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Biomedical subjects

M Weber

Publications and source records attributed to M Weber.

At least 253 records · Page 14Linked to original sources

Acute bacterial meningitis in The Gambia: a four-year review of paediatric hospital admissions.

Over a 4 year period, 1991 to 1994, 420 patients with acute bacterial meningitis were admitted to a tertiary urban hospital in The Gambia. Organisms were isolated from the cerebrospinal fluid in 64 per cent of cases. In the neonatal period Streptococcus pneumoniae was the single most common organism isolated. Amongst infants and children the two major pathogens were Haemophilus influenzae and S. pneumoniae. In the first year of life, children with S. pneumoniae meningitis were younger than those with H. influenzae infection (median age 3 months versus 6 months, p < 0.00003) and they had a higher case fatality rate (37 per cent versus 17 per cent, p = 0.002). In view of the high case fatality rate, there is a need to review overall case management. This will include a review of more effective antibiotics, the possible role of dexamethasone, and the inclusion of efficacious vaccines against H. influenzae and S. pneumoniae disease.

Acute Disease↗

Inhibition of tumor necrosis factor-alpha release in rat experimental endotoxemia by treatment with the 21-aminosteroid U-74389G.

OBJECTIVE: To determine the effect of the 21-aminosteroid U-74389G on tumor necrosis factor (TNF)-alpha release in experimental endotoxemia. DESIGN: Prospective, randomized, controlled animal study. SETTING: Experimental laboratory. SUBJECTS: Twenty-one male Wistar rats weighing 190+/-40 g. INTERVENTIONS: The rats were divided equally into 3 groups: a) control; b) endotoxemia (5 mg/kg lipopolysaccharide [LPS] from Escherichia coli 055:B5); and c) endotoxemia and U-74389G administration 30 mins before (3 mg/kg) and 60 mins after (1.5 mg/kg) endotoxin challenge. MEASUREMENTS AND MAIN RESULTS: At 0, 120, and 240 mins, serum levels of TNF-alpha were measured using a specific rat TNF-alpha ELISA kit. U-74389G-treated endotoxemic animals showed significantly reduced TNF-alpha release 120 mins after endotoxin challenge (control, 2.5+/-2.1 pg/mL; LPS, 4041+/-871 pg/mL; U-74389G, 1627+/-474 pg/mL [p < .05]). Two hundred forty minutes after LPS administration, TNF-alpha levels decreased, whereas values in the untreated LPS group remained twice as high as those in the U-74389G group (LPS, 863+/-182 pg/mL; U-74389G, 369+/-54 pg/mL [p < .05]). CONCLUSIONS: The study demonstrated that administration of U-74389G, which has radical-scavenging and membrane-stabilizing properties, decreased TNF-alpha release during endotoxemia. Thus, 21-aminosteroids may lend themselves to evaluation in the treatment of septic states.

Analysis of Variance↗

Etiology of serious infections in young Gambian infants.

BACKGROUND: Despite improvements in infant mortality rates in many developing countries including The Gambia, neonatal mortality remains high and many neonatal deaths are caused by infection. The study described in this paper was conducted to determine the bacterial and viral etiology of serious infections in Gambian infants younger than 91 days old. METHODS: At a first level health facility 497 infants with symptoms that could indicate serious infection were enrolled, of whom 239 with 1 or more signs of serious infection and 55 with no signs were investigated, yielding 17 cases with positive bacterial cultures of blood and/or cerebrospinal fluid. At a nearby pediatric referral hospital 198 infants were seen and 182 were investigated, yielding 35 positive bacterial cultures. RESULTS: There were 15 culture positive cases of meningitis caused by Streptococcus pneumoniae (7), Streptococcus pyogenes (2), Enterobacter cloacae (2), Escherichia coli (1), Haemophilus influenzae type b (1), Streptococcus agalactiae (1) and Salmonella spp. (1). Six of these children died. Thirty-three infants without meningitis had positive blood cultures for Staphylococcus aureus (17), S. pneumoniae (3), Salmonella spp. (5), E. coli (3), other enterobacteria (4) and S. agalactiae (1), of whom 14 died. Nasopharyngeal aspirates from 438 children were investigated for common respiratory viruses. Respiratory syncytial virus was found in 51, influenza A in 46, influenza B in 22, parainfluenza in 26 and adenovirus in 16. Respiratory syncytial virus and influenza A isolates were found most frequently toward the end of the wet season. Nasopharyngeal carriage of S. pneumoniae and H. influenzae was studied in 320 infants recruited during the first year. Of these 184 (58%) were positive for S. pneumoniae and 141 (44%) were positive for H. influenzae, 18 of which were type b. Infants with a bacterial isolate from blood or cerebrospinal fluid were more likely than the rest to die, whereas those with a viral isolate were less likely to die. CONCLUSIONS: The most important causes of serious infections in young Gambian infants are Staphylococcus aureus, S. pneumoniae and Salmonella spp.

Bacteria↗

Efficacy and safety of the initial use of stability and onset criteria in implantable cardioverter defibrillators.

INTRODUCTION: Inappropriate therapies are the most frequent adverse event in patients with implantable cardioverter defibrillators (ICDs). Most ICDs offer a stability criterion to discriminate ventricular tachycardia (VT) from atrial fibrillation and an onset criterion to discriminate VT from sinus tachycardia. The efficacy and safety of these criteria, if used immediately after implantation, is unknown. METHODS AND RESULTS: In a case control study, 87 patients in whom stability and onset criteria had been activated immediately after ICD implantation were matched to 87 patients in whom these criteria had not been activated. The groups were matched for known predictors of inappropriate therapies. With stability and onset criteria off, 24 patients (28%) received inappropriate therapies due to atrial fibrillation (n = 14) or sinus tachycardia (n = 11); with stability and onset on, only 11 patients (13%) were treated by the ICD due to atrial fibrillation (n = 5) or sinus tachycardia (n = 7) (log rank: P = 0.029). Five patients suffered inappropriate therapies despite the fact that onset (n = 4) or stability (n = 1) criteria were not fulfilled once tachycardias continued for a prespecified duration. Only one patient experienced a failure to detect VT due to the onset criterion; none because of stability. CONCLUSION: The immediate use of stability and onset criteria after ICD implantation reduces inappropriate therapies due to atrial fibrillation and sinus tachycardia. Because of the potential for underdetection of VT, this approach should be limited to tachycardia rates hemodynamically tolerated by the patient.

Atrial Fibrillation↗

Gastric penetration of amoxicillin in a human Helicobacter pylori-infected xenograft model.

The delivery of antibiotics into Helicobacter pylori-infected human stomachs is still poorly understood. Human embryonic gastric xenografts in nude mice have recently been proposed as a new model for the study of H. pylori infection. Using this model, we compared the penetration of amoxicillin, after intraperitoneal administration of a dose of 20 mg/kg of body weight, into the gastric mucosae of infected and uninfected xenografts. The concentrations of this drug in serum and superficial gastric mucosae were determined at 20 min and 1 and 3 h after injection. Ten mice with H. pylori-infected grafts (n = 5) or uninfected grafts (n = 5) were studied. Mucosal samples were obtained by cryomicrotomy. The concentrations in serum were similar to those obtained in the serum of humans after oral administration of 1 g of amoxicillin. The mean area under the tissue concentration-versus-time curve from 0 to 3 h obtained for mice with infected grafts was significantly higher than that obtained for the animals with uninfected grafts (P = 0.01). These results suggest that the penetration of amoxicillin into the superficial gastric mucosa may be substantially increased in the case of H. pylori infection. Thus, human xenografts in nude mice represent a new, well-standardized model for investigation of systemic delivery of drugs into H. pylori-infected gastric mucosa.

Amoxicillin↗

Effect of methodology on the tuberculocidal activity of a glutaraldehyde-based disinfectant.

Although official guidelines recommend a plate counting method for testing the susceptibility of mycobacteria to disinfectants, manufacturers usually prefer to employ the BACTEC procedure. Data showing that the BACTEC method overestimates the activity of a glutaraldehyde-based disinfectant against Mycobacterium tuberculosis in comparison with a conventional plate counting procedure are presented.

Bacteriological Techniques↗

Human embryonic gastric xenografts in nude mice: a new model of Helicobacter pylori infection.

In vitro or animal models have been used to investigate the pathogenesis of Helicobacter pylori infection. However, extrapolation to humans of results obtained with these heterologous models remains difficult. We have developed a new model for the study of H. pylori infection that uses human entire embryonic stomachs engrafted in nude mice. At 80 days after implantation, 22 of these xenografts, which exhibited a mature gastric epithelium, were inoculated with 10(7) to 10(8) CFU of either H. pylori LB1, a freshly isolated H. pylori strain (n = 12), or H. pylori ATCC 49503 (n = 10). After 12-week examination, H. pylori LB1 persistently colonized the antrum of all inoculated grafts, as assessed by culture (mucus and mucosa), immunohistochemistry (mucosa), and a rapid urease test (mucus). H. pylori ATCC 49503, either before or after in vivo passage, permitted only a transient 2-week colonization in one of the five inoculated grafts in both groups. Colonization was always associated with an increase of gastric juice pH. A mild neutrophil infiltration of the gastric mucosa was noted solely in infected grafts. Transmission electron microscopy showed adherence of H. pylori organisms to epithelial cell surface. In six animals, intracytoplasmic location of this bacterium was observed in the antrum or the fundus. These results allow us to propose this model as a new ex vivo model for the study of specific H. pylori-gastric cell interactions.

Animals↗

Value of enterobacterial repetitive intergenic consensus PCR for study of Pasteurella multocida strains isolated from mouths of dogs.

Fifty-six Pasteurella multocida strains (40 P. multocida subsp. septica and 16 P. multocida subsp. multocida strains) isolated from the mouths of 56 dogs among the 134 living in a French canine military training center (132e Groupe Cynophile de l'Armée de Terre, Suippes, France) were studied by use of enterobacterial repetitive intergenic consensus-PCR (ERIC-PCR) and restriction fragment length polymorphism (RFLP) techniques. Both techniques showed genomic heterogeneity of the strains studied. However, RFLP was more discriminatory than ERIC-PCR for differentiating P. multocida strains. All but three pairs of strains were discriminated by RFLP, suggesting a limited circulation of strains between these dogs living in proximity. Although ERIC-PCR is easier and faster to perform, it cannot be recommended for epidemiological studies of P. multocida strains.

Animals↗

Clinical efficacy of eprosartan.

Eprosartan is a new, structurally distinct, nonbiphenyl, nontetrazole, nonpeptide, orally active angiotensin II receptor antagonist that is highly selective for the AT1 receptor. In placebo-controlled trials, it led to a dose-related antihypertensive response, clinically significant reductions in blood pressure and full 24-hour blood pressure control with once/day administration of 600 mg. Eprosartan provides clinically significant reductions in blood pressure in patients with mild to severe hypertension regardless of age, gender, and race. The antihypertensive effect of eprosartan is comparable with those of other antihypertensive agents. Whereas a relationship exists between dosage and antihypertensive effect, there is no such relationship between dosage and adverse events, the frequency of which is comparable with that with placebo.

Acrylates↗

Treatment of amyotrophic lateral sclerosis.

Survival of patients with amyotrophic lateral sclerosis (ALS) is improving. Timely and more frequent implementation of bimodal passive airway pressure (BIPAP) and percutaneous endoscopically placed gastrostomy (PEG) may be the major factors impacting on longer survival. However, several drugs recently subjected to rigorous clinical trials have demonstrated significant results or encouraging trends. ALS is a complex disease in which aging neurons are subjected to a variety of susceptibility genes, most of which remain to be discovered, that interact with equally unrecognised environmental factors. This makes it unlikely that a single therapeutic agent will be of value. The thrust must be on polypharmacy. The 'cocktail' that will eventually be of greatest benefit has yet to be formulated. It might contain glutamate N-methyl-D-aspartate (NMDA) and non-NMDA receptor antagonists, antioxidants or a combination of trophic factors and neuroprotective agents. This statement is made with the understanding that the aetiopathogenesis of ALS is far from clear. Drug delivery is a problem and better delivery systems are needed. The efficacy of some of the medications that presently only induce modest benefit may be improved by liposomal packaging, use of a patch or inhalation delivery or intraventricular pump reservoirs. There is a great need to develop an early marker of ALS and sensitive reproducible measures of disease progression. This will curtail the present need for large, lengthy and very expensive clinical trials. The new millennium will see the advent of targeted therapy using viral vectors which can deliver replacement genes, trophic factors and other drugs to degenerating neurons; transplantation of neural progenitor cells which can become mature functioning neurons; anti-apoptotic agents which will allow neurons to survive longer; and mechanisms that can protect the telomerase maintenance system which is so crucial in the immortalisation of cells.

Amyotrophic Lateral Sclerosis↗

Total hip arthroplasty in patients with cerebral palsy.

The records of 16 patients (16 hips) with cerebral palsy who underwent total hip arthroplasty were reviewed. There were no dislocations, and other complications were rare. Pain relief was good to excellent in 87%. Function, as assessed by ambulatory status, was improved in 79%. Reasonable longevity of the implants can be expected even in patients <50 years. Total hip arthroplasty is a valuable option for the cerebral palsy patient with incapacitating hip pain.

Adult↗

[Leg ulcers. Allergologic studies of 359 cases].

INTRODUCTION: Leg ulcers are a common disease in dermatology. Their social and economic implications are important, especially when contact dermatitis complicates these wounds. PATIENTS AND METHODS: In this study a total of 359 patients had contact dermatitis investigations over a period of 5 years. Patch-tests were performed on 116 men and 243 women hospitalized with venous and/or arterial leg ulcers, with or without clinical appearance of periulcerous contact dermatitis. Standard patch-tests of the ICDRG (International Contact Dermatitis Research Group) were systematically performed as well as a specific series of 40 tests. RESULTS AND DISCUSSION: Positive patch tests were observed in 82.5 p. 100 of the patients, indicating a very high rate of contact allergy in patients with leg ulcers. Peru balsam, lanolin and neomycin were the most frequent culprits of positive patch-tests in this population. Five percent of patch-tests with eosin were positive in our study. This is not common in the literature. Moreover, we highlight the high rate of contact sensitization to corticosteroids in this population. According to these results and to the literature, a new series of patch-tests for leg ulcers is suggested. CONCLUSION: Polysensitization in patients with chronic wounds is very frequent. A series of patch-tests in leg ulcers may lead to some interesting conclusions but a good questioning of the patient is always necessary to complete this series.

Adult↗

[Cerebral ischemic accidents in young subjects. A prospective study of 296 patients aged 16 to 45 years].

From 1990 to 1997, June, 296 patients (156 males and 140 females), aged 16 to 45 years, admitted in the Neurology Department of the University Hospital of Nancy (F) for ischemic stroke, were prospectively evaluated according to a standardized analysis of anamnestic and clinical data, angiography (90 p. 100 of cases), TEE (78 p. 100), hemostasis. Women were younger (mean age = 34.82 y) than men (36.87 y; p = 0.003), with a peak in the 4th decade. Clinical event was a TIA in 14.2 p. 100, a stroke in 51.7 p. 100; it concerned the anterior circulation in 64.5 p. 100, posterior circulation in 25 p. 100, multiple territories in 10.5 p. 100. History of TIA, cervical-cranial pain or Horner syndrome suggestive of dissection, pregnancy or post-partum were found respectively in 60 (20.3 p. 100), 34 (11.1 p. 100) and 13 (9.3 p. 100) cases. Risk factors concerned 87.2 p. 100 of patients, mainly smoking (55.1 p. 100), oral contraceptive (53 p. 100), hyperlipemia (35 p. 100), and were more frequent in case of atheroma and lacunar stroke (p < 0.0000). Etiology, according to TOAST classification, was: atheroma (8.4 p. 100), cardioembolism (8.7 p. 100), small-artery disease (7.1 p. 100), dissection (15.5 p. 100), other determined causes (11.1 p. 100), multiple causes (5.7 p. 100), undetermined cause (34.8 p. 100). Septal pathology was found 34 times. Patients whose stroke remained unexplained were younger (33.7 y vs 37.7, p = 0.002), had less risk factors (p < 0.0000), had more TIA (p = 0.005), more often in the carotid territory (p = 0.008), had a better prognosis (p = 0.01), and showed more often emboli at angiography (p = 0.001). During a mean follow-up of 33 months (median = 19), 21 recurrent strokes occurred and 6 patients died. 134 (46 p. 100) patients had no sequelae, 101 (34.7 p. 100) minor disability, 42 (14.4 p. 100) major sequelae. These results, compared to the main studies of the literature, suggest the interest of common definition criteria and classification of etiologies. In practice, hierarchisation of investigations may be proposed, and vascular risk factors should be tracked in young patients. In patients whose stroke remains unexplained, further studies, as atrial vulnerability, are needed.

Adolescent↗

Classification of an intermediate group of patients with antiphospholipid syndrome and lupus-like disease: primary or secondary antiphospholipid syndrome?

OBJECTIVE: (1) To classify an intermediate group of patients (IntAPS) with antiphospholipid syndrome (APS) and lupus-like disease either as primary (PAPS) or secondary APS (SAPS) and to discuss 2 different classifications. (2) To compare patients of a division of rheumatology with either PAPS or SAPS. METHODS: Patients with APS and patients with systemic lupus erythematosus (SLE) followed at the Department of Rheumatology, University Hospital Bichat, Paris, from 1987 to 1996 were analyzed. A chart review and a standardized telephone interview in 1997 completed the data of this study. RESULTS: (1) We found a total of 108 patients with APS: 22 with PAPS, 69 with SAPS, and 17 with IntAPS. The group of IntAPS did not differ from PAPS in any clinical or laboratory signs with the exception of antibodies to dsDNA and to extractable nuclear antigen (ENA). Between IntAPS and SAPS, there were several significant differences in clinical signs of SLE (malar rash, discoid rash, arthralgia) and in laboratory values (leukocytopenia). (2) Comparison of PAPS and SAPS showed statistically significant differences for positive Coombs' test, leukocytopenia, lymphocytopenia, antinuclear antibodies, antibodies to dsDNA and to ENA, and hypocomplementemia. CONCLUSION: The mainstay of the diagnosis of APS is the clinical event of thrombosis or miscarriage in the presence of antiphospholipid antibodies. Less important are laboratory values, which may help to differentiate PAPS from SAPS in order to initiate adequate therapy (e.g., anticoagulation in the first and additional corticosteroids in the second). Patients with IntAPS are more likely to be integrated into the group of PAPS than in the group of SAPS; therefore, special exclusion criteria for PAPS are not appropriate.

Adult↗