Antibiotics

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 and ninety-two studies were identified which included 264 treatment arms of a 1-week triple therapy composed of clarithromycin with amoxycillin or a nitroimidazole (metronidazole or tinidazole), and either ranitidine bismuth citrate or a proton pump inhibitor (omeprazole, lansoprazole or pantoprazole) . From reports of these studies, an intention-to-treat H . pylori eradication rate could be determined from 210 treatment arms of 151 studies . CONCLUSIONS: There is little to choose between the efficacies of 1-week clarithromycin-based triple therapy eradication regimens . However, those comprising clarithromycin, a nitroimidazole and either ranitidine bismuth citrate or a high dose of omeprazole are, in general, the most effective . Against antibiotic-resistant strains of H . pylori, regimens including ranitidine bismuth citrate may be more effective than those including a proton pump inhibitor.

Ann Chir Plast Esthet, 1997 Apr, 42(2), 110 - 7
{Breast reconstruction after breast cancer: a review of a 12-year-long experience}; Faucher A et al.; The experience of 428 mammary reconstructions (MR) performed by the same surgeon, evaluated more than two years after surgery, enable the authors to try to determine possible correlations between results of MR and methods employed . Antibiotic prevention and tissue expansion only appear to have a significant influence on MR issue, whereas capsular contracture and aesthetic result did not seem correlated with prior radiotherapy or texture of the wall implant . This study confirms the low morbidity of MR . As regards quality of life, MR provides a noticeable benefit to a wide majority of patients . No method has been proved to be higher, or not advisable, against others . So, indications must be modulated in every case, patronizing better compromise between safety, quality and stability of morphologic result, and need expressed by each patient.

Presse Med, 1998 May 2-9, 27(17), 800 - 3
{Osteoarticular Mycobacterium xenopi infection}; Ollagnier E et al.; BACKGROUND: Mycobacterium xenopi is a potential pathogen for man and can cause bone and joint infections, particularly spondylodiscitis . Most cases of infection occur in fragilized patients and are found more and more often in AIDS patients . CASE REPORT: A 41-year-old HIV+ woman developed cervical spondylodiscitis due to Mycobacterium xenopi infection . The strain was isolated from a discovertebral biopsy and was resistant to several antibiotics . Outcome was unfavorable . DISCUSSION: Most of the cases reported to date have involved spondylodiscitis of the thoracic or lumbar spine . To our knowledge, this is the first report of cervical spondylodiscitis dut to Mycobacterium xenopi in an HIV+ patient . Antibiotic combinations using fluoroquinolones and new macrolides are usually prescribed . Such protocols may provide cure of these opportunistic infections in immunodeficient patients.

Presse Med, 1998 Jun 27, 27(23), 1135 - 9
{Procalcitonin, C-reactive protein and interleukin 6 in bacterial and viral meningitis in children}; Gendrel D et al.; OBJECTIVES: In young children with meningitis, blood or cerebrospinal fluid (CSF) analysis cannot differentiate all cases of viral meningitis (VM) from bacterial meningitis (BM) . Empirical antibiotic therapy is often given . As new markers are needed, we compared serum proCalcitonin (PCT) with CSF analysis for C-reactive protein (CRP) and interleukin-6 (IL6) . PATIENTS AND METHODS: PCT was measured with a chemoluminescent assay in the sera of 23 children (aged 3 months to 14 years) hospitalized for BM and in 51 patients with VM . RESULTS: Initial CRP (mean 143.3 mg/l, range 28-351 and mean 13.9, range 1-48), CSF proteins (mean 2.2, range 0.4-4.74 and mean 0.57, range 0.12-2.72) and white blood cell count in CSF (range 240-17500 and 20-3200) in BM and VM respectively, were not sufficiently discriminative to distinguish between BM and VM . Twenty-four of the 51 patients with VM were given antibiotics . IL6 values at admission showed an overlap zone (> 100 pg/ml in 7/19 patients with VM and < 100 pg/ml in 1/8 patients with BM . PCT was discriminative in all cases: mean PCT in BM was 61 micrograms/l (range 4.8-335) and 0.33 in VM (range 0-1.7; p < 0.001) . No production of PCT was detected in CSF . After antibiotic therapy, PCT decreased and reached undetectable levels after recovery . CONCLUSION: PCT is a sensitive and specific marker for early diagnosis of viral meningitis versus bacterial meningitis in children.

Gene, 1998 Oct 5, 220(1-2), 109 - 17
NCL1, a novel gene for a non-essential nuclear protein in Saccharomyces cerevisiae; Wu P et al.; The nucleolar protein Nop2p is an essential gene product that is required for pre-rRNA processing and ribosome biogenesis in Saccharomyces cerevisiae (Hong, B . et al., 1997, Mol . Cell . Biol., 17, 378-388) . A search for proteins similar to Nop2p identified a novel yeast gene product that also shares significant homology with the human proliferation associated nucleolar protein p120 . The gene encoding this 78kDa protein was termed NCL1 (for nuclear protein 1; corresponding to YBL024w) . Ncl1p and Nop2p contain an evolutionarily conserved motif that has been termed the 'NOL1/NOP2/fmu family signature' (NOL1 encodes p120) . Epitope tagged Ncl1p was found to be localized to the nucleus, including the nucleolus, and was concentrated at the nuclear periphery . NCL1 is not essential . Strains containing a disruption of NCL1, or strains overexpressing NCL1, grow essentially identically to wildtype NCL1 strains on a number of different media and at different temperatures . Disruption of NCL1 does not affect steady-state levels of large and small ribosome subunits, monoribosomes, and polyribosomes . However, disruption of NCL1 leads to increased sensitivity to the antibiotic paromomycin.

J Chromatogr B Biomed Sci Appl, 1998 Sep 4, 714(2), 341 - 53
Assay for the quinocarmycin analog DX-52-1 in human plasma using high-performance liquid chromatography with automated column switching and low wavelength ultraviolet detection; Supko JG et al.; The hydrocyanated derivative of the antitumor antibiotic quinocarmycin, DX-52-1 (I), exhibits impressive activity against human melanoma xenograft models in vivo . Phase I clinical trials to evaluate this compound as an antineoplastic agent have been initiated by the US National Cancer Institute . We have developed an HPLC assay for the determination of I in human plasma involving automated column switching and UV detection at 210 nm . The preparation of samples for chromatographic analysis entails the preliminary removal of plasma proteins by precipitation with acetonitrile, acidifying the clear supernatant to pH 4.5, then extracting twice with tert.-butyl methyl ether to recover the drug . A heart-cutting procedure employing two HPLC columns with contrasting retention characteristics under isocratic reversed-phase conditions was used to achieve the selectivity required for low wavelength UV detection of the analyte . The sample extract was initially loaded onto a column packed with a cyanopropyl stationary phase . During the predetermined time interval that I eluted from this column, a fully automated six-position switching valve was used to direct the effluent onto an octadecylsilane analytical column . The assay has been thoroughly validated with regard to linearity, inter- and intra-day accuracy and precision, recovery, selectivity and specificity . Using a sample volume of 1.0 ml, the lowest concentration of I quantified with acceptable day-to-day reproducibility was found to be 2.56 ng/ml (R.S.D . 18.9%, n=21, 4 months) . This proved to be sufficiently sensitive for pharmacokinetic drug level monitoring in cancer patients treated with a 6-h continuous intravenous infusion of I, even at the starting dose of 3 mg/m2 . The successful performance and reliability of the assay has been demonstrated through extensive application to the routine analysis of plasma specimens acquired during a phase I clinical trial of the drug.

Oncol Nurs Forum, 1998 Sep, 25(8), 1427 - 32
Clinical care for patients receiving autologous hematopoietic stem cell transplantation in the home setting; Herrmann RP et al.; PURPOSE/OBJECTIVES: To undertake a pilot study of autologous hematopoietic stem cell transplantation (HSCT) in the patient's home to improve satisfaction of care, reduce financial costs, and relieve pressure on inpatient accommodation . DESIGN: Descriptive, cross-sectional, qualitative . SETTING: Patients' homes within the metropolitan area of Perth, Australia . SAMPLE: 25 Caucasian adults with recurrent multiple myeloma, non-Hodgkin's lymphoma, or Hodgkin's disease requiring autologous HSCT . METHODS: A program was developed to use the bone marrow transplant team from a major tertiary hospital to permit home visiting, treatment with cytotoxic chemotherapy at home, treatment of complications at home, and an integrated home/hospital caring facility to expedite hospital admission if complications developed . FINDINGS: The program was practical to administer, improved overall patient satisfaction, and was significantly less costly than inpatient transplantation . Fifteen patients (60%) of the total study group of 25 required hospital admission for a median of five days (range 1-13 days) for management of complications, predominantly febrile neutropenia . Nineteen (76%) of the 25 patients received i.v . antibiotic therapy at home during the period of neutropenia . Two patients died of transplant-related complications--one from respiratory syncytial virus infection and one from veno-occlusive disease of the liver . These complications were not attributable to the home setting . IMPLICATIONS FOR NURSING PRACTICE: This program increased the responsibility and sense of autonomy of advanced practice nurses and developed their counseling skills as well as their ability to participate more actively in the decision-making process of those involved . MAIN RESEARCH VARIABLES: Participation in the home transplant program, patient satisfaction, nursing development, and cost-effectiveness of the program.

Res Microbiol, 1997 Feb, 148(2), 163 - 75
Effect of natural amphipathic peptides on viability, membrane potential, cell shape and motility of mollicutes; Beven L et al.; The antibiotic activity of ten amphipathic peptides was investigated in six species of mollicutes belonging to the genera Acholeplasma, Mycoplasma and Spiroplasma . A . laidlawii was the most sensitive and M . mycoides subsp . mycoides SC the most resistant . Animal defence peptides (cecropins A and P1, and magainin 2) proved to be less potent than bee-venom mellitin and most of the peptides produced by bacteria (globomycin, gramicidin S, surfactin and valinomycin) or fungi (alamethicin) . Gramicidin S was by far the most active peptide, with minimal inhibitory concentrations ranging from 2 to 50 nM . Alamethicin, gramicidin S, mellitin and surfactin had a cidal effect, whilst cecropins, globomycin, magainin 2, polymyxin B and valinomycin proved to be static . The peptides altered the membrane potential of spiroplasma cells with a potency independent of their linear or cyclic structure . However, globomycin depolarized the plasma membrane only weakly, whilst polymyxin B, in order to be active, required prior hyperpolarization of the membrane . The peptides also induced the loss of cell motility and helicity in spiroplasmas, suggesting that motility and cell shape in these bacteria are coupled to the transmembrane electrochemical gradient . Globomycin, an inhibitor of signal-peptidase II, prevented the growth of spiroplasmas, M . gallisepticum, and M . genitalium, but not that of A . laidlawii and M . mycoides subsp . mycoides SC, although the latter also synthesized membrane lipoproteins . Inhibition of spiralin processing by globomycin was demonstrated in S . citri and S . melliferum, with a more pronounced effect in the second species.

Ann Otolaryngol Chir Cervicofac, 1998 Jun, 115(3), 106 - 16; quiz 117
{Acute and chronic sphenoid sinusitis . Review of the literature}; Erminy M et al.; Isolated involvement of the sphenoid sinus is a relatively uncommon entity . We present a review of the most important series . Acute and chronic diseases are separated . Acute sphenoid sinusitis is a potentially catastrophic infectious disease . It is frequently initially misdiagnosed, and, due to the severe intracranial complications, a genuine medical and surgical treatment is recommended . Chronic sphenoid lesions may pose a problem of etiologic diagnosis . It may be difficult to differentiate between benign and malignant lesions . The most common presenting symptom is headache, followed by visual symptoms and cranial nerves palsies . Radiographically, computed tomography is the gold standard . Treatment includes antibiotic therapy and surgical drainage . This drainage is now done through an endoscopic approach.

J Bacteriol, 1998 Oct, 180(20), 5489 - 94
The nine genes of the Nocardia lactamdurans cephamycin cluster are transcribed into large mRNAs from three promoters, two of them located in a bidirectional promoter region; Enguita FJ et al.; The nine biosynthesis genes of the Nocardia lactamdurans cephamycin cluster are expressed as three different mRNAs initiating at promoters latp, cefDp, and pcbABp, as shown by low-resolution S1 nuclease protection assays and Northern blotting analysis . Bidirectional expression occurred from divergent promoters (latp and cefDp) located in a 629-bp intergenic region that contains three heptameric direct repeats similar to those recognized by members of the SARP (Streptomyces antibiotic regulatory proteins) family . The lat gene is transcribed in a single monocistronic transcript initiating at latp . A second unusually long polycistronic mRNA (more than 16 kb) corresponding to six biosynthesis genes (pcbAB, pcbC, cmcI, cmcJ, cefF, and cmcH) started at pcbABp . A third polycistronic mRNA corresponding to the cefD and cefE genes started at cefDp.

J Hepatol, 1998 Sep, 29(3), 369 - 74
Treatment of chronic hepatitis C with alpha-interferon plus ofloxacin in patients not responding to alpha-interferon alone; Negro F et al.; BACKGROUND/AIMS: Ofloxacin, a quinolone antibiotic, was recently shown to increase the primary response rate to alpha-interferon treatment of chronic hepatitis C . METHODS: Fifty-five patients with chronic hepatitis C were scheduled to receive 3 MU of a-interferon, three times a week, for 1 year . After 3 months of therapy, patients who were still HCV RNA-positive in serum started receiving a combined regimen with 3 MU of alpha-interferon, three times a week, plus ofloxacin, 600 mg daily, per os . After 3 months of combined therapy, patients with undetectable serum HCV RNA continued the combined regimen for another 6 months, whereas patients who were still HCV RNA-positive were definitively considered as non-responders and withdrawn from the study . Serum HCV RNA levels were quantitatively evaluated after 3 months of therapy with a-interferon alone and compared with those detected after 3 months of combined regimen . RESULTS: Among the 54 patients who completed the first 3 months of treatment, 32 (59.3%) still had HCV RNA detectable in serum and started receiving the ofloxacin/alpha-interferon therapy . Among the 26 patients who completed the 3 additional months of combined regimen, only one showed a virological response: this patient maintained a complete response to the end of combined treatment, but relapsed thereafter . The combination therapy had no effect on the serum HCV RNA or alanine aminotransferase levels . CONCLUSIONS: The combined administration of alpha-interferon and ofloxacin to patients with chronic hepatitis C who have not responded to alpha-interferon alone does not increase the primary virological response rate.

Eur J Clin Microbiol Infect Dis, 1998 Jul, 17(7), 501 - 4
Ceftriaxone in the outpatient treatment of cancer patients with fever and neutropenia; Karthaus M et al.; A study was performed in low-risk cancer patients with chemotherapy-induced febrile neutropenia to determine the safety and efficacy of ceftriaxone given in an outpatient setting . A total of 126 episodes of febrile neutropenia in 120 clinically stable outpatients were treated with intravenous ceftriaxone alone (n=100) or in combination with other antibiotics (n=26) . The mean neutrophil count was 460/mm3; severe neutropenia (< 100/mm3) was observed in 18 episodes . The initial treatment with ceftriaxone (alone or in combination) was successful in 99 episodes (78%) . Ninety-five episodes (76%) were successfully treated in an outpatient setting only; admission to hospital was necessary in 31 episodes (24%), but no infection-related death was observed . Ceftriaxone seems to be safe and effective for outpatient therapy of patients with low-risk febrile neutropenia.

Analyst, 1998 Jun, 123(6), 1279 - 82
Determination of tylosin residues in pig tissues using high-performance liquid chromatography; De Liguoro M et al.; In accordance with the maximum residue limit of 100 micrograms kg-1 established by EU legislation, a simple and sensitive high-performance liquid chromatographic (HPLC) method was developed for the measurement of tylosin residues in pig tissues (fat, kidney, liver and muscle) . Tylosin, a macrolide antibiotic, is extracted with water-methanol and cleaned-up by solid-phase extraction (SPE) on cation-exchange cartridges using methanol elution . Tylosin was determined by reversed-phase HPLC with UV detection at 280 nm and the mean recovery from pig tissues fortified in the range 50-200 micrograms kg-1 was 70-85%, with intra- and inter-day RSDs in the ranges 3.4-9.1 and 3.9-10.1% respectively.

J Vet Med Sci, 1998 Aug, 60(8), 889 - 95
Cytotoxicity induced by recombinant human tumor necrosis factor-alpha dependent on the types of its receptors on canine cells; Aoki M et al.; Based on the recent findings that show how recombinant human tumor necrosis factor (rh-TNF)-alpha has potent antitumor activity on human cancer patients when it locally administrated, we have tested the cytotoxicity of rh-TNF-alpha on 3 canine cultured cells: (1) canine kidney carcinoma (CKCa-1), (2) mastocytoma and (3) Mardin Darby canine kidney cells (MDCK) . The cell surface expression of TNF-alpha receptors on these canine cells was also determined with anti-human TNF RI and RII polyclonal antibodies . Our data shows that on CKCa-1 which has TNF RI receptors rh-TNF-alpha induced cytotoxicity . By contrast, it exhibited no toxicity on canine mastocytoma which has mainly RII receptors . The data also suggest actinomycin D (ACT-D), an anticancer antibiotic, enhanced the cytotoxicity of rh-TNF-alpha . Combined with ACT-D, rh-TNF-alpha showed the cytotoxicity on MDCK which possessed both TNF RI and RII receptors . The results indicate that the cytotoxicity of rh-TNF-alpha depends on the presence of TNF RI receptors on canine tumor cells.

Gut, 1998 Jul, 43 Suppl 1, S70 - 3
Treatment of Helicobacter pylori: future therapeutic and prophylactic perspectives; Axon AT; Helicobacter is one of the most widespread, chronic infections in the world and causes a serious disease with a significant mortality . The organism is difficult to eradicate using antibiotic therapy and to date no vaccine is available for use in humans . The most successful treatments comprise acid suppression in combination with two antibiotics and a series of seven day courses will reliably cure around 85% of infected individuals . Further modifications of these regimens via the introduction of newer and more effective antibiotics and acid suppressants may enable the treatment to be simplified, made more effective and cause fewer side effects . However, the major challenge is to develop a specific monotherapy targeted against Helicobacter pylori . The H pylori genome has now been sequenced and this provides an opportunity both to identify specific targets for drug therapy, and to facilitate the identification and production of antigens that may be helpful in manufacturing a vaccine . This paper discusses the future of helicobacter therapy and vaccination.

Minerva Ginecol, 1998 Jun, 50(6), 265 - 76
{The role of vaginal pH . Importance of its normalization in the prevention of recurrent vaginitis}; Blasi N et al.; BACKGROUND: A sample of 100 women was clinically examined for a very various vulvovaginal symptomatology and an individual diagnosis of vulvovaginitis of different aetiology was established . METHODS: All women were treated with antibiotic and/or antimycotic drugs on the basis of individual diagnosis . Sixty women had only this treatment, while 40 women had also a supplementary treatment with a cleanser emulsion characterized by physiologic pH value and an antiseptic activity due to a vegetable extract (Saugella Attiva, Lab . Guieu) . The symptomatologic changes due to the two treatments were compared . RESULTS AND CONCLUSIONS: Combined treatment (drug + antiseptic) obtained better results mostly in subjective symptomatology; this combined treatment was very useful in the recovery of the Doderlein population.

Urology, 1998 Oct, 52(4), 644 - 6
Variability in patient preparation for prostate biopsy among American urologists; Shandera KC et al.; OBJECTIVES: To assess the variability in patient preparation for prostate biopsy (PBX) among practicing American urologists . METHODS: A survey was sent to 900 practicing American urologists randomly selected by the American Urological Association computer files . The survey asked about their pre-PBX protocol . RESULTS: Approximately 63% (568 of 900) of the surveys were returned and showed considerable differences in pre-PBX protocol among those urologists . The pre-PBX regimen included prophylactic antibiotics in 98.6% and a cleansing rectal enema in 81% . Eleven different antibiotics were used, with 20 different doses and 23 different timing-duration regimens . CONCLUSIONS: The pre-PBX preparation is not standardized among American urologists.

J Clin Periodontol, 1998 Sep, 25(9), 737 - 45
Evaluation of tetracycline fiber therapy with digital image analysis; Fourmousis I et al.; The aims of the present study were to assess radiographically the effects of scaling/root planing combined with antibiotic therapy using tetracycline fibers (TCF): (I) on alveolar bone density and linear descriptors and (II) on supracrestal soft tissue density . 19 subjects with generalized adult periodontitis (with at least 20 teeth present, at least 4 teeth with pockets >4 mm and bleeding upon controlled force probing) and high cultural counts of Porphyromonas gingivalis were recruited from a pool of 57 patients . The full mouth treatment group (FT) consisted of 10 patients, who underwent a full mouth supra-gingival scaling and prophylaxis treatment and were instructed to rinse 2x daily with a 0.1% chlorhexidine solution . 1 week later, tetracycline-hydrochloride-containing fibers (Actisite periodontal fiber) were applied around all teeth . After 7-12 days, the fibers were removed and all teeth were scaled and root planed under local anaesthesia . The chlorhexidine rinsing continued for another 2 months . In 9 subjects (local treatment group LT), 2 teeth with periodontal lesions with pocket probing pepth (PPD) > or =5 mm were treated by placement of tetracycline fibers, which remained in place for 7 to 12 days . Upon removal of the fibers, scaling and root planing was performed on these 2 teeth, while the rest of the dentition remained untreated, and no chlorhexidine rinse was applied . 2 of the untreated teeth revealing similar periodontal lesions were chosen to represent sites affected by untreated periodontitis (NT) . In this group, a limited local treatment was performed (2 teeth) with the inherent potential for recolonization from the untreated pocket sites . Standardized periapical radiographs were obtained from the 4 monitored sites within each patient at baseline (before treatment) and 2 and 6 months thereafter . One radiograph was exposed in a standard way for bone assessment . The second radiograph was underexposed, at about a 1/5 of the original exposure time to allow the evaluation of soft tissue . Mean changes in the linear parameters and changes in density (CADIA) observed at multiple sites within each patient and treatment group were used as the best estimate of treatment outcome . Over the observation period of 6 months, a significant difference in bone height changes was found between the untreated sites (median loss -0.29 mm) and the sites from full-mouth treated patients (median gain 0.24 mm, p=0.008) . When comparing the baseline to the 6 months radiographs, a loss in bone density was observed for the untreated group (median=-2.13 CADIA) . Both treatment groups revealed a gain in density (median=1.58 and 2.43 CADIA for the locally and the full-mouth treated groups, respectively) . Differences in density were significant, both between the nontreated and locally treated sites (p=0.026) and between the nontreated sites and the sites from the full mouth treated patients (p=0.002) . The analysis of the soft tissues showed a similar pattern of changes in density to those seen in the bone defect . At 2 months, there was a tendency for loss in density for the nontreated group (median=-0.17 CADIA) that continued over the 6 month period (median=-0.31 CADIA) . A significant increase in density was observed for the full-mouth treated sites (median=1.57 and 0.64 CADIA for the 2 and 6 months radiographs, respectively) . A significant increase was also observed for the locally treated group when compared to the untreated sites (median=0.13 and 0.10 CADIA for the 2 and 6 months radiographs, respectively) . Comparing untreated sites with full-mouth treated sites, a significant difference was observed for CADIA measurements (p<0.001) . No significant difference was observed comparing locally treated and untreated sites (p=0.24) . It was concluded that scaling and root planing combined with TCF therapy can result in increased bone density and alveolar bone height . Full-mouth treatment seemed to result in more pronounced gains compared to local tre

Biol Blood Marrow Transplant, 1998, 4(2), 84 - 92
Effect of CD34+ peripheral blood progenitor cell dose on hematopoietic recovery; Shpall EJ et al.; The CD34+ cell surface antigen is expressed on progenitor cells required for blood stem cell transplantation . The number of cells expressing CD34+ can be used to assess the peripheral blood progenitor cell (PBPC) graft quality and predict hematopoietic recovery after engraftment . Because there is considerable variability among centers in the determination of CD34+ cell counts, standardizing flow cytometry methodology is essential . It is necessary to define a minimum safety threshold CD34+ cell dose for hematopoietic cell transplantation . This minimum dose would define a cell number in the graft, below which a proportion of patients would be expected to have delayed hematopoietic recovery or failure to engraft . We reviewed data from numerous studies . Although 1-2 x 10(6) CD34+ cells/kg can be considered an adequate graft, available data suggested that doses >5 x 10(6) CD34+ cells/kg were associated with more rapid engraftment and a lower probability of graft failure . The risk of delayed recovery was inversely related to CD34+ cell dose . Delayed recovery may result in greater transfusion requirements, longer hospitalization, increased antibiotic use and growth factor support, and higher health care costs . The extent of prior chemotherapy and radiation treatment are major risk factors for poor PBPC collection . To achieve an optimal CD34+ cell yield, PBPC collection should be initiated early during therapy . PBPC collection should be coordinated with the anticipated number of chemotherapy cycles, duration of chemotherapy, interval between chemotherapy and apheresis, need for radiotherapy, and exposure to the more progenitor cell-toxic drugs such as carmustine or busulfan.

Biochemistry, 1998 Oct 6, 37(40), 14279 - 91
Environment- and sequence-dependent modulation of the double-stranded to single-stranded conformational transition of gramicidin A in membranes; Salom D et al.; The role of the membrane lipid composition and the individual Trp residues in the conformational rearrangement of gramicidin A along the folding pathway to its channel conformation has been examined in phospholipid bilayers by means of previously described size-exclusion high-performance liquid chromatography HPLC-based strategy (Bano et al . (1991) Biochemistry 30, 886) . It has been demonstrated that the chemical composition of the membrane influences the transition rate of the peptide rearrangement from double-stranded dimers to beta-helical monomers . The chemical modification of Trp residues, or its substitution by the more hydrophobic residues phenylalanine or naphthylalanine, stabilized the double-stranded dimer conformation in model membranes . This effect was more notable as the number of Trp-substituted residues increased (tetra > tri > di > mono), and it was also influenced by the specific position of the substituted amino acid residue in the sequence, in the order Trp-9 approximately Trp-13 > Trp-11 > Trp-15 . Moreover, it was verified that nearly a full contingent of indoles (Trp-13, -11, and -9) is necessary to induce a quantitative conversion from double-stranded dimers to single-stranded monomers, although Trp-9 and Trp-13 seemed to be key residues for the stabilization of the beta-helical monomeric conformation of gramicidin A . The conformation adopted for monomeric Trp --> Phe substitution analogues in lipid vesicles resulted in CD spectra similar to the typical single-stranded beta6.3-helical conformation of gramicidin A . However, the Trp --> Phe substitution analogues showed decreased antibiotic activity as the number of Trp decreased.

J Bone Joint Surg Am, 1998 Sep, 80(9), 1306 - 13
Treatment of infection with débridement and retention of the components following hip arthroplasty; Crockarell JR et al.; Forty-two patients (forty-two hips) who had an infection following a hip arthroplasty were managed with open debridement, retention of the prosthetic components, and antibiotic therapy . After a mean duration of follow-up of 6.3 years (range, 0.14 to twenty-two years), only six patients (14 per cent) -- four of nineteen who had had an early postoperative infection and two of four who had had an acute hematogenous infection -- had been managed successfully . Of the remaining thirty-six patients, three (7 per cent of the entire group) were being managed with chronic suppression with oral administration of antibiotics and thirty-three (79 per cent of the entire group) had had a failure of treatment . All nineteen patients who had a late chronic infection were deemed to have had a failure of treatment . Debridement had been performed at a mean of six days (range, two to fourteen days) after the onset of symptoms in the patients who had been managed successfully and at a mean of twenty-three days (range, three to ninety-three days) in those for whom treatment had failed . Debridement with retention of the prosthesis is a potentially successful treatment for early postoperative infection or acute hematogenous infection, provided that it is performed in the first two weeks after the onset of symptoms and that the prosthesis previously had been functioning well . In our experience, this procedure has not been successful when it has been performed more than two weeks after the onset of symptoms . Retention of the prosthesis should not be attempted in patients who have a chronic infection at the site of a hip arthroplasty as this approach universally fails.

Infect Control Hosp Epidemiol, 1998 Aug, 19(8), 590 - 2
Strategies for prevention of infection in short-duration neutropenia; Fenelon L; Although infection continues to be a major cause of morbidity and mortality in neutropenic patients, newer strategies have resulted in a shorter duration of neutropenia . The prime risk to patients with short-duration neutropenia (defined as neutropenia of less than 14 days) is bacterial infection, which is reduced by the administration of prophylactic antibiotics, and possibly by the use of clean food, sterile water, and protection against transmission of organisms from healthcare workers' hands.

Orv Hetil, 1998 Sep 6, 139(36), 2141 - 3
{Renal candidiasis following treatment of infantile osteomyelitis}; Balogh L et al.; Systemic candidiasis with renal complications is a rather rare phenomenon in young infants . Authors report on a 4.5 month-old baby (preterm) who, during an antibiotic therapy of wide spectrum--because of osteomyelitis--acquired a mycotic infection causing bilateral pyelon and pyeloureteral obstruction . In addition to systemic antimycotic therapy surgical intervention was needed to eliminate the mycotic bezoar.

Antimicrob Agents Chemother, 1998 Oct, 42(10), 2668 - 73
Antiparasitic effects of the intra-Golgi transport inhibitor megalomicin; Bonay P et al.; The macrolide antibiotic megalomicin (MGM) has been shown to inhibit vesicular transport between the medial- and trans-Golgi, resulting in the undersialylation of cellular proteins (P . Bonay, S . Munro, M . Fresno, and B . Alarcon, J . Biol . Chem . 271:3719-3726, 1996) . Due to the effects of MGM on the Golgi and on the replication of enveloped viruses, we decided to test whether it has any antiparasitic activity . The results showed that MGM has potent activity against the epimastigote stage of Trypanosoma cruzi, producing a 50% inhibitory concentration (IC50) of 0.2 microg/ml . Furthermore, MGM was also active against the intracellular replicative, amastigote form of T . cruzi, completely preventing its replication in infected murine LLC/MK2 macrophages at a dose of 5 microg/ml . Although less potent, MGM was also active against Trypanosoma brucei epimastigotes (IC50, 2 microg/ml) and Leishmania donovani and Leishmania major promastigotes (IC50, 3 and 8 microg/ml, respectively) . MGM also blocked intracellular replication of the asexual stage of Plasmodium falciparum-infected erythrocytes at 1 microg/ml . Finally, MGM was active in an in vivo model, resulting in the complete protection of BALB/c mice from death caused by acute T . brucei infection and significantly reducing the parasitemia . These results suggest that MGM is a potential drug for the treatment of veterinary and human parasitic diseases.

Antimicrob Agents Chemother, 1998 Oct, 42(10), 2612 - 9
Characterization of a glycosyl transferase inactivating macrolides, encoded by gimA from Streptomyces ambofaciens; Gourmelen A et al.; In Streptomyces ambofaciens, the producer of the macrolide antibiotic spiramycin, an open reading frame (ORF) was found downstream of srmA, a gene conferring resistance to spiramycin . The deduced product of this ORF had high degrees of similarity to Streptomyces lividans glycosyl transferase, which inactivates macrolides, and this ORF was called gimA . The cloned gimA gene was expressed in a susceptible host mutant of S . lividans devoid of any background macrolide-inactivating glycosyl transferase activity . In the presence of UDP-glucose, cell extracts from this strain could inactivate various macrolides by glycosylation . Spiramycin was not inactivated but forocidin, a spiramycin precursor, was modified . In vivo studies showed that gimA could confer low levels of resistance to some macrolides . The spectrum of this resistance differs from the one conferred by a rRNA monomethylase, such as SrmA . In S . ambofaciens, gimA was inactivated by gene replacement, without any deleterious effect on the survival of the strain, even under spiramycin-producing conditions . But the overexpression of gimA led to a marked decrease in spiramycin production . Studies with extracts from wild-type and gimA-null mutant strains revealed the existence of another macrolide-inactivating glycosyl transferase activity with a different substrate specificity . This activity might compensate for the effect of gimA inactivation.

Radiother Oncol, 1998 Jul, 48(1), 23 - 7
Haematological toxicity of cranio-spinal irradiation; Jefferies S et al.; BACKGROUND: To assess the frequency and severity of myelosuppression due to cranio-spinal irradiation either alone or in combination with chemotherapy and to identify patients at high risk of haematological toxicity who may require supportive therapy . MATERIALS AND METHODS: Between 1965 and 1994, 210 patients received cranio-spinal axis (CSA) radiotherapy as a component of treatment for primary CNS tumours at the Royal Marsden Hospital . Full blood counts (FBC) were obtained before, during and after radiotherapy in 200 patients . Haematological toxicity was graded according to the WHO criteria and duration was measured from the onset of grades 3 and 4 toxicity until recovery to grade 2 . RESULTS: Sixty-six (33%) patients developed grades 3 and 4 haematological toxicity . Nadir occurred during radiotherapy and was most frequent during the second week of spinal radiotherapy . Low haemoglobin and white cell counts prior to radiotherapy increased the likelihood of myelosuppression . Nine patients had febrile episodes requiring antibiotic therapy . Treatment was interrupted in 49 patients but treatment time was extended beyond 12 weeks in only 17 (8%) patients of which nine were due to haematological toxicity . Chemotherapy (vincristine) during radiotherapy did not impact on haematological toxicity . Age and prior chemotherapy were independent predictive factors for haematological toxicity . The relative risk of leukopaenia in children compared to adults was 7.9 (95% CI 3.4-18.6%) . Patients who received prior chemotherapy had a relative risk of toxicity of 6.1 (95% CI 2.9-12.8%) . CONCLUSION: One-third of patients undergoing CSA radiotherapy develop grades 3 and 4 haematological toxicity . The risk is higher in children and in patients who receive chemotherapy prior to radiation . There was no treatment-related mortality and only nine of 200 patients (9/60 of those with toxicity) required supportive treatment for neutropaenic sepsis . The low incidence severe haematological toxicity does not warrant routine use of haemopoietic growth factors during CSA irradiation and future studies should target high risk subgroups.

Hepatogastroenterology, 1998 Jul-Aug, 45(22), 990 - 3
Continuous maintenance with low-dose lansoprazole versus Helicobacter pylori eradication in the prevention of duodenal ulcer recurrence; Parente F et al.; BACKGROUND/AIMS: Reduction of gastric acid secretion by maintenance treatment with antisecretory agents and eradication of H . pylori by antibiotics constitute the most effective therapeutic options in preventing duodenal ulcer relapse . The aim of this study was to compare the effect of a 12-month low-dose lansoprazole maintenance treatment with H . pylori eradication on the rate of ulcer relapse in H . pylori-positive duodenal ulcer patients . METHODOLOGY: After a healing phase with lansoprazole 30 mg/die or lansoprazole 30-60 mg/die plus antibiotics (amoxycillin, tinidazole and colloidal bismuth subcitrate), 84 patients with healed duodenal ulcer entered the follow-up phase . Thirty-eight patients with persistent H . pylori infection received lansoprazole 15 mg at bedtime, whereas 46 in whom H . pylori was eradicated during the acute phase received no active therapy during the 12-month follow-up . The two groups were well balanced concerning all demographic characteristics . Clinical controls were performed every 3 months or sooner in the event of symptomatic relapse . RESULTS: In terms of per protocol analysis, the overall rate of ulcer relapse at 6 months was 5.5% (2/36) in the maintenance group and 0 (0/42) in the antibiotic group . The corresponding figures at 12 months were 20.5% (7/34) and 5.7% (2/35), respectively (p:ns, 95% CI for the difference -0.30+0.02) . On intent to treat analysis, the rate of ulcer relapse at 6 months was 5.2% (2/38) in the first group and 0% (0/46) in the second group: at 12 months the corresponding figures were 19.4% (7/36) and 4.3% (2/46), respectively (p=0.06; CI 95%: +0.016+0.28) . No significant side effects were observed during long-term maintenance with lansoprazole . CONCLUSIONS: Continuous maintenance with low-dose lansoprazole may constitute a valuable alternative to H . pylori eradication for the prevention of relapse and complications in duodenal ulcer patients not suitable for, or who have failed, H . pylori eradication.

Am J Physiol, 1998 Oct, 275(4 Pt 1), C913 - 20
Exocytosis is not involved in activation of Cl- secretion via CFTR in Calu-3 airway epithelial cells; Loffing J et al.; Cystic fibrosis is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channel, which mediates transepithelial Cl- transport in a variety of epithelia, including airway, intestine, pancreas, and sweat duct . In some but not all epithelial cells, cAMP stimulates Cl- secretion in part by increasing the number of CFTR Cl- channels in the apical plasma membrane . Because the mechanism whereby cAMP stimulates CFTR Cl- secretion is cell-type specific, our goal was to determine whether cAMP elevates CFTR-mediated Cl- secretion across serous airway epithelial cells by stimulating the insertion of CFTR Cl- channels from an intracellular pool into the apical plasma membrane . To this end we studied Calu-3 cells, a human airway cell line with a serous cell phenotype . Serous cells in human airways, such as Calu-3 cells, express high levels of CFTR, secrete antibiotic-rich fluid, and play a critical role in airway function . Moreover, dysregulation of CFTR-mediated Cl- secretion in serous cells is thought to contribute to the pathophysiology of cystic fibrosis lung disease . We report that cAMP activation of CFTR-mediated Cl- secretion across human serous cells involves stimulation of CFTR channels present in the apical plasma membrane and does not involve the recruitment of CFTR from an intracellular pool to the apical plasma membrane.

Inflamm Res, 1998 Aug, 47(8), 339 - 44
Sirolimus (rapamycin, Rapamune) and combination therapy with cyclosporin A in the rat developing adjuvant arthritis model: correlation with blood levels and the effects of different oral formulations; Carlson RP et al.; OBJECTIVE AND DESIGN: To determine whole blood levels of sirolimus, a macrolide antibiotic in the rat developing adjuvant arthritis (AA) model after dosing orally with two different vehicles, and whether combinational doses of sirolimus and cyclosporin A (CsA) produced additive or synergistic inhibitory effects in this model . MATERIAL: Male Lewis rats (150-180g) . TREATMENT: Arthritis was induced by the injection (0.5 mg/ rat) of heat-killed Mycobacterium butyricum suspended in light mineral oil . Drugs were administered orally either in fine suspension (0.5% Tween 80) or in emulsion (phosal 50 PG in 1% Tween 80) at doses of 0.1 to 5 mg/kg in a 7 day, MWF or daily regimen . METHOD: Paw volumes (ml) were measured by automated mercury plethysmograph and sirolimus concentrations in whole blood were quantitated by liquid chromatography/ mass spectroscopy . RESULTS: At 72h (7 days after adjuvant) after receiving the third oral dose (4.5 mg/kg p.o.), the phosal vehicle resulted in higher sirolimus blood levels (2.5 ng/ml) than in Tween 80 (1.6 ng/ml) . After the rats received the last oral dose on day 14, (7 total doses of sirolimus at 4.5 mg/kg) the sirolimus blood levels (2h after the last dose) were about 2 times higher for the phosal dosed rats (9.8 ng/ml) compared to Tween 80 dosed rats (4.6ng/ml) . Even 24h after the last dose, sirolimus blood levels were still elevated in the phosal dosed rats (0.8 ng/ml) relative to 0.5% Tween 80 dosed rats (0.5 ng/ml) . At day 16 in the rat developing model, sirolimus, when given in phosal vehicle, produced an ED50 of 0.28 mg/ kg (i.e . inhibition of uninjected paw edema) that was about 5.5 times lower than using 0.5% Tween 80 as the suspending agent (ED50 = 1.6mg/kg) . When combining sirolimus and CsA using precalculated doses for producing an additive effect in this adjuvant model, an additive inhibitory effect on uninjected paw edema was observed at equal combinational doses of 0.5 and 2 mg/kg, respectively . CONCLUSIONS: The phosal vehicle used in administering sirolimus increases the absorption and whole blood levels in the rat and the elevated blood levels correlated positively with the therapeutic effect in the rat developing AA model . In addition, combination therapy using sirolimus and CsA produced an additive effect in rat developing AA.

Mutat Res, 1998 Oct 12, 421(1), 9 - 25
Genetic analysis of adenovirus E1A: induction of genetic instability and altered cell morphologic and growth characteristics are segregatable functions; Drews R et al.; Single multifunctional oncoproteins contribute to genomic instability development, but relationships between one or more oncoprotein-associated activities and genetic changes accompanying tumor cell progression are uncertain . Using NIH 3T3 derivative EN/NIH 2-20 containing transcriptionally silent neomycin phosphotransferase gene (neo) integrants with undetectable spontaneous reactivations, we studied wild-type (WT) and mutant adenovirus E1A-induced neo reactivation by neo-allelic rearrangement . WT E1A expression, yielding differential splice transcripts 12S and 13S and resulting in altered cell morphologic and growth characteristics, produced neo reactivations in 9 of 21 subclones (median rate per cell, 35 x 10(-6); range, 0.33 x 10(-6) to 936 x 10(-6)) . Only 3 of 17 cell lines expressing CTdl976, a '12S' functional equivalent inducing altered cell morphologic and growth characteristics while lacking the 13S trans activation domain, yielded neo reactivations (range, 0.33 x 10(-6) to 0.67 x 10(-6)) . One of 21 subclones expressing NTdl646, an E1A mutant retaining the trans domain but lacking p300 binding activity and the ability to alter cell morphologic and growth characteristics, produced neo reactivations (8.7 x 10(-6)) . Other E1A mutants, all lacking the ability to alter cell morphologic and growth characteristics while binding pRb but variously lacking the trans domain and binding for p107 and/or p300, displayed undetectable neo-reactivations . 98 EN/NIH 2-20 derivatives coexpressing complementary mutant E1As exhibited altered morphologic and growth features, but only 10 of these produced neo reactivations, and maximum rates (14 x 10(-6)) were substantially lower than those in comparably derived, morphologically altered E1AWT-expressing counterparts (497 x 10(-6)) . These findings suggest that maximum rates of gene reactivations by genomic rearrangement require the collective activities of functional domains assembled in single multifunctional proteins (or complexes) while altered cell morphologic and growth characteristics may arise through comparable sets of functional domains distributed across more than one protein (or complex) .

J Bacteriol, 1998 Oct, 180(19), 5235 - 9
Genetic analysis of mecillinam-resistant mutants of Caulobacter crescentus deficient in stalk biosynthesis; Seitz LC et al.; Stalk synthesis in Caulobacter crescentus is a developmentally controlled and spatially restricted event that requires the synthesis of peptidoglycan at the stalk-cell body junction . We show that the beta-lactam antibiotic mecillinam prevents stalk synthesis by inhibiting stalk elongation . In addition, mecillinam causes an increase in the diameter of the stalk at the stalk-cell body junction . We describe two mutations that confer resistance to mecillinam and that prevent stalk elongation . These mutations are probably allelic, and they map to a locus previously not associated with stalk synthesis.

Epidemiol Infect, 1998 Aug, 121(1), 31 - 42
Epidemiology and properties of heat-stable enterotoxin-producing Escherichia coli serotype O169:H41; Nishikawa Y et al.; Enterotoxigenic Escherichia coli (ETEC) serotype O169:H41 organisms have become the most prevalent ETEC in Japan since the first outbreak in 1991 . It was assumed that the outbreaks were due to clonal spread of this new ETEC serotype . The relationship of 32 strains isolated from 6 outbreaks were examined for biotype, antibiotic susceptibility, enterotoxigenicity, protein banding pattern, lipopolysaccharide banding pattern, plasmid analysis, and ribotyping . Further, the strains were examined by haemagglutination, surface hydrophobicity, and the ability to adhere to HEp-2 cells . The present study suggests that the outbreaks were caused by multiple clones of STp-producing O169:H41 since they showed differences in ribotype and outer membrane protein banding patterns . The strains did not agglutinate human or bovine red blood cells in a mannose-resistant manner . They adhered to HEp-2 cells in a manner resembling enteroaggregative E . coli . Five strains were examined by dot-blot tests for the colonization factor antigens CFA/I, CS1, CS2, CS3, CS4, CS5, CS6, CS7, PCFO159, PCFO166 and CFA/III . Although four strains expressed CS6, no structure for CS6 was identified . A strain that the anti-CS6 MAbs did not react with could adhere to HEp-2 cells in mannose resistant manner; thus, it is unlikely that CS6 play an important role in the adhesion to the cells . Electron microscopy studies of the O169:H41 strains suggested that curly fimbriae, a possible new colonization factor, may be playing an important role in the adhesion of the bacteria to HEp-2 cells . In conclusion, outbreaks due to ETEC O169:H41 were caused by multiple clones, and the strains should be examined in detail for a possible new colonization factor.

Biophys J, 1998 Oct, 75(4), 1915 - 25
Cholesterol distribution in living cells: fluorescence imaging using dehydroergosterol as a fluorescent cholesterol analog; Mukherjee S et al.; Cholesterol is an important constituent of most mammalian cell membranes and its concentration in various cellular membranes is tightly regulated . Although there is much information about cholesterol distribution and trafficking in cells, it is primarily derived from indirect measurements, and the results obtained using different approaches are often conflicting . A cholesterol analog that faithfully mimics the properties of cholesterol and can be followed in living cells would thus be very useful . In this study, we report the fluorescence imaging of such an analog, dehydroergosterol (DHE), in living cells . DHE differs from cholesterol in having three additional double bonds and an extra methyl group . In model systems, DHE closely mimics the behavior of native cholesterol . Using triple-labeling studies, we show that DHE colocalizes extensively with endocytosed transferrin, an endocytic recycling compartment marker, and with a marker for the trans-Golgi network, Tac-TGN38 . This distribution of DHE is qualitatively similar to that observed when cells are labeled with the fluorescent cholesterol-binding polyene antibiotic, filipin, although there are differences in apparent proportions of DHE and filipin that are localized at the plasma membrane . Another cholesterol derivative, 25-NBD-cholesterol, has a structure that is compromised by the presence of a bulky NBD group and does not distribute to the same organelles as DHE or filipin . In addition, we show in this manuscript that kinetic processes can be followed in living cells by monitoring recovery of DHE fluorescence in a photobleached region over time . Our observations provide evidence for the presence of a large intracellular cholesterol pool in the endocytic recycling compartment and the trans-Golgi network that might play important roles in the trafficking of lipids, lipid-anchored proteins, and transmembrane proteins that preferentially partition into cholesterol-enriched membrane domains . In addition, this intracellular cholesterol pool might be involved in the maintenance of cellular cholesterol homeostasis.

Bull Soc Belge Ophtalmol, 1997, 267, 45 - 52; discussion 53
Indocyanine green angiographic findings in multifocal choroidopathies; Giovannini A et al.; With high definition videoangiography (TOPCON IMAGEnet H1024) the Authors studied 41 patients affected by multifocal choroidopathies (MC) (68 eyes with ophthalmoscopic or indocyanine green angiographic evidences): 29 females and 12 males; age 21-51 years with a follow up of 6-29 months . In the light of the evidence provided by FA and ICG the Authors present a classification of MC in three stages: Stage 1 of subclinical choroidal activity (5 eyes) characterised by the presence of hypofluorescent or hyperfluorescent spots visible only in the late phases of ICGA; stage 2 of clinically evident choroidal activity (45 eyes) in FA the spots are hypofluorescent in the early phases and hyperfluorescent with a slight diffusion in the late phases, in ICGA either hypofluorescent spots or less frequently hyperfluorescent spots and choroidal permeability alterations can be observed; stage 3 or healed stage (18 eyes) in FA the spots are hyperfluorescent without late leakage, in ICGA hypofluorescence can be observed during all angiographic phases . In 5 patients in stage 1 of subclinical activity, a systemic steroid therapy induced a regression of the hypofluorescent spots in ICGA, in 2 cases the regression of hyperfluorescent spots in ICGA was observed after systemic antibiotic therapy . The authors underline that ICGA could be a particularly useful tool for an early diagnosis and clinical monitoring of MC.

J Immunol Methods, 1998 Jun 1, 215(1-2), 145 - 50
Expressed luciferase viability assay (ELVA) for the measurement of cell growth and viability; Coombe DR et al.; An expressed luciferase viability assay (ELVA) has been developed for cell viability and cell number based on detecting the expression of luciferase transfected into the cells . Stable transfectants were produced that expressed luciferase constitutively . Like many endogenous enzymes, luciferase is rapidly degraded following cell death, so that the enzyme can be used as a measure of cell viability . A modified luciferase assay was used in which the reagents were added directly to the cells in a microplate . The main advantages compared to other cell viability assays are the wide dynamic range, high sensitivity, low background, and the absence of any requirement to wash or harvest the cells . Stable transfectants of three factor-dependent cell lines (B13, Ba/F3 and CTLL) were produced and used in cytokine assays . Three strategies of selection after electroporation were tested: (1) using a plasmid containing both the genes encoding firefly luciferase and a selectable marker (neo), (2) cotransfection of a plasmid containing luciferase and a plasmid containing a selectable marker (puromycin resistance), and (3) cotransfection of a plasmid containing luciferase and a plasmid containing the human IL-5Ralpha-chain, and selecting in IL-5 . This latter strategy produces an IL-5 responsive cell line expressing luciferase in a single step without the need for antibiotic selection.

Eur J Gynaecol Oncol, 1998, 19(4), 350 - 1
Brachytherapy in the presence of pyuria after pelvic irradiation for cervical cancer; Ampil FL et al.; Little is known about the effects of intracavitary brachytherapy (ICB) performed in the presence of pyuria resulting from external beam pelvic irradiation for cervical cancer (CC) . A retrospective study of one decade of ICB for CC showed that brachytherapy was performed in the presence of pyuria in 26 women . Twelve women without pyuria during ICB served as a control group . Antibiotic therapy was routinely administered during intracavitary application . The crude survival rate at 5 years was 39% in patients with pyuria and 42% in women without pyuria; the corresponding local recurrence rates were 23% and 17%; the serious complication rates were 12% and 0% respectively . Intracavitary brachytherapy in the presence of pyuria may have a limited adverse effect on the outcome of women with cancer of the cervix.

Clin Exp Obstet Gynecol, 1998, 25(1-2), 54 - 5
Conservative treatment of multiple pregnancies after delivery and a fetal miscarriage: two case reports; Giannacopoulou C et al.; Due to the increased availability of infertility treatment, multiple pregnancies, with various resulting complications, have become more common . Two cases of triplet pregnancies with delayed delivery--interval ranged from 6 to 56 days--are reported . The first woman in the 23rd week of a triplet pregnancy came to the hospital because of premature rupture of membranes of one amniotic sac and had a miscarriage of one of the fetuses the same day . The second woman in the 26th week of a triplet pregnancy also came to the hospital because of bleeding and contractions and had vaginal delivery of the first triplet a few hours later . After confirming that the remaining two fetuses were in good condition, both patients were kept under observation with only antibiotic therapy for the first one and antibiotic and tocolysis for the second . Fifty-six days following admission to our hospital the first woman gave birth to twins while in her 32nd week . The second woman gave birth six days following admission (in her 27th week) . The successful outcome of these cases demonstrates that non-intervening conservative methods could be a feasible alternative to invasive intervention . We hope that our cases will encourage more physicians to try out and report non-intervening methods so that enough information can be gathered to help make correct management decisions in the future.

Pediatrics . 1998 Apr;101(4):E6.
A proactive, data-based determination of the standard of medical care in pediatrics; Meadow W et al.; A 3-week-old infant awoke with a fever . He was taken to the doctor who noted that the child was irritable . The doctor took him to the hospital where a resident performed a spinal tap, started an intravenous (IV) line, and ordered antibiotics . The entire drama, from entering the doctor's office to infusion of ampicillin, took 2 hours . The doctor was sued for malpractice . Expert witnesses for the plaintiff testified that he had deviated from the standard of medical care by taking too long to administer antibiotics, which, in their view, ought to have been given within 30 minutes . Expert witnesses for the defense testified that 2 hours to administer antibiotics in this case was within the standard of care . What ought to be the response of the pediatric community to discrepant expert testimony such as this? One possible response is nothing . Lawyers from both sides will find expert medical witnesses who articulate positions favorable to their clients (as they did in this case), and the truth will emerge after vigorous cross-examination . This, we suggest, is inadequate . We believe that some expert opinions can be viewed as better than others . That is, some opinions describe the standard of medical care correctly while other expert opinions are (to put it charitably) idiosyncratic, failing to depict accurately the skill and care ordinarily administered in comparable situations . Currently, jurors are informed about the standard of care by expert witnesses, who rely on their own medical knowledge and experience . However, a huge body of literature demonstrates that recollections of individual experience are inevitably flawed, and flawed in a nonrandom direction (the Monday morning quarterback phenomenon) . Consider the infant with meningitis . When experts in pediatric emergency medicine and pediatric infectious diseases (ID) were asked about the median time from emergency room (ER) presentation to administration of antibiotics in a child with suspected meningitis, their opinions were wrong and slanted toward the outcome known to be desired (namely, a shorter elapsed time) . ER physicians (median estimated time to antibiotic administration {AB-TIME} = 46 minutes) and ID physicians (median estimated AB-TIME = 80 minutes) consistently underestimated the actual median value of AB-TIME determined by chart review (120 minutes) . From the judicial perspective such potential flaws in expert testimony are assumed to be equally distributed among experts . All admissible evidence is a priori of equal weight until a jury decides otherwise . The standard of medical care is created anew by expert testimony in each individual case, disappearing, like Brigadoon, upon resolution of the dispute . However, to anyone but a lawyer, the standard of medical care must exist as something outside the courtroom testimony of experts, and if it does exist, it should be easily described so that expert testimony can be judged more (or less) accurate in depicting it . We contend that medical care is not a single behavior that conforms to or deviates from an idiosyncratic and retrospectively determined standard, but rather a distribution of behaviors in response to a variety of medical circumstances . For a given scenario, each of several possible responses can be ascribed a relative frequency based on empirical data, and the consequent normal curve depicts the totality of medical care . Substandard care then falls out neatly as behaviors lying outside the large majority of cases . Juries would be empowered (as they are currently) to determine exactly where on this curve substandard care lies, but at least the debate would share the same description of reality . Recent US Supreme Court guidelines regarding expert testimony provide an opportunity to expand the use of databases in medical negligence cases . The Court restricted expert testimony to "scientific knowledge .. . based on generating hypotheses and testing them to see if they can be falsified .. . (ABSTRACT TRUNCATED)

Curr Probl Pediatr, 1998 Aug, 28(7), 205 - 34
A rational approach to the outpatient management of lacerations in pediatric patients; Kanegaye JT; Lacerations are a frequent reason for pediatric health care visits . Many are referred to EDs or to surgical specialists but may be treated by the pediatrician who has the time and interest in maintaining wound care skills . Although skin closure is often viewed as the primary event in wound care, local anesthesia and wound toilet are equally important aspects in which expertise is often undervalued . On occasion, patient anxiety and resistance complicates wound care, and a variety of sedative techniques facilitates completion of procedures that otherwise would require general anesthesia . Adherence to basic principles and the occasional use of innovations in wound care enable the clinician to bring about optimal outcomes.

J Pediatr Gastroenterol Nutr, 1998 Sep, 27(3), 323 - 32
Use of probiotics in childhood gastrointestinal disorders; Vanderhoof JA et al.; Probiotics appear to be useful in the prevention or treatment of several gastrointestinal disorders, including infectious diarrhea, antibiotic diarrhea, and traveler's diarrhea . Results of preliminary human and animal studies suggest that patients with inflammatory diseases, and even irritable bowel syndrome, may benefit from probiotic therapy . Probiotics represent an exciting therapeutic advance, although much investigation must be undertaken before their role in gastroenterology is clearly delineated . Questions related to probiotic origin, survivability, and adherence are all important considerations for further study . More important, each probiotic proposed must be studied individually and extensively to determine its efficacy and safety in each disorder for which its use may be considered.

Khirurgiia (Sofiia), 1997, 50(2), 23 - 4
{The surgical treatment of pancreatic pseudocysts following acute pancreatitis}; Petrov P et al.; The tactics and results of the operative treatment of pancreatic cysts, complicating severe destructive pancreatitis in a series of thirteen patients, are discussed . The following operative methods are made use of: marsupialization (1), Yurash (10), cystojejunoanastomosis with Braunova (2) . The character and scope of surgical intervention are determined intraoperatively, depending on the anatomical situation faced . In pancreatic cysts operated according to Yurash (cystogastroanastomosis), an original drainage method with two probes introduced nasally is used--one wider into the anastomosis, and a narrower one into the duodenum for feeding . The probes are retained for periods ranging from 9 to 35 days . No relapse of the cysts operated by different methods are registered, with the exception of a female patient undergoing marsupialization . In one case operated according to Yurash where no preoperative preparation is done the outcome is fatal, with the patient dying of hemorrhage on the third postoperative day . All patients are operated within 3 months after the formation of cysts . The preoperative preparation includes Kontrikal, Petphtoruracil, atropine, heparin and antibiotic; in some patients the listed drugs are introduced intraarterially into truncus celiacus . A number of inferences are reached and recommendations made: 1 . Waiting for the generally accepted 3-month term is unnecessary . 2 . In cysts involving the head of the pancreas, tightly adherent to the posterior wall of the stomach, the method of Yurash with the modification suggested for probing should be given preference . 3 . In cysts of the body region and tail cystojejunoanastomosis with Braunova is practicable . 4 . Proceeding with the preoperative medication in the postoperative period is advisable.

J Leukoc Biol, 1998 Sep, 64(3), 302 - 10
Macrophage cytoplasmic vesicle pH gradients and vacuolar H+-ATPase activities relative to virus infection; Natale VA et al.; A number of viruses replicate in macrophages, some having an obligate requirement for a macrophage host . This raised the question concerning the role of the macrophage endosomal/lysosomal compartment during such infections . Both lysosomotropic weak bases, amantadine and chloroquine, which interfere with endosomal/lysosomal pH gradients, and the macrolide antibiotic bafilomycin A1, which interferes with vacuolar H+-ATPase, inhibited African swine fever (ASF) virus replication in porcine macrophages . This inhibition was reversible: replenishment of bafilomycin, but not amantadine or chloroquine, maintained the inhibition . The characteristics of the inhibition, and the capacity of virus to escape and re-commence replication, related to the capacity of each drug to interfere with the endosomal/lysosomal proton pump . These results demonstrate that the virus actually requires macrophage endosomal/lysosomal activity for its replication . Therein, vacuolar H+-ATPase activity is particularly critical for successful virus replication, which is interesting considering the importance of this for endosomal/lysosomal activity and macrophage function.

Biopharm Drug Dispos, 1998 Sep, 19(6), 407 - 12
Chronopharmacokinetics and calcium in the prevention of gentamicin-induced nephrotoxicity in rabbits; Perez de la Cruz MJ et al.; The study used 36 New Zealand white rabbits organized into three groups of 12 animals each . Group I received gentamicin; Group II received joint administration of gentamicin and calcium chloride and Group III received gentamicin, calcium chloride and verapamil . All the drugs were administered over 16 day periods . Groups I and II were divided in two subgroups, one subgroup receiving the treatment in winter and the other in summer . The results obtained for Group I indicate that there is an influence of the seasonal period on the gentamicin elimination and/or distribution . Mean plasma levels of the antibiotic at steady-state as well as the amounts of gentamicin accumulated in renal tissue are higher in winter than in summer . On the other hand, when calcium was administrated with the antibiotic, no significant circannual variations were observed in the renal toxicity of gentamicin . Under our study conditions the presence of calcium diminishes gentamicin plasma levels and the amount accumulated in kidney . Calcium, probably, generated a diminution in renal damage and consequently gentamicin renal excretion increases . The differences between Group II and Group III are due to the effect of verapamil . This agent blocks the calcium channels reducing the calcium protective effect on the nephrotoxicity of gentamicin.

Leukemia, 1998 Sep, 12(9), 1355 - 66
Inhibition of erythroid differentiation and induction of megakaryocytic differentiation by thrombopoietin are regulated by two different mechanisms in TPO-dependent UT-7/c-mpl and TF-1/c-mpl cell lines; Goncalves F et al.; Thrombopoietin (TPO) regulates megakaryocytic (MK) maturation and platelet production . Molecular and cellular mechanisms of the TPO-induced MK differentiation are not totally understood . In order to develop cellular models to study these mechanisms, we introduced c-mpl into UT-7 and TF-1 cells by means of a retroviral vector and compared the effects of TPO on these two cell lines . UT-7 and TF-1 cell lines are two factor-dependent leukemic cell lines with an erythroid and MK phenotype . They proliferate in response to IL-3, GM-CSF and EPO, but not to TPO . The erythroid differentiation of both cell lines can be markedly increased by EPO . Several UT-7/c-mpl and TF-1/c-mpl cell clones which express different levels of the c-mpl protein (Mpl) were obtained and all became TPO-dependent for their proliferation . The UT-7/c-mpl clones, but not the TF-1/c-mpl clones, were capable of undergoing MK differentiation in response to TPO . This was demonstrated by the increase in MK markers (GPIIb, GPIIIa, GPIb alpha, GPIX and vWF), the appearance of cytoplasmic alpha-granules, intracellular membranes resembling demarcation membranes which were immunologically labeled with an GPIIb/IIIa anti-antibody, and a small percentage of polyploid cells (8N and 16N) . In contrast, TPO inhibited the erythroid program of differentiation (glycophorin A, beta-globin and EPO receptor) as well as the differentiative activity of EPO in both UT-7/c-mpl and TF-1/c-mpl clones . It is noteworthy that the differentiative effect of EPO in TF-1/c-mpl cells was associated with an increase in GATA-1 transcripts which was totally suppressed by TPO . Overall the effects of TPO are the same as those of phorbol myristate acetate (PMA) which also induces MK differentiation and inhibits erythroid differentiation . These results suggest that: (1) Mpl expression is necessary but not sufficient for induction of MK differentiation; and (2) induction of Mk differentiation and inhibition of erythroid differentiation by TPO involve different signaling pathways; the pathway involved in the inhibition of erythroid differentiation might be related to a downregulation of GATA-1 expression in TF-1 cells.

J Med Assoc Thai, 1998 Aug, 81(8), 602 - 7
Comparison of short versus long duration of ampicillin and gentamicin for radical hysterectomy; Maleemonkol S et al.; Prophylactic antibiotic therapy for radical hysterectomy is still controversial . Although the efficacy of antibiotics have been demonstrated, there remains the question of duration of administration . In this study, we retrospectively reviewed 95 patients who underwent radical hysterectomy and pelvic lymphadenectomy for cervical cancer at our institute . The management was uniform except for the duration of antibiotic administration . Group I (34 cases) had ampicillin and gentamicin for 3 days while group II (61 cases) had the same regimen for 7 days . No significant difference was found in terms of postoperative infection (2.9% in group I and 1.6% in group II) or febrile morbidity (32.4% versus 50.8%) . Other factors such as the patients' age, body weight, preoperative hemoglobin level, amount of blood loss and blood transfused, operative time, duration of retroperitoneal drain and duration of suprapubic cystostomy . Only operative time had a significant influence on febrile morbidity regardless of the duration of antibiotics administered . In conclusion, the antibiotic administration gave a radical hysterectomy and pelvic lymphadenectomy a very low incidence of postoperative infection . Longer duration of treatment did not appear to lessen postoperative infection nor febrile morbidity . Shorter duration of antibiotic administration needs further evaluation.

Z Orthop Ihre Grenzgeb, 1998 May-Jun, 136(3), 268 - 71
{Development of gentamicin-resistant Small Colony Variants of S . aureus after implantation of gentamicin chains in osteomyelitis as a possible cause of recurrence}; von Eiff C et al.; AIM: Recently, S . aureus small colony variants (SCVs) were reported to persist within cultured endothelial cells and to cause persistent and antibiotic resistant infections in humans . Because gentamicin can very reproducably select for electron transport deficient SCVs as shown in earlier in vitro experiments, we searched for SCVs in a patient with chronic osteomyelitis, who received gentamicin beads . METHOD: Special culture and identification procedures for determination of SCVs were used, including testing of the S . aureus specific nuc gene, pulsed field gel electrophoresis (PFGE) as a typing method and characterization of the auxotrophism of the SCVs . RESULTS: In a case of a 34-year-old patient with chronic osteomyelitis who had previously been treated with gentamicin beads, menadione auxotrophic S . aureus SCVs as well as wild type S . aureus were recovered in multiple bone specimen . All different colony types isolated from simultaneous or from sequential specimen were shown to be clonal by PFGE . CONCLUSION: Recovery of S . aureus SCVs from a patient treated with gentamicin beads suggests that the slow release of gentamicin into the local environment may be an efficient way to select for and/or induce SCVs . These data should alert physicians to also consider SCVs when a treatment failure occurs in a patient that has received gentamicin beads.

Chir Narzadow Ruchu Ortop Pol, 1998, 63(3), 273 - 9
{Chronic bone abscess}; Bielawski J et al.; The review of 68 patients with chronic bone abscess as a long-term sequel to ostomyelitis is presented . Antibiotic instillation within abscess cavity is recommended by the authors . Once the drainage is concluded immunotherapy should be introduced to secure long-lasting remission as in 90% of presented cases.

Biochim Biophys Acta, 1998 Aug 14, 1373(1), 179 - 94
Structural studies of the H+/oligopeptide transport system from rabbit small intestine; Kramer W et al.; A 127-kDa protein was identified as a component of the H+/oligopeptide transport system in brush-border membrane vesicles from rabbit small intestine by photoaffinity labeling with {3H}cephalexin and further photoreactive beta-lactam antibiotics and dipeptides . Reconstitution of stereospecific transport activity revealed the involvement of the 127-kDa protein in H+-dependent transport of oligopeptides and orally active alpha-amino-beta-lactam antibiotics (Kramer et al., Eur . J . Biochem . 204 (1992) 923-930) . H+-Dependent transport activity was found in all segments of the small intestine concomitantly with the specific labeling of the 127-kDa protein . By enzymatic deglycosylation, fragments of Mr 116 and 95 kDa were obtained from the 127-kDa protein with endoglucosidase F and N-glycanase, whereas with endoglucosidase H, a fragment of Mr 116 kDa was formed . These findings indicate that the photolabeled 127-kDa protein is a microheterogenous glycoprotein . Surprisingly, it was found that the solubilized and purified 127-kDa protein showed enzymatic sucrase and isomaltase activity . Inhibition of the glucosidase activities with the glucosidase inhibitor HOE 120 influenced neither H+/oligopeptide transport nor photoaffinity labeling of the 127-kDa protein . With polyclonal antibodies raised against the purified 127-kDa protein, a coprecipitation of sucrase activity and the photolabeled 127-kDa beta-lactam antibiotic binding protein occurred . Target size analysis revealed a functional molecular mass of 165+/-17 kDa for photoaffinity labeling of the 127-kDa protein, suggesting a homo- or heterodimeric functional structure of the 127-kDa protein in the brush-border membrane . These findings indicate that the H+/oligopeptide binding protein of Mr 127000 is closely associated with the sucrase/isomaltase complex in the enterocyte brush-border membrane.

Biochim Biophys Acta, 1998 Aug 14, 1373(1), 76 - 86
The structuring effects of amphotericin B on pure and ergosterol- or cholesterol-containing dipalmitoylphosphatidylcholine bilayers: a differential scanning calorimetry study; Fournier I et al.; Amphotericin B (AmB) is the most widely used polyene antibiotic to treat systemic fungal infections which affect an increasing number of immunocompromised patients . It is generally thought that AmB forms pores within the fungi membranes by interacting with ergosterol, the main sterol of fungi . However, it also interacts with the cholesterol contained in mammalian cells, hence its toxicity . In order to have a better understanding of the interactions prevailing between AmB and sterols, differential scanning calorimetry was used to study various mixtures incorporating from 6.5 to 25 mol% of AmB in pure dipalmitoylphosphatidylcholine (DPPC) vesicles and in ergosterol- or cholesterol-containing DPPC vesicles . The sterol concentration was kept constant at 12.5 mol% with respect to the phospholipid . Our results show that three phases co-exist when AmB is dispersed in the pure phospholipid . One corresponds to the phospholipid phase alone . The two others are characterised by a broad transition at temperatures higher than the main transition temperature of the pure phospholipid, corresponding to the drug in interaction with the aliphatic chains of the lipid . The fact that the transition temperatures of these additional components are higher than that of the pure phospholipid suggests that AmB interacts strongly with the aliphatic chains of the lipid, consistent with the idea prevailing in the literature that AmB by itself may form pores in a lipid matrix . When AmB interacts with cholesterol-containing bilayers the thermograms also present three components . Upon increasing the concentration of AmB, though, an important broadening of these components is observed which is explained in terms of destabilisation of the organisation of the aliphatic chains . The situation is strikingly different if ergosterol is present in the lipid matrix . The thermograms remain unmodified as the concentration of AmB is increased and a broad transition, now involving only two components when the thermograms are decomposed, is observed . An analysis of the results shows that various interacting units, e.g . AmB+DPPC and (AmB+ergosterol)+DPPC, are present within the membrane . These units involve the phospholipid and hence contribute to its structurisation . The important differences between the thermograms obtained with the ergosterol- as compared to the cholesterol-containing bilayers, in spite of the structural similarity of these two sterols, provides strong evidence for the selectivity of interaction of AmB with ergosterol as compared to cholesterol . It is thus clear that the action of AmB on cholesterol- as compared to ergosterol-containing membranes results from different mechanisms . Finally, UV-visible spectra of AmB in pure as well as sterol-containing DPPC vesicles show the presence of absorption bands that give support to the interpretation derived from the calorimetric data.

J Biol Chem, 1998 Sep 18, 273(38), 24693 - 700
Identification and characterization of novel clathrin adaptor-related proteins; Takatsu H et al.; We have identified a human approximately 87-kDa protein, designated as gamma2-adaptin, that is similar to gamma-adaptin (called gamma1-adaptin in this paper), a large chain of the AP-1 clathrin-associated adaptor complex, not only in the primary structure (60% amino acid identity) but also in the domain organization . Northern blot analysis has shown that its mRNA is expressed in a variety of tissues . Analysis using a yeast two-hybrid system has revealed that, similarly to gamma1-adaptin, gamma2-adaptin is capable of interacting not only with the sigma1 chain (called as sigma1A in this paper), the small chain of the AP-1 complex, but also with a novel sigma1-like protein, designated as sigma1B, which shows an 87% amino acid identity to sigma1A; and that, unlike gamma1-adaptin, it is unable to interact with beta1-adaptin, another large chain of the AP-1 complex . Immunofluorescence microscopy analysis has revealed that gamma2-adaptin is localized to paranuclear vesicular structures that are not superimposed on structures containing gamma1-adaptin . Furthermore, unlike gamma1-adaptin, gamma2-adaptin is recruited onto membranes in the presence of a fungal antibiotic, brefeldin A . These data suggest that gamma2-adaptin constitute a novel adaptor-related complex that participates in a transport step different from that of AP-1.

J Bacteriol, 1998 Sep, 180(18), 4929 - 37
Identification of two genes from Streptomyces argillaceus encoding glycosyltransferases involved in transfer of a disaccharide during biosynthesis of the antitumor drug mithramycin; Fernandez E et al.; Mithramycin is an antitumor polyketide drug produced by Streptomyces argillaceus that contains two deoxysugar chains, a disaccharide consisting of two D-olivoses and a trisaccharide consisting of a D-olivose, a D-oliose, and a D-mycarose . From a cosmid clone (cosAR3) which confers resistance to mithramycin in streptomycetes, a 3-kb PstI-XhoI fragment was sequenced, and two divergent genes (mtmGI and mtmGII) were identified . Comparison of the deduced products of both genes with proteins in databases showed similarities with glycosyltransferases and glucuronosyltransferases from different sources, including several glycosyltransferases involved in sugar transfer during antibiotic biosynthesis . Both genes were independently inactivated by gene replacement, and the mutants generated (M3G1 and M3G2) did not produce mithramycin . High-performance liquid chromatography analysis of ethyl acetate extracts of culture supernatants of both mutants showed the presence of several peaks with the characteristic spectra of mithramycin biosynthetic intermediates . Four compounds were isolated from both mutants by preparative high-performance liquid chromatography, and their structures were elucidated by physicochemical methods . The structures of these compounds were identical in both mutants, and the compounds are suggested to be glycosylated intermediates of mithramycin biosynthesis with different numbers of sugar moieties attached to C-12a-O of a tetracyclic mithramycin precursor and to C-2-O of mithramycinone: three tetracyclic intermediates containing one sugar (premithramycin A1), two sugars (premithramycin A2), or three sugars (premithramycin A3) and one tricyclic intermediate containing a trisaccharide chain (premithramycin A4) . It is proposed that the glycosyltransferases encoded by mtmGI and mtmGII are responsible for forming and transferring the disaccharide during mithramycin biosynthesis . From the structures of the new metabolites, a new biosynthetic sequence regarding late steps of mithramycin biosynthesis can be suggested, a sequence which includes glycosyl transfer steps prior to the final shaping of the aglycone moiety of mithramycin.

Neurosurgery, 1998 Sep, 43(3), 616 - 9
Abscess formation in invasive pituitary adenoma: case report; Jadhav RN et al.; OBJECTIVE AND IMPORTANCE: Pituitary abscess is rare, with few cases of secondary pituitary abscess reported . To our knowledge, only 14 cases of pituitary adenomas with abscess have been reported, and this is the first report to include a magnetic resonance image of a pituitary adenoma with abscess . CLINICAL PRESENTATION: A 22-year-old man presented with decreasing vision, headache, and vomiting . His higher functions were normal, with visual disturbance in both eyes . Computed tomographic scans and magnetic resonance images were suggestive of a sellar tumor with a cystic component . INTERVENTION: A right pterional craniotomy was performed, and the tumor was debulked, revealing an abscess in the center . Postoperatively, the patient received a regimen of antibiotics . CONCLUSION: Early surgical intervention plus follow-up antibiotic therapy are the mainstay of treatment for abscess formation in pituitary adenomas.

Curr Microbiol, 1998 Oct, 37(4), 274 - 80
Methods for detection of conjugative plasmid transfer in aquatic environments; Sengelov G et al.; Donor and recipient counter selection was evaluated by selecting bacteria that received plasmid RP4 by conjugation on filters and in lake water microcosms . Three counter selection systems were compared; (i) Use of antibiotic-resistant recipients, (ii) use of an auxotrophic donor, and (iii) use of a donor with chromosomal suicide genes . Transfer efficiencies of transconjugants per recipient obtained with the three different counter selection systems in filter-matings were not significantly different . Some nalidixic acid-resistant recipients became partly sensitive to nalidixic acid after receiving the plasmid . Use of an auxotrophic donor was a feasible and easy way to recover indigenous transconjugants . A strain with two copies of the suicide gene gef was successfully eliminated in filter-matings, but elimination of the donor in microcosms by induction of the suicide genes did not succeed . Thus, this counter selection system was not usable in microcosm experiments.

Arch Microbiol, 1998 Oct, 170(4), 309 - 12
Effects of pisatin on Dictyostelium discoideum: its relationship to inducible resistance to nystatin and extension to other isoflavonoid phytoalexins; Prasanna TB et al.; Dictyostelium discoideum amoebae can acquire resistance to otherwise inhibitory concentrations of pisatin, an isoflavonoid phytoalexin of pea, and nystatin, a polyene antibiotic, following pretreatment with sublethal concentrations of these compounds . Additionally, growth on medium containing pisatin can induce nystatin resistance . We show here that distinct mechanisms mediate the inducible resistance to these two compounds because it is possible to isolate mutations that specifically block the induction of nystatin resistance but do not affect the induction of pisatin resistance . Pisatin did not affect wild-type sterol biosynthesis; therefore, the induction of nystatin resistance by pisatin is probably not via an alteration of membrane sterols . The inducible pisatin resistance phenotype was shown to extend to the isoflavonoid phytoalexins maackiain and biochanin A, and all three compounds inhibited the aggregation of amoebae that is normally triggered by starvation.

Am J Orthop, 1998 Aug, 27(8), 561 - 2
Salvage of failed amputation about the hip in peripheral vascular disease by open wound care and nutritional support; Pinzur MS et al.; Five consecutive patients with wound and/or plastic surgical flap failure after hip disarticulation or amputation at the lesser trochanteric transfemoral level were treated with local tissue debridement, open wound management, culture-specific antibiotic therapy, and nutritional supplementation . All of the patients underwent amputation about the hip as a result of ischemic necrosis of the lower extremity . Four of the five patients were able to achieve wound healing by second intention . The fifth patient died 2 months after the surgery . None of the patients required revision surgery . One patient underwent split-thickness skin grafting to minimize the need for continued wound care . Local wound management combined with nutritional support and culture-specific antibiotic therapy is an acceptable alternative to major amputation stump revision in patients with potentially high morbidity who fail to heal after amputation about the hip.

Helicobacter, 1998 Sep, 3(3), 179 - 83
Performance of a rapid whole blood test for Helicobacter pylori in primary care: a German multicenter study; Hackelsberger A et al.; BACKGROUND: Serological rapid whole-blood tests for the detection of H . pylori are presently being promoted for use in primary care . We conducted a multi-center study to investigate the diagnostic accuracy of the Boehringer Mannheim Helicobacter pylori test (BM test), which is identical with the Cortecs Helisal test . PATIENTS AND METHODS: A previous diagnosis of H . pylori, a history of peptic ulcer diseases, or proton-pump inhibitor, bismuth or antibiotic use during the preceding month were exclusion criteria . The BM test was performed prior to endoscopy by 7 primary care physicians, 5 practicing gastroenterologists, or a single physician in the university hospital outpatient service . During endoscopy, antral and corpus biopsies were obtained for histology and rapid urease testing (RUT) . H . pylori positivity was defined by histology and/or RUT as reference methods . H . pylori IgG-ELISA was performed additionally . RESULTS: Of the 203 patients included, 151 were H . pylori-positive by reference methods (74.4%) . The overall accuracy of the BM test was 77.3% . Eight BM tests were indeterminate, and in the other 195 patients the test performed as follows: sensitivity 80.3%, specificity 81.3%, positive predictive value 92.9%, negative predictive value 57.4% . Using IgG-ELISA as reference, the BM test performance was similar . It also did not differ substantially among the three groups of physicians involved . CONCLUSIONS: We found the performance of the BM test to be insufficiently accurate, as both over- and underdiagnosis of H . pylori infection were not infrequent . This test needs to be improved before its use in primary care can be recommended.

J Vet Pharmacol Ther, 1998 Aug, 21(4), 257 - 68
Intracellular accumulation, subcellular distribution and efflux of tilmicosin in swine phagocytes; Scorneaux B et al.; Tilmicosin is a semi-synthetic macrolide antibiotic, currently approved for veterinary use in cattle and swine respiratory disease . As the concentrations of tilmicosin are generally low in swine lung tissue, the interaction of tilmicosin with three types of swine phagocytes (monocyte-macrophages, alveolar macrophages, and neutrophils) was evaluated to provide an understanding of clinical efficacy . After incubation with radiolabelled tilmicosin, uptake was determined and expressed as the ratio of the intracellular (Ci) to the extracellular (Ce) drug concentration (Ci/Ce) . Tilmicosin was avidly accumulated by the swine phagocytes (Ci/Ce 48-69 at 4 h incubation) with 51 to 85% localized in the lysosomes . Uptake was dependent on cell viability, temperature and pH, but was not influenced by the metabolic inhibitors, sodium cyanide or potassium fluoride . However, lipopolysaccharide (LPS) exposure increased tilmicosin uptake by the swine phagocytes . In neutrophils, upon removal of extracellular tilmicosin, 60% of the intracellular tilmicosin was effluxed within the first 30 min, but after 4 h of incubation in drug-free medium, 25% remained cell-associated . In contrast, after 4 h of incubation in drug-free medium, 60% and 45% of tilmicosin remained cell-associated, within alveolar macrophages and monocyte-derived macrophages, respectively . Tilmicosin uptake was observed to increase lysosomal enzyme (acid phosphatase, lysozyme and beta-glucuronidase) production . Finally, neutrophils were shown to transport and efflux bioactive tilmicosin in a test system measuring both neutrophil chemotaxis under agarose and a bioassay measuring inhibition of bacterial growth in the presence of antibiotic in agar . These in vitro interactions of tilmicosin with swine phagocytes suggest an integral role in effecting clinical efficacy.

Nat Struct Biol, 1998 Sep, 5(9), 769 - 74
Solution structure of the tobramycin-RNA aptamer complex; Jiang L et al.; We have solved the solution structure of the aminoglycoside antibiotic tobramycin complexed with a stem-loop RNA aptamer . The 14 base loop of the RNA aptamer 'zippers up' alongside the attached stem through alignment of four mismatches and one Watson-Crick pair on complex formation . The tobramycin inserts into the deep groove centered about the mismatch pairs and is partially encapsulated between its floor and a looped out guanine base that flaps over the bound antibiotic . Several potential intermolecular hydrogen bonds between the charged NH3 groups of tobramycin and acceptor atoms on base pair edges and backbone phosphates anchor the aminoglycoside antibiotic within its sequence/structure specific RNA binding pocket.

Am J Respir Crit Care Med, 1998 Sep, 158(3), 885 - 90
Lung resection for invasive pulmonary aspergillosis in neutropenic patients with hematologic diseases; Reichenberger F et al.; Invasive pulmonary aspergillosis (IPA) is associated with a high mortality . In 27 consecutive neutropenic patients who underwent lung resection for suspected IPA, we analyzed preoperative diagnostic evaluation, operative procedure, perioperative management, histological findings, outcome concerning recurrence of aspergillosis, and survival to evaluate the morbidity and mortality of a surgical treatment of IPA . Seventeen patients with hematologic diseases had previously undergone high-dose chemotherapy and four stem cell transplantation . Six patients with aplastic anemia were treated with antilymphocyte globulin . IPA was suspected if localized infiltrates developed on thoracic CT scan, and fever persisted under antibiotic therapy in neutropenic patients . In only one case a diagnosis of IPA could be made preoperatively . Twenty patients underwent lobectomy and seven wedge resection . At day of surgery the neutrophil count was below 500 x 10(9)/L in 78% of patients, and the platelet count below in 50 x 10(9)/L in 58% of patients . Invasive fungal infection was confirmed histologically in 22 of 27 patients (81.5%); in five patients no fungal infection was documented . The median duration of surgery was 120 min . Postoperatively, patients stayed one night in the intensive care unit, and chest tubes were removed after 2 d . Within 7 d a median of four erythrocyte packs and two platelet packs per patient were replaced . Major surgical complications occurred in two patients (bronchial dehiscence; pleural aspergillosis) . Minor surgical complications included prolonged chest tube drainage (recurrent pneumothorax, n = 2; air leakage, n = 1; hematothorax, n = 1), pleural effusion (n = 4), and seroma (n = 2) . Postoperatively, two patients suffered from histologically proven disseminated aspergillosis (pleural aspergillosis, renal aspergilloma) and another patient from suspected orbital aspergillosis . At 30 d postoperative mortality was 11% and 3-mo survival was 77% . After lung resection, seven patients underwent stem cell transplantation without recurrence of IPA . In conclusion, we suggest lung resection is a therapeutic option for invasive pulmonary aspergillosis in neutropenic patients with hematologic diseases and is associated with a low surgery-related morbidity and mortality.

Obes Surg, 1997 Jun, 7(3), 215 - 7; discussion 218-9
An approach to the treatment of recurring polyarthralgia after jejunoileal bypass; Cannova JV et al.; Polyarthralgia after jejunoileal bypass (JI) is a well-documented complication . In the past, this was treated by antibiotic therapy, but definitive therapy uncommonly necessitated surgical reversal of the JI bypass . This case report discusses the etiology of arthralgias and presents a technique for its treatment without bypass reversal.

J Auton Pharmacol, 1998 Apr, 18(2), 105 - 13
The L-arginine inhibition of rat middle cerebral artery contractile responses is mediated by inducible nitric oxide synthase; Alonso MJ et al.; 1 . The effect of L-arginine (L-Arg), the nitric oxide synthase (NOS) substrate, on the responses to prostaglandin F2alpha (PGF2alpha, 10 microM) and K+ (120 mM) in rat middle cerebral artery (MCA) segments was analysed . 2 . PGF2alpha induced a stable contraction of 0.35+/-0.06 mN mm(-1); the subsequent addition of bradykinin (BK, 1 microM) produced a relaxation of 42+/-9% of the PGF2alpha-induced tone . K+ induced a response consisting of a rapid basal tone increase (1.42+/-0.16 mN mm(-1)) followed by a decrease to a stable phase (1.24+/-0.15 mN mm(-1)) . 3 . L-Arg (0.1 mM), but not D-Arg, decreased the basal tone and reduced the contraction to PGF2alpha in segments with and without endothelium . The contractile response to K+ was also reduced and not maintained in the presence of L-Arg . 4 . The inhibitory effect of L-Arg on the PGF2alpha- and K+-induced contractions was completely reversed by the NOS inhibitor, NG-monomethyl-L-arginine (L-NMMA, 0.1 mM) . 5 . Pre-incubation of segments with dexamethasone (1 microM), to inhibit inducible NOS (iNOS), or with the antibiotic polymyxin B (10 microg ml(-1)) reduced the L-Arg inhibition, whereas it was increased by lipopolysaccharide (LPS, 100 ng ml(-1)), an inductor of iNOS . L-NMMA antagonized the effects of dexamethasone and LPS . 6 . The present results suggest that L-Arg inhibition of the PGF2alpha- and K+-induced contractions in rat MCA is the result of NO synthesis by iNOS stimulation.

Rozhl Chir, 1998 Jul, 77(7), 291 - 3
{Use of collagen with gentamycin in abdominal and thoracic surgery}; Vyhnanek F et al.; Based on an analysis of a group of 16 patients operated at the Surgical Clinic of the Third Medical Faculty, Charles University Prague the indication of collagen with gentamycin was established . Collagen with gentamycin is used locally for prophylaxis and treatment of intraabdominal and intrathoracic infections . In a group of patients it was used for prophylaxis of postoperative infections in elective abdominal operations such as plastic operations of the abdominal wall, anastomoses in the aboral part of the GIT, in operations of fistulae as part of treatment of intraabdominal abscesses and advanced cholecystitis and appendicitis . In thoracic surgery for prophylaxis of postoperative infections in plastic operations of the thoracic wall and also after surgery on account of inflammatory complications (lung abscess, bronchopleural fistula).

Int J Periodontics Restorative Dent, 1998 Jun, 18(3), 266 - 75
Implant placement in large edentulous ridges expanded by GBR using a bioresorbable collagen membrane; Parodi R et al.; The purpose of this study is to evaluate the possibility of expanding an edentulous ridge spanning two or more teeth by a two-step technique with bioresorbable collagen membranes . Sixteen healthy patients were treated, four in the mandible and 12 in the maxilla . The borderline of the crest width was less than or equal to 4 mm . In each patient only one ridge augmentation was performed . After elevation of a full-thickness flap, a surgical stent was positioned to identify the area of ideal implant positioning . The width of the crest at the location of the surgical stent was measured at the time of GBR procedure and 7 to 12 months later during implant insertion . Native collagen sponges were placed buccally and lingually, and a collagen membrane was shaped and trimmed to completely cover the edentulous ridge . The flaps were sutured to achieve primary closure . Antibiotic and clorhexidine mouthrinse were prescribed, and the patients were recalled every 2 weeks . At implant placement, the mean increase in the size of the crest was 2.49 mm (+/- 1.61 mm) . In 12 out of 16 patients (75%) it was possible to insert 27 implants according to the prosthetic need established previously . All implants were successfully loaded, and in the four cases where no appreciable results were obtained, no clinical complications or loss of hard and soft tissue were observed.

Plast Reconstr Surg, 1998 Sep, 102(3), 822 - 4
Hyperbaric oxygen therapy for cutaneous/soft-tissue zygomycosis complicating diabetes mellitus; Bentur Y et al.; A 24-year-old female diabetic patient was hospitalized because of ketoacidosis and a necrotic wound on the hand . Debridement and antibiotic therapy failed to halt the process . After demonstration of Mucor in cultures from the wound, the patient underwent extensive surgery and amphotericin B was administered . When the necrotic process continued despite these measures, adjunctive hyperbaric oxygen (100% O2 at 2.5 ATA for 90 minutes) was administered daily for a total of 21 treatment sessions . She gradually improved, and at 2 months follow-up most of the wound had healed . Although the mortality rate of cutaneous/soft-tissue zygomycosis is markedly lower than that of the rhinocerebral form, morbidity is still considerably high . Successful use of hyperbaric oxygen has been reported in rhinocerebral zygomycosis, and it may have been of benefit in this high-risk patient by preventing local and systemic spreading of the fungus . This report is the first case of the use of hyperbaric oxygen for cutaneous/soft-tissue zygomycosis . It is suggested that hyperbaric oxygen be considered for this indication in diabetic patients as an adjunct to surgery and amphotericin B.

Plast Reconstr Surg, 1998 Sep, 102(3), 814 - 7
Necrotizing fasciitis of the face and neck; Sepulveda A et al.; Necrotizing fasciitis is a rare infection in the surgical and infectious medical services, but when it is present, in most cases, the affected areas are the lower extremities and the abdominal and thoracic walls, and more frequently in perineum and genital areas, which is commonly known as Fournier's gangrene . This type of infection is extremely rare in the face and neck, because the great vascularity in these regions makes the tissues rarely susceptible to ischemia and infection, even when large flaps are lifted in reconstructive and aesthetic procedures . We present a case of necrotizing fasciitis in face and neck, with emphasis on the medical and surgical treatment that should be based on antibiotic therapy of broad spectrum; secondary reconstructive procedures should be planned.

Allergy Asthma Proc, 1998 Jul-Aug, 19(4), 181 - 4
Treatment of sinusitis in the next millennium; Kaliner M; Sinusitis is an increasingly more important disease due to its increasing prevalence, costs, and recognition . Most acute sinusitis episodes follow colds or acute allergic rhinitis . Chronic sinusitis is most commonly due to allergic and nonallergic rhinitis or anatomical defects in the nose . Several common immunologic abnormalities usually present as sinusitis and may be recognized first by the allergist-immunologist . Treatment involves a carefully selected antibiotic prescribed for an adequate period of time, nasal hygiene using nasal saline washes, topical nasal corticosteroids, and decongestants . Medical management of sinusitis tends to be effective, even in patients with long-standing sinus disease.

Am J Emerg Med, 1998 Sep, 16(5), 512 - 3
Anaphylaxis to topical bacitracin zinc ointment; Saryan JA et al.; This report describes a case of systemic anaphylaxis to bacitracin zinc ointment in a 24-year-old man who was injured in a motorcycle accident . Extensive abrasions on the patient's extremities were cleaned with Shurclens before application of viscous Xylocaine and bacitracin zinc ointment . Five minutes later, the patient exhibited symptoms of severe anaphylaxis and required the administration of epinephrine, antihistamines, intravenous fluids, and corticosteroids . Two weeks later, he underwent prick/puncture skin testing to Shurclens and bacitracin zinc ointment as well as prick/puncture, intracutaneous, and subcutaneous challenge with Xylocaine . Only the result of the prick test to bacitracin zinc ointment was positive . Although bacitracin is considered to be a safe topical antibiotic, physicians should be aware of the potential not only for delayed hypersensitivity but also for acute IgE-mediated allergic reactions and life-threatening anaphylaxis.

J Pharm Sci, 1998 Sep, 87(9), 1101 - 8
A theoretical study of the interaction of anhydrotetracycline with Al(III); De Almeida WB et al.; In this article the complexation of anhydrotetracycline (AHTC), the major toxic decomposition product of the antibiotic tetracycline, with Al(III) has been investigated using the AM1 semiempirical and ab initio Hartree-Fock levels of theory . Different modes of complexation have been considered with the structure of tetra- and pentacoordinated complexes being fully optimized . In the gas phase, processes ii and iii, which lead to the complexes with stoichiometry MHL2+, are favored . Structure II ({AlLH2(OH)(H2O)}2+) has the metal coordinated to the O11 and O12 groups and the O3 group protonated and is the global minimum on the potential energy surface for the interaction . In water solution, the Al(III) is predicted to form predominantly a tetracoordinated complex at the Oam and O3 site (V) of the AHTC with the stoichiometry MH2L3+ (process i) . The experimental proposal is the complexed form with the metal ion coordinated to the O11-O12 moiety (site II) . The intramolecular proton transfer, which leads to the most stable Al(III)-AHTC MHL2+ complex, has not been considered by the experimentalists . The experimental structure was found to be unfavorable in our calculations in both gas phase and water solution . All the semiempirical results are in perfect agreement with the ab initio calculations . So, we suggest that the experimental assignments should be revised, taking into account the results obtained in the present study.

Clin Nephrol, 1998 Aug, 50(2), 90 - 3
Dihydropyridine type calcium channel blocker-induced turbid dialysate in patients undergoing peritoneal dialysis; Yoshimoto K et al.; We previously reported that manidipine, a new dihydropyridine type calcium channel blocker, produced chylous peritoneal dialysate being visually indistinguishable from infective peritonitis in 5 patients undergoing continuous ambulatory peritoneal dialysis (CAPD) {Yoshimoto et al . 1993} . To study whether such an adverse drug reaction would also be elicited by other commonly prescribed calcium channel blockers in CAPD patients, we have conducted postal inquiry to 15 collaborating hospitals and an institutional survey in International Medical Center of Japan as to the possible occurrence of calcium channel blocker-associated non-infective, turbid peritoneal dialysate in CAPD patients . Our diagnostic criteria for drug-induced turbidity of dialysate as a) it developed within 48 h after the administration of a newly introduced calcium channel blocker to the therapeutic regimen, b) absence of clinical symptoms of peritoneal inflammation (i.e., pyrexia, abdominal pain, nausea or vomiting), c) the fluid containing normal leukocyte counts and being negative for bacterial and fungal culture of the fluid, and d) it disappeared shortly after the withdrawal of the assumed causative agent . Results showed that 19 out of 251 CAPD patients given one of the calcium channel blockers developed non-infective turbid peritoneal dialysis that fulfilled all the above criteria . Four calcium channel blockers were suspected to be associated with the events: benidipine {2 out of 2 (100%) patients given the drug}, manidipine {15 out of 36 (42%) patients}, nisoldipine {1 out of 11 (9%) patients} and nifedipine {1 out of 159 (0.6%)} in descending order of frequency . None of the patients who received nicardipine, nilvadipine, nitrendipine, barnidipine and diltiazem (25, 7, 2, 1 and 8 patients, respectively) exhibited turbid dialysate . In conclusion, we consider that certain dihydropyridine type calcium channel blockers would cause turbid peritoneal dialysate being similar to that observed in patients developing infective peritonitis . To avoid unnecessary antibiotic therapy the possibility of this adverse reaction should be ruled out whenever a CAPD patient receiving a dihydropyridine type calcium channel blocker develops turbid dialysate.

Cardiovasc Surg, 1998 Aug, 6(4), 415 - 8
Radical debridement and omental transposition for post sternotomy mediastinitis; d'Udekem Y et al.; OBJECTIVE: Reported mortality for postoperative mediastinitis treated by debridement alone can reach 40% . The authors' experience with radical debridement and omental transposition is reviewed . METHODS: Between May 1990 and August 1996, 14 patients with untractable mediastinitis had a transfer of the greater omentum: 11 after coronary artery bypass grafting (CABG) (6 bilateral internal thoracic arteries ITA grafts), one after a heart transplant, one after an aortic valve replacement and CABG, and one after a repair of the aortic isthmus related to a motor vehicle accident . The mean age was 63 +/- 8 years . Infection was proven in all patients by cultures of intraoperative specimens . Two patients had such a large sternal defect that no primary closure could be attempted . The remaining 12 patients had a mean of 1.4 +/- 0.7 previous debridement . Five patients had a total sternectomy . After radical debridement, the omentum was transferred over the entirety of the wound and covered with a meshed thin skin graft . All patients had a minimum of 4 weeks of i.v . antibiotic therapy . RESULTS: There was no operative death . Apart from one focal necrosis and one traumatic dehiscence of the omentum, there was no hospital complication . Sepsis was controlled in all patients . The median hospital stay was 31 days (range 20-154 days) . At a median follow-up of 20 months (range: 6-44 months), there were two late deaths: one sudden and unexpected death and one after a re-do CABG . The remaining patients had resumed their previous activities . One patient had developed an incisional hernia and another underwent further surgery for cosmetic reasons . CONCLUSION: Radical debridement and omental transposition may achieve a cure for postoperative mediastinitis with good mid-term results.

Curr Opin Rheumatol, 1998 Jul, 10(4), 306 - 13
Undifferentiated arthritis and reactive arthritis; Wollenhaupt J et al.; The terms undifferentiated arthritis and undifferentiated characterize arthritides that do not fit into well-known clinical disease categories (e.g., seronegative rheumatoid arthritis and reactive arthritis) and that are an early stage or forme fruste of a definite rheumatic disease, an overlap syndrome between such diseases, or an unknown, etiologically undefined disease that remains to be differentiated from other types of arthritis or spondylarthritis . Undifferentiated arthritis and undifferentiated spondylarthritis share some clinical features with reactive arthritides . Recent data suggest that, at least in Chlamydia-induced reactive arthritis, the triggering bacteria persist in affected joints for some time during the course of the disease in a viable but nonreplicative state, providing an antigenic stimulus for a bacteria-specific immune reaction in the joint . The clinical manifestations of reactive arthritis include not only Reiter's syndrome or clinically suspected postinfectious arthritis but also undifferentiated oligoarthritis and spondylarthritis . The optimal treatment remains to be defined, but there is increasing data that antibiotic therapy is not as effective in cases of well-established reactive arthritis as has been suggested.

Bone Marrow Transplant, 1998 Aug, 22(4), 339 - 44
Effect of low-dose oral glutamine on painful stomatitis during bone marrow transplantation; Anderson PM et al.; Painful oral mucositis is a common complication after bone marrow transplantation (BMT) . Glutamine is a nutrient for rapidly dividing cells and the major energy source for intestinal epithelium . This study tested whether an oral glutamine preparation could decrease the severity of oral mucositis in patients undergoing BMT . Glutamine or a placebo (glycine) were administered from admission until day +28 in 193 BMT patients in a randomized, double-blind, placebo-controlled study at a dose of 1.0 g amino acid/m2/dose swish and swallow four times a day . In autologous BMT patients (n = 87) glutamine was associated with significantly less mouth pain by self report and by opiate use (5.0+/-6.2 days of morphine for glutamine vs 10.3+/-9.8 days for placebo; P= 0.005) . Matched sibling BMT patients had no effect by self report and an increased duration of opiate use (23.2+/-5.7 days for glutamine vs 16.3+/-8.3 days for placebo) (P = 0.002) . However, day 28 survival of allogeneic patients was improved by glutamine . No significant differences in TPN use, rate of relapse or progression of malignancy, parenteral antibiotic use, acute or chronic GVHD, or days of hospitalization were observed in either autologous or allogeneic recipients . No toxicity of glutamine was observed . We conclude that oral glutamine can decrease the severity and duration of oropharyngeal mucositis in autologous BMT patients but not in allogeneic BMT patients, possibly due to interaction with methotrexate.

Am J Perinatol, 1998 Jun, 15(6), 387 - 8
Delayed interval delivery: infection is not an absolute contraindication; Watson WJ et al.; Chorioamnionitis has generally been thought to be a contraindication to attempting a delayed interval delivery in a multiple gestation . We present a twin gestation in which a delay of 88 days between the birth of the two infants occurred . Chorioamnionitis observed immediately after the delivery of Twin A was successfully treated with antibiotic therapy.

J Pediatr Surg, 1998 Aug, 33(8), 1312 - 4
Endoscopic sphincterotomy and laparoscopic cholecystectomy in an infant with cholecysto-choledocholithiasis; Sanada Y et al.; Laparoscopic cholecystectomy (LC) and endoscopic sphincterotomy (EST) are widely accepted procedures for cholecysto-choledocholithiasis in adults . However, their use in infants has not been reported . An 8-month-old girl presented with high fever and obstructive jaundice . Ultrasound scan showed acute cholecystitis with stones in the bile duct . After 2-week-long antibiotic therapy the acute cholecystitis and hepatic impairment resolved . An endoscopic retrograde cholangiopancreatography (ERCP) confirmed choledocholithiasis and cholecystolithiasis . Risk factors for the development of biliary calculi were not detected . One month after the restoration of her liver function, she underwent EST using a side-viewing endoscope with a small sphincterotome . A common bile duct stone was extracted using a basket catheter . LC was then carried out . The time interval between the EST and LC was 34 days . No complications have been noted for 6 months.

Rinsho Byori, 1998 Jul, 46(7), 623 - 8
{Helicobacter pylori infection}; Kubota T et al.; Since Helicobacter pylori was first isolated by Warren and Marshall in 1983, many investigators have reported that it is closely associated with gastro-duodenal diseases . Several diagnostic methods, C-urea breath tests, rapid urea test, histological exam and culture, are used for detecting H . pylori . Japanese monkey and Mongolian gerbils is the animal model that can sustain persistent colonization with H . pylori . Japanese monkeys persistently infected with H . pylori can develop histological gastritis quite similar to that in humans . Eradicating H . pylori markedly reduces the recurrence of peptic ulcers . The new triple therapy regimen consisting of proton pump inhibitor (PPI) plus two antibiotics is effective for eradicating H . pylori . This therapy has shown high rates of H . pylori eradication (90%) with few side effects . An increase in the prevalence of antibiotic-resistant H . pylori strains has been reported worldwide . Failed attempts to eradicate the bacteria resulted in an increased number of H . pylori resistant strains . The relationship between H . pylori infection and gastric cancer has been recently investigated.

Bone Marrow Transplant, 1998 Aug, 22(3), 273 - 6
A trend towards an increased incidence of chronic graft-versus-host disease following allogeneic peripheral blood progenitor cell transplantation: a case controlled study; Scott MA et al.; Allogeneic peripheral blood progenitor cell transplantation (alloPBPCT) is increasingly used as an alternative to bone marrow transplantation (alloBMT) . Early data suggest that the incidence and severity of acute graft-versus-host disease (GVHD) following alloPBPCT is no higher than that seen with alloBMT, despite the increased number of cytotoxic T cells infused with mobilised blood . We compared 12 patients undergoing alloPBPCT with 12 well-matched alloBMT controls . All patients received identical GVHD prophylaxis . No T cell depletion or CD34 purification was performed . Median engraftment times for neutrophils >0.5 x 10(9)/l and platelets >20 x 10(9)/l were 14 and 12 (alloPBPCT) and 21 and 23 days (alloBMT), respectively (P = 0.0035 and P = 0.002) . There was no difference in antibiotic requirements (P = 0.83), platelet support (P = 0.59) or days in hospital (P = 0.51) . After alloPBPCT, five patients developed > or =grade II acute GVHD vs five patients after alloBMT (P = 0.99) . There was one death (alloBMT) at 100 days and three at 1 year (all due to relapse) . There was one death at 100 days with alloPBPCT, and 11 patients remain alive (range 9-21 months) to date . Chronic GVHD occurred in five patients in the PBPC arm and one patient in the BM arm (P = 0.14) . This case-controlled analysis indicates that alloPBPCT results in more rapid engraftment kinetics but in no significant difference in transplant-related morbidity or mortality . There is no difference in the incidence of acute GVHD . However, there is a trend towards increased incidence of chronic GVHD in patients allografted with PBPC . Prospective randomised trials are required to determine further the role of alloPBPCT.

Clin Infect Dis, 1998 Aug, 27(2), 296 - 302
Randomized, double-blind clinical trial of amphotericin B colloidal dispersion vs . amphotericin B in the empirical treatment of fever and neutropenia; White MH et al.; We conducted a prospective, randomized, double-blind study comparing amphotericin B colloidal dispersion (ABCD) with amphotericin B in the empirical treatment of fever and neutropenia . Patients with neutropenia and unresolved fever after > or = 3 days of empirical antibiotic therapy were stratified by age and concomitant use of cyclosporine or tacrolimus . Patients were then randomized to receive therapy with ABCD (4 mg/{kg.d}) or amphotericin B (0.8 mg/{kg.d}) for < or = 14 days . A total of 213 patients were enrolled, of whom 196 were evaluable for efficacy . Fifty percent of ABCD-treated patients and 43.2% of amphotericin B-treated patients had a therapeutic response (P = .31) . Renal dysfunction was less likely to develop and occurred later in ABCD recipients than in amphotericin B recipients (P < .001 for both parameters) . Infusion-related hypoxia and chills were more common in ABCD recipients than in amphotericin B recipients (P = .013 and P = .018, respectively) . ABCD appeared comparable in efficacy with amphotericin B, and renal dysfunction associated with ABCD was significantly less than that associated with amphotericin B . However, infusion-related events were more common with ABCD treatment than with amphotericin B treatment.

Biochemistry, 1998 Aug 25, 37(34), 11797 - 805
Role of the sterol superlattice in the partitioning of the antifungal drug nystatin into lipid membranes; Wang MM et al.; Nystatin isolated from Streptomyces is a polyene antibiotic that is frequently used in the treatment and prophylaxis of fungal infections . Here, the fractional sterol concentration dependencies of the partition coefficient for partitioning of nystatin into ergosterol/dimyristoyl-L-alpha-phosphatidylcholine (DMPC), cholesterol/DMPC, ergosterol/1-palmitoyl-2-oleoyl-L-alpha-phosphatidylcholine (POPC), and ergosterol/POPC/1-palmitoyl-2-oleoyl-L-alpha-phosphatidylethano lam ine (POPE) multilamellar vesicles have been determined fluorometrically at 37 degrees C using approximately 0.3-1.0 mol % sterol concentration increments over a wide concentration range (e.g., 18-54 mol % sterol) . This unconventional approach of varying membrane sterol content, in contrast to previous studies using large sterol concentration increments (e.g., 10 mol %), leads to a striking observation . The partition coefficient of nystatin changes dramatically with membrane sterol content in a well-defined alternating manner, displaying a local minimum at or very close to the critical sterol mole fractions (e.g., 20.0, 22.2, 25.0, 33.3, 40.0, and 50.0 mol % sterol) predicted for sterols regularly distributed in either hexagonal or centered rectangular superlattices . In ergosterol/DMPC bilayers, for example, there is a >3-fold increase in nystatin partitioning with a minute change (approximately 1 mol %) in sterol content on either side of the critical sterol mole fraction, 25.0 mol % . These results provide semifunctional evidence supporting the sterol regular distribution model {Chong, P . L.-G . (1994) Proc . Natl . Acad . Sci . U.S.A . 91, 10069-10073} . More importantly, these results reveal a new membrane phenomenon, that is, that nystatin partitioning is affected by the extent of sterol regular distribution in the plane of the membrane . This phenomenon occurs not only in saturated (e.g., DMPC) but also in unsaturated (e.g., POPC) lipid membranes, and persists in the presence of polar headgroup heterogeneity (e.g., POPC/POPE) . This membrane property points to a new method for studying the interactions of polyene antibiotics with sterol-containing membranes, and the need to consider the membrane sterol content of the target cells when administering nystatin or other polyene antibiotics.

Br J Surg, 1998 Aug, 85(8), 1111 - 3
Abscess after appendicectomy in children: the role of conservative management; Okoye BO et al.; BACKGROUND: Intra-abdominal abscess remains a significant cause of morbidity following appendicectomy . In children, little emphasis has been placed on the non-invasive management of this complication using antibiotic therapy alone . This study reviews the experience of a paediatric surgical department in managing abscess arising after appendicectomy . METHODS: Hospital records of all children undergoing appendicectomy between January 1992 and January 1997 were reviewed retrospectively . RESULTS: Some 1024 children underwent appendicectomy over a 5-year period . Twenty three patients (2.2 per cent) developed abscesses after appendicectomy . Non-operative management with intravenous or oral antibiotics alone was successful in 21 patients, with complete clinical and radiological resolution of the abscess . Drainage of the septic collection was performed in only two patients: by laparotomy (n=1) and by the transrectal route (n=1) . CONCLUSION: Antibiotic therapy alone is an efficacious and safe first-line treatment modality in children who develop this complication . Drainage of an abscess developing after appendicectomy is rarely necessary in children.

S Afr Med J, 1998 Feb, 88(2), 150 - 2
Human bites of the face . A review of 22 cases; Chidzonga MM; OBJECTIVE: To compare experience with human bites of the face in a unit in Harare, Zimbabwe, with other similar studies in respect of reasons for the assaults, age and sex of the patients, timespan between injury and treatment, surgical management and incidence of infection . DESIGN: Prospective study . SETTING: Department of Oral and Maxillofacial Surgery Outpatients Clinic, Harare Central Hospital, Harare, Zimbabwe . PATIENTS: Twenty-two consecutive patients with human bites of the face . MAIN OUTCOME MEASURES: The black female is the predominant victim and assailant, with the lower lip most commonly involved . RESULTS: Of the patients 81.8% were female . The mean age was 32.5 years . Interpersonal violence was the commonest cause of the injury, with the lower lip involved in 90.9% of cases . Early presentation reduces the risk of infection . CONCLUSION: The results indicate that the black female predominates both as victim and assailant . Early presentation with thorough surgical debridement under antibiotic cover produces satisfactory results.

Pneumologie, 1998 Jun, 52(6), 325 - 32
{Bleomycin-induced pulmonary fibrosis following chemotherapy of ovarian granulosa cell tumor}; Theile A et al.; Bleomycin is used in the cytostatic therapeutical management of a variety of malignant tumours . The development of an interstitially accentuated pulmonary disease is a dreaded complication; this side effect may occur dose-related or not dose-related . We report on a 52-year old female patient with recurrent tumour after adnexectomy because of granulosa cell tumour, surgical re-intervention and subsequent polychemotherapy with cisplatin, etoposid and bleomycin (PEB regimen) . Following this, the patient developed rapidly progressing lung fibrosis . There was no improvement in spite of combined high dose antibiotic and corticosteroid therapy . The patient finally died of respiratory insufficiency . Upon autopsy, apart from a circumscribed loco-regional tumour recurrence the clinical diagnosis of well advanced interstitial lung fibrosis presenting as so-called cytostatic pneumopathy was found . Immunohistochemical investigations using so-called proliferation markers revealed a markedly increased, centrifugally accentuated proliferative activity of both mesenchymal cells and of atypical pneumocyte regenerates, originating in areas of advanced parenchymal transformation and proceeding towards areas of supposedly intact lung tissue, a finding seen as an impressive histomorphological correlate of the clinically observed rapid progression of the disease . The development of a so-called bleomycin lung ist demonstrated from the formal pathogenetical point of view and correlated with the clinical course . The comparatively rapid shift of an expression of mediator systems with inflammatory properties towards local pulmonary or mesenchymal cells must be interpreted as the reason for the course of the disease, which in later phases could no longer be influenced by anti-inflammatory medication . These findings underline impressively the importance of early detection of developing pulmonary complications following cytostatic therapy . Apart from imaging techniques such as chest x-rays and HRCT, monitoring by 99mTc-DPTA inhalation is a very promising method for early demonstration of pulmonary alterations caused by cytostatically acting medication . This method registers precisely disturbances in pulmonary membrane permeability by measuring the radio nucleotide absorption rate along the alveolar-capillary membrane . In a therapeutical approach, next to the standard procedure of high-dose administration of corticosteroids, the influence of non-steroidal antiphlogistics and antioxidants is analysed, the growing knowledge on the cellular and molecular level possible leading to future therapeutical strategies, although the complex interactive mechanisms are still not completely understood.

Mycoses, 1998 May-Jun, 41(5-6), 223 - 7
Outbreak of systemic aspergillosis in a neonatal intensive care unit; Singer S et al.; Small pre-term neonates are susceptible to cutaneous aspergillosis because of their immature immune system and because of the vulnerability of their skin . In addition, the common therapy with broad-spectrum antibiotic drugs and corticoids creates a favourable milieu for fungal superinfections . We present four pre-term neonates who succumbed to cutaneous aspergillosis that subsequently developed into a systemic infection . The source of the infection proved to be contaminated latex finger stalls . Three of the four patients died . The poor prognosis for systemic aspergillosis can only be improved by an early therapy with amphotericin B, possibly in liposomal form.

J Reconstr Microsurg, 1998 Jul, 14(5), 309 - 12
Vascularized partial first metatarsal transfer for the treatment of phalangeal osteomyelitis; McFadden JA; The author reports the salvage of the index finger in a patient with extensive osteomyelitis of the proximal phalanx . Salvage was achieved by a staged reconstruction, using external fixation combined with aggressive debridement, and an antibiotic/methylmethacrylate spacer, followed by a vascularized bone flap from the first metatarsal . Union was achieved with an excellent functional outcome of 205 degrees of total active motion . The literature addressing the management of osteomyelitis in this particular location is incomplete . This author believes that loss of a large portion of the diaphysis is difficult to treat by conventional bone grafting because of the poorly vascularized bed following extensive infection . The case reported is unique because of the choice of donor site . Vascularized bone grafting is suggested as offering the best chance for success, and the donor-site material can be easily tailored to fit the phalangeal defects.

Singapore Med J, 1998 May, 39(5), 226 - 8
Necrotising fasciitis originating from a vulval abscess--a case report; Razvi K et al.; This article reports a rare case of necrotising fasciitis starting out as a vulval abscess with rapid progression to a potentially lethal condition . Elderly people with medical conditions such as diabetes are especially prone to it . A high index of suspicion and an early surgical consult are essential in improving outcome in this condition . Once diagnosed, aggressive surgical debridement with antibiotic cover is crucial . This is followed up with meticulous nursing care of the large wound till it heals . The various diagnostic points and treatment modalities are also discussed.

Rofo, 1998 Jul, 169(1), 63 - 7
{The fluoroscopy-guided implantation of subcutaneous venous ports: the complications and long-term results}; Kluge A et al.; PURPOSE: Evaluation of technical success rate, long-term outcome and initial complication rate in patients with fluoroscopically guided port implantation . MATERIAL AND METHODS: Between January 1994 and April 1997 124 ports were implanted under fluoroscopic guidance in 120 patients . Indications for port implantation were anti-cancer chemotherapy, antibiotic and supportive therapy in patients with tumours or cachexia . RESULTS: Implantation was technically successful in 98.4% of the patients . We had a 3.2% minor complication rate that did not necessitate further treatment . One pneumothorax required a chest tube (0.8%) . During a total of 17,534 days, complications occurred in 10.8% of all ports, 6.9% of the ports had to be explanted because of these complications . CONCLUSIONS: Insertion of ports under fluoroscopic guidance has a low complication rate and good long-term results . The rate of 93.1% of functioning ports is superior to that reported in other studies . It is less costly and has a lower complication rate than surgical implantation . Therefore it seems to be the method of choice for patients requiring long-term subcutaneous venous access for chemotherapy or supportive therapy in malignant tumours or other emaciating diseases.

Clin Infect Dis, 1998 Aug, 27(2), 376 - 9
Pneumococcal peritonitis in previously healthy adults: case report and review; Hemsley C et al.; We report a case of primary pneumococcal peritonitis in a young woman with no predisposing features, and we review 26 other cases of pneumococcal peritonitis in previously healthy adults . This disease is very rare in adults without cirrhosis, ascites, nephrotic syndrome, autoimmune disease, or immunocompromise . It occurs almost exclusively in women, and in most of these patients, there is a probable genital tract source of the organism . A few cases are associated with acute appendicitis . Although pneumococcal peritonitis was usually fatal in the preantibiotic era, with antibiotic therapy and surgical intervention the outcome for patients with this infection is excellent.

J Pediatr, 1998 Aug, 133(2), 290 - 2
MALT lymphoma of labial minor salivary gland in an immunocompetent child with a gastric Helicobacter pylori infection; Berrebi D et al.; We report a pediatric case of a mucosa-associated lymphoid tissue lymphoma of the labial minor salivary gland in an immunocompetent patient . Chronic gastritis with Helicobacter pylori was disclosed and managed with antibiotic therapy . With eradication of Helicobacter pylori there was complete remission of the lymphoma.

Lippincotts Prim Care Pract, 1998 Jul-Aug, 2(4), 358 - 68
Acid peptic diseases in the era of Helicobacter pylori; Schoenfeld PS; The treatment of peptic ulcers has been revolutionized by the discovery that Helicobacter pylori (H . pylori) bacteria is a causative agent for ulcer formation . However, when patients present with dyspepsia or epigastric discomfort, more than 80% of patients will not have ulcer disease and empiric treatment of H . pylori is not recommended for these patients . Eradication of H . pylori has not been demonstrated to improve the symptoms of non-ulcer dyspepsia compared with non-ulcer dyspepsia patients treated with placebo . Therefore, we recommend that patients should first be evaluated for peptic ulcers with endoscopy or upper gastrointestinal series before the diagnosis and treatment of H . pylori . Generally, the treatment of H . pylori should be limited to patients with peptic ulcers, mucosal-associated lymphoid tissue lymphomas, and gastric cancers . Most diagnostic tests for H . pylori, including quantitative IgG antibody, urea breath tests, rapid urease tests (CLO), tests of gastric mucosal biopsies, and staining of gastric mucosal biopsies, have equivalent diagnostic characteristics . Therefore, the choice of diagnostic test for H . pylori should be based on cost, ease of use, and lack of complications . Multiple antibiotic regimens are available for the treatment of H . pylori . Triple antibiotic therapy is the least expensive but has the highest rate of side effects and the least compliance . Combining a proton pump inhibitor with clarithromycin and another antibiotic will eradicate H . pylori with fewer side effects and better compliance but this is the most expensive antibiotic regimen.

EMBO J, 1998 Aug 17, 17(16), 4829 - 36
ATP binding and hydrolysis are essential to the function of the Hsp90 molecular chaperone in vivo; Panaretou B et al.; Hsp90 is an abundant molecular chaperone essential to the establishment of many cellular regulation and signal transduction systems, but remains one of the least well described chaperones . The biochemical mechanism of protein folding by Hsp90 is poorly understood, and the direct involvement of ATP has been particularly contentious . Here we demonstrate in vitro an inherent ATPase activity in both yeast Hsp90 and the Escherichia coli homologue HtpG, which is sensitive to inhibition by the Hsp90-specific antibiotic geldanamycin . Mutations of residues implicated in ATP binding and hydrolysis by structural studies abolish this ATPase activity in vitro and disrupt Hsp90 function in vivo . These results show that Hsp90 is directly ATP dependent in vivo, and suggest an ATP-coupled chaperone cycle for Hsp90-mediated protein folding.

Am J Gastroenterol, 1998 Aug, 93(8), 1363 - 5
An unusual case of amoxicillin/clavulanic acid-related hepatotoxicity; Nathani MG et al.; Amoxicillin/clavulanic acid is a widely used antibiotic . Hepatic dysfunction is a rare adverse reaction associated with this combination antibiotic . We report the case of a 40-yr-old woman with a somewhat unusual presentation of amoxicillin/clavulanate-related cholestatic hepatotoxicity and multiple duodenal erosions whose diagnosis was delayed until inadvertent rechallenge with the antibiotic combination . The relevant literature is also reviewed and discussed . The diagnosis may be missed because the onset of signs/symptoms may occur several weeks after the cessation of therapy . The hepatic dysfunction, which may be severe and is more prevalent in elderly patients, is usually reversible, although chronic liver disease and deaths have been reported . Immunological hypersensitivity is considered to be the most likely mechanism resulting in liver injury . Amoxicillin/clavulanate should be used with caution in patients with underlying liver disease and in the elderly.

J Periodontol, 1998 Jul, 69(7), 772 - 6
Clinical evaluation of systemic doxycycline and ibuprofen administration as an adjunctive treatment for adult periodontitis; Ng VW et al.; The objective of this study was to compare the efficacy of a systemic antibiotic (doxycycline) and a non-steroidal anti-inflammatory drug (ibuprofen), administered either separately or combined, as an adjunctive treatment of scaling/root planing (SRP) . Thirty-two subjects diagnosed with generalized moderate adult periodontitis and having at least 2 teeth with > or =5 mm probing depth were randomly divided into 4 groups . Each group was treated with oral doxycycline and/or ibuprofen for 6 weeks as follows: group 1, doxycycline 200 mg the first day followed by 100 mg per day; group 2, ibuprofen 800 mg per day; group 3, doxycycline plus ibuprofen scheduled as in groups 1 and 2; group 4, one placebo capsule/day (control) . A split mouth design was utilized in each subject such that half of the teeth received one session of scaling/root planing (SRP), while the other half received no SRP . Plaque index (PI), gingival index (GI), probing depth (PD), and clinical attachment level (CAL) using a customized acrylic stent were recorded at baseline and at 3, 6, 12, and 24 weeks following SRP . Analysis using ANOVA and Student t-test showed statistical significance (P< or =0.05) from baseline data in: 1) gains of 0.4 mm and 0.5 mm of CAL for groups 1 and 3, respectively; 2) reduction of 0.7 mm PD for group 3; 3) reduction of 0.4 and 0.1 GI scores for groups 1 and 3, respectively; and 4) gain of 0.5 mm CAL and reductions of 0.4 mm PD and 0.2 GI score for the SRP group when compared to the no SRP group at 24 weeks . It may be concluded that the adjunctive use of systemic doxycycline alone or in combination with ibuprofen results in a statistically significant, yet modest clinical, improvement beyond that obtained by scaling/root planing.

J Clin Microbiol, 1998 Sep, 36(9), 2580 - 5
Use of an amplified-fragment length polymorphism technique to fingerprint and differentiate isolates of Helicobacter pylori; Gibson JR et al.; Amplified-fragment length polymorphism (AFLP) analysis is the name given to a genotypic technique in which adapter oligonucleotides are ligated to restriction enzyme fragments and then used as target sites for primers in a PCR amplification process . The amplified fragments are electrophoretically separated to give strain-specific band profiles . We have developed a single-enzyme approach that did not require costly equipment or reagents for the fingerprinting of strains of Helicobacter pylori . The method was assessed with 46 isolates of H . pylori from 28 patients, and the results were compared with those from other genotypic tests . The AFLP profiles derived from HindIII fragments differentiated strains of H . pylori from unrelated individuals and confirmed the common origin of strains in some family members . AFLP analysis was also applied to investigate persistent infection following antibiotic therapy . Overall, the modified technique was relatively rapid and technically simple yet gave reproducible and discriminatory results . AFLP analysis samples variation throughout the genome and is a valuable addition to the existing genotypic fingerprinting methods for H . pylori.

Biol Chem, 1998 Jul, 379(7), 841 - 6
Quinupristin (RP 57669): a new tool to investigate ribosome-group B streptogramin interactions; Beyer D et al.; Streptogramin antibiotics consist of two types of molecules, group A and group B . The group B molecule quinupristin (RP 57669) and the group A molecule dalfopristin (RP 54476) constitute the first water-soluble semisynthetic streptogramin, quinupristin/dalfopristin (RP 59500) . When group B molecules bind to 50S subunits or to tightly coupled ribosomes, there is an increase in their fluorescence intensity, which is proportional to the concentration of the antibiotic-ribosome complex formed . We found here that the background fluorescence of unbound quinupristin is 10-fold lower than that of unbound virginiamycin S, a natural group B molecule often used experimentally . The association constants were found (i) to be similar for the binding of the two group B molecules to tightly coupled 70S ribosomes in the absence of the group A molecules (quinupristin: 3.5 x 10(7) M(-1); virginiamycin S: 2.8 x 10(7) M(-1)) and (ii) to similarly increase about 20-fold in the presence of the corresponding group A molecule (quinupristin + dalfopristin: 69 x 10(7) M(-1); virginiamycin S + virginiamycin M: 60 x 10(7) M(-1)) . Similar results were obtained with 50S ribosomal subunits . Additionally, we provide evidence that the failure of the group B molecules to inhibit poly(Phe) synthesis is due to the displacement of the group B molecule during poly(Phe) polymerization on the ribosome, indicating that the artificial poly(Phe) peptide competes with the binding of the group B molecule.

Biol Chem, 1998 Jul, 379(7), 819 - 29
A novel cell-free system for peptide synthesis driven by pyridine; Nitta I et al.; Previously we demonstrated that ribosomes can synthesize polypeptides in the presence of high concentrations (40-60%) of pyridine without any protein factors . Here we analyze additional ribosomal parameters in 60% pyridine using Escherichia coli ribosomes . Ribosomal subunits once exposed to pyridine failed to re-associate to 70S ribosomes in aqueous buffer systems even in the presence of 20 mM Mg2+, whereas they formed 70S complexes in the presence of 60% pyridine . Two-dimensional gel electrophoresis of ribosomal proteins revealed that some proteins located at the protuberances of the large subunit, e . g . L7/L12 and L11 forming the elongation factor-binding domain, were released in the pyridine system . The aminoglycoside neomycin, a strong inhibitor of the ribosomal (factor-independent) translocation reaction, completely blocked poly(Phe) synthesis and translocation activities in the pyridine system, whereas these activities were not affected at all by gypsophilin, a ribotoxin that inhibits factor-dependent translocation . Another inhibitor of the ribosomal translocation, thiostrepton, had no effect concerning the two activities, which is consistent with the fact that this antibiotic requires L11 for its binding to the ribosome . These results suggest that the ribosomes can perform a translocation reaction in the pyridine system, but in a factor-independent (spontaneous) manner.

Biotechnol Annu Rev, 1995, 1, 5 - 68
Biotechnology domain; el-Gewely MR; Biotechnology and the use of biologically based agents for the betterment of mankind is an active field which is founded on the interaction between many basic sciences . This is achieved in coordination with engineering and technology for scaling up purposes . The application of modern recombinant DNA technology gave momentum and new horizons to the field of biotechnology both in the academic setting and in industry . The applications of biotechnology are being used in many fields including agriculture, medicine, industry, marine science and the environment . The final products of biotechnological applications are diverse . In the medical applications of biotechnology, for example, the field has been evolving in such a way that the final product could be a small molecule (e.g . drug/antibiotic) that can be developed based on genetic information by drug design or drug screening using a cloned and expressed target protein.

Biochem Biophys Res Commun, 1998 Jul 30, 248(3), 559 - 61
Catalytic activity in Cephalosporium acremonium isopenicillin N synthase does not involve glutamine-234; Loke P et al.; The catalytic activity of isopenicillin N synthase (IPNS), a crucial enzyme which converts delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine to isopenicillin N in the beta-lactam antibiotic biosynthetic pathway, is known to be dependent upon the ligation of two histidines and an aspartate to the iron active centre . Recent studies have ruled out the suggested requirement of the penultimate glutamine, Q330 and Q328 in Aspergillus nidulans and Streptomyces jumonjinensis IPNS respectively, for catalysis . As a counter proposal, glutamine-230 from S . jumonjinensis IPNS was presented to be crucial for activity . However, we report differing results from the site-directed mutagenesis of the corresponding glutamine-234 in Cephalosporium acremonium IPNS . Based on IPNS enzymatic assays, we conclude that glutamine-234 is not essential for catalysis in cIPNS . Furthermore, we advocate the use of soluble proteins over solubilized proteins especially for studies which involve enzymatic catalysis.

Anticancer Res, 1998 May-Jun, 18(3C), 2227 - 30
Sodium selenite as prophylaxis against erysipelas in secondary lymphedema; Kasseroller R; In a randomised, double-blind study, the efficacy of sodium selenite application in combination with physical therapy to relieve congestion was investigated in a cohort of 60 cancer patients with secondary lymphedema, with special reference to the development of the incidence of erysipelas . All of the patients investigated in this study had erysipelas infection of the skin . Selenium was administered in pharmacological doses . The duration of physical therapy was three weeks . Patients were under observation for a further three months . The incidence of erysipelas among our patients was 11% . During the three-week period of intensive treatment, there was not a single case of erysipelas in the treatment group, whereas there was one single case in the placebo group . In the follow-up period (3 months), once again there was not a single case of erysipelas in the treatment group, but 50% of the patients in the placebo group exhibited erysipelas . In spite of higher doses, the selenium level did not rise above normal values . Patients under long-term antibiotic therapy suffered no relapse when the antibiotic therapy was stopped and instead, selenium was administered . It could be shown, in addition, that by administration of a single high-dose of sodium selenite, inflammation could be immediately brought under control.

Plast Reconstr Surg, 1998 Aug, 102(2), 385 - 9; discussion 390-2
Muscle and musculocutaneous flap coverage of exposed spinal fusion devices; Hochberg J et al.; Midline wound dehiscence in the back with exposure of spinal stabilization devices remains a challenging problem, mainly in the presence of infection . Usually, the treatment consists of instrumentation removal, wound debridement, and antibiotic therapy . These can result in instability of the spine and significantly prolong the hospitalization . The use of muscle and musculocutaneous flaps provides excellent soft-tissue coverage, obliterates the dead space, controls the infection, and creates conditions to salvage the hardware . Eight cases of spinal rod instrumentation, complicated by wound infection and dehiscence, have been treated successfully with single or multiple muscles and musculocutaneous flaps . Our method of treatment for these complex wounds, in two institutions, is discussed.

Infect Dis Obstet Gynecol, 1998, 6(2), 66 - 8
Ovarian abscess caused by Peptostreptococcus magnus following transvaginal ultrasound-guided aspiration of ovarian endometrioma and fixation with pure ethanol; Mikamo H et al.; BACKGROUND: Transvaginal ultrasound-guided aspiration of ovarian endometrioma has been applied and emphasized as a safe and simple procedure . CASE: Two 27-year-old infertile women, both gravida 0, para 0, underwent medical follow-up examinations for cases of ovarian endometrioma . Both had undergone transvaginal ultrasound-guided aspiration of ovarian endometrioma . Because both were continuously febrile and had abdominal pain and cysts with tenderness in spite of antibiotic therapies, both underwent laparotomies for treatment . In both cases, enucleation of the ovarian abscess revealed purulent and malodorous fluid that demonstrated Peptostreptococcus magnus in culture . CONCLUSION: We theorize that following transvaginal ultrasound-guided aspiration of ovarian endometrioma and fixation with pure ethanol, anaerobic infection by P . magnus occurred, and a cyst formed in the abscess.

Artif Organs, 1998 Aug, 22(8), 666 - 71
Changes in pericardial calcification due to antiplatelet agents: in vitro studies; Chandy T et al.; To develop tissue valves for prolonged use in the cardiovascular system, the complicated process of surface induced calcification must be better understood . Calcification was examined for 60 days on glutaraldehyde treated bovine pericardium (GABP) and enzyme extracted tissues fixed in glutaraldehyde (GATBP) incubated in metastable solutions of calcium phosphate, and the roles of aspirin and persantine in conjunction with vitamins C, B, or E, gentamycin (antibiotic), or pentothal sodium (anesthetic) in the medium were examined . Further, the diffusion of calcium across the GATBP was evaluated using a diffusion cell with 2 compartments . Pericardial calcification was also observed using scanning electron microscopy (SEM) techniques . It seems that the examined antiplatelet agents can modify the pericardial surfaces and subsequently their mineralization processes (GATBP, 31.7 micrograms/mg tissue; in the presence of 5 mg% vitamin C, 13.1 micrograms/mg tissue; in 1.5 mg% aspirin, 17.2 micrograms/mg tissue; and 1 mg% gentamycin, 14.8 micrograms/mg tissue) on exposure with the metastable calcium phosphate solution for 60 days . In addition, these agents may modify calcium transport and interfere with the adsorption at the surface, hence reducing calcium nodulation on GATBP . Scanning electron micrographs also revealed a reduction in calcium deposition on the pericardium due to these antiplatelet agents . It may be hypothesized that the influx of calcium on GATBP may be due to the cellular components or the involvement of plasma proteins like the fibrinogen molecule . The exact mechanism of these changes in the calcification of the pericardium are still unknown . From these in vitro findings, it appears that a combined vitamin therapy with low doses of aspirin may be beneficial for platelet suppression and thereby for prevention of thrombosis and calcification . However, more in vivo studies are needed to develop applications.

J Am Vet Med Assoc, 1998 Aug 1, 213(3), 365 - 9
Perioperative management and mortality rates of dogs undergoing cesarean section in the United States and Canada; Moon PF et al.; OBJECTIVE: To describe dogs undergoing cesarean section in the United States and Canada, to determine perioperative management, and to calculate survival proportions . DESIGN: Multicenter prospective case series . ANIMALS: 3,908 puppies from 808 dams . RESULTS: Survival rates immediately, 2 hours, and 7 days after delivery were 92, 87, and 80%, respectively, for puppies delivered by cesarean section (n = 3,410) and 86, 83, and 75%, respectively, for puppies born naturally (498) . For 614 of 807 (76%) litters, all puppies delivered by cesarean section were born alive . Maternal mortality rate was 1% (n = 9) . Of 776 surgeries, 453 (58%) were done on an emergency basis . The most common breeds of dogs that underwent emergency surgery were Bulldog, Labrador Retriever, Boxer, Corgis, and Chihuahua . The most common breeds of dogs that underwent elective surgery were Bulldog, Labrador Retriever, Mastiff, Golden Retriever, and Yorkshire Terrier . The most common methods of inducing and maintaining anesthesia were administration of isoflurane for induction and maintenance (n = 266; 34%) and administration of propofol for induction followed by administration of isoflurane for maintenance (237; 30%) . CLINICAL IMPLICATIONS: Mortality rates of dams and puppies undergoing cesarean section in the United States and Canada are low . Knowledge of mortality rates should be useful to veterinarians when advising clients on the likelihood of puppy and dam survival associated with cesarean section.

Acta Biochim Pol, 1998, 45(1), 13 - 8
Modified RNAs as potential drug targets; Guenther R et al.; Bleomycin (BLM) is a natural antibiotic that is effective in treatment of selected cancers . Although the exact therapeutic mechanism of bleomycin is not known, its target is thought to be a nucleic acid . Besides cleaving DNA, in vitro, Fe-bleomycin cleaves the anticodon of yeast tRNA(Phe) specifically . Using CD and fluorescence spectroscopy we have found that apo-bleomycin binds to synthetic RNA analogs of the anticodon of yeast tRNA(Phe) with an affinity similar to that previously reported for DNA . In order to understand BLM's selectivity, the role magnesium ions play in RNA recognition should be explained . Many RNA substrates for Fe-BLM, including yeast tRNA(Phe), are not cleaved by the drug when the Mg2+ concentration exceeds 1 mM . Competition experiments with anticodon analogs provide insight into the role of magnesium ions in RNA recognition by BLM . These simple modified RNAs may be useful as model systems for investigating BLM/RNA recognition and development of highly selective drugs toward RNA targets.

Arch Pediatr Adolesc Med, 1998 Aug, 152(8), 739 - 44
Standardizing the care of bronchiolitis; Adcock PM et al.; OBJECTIVE: To study the effect of an educational intervention on the management of hospitalized infants with bronchiolitis . DESIGN: Sequential, prospective cohort study . SETTING: A 235-bed children's hospital with nearly all private rooms . PATIENTS: Consecutively admitted, previously healthy children younger than 24 months with symptoms of bronchiolitis . The first cohort was enrolled between January 1 and January 21, 1996; the second cohort between January 29 and February 18, 1996, following a 1-week intervention period; the third (follow-up) cohort between December 1996 and February 1997 . INTERVENTION: Educational program and practice guidelines aimed at appropriate utilization of diagnostic tests, decreased antibiotic and bronchodilator use, increased compliance with isolation, decreased length of stay, and maintenance of quality care . MAIN OUTCOME MEASURES: Utilization of respiratory syncytial virus (RSV) enzyme immunoassay, initiation and duration of parenteral antibiotic therapy, number of nebulized bronchodilator treatments, isolation orders, length of stay, and readmission rate . RESULTS: A total of 90 patients were studied preintervention, 63 postintervention, and 90 during the follow-up period . The groups were comparable in demographic and clinical features . No patient had a documented serious bacterial infection; however, almost half in each group received parenteral antibiotics, despite recommendations against this . Immediately postintervention, children with positive RSV test results received antibiotics on fewer days than other children (median 0.6 vs 2.4 days; P=.004), suggesting that physicians stopped treatment with antibiotics once a viral diagnosis was confirmed . This effect did not persist into the follow-up period . Viral testing was reduced and isolation orders increased . Use of bronchodilators was reduced from 91% preintervention to 80% during the follow-up period (P=.046), and the median number of treatments was reduced from 15.0 to 10.0 (P=.005) . There was no change in length of stay, which was 2 to 3 days, or in readmission rate, which was 1% to 4% . CONCLUSION: Educational efforts centered around practice guidelines can improve some aspects of the treatment of patients hospitalized with bronchiolitis.

Aliment Pharmacol Ther, 1998 Feb, 12 Suppl 1, 111 - 21
Review article: Medical decision models of Helicobacter pylori therapy to prevent gastric cancer; Sonnenberg A et al.; The aim of the present article is to study the utility of Helicobacter pylori eradication programmes in decreasing the incidence of gastric cancer . Three types of decision models are employed to pursue this aim, i.e . decision tree, present value, and declining exponential approximation of life expectancy (DEALE) . 1) A decision tree allows one to model the interaction of multiple variables in great detail and to calculate the marginal cost, as well as the marginal cost-benefit ratio, of a preventive strategy . The cost of gastric cancer, the efficacy of H . pylori therapy in preventing cancer, and the cumulative probability of developing gastric cancer exert the largest influence on the marginal cost of cancer prevention . The high cost of future gastric cancer and a high efficacy of therapy make screening for H . pylori and its eradication the preferred strategy . 2) The present value is an economic method to adjust future costs or benefits to their current value using a discount rate and the length of time between now and a given time point in the future . It accounts for the depreciation of money and all material values over time . During childhood, the present value of future gastric cancer is very low . Vaccination of children to prevent gastric cancer would need to be very inexpensive to be practicable . Cancer prevention becomes a feasible option, only if the time period between the preventive measures and the occurrence of gastric cancer can be made relatively short . 3) The DEALE provides a means to calculate the increase in life expectancy that would occur, if death from a particular disease became preventable . Life expectancy of the general population is hardly affected by gastric cancer . For life expectancy to increase appreciably by vaccination or antibiotic therapy directed against H . pylori infection, these interventions would need to be focused towards a sub-population with an a priori high risk for gastric cancer.

Invest Ophthalmol Vis Sci, 1998 Aug, 39(9), 1658 - 66
Retroviral cDNA transfer to the RPE: stable expression and modification of metabolism; Ray J et al.; PURPOSE: To determine the versatility of retroviral vector-mediated rat beta-glucuronidase cDNA expression in the normal retinal pigment epithelium (RPE) of eyes of various species and in RPE of eyes with three types of mucopolysaccharidosis (MPS types I, VI, and VII) and to evaluate the effect of multiple transductions and long-term stable expression in the RPE . METHODS: A retroviral construct containing a rat beta-glucuronidase cDNA (NTK-BGEO) was used to infect RPE cells at subconfluence . The transduced cells were selected in G418, an antibiotic toxic to normal mammalian cells . Beta-glucuronidase activity was measured in transduced cells and media, using a fluorogenic substrate . Glycosaminoglycan profiles were examined by metabolically labeling RPE with Na2(35)SO4 . RESULTS: Transduced RPE cells, regardless of species or disease status, expressed rat beta-glucuronidase . The expressed enzyme restored normal levels of glycosaminoglycans in the RPE cells of homozygous MPS VII-affected dogs by metabolizing stored glycosaminoglycans . The expressed enzyme failed to metabolize stored glycosaminoglycans of MPS I and MPS VI, indicating that overexpression could not bypass the exoglycosidase restriction . Multiple transductions increased beta-glucuronidase activity several times in the cell layer and in the media . The expression was stable in vitro for at least 12 weeks . CONCLUSIONS: A retroviral vector can mediate transfer of beta-glucuronidase in various species of normal and MPS-affected RPE . The expression is stable in vitro . The metabolism of stored glycosaminoglycans in MPS needs replacement of only the deficient enzyme to reverse the storage.

J Am Optom Assoc, 1998 Jul, 69(7), 465 - 72
Review of the medical management of postoperative cataract complications; Hsieh WC; BACKGROUND: With the increasing number of surgeons using phacoemulsification techniques combined with sutureless scleral tunnel and clear corneal incisions for cataract surgery, the majority of patients will undergo an uncomplicated course of visual rehabilitation requiring no more than standard topical antibiotic and steroid regimen . Occasionally--even with an uneventful surgical course--postoperative complications arise . Many of these postoperative complications can be managed medically, without surgical intervention . Topical and oral glaucoma and nonsteroidal anti-inflammatory agents play an important role in the management of postoperative cataract complications . METHODS: A review of the common postoperative complications and their medical management using topical and oral pharmaceutical agents are presented . Emphasis is placed on current trends in treatment following contemporary cataract surgery . CONCLUSION: Although the complication rate is reduced with modern cataract surgery techniques, the primary care clinician should be prepared to identify and manage the most common clinical conditions . Armed with the proper knowledge of ophthalmic medications and their possible ocular and systemic interactions, optometrists can successfully manage and co-manage many postoperative cataract complications . Common postoperative complications are reviewed, along with current treatment regiments and dosage forms.

Dtsch Tierarztl Wochenschr, 1998 Jul, 105(7), 274 - 6
Effect of sodium methyl arsinate and imidocarb dipropionate antiprotozoal drugs on the pharmacokinetic of gentamicin in equines; Soliman GA; The pharmacokinetic behaviour of gentamicin sulphate (3.4 mg/kg bwt) was studied following its intramuscular injection to a group of horses and to another group of horses premedicated with sodium methyl arsinate (2 mg/kg bwt) or imidocarb dipropionate (4.8 mg/kg bwt) . Considerable differences were observed in the pharmacokinetics of gentamicin in pre-medicated horses and in horses which had received the antibiotic alone . Peak serum concentration of gentamicin (9.85 +/- 0.05 and 11.15 +/- 0.15 micrograms/ml) were attained within 1.45 +/- 0.05 and 0.92 +/- 0.04 h in arsinate and imidocarb-medicated horses, respectively, but reached a level of 9.18 +/- 0.07 micrograms/ml at 1.87 +/- 0.12 h in non-medicated animals . Gentamicin elimination half-life (+/- 0.5(el)) was faster in arsinate (7.82 +/- 0.31 h) and imidocarb (6.12 +/- 0.14 h) pre-medicated horses than in non medicated horses (9.88 +/- 0.19 h) . In addition, the interval between doses (lbd) necessary to maintain a therapeutic level were shorter in the pre-medicated animals . In summary, the hypothesis that the pharmacokinetics of gentamicin are altered by concomitant therapy with antiprotozoal drugs was confirmed by this study.

J Bacteriol, 1998 Aug, 180(16), 4123 - 32
The relA/spoT-homologous gene in Streptomyces coelicolor encodes both ribosome-dependent (p)ppGpp-synthesizing and -degrading activities; Martinez-Costa OH et al.; Streptomyces coelicolor (p)ppGpp synthetase (Rel protein) belongs to the RelA and SpoT (RelA/SpoT) family, which is involved in (p)ppGpp metabolism and the stringent response . The potential functions of the rel gene have been examined . S . coelicolor Rel has been shown to be ribosome associated, and its activity in vitro is ribosome dependent . Analysis in vivo of the active recombinant protein in well-defined Escherichia coli relA and relA/spoT mutants provides evidence that S . coelicolor Rel, like native E . coli RelA, is functionally ribosome associated, resulting in ribosome-dependent (p)ppGpp accumulation upon amino acid deprivation . Expression of an S . coelicolor C-terminally deleted Rel, comprised of only the first 489 amino acids, catalyzes a ribosome-independent (p)ppGpp formation, in the same manner as the E . coli truncated RelA protein (1 to 455 amino acids) . An E . coli relA spoT double deletion mutant transformed with S . coelicolor rel gene suppresses the phenotype associated with (p)ppGpp deficiency . However, in such a strain, a rel-mediated (p)ppGpp response apparently occurs after glucose depletion, but only in the absence of amino acids . Analysis of ppGpp decay in E . coli expressing the S . coelicolor rel gene suggests that it also encodes a (p)ppGpp-degrading activity . By deletion analysis, the catalytic domains of S . coelicolor Rel for (p)ppGpp synthesis and degradation have been located within its N terminus (amino acids 267 to 453 and 93 to 397, respectively) . In addition, E . coli relA in an S . coelicolor rel deletion mutant restores actinorhodine production and shows a nearly normal morphological differentiation, as does the wild-type rel gene, which is in agreement with the proposed role of (p)ppGpp nucleotides in antibiotic biosynthesis.

J Bacteriol, 1998 Aug, 180(16), 4089 - 92
Binding interaction between Tet(M) and the ribosome: requirements for binding; Dantley KA et al.; Tet(M) protein interacts with the protein biosynthesis machinery to render this process resistant to tetracycline by a mechanism which involves release of the antibiotic from the ribosome in a reaction dependent on GTP hydrolysis . To clarify this resistance mechanism further, the interaction of Tet(M) with the ribosome has been examined by using a gel filtration assay with radioactively labelled Tet(M) protein . The presence of GTP and 5'-guanylyl imido diphosphate, but not GDP, promoted Tet(M)-ribosome complex formation . Furthermore, thiostrepton, which inhibits the activities of elongation factor G (EF-G) and EF-Tu by binding to the ribosome, blocks stable Tet(M)-ribosome complex formation . Direct competition experiments show that Tet(M) and EF-G bind to overlapping sites on the ribosome.

Ginekol Pol, 1998 Jun, 69(6), 545 - 50
{Percutaneous sperm retrieval for ICSI procedures in men with obstructive azoospermia: ICSI-PESA and ICSI-TESE micromanipulation: our experience}; Wolski JK et al.; OBJECTIVES: The sperm retrieval for ICSI procedures is possibly using following procedures: ejaculate sperm, epididymal sperm obtained by microsurgical aspiration or percutaneous puncture and testicular sperm that are obtained by surgical excision or percutaneous biopsy . Percutaneous techniques seem to be rather simple and effective procedures . DESIGN: The authors present their own experiences with percutaneous sperm retrieval for micromanipulation ICSI from the epididymis (ICSI-PESA) and from the testicular tissue (ICSI-TESE) in men with obstructive azoospermia and with reactive impotence . First time in Poland ICSI-PESA was done on April 11, 1996 in Private Infertility Center "Novum", Warsaw . MATERIAL AND METHODS: From April 1996 to the end of January 1998, 10 ICSI-PESA procedures (in 9 couples) and 8 ICSI-TESE (in 6 couples) were performed . In one case ICSI-PESA was performed in man with psychological inability of masturbation during his wife's IVF protocol . All procedures were performed as the day case urology, under general anesthesia . The fine needles No 6 in PESA or biopsy needle from Hepafix Set B . Braun in TESE were used . The therapy of antibiotic and common analgesic drug was used routinely after puncture . RESULTS: The effectiveness of obtaining sperm for micromanipulation were 100% ICSI-PESA and 75% ICSI-TESE . The pregnancy rate in PESA was 50% and 5 healthy children were born . In TESE only 1 woman (17%) was pregnant, but early spontaneous miscarriage was reported . No surgical and anesthesiological complications were noticed . CONCLUSIONS: Obtaining sperm for micromanipulation ICSI using percutaneous epididymal puncture or testicular tissue needle biopsy seems to be effective and safe for patients with obstructive azoospermia or reactive impotence.

Nippon Ishinkin Gakkai Zasshi, 1998, 39(3), 129 - 34
{Ultrastructure of fungal plasma membranes as revealed by freeze-replica}; Takeo K; This is a short review of fungal plasma membrane ultrastructure as revealed by freeze-replica . Characteristic features of growth polarity, growth phases, cell division, and ultrastructural characteristics after antibiotic treatments have been described.

Fam Pract, 1998 Jun, 15(3), 244 - 51
A study of clinical features and treatment of acute bronchitis by Japanese primary care physicians; Kawamoto R et al.; OBJECTIVE: This study aimed to examine the factors affecting prescription of antibiotics for acute bronchitis in ambulatory care settings in Japan . METHOD: A prospective study was conducted on 92 physicians engaged in primary care regarding their prescription behaviour for a series of 20 new patients with acute respiratory diseases seen during November 1996 and the background factors affecting the behaviour . RESULTS: A total of 1755 patients were registered during the study period, 302 (17.2%) of whom were diagnosed with acute bronchitis and 1165 (66.4%) with upper respiratory tract infection . Independent background factors related to diagnosis of acute bronchitis included self-care prior to visit (odds ratio 1.93, 95% CI 1.33-2.80), complaints such as cough (8.80, 4.77-16.2), sputum (2.24, 1.59-3.14) and purulent sputum (6.47, 3.02-13.9) . The odds ratio was high in patients with more severe findings of the chest (5.00, 3.64-6.85), given chest X-ray (2.68, 1.33-5.38) while it was low in those feeling cold (0.68, 0.48-0.96), and those with a sore throat (0.63, 0.45-0.90), nasal symptoms (0.75, 0.54-1.04) and more severe findings of the pharynx (0.74, 0.58-0.92) . In those with an upper respiratory tract infection, the odds ratio was high for complaints such as feeling cold (1.51, 1.11-2.05) and nasal symptoms (1.39, 1.04-1.86), while it was low for complaints such as cough (0.67, 0.48-0.95), sputum (0.43, 0.30-0.62), purulent sputum (0.19, 0.08-0.44), wheeze (0.34, 0.13-0.92), in those with more severe findings of the tonsil (0.36, 0.29-0.44) and the chest (0.30, 0.19-0.47) and given chest X-rays (0.29, 0.12-0.66) . For acute bronchitis, antibiotics were administered to 67.5% and symptomatic therapy concurrently given to 64.9% . As for independent background factors related to prescription of antibiotics for acute bronchitis, the odds ratio was higher in physicians denying the efficacy of antibiotics for treating a cold (4.58, 1.94-10.8), and the patients with complaints such as purulent sputum (22.9, 2.66-197.2), more severe findings of the pharynx (2.26, 1.34-3.79) and of the chest (2.73, 1.53-4.88), and those who had a body temperature measurement taken (4.42, 1.71-11.4) and a chest X-ray (6.11, 1.07-34.9), but was lower in those complaining of chills (0.16, 0.04-0.66) and diarrhoea (0.11, 0.01-1.11) . CONCLUSIONS: A majority of patients receiving medical care for acute bronchitis are given an unnecessary antibiotic prescription . The result of this study may be useful for the finding of appropriate forms of intervention for changing physicians' prescription behaviour.

Hum Gene Ther, 1998 Jul 20, 9(11), 1571 - 85
In utero gene therapy: transfer and long-term expression of the bacterial neo(r) gene in sheep after direct injection of retroviral vectors into preimmune fetuses; Porada CD et al.; We investigated whether directly injecting retroviral vectors into preimmune fetuses could result in the transfer and long-term expression of exogenous genes . Twenty-nine preimmune sheep fetuses were injected with helper-free retroviral vector preparations . Twenty-two fetuses survived to term, 4 of which were sacrificed at birth . Of the remaining 18 animals, 3 were controls and 15 had received vector preparations . Twelve of these 15 animals demonstrated transduction of hematopoietic cells when blood and marrow were analyzed by neo(r)-specific PCR . Eight experimental sheep have been followed for 5 years, during which time we have consistently observed proviral DNA and G418-resistant hematopoetic progenitors . The G418-resistant colonies were positive when analyzed by neo(r)-specific PCR . neo(r) gene expression was also demonstrated using several immunological and biochemical methods . The transduction of hematopoietic stem cells was confirmed when lambs transplanted with bone marrow from in utero-transduced sheep exhibited neo(r) activity in marrow and blood . Vector distribution was widespread in primary animals without pathology . PCR analysis indicates that the germ line was not altered . These studies demonstrate that direct injection of an engineered retrovirus is a feasible means of safely delivering a foreign gene to a developing fetus and achieving long-term expression without modifying the germ line of the recipient.

Jpn J Antibiot, 1998 May, 51(5), 319 - 24
{Clinical studies on tazobactam/piperacillin (YP-14) in the pediatric field}; Takamuro M et al.; Tazobactam/piperacillin (TAZ/PIPC) was given intravenously to 15 children with acute bacterial infections including 1 with purulent tonsillitis, 11 with pneumonia, 3 with acute pyelonephritis (2 cases are omitted from evaluation because of Mycoplasma pneumonia and intramuscular injection of gammaglobulin) Daily dosages per kg bodyweight ranging from 132 to 156 mg were given in 3 divided doses per day for 4 to 7 days . Clinical responses were excellent in 7 (54%), good in 6 (46%), fair and poor in 0, with an overall efficacy rate of 100% . Good bacterial responses were obtained in all of the 8 cases from which pathogens were identified . Any side effect was not observed . The above results suggest that TAZ/PIPC is a useful new antibiotic for the treatment of bacterial infections in children.

Oral Oncol, 1998 May, 34(3), 219 - 23
Cytotoxic effect of pingyangmycin on cultured KB cells; Tai KW et al.; The antitumour antibiotic pingyangmycin (PYM; bleomycin A5) was isolated from many components of bleomycin (BLM) produced by Streptomyces pingyangensisn . PYM has a similar chemical structure to that of BLM but the terminal amine moiety is different . Therefore, it would be of significance to demonstrate the antitumour effect and action mechanism of PYM on cultivated tumour cells . In this study, we used the cell growth curve, plating efficiency, and DNA synthesis inhibition assay to demonstrate the cytotoxicity of PYM on cultured KB cells . In the meantime, the morphological variations of drug-treated cells were also observed . In addition, we used the DNA precipitation assay, a simple and rapid assay, for detecting DNA damage caused by PYM on cultured KB cells for potential genotoxicity . Our results indicate that the effect of PYM significantly inhibits the cell growth, colonyforming ability, and DNA synthesis of KB cells in a dose-dependent manner . Furthermore, when treated with 5 micrograms/ml of PYM for 24 h on cultured KB cells, DNA strand breaks can be induced (P < 0.05) . Therefore, it is considered that the action mechanism of PYM is due to its ability to inhibit the synthesis of DNA and split the DNA chains.

J Chromatogr A, 1998 Jul 3, 812(1-2), 327 - 37
Iso- and epi-iso-chlortetracycline and the principal metabolites of chlortetracycline in the hen's egg; Kennedy DG et al.; Chlortetracycline (CTC) is a broad spectrum antibiotic, licensed for use without any withdrawal period, in chickens laying eggs intended for human consumption . In the European Union, a maximum residue limit (MRL) in eggs of 200 microgram/kg for the sum of the concentrations of CTC and its 4-epimer (4-epi-CTC) has been established . Two major CTC metabolites have been identified in eggs . These compounds, iso-CTC and 4-epi-iso-CTC, have never previously been shown to be significant products of CTC metabolism in poultry or in any other species . The total amount of CTC present in eggs, as all of the chemical forms measured, can exceed the MRL by anything up to a factor of four (170-820 micrograms/kg).

Cancer, 1998 Aug 1, 83(3), 409 - 14
Neutropenic enterocolitis as a complication of high dose chemotherapy with stem cell rescue in patients with solid tumors: a case series with a review of the literature; Avigan D et al.; BACKGROUND: This case series with an accompanying review of the literature describes neutropenic enterocolitis as a complication of high dose chemotherapy with stem cell rescue in patients with solid tumors . METHODS: Neutropenic enterocolitis is documented in two patients undergoing autologous stem cell transplantation . A review of MEDLINE from 1970 to the present was performed to delineate the prior related disease settings in which this condition has been described . The nature of the clinical syndrome and controversies regarding management are discussed . RESULTS: The authors report two patients who each received autologous stem cell transplantation for the treatment of a solid tumor . Both patients presented with progressive abdominal pain, signs of peritoneal irritation on examination, and pneumatosis intestinalis . In the first case, the syndrome developed rapidly over several hours, requiring emergent surgical intervention during the period of postchemotherapy nadir . In the second case, the patient developed a slowly progressive clinical picture that was managed successfully with medical therapy alone . A review of the literature suggests that neutropenic enterocolitis arises due to drug-induced bowel wall mucosal injury followed by superinfection with colonic and opportunistic organisms . Surgical intervention potentially is beneficial in patients who develop an acute syndrome that is unresponsive to antibiotic and supportive therapy . Those patients who can be stabilized with medical management often will recover once reengraftment occurs . CONCLUSIONS: Neutropenic enterocolitis is described in two patients undergoing autologous stem cell transplantation for solid tumors . The management of this life-threatening complication is controversial and governed by the nature of the clinical presentation.

Eksp Klin Farmakol, 1998 May-Jun, 61(3), 50 - 3
{The effect of gentamycin on immunity in immunodeficiency and the action of immunomodulators}; Sakaeva DD et al.; The effect of 3 and 6 mg/kg gentamicin on the immunity of intact mice and cyclophosphan- and azathioprine-induced immunodeficiency was studied . Gentamicin deepens the severe suppression of antibody genesis against the background of cyclophosphan and azathioprine, inhibits the reaction of GZT in intact mice . The antibiotic does not prevent stimulation of AOK production by methyluracil and prodigiosan, and does not change the effect of immunostimulators on GZT in immunosuppression . Gentamicin has no effect on the phagocytic activity of neutrophils and macrophages in intact animals . The character of the effect of the antibiotic on phagocytosis depends on the genesis of immunosuppression . The effectiveness of gentamicin in experimental infection is maintained in immunosuppression also.

Acta Orthop Belg, 1998 Jun, 64(2), 242 - 8
The Madura foot: an "innocent foot mycosis"?
Ten Broeke R, Walenkamp G.
With the increased movement of the world population, acquaintance with the clinical picture of the Madura foot is of growing importance beyond its original endemic areas . The characteristic triad of symptoms consists of indurated swelling, multiple sinus tracts with purulent discharge filled with grains and localization at the foot . An increasing number of new etiologic agents are recognized today . For a better choice of therapy an adequate diagnostic procedure is essential ; a deep biopsy for histology appears to give a more substantial contribution to identification of the causal organism than culture . The treatment which should be started early, is at first essentially a drug treatment . However, in spite of high expectations with regard to new antimycotic drugs, amputation or disarticulation is often inevitable even today, particularly when the lesion is caused by Eumycetes . The first two documented patients with this disease in the Netherlands are described . They developed serious deformities of the lower extremity despite long-term use of antimycotic and antibiotic medication.

Antimicrob Agents Chemother, 1998 Aug, 42(8), 1931 - 7
Molecular cloning and functional analysis of a novel tetracycline resistance determinant, tet(V), from Mycobacterium smegmatis; De Rossi E et al.; The nucleotide sequence and mechanism of action of a tetracycline resistance gene from Mycobacterium smegmatis were determined . Analysis of a 2.2-kb sequence fragment showed the presence of one open reading frame, designated tet(V), encoding a 419-amino-acid protein (molecular weight, 44,610) with at least 10 transmembrane domains . A database search showed that the gene is homologous to membrane-associated antibiotic efflux pump proteins but not to any known tetracycline efflux pumps . The steady-state accumulation level of tetracycline by M . smegmatis harboring a plasmid carrying the tet(V) gene was about fourfold lower than that of the parental strain . Furthermore, the energy uncoupler carbonyl cyanide m-chlorophenylhydrazone blocked tetracycline efflux in deenergized cells . These results suggest that the tet(V) gene codes for a drug antiporter which uses the proton motive force for the active efflux of tetracycline . By primer-specific amplification the gene appears to be restricted to M . smegmatis and M . fortuitum.

Proc Assoc Am Physicians, 1998 Jul-Aug, 110(4), 361 - 8
Mechanism of dipeptide stimulation of its own transport in a human intestinal cell line; Thamotharan M et al.; The initial objective of this study was to investigate whether the presence of dipeptide in the culture medium stimulates the uptake of dipeptide by a human intestinal cell line that expresses the oligopeptide transporter (Pept-1) . The results showed that addition of glycylsarcosine (Gly-Sar) for 24 hr to the culture medium significantly increased the rate of glycylglutamine (Gly-Gln) uptake by Caco-2 cells . Furthermore, this stimulation in transport was also observed when Cefadroxil (beta-lactam antibiotic) instead of Gly-Gln was used as a probe but did not occur when Gly-Sar was added to the culture medium for only 2 hr or when Gly-Sar was substituted by a corresponding mixture of glycine plus sarcosine . The subsequent objective of the study was to investigate the mechanism of stimulation in transport described earlier . The results showed that the addition of Gly-Sar for 24 hr to the culture medium: (1) increased the Vmax of Gly-Gln transport by two-fold without affecting its Km, (2) increased the protein mass of Pept-1 by more than two-fold, (3) increased the abundance of Pept-1 mRNA by three-fold, and (4) had no effect on Gly-Gln transport when an inhibitor of trans-Golgi network (brefeldin) was added to the culture medium, but still increased the abundance of Pept-1 mRNA . In conclusion, the results show that dipeptides stimulate their own transport by increasing the membrane population of Pept-1 . The molecular mechanism appears to be an increase in expression of the gene encoding Pept-1 . A therapeutic application of the present results is that if bioavailability of orally administered peptidomimetic drugs is limited, patients may be tried on a high-protein diet to enhance their absorption.

Braz J Med Biol Res, 1998 Jan, 31(1), 49 - 53
New strategies in hematopoietic stem cell transplantation: G-CSF-mobilized unprocessed whole blood; Drager AM et al.; Transplantation of mobilized peripheral blood stem cells (PBSC) for rescue of bone marrow function after high-dose chemo-/radiotherapy is widely used in hematologic malignancies and solid tumors . Mobilization of stem cells to the peripheral blood can be achieved by cytokine treatment of the patients . The main advantage of autologous PBSC transplantation over bone marrow transplantation is the faster recovery of neutrophil and platelet counts . The threshold number of PBSC required for adequate rescue of bone marrow is thought to be about 2 x 10(6) CD34+ cells/kg, if the stem cells are collected by leukapheresis and subsequently cryopreserved . We show that this critical number could be further reduced to as few as 0.2 x 10(6) cells/kg . In 30 patients with multiple myeloma and 25 patients with bad risk lymphoma 1 liter of granulocyte colony-stimulating factor (G-CSF)-mobilized unprocessed whole blood (stored at 4 degrees C for 1-3 days) was used for transplantation . Compared to a historical control group, a significant reduction in the duration of neutropenia, thrombocytopenia and the length of hospital stay was documented . Furthermore, the effect of stem cell support was reflected by a lower need for platelet and red cell transfusions and a reduced antibiotic use . Considering the data as a whole, a cost saving of about 50% was achieved . To date, this easy to perform method of transplantation is only feasible following high-dose therapies that are completed within 72 h, since longer storage of unprocessed blood is accompanied by a substantial loss of progenitor cell function . Ongoing investigations include attempts to prolong storage times for whole blood.

Ann Dermatol Venereol, 1997, 124(3), 251 - 3
{Mycobacterium chelonae cutaneous infection: efficacy of prolonged treatment by clarithromycin}; Bordet AL et al.; INTRODUCTION: Mycobacterium chelonae is an ubiquitous mycobacterium which is exceptionally pathogenic . It can cause localized skin infections which are difficult to treat because of multiple drug-resistance . CASE REPORT: A 87-year-old woman with bullous pemphigoid was treated with long-term prednisone and developed a skin infection due to M . Chelonae . Treatment with clarithromycin was successful, but relapse occurred 6 months after withdrawal of the antibiotic . DISCUSSION: Clarithromycin is effective in single drug regimen for M . Chelonae infection, but the duration of treatment should be long when immunosuppression cannot be avoided.

J Vasc Interv Radiol, 1998 Jul-Aug, 9(4), 565 - 71
Percutaneous catheter-directed debridement of infected pancreatic necrosis: results in 20 patients; Echenique AM et al.; PURPOSE: To evaluate the usefulness of transcatheter debridement of infected pancreatic necrosis . MATERIALS AND METHODS: Transcatheter debridement was performed on 20 patients who ranged in age from 20 to 78 years during the 8-year study period . All patients had infected pancreatic necrosis and were hemodynamically stable . Necrosis was defined as nonenhancing pancreatic tissue, as seen on contrast-enhanced computed tomography (CT) . Infection was suspected clinically and documented by cultures of the pancreatic fluid at its initial drainage . Debridement was performed in multiple sessions in close succession (duration, 30-120 minutes; mean, 60 minutes) via large-bore catheters with enlarged side holes . Debris was removed with use of suction catheters, stone baskets, and copious amounts of lavage fluid . RESULTS: All patients underwent successful catheter debridement . Success was determined by clinical course, as well as lesion appearance, at fluoroscopy and CT . Patients underwent 7-32 (average, 17) episodes of debridement and stayed 0-36 days (average, 9 days) in the intensive care unit, 13-118 days (average, 42 days) on the regular floor, and spent 0-98 days (average, 32 days) with the catheters as an outpatient . No deaths occurred . CONCLUSION: Percutaneous catheter-directed debridement is a safe and effective treatment and it can be used as the primary means of treatment for the hemodynamically stable patient with infected pancreatic necrosis.

Arch Microbiol, 1998 Sep, 170(3), 147 - 54
Biochemical properties of the products of cytochrome P450 genes (PDA) encoding pisatin demethylase activity in nectria haematococca
George HL, Hirschi KD, VanEtten HD.
Pea plants produce the antibiotic (+)pisatin in response to infection by the fungus Nectria haematococca, which can detoxify pisatin utilizing a cytochrome P450 monooxygenase called pisatin demethylase . Genes (PDA) have been identified that encode different whole-cell Pda phenotypes that can be distinguished by the length of the lag period and the resulting amount of enzyme activity produced: PdaSH = short lag, high activity; PdaSM = short lag, moderate activity; and PdaLL = long lag, low activity . Only the PdaSH and PdaSM phenotypes have been correlated with pathogenicity on pea . In this study, we utilize heterologous expression of the PDALL gene PDA6-1 in Aspergillus nidulans to compare the biochemical properties of the product of this gene with the products of the PDASH gene PDA1 expressed in N . haematococca . Preliminary measurements were also done on the PDASM gene PDA5 expressed in N . haematococca . The PDA gene products differed somewhat in their substrate specificity and in their sensitivity to a few cytochrome P450 inhibitors . However, the enzymes produced by PDA6-1 and PDA1 both had low apparent Km values toward (+)pisatin (< 0.25 &mgr;M) and a common high degree of insensitivity to most P450 inhibitors, suggesting similar shared biochemical traits as would be expected of products of a highly homologous gene family . Our results indicate that the different whole-cell phenotypes of N . haematococca are not due to significant differences in the biochemical properties of the gene products and are consistent with recent results that indicate that the phenotypic differences are due to different degrees of expression of the genes.

Exp Cell Res, 1998 Aug 1, 242(2), 495 - 514
Distribution of cytoskeletal proteins in neomycin-induced protrusions of human fibroblasts; Safiejko-Mroczka B et al.; The organization of actin, tubulin, and vimentin was studied in protruding lamellae of human fibroblasts induced by the aminoglycoside antibiotic neomycin, an inhibitor of the phosphatidylinositol cycle . Neomycin stimulates the simultaneous protrusion of lamellae in all treated cells, and the lamellae remain extended for about 15-20 min, before gradually withdrawing . The pattern and distribution of actin, tubulin, and vimentin during neomycin stimulation were analyzed by fluorescence and electron microscopy . F-actin in the newly formed lamellae is localized in a marginal band at the leading edge . Tubulin is colocalized with F-actin in the marginal band, but the newly formed lamellae are initially devoid of microtubules . Over a period of 10 to 20 min after the addition of neomycin, microtubules grow into the lamellae from the adjacent cytoplasm, while the intensity of tubulin staining of the marginal band decreases . Distribution of vimentin remains unchanged in neomycin-treated cells and vimentin filaments do not enter the new protrusions . Treatment of cells with colchicine and Taxol do not inhibit neomycin-induced protrusion but protrusions are no longer localized at the ends of cell processes and occur all around the cell periphery . We conclude that actin filaments are the major component of the cytoskeleton involved in generating protrusions . Microtubules and, possibly, intermediate filaments control the pattern of protrusions by their interaction with actin filaments .

J Investig Allergol Clin Immunol, 1998 May-Jun, 8(3), 184 - 5
Occupational allergic contact dermatitis due to airborne spiramycin; Acero S et al.; We report the case of a man who worked in a feed factory . He developed allergic contact dermatitis due to airborne spiramycin, a commonly used antibiotic in veterinary medicine . The patient suffered recurrent outbreaks of eczematous lesions on uncovered areas during working periods . Diagnosis was made based on history, positive patch tests to spiramycin and to some feed compounds containing spiramycin, and on disappearance of lesions on leaving the work place.

Hepatogastroenterology, 1998 May-Jun, 45(21), 783 - 5
Evaluation of the therapeutic effect of pefloxacin in comparison with ampicillin and gentamicin in cirrhotic patients with spontaneous bacterial peritonitis; Rastegar LA et al.; BACKGROUND/AIMS: Hepatic cirrhosis is a common, chronic disease . Spontaneous bacterial peritonitis (SBP) is a dangerous complication, which must be treated as soon as it has been diagnosed . This usually requires hospitalization of the patient and parenteral antibiotic therapy for 10 to 14 days . The present study was carried out to compare the therapeutic effects of pefloxacin with ampicillin plus gentamicin in the management of SBP . METHODOLOGY: The patients were divided into two groups at random . Group A consisted of nine patients who received parenteral ampicillin plus gentamicin . Group B consisted of thirteen patients who received pefloxacin . RESULTS: 55% of patients in group A and 100% of patients in group B responded to treatment . No major side effects were observed in either of the groups . CONCLUSIONS: Considering the benefits of oral treatment and the low incidence of side effects of pefloxacin we conclude that this regimen should be the treatment of choice for SBP patients, especially when there is a shortage of hospital beds.

Allerg Immunol (Paris), 1998 Jun, 30(6), 180 - 2
{Predictive value of the allergologic profile in anesthesia and resuscitation}; Hassoun S et al.; The allergic history to anaesthetics in general and especially to synthetic myorelaxants, poses few etiological diagnostic problems in practice, because of on one hand the excellent collaboration between Anesthetists and Allergologists in the CHU at Angers and on the other because of the great sensitivity of skin testing . Why then have a predictive history for myorelaxants? The results of a study at the CHU at Angers on 15 patients showed sensitivity to anaesthetics in general (myorelaxants 86%, Diprivan) and/or an antibiotic, latex were very encouraging . One 15 new general anaesthetics a single minor incident was seen: the 15 patients had benefited from a predictive history.

Rev Neurol (Paris), 1997 Jul, 153(6-7), 433 - 5
{Acute polyradiculoneuritis and Lyme disease}; Diraison P et al.; A thirty-three-year-old patient developed polyradiculoneuritis with several post-therapeutic relapses despite excellent response to treatment by intravenous polyvalent gammaglobulin . After the second relapse, positive titres for Borrelia burgdorferi were found in serum and C.S.F . We gave her intravenous antibiotic and clinical signs and electrophysiological data improved . Our report and the literature can distinguish two clinical and electrophysiological presentations of neurological peripheral involvement in Lyme disease: meningoradiculoneuritis with axonal involvement and polyradiculoneuritis with demyelinization.

Eye, 1998, 12 ( Pt 2), 278 - 81
National survey of corneal abrasion treatment; Sabri K et al.; PURPOSE: To survey the different methods used in the management of corneal abrasions (including iatrongenic cases) nationally . METHOD: A questionnaire survey of all 162 ophthalmic units in the UK was carried out in 1997 . RESULTS: The response rate was 134 of 162 (83%) . The majority of units do not have an established policy for the treatment of corneal abrasions . Topical antibiotic alone and antibiotic together with a cycloplegic are the commonest immediate treatments, whilst the most common treatment course is topical antibiotic . Padding and patient follow-up is practised some of the time by most units and all of the time by the remaining minority . Use of a soft bandage contact lens is uncommon . There is no statistically significant difference (p > 0.05) between the policy-holders and non-policy-holders in their use of the various topical regimes, padding and soft bandage contact lens . CONCLUSION: The traditional trio of topical antibiotic, cycloplegic and padding is still the mainstay of corneal abrasion treatment amongst units nation-wide . However, there is a lack of reproducible scientific evidence to support this treatment . Larger randomised trials looking at the efficacy of the different treatment options are needed.

Am J Surg, 1998 Jul, 176(1), 81 - 5
Misdiagnosis of primary epiploic appendagitis; Rao PM et al.; BACKGROUND: The authors determined the radiological misdiagnosis rate of primary epiploic appendagitis (PEA) and its impact on patient management and hospital resource use . METHODS: A total of 660 computed tomography scans performed for clinically suspected diverticulitis (348 cases) or appendicitis (312 cases) were reviewed for cases meeting strict radiological criteria for PEA . Retrospective interpretations were compared with radiological reports . Medical records and hospital cost data were reviewed to estimate impact on patient management and resource use . RESULTS: Eleven scans (2%) met criteria for PEA . Seven scans were initially misdiagnosed as diverticulitis (6 patients) or appendicitis (1 patient) . All misdiagnosed patients were hospitalized (mean 4.3 days); 6 received antibiotic therapy . Average cost per patient was $4,117 . Four scans were initially correctly diagnosed as PEA . One patient was hospitalized (1 day); none received antibiotic therapy . Average cost per patient was $1,205 . CONCLUSIONS: Radiological misdiagnosis of PEA leads to unnecessary hospitalization, medical treatment, and overuse of hospital resources.

Am J Surg, 1998 Jul, 176(1), 12 - 4
Late-onset deep prosthetic infection following mesh repair of inguinal hernia; Mann DV et al.; BACKGROUND: The use of prosthetic biomaterials for the primary repair of inguinal hernias is now commonplace . Late-onset deep-seated prosthetic infection can be an unexpected complication . METHODS: The literature from a Medline search relating to the biology of mesh in the setting of hernia repair is discussed . CONCLUSIONS: The use of a foreign body for hernia repair does not appear to alter the incidence of superficial wound infection . Late-onset deep graft infection has been rarely reported, and the true incidence is yet to be established . With the more widespread use of mesh materials, this complication may become increasingly evident.

J Pharm Biomed Anal, 1998 Aug, 17(4-5), 751 - 5
A high-performance liquid-chromatographic assay for amphotericin B in a hydrophilic colloidal paste base; Wilkinson JM et al.; A stability-indicating high-performance liquid-chromatographic (HPLC) assay has been developed for amphotericin B (AmB) in a paste, containing AmB, tobramycin (or gentamicin) sulphate, colistin sulphate, liquid paraffin and Orabase . Extraction of AmB was performed by partitioning the antibiotic between N,N-dimethylformamide (DMF) and cyclohexane, which led to precipitation of the polymeric materials and extraction of the liquid paraffin into the cyclohexane and AmB into the DMF . Analysis by HPLC of the latter layer gave a linear relationship between concentration and peak area response for the AmB over the range 5.0 x 10(-4) to 7.5 x 10(-3)% (w/v) (r = 0.9995) with a relative standard deviation of +/- 1.46% (n = 8) . The efficiency of extraction was 1006 +/- 2.4% (n = 5).

Cancer Invest, 1998, 16(6), 366 - 73
A comparison of efficacy of sargramostim (yeast-derived RhuGM-CSF) and filgrastim (bacteria-derived RhuG-CSF) in the therapeutic setting of chemotherapy-induced myelosuppression; Beveridge RA et al.; A randomized, double-blind, multicenter study in 181 afebrile cancer patients with ANC levels < 500/microL receiving myelosuppressive chemotherapy was undertaken to compare sargramostim (yeast-derived recombinant human granulocyte-macrophage colony-stimulating factor, RhuGM-CSF) and filgrastim (bacteria-derived recombinant human granulocyte colony-stimulating factor, RhuG-CSF) in the treatment of chemotherapy-induced myelosuppression . Patients received daily subcutaneous (SC) injections of either agent until ANC levels reached at least 1500/microL . There was no statistical difference between treatment groups in the mean number of days to reach an ANC of 500/microL, but the mean number of days to reach ANC levels of 1000/microL and 1500/microL was approximately one day less in patients receiving filgrastim . Fewer patients in the sargramostim arm were hospitalized, and they had a shorter mean length of hospitalization, mean duration of fever, and mean duration of i.v . antibiotic therapy compared with patients who received filgrastim . Both growth factors were well tolerated . No patient was readmitted to the hospital after growth factor was discontinued . Sargramostim and filgrastim have comparable efficacy and tolerability in the treatment of standard-dose chemotherapy-induced myelosuppression in community practice.

Soc Sci Med, 1998 Aug, 47(3), 341 - 6
Physicians' prescribing behaviour for diarrhoea in children: an ethnoepidemiological study in Southern Brazil; Beria JU et al.; With the aim of implementing an intervention program on physician's prescribing behaviour for diarrhoea in children under five, an ethnoepidemiological study was conducted in Pelotas (Brazil), from February to April 1993 . Information on prescription of drugs was obtained through record review of 381 cases of diarrhoea provided by 33 medical doctors from eight health centres . Trained field workers observed a total of 54 clinical consultations due to diarrhoea . Brief exit interviews with the mothers were performed just after the observations . Twenty-seven open-ended home interviews were made with the mothers the day after they had been observed . After all observations had been completed, open-ended interviews were conducted with 21 physicians . The results showed that there is a misunderstanding of the role of ORS in the treatment of diarrhoea: mothers want something to "cut" diarrhoea and they notice that ORS does not act in this way and doctors do not explain the action of ORS in diarrhoea management . Comparing with record reviews, during observations a child had a lower probability of receiving an antibiotic or antidiarrheal drug prescription . This finding indicates that other variables than technical skills are involved in doctor's prescribing behaviour . A lack of ability or of motivation to deal with "anxious or difficult mothers" led some doctors to enhance antibiotic or other non-recommended drugs to manage diarrhoea . Therefore, efforts to improve the quality of case management of diarrhoea, through intervention programmes in the government health sector, are needed in Pelotas.

J Dent Hyg, 1998 Spring, 72(2), 35 - 40
Systemic lupus erythematosus: a review for dental professionals; Hughes CT et al.; Systemic lupus erythematosus is a chronic, autoimmune disorder of unknown etiology with an annual incidence of 2 to 8 cases per 100,000 adults . Symptoms include fevers, arthralgias, and a characteristic rash over the cheeks and nose . More serious manifestations involve the cardiac, renal, and central nervous systems . Due to the valvular damage associated with SLE, prophylactic antibiotic premedication is recommended prior to invasive dental procedures . Drug therapy consists of nonsteroidal anti-inflammatory agents, antimalarials, and corticosteroids . Appropriate dental management of these patients requires an understanding of the etiology, clinical manifestations, current treatment recommendations, and psychological aspects of the disease.

Radiology, 1998 Aug, 208(2), 525 - 8
Intraperitoneal abscesses: diagnostic accuracy of and appearances at MR imaging; Noone TC et al.; PURPOSE: To prospectively investigate the diagnostic accuracy of and appearances at magnetic resonance (MR) imaging of patients clinically suspected to have intraperitoneal abscesses . MATERIALS AND METHODS: Sixty-seven consecutive patients underwent MR imaging for suspected intraperitoneal abscesses . MR images were prospectively interpreted for intraperitoneal abscesses; the results were correlated with surgical, histopathologic, and laboratory findings . RESULTS: MR imaging revealed 25 fluid collections consistent with intraperitoneal abscesses in 22 of 67 patients (33%) . Of these collections, 22 were intraperitoneal abscesses; one, a giant sigmoid diverticulum; and two, sterile fluid collections . The latter two patients had been receiving antibiotic therapy . MR imaging allowed exclusion of intraperitoneal abscesses in 45 patients (67%) . All collections demonstrated decreased signal intensity on T1-weighted images; on T2-weighted images, 13 collections demonstrated homogeneously increased signal intensity and 12 demonstrated heterogeneously increased signal intensity . The abscesses were best demonstrated on gadolinium-enhanced T1-weighted fat-suppressed images as well-defined fluid collections with peripheral rim enhancement . Sensitivity was 100%; specificity, 94% (95% confidence interval = 83%, 99%); positive predictive value, 88% (95% confidence interval = 69%, 97%); negative predictive value, 100%; and accuracy, 96% (95% confidence interval = 88%, 99%) . CONCLUSION: MR imaging has high diagnostic accuracy in evaluation of acute intraperitoneal abscesses.

Drugs Aging, 1998 Jul, 13(1), 1 - 7
Is there an infective aetiology to atherosclerosis?
Gupta S, Camm AJ.
Conventional cardiovascular risk factors fail to completely explain the observed variations in the prevalence and severity of coronary heart disease (CHD) . Common chronic infections may have an aetiological role in the development of atherosclerosis and CHD, either independently or by interacting with traditional atherogenic risk factors . The evidence for Chlamydia pneumoniae as a potential causative agent is strongest, and is based on findings of numerous sero-epidemiological studies, examination of atheromatous plaque specimens, in vitro animal models and, recently, pilot antichlamydial antibiotic intervention trials . However, the complete natural history of C . pneumoniae, its mechanisms of damage in atherosclerotic disease, and the temporal sequence of infection and CHD remain unclear . Confirmation of true causality for the link between C . pneumoniae and CHD could come after the results of large-scale prospective antibiotic trials, which are to be conducted over the next few years . A proven association could have important implications for public health worldwide, potentially leading to novel and relatively inexpensive therapeutic measures in the secondary prevention of CHD--broad-spectrum antibiotics.

Aliment Pharmacol Ther, 1998 Jun, 12(6), 569 - 76
Factors affecting solubility and penetration of clarithromycin through gastric mucus; Grubel P et al.; BACKGROUND: Factors influencing the pharmacokinetics of clarithromycin in gastric mucus are poorly defined . AIM: To determine: (i) whether the clinical formulation of clarithromycin (Biaxin granules and powdered Biaxin tablets) affects the water solvency of the antibiotic or changes the barrier properties of pig gastric mucus (PGM), thereby influencing the penetration of clarithromycin through the gastric mucus layer; and (ii) whether topically active anti-ulcer agents affect clarithromycin penetration through gastric mucus . METHODS: Solubility of clarithromycin in aqueous solution was studied at pH 7 . PGM viscosities were determined using a falling ball microviscometer . Permeability of clarithromycin through PGM with and without added anti-ulcer drugs at pH 7 was monitored using a microfiltration device and an agar diffusion bioassay . RESULTS: Clarithromycin showed the poorest solubility at pH 7, whereas both Biaxin formulations demonstrated identical solubility of their antibiotic ingredient . Clarithromycin and both Biaxin formulations markedly increased mucin viscosity over the pH range 2-7 . PGM markedly retarded the penetration of clarithromycin: unformulated clarithromycin and Biaxin tablets penetrated more rapidly through mucus than Biaxin granules . Pre-treatment of PGM with aluminium-magnesium-containing antacids (Riopan and Talcid preparations) decreased the rate of clarithromycin penetration, whereas Carafate and Peptobismol had no significant effect on mucus penetration of clarithromycin . CONCLUSIONS: The availability of clarithromycin in gastric mucus is significantly influenced by its clinical formulation, which affects its solubility as well as the viscous properties of mucus . Pulverized Biaxin tablets provide better local distribution of clarithromycin in mucus than Biaxin granules . Pre-treatment of mucus with anti-ulcer medications does not increase the penetration of clarithromycin through mucus.

Aliment Pharmacol Ther, 1998 Jun, 12(6), 551 - 5
Lansoprazole and secnidazole with clarithromycin, amoxycillin or pefloxacin in the eradication of Helicobacter pylori in a developing country; Ahuja V et al.; BACKGROUND: A number of triple drug regimens using proton pump inhibitors and two antibiotics have been evaluated in the West and reported to achieve Helicobacter pylori eradication rates of over 90% . In developing countries however, these combinations have neither been well evaluated, nor the optimum treatment for H . pylori infection well defined . AIM: To compare the combination of a proton pump inhibitor with a nitroimidazole and another antibiotic in eradicating H . pylori infection and healing duodenal ulcer . METHODS: Sixty consecutive patients with active duodenal ulcer who were positive for H . pylori (by rapid urease test and 14C-urea breath test) were randomized into three treatments groups: (1) LAS (n=21): lansoprazole 30 mg o.m., amoxycillin 500 mg q.d.s . and secnidazole 2 g on alternate days for 2 weeks; (2) LCS (n=18): lansoprazole 30 mg o.m., clarithromycin 500 mg b.d . and secnidazole 2 g on alternate days for 1 week; (3) LPS (n=21): lansoprazole 30 mg o.m., pefloxacin 400 mg o.m . and secnidazole 2 g on alternate days for 2 weeks . Urease and breath tests were performed at 0, 6 and 12 weeks to check for H . pylori eradication . RESULTS: Intention-to-treat eradication rates were as follows: LAS 86%, LCS 83%, LPS 71%; the overall ulcer healing rate was 90% at 6 weeks . CONCLUSIONS: High H . pylori eradication rates were achieved using the amoxycillin- and clarithromycin-based therapies . Fewer side-effects, better compliance and low cost favoured the amoxycillin-based therapy.

Obes Surg, 1998 Jun, 8(3), 283 - 8
The surgical technique of the Fobi-Pouch operation for obesity (the transected silastic vertical gastric bypass); Fobi MA et al.; The Fobi-Pouch operation (FPO) for obesity is the product of clinical trials, more than 15 years of personal clinical experience and information gathered from publications, scientific meetings, and personal communications with other bariatric surgeons . The essence of the operation is the small vertical pouch (< 25 ml), an externally supported stoma, the interposed Roux-en-Y limb, the gastrostomy and the bypassed stomach marker to facilitate percutaneous transabdominal access to the bypassed segment . Patients undergoing this operation are usually given bowel prep the day before the operation, admitted the morning of the operation and started on subcutaneous heparin, prophylactic antibiotic and hydration . Antithrombotic sequential compression devices are regularly used . The hospital stay is usually 4 days . Our results and those of other surgeons who have used this modification substantiate the rationale for the modifications entailed in the FPO . Our longer-term experience and results are being compiled for publication.

Singapore Med J, 1998 Apr, 39(4), 156 - 9
The effect of enteral fibre-containing feeds on stool parameters in the post-surgical period; Khalil L et al.; BACKGROUND/AIM OF STUDY: Specialised nutritional support includes both enteral and parenteral routes . When oral intake is not an option, but gastro-intestinal function is present, enteral tube feeding should be considered . However, one of the complications of enteral feeding access is diarrhoea . The aim of this study was to test the effect of fibre on a local population, in a prospective, single-blinded trial to determine whether the presence of fibre in enteral feeds reduced the incidence of diarrhoea in Asian patients . METHODS: Sixteen post-surgical candidates were randomly assigned to receive a fibre-supplemented (FSF) enteral formula or a fibre-free formula (FFF) for 10 days post-surgery to assess the usefulness of FSF in reducing the incidence of diarrhoea in tube-fed patients . Differences in stool consistency, stool frequency, capillary blood glucose and serum albumin levels between the two groups were determined . Antibiotic usage in both groups was noted . RESULTS: Patients in the FSF group had more bowel movements throughout the 10-day period and firmer stools than the FFF group, but this difference was not statistically significant (p = 0.39) . There were no significant differences in daily mean glucose levels between both groups . CONCLUSION: We conclude that there is insufficient evidence that fibre-containing enteral formulae reduce the incidence of diarrhoea in tube-fed patients in the short term . However, these products could inherently be included for patients on tube-feeds during extended periods, with the prospect of maintaining gut function integrity and flora.

Haematologica, 1998 Jun, 83(6), 550 - 63
Transplant of hematopoietic stem cells in childhood: where we are and where we are going; Locatelli F et al.; Over the past decade, relevant improvements and refinements have significantly changed the indications, technique and results obtained with allogeneic transplantation of hematopoietic stem cells (HSC) in childhood . In this review the most important innovations that have characterized the practice of HSC transplantation in childhood during this decade will be discussed . We will analyze the clinical and biological advantages or disadvantages which characterize most typically HSC transplantation procedure in terms of the source of these cells (bone marrow, peripheral blood, placental blood) . A fundamental turning point in the history of allogeneic transplantation of HSC is represented by the use of placental blood, which was first employed in 1988 . Autologous, peripheral blood progenitor cells are increasingly being used as a source of HSC following high-dose therapy for malignant disease, because of the ease of collection and the markedly faster kinetics of engraftment in comparison with bone marrow . In particular, over the past decade, due to the much faster recovery of all hematopoietic lineages in comparison with bone marrow and due to the short duration of antibiotic therapy and hospitalization, also in pediatric patients, auto-transfusion of circulating hematopoietic progenitors is rapidly replacing autologous bone marrow transplantation after high-dose chemotherapy for lymphomas and solid tumors . On the contrary, due to concerns in pediatric patients related to the use of hematopoietic growth factors in a healthy donor, allograft of peripheral blood progenitor cells is not routinely used . Since indications for allogeneic HSC transplantation that had already been well established in the recent past have been complemented by others and a relevant number of disorders are no longer considered to be eligible for allograft, the evolution in the indications for allogeneic transplant of HSC in childhood will be discussed . Likewise, biotechnological, social and organizational refinements which have allowed the greatest advances of allogeneic HSC transplantation in this decade will be analyzed, as well as some still open bioethical question regarding this procedure.

Clin Infect Dis, 1998 Jul, 27(1), 191 - 204
Use of dapsone in the prevention and treatment of Pneumocystis carinii pneumonia: a review; Hughes WT; Dapsone, with or without trimethoprim or pyrimethamine, has strong anti-Pneumocystis carinii activity, as demonstrated by in vitro methods, animal studies, and clinical trials . The drug blocks folic acid synthesis of P . carinii by inhibition of dihydropteroate synthetase activity . Dapsone is efficiently absorbed (70%-80%) from the gastrointestinal tract, reaches peak serum concentration in 2-6 hours, and is adequately distributed to the fluid of the alveolar spaces . Synergistic effects against P . carinii are noted when trimethoprim is combined with dapsone . This combination is recommended for therapeutic use for P . carinii pneumonia (PCP) as an alternative for patients who cannot take trimethoprim-sulfamethoxazole (TMP-SMZ) . Evidence from more than 40 studies of dapsone as prophylaxis for PCP in AIDS patients shows that dapsone, either alone or in combination with pyrimethamine, is as effective as aerosolized pentamidine or atovaquone but slightly less effective than TMP-SMZ . Adverse effects include rash, anemia, methemoglobinemia, agranulocytosis, and hepatic dysfunction . Desensitization can be accomplished with many cases . Dapsone is the most cost-effective prophylaxis currently available for PCP.

Clin Infect Dis, 1998 Jul, 27(1), 97 - 9
Legionella bozemanii pneumonia in three patients with AIDS; Harris A et al.; Legionella bozemanii is known to cause pneumonia often in immunocompromised hosts . To our knowledge, we describe the first three cases of L . bozemanii pneumonia in patients with AIDS . At the time of presentation, these patients had varied histories, physical findings, and radiological findings . All three patients had a uniformly excellent response to treatment despite receiving different antibiotic regimens . The cases illustrate the need for thorough diagnostic workups and prompt institution of antibiotic therapy when clinical suspicion for L . bozemanii infection is high.

J Dermatol, 1998 Jun, 25(6), 415 - 7
Contact dermatitis due to sodium colistimethate; Sasaki S et al.; Colistin methanesulfonate sodium (CLMS) is a widely-used antibiotic . To our best knowledge, only two cases of contact allergy to CLMS have been reported . We described a 4-year-old girl with contact dermatitis evoked by CLMS that had been applied as an ophthalmic solution . The dermatitis started after administration for 21 days . The diagnosis was confirmed by as is and constituent patch tests . We reviewed the literature in which contact allergy due to CLMS and colistin sulfate is described.

Biochim Biophys Acta, 1998 Jul 28, 1386(1), 132 - 44
Studies of the allosteric properties of maize leaf phosphoenolpyruvate carboxylase with the phosphoenolpyruvate analog phosphomycin as activator; Mujica-Jimenez C et al.; The antibiotic phosphomycin (1,2-epoxypropylphosphonic acid), an analog of phosphoenolpyruvate (PEP), behaved not as an inhibitor, but as an activator, of the enzyme phosphoenolpyruvate carboxylase (PEPC) from maize leaves . Multiple activation studies indicated that the analog binds to the Glc6P-allosteric site producing a more activated enzyme than Glc6P itself . Because of this, we used phosphomycin as a tool to further extend our understanding of the mechanisms of allosteric regulation of C4-PEPC . Initial velocity data from detailed kinetic studies, in which the concentrations of free and Mg-complexed PEP and phosphomycin were controlled, are consistent with: (1) the true activator is free phosphomycin, which competes with free PEP for the Glc6P-allosteric site; and (2) the Mg-phosphomycin complex caused inhibition by binding to the active site in competition with MgPEP . Therefore, although the Glc6P-allosteric site and the active site are able to bind the same ligands, they differ in the form of substrate and activator they bind . This important difference allows the full expression of the potential of activation and prevents inhibition by the activators, including the physiological ones, which are mostly uncomplexed at physiological free Mg2+ concentrations . At fixed low substrate concentrations, the saturation kinetics of the enzyme by phosphomycin showed positive cooperativity at pH 7.3 and 8.3, although at the latter pH, the kinetics of saturation by the substrate was hyperbolic . The cosolute glycerol greatly increased the affinity of the enzyme for phosphomycin and abolished the cooperativity in its binding, but did not eliminate the heterotropic effects of the activator . Therefore, the heterotropic and homotropic effects of the activator are not always coupled to the homotropic effects of the substrate, which argues against the two-state model previously proposed to explain the allosteric properties of maize-leaf PEPC.

Biophys J, 1998 Aug, 75(2), 635 - 40
Shifting the equilibrium mixture of gramicidin double helices toward a single conformation with multivalent cationic salts; Doyle DA et al.; The conformation of the polypeptide antibiotic gramicidin is greatly influenced by its environment . In methanol, it exists as an equilibrium mixture of four interwound double-helical conformers that differ in their handedness, chain orientation, and alignment . Upon the addition of multivalent cationic salts, there is a shift in the equilibrium to a single conformer, which was monitored in this study by circular dichroism spectroscopy . With increasing concentrations of multivalent cations, both the magnitude of the entire spectrum and the ratio of the 229-nm to the 210-nm peak were increased . The spectral change is not related to the charge on the cation, but appears to be related to the cationic radius, with the maximum change in ellipticity occurring for cations with a radius of approximately 1 A . The effect requires the presence of an anion whose radius is greater than that of a fluoride ion, but is otherwise not a function of anion type . It is postulated that multivalent cations interact with a binding site in one of the conformers, known as species 1 (a left-handed, parallel, no stagger double helix), stabilizing a modified form of this type of structure.

Biopharm Drug Dispos, 1998 Jul, 19(5), 303 - 8
Pharmacokinetics of a new carbapenem, DA-1131, after intravenous administration to rats with alloxan-induced diabetes mellitus; Kim SH et al.; Because physiological changes occurring in diabetes patients could alter the pharmacokinetics of drugs used to treat the disease, the pharmacokinetics and tissue distribution of DA-1131, a new carbapenem antibiotic, were investigated after 1-min intravenous (i.v.) administration of the drug, 50 mg kg-1, to control and alloxan-induced diabetes mellitus (AIDM) rats . The impaired kidney function was observed by pretreatment with alloxan based on physiological parameters of plasma, creatinine clearance, and the kidney microscopy . After 1-min i.v . infusion of DA-1131, the plasma concentrations of DA-1131 and the total area under the plasma concentration-time curve of DA-1131 from time zero to time infinity (AUC) increased significantly in the AIDM rats (7350 versus 4400 micrograms min mL-1) when compared with those in control rats . This was due to significantly slower total body clearance (Cl) of DA-1131 (6.80 versus 11.4 mL min-1 kg-1) in AIDM rats than that in control rats . The significantly slower Cl of DA-1131 in AIDM rats was due to significantly slower renal (2.62 versus 4.95 mL min-1 kg-1, because of the considerably decreased glomerular filtration rate of DA-1131) and nonrenal (3.99 versus 6.34 mL min-1 kg-1, possibly because of the considerably slower metabolism in rat liver and kidney) clearance in AIDM rats . The amount of DA-1131 recovered from each rat tissue studied was significantly higher in AIDM rats than that in control rats, however, the tissue to plasma ratios were not significantly different between the two groups of rats.

Bone Marrow Transplant, 1998 Jun, 21(12), 1275 - 7
Bile duct adenocarcinoma mimicking veno-occlusive disease after autologous bone marrow transplantation for acute leukaemia; Becherer A et al.; A 52-year-old female underwent autologous BMT because of acute myeloid leukaemia FAB M4 in second remission . Since the patient had no HLA-identical sibling she received a purged autologous BM transplant . On day +5 she developed signs of a sepsis syndrome with fluid retention and was treated with broad-spectrum antibiotic therapy . However, her body weight remained high, ascites and an increase of total serum bilirubin and alkaline phosphatase developed . The icterus worsened to a total bilirubin level of 25 mg/100 ml . Sonographic and endoscopic imaging showed a dilated gall bladder but disclosed a post-hepatic cause for the icterus . A transjugular liver biopsy on day +71 revealed severe cholestasis and siderosis . The patient remained aplastic with constantly increased bilirubin levels . On day +73 septic shock syndrome occurred and the patient died of multiorgan failure 3 days later . At autopsy, a highly differentiated bile duct adenocarcinoma at the porta hepatis, so-called Klatskin tumour, was found, explaining the fatal course with intractable cholestasis.

Bone Marrow Transplant, 1998 Jun, 21(12), 1231 - 8
Influence of protective isolation on outcome of allogeneic bone marrow transplantation for leukemia; Passweg JR et al.; Various isolation strategies are used to prevent infections during bone marrow transplantation; data on their efficacy are lacking . We studied whether use of high efficiency particulate air filtration (HEPA) and/or laminar airflow (LAF) units affect transplant-related mortality (TRM) or survival in the first year after allogeneic transplantation . 5065 patients with leukemia receiving bone marrow transplants from an HLA identical sibling (n = 3982) or alternative related or unrelated donors (n = 1083) between 1988 and 1992 were reported to the International Bone Marrow Transplant Registry by 222 teams . Two types of isolation were considered: (1) conventional protective isolation with single patient room and any combination of hand-washing, gloves, mask and gown; and (2) HEPA and/or LAF . Cox proportional hazards regression models were used to determine the relative risks (RRs) of transplant-related mortality (TRM) and of deaths from any cause in patients treated in HEPA/LAF units compared to patients treated in conventional isolation . HLA-identical sibling and alternative donor transplants were analyzed separately . Risks of TRM and overall mortality in the first 100 days post-transplant were significantly lower among patients treated in HEPA/LAF units than in those treated conventionally . RRs of TRM were 0.76 (P = 0.009) for recipients of HLA-identical sibling transplants and 0.65 (P = 0.003) for recipients of alternative donor transplants . Correspondingly RRs of overall mortality were 0.80 (P = 0.02) and 0.65 (P = 0.0006) . Decreased risks of TRM and of death in the first 100 days post-transplant resulted in significantly higher 1-year survival rates in patients treated in HEPA/LAF rather than in conventional isolation units . Use of HEPA and/or LAF to prevent infections decreases TRM and increases survival after allogeneic bone marrow transplants for leukemia.

Am J Med, 1998 Jun, 104(6), 559 - 64
Oral lesions among women living with or at risk for HIV infection . HIV Epidemiology Research Study (HERS) Group; Schuman P et al.; PURPOSE: Our objectives were to compare the prevalence of oropharyngeal mucosal lesions among human immunodeficiency virus (HIV) seropositive and demographically similar seronegative women, and to determine the association of oral lesions with immunosuppression, substance abuse, use of medications, and utilization of dental services . POPULATION AND METHODS: Participants in a multicenter, longitudinal cohort study of HIV infection in women were evaluated at baseline by interview, physical examination, and laboratory studies . RESULTS: Oropharyngeal pathology was found in 40% of seropositive and 23% of seronegative women . Oral candidiasis was identified in 15% of seropositive and 3% of seronegative women . Among seropositive women, history of previous oral candidiasis, lower CD4 lymphocyte counts, and current antibiotic use were associated with oral candidiasis . Hairy leukoplakia was identified in 5% of seropositive women and was significantly associated with lower CD4 lymphocyte counts . Gingival erythema and ulcerative gingivitis were found in 23% of participants overall, but were unrelated to HIV serostatus or CD4 lymphocyte count . Substance abuse, lack of dental care, and African-American race were associated with gingival pathology . CONCLUSION: The high prevalence of oral lesions among HIV seropositive and at-risk seronegative women underscores the need for routine oral examination and targeted treatment of this population.

Otolaryngol Head Neck Surg, 1998 Jul, 119(1), 117 - 20
Prophylactic treatment after ventilation tube insertion: comparison of various methods; Golz A et al.; Otitis media is recognized as one of the most common diseases of childhood . Insertion of tympanostomy tubes for the treatment of otitis media is the most frequently performed otologic operation, and postoperative otorrhea is its most common complication . Many authors have suggested various reasons for posttympanostomy otorrhea, and many different prophylactic treatments were proposed in recent years to prevent this bothersome and frustrating complication . This retrospective study was designed to investigate and compare the efficacy of various prophylactic treatments and to define the most effective method of reducing the rate of postoperative otorrhea.

Otolaryngol Head Neck Surg, 1998 Jul, 119(1), 14 - 20
Contribution of membrane cholesterol to outer hair cell lateral wall stiffness; Nguyen TV et al.; The outer hair cell can be divided into three domains: the apex, the base, and the lateral wall . With the use of filipin, a polyene fluorescent antibiotic that binds to cholesterol, we found under fluorescence microscopy that the lateral wall membranes were less intensely stained than the apical and basal membranes . This difference in filipin fluorescence between the lateral walls and the ends diminished when cells were incubated in water-soluble cholesterol before staining, suggesting that exogenous cholesterol enters the lateral wall . Under confocal microscopy, we studied the incorporation pattern of a fluorescent cholesterol analogue, NBD-cholesterol . NBD-cholesterol did not stain the apical membranes whereas it intensely labeled the lateral wall . The micropipette aspiration technique was used to assess the effect of cholesterol on lateral wall stiffness . The lateral wall stiffness parameter of cells treated with water-soluble cholesterol (n = 23) was significantly higher than that of controls (n = 27): 0.76+/-0.24 (mean +/- SD) versus 0.46+/-0.10 (Student's t-test, p < 0.001) . In conclusion, cholesterol has different distributions among outer hair cell membranes, and when water-soluble cholesterol is incorporated into the cells, the outer hair cell lateral wall stiffness parameter increases.

Prostaglandins Other Lipid Mediat, 1998 May, 56(1), 33 - 42
G-CSF after autologous hemopoietic stem cell transplantation in malignant lymphoma; Deliliers GL et al.; Forty-eight autografted patients were studied after treatment with granulocyte-colony stimulating factor (G-CSF) and were compared with a historical series of 24 patients autografted with bone marrow (BM) without G-CSF . When the patients were divided on the basis of G-CSF administration, type of lymphoma and the source of hemopoietic stem cells, no significant difference was found in the median number of infused BM cells, duration of febrile episodes, platelet and hemoglobin recovery, or in the number of transfusions . The patients receiving peripheral blood (PB) + G-CSF had significantly shorter median durations of antibiotic therapy, hospital stay and polymorphonucleate (PMN) recovery . When the Hodgkin disease (HD) and non-Hodgkin lymphoma (NHL) cases were considered separately, a significant difference between those receiving and those not receiving G-CSF was observed only in the HD group . The advantage offered by PB + G-CSF over BM + G-CSF was far more evident in the NHL group than in HD . It can be concluded that G-CSF improves the outcome of BM transplant in HD, and that the use of PB + G-CSF adds a further advantage; conversely, in NHL, PB + G-CSF is strikingly superior to BM + G-CSF, but the addition of G-CSF adds little advantage.

Prostaglandins Other Lipid Mediat, 1998 May, 56(1), 19 - 31
Effect of different inhibitors on phospholipase C activity in Catharanthus roseus transformed roots; Pina-Chable ML et al.; We have previously reported that Catharanthus roseus transformed roots contain at least two phosphatidylinositol 4,5-bisphosphate-phospholipase C (PLC) activities, one soluble and one membrane associated . In this paper, the effect of neomycin and several divalent cations was analyzed, both in the soluble and the membrane-associated PLC activity in C . roseus transformed roots . In this system, neomycin, an aminoglycoside antibiotic, inhibited PLC in a concentration-dependent fashion . The neomycin IC50 (100 microM) was the same for the inhibition of the soluble and the membrane associated PLC activity . The effect of different divalent cations such as Ni2+, Cu2+, and Zn2+ was studied as well . In order to see the effect of these cations on PLC activity, we selected two conditions: a) in the presence of and b) in the absence of calcium . In the presence of calcium, these three divalent cations were able to inhibit PLC activity in both fractions in a concentration-dependent manner; however, the IC50s were different for the membrane and the soluble activities . For the soluble activity, the inhibition due to the three cations was very similar (IC50s between 0.2 and 0.3 mM) . For the membrane associated PLC activity, Cu2+ was the most potent inhibitor (IC50 3.6 microM), then Ni2+ and then Zn2+ . In the absence of calcium, higher concentrations of Cu2+ and Zn2+ demonstrated some inhibitory effect . We discuss the possible physiological role of these inhibitors on PLC activity.

Infect Immun, 1998 Aug, 66(8), 3874 - 83
Paromomycin and geneticin inhibit intracellular Cryptosporidium parvum without trafficking through the host cell cytoplasm: implications for drug delivery; Griffiths JK et al.; Cryptosporidium parvum, which causes intractable diarrhea and lethal wasting in people with AIDS, occupies an unusual intracellular but extracytoplasmic niche . No reliable therapy for cryptosporidiosis exists, though the aminoglycoside paromomycin is somewhat effective . We report that paromomycin and the related compound geneticin manifest their major in vitro anti-C . parvum activity against intracellular parasites via a mechanism that does not require drug trafficking through the host cell cytoplasm . We used both normal and transformed aminoglycoside-resistant Caco-2 or MDBK cells in these studies . Timed-exposure experiments demonstrated that these drugs inhibit intracellular but not extracellular parasites . Apical but not basolateral exposure of infected cells to these drugs led to very significant parasite inhibition, indicating an apical topological restriction of action . We estimated intracytoplasmic concentrations of paromomycin, using an intracellular bacterial killing assay, and found that C . parvum infection did not lead to increased paromomycin concentrations compared to those in uninfected cells . Global {3H}paromomycin uptake by Caco-2 cells was approximately 200-fold higher than the estimated intracytoplasmic paromomycin concentration, suggestive of host cell vesicular uptake and concentration (as has been reported with other cell lines) . However, preinfection exposure of Caco-2 cells to paromomycin did not result in subsequent inhibition of parasite development, indicating that if exogenous paromomycin enters the infected host cell vesicular compartment, it does not effectively communicate with the parasite . Thus, the apical membranes overlying the parasite and parasitophorous vacuole may be the unsuspected major route of entry for paromomycin and may be of importance in the design and discovery of novel drug therapies for the otherwise untreatable C . parvum.

FEMS Microbiol Lett, 1998 Jun 15, 163(2), 193 - 202
Engineering the luxCDABE genes from Photorhabdus luminescens to provide a bioluminescent reporter for constitutive and promoter probe plasmids and mini-Tn5 constructs; Winson MK et al.; The luxCDABE operon of Photorhabdus luminescens has been cloned and engineered as an easily mobilisable cassette flanked by sites for commonly used restriction enzymes . Constitutive and promoter probe plasmids utilising the P . luminescens luxCDABE have been constructed using a number of compatible replicons and antibiotic markers . Complementary to these plasmids, a range of promoterless and constitutive luxCDABE mini-Tn5 derivatives has been constructed . The potential of coupling mini-Tn5 luxCDABE promoter probe transposons with automated luminometry and photometry to screen for mutants that exhibit growth phase variation in gene expression is demonstrated.

Arch Virol, 1997, 142(11), 2303 - 8
Infectious pancreatic necrosis virus (IPNV) does not require acid compartments for entry into cells; Espinoza JC et al.; The early events in the infection of unenveloped viruses are still rather unknown and puzzling . However, as in the case of enveloped viruses, the acid pH of endosomes can be important to trigger the virus entry into the cytosol . To test if the infectious pancreatic necrosis virus (IPNV), an unenveloped virus, requires acid endosomal pH to infect cells, we assayed the effect of Bafilomycin A1 on IPNV replication . Concentrations of the antibiotic which inhibited the endosomal acidification of the host cells were unable to affect IPNV replication in CHSE-214 cells; therefore, the acid pH of endosomes seems not to be a mandatory condition for the entry of IPNV into cells.

Eur J Oral Sci, 1998 Jun, 106(3), 721 - 64
Biological factors contributing to failures of osseointegrated oral implants . (II) . Etiopathogenesis; Esposito M et al.; The aim of the present review is to evaluate the English language literature regarding factors associated with the loss of oral implants . An evidence-based format in conjunction, when possible, with a meta-analytic approach is used . The review identifies the following factors to be associated with biological failures of oral implants: medical status of the patient, smoking, bone quality, bone grafting, irradiation therapy, parafunctions, operator experience, degree of surgical trauma, bacterial contamination, lack of preoperative antibiotics, immediate loading, nonsubmerged procedure, number of implants supporting a prosthesis, implant surface characteristics and design . Excessive surgical trauma together with an impaired healing ability, premature loading and infection are likely to be the most common causes of early implant losses . Whereas progressive chronic marginal infection (peri-implantitis) and overload in conjunction with the host characteristics are the major etiological agents causing late failures . Furthermore, it appears that implant surface properties (roughness and type of coating) may influence the failure pattern . Various surface properties may therefore be indicated for different anatomical and host conditions . Finally, the histopathology of implant losses is described and discussed in relation to the clinical findings.

Proc Natl Acad Sci U S A, 1998 Jul 21, 95(15), 8721 - 6
The upf3 protein is a component of the surveillance complex that monitors both translation and mRNA turnover and affects viral propagation; Ruiz-Echevarria MJ et al.; The nonsense-mediated mRNA decay pathway functions to degrade aberrant mRNAs that contain premature translation termination codons . In Saccharomyces cerevisiae, the Upf1, Upf2, and Upf3 proteins have been identified as trans-acting factors involved in this pathway . Recent results have demonstrated that the Upf proteins may also be involved in maintaining the fidelity of several aspects of the translation process . Certain mutations in the UPF1 gene have been shown to affect the efficiency of translation termination at nonsense codons and/or the process of programmed -1 ribosomal frameshifting used by viruses to control their gene expression . Alteration of programmed frameshift efficiencies can affect virus assembly leading to reduced viral titers or elimination of the virus . Here we present evidence that the Upf3 protein also functions to regulate programmed -1 frameshift efficiency . A upf3-Delta strain demonstrates increased sensitivity to the antibiotic paromomycin and increased programmed -1 ribosomal frameshift efficiency resulting in loss of the M1 virus . Based on these observations, we hypothesize that the Upf proteins are part of a surveillance complex that functions to monitor translational fidelity and mRNA turnover.

Mol Cell Biol, 1998 Aug, 18(8), 4463 - 70
Rapamycin induces the G0 program of transcriptional repression in yeast by interfering with the TOR signaling pathway; Zaragoza D et al.; The macrolide antibiotic rapamycin inhibits cellular proliferation by interfering with the highly conserved TOR (for target of rapamycin) signaling pathway . Growth arrest of budding yeast cells treated with rapamycin is followed by the program of molecular events that characterizes entry into G0 (stationary phase), including the induction of polymerase (Pol) II genes typically expressed only in G0 . Normally, progression into G0 is characterized by transcriptional repression of the Pol I and III genes . Here, we show that rapamycin treatment also causes the transcriptional repression of Pol I and III genes . The down-regulation of Pol III transcription is TOR dependent . While it coincides with translational repression by rapamycin, transcriptional repression is due in part to a translation-independent effect that is evident in extracts from a conditional tor2 mutant . Biochemical experiments reveal that RNA Pol III and probably transcription initiation factor TFIIIB are targets of repression by rapamycin . In view of previous evidence that TFIIIB and Pol III are inhibited when protein phosphatase 2A (PP2A) function is impaired, and that PP2A is a component of the TOR pathway, our results suggest that TOR signaling regulates Pol I and Pol III transcription in response to nutrient growth signals.

Klin Khir, 1998, (3), 27 - 8
{Surgical treatment of putrid neck phlegmon}; Desiaterik VI et al.; The experience of treatment of 236 patients with cervical phlegmon, in 7 of whom with putrefactive phlegmon, was summarized . The treatment difficulties are due to rapid infection spreading, the possibility absence of timely laboratory confirmation of diagnosis . Operative intervention was conducted during two hour period of time after the hospitalization moment . An adequate detoxication therapy, hyperbaric oxygenation, antibiotic therapy was conducted to all of the patients, metrogyl was administered without fail . Two patients died because of mediastinitis (1) and the pulmonary artery thromboembolism (1).

Klin Khir, 1998, (3), 3 - 4
{Prevention and treatment of complications after reconstructive surgery on the trachea}; Bagirov MM et al.; The results of treatment of 590 patients are analyzed, to whom the operations on trachea were conducted . In 91 patient 99 complications have occurred, 35 (6.4%) patients died . But due to the operation method refinement, new approaches elaboration, improvement of the measures of tracheoplasty complications prophylaxis and treatment, 2 (1.4%) patients died of 142 operated on during last years.

Spine, 1998 Jul 1, 23(13), 1503 - 5
Late complication after single-rod instrumentation; Hatch RS et al.; STUDY DESIGN: A case report of late complication after single-rod instrumentation . OBJECTIVES: To report a case of symptomatic, perispinal, soft-tissue complication after successful fusion of a scoliotic curve using a unilateral, posterior, multiple hook-rod construct . SUMMARY OF BACKGROUND DATA: Delayed perispinal soft-tissue complications recently have been observed with two-rod, multihook system constructs . The etiology is believed to be low, virulence bacteria causing delayed infection, or metal fretting causing chronic inflammation . This phenomenon has not been linked to single-rod constructs . METHODS: The observation of perispinal soft-tissue inflammation was made during exploratory surgery for progressive pain overlying the rod . The diagnosis was supported by laboratory findings . RESULTS: Complete pain relief was obtained after removal of the hardware and empiric treatment with an oral antibiotic . CONCLUSIONS: Delayed chronic inflammation may occur as a late complication of the use of a unilateral, posterior, multiple hook-rod construct in the spine . This problem can be managed successfully with hardware removal, and, because the etiology of this type of inflammation is unclear, infection with a low virulence organism should be considered.

Leuk Lymphoma, 1998 Jun, 30(1-2), 163 - 74
Prophylactic use of itraconazole for the prevention of invasive pulmonary aspergillosis in high risk neutropenic patients; Lamy T et al.; Invasive pulmonary aspergillosis (IPA) is an increasing cause of morbidity and mortality in patients with hematologic malignancies . A major program of construction work close to our unit prompted us to evaluate the efficacy of itraconazole prophylaxis in preventing IPA in these patients . During September 1994 to December 1995, 77 patients undergoing 96 neutropenic episodes (mean duration, 19.3 days +/- 9.1) received itraconazole as antifungal prophylaxis . All patients were treated in laminar air flow rooms . Itraconazole was administered at a loading dose of 600mg/d, (day 1 to day 3) and 400mg/d on the following days, in 87 instances . In the remaining episodes, the daily dose was 200 or 400mg . Oral doses were adjusted to reach a plasma itraconazole level (PIL) above 1000ng/l . In cases of inadequate PIL or poor oral intake, IV AmphoB was started at a 20 mg daily dose . Five cases of IPA (proven n = 2, probable n = 3) were observed . This represents an incidence of 5.2% of the total number of episodes . One out of 67 (2%) treatment episodes with adequate PIL were associated with IPA as compared to 4 of 29 (14%) episodes with inadequate PIL, (p < 0.02) . AmphoB was added in 28 cases because of low PIL (n = 25), and/or antibiotic-resistant fever persistent pulmonary infiltrate (n = 8) . These results need to be interpreted with caution, because of the absence of randomization or a control group . The efficacy of Itraconazole in neutropenic patients with high risk IPA has to be confirmed on larger and prospective studies.

Can J Anaesth, 1998 Jun, 45(6), 568 - 70
Deafness and prolonged neuromuscular blockade following single-dose peritoneal neomycin irrigation; Gilbert TB et al.; PURPOSE: A case of deafness is reported in a patient undergoing bilateral nephrectomy after single irrigation of the peritoneal cavity with a neomycin containing solution for surgical prophylaxis . CLINICAL FEATURES: In this patient, profound, late-postoperative deafness was heralded by prolonged neuromuscular blockade and respiratory insufficiency . Additional risk factors for ototoxicity in this particular patient included the presence of end-stage renal disease requiring daily peritoneal dialysis and, possibly, the concomitant use of clonazepam and clindamycin . CONCLUSIONS: Antibiotic irrigation solutions containing neomycin may produce unwanted adverse systemic effects of deafness and prolonged neuromuscular blockade, even with only brief application within the peritoneal cavity . Concurrent end-stage renal disease, visceral inflammation from chronic dialysis and laparotomy, and the concomitant use of other medications may have contributed to these unwanted effects.

Pediatr Res, 1998 Jul, 44(1), 20 - 6
Enteric defensin expression in necrotizing enterocolitis; Salzman NH et al.; Immaturity of local innate defenses has been suggested as a factor involved in the pathophysiology of necrotizing enterocolitis (NEC) . The mRNA of enteric human defensins 5 (HD5) and 6 (HD6), antibiotic peptides expressed in Paneth cells of the small intestine, have significantly lower levels of expression in fetal life compared with the term newborn and adult . In the current study, intracellular HD5 was demonstrated by immunohistochemistry at 24 wk of gestation, but at low levels, consistent with findings at the mRNA level . These data suggest that the low level enteric defensin expression, characteristic of normal intestinal development, may contribute to the immaturity of local defense, which predisposes the premature infant to NEC . To test if levels of defensin expression are altered in NEC, specimens from six cases of patients with NEC and five control subjects (four patients with atresia and one with meconium ileus) were analyzed to determine HD5 and HD6 mRNA levels by in situ hybridization . Compared with the control group, the level of enteric defensin expression per Paneth cell assessed by image analysis was increased 3-fold in cases of NEC (p = 0.02, analysis of variance and covariance) . In addition, the number of Paneth cells was increased 2-fold in the small intestinal crypts of NEC specimens compared with those of control subjects (p < 0.01, covariance analysis) . In healthy tissue, peptide levels within Paneth cells paralleled mRNA levels through development . In tissue from infants with NEC, the steady state level of intracellular peptide was not increased in conjunction with the observed rise in defensin mRNA . A straightforward interpretation of this finding is that HD5 is actively secreted in this setting and the Paneth cells maintain a constant steady state level of intracellular peptide, but the possibility of translational regulation of peptide expression is also consistent with these data . The associations between NEC and enteric defensin expression reported here offer support for future studies to address the role of these endogenous host defense factors in the pathophysiology of this disease.

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