Skin Therapy Lett, 2002 Mar, 7(3), 1 - 4 Topical tazarotene therapy for psoriasis, acne vulgaris, and photoaging; Guenther LC; Psoriasis, acne vulgaris and photoaging are common conditions . Tazarotene is a pro-drug of tazarotenic acid, a receptor-selective retinoid, which has shown efficacy in the treatment of these disorders . In the treatment of acne vulgaris, it has greater comedolytic activity than the currently available topical retinoids . In psoriasis, tazarotene normalizes keratinocyte differentiation, reverses keratinocyte hyperproliferation and has better anti-inflammatory effects than any of the currently available topical retinoids . It is most commonly used as combination therapy with a topical corticosteroid or phototherapy in psoriasis, or with an antibiotic in acne. Chest, 2002 May, 121(5), 1703 - 4 Delayed closure of persistent postpneumonectomy bronchopleural fistula; Mueller DK et al.; A 73-year-old man with a history of postpneumonectomy empyema and a long-term chest tube since 1979 presented with fever, chills, leukocytosis, and purulent fluid from the left tube thoracostomy . CT scan and bronchoscopy demonstrated a right lower lobe pneumonia and a left mainstem dehiscence with direct communication to the left tube thoracostomy . He underwent primary closure of the bronchopleural fistula with latissimus dorsi muscle flap coverage after antibiotic therapy for right lower lobe pneumonia. BMC Health Serv Res . 2002 May 13;2(1):9. Management of obstetric anal sphincter injury: a systematic review & national practice survey; Fernando RJ et al.; BACKGROUND: We aim to establish the evidence base for the recognition and management of obstetric anal sphincter injury (OASI) and to compare this with current practice amongst UK obstetricians and coloproctologists . METHODS: A systematic review of the literature and a postal questionnaire survey of consultant obstetricians, trainee obstetricians and consultant coloproctologists was carried out . RESULTS: We found a wide variation in experience of repairing acute anal sphincter injury . The group with largest experience were consultant obstetricians (46.5% undertaking > or = 5 repairs/year), whilst only 10% of responding colorectal surgeons had similar levels of experience (p < 0.001) . There was extensive misunderstanding in terms of the definition of obstetric anal sphincter injuries . Overall, trainees had a greater knowledge of the correct classification (p < 0.01) . Observational studies suggest that a new 'overlap' repair using PDS sutures with antibiotic cover gives better functional results . However, our literature search found only one randomised controlled trial (RCT) on the technique of repair of OASI, which showed no difference in incidence of anal incontinence at three months . Despite this, there was a wide variation in practice, with 337(50%) consultants, 82 (55%) trainees and 80 (89%) coloproctologists already using the 'overlap' method for repair of a torn EAS (p < 0.001) . Although over 50% of colorectal surgeons would undertake long-term follow-up of their patients, this was the practice of less than 10% of obstetricians (p < 0.001) . Whilst over 70% of coloproctologists would recommend an elective caesarean section in a subsequent pregnancy, only 22% of obstetric consultants and 14% of trainees (p < 0.001) . CONCLUSION: An agreed classification of OASI, development of national guidelines, formalised training, multidisciplinary management and further definitive research is strongly recommended. Arch Intern Med, 2002 May 13, 162(9), 1033 - 6 Autoimmune thrombocytopenic Purpura and Helicobacter pylori infection; Michel M et al.; BACKGROUND: The mechanisms triggering the production of platelet autoantibodies in autoimmune thrombocytopenic purpura (AITP) are poorly understood . Recently, marked improvements in platelet counts have been reported in patients with AITP and concurrent Helicobacter pylori infection after eradication of H pylori by a standard antibiotic regimen . We looked for an association between H pylori infection and AITP in adults . METHODS: Fifty-one adults of white French origin, negative for human immunodeficiency virus (mean +/- SD age, 40 +/- 19.8 years), with AITP and a platelet count of less than 50 x 10(3)/microL at onset were included . Thirty-five consecutive nonthrombocytopenic patients (mean +/- SD age, 43 +/- 22 years) of the same origin and with unknown H pylori status served as control subjects . Antibodies against H pylori were detected by means of an agglutination method in both patients and control subjects . Sex ratio, mean age, hemorrhagic manifestations, response to corticosteroid therapy, and final outcome were compared in H pylori-negative and H pylori-positive patients with AITP . To test for a possible molecular mimicry mechanism, we also used an immunoblot assay to look for specific H pylori antibodies in platelet eluates from 3 H pylori-positive patients with AITP . RESULTS: Seroprevalence of H pylori in patients with AITP (15 {29%}) was not significatively different from that in control subjects (10 {29%}) . The H pylori-positive and H pylori-negative patients with AITP did not differ in main characteristics at AITP onset, response rate to corticosteroids, and final outcome . None of the 3 patients investigated had H pylori antibodies in platelet eluates . CONCLUSION: Although the role of H pylori in a subgroup of patients with AITP cannot be excluded, we found no evidence of an association between H pylori infection and AITP. Spine, 2002 May 15, 27(10), E253 - 7 Nocardia farcinica spinal osteomyelitis; Graat HC et al.; STUDY DESIGN: A case of disseminated Nocardia farcinica infection with spine involvement is reported . OBJECTIVE: To describe the first case of Nocardia farcinica spinal osteomyelitis, and to propose spine instrumentation with debridement and multiple antibiotics for treatment of nocardia spinal osteomyelitis . SUMMARY OF BACKGROUND DATA: Only 11 cases involving Nocardia asteroides spinal osteomyelitis have been reported over the past 40 years . These case reports describe various presentations and treatments of nocardia spinal osteomyelitis . METHODS: A 54-year-old nonambulant, paraparetic man was admitted to the authors' hospital with acutely increased low back pain, fever, and signs of dementia . A disseminated Nocardia farcinica infection including spinal osteomyelitis at T11, T12, L1, L2, and L4; epidural abscess T10-L4, L5-S1 discitis, empyemas, cerebral abscess, and bilateral psoas abscess was noted . RESULTS: Antibiotic therapy, multiple debridements, and posterior instrumentation were performed to palliate the Nocardia farcinica infection . At a recent 3-year follow-up assessment, the patient was independent and ambulant . He had been off antibiotics for 5 months . CONCLUSIONS: Previous case reports of nocardia spinal osteomyelitis describe treatment with antibiotics, debridements, and arthrodesis with autologous bone graft . Prolonged recumbency ensued . In the reported case, a combination of antibiotics, debridements, arthrodesis, and posterior instrumentation for immediate stabilization of the spine resulted in a favorable outcome at 3 years. J Org Chem, 2002 May 17, 67(10), 3272 - 6 First synthesis of caerulomycin B . A new synthesis of caerulomycin C; Mongin F et al.; Caerulomycins produced by Streptomyces caeruleus are bipyridinic molecules endowed with antibiotic properties . The first synthesis of caerulomycin B (1) as well as a new synthesis of caerulomycin C (2) are reported . Starting from 3-hydroxypyridine, the same methodology was used to prepare both compounds 1 and 2 . Efficiently controlled reactions such as metalation to allow the synthesis of 2,6-diiodo-3,4-dialkoxypyridines, which are key intermediates, and further halogen-lithium exchange and cross-coupling to reach the targets molecules 1 and 2 have been developed. J Med Assoc Thai, 2001 Dec, 84 Suppl 3, S669 - 75 Roxithromycin in prevention of acute coronary syndrome associated with Chlamydia pneumoniae infection: a randomized placebo controlled trial; Leowattana W et al.; The role of Chlamydia pneumoniae infection in precipitating acute coronary syndrome (ACS) is unclear . Some studies have indicated that intervention with macrolide antibiotics might reduce coronary events in patients with ACS . A double blind, randomized, placebo-control trial was conducted on 84 ACS patients . Patients were randomized to 30 days of treatment with roxithromycin (150 mg, twice daily) or matching placebo . The follow-up period was 90 days, and the primary clinical end point included cardiovascular death, unplanned revascularization and recurrent angina/MI . Anti-C . pneumoniae IgG positive in 24 of 43 (55.8%) patients in the roxithromycin group and 23 of 41 (56.1%) patients in the placebo group . Anti-C . pneumoniae IgA positive in 20 of 43 (46.5%) patients in the roxithromycin group and 13 of 41 (31.7%) patients in the placebo group . Thirty-three cardiac events occurred (2 cardiovascular deaths, 9 CABG, 12 PTCA and 10 recurrent angina/MI) with 17 events in the roxithromycin group and 16 events in the placebo group . There was no significant difference of cardiac events between the roxithromycin and placebo groups . The present study suggests that antibiotic therapy with roxithromycin is not associated with reduction of cardiac events as reported by other investigators . However, therapeutic interventions may need to be specifically targeted to a group of patients who are confirmed with chronic C . pneumoniae infection. Can Vet J, 1999 Aug, 40(8), 583 - 7 The effect of administering long-acting oxytetracycline and tilmicosin either by dart gun or by hand on injection site lesions and drug residues in beef cattle; Van Donkersgoed J et al.; Forty yearling cattle were injected intramuscularly with long-acting oxytetracycline and subcutaneously with tilmicosin by dart gun or by hand in a chute 28 days prior to slaughter . The drugs caused injection site lesions and antibiotic residues in the neck and thigh that varied by technique, dose, and site. Pediatr Pulmonol, 2002 Jun, 33(6), 492 - 6 Bronchiectasis in children: orphan disease or persistent problem? Callahan CW, Redding GJ. More than a decade ago, bronchiectasis unrelated to cystic fibrosis was termed an "orphan disease", because it had become an uncommon clinical entity among children in the developed world . Bronchiectasis is more common among children in lower socioeconomic classes and in developing countries, presumably due to more frequent and recurrent respiratory infections, environmental airway irritants, poor immunization rates, and malnutrition . Reports from the Southern Pacific and from Alaska Native children reveal persistently high rates of childhood bronchiectasis . Better epidemiologic data throughout the world are needed to reassess the importance of this condition . The pathophysiology includes airway inflammation, mucus production, and regional airway obstruction, yet the reasons why some children develop bronchiectasis while other do not is unclear . The coexistence of asthma with bronchiectasis is associated with more severe disease, yet the impact of asthma therapy in children with both disorders has not been studied . Similarly, the pattern of antibiotic use for children with bronchiectasis varies by region with little data to justify one particular approach . It may be that public health measures aimed at improving living conditions for children and prevention of respiratory infections with antiviral vaccines will have more impact on childhood bronchiectasis than medical treatments in the future . Indian Heart J, 2002 Jan-Feb, 54(1), 54 - 8 A community-based rheumatic fever/rheumatic heart disease cohort: twelve-year experience; Kumar R et al.; BACKGROUND: A pilot rheumatic fever and rheumatic heart disease control porject was started in 1988 in blocks of district Ambala (Haryana) to test the feasibility of early detection, treatment and secondary prophylaxis for rheumatic fever/rheumatic heart disease cases . School teachers, students and health workers were trained to identify and refer suspected cases of rheumatic fever/rheumatic heart disease to the community health center where physicians examined the suspected cases and monthly secondary prophylaxis was provided to the confirmed cases . METHODS AND RESULTS: A survey of registered cases was done in 1999 to determine the compliance rate of secondary prophylaxis and to describe clinical and epidemiologic features of the registered cohort of rheumatic fever/rheumatic heart disease patients . A total of 257 patients had been registered till the end of 1999 with 1263 person-years of follow-up . Out of these registered patients, 132 were receiving secondary prophylaxis, 52 had died, 17 had migrated, 8 were lost to follow-up, 18 had stopped prophylaxis and 30 completed the prophylaxis course . The mean age at registration was 18 years . Half of the cases were in the 6-15 years age group at registration . Over half of the patients were registered with a history of rheumatic fever . Fever was the most common symptom (75.9%) . Carditis was more common among cases with recurrent attacks of rheumatic fever than after a first attack . The mortality in rheumatic fever/rheumatic heart cases was 32.5/1000 person-years . The mean age at death was 24.4 years . Compliance with secondary prophylaxis was 92% during the past 12 years . CONCLUSIONS: A rheumatic fever/rheumatic heart disease control program can be sustained within the primary health care system and the case registry can be utilized not only for monitoring the program but also to gain insight into the epidemiology of the disease. Anesteziol Reanimatol, 2002 Jan-Feb, (1), 58 - 61 {Ways to reduce mortality of newborns with developmental defects}; Stepanenko SM et al.; Technological progress contributed to progress in surgery on the newborns . However, despite the progress in surgery and intensive care of the newborns, the results of treatment of patients with congenital defects are sometimes disappointing . The priority problems for today are the respiratory distress syndrome, hemodynamic disorders, and renal dysfunction, which can be united into the syndrome of general dysadaptation of the newborns . Based on experience gained in the treatment of newborns in pediatric surgical hospital, protocols of treating newborns with developmental defects (congenital diaphragmatic hernia, esophageal atresia, and gastroschisis) have been developed . These protocols are a stage and a prerequisite for development of more effective methods for treating such patients . Common intensive care should be supplemented by such important measures as maintenance of adequate temperature regimen at all stages of medical transportation and therapy of a newborn, obligatory preoperative preparation for stabilization of vital functions, multicomponent endotracheal anesthesia, use of inotropic agents (dopamine and dobutrex), synchronic prolonged artificial ventilation of the lungs and prolonged analgesia, limitation of indications to the use of blood preparations and wide use of hydroxyethylated starch solutions in infusion therapy, rational antibiotic therapy with constant monitoring of the microecological status, and early detection and correction of concomitant diseases . Solution of these problems will essentially decrease the postoperative mortality of newborns with developmental defects. Int J Pediatr Otorhinolaryngol, 2002 May 15, 63(3), 185 - 8 Mastoid subperiosteal abscess management in children; Bauer PW et al.; The management of a mastoid subperiosteal abscess has traditionally required mastoidectomy . With the improvement of antibiotic therapy current literature supports the treatment of uncomplicated acute mastoiditis with myringotomy and intravenous antibiotics . Treatment of a mastoid subperiosteal abscess with tympanostomy tube insertion, intravenous antibiotics, and postauricular incision and drainage of the abscess avoids the morbidity and potential complications of mastoid surgery in young children . Three patients diagnosed with a mastoid subperiosteal abscess were managed in this way . The outcome of their treatment has been documented with lengthy otologic follow-up . Complete resolution of the acute infectious process was achieved in all cases with no evidence of recurrent disease. Biochim Biophys Acta, 2002 Apr 12, 1561(2), 188 - 201 Improved retention of idarubicin after intravenous injection obtained for cholesterol-free liposomes; Dos Santos N et al.; To date there has been a focus on the application of sterically stabilized liposomes, composed of saturated diacylphospholipid, polyethylene glycol (PEG) conjugated lipids (5-10 mole%) and cholesterol (CH) (>30 mole%), for the systemic delivery of drugs . However, we are now exploring the utility of liposome formulations composed of diacylphospholipid conjugated PEG mixtures prepared in the absence of added cholesterol, with the primary objective of developing formulations that retain encapsulated drug better than comparable formulations prepared with cholesterol . In this report the stability of cholesterol-free distearoylphosphatidylcholine (DSPC):distearoylphosphatidylethanolamine (DSPE)-PEG(2000) (95:5 mol/mol) liposomes was characterized in comparison to cholesterol-containing formulations DSPC:CH (55:45 mol/mol) and DSPC:CH:DSPE-PEG(2000) (50:45:5 mol/mol/mol), in vivo . Circulation longevity of these formulations was determined in consideration of variables that included varying phospholipid acyl chain length, PEG content and molecular weight . The application of cholesterol-free liposomes as carriers for the hydrophobic anthracycline antibiotic, idarubicin (IDA), was assessed . IDA was encapsulated using a transmembrane pH gradient driven process . To determine stability in vivo, pharmacokinetic studies were performed using 'empty' and drug-loaded {(3)H}cholesteryl hexadecyl ether radiolabeled liposomes administered intravenously to Balb/c mice . Inclusion of 5 mole% of DSPE-PEG(2000) or 45 mole% cholesterol to DSPC liposomes increased the mean plasma area under the curve (AUC(0-24h)) 19-fold and 10-fold, respectively . Cryo-transmission electron micrographs of IDA loaded liposomes indicated that the drug formed a precipitate within liposomes . The mean AUC(0-4h) for free IDA was 0.030 micromole h/ml as compared to 1.38 micromole h/ml determined for the DSPC:DSPE-PEG(2000) formulation, a 45-fold increase, demonstrating that IDA was retained better in cholesterol-free compared to cholesterol-containing liposomes. Burns, 2002 May, 28(3), 264 - 6 The rate of re-epithelialization across meshed skin grafts is increased with exposure to silver; Demling RH et al.; The objective in this study was to determine whether exposure to pure silver increases the rate of re-epithelialization across a partial thickness wound . A meshed skin graft, placed on an excised burn wound was used as a healing model . Methods: The rate of meshed skin graft epithelial closure on an exposed burn using a moist healing environment was shown . A moistened silver delivery system (Acticoat) was compared with a standard xeroform and eight ply gauze dressing continually moistened with a 0.01% neomycin and polymyxin solution (NP) . Twenty burn patients with deep burns of over 15% of TBS were excised and grafted with 2:1 meshed grafts . One graft area was treated with the antibiotic solution and another with the silver delivery . The meshed graft was performed within 3 days of injury . Results: No infections were noted and quantitative swab cultures gave less than 10(2) bacteria in all cases at wound closure . At day 7, re-epithelialization was complete with silver and 55% closed with NP solution . Wound closure was complete in the NP solution group at day 10 . Silver increased re-epithelialization rate by over 40%, a significant increase . Graft take was over 95% in both groups . Conclusion: Silver released in a moist wound surface environment significantly increases the rate of re-epithelialization compared to a standard antibiotic solution. J Assoc Physicians India, 2001 Dec, 49, 1200 - 2 A fatal case of systemic brucellosis; Gupta S et al.; A 65 years man presented with fever, drenching sweats, progressive dyspnoea, backache and weight loss . On examination, he had wide pulse pressure, clubbing, retinal hemorrhages, aortic and mitral regurgitation, hepatosplenomegaly, lower spinal tenderness and bilateral basal crepitations . Transthoracic 2D-echocardiography showed a large vegetation on the aortic valve . Antibody titers for brucella were positive . X-ray spine was suggestive of brucella spondylitis . Early surgical intervention was planned and the patient was given combination antibiotic therapy . The course was complicated by renal failure and the patient succumbed while being taken up for surgery. Clin Oral Investig, 2002 Mar, 6(1), 28 - 38 Statistical modeling of tooth mobility after treating adult periodontitis; Groselj D et al.; The healing process following periodontal surgery for advanced adult periodontitis is described . Of the various indicators, tooth mobility (TM) is considered, and its relation to surgical treatment and the time lapse from the flap surgery is quantitatively modeled by non-parametric regression . Mobility is measured by an electronic apparatus, which also automatically performs the modeling . A new statistical method for TM prediction is demonstrated, and its quality is estimated . We show that the quality at the first step of prediction is approximately 0.7 . This indicates that the prediction method is able to model the effect of surgery on the healing process, although the random scattering of TM data recorded in the examined group is relatively large . The influence of periodontal surgery on TM, alone and in combination with systemic metronidazole, is quantitatively characterized in two groups of 12 patients each . In the test group, which received metronidazole, TM decreased significantly 1 week postoperatively, compared to the control group without the antibiotic . The gingival fluid flow rate (GFFR) and the percentage of spirochete morphotypes detected by darkfield microscopy exhibited a similar dependence . Significant differences in TM, GFFR and the percentage of spirochetes between the two groups were observed over a period of several weeks . Probing depths (PD) in both groups at 2 and 12 months after surgery did not reveal any category with pockets deeper than 4 mm . A gain of clinical attachment level of more than 2 mm (CAL) was observed at measurements of 16.7% and 10.6% on the test and control groups, respectively, 1 year after surgery. Hepatogastroenterology, 2002 Mar-Apr, 49(44), 497 - 500 The biochemical and histopathological effects of ursodeoxycholic acid and metronidazole on total parenteral nutrition-associated hepatic dysfunction: an experimental study; Gunsar C et al.; BACKGROUND/AIMS: Total parenteral nutrition causes many complications such as cholestasis . Ursodeoxycholic acid is used for the treatment of several cholestatic problems . Metronidazole was investigated before for preventing some components of total parenteral nutrition-associated hepatic dysfunction . This study was designed to investigate the effects of ursodeoxycholic acid alone and ursodeoxycholic acid + metronidazole combination on total parenteral nutrition-associated cholestasis . METHODOLOGY: Eighteen rabbits were divided into three groups as follows: group A received a standard formula of total parenteral nutrition only, group B received total parenteral nutrition + ursodeoxycholic acid (3 mg/kg/day), and group C were given total parenteral nutrition + ursodeoxycholic acid + metronidazole (25 mg/kg/day) for eight days, respectively . Several parameters of liver function tests were compared among these groups . These were transaminases, alkaline phosphatase, total bilirubin, total cholesterol, triglycerides, and serum bile acids . Liver histology was detected in each group at the end of the experiment . RESULTS: In group A, total parenteral nutrition administration resulted in remarkably higher serum values of transaminases, alkaline phosphatase, total cholesterol, total bilirubin, triglycerides, and free bile acids whereas ursodeoxycholic acid administration showed important improvements in the serum values of these parameters in group B animals . The metronidazole group showed nearer or similar laboratory values with group B, but significant differences appeared in bilirubin values (P < 0.05) among these groups . Liver histology presented marked differences between group A and group B . Steatosis formed the main component of liver histology in 4 animals out of 6 in group A . Contrary to this, all of the specimens showed normal liver structure except one in group B . In the third group we did not see better morphology than in group B . CONCLUSIONS: These results suggested that oral ursodeoxycholic acid therapy during total parenteral nutrition reduces bilirubin levels and improves the other indicators of cholestasis and helps prevent disturbances of liver histology . When it is combined with metronidazole a significant decrease in bilirubin levels has been gained . With the help of ursodeoxycholic acid we can provide enterohepatic circulation of bile acids and regulate lipid metabolism . Metronidazole can be an antibiotic of choice during total parenteral nutrition when needed. Acta Vet Scand Suppl, 2001, 95, 69 - 75 Recycling biowaste--human and animal health problems; Albihn A; Biowaste from the food chain is of potential benefit to use in agriculture . Agriculture in general and organic farming in particular needs alternative plant nutrients . However, the quality concerning hygiene and soil contaminants must be assured . This recycling has to be regulated in a way that harmful effects on soil, vegetation, animals and man are prevented . The problems with heavy metals and organic contaminants have been focused on . Still, maximum threshold values are continuously discussed to avoid an increase of soil concentrations . The effect on the ecosystems of residues from use of medicines needs further attention . There is also a risk for a spread of antibiotic resistant micro-organisms in the environment and then to animals and man . Infectious diseases may be spread from biowaste and new routes of disease transmission between animals and humans can be created . Zoonotic diseases in this context play a central role . Pathogens recently introduced to a country may be further spread when biowaste is recycled . The very good health status of domestic animals in the Nordic countries may then quickly change . The quality of biowaste is of enormous importance if biowaste is to gain general acceptance for agricultural use, especially for organic production . A balance needs to be maintained between risk and advantage for its use. J Biol Chem, 2002 Jul 12, 277(28), 25457 - 64 Epub 2002 May 06. Filipin prevents pathological prion protein accumulation by reducing endocytosis and inducing cellular PrP release; Marella M et al.; Conversion of the normal membrane-bound prion protein (PrP-sen) to its pathological isoform (PrP-res) is a key event in the pathogenesis of transmissible spongiform encephalopathies . Although the subcellular sites of conversion are poorly characterized, several lines of evidence have suggested the involvement of membrane lipid rafts in the conversion process . Here we report that copper stimulates the endocytosis of PrP-sen via a caveolin-dependent pathway in both microglia and neuroblastoma cells . We show that the polyene antibiotic filipin both limits endocytosis of PrP-sen and dramatically reduces the amount of membrane-bound PrP-sen . This reduction results from a rapid and massive release of full matured PrP-sen into the culture medium . Finally, we demonstrate that filipin is a potent inhibitor of PrP-res formation into chronically infected neuroblastoma cells . Our results reinforce the role of rafts in PrP trafficking and raise the possibility that the release of PrP-sen from the plasma membrane decreases the amount of available substrate PrP-sen at the conversion sites. Hinyokika Kiyo, 2002 Mar, 48(3), 163 - 5 {A case of extensive Fournier's gangrene}; Oida T et al.; A 52-year-old man was admitted to our hospital complaining of high grade fever and painful swelling of the scrotum . Although debridement of the scrotum and inguinal region was immediately carried out, the inflammation extended to the right abdominal region 2 days later . We tunneled the newly infected areas and placed Penrose drains through the tunnels, so that complete drainage was achieved with minimal tissue loss . The infection was controlled by frequent irrigation of the wound and antibiotic administration . Forty days after the admission the defect of the skin was reconstructed by using a meshed skin graft, and the patient was discharged on the 68th hospital day . We concluded that limited debridement with placement of through-and-through drains might have produced a good result with minimal tissue loss. Prog Transplant, 2002 Mar, 12(1), 17 - 21; quiz 22-3 Drug-induced gingival hyperplasia in transplant recipients; Hood KA; Gingival hyperplasia is a common occurrence in transplant recipients who are taking cyclosporine . This condition can be complicated when calcium channel blockers or phenytoin are added to the armamentarium of medications; it can be painful and may interfere with eating, speech, and appearance . Multiple mechanisms exist for gingival overgrowth . Prevention with appropriate oral hygiene appears important in controlling the inflammatory component and decreasing the severity of the overgrowth . Patients must be aware of the potential for the development of gingival hyperplasia and must follow up with regular professional cleanings . If the overgrowth persists, treatment options should be discussed between patients and their physician . Conversion from cyclosporine to tacrolimus, treatment with antibiotic therapy, and surgical excision or laser therapy are all potential therapies to consider. Semin Thromb Hemost, 2002 Apr, 28(2), 149 - 60 Comparative study on collagen-binding enzyme-linked immunosorbent assay and ristocetin cofactor activity assays for detection of functional activity of von Willebrand factor; Turecek PL et al.; For more than two decades, the ristocetin cofactor (RCo) assay, which measures the von Willebrand factor (vWF)-mediated agglutination of platelets in the presence of the antibiotic ristocetin, has been the most common method for measuring the functional activity of vWF . There is, however, general agreement among clinical analysts that this method has major practical disadvantages in performance and reproducibility . Today, collagen-binding assays (CBA) based on the enzyme-linked immunosorbent assay (ELISA) technique that measure the interaction of vWF and collagen are an alternative analytic procedure based on a more physiological function than that of the RCo procedure . We used both assay systems in a comparative study to assess the functional activity of vWF in plasma as well as in therapeutic preparations . We measured RCo activities of plasma from healthy donors and patients with different types of von Willebrand disease (vWD) and of vWF as a drug substance in factor (F) VIII/vWF concentrates using both the aggregometric and the macroscopic methods . In addition, we measured collagen-binding activity (vWF:CB) using a recently developed commercially available CBA system . To investigate the relation between the structure and the functional activity of vWF, we isolated vWF species with different numbers of multimers from FVIII/vWF concentrates by affinity chromatography on immobilized heparin . The vWF:RCo and vWF:CB of the different fractions were measured, and the multimeric structure of vWF was analyzed by sodium dodecyl sulfate (SDS) agarose gel electrophoresis . (vWF:CB and vWF:RCo are part of the nomenclature proposed by the International Society on Thrombosis and Hemostasis Scientific and Standardization Committee {ISTH SSC} subcommittee on von Willebrand factor, in Maastricht, Germany, June 16, 2000.) Measurement of functional vWF activity by CBA can be carried out with substantially higher interassay reproducibility than can measurement of RCo . Both assay systems can be used for diagnosis and subtyping of vWD, but CBA is more sensitive than either of the two RCo methods . The analysis of vWF multimers in the different fractions obtained by affinity chromatography on heparin Sepharose showed that the activity measured both with RCo assay and CBA correlated with the degree of multimerization . Our results suggest that measurement of the functional activity of vWF by the RCo procedure can be replaced by the more reliable CBA, reflecting the physiological hemostatic activity of vWF . The CBA method appears not only to be more sensitive and easier to carry out than the RCo method is but also to have a higher reproducibility and allow better standardization. J Cutan Med Surg, 2002 Mar-Apr, 6(2), 103 - 8 Epub 2002 Feb 13. Chronic pruritus associated with Helicobacter pylori; Kandyil R et al.; BACKGROUND: Helicobacter pylori is an established cause of gastritis and has been implicated in extradigestive diseases . OBJECTIVE: To investigate the role of H . pylori in patients with unexplained refractory pruritus . METHODS: Ten patients with severe pruritus unresponsive to conventional therapy were evaluated for active H . pylori infection by H . pylori serology followed by either esophagogastroduodenoscopy (EGD) or urea breath test . Of the 10 patients, 8 were found to have active infection . All 10 received anti-H . pylori antibiotic therapy and were reevaluated for relief of pruritus . RESULTS: Of 8 patients with active H . pylori infection, 87.5% (7/8) had some type of pruritus relief after triple therapy . Of these, 62.5% (5/8) had complete relief and 25% (2/8) had temporary relief of pruritus . The remaining 12.5% (1/8) did not respond . Two control patients without active H . pylori infection had no relief of pruritus with therapy . CONCLUSIONS: We have identified a population of patients with refractory pruritus and active H . pylori infection whose pruritus resolved after eradication of H . pylori. Mol Ther, 2002 May, 5(5 Pt 1), 589 - 98 Topological constraints governing the use of the chicken HS4 chromatin insulator in oncoretrovirus vectors; Yannaki E et al.; The expression of integrated oncoretrovirus vectors is subject to the inhibitory effects of surrounding chromatin . A previous report from our laboratory indicated that such position effects can be overcome by flanking a reporter vector with the cHS4 chromatin insulator . To characterize this activity more thoroughly, we switched the promoter-gene combinations in the reporter vector and analyzed expression of these vectors flanked with the cHS4 fragment in both orientations following bone marrow transduction and transplantation in mice . The results indicate that the cHS4 fragment can function in both orientations and can insulate both the virus long-terminal-repeat (LTR) promoter and an internal phosphoglycerate kinase (Pgk) promoter . However, insulation of the LTR promoter diminished when the orientation of the cHS4 fragment placed the CTCF-binding core element immediately proximal to the U3 region, suggesting a minimal distance requirement . Moreover, placement of the cHS4 fragment in the U3 region of the 3' LTR dramatically decreased the level of expression from an internal Pgk promoter, presumably by blocking interaction with the 3' LTR enhancer . Finally, sorting studies suggest that the severity of position effects or autonomous promoter silencing increases as transduced progenitors differentiate into mature progeny . These findings have direct implications for the use of chromatin insulators such as cHS4 in oncoretrovirus vectors. RNA, 2002 Apr, 8(4), 401 - 11 Osmolytes stimulate the reconstitution of functional 50S ribosomes from in vitro transcripts of Escherichia coli 23S rRNA; Semrad K et al.; Functional Escherichia coli 50S ribosomal subunits can be reconstituted from their natural rRNA and protein components . However, when the assembly is performed with in vitro-transcribed 23S rRNA, the reconstitution efficiency is diminished by four orders of magnitude . We tested a variety of chemical chaperones (compounds that are typically used for protein folding), putative RNA chaperones (proteins) and ribosome-targeted antibiotics (small-molecule ligands) that might be reasoned to aid in folding and assembly . Addition of the osmolyte trimethylamine-oxide (TMAO) and the ketolide antibiotic telithromycin (HMR3647) to the reconstitution stimulates its efficiency up to 100-fold yielding a substantially improved system for the in vitro analysis of mutant ribosomes. Br J Anaesth, 2002 Mar, 88(3), 434 - 8 Management of life-threatening autonomic hyper-reflexia using magnesium sulphate in a patient with a high spinal cord injury in the intensive care unit; Jones NA et al.; We report the successful use of i.v . magnesium sulphate to control life-threatening autonomic hyper-reflexia associated with chronic spinal cord injury in the intensive care environment . A 37-yr-old, male was admitted to the intensive care unit with a diagnosis of septic shock and acute renal failure secondary to pyelonephritis . He had been found unresponsive at home following a 2-day history of pyrexia and purulent discharge from his suprapubic catheter . He had sustained a T5 spinal cord transection 20 yr previously . Initial management included assisted ventilation, fluid resuscitation, vasopressor support, and continuous veno-venous haemofiltration . The sepsis was treated with antibiotic therapy and percutaneous nephrostomy drainage of the pyonephrosis . On the fifth day, the patient developed profuse diarrhoea . This was associated with paroxysms of systemic hypertension and diaphoresis, his arterial pressure rising on occasion to 240/140 mm Hg . A diagnosis of autonomic hyper-reflexia was made and a bolus dose of magnesium sulphate 5 g was administered over 15 min followed by an infusion of 1-2 g h(-1) . There was an almost immediate decrease in the severity and frequency of the hypertensive episodes . There were no adverse cardiac effects associated with the administration of magnesium, only a slight decrease in minute ventilation as the plasma level approached the upper end of the therapeutic range (2-4 mmol litre(-1)) . In view of the beneficial effects observed in this case we advocate further research into the use of magnesium sulphate in the treatment or prevention of autonomic hyper-reflexia secondary to chronic spinal cord injury in the intensive care unit. J Comput Aided Mol Des, 2001 Nov, 15(11), 1035 - 52 One site fits both: a model for the ternary complex of folate + NADPH in R67 dihydrofolate reductase, a D2 symmetric enzyme; Howell EE et al.; R67 dihydrofolate reductase (DHFR) is a novel enzyme that confers resistance to the antibiotic trimethoprim . The crystal structure of R67 DHFR displays a toroidal structure with a central active-site pore . This homotetrameric protein exhibits 222 symmetry, with only a few residues from each chain contributing to the active site, so related sites must be used to bind both substrate (dihydrofolate) and cofactor (NADPH) in the productive R67 DHFR.NADPH.dihydrofolate complex . Whereas the site of folate binding has been partially resolved crystallographically, an interesting question remains: how can the highly symmetrical active site also bind and orient NADPH for catalysis? To model this ternary complex, we employed DOCK and SLIDE, two methods for docking flexible ligands into proteins using quite different algorithms . The bound pteridine ring of folate (Fol I) from the crystal structure of R67 DHFR was used as the basis for docking the nicotinamide-ribose-Pi (NMN) moiety of NADPH . NMN was positioned by both DOCK and SLIDE on the opposite side of the pore from Fol I, where it interacts with Fol I at the pore's center . Numerous residues serve dual roles in binding . For example, Gln 67 from both the B and D subunits has several contacts with the pteridine ring, while the same residue from the A and C subunits has several contacts with the nicotinamide ring . The residues involved in dual roles are generally amphipathic, allowing them to make both hydrophobic and hydrophilic contacts with the ligands . The result is a 'hot spot' binding surface allowing the same residues to co-optimize the binding of two ligands, and orient them for catalysis. N Y State Dent J, 2002 Mar, 68(3), 25 - 9 Geriatric dentistry . A review for the general dentist; Su J et al.; In the 20th century, the oral health of Americans, along with their life expectancy, improved dramatically . The 21st century offers dental professionals the opportunity to help patients maintain their oral health for a lifetime. Biochim Biophys Acta, 2002 Mar 19, 1561(1), 109 - 18 Differential destabilization of membranes by tryptophan and phenylalanine during freezing: the roles of lipid composition and membrane fusion; Popova AV et al.; The stability of cellular membranes during dehydration can be strongly influenced by the partitioning of amphiphilic solutes from the aqueous phase into the membranes . The effects of partitioning on membrane stability depend in a complex manner on the structural properties of the amphiphiles and on membrane lipid composition . Here, we have investigated the effects of the amphiphilic aromatic amino acids Trp and Phe on membrane stability during freezing . Both amino acids were cryotoxic to isolated chloroplast thylakoid membranes and to large unilamellar liposomes, but Trp had a much stronger effect than Phe . In liposomes, both amino acids induced solute leakage and membrane fusion during freezing . The presence of the chloroplast galactolipids monogalactosyldiacylglycerol or digalactosyldiacylglycerol in egg phosphatidylcholine (EPC) membranes reduced leakage from liposomes during freezing in the presence of up to 5 mM Trp, as compared to membranes composed of pure EPC . The presence of the nonbilayer-forming lipid phosphatidylethanolamine increased leakage . Membrane fusion followed a similar trend, but was dramatically reduced when the anthracycline antibiotic daunomycin was incorporated into the membranes . Daunomycin has been shown to stabilize the bilayer phase of membranes in the presence of nonbilayer lipids and was therefore expected to reduce fusion . Surprisingly, this had only a small influence on leakage . Collectively, these data indicate that Trp and Phe induce solute leakage from liposomes during freezing by a mechanism that is largely independent of fusion events. J Pediatr Surg, 2002 May, 37(5), 770 - 2 Neutropenic enterocolitis (typhlitis) after pediatric bone marrow transplant; Otaibi AA et al.; BACKGROUND/PURPOSE: Neutropenic enterocolitis (typhlitis) is a common consideration after bone marrow transplantation . This study reviews the authors' experience with abdominal pain and typhlitis in an active pediatric bone marrow transplant program . METHODS: The Pediatric Bone Marrow Transplant Program Database was reviewed for patients presenting with abdominal pain or typhlitis . RESULTS: From 1993 to 2000 a total of 142 transplants have been performed . Of these, 97 patients had abdominal pain, and 5 had radiologically proven typhlitis . Nonspecific abdominal pain developed on the 12 +/- 11th day posttransplant, whereas patients in whom typhlitis developed were diagnosed on day 15.5 +/- 7 . All patients were treated with prophylactic antibiotics consisting of acyclovir, fluconazole, and septra . With the onset of abdominal pain, 73 of 97 patients were placed on therapeutic antibiotics; patients identified with typhlitis had amphotericin plus GCSF added . No clinical features differentiated abdominal pain patients from typhlitis . Oral feeding and time of discharge was similar in both groups . Surgical intervention was not required, and no patients died with typhlitis . CONCLUSIONS: Abdominal pain is a common symptom after bone marrow transplant; however, typhlitis is relatively rare, and surgical intervention was not required in this series . Broad-spectrum (including fungal) antibiotic therapy appears to be an effective treatment for typhlitis in this patient population . Klin Monatsbl Augenheilkd, 2002 Mar, 219(3), 143 - 8 {Standard designs of epidemiological studies and their characteristics in ophthalmology}; Krummenauer F et al.; This text gives an overview on standard epidemiological study designs and their main advantages and limitations concerning clinical and economical aspects, of performance . Ophthalmological examples are used to illustrate the design characteristics of cross-sectional, cohort and case control studies . These designs are compared by the fictitious planning of an epidemiological study to assess the prophylactical relevance of intraocular antibiotics against post-cataract endophthalmitis; general practical hints for the designing of epidemiological studies are given. J Ind Microbiol Biotechnol, 2002 Apr, 28(4), 219 - 24 Inactivation of a transcriptional repressor during empirical improvement of the tylosin producer, Streptomyces fradiae; Stratigopoulos G et al.; Remarkably few changes of significance seem to have occurred within the tylosin-biosynthetic gene cluster of Streptomyces fradiae during an extensive portion of the empirical strain improvement programme carried out at Lilly Research Laboratories over many years . None of the promoters for polyketide synthase (PKS) genes or for regulatory elements changed within this part of the lineage, nor were any mutations detected in other tyl promoters, although the full set was probably not analysed . Of five regulatory genes within the tyl cluster, only tylQ was altered, having undergone a single point mutation that inactivated its product (a transcriptional repressor) . Also unchanged was a gene with unassigned function . Since point mutations affecting antibiotic-biosynthetic enzymes are unlikely to have played a major role in empirical strain improvement, enhanced tylosin production levels appear to have resulted, in large measure, from uncharacterized mutations occurring outside the tyl cluster. Gastroenterol Hepatol, 2002 May, 25(5), 310 - 2 {Constipation and digestive bleeding as an atypical presentation of Whipple's disease}; Saracibar Serrador E et al.; Whipple's disease is a rare systemic disease of infectious etiology . Its clinical presentation is highly variable . The most common symptoms are diarrhea, weight loss, abdominal pain and joint manifestations . Non-digestive manifestations frequently precede digestive symptoms by several years . For all these reasons, diagnosis is difficult . Definitive diagnosis is established by the finding of PAS-positive macrophages in the lamina propria of the thin intestine . It is important to start appropriate antibiotic therapy early, as this improves the prognosis . We present the case of a male patient in whom the first manifestations of the disease were constipation and upper gastrointestinal hemorrhage, two forms of clinical presentation that have rarely been described in the literature on Whipple's disease. Clin Lab Haematol, 2002 Apr, 24(2), 99 - 106 Nonchemotherapy drug-induced agranulocytosis: experience of the Strasbourg teaching hospital (1985-2000) and review of the literature; Andres E et al.; Agranulocytosis is a life-threatening disorder that frequently occurs as an adverse reaction to drugs . The overall incidence of nonchemotherapy drug-induced agranulocytosis (DIA) ranges from 2.6 to 10 cases per million patients exposed to drugs per year . Although patients experiencing DIA may initially be asymptomatic, the severity of the neutropenia usually leads to severe sepsis, requiring intravenous broad-spectrum antibiotic therapy . In this setting, old age, septicaemia, shock, and the metabolic complications of infection, such as renal failure, are poor prognostic variables . The severity of neutropenia (< 0.1 x 10(9))/l) and its duration (> 10 days) may also impact negatively on the outcome . With appropriate management using pre-established procedures, the mortality rate is now around 5% . Haematopoietic growth factors have been shown to shorten the duration of neutropenia in DIA . However, it has yet to be determined whether their use translates into a better outcome in DIA patients experiencing sepsis . DIA still remains a rare event . However, given the increased life expectancy and subsequent longer exposure to drugs, as well as the development of new agents, physicians should be aware of this complication and its management. Przegl Epidemiol, 2001, 55 Suppl 3, 14 - 22 {Infective endocarditis in adults}; Rozwodowska M et al.; OBJECTIVE: The aim of the research was to demonstrate that the early diagnosis of infective endocarditis influences significantly the results of treatment . METHODS: The following clinical analysis covered 56 patients, aged 18 to 81 (the average age--50 years) with infective endocarditis treated in the years 1998-2000 . Data from patient history, physical examination, laboratory investigations and treatment were analysed . Apart from clinical symptoms for infective endocarditis diagnosis, also blood cultures and echocardiography were important . MAIN OBSERVATIONS: Infective endocarditis was present in 24 patients (42.8%) with heart defects, 7 (12.5%) with prosthetic heart valves, and 4 (7.1%) treated with haemodialysis . RESULTS: In 38 (67.8%) individuals, the echocardiography showed vegetations, and in 14 (25.0%) other abnormalities . Blood cultures were positive in 33 (58.9%) patients . Fever was present in 47 (83.9%) patients . The progression of heart failure appeared in 26 (46.4%) individuals . The average time of antibiotic therapy was 34 days . 11 (19.6%) patients died . 9 (16.1%) individuals had cardiosurgery operations . CONCLUSIONS: Early diagnosis of infective endocarditis is substantial as it improves patients' prognosis as to health and life. J Infus Nurs, 2002 Mar-Apr, 25(2), 109 - 20 Comparing the effect of a skills checklist on teaching time required to achieve independence in administration of infusion medication; Grimes-Holsinger V; This study evaluated the efficacy of a skills checklist, which included a standardized instruction sheet based in part on Rutledge and Donaldson's recommendations for reducing the amount of time required to make a patient independent in the administration of an antibiotic . The use of a skills checklist was found to reduce the time it takes for a patient to become independent with their therapy by reducing the number of teaching visits, and thereby the total time of instruction . Time-saving and a decrease in the number of individuals providing instruction to a patient offer the prospect of lowering the cost of care . The skills checklist also improves communication between nurses providing instruction. J Biol Chem, 2002 Jul 12, 277(28), 25480 - 5 Epub 2002 Apr 30. Geldanamycin leads to superoxide formation by enzymatic and non-enzymatic redox cycling . Implications for studies of Hsp90 and endothelial cell nitric-oxide synthase; Dikalov S et al.; The ansamycin antibiotic geldanamycin has frequently been used as an inhibitor of heat shock protein 90 (Hsp90), and this agent has been widely employed as a probe to examine the interactions of Hsp90 with endothelial nitric-oxide synthase . Geldanamycin contains a quinone group, which may participate in redox cycling . When geldanamycin was exposed to the flavin-containing enzyme cytochrome P-450 reductase, both semiquinone and superoxide (O(2)(*)(-)) radicals were detected using electron spin resonance . The treatment of endothelial cells with geldanamycin resulted in a dramatic increase in O(2)(*)(-) generation, which was independent of endothelial nitric-oxide synthase, because it was not inhibited by N-nitro-l-arginine methyl ester and also occurred in vascular smooth muscle cells . Diphenylene iodinium inhibited this increase in O(2)(*)(-) by 50%, suggesting that flavin-containing enzymes are involved in geldanamycin-induced O(2)(*)(-) generation . In the absence of cells, geldanamycin directly oxidized ascorbate, consumed oxygen, and produced O(2)(*)(-) . Geldanamycin decreased the bioavailable nitric oxide generated by 3,4-dihydrodiazete 1,2-dioxide in smooth muscle cells by 50%, whereas pretreatment with superoxide dismutase inhibited the effect of geldanamycin . These findings demonstrate that geldanamycin generates O(2)(*)(-), which scavenges nitric oxide, leading to loss of its bioavailability . This effect is independent of the inhibition of Hsp90 and indicates that geldanamycin cannot be used as a specific inhibitor of Hsp90 . In light of these findings, the studies using geldanamycin as an inhibitor of Hsp90 should be interpreted with caution. J Biochem (Tokyo), 2002 May, 131(5), 729 - 38 Design, production, and characterization of recombinant neocarzinostatin apoprotein in Escherichia coli; Nozaki S et al.; Neocarzinostatin (NCS) is the first discovered anti-tumor antibiotic having an enediyne-containing chromophore and an apoprotein with a 1:1 complex . An artificial gene library for NCS apoprotein (apo-NCS) production in Escherichia coli was designed and constructed on a phage-display vector, pJuFo . The recombinant phages expressing pre-apo-NCS protein were enriched with a mouse anti-apo-NCS monoclonal antibody, 1C7D4 . The apo-NCS gene (encsA) for E . coli was successfully cloned, and then re-cloned into the pRSET A vector . After the his-tagged apo-NCS protein had been purified and cleaved with enterokinase, the binding properties of the recombinant protein as to ethidium bromide (EtBr) were studied by monitoring of total fluorescence intensity and fluorescence polarization with a BEACON 2000 system and GraphPad Prism software . A dissociation constant of 4.4 +/- 0.3 microM was obtained for recombinant apo-NCS in the fluorescence polarization study . This suggests that fluorescence polarization monitoring with EtBr as a chromophore mimic may be a simplified method for the characterization of recombinant apo-NCS binding to the NCS chromophore . When Phe78 on apo-NCS was substituted with Trp78 by site-directed mutagenesis using a two stage megaprimer polymerase chain reaction, the association of the apo-NCS mutant and EtBr observed on fluorescence polarization analysis was of the same degree as in the case of the wild type, although the calculated maximum change (DeltaIT(max)) in total fluorescence intensity decreased from 113.9 to 31.3 . It was suggested that an environmental change of the bound EtBr molecule on F78W might have dramatically occurred as compared with in the case of wild type apo-NCS . This combination of monitoring of fluorescence polarization and total fluorescence intensity will be applicable for determination and prediction of the ligand state bound or associated with the target protein . The histone-specific proteolytic activity was also re-investigated using this recombinant apo-NCS preparation, and calf thymus histone H1, H2A, H2B, H3, and H4 . The recombinant apo-NCS does not act as a histone protease because a noticeable difference was not observed between the incubation mixtures with and without apo-NCS under our experimental conditions. Crit Care, 2002 Apr, 6(2), 99 - 101 Epub 2002 Mar 12. Toll-like receptors: the key to the stable door? Hopkins P, Cohen J. Severe sepsis continues to lead to critical illness . Few therapeutic options exist other than antibiotic therapy and general supportive care . Large numbers of patients continue to die as a consequence of overactivation of the host inflammatory response and the resultant coagulopathy and disregulation of the normal controls of vasoactive tone . It is now known that a critical part of this host response occurs at the level of innate defence, without the need for antigen processing or the clonal expansion of cells targeted against the invading pathogen . This commentary will discuss the therapeutic targets revealed by our new understanding of the Toll-like receptor . The potential clinical difficulties that may result from intervention at this pattern-recognition receptor will also be explored. Ther Apher, 2002 Apr, 6(2), 103 - 8 Removal of endotoxin in blood by polymyxin B immobilized polystyrene-derivative fiber; Teramoto K et al.; Polymyxin B, a cationic cyclic decapeptide antibiotic, is well known to bind endotoxin and to neutralize its toxicity . Based on this principle, polymyxin B was immobilized on the chloroacetamidomethylated polystyrene fiber that is reinforced by polypropylene . The adsorbing capacity of the obtained fibers (polymyxin B immobilized fiber {PMX-F}) was evaluated on endotoxin and other serum components in serum and on heparin in phosphate-buffered saline . Fluorescein isothiocyanate-labeled or tetramethylrhodamine isothiocyanate-labeled lipopolysaccharide (LPS) was used as endotoxin . The measurement of the fluorescence intensity showed that PMX-F adsorbed these LPSs depending on their concentration and on amount . The adsorption of endotoxin was confirmed by desorption of LPS from PMX-F as well . PMX-F adsorbed serum amyloid protein A besides LPS, but neither C-reactive protein nor low-density lipoprotein . The adsorbing property of heparin was low. Pediatr Int, 2002 Jun, 44(3), 269 - 72 Detection of neutrophil-associated immunoglobulin using flow cytometry in autoimmune neutropenia of infancy; Yamada S et al.; BACKGROUND: Autoimmune neutropenia of infancy (ANI) is a common form of chronic childhood neutropenia, which is caused by antineutrophil antibodies . The syndrome is characterized by a severe selective neutropenia accompanied with recurrent bacterial infections . METHODS: We investigated 10 ANI patients in our hospital . Neutropenia in ANI patients was found in patients aged between 9 and 19 months . They had no life-threatening infections and their infections episode could be controlled by the conventional antibiotic therapy in general . The correlation of absolute neutrophil counts (ANC) and neutrophil-associated immunoglobulin (NAIg) levels in each case was analyzed and their clinical courses followed . RESULTS: The NAIg levels were high in all cases at the diagnosis, however, they had no relationship with ANC . The severity of infection and the period of neutropenia in our patients have no correlation to NAIg levels either . In our four cases, neutropenia disappeared after a median of 26 months (range, 18-29 months) . The periods of neutropenia were nearly similar to previous reports . After the NAIg level began to wane, neutrophil counts increased in four patients whose neutrophil counts had recovered finally . CONCLUSIONS: Detection of NAIg is useful for the diagnosis, and the observation of changes in NAIg may be helpful one by one for prediction of the prognosis. Med Clin North Am, 2002 Mar, 86(2), 297 - 309 Lyme arthritis; Massarotti EM; Infection with B . burgdorferi can cause a large joint inflammatory arthritis in patients who have not been treated for early Lyme disease; the knee is the most common joint affected . The diagnosis depends on a history of known exposure to the spirochete, characteristic clinical features, and serologic studies (ELISA and Western blot) confirming exposure to the spirochete . In most patients, antibiotic therapy is curative, but in a smaller percentage of patients, the presence of the HLA-DR beta 1*0401 haplotype can trigger treatment-resistant arthritis, in which antibiotic therapy is ineffective; in these instances, remittive agents, such as hydroxychloroquine and methotrexate, are indicated . Arthroscopic synovectomy may be considered when antibiotic therapy is not curative . Fibromyalgia can follow infection with B . burgdorferi but is unresponsive to antibiotic therapy; it is treated with tricyclic antidepressants and an exercise program . Lyme arthritis is the only chronic inflammatory arthritis in which the specific cause is known and can be cured . As such, it serves as an excellent model with which to study the pathogenesis of more common inflammatory arthritides, such as rheumatoid arthritis. Med Clin North Am, 2002 Mar, 86(2), 285 - 96 Cardiac manifestations of Lyme disease; Pinto DS; Lyme disease is a vector-borne illness that can affect numerous organ systems during the early disseminated phase, including the heart . The clinical course of Lyme carditis is usually benign with most patients recovering completely . In rare instances, death from Lyme carditis has been reported . The cardinal manifestation of Lyme carditis is conduction system disease, which generally is self-limited . Heart block occurs usually at the level of the atrioventricular node but often is unresponsive to atropine sulfate . Temporary pacing may be necessary in more than 30% of patients, but permanent heart block rarely develops . Myocardial and pericardial involvement can occur but generally is mild and self-limited . Diagnosis is made by associating the clinical and historical features of borreliosis, such as previous tick bite, EM, or neurologic involvement, with electrocardiographic abnormalities and symptoms such as chest pain, palpitations, syncope, and dyspnea . Serologic studies and endomyocardial biopsy can support the diagnosis in the correct clinical setting, and MR imaging, echocardiography, and gallium scanning have utility in selected circumstances . No treatment has been shown clearly to attenuate or prevent the development of Lyme carditis, but mild carditis generally is treated with oral antibiotics and severe carditis with intravenous antibiotics in an effort to eradicate the infection and prevent late complications of Lyme disease . There is conflicting evidence regarding the role that B . burgdorferi plays in the development and progression of chronic congestive heart failure . Because of the significant false-positive ELISA rate in this population and the unclear benefit of antibiotic therapy, confirmatory Western blot analysis is recommended . Routine therapy and screening of patients with idiopathic dilated cardiomyopathy is of limited utility and should be reserved for patients with clear history of antecedent Lyme disease or tick bite. Med Clin North Am, 2002 Mar, 86(2), 239 - 60 Erythema migrans; Edlow JA; EM is the most common manifestation of early Lyme disease, occurring in a high percentage of cases . Because this phase of infection with B . burgdorferi offers an excellent opportunity to treat this potentially systemic infection, front-line physicians must be familiar with its diagnosis . Although much attention has been paid to the classic form--the target lesion or bull's eye--there are variations that are more common . These include uniform coloration, lesions with necrotic or vesicular centers, and lesions with shapes that are not circular or oval . These findings must be interpreted in epidemiologic context . Serologic testing at this phase of the illness should not be done . It is unnecessary and potentially misleading; false-positive and false-negative tests can occur . Diagnosis is clinical . Prompt initiation of appropriate antibiotic therapy for 3 weeks cures most patients at this early stage of the disease . Clinicians should be aware that 15% of patients may be coinfected with a second tick-borne pathogen, which could alter the usual clinical manifestations and the response to treatment. Dynamics, 2001 Spring, 12(1), 17 - 21 Liposomal amphotericin B for the treatment of severe fungal infection; Michaud D; Amphotericin B is commonly used in the intensive care unit to treat invasive fungal infection . This medication is associated with a number of adverse events during infusion, such as fever, rigors, chills, electrolyte disorders and renal insufficiency . Liposomal amphotericin B can be used as an alternative to conventional amphotericin B to treat fungal infection . Patients receiving liposomal amphotericin B experience fewer adverse events than recipients of the conventional formulation; moreover, the liposomal formulation has been found to be as effective as the conventional amphotericin B to treat specific fungal infections . Unfortunately, the pharmacoeconomics of the liposomal formulation has limited the use of this medication . The purpose of this article is to present a brief summary of conventional amphotericin B with an emphasis on the narrow therapeutic index of this antibiotic . The liposomal amphotericin B solution is compared to conventional amphotericin B regarding the pharmacokinetics and pharmacodynamics . Therapeutic use, tolerability, and pharmacoeconomic implications of liposomal amphotericin B are discussed. Curr Opin Pulm Med, 2002 May, 8(3), 195 - 200 Invasive pulmonary aspergillosis; Oren I et al.; Invasive pulmonary aspergillosis is the most common fungal pulmonary infection in certain immunocompromised patients . The most commonly affected patients are hematopoietic stem cell transplant recipients and patients with hematological malignancies undergoing intensive chemotherapy . The survival of patients with invasive pulmonary aspergillosis is very poor because of difficulties in early diagnosis and lack of effective treatment options . Research efforts are being made constantly to improve different diagnostic techniques . Early, repeated, high resolution computed tomography of the chest, and sequential nonculture-based monitoring of Aspergillus antigen and DNA can improve earlier diagnosis . New antifungal drugs for treatment and prevention of invasive pulmonary aspergillosis continue to emerge, with better safety, efficacy, and pharmacologic profiles. Ann Plast Surg, 2002 May, 48(5), 546 - 52; discussion 552-3 Pyoderma gangrenosum: a great marauder; Ma G et al.; Pyoderma gangrenosum is a progressively necrotizing and ulcerative skin disease that mimics a severe bacterial infection . However, the cause is not infectious in nature and the lesions are refractory to local wound care and antibiotic therapy . The etiology of pyoderma remains unknown, although pathogenic mechanisms may involve immunologically mediated cutaneous damage . The authors report a 67-year-old woman in whom a necrotic ulcer developed at a chest tube site . Treated with local wound care and antibiotics, this lesion spread progressively to involve 15% of her body surface area . A septic clinical picture developed despite sterile cultures, and she required several operative debridements . Her disease continued to spread and finally a diagnosis of pyoderma gangrenosum was considered . Treated with systemic steroids, hyperbaric oxygen (HBO), and local wound care, she eventually underwent skin grafts. Rev Med Interne, 2002 Apr, 23(4), 378 - 85 {Rheumatologic manifestations of Lyme borreliosis}; Sibilia J et al.; PURPOSE: Lyme borreliosis is a multisystemic infection caused by the spirochaete Borrelia burgdorferi . In European endemic areas like northeast France, articular manifestations are, after neuroborreliosis, the most frequent extra-cutaneous features observed . Among the pathogenic species of Borrelia, Borrelia burgdorferi sensu stricto is the most frequently identified during Lyme arthritis, but others species also seem to be involved . CURRENT KNOWLEDGE AND KEY POINTS: The diagnosis of Lyme arthritis is usually based on combined clinical data and serological laboratory tests . In atypical forms, detection of bacterial DNA could be useful . While mechanisms involved in acute Lyme arthritis are beginning to be better understood, the pathogenesis of chronic arthritis, which concerns about 10% of the patients, remains unknown . Two hypotheses are proposed to explain the prolonged evolution of the articular disease: a chronic persistence of Borrelia burgdorferi, which evades the host immune system within the joint and/or an autoimmune mechanism by molecular mimicry . The antibiotic therapy is codified in acute arthritis, but is not really adapted in chronic Lyme arthritis or post-Lyme syndrome . FUTURE PROSPECTS AND PROJECTS: To prevent the disease, the vaccine available in the United States does not offer complete protection and is not useful in Europe since the species heterogeneity is important for the outer surface protein A . A better understanding of Lyme disease pathogenesis can subsequently lead to new therapeutic or preventive approaches. Pharmacoepidemiol Drug Saf, 2001 Dec, 10(7), 613 - 8 Ethical challenges in pharmacoepidemiological research in Colombia; Dennis RJ et al.; PURPOSE: To illustrate and to discuss some ethical challenges encountered during pharmacoepidemiological research in a developing country (Colombia), as well as the decisions made to solve them . METHODS: The authors in Bogota describe three recent studies . The first one collected data from clinical records to evaluate the prescriptions patterns in recently graduated physicians . The second used an interrupted time series design, with a set of observations prior and after a combined intervention, to assess whether it improved the quality of intravenous antibiotic prescribing practices in a university-based hospital . The third evaluated pharmacists' advice in childhood acute respiratory infection and acute diarrhea through a community survey, followed by focus groups and in-depth interviews of key informers . RESULTS: The ethical issues raised by these studies include the need for obtaining informed consent from participants (physicians in Study 1 and drug sellers in Study 3), deciding when to intervene in case of gross prescription mistakes detected during the collection of data as part of the time series assessment (Study 2), the use of simulated clients to collect data in the community survey, and the use of study resources to buy, in some cases, useless medications (Study 3) . CONCLUSION: Although ethical challenges in pharmacoepidemiology in non-industrialized countries like Colombia may be different from those in developed nations, ethical principles that guide research remain the same . The processes to safeguard these principles in Colombia for virtually all research are also universal in nature, and include the ethical review committee, subject privacy, informed consent, and disclosure of funding sources. Pharmacoepidemiol Drug Saf, 2001 Dec, 10(7), 587 - 94 Privacy considerations in the context of an Australian observational database; Duszynski KM et al.; Observational databases are increasingly acknowledged for their value in clinical investigation . Australian general practice in particular presents an exciting opportunity to examine treatment in a natural setting . The paper explores issues such as privacy and confidentiality--foremost considerations when conducting this form of pharmacoepidemiological research . Australian legislation is currently addressing these exact issues in order to establish clear directives regarding ethical concerns . The development of a pharmacoepidemiological database arising from the integration of computerized Australian general practice records is described in addition, to the challenges associated with creating a database which considers patient privacy . The database known as 'Medic-GP', presently contains more than 950,000 clinical notes (including consultations, pathology, diagnostic imaging and adverse reactions) over a 5-year time period and relates to 55,000 patients . The paper then details a retrospective study which utilized the database to examine the interaction between antibiotic prescribing and patient outcomes from a community perspective, following a policy intervention . This study illustrates the application of computerized general practice records in research. Spine, 2002 May 1, 27(9), E250 - 2 Spinal brucellosis: case report in the United States; Reitman CA et al.; STUDY DESIGN: Case report . OBJECTIVE: To increase awareness of spinal brucellosis and discuss demographics, diagnosis, and treatment . SUMMARY OF BACKGROUND DATA: Brucellosis is a rare cause of spinal infections in the United States, although there have been regional increases in its prevalence . METHODS: Retrospective review of a patient with spinal brucellosis . She underwent a protracted course of treatment, with a long delay in diagnosis . History ultimately revealed regular consumption of unpasteurized goat cheese . Appropriate testing subsequently led to the diagnosis . RESULTS: After multiple surgeries and medications, the condition responded well to definitive antibiotic therapy . CONCLUSION: Brucellosis is rare in the United States and thus often overlooked in the differential diagnosis of back pain . The changing risk pattern for this disease requires a high index of suspicion, which can result in early diagnosis and predictably favorable results to treatment. J Fam Pract, 2002 Apr, 51(4), 317 - 23 Does amoxicillin improve outcomes in patients with purulent rhinorrhea? A pragmatic randomized double-blind controlled trial in family practice; De Sutter AI et al.; OBJECTIVE: To compare the efficacy of amoxicillin vs placebo in patients with an acute upper respiratory tract infection and purulent rhinorrhea . STUDY DESIGN: Double-blind randomized placebo-controlled trial . POPULATION: The 416 patients included from 69 family practices were 12 years or older, presenting with acute upper respiratory complaints, and having a history of purulent rhinorrhea and no signs of complications of sinusitis . OUTCOMES MEASURED: Therapy success (disappearance of symptoms that most greatly affected the patient's health) at day 10 and duration of general illness, pain, and purulent rhinorrhea . RESULTS: Therapy was successful in 35% of patients with amoxicillin and in 29% of patients with placebo (relative risk {RR} 1.14, 95% confidence interval {CI}, 0.92-1.42) . There was no effect on duration of general illness or pain . Duration of purulent rhinorrhea was shortened by amoxicillin (9 days vs 14 for clearing of purulent rhinorrhea in 75% of patients; P =.007) . Diarrhea was more frequent with amoxicillin (29% vs 19%, RR 1.28, 95% CI, 1.05-1.57) . No complications were reported . One patient (0.5%) receiving amoxicillin and 7 (3.4%) receiving placebo discontinued trial therapy because of exacerbation of symptoms (RR 0.25, 95% CI 0.04-1.56, P =.07) . All 8 patients recovered with antibiotic therapy . CONCLUSIONS: Amoxicillin has a beneficial effect on purulent rhinorrhea caused by an acute infection of the nose or sinuses but not on general recovery . The practical implication is that all such patients, whatever the suspected diagnosis, can be safely treated with symptomatic therapy and instructed to return if symptoms worsen. Ann Pharmacother, 2002 May, 36(5), 927 - 32 Clinical pharmacy in a South Indian teaching hospital; Parthasarathi G et al.; OBJECTIVE: To describe how clinical pharmacy is helping to improve medication use at a South Indian teaching hospital by addressing medication use problems, which are commonly encountered in India . SUMMARY: Clinical pharmacy is practiced in many countries and makes a significant contribution to improved drug therapy and patient care . India is a country with significant problems with medication use, but until recently Indian pharmacists have not been educated for a patient-care role . Postgraduate pharmacy practice programs have been established at 2 pharmacy colleges in South India as a result of a joint Indo-Australian program of cooperation . At a teaching hospital associated with the colleges, clinical pharmacy services such as drug information, medication counseling, drug therapy review, adverse drug reaction reporting, and the preparation of antibiotic guidelines are assisting clinicians to improve drug therapy and patient care . Seven hundred twenty-seven requests for drug information were received from July 1997 to February 2001, and 543 suspected adverse drug reactions were evaluated from November 1997 to February 2001 . The most common drug classes causing adverse drug reactions were antibiotics, nonsteroidal antiinflammatory drugs, and antitubercular agents . Physician opinion and service utilization have also been surveyed: 82% of respondents had sought drug information from the Clinical Pharmacy Department and 71% of respondents had sought advice on individual patient management . The success of this program is raising awareness of clinical pharmacy among pharmacy educators elsewhere in India and has led to the introduction of clinical pharmacy services at other Indian hospitals. Rev Neurol (Paris), 2002 Mar, 158(3), 361 - 3 {Acute polyradiculoneuropathy after Chlamydia pneumoniae infection}; Coste S et al.; A 36-year-old woman presented acute polyradiculoneuropathy following Chlamydia pneumoniae infection . Although electrophysiologic studies were normal, clinical features were typical of Guillain-Barre syndrome (GBS) . Anti-ganglioside GM1 antibodies were positive . Two other cases of GBS following Chlamydia pneumoniae infection have been reported, but no specific feature emerges . Outcome was good in our patient after intravenous globulin then antibiotic therapy . Our case supports the notion that Chlamydia pneumoniae infection can induce GBS . The association is probably underestimated. Gastroenterol Hepatol, 2002 Apr, 25(4), 240 - 3 {Amoxicillin-clavulanic acid induced hepatotoxicity with progression to cirrhosis}; Jordan T et al.; Amoxicillin-clavulanic acid is a commonly used antibiotic in clinical practice . It is usually prescribed on an empirical basis and several cases of hepatotoxicity with cholestasis have been described . We report the case of a 42-year-old man who developed an acute hepatocellular lesion with progression to cirrhosis . The patient received amoxicillin-clavulanic acid twice with an interval of four months . Other causes of hepatic failure were excluded . Although amoxicillin-clavulanic acid-induced hepatotoxicity has been widely documented, there are no other reports describing its progression to cirrhosis in an adult. Reprod Domest Anim, 2002 Apr, 37(2), 75 - 80 Intraperitoneal insemination in mammals: a review; Yaniz JL et al.; This review focuses on factors associated with the development of intraperitoneal insemination in mammals . Findings to date indicate that fertility improves as the sperm cell concentration rises, but that the optimal sperm number differs in each species . Sperm washing before intraperitoneal insemination favours fertility . Peritoneal fluid shows a variable effect on spermatozoa, depending on the hormonal status of the female . The optimal time for insemination appears to be just prior to ovulation . The technique may be performed either through the abdominal or the vaginal wall . Verification of sperm deposition in the proximity of the ovaries improves fertility rates . Although associated with some risk of infection and an immune reaction against spermatozoa, the intraperitoneal technique rarely gives rise to severe anaphylactic shock, peritonitis, adhesion formation and the production of anti-sperm antibodies and these complications may be prevented by adequate sperm pretreatment and antibiotic therapy . The success of intraperitoneal insemination in humans, with results comparable with those of intrauterine insemination in the treatment of infertility, suggest the potential use of this technique in domestic mammals, especially in those in which intrauterine insemination poses practical difficulties . Some of the methods applied in human intraperitoneal insemination, such as confirming the position of the needle in the peritoneal cavity, and sperm pre-treatments might also improve results in domestic species . Conversely, the use of the animal model should help to develop some aspects of this technique in humans. J Clin Pharm Ther, 2002 Apr, 27(2), 79 - 84 Application of dynamic laser scattering to the quality control of injectable drugs: polymer formation in ampicillin solution; Sendo T et al.; OBJECTIVE: To assess the usefulness of dynamic laser scattering for monitoring the stability of ampicillin after reconstitution from commercially available vials with respect to the polymer formation and potency . METHODS: Polymer formation and the remaining potency of the reconstituted ampicillin solution were estimated using dynamic laser scattering and high-performance liquid chromatography . RESULTS: The laser light-scattering submicron particle analyser was sufficiently sensitive for detecting both monomer and polymer aggregates with the average diameter of 1.1 +/- 0.2 and 7.3 +/- 1.7 nm, respectively, in the ampicillin solution . Polymer formation was dependent on both the storage temperature and the storage period, but it was detected, even when no precipitates were visible and when loss of potency was less than 10% of the initial value following storage at 4 or -15 degrees C . CONCLUSION: Submicron particle analysis using scanning electron microscopy, when used in combination with high-performance liquid chromatography, provides a useful method for studying polymer formation in antibiotic solutions and for the quality control of antibiotic injections during storage. J Org Chem, 2002 May 3, 67(9), 2874 - 80 Total synthesis of spicamycin; Suzuki T et al.; The first total synthesis of one of the spicamycin congeners, SPM VIII (3), is described . A preliminary model study for construction of the characteristic N-glycoside linkage in spicamycin using tetra-O-benzyl-beta-D-mannopyranosylamine (13) and halopurines 5 revealed that Pd-catalyzed conditions successfully provided the coupling products 14 and 15 in good yields . It was also shown that thermal anomerization of the N-glycosides easily occurred, which resulted in the predominant formation of the beta-anomer as the thermodynamically favored compound, and the activation energy of anomerization of 15 was estimated to be ca . 30 kcal/mol . The novel aminoheptose unit of spicamycin 6 was prepared stereoselectively by carbon elongation of an acyclic aldehyde, prepared by ring cleavage reaction of a highly functionalized cyclohexane derived from naturally abundant myo-inositol . The Pd-catalyzed coupling reaction of the beta-heptopyranosylamine 6 with protected 6-chloropurine 5d, followed by deprotection, provided spicamycin amino nucleoside 2, whose condensation with dodecanoylglycine completed the total synthesis of 3 . This study confirmed the proposed unique structure of a novel nucleoside antibiotic. Acta Anaesthesiol Belg, 2002, 53(1), 41 - 2 Large subcutaneous hematoma complicating epidural block; Katz Y et al.; We present a case of a large subcutaneous hematoma in the lumbar region that occurred after epidural block was performed for the relief of labor pain . Epidural analgesia was begun in a young and healthy primigravida . Eight hours later, she needed an emergency cesarean section . Before anesthesia, blood was observed flowing freely around the site of the catheter insertion . General anesthesia was administered . Postoperative computed tomography showed a large subcutaneous hematoma in the lumbar region . Her postpartum course was complicated by an unexplained fever, which responded to antibiotic therapy and warranted prolonged hospitalization . Coagulation and bleeding studies were normal . We conclude subcutaneous hematoma after epidural block can cause significant morbidity and should be added to the list of neuroaxial block complications. Nihon Kokyuki Gakkai Zasshi, 2002 Mar, 40(3), 270 - 4 {Pulmonary empyema 48 years after Lucite-ball Plomb implantation for tuberculosis}; Ohkouchi M et al.; A 68-year-old woman was diagnosed as having empyema on the left side . She had a history of pulmonary tuberculosis and tuberculous pleurisy in 1949 . She was treated with artificial pneumothorax and implantation of 7 Lucite-ball plombs in the left upper thorax . A chest radiograph taken 14 years after initial operation, revealed an increase in density inside some of the Lucite-ball plombs . She was again admitted after experiencing fever and dyspnea 48 years after initial operation . The chest radiograph then showed a large mass on the left side, which compressed the mediastinum to the right . Inside the mass, Lucite-ball plombs were detected . The fever and inflammatory findings were improved with antibiotic therapy, but the dyspnea was persistent . The Lucite-ball Plombs and coagulating tissue were removed successfully . The patient's symptoms and respiratory function improved after the second operation. Laryngorhinootologie, 2002 Apr, 81(4), 285 - 8 {Interdisciplinary endoscopic outpatient management of connatal dacryocystoceles}; Hosemann W et al.; Dacryocystocele may represent a rare type of connatal stenosis of the lacrimal duct . If conservative measures fail and in case of secondary inflammation, probing or regular surgery is usually recommended . We report on 15 neonates suffering from 18 connatal dacryocystoceles which were presented to the clinic of ophthalmology at the 16th (6 - 44) day of life . There was a definite female preponderance (65 %) . Conservative treatment (external massage, at times i . v . antibiotic therapy) had proven to be ineffective . The neonates were subjected to outpatient nasal endoscopy and the ballooning cyst of the inferior nasal meatus was managed by endoscopic marsupialization in 14 cases applying local anesthesia . Two nasal cysts had to be operated on in general anesthesia due to obstructing local anatomy which obviated endoscopical microsurgery . Three additional dacryocystoceles have been detected incidentally in 2 neonates being subjected to surgery in general anesthesia for choanal atresia and lacrimal probing respectively . The corresponding dacryocystoceles were managed by concomitant endonasal microsurgery . We advocate interdisciplinary (ophthalmological and rhinological) outpatient examination in all neonates with suspected dacryocystoceles . Diagnosis is based on palpation, probing and nasal endoscopy applying local anesthesia together with mucosal decongestion . Microsurgical marsupialization immediately follows and will lead to persisting relief of symptoms. Mol Microbiol, 2002 Apr, 44(2), 449 - 60 Mapping the DNA-binding domain and target sequences of the Streptomyces peucetius daunorubicin biosynthesis regulatory protein, DnrI; Sheldon PJ et al.; Streptomyces antibiotic regulatory proteins (SARPs) constitute a novel family of transcriptional activators that control the expression of several diverse anti-biotic biosynthetic gene clusters . The Streptomyces peucetius DnrI protein, one of only a handful of these proteins yet discovered, controls the biosynthesis of the polyketide antitumour antibiotics daunorubicin and doxorubicin . Recently, comparative analyses have revealed significant similarities among the predicted DNA-binding domains of the SARPs and the C-terminal DNA-binding domain of the OmpR family of regulatory proteins . Using the crystal structure of the OmpR-binding domain as a template, DnrI was mapped by truncation and site-directed mutagenesis . Several highly conserved residues within the N-terminus are crucial for DNA binding and protein function . Tandemly arranged heptameric imperfect repeat sequences are found within the -35 promoter regions of target genes . Substitutions for each nucleotide within the repeats of the dnrG-dpsABCD promoter were performed by site-directed mutagenesis . The mutant promoter fragments were found to have modified binding characteristics in gel mobility shift assays . The spacing between the repeat target sequences is also critical for successful occupation by DnrI and, therefore, competent transcriptional activation of the dnrG-dpsABCD operon. Clin Lymphoma, 2002 Mar, 2 Suppl 1, S29 - 34 Acute and long-term toxicities associated with gemtuzumab ozogamicin (mylotarg(r)) therapy of acute myeloid leukemia; Leopold LH et al.; Gemtuzumab ozogamicin (Mylotarg(R)) targets leukemia cells that express CD33 by means of a humanized anti-CD33 monoclonal antibody conjugated to a modified antitumor antibiotic, calicheamicin . The effects of gemtuzumab ozogamicin (given intravenously at a dose of 9 mg/m2 for 2 doses separated by 2 weeks) have been evaluated in 3 phase II studies involving patients (n = 188) with acute myeloid leukemia (AML) in first relapse . Interim analysis has revealed that 30% of patients achieved remission, characterized by = 5% blasts in the marrow, neutrophil count = 1500/mL, hemoglobin = 9 g/dL, and independence from red blood cell and platelet transfusion . Grade 3/4 acute toxicities included nausea or vomiting (11%); elevated serum aminotransferase enzyme (16%) and bilirubin (26%) levels; and infusion-related chills (9%), fever (6%), and hypotension (5%) . As predicted with CD33-targeted therapy, most patients had neutropenia (98%) and thrombocytopenia (99%) . However, the incidence of grade 3/4 bleeding events (14%) and infection rates (pneumonia, 7%; sepsis, 15%) was low . No patients were reported to have treatment-related cardiotoxicity, cerebellar toxicity, or alopecia . Veno-occlusive disease (VOD) after gemtuzumab ozogamicin treatment (but prior to other therapies) occurred in 2% of patients (4/188), and the VOD-related death rate was < 1% (1/188) . Prior hematopoietic stem cell transplant may be a risk factor for VOD (P = 0.002, univariate analysis) . Gemtuzumab ozogamicin is a safe and effective treatment in carefully selected patients with AML in first relapse. Clin Lymphoma, 2002 Mar, 2 Suppl 1, S19 - 23 Early Phase I/II Trials with Gemtuzumab Ozogamicin (Mylotarg(R)) in Acute Myeloid Leukemia; Nabhan C et al.; Relapsed acute myeloid leukemia (AML) carries a poor prognosis . Treatment options are limited, and their toxicities are substantial . There is an urgent need for novel therapies that are effective and have acceptable side effects . Gemtuzumab ozogamicin (Mylotarg(R)) is an immunoconjugate targeted against CD33, which is expressed on more than 90% of myeloid leukemic blasts . The antibody is attached to calicheamicin, a potent cytotoxic enediyne antibiotic that inhibits DNA synthesis and induces apoptosis . In vitro studies showed excellent activity of gemtuzumab ozogamicin in leukemic cell lines and encouraged the evaluation of this agent in patients . In this review, early phase I/II studies that led to the US Food and Drug Administration approval of this immunoconjugate for older patients with relapsed AML are discussed . Potential adverse events reported with this agent, particularly the recent data of possible veno-occlusive disease and increased hepatotoxicity, are addressed . This agent is currently being investigated in many clinical trials as a front-line approach in previously untreated individuals, and it is likely that it will have many more indications in the near future. Jpn J Thorac Cardiovasc Surg, 2002 Mar, 50(3), 137 - 9 Infected left atrial myxoma with mitral valve endocarditis; Tanaka M et al.; We report a rare case of infected left atrial myxoma associated with mitral valve endocarditis . The tumor and a small amount of vegetative growth on the anterior mitral leaflet were surgically excised . Subsequent antibiotic therapy may have prevented the infection from recurring . Histological findings showed myxoma cells embedded in mucinous stroma at the tumor base and an organized thrombus with bacterial colonization at the tumor tip. Intensive Care Med, 2002 Apr, 28(4), 432 - 7 Epub 2002 Mar 06. Selective decontamination of subglottic area in mechanically ventilated patients with multiple trauma; Pneumatikos I et al.; OBJECTIVE: To determine whether selective decontamination locally in the subglottic area (SDSA) reduces tracheal colonization and prevents ventilator-associated pneumonia (VAP) in patients with multiple trauma . DESIGN AND SETTING: A prospective randomized, controlled, clinical study in a 14-bed general intensive care unit of a university hospital . PATIENTS: 79 consecutive multiple trauma patients admitted to the ICU who were expected to be mechanically ventilated for more than 5 days; 61 patients completed the protocol . INTERVENTION: Patients were randomly assigned to receive SDSA using a continuous infusion of a suspension containing three nonabsorbable antibiotics (polymyxin, tombramycin, and amphotericin B; n=30) or placebo ( n=31) . MEASUREMENTS: The incidence of bronchial and gastric colonization and the number of cases of VAP were recorded . Gastric fluid and tracheal secretion cultures were obtained soon after intubation and thereafter every 4 days . Etiological diagnosis of VAP was based on samples taken by a specific protected double catheter set . RESULTS: VAP developed in 5 of 30 (16.6%) patients receiving SDSA and 16 of 31 (51.6%) patients receiving placebo . Negative bronchial secretion cultures were found in 14 of 30 (46.6%) patients in the SDSA group and in only 3 of 31 (9.6%) patients in the control group . No patient with negative bronchial secretion culture developed VAP . No significant differences in outcome were found . CONCLUSIONS: The SDSA is an effective and safe type of chemoprophylaxis against tracheal colonization and can significantly reduce the incidence of VAP in mechanically ventilated patients with multiple trauma. Int J Paediatr Dent, 2002 Mar, 12(2), 124 - 31 Knowledge, attitudes and status of oral health in children at risk for infective endocarditis; da Silva DB et al.; AIM: The purpose of this study was to assess the oral health status of 104 children (2-17 years of age) at risk for infective endocarditis attending the Paediatric Cardiology Service of the Martagao Gesteira Institute of Child Care and Paediatrics, Rio de Janeiro, Brazil, and their guardians' attitudes towards and knowledge about endocarditis risks . METHODS: A structured interview was carried out with guardians and an oral examination was performed on each child to determine scores for the plaque index (PI), gingival index (GI) and dmft/DMFT index . RESULTS: The percentage of guardians who understood the meaning of 'heart infection' was 9.6%, who knew the possibility of heart disease caused by dental procedures was 60.6%, who understood the requirement for antibiotic cover before dental treatment was 72.1%, and who understood the importance of good oral health to prevent infective endocarditis was 41.3% . As regards oral health behaviours, 46.1% of children brushed their teeth three times or more a day, 28.8% had never visited a dentist before, and only 24.3% attended the dentist for prevention . There was visible plaque in 98% and gingival bleeding in 99% of children in this study . The caries experience for primary dentition (dmft) was 2.62%, and 3.97 for permanent dentition (DMFT) . CONCLUSIONS: Based on these results, we can conclude that the guardians' knowledge and attitudes about oral health were not good . This group at risk has poor oral health, which may give rise to a frequent bacteraemia under physiological conditions. Br J Dermatol, 2002 Apr, 146(4), 643 - 8 Cutaneous adverse reactions to clindamycin: results of skin tests and oral exposure; Lammintausta K et al.; BACKGROUND: Clindamycin is an antibiotic used in anaerobic and severe complicated infections . It is often selected for patients with a history of allergy to other antibiotics . OBJECTIVES: To study the occurrence of clindamycin hypersensitivity and to determine whether skin tests are useful in cases of suspected clindamycin allergy . METHODS: Six patients with an exanthematous rash and a history strongly suggestive of clindamycin hypersensitivity were studied with skin tests and oral exposure . Cases of suspected adverse drug reactions to clindamycin reported to the National Register of Adverse Effects of Drugs (NRAED) in Finland during 1973-2000 were analysed . RESULTS: In the skin tests true-positive patch test reactions were seen in four of six patients, while 22 healthy control patients were negative . One false-positive and one false-negative patch test reaction were seen . During 1973-2000, 29 suspected cases of skin and/or mucosal membranes affected by clindamycin were reported to the NRAED . CONCLUSIONS: Clindamycin hypersensitivity is not common . Delayed-type allergic reactions occur and patch tests are useful in those cases . Oral exposure is the method of choice if possible, as false-negative and false-positive reactions may occur. Aliment Pharmacol Ther, 2002 Apr, 16 Suppl 2, 204 - 9 Successful eradication of Helicobacter pylori prevents relapse of peptic ulcer disease; Tomita T et al.; BACKGROUND: The NIH consensus conference in 1994 recommended that all patients with peptic ulcers should be tested and treated for Helicobacter pylori . Recent studies have shown that the eradication of H . pylori is associated with a significant reduction in the relapse rate of peptic ulcers, but there are few reports about long-term outcome . AIMS: To evaluate the relapse rate of peptic ulcer in the long-term follow-up of patients after H . pylori eradication therapy . PATIENTS AND METHODS: Patients infected with H . pylori (445; 88 duodenal ulcer, 357 gastric ulcer) were randomly divided into three groups . In group A, patients received 'conventional treatment' including acid decreasing therapy with a histamine H2-receptor antagonist or proton pump inhibitor (PPI) . In group B, patients received 'dual therapy' including one antibiotic plus acid-decreasing therapy . In group C, patients received 'triple therapy' with PPI plus amoxicillin and clarithromycin . Eradication of H . pylori infection was assessed by histology of biopsy specimens from both the antrum and body corpus at 4 weeks, and 6 and 12 months after stopping therapy . Endoscopy was performed at intervals of 6 months for 5 years . RESULTS: Intention-to-treat eradication rates for the duodenal ulcer patients were 0% for group A, 46% for group B and 80% for group C; eradication rates for the gastric ulcer patients were 0%, 33% and 83% respectively . No recurrence was noted in the duodenal ulcer patients and only 4% of gastric ulcers recurred after successful eradication during follow-up for 5 years . In contrast, in patients with persistent H . pylori infection all DU and 92% of gastric ulcers recurred . CONCLUSION: Eradication of H . pylori infection changes the natural course of peptic ulcer. Curr Med Chem, 2002 May, 9(9), 929 - 39 Aminoglycoside mimetics as small-molecule drugs targeting RNA; Xin-Shan Y et al.; The potential of RNA as a new drug target has recently come to the fore, with the recognition that RNA molecules can adopt complex three-dimensional structures that, as with proteins, enable the design of specific ligands . Another reason for the present interest comes from the fact that many pathogenic agents, such as retroviruses, encode their genetic information in RNA strands . Unfortunately, the high toxicity and rapid emergence of high-level resistance have severely limited the usefulness of naturally occurring aminoglycoside antibiotics . To tackle these problems, it is an important concern to design new synthetic compounds with smaller, simpler structures which possess higher RNA binding affinity, better selectivity, better antibiotic activity, and stronger resistance against the aminoglycoside-modifying enzymes compared to their parent structures . Here, we will attempt a survey of current efforts to develop aminoglycoside mimetics or derivatives that target RNA . The latest advances in this field including rational design, synthetic strategy, and structure activity relationships are reviewed. Surg Endosc . 2001 Dec;15(12):1489. Portal vein thrombosis following laparoscopic splenectomy for beta-thalassemia: a case study; Sok J et al.; Portal vein thrombosis is a rare but well-recognized complication of splenectomy . We present the case of a 31-year-old woman with transfusion-dependent b-thalassemia who underwent a laparoscopic splenectomy to reduce her transfusion requirements . Postoperatively, she developed portal vein thrombosis, diagnosed by abdominal CT scanning on postoperative day 4 . After being treated with anticoagulation and antibiotic therapy, she obtained prompt resolution of her symptoms . This report summarizes the first reported incidence of portal vein thrombosis following laparoscopic splenectomy and presents the current theories regarding the etiology and treatment of postsplenectomy portal vein thrombosis. J Fr Ophtalmol, 2002 Jan, 25(1), 78 - 80 {Intraocular cysticercosis: a difficult diagnosis}; Guigon B et al.; The authors describe a case of intraocular cysticercosis discovered in the ophthalmology department ef Edouard Herriot Hospital . With no biological signs, the diagnosis was made after vitrectomy because the visit was late in the course of the disorder, the patient lived in the mountains, and he had failed to mention a trip to the West Indies 3 months before . The symptomatology began with uveitis worsened in 10 days by greater inflammation in spite of successive corticosteroids, antibiotic, and antiviral therapy . Repeated examination and serological and radiological investigations did not help establish the etiology . Only vitrectomy provided the diagnosis, the vitreous containing cysticercus . This discover was all the more surprising that the patient lived in the French Alps and a trip 3 months before had been forgotten . A review ol the literature allowed us to rapidly start a postoperative parasite examination to check for cerebral, muscular, cardiac, and subcutaneous localizations and to start treatment with praziquantel (50 mg/kg per day) with corticotherapy (1 mg/kg per day) . The eye evolved toward a very inflammatory phthisis, which led to evisceration. J Fr Ophtalmol, 2002 Jan, 25(1), 48 - 51 {Penetrating keratoplasty in ocular cicatricial pemphigoid}; Trigui A et al.; PURPOSE: Ocular cicatricial pemphigoid (OCP) is a chronic progressive disease characterised by exacerbations of immunologically driven conjunctival inflammation . In the advanced stages of the disease, severe xerosis with mechanical factors may contribute to the development of blinding keratopathy . The authors report two cases of penetrating keratoplasty (PK) in patients with OCP and discuss the modalities of the surgical procedure for this particular disease . METHODS: Two patients with stage III OCP according to Foster's classification, underwent PK . Initial and final visual acuity, indications of PK, surgical procedure, postoperative therapy, and complications were recorded . RESULTS: For the first patient, after 3 months of follow-up, the graft is still clear, with a remarkable improvement in vision (3/10) . For the second patient, however, graft rejection developed 15 days after the operation, complicated later by endophthalmitis, which was controlled with an antibiotic . DISCUSSION: The progression of ocular pemphigoid involves the filling of the conjunctival fornices, formation of symblepharon with lagophthalmos, and dry eye, from which blinding keratopathy can originate . A corticosteroid-based or immunosuppressant treatment blocks the progression of the fibrosis but does not get rid of palpebrale or corneal anomalies, making surgery necessary . This surgery generally gives disappointing results and should be planned when the disease is perfectly under control, during a lull in the disease so as to avoid reactivation of the fibrosis process . Reconstruction of the conjunctival fornices should also precede any corneal transplantation . CONCLUSION: These results indicate that PK may be performed to restore of sight in patients with advanced OCP after controlling the primary immunological process and aggressive treatment of the mechanical factors damaging the ocular surface. Curr Opin Infect Dis, 2002 Apr, 15(2), 169 - 74 Community-acquired pneumonia: process of care studies; Metersky ML; New insight has been gained into the relationship between the processes of care undertaken for patients with community-acquired pneumonia and the resulting outcomes . Better insight into the risks for a complicated course can increase the percentage of patients treated as outpatients . Studies have also suggested that both the promptness and the choice of antibiotic therapy can affect patient outcomes . Promptly switching to oral antibiotic therapy can often lead to a shorter length of hospital stay; however, concern has arisen regarding the effect of shorter lengths of stay on patient outcomes. Curr Opin Infect Dis, 2001 Aug, 14(4), 427 - 31 Infection control issues after bone marrow transplantation; Kusne S et al.; Bone marrow transplant recipients are at increased risk of a variety of infections from endogenous and exogenous sources . Various practices, including the use of prophylactic agents and a controlled environment are often employed in the name of infection control . Comparable data are lacking because of non-unified definitions of infection and endpoints . Antibiotic-resistant bacteria and fungi are being isolated more frequently as a result of selective pressure. Curr Opin Infect Dis, 2000 Aug, 13(4), 377 - 384 Nosocomial pneumonia: epidemiology, pathogenesis, diagnosis, treatment and prevention; Lode H et al.; Nosocomial pneumonia is the second most common nosocomial infection and the leading cause of death from hospital-acquired infection . Supine body position in mechanically ventilated patients, and cardiopulmonary resuscitation and continuous sedation are significant risk factors for developing nosocomial pneumonia . During the past 2 years some new therapeutic approaches for nosocomial pneumonia and modifications to established therapies have been described, such as optimal pharmacodynamic evaluations, monotherapy versus combination therapy, computer-assisted management programmes and antibiotic rotations. EMBO Rep, 2002 May, 3(5), 433 - 7 Epub 2002 Apr 18. Efficient biallelic mutagenesis with Cre/loxP-mediated inter-chromosomal recombination; Koike H et al.; The isolation of mutant cells with phenotypes caused by random mutagenesis has been hampered in mammalian cells because there are two alleles per gene and the disruption of both alleles is extremely rare . We describe a method for the efficient biallelic mutagenesis in embryonic stem cells . loxP sites were introduced near the centromeric regions of a pair of chromosome 1s . A mutant neo gene was inserted at the distal part of one of the loxP sites so that biallelic mutants would be selected by high-dose G418 . Expression of Cre induced the recombination between homologous chromosomes and led to an elevation in the number of biallelic mutants . This system will facilitate phenotype-driven gene function study in the mammalian system. Int J Health Plann Manage, 2002 Jan-Mar, 17(1), 23 - 40 Prescription practices of public and private health care providers in Attock District of Pakistan; Siddiqi S et al.; The irrational use of drugs is a major problem of present day medical practice and its consequences include the development of resistance to antibiotics, ineffective treatment, adverse effects and an economic burden on the patient and society . A study from Attock District of Pakistan assessed this problem in the formal allopathic health sector and compared prescribing practices of health care providers in the public and private sector . WHO recommended drug use indicators were used to study prescription practices . Prescriptions were collected from 60 public and 48 private health facilities . The mean (+/- SE) number of drugs per prescription was 4.1 +/- 0.06 for private and 2.7 +/- 0.04 for public providers (p < 0.0001) . General practitioners (GPs) who represent the private sector prescribed at least one antibiotic in 62% of prescriptions compared with 54% for public sector providers . Over 48% of GP prescriptions had at least one injectable drug compared with 22.0% by public providers (p < 0.0001) . Thirteen percent of GP prescriptions had two or more injections . More than 11% of GP prescriptions had an intravenous infusion compared with 1% for public providers (p < 0.001) . GPs prescribed three or more oral drugs in 70% of prescriptions compared with 44% for public providers (p < 0.0001) . Prescription practices were analysed for four health problems, acute respiratory infection (ARI), childhood diarrhoea (CD), fever in children and fever in adults . For these disorders, both groups prescribed antibiotics generously, however, GPs prescribed them more frequently in ARI, CD and fever in children (p < 0.01) . GPs prescribed steroids more frequently, however, it was significantly higher in ARI cases (p < 0.001) . For all the four health problems studied, GPs prescribed injections more frequently than public providers (p < 0.001) . In CD cases GPs prescribed oral rehydration salt (ORS) less frequently (33.3%) than public providers (57.7%) . GPs prescribed intravenous infusion in 12.3% cases of fever in adults compared with none by public providers (p < 0.001) . A combination of non-regulatory and regulatory interventions, directed at providers as well as consumers, would need to be implemented to improve prescription practices of health care providers . Regulation alone would be ineffective unless it is supported by a well-established institutional mechanism which ensures effective implementation . The Federal Ministry of Health and the Provincial Departments of Health have to play a critical role in this respect, while the role of the Pakistan Medical Association in self-regulation of prescription practices can not be overemphasized . Improper prescription practices will not improve without consumer targeted interventions that educate and empower communities regarding the hazards of inappropriate drug use. Anticancer Drug Des, 2001 Apr-Jun, 16(2-3), 99 - 107 DNA binding properties of the indolocarbazole antitumor drug NB-506; Carrasco C et al.; Indolocarbazoles derived from the antibiotic rebeccamycin represent an important group of antitumor agents . Several indolocarbazoles are currently undergoing clinical trials . These compounds inhibit topoisomerase 1 to produce DNA breaks that are responsible for cell death . Unlike classical topoisomerase I poisons like camptothecin, glycosyl indolocarbazoles can form stable complexes with DNA even in the absence of topoisomerase I . At least in part, their mode of action is reminiscent of that of the anthracyclines, which also bind to nucleic acids and interfere with topoisomerase II . The lead synthetic compound in the series is the uncharged drug NB-506, which bears a glucose residue attached to the indolocarbazole chromophore substituted with two hydroxyl groups at positions 1 and 11 . Here we report a detailed biophysical study aimed at characterizing the DNA binding properties of NB-506 . Molecular modeling was used to compare the conformation and electronic properties of NB-506 and its analogue ED-571 bearing the two hydroxyl groups at positions 2 and 10 . Surface plasmon resonance experiments, performed with DNA hairpin oligomers, indicate that NB-506 binds almost equally well to both AT and GC base pairs, and the binding affinity (K = 10(5) M(-1)) is similar to that of certain classical intercalators such as amsacrine and bisantrene . Isothermal titration calorimetry experiments show that the binding of NB-506 is enthalpy-driven (deltaH = -7.2 kcal/mol) . The binding enthalpy measured for NB-506 is similar to that obtained with doxorubicin but the DNA interaction processes for the two drugs differ markedly in terms of entropy and deltaG . The free energy of NB-506 binding to DNA is considerably less favorable than that of doxorubicin . These biophysical data help us to understand further how rebeccamycin-type anticancer drugs interact with DNA. Rev Med Chil, 2002 Jan, 130(1), 61 - 5 {An Elisa stool test to detect Helicobacter pylori infection}; Morales A et al.; BACKGROUND: Infection with Helicobacter pylori is frequent in Chile, and a good test for its diagnosis ideally should be non-invasive, fast, easy and inexpensive . AIM: To report the use of an immunoassay test, that detects antigens of Helicobacter pylori in stools . MATERIAL AND METHODS: One hundred and four patients that required an upper gastrointestinal endoscopy were studied . Stool samples were analyzed using an enzymatic immunoassay . These results were compared with those obtained with the urease test and microscopic examination of smears taken from biopsies obtained during the diagnostic endoscopy . RESULTS: In 81 of 83 patients considered to have the infection according to the endoscopic tests, the antigen was also present in the stools . The test was negative in 16 of 21 patients considered to be without the infection . The resulting sensitivity and specificity for the immunoassay was thus 97.6 and 76.2% respectively, with positive and negative predictive values of 92.4 and 88.9%, respectively . CONCLUSIONS: These resul