suggest that CAT does not improve the survival of non-HIV-infected patients as has been described for HIV-infected patients with severe PCP. Immunol Lett, 1999 Sep 1, 69(3), 355 - 8 Serum procalcitonin concentrations in transplant patients with acute rejection and bacterial infections; Jaresova M et al.; Procalcitonin (PCT) represents a new marker of systemic inflammatory reactions of the body to infections . PCT is selectively induced by severe bacterial infections leading to sepsis or multiorgan dysfunction syndrome . The aim of our study was to test PCT as a postoperative infection marker in heart and kidney transplant patients compared with healthy subjects and patients with localized lung-inflammatory processes without a manifest systemic response . PCT concentrations were measured by an immunoluminometric assay (ILMA) in a total of 419 serum samples . Normal serum levels were in the range of 0.08-0.6 ng/ml . Operative trauma associated with heart (not kidney) transplantation induced a transient increase in PCT levels to 7-10 ng/ml with a decline to normal levels within 2-3 days in most patients . Severe bacterial infections dramatically augmented serum PCT concentrations reaching values of 46-297 ng/ml in the most critical periods . Good response to antibiotic therapy was associated with a decline in serum PCT concentrations . Acute rejection or cytomegalovirus infections did not significantly increase the serum PCT levels . Localized pulmonary infections showed either no, or only a limited increase, in the serum PCT levels (max . 7 ng/ml) . We conclude from our data that PCT can be used as a sensitive marker to differentiate systemic bacterial infections from other complications in organ transplantation. Toxicol Pathol, 1999 Sep-Oct, 27(5), 563 - 72 Prompt recovery of damaged adrenal medullae induced by salinomycin; Chen-Pan C et al.; The morphologic changes in the adrenal medullae of rats treated with an ionophore antibiotic, salinomycin, are described . Male rats of approximately 7 wk of age were treated orally with a single dose of salinomycin at 80 mg/kg body weight . Following this treatment, the adrenal glands were examined, using immunohistochemistry, for neurofilament, laminin, fibronectin, and S-100 protein; the glands were also examined using transmission electron microscopy . One hour after the treatment, a karyopyknosis was observed in the clusters of affected chromaffin cells in which the neurofilament, laminin, and fibronectin were present . The lesions became progressively conspicuous between hours 5 and 10 . Ultimately, the outcome was cell lysis . Five hours after salinomycin treatment, unaffected chromaffin cells strongly stained to tyrosine hydroxylase . At 10 hr, new chromaffin cells, which were irregular in shape with electron-dense cytoplasm (dark cell), that were strongly stained for tyrosine hydroxylase appeared at the basement membrane site of the necrotic clusters, and these cells contained very few immature catecholamine granules of less than 80 nm . At 17 hr, the catecholamine granules increased in number and size to about 200 nm . The newly formed chromaffin cells grew within the clusters to fill in the medulla by 24 hr, and cytoplasmic granules progressively increased in number and size . The interstitial tissue was seen to be edematous at 5 hr . New capillaries were found in the adrenal medullae of both control and salinomycin-treated rats . The protruding chromaffin cells (protruding cells), which we previously described in normal rats, were also observed in salinomycin-treated rats, which suggests that holocrine secretion is performed in the adrenal medullae . The results indicated that the rat adrenal medullae have the ability to make a rapid recovery after an insult by salinomycin. J Calif Dent Assoc, 1999 May, 27(5), 393 - 9 The 1997 prevention of bacterial endocarditis recommendations by the American Heart Association: questions and answers; Pallasch TJ et al.; Since the publication of the American Heart Association 1997 recommendations for the prevention of bacterial endocarditis, questions have arisen regarding the application of these guidelines . It is impossible for any such recommendations to include all conceivable clinical situations that might arise, and therefore questions are appropriate . Frequently asked questions are included in this article . Answers provided for the questions are the opinions of the authors, who participated in the formulation of these guidelines, and are not intended to supplant the judgment of the dental health professional who is privy to all the facts when the individual clinical decision is made. Clin Ter, 1999 May-Jun, 150(3), 203 - 7 {Iatrogenic sequelae of pulmonary tuberculosis}; Giancaspro G et al.; OBJECTIVES: The purpose of this study is to underline how topical is the chapter of the sequelae of pulmonary tuberculosis and to try to make a classification . Pulmonary tuberculosis can be cured definitely or hesitate in disease (BK negative) that is totally independent from tuberculosis about their pathogenesis and clinical features . They are called sequelae . MATERIALS AND METHODS: We made a statistical analysis that investigate a group of 110 patients without active infection (BK negative) admitted in the hospital because of a sequela of pulmonary tuberculosis . Patients were treated in the past by collapse-therapy or by antibiotic-therapy until their spittle became negative for BK . RESULTS: A significant (p < 0.05) relationship between each kind of sequela, among the most important ones (fibrothorax, interstitial fibrosis, bronchiectasis, empyema with or without pleural fistula, parafibrotic emphysema), and type of treatment, results . CONCLUSIONS: The sequelae of tuberculosis of the lung are highly disadvantageous for people who are affected; are observed frequently; are closely dependent on what kind of treatment the patient has received; are classified in iatrogenic, not iatrogenic or mixed. Tech Urol, 1999 Sep, 5(3), 166 - 8 Right intrathoracic renal ectopia: a case report and review of the literature; Stein JP et al.; We report a case of right intrathoracic renal ectopia associated with a previously unreported congenital anomaly (trisomy 21) and review of the literature. Intern Med, 1999 Oct, 38(10), 796 - 9 Rapidly growing primary gastric B-cell lymphoma after eradication of Helicobacter pylori; Furusyo N et al.; Helicobacter pylori (H . pylori) infection plays a decisive role in primary gastric B-cell lymphoma especially of mucosa-associated lymphoid tissue (MALT)-type . We treated a 47-year-old male patient with primary gastric B-cell lymphoma associated with H . pylori infection . Although antibiotic therapy for eradication of H . pylori caused great improvement in the low-grade MALT lymphoma-like lesion, the small areas of high-grade lesion rapidly formed a new bulky mass in only 8 weeks . This suggests that eradication of H . pylori is not effective for high-grade lymphoma. Cancer J Sci Am, 1999 Sep-Oct, 5(5), 293 - 300 Treatment of Ras-induced cancers by the F-actin cappers tensin and chaetoglobosin K, in combination with the caspase-1 inhibitor N1445; Tikoo A et al.; For transforming normal fibroblasts to malignant cells, oncogenic Ras mutants such as v-Ha-ras require Rho family GTPases (Rho, Rac, and CDC42) that are responsible for controlling actin-cytoskeleton organization . Ras activates Rac through a PI-3 kinase-mediated pathway . Rac causes uncapping of actin filaments (F-actin) at the plus-ends, through phosphatidylinositol 4,5 bisphosphate (PIP2), and eventually induces membrane ruffling . Several distinct F-actin/PIP2-binding proteins, such as gelsolin, which severs and caps the plus-ends of actin filaments, or HS1, which cross-links actin filaments, have been shown to suppress v-Ha-Ras-induced malignant transformation when they are overexpressed . Interestingly, an F-actin cross-linking drug (photosensitizer) called MKT-077 suppresses Ras transformation . Thus, an F-actin capping/severing drug might also have an anticancer potential . PURPOSE: This study was conducted to determine first whether Ras-induced malignant phenotype (anchorage-independent growth) is suppressed by overexpression of the gene encoding a large plus-end F-actin capping protein called tensin and second to test the anti-Ras potential of a unique fungal antibiotic (small compound) called chaetoglobosin K (CK) that also caps the plus-ends of actin filaments . METHODS AND RESULTS: DNA transfection with a retroviral vector carrying the tensin cDNA was used to overexpress tensin in v-Ha-Ras-transformed NIH 3T3 cells . All stable tensin transfectants rarely formed colonies in soft agar, indicating that tensin suppresses the anchorage-independent growth . The anti-Ras action of CK was determined by incubating the Ras-transformants in the presence of CK in soft agar . Two microM CK almost completely inhibited their colony formation, indicating that CK also suppresses the malignant phenotype . However, unlike tensin, CK causes an apoptosis of Ras-transformed NIH 3T3 cells and, less effectively, of normal NIH 3T3 cells, indicating that CK has an F-actin capping-independent side effect(s) . CK-induced apoptosis is at least in part caused by CK-induced inhibition of the kinase PKB/AKT . However, a specific ICE/caspase-1 inhibitor called N1445 completely abolished the CK-induced apoptosis by reactivating PKB, but without affecting the CK-induced suppression of Ras transformation . CONCLUSIONS: Like the F-actin cross-linking drug MKT-077, the F-actin capping drug CK may be useful for the treatment of Ras-associated cancers if it is combined with the ICE inhibitor N1445, which abolishes the side effect of CK . Our observations that two distinct F-actin capping molecules (i.e., tensin and CK) suppress Ras-induced malignant phenotype strongly suggest, if not prove, that capping of actin filaments at the plus-ends alone is sufficient to block one of the Ras signaling pathways essential for its oncogenicity . This notion is compatible with the fact that Ras induces the uncapping of actin filaments at the plus-ends through the Rac/PIP2 pathway. Chem Res Toxicol, 1999 Oct, 12(10), 993 - 1001 Maitotoxin-induced calcium influx in erythrocyte ghosts and rat glioma C6 cells, and blockade by gangliosides and other membrane lipids; Konoki K et al.; Maitotoxin (MTX) at 0.3 nM elicited a 10-20-fold increase in the level of Ca(2+) influx in rat glioma C6 cells . At higher doses (3-30 nM), MTX induced marked Ca(2+) influx in human erythrocyte ghosts when monitored with the fluorescent dye Fura-2 . Although the ghosts were not as susceptible to MTX as intact erythrocytes or other cell lines, Fura-2 experiments under various conditions suggested that the MTX-induced entry of ions into the ghosts was mediated by a mechanism similar to that reported for cells or tissues . These ghosts are the simplest system known to be sensitive to MTX and thus may be suitable for research on the direct action of MTX . Gangliosides GM1 and GM3, glycosphingolipids which have a sialic acid residue, strongly inhibited MTX-induced Ca(2+) influx in C6 cells, while the inhibitory action by asialo-GM1, which lacks a sialic acid residue, was somewhat weaker . Their inhibitory potencies were in the following order: GM1 (IC(50) approximately 2 microM) > GM3 (IC(50) approximately 5 microM) > asialo-GM1 (IC(50) approximately 20 microM) . GM1 (3 microM) completely blocked MTX (30 nM)-induced Ca(2+) influx in human erythrocyte ghosts . When C6 cells were pretreated with tunicamycin, an antibiotic which inhibits N-linked glycosylation, or concanavalin A, a lectin which exhibits a high affinity for cell-surface oligosaccharides, MTX-induced Ca(2+) influx was significantly potentiated . This suggests that removal of oligosaccharides from the cell surface by tunicamycin or capping of sugar chains on plasma membranes by concanavalin A can potentiate the action of MTX. Arch Dis Child Fetal Neonatal Ed, 1999 Nov, 81(3), F206 - 7 Unexplained fever in neonates may be associated with hepatitis B vaccine; Linder N et al.; AIM: To investigate whether hepatitis B vaccination has increased the number of cases of unexplained neonatal fever . METHOD: The files of all infants born from 1 January 1991 to 31 December 1992, in whom a diagnosis of "injected antibiotic" or "disease of temperature regulation" was recorded, were reviewed . Those who had unexplained fever of 38 degrees C or higher during the first three days of life were divided into two groups: infants who did not receive the hepatitis B vaccine (1991) and infants who did (1992) . RESULTS: In 1992 the incidence of unexplained fever in hepatitis B vaccinated neonates was significantly higher than in the 1991 group of pre-vaccination neonates (35 out of 5819 (0.6%) vs 14 out of 5010 neonates (0.28%) respectively, p=0.013) . CONCLUSIONS: The increase in the number of cases of unexplained neonatal fever seems to be associated with the introduction of routine hepatitis B vaccination on the first day of life . The possibility that an excess number of neonates will undergo unnecessary procedures and treatment to diagnose unexplained fever justifies planning a controlled study to determine whether these preliminary findings point to a significant problem. Clin Rheumatol, 1999, 18(5), 406 - 9 Candida glabrata arthritis: case report and review of the literature of Candida arthritis; Zmierczak H et al.; We report a case of arthritis due to Candida (Torulopsis) glabrata in two different joints at different times in the same patient . The first episode of arthritis was situated in the right ankle and lasted more than 1 year before the patient agreed to the proposed treatment . Therapy with intravenous amphotericin B and oral fluconazole failed . A cure was achieved with weekly intra-articular administration of amphotericin B, which was continued for more than 20 weeks and combined with oral itraconazole . Several weeks later the patient developed Candida glabrata arthritis of the left knee while still taking itraconazole . Immediately, intravenous amphotericin B therapy was started and was successful . Because there were no previous invasive point manipulations or trauma, the infections were considered to be haematogenously disseminated . Chronic corticosteroid and repeated antibiotic therapy for infectious exacerbations of chronic obstructive pulmonary disease and alcohol abuse are the presumed risk factors in this otherwise immunocompetent patient. Nippon Yakurigaku Zasshi, 1999 Jun, 113(6), 339 - 47 {Gramicidin perforated patch recording technique}; Akaike N; Cl- is one of the major ionic constituents of cells and extracellular spaces . Intracellular Cl- plays an important role in regulating the cell volume and pH, in both salt secretion and reabsorption, in membrane excitability, and G-protein-dependent intracellular signal transduction . GABA and glycine are the primary inhibitory neurotransmitters . Such agonist-stimulated responses are affected by the intracellular Cl- concentration ({Cl-}i) . However, it was difficult to make an electrical recording of the physiological Cl- response from cells with native intracellular Cl- activity because of the limitations of present recording techniques using conventional glass-microelectrode, whole-cell patch and nystatin perforated patch recording modes . Recently, this difficulty was overcome by developing the gramicidin perforated patch recording mode in our laboratory . Gramicidin is a polypeptide antibiotic that forms pores in the cell membrane as well as nystatin but allows only monovalent cations to permeate the membrane, enabling both {Cl-}i and the second messenger system to remain undisturbed . Here, I would like to primarily focus on the GABA- and glycine-induced Cl- responses to in mammalian CNS neurons maintaining native cellular {Cl-}i under normal and pathological neuronal conditions by use of gramicidin perforated patch recording configuration . Age-related and developmental changes in neuronal {Cl-}i are also described in detail. Rev Med Brux, 1999 Sep, 20(4), A313 - 5 {Vaccinations: a necessity}; Duchateau J; The preventive efficiency of vaccination for numerous infectious diseases remains up to date . Multiple epidemiological data are documenting the underuse of this approach . Risk situations are briefly reviewed, specially those related to unappropriated immunologic functions associated with ageing . Both extremes of life can display insufficient responses to vaccines, either by immaturity or immunosenescence . The diagnostic interest of these situations, by following the vaccinal responses, resides in allowing some prophylactic treatments (antibiotics, gammaglobulins) or consider immunostimulating treatments . This is not to speak, for the older subjects, about the repletion of multiple deficits of their nutritional status. J Clin Microbiol, 1999 Nov, 37(11), 3746 - 8 Novel method for rapid determination of clarithromycin sensitivity in Helicobacter pylori; Gibson JR et al.; A novel PCR-hybridization assay, performed in single closed capillaries, was developed to detect clarithromycin resistance-associated gene mutations in Helicobacter pylori . Mutations were detected by thermal analysis in 33 of 34 (97%) resistant isolates but not in 66 isolates determined to be sensitive by conventional antibiotic assays . The method was rapid and reproducible, and it reduced PCR product contamination risk. Indian J Exp Biol, 1999 Jul, 37(7), 710 - 2 Induction of stable benomyl-tolerant phenotypic mutants of Trichoderma pseudokoningii MTCC 3011, and their evaluation for antagonistic and biocontrol potential; Mukherjee PK et al.; Trichoderma pseudokoningii MTCC 3011 is a very useful strain for biological control of the plant pathogen Sclerotium rolfsii under post-harvest conditions . In the present investigation, several benomyl-tolerant phenotypic mutants of this strain have been generated using a two step mutagenesis-chemical followed by gamma irradiation . The mutants differed from the wild type strain in antibiotic and disease control potential . Some of the mutants are superior to the wild type in biocontrol potential on S . rolfsii. Am J Gastroenterol, 1999 Oct, 94(10), 2972 - 6 Unsuspected infection is infrequent in asymptomatic outpatients with refractory ascites undergoing therapeutic paracentesis; Jeffries MA et al.; OBJECTIVE: Large-volume paracentesis is a safe and effective means of treating patients with refractory ascites . However, there is limited information regarding the need for ascitic fluid studies in asymptomatic outpatients presenting for therapeutic paracentesis . The aim of this prospective study was to define the incidence and natural history of peritoneal fluid infection in asymptomatic outpatients undergoing therapeutic paracentesis . METHODS: Over a 13-month period, 118 therapeutic paracenteses were performed in 29 outpatients with decompensated cirrhosis (Child-Pugh class B = 38%, C = 62%) . After a brief medical history and physical examination, ascitic fluid cell count with differential and culture were obtained from all participating subjects . Seven (24%) of the subjects were receiving norfloxacin prophylaxis, accounting for antibiotic coverage during 40% of the procedures performed . The clinical course and outcome of study subjects during a mean follow-up of 137 days was reviewed . RESULTS: All 118 (100%) of the ascitic fluid samples demonstrated absolute neutrophil counts of <250/mm3 (mean = 6.5 +/- 22.5 pmn/mm3) . Asymptomatic bacterascites was identified from three of the 118 (2.5%) fluid samples, but all of these subjects spontaneously recovered without treatment or sequelae . During follow-up, six episodes of symptomatic or hospital-associated peritoneal fluid infection were identified in study participants, emphasizing the importance of fluid studies in other clinical settings . CONCLUSIONS: Although further studies are needed, the routine culture of ascitic fluid in asymptomatic outpatients with refractory ascites requiring therapeutic paracentesis may not be necessary when there is a low index of suspicion for occult infection . In circumstances of clinical uncertainty, however, obtaining ascitic fluid cell counts with differential is recommended to insure patient safety. Am J Gastroenterol, 1999 Oct, 94(10), 2912 - 7 Predictive value of the Rome criteria for diagnosing the irritable bowel syndrome; Vanner SJ et al.; OBJECTIVE: Our aim was to examine the predictive value of the Rome criteria and absence of so-called "red flags" of clinical practice for diagnosing irritable bowel syndrome . Red flags were relevant abnormalities on physical examination, documented weight loss, nocturnal symptoms, blood in stools, history of antibiotic use, and family history of colon cancer . METHODS: In retrospective studies, 98 patients who had one or more Rome criteria and lacked red flags were identified by chart review of a 1-yr period . In prospective studies, 95 patients were identified who met the Rome criteria and lacked red flags . Sensitivity, specificity, predictive value of Rome criteria, and absence of red flags were determined . Consultant's final diagnosis was the gold standard . Investigations before and after referral were recorded and reason for referral was determined in prospective studies . RESULTS: In the retrospective series, the Rome criteria and absence of red flags had a sensitivity of 65%, specificity of 100%, and positive predictive value of 100% . None of these patients required revision of their diagnosis during a 2-yr follow-up . In the prospective study, the positive predictive value was 98% . More than 50% of the patients in this group had been referred because of diagnostic uncertainty and 24% had had an abdominal ultrasound; 66% of those <45 yr old underwent at least partial colonic evaluation . CONCLUSIONS: These findings suggest that the Rome criteria combined with a lack of red flags have a very high predictive value for diagnosing irritable bowel syndrome . Application of these diagnostic criteria has the potential to alter utilization of health care resources. Can J Gastroenterol, 1999 Sep, 13(7), 607 - 10 Helicobacter pylori infection and childhood recurrent abdominal pain: lack of evidence for a cause and effect relationship; Macarthur C; BACKGROUND: Recurrent abdominal pain is a common complaint among children and adolescents . Apley's criteria - at least three discrete episodes of abdominal pain of sufficient severity to interrupt normal activities that occur over a period of three or more months - are often used to define this chronic pain syndrome . OBJECTIVE: To summarize the extent and quality of the published evidence for a cause-and-effect relationship between Helicobacter pylori infection and childhood recurrent abdominal pain . MATERIALS AND METHODS: The MEDLINE bibliographic database (January 1983 to July 1998) was searched to identify pertinent (English language) studies . The search was restricted to prospective, controlled studies reporting empirical data on children up to 18 years of age . RESULTS: Six studies were identified . Five of the six were case-control studies, while the remaining study assessed the effectiveness of antibiotic therapy . Only one study was community based, with the remaining studies conducted in the tertiary hospital setting . The evidence for a causal relationship was inconsistent; of the five case-control studies reviewed, the odds ratios ranged from 0.32 to 1.80 . Two studies demonstrated statistically significant results; however, the findings were conflicting . The only treatment trial was limited because of methodological flaws . CONCLUSIONS: Current evidence suggests no association between H pylori infection and recurrent abdominal pain in children . The evidence to date indicates that routine investigation for H pylori infection in children who present with the classical symptoms of recurrent abdominal pain based on Apley's criteria is not warranted. Can J Gastroenterol, 1999 Sep, 13(7), 599 - 603 Pathobiology of Helicobacter pylori infection in children; Riddell RH; In the pediatric population, the associations of Helicobacter pylori with gastritis, gastric ulcer, duodenitis and duodenal ulcer, and with duodenal gastric surface metaplasia and disorders of the D cell- G cell axis resulting in hypergastrinemia, are well established and in many ways resemble their counterparts in adults . Eradication of H pylori invariably results in the reversal of these diseases with time . There are also suggestions that gastric surface metaplasia is more extensive in children with H pylori, and may be the site of duodenal H pylori infection and associated duodenal erosions or ulcers . There is no consensus as to whether H pylori in children is more or less severe than in adults . In one pediatric cohort, H pylori was associated with increased intensity of inflammation, while other studies suggest that acute inflammation may be less intense in children overall but that chronic inflammation may be increased in intensity, including lymphoid hyperplasia, which in turn may correlate with endoscopic nodularity . Lymphoid hyperplasia and nodular gastritis appear to be more frequent in children than in adults and usually regress following H pylori eradication . However, in children, other diseases or morphological abnormalities, including some loss of glands (atrophy), occasionally intestinal metaplasia, lymphoproliferative diseases including low grade mucosal-associated lymphoid tissue lymphoma, lymphocytic gastritis and hypertrophic gastritis/Menetrier's disease, are much less frequently associated with H pylori than in adults . Other associations are rarely seen in children, primarily because the time required for these to develop takes the individual to adulthood; for example, while intestinal metaplasia occurs in the pediatric population, the complications of adenoma/dysplasia and carcinoma are rare . In adults, inflammatory and hyperplastic polyps, atrophic gastritis and pernicious anemia, and in some patients granulomas (granulomatous gastritis), may also be associated with H pylori infection . Greater awareness of the spectrum of diseases associated with H pylori may well lead to their increased recognition in the pediatric population . Some diseases, particularly Crohn's disease, but also human immunodeficiency virus infection, have a negative association with H pylori that appears not to be simply a result of the excess antibiotic therapy that these patients receive . These variations in association and reactions to H pylori, some of which are age-related, may allow the different host responses to H pylori that occur in humans to be examined. Ophthalmology, 1999 Oct, 106(10), 1869 - 77 Endophthalmitis in cataract surgery: results of a German survey; Schmitz S et al.; OBJECTIVE: To document perioperative prophylactic treatment and to evaluate the risk factors for endophthalmitis after cataract surgery . DESIGN: Cross-sectional study via anonymous survey . PARTICIPANTS: Four hundred sixty-nine centers in Germany were queried . RESULTS: A total of 311 (67%) questionnaires were received, with each center reporting an average of 900 cataract surgeries per year (total, 340,633 surgeries in 1996) . Respondents reported a total of 267 cases of endophthalmitis, which resulted in a mean responder-specific endophthalmitis rate of 0.148% versus a median rate of 0% . Statistical analysis via Poisson regression suggested that sclerocorneal incisions were associated with a reduced incidence of endophthalmitis (odds ratio, 0.35; 95% confidence interval, 0.24-0.51) . Antibiotics used intraocularly (odds ratio, 0.65; 95% confidence interval, 0.43-0.98) and the preoperative application of diluted povidone-iodine on the conjunctiva (odds ratio, 0.59; 95% confidence interval, 0.36-0.99) were associated with a reduced risk of postoperative infection . Immune deficiencies (66%), diabetes mellitus (62%), occlusion of the lacrimal system (40%), and skin diseases (33%) were regarded as risk factors for endophthalmitis by the respondents . When cataract surgery is performed solely under inpatient conditions, the use of systemic antibiotics as well as the periocular injection of antibiotics at the end of the operation were associated (although not significantly) with a trend toward reducing the incidence of postoperative infection . Conversely, flushing the lacrimal drainage system, using eye shields, and cutting the eyelashes had no demonstrable effect in preventing endophthalmitis . The use of preoperative topical antibiotics (odds ratio, 2.38; 95% confidence interval, 1.21-4.68) and the performance of more than 20% of the surgeries in an outpatient center (odds ratio, 2.0; 95% confidence interval, 1.24-3.21) were associated with a detrimental effect on the development of endophthalmitis . CONCLUSIONS: Although the appropriate antibiotic agent and dosage are not yet established, the administration of intracameral antibiotics and the application of povidone-iodine on the conjunctiva significantly reduced the relative risk of postoperative endophthalmitis in this survey . Because the study was not individual based but rather on aggregate questionnaire, the results have to be interpreted with care. Minerva Med, 1999 Apr, 90(4), 123 - 31 {Hepatic and pancreatic disease in patients with acquired immunodeficiency syndrome (AIDS)}; Danesi G et al.; AIDS is frequently expressed through gastrointestinal o abdominal symptoms . In addition, patients with AIDS or ARC frequently have hepatic and biliary symptoms, while pancreatic alterations are found in 4-30% of patients hospitalised for AIDS . Since AIDS patients are immunodepressed, they are subject to opportunistic infection often multifocal and the pathological processes can be present simultaneously . About 2/3 of patients have enlarged liver, steatosis, splenomegaly, lymphoadenopathy, cholecystic and biliary tract abnormalities, alterations of liver function tests, and abdominal discomfort in the upper right quadrant . Jaundice is rare and hepatic failure is not common . Hepatic biopsy is often necessary to establish the diagnosis . The hepatic localisation of an opportunistic pathogenic agent is generally a sign of systemic dissemination which is expressed as granulomatous hepatitis (atypical mycobacteria, frequently mycobacterium avium, or M . tuberculosis representing the reactivation of latent diseases), peliosis hepatis, infection from CMV, HSV, EBV, Pneumocystis carinii, and mycotic infections . Coinfections with the hepatic virus (HBV, HDV, HCV) are also often present . Pharmacological damage may also be present (mainly caused by antibiotic therapies) . Neoplasia are rare (hepatic Kaposi's sarcoma associated with cutaneous and gastrointestinal manifestations, or generally metastatic lymphoma) . Damage of the biliary tract usually develops after other manifestations of the illness; the most frequent pictures are cholestatic syndromes and cholangitis, while cholecystitis and jaundice are rare . Pancreatic lesions are generally asymptomatic . They are diagnosed during autopsy and are caused principally by opportunistic agents. Clin Chest Med, 1999 Sep, 20(3), 623 - 51 Nonresolving or slowly resolving pneumonia; Kuru T et al.; Given the variability in rate of radiographic resolution, it remains controversial to decide when to initiate an invasive diagnostic work-up for nonresolving or slowly resolving pulmonary infiltrates . In immunocompetent patients who present with classical features of CAP (i.e., fever, chills, productive cough, new pulmonary infiltrate), clinical response to therapy is the most important determinant for further diagnostic studies . Within the first few days, persistence or even progression of infiltrates on chest radiographs is not unusual . Defervescence, diminished symptoms, and resolution of leukocytosis strongly support a response to antibiotic therapy, even when chest radiographic abnormalities persist . In this context, observation alone is reasonable, and invasive procedures can be deferred . Serial radiographs and clinical examinations dictate subsequent evaluation . In contrast, when clinical improvement has not occurred and chest radiographs are unchanged or worse, a more aggressive approach is warranted . In this setting, we advise fiberoptic bronchoscopy with BAL and appropriate cultures for bacteria, legionella, fungi, and mycobacteria . When endobronchial anatomy is normal and there is no purulence to suggest infection, TBBs should be done to exclude noninfectious causes (discussed earlier) or infections attributable to mycobacteria or fungi . An aggressive approach is also warranted in patients who are clinically stable or improving when the rate of radiographic resolution is delayed . As discussed earlier, what constitutes excessive delay is controversial, and depends upon the acuity of illness, specific pathogen, extent of involvement (i.e., lobar versus multilobar), comorbidities, and diverse host factors . Stable infiltrates even 2 to 4 weeks after institution of antibiotic therapy does not mandate intervention provided patients are improving clinically . Invasive techniques can also be deferred when unequivocal, albeit incomplete, radiographic resolution can be demonstrated . Lack of at least partial radiographic resolution by 6 weeks, even in asymptomatic patients, however, deserves consideration of alternative causes (e.g., endobronchial obstructing lesions, or noninfectious causes) . Fiberoptic bronchoscopy with BAL and TBBs has minimal morbidity and is the preferred initial invasive procedure for detecting endobronchial lesions or substantiating noninfectious causes . The yield of bronchoscopy depends on demographics, radiographic features, and pre-test likelihood . In the absence of specific risk factors, the incidence of obstructing lesions (e.g., bronchogenic carcinomas, bronchial adenomas, obstructive foreign body) is low . Bronchogenic carcinoma is rare in nonsmoking, young (< 50 years) patients but is a legitimate consideration in older patients with a history of tobacco abuse . Non-neoplastic causes (e.g., pulmonary vasculitis, hypersensitivity pneumonia, etc.) should be considered when specific features are present (e.g., hematuria, appropriate epidemiologic exposures) . Ancillary serologic tests or biopsies of extrapulmonary sites are invaluable in some cases . In rare instances, surgical (open or VATS) biopsy is necessary to diagnose refractory or non-resolving "pneumonias." Microbiology, 1999 Sep, 145 ( Pt 9), 2365 - 74 The Streptomyces coelicolor A3(2) lipAR operon encodes an extracellular lipase and a new type of transcriptional regulator; Valdez F et al.; A region of the Streptomyces coelicolor A3(2) chromosome was identified and cloned by using as a probe the lipase gene from Streptomyces exfoliatus M11 . The cloned region consisted of 6286 bp, and carried a complete lipase gene, lipA, as well as a gene encoding a transcriptional activator (lipR) . The S . coelicolor A3(2) lipA gene encodes a functional extracellular lipase 82% identical to the S . exfoliatus M11 lipase; the partially purified S . coelicolor enzyme showed a preference for substrates of short to medium chain length . Transcription of lipA was completely dependent on the presence of lipR, and occurred from a single promoter similar to the lipA promoters of S . exfoliatus M11 and Streptomyces albus G . These three Streptomyces lipA promoters have well-conserved -10 and -35 regions, as well as additional conserved sequences upstream of the -35 region, which could function as targets for transcriptional activation by the cognate LipR regulators . The Streptomyces LipR activators are related to other bacterial regulators of a similar size, constituting a previously unidentified family of proteins that includes MalT, AcoK, AlkS, AfsR, five mycobacterial proteins of unknown function and some Streptomyces regulators in antibiotic synthesis clusters . A lipase-deficient strain of S . coelicolor was constructed and found to be slightly affected in production of the polyketide antibiotic actinorhodin. Ther Umsch, 1999 Sep, 56(9), 541 - 3 {46-year-old woman with multiple hematomas and bleeding of the base of the tongue: phenprocoumon poisoning}; Kriz-Kozak K et al.; A 46-year old nurse complaining of multiple hematomas including bleeding into the tongue was referred for hemostasis evaluation . A very low Quick percentage value, i.e . a severely prolonged prothrombin time with severely depressed vitamin K-dependent coagulation factors (FII:C, FVII:C, FX:C) and normal FV:C and fibrinogen level was found . In the absence of cholestasis, malabsorption and broad-spectrum antibiotic therapy, ingestion of vitamin K antagonists was suspected . Three years previously, she had been on oral anticoagulant treatment with phenprocoumon (Marcoumar) for postoperative pulmonary embolism . She denied having voluntarily ingested anticoagulant drugs . A high plasma level of coumarins was found . To exclude accidental ingestion, the patient's son living in the same household was tested as well . Surprisingly, a low level of coumarin was found also in his plasma . We suspect that the patient voluntarily intoxicated herself and gave a low dose of coumarin anticoagulant to her son as well. Ren Fail, 1999 Sep, 21(5), 533 - 9 Dialysis and pregnancy--a case report and review of the literature; Reister F et al.; We report on a patient with an eight-year history on maintenance hemodialysis treatment without residual renal function in whom pregnancy was successfully managed through to the 29th week . During this time, under carefully modified dialysis treatment, the nephrologic course, as well as materno-fetal flow relationships were unremarkable . Fetal development was appropriate for gestational age . However, pregnancy was complicated by polyhydramnios, which necessitated i.v . tocolysis . In the 28 + 6th week of gestation, cesarean section was performed because of an antibiotic-resistant fever of unclear origin which ceased within two days of delivery . Although the postnatal course of the adequately developed baby was complicated by the respiratory distress syndrome, normal development continued . We emphasize that the intensive interdisciplinary cooperation of nephrologists and obstetricians is imperative for the successful management of pregnancy under these conditions . In these pregnancies, the main fetal problems consist of premature labor because of polyhydramnios, preterm delivery, intrauterine growth retardation and stillbirth . The mother is threatened by the development of superimposed pre-eclampsia, left ventricular failure because of volume overload and progressive anemia . In order to maintain a well-balanced homeostasis, intensification of dialysis therapy by an increase in frequency and duration is the most important therapeutic approach . Accurate fetal monitoring including frequent examination of the feto-maternal circulation by Doppler sonography as well as attentive surveillance of the mother is required to recognize the above mentioned complications. Clin Chest Med, 1999 Sep, 20(3), 681 - 91, xi Therapy for ventilator-associated pneumonia; Carter AB et al.; Pneumonia is a serious complication of mechanical ventilation . Pneumonia occurs despite the best efforts at prevention . Multiple methods available to prevent ventilator-associated pneumonia are reviewed, and ventilation-associated pneumonia (VAP) is divided into early versus late onset . The authors discuss the organisms associated with each of these situations, the empiric antibiotic choices, and specific issues related to antibiotic therapy such as resistance, pharmcodynamics, tissue penetration, and types of modifications necessary in empiric choice when the cause of VAP is identified. Clin Chest Med, 1999 Sep, 20(3), 599 - 605 Strategies for early discharge of the hospitalized patient with community-acquired pneumonia; Siegel RE; The treatment of the hospitalized patient with uncomplicated CAP is changing, to include a brief period of intravenous antibiotics followed by oral therapy . The Classification of Community-Acquired Pneumonia or CoCAP is a stratification tool that categorizes patients as low-risk pneumonia, unstable pneumonia, or complicated pneumonia . Use of validated hospital admission criteria, combined with the CoCAP algorithm and evolving criteria for switching patients from intravenous to oral therapy provides a structure for organizing treatment of patients with CAP for caregivers . Patients who can be discharged early are those from the unstable pneumonia group, which includes patients who have had reversal of their metabolic problems and stabilization of comorbid conditions, and who have not developed any serious pneumonia-related complications . Prolonged courses of intravenous antibiotic therapy are being replaced with 2 to 3 day courses of intravenous hydration and antibiotics; a switch to oral therapy and hospital discharge can be achieved after the patient tolerates one dose of oral therapy . Parameters to watch include vital signs and white blood cell count . Provided these parameters are improving, although they may not have returned to normal, the patient can be switched to oral therapy . Although patient treatment guidelines and critical pathways are becoming widespread in disease management, CAP is one disease in which prospective studies have demonstrated that a reduction in hospital stay is safe . Patients, caregivers, and administrators are happy with the reduction in hospital LOS . Other treatment protocols are being explored, including a single dose of intravenous antibiotic prior to oral switch and all-oral regimens employing the newer fluoroquinolones. Clin Chest Med, 1999 Sep, 20(3), 563 - 73 Pneumonia in the elderly; Feldman C; Pneumonia, including community-acquired, long-term care facility-associated, and nosocomial infections, is a major cause of morbidity and mortality in the elderly . The aged with pneumonia often present with atypical features, including confusion, lethargy, and general deterioration of condition (so-called "silent infection") . Further investigations, such as a chest radiograph, are more frequently required for diagnosis, but even these results may be normal early in the course of infection, particularly in dehydrated patients . The elderly are more frequently hospitalized for pneumonia and have a greater need for intravenous therapy, longer hospital stay, more prolonged course, greater morbidity, and, ultimately, a poorer outcome . Yet in many studies it is not chronological age per se that impacts negatively on the manifestations of pneumonia in the elderly but rather the presence of comorbid illness . Antibiotic therapy remains the mainstay of therapy for pneumonia, and both community and hospital-based studies confirm the important positive impact of early appropriate empiric antibiotic therapy on outcome . Attention to nutrition and hydration, the use of pneumococcal and influenza vaccination, and a number of diverse procedures in the hospital setting may help limit the occurrence and impact of such infections. Soc Sci Med, 1999 Dec, 49(11), 1501 - 17 Online commentary in acute medical visits: a method of shaping patient expectations; Heritage J et al.; This paper conceptualizes a type of physician communication, termed 'online commentary' . Online commentary is talk that describes what the physician is seeing, feeling or hearing during physical examination of the patient . Some dimensions of online commentary are described, and its functions in routine and acute medical consultations are distinguished . Using a case study method, the paper focuses on the role of online commentary in pre-empting patient resistance to upcoming 'no problem' diagnostic evaluations which could delegitimize patients' decisions to seek medical assistance, or deprive them of anticipated medical benefits . It is hypothesized that this role for online commentary may be associated with successful physician resistance to implicit or explicit patient demands for inappropriate antibiotic medication. Ter Arkh, 1999, 71(8), 40 - 3 {Importance of microcirculatory disorders in combined treatment of acute pleural empyema and pyopneumothorax}; Tseimakh EA; AIM: To investigate responses to application of quick-frozen or cryosupernatant plasma, heparin and proteinases inhibitors of DIC-syndrome in patients with pleural empyema and pyopneumothorax . MATERIALS AND METHODS: Transfusions of quick-frozen or cryosupernatant plasma, injections of heparin and inhibitors of proteinases were used as an adjuvant to conventional treatment in 548 patients with acute pleural empyema and pyopneumothorax . RESULTS: The addition of cryoplasm-antienzyme complex to conventional treatment of acute pleural empyema resulted in reduced number of lethal outcomes compared to the conventional treatment alone (5.9 vs 14.4%, respectively) . CONCLUSION: Transfusion of quick-frozen or cryosupernatant plasma, injection of heparin and inhibitors of proteinases improve microcirculation around the inflammatory focus . In addition to antibiotic therapy and evacuation of the pus from the pleural cavity, the above methods contribute to better outcomes of pleural empyema and pyopneumothorax. J Biol Chem, 1999 Oct 15, 274(42), 29624 - 7 Surface plasmon resonance studies resolve the enigmatic endotoxin neutralizing activity of polymyxin B; Thomas CJ et al.; Polymyxin B (PMB), a cyclic cationic peptide antibiotic, despite its severe side effects continues to occupy a premiere position for treating endotoxicosis . Its mode of neutralization of endotoxin has remained elusive for the last three decades . Several synthetic peptide mimics of PMB, capable of binding endotoxin, have been made . However, the binding ability alone appears to be a deceptive indicator of endotoxin neutralizing activity as molecules with similar binding propensities could either sequester or opsonize the toxin . Hence identification of additional physical parameters which describe adequately the outcome of PMB-endotoxin interaction become imperative . Surface plasmon resonance (SPR) studies reported here show that several mimics of PMB despite exhibiting lipopolysaccharide binding affinities comparable with it but, unlike it, do not sequester the endotoxin . These studies thus provide a striking illustration of the difference in the behavior of PMB, vis a vis its mimics toward the endotoxin lamellae, and define further, in chemical terms, mechanism of the action of PMB and allow us to posit that the design of molecules as effective antidotes for sepsis should incorporate the ability to sequester endotoxin specifically. J Nat Prod, 1999 Sep, 62(9), 1218 - 21 Biologically active secondary metabolites from fungi . 12.(1) oidiolactones A-F, labdane diterpene derivatives isolated from oidiodendron truncata John M, Krohn K, Florke U, Aust HJ, Draeger S, Schulz B. Two known (1 and 2) and four new (3-6) diterpenes named oidiolactones A-F, respectively, and the antibiotic cladosporin were isolated from the fungus Oidiodendron truncata . The structure determination was mainly based on 1D and 2D NMR spectroscopy . The structures of compound 4, displaying an equilibrium between open-chain and cyclized form, and of cladosporin were confirmed by X-ray analysis. Plast Reconstr Surg, 1999 Oct, 104(5), 1397 - 405 Differences between scar and dermal cultured fibroblasts derived from a patient with recurrent abdominal incision wound herniation; Boemi L et al.; Fibroblasts were derived from dermis and scar of a 47-year-old white man with a recurrent incisional hernia as a result of fractured ribs . The scar was thin and stretched, suggesting a defect in the maturation of granulation tissue . After surgical repair, biopsy specimens of discarded scar and skin were used to generate fibroblast cell lines . Fibroblasts maintained in medium containing 10% fetal bovine serum and antibiotic were studied between their third and eighth passage . By phase contrast microscopy, no structural differences were obvious, but it was noted that to pass scar fibroblasts, a more aggressive trypsin regimen was required . Immunohistologic and Western blot analysis of patient scar fibroblasts showed (1) more a smooth muscle actin within stress fibers, (2) increased expression of the vitronectin integrin receptor alpha(v) (CD 51), and (3) reduced expression of the collagen integrin receptor alpha2 (CD 49b) . The expression of vinculin from focal adhesions or a tubulin from microtubules was the same among cell lines . Contractions of scar and dermal fibroblast-populated collagen lattice were compared . At 24 hours, contractions were 69 percent with newborn fibroblasts (normal); 68 percent for patient dermal fibroblasts; and only 48 percent for patient scar fibroblasts . The retarded contraction of scar fibroblast-populated collagen lattice was significant (p > or = 0.002) . Myosin ATPase activity, critical for lattice contraction, and cell migration were equivalent among all cell lines . A plausible mechanism for the retardation of scar lattice contraction is disruption of fibroblasts and collagen interactions, for which the attachment of cells to collagen is altered . It is proposed that either the decrease in the expression of collagen integrin receptor alpha2 (CD 49b), an increase in the expression of the vitronectin receptor alpha(v) (CD 51), or a combination of both is responsible for disruption of collagen fibroblast interactions. Arthritis Rheum, 1999 Sep, 42(9), 2002 - 6 Hypertrophic osteoarthropathy can indicate recurrence of Whipple's disease; Marie I et al.; We report the case of a patient with Whipple's disease (WD) who developed hypertrophic osteoarthropathy (HOA) characterized by digital clubbing, periostosis of the tubular bones, and polysynovitis . The HOA disclosed the recurrence of the patient's WD, since polymerase chain reaction (PCR) analysis clearly demonstrated the presence of Tropheryma whippelii in the synovial fluid from the patient's left knee . Initiation of appropriate antibiotic therapy resulted in complete healing of all clinical rheumatologic manifestations within 2 months and in disappearance of radiographic bone changes at 7-month followup . We suggest that HOA be included within the spectrum of rheumatologic manifestations of WD, and that an evaluation for WD should be considered in patients, especially middle-aged men, presenting with HOA even without gastrointestinal symptoms . PCR analysis may be useful in accurate diagnosis and management of early WD with unusual clinical manifestations, and may contribute to decreased morbidity and mortality. J Investig Allergol Clin Immunol, 1999 Jul-Aug, 9(4), 215 - 21 Allergy to betalactams: relationship between chemical structure and antigenicity of molecules; Patriarca G et al.; As betalactams (penicillins, cephalosporins, carbapenems, monobactams, betalactamase inhibitors) are the most widely used antibiotic drugs worldwide, allergy to betalactams is a frequent problem encountered in clinical practice, concerning from 0.7-8% of treated patients . It is now clear that the antigenicity of these drugs is strictly related to the chemical structure of the various molecules and of their constituent parts . In this paper we first describe the chemical structure of betalactams and then try to establish a correlation between this structure and their antigenicity. Eksp Klin Farmakol, 1999 Jul-Aug, 62(4), 65 - 6 {The effect of polikatan on the ototoxic action of kanamycin}; Spasov AA et al.; Experiments on guinea pigs demonstrated that preliminary injection of polycatan (standardized magnesium solution containing the mineral bischofite) into the parotid region by means of electrophoresis reduces the ototoxic effect of the aminoglycoside antibiotic kanamycin . Polycatan prevents kanamycin-induced degenerative changes of the hair cells found in the labyrinth of the internal ear and improves the local blood flow. J Mol Biol, 1999 Oct 15, 293(1), 1 - 8 Isolation of kasugamycin resistant mutants in the 16 S ribosomal RNA of Escherichia coli; Vila-Sanjurjo A et al.; Three ribosomal RNA mutations conferring resistance to the antibiotic kasugamycin were isolated using a strain of Escherichia coli in which all of the rRNA is transcribed from a plasmid-encoded rrn operon . The mutations, A794G, G926A, and A1519C, mapped to universally conserved sites in the 16 S RNA gene . Site-directed mutagenesis studies showed that virtually all mutations at these three sites conferred kasugamycin resistance and had very slight effects on cell growth . It has been known for many years that the absence of post-transcriptional modification at A1519 and the adjacent A1518 in strains lacking a functional KsgA methylase produces a kasugamycin resistance phenotype . Mutations at A1519 conferred kasugamycin resistance and had minor effects on cell growth, whereas mutations at 1518 did not confer resistance and increased the doubling time of the cells dramatically . Expression of mutations at A1518/A1519 in a methylase deficient ksgA(-)strain had divergent effects on the phenotype of the rRNA mutants, suggesting that the base identity at either position does not affect methylation at the adjacent site . Residues A794 and G926 are protected from chemical modification by kasugamycin and tRNA, and have been implicated in the initiation of protein synthesis . Despite the universal conservation and functional importance of these residues, the results presented here show that the identity of the bases is not critical for ribosomal function . Antibiot Khimioter, 1999, 44(9), 7 - 9 {Hypolipidemic action of ascofuranone in hepatoblastoma G2 cell culture}; Trenin AS; Ascofuranone, an isoprenoid antibiotic, suppressed 14C acetate incorporation into cholesterol, cholesterol ethers, triglycerides, phospholipids and free fatty acids in Hep G2 cell culture . Such a complex action of the antibiotic on lipid synthesis and metabolism was not connected with the inhibition of protein synthesis and the antibiotic toxicity. J Med Microbiol, 1999 Oct, 48(10), 891 - 6 Molecular characterisation of verocytotoxin-producing Escherichia coli of serogroup O111 from different countries; Morabito S et al.; A collection of epidemiologically unrelated verocytotoxin (VT)-producing Escherichia coli (VTEC) strains of serogroup O111 isolated from human patients and cattle with diarrhoeal disease in five different countries were characterised by determination of their VT genotypes, the presence of other virulence factors such as the intimin-coding eae gene and the enterohaemorrhagic E . coli (EHEC) plasmid, and their antibiotic susceptibility patterns . The genetic relatedness among isolates was evaluated by genomic DNA fingerprinting techniques such as restriction fragment length polymorphism analysis of ribosomal RNA genes (ribotyping) and pulsed-field gel electrophoresis . The results indicated that the VTEC O111 examined belong to two distinct clonal lineages . The first group was constituted mainly of non-motile, eae-positive, EHEC plasmid-positive isolates from both man and cattle . The second lineage was represented by an O111:H2 epidemic strain, isolated during an outbreak of haemolytic uraemic syndrome in France and exhibiting an unusual combination of virulence factors: VT production and aggregative adhesion to HEp-2 cells associated with an enteroaggregative E . coli (EAEC) plasmid. Ann Urol (Paris), 1999, 33(4), 271 - 3 {Prostatic abscesses . A review}; Rabii R et al.; We review the literature to the diagnosis and therapeutic aspect of prostatic abscess . The prostatic abscess having become an uncommon disease . The diagnosis of prostatic abscess has been nearly made by transrectal ultrasound and computed tomography scan . The best diagnostic method is considered to be the transrectal ultrasound . The choice therapy was intravenous antibiotic, and drainage by ultrasound guided transperineal percutaneous puncture. Ann Thorac Surg, 1999 Sep, 68(3), 1080 - 2 Management of wound and left ventricular assist device pocket infection; Holman WL et al.; Our patient developed a wound infection that involved an implanted left ventricular assist device . At surgery, the pump was washed with a detergent-containing bacteriocidal solution, then antibiotic-impregnated polymethylmethacrylate beads were placed around the pump . The wound was revised using rectus muscle to cover the pump . The incisions have healed and the patient is now at home . She is on no systemic antibiotics and has no evidence of infection 11 months postoperatively. Antimicrob Agents Chemother, 1999 Oct, 43(10), 2524 - 7 Effects of cilastatin on the pharmacokinetics of a new carbapenem, DA-1131, in rats, rabbits, and dogs; Kim SH et al.; DA-1131, a new carbapenem antibiotic, undergoes renal metabolism by renal dehydropeptidase I (DHP-I), located on the brush border of the proximal tubular cell . Species differences with regard to the effects of cilastatin, a renal DHP-I inhibitor, were investigated after a 1-min intravenous infusion of DA-1131, with or without cilastatin, to rats, rabbits, and dogs . After intravenous infusion, the nonrenal clearance (CL(NR)) of DA-1131 was significantly slower in rats (3.00 versus 8.01 ml/min/kg) and rabbits (2.41 versus 6.77 ml/min/kg) when the drug was coadministered with cilastatin; this could be due to the slower metabolism of DA-1131 by rat and rabbit kidney DHP-I . This indicated that renal metabolism of DA-1131 by renal DHP-I was inhibited by cilastatin . However, coadministration with cilastatin to dogs did not affect the CL(NR) of DA-1131. Am J Forensic Med Pathol, 1999 Sep, 20(3), 240 - 2 Pulmonary thromboembolism following calf cellulitis: report of an unusual complication of dog bite; Falconieri G et al.; We report a case of a 75-year-old woman who died of pulmonary thromboembolism following a dog bite to the calf . The bite caused laceration of the skin and gangrenous cellulitis of leg soft tissues . Six days after hospitalization, the patient died suddenly, despite early antibiotic and heparin administration . Postmortem examination revealed extensive thrombosis of the deep veins of the calf and massive thromboembolism of the main pulmonary arteries. Crit Care Med, 1999 Sep, 27(9), 1768 - 74 Results of a collaborative quality improvement program on outcomes and costs in a tertiary critical care unit; Clemmer TP et al.; OBJECTIVE: To demonstrate that by using the knowledge and skills of the primary care provider and by applying statistical and scientific principles of quality improvement, outcomes can be improved and costs significantly reduced . DESIGN: A before and after quasi-experimentally designed trial using historical controls plus an analysis of costs in areas not influenced by intensive care unit (ICU) practice to control for possible secular changes . SETTING: A tertiary ICU . PATIENTS: All patients admitted to the above-mentioned ICU from January 1, 1991, through December 31, 1995 . INTERVENTIONS: a) A focused program that applied statistical and scientific quality improvement processes to the practice of intensive care . b) An organized effort to modify the culture, thinking, and behavior of the personnel who practice in the ICU . MEASUREMENTS: Severity of illness, ICU and hospital lengths of stay, ICU and hospital mortality rates, total hospital costs as analyzed by the cost center, and measures of improvement in specific areas of care . MAIN RESULTS: Significant improvement in glucose control, use of enteral feeding, antibiotic use, adult respiratory distress syndrome survival, laboratory use, blood gases use, radiograph use, and appropriate use of sedation . A severity adjusted total hospital cost reduction of $2,580,981 in 1991 dollars when comparing 1995 with the control year of 1991, with 87% of the reduction in those cost centers directly influenced by the intervention . CONCLUSIONS: A focused quality improvement program in the ICU can have a beneficial impact on care and simultaneously reduce costs. Otolaryngol Head Neck Surg, 1999 Oct, 121(4), 435 - 40 Quality-of-life outcomes after osteoplastic frontal sinus obliteration; Alsarraf R et al.; Frontal sinusitis and its treatment remain controversial . Although several authors have evaluated the results of traditional endoscopic sinus surgery, few have assessed patient outcomes and quality of life after osteoplastic frontal sinus obliteration . This retrospective study evaluates these outcomes in a postoperative review and questionnaire of 39 patients treated at the University of Washington from 1991 to 1994 . Most patients were satisfied with the results of this procedure, had significant improvements in their Chronic Sinusitis Survey scores, and reported decreased clinic visits and antibiotic use . However, approximately half thought nonsurgical treatments were more effective and continued to require other medical therapy; 30% required additional surgical intervention . Such outcomes may reflect the ineffectiveness of frontal sinus obliteration to treat the chronic symptoms of patients affected by the refractory underlying disease process of chronic sinusitis; however, despite these mixed results, we found a significant decrease in annual days of lost work or activity in this study group after osteoplastic obliteration. Otolaryngol Head Neck Surg, 1999 Oct, 121(4), 398 - 405 Retropharyngeal abscess management in children: current practices; Lalakea M et al.; Retropharyngeal abscesses (RAs) in children are uncommon in the modern antibiotic era . As a result, there are few large series outlining the management of these infections in contemporary literature . The goal of this study is to determine the current standard of care for RA . The membership of the American Society of Pediatric Otolaryngology was surveyed, and the response rate was 77.5% . Seventy-two percent of practitioners reported that CT is their preferred diagnostic method . Nearly two thirds recommended a trial of intravenous antibiotics at least occasionally for suspected RA before operative drainage was considered; 51% of respondents indicated that 20% to 40% of RA may resolve with antibiotics alone . Intraoral incision and drainage is the surgical technique preferred by 83% of respondents . Tracheotomy and short-term intubation (24 to 72 hours) are rarely required . This study defines current management practices for RA in children among pediatric otolaryngologists . Results are compared with those in the existing literature. Otolaryngol Head Neck Surg, 1999 Oct, 121(4), 378 - 80 Early detection and treatment of postoperative pharyngocutaneous fistula; Friedman M et al.; Fever during the early postoperative period traditionally has not been considered an indication of a postoperative wound infection or breakdown . Atelectasis is considered the most likely source for these early fevers . We studied 200 consecutive patients who underwent major head and neck surgery that involved reconstruction with a pharyngeal suture line . Patients were divided into 2 groups: those who had preoperative irradiation and those who did not . All patients had prophylactic antibiotic coverage, and all patients had identical suture material for closure . We showed a high correlation between fever (>101.5 degrees F) that developed in the first 48 hours and eventual fistula formation and wound infection . We also studied length of hospitalization and number of days until decannulation and resumption of oral feedings . Our data indicate that in those patients in whom fistulas developed, early detection led to earlier healing and rehabilitation. Int J Pediatr Otorhinolaryngol, 1999 Aug 5, 49(2), 143 - 9 Efficacy of tympanostomy tube insertion for otitis media with effusion in children with Down syndrome; Iino Y et al.; OBJECTIVE: Although the insertion of tympanostomy tubes is regarded as an effective treatment for otitis media with effusion in the general population, it remains to be determined whether tympanostomy tube insertion is also effective for otitis media with effusion in children with Down syndrome . The present study was carried out to determine the efficacy of tympanostomy tube insertion in children with Down syndrome . PATIENTS AND METHODS: We studied 28 children (18 males and ten females) with Down syndrome and 28 age-matched control children who underwent tympanostomy tube insertion and were followed up for more than 2 years, up to 7 years of age or older . The children were followed up every month for 6 months after the operation and every 2 months thereafter . The tympanostomy tubes were not removed unless granulation tissue appeared around the ventilation tubes . RESULTS: The cure rate for otitis media with effusion was lower in the children with Down syndrome than in the age-matched control children . Sequelae of otitis media with effusion (atelectatic eardrum, permanent perforation of the eardrum and middle ear cholesteatoma) were significantly often encountered in the former group . The children with Down syndrome had more frequent episodes of otorrhea from the tympanostomy tubes than the control children and antibiotic-resistant-bacteria were frequently isolated . Moreover, improvement in hearing acuity after the placement of tympanostomy tubes was not always achieved in children with Down syndrome . CONCLUSION: The efficacy of the tympanostomy tube insertion for children with Down syndrome was much lower than in control children . We propose that in children with Down syndrome conservative management should be the treatment of first choice and that the insertion of tympanostomy tubes should be indicated only when hearing loss due to middle ear effusion is in a severe degree and when pathological changes of the eardrum, such as adhesion and deep retraction pocket formation, are going to occur. Eur J Gastroenterol Hepatol, 1999 Aug, 11 Suppl 2, S25 - 8; discussion S43-5 Is there any difference in Helicobacter pylori eradication rates in patients with active peptic ulcer, inactive peptic ulcer and functional dyspepsia? Spiller RC. Omeprazole triple therapy has been shown to produce Helicobacter pylori eradication rates of up to 96% in patients with current or recent peptic ulceration . Such therapy is also now being used without endoscopy in H . pylori-positive patients who may have an inactive ulcer or dyspepsia, and in whom their effectiveness has been less well documented . Compliance is an important variable affecting H . pylori eradication; with 1-week omeprazole triple therapy, however, compliance is uniformly high, and this allows more detailed analysis of other causes of treatment failure . The strains of H . pylori in patients with functional dyspepsia may be associated with a lower degree of inflammation . Two new, large studies (DU-MACH and GU-MACH) have therefore looked at the impact of inflammation on H . pylori eradication . Polymorph infiltration in the antrum of patients with inflammation of grades 2/3 was associated with a significantly higher eradication rate when compared with inflammation of grades 0/1 . Inflammation may be important for a number of reasons, including degradation of the mucus and epithelial layers (which may allow better penetration of charged antibiotics from the gastric lumen) and altered vascular and epithelial permeability (which may allow better systemic delivery of drugs) . Alternatively, inflammation may be a marker for more aggressive H . pylori subtypes, which are also more vulnerable to antibiotic therapy. Curr Opin Rheumatol, 1999 Sep, 11(5), 364 - 71 Current issues in the diagnosis and treatment of Sjögren's syndrome; Fox RI et al.; Modification of the European Cooperative Group (EEC) criteria for Sjogren's Syndrome (SS) should lead to less confusion in diagnosis and therapeutic trials . The proposed EEC modification will require either a positive minor salivary gland biopsy or a positive autoantibody against Sjogren's-associated A (Ro) or B (La) antigen . This modification will decrease the proportion of women fulfilling EEC criteria from 3-5% to about 0.5%, which is similar to San Diego and San Francisco criteria . Genetic studies have shown increased frequency of alleles for peptide transporter genes TAP1 (0101) and TAP2 (0101) genes as well as tumor necrosis factor microsatellite a2 alleles . Although these markers confer markedly increased risk, they are found in only a small proportion of patients . An increased frequency of drug (antibiotic) allergy and other allergic manifestations appears present in patients with SS and may be linked to HLA-DR3 . Hepatitis C as a cause of sicca symptoms, positive anti-nuclear autoantibodies, and mixed cryoglobulinemia is increasingly reported in different parts of the world . Antibodies against muscarinic M3 receptor and expression of costimulatory molecules (CD80 and CD86) by ductal epithelial cells may play a role in pathogenesis . Treatment with pilocarpine is effective in double-blind trials and low dose oral alpha interferon looks promising in initial open studies . In pregnant patients who exhibit evidence of neonatal heart block, treatment with dexamethasone is preferred over prednisone, since the placenta is unable to metabolically activate the latter compound. Acta Otorrinolaringol Esp, 1999 Aug-Sep, 50(6), 467 - 72 {The nonserological diagnostic approach to infectious mononucleosis in an emergency service}; Garcia Callejo FJ et al.; Patients with infectious mononucleosis often are seen in Emergency Services because the infection may produce tonsillitis resistant to antibiotic therapy . However, the diagnosis of choice is specific serology, which usually takes days or weeks before results become available . Detection of lymphocytosis in peripheral blood, heterophilic antibodies, and the characteristic mononuclear cells by means of specialized blood counters, together with the clinical signs, have improved the quality of diagnosis in emergency services (93% sensitivity and 97.2% specificity) . We found that simple identification by optical microscopy of the lymphomonocytes typical of infectious mononucleosis in a drop of peripheral blood, together with the clinical findings, have a better diagnostic sensitivity (96 . 5%) and specificity (99.1%) than any other method available in emergency services. Br J Ophthalmol, 1999 Oct, 83(10), 1183 - 5 Penetration of topical, oral, and combined administered ofloxacin into the subretinal fluid; Cekic O et al.; AIMS: To assess the subretinal fluid (SRF) levels of ofloxacin following topical, oral or combined administration . METHODS: 31 patients undergoing conventional retinal reattachment surgery were randomly assigned to three groups . Nine patients received topical ofloxacin, 11 patients received oral ofloxacin, and the other 11 patients received combined administration . Collected SRF samples were analysed for drug level by using high performance liquid chromatography . RESULTS: SRF drug levels after oral and combined administration were significantly higher than that after topical administration (p=0.0002 and p=0.0002, respectively) while there was no significant difference between oral and combined administration (p=0.0844) . CONCLUSIONS: Ocular bioavailability of ofloxacin in SRF after oral and combined administration is equivalent . The addition of oral ofloxacin to topical therapy increased drug SRF penetration sixfold. Urologe A, 1999 Sep, 38(5), 486 - 9 {Ureteral stent placement in hydronephrosis during pregnancy}; John H et al.; In this study we describe 22 cases of retrograde ureteral stent placement in pregnant women with therapy-resistant flank pain due to hydronephrosis . Eleven were primiparous and one patient expected twins . Eight of 22 patients presented symptoms of pyelonephritis . In 21 cases the hydronephrosis was located on the right and in 4 cases it was bilateral . Maximal lower calix diameter was 12 mm (range 9-22 mm) . With the exception of two cases, sonographically controlled stent placement was performed under local anesthesia without sedation . All patients were painfree within 6 days and were given prophylactic low doses of antibiotic until the day of delivery . Renal function remained within the normal limits . Double-J stent displacement occurred in 3 patients - of which one underwent nephrostomy . Postnatal examination demonstrated urolithiasis in 4 of 19 patients . This study provides evidence for effectiveness of retrograde ureteral Double-J stent placement as a therapeutic option in cases of severe symptomatic hydronephrosis during pregnancy with a low morbidity rate. Anticancer Drug Des, 1999 Jun, 14(3), 291 - 303 Recognition elements that determine affinity and sequence-specific binding to DNA of 2QN, a biosynthetic bis-quinoline analogue of echinomycin; Bailly C et al.; Footprinting experiments with DNase I provide a starting-point for investigating the molecular basis of nucleotide sequence recognition by 2QN, a bis-quinoline derivative of the quinoxaline antibiotic echinomycin produced by directed biosynthesis in Streptomyces echinatus . Using tyrT DNA molecules variously substituted with inosine and/or 2,6-diaminopurine residues it is shown that the location of the 2-amino group of purine nucleotides in the minor groove of the double helix exerts a dominant influence in determining where the antibiotic will bind, as it does for echinomycin . However, newly created binding sites in DNA molecules substituted with diaminopurine (D), all located round TpD steps, bind 2QN with so much higher affinity than the canonical CpG steps that the latter fail completely to appear as footprints in D-substituted DNA; indeed CpG sequences appear in regions of enhanced susceptibility to nuclease cleavage as do CpI steps in doubly D + I-substituted DNA . Quantitative footprinting plots confirm that sequences surrounding TpD steps bind 2QN several hundred-fold more tightly than do CpG-containing sequences, with dissociation constants of the order of 25 nM . To test the hypothesis that differences in stacking interactions between the chromophores of the drug and the DNA base pairs could account for the differences in binding affinities, models of 2QN bound to two DNA hexamers containing either a central CpG or a central TpD step were built . Calculation of the molecular electrostatic potential (MEP) of 2QN in solution using a continuum method revealed a distinctive pattern that is considered relevant to DNA binding . When the MEPs calculated for the two DNA hexamers in the complexed state were compared, substantial differences were found in the major groove and in the space between the base pairs that is occupied by the chromophores of the drug upon binding . The modelling data support the notion that electrostatic stacking interactions underlie the considerably preferred binding of echinomycin and 2QN around TpD steps rather than CpG steps. Scand J Gastroenterol Suppl, 1999, 230, 23 - 8 Disease management in ulcer disease; de Boer WA et al.; BACKGROUND: Our knowledge of Helicobacter pylori infection indicates that it is possible to eliminate ulcer disease and improve quality of life for ulcer patients . Treatment is evidence-based and cost-effective . However, though we now have the tools, we have not yet been able to eliminate ulcer disease from society . Dissemination of knowledge and treatment implementation have been problematic . In primary care, there is diagnostic and therapeutic chaos regarding this infection . Disagreement exists on indications for treatment . Expenditure on acid-reducing drugs has greatly increased . Clearly we are not treating all ulcer patients properly (undertreatment); instead we have incorporated H . pylori therapy ('test and treat') into our approach to dyspepsia (overtreatment) . Anti-H . pylori therapy in patients with non-ulcer dyspepsia may increase costs because most patients still suffer from symptoms after antibiotic therapy, and therefore require further diagnostic procedures and prescription of new drugs . In order to redeem the great promise of H . pylori, we must focus less on new ulcer patients, because the incidence is rapidly decreasing in Western Europe . Prevalence of ulcer disease, however, is still high . Thus we need to focus more on prevalent cases . We ought to seek and treat those persons already known to have ulcer disease . Systematic 'case-finding' strategies must be performed using standard protocols . Only such 'disease management' programmes performed at the primary care level will suffice to eliminate ulcer disease while also being cost-effective. J Fam Pract, 1999 Sep, 48(9), 690 - 7 Performance failure of an evidence-based upper respiratory infection clinical guideline; O'Connor PJ et al.; BACKGROUND: We evaluated an upper respiratory infection (URI) clinical guideline to determine if it would favorably affect the quality and cost of care in a health maintenance organization . METHODS: Patients with URI symptoms contacting 4 primary care practices before and after guideline implementation were compared to ascertain what proportion of all patients with respiratory symptoms were eligible for treatment in accordance with the URI guideline; what proportion of eligible patients were managed without an office visit; and what proportion of eligible patients were treated with antibiotics, before and after guideline implementation . RESULTS: A total of 3163 patients with respiratory symptoms were identified . Of these, 59% (n = 1880) had disqualifying symptoms or comorbid conditions for URI guideline care, and 28% (n = 1290) received disqualifying diagnoses on the day of first contact, leaving 13% (n = 408) who received a diagnosis of URI and were eligible for care in accordance with the guideline . Among this group of patients, the proportion who received guideline-recommended initial telephone care was 45% preguideline and 47% postguideline (chi2 = 0.40; P = .82) . Likelihood of a subsequent office visit increased from pre- to postguideline (chi2 = 17.1; P <.01), although the majority of patients had no further diagnoses other than URI . Antibiotic use for the initial URI diagnosis declined from 24% preguideline to 16% postguideline (chi2 = 3.97; P = .046), but antibiotic use during 21-day follow-up did not change (F = 0.46, P = .66) . The mean cost of initial care was $37.80 preguideline and $36.20 postguideline (P >.05) . CONCLUSIONS: Only 13% of primary care patients with respiratory symptoms were eligible for URI guideline care . Among eligible patients, use of the guideline failed to decrease clinic visits, decrease antibiotic use during a 21-day period, or reduce cost of care to the health plan. Nihon Kokyuki Gakkai Zasshi, 1999 Aug, 37(8), 619 - 22 {Pyothorax associated lymphoma treated by chemotherapy after thoracostomy}; Yoshitomi A et al.; A 62-year-old man with a medical history that included artificial pneumothorax therapy at the age of 18 was admitted to our hospital because of persistent cough . Chest computed tomographic scans disclosed atelectasis in the right lung and pyothorax surrounded by calcifications . Radiographic examination failed to disclose any tumors . After admission, high grade fever developed due to aggravated pyothorax infection . Because antibiotic therapy and drainage failed, open window thoracostomy was performed . Tumors were found along the wall of the pyothorax cavity, and examination of resected specimens yielded a diagnosis of non-Hodgkin's lymphoma, diffuse large cell type (B-cell lineage) . It was difficult to close the pyothorax cavity due to infection and lymphoma . Therefore, with the thoracic window open, the patient was given combination chemotherapy including CHOP (6 courses) and DeVIC (7 courses) . He died of disseminated intravascular coagulation 17 months after thoracostomy . In patients with pyothorax associated lymphoma, chemotherapy is sometimes difficult to perform because of persistent pyothorax infection . Although edema and ascites due to protein loss from the tumor complicated the treatment of our patient, we concluded that open window thoracostomy is effective in managing pyothorax prior to and during chemotherapy. Mol Gen Mikrobiol Virusol, 1999, (3), 34 - 40 {Ionophore characteristics of heliomycin}; Sverdlova AN et al.; A highly purified product, identified as a well-known antibiotic geliomycin, has been derived by gradient extraction of the mycelium from Streptomyces robefuscus isolated from soil specimens as a result of purposeful search for a producer of hydrophobic ionophore antibiotics . The ionophore properties of geliomycin are highly labile and inducible . Cationic or anionic nature and the angle of the function performed depend on the concentration, type of electrolyte, protocol of measurements, and some additives used for the preparation of geliomycin electrodes to measurements . Stable development of the cationic function was detected for potassium chloride . The lability of ionophore properties was the highest with ammonium chloride as the electrolyte . Ammonium acetate and potassium and sodium chlorides notably increased the stability of geliomycin electrodes . Selective activity of geliomycin towards potassium ion is a more permanent characteristic . The results permit a conclusion about the inducibility of ionophore properties of geliomycin, which may play an important role in the vital activity of the producer and manifest as a regulatory factor in maintenance of water and acid base balance. Sex Transm Dis, 1999 Sep, 26(8), 426 - 30 Enzyme-linked immunospot assay for the diagnosis of active Treponema pallidum infection during the various stages of syphilis; Tabidze IL et al.; BACKGROUND: Specific serologic assays for syphilis cannot differentiate current infections from past infections and are inefficient to monitor efficacy of antibiotic therapy . GOAL: To develop a new immunologic assay for the identification of active Treponema pallidum infection during the various stages of syphilis . STUDY DESIGN: Peripheral blood mononuclear cells obtained from patients with syphilis in an STD clinic were tested for T . pallidum-specific circulating antibody-secreting cells (ASC) by an enzyme-linked immunospot assay (ELISPOT) . RESULTS: Specific ASC were demonstrated in all six patients with primary syphilis and in 14 of 16 patients diagnosed with secondary syphilis . ASCs were undetectable in five patients 8 to 16 days after appropriate therapy, but persisted in one case that was considered treatment failure . Among the 13 patients diagnosed with latent syphilis, six (46%) demonstrated ASC, reflecting antigenic stimulation . CONCLUSION: The ELISPOT assay is effective for the diagnosis of primary and secondary syphilis . The presence of circulating ASC suggests persistent active infection in some patients during the latent disease stage. J Am Anim Hosp Assoc, 1999 Sep-Oct, 35(5), 405 - 9 Cryptosporidiosis, coccidiosis, and total colonic mucosal collapse in an immunosuppressed puppy; Willard MD et al.; An eight-week-old puppy with chronic diarrhea was diagnosed with simultaneous opportunistic pathogens (i.e., cryptosporidiosis, coccidiosis) and total colonic mucosal collapse . Lack of lymphoid follicles in the spleen and lymph nodes suggested a primary underlying immunosuppression that most likely permitted infection with these pathogens . Intensive antibiotic therapy was most likely responsible for the severe colonic lesion, and bismuth subsalicylate administration in this severely dehydrated puppy may have contributed to renal failure as the ultimate cause of death. Chest, 1999 Sep, 116(3), 830 - 2 Unilateral leptospiral pneumonia and cold agglutinin disease; Bowsher B et al.; Pneumonia that is unresponsive to appropriate antibiotic therapy suggests an infection due to more unusual or resistant organisms . In this report, a child with unilateral pneumonia, pleural effusion, and anti-I cold hemagglutinin antibodies is presented . The usual causes of this clinical picture were suspected and treated, but the child did not improve . Features of her history suggested a more unusual etiology, and a diagnosis of leptospirosis was made . A brief discussion of leptospiral disease in children is provided. J Urol, 1999 Oct, 162(4), 1273 - 6 Clinical and radiological findings in patients with gas forming renal abscess treated conservatively; Best CD et al.; PURPOSE: Emphysematous pyelonephritis in diabetics is considered a potentially lethal infection . Mortality rates of patients treated conservatively approaches 80% in some series . These patients often present with signs of sepsis or septic shock . In contrast, gas forming renal abscess is rare, with patients presenting entirely differently from those with emphysematous pyelonephritis . To our knowledge this process has been previously described only in isolated case reports . We describe a series of 5 patients with this distinct process . MATERIALS AND METHODS: We reviewed the clinical and radiological features of 5 patients with gas forming renal abscesses . RESULTS: Each patient presented with diabetes mellitus with initial blood glucose ranging from 313 to 552 mg./dl., fever (average 101F), flank or abdominal pain and pyuria . No patient had evidence of septic shock at hospitalization . Escherichia coli was the documented organism in each case . Mild renal insufficiency was noted in most patients based on serum creatinine . Radiological evaluation revealed gas filled pockets within the renal parenchyma, which were most effectively shown by computerized tomography (CT) of the abdomen . There was no radiological evidence of pus . Percutaneous drainage of an abscess in 1 case did not produce any purulent material or alter the clinical course . Each patient responded to correction of the underlying metabolic abnormalities with intravenous antibiotics (average 23 days) followed by prolonged oral antibiotic therapy (average 9 weeks) . In contrast to the management of emphysematous pyelonephritis, surgical or percutaneous drainage was not necessary . Serial CT revealed complete resolution of gas in the parenchyma within 6 months in patients with long-term followup . Of note, gas was persistent on CT months after infection had clinically resolved . CONCLUSIONS: We describe a unique entity within the spectrum of pyelonephritis . The clinical appearance of gas forming abscesses within the renal parenchyma without liquefaction in diabetic patients was remarkably benign compared to the radiographic appearance of the disease process . Conservative management with intravenous and oral antibiotics was successful in each patient, avoiding the need for invasive intervention. Dig Dis Sci, 1999 Aug, 44(8), 1721 - 31 Gastroprotective effect of intragastric clarithromycin against damage induced by ethanol in rats; Gutierrez-Cabano CA et al.; Intragastric administration of clarithromycin, a macrolide antibiotic, macroscopically protected the rat gastric mucosa from 96% ethanol-induced lesions . This protective effect was dose-dependent, the reduction being 92.3, 81.4, 52.2, and 5.4% at doses of 400, 200, 100, and 50 mg/kg, respectively . Clarithromycin protection was not significantly modified by pretreatment with either subcutaneous indomethacin (5 mg/kg), a selective cyclooxygenase inhibitor, or iodoacetamide (100 mg/kg), a specific sulfhydryl blocker . Gastric motor activity, measured by the balloon method, was inhibited by clarithromycin in a dose-dependent fashion . The inhibited gastric motor activity induced by clarithromycin was not modified by pretreatment with either indomethacin or iodoacetamide . Ethanol (1 ml/rat, gavage needle) induced hemorrhagic bandlike lesions in the mucosa of the glandular stomach along the long axis of the greater curvature with the occurrence of a complete inhibition of gastric motor activity . This inhibition was not modified by pretreatment with clarithromycin, indomethacin, or iodoacetamide . There was an increase in the fluid volume for clarithromycin at 100, 200, and 400 mg/kg at 30 min and in the mucus volume only for clarithromycin at 400 mg/kg at 30 min . Gastric mucosal blood flow was absent in the ethanol-induced lesions but in the nonlesion areas was the same in clarithromycin-pretreated and vehicle-pretreated rats as in control (no ethanol) rats . Clarithromycin protection was significantly diminished, although not completely abolished by subcutaneous yohimbine (5 mg/kg), a selective alpha2-adrenoceptor antagonist . Yohimbine also significantly reduced both basal and clarithromycin-stimulated gastric mucus secretion . Our data support the conclusion that the protective effect of intragastric clarithromycin was not mediated by endogenous prostaglandins, sulfhydryl compounds of the gastric mucosa, or changes in the gastric contractile patterns . The protection may be the result of an increase in both the fluid volume and the mucus volume retained in the gastric lumen . alpha2-Adrenoceptors possibly are involved by the mucus-dependent mechanism. Am J Vet Res, 1999 Sep, 60(9), 1102 - 5 Subconjunctivally implanted micro-osmotic pumps for continuous ocular treatment in horses; Blair MJ et al.; OBJECTIVE: To evaluate the feasibility of using a subconjunctivally implanted micro-osmotic pump for continuous delivery of medication to the eyes of horses- during a 7-day period . ANIMALS: 4 healthy adult horses . PROCEDURE: With horses restrained in a standing position, micro-osmotic pumps were implanted subconjunctivally in each eye for 7 days . The treatment eye received an atropine-loaded micro-osmotic pump (100 microl of 1.5% atropine), and the contralateral eye received a sterile saline-loaded pump (100 microl of 0.9% NaCl) as a control treatment . Pupil size was measured at 12-hour intervals until values returned to baseline . RESULTS: The micro-osmotic pumps were tolerated and did not migrate or become dislodged . During the 7-day treatment period, pupils were significantly larger in the eyes implanted with atropine-loaded pumps, compared with saline-implanted control eyes . CONCLUSIONS AND CLINICAL RELEVANCE: Micro-osmotic pumps were implanted and removed easily from standing horses and were not associated with complications during the 7-day treatment period . Therefore, subconjunctivally implanted micro-osmotic pumps can potentially be used when treating ophthalmic disease in horses. Respirology, 1999 Sep, 4(3), 279 - 81 Malignant mesothelioma presenting as pulmonary metastasis ahead of growth of primary tumour; Heki U et al.; A 59-year-old woman was admitted to Houju Memorial Hospital, Ishikawa, Japan, because of cough and fever on 30 March 1997 . A diagnosis of pneumonia was made and she was given antibiotics . Her symptoms improved but failed to resolve completely on antibiotic therapy . On 9 September 1997, she revisited the hospital because of bodyweight loss and malaise . There was no history of exposure to asbestos . The chest roentgenogram revealed infiltrative shadows with vague and indistinct margins suggesting inflammatory processes, which were more extensive than those investigated on her last visit . One month later, a giant tumour was detected rapidly growing from the mediastinum and open biopsy was performed . The histological examination confirmed that the tumour was a malignant mesothelioma and the intrapulmonary nodules were its metastases . This is a rare case of pulmonary metastasis being present for several months before an appearance of primary mesothelioma. J Pediatr Orthop, 1999 Sep-Oct, 19(5), 655 - 9 Culture-negative septic arthritis in children; Lyon RM et al.; To compare the incidence, characteristics, treatment course, and clinical outcome of children with culture-negative versus culture-positive septic arthritis, we reviewed all 105 children treated for septic arthritis at our institution from 1990 to 1997 . Seventy-six children had a clinical presentation consistent with an isolated joint infection . All underwent a joint aspiration with fluid analysis including culture . All were followed up until resolution of their symptoms . Culture of the synovial aspirates identified an etiologic organism in only 30% of cases . No significant differences existed between the culture-positive and culture-negative groups in most clinical and laboratory criteria . No other diagnoses were demonstrated . All patients underwent joint drainage, received comparable antibiotic therapy, and had complete resolution of their infections . The current literature reports deceptively low rates of 18-48% for culture-negative septic arthritis . Seventy percent of children with clinical findings of septic arthritis had negative synovial fluid cultures . As the two culture groups were comparable and no other diagnoses were demonstrated, the culture-negative cases were likely infections . Thus we recommend the same aggressive treatment in those cases with and without identification of a causative organism. S Afr Med J, 1999 Aug, 89(8), 865 - 70 The use of dexamethasone in women with preterm premature rupture of membranes--a multicentre, double-blind, placebo-controlled, randomised trial . Dexiprom Study Group; Pattinson RC et al.; OBJECTIVE: To assess whether administration of dexamethasone in women with preterm premature rupture of membranes (PPROM) has an effect on the prevalence of maternal sepsis, neonatal respiratory distress syndrome (RDS), perinatal mortality and neonatal sepsis in a developing country . SETTING: Six public hospitals in South Africa that deal mainly with indigent women . METHOD: A multicentre, double-blind, placebo-controlled, randomised trial was performed on women with PPROM and fetuses of 28-34 weeks' gestation or clinically estimated fetal weight between 1,000 and 2,000 g if the gestational age was unknown . Women were randomised to receive either dexamethasone 24 mg intramuscularly or placebo in two divided doses 24 hours apart . All women received amoxycillin and metronidazole and were managed expectantly . Hexoprenaline was administered if contractions occurred within the first 24 hours after admission to the trial . OUTCOME MEASURES: The maternal outcome measures were clinical chorio-amnionitis and postpartum sepsis . The outcome measures for infants were perinatal death, RDS, mechanical ventilation, necrotising enterocolitis, and neonatal infection within 72 hours . RESULTS: One hundred and two women who delivered 105 babies were randomised to the dexamethasone group and 102 women who delivered 103 babies, to the placebo group . The groups were well balanced with regard to clinical features . There was a trend towards fewer perinatal deaths in the dexamethasone group: 4 compared with 10 (P = 0.16, odds ratio 0.37, 95% confidence intervals 0.09-1.34) . A subanalysis of mothers who delivered more than 24 hours after admission to the study and their infants revealed a significant reduction in perinatal deaths; 1 death in the dexamethasone group and 7 in the placebo group, P = 0.047 (Fisher's exact test) . No woman in either group developed severe sepsis, and the incidence of sepsis in the women did not differ significantly . Eleven infants in each group developed sepsis . CONCLUSION: This is the first randomised trial in women with PPROM to compare the effects of the use of corticosteroids with placebo, where all women received prophylactic antibiotics concomitantly with the corticosteroids . A trend towards an improved perinatal outcome was demonstrated in the women who received dexamethasone . There was no increased risk of infection in the women or their infants where dexamethasone was administered . Administration of corticosteroids to women with PPROM has more advantages than disadvantages in developing countries. Ann Fr Anesth Reanim, 1999 Aug, 18(7), 783 - 6 {Post-partum suppurating thrombophlebitis of the ovarian vein presenting with pleuropulmonary manifestations}; Leroy B et al.; Following a normal delivery, a 22-year-old primigravida experienced fever resistant to antibiotic therapy . On the tenth post partum day, thoracic pain and chest X-ray were in favour of acute pneumonitis of left inferior lobe . Considering the extension to the right lung and a normal bronchic fibrescopy, a computed tomography (CT) was performed which showed a right ovarian vein thrombophlebitis, right minor subpleural opacities and left pneumopathy . The final diagnosis was post partum ovarian vein suppurated thrombophlebitis with pulmonary septic metastases from haematogenic diffusion . Post partum thrombophlebitis is a rare event with an incidence of 1 per 2,000 deliveries . Pulmonary inaugurating symptoms result rather from pulmonary embolism than from septic metastases . Post partum persisting and unexplained fever should be explored with abdominal CT-scan. Gut, 1999 Oct, 45(4), 503 - 7 Simultaneous colonisation of Helicobacter pylori with and without mutations in the 23S rRNA gene in patients with no history of clarithromycin exposure; Matsuoka M et al.; BACKGROUND: It was recently reported that A to G transition mutations at positions 2143 and 2144 in the 23S rRNA gene are associated with clarithromycin resistance in Helicobacter pylori . AIMS: To study the incidence and mechanism of development of clarithromycin resistance by analysing these mutations . SUBJECTS: Eighty two H pylori positive patients who had an endoscopic examination and no history of treatment with macrolide antibiotics . METHODS: Clarithromycin resistance was screened for by polymerase chain reaction-restriction fragment length polymorphism of the 23S rRNA gene coupled with antibiotic susceptibility testing . In clinical isolates with mutations or resistance, mutations in individual colonies were analysed by direct sequencing . RESULTS: Of the 79 amplicons (DNA fragments amplified by polymerase chain reaction), Alw26I and MboII digestion disclosed the mutation in four (5%) and one (1%) respectively . However, the Alw26I cleavage was incomplete in two of the four amplicons, as was the MboII cleavage . Individual colony analysis of the isolates with incomplete cleavage patterns showed the presence of both wild type and mutated strains in the 23S rRNA genes . CONCLUSIONS: Both clarithromycin sensitive and resistant strains colonised in some patients with no history of exposure to macrolides . The results suggest that resistant strains may not be formed but selected by clarithromycin administration. Clin Ther, 1999 Aug, 21(8), 1286 - 300; discussion 1285 Chlamydia pneumoniae and anti-infective therapy: their role in the pathogenesis and treatment of coronary artery disease; Behbahani R et al.; Cardiovascular disease remains the most common cause of death in the United States; however, conventional cardiovascular risk factors fail to explain completely the pathogenesis of atherosclerosis and coronary artery disease . There has been recent interest in the association between Chlamydia pneumoniae and the risk of development or progression of atherosclerotic disease . This association has become evident through serologic, pathologic, and animal-based models and, more recently, through limited trials of antichlamydial antibiotics in humans . Whether C . pneumoniae is a causative agent or "innocent bystander" or whether antibiotic therapy has any role in the treatment of cardiovascular disease remains to be determined. Am Surg, 1999 Sep, 65(9), 805 - 9; discussion 809-10 The chest radiograph in critically ill surgical patients is inaccurate in predicting ventilator-associated pneumonia; Butler KL et al.; Chest radiographs (CXRs) are frequently obtained in surgical intensive care unit (SICU) patients when a diagnosis of ventilator-associated pneumonia (VAP) is suspected . The purpose of this study was to determine if the interpretation of the CXR correlated with a diagnosis of VAP in SICU patients . Prospective evaluation of 20 SICU patients clinically suspected of VAP was performed from July 1997 through December 1998 . All patients required mechanical ventilation for at least 48 hours, and antibiotic use was discontinued 24 hours before entry into the study . Bronchoscopy with protected specimen brush (PSB) sampling of secretions from the right and left lung was performed . A positive PSB was present if quantitative analysis yielded > or = 10(4) colony-forming units/mL of bacteria . VAP was diagnosed if either the right or left PSB was positive and ruled-out if both the right and left PSB yielded < 10(4) colony-forming units/mL . Twelve of 20 patients (60%) were diagnosed to have VAP by PSB criteria . Eight of 20 patients (40%) had CXRs interpreted as negative for infiltrates; four patients had VAP by PSB criteria . There were four patients with focal infiltrates; two patients had VAP . The remaining eight patients had radiographs interpreted as bilateral infiltrates (one) or pulmonary edema (seven); of these, six patients (75%) had VAP . The sensitivity of the CXR in determining the presence of VAP was 25 per cent, the specificity was 75 per cent, and the accuracy was 0.45 . The CXR does not improve the clinician's ability to diagnose VAP: a normal CXR does not exclude the presence of VAP and the finding of a focal infiltrate does not confirm the diagnosis of VAP. Am J Gastroenterol, 1999 Sep, 94(9), 2367 - 72 Noninvasive evaluation of Helicobacter pylori therapy: role of fasting or postprandial gastrin, pepsinogen I, pepsinogen II, or serum IgG antibodies; Al-Assi MT et al.; OBJECTIVE: We evaluated the potential value of a change in serum IgG antibodies, fasting or meal-stimulated gastrin levels, and pepsinogen I (PGI) or pepsinogen II (PGII) levels for identifying Helicobacter pylori (H . pylori) status after antibiotic therapy . METHODS: A total of 32 men and one woman with peptic ulcer disease and documented H . pylori infection were enrolled . Fasting and 30-min postprandial blood samples were obtained at 0, 2, 7, 11, 17, 23, 27, and 39 wk of the study and were analyzed for the factors evaluated . RESULTS: Treatment was successful in 25 patients and failed in seven . Serum IgG antibodies, meal-stimulated gastrin, and both fasting and meal-stimulated pepsinogen I and II levels fell throughout the study, and pepsinogen I:II ratios increased in those whose infection was cured . The mean levels at wk 0 versus wk 7 were: fasting gastrin (fmol/ml) 12.4 and 11, meal-stimulated gastrin 26.5 and 15.4, PGI (ng/ml) 83.7 and 59, PGII (ng/ml) 24.5 and 13.6, PGI/PGII 3.5 and 4.7, and enzyme-linked immunosorbent assay value 4.8 and 4.55 . The sensitivity, specificity, and positive and negative predictive values for the data analyzed using different percent changes (e.g., 80%, 50%, and 20%) were calculated . The specificity and sensitivity remained <80% at all time points . CONCLUSIONS: Despite a significant fall in serum markers of H . pylori infection in groups of individuals, no marker tested could be used to reliably determine posttherapy H . pylori status for individual patients. Arch Pediatr Adolesc Med, 1999 Sep, 153(9), 984 - 8 Myeloid colony-stimulating factors: use in the newborn; Sreenan C et al.; Bacterial and fungal sepsis are major causes of morbidity and mortality in the newborn . Multiple factors contribute to this increased susceptibility to infection, including quantitative and qualitative neutrophil defects, with a reduction in neutrophil number and function . Neutropenia in the newborn may occur in association with sepsis and has a poor prognosis . In addition to antibiotic therapy and supportive care, granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) have been used to reduce morbidity and mortality . Granulocyte CSF is the physiological regulator of neutrophil production and function . Administration of G-CSF results in increased neutrophil production and counts and improved neutrophil function . Several studies of animal and human newborns having neutropenia or suspected sepsis investigated the use of G-CSF and GM-CSF to elevate neutrophil counts and reduce morbidity and mortality in this population . Results of small clinical trials using G-CSF and GM-CSF in very low-birth-weight infants having neutropenia show increased neutrophil counts and a reduced incidence of sepsis during the neonatal period . Despite these promising early results, further studies of the safety and efficacy of G-CSF and GM-CSF administration in neonates are required before their routine use can be recommended as either prophylaxis or treatment for neonatal sepsis. An Med Interna, 1999 Jul, 16(7), 333 - 7 {Septic polyarthritis: treatment complications and results}; Cabo Cabo J et al.; OBJECTIVE: The rare polyarticular clinical presentation of peripheric septic arthritis has worst prognosis than monoarticular one . We studied 10 patients with polyarticular septic arthritis treated during the last 8 years, to evaluate functional result and complications after surgical treatment . MATERIAL AND METHODS: We studied 5 men and 5 women, with an average age of 46.5 years (range 18-75 years), they presented septic arthritis in two or more joints . We discuss aetiology, clinical presentation and treatment . RESULTS: Treatment was surgical debridement and parenteral antibiotic therapy . Functional result was poor in 54% of the joints treated, 50% of patients presented septic shock and three died. J Autoimmun, 1999 Sep, 13(2), 187 - 95 Amelioration of experimental allergic neuritis by sodium fusidate (fusidin): suppression of IFN-gamma and TNF-alpha and enhancement of IL-10; Di Marco R et al.; The immunomodulating antibiotic drug fusidic acid and its sodium salt sodium fusidate (fusidin) ameliorate several organ-specific immunoinflammatory diseases . Because preliminary observations suggest that fusidin may also exert a beneficial effect in Guillain-Barre syndrome (GBS), here we have studied the effects of fusidin on actively induced experimental autoimmune neuritis (EAN) in rats, a known animal model for GBS . Both prophylactic and therapeutic treatment with fusidin (4 mg/rat day ip) markedly ameliorated the clinical course of the disease compared to vehicle-treated animals . The beneficial effects were associated with profound modifications of the capacity of these rats to produce and release pro- and anti-inflammatory cytokines such as IFN-gamma, TNF-alpha and IL-10, which are important in regulating the development of EAN . Clin Nephrol, 1999 Aug, 52(2), 67 - 75 A pilot study of low-dose fludarabine in membranous nephropathy refractory to therapy; Boumpas DT et al.; BACKGROUND: Lymphocytes are believed to play a role in the induction and perpetuation of membranous nephropathy . Fludarabine is a purine nucleoside analog with selective activity against both dividing and resting lymphocytes . We evaluated the tolerance, toxicity, pharmacokinetics, immunologic, and clinical effects of fludarabine in patients with membranous nephropathy in an single arm pilot study . PATIENTS AND METHODS: Eight patients with idiopathic (n = 7) or lupus (n = 1) membranous nephropathy who had failed high-dose prednisone (n = 8) and/or alkylating agents (n = 2), or cyclosporine (n = 1) were treated with 6-monthly cycles of fludarabine (cycles 1-2, 20 mg/m2/day x 2 days, cycles 3-6, 20 mg/m2/day x 3 days) . Mean proteinuria was 9 g/day with a mean duration of disease of 25 months (range 12-48) . Proteinuria, GFR and effective renal plasma flow were compared before and after completing the treatment . RESULTS: Seven patients completed the protocol . CD3, CD4, CD8 and B cell counts decreased by 53%, 46%, 61% and 84%, respectively, at the end of treatment and remained at lower than pretreatment levels 6 months after completing the trial . Despite lymphopenia, serum immunoglobulin levels remained unchanged . Both naive (CD45RA+) and memory CD4+ T cells (CD45RO+) were reduced (naive > memory) . Proteinuria decreased by > or = 50% in 5 out of 7 patients (p = 0.11) . Filtration fraction improved in all patients with decreased filtration fraction at baseline . The only side-effect observed was one episode of acute bacterial sinusitis that responded promptly to antibiotic therapy . CONCLUSION: We conclude that low-dose fludarabine treatment in patients with membranous nephropathy is well tolerated and results in significant lymphopenia involving B more than T cells . In this pilot study improvement in proteinuria and filtration rate were observed . Additional studies are required to determine the optimal dose and clinical efficacy of fludarabine. J Infect Dis, 1999 Oct, 180(4), 1252 - 8 The effect of doxycycline treatment on the development of protective immunity in a murine model of chlamydial genital infection; Su H et al.; Chlamydia trachomatis is a major cause of sexually transmitted disease (STD) worldwide . Antibiotics are effective in treating infection; however, reinfection is common . This observation has led to the conclusion that infection fails to elicit a protective antichlamydial immune response . It was postulated that high reinfection rates might be due to early eradication of organisms from genital tissue after antibiotic intervention, which could negatively influence the development of naturally acquired protective immunity . This hypothesis was tested by use of a murine model of female genital infection . The findings show that doxycycline intervention of infection, although very effective in eradicating chlamydiae from genital tissue and preventing upper genital tract disease, significantly inhibits the development of protective immunity . If antibiotic intervention of human chlamydial genital infection has a similar effect on protective immunity, it could have important implications in the understanding of immunity to infection and future public health efforts to control chlamydial STD. Am J Clin Nutr, 1999 Sep, 70(3), 378 - 82 Prevalence of vitamin K deficiency in cystic fibrosis; Rashid M et al.; BACKGROUND: Patients with cystic fibrosis (CF) are at risk of developing vitamin K deficiency because of pancreatic insufficiency, hepatobiliary disease, or both . OBJECTIVE: Our objective was to determine the prevalence of vitamin K deficiency in unsupplemented patients with CF and to identify risk factors that might be associated with the deficiency . DESIGN: Ninety-eight patients with CF-83 who were pancreatic insufficient (age: 15.2 +/- 10.7 y; range: 0.6-45.8 y), 15 who were pancreatic sufficient (age: 26.2 +/- 11.6 y; range: 6.5-45.3 y), and 62 healthy individuals (age: 16.2 +/- 12 . 8 y; range: 1-45 y)-were studied prospectively . None had taken vitamin K supplements . Eight pancreatic-insufficient patients had advanced CF-associated liver disease . Plasma prothrombin in vitamin K absence (PIVKA-II) was measured by immunoassay . All control subjects had PIVKA-II concentrations <3 microg/L . RESULTS: Seventy-eight percent of pancreatic-insufficient patients had PIVKA-II concentrations >/=3 microg/L (22.8 +/- 35.7 microg/L) . All patients with CF-associated liver disease had abnormal PIVKA-II concentrations . The mean PIVKA-II concentration of pancreatic-insufficient patients with liver disease was greater than that of those without liver disease (46.6 +/- 65.3 compared with 15 . 3 +/- 26.1 microg/L; P < 0.05) . Five pancreatic-sufficient patients had mildly elevated PIVKA-II concentrations . Six (7%) pancreatic insufficient patients (3 with CF-associated liver disease) had mildly prolonged prothrombin time but no clinical bleeding . There was no correlation between PIVKA-II concentrations and severity of fat malabsorption or antibiotic use . CONCLUSIONS: Vitamin K deficiency is common in unsupplemented patients with CF and pancreatic insufficiency and routine supplementation should be considered in all of these patients. Mol Endocrinol, 1999 Sep, 13(9), 1435 - 48 Interaction of radicicol with members of the heat shock protein 90 family of molecular chaperones; Schulte TW et al.; The Hsp90 family of proteins in mammalian cells consists of Hsp90 alpha and beta, Grp94, and Trap-1 (Hsp75) . Radicicol, an antifungal antibiotic that inhibits various signal transduction proteins such as v-src, ras, Raf-1, and mos, was found to bind to Hsp90, thus making it the prototype of a second class of Hsp90 inhibitors, distinct from the chemically unrelated benzoquinone ansamycins . We have used two novel methods to immobilize radicicol, allowing for detailed analyses of drug-protein interactions . Using these two approaches, we have studied binding of the drug to N-terminal Hsp90 point mutants expressed by in vitro translation . The results point to important drug contacts with amino acids inside the N-terminal ATP/ADP-binding pocket region and show subtle differences when compared with geldanamycin binding . Radicicol binds more strongly to Hsp90 than to Grp94, the Hsp90 homolog that resides in the endoplasmic reticulum . In contrast to Hsp90, binding of radicicol to Grp94 requires both the N-terminal ATP/ADP-binding domain as well as the adjacent negatively charged region . Radicicol also specifically binds to yeast Hsp90, Escherichia coli HtpG, and a newly described tumor necrosis factor receptor-interacting protein, Trap-1, with greater homology to bacterial HtpG than to Hsp90 . Thus, the radicicol-binding site appears to be specific to and is conserved in all members of the Hsp90 family of molecular chaperones from bacteria to mammals, but is not present in other molecular chaperones with nucleotide-binding domains. Dent Update, 1998 Oct, 25(8), 325 - 31 Recognizing and caring for the medically compromised child: 1 . Disorders of the cardiovascular and respiratory systems; Parry JA et al.; This paper describes important disorders of the cardiovascular and respiratory systems and the management of dental treatment for patients with these diseases. Mutat Res, 1999 Jul 21, 444(1), 181 - 92 Enhancement of bleomycin-induced micronucleus formation in V79 cells as a rapid and sensitive screen for non-covalent DNA-binding compounds; Snyder RD et al.; Non-covalent drug/DNA interactions are difficult to study and because of this, the significance of such interactions from a safety standpoint and their contribution to positive genetic toxicology test findings is poorly understood . It is shown in the present study that such interactions may be detected and quantified in Chinese hamster V79 cells by an adaptation of the bleomycin amplification assay . This assay measures the ability of a test compound to enhance the DNA damaging activity of the antibiotic bleomycin using micronucleus formation as an endpoint . Results are presented examining the bleomycin amplification activity of known intercalating agents, groove-binding agents and other structurally diverse classes of compounds for which intercalative status has not been reported . The assay reveals a strong and predictable SAR for amplification activity based on number and orientation of aromatic rings . Moreover, excellent correlations are observed between DNA binding (viscometric analyses) and DNA amplification in V79 cells for a series of seven experimental compounds . The assay is shown to be useful in understanding the genotoxicity of marketed antihistamines and to help explain genetic toxicology findings observed in a series of novel pharmaceutical entities . It is proposed that assessment of bleomycin amplification activity of novel compounds in early genotoxicity prescreening may provide important information upon which to base synthesis of compounds with minimal or no genotoxic liability. Lik Sprava, 1999 Jun, (4), 117 - 21 {The use of substitute surfactant therapy in treating acute destructive pneumonia in children}; Protsiuk RG et al.; The article presents results of employment of replacement surfactant therapy with the exogenous surfactant preparation sukrim as treatment of the infiltrative-destructive form of acute purulent destructive pneumonia in children . Based on clinical, laboratory, and roentgenological findings a comparative evaluation was done of the course of disease in 20 patients having received substitution surfactant therapy and in 25 those having not been given it . Employment of the preparation suchrim and a short-term course of antibiotic therapy combined in treatment of acute destructive pneumonia in pediatric patients proved to be a highly efficient treatment option for this pathology. Clin Excell Nurse Pract, 1999 Jan, 3(1), 2 - 6 Severe neutropenia as an adverse effect of methimazole in the treatment of hyperthyroidism; Ryan JA; Ms . K., a white, 47-year-old female with a history of hyperthyroidism had been treated with methimazole daily for a period of 9 years . She presented with a 2-day history of fever higher than 103 degrees F and cellulitis of the right arm after a scratch injury . White blood cell count (WBC) was noted at 0.4 x 10(3)/microL and neutrophils at 5.6%, indicating agranulocytosis . Methimazole was discontinued by the patient with the onset of symptoms . Appropriate intravenous antibiotic therapy and reverse isolation were provided in the acute-care setting, as well as administration of the granulocyte colony-stimulating factor (G-CSF) filgrastim . No recovery of the granulocyte count or improvement of clinical condition was noted until her sixth day of admission, at which time her WBC increased to 2.6 x 10(3)/microL . The administration of intravenous antifungals and antibiotics prevented overwhelming sepsis, while giving the G-CSF the opportunity to stimulate growth of granulocytes to finally fight the offending organisms and save this patient. Br J Oral Maxillofac Surg, 1999 Aug, 37(4), 312 - 5 Randomized prospective study of the influence of steroids on postoperative eye-opening after exploration of the orbital floor; Flood TR et al.; OBJECTIVE: To find out if giving steroids reduces postoperative swelling in orbital surgery . DESIGN: Prospective, randomized, double-blind trial . SETTING: Regional unit, teaching hospital, UK . SUBJECTS AND INTERVENTIONS: 20 patients who require orbital floor exploration after injuries . Patients were given methylprednisolone 250 mg (or placebo identically packaged) at induction of anaesthesia, with a further three doses at 6-hourly intervals postoperatively . MAIN OUTCOME MEASURE: Differences in interpalpebral width before and after operation . RESULTS: Those given steroids (n=11) had a significantly increased interpalpebral width compared with placebo (n=9) postoperatively (P < 0.01, 95% confidence intervals of the difference = 1 mm-6 mm) . CONCLUSION: Short courses of steroids therapy should be considered in orbital surgery for appropriate patients . There is an advantage in being able to assess the globe postoperatively. FEMS Microbiol Lett, 1999 Aug 15, 177(2), 297 - 304 Molecular cloning and analysis of a pleiotropic regulatory gene locus from the nystatin producer Streptomyces noursei ATCC11455; Sekurova O et al.; A regulatory gene locus from Streptomyces noursei ATCC14455, the producer of the antifungal antibiotic nystatin, was cloned in Streptomyces lividans based on its ability to activate actinorhodin (Act) production in this host . Deletion and DNA sequencing analyses showed that a small gene, designated ssmA, located downstream of an afsR homologue (a known pleiotropic regulator) was responsible for the Act overproduction in S . lividans . Database searches for the ssmA gene product revealed its limited similarity to the AfsR2 regulatory protein from S . lividans and CREA catabolite repressor from Aspergillus nidulans . To study the effect of ssmA on nystatin production, this gene was either deleted from S . noursei genome, or placed under control of PermE* promoter and introduced in S . noursei . The properties of the corresponding strains indicate that ssmA is involved in regulation of growth and antibiotic production only in the media with certain carbon sources. J Antimicrob Chemother, 1999 Aug, 44(2), 275 - 7 Endothelial cell compatibility of clindamycin, gentamicin, ceftriaxone and teicoplanin in Bier's arterial arrest; Vorbach H et al.; In patients with infected diabetic foot lesions, and gangrenous, peripheral, occlusive arterial disease, it is important to achieve high concentrations of antibiotics in the tissues, as the extent of amputation is often influenced by the presence of infection . Local transvenous pressure injection of antibiotics, in Bier's arterial arrest, allows high local tissue concentrations to be attained in the extremities . Information on the endothelial compatibility of antibiotics in high concentrations combined with the effect of reperfusion injury following tissue hypoxia is lacking . To evaluate the effect of clindamycin, gentamicin, ceftriaxone and teicoplanin injected in Bier's arterial arrest, on endothelial cells, an in-vitro model using human umbilical venous endothelial cells (HUVEC) has been devised . The intracellular levels of purine nucleotides, reflecting DNA/RNA synthesis, energy production and signal transduction of these cells were measured by means of high-performance liquid chromatography . Incubation of cells with 10 mg/mL clindamycin, gentamicin, ceftriaxone and teicoplanin for 20 min resulted in no significant decline of intracellular purines . Levels of purines obtained after exposure of the cells to 0.1 mmol/L hydrogen peroxide (H2O2), to simulate reperfusion injury, were not significantly different from those obtained from cells allowed to recover after antibiotic exposure . These findings indicate that the infusion of high doses of antibiotics, during Bier's arterial arrest, is compatible with maintenance of endothelial cell function, even in the presence of increased free radical activity, provided the exposure is limited to 20 min. J Ethnopharmacol, 1999 Sep, 66(3), 343 - 6 Occurrence of usnic acid in Usnea laevis Nylander (lichenized ascomycetes) from the Venezuelan Andes; Marcano V et al.; The presence of usnic acid in the lichen Usnea laevis Nyl . from the Venezuelan Andes was detected through chromotographic (TLC) and spectroscopic (IR, MS, 1H-NMR) methods . This compound was present in a concentration of 2.7% in the thallus . Usnic acid has a reported antibiotic activity and the lichen is utilized for medicinal purposes by Andean farmers. J Am Coll Surg, 1999 Sep, 189(3), 305 - 13 Surgical complications after pancreas transplantation with portal-enteric drainage; Reddy KS et al.; BACKGROUND: Despite recent advances, surgical complications remain an important source of morbidity after pancreas transplantation (PTX) . Several previous studies have delineated the surgical complications after PTX with systemic-bladder (S-B) drainage, but data are limited regarding the incidence and outcomes of surgical complications after PTX with portal-enteric (P-E) drainage . STUDY DESIGN: We retrospectively studied surgical complications after 83 vascularized PTXs with P-E drainage in 79 patients (65 simultaneous kidney-PTXs {SKPT} and 18 solitary PTXs {SPT}, 8 pancreas alone and 10 pancreas after kidney transplantation) . Twelve (15%) were retransplants . A surgical complication was defined as the need for repeat laparotomy within the first 3 months after PTX . RESULTS: A total of 53 surgical complications requiring repeat laparotomy occurred in 31 patients (37%) . The incidence of surgical complications in SKPT and SPT was 38% and 33%, respectively . The most common indications for repeat laparotomy were: vascular thrombosis in 13% (SKPT 14% and SPT 11%), intraabdominal infection in 10% (SKPT 12% and SPT 0%), intraabdominal bleeding in 8% (SKPT 8% and SPT 11%), and duodenal allograft leak in 4% (SKPT 3% and SPT 6%) . Patient survival rates at 1 and 3 years with versus without surgical complications were 84% and 80% versus 94% and 86%, respectively (p = NS) . Pancreas graft survival rates at 1 and 3 years with versus without surgical complications were 48% and 44% versus 89% and 76%, respectively (p < 0.0001) . The incidence of surgical complications was 45% in the first 42 P-E transplantations performed between 1990 and 1995, compared with 29% in the next 41 transplantations performed during 1996 and 1997 (p = NS) . The mean number of repeat laparotomies per patient decreased from 1.2 in the former group to 0.5 in the latter group (p = NS) . The incidence rates of vascular thrombosis, intraabdominal infection, and duodenal leak in the former and latter groups were 17% versus 10%, 12% versus 7%, and 2% versus 5%, respectively . CONCLUSIONS: Surgical complications after PTX are common, and their incidence and outcomes with P-E drainage are similar to those with S-B drainage . The complication rate does not vary according to the type of transplant (SKPT versus SPT) . Increasing experience with P-E drainage results in a decreased incidence of surgical complications. Antimicrob Agents Chemother, 1999 Sep, 43(9), 2307 - 10 Cefoperazone prevents the inactivation of alpha(1)-antitrypsin by activated neutrophils; Dallegri F et al.; At sites of neutrophilic inflammation, tissue injury by neutrophil elastase is favored by phagocyte-induced hypochlorous acid-dependent inactivation of the natural elastase inhibitor alpha(1)-antitrypsin . In the present study, cefoperazone prevented alpha(1)-antitrypsin inactivation by neutrophils and reduced the recovery of hypochlorous acid from these cells . Moreover, the antibiotic reduced the free elastase activity in a neutrophil suspension supplemented with alpha(1)-antitrypsin without affecting the cells' ability to release elastase . These data suggest that the drug inactivates hypochlorous acid before its reaction with alpha(1)-antitrypsin, thereby permitting the antiprotease-mediated blockade of released elastase . In conclusion, cefoperazone appears to have the potential for limiting elastase-antielastase imbalances, attenuating the related tissue injury at sites of inflammation. Int J Med Inform, 1999 Jul, 55(1), 61 - 4 Detecting adverse drug reactions to improve patient outcomes; Hannan TJ; Adverse drug reactions and inappropriate administration of medications account for poor outcomes for patients . They place patients in life-threatening situations, lead to increased health care costs, extend length of stay in hospitals, as well as increasing litigation . This paper will highlight the incidence of adverse drug events (ADE) in health care and show the low rate of detection within conventional medical records . I will also show how electronic medical records (EMR) improve detection of ADE, enhance clinician compliance to their management, improve patient outcomes, and reduce health care costs. J Neurosurg, 1999 Sep, 91(3), 499 - 502 Infectious meningitis mimicking recurrent medulloblastoma on magnetic resonance imaging . Case report; Fouladi M et al.; This report and the accompanying review of the literature address the challenges, when using surveillance magnetic resonance (MR) imaging, of establishing the origin of newly detected central nervous system lesions . Routine surveillance MR imaging in a 16-year-old boy, whose medulloblastoma had been successfully treated, demonstrated asymptomatic nodular leptomeningeal enhancement of the brain and spinal cord, which was consistent with recurrent disease . Examination of the cerebrospinal fluid, however, led to the diagnosis of bacterial meningitis . Two weeks after completion of antibiotic therapy, the original MR imaging findings were seen to have resolved . This case illustrates the importance of considering clinical and laboratory data, including results from a complete examination of the cerebrospinal fluid, when interpreting the origin of new lesions revealed by MR imaging. Compr Ther, 1999 Jun-Jul, 25(6-7), 370 - 5 Appendicitis in childhood; Joffe MD et al.; Ultrasonography, CT scanning, and prolonged observation may improve diagnostic accuracy of appendicitis in children with atypical presentations . This article describes diagnostic pitfalls, including early presentation and abnormal appendiceal location. S Afr Med J, 1999 Jul, 89(7 Pt 2), 791 - 4 The cost-effectiveness of isotretinoin in the treatment of acne . Part 3 . A cost-minimisation pharmaco-economic model; Wessels F et al.; OBJECTIVES: The cost-effectiveness of systemic isotretinoin therapy in the treatment of moderate to severe acne was assessed in a comparative cost-minimisation analysis . Systemic isotretinoin at the recommended daily dose of 1 mg/kg (cumulative dose of 120 mg/kg) was compared with: (i) oral antibiotics taken as chronic medication; (ii) a combination of chronic oral antibiotics and anti-androgen therapy; and (iii) isotretinoin prescribed only after two failed courses of oral antibiotics, as per South African guidelines . The perspective taken was that of the funder of health care, and the resources used were funder charges as a proxy for costs . METHODOLOGY: Statistical and epidemiological data as well as relevant costs from the previously reported meta-analysis and profiling study for acne therapy were used as the clinical basis for the construction of a cost-minimisation model . Additional costs were sourced from published pharmaceutical retail prices and professional rates . The South African treatment guidelines were used to define the frequencies associated with physician visits and pathology testing . Standard statistical methods were applied, as appropriate . From the above, a modified Markov process was used to model the costs associated with the four comparator treatment regimens over a period of 120 months . Suitable clinical and economic endpoints were defined so that comparison could be made between regimens . RESULTS: Assuming a relapse rate of 21.45%, it was found that isotretinoin therapy compares favourably with the other regimens . After 50 and 35 months, systemic isotretinoin cumulative costs were less than those incurred in oral antibiotic and oral antibiotic/anti-androgen therapy, respectively . For the stepped therapy of oral antibiotics followed by systemic isotretinoin, these break-even periods were 56 and 39 months, respectively . The cost per successfully treated patient receiving isotretinoin was R8941 . This compares well with the cost for those patients receiving chronic oral antibiotics, which after 5 years amounted to R10 428 per patient . Sensitivity analyses proved these findings to be robust to variations in the isotretinoin relapse rate, and the cost of oral antibiotic therapy and the concomitant use of topical therapies . CONCLUSION: From the cost-minimisation model it is clear that where systemic isotretinoin is clinically indicated, the sooner such therapy is initiated the more cost-effective the outcome will be . If isotretinoin is prescribed on diagnosis of moderate to severe acne, then the cost of treatment is significantly reduced in the long term when compared with standard chronic oral antibiotic therapy. S Afr Med J, 1999 Jul, 89(7 Pt 2), 785 - 90 The cost-effectiveness of isotretinoin in the treatment of acne . Part 2 . A chronic medication plan profiling study; Wessels F et al.; OBJECTIVES: Aspects of current clinical practice, needed for a pharmaco-economic model of isotretinoin, were determined from an acne-profiling study on chronic medication plan data . The patient sample was analysed as a whole and as two subgroups, representing isotretinoin and oral antibiotic patients . The study focused on the prevalence of the condition, patient age and gender distributions, and pharmacotherapeutic patterns and costs . METHODOLOGY: Anonymous patient records from the Pharmaceutical Benefit Management (Pty) Ltd, Cape Town, chronic medication plan were screened and analysed using descriptive and inferential statistical methods . For all hypothesis tests, the significance level (alpha) was set a priori at 5% (0.05) . In order to determine the distribution of costs among patient groups, cost-concentration curves were constructed . RESULTS: A total of 5,198 patient records were analysed, representing 3,546 acne patients (2.7% of applicants to the plan) . The majority of patients were female (72.2%, median age 23 years), with male patients treated at a younger age (median age 19 years) . The cyproterone/oestrogen combination was found to be the most frequently prescribed agent (25.2% of script items), followed by isotretinoin (15.6%) . The oral antibiotics as a group accounted for 24.9% of script items, the leading agents being minocycline (10.1%) and doxycycline (7.1%) . Isotretinoin (44.1%) represented the greatest expense, followed by hormonal therapies (24.7%) and oral antibiotics (16.7%) . Female isotretinoin patients (55.1%) were older (median age 25 years), while the male patients were of an equivalent age to the collective sample . Patients treated with oral antibiotics represented the youngest group of patients (median age 20 years), with 57.8% being female . The annual pharmacotherapy expense per patient on oral antibiotics was R1 971.81 compared with R2 670.20 for all patients, and R6 140.81 for the isotretinoin group . For each of these groups there was an uneven cost distribution among patients . CONCLUSION: The treatment of acne represents a significant burden to funders, estimated at R7.2 million per 100,000 beneficiaries . The distinct age and gender distribution patterns, together with the uneven distribution of costs among patients, provide valuable information for the treatment and management of the condition . This information indicates that the introduction of clinically based, focused management principles supported by sound pharmaco-economic arguments will be required to manage acne effectively. Zentralbl Bakteriol, 1999 Jul, 289(3), 265 - 84 Taxonomic study and morphological differentiation of an actinomycete genus, Kitasatospora; Takahashi Y et al.; The history and taxonomic criteria of the actinomycete genus, Kitasatospora, are described . The reasons for a change of the position of the genus in the classification system are given and a restriction length polymorphism (RFLP) method for rapid identification is described . Although the bacterial genus, Kitasatospora, resembles the fungal one, Streptomyces, in its morphology, it is clearly different in its cell-wall composition which includes LL- and meso-DAP, glycine and galactose . Following a change in its taxonomic position as a result of insufficient gene analysis, it was re-established by phylogenetic analysis of the entire 16S rRNA gene . Most actinomycetes produce bioactive compounds but the relationship between antibiotic production and morphology has not been studied in detail . Kitasatospora strains may be used as a model because they grow in submerged culture like those actinomycetes strains which produce bioactive compounds . The authors suggest further studies of the correlation between metabolic and morphological differentiation and the mechanism of the production of submerged spores. Am J Hematol, 1999 Sep, 62(1), 1 - 6 Outpatient management of fever in children with sickle cell disease (SCD) in an African setting; Rahimy MC et al.; Because hospitalization and intravenous antibiotics for treatment of a potentially fatal bacterial infection in febrile children with sickle cell disease (SCD) are difficult to apply, outpatient treatment has been considered in developed countries for selected patients . Eligibility criteria and procedures may differ in developing countries because of unique economic and social conditions . After clinical evaluation within 36 hr of the onset of a fever exceeding 38.5 degrees C, children with SCD who are being closely followed as a part of a SCD cohort in Cotonou (West Africa), were treated as outpatients . The antibiotic regimen consisted of intramuscular injection of ceftriaxone 50 mg/kg/day for 2 days followed by amoxicillin 25 mg/kg x 3/day x 4 days and oral hyper-hydration . Patients were observed for 6 hr and thereafter discharged with a medical control at day 2, day 8 + day 15 . All 60 children included completed their treatment, and none were lost to follow-up . A definite or a presumed bacterial infection was the cause of the febrile episode in 76.7% of cases . An appreciable decrease in fever was observed from day 2 and only 2 patients were hospitalized at day 3, one for abdominal painful crisis and one other for persistent fever without documented infection . No severe bacterial infections, recurrence of febrile episode, nor death were encountered during the follow-up . The cost of this outpatient approach is US $30 per patient as compared to US $140 per patient if the patient had been hospitalized . Outpatient management of febrile episode in children with SCD is feasible and cost-effective in Sub-Saharan African . It requires, however, improved medical education on SCD and immediate medical attention after the onset of fever . Ann Ital Chir, 1999 May-Jun, 70(3), 421 - 4; discussion 425 {Lesions of the main bile duct: combined percutaneous-endoscopic treatment}; Montesano G et al.; The authors report their experience in "minimally invasive" treatment of benign biliary lesions . More than 80% of them occur after injury to the bile ducts during cholecystectomy . The clinical experience reported in this work concerns three patients managed with a coordinated--percutaneous and endoscopic--approach . In all patients an ERCP with biliary sphincterectomy has been performed at first, followed by percutaneous biliary drainage with external-internal catheters . All drainage catheters have been removed after one year . No patient has evidence of recurrence after a mean follow up of 18 months . Only in a patient a recurrent cholangitis treated with antibiotic therapy has been observed . This preliminary study suggests that the "rendez-vous" technique may be useful for the initial management of biliary strictures in most patients . This association improves the success rate and can avoid surgery . The role of surgery is reserved to few selected cases and particularly to lesions which are detected at the time of the operation. J Exp Clin Cancer Res, 1999 Jun, 18(2), 201 - 8 Graft versus host disease in autologous stem cell transplantation; Marin GH et al.; Relapse remains the major cause of mortality in haematological malignancies treated with autologous stem cell transplantation (ASCT) . Graft versus tumour reaction (GVT) associated to autologous graft versus host disease (GVDH) may contribute to eliminate minimal residual disease (MRD) after ASCT . Eighty patients with several diagnostics were submitted to ASCT . After stem cell infusion, patients randomised in 4 groups . Groups were treated as follows: Group A received either a IFN (alpha Interferon--1,000,000 U/d), Cyclosporine A (CSA--1 mg/-kg/d intravencus) for 28 days, and granulocyte-macrophage colony stimulating factor (GM-CSF-250/m2/d) until engraftment; B: CSA (same dose and way) and GM-CSF; C: CSA (1 mg/kg/d orally) and GM-CSF and D: only GM-CSF . Patients were inspected daily and if skin rash was detected, a skin biopsy was obtained at that moment, otherwise biopsies were obtained at day 21 after ASCT . GVHD was positive in 23 patients (13 from group A and 10 from group B) . All cases were grades I and II . A majority of CD4+ T lymphocytes was seen in skin infiltrates . No significant differences were seen in WBC and platelets engraftment times, antibiotic administration or hospitalisation days required among the four groups . With a median follow up of 18 months, there were no differences in disease free survival (DFS) or overall survival (OS) between the patients who developed GVHD and the others . However, considering that myeloma cells do not express antigen MCH II, which is necessary for GVT effect, we excluded patients with multiple myeloma (MM) from survival analysis, thus obtaining a significant difference in OS results between patients who developed GVHD and those in whom this reaction was not observed (81% vs 58% p:0.05) . We conclude that pharmacological induction of GVHD in ASCT is possible with CSA administration (1 mg/kg/d i.v.) . Development of GVHD showed a better outcome for patients in our study except for those patients with MM . This results must be confirmed by a longer follow up of our patients and further studies. Anasthesiol Intensivmed Notfallmed Schmerzther, 1999 Jul, 34(7), 409 - 13 {Cost analysis concerning MRSA-infection in ICU}; Geldner G et al.; OBJECTIVE: MRSA-infection incidences are still rising, because of unreflected use of antibiotic drugs in man and animals . Although some European countries already have an incidence as high as 30% of MRSA infection in ICU-patients, there is no additional financial support for the treatment of MRSA infected patients . METHODS: We investigated all MRSA infected patients of the operative ICU ward of the department of anaesthesia at the university Ulm within the last three years . We calculated all costs for decontamination and special treatment of the MRSA infection as well as the costs for closing beds, because of MRSA precaution and isolation reasons . RESULTS: The average monthly costs for MRSA infected patients is about 3848 EURO for decontamination and treatment, and another 5560 EURO fix costs . The average monthly ICU duration for MRSA patients was 5.8 days, which means a financial loss of 1622 EURO per "MRSA-patient day" . This loss is more than two times the price the social security system pays for an ICU-patient . CONCLUSION: These extra costs should be calculated and additionally paid for patients with MRSA-infection in order to obtain a certain quality standard . By achieving this standard the total economy costs for MRSA infection treatment could be reduced. J Biol Chem, 1999 Sep 3, 274(36), 25801 - 6 Different mechanisms of c-Jun NH(2)-terminal kinase-1 (JNK1) activation by ultraviolet-B radiation and by oxidative stressors; Iordanov MS et al.; Irradiation of mammalian cells with ultraviolet-B radiation (UV-B) triggers the activation of a group of stress-activated protein kinases known as c-Jun NH(2)-terminal kinases (JNKs) . UV-B activates JNKs via UV-B-induced ribotoxic stress . Because oxidative stress also activates JNKs, we have addressed the question of whether the ribotoxic and the oxidative stress responses are mechanistically similar . The pro-oxidants sodium arsenite, cadmium chloride, and hydrogen peroxide activated JNK1 with slow kinetics, whereas UV-B potentiated the activity of JNK1 rapidly . N-acetyl cysteine (a scavenger of reactive oxygen intermediates) abolished the ability of all oxidative stressors tested to activate JNK1, but failed to affect the activation of JNK1 by UV-B or by another ribotoxic stressor, the antibiotic anisomycin . In contrast, emetine, an inhibitor of the ribotoxic stress response, was unable to inhibit the activation of JNK1 by oxidative stressors . Although UV-A and long wavelength UV-B are the spectral components of the ultraviolet solar radiation that cause significant oxidative damage to macromolecules, the use of a filter to eliminate the radiation output from wavelengths below 310 nm abolished the activation of JNK1 by UV . Our results are consistent with the notion that UV-B and oxidative stressors trigger the activation of JNK1 through different signal transduction pathways. Cancer Res, 1999 Aug 15, 59(16), 3935 - 40 Effects of geldanamycin on signaling through activator-protein 1 in hypoxic HT29 human colon adenocarcinoma cells; Vasilevskaya IA et al.; One of the characteristic responses of HT29 human colon adenocarcinoma cells to hypoxic stress is the induction of c-jun expression and binding to the activator-protein 1 (AP-1) element . To study the mechanism of c-jun activation during hypoxia, inhibitors of signaling pathways leading to the activation of AP-1 transcription factor were used . One of them, the benzoquinone ansamycin geldanamycin (GA) Mr-90,000 heat-shock protein (hsp90)-binding antibiotic, is known to disrupt signaling pathways by inducing destabilization of the enzyme complexes and degradation of signaling intermediates involving the proteasome . In our experiments, GA inhibited both basal and hypoxia-induced c-jun expression (IC50 = 75 nM) . GA also abolished the hypoxia-induced increase in c-Jun NH2-terminal kinase (JNK1) catalytic activity and demonstrated an inhibitory effect on stress-activated protein kinase/ERK kinase-1 (SEK1); other participants in the mitogen-activated protein kinase and p38 signal transduction pathways were not affected to the same degree . GA treatment led to a decrease in the nuclear content of c-Jun but not that of c-Fos or of activating transcription factor 2 . Functional consequences of these effects were suggested by the inhibition of AP-1 binding in hypoxic HT29 cells in the presence of GA . Pretreatment with the proteasome inhibitor lactacystin before the addition of GA resulted in the elevation of overall c-jun level, but it was unable to restore the hypoxia-induced c-jun expression . Our results demonstrate that GA acts as a highly potent inhibitor of hypoxia-induced c-jun expression, affecting the activation of JNK and of the AP-1 transcription factor . However, the effect of GA cannot be attributed solely to the inhibition of signaling through JNK, and additional mechanisms remain to be identified. Naunyn Schmiedebergs Arch Pharmacol, 1999 Jul, 360(1), 69 - 79 Evidence for a contribution of store-operated Ca2+ channels to NO-mediated endothelium-dependent relaxation of guinea-pig aorta in response to a Ca2+ ionophore, A23187; Taniguchi H et al.; A23187 (6S-{6alpha,8beta,9beta,11alpha}-5-(methylamino) -2-{{3,9,11-trimethyl-8-{1-methyl-2-oxo-2-(1H-pyrrol-2-yl)ethyl}-1,7- dioxaspiro{5.5}undec-2-yl}methyl}-4-benzoxazolecarboxylic acid, calcimycin), an antibiotic Ca2+ ionophore, produces an endothelium-dependent vascular relaxation . In the present study, pharmacological features were functionally characterized of endothelium-dependent relaxant response of guinea-pig aorta to A23187, especially focusing on the possible Ca2+ source and Ca2+ mobilization mechanisms in endothelial cells responsible for the vasorelaxant response to the Ca2+ ionophore . A23187-induced endothelium-dependent relaxation was suppressed profoundly by N(G)-nitro-L-arginine (L-NNA; 3 x 10(-4) M) or calmidazolium (3 x 10(-5) M), suggesting that nitric oxide (NO) produced by the enhanced activation of Ca2+/calmodulin-dependent endothelial NO synthase (eNOS) is largely responsible for the relaxant response of this artery to A23187 . In the Ca2+-free solution without EGTA, NO-mediated endothelium-dependent relaxation induced by A23187 was almost abolished, which suggests that Ca2+ entry from extracellular space into endothelial cells plays the key role in the A23187-induced functional vasorelaxation . On the other hand, SK&F96365 (1-{beta-{3-(4-methoxyphenyl)propoxy}-4-methoxyphenethyl}-1H-imidazole; 5 x 10(-5) M) and Ni2+ (3 x 10(-4) M), both of which inhibit capacitative Ca2+ influx through store-operated Ca2+ channels (SOCCs), attenuated significantly NO-mediated endothelium-dependent relaxation by A23187 . Furthermore, A23187-induced endothelium-dependent relaxation was suppressed more strongly than endothelium-independent relaxation induced by SIN-1 (3-morpholino-sydnonimine), an NO donor, when aortic preparation was preconstricted with high KCl instead of agonistic stimulation (prostaglandin F2alpha) . These findings suggest that NO-mediated endothelium-dependent relaxant response of guinea-pig aorta to A23187 is preceded by the increase in endothelial cytosolic free Ca2+ concentration ({Ca2+}cyt) due to the enhanced Ca2+ influx from extracellular space . In the enhanced Ca2+ entry leading to the stimulation of eNOS and NO-mediated functional relaxant response of guinea-pig aorta to A23187, activation of SOCCs but not the Ca2+ entry through plasma membrane Ca2+-specific routes made by A23187 seems to play the predominant role . It is most likely that A23187 acts primarily at the Ca2+ store sites in endothelial cells, which subsequently depletes stored Ca2+ to activate SOCCs via unidentified mechanisms. Neurol Neurochir Pol, 1998 Sep-Oct, 32(5), 1281 - 7 {Lymphocytic meningitis with the involvement of the skull in the course of spinal cord neoplasm simulating neuroborreliosis . Case report}; Zajkowska JM et al.; We describe a case of 48 year old male patient treated in the Department of Parasitic Diseases and Neuroinfections AMB with suspected neuroborreliosis . Clinical symptoms: lymphocytic meningitis with cranial neuropathies n . VII palsy and radiculitis after numerous tick bites in endemic area--indicated neuroborreliosis . Because there was no effect of antibiotic therapy and lack antibodies against B-burgdorferi in serum and CSF we excluded neuroborreliosis . Developing neuropathies III-XII, increasing cytosis and protein concentration, radiculalgia and difficulties in walking, cachexia made us think of tbc etiology . Patient failed to improve after anti-tbc treatment . CT and MR showed presence of neoplasmatic masses in spinal canal . In cytologic examination "neoplasma malignum male differentiatum probabiliter metastaticum" was found . Primary focus of neoplasmatic process was not found. Childs Nerv Syst, 1999 Jul, 15(6-7), 292 - 4 Intracranial hemorrhage in an infant owing to vitamin K deficiency despite prophylaxis; Suzuki K et al.; A 3-month-old male infant with intracranial hemorrhage attributable to a vitamin K deficiency is reported . Vitamin K2 was administered orally at birth and then at 5 days and I month of age . Oral antibiotics were also given 2 days before the onset of bleeding . Although the incidence of intracranial hemorrhage resulting from vitamin K deficiency has decreased since the introduction of vitamin K2 prophylaxis, spontaneous intracranial hemorrhages are still being reported in infants . We suggest that vitamin K prophylaxis is needed especially for breast-fed infants and for those undergoing antibiotic therapy. Conn Med, 1999 Jul, 63(7), 425 - 31 Improving the care of patients with community-acquired pneumonia: a multihospital collaborative QI project; Metersky ML et al.; BACKGROUND: Performance of several processes of care was measured in eight acute care hospitals in Connecticut which provided inpatient treatment to 713 elderly patients with community-acquired pneumonia (CAP) . BASELINE DATA ABSTRACTION AND FEEDBACK: Chart review feedback was provided, and the hospitals were requested to design their own quality improvement (QI) interventions, after which re-examination of process of care performance was conducted . HOSPITAL QI INTERVENTIONS: Six of the eight hospitals had submitted QI plans . The quality indicators dealing with timeliness of antibiotic delivery were specifically addressed by five hospitals . However, each hospital also picked one or two other process of care for intervention . RESULTS: The mean time to antibiotic administration decreased from 5.5 hours (+/- 0.2) to 4.7 hours (+/- 0.3; P < 0.0001), and the percentage of patients who received antibiotics within four hours increased from 41.5% to 61.6% (P < 0.0001) . DISCUSSION: This project called for obtaining buy-in from both the clinician and administrative representatives of each hospital early in the process . In this way, the targeted processes of care were likely to have relevance for each of the participating hospitals . Education of practicing physicians and other health professionals, as the method chosen by each hospital to address delays in antibiotic administration, appears to have been successful in this project as part of a multifaceted intervention . The project also helped establish a collegial environment that has served as the basis for more ambitious pneumonia QI projects . SUMMARY AND CONCLUSIONS: Widespread improvements in process of care performance can result from hospitals' participation in a Quality improvement Organization collaboration. Drug Metab Dispos, 1999 Sep, 27(9), 1039 - 44 Oxidative metabolism of monensin in rat liver microsomes and interactions with tiamulin and other chemotherapeutic agents: evidence for the involvement of cytochrome P-450 3A subfamily; Nebbia C et al.; Monensin (MON) is an ionophore antibiotic widely used in veterinary practice as a coccidiostatic or a growth promoter . The aims of this study were to characterize the P-450 isoenzyme(s) involved in the biotransformation of the ionophore and to investigate how this process may be affected by tiamulin and other chemotherapeutic agents known to produce toxic interactions with MON when administered concurrently in vivo . In liver microsomes from untreated rats (UT) or from rats pretreated, respectively, with ethanol (ETOH), beta-naphthoflavone (betaNAF), phenobarbital (PB), pregnenolone 16alpha-carbonitrile (PCN), or dexamethasone (DEX), the rate of MON O-demethylation was the following: DEX > PCN > PB >> UT = ETOH > betaNAF; similar results were obtained by measuring total MON metabolism . In addition, the extent of triacetyloleandomycin-mediated P-450 complexes was greatly reduced by the prior addition of 100 microM MON . In DEX-treated microsomes, MON O-demethylation was found to fit monophasic Michaelis-Menten kinetics (K(M) = 67.6 +/- 0.01 microM; V(max) = 4.75 +/- 0.76 nmol/min/mg protein) . Tiamulin markedly inhibited this activity in an apparent competitive manner, with a calculated K(i) (Dixon plot) of 8.2 microM and an IC(50) of about 25 microM . At the latter concentration, only ketoconazole or metyrapone, which can bind P-450 3A, inhibited MON O-demethylase to a greater extent than tiamulin, whereas alpha-naphthoflavone, chloramphenicol, or sulphametasine was less effective . These results suggest that P-450 3A plays an important role in the oxidative metabolism of MON and that compounds capable of binding or inhibiting this isoenzyme could be expected to give rise to toxic interactions with the ionophore. Am J Med, 1999 Aug, 107(2), 144 - 8 Clinical features and costs of care for hospitalized adults with primary Epstein-Barr virus infection; Borer A et al.; PURPOSE: To study the clinical and laboratory features of primary infection with the Epstein-Barr virus in adults who required hospitalization and to assess the difficulty in its diagnosis, the use of diagnostic procedures, and the associated costs of care . PATIENTS AND METHODS: We retrospectively identified all adult patients who were diagnosed with primary Epstein-Barr virus infection in our region between 1988 and 1997 using strict serologic criteria . The added costs of unnecessary diagnostic tests and treatment were estimated . RESULTS: The analysis included 47 patients (60% men) with a mean (+/-SD) age of 30 +/- 14 years . The prime cause of admission was fever (83%) . Compared with patients 35 years of age and older, those younger than 35 years were more likely to have pharyngitis (45% vs 10%) and lymphadenopathy (66% vs 17%) . Younger patients also had a greater mean atypical lymphocyte count (17% +/- 14% vs 8% +/- 6%) and more abnormal hepatic enzyme levels . Inpatient work-ups resulted in 309 days of hospitalization, many diagnostic tests, and unnecessary empiric treatments (total 203 days of antibiotic therapy) . Overall, unnecessary diagnostic procedures and medical treatments contributed an average of approximately $12,000 in health-care costs per patient . CONCLUSIONS: Testing for primary Epstein-Barr virus infection should be a routine step in the investigation of fever in adults of all ages . A higher index of suspicion might prevent unnecessary, sometimes hazardous inpatient work-ups from being performed, thereby reducing health-care expenses. Graefes Arch Clin Exp Ophthalmol, 1999 Aug, 237(8), 678 - 84 Transfection of basic fibroblast growth factor (bFGF) gene or bFGF antisense fene into human retinal pigment epithelial cells; Ogata N et al.; BACKGROUND: Transplantation of RPE cells offers a potential of restoring retinal pigment epithelium (RPE) function and has been shown to be effective in the dystrophic RCS rat model . Recently, RPE transplantation was attempted in patients with age-related macular degeneration . Basic fibroblast growth factor (bFGF) plays important roles in maintaining normal retinal function . The purpose of this study was to introduce bFGF sense or antisense cDNA into human RPE cells to alter the expression of bFGF . METHODS: Human bFGF sense cDNA or antisense cDNA was inserted into the pBK-CMV vector . For stable gene expression, we introduced the plasmids into RPE cells using the electroporation method . Following electroporation, transfected RPE cells were cultured and resistant cells were selected in the presence of antibiotic G418 . We analyzed the expression of the transfected genes in the cloned RPE cells by polymerase chain reaction (PCR) and by reverse transcription (RT)-PCR . RESULTS: Cloned RPE cells in which the bFGF sense or antisense cDNA had been efficiently transfected were established . PCR and RT-PCR analysis demonstrated not only the presence but also the expression of bFGF sense or antisense cDNA in the transfected RPE cells . CONCLUSIONS: Human bFGF sense cDNA or antisense cDNA can be efficiently introduced into cultured RPE cells by the electroporation method . The successful expression of the genes into RPE cells demonstrated that this technique can be used to regulate bFGF expression and thus increase the scope of RPE transplantation for the treatment of retinal diseases. Nippon Jibiinkoka Gakkai Kaiho, 1999 Jul, 102(7), 871 - 7 {Endoscopic sinus surgery for unilateral chronic sinusitis}; Ishibashi T et al.; Functional endoscopic sinus surgery has become an increasingly popular treatment for chronic sinusitis . This approach is aimed at re-establishment of ventilation and mucociliary clearance of the sinuses . However, some otolaryngologists believe that the Caldwell-Luc procedure should be routinely used for unilateral chronic sinusitis, because it is often associated with the maxillary sinus carcinomas . To evaluate the state of endoscopic sinus surgery for the diagnosis and treatment of unilateral chronic sinusitis, we analyzed the cases of 39 patients with unilateral chronic sinusitis who underwent endoscopic sinus procedures . These patients were unresponsive to appropriate antibiotic management for more than 6 months . Generally, endoscopic ethmoidectomy and antrostomy were performed with preservation of the middle turbinate . After the ostium was enlarged, the maxillary sinus was cleaned and carefully inspected for the presence of associated neoplasms using 30 and 70 degree endoscopes . Preoperative computed tomography (CT), postoperatve pathologic diagnosis, fiberscopic findings of the maxillary sinus, and symptomatic improvement were evaluated . Three patients had CT evidence of bone destruction of the lateral nasal wall . Pathological diagnosis demonstrated that three patients had maxillary sinus mycoses caused by Aspergillus species, one patient had inverted papilloma, and the other 35 patients had chronic sinusits . No associated malignancy was found . Eighty-one percent of the patients had almost normal endoscopic findings of the maxillary sinus by postoperative fiberscopic examination 4 to 8 months following surgery . With an average follow-up of 26 months, 88% of the patients were judged as having significantly improved in their presenting complaints of mucopurulent rhinorrhea, nasal obstruction, and facial pain . The results of this series suggest that endoscopic sinus surgery is an effective procedure for the diagnosis and treatment of unilateral chronic sinusitis. J Urol, 1999 Sep, 162(3 Pt 1), 829 - 31 Progressive dilation for bladder tissue expansion; Satar N et al.; PURPOSE: The use of gastrointestinal tissue for augmentation cystoplasty is associated with numerous complications . We previously reported the development of a system in which ureters were progressively dilated and used for ureterocystoplasty . We have now applied a similar system for the progressive expansion of native bladder tissue . We investigated whether the expanded bladder tissue retained normal functional and phenotypic characteristics . MATERIALS AND METHODS: Urodynamic studies were performed in 5 beagle dogs and the bladder was divided horizontally into a superior bladder neo-reservoir, and an intact smaller bladder inferiorly with both ureters left intact and draining . A silicone catheter was threaded into the newly formed, superiorly located neo-reservoir, and connected to an injection port which was secured subcutaneously . A saline antibiotic solution was injected daily into the palpable injection port 4 weeks after surgery, dilating the neo-reservoir through the silicone catheter . Baseline and weekly cystograms were performed . Urodynamic studies of the neo-reservoirs were done immediately before sacrifice . Animals were sacrificed 3 months after the initial intervention and the bladder was examined grossly and microscopically . RESULTS: Within 30 days after progressive dilation, the neo-reservoir volume was expanded at least 10-fold according to radiography and cystometrograms . Urodynamic studies of the dilated neo-reservoirs showed normal compliance in all animals . Microscopic examination of the expanded neo-reservoir tissue revealed normal histology . A series of immunocytochemical studies demonstrated that the dilated bladder tissue maintained normal phenotypic characteristics . CONCLUSIONS: The system of progressive dilation is effective in expanding bladder tissue which is able to retain normal phenotypic and functional characteristics. Rev Chir Orthop Reparatrice Appar Mot, 1999 Jul, 85(4), 328 - 36 {Infection prophylaxis in open leg fractures . Comparison of a dose of pefloxacin and 5 days of cefazolin-oxacillin . A randomized study of 616 cases}; Gagey O et al.; THE PURPOSE OF THE STUDY: Was to compare the efficacy of a single 800 mg injection of Pefloxacin (PF) versus 2 days of cefazolin (1 gr.Q.6 H) followed by 3 days of oxacillin (1 gr.Q.8 H) in patients with an open tibial fracture and to examine the predictive factors for infection . A double-blind double dummy, multicentric, randomized trial was performed . 616 adults with an open tibial fracture requiring single-stage bone coverage were included . The end point was wound infection within 3 months . RESULTS: Within 3 months, 21/316 patients were infected in the PF group (6.6 p . 100) versus 24/300 in the CZ-OX group (8 p . 100), the difference was not significant (95 p . 100 Cl for difference: -4.8 p . 100 to 2.1 p . 100) . Twenty one strains were isolated in 18 infected patients in the PF group, and 27 in 20 patients in the CZ-OX group . Negative gram bacteria were less frequent in the PF group (10 p . 100) than in the CZ-OX group (48 p . 100), and positive gram bacteria were more frequent in the PF group (90 p . 100) than in the CZ-OX group (52 p . 100) . Independent risk factors for infection were severe contamination, widespread contusion, unstable fracture, positive sample in the emergency room and at the end of surgery . Resistant infecting bacteria rate was 24 p . 100 in infected cases . CONCLUSION: There was no difference in infection rates after surgery for open tibial fractures between a 800 mg injection of Pefloxacin and 2 days of pephazolin followed by 3 days of oxacillin . Infecting bacteria were mainly nosocomially acquired. Gut, 1999 Jul, 45 Suppl 1, I40 - 4 Treatment after failure: the problem of "non-responders"; Huang JQ et al.; Although the currently most effective treatment regimens cure about 90% of infections, 10% of patients remain Helicobacter pylori positive . Several factors contribute to treatment failure . These include patient compliance, bacterial resistance to antibiotics, and treatment related issues . Treatment failure leads to the development of bacterial resistance to metronidazole and clarithromycin . Retreatment can be undertaken after considering several different strategies: to repeat the same regimen with full doses of medications and a longer treatment duration, or to choose different regimens to avoid the antibiotic previously used, or to switch to proton pump inhibitor (PPI) based quadruple therapy or ranitidine bismuth citrate (RBC) based triple therapy . In principle, full doses and longer treatment durations are advisable . As retreatment is always difficult, choosing the best available first line treatment regimen is still the best "rescue" treatment. Clin Excell Nurse Pract, 1998 Sep, 2(5), 260 - 2 Amoxicillin: a pharmacologic description; Albu RE; This article discusses several pharmacokinetic aspects of amoxicillin pertinent in a maternal and pediatric population . Life stages impact both dosage requirements as well as actual pharmacokinetic properties of this antibiotic. J Ind Microbiol Biotechnol, 1999 Jul, 23(1), 701 - 8 Comparative stability of ethanol production by Escherichia coli KO11 in batch and chemostat culture; Dumsday GJ et al.; Differing claims regarding the stability of the recombinant ethanologen E . coli KO11 are addressed here in batch and chemostat culture . In repeat batch culture, the organism was stable on glucose, mannose, xylose and galactose for at least three serial transfers, even in the absence of a selective antibiotic . Chemostat cultures on glucose were remarkably stable, but on mannose, xylose and a xylose/glucose mixture, they progressively lost their hyperethanologenicity . On xylose, the loss was irreversible, indicating genetic instability . The loss of hyperethanologenicity was accompanied by the production of high concentrations of acetic acid and by increasing biomass yields, suggesting that the higher ATP yield associated with acetate production may foster the growth of acetate-producing revertant strains . Plate counts on high chloramphenicol-containing medium, whether directly, or following preliminary growth on non-selective medium, were not a reliable indicator of high ethanologenicity during chemostat culture . In batch culture, the organism appeared to retain its promise for ethanol production from lignocellulosics and concerns that antibiotics may need to be included in all media appear unfounded. Bone Marrow Transplant, 1999 Aug, 24(3), 339 - 42 Donor lymphocyte infusion post-non-myeloablative allogeneic peripheral blood stem cell transplantation for chronic granulomatous disease; Nagler A et al.; Chronic granulomatous disease (CGD) is a primary immunodeficiency disease symptomized by failure to generate superoxide and recurrent bacterial and fungal infections . Allogeneic bone marrow transplantation (BMT) is one of the therapeutic options available . However, it presents considerable risk to the recipient, especially if the patient is already at an advanced stage of disease, after repeated bacterial and fungal infections and organ damage . We present a case report of a 6-year-old child with long-standing CGD, severe clubbing, and jeopardized pulmonary function after multiple bacterial pulmonary infectious episodes, who had failed treatment with sulphamethazole trimethoprim, multiple antibiotic courses, itraconazole, as well as steroid and interferon-y therapy . He underwent allogeneic peripheral blood stem cell transplantation (alloPBSCT) from his HLA-matched MLC non-reactive sister following non-myeloablative conditioning . His ANC did not fall below 0.2 x 10(9)/l, his lowest WBC was 0.6 x 10(9)/l, and his platelets did not fall below 28 x 10(9)/l . He had normal engraftment, with no mucositis or organ toxicity . Neither parenteral nutrition nor platelet infusions were necessary . Partial donor chimerism following alloPBSCT was converted to full donor chimerism and superoxide production reverted to normal after donor lymphocyte infusions (DLI) from his HLA-matched sister . Twenty four months post transplant the patient is well, with stable and durable engraftment, 100% donor chimerism, normal superoxide production, no GVHD, and stabilization of his pulmonary condition . We suggest that alloPBSCT preceded by non-myeloablative conditioning and followed by DLI may constitute a successful mode of therapy for patients suffering from advanced CGD with recurrent infectious episodes resulting in organ dysfunction, enabling them to achieve full donor chimerism and normal superoxide production with minimal risk of transplant-related toxicity and GVHD. Nucleic Acids Res . 1999 Aug 1;27(15):e10. Simultaneous Cre catalyzed recombination of two alleles to restore neomycin sensitivity and facilitate homozygous mutations; Milstone DS et al.; Cells homozygous for neo-expressing mutations can be derived by culturing heterozygotes with elevated G418 . We demonstrate that this strategy is significantly less efficient if hyg is substituted for neo . Therefore, to introduce additional mutations Cre recombinase was used to remove floxed neo from both alleles of homozygotes at two different loci . The rate-determining step in Cre excision appeared independent of substrate copy number . Incorporating cytosine deaminase and Herpes simplex virus thymidine kinase allowed negative selection for both targeting and Cre excision . The resulting G418-sensitive homozygous mutants should allow mutagenesis at additional loci and avoid untoward effects of retained selection markers. Nucleic Acids Res, 1999 Aug 1, 27(15), 3168 - 72 Faithful expression of a heterologous gene carried on an artificial macronuclear chromosome in Euplotes crassus; Bender J et al.; Macronuclear chromosomes of hypotrichous ciliates are gene-sized molecules carrying the coding sequence flanked by short non-translated regions and bounded by telomeres . We have constructed artificial chromosomes for investigation of transcription in the macronucleus of Euplotes crassus . The neo gene was put under the control of the 5"-non-translated region of the TBP gene of E.crassus . These molecules were introduced into the cell with the help of liposomes . The cells were transformed and survived high concentrations of geneticin . The artificial chromosomes were kept in the macro-nucleus for at least 50 days at a copy number of about 200 per macronucleus . Expression of the gene was shown by reverse transcription of the neo messenger . The transcription start was mapped and found to coincide with that found on the natural macronuclear chromosome encoding TBP in E.crassus. Mol Cell Biol, 1999 Sep, 19(9), 6041 - 7 Cell cycle progression and proliferation despite 4BP-1 dephosphorylation; Marx SO et al.; Proliferation and cell cycle progression in response to growth factors require de novo protein synthesis . It has been proposed that binding of the eukaryotic translation initiation factor 4E (eIF-4E) to the inhibitory protein 4BP-1 blocks translation by preventing access of eIF-4G to the 5' cap of the mRNA . The signal for translation initiation is thought to involve phosphorylation of 4BP-1, which causes it to dissociate from eIF-4E and allows eIF-4G to localize to the 5' cap . It has been suggested that the ability of the macrolide antibiotic rapamycin to inhibit 4BP-1 phosphorylation is responsible for the potent antiproliferative property of this drug . We now show that rapamycin-resistant cells exhibited normal proliferation despite dephosphorylation of 4BP-1 that allows it to bind to eIF-4E . Moreover, despite rapamycin-induced dephosphorylation of 4BP-1, eIF-4E-eIF-4G complexes (eIF-4F) were still detected . In contrast, amino acid withdrawal, which caused a similar degree of 4BP-1 dephosphorylation, resulted in dissociation of the eIF-4E-eIF-4G complex . Thus, 4BP-1 dephosphorylation is not equivalent to eIF-4E inactivation and does not explain the antiproliferative property of rapamycin. Ann Plast Surg, 1999 Aug, 43(2), 148 - 53 Splitting advancement genioplasty: a new genioplasty technique; Celik M et al.; A new genioplasty technique has been described and performed on 16 patients since 1995 . The technique has been developed to avoid some undesired results of the current osseous genioplasty techniques and to achieve a more natural appearance in advancement genioplasty . According to the authors' technique, a rectangular part of the outer table of the mentum is split away from the mandible, and is advanced and fixated to the mandible . This technique can be used for advancement cases but not for reduction genioplasty . This technique was performed on 16 patients with only minor complications, including one case of wound dehiscence, one hematoma, and one case of osteomyelitis, which was managed with systemic antibiotic therapy . Aesthetic results were found to be satisfactory according to an evaluation by the authors . When the results were evaluated using pre- and postoperative photos, lip position and projection of the mentum were found to be natural in shape appearance . During the late postoperative period, the new bone formation between the advanced segment and the mandible was demonstrated radiographically . Advantages of the technique include having more contact surfaces for bony healing, a natural position of the lower lip, more natural projection of the mentum, tridimensional movement of the mentum, and improvement in the soft tissue of the neck . The disadvantages of the technique are the potential risk of infection due to dead space from the advancement, manipulation problems during surgery, and possible mental nerve injury . Splitting advancement genioplasty was found to be a useful technique for advancement genioplasty . Splitting advancement genioplasty is a more physiological osteotomy technique than most of osseous genioplasty techniques. Leukemia, 1999 Aug, 13(8), 1207 - 13 A randomized study of granulocyte colony-stimulating factor applied during and after chemotherapy in patients with poor risk myelodysplastic syndromes: a report from the HOVON Cooperative Group . Dutch-Belgian Hemato-Oncology Cooperative Group; Ossenkoppele GJ et al.; The purpose of this study was to determine the safety and efficacy of filgrastim as an adjunct to induction and consolidation chemotherapy in poor risk patients with myelodysplastic syndrome (MDS) . Filgrastim was given both during and after chemotherapy with the objective to accelerate hematopoietic repopulation and enhance the efficacy of chemotherapy . In a prospective randomized multicentre phase II trial, a total of 64 patients with poor risk primary MDS were randomized to receive either granulocyte colony-stimulating factor (G-CSF, filgrastim, AMGEN, Breda, The Netherlands) 5 microg/kg/day subcutaneously or no G-CSF in addition to daunomycin (30 mg/m2/days 1, 2 and 3 intravenous bolus) and cytarabine (200 mg/m2 days 1-7, continuous infusion) . The overall complete response rate was 63%: 73% for patients receiving filgrastim as compared to 52% in the standard arm (P = 0.08) . Overall survival at 2 years was estimated at 29% for patients assigned to the filgrastim arm and 16% for control patients (P = 0.22) . The median time for recovery of granulocytes towards 1.0 x 10(9)/l post-chemotherapy was 23 days in the filgrastim-treated patients vs 35 days in the standard arm (P = 0.015) . There were no differences in time of platelet recovery, length of hospital stay, duration of antibiotic use or infectious complications between the two treatment groups . However the earlier recovery of neutrophils in the filgrastim group was associated with a reduced interval of 9 days between the induction and consolidation cycle . In patients with poor risk MDS the use of filgrastim during and after induction therapy results in a significantly reduced neutrophil recovery time . Further study may be warranted to see if the apparent trend of the improved response to chemotherapy in combination with filgrastim can be confirmed in greater number of patients and to assess the effect of the addition of filgrastim on survival. J Inorg Biochem, 1999 Jun 15, 75(2), 105 - 15 How Fe3+ binds anthracycline antitumour compounds . The myth and the reality of a chemical sphinx; Fiallo MM et al.; The interaction of Fe3+ with several anthracycline antitumour antibiotics has been reinvestigated . Absorption and circular dichroism (CD) measurements were carried out (i) in aqueous solution and (ii) in semi-aqueous MeOH to avoid the stacking of the anthracycline molecules . The Fe3+ binding to anthracycline was dependent on the metal-to-ligand molar ratio, antibiotic concentration, ionic strength, and pH . The formation of two major Fe3(+)-anthracycline complexes, I and II, was observed for all the drugs . These species differed in their coordination modes to the anthracycline ligands . Complex I was a monomeric species, where Fe3+ was bound to the anthracycline through the inverted question markC(11)-O-; C(12) = O inverted question mark chelating site . In complex II, Fe3+ was also bound through the inverted question markC(5) = O; C(6)-O- inverted question mark coordination site . Thus, the antibiotic ligand was acting as a bridge between two metal ions, forming oligomeric (or polymeric) structures . The different degree of association of the anthracyclines could be responsible for the reactivity of the metal ion . In fact, complexes I and II could constitute mononuclear, binuclear or polynuclear Fe3+ species depending on the competitive kinetics of both coordination and hydrolysis of the metal ion. Surg Endosc, 1999 Sep, 13(9), 932 - 4 Bronchoscopic sclerotherapy combined with thoracoscopic drainage for postpneumonectomy bronchial fistula and empyema; Urschel JD et al.; A postpneumonectomy bronchial fistula is a very morbid complication that often requires major surgical procedures for treatment . Since patients with postpneumonectomy bronchial fistula and empyema are physiologically compromised, corrective surgical interventions pose considerable risk . We report a case of a postpneumonectomy fistula with an associated empyema . Our patient's empyema was treated with thoracoscopic debridement and antibiotic instillation (modification of the Clagett procedure) . Bronchoscopic and thoracoscopic treatment strategies that are appropriate for selected patients with postpneumonectomy bronchial fistula and empyema are discussed. Proc Natl Acad Sci U S A, 1999 Aug 17, 96(17), 9586 - 90 Thiostrepton inhibits the turnover but not the GTPase of elongation factor G on the ribosome; Rodnina MV et al.; The region around position 1067 in domain II of 23S rRNA frequently is referred to as the GTPase center of the ribosome . The notion is based on the observation that the binding of the antibiotic thiostrepton to this region inhibited GTP hydrolysis by elongation factor G (EF-G) on the ribosome at the conditions of multiple turnover . In the present work, we have reanalyzed the mechanism of action of thiostrepton . Results obtained by biochemical and fast kinetic techniques show that thiostrepton binding to the ribosome does not interfere with factor binding or with single-round GTP hydrolysis . Rather, the antibiotic inhibits the function of EF-G in subsequent steps, including release of inorganic phosphate from EF-G after GTP hydrolysis, tRNA translocation, and the dissociation of the factor from the ribosome, thereby inhibiting the turnover reaction . Structurally, thiostrepton interferes with EF-G footprints in the alpha-sarcin stem loop (A2660, A2662) located in domain VI of 23S rRNA . The results indicate that thiostrepton inhibits a structural transition of the 1067 region of 23S rRNA that is important for functions of EF-G after GTP hydrolysis. AIDS, 1999 Jul 30, 13(11), 1367 - 72 Prevention of disseminated Mycobacterium avium complex infection with reduced dose clarithromycin in patients with advanced HIV disease; Hewitt RG et al.; OBJECTIVE: To evaluate the ability of once daily reduced dose clarithromycin to prevent disseminated Mycobacterium avium complex (dMAC) infection in patients with advanced HIV disease . DESIGN: Non-randomized, retrospective study . SETTING: Outpatient clinic of an urban university-affiliated municipal hospital . PATIENTS: A group of 192 HIV-infected patients with a CD4 count < 100 x 10(6) cells/l who were followed for at least 90 days during a 6-year period (1991-1996) before the use of protease inhibitors . INTERVENTIONS: Clarithromycin 500 mg orally once daily (n = 84), rifabutin 300 mg orally once daily (n = 47) or no prophylaxis (n = 61) . MAIN OUTCOME MEASURES: Positive blood culture for M . avium complex (MAC), time to development of dMAC, and time to death . RESULTS: When compared with no prophylaxis or rifabutin, the incidence of dMAC and time to development of dMAC were improved among those patients receiving clarithromycin (P < 0.001) . Prolonged survival was associated with both clarithromycin and rifabutin use when compared with no prophylaxis (P < 0.002) . In patients who failed prophylaxis, resistance to clarithromycin and rifabutin was observed . CONCLUSIONS: In the era prior to protease inhibitor use, once daily clarithromycin at a dose of 500 mg was associated with a reduction in the incidence of dMAC, appeared to be superior to rifabutin, and was associated with prolonged survival in patients with advanced HIV disease. Postgrad Med J, 1999 Mar, 75(881), 141 - 4 Lemierre's syndrome (necrobacillosis); Golpe R et al.; Lemierre's syndrome or postanginal septicaemia (necrobacillosis) is caused by an acute oropharyngeal infection with secondary septic thrombophlebitis of the internal jugular vein and frequent metastatic infections . Fusobacterium necrophorum is the most common pathogen isolated from the patients . The interval between the oropharyngeal infection and the onset of the septicaemia is usually short . The most common sites of septic embolisms are the lungs and joints, and other locations can be affected . A high degree of clinical suspicion is needed to diagnose the syndrome . Computed tomography of the neck with contrast is the most useful study to detect internal jugular vein thrombosis . Treatment includes intravenous antibiotic therapy and drainage of septic foci . The role of anticoagulation is controversial . Ligation or excision of the internal jugular vein may be needed in some cases. Sex Transm Infect, 1999 Jun, 75(3), 156 - 61 A collaborative approach to management of chlamydial infection among teenagers seeking contraceptive care in a community setting; James NJ et al.; OBJECTIVES: To develop and assess a coordinated model of care for effective management of genital chlamydial infection in young women, identified through a selective screening programme in a community based teenage health clinic . METHODS: Selective screening for genital Chlamydia trachomatis was undertaken among young women aged 13-19 years who were having a routine cervical smear test, being referred for termination of pregnancy, or who reported behavioural risk factors, for, and/or symptoms of, genital infection . Collaboration among family planning, genitourinary medicine (GUM), and public health staff was used to enhance management of infected individuals, with particular focus on partner notification . RESULTS: 94 young women had confirmed genital chlamydial infection, representing 11% of those tested . All index patients received appropriate antibiotic therapy and follow up; 93 (99%) of these were counselled by a health adviser, of whom 62 (66%) were able to provide sufficient details for partner notification, resulting in treatment of male partners associated with 51 (82%) of these young women . Younger age (< or = 16 years) was significantly associated with delay in attending for treatment . CONCLUSIONS: Effective management of genital chlamydial infection is achievable in settings outside GUM clinics using a collaborative approach which incorporates cross referencing between community based services and GUM clinics. Sex Transm Infect, 1999 Apr, 75(2), 116 - 9 Integrated clinical service for sexual assault victims in a genitourinary setting; Bottomley CP et al.; BACKGROUND: Reported sexual assault is increasing, and the diverse immediate and longer term needs of the victim are usually met by exposure to a number of healthcare professionals often in different locations, involving delays and travel, increasing the trauma for the victim . OBJECTIVES: To set up a centre to address the immediate and longer term needs of the sexual assault victim and review issues arising during the development of the service . METHODS: Description of setting up the service in the genitourinary medicine department of Kings College Hospital, south London, and the aspects of care offered . RESULTS: The number of victims referred by police increased from 15 in 1992 to 58 in 1996 . In 1996, 55 female and three male victims were seen . 23 different police stations brought victims for examination; mean age of the victim was 27 years (range 14-60), median time between assault and examination was 22 hours (range 3 hours-3 months); 23% had genital injuries, 59% had other physical injury, and 11% needed further hospital care . 71% accepted screening for sexually transmitted infection (STI), 21% had an STI diagnosed, 16% of the women required emergency contraception, 26% received prophylactic antibiotics, and 58% saw a health adviser . 70% had a follow up appointment arranged of which 50% attended . CONCLUSION: The high uptake of STI screening, emergency contraception, health adviser consultation, and follow up supports the concept of a comprehensive integrated system to meet the disparate needs of the victim while still obtaining the necessary forensic evidence . The wide catchment area of service users indicates gaps in services available for the assault victim . Earlier genitourinary involvement after sexual assault is becoming increasingly pertinent in relation to HIV prophylaxis. Arch Orthop Trauma Surg, 1999, 119(5-6), 340 - 3 Transoral missile removal from the anterior C1 region following transpharyngeal missile wound; Hecimovic I et al.; We present a successful treatment result in a rare case of low velocity missile transpharyngeal wound to the upper cervical area in a 33-year-old man . There are very few reports concerning related cases, with some disagreement regarding their treatment . The retained missile was successfully removed from the anterior region of the C1 vertebra through a transoral-transpharyngeal approach using the explosive transpharyngeal wound sustained . Neurological status and spine stability were not affected due to the missile's low velocity . The early soft-tissue debridement, missile removal, pharyngeal closure without wound drainage and broad-spectrum antibiotic coverage resulted in an uneventful postoperative course and good long-term outcome . Early surgery is important to prevent complications in such cases . However, the prophylactic tracheostomy, wound drainage and applying of a nasogastric tube could be left to the surgeon's judgment based on the individual patient's respiratory status, intraoperative findings and wound contamination/colonization. Eur Respir J, 1999 Jun, 13(6), 1371 - 9 Clinical and immunoregulatory effects of roxithromycin therapy for chronic respiratory tract infection; Nakamura H et al.; The clinical and immunoregulatory effects of long-term macrolide antibiotic therapy for patients with chronic lower respiratory tract infections (CLRTI) were investigated . Clinical parameters and neutrophil chemotactic mediators in the epithelial lining fluid (ELF) of CLRTI patients (n = 10) were examined before and after 3 months oral administration of roxithromycin (RXM) . The in vitro effects of RXM were also examined on the release of these mediators from alveolar macrophages (AM) and neutrophils . Arterial oxygen tension (p<0.05), vital capacity (VC) (p<0.001), %VC (p<0.05) and forced expiratory volume in one second (p<0.01) were improved after RXM treatment, but airway bacteria were not eradicated . Among the mediators, the levels of interleukin (IL)-8, neutrophil elastase (NE) and leukotriene B4 (LTB4) were higher in ELF than in plasma of CLRTI patients and they decreased after RXM treatment (n = 7, p<0.05 for each) . RXM concentrations were significantly increased in the bronchoalveolar lavage cells of the treated patients . In in vitro experiments, RXM showed inhibitory effects on IL-8 release from AM and neutrophils . In conclusion, interleukin-8, neutrophil elastase and leukotriene B4 contribute to the neutrophilic inflammation in the airways of chronic lower respiratory tract infection patients and the clinical effects of roxithromycin may, in part, be attributable to the suppression of excess release of the chemotactic mediators from inflammatory cells. Schweiz Rundsch Med Prax, 1999 Jul 8, 88(27-28), 1196 - 9 {The diabetic foot--state of the art from the orthopedic point of view}; Schaefer D; A 15-30% rate of amputation of diabetic feet suggests that efforts have to be directed towards improvement of preventive measure including instruction of patients and relatives concerning foot wear . So called foot rules have been established . If surgery is indicated, an angiological and neurological assessment should be performed preoperatively . An ulcer should undergo debridement, plantar pressure release with a full contact cast and antibiotic therapy, if infected . The goal of treatment of Charcot's disease is prevention of deformity . Usually orthoses are sufficient, in irreducible deformities an arthrodesis should be considered . There is no doubt that the interdisciplinary approach improves the treatment of the diabetic foot. Schweiz Rundsch Med Prax, 1999 Jul 8, 88(27-28), 1170 - 7 {Dermatological aspects in prevention and treatment of the diabetic foot syndrome}; Hafner J et al.; Diabetic neuropathy, osteoarthropathy, macro- and microangiopathy and susceptibility to infection are the major factors that contribute to the diabetic foot syndrome . Therefore, these patients benefit from a multidisciplinary treatment by the general practitioner, diabetologist, orthopaedic surgeon and shoemaker, angiologist and vascular surgeon . The role of the dermatologist is to recognize early diabetic foot lesions when the diabetic patient comes for a skin problem on his feet and more specifically to manage dermatologic aspects in diabetic foot patients . These should include recommendations for general skin care, examination and treatment for onychomycosis, patch testing in contact eczema or treatment of other dermatoses, such as plantar psoriasis . Therefore, dermatology has an important impact on the prevention of complications of the diabetic foot syndrome by keeping the skin intact and avoiding potential lesions of entry for bacterial soft tissue infection . The dermatologist must educate the diabetic patient to control his feet daily, to avoid foot-baths with hot water, to use hypoallergenic moisturizers for skin care . "Bathroom surgery" with sharp instruments for nail care or trimming of corns should be discouraged . Diabetics should wear wide, well-fitting shoes without sutures on the inner side . The inside of the shoes should always be checked for foreign bodies or irregular surfaces before they are put on . Diabetics should not walk barefoot . Callosities (calluses, corns) should be shown to the podologist or to the doctor . They are always a sign of increased mechanical stress and therefore, require an adjustment of footwear . Trimming of callosities can only aim at giving symptomatic relief and does not replace an appropriate correction of the mechanical stress . Semi-occlusive synthetic dressings have facilitated the treatment of non-infected chronic wounds . When probing of the bone is positive, however, osteomyelitis has to be assumed and empirical antibiotic therapy started . With the development of catheter-based interventional procedures and of cruro-pedal arterial bypasses the potiential of revascularization in diabetic foot with peripheral arterial occlusive disease has greatly improved . Retrograde intravenous antibiotic therapy under Bier's arterial arrest and the use of G-CSF improve the chance of healing bacterial soft tissue infection in a diabetic foot . In summary, optimization of prevention and treatment of the diabetic foot syndrome should allow for substantial reduction of amputations. Eur J Gastroenterol Hepatol, 1999 Jun, 11 Suppl 1, S37 - 41 My approach to Helicobacter pylori eradication; Bazzoli F; The eradication of Helicobacter pylori is advantageous in many diseases of the upper gastrointestinal tract and can result in the cure of conditions such as peptic ulcer disease . It may also potentially prevent the development of gastric cancer . Complete eradication of H . pylori can be difficult to achieve, and the effectiveness of many combinations of agents has been tested in clinical trials over the years . No agent has been found to be effective at eradicating H . pylori when given alone and this has resulted in the development of combination therapies comprising an antisecretory agent and one or more antibiotics . Bismuth-based triple therapies, while considered for years as the 'gold standard', have limited efficacy and may be associated with significant side effects . Dual therapies, comprising a proton pump inhibitor (PPI) and one antibiotic, marked a milestone in the history of H . pylori eradication therapy but have shown inconsistent results and eradication rates of less than 60% . However, these have provided the basis for the development of short-term, low-dose PPI triple therapies, including two antibiotics from among metronidazole, clarithromycin and amoxycillin plus a PPI that have demonstrated excellent eradication rates approaching 100%. Antiviral Res, 1999 Jul, 42(3), 197 - 209 Anti-HIV activity of amphotericin B-cholesteryl sulfate colloidal dispersion in vitro; Konopka K et al.; We examined whether the anti-HIV-1 activity of the polyene antibiotic Amphotericin B (AMB) is retained following incorporation into sterically stabilized 'Stealth' liposomes (L-AMB) with prolonged circulation in vivo, or cholesteryl sulfate colloidal dispersions (CD-AMB) . The effects of the different preparations on acute infection of H9 cells with HIV-1IIIB, spreading of the virus from chronically infected H9/HTLV-IIIB cells to SupT1 cells, and HIV-1-induced syncytium formation were evaluated . Infection was monitored by p24 levels in culture supernatants . L-AMB did not affect HIV-1 infection . When present only during initial infection, AMB (3-20 microg/ml) reduced p24 levels by 70-80% after 7 and 10 days post-infection, while CD-AMB inhibited p24 production by approximately 30-40% at day 7 and 50-60% at day 10 . The inhibitory effect of CD-AMB and AMB was enhanced by continuous treatment of acutely infected cells . The reduction of p24 production during continuous treatment was not due to cytotoxicity . During spreading of infection from infected to uninfected cells, AMB almost completely inhibited virus production while CD-AMB reduced both p24 production and the cytopathic effect in a dose-dependent manner . HIV-1 induced syncytium formation was slightly inhibited by AMB but not by CD-AMB . Because CD-AMB is considerably less cytotoxic than AMB, its ability to inhibit HIV infection in vivo needs to be evaluated further. Biol Pharm Bull, 1999 Jul, 22(7), 721 - 4 pH-dependent inhibitory effects of angiotensin-converting enzyme inhibitors on cefroxadine uptake by rabbit small intestinal brush-border membrane vesicles and their relationship with hydrophobicity and the ratio of zwitterionic species; Kitagawa S et al.; The inhibitory effects of five angiotensin-converting enzyme (ACE) inhibitors on the uptake of an aminocephalosporin antibiotic, cefroxadine, by rabbit small intestinal brush-border membrane vesicles were examined in the presence of an inward H+ gradient . Dixon plot analysis showed that all these ACE inhibitors inhibited the uptake of cefroxadine, which is transported by a H+/oligopeptide transporter in the membrane, in the order of enalapril<quinapril, benazepril<temocapril, trandolapril at extravesicular pH 6.0 . These drugs, except for enalapril, which are relatively hydrophobic, exhibited a mix of competitive and noncompetitive inhibition . We also examined the inhibitory effects of quinapril and temocapril at extravesicular pH 5.5, at which the ratio of the zwitterionic species of the drugs increased . The inhibition occurred in a nearly competitive manner at this pH and the inhibitory effects were stronger than at pH 6.0 . Regression analysis of the inhibitory effects suggested that the affinity of these ACE inhibitors for the transporter was regulated by the hydrophobicity of these ACE inhibitors and the ratio of the zwitterionic species of the drugs. J Med Assoc Thai, 1999 May, 82(5), 511 - 4 Infected ovarian cyst in a homozygous beta-thalassemic patient; Sukcharoen N et al.; An infected ovarian cyst in a thalassemic patient is rarely reported . We describe the case of a 22-year old woman with splenectomized homozygous beta-thalassemia who developed high fever and was diagnosed as having an infected ovarian cyst . The mechanisms which beta-thalassemia might predispose to infection and considered to be immunocompromized are discussed . She was given an intravenous antibiotic regimen and the infected ovarian cyst was removed . The difficulties in the diagnosis of an infected ovarian cyst is because of its rarity and the paucity of information on it in the literature . Therefore, the triad of ovarian cyst, immunocompromized host, and signs of infection with failure to identify any other source of infection should raise the suspicion of an infected ovarian cyst. J Cardiovasc Pharmacol, 1999 Jun, 33 Suppl 3, S37 - 41 Different causes of heart failure need different treatment strategies; Hampton JR; No one would now believe that all infections will respond to a single antibiotic, nor that all known antibiotics should be given to all patients with infection . It is obvious that some patients with specific causes of heart failure need specific treatment, but whether heart failure of ischaemic or nonischaemic origin need different treatments is not certain . Only when parallel clinical trials have been conducted with individual drugs in separate groups of patients with ischaemic or nonischaemic heart failure will the need for different treatment strategies be known . Until then, there will be a dependency on second-rank evidence (that which can be derived from trials with 'surrogate' end-points, from meta-analysis of small trials and from subset analysis of different patient groups within single trials) . The best evidence at present comes from subset analysis of two studies, with bisoprolol (Cardiac Insufficiency Bisoprolol Study; CIBIS) and amlodipine (Prospective Randomised Amlodipine Survival Evaluation; PRAISE) . These suggest that patients with different causes of heart failure respond to treatment in different ways. J Pediatr Surg, 1999 Jul, 34(7), 1064 - 7 The morbidity and mortality of pediatric splenectomy: does prophylaxis make a difference? Jugenburg M, Haddock G, Freedman MH, Ford-Jones L, Ein SH. PURPOSE: The aim of this study was to analyze the incidence of postsplenectomy sepsis morbidity and mortality after prophylaxis, in comparison with our previous 13-year study (1958 to 1970, inclusive) . METHODS: All patients who had splenectomy at the Hospital for Sick Children, Toronto, between 1971 and 1995, inclusive (to give a minimum of 2 years for follow-up), were reviewed for infection and mortality . The criterion for classifying a patient as "infected" was the recovery of an invading encapsulated organism from the blood culture in a patient admitted to the hospital . RESULTS: Of the 264 patients studied, 10 had a postsplenectomy infection (3.8%); nine occurred in patients who underwent splenectomy between the ages of 0 and 5 years . Infection took place within 2 +/- 3 years (mean +/- SD) after splenectomy for the immunized patients and 11 +/- 5 days (mean +/- SD) for the nonimmunized children . A significant number of patients were admitted for an apparent respiratory infection, but no serum organisms were isolated . One died of overwhelming sepsis, but the responsible organism was not identified . CONCLUSION: Although there has not been a decrease in the number of splenectomies performed per year, the incidence of infection and mortality has decreased by 47% and 88%, respectively, with prophylaxis. Arch Biochem Biophys, 1999 Aug 15, 368(2), 421 - 8 Cell-permeable superoxide dismutase and glutathione peroxidase mimetics afford superior protection against doxorubicin-induced cardiotoxicity: the role of reactive oxygen and nitrogen intermediates; Konorev EA et al.; The use of the potent antitumor antibiotic doxorubicin (DOX) is hampered because of its severe cardiac toxicity that leads to the development of cardiomyopathy and heart failure . In this study, we have developed a cell culture model for DOX-induced myocardial injury using primary adult rat cardiomyocytes that were cultured in serum-free medium and exposed to 1 to 40 microM DOX . DOX caused a dose-dependent release of sarcosolic enzyme lactate dehydrogenase (LDH) from cultured myocytes . The release of LDH was prevented by the cell-permeable superoxide dismutase (SOD) mimetic (MnTBAP), but was unaffected by either cell-impermeable SOD enzyme, or manganese (II) sulfate . Ebselen, a glutathione peroxidase (GPx) mimetic, enhanced the protection of cardiomyocytes afforded by MnTBAP . DOX caused the increased formation of oxidants in cardiomyocytes, and MnTBAP lowered the amount of intracellular oxidants induced by DOX . In addition, DOX selectively inactivated aconitase in cardiomyocytes, and MnTBAP partially reversed this inactivation . Ebselen further amplified the protective effect of MnTBAP on aconitase activity . These results suggest that the SOD mimetic MnTBAP prevents DOX-induced damage to cardiomyocytes and that the GPx mimetic ebselen synergistically enhanced the cardioprotection afforded by MnTBAP . Relevance of these findings to minimizing cardiotoxicity in cancer treatment is discussed . Biochemistry, 1999 Aug 10, 38(32), 10415 - 23 PF1070A, a novel and potent inducer of the synthesis of metallothionein; Asahi I et al.; Using mouse Ltk(-) cells (L13-17 cells) that had been transfected with a plasmid in which the lacZ gene had been ligated downstream of 1.4 kbp of the sequence of the promoter of the mouse gene for metallothionein-I (MT-I) as a reporter gene, we examined 268 organic compounds for the ability to activate this promoter . We found that PF1070A, an antibiotic produced by Humicola sp., efficiently activated the MT promoter and caused marked enhancement of beta-galactosidase activity in L13-17 cells . The extent of activation by PF1070A was almost equivalent to that by of zinc ions, the most effective known inducer of the synthesis of MT . PF1070A also caused marked elevation of the levels of the mRNA for MT and of MT itself in L13-17 cells . A similar result was obtained in human HeLa-S3 cells . When PF1070A was added to the culture medium simultaneously with cadmium ion or dexamethasone, the level of expression of the reporter gene was markedly elevated, compared to the level of expression induced by each agent independently . The effect of PF1070A was reduced considerably by deletion of nucleotides at positions -150 and -149 from the site of initiation of transcription in the promoter region of the MT gene and also by deletion of the seven bases located at positions -49 to -43 . Since no known cis element was found in these two regions, PF1070A might be a new type of inducer of MT synthesis that promotes expression of the gene for MT via a mechanism completely different from those exploited by other known agents . These results also suggest the presence of a system for control of transcription of the gene for MT that has not previously been recognized . Both cadmium ions and bismuth ions induce the synthesis of MT by acting on the metal response element (MRE) . Bismuth ions had no significant effect on the promoter activity that had already reached a maximum level in response to treatment with the optimal concentration of cadmium ion . By contrast, PF1070A further and markedly increased the promoter activity . This result suggests that it is possible to increase the concentration of MT in tissue using PF1070A as an inducer even in cases where the MRE-mediated activation of the MT promoter has already been induced by the accumulation of cadmium, as is the case in a clinical setting . PF1070A may prove to be an excellent inducer of MT synthesis that is effective and clinically applicable . Moreover, use of PF1070A in combination with salts of heavy metals might be useful in controlling expression of a transfected gene that is regulated by the MT promoter since PF1070A can activate the MT promoter to an extent that cannot be achieved with heavy metal ions alone, when PF1070A is used in combination with zinc ions at a concentration of the latter considerably below the toxic level. Acta Chir Plast, 1999, 41(2), 50 - 3 Suction lipectomy; Duskova M et al.; Suction lipectomy is a very effective and safe method, if performed by an experienced plastic surgeon . The authors demonstrate using a group of 284 patients operated on at the University Clinic of Plastic Surgery in Prague between 1994-1998, indications, the method and complications. J Bacteriol, 1999 Aug, 181(16), 5075 - 80 Characterization of binding sequences for butyrolactone autoregulator receptors in streptomycetes; Kinoshita H et al.; BarA of Streptomyces virginiae is a specific receptor protein for a member of butyrolactone autoregulators which binds to an upstream region of target genes to control transcription, leading to the production of the antibiotic virginiamycin M(1) and S . BarA-binding DNA sequences (BarA-responsive elements {BAREs}), to which BarA binds for transcriptional control, were restricted to 26 to 29-nucleotide (nt) sequences on barA and barB upstream regions by the surface plasmon resonance technique, gel shift assay, and DNase I footprint analysis . Two BAREs (BARE-1 and BARE-2) on the barB upstream region were located 57 to 29 bp (BARE-1) and 268 to 241 bp (BARE-2) upstream from the barB translational start codon . The BARE located on the barA upstream region (BARE-3) was found 101 to 76 bp upstream of the barA start codon . High-resolution S1 nuclease mapping analysis revealed that BARE-1 covered the barB transcription start site and BARE-3 covered an autoregulator-dependent transcription start site of the barA gene . Deletion and mutation analysis of BARE-2 demonstrated that at least a 19-nt sequence was required for sufficient BarA binding, and A or T residues at the edge as well as internal conserved nucleotides were indispensable . The identified binding sequences for autoregulator receptor proteins were found to be highly conserved among Streptomyces species. J Chromatogr B Biomed Sci Appl, 1999 Jun 25, 730(1), 55 - 9 Simple and sensitive high-performance liquid chromatographic method for the determination of an everninomycin, SCH 27899, in rat plasma; Lin CC et al.; A simple and sensitive high-performance liquid chromatographic (HPLC) method was developed for the determination of SCH 27899, an everninomycin antibiotic, in rat plasma . The method involved plasma protein precipitation with acetonitrile, followed by reversed-phase HPLC analysis using a polymeric column and a mobile phase containing acetonitrile and ammonium phosphate, pH 7.8 . The linear relationship between detector response and concentration was demonstrated with a correlation coefficient of larger than 0.996 at concentrations ranging from 0.2 to 100 microg/ml . The results showed that the HPLC method was accurate (bias < or = 6%) and precise (coefficient of variation, C.V . < or = 6%) . The limit of quantitation was 0.2 microg/ml with a C.V . of 2.6% and bias of 5% . SCH 27899 was stable in rat plasma at -20 degrees C for at least 40 days . The HPLC method has been utilized for the determination of SCH 27899 in plasma samples from rats following single intravenous administration (3 mg/kg). Zhonghua Yan Ke Za Zhi, 1997 May, 33(3), 213 - 5 {Pseudohypopyon after vitrectomy for vitreous hemorrhage}; Zhang S et al.; OBJECTIVE: To describe an uninfective hypopyon phenomenon after vitrectomy (pseudohypopyon) . METHODS: 1,250 cases (consecutive cases) who had undergone vitrectomy were collected . Among them, 418 cases were vitreous hemorrhage due to various disorders . Pseudohypopyon was found in 7 cases . All of them were the patients with vitreous hemorrhage . RESULTS: Pseudohypopyon occurred in 3-5 days after vitrectomy, like precipitation of muddy sand; systemic and local treatment of antibiotic and steroid were not effective, intraocular centesis for smear and culture could not find any germs; and the patients were painless and no irritation in the eyes . The relatively effective method for this kind of hypopyon was paracentesis of anterior chamber and its natural absorption . After a follow-up period of 3 months, 3 cases obtained the vision above 0.05 . CONCLUSIONS: Pseudo-hypopyon might happen after vitrectomy for vitreous hemorrhage, and it should be differentiated from infective ophthalmitis. Pediatr Dent, 1999 Jul-Aug, 21(4), 242 - 7 Sequelae and prognosis of intruded primary incisors: a retrospective study; Holan G et al.; PURPOSE: This study was designed to assess the sequelae and prognosis of intruded primary incisors . METHODS: Of 196 children who visited the emergency clinic due to intrusion of 310 maxillary primary incisors, 110 children (172 teeth) were available for follow-up examination (study group) . Eighty-six children (138 teeth) did not show for the follow-up examination (non-respondents group) . Male/female ratio was 1.7:1 . Age range of children at time of injury was 12-72 months (mean 28) . Follow-up time ranged between 0 and 59 months (mean 27) . RESULTS: Fifty-seven percent of all teeth were completely intruded . In 80%, the root was pushed labially . All but two ankylosed teeth re-erupted, and 37% of these re-erupted into an ectopic position . Completely intruded incisors re-erupted into an ectopic position in a higher percentage (45%) than partially intruded teeth (30%) . Fifty-two percent of the teeth presented pulp canal obliteration (PCO) . Sixty-four percent of the completely intruded incisors presented PCO compared to 40% of partially intruded teeth . Arrest of dentin apposition was found in 15% of the teeth, and was not affected by the degree of intrusion . Twenty-three teeth were extracted shortly after the injury due to suspect of contact with the developing permanent successor (19 teeth) and severe caries (4 teeth) . Sixty-eight percent of the intruded teeth survived more than 36 months after the injury . Twenty-three percent were extracted due to periodontal breakdown and 5% due to repeated trauma . Antibiotic therapy did not have any effect on the survival rate . CONCLUSION: The majority of intruded primary incisors may re-erupt and survive with no complications after more than 36 months post trauma even in cases of complete intrusion and fracture of the labial bone plate. Biochemistry, 1999 Aug 3, 38(31), 9840 - 9 Crystal structure of 3-amino-5-hydroxybenzoic acid (AHBA) synthase; Eads JC et al.; The biosynthesis of ansamycin antibiotics, including rifamycin B, involves the synthesis of an aromatic precursor, 3-amino-5-hydroxybenzoic acid (AHBA), which serves as starter for the assembly of the antibiotics' polyketide backbone . The terminal enzyme of AHBA formation, AHBA synthase, is a dimeric, pyridoxal 5'-phosphate (PLP) dependent enzyme with pronounced sequence homology to a number of PLP enzymes involved in the biosynthesis of antibiotic sugar moieties . The structure of AHBA synthase from Amycolatopsis mediterranei has been determined to 2.0 A resolution, with bound cofactor, PLP, and in a complex with PLP and an inhibitor (gabaculine) . The overall fold of AHBA synthase is similar to that of the aspartate aminotransferase family of PLP-dependent enzymes, with a large domain containing a seven-stranded beta-sheet surrounded by alpha-helices and a smaller domain consisting of a four-stranded antiparallel beta-sheet and four alpha-helices . The uninhibited form of the enzyme shows the cofactor covalently linked to Lys188 in an internal aldimine linkage . On binding the inhibitor, gabaculine, the internal aldimine linkage is broken, and a covalent bond is observed between the cofactor and inhibitor . The active site is composed of residues from two subunits of AHBA synthase, indicating that AHBA synthase is active as a dimer. N Engl J Med, 1999 Aug 5, 341(6), 403 - 9 Effect of intravenous albumin on renal impairment and mortality in patients with cirrhosis and spontaneous bacterial peritonitis; Sort P et al.; BACKGROUND: In patients with cirrhosis and spontaneous bacterial peritonitis, renal function frequently becomes impaired . This impairment is probably related to a reduction in effective arterial blood volume and is associated with a high mortality rate . We conducted a study to determine whether plasma volume expansion with intravenous albumin prevents renal impairment and reduces mortality in these patients . METHODS: We randomly assigned 126 patients with cirrhosis and spontaneous bacterial peritonitis to treatment with intravenous cefotaxime (63 patients) or cefotaxime and intravenous albumin (63 patients) . Cefotaxime was given daily in dosages that varied according to the serum creatinine level, and albumin was given at a dose of 1.5 g per kilogram of body weight at the time of diagnosis, followed by 1 g per kilogram on day 3 . Renal impairment was defined as nonreversible deterioration of renal function during hospitalization . RESULTS: The infection resolved in 59 patients in the cefotaxime group (94 percent) and 62 in the cefotaxime-plus-albumin group (98 percent) (P=0.36) . Renal impairment developed in 21 patients in the cefotaxime group (33 percent) and 6 in the cefotaxime-plus-albumin group (10 percent) (P=0.002) . Eighteen patients (29 percent) in the cefotaxime group died in the hospital, as compared with 6 (10 percent) in the cefotaxime-plus-albumin group (P=0.01); at three months, the mortality rates were 41 percent (a total of 26 deaths) and 22 percent (a total of 14 deaths), respectively (P=0.03) . Patients treated with cefotaxime had higher levels of plasma renin activity than those treated with cefotaxime and albumin; patients with renal impairment had the highest values . CONCLUSIONS: In patients with cirrhosis and spontaneous bacterial peritonitis, treatment with intravenous albumin in addition to an antibiotic reduces the incidence of renal impairment and death in comparison with treatment with an antibiotic alone. Cutis, 1999 Jul, 64(1), 23 - 8 Miliary tuberculosis presenting with rigors and developing unusual cutaneous manifestations; Lowry KJ et al.; We report a case of miliary tuberculosis presenting with high fevers and rigors . While undergoing evaluation, the patient developed a diffuse, erythematous, maculopapular eruption coalescing to form erythematous plaques involving the abdomen, trunk, and proximal extremities . Biopsies of the lesions were smear- and culture-negative for Mycobacterium tuberculosis . Rigors are an unusual presenting symptom of miliary tuberculosis and have only been reported three times in the (post-antibiotic era) literature . Chills have been reported to occur 28% of the time . This symptom can be confusing to the practitioner, leading to delay in diagnosis . The skin lesions were most consistent with a lichenoid tuberculid eruption . The patient had a negative purified protein derivative and non-reactive anergy panel, and the lesions involved only the cutis and healed without scarring . The patient had a dramatic response to antituberculous therapy, with resolution of the fever within 2 days and resolution of the rash within 2 weeks. Minerva Stomatol, 1999 Apr, 48(4), 161 - 4 Diffuse acute cellulitis with severe neurological sequelae . A clinical case; Mallagray R et al.; The incidence of head and neck odontogenic infections considerably diminished in the last decades due to appropriate antibiotic therapy . Herein we describe a case of acute diffuse facial cellulitis following tooth extraction in a patient with no apparent risk factor . During the acute process, injury was caused to the hypoglossal, vagal, glossopharyngeal and recurrent nerves of both sides . For this reason the patient currently has a nasogastric line for enteral feedings and a tracheotomy tube, which significantly affects his quality of life.
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