J Biol Chem, 1998 Nov 27, 273(48), 32304 - 11 Plasma membrane cholesterol is a key molecule in shear stress-dependent activation of extracellular signal-regulated kinase; Park H et al.; Shear stress, the dragging force generated by fluid flow, differentially activates extracellular signal-regulated kinase (ERK) and c-Jun NH2-terminal kinase (JNK) in bovine aortic endothelial cells (BAEC) (Jo, H., Sipos, K., Go, Y . M., Law, R., Rong, J., and McDonald, J . M . (1997) J . Biol . Chem . 272, 1395-1401) . Here, we examine whether cholesterol-enriched compartments in the plasma membrane are responsible for such differential regulation . Pretreatment of BAEC with a cholesterol-binding antibiotic, filipin, did not inhibit shear-dependent activation of JNK . In contrast, filipin and other membrane-permeable cholesterol-binding agents (digitonin and nystatin), but not the lipid-binding agent xylazine, inhibited shear-dependent activation of ERK . The effect of cholesterol-binding drugs did not appear to be due to membrane permeabilization, since treatment of BAEC with a detergent, Triton X-100 which also permeabilizes membranes, did not inhibit shear-dependent activation of ERK . Furthermore, shear-dependent activation of ERK, but not JNK, was inhibited by cyclodextrin, a membrane-impermeable cholesterol-binding agent, which removes cell-surface cholesterol . Moreover, the effects of cyclodextrin were prevented by adding cholesterol during the incubation . These results indicate that cholesterol or cholesterol-sensitive compartments in the plasma membrane play a selective and essential role in activation of ERK, but not JNK, by shear stress . Although exposure to shear stress (1 h) increased the number of caveolae by 3-fold, treatment with filipin had no effect in either control or shear-exposed cells suggesting that caveolae density per se is not a crucial determinant in shear-dependent ERK activation . In summary, the current study suggests that cholesterol-sensitive microdomains in the plasma membrane, such as caveolae-like domains, play a critical role in differential activation of ERK and JNK by shear stress. J Oral Maxillofac Surg, 1998 Nov, 56(11), 1303 - 11 Hydroxyapatite-coated implants: a case for their use; Morris HF et al.; The information on which this article is based comprises a small fraction of the large database compiled from the DICRG study . These results represent the early performance for HA implants (up to 36 months) . The study has been ongoing for 6 years, and there are more than 2,000 implants with 4-year data and 1,500 with 5-year data . These data are similar to the 36-month data, and when they are eventually released, they are likely to reinforce the results reported here . Meanwhile, the evidence presented in this article, along with other corroborating studies cited in the introduction, are sufficient grounds to reach the following conclusion: The ideal implant design and material is one that is easy to use, requires average skills, involves minimal bone trauma, presents a biocompatible contact surface, and produces a high rate of survival in most patients . Based on 36-month survival in the DICRG study, HA-coated implants appeared to satisfy these basic requirements better than the other implants used in the study . HA-coated implants were placed in the most challenging bone types and jaw region, in patients with compromised medical histories, by dentists with different training, skills, and experience, under less than ideal clinical conditions, and still showed the highest survival rates of all implants at every point in the treatment up to 36 months. J Infect, 1998 Jul, 37(1), 59 - 62 Paediatric neurobrucellosis: case report and literature review; Habeeb YK et al.; Neurological complications are rare in childhood brucellosis: there are only 33 reported cases . In children, neurobrucellosis is usually of acute presentation involving the central nervous system . We report our experience with an 8-year-old boy with brucella meningitis who demonstrated a Jarisch-Herxheimer-like reaction, i.e . initial clinical deterioration following the commencement of antibrucella treatment, associated with increased pleocytosis and shift from lymphocytic to polymorphic predominance and an already increased CSF lactate . These CSF findings have not been previously described . The patient recovered completely after 3 months' therapy consisting of rifampicin, doxycycline and gentamicin . Paediatric neurobrucellosis therapy should be a combination of three antibrucella antibiotic that include an aminoglycoside; for a period of 8-12 weeks, steroids may be added to treat complications . The prognosis of neurobrucellosis in children is usually good. J Infect, 1998 Mar, 36(2), 203 - 7 Candidaemia in an Australian teaching hospital: relationship to central line and TPN use; Stratov I et al.; We performed a retrospective review of patient case records to identify risk factors for candidaemia and to assess incidence, management and outcome of candidaemia in an Australian teaching hospital . Between January 1994 and June 1996, 38 cases of candidaemia were identified . The incidence was 0.74 per 1000 admissions of 24 h duration, and 1.54 per 1000 admissions of 5 days or more . The mortality rate was 34%, with eight of 13 (62%) of these deaths attributable to candidaemia . Risk factors included underlying gastrointestinal disease (66%) and recent abdominal surgery (61%), while recent broad spectrum antibiotic use was a contributing factor in 95% . Twenty-nine patients (76%) had a vascular access device in situ at time of detection . This was the apparent source of candidaemia in 28 (97%) . Twenty-six (90%) were being used for TPN administration . Of patients receiving TPN, 5.2% developed candidaemia . Standard central venous catheters (CVC) were present in 21 patients (55%), having been in situ for an average of 12.7 days . Eighteen (86%) had been in situ for 7 days or more . Management involved removal of any implicated intravascular device . Thirty of 33 early survivors received antifungal chemotherapy . Therapy with amphotericin B, fluconazole alone or amphotericin B followed by fluconazole was equally effective . Concurrent corticosteroid use and neutropaenia contributed to increased mortality . Candidaemia is not benign . Policies regarding regular changing of central lines, especially in the setting of TPN administration and control of broad spectrum antibiotic use are appropriate measures aimed to reduce incidence . Management involves removal of implicated lines and antifungal chemotherapy . Pre-emptive therapy for candida infection should be considered in selected patients with the likelihood of TPN-related central line sepsis . Fluconazole is an effective alternative to amphotericin B in non-neutropenic patients. J Infect, 1998 Jan, 36(1), 93 - 100 Escherichia coli bacteraemia in patients with and without haematological malignancies: a study of strain characters and recurrent episodes; Olesen B et al.; We compared serotypes, virulence factors and susceptibility to antibiotics of Escherichia coli strains isolated from 282 patients with bacteraemia . Thirty-five of these were neutropenic patients with haematological malignancy and 247 were patients with a normal or raised total white blood cell count and no haematological malignancy . Strains isolated from recurrent bacteraemia were also bio- and ribotyped . Overall, no significant difference was found between O serogroups, K antigens, serum sensitivity, production of haemolysin, expression of P-fimbriae and patterns of antibiotic susceptibility in the two groups of strains . The haematological patients more often than the non-haematological patients had an unknown focus of infection, recurrent bacteraemia, shorter intervals between recurrences and recurrences caused by identical strains . Despite a well-defined focus, six of eight non-haematological patients had recurrences with a strain different from the strain isolated in a previous episode . A possible connection between shorter intervals and recurrence with identical strains is discussed . We suggest that strains from recurrent E . coli bacteraemia are sent to a reference laboratory for serotyping and possibly ribotyping. Ear Nose Throat J, 1998 Oct, 77(10), 832 - 3, 837-8 First branchial cleft anomalies: report of 12 cases; Leu YS et al.; First branchial cleft anomalies account for only 1-8% of all branchial anomalies . Several classification systems have been proposed to aid in the diagnosis of these defects . We present a series of 12 patients with first branchial cleft anomalies classified according to anatomic criteria . The preferred treatment is complete excision . For patients with acutely inflamed masses, surgery should be performed only after resolution of the infection has been achieved with adequate drainage in combination with antibiotic therapy. J Clin Microbiol, 1998 Dec, 36(12), 3703 - 6 Isolation of blood-borne Mycobacterium avium by using the nonradioactive BACTEC 9000 MB system and comparison with a solid-culture system; Jacomo V et al.; We conducted a 12-month prospective study comparing two approaches to the detection of Mycobacterium avium in the blood of human immunodeficiency virus type 1-infected patients, namely, a lytic centrifugation system combined with Middlebrook solid culture medium (the conventional procedure) and the nonradiometric BACTEC 9000 MB system . Species identification relied on 16S rRNA probe hybridization and cell wall fatty acids chromatography . M . avium was isolated in 17 of 345 (5%) blood specimens by the BACTEC 9000 MB automated system and in 14 of 345 (4%) blood specimens by the conventional procedure (nonsignificant, chi2 test) . Detection time was 16 +/- 6 days by the BACTEC 9000 MB automated system and 27 +/- 3 days by the conventional procedure (P < 0.001, Student t test) . Non-M . avium mycobacteria were not recovered during the study period . Contamination rate was 8% (30 specimens) by the BACTEC 9000 MB system and 0% by the conventional procedure, indicating the necessity of using an antibiotic mixture (PANTA, consisting of polymyxin B, amphotericin B, nalidixic acid, trimethoprim, and azlocillin) . Working time was 1 min 30 s by the BACTEC 9000 MB system and 8 min by the conventional procedure, which was 1.8 times more expensive than the BACTEC system . Use of the BACTEC 9000 MB system increased the sensitivity of M . avium detection and reduced detection time in blood culture. Scand J Infect Dis, 1998, 30(4), 424 - 5 Isolated right-sided Bartonella quintana endocarditis in an immunocompetent adult; Bruneel F et al.; Bartonella quintana is a recently recognized cause of culture-negative left-sided endocarditis . We report a case of isolated tricuspid endocarditis caused by B . quintana in a 65-year-old alcoholic man, who also had immune-complex glomerulonephritis . B . quintana was established as the cause of the endocarditis based on serological tests and on failure of extensive efforts to isolate an alternative organism . The patient improved gradually on antibiotic therapy and did not require surgery . To our knowledge, this is the first report of isolated right-sided endocarditis caused by B . quintana . Although uncommon, Bartonella should be considered in patients with isolated right-sided culture-negative endocarditis. J Urol, 1998 Dec, 160(6 Pt 1), 2115 - 20 Risks and complications of transrectal ultrasound guided prostate needle biopsy: a prospective study and review of the literature; Rodriguez LV et al.; PURPOSE: Transrectal ultrasound guided needle biopsy of the prostate is routinely performed to diagnose and stage prostate cancer . We prospectively evaluated the true incidence of complications and identified risk factors of needle biopsy . MATERIALS AND METHODS: We prospectively studied 128 patients who underwent transrectal ultrasound guided needle biopsy . A pre-biopsy questionnaire provided demographic information . Immediate complications were recorded by the surgical team at the procedure . Information on delayed complications was obtained by telephone interview . Univariate and multivariate analyses were performed . RESULTS: There was 1 major and 135 minor complications in 77 patients with at least 1 complication in 63.6% . Most patients tolerated the procedure with minimal discomfort regardless of the number and location of biopsies but younger patients had significantly more discomfort than older men (R = -0.26, p = 0.005) . The most common complication was persistent hematuria in 47.1% of cases . None of the hemorrhagic complications was related to previous aspirin or nonsteroidal anti-inflammatory drug use, or the total number of biopsies performed . Infectious complications were rare with only a 1.7% incidence of fever . This rate was associated with the choice of antibiotic combination used (R = 0.25, p = 0.006) . CONCLUSIONS: Transrectal ultrasound guided needle biopsy is safe for diagnosing prostate cancer with few major but frequent minor complications . Patients are likely to have persistent hematuria for up to 3 to 7 days after the procedure . Recent use of aspirin or nonsteroidal anti-inflammatory drugs is not an absolute contraindication for this procedure . Additional analgesics are not required in patients who undergo anterior or multiple biopsies but they may be useful in younger patients. Unfallchirurg, 1998 Sep, 101(9), 662 - 73 {Diagnosis and therapy of pediatric and juvenile hematogenous osteomyelitis}; Dresing K et al.; Haematogen osteomyelitis is mostly found in children and adolescents . In western Europe acute haematogen osteomyelitis (AHOM) is a rare disease . This is the cause why AHOM is often diagnosed with delay . The treatment usually is an antibiotic medication and/or surgical interventions . Uncharacteristic pain of extremities in children should always consider the diagnosis of acute osteomyelitis . Investigation should include conventional X-rays, ultrasounds or MRI to prevent the spreading of infection . In cases of multifocal infection radionuclide imaging should be undergone . Differential diagnosis should always include malignant tumor . If under treatment of antibiotics the clinical signs of illness do not decrease within 24 h surgery with fenestration of the involved bone, debridement and local application of antibiotics is indicated . In unusual cases or in cases with clinical signs of AHOM but no bacteria specification a malignant tumor has to be excluded. J R Soc Med, 1998 Aug, 91(8), 414 - 6 Primary repair of dog bites to the face: 40 cases; Javaid M et al.; Dog bites to the face can be life-threatening if major infection occurs, and traditional management consists of wound toilet and debridement, with repair only when the possibility of infection has been eliminated . Surgical opinion is now swinging towards earlier repair . We have analysed retrospectively the outcome of 40 cases that, irrespective of time delay between injury and presentation, underwent primary repair or reconstruction after wound toilet, debridement and administration of prophylactic antibiotics . The victims were 17 males and 23 females with ages ranging from 2 to 76 years (mean 25) . Median delay between the injury and presentation in the emergency department was 60 minutes (range 7 minutes to 5 days) . All patients received surgical treatment within 24 hours of admission, 18 being operated on within 6 hours . 31 had primary repairs and 9 patients had reconstructive procedures with local skin flaps or skin grafts . Primary healing was achieved in all but 2 patients, of whom one developed minor wound infection and one had necrosis of a composite graft . These results support the view that, for dog bites to the face, primary repair is the method of choice. Rev Prat, 1998 Sep 15, 48(14), 1535 - 40 {Good practices and measures of prevention of nosocomial infections}; Alfandari S et al.; Prevention of nosocomial infections is a long-term task needing coordination and habits modifications of numerous health care workers . The infection control unit must be independent and staffed by trained personnel . Its main goals are: to monitor nosocomial infections and antibiotic use; to implement written procedures; to distribute hospital-wide information on local epidemiology, incidence rates as well as results of preventive measures used in the hospital. J Tongji Med Univ, 1997, 17(3), 160 - 4 A new drug delivery system--ciprofloxacine/tricalcium phosphate delivery capsule (CTDC) and its in vitro drug release pattern; Wu H et al.; A new drug delivery system (DDS), ciprofloxacine/tricalcium phosphate delivery capsule (CTDC) was developed by loading a broad-spectrum antibiotic ciprofloxacine into the central cylindrical cavity of tricalcium phosphate capsule . The new system showed good biocompatibility and could degrade gradually in our preliminary studies . In vitro study showed that CTDC could maintain high-level and long-term release of ciprofloxacine and that ultrasonic irradiation within the range of physical therapy could increase the drug release amount from CTDC ( P < 0.02), and might become a new technique to achieve the control of drug release from DDS. Clin Pharmacokinet, 1998 Oct, 35(4), 313 - 29 Drug disposition in cystic fibrosis; Rey E et al.; There are many pathological changes in patients with cystic fibrosis (CF) which can lead to alterations in drug disposition . Although, in patients with CF, the extent of drug absorption varies widely and the rate of absorption is slower, bioavailability is not altered . Plasma protein binding for the majority of drugs studied did not differ in patients with CF compared with control groups . The difference in volume of distribution of most drugs between patients with CF and healthy individuals vanished when corrected for lean body mass . Despite hepatic dysfunction, patients with CF have enhanced clearance of many, but not all, drugs . Phase I mixed-function oxidases are selectively affected: cytochrome P450 (CYP) 1A2 and CYP2C8 have enhanced activity, while other CYP isoforms such as CYP2C9 and CYP3A4 are unaffected . Increased phase II activities are also demonstrated: glucuronyl transferase, acetyl transferase (NAT1) and sulfotransferase . The increased hepatic clearance of drugs in the presence of CF may be the consequence of disease-specific changes in both enzyme activity and/or drug transport within the liver . The renal clearance (CLR) of many drugs in patients with CF is enhanced although there has been no pathological abnormality identified which could explain this finding: glomerular filtration rate and tubular secretion appear normal in patients with CF . The precise mechanisms for enhanced drug clearance in patients with CF remain to be elucidated . The optimisation of antibiotic therapy in patients with CF includes increasing the dose of beta-lactams by 20 to 30% and monitoring plasma concentrations of aminoglycosides . The appropriate dosage of quinolones has not been definitively established. Plant Cell, 1998 Nov, 10(11), 1903 - 14 Impaired fungicide activity in plants blocked in disease resistance signal transduction; Molina A et al.; Fungicide action is generally assumed to be dependent on an antibiotic effect on a target pathogen, although a role for plant defense mechanisms as mediators of fungicide action has not been excluded . Here, we demonstrate that in Arabidopsis, the innate plant defense mechanism contributes to the effectiveness of fungicides . In NahG and nim1 (for noninducible immunity) Arabidopsis plants, which normally exhibit increased susceptibility to pathogens, the fungicides metalaxyl, fosetyl, and Cu(OH)2 are much less active and fail to control Peronospora parasitica . In contrast, the effectiveness of these fungicides is not altered in Arabidopsis mutants defective in the ethylene or jasmonic acid signal transduction pathways . Application of the systemic acquired resistance activator benzothiadiazole (BTH) in combination with these fungicides results in a synergistic effect on pathogen resistance in wild-type plants and an additive effect in NahG and BTH-unresponsive nim1 plants . Interestingly, BTH treatment normally induces long-lasting pathogen protection; however, in NahG plants, the protection is transient . These observations suggest that BTH treatment can compensate only partially for an impaired signal transduction pathway and support the idea that pathogen defense mechanisms are under positive feedback control . These observations are strikingly reminiscent of the reduced efficacy of antifungal agents in immunocompromised animals. Arch Pediatr Adolesc Med, 1998 Nov, 152(11), 1132 - 6 Minocycline-related autoimmune hepatitis: case series and literature review; Teitelbaum JE et al.; BACKGROUND: Minocycline is an antibiotic commonly used in the treatment of adolescent acne . OBJECTIVES: To describe the clinical, laboratory, and histological features in 3 cases of minocycline-related autoimmune hepatitis and to review the literature of similar cases in the adolescent population . DESIGN: Case series . SETTING: Patients were cared for in the Division of Gastroenterology, Children's Hospital, Boston, Mass . RESULTS: Three adolescents (age, 15-16 years), while being treated with therapeutic doses of minocycline for periods of 12 to 20 months, met the 1993 International Autoimmune Hepatitis Group criteria for autoimmune hepatitis . All had a positive antinuclear antibody titer . Other features included hypergammaglobulinemia and a positive anti-smooth muscle antibody titer . Two patients underwent liver biopsy that revealed severe chronic lymphoplasmacytic inflammation, necrosis, and fibrosis . All other causes of liver disease were excluded . One patient had resolution of symptoms with withdrawal of the drug, while 2 required immunosuppression therapy . A review of the literature yielded only 18 similar cases, none in the pediatric literature, the majority of which contained incomplete pertinent data . CONCLUSIONS: Minocycline is related to the development of autoimmune hepatitis in some adolescents . Pediatricians who use this drug for treatment of acne should be aware of this serious potential relation and stop the drug immediately when suspicion is raised. J Am Acad Dermatol, 1998 Nov, 39(5 Pt 2), 876 - 8 Melanoma-in-transit presenting as panniculitis; Cotton J et al.; Malignant melanoma presenting as an inflammatory skin metastasis has been described but is an exceedingly rare phenomenon . We report an unusual case of a patient who developed right leg lesions that were initially thought to be infectious in origin . There was no resolution of these lesions with antibiotic therapy, and the patient subsequently underwent an incisional biopsy that showed atypical S-100 positive cells within dermal vessels . On further questioning, the patient revealed that 20 years earlier she had a pigmented lesion removed from her right posterior calf . Review of that material revealed malignant melanoma, approximately 3.2 mm in depth . Although the patient was subsequently treated with a right groin lymph node dissection and isolated limb perfusion chemotherapy, she has continued to develop locally recurrent disease . This case is unusual both in terms of clinical presentation and interval of disease progression. Hiroshima J Med Sci, 1998 Sep, 47(3), 109 - 13 Prediction for the development of postoperative infections in the operation of esophageal cancer compared with gastric surgery; Takesue Y et al.; The purpose of this study was to assess the point at which the postoperative infection has occurred in order to decide upon the proper duration of prophylactic antibiotic use . Another goal of this study was to determine whether prediction for the development of postoperative infections in major surgery such as esophagectomy should be the same as that in routine gastroenterological surgery . Twenty-five patients who underwent transthoracic esophagectomy and 127 patients who underwent gastrectomy were studied . On the third day after gastric surgery, the body temperature of patients who developed an infection was higher than that of the patients who did not develop an infection . The relative changes in peripheral white blood count (WBC), and C-reactive protein (CRP) concentration on the third and fourth days were more predictive of the development of infection than the absolute values . Almost all patients with systemic inflammatory response syndrome (SIRS) on the third day after gastric surgery developed an infection . On the other hand, the incidence of SIRS in patients who did not develop an infection was high on both the third and fourth days after esophageal surgery . It was nearly impossible to predict who would develop an infection in esophageal surgery . The high incidence of postoperative infections, and their significant consequences justify planned successive postoperative antibiotic use in esophageal surgery. Otolaryngol Head Neck Surg, 1998 Nov, 119(5), 444 - 54 Intratemporal complications of acute otitis media in infants and children; Goldstein NA et al.; We reviewed our experience with 100 children admitted to Children's Hospital of Pittsburgh between 1980 and 1995 with an intratemporal complication of acute otitis media . Seventy-two patients were treated for acute mastoiditis . Of these 72 children, 54 (75.0%) were treated conservatively with broad-spectrum intravenous antibiotics and myringotomy . Eighteen (25.0%) required mastoidectomy for treatment of a subperiosteal or Bezold's abscess or cholesteatoma, or because of poor response to conservative therapy . Twenty-two children presented with facial paralysis, complete in 5 (22.7%) and incomplete in 17 (77.3%) . Eighteen (81.8%) were treated conservatively, but four required mastoid surgery . Nineteen patients had adequate follow-up; of these, 15 recovered normal facial function but 4 were left with partial paralysis . Three patients presented with serous labyrinthitis and recovered completely with conservative therapy . Of the two patients who presented with suppurative labyrinthitis, one was treated conservatively, but the other required tympanomastoidectomy with cochleotomy; both patients had permanent, profound sensorineural hearing loss in the affected ear . Four patients presented with acute petrositis, and in all four it resolved with mastoidectomy . In the antibiotic era, intratemporal complications of acute otitis media still occur in otherwise healthy children, often after inadequate treatment of acute otitis media. Cell Biol Toxicol, 1998 Oct, 14(5), 323 - 32 Cytotoxicity of nephrotoxic fungal toxins to kidney-derived LLC-PK1 and OK cell lines; Bondy GS et al.; The nephrotoxic fungal toxins ochratoxin A (OA), ochratoxin B (OB) and citrinin (CIT) are natural contaminants of foods and feeds . While cytotoxicity assays have proven useful for establishing relative toxicity and structure function relationships within groups of fungal toxins, a drawback of in vitro bioassays is their susceptibility to variation depending on endpoint, target cell, and dosing strategy . These variables were explored for OA, OB, CIT using two continuous kidney cell lines (LLC-PK1 and OK) and four cytotoxicity assay endpoints . The nephrotoxic antibiotic gentamicin was used as a positive control for cytotoxicity throughout . In general, fungal toxin-induced cytotoxicity was more pronounced in LLC-PK1 cultures using mitochondrial dehydrogenase inhibition (MTT assay) as the endpoint . Altered dosing strategy, but not seeding density, consistently influenced cytotoxicity: CIT was more toxic to cells when added at the time of seeding, whereas OA was more toxic when added 24 h after cultures were seeded . Toxicity rankings for the fungal toxins were consistent with in vivo studies and were, in order of most to least toxic, OA > OB > CIT . The data indicate that LLC-PK1 and OK cells compare favorably to existing models in terms of sensitivity to nephrotoxic fungal toxins, but also that relatively minor changes in assay protocols can affect the cytotoxicity of individual toxins and comparative toxicity within a group of toxins. Childs Nerv Syst, 1998 Sep, 14(9), 463 - 6 Intracranial actinomycosis in juvenile patients . Case report and review of the literature; Puzzilli F et al.; A case of actinomycotic brain infection in a juvenile patient is described . Cases of actinomycosis affecting the head and neck are rare, particularly in juvenile patients . In this case complete resolution of the infection was achieved by means of surgical treatment and prolonged antibiotic therapy . The authors emphasize the importance of a combined approach for treatment of this unusual brain infection and stress the difficulties involved in the diagnosis of this pathology. Drugs, 1998 Oct, 56(4), 607 - 16; discussion 617 Rifapentine; Jarvis B et al.; Rifapentine is a rifamycin antibiotic with antimycobacterial activity . Rifapentine is generally more active against Mycobacterium tuberculosis than rifampicin (rifampin), although strains resistant to rifampicin are usually cross-resistant to rifapentine . Sputum culture conversion rates were slightly higher after 6 months of rifapentine- versus rifampicin-based therapy in patients with pulmonary tuberculosis in a Western study; however, relapse rates were higher in rifapentine recipients during follow-up . The excess relapses in the rifapentine group appeared to be related to poor compliance with nonrifamycin antituberculosis drugs during the intensive phase (first 2 months) of therapy . Rifapentine- and rifampicin-containing regimens produced similar sputum culture conversion rates with low rates of relapse in 2 randomised clinical trials in patients with smear-positive tuberculosis in China . In one trial, there was no difference in sputum culture conversion rates in patients treated with rifapentine once weekly or rifampicin twice weekly in combination with isoniazid and ethambutol during the continuation phase of treatment . Hyperuricaemia, which was reported only during the intensive phase, elevated ALT and AST levels and neutropenia were the most common treatment-related adverse events reported in patients receiving rifapentine- or rifampicin-containing regimens for tuberculosis in 1 Western study. J Biol Chem, 1998 Nov 13, 273(46), 30695 - 703 Purification, characterization, and cloning of an S-adenosylmethionine-dependent 3-amino-3-carboxypropyltransferase in nocardicin biosynthesis; Reeve AM et al.; S-Adenosylmethionine:nocardicin 3-amino-3-carboxypropyltransferase catalyzes the biosynthetically rare transfer of the 3-amino-3-carboxypropyl moiety from S-adenosylmethionine to a phenolic site in the beta-lactam substrates nocardicin E, F, and G, a late step of the biosynthesis of the monocyclic beta-lactam antibiotic nocardicin A . Whereas a number of conventional methods were ineffective in purifying the transferase, it was successfully obtained by two complementary affinity chromatography steps that took advantage of the two substrate-two product reaction scheme . S-Adenosylhomocysteine-agarose selected enzymes that utilize S-adenosylmethionine, and a second column, nocardicin A-agarose, specifically bound the desired transferase to yield the enzyme as a single band of 38 kDa on a silver-stained SDS-polyacrylamide gel . The transferase is active as a monomer and exhibits sequential kinetics . Further kinetic characterization of this protein is described and its role in the biosynthesis of nocardicin A discussed . The gene encoding this transferase was cloned from a sublibrary of Nocardia uniformis DNA . Translation gave a protein of deduced mass 32,386 Da which showed weak homology to small molecule methyltransferases . However, three correctly disposed signature motifs characteristic of these enzymes were observed. ASAIO J, 1998 Sep-Oct, 44(5), M411 - 4 Intermittent intraperitoneal ceftazidime dosing in end-stage renal disease; Dumler F et al.; Infections are a common problem in dialysis patients . As hospital stay shortens, many require outpatient antibiotic therapy . Parenteral administration may pose considerable logistic and financial burdens, whereas daily intraperitoneal dosing increases the risk of contamination . Ceftazidime, with its long half-life, may provide adequate dosing when administered intraperitoneally thrice weekly . The authors therefore studied the kinetics of a 2 g loading dose followed by a 1.5 g dose every 48 hr in seven stable chronic peritoneal dialysis patients . In vitro stability at 4 degrees C (measured by high performance liquid chromatography) was 91% at 120 hr . Peak serum concentration (60 +/- 22 microg/ml) was reached at 4.9 +/- 2.2 hr . Serum values were 25 +/- 9 and 8 +/- 3 microg/ml at 24 and 48 hr, respectively . However, median trough levels at 48 hr in dialysate were significantly lower than in serum (2.8 vs 8.5 microg/ml, respectively; p = 0.0425) . Pharmacokinetic parameters were as follows: bioavailability (F), 88% +/- 8%; volume of distribution at steady state (VDss), 20 +/- 8 L; absorption half-life (T1/2(abs)), 1.8 +/- 1.3 hr; elimination half-life (T1/2(el)), 11.4 +/- 4.5 hr; and clearance (CL), 22 +/- 10 ml/min . Intraperitoneal ceftazidime every 48 hr is a practical alternative to parenteral therapy of nonperitoneal infections . In peritonitis, whether increased permeability results in improved dialysate levels remains to be defined. East Afr Med J, 1998 Jul, 75(7), 439 - 40 Single-layer closure for typhoid perforations of the small intestine: case report; Connolly DP et al.; The case of a 13-year old girl who presented with generalised peritonitis, septic shock and laboratory features of perforated typhoid enteritis is presented . At laparotomy 25 perforations involving the distal jejunum and the entire ileum were noted with extensive peritoneal soilage . The perforations were successfully closed in single layer using vicryl (polyglactin 910) sutures and the peritoneum thoroughly lavaged . The patient has been followed up for thirty months with only minimal complications . We believe that single layer closure of extensive multiple typhoid perforations in a poor risk patient when weighed against resection and anastomosis with the possibility of short bowel syndrome is safer, quicker and more effective as long as the procedure is undertaken after adequate resuscitation and under appropriate antibiotic cover. East Afr Med J, 1998 Jun, 75(6), 370 - 3 Management of Fournier's gangrene at the Kenyatta National Hospital, Nairobi; Ayumba BR et al.; A prospective study involving the management of forty six patients with Fournier's gangrene was carried out at the Kenyatta National Hospital, Nairobi over a period of two years . The age range was nine to 81 years with a mean of 40.27 years indicating that the lesion is common and affects all age groups in this locality . The majority of patients (60.86%) presented with advanced lesions involving scrotal ulcers (45.65%) and gangrene (15.22%) . Results of bacterial culture from scrotal wound swabs isolated multiple organisms in 8.15% of the patients, a point which should be taken into consideration during antibiotic selection . Forty one patients (89.13%) had surgical procedures in addition to antibiotics and other supportive measures . Five other patients (10.87%) who presented with early lesions had medical treatment only with antibiotics, antipyretics and analgesics . The average duration of hospitalisation was sixteen days . Two patients (4.35%) one of whom was HIV positive died from septicaemia during the study period . Recurrent scrotal infection occurred in two patients (4.35%) after discharge from the hospital and were treated satisfactorily at the surgical outpatient clinic. An Esp Pediatr, 1998 Sep, 49(3), 280 - 3 {Whooping cough: a retrospective study of the cases diagnosed over a period of 15 years}; Francis Centeno M et al.; OBJECTIVE: Our objective was to study the whooping cough cases diagnosed in a 15-year period in our hospital, referring to its clinical features, epidemiology and analytical findings . PATIENTS AND METHODS: A retrospective study based on 144 cases with a clinical diagnosis of whooping cough, from 1981 to 1995, was carried out . Special attention was paid to those cases with cultures positive for B . pertussis . RESULTS: Nasopharyngeal specimens for culture were taken in 119 cases . This was not carried-out in those with previous antibiotic therapy . Cultures were positive for B . pertussis in 46 patients (38.7%) . The age varied between 20 days and 30 months . Twenty-one were female . The initial symptoms were: paroxysmal cough in 44 (95.7%), cyanosis in 34 (73.9%), inspiratory whoop in 27 (58.7%), respiratory distress in 12 (26.1%) and post-tussive vomiting in 10 (21.7%) . Thirty-nine children (84.8%) of this group had not received any pertussis vaccine, the rest had received just the first dose . It had been contacted by persons having cough in 19 patients (41.3%) . Leukocytosis (mean: 19,818/mm3), lymphocytosis (mean: 13,047/mm3) and high platelet count (mean 459,522/mm3) were common findings . CONCLUSIONS: Cultures were positive in 38.7% of the patients . There are similar findings by other authors . In this group, most of the children were unvaccinated, and less than 3 months of age . Typical symptoms of pertussis were observed in the majority of patients . In one forth of them respiratory distress was found, probably related to their young age . Vaccinated adults emerge as a contact group that should be studied. J Pediatr Surg, 1998 Oct, 33(10), 1521 - 5 Liposome drug delivery system for murine neuroblastoma; Nagae I et al.; PURPOSE: The effects of liposome-infused doxorubicin on C-1300 murine neuroblastoma were studied . The liposome surface was covered with polyethylene glycol to avoid migration toward the reticuloendothelial system and to prolong its presence in the bloodstream . Liposome-infused doxorubicin hydrochloride (DXR), an anthracycline was used as an anticancer antibiotic substance . METHODS: Each A/J mouse was transplanted with 1 x 10(5) C-1300 murine neuroblastoma cells subcutaneously in the thigh . The experiment was conducted when the maximum tumor dimension was 1 cm . The control group was given only physiological saline solutions, the second group was given DXR alone, and the third group received liposome-infused DXR (Lip-DXR) . The survival and doubling times were measured . One, 12, and 24 hours after the injection, the DXR concentration in the cardiac tissues was measured for statistical comparison . RESULTS: The survival time of the mice was found to be 27+/-5.10 days in the control group, 31.40+/-3.15 days in the DXR group, and 43.86+/-2.13 days in the Lip-DXR group . The Lip-DXR group showed the longest survival time . The tumor-doubling time was found to be 9.07+/-2.30, 10.75+/-3.49, and 19.80+/-3.26 days, for each group, respectively . When comparing the DXR concentration in the heart tissues, the Lip-DXR-administered mice showed significantly lower DXR accumulation in the cardiac tissues after 1 and 12 hours than the DXR-administered mice . CONCLUSION: This study proved that liposome-infused DXR could be used effectively on murine neuroblastoma (C-1300 tumor cell model) and may reduce the incidence of cardiac toxicity as compared with DXR alone. Breast Cancer Res Treat, 1998 Jul, 50(1), 83 - 93 Reduction of mouse mammary tumor formation and metastasis by lovastatin, an inhibitor of the mevalonate pathway of cholesterol synthesis; Alonso DF et al.; Lovastatin, a fungal antibiotic used in the treatment of hypercholesterolemia, is an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, the key regulatory enzyme in the mevalonate pathway of cholesterol synthesis . We examined the antitumor properties of lovastatin on the F3II sarcomatoid mammary carcinoma, a highly invasive and metastatic murine tumor model . Female BALB/c inbred mice were inoculated subcutaneously with F3II tumor cells and injected i.p . daily with 10 mg/kg body weight of lovastatin or administered p.o . at a level corresponding to the human dosage of 1-2 mg/kg/day . Treatment significantly prolonged tumor latency and reduced tumor formation and metastatic dissemination to the lungs from established mammary tumors . In vitro, antitumor properties of lovastatin were strongly associated with inhibition of tumor cell attachment and migration . These actions were prevented by addition of mevalonate but not by equivalent concentrations of farnesyl pyrophosphate . In accordance, Western blot assays showed that lovastatin effects did not appear to be related to modifications in Ras oncoproteins in our model . The present data indicate that lovastatin could be an antitumor agent with potentially useful clinical applications in breast cancer. Minim Invasive Neurosurg, 1998 Sep, 41(3), 161 - 5 Anterior cervical epidural abscess treated by endoscopy-assisted minimally invasive microsurgery via posterior approach; Roselli R et al.; This is a report of clinical manifestation, physical findings, neurophysiological data, magnetic resonance imaging, and results after surgery in a 71-years-old man with cervical abscess . Magnetic resonance imaging after two weeks of empiric antibiotic therapy demonstrated the persistence of an anterior cervical epidural collection and signs of spondylodiscitis at the C5-C6 and C6-C7 levels . Surgery was performed by posterior endoscopy assisted key-hole approach at the C2-C3 level to drain the abscess and to decompress the spinal cord . Postoperative specific medical treatment was then administered . A successful outcome, at 24 months follow-up, was achieved by surgery with complete clinical recovery, resolution of the abscess and healing of the spondylodiscitis . After unsuccessful blind medical therapy the minimally invasive microsurgical technique allowed us to keep the surgical injury of the healthy tissue to a minimum while producing the maximum therapeutic effect. Microbiology, 1998 Oct, 144 ( Pt 10), 2819 - 25 Identification of two linear plasmids in the actinomycete Planobispora rosea; Polo S et al.; Two linear plasmids (pPR1, 27.5 kb, and pPR2, 16 kb) were identified in Planobispora rosea, an actinomycete that produces the antibiotic GE2270, an inhibitor of the elongation factor Tu . Strains lacking both plasmids still produce and are resistant to GE2270 . The two plasmids share an internal region of high similarity, but no cross-hybridization was detected between their telomeric regions or between plasmid and chromosomal DNA . The 5' ends of the plasmids appear to be linked to terminal proteins . The telomeric regions of pPR2 were cloned after 3'-end homopolymer tailing and PCR amplification . The approximately 650 nt telomeric DNA sequences of pPR2 are repeated in inverted orientation and are rich in direct and inverted repeats; the 350 bp terminal region is less G + C-rich than the rest of the plasmid . The structural organization of these plasmids appears to be similar to Streptomyces linear replicons. Tech Urol, 1998 Sep, 4(3), 169 - 71 Transrectal puncture and drainage of seminal vesicle abscess; Kerbl K et al.; Seminal vesical abscesses are extremely rare . We report a case in which successful treatment was achieved using a minimally invasive transrectal approach. Ann Thorac Surg, 1998 Oct, 66(4), 1312 - 7 Coronary artery operation in patients after breast cancer therapy; Erez E et al.; OBJECTIVE: The purpose of this investigation was to retrospectively study the outcome of patients undergoing coronary artery operation who were previously treated for breast cancer . METHODS: Between July 1992 and December 1996, 28 patients with a history of breast cancer underwent coronary artery bypass graft operation and were randomly matched against a noncancer group of similar size (n = 36) to allow for comparison of their preoperative characteristics, operative course, and postoperative outcome . RESULTS: The incidence of sternal wound infection was significantly higher in the cancer group than in the control group (25% versus 6%; p = 0.027) . Postoperative noncardiac chest pain occurred more frequently in the cancer group than in the control group (52% versus 31%; not significant) . In the study group, radiotherapy and recent myocardial infarction were the only two independent factors associated with sternal wound complications . Patients with a less than 17-year interval between the breast cancer therapy and the coronary artery operation had a higher incidence of sternal wound infection (46%) as opposed to patients with a longer time interval (7%; p = 0.028; odds ratio = 12) . Sternal wound complications were more frequent in patients with a history of right-sided breast cancer (50%) compared with left-sided lesions (12.5%; p = 0.068; odds ratio = 7) . CONCLUSIONS: Coronary artery operation in patients after breast cancer therapy may be associated with an increased sternal wound infection rate . To decrease this risk of infection, an approach through a right thoracotomy, minimally invasive techniques, the use of skeletonized internal mammary artery, and broad spectrum antibiotic therapy may be considered. Aust Fam Physician, 1998 Oct, 27(10), 895 - 901 Concurrent prescribing . Beware of drug interactions; Munckhof WJ; BACKGROUND: Antibiotics are commonly prescribed to patients who are also taking other medications . Pharmacology textbooks contain long lists of potential interactions between antibiotics and other drugs, but only a few of these interactions have serious clinical consequences . OBJECTIVE: This review will highlight antibiotic interactions that are clinically significant, and the relative incidence and importance of each interaction will be considered . It will concentrate primarily on drugs commonly prescribed in general practice, such as the oral contraceptive pill and warfarin . DISCUSSION: Quinolones and macrolides are the groups of antibiotics most commonly associated with clinically significant drug interactions . Warfarin interacts with many antibiotics, although the incidence of this interaction can range from predictable to rare . The association between most antibiotics and oral contraceptive failure is weak, with only sporadic case reports in the literature. Aust Fam Physician, 1998 Oct, 27(10), 883 - 7 Respiratory infections in the community . A concise update; Ferguson J; BACKGROUND: The decision to institute antibiotic therapy is often empirical and based on historical precedent . As respiratory tract infections are the commonest reason for prescribing antibiotics and bacterial resistance to many drugs is increasing, it is important to look at the evidence for using antibiotics . OBJECTIVE: This article reviews the various components of the respiratory tree addressing the indications for instituting antibiotic therapy and the most appropriate antibiotic . DISCUSSION: The information contained in this article is based on the 10th edition of the Therapeutic Guidelines: Antibiotics . It is acknowledged that the decision of when and which antibiotics to prescribe must be made on an individual basis, however, by considering the broader ramifications of antibiotic use and the evidence of outcome studies, the decision can be based on a more rational approach. Gene Ther, 1998 May, 5(5), 692 - 9 Gene transfer into human umbilical cord blood-derived CD34+ cells by particle-mediated gene transfer; Verma S et al.; Delivery of genes into hematopoietic progenitor cells offers an attractive means for the introduction of corrective or protective genes into cells of both the myeloid and lymphoid lineage . Previously, investigators have often used murine retroviral vectors for gene delivery which require cells to be cycling for efficient delivery . We describe a nonviral method of gene delivery using particle-mediated gene transfer to obviate many disadvantages of viral vectors related to safety, production costs and the need for cell cycle proliferation . Using a CMV-CAT reporter plasmid, we show transfection of highly purified CD34+ cells isolated from umbilical cord blood . Effective gene transfer was shown in unstimulated and in growth-stimulated cells . Following transfection with a neomycin resistance gene, differentiation into cells of the myeloid lineage was observed, assayed by CFU-GM in the presence of G-418 . Both unstimulated and stimulated cells gave rise to CFU-GM in the presence of G-418, indicating that stable expression of the neomycin resistance gene was maintained in early progenitors . These results demonstrate that particle-mediated gene transfer into human hematopoietic cells from umbilical cord blood can be achieved without affecting their CFU-GM differentiation potential . This gene transfer method offers an alternative approach to gene therapy studies involving human hematopoietic progenitor cells. Clin Pharmacol Ther, 1998 Oct, 64(4), 355 - 62 Pharmacokinetic interaction between ritonavir and clarithromycin; Ouellet D et al.; BACKGROUND: Because ritonavir, a human immunodeficiency virus (HIV) protease inhibitor, and clarithromycin, a macrolide antibiotic used in the treatment of disseminated infection caused by Mycobacterium avium complex, are likely to be administered concurrently for treatment of patients with HIV and acquired immunodeficiency syndrome (AIDS), the drug interaction potential of these 2 agents was evaluated . Both clarithromycin and ritonavir are metabolized to a significant extent through cytochrome P450-mediated biotransformation and are potential inhibitors of these enzymes . OBJECTIVE: To evaluate the pharmacokinetic effects of concomitant administration of multiple doses of ritonavir and clarithromycin . METHODS: This was an open-label, randomized, 3-period crossover study . Ritonavir alone (200 mg every 8 hours), clarithromycin alone (500 mg every 12 hours), and ritonavir and clarithromycin in combination were administered to 22 healthy volunteers . Blood samples were collected on day 4 for determination of ritonavir, clarithromycin, and its metabolite 14-(R)-hydroxyclarithromycin . RESULTS: Ritonavir practically completely inhibited the formation of 14-(R)-hydroxyclarithromycin . The mean area under the plasma concentration-time curve (AUC) for clarithromycin increased by 77% with concomitant ritonavir, and the harmonic mean terminal half-life increased from 5 hours to 14 hours . Statistically significant increases in peak plasma concentration (31%) and minimum plasma concentration (182%) were also observed . The effect of concomitant clarithromycin administration on ritonavir pharmacokinetics was statistically significant but small, with a 12.5% increase in mean AUC and a 15.3% increase in peak plasma concentration . The terminal half-life increased from 3.47 to 3.87 hours with concomitant clarithromycin . CONCLUSIONS: No adjustment of the ritonavir dose is necessary when administered with clarithromycin . In addition, no changes in clarithromycin dose are warranted in patients with normal renal function. Antimicrob Agents Chemother, 1998 Nov, 42(11), 2985 - 8 Purification and characterization of virginiamycin M1 reductase from Streptomyces virginiae; Suzuki N et al.; Virginiamycin M1 (VM1), produced by Streptomyces virginiae, is a polyunsaturated macrocyclic lactone antibiotic belonging to the virginiamycin A group . S . virginiae possesses an activity which stereospecifically reduces a 16-carbonyl group of VM1, resulting in antibiotically inactive 16R-dihydroVM1 . The corresponding VM1 reductase was purified to homogeneity from crude extracts of S . virginiae in five steps, with 5,650-fold purification and 23% overall yield . The N-terminal amino acid sequence was determined to be MAIKLVIA . The purified enzyme showed an apparent Mr of 73,000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and an Mr of 280,000 by native molecular sieve high-performance liquid chromatography, indicating the tetrameric nature of the native enzyme . NADPH served as a coenzyme for the reduction, with a Km value of 0.13 mM, but NADH did not support the reaction, even at a concentration of 5 mM, indicating the NADPH-specific nature of the enzyme . The Km for VM1 was determined to be 1.5 mM in the presence of 2 mM NADPH . In the reverse reaction, only 16R-dihydroVM1, not the 16S-epimer, served as a substrate, with a less than 0.1% overall reaction rate compared to that of the forward reaction, confirming that the VM1 reductase participates solely in VM1 inactivation in vivo. J Miss State Med Assoc, 1998 Oct, 39(10), 366 - 9 Sexual assault: the physician's role in prevention and treatment; Beebe DK; Rape is a crime which occurs to over 12 million women . It has a substantial impact on the physical, psychological and social health of the victim . It is defined as the carnal knowledge of a person forcibly and against their will and includes successful and unsuccessful assaults . In this sense, the terms rape and sexual assault are used interchangeably . Physicians should responsibly counsel patients when appropriate concerning prevention of sexual assault and should be knowledgeable about the acute medical and psychological management of a sexual assault victim, including the collection of evidence . This article provides basic information regarding examination, evidence collection and treatment. Infection, 1998 Sep-Oct, 26(5), 335 - 41 Operative and nonoperative therapy of intraabdominal infections; Wittmann DH; The basic principles for treating intraabdominal infections are fourfold: (1) to obliterate the infectious source; (2) to purge bacteria and toxins; (3) to maintain organ system function and (4) to tame the inflammatory process . Operative and nonoperative treatment options are available . Operative therapy includes different strategies: (1) the standard operation; (2) advanced procedures to decompress the abdominal compartment syndrome and (3) percutaneous drainage of abscesses . Nonoperative management includes: (1) antibiotic therapy; (2) hemodynamic and pulmonary support; (3) nutrition and metabolic support; (4) detoxification support (including support of renal and hepatic function) and (5) inflammation modulating therapy . Standard operative management addresses the first two principles and has been shown to reduce mortality by more than 50% . A recent extensive series of studies reports mortality rates around 20% . Patients with an abdominal compartment syndrome (intraabdominal pressure over 25 torr) and patients with advanced disease and compounding risk factors best documented by high APACHE-II scores are candidates for more advanced operations . The mortality rate following abdominostomy (leaving the abdomen open) in 869 patients participating in 37 studies was 42%, when the abdomen was simply left open for decompression (open abdominostomy) . When a mesh was used to cover the abdominal wound (mesh abdominostomy) 39% of 439 patients enrolled in 12 studies died . Patients who underwent staged abdominal repair (STAR abdominostomy) faired better . Of 385 patients in 11 studies 28% died . Data from antibiotic studies as well as from immunomodulating therapy are nonconclusive at this point with respect to reducing mortality in intraabdominal infection. Biochim Biophys Acta, 1998 Oct 23, 1425(2), 311 - 8 Nystatin-induced changes in yeast monitored by time-resolved automated single cell electrorotation; Holzel R; A widespread use of electrorotation for the determination of cellular and subcellular properties has been hindered so far by the need for manual recording of cell movements . Therefore a system has been developed that allows the automatic collection of electrorotation spectra of single cells in real time . It employs a hardware based registration of image moments from which object orientation is calculated . Since the camera's video signal is processed without intermediate image storage a high data throughput of about two recordings per second could be achieved independently of image resolution . This made it possible to monitor changes in cell membrane and cytoplasm of the yeast Saccharomyces cerevisiae under the influence of the antibiotic nystatin with a temporal resolution of 3 min . Up to 20 electrorotation spectra of an individual cell could be collected in the frequency range between 1 kHz and 1 GHz . Two distinct events 7 and 75 min after addition of nystatin were observed with a fast increase in membrane permeability accompanied by a nearly simultaneous drop in cytoplasmic conductivity. J Gastroenterol Hepatol, 1998 Sep, 13(9), 961 - 7 Endoscopic diagnosis of lower intestinal lesions of leukaemia and malignant lymphoma; Kishida T et al.; There have been only a few endoscopic studies with respect to lower intestinal lesions of leukaemia and malignant lymphoma, although there have been many autopsy studies of these lesions . The aim of this study was to clarify these lesions using endoscopy . Colonoscopy was performed on 11 of 341 patients with leukaemia and on 32 of 105 patients with malignant lymphoma for frequent diarrhoea, anal bleeding or abnormal findings on barium enema examination, between April 1984 and September 1994 . In eight of the 11 patients with leukaemia on whom endoscopy was performed, nine lesions were found; aphthoid ulcers, small ulcers or large tumours due to leukaemic infiltration were found in five, and colorectal adenoma was found in only one patient . Antibiotic-associated haemorrhagic colitis or pseudomembranous colitis was found in one patient each . In 10 of the 32 patients with malignant lymphoma, 11 lesions were found . The following were found in one patient each: large lymphomatous tumours, a large lymphomatous ulcer, multiple small polypoid lesions, multiple lymphomatous polyposis; and colorectal cancer or adenoma in six patients . However, the autopsy findings in patients with both diseases were mostly pseudomembrane formation or ulcers due to fungal and/or bacterial infection . It is concluded that accurate endoscopic diagnosis of lower intestinal lesions in patients with leukaemia or malignant lymphoma is essential for staging and treatment of these diseases and for determining their prognosis . Most lesions in leukaemia are aphthoid and small ulcers are due to leukaemic infiltration or antibiotics; most lesions in malignant lymphoma are elevated lesions such as cancer, adenoma or lymphomatous lesions as determined by endoscopy . This is in contrast to pseudomembrane formation or ulcers due to fungal and/or bacterial infection which are detected at autopsy. Mo Med, 1998 Oct, 95(10), 576 - 82 Challenging questions in treating bronchitis; Bode FR; Whatever facts we gather and no matter how many we have, you and I must eventually put the journal down and pick up our stethoscope, pen, and prescription pad and go to work . Hopefully we can do better than, "Therapy is not uniform and specific antibiotic regimens are usually selected based on local tribal custom." We can discard an old paradigm, "The absence of data bears no relation to the strength of opinion." Personally, I have used these new scientific data before I reached my conclusion . I have developed 10 points to structure my new approach . I invite you to compare my conclusions to yours . 1 . In acute bronchitis, in otherwise healthy adults, my preference is to not prescribe an antibiotic . If I do, it is not over the phone . You should want to see and examine the patient . If there are no helpful hints to etiology, I choose a newer macrolide for those under age 50 and use a short course, five-seven days . For patients over age 50, especially if they are "healthy smokers," consider a short course of cefuroxime . (You can see, even in these acute bronchitis patients, you want an antibiotic effective against today's pathogens.) 2 . In all chronic bronchitis patients, prevention of further damage to the airways should be attempted by instituting a program of smoking cessation and appropriate immunizations against influenza and pneumococcus . 3 . Treatment outcomes will also improve if we recognize that in some patients the progressing SOB, cough, and increasing sputum production are due to congestive heart failure and not due to infection . I try to think about congestive heart failure in all of my patients, but especially in those with known heart disease and cardiomegaly on their chest x-ray . 4 . Routine pulmonary function testing is important in smoking patients . Physicians underestimate the degree of obstruction present when they rely on physical exam alone . Hopefully long before the patient's acute illness you have established whether or not obstruction is present . This information helps identify the high risk patient for not only recurrent bouts of infection but also those at increased risk for lung cancer . 5 . We will have more success in treating AECB when we elect to use an antibiotic only for patients with at least two of the following three cardinal symptoms: increased dyspnea, increased sputum production, and increased purulent sputum . COPD patients have many days when they feel more SOB . To use this or any one sign as the sole indication for starting an antibiotic has been proven not to make a statistically significant difference in outcome in most patients . Also, the value of prophylactic antibiotic therapy has not been established . 6 . When airflow obstruction is moderately severe or more pronounced, AECB should usually be treated with oral steroids . Other measures such as chronic bronchodilator therapy, supplemental and home oxygen use, and pulmonary rehabilitation have been extensively reviewed elsewhere. Jpn J Clin Oncol, 1998 Sep, 28(9), 571 - 3 Neutropenic colitis as a complication of high-dose chemotherapy for refractory testicular cancer; Kawai K et al.; A 44-year-old man received high-dose chemotherapy with carboplatin, etoposide and cyclophosphamide followed by autologous peripheral-blood stem-cell transplantation for treatment of refractory nonseminomatous testicular cancer (seminoma plus choriocarcinoma) . The patient developed fever, watery diarrhea and abdominal pain at 10 days after the initiation of high-dose chemotherapy . Radiological examinations revealed adynamic ileus with thickened colon and small bowel wall and increasing ascites over the next 3 days . The patient subsequently suffered from disseminated intravascular coagulation, renal failure and hyperbilirubinemia despite systemic antibiotic therapy . Intensive medical care could barely avoid the fatal outcome . Neutropenic colitis has been recognized as a complication of acute leukemia or aplastic anemia . The present case indicates that this serious gastrointestinal complication can occur under profound neutropenic conditions induced by intensive chemotherapy for solid cancer. Scand J Infect Dis, 1998, 30(3), 301 - 3 Clinical cowpox cases in Norway; Tryland M et al.; In 1994, a human and a feline case of cowpox virus infection appeared in the western part of Norway . Cowpox has not been diagnosed with certainty in Norway since the beginning of this century, when it was associated with the use of cowpox virus as a vaccine against smallpox . The human infection manifested as a spontaneously emerged, severe ulceration at the medial angle of the right eye in a 37-y-old woman, and developed into a relatively severe dermatitis . The ulcer healed slowly, leaving a scar . The feline infection was represented by a febrile, dehydrated and anorectic 6-months-old non-pedigree short-hair, with crater-like ulcers all over the body . After antibiotic and fluid therapy, revision of the skin lesions and amputation of a gangrenous toe, the cat recovered . Electron microscopy of the isolates and cultivation of virus on chorioallantoic membrane of chicken embryos confirmed the suspicion of cowpox virus infection. Ther Umsch, 1998 Sep, 55(9), 551 - 4 {Therapy of acute variceal hemorrhage and spontaneous bacterial peritonitis in liver cirrhosis}; Guldenschuh I; Spontaneous bacterial peritonitis (SBP) and varices bleeding are the most dangerous complications of liver cirrhosis . Symptoms of SBP are often nonspecific . SBP is diagnosed in the presence of more than 250 granulocytes/ml ascites and/or positive ascites cultures . Antibiotic prophylactic therapy is indicated after the first episode of SBP or primarily if ascites proteins is low (< 10 g/l) . The varices bleeding should by treated endoscopically . In case of bleeding portal venous pressure can be lowered by infusion of somatostatin or vasopressin long-active analogues . In long-term therapy of portal hypertension non-selective betablockers or nitrates are effective. Ital J Gastroenterol Hepatol, 1998 Aug, 30(4), 370 - 4 Strategy for the retreatment of failed Helicobacter pylori eradication therapy: a case series; Battaglia G et al.; BACKGROUND: Helicobacter pylori eradication therapy can be unsuccessful in 5 to 20% of patients . AIM: To investigate the validity of a strategy using triple therapies for the retreatment of patients with eradication failure, avoiding retreatment with antibiotics prone to induce resistance after use in the first treatment . PATIENTS AND METHODS: From a consecutive sampling of 108 patients still Helicobacter pylori-positive after a first course of antibiotic-based treatment, 74 (68.5%) agreed to a second course of triple therapy . Group 1 (N = 17): treatment failures on an imidazole (1)-based therapy were retreated with clarithromycin (C)-based regimen; Group 2 (N = 28): failures on a C-based therapy with an I-based regimen; Group 3 (N = 7): failures on an IC-based therapy using an I-based regimen and Group 4 (N = 22): failures on a non-I/non-C based therapy with either an I-based, C-based or IC-based regimen . The presence of Helicobacter pylori was assessed by histology and the CLO-test at study entry and two months after stopping therapy . RESULTS: Nine patients were withdrawn from the study (12.2%) due to a lack of end point endoscopy . Helicobacter pylori was cured after the second course of therapy in all but seven patients {10.7% failure by Per Protocol analysis, 21.6% by Intention-To-Treat analysis} . No statistically significant differences were found between the four groups (Group 1: 92.9% PP, 76.5% ITT; Group 2: 90.9% PP, 71.4% ITT; Group 3: PP and ITT 85.7%; Group 4: PP and ITT 86.4%) . Minor adverse events were experienced in nine, none of whom required withdrawal from the drug therapy . CONCLUSIONS: A second course of triple therapy with alternate antibiotics effectively eradicated Helicobacter pylori, with only very few treatment failures . This suggests that the therapeutic strategy employed may be recommended. J Clin Invest, 1998 Oct 15, 102(8), 1591 - 8 HLA-restricted, processing- and metabolism-independent pathway of drug recognition by human alpha beta T lymphocytes; Zanni MP et al.; T cell recognition of drugs is explained by the hapten-carrier model, implying covalent binding of chemically reactive drugs to carrier proteins . However, most drugs are nonreactive and their recognition by T cells is unclear . We generated T cell clones from allergic individuals specific to sulfamethoxazole, lidocaine (nonreactive drugs), and cef-triaxone (per se reactive beta-lactam antibiotic) and compared the increase of intracellular free calcium concentration ({Ca2+}i) and the kinetics of T cell receptor (TCR) downregulation of these clones by drug-specific stimulations . All drugs tested induced an MHC-restricted, dose- and antigen-presenting cell (APC)-dependent TCR downregulation on specific CD4(+) and CD8(+) T cell clones . Chemically nonreactive drugs elicited an immediate and sustained {Ca2+}i increase and a rapid TCR downregulation, but only when these drugs were added in solution to APC and clone . In contrast, the chemically reactive hapten ceftriaxone added in solution needed > 6 h to induce TCR downregulation . When APC were preincubated with ceftriaxone, a rapid downregulation of the TCR and cytokine secretion was observed, suggesting a stable presentation of a covalently modified peptide . Our data demonstrate two distinct pathways of drug presentation to activated specific T cells . The per se reactive ceftriaxone is presented after covalent binding to carrier peptides . Nonreactive drugs can be recognized by specific alphabeta+ T cells via a nonconventional presentation pathway based on a labile binding of the drug to MHC-peptide complexes. Biophys J, 1998 Nov, 75(5), 2135 - 46 Heterodimer formation and crystal nucleation of gramicidin D; Burkhart BM et al.; The linear pentadecapeptide antibiotic gramicidin D is a heterogeneous mixture of six components . Precise refinements of three-dimensional structures of naturally occurring gramicidin D in crystals obtained from methanol, ethanol, and n-propanol demonstrate the unexpected presence of stable left-handed antiparallel double-helical heterodimers that vary with the crystallization solvent . The side chains of Trp residues in the three structures exhibit sequence-specific patterns of conformational preference . Tyr substitution for Trp at position 11 appears to favor beta ribbon formation and stabilization of the antiparallel double helix that acts as a template for gramicidin folding and nucleation of different crystal forms . The fact that a minor component in a heterogeneous mixture influences aggregation and crystal nucleation has potential applications to other systems in which anomalous behavior is exhibited by aggregation of apparently homogeneous materials, such as the enigmatic behavior of prion proteins. Arthroscopy, 1998 Oct, 14(7), 717 - 25 Septic arthritis of the knee following anterior cruciate ligament reconstruction: results of a survey of sports medicine fellowship directors; Matava MJ et al.; To determine the incidence of joint sepsis following anterior cruciate ligament (ACL) reconstruction and the prevailing attitudes toward its treatment, we surveyed the directors of Sports Medicine Fellowship programs about their practices in treating and preventing this complication . Of the 74 surgeons surveyed, 61 (82%) responded . These 61 surgeons performed an average of 98 ACL reconstructions yearly; 31 (51 %) routinely used a drain after ACL surgery, 18 (30%) had treated an ACL infection within the past 2 years, and 26 (43%) had treated an infection within the past 5 years . There was no significant difference in the number of infections and the surgeons' case load, graft choice, or method of reconstruction . Fifty-two surgeons (85%) selected culture-specific intravenous (IV) antibiotics and surgical irrigation of the joint with graft retention as initial treatment for the infected patellar tendon autograft, and 39 (64%) chose this regimen to treat the infected allograft . For the resistant infection unresponsive to initial treatment, IV antibiotics with surgical irrigation and graft retention were also selected as the most common treatment combination for 25 (39%) of the 61 respondents . After graft removal, the earliest a revision procedure would be considered was 6 to 9 months . The results of this survey confirm the widely held belief that septic arthritis of the knee is a relatively rare complication following ACL reconstruction . Once an infection is encountered, culture-specific IV antibiotics and surgical joint irrigation with graft retention are recommended as initial treatment . Graft excision and hardware removal is considered only for those infections resistant to initial treatment and for the infected allograft. Eur J Radiol, 1998 Sep, 28(2), 167 - 70 Ultrasound-guided interventional procedures in splenic abscesses; Chou YH et al.; The results of ultrasound (US)-guided interventional procedures over a period of 12 years in 21 consecutive patients with splenic abscess were reviewed . The interventional procedures were done with 21- or 18-gauge needles for aspiration of relatively small abscesses (< 3.5 cm) in eight patients and with an 8.3-9.0 French pigtail catheter for continuous drainage in 13 patients with larger abscesses (> or = 3.5 cm) . In some patients, multiple abscesses were treated separately according to their various sizes . More than one catheterization were done in three patients because of detached catheter or recurrent abscesses . The interventional procedures were followed by at least eight weeks of appropriate antibiotic therapy . Only one patient had the complication of minimal subcapsular hematoma which needed no further treatment . All the patients had uneventful clinical courses . US-guided interventional procedure proved to be a treatment-of-choice for splenic abscess, and may avoid splenectomy by conserving the spleen. Ear Nose Throat J, 1998 Sep, 77(9), 737, 740 - 2 Autoinflation: historical highlights and clinical implications; Stangerup SE; In 1563, Eustachius first described the tube that came to be named for him . In 1704, Valsalva described the maneuver that bears his name, and in 1836 Deleau became one of the first to advocate infusion of pure air through the eustachian tube using a catheter . Politzer devised his own method for actively inflating the middle ear without using a catheter in 1863 . Most modern studies examining the use of autoinflation in the treatment of secretory otitis media have shown a beneficial effect, with effusion being cleared in 52 to 62% of ears up to nine months after the treatment . In two studies, no effect of autoinflation could be demonstrated, and in one publication the autoinflation group had deteriorated compared to the control group . In light of the fact that secretory otitis media is a benign and transient condition, that treatment with antibiotics or insertion of ventilation tubes is not without problems, and that the chance of improving the condition by autoinflation is approximately 50%, it is concluded that autoinflation should be considered first-line treatment, before antibiotic or surgical treatment is planned. Infect Immun, 1998 Nov, 66(11), 5132 - 9 Differential growth characteristics and streptomycin susceptibility of virulent and avirulent Mycobacterium tuberculosis strains in a novel fibroblast-mycobacterium microcolony assay; Byrd TF et al.; The ability to spread from cell to cell may be an important virulence determinant of Mycobacterium tuberculosis . An in vitro assay was developed to characterize this ability among four strains of M . tuberculosis: the attenuated strain H37Ra, the virulent strains H37Rv and Erdman, and a virulent clinical isolate (Stew) . Confluent monolayers of human skin fibroblasts were infected with these strains and overlaid with agar-medium . M . tuberculosis infection developed over 21 days as microcolonies originating within the plane of the fibroblasts . Microcolonies of the virulent strains had an elongated appearance and exhibited extensive cording . The cords appeared to invade adjacent cells within the plane of the monolayer . Microcolony diameter of the Erdman strain was significantly larger than that of the other virulent strains, indicating that virulent strains can have distinguishing phenotypes in this assay . In contrast, avirulent H37Ra microcolonies were rounded and noncorded . H37Ra microcolonies were significantly smaller than those of the virulent strains . Microcolony diameter of the virulent strains was not reduced by the extracellularly acting antibiotic streptomycin at concentrations of up to 5.0 microgram/ml . In contrast, H37Ra microcolony size was reduced at concentrations as low as 0.5 microgram/ml . Growth of all strains was similarly inhibited by 1.0 microgram of streptomycin per ml in fibroblast-conditioned tissue culture medium alone . When fibroblasts were infected with the M . tuberculosis strains without an agar overlay, with and without streptomycin, numbers of CFU mirrored the changes observed in the microcolony assay . There was a statistically significant decrease in H37Ra CFU compared to virulent strains after treatment with streptomycin . These differences between H37Ra and virulent strains in human fibroblasts suggest that H37Ra may be lacking a virulence determinant involved in cell-to-cell spread of M . tuberculosis. J Nat Prod, 1998 Oct, 61(10), 1248 - 51 Tenuecyclamides A-D, cyclic hexapeptides from the cyanobacterium Nostoc spongiaeforme var . tenue; Banker R et al.; Four modified cyclic hexapeptides, tenuecyclamides A-D (1-4), were isolated along with the known antibiotic, borophycin (5), from the methanol extract of Nostoc spongiaeforme var . tenue (TAU strain IL-184-6) . The planar structure of tenuecyclamides A-D (1-4) was determined by homonuclear and inverse-heteronuclear 2D-NMR techniques as well as by high-resolution mass spectrometry measurements . The absolute configuration of the asymmetric centers was studied by Marfey's method for HPLC . The stereochemistry of the asymmetric centers in tenuecyclamides A and B (1 and 2) could not be fully determined, while that of tenuecyclamides C and D (3 and 4) was unambiguously determined. Semin Oncol, 1998 Oct, 25(5), 552 - 61 Hematopoietic growth factors in the reduction of chemotherapeutic toxicity; Johnston EM et al.; Neutropenia is the most common dose-limiting toxicity of conventional chemotherapy . The colony-stimulating factors (CSFs), granulocyte (G)-CSF and granulocyte-macrophage (GM)-CSF, stimulate proliferation and maturation of myeloid progenitors and have been effective in reducing neutropenia and its complications . The primary use of CSFs in patients receiving chemotherapy for small cell lung cancer has resulted in a reduction in the incidence of febrile neutropenia, a decrease in the duration of grade IV neutropenia, and a reduction in hospitalization time and antibiotic use . Although CSF use allows for higher dose intensity, a survival benefit has not been proven . The use of CSFs after the occurrence of neutropenic fever decreases the duration of grade IV neutropenia, but effects on hospitalization and antibiotic use are less well-defined . The therapeutic use of CSFs in the setting of established neutropenia, regardless of the presence or absence of fever, is not supported in the literature . The administration of CSFs to patients with acute myeloid leukemia is safe in that no trial has demonstrated evidence of leukemic stimulation with these drugs . As in other settings, the duration of neutropenia is shortened if CSFs are used postchemotherapy with evidence of clinical benefit . CSFs also decrease chemotherapeutic toxicity via other mechanisms . The use of G-CSF reduces the incidence of mucositis, in normal donors enhances the yield of leukapheresis for granulocyte transfusion, and is beneficial in the autologous transplant setting . These effects of CSFs in mitigating chemotherapeutic toxicity are reviewed. Hinyokika Kiyo, 1998 Aug, 44(8), 547 - 52 {Short-term intravesical instillation of pirarubicin (THP) in prophylactic treatment after transurethral resection of superficial bladder tumor}; Kuroda K et al.; We conducted a prospective randomized controlled study on the prophylactic effects of short-term intravesical instillation of pirarubicin (THP) against recurrence to determine the effective administration schedule . All patients gave their informed consent . The subjects included bladder cancer patients who had pTa or pT1, and G1 or G2 cancer, and became tumor-free after transurethral resection of the bladder tumor (TUR-BT) . After dissolving 30 mg of THP into 5 ml of distilled water, physiological saline was added to adjust the total volume to 50 ml, which was then instilled into the bladder, and was retained for 5 minutes . The schedule of instillation was for daily for 7 consecutive days from the day of TUR-BT and subsequently once a week for 10 weeks, 17 times in total for Group I, and once every two weeks for 6 months (12 times) starting 2 weeks after TUR and subsequently once a month until one year had passed after surgery (6 times), 18 times in total for Group II . The total number of cases was 69 (36 in Group I, 33 in Group II) . The tumor-free ratios determined by the Kaplan-Meier analysis were 93.9% in Group I and 72.7% in Group II for one year, and 86.8% in Group I and 59.5% in Group II for two years . There was a statistically significant difference in the tumor-free ratios between the two groups by the generalized Wilcoxon test and the Log rank test (p = 0.0145 and 0.0107, respectively) . Multivariated analysis using Cox's comparison hazard model produced p-values of 0.0002, 0.0007, 0.0009 and 0.0040 in the order of therapeutic mode, initial onset/recurrence, stage and number of tumor . Adverse events that forced discontinuation of the therapy for a while occurred in 4.3% . These results demonstrated that short-term intensive intravesical instillation of THP immediately after TUR-BT was a safe and effective therapy. J Pak Med Assoc, 1998 Apr, 48(4), 100 - 3 Haemolytic uraemic syndrome in childhood: an experience of 7 years at the Aga Khan University; Ibrahim SH et al.; We reviewed the case records of all children admitted to the Aga Khan University Hospital (AKUH) with a diagnosis of Haemolytic Uremic Syndrome (HUS) over a 7 year period (July, 1988-June, 1995) . A total of 33 patients were admitted to the Pediatric ward at (AKUH) with a median age of 16 months (range 4 months-9 years) . 97% cases identified were of the classic variety and no familial case was identified . The mean duration of illness was 27 days, 39% had an illness > 28 days . Diarrhoea and prior antibiotic used was in 97% patients . Oliguria at admission was seen in 52.5% and seizures in 24% of cases . Thrombocytopenia, anemia and leucocytosis at admission was present in > 72% of children . Hyponatremia was present in 42% while acidosis, hypocalcemia and hyperkalemia was seen in 30% of children . Despite optimal management and peritoneal dialysis in 14 (42%) patients, 8 (24%) died . No specific relationship was found between mortality and any clinical or laboratory feature at presentation . Our data highlights the importance of HUS in the Pediatric age group and the need for further studies to delineate risk factors for adverse outcome. Unfallchirurg, 1998 Aug, 101(8), 649 - 54 {Vacuum sealing as carrier system for controlled local drug administration in wound infection}; Fleischmann W et al.; Between 1.4.96 and 1.3.97 27 patients with acute infections of bone and soft tissues (n = 13), chronic osteomyelitis (n = 8), and chronic wounds (n = 6) were treated by using Instillation-Vacuum-Sealing . Polyvinylalcohol sponges with drainage tubes were used to cover the internal or external wound surfaces which resulted from surgical debridement . Having hermetically covered the wound with a transparent film dressing a vacuum source generated a partial vacuum in the sponge which was modified according to the type of wound between 20 and 80 kPa . Several times daily, the vacuum line was blocked and, in an alternating fashion, antiseptic or antibiotic solution instilled for 30 minutes . Then, the vacuum was reestablished and the fluids drained from the wound . Seven days later, intermittent drug instillation was stopped and there was either immediate or delayed wound closure by secondary suturing (n = 22), skin grafting (n = 3) or spontaneous epithelialization (n = 2) . During a follow-up from the beginning of the instillation treatment of 4.2 (3-14) months there was one recurrency of infection in a patient with chronic osteomyelitis. Schweiz Med Wochenschr, 1998 Aug 29, 128(35), 1298 - 304 {Political and economic aspects of heart transplantation}; Carrel T et al.; Organ transplant, like any other area of modern medicine, has manifold implications for human values and ethics, while sociology, law, economics and politics are equally involved . A brief review is presented of the political and economic aspects of cardiac transplantation, covering a short overview of current Swiss legislation, the problem of organ allocation, limitation of transplant centres, restriction of transplant medicine to public hospitals, cost of transplant procedures and subsequent treatment, and costs generated by alternative options such as ventricular assist devices . Current transplant medicine is affected by a growing shortage of organs, despite the fact that organ transplantation is generally well accepted by the public . On the other hand, the steadily growing disproportion between the number of organs available and the overall number of potential recipients is a source of concern for transplant surgeons and the medical profession, as well as the community at large . To be able to face these significant problems, transplant centres should offer all aspects of treatment for heart failure . In particular, before cardiac transplant is offered to a patient, all aspects of more conservative treatment should be exhaustively discussed . The economic aspects of each type of transplantation are usually discussed, but the cost of a transplant procedure should be compared with that of conventional treatment . The increasing use of all currently available options (including mechanical and antiarrhythmic bridging) makes a critical confrontation with the economic implications necessary . Assumptions based on current literature suggest that heart transplant generates additional costs of approximately CHF 50,000 per year of extended life . The treatment of heart failure involves additional costs of CHF 20,000 per year, provided only a few hospitalizations are necessary . CHF 80,000 of the cost of a heart transplant is refunded . Medical treatment in the first year after transplant mainly includes immunosuppressive drugs, antibiotic and antihypertensive medication, involving additional costs of CHF 20,000 . The future will require complete use of all conventional treatment modalities, recipient selection, strengthened social rehabilitation and a quality control database, as well as consensual recommendations and coordination in research, follow-up and basic treatment. Chirurg, 1998 Aug, 69(8), 813 - 20 {Intra-abdominal abscess}; Witzigmann H et al.; In more than 80% of cases, intra-abdominal abscesses derive from an intra-abdominal organ, and in most cases they develop after operative procedures . Regarding anatomy, intra-abdominal abscesses can be divided into intra-peritoneal and visceral abscesses and those located in the anterior retroperitoneal space . Despite improvements in ultrasonography, CT is still the most effective method in diagnosis and therapy . Percutaneous ultrasound or CT-guided drainage is a therapy characterized by low procedural morbidity and is successful in 80% of cases if strict criteria are met . Complicated abscesses and those cases in which the underlying disease has to be treated require surgical intervention . Most liver abscesses are treated interventionally; in abscesses of the pancreas or spleen and in Crohn's disease, surgery is necessary . The combination with sufficient antibiotic drug therapy is very important . Specific infectious diseases appearing as intra-abdominal conglomerates (tuberculosis, actinomycosis, amebiasis) lead to a delay in diagnostics because of their scarcity and are characterized by special patho-anatomical, diagnostic and therapeutic features . The crucial thing is to take a specific infection into consideration. Pharmacol Res, 1998 Sep, 38(3), 225 - 30 Effects of L-histidinol on the antitumour activity and acute cardiotoxicity of doxorubicin in mice; Al-Shabanah OA et al.; L-Histidinol (LHL), a structural analogue of the essential amino acid l-histidine, can improve the therapeutic index of antimetabolites and alkylating agents . The objective of the study was to determine whether LHL would modulate the antitumour activity and acute cardiotoxicity of the anthracycline antibiotic, doxorubicin (DOX) . LHL (1.0 mM) potentiated the cytotoxicity of DOX (0.05-0.8 microg ml-1) in cultured Ehrlich ascites carcinoma (EAC) cells . LHL (250 mg kg-1, i.p.) administered for five consecutive doses at 2-h intervals starting 2 h before DOX (5 mg kg-1, i.p.) single injection, enhanced the antitumour activity of DOX in EAC-bearing mice as manifested by a significant increase in average life span and cure rate of mice . In normal mice, LHL, in the same dose regimen, could not alter the acute cardiotoxicity and lethality of DOX (10 mg kg-1, i.p.) . The present data indicate that LHL may improve the therapeutic efficacy of DOX in EAC-bearing mice without compromising its toxicity . Also, our finding supports the LHL/anticancer drug combination approach . Neurology, 1998 Oct, 51(4), 1200 - 2 Coma in fulminant pneumococcal meningitis: new MRI observations; Vernino S et al.; We report a 45-year-old man with fulminant pneumococcal meningitis . Fluid attenuated inverse ratio MR images showed the ravaging consequences of occlusive vasculopathy and a transient purulent basal exudate . Bilateral thalamic lesions may have explained the failure to awaken despite appropriate antibiotic therapy. Rev Prat, 1998 Mar 1, 48(5), 519 - 22 {Prevention of infectious endocarditis}; Bouhour D et al.; Although prophylaxis with antibiotics cannot avoid all cases of infectious endocarditis, it remains the main approach capable of reducing the frequency of this severe disease . It consists in using an adapted antibiotic cover in situations exposing to bacteraemia in patients at-risk with known cardiopathy . In France, recommendations have been established by a consensus conference in 1992 . The fact that the incidence of this infection has not decreased merits recalling these recommendations. Rev Prat, 1998 Mar 1, 48(5), 492 - 6 {The contribution of experimental models to the physiopathology and treatment of infectious endocarditis}; Fantin B; The model of experimental endocarditis can be used for the investigation of the different steps in the physiopathologic process leading to the formation of the infected cardiac vegetation . It has also greatly contributed to the knowledge of the characteristics of the infected vegetation . These data allow a better understanding of the therapeutic consequences (both preventive and curative) of the physiopathologic process. Nippon Rinsho, 1998 Sep, 56(9), 2365 - 8 {Ischemic disease of the intestine}; Suzuki K et al.; With the remarkable progress in diagnostic techniques, the recent increase in the incidence of arteriosclerosis and the gradually aging population, a great deal of attention is now being focused on intestinal ischemia and this disease has come to be regarded as one of the clinically important pathological conditions . From the clinic aspect, special attention should be directed to the artery which is involved in intestinal ischemia . Furthermore acute superior mesenteric arterial ischemia (SMA ischemia), ischemic colitis, non-occlusive mesenteric ischemia (NOMI) require serious attentions . Few specific findings of these pathological conditions can be obtained in general examinations, therefore angiography is the most useful technique for making difinitive diagnoses . SMA ischemia and NOMI are progressive diseases and their prognoses are poor . The progress of ischemic colitis is gradual and the conservative therapy consisting of fasting, drip infusion and antibiotic administration is generally effective in treating this disease. Int J Technol Assess Health Care, 1998 Summer, 14(3), 535 - 43 Home drug infusion therapy . A literature update; Balinsky W et al.; This paper is a literature review and update of home drug infusion therapy (HDIT) in the United States . It concentrates on cost-effectiveness studies of parenteral antibiotic therapy administered in an outpatient setting . This update is timely because Medicare and other payors are under the pressure of cost containment with respect to this modality . Additionally, managed care is redefining reimbursement programs, which will affect HDIT in the future. Yeast, 1998 Sep 15, 14(12), 1127 - 38 Functional analysis of yeast essential genes using a promoter-substitution cassette and the tetracycline-regulatable dual expression system; Belli G et al.; A promoter-substitution cassette has been constructed that allows one-step substitution of chromosomal gene promoters for the tetracycline-regulatable tetO promoter in yeast cells, which uses kanMX4 as selective marker for geneticin resistance . Oligonucleotides for PCR amplification of the cassette are designed to allow homologous recombination through short flanking regions of homology with the upstream sequences of the chromosomal gene, upon transformation of target cells . By testing three essential genes of chromosome XV (YOL135c, YOL142w and YOL144w), the system causes tetracycline-dependent conditional growth of the cells, being modulatable by intermediate concentrations of the effector . Analysis of terminal phenotypes of the promoter-substituted cells in the presence of the antibiotic may facilitate functional analysis of essential orphan genes. J Commun Disord, 1998 Sep-Oct, 31(5), 423 - 34; quiz 434-5 Sensorineural hearing loss caused by mitochondrial DNA mutations: special reference to the A1555G mutation; Usami S et al.; Mutations in mitochondrial DNA, which are maternally inherited, have been thought to be one of the causes of sensorineural hearing loss . Two mitochondrial mutational sites (A1555G, A7445G) have been reported to be responsible for non-syndromic hearing impairments . The A1555G mutation causes increased susceptibility to aminoglycoside antibiotic-induced hearing loss as well as non-syndromic sensorineural hearing loss . Our wide screening study showed that there may be a great number of subjects within the Japanese population who have the A1555G mutation . Recent reports suggest that high-risk populations may exist throughout the world . The aminoglycoside-induced hearing loss associated with a mitochondrial mutation is commonly bilateral, symmetric, high frequency involved, and is sometimes associated with progressive sensorineural hearing loss. Orig Life Evol Biosph, 1998 Oct, 28(4-6), 571 - 82 Functional phylogeny: the use of the sensitivity of ribosomes to protein synthesis inhibitors as a tool to study the evolution of organisms; Briones C et al.; In order to study the functional phylogeny of organisms, forty different protein synthesis inhibitors with diverse domain and functional specificities have been used to analyze forty archaeal, bacterial and eukaryotic translational systems . The inhibition curves generated with the different ribosome-antibiotic pairs have shown very interesting similarities among organisms belonging to the same phylogenetic group, confirming the feasibility of using such information in the development of evolutionary studies . A new method to extract most of the information contained in the inhibition curves is presented . Using a statistical treatment based on the principal components analysis of the data, we have defined coordinates for the organisms which have allowed us to perform a functional clustering of them . The phenograms obtained are very similar to those generated by 16/18S rRNA sequence comparison . These results prove the phylogenetic value of our functional analysis and suggest an interesting intersection between genotypic and phenotypic (functional) information. Therapie, 1998 Mar-Apr, 53(2), 113 - 20 {Drug prescription and utilization in Morocco}; Simon N et al.; The aim of this study was to assess drug prescription and utilization in Morocco 8 years after the statement of the Action Program for Essential Drugs . To evaluate the role of essential drugs in these prescriptions, a study of about 600 prescriptions and questionnaires sent to a random sample of 111 prescribers and a series of visits with the investigator as a neutral observer was undertaken . The average number of drugs prescribed was 3.27, which reflected the feelings of most of the clinicians, for whom 3 drugs per patient is the required number . The number of drugs prescribed is lower in the public health structure (2.0 +/- 0.14 depending on the type of institution: hospital or primary health care centre) . Specialties from the national list of essential drugs accounted for 15.48 per cent of all drugs which is to be compared with 16.2 per cent of the clinicians stating knowledge of the action programme for essential drugs . In public structures, these prescriptions ranged between 29.8 per cent and 82.4 per cent of the essential drugs (WHO general list) . The length of the visit ranged between 3.27 +/- 0.96 min and 4.87 +/- 1.04 min according to the health centres and prescriptions included at least one antibiotic in 47.5 per cent of cases (25 per cent to 64 per cent) . At least one antibiotic was prescribed in 43.3 per cent of cases in the study of prescriptions and 17.3 per cent of prescriptions included at least one injectable drug . The average cost of one prescription was 146.25 dirhams (ranging between 4 and 1200 dirhams = US $17) . According to 68.6 per cent of the prescribers, the patients felt there to be a strong relation between efficacy and cost . Among the prescription motivations, cost ranked above availability of the drug and after efficacy. J Chir (Paris), 1997 Dec, 134(7-8), 271 - 4 {The value of peroperative colonic lavage in urgent colonic surgery . Apropos of 54 patients}; Meyer C et al.; The effects of on-table colonic irrigation followed by primary large bowel resection and anastomosis for emergency left colonic disease were prospectively studied in 54 patients . PATIENTS AND METHODS: Eighteen patients had a diverticular sigmoiditis complicated by localized (8) or generalized (4) peritonitis, 6 presented a complete sigmoid obstruction . Thirty six patients had a left colonic occlusive (33) or perforated (3) cancer . Anterograde colonic irrigation was carried out with a mean volume of 7.7 l . All patients received a double or triple antibiotic combination . The anastomosis was handsewn in 33 cases and stapled (Knight-Griffen) in 21 . Seven patients with severe peritonitis had a proximal transitory stoma which was closed within 4 months . RESULTS: Two patients (3.7%) died postoperatively, one for anastomotic dehiscence and the second for evisceration . We observed 7 cases of hypothermia (< 34 degrees C) during the irrigation . Six patients developed a sepsis of the surgical wound, 2 a septicemia and l an abscess in the right iliac fossa which was percutaneously drained . All complications had a favourable outcome . CONCLUSION: This study confirms that in selected cases a single stage surgery for colonic emergencies preceded by on-table irrigation grants good results and is a safe and effective alternative to Hartmann's procedure. Medicine (Baltimore), 1998 Sep, 77(5), 337 - 44 Infected cardiac myxoma . Case report and literature review; Revankar SG et al.; We present a case of a left atrial myxoma infected with Porphyromonas asaccharolytica in a 55-year-old man, successfully treated with surgical excision and a brief course of antibiotic therapy . Infected cardiac myxomas are extremely rare, with only 39 cases previously reported . They can be difficult to diagnose due to their protean clinical manifestations, which can often be seen in uninfected myxomas as well . We suggest that blood cultures and careful pathologic examination be performed in all cases of cardiac myxoma with constitutional symptoms . However, fever and elevated sedimentation rate are significantly more common in infected tumors . Organisms responsible are similar in distribution to those causing bacterial endocarditis . Emboli, though frequent, may not be more common in infected than uninfected myxomas . Case reports have become more common since the development of better diagnostic techniques . Echocardiography, especially by the transesophageal approach, is the diagnostic procedure of choice, and sensitivity approaches 100% . Surgical excision is curative and generally has low morbidity and mortality. Zhongguo Zhong Xi Yi Jie He Za Zhi, 1996 Nov, 16(11), 658 - 60 {Clinical and experimental study on bushen cong-er tablet in treating sensorineural hearing loss}; Lin WS et al.; According to the "Kidney has its orfice in the ear" in TCM theory, the authors adopted Bushen Cong-er tablet, a TCM preparation with the treating principles of the Kidney reinforcing and blood circulation promoting to remove stasis as well as to open up the apertures in treating 310 cases of sensorineural hearing loss . The results showed that therapeutical effect was satisfactory . The total effectve rate was 71.9% . Animal experiment also demonstrate the drug could prevent and cure the aminoglycoside antibiotic ototoxic hearing loss, could adjust the cochlear cyclic neucleotides as well as its SOD level and reduce the LPO level, raise the thyroid function and the function of sexual gland. J R Soc Med, 1998 Jul, 91(7), 360 - 4 Targeting of dornase alpha therapy in adult cystic fibrosis; Ledson MJ et al.; Although dornase alpha (recombinant human DNase) can thin the viscid pulmonary secretions of cystic fibrosis (CF), clinical trials in groups of unselected patients have shown only modest average improvements in pulmonary function . The product is very expensive, so in conjunction with purchasers we designed selection criteria and a protocol for a 2-week trial to target CF individuals who might gain most benefit . Treatment was to be continued in those showing > or = 10% improvement in pulmonary function . Those who had a trial of dornase alpha were followed up for 2 years . Of 25 patients who had a 2-week trial of dornase alpha, 17 met the criteria for continuation (average gain in forced expiratory volume 37%) . The 11 of these who were still alive at 2 years had a greater initial average FEV1 improvement than those who had died (45% versus 22%), and still had an average improvement of 31% at 2 years . The 8 patients who did not meet the criteria for continuation were older and had required fewer intravenous antibiotic courses . All these were alive at 2 years with unchanged clinical indices . This method of selection for dornase alpha treatment allows targeting to those who gain most benefit without disadvantaging the remaining patients . Furthermore, production of such guidelines in conjunction with purchasers obviates funding difficulties and allows rational prescribing. Pediatr Cardiol, 1998 Nov-Dec, 19(6), 468 - 70 Rapamycin (sirolimus) inhibits heart cell growth in vitro; Burton PB et al.; The success of infant and neonatal heart transplantation has increased dramatically since the mid-1980s . This success is due both to improved medical and surgical techniques and better pharmacological management of rejection episodes . We report here the results of in vitro studies designed to investigate the effect of rapamycin (a macrolide antibiotic with potent antirejection activity) on the proliferation of fetal cardiac myocytes . Our data suggest that rapamycin inhibits the proliferation of these cells, which is an effect that appears to be irreversible . This inhibition is relevant to the use of rapamycin in the treatment of rejection episodes in the infant and neonate, in which cardiac myocyte development is incomplete. Proc Natl Acad Sci U S A, 1998 Oct 13, 95(21), 12208 - 13 Identification of a human nuclear receptor defines a new signaling pathway for CYP3A induction; Bertilsson G et al.; Nuclear receptors regulate metabolic pathways in response to changes in the environment by appropriate alterations in gene expression of key metabolic enzymes . Here, a computational search approach based on iteratively built hidden Markov models of nuclear receptors was used to identify a human nuclear receptor, termed hPAR, that is expressed in liver and intestines . hPAR was found to be efficiently activated by pregnanes and by clinically used drugs including rifampicin, an antibiotic known to selectively induce human but not murine CYP3A expression . The CYP3A drug-metabolizing enzymes are expressed in gut and liver in response to environmental chemicals and clinically used drugs . Interestingly, hPAR is not activated by pregnenolone 16alpha-carbonitrile, which is a potent inducer of murine CYP3A genes and an activator of the mouse receptor PXR.1 . Furthermore, hPAR was found to bind to and trans-activate through a conserved regulatory sequence present in human but not murine CYP3A genes . These results provide evidence that hPAR and PXR.1 may represent orthologous genes from different species that have evolved to regulate overlapping target genes in response to pharmacologically distinct CYP3A activators, and have potential implications for the in vitro identification of drug interactions important to humans. Pathology, 1998 Aug, 30(3), 289 - 94 Monitoring of serum aminoglycoside levels with once-daily dosing; Paterson DL et al.; There is considerable confusion as to how to monitor serum aminoglycoside levels when using once-daily dosing . At least five methods are in use in Australia . We prospectively assessed 100 consecutive once-daily courses of gentamicin or tobramycin, during which 120 pre-dose and 213 sets of immediate post-dose and six hour post-dose levels were taken . By using the six hour post-dose level we were able to compare dosage recommendations made using methods known as ALADDIN, DOSECALC and the Australian Antibiotic Guidelines nomogram (AAGN) . There were statistically significant differences in the doses recommended by each method . When comparing each of the three methods, at least 25% of dosage recommendations differed by more than 80 mg per dose . Although we have not been able to determine the clinical significance of these differences, we are concerned that methods used in dosage adjustment of aminoglycosides differ so widely in their recommendations . Presumably the ALADDIN method, which utilises two post-dose levels to determine an area under aminoglycoside concentration-time curve, gives more accurate pharmacokinetic information than methods which rely on a single level . Comparative cost-effectiveness studies of different methods, although in practice difficult to perform, should be undertaken to resolve the optimal management of patients receiving aminoglycosides once-daily. Clin Infect Dis, 1998 Sep, 27(3), 559 - 65 Comparative study of mortality and morbidity in premature infants (birth weight, < 1,250 g) with candidemia or candidal meningitis; Lee BE et al.; Little information is available on long-term neurodevelopment of premature neonates with invasive candidal infections . We retrospectively studied the outcomes for 25 premature neonates (birth weight, < 1,250 g) with candidemia or candidal meningitis (cases) and compared them with 25 neonates matched for birth weight (+/- 100 g) and gestational age (+/- 1 week) (controls) . Durations of antibiotic therapy, artificial ventilation, invasive catheterizations, and hyperalimentation were longer for cases than for controls . Cases had a higher final grade of intraventricular hemorrhage than did controls (median: 3.0 vs . 2.5, respectively; P < .05) . Forty-four percent (11 of 25) of cases and 16% (4 of 25) of controls died (P > .05), and 29% (4 of 14) of surviving cases and 14% (3 of 21) of controls were disabled (P > .05) . More cases had combined mortality and neurodevelopmental disabilities than did controls (60% vs . 28%, respectively; P < .05) . Use of invasive therapies should be minimized for premature neonates at risk for invasive candidal infection that is associated with adverse outcomes. Clin Infect Dis, 1998 Sep, 27(3), 424 - 8 Human granulocytic ehrlichiosis in Europe: clinical and laboratory findings for four patients from Slovenia; Lotric-Furlan S et al.; Febrile illnesses following a tick bite in patients from Slovenia were evaluated for an ehrlichial etiology . A case of acute human granulocytic ehrlichiosis (HGE) was confirmed by seroconversion to the HGE agent or molecular identification of ehrlichial organisms . Acute infection with the HGE agent was confirmed in four patients . None of the patients had detectable antibodies to the HGE agent at their first visit, but polymerase chain reaction analysis was positive for three patients . All four patients subsequently seroconverted to the HGE agent as shown by high titers of antibody . Clinical features and laboratory findings were similar to those in reports from the United States, although the disease course was relatively mild in the Slovenian cases . All patients recovered rapidly and without sequelae, although only two received antibiotic therapy (of whom only one was treated with doxycycline) . HGE is an emerging tick-borne disease in the United States and should now be included in the differential diagnosis of febrile illnesses occurring after a tick bite in Europe. Rev Laryngol Otol Rhinol (Bord), 1998, 119(3), 199 - 201 Unusual extracranial complications of otitis media in a young HIV patient: retropharyngeal and Mouret's abscess; Mevio E et al.; Since the introduction of antibiotic therapy, the incidence of intra- and extracranial suppurative complication of acute and chronic purulent otitis media has sharply decreased . In particular, reports of laterocervical abscesses secondary to this disorder are quite rare, not more than twenty cases of Bezold's or Mouret's abscesses having been reported in the literature during the last ten years . The authors present a case of retropharyngeal and Mouret's abscess developed as a consequence of acute purulent otitis media in a young Aids patient . True otologic manifestations of Aids are rare while the incidental association of otologic disease with Aids is more common . The development of complication in the present case is favoured by the patients severe immunodepression. Aliment Pharmacol Ther, 1998 Sep, 12(9), 881 - 5 Helicobacter pylori eradication and ulcer healing with daily lansoprazole, plus 1 or 2 weeks co-therapy with amoxycillin and clarithromycin; Louw JA et al.; BACKGROUND: Proton pump inhibitor based combination therapy is one standard strategy for Helicobacter pylori eradication . AIM: To compare the eradication and duodenal ulcer healing efficacy of two 2-week, single dose, lansoprazole based combination therapies . METHODS: Healthy adult patients with endoscopically confirmed, H . pylori associated duodenal ulcer disease (3 mm > ulcer < 20 mm) were eligible for the study . All patients received a 14 day course of lansoprazole 30 mg o.m., and were randomized to receive either 7 or 14 days of amoxycillin 1 g b.d . and clarithromycin 500 mg b.d . Patients were endoscoped at entry and 14-17 days later . Symptomatic, unhealed patients received a further 14 days of therapy with lansoprazole 30 mg o.m . Eradication was confirmed a minimum of 28 days after cessation of all therapy by urease reaction and histological assessment of gastric body and antral biopsies (three biopsies each site) . RESULTS: Sixty-two patients were randomized to a treatment arm, of which 58 could be included in an intention-to-treat and key-point-available analysis . H . pylori eradication rates were identical, at 93% (95% CI: 73-98% (1 week), 78-99% (2 week)) . In the combined group, all but 13 ulcers were healed at 2 weeks; six required further therapy because of symptoms, while six of the seven asymptomatic patients went on to heal . CONCLUSION: An eradication regimen, based on a 2-week course of single dose lansoprazole with 1 week of antibiotic co-therapy, is effective in eradicating H . pylori, while the 2 weeks of acid suppression is usually effective in duodenal ulcer healing. Aliment Pharmacol Ther, 1998 Sep, 12(9), 823 - 37 Review article: one-week clarithromycin triple therapy regimens for eradication of Helicobacter pylori; Pipkin GA et al.; BACKGROUND: One-week triple therapies have been endorsed as the treatment regimens of choice for eradication of Helicobacter pylori infection . Those that include clarithromycin appear to be the most effective . AIM: To review reports of triple therapies that include clarithromycin . METHODS: Reports were identified from the literature to May 1998 . The variation between study designs prevents a formal meta-analysis . A measure of the relative efficacies of regimens has, however, been gained by comparison and by pooling of intention-to-treat eradication rates . RESULTS: One hundred an