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Biomedical subjects

M Weber

Publications and source records attributed to M Weber.

At least 235 records · Page 13Linked to original sources
PubMed1999

Clinical predictors of hypoxaemia in Gambian children with acute lower respiratory tract infection: prospective cohort study.

OBJECTIVES: To determine clinical correlates and outcome of hypoxaemia in children admitted to hospital with an acute lower respiratory tract infection. DESIGN: Prospective cohort study. SETTING: Paediatric wards of the Royal Victoria Hospital and the hospital of the Medical Research Council's hospital in Banjul, the Gambia. SUBJECTS: 1072 of 42 848 children, aged 2 to 33 months, who were enrolled in a randomised trial of a Haemophilus influenzae type b vaccine in the western region of the Gambia, and who were admitted with an acute lower respiratory tract infection to two of three hospitals. MAIN OUTCOME MEASURES: Prevalence of hypoxaemia, defined as an arterial oxygen saturation <90% recorded by pulse oximetry, and the relation between hypoxaemia and aetiological agents. RESULTS: 1072 children aged 2-33 months were enrolled. Sixty three (5.9%) had an arterial oxygen saturation <90%. A logistic regression model showed that cyanosis, a rapid respiratory rate, grunting, head nodding, an absence of a history of fever, and no spontaneous movement during examination were the best independent predictors of hypoxaemia. The presence of an inability to cry, head nodding, or a respiratory rate >/= 90 breaths/min formed the best predictors of hypoxaemia (sensitivity 70%, specificity 79%). Hypoxaemic children were five times more likely to die than non-hypoxaemic children. The presence of malaria parasitaemia had no effect on the prevalence of hypoxaemia or on its association with respiratory rate. CONCLUSION: In children with an acute lower respiratory tract infection, simple physical signs that require minimal expertise to recognise can be used to determine oxygen therapy and to aid in screening for referral. The association between hypoxaemia and death highlights the need for early recognition of the condition and the potential benefit of treatment.

Acute Disease↗
PubMed1999

Assessment of upper and lower motor neurons in Kennedy's disease: implications for corticomotoneuronal PSTH studies.

We used peristimulus time histograms (PSTHs) to estimate characteristics of the composite excitatory postsynaptic potentials (EPSPs) generated at the anterior horn cell by a descending cortical volley induced by subthreshold transcranial magnetic stimuli in 11 normal subjects, 9 patients with DNA-confirmed Kennedy's disease, and 10 patients with amyotrophic lateral sclerosis (ALS). In Kennedy's disease the mean of the estimated EPSP amplitude (3.5 +/- 1.6 mV), as well as the means of duration (4.1 +/- 1.3 ms) and onset latency (20.4 +/- 2.7 ms) of the primary peak of 35 different motor units were not significantly different from normal subjects, in whom corresponding values of 49 motor units measured 2.9 +/- 1.6 mV (EPSP amplitude), 3.5 +/- 1.4 ms (duration) and 19.3 +/- 2.8 ms (onset latency). In 48 motor units of patients with ALS the mean of the estimated EPSP amplitude, duration, and latency measured 2.7 +/- 1.8 mV, 7.8 +/- 5.7 ms, and 24.0 +/- 6.5 ms, respectively, differing significantly from normal subjects and patients with Kennedy's disease. The normal cortically induced EPSP in Kennedy's disease is very different from the range of EPSP abnormalities in ALS, indicating that lower motor neuron disease per se does not result in an abnormal cortically induced EPSP derived from PSTHs. The normal findings in Kennedy's disease support our previous suggestions that the EPSP abnormalities in ALS are supraspinal in origin.

Adult↗
PubMed1999

Frequent enrichment for CD8 T cells reactive against common herpes viruses in chronic inflammatory lesions: towards a reassessment of the physiopathological significance of T cell clonal expansions found in autoimmune inflammatory processes.

We recently evidenced a dramatic enrichment for T cells reactive against Epstein-Barr virus (EBV) within inflamed joints of two rheumatoid arthritis patients. To assess the generality of this phenomenon and its relevance to autoimmunity, we studied the responses of CD8 T cells from patients with either acute or chronic inflammatory diseases (rheumatoid arthritis: n = 18, ankylosing spondylitis: n = 5, psoriatic arthritis: n = 4, Reiter's syndrome: n = 3, arthrosis: n = 2, uveitis: n = 2, multiple sclerosis: n = 2, encephalitis: n = 1) against viral proteins derived from EBV and another common herpes virus, human cytomegalovirus (CMV). T cell responses against EBV and/or CMV epitopes were frequently observed within CD8 T cells derived from chronic inflammatory lesions, irrespective of their location (knee, eye, brain) and autoimmune features. In most cases, CD8 T cells derived from affected organs yielded stronger anti-viral T cell responses than CD8 T cells derived from patients' PBL, even in chronic inflammatory diseases devoid of autoimmune features or induced by defined bacterial agents. Taken together, these results suggest that the presence of virus-specific T cells within inflamed lesions of patients suffering from autoimmune diseases is a general phenomenon associated with chronic inflammation rather than the initiating cause of the autoimmune process. Since this phenomenon was sometimes associated with long-term T repertoire biases within inflamed lesions, the physiopathological significance of T cell clonal expansions found in a recurrent fashion within chronically inflamed autoimmune lesions should be interpreted with caution.

Adult↗
PubMed1999

[Focus debridement of chronic sequestered talus osteomyelitis by TCNC arthrodesis. A new technique with ring fixateur].

A technique utilizing the Ilizarov ring fixator to stabilize a tibio-calcaneo-naviculo-cuboideal arthrodesis following talus resection is introduced. The advantages of this method will be demonstrated with the help of a case history. The described method permits early weight bearing, while supplying stability and compression of the fusion, thereby avoiding further loss of bone stock, while reducing the risk of thromboembolic complications. The Ilizarov ring fixator construction allows for the combination of the fusion with the correction of a preexisting or ensueing leg length discrepancy.

Adolescent↗
PubMed1999

Laparoscopic gastro- and hepaticojejunostomy for palliation of pancreatic cancer: a case controlled study.

BACKGROUND: Most patients presenting with pancreatic cancer are irresectable at the time the diagnosis is made. Therefore, they are in need of palliative treatment that can guarantee minimal morbidity, mortality, and hospital stay. To address this need, we designed a study to test the feasibility of laparoscopic gastroenterostomy and hepaticojejunostomy and to compare their results with those achieved with open techniques. METHODS: We performed a case control study of a new concept in laparoscopic palliation based on the findings of preoperative imaging and diagnostic laparoscopy. Laparoscopic side-to-side gastroenterostomy and end-to-side hepaticojejunostomy (Roux-en-Y) were done in irresectable cases. Of 14 patients who underwent laparoscopic palliation, three had a laparoscopic double bypass, seven had a gastroenterostomy, and four underwent staging laparoscopy only. The results were compared with a population of 14 matched patients who had conventional palliative procedures. RESULTS: Postoperative morbidity was 7% vs 43% for laparoscopic and open palliation, respectively (p < 0.05). There were no mortalities in the laparoscopic group, as compared to 29% in the group who had open bypass surgery (p < 0.05). Postoperative hospital stay averaged 9 days in the laparoscopic group and 21 days in the open group (p < 0.06). Operating time tended to be shorter in the laparoscopic group (p < 0.25). Morphine derivatives were necessary for a significantly shorter period after laparoscopic surgery (p < 0.03). CONCLUSIONS: Our preliminary experience strongly suggests that laparoscopic palliation can reduce the three major drawbacks of open bypass surgery-i.e., high morbidity, high mortality, and long hospital stay.

Adult↗
PubMed1999

Spondylodiscitis caused by viridans streptococci: three cases and a review of the literature.

Three cases of spondylodiscitis caused by viridans streptococci were observed within the course of 1 month. Although streptococci have been reported as the third most frequent cause of spondylodiscitis after staphylococci and gram-negative bacteria, alpha-haemolytic streptococci are rarely seen. The three patients presented with symptoms of low back pain; they felt well and did not have a fever or chills. Laboratory examinations revealed inflammation. Further examinations such as scintigraphy, computed tomography or magnetic resonance imaging were done. Bacteriological diagnosis was established by blood cultures in two cases and by needle biopsy of the disco-vertebral space in one. In one patient endocarditis was also documented. Because the prevalence of endocarditis was found to be higher in our cases of spondylodiscitis due to Streptococcus viridans than for other bacteria, the exclusion of this diagnosis must be pursued aggressively. These observations lead us to question if the spectrum of bacteria causing spondylodiscitis is undergoing a change. an aetiological agent could be isolated in 1168 patients (85.4%): in 48% a staphylococcus, in 28% a gram-negative bacterium and in only 10% a streptococcus. There were two cases of viridans streptococci (0.2%). These two cases together with other single case reports [14-22] account for 15 cases of spondylodiscitis due to alpha-haemolytic streptococci. Differentiation of the organisms to the species level was accomplished in six cases: S. mitis (3), S. sanguis (2) and S. anginosus (1). Although a multitude of organisms, bacterial as well as fungal, causing spondylodiscitis has been reported in recent years, almost all were single cases [23-42]. The unusual observation of three cases of spondylodiscitis due to alpha-haemolytic streptococci within 1 month prompted us to review the clinical and laboratory findings and to compare these cases with those caused by Staphylococcus aureus.

Adult↗
PubMed1999

Efficacy and tolerability of tasosartan, a novel angiotensin II receptor blocker: results from a 10-week, double-blind, placebo-controlled, dose-titration study. Tasosartan Investigators Group.

BACKGROUND: Angiotensin II receptor antagonists are selective blockers of the renin-angiotensin system and represent an alternative to angiotensin-converting enzyme inhibitors in the treatment of hypertension. Tasosartan is a newly developed nonpeptide AT1 receptor blocker. METHODS AND RESULTS: In this double-blind, randomized, dose-titration, multicenter trial, tasosartan and placebo were compared in patients with stage I and stage II hypertension. A prequalification washout period (antihypertensive medications withdrawn) and a 2-week qualification period (patients received single-blind placebo) preceded a 10-week, double-blind treatment period. The patients received either 50 mg tasosartan (n = 132) or placebo (n = 130) once per day and were evaluated once per week. The dose of tasosartan was increased at 3-week intervals to 100 mg and then to 200 mg if the mean sitting diastolic blood pressure (SiDBP) exceeded 90 mm Hg. Compared with placebo, tasosartan produced significantly (P <.05) greater reductions in both SiDBP (-9.4 +/- 0.7 vs -2.0 +/- 0.7 mm Hg) and sitting systolic blood pressure (SBP) (-12.2 +/- 1.2 vs +0.4 +/- 1.2 mm Hg). The rate of response (SiDBP </=90 mm Hg or a decrease from baseline of >/=10 mm Hg) was significantly (P <.05) greater in the tasosartan group than in the placebo group (55% vs 19%). The mean 24-hour blood pressure reduction with tasosartan was -12.6 +/- 0. 9/-8.1 +/- 0.6, significantly greater (P <.05) than the reduction with placebo (+0.6 +/- 0.9/+0.5 +/- 0.6 mm Hg). The trough-to-peak ratio (determined from the ambulatory data) was 0.66 for DBP and 0. 72 for SBP for the tasosartan treatment group, demonstrating 24-hour efficacy with once-a-day administration. The safety profile of tasosartan was similar to placebo. CONCLUSIONS: These results demonstrate that tasosartan at 50 to 200 mg given once a day over a titration period of 10 weeks was effective and safe in the treatment of essential hypertension.

Adult↗
PubMed1999

Antibacterial activity of Aristolochia paucinervis Pomel.

Several fractions of the methanolic extract of the rhizome or the leaves of Aristolochia paucinervis Pomel were screened for antibacterial activity using the agar dilution method against fourteen reference bacterial strains. Only three fractions (defatted chloroformic rhizome fraction: APRC, rhizome ethyl acetate fraction: APRE and leaf chloroform fraction: APLC) showed an activity against at least one of the microorganisms tested. The minimum inhibitory concentration (MIC) determination showed that APRC was the most active against Clostridium perfringens, Clostridium difficile, Enterococcus faecalis, Micrococcus luteus and Bacillus subtilis. The high bacteriostatic activity of APRC was confirmed by its MIC determination against clinical strains of C. perfringens (n = 32), C. difficile (n = 31), and E. faecalis (n = 22). Results of this study suggest the potential interest of this highly active fraction and support the use of A. paucinervis Pomel in Moroccan traditional medicine to treat skin and soft-tissue infections, especially gas gangrene and intestinal diseases.

Anti-Bacterial Agents↗
PubMed1999

Documentation of severe pain, opioid doses, and opioid-related side effects in outpatients with cancer: a retrospective study.

Pain severity, prescribed opioids including "rescue" medication for breakthrough pain, bowel movements, and laxative prescription were evaluated in 54 cancer patients treated in an outpatient department devoted to hematology and oncology during 1996. Median number of visits per patient was 5.5 (range 1-48), and median duration of patient care during opioid therapy was 44.5 days (range 1-363). Pain severity and opioid dose were not documented, or documented in less than 25% of visits, in 62.9% and 48.2%, respectively. Rescue doses for breakthrough pain, laxative prescription and bowel movements were never mentioned in 70.4%, 68.5%, and 87% respectively, of all patient charts. Only 3 of 12 physicians documented pain severity in more than 15% of visits, and opioid dose was recorded in more than 30% of all visits only by four physicians. Rescue doses for breakthrough pain, laxative prescription, and bowel movements were never or only scarcely documented by all physicians. Pain measurement using a visual analog scale was recorded by one physician. Our data show inadequate documentation of important aspects of cancer pain in a large outpatient department of hematology and oncology. These deficiencies may have a major negative impact on the quality of cancer pain treatment.

Adult↗
PubMed1999

Emerging treatments for hypertension: potential role for vasopeptidase inhibition.

Hypertension remains uncontrolled worldwide despite the availability of several classes of antihypertensive agents. There is an increased risk of serious cardiovascular, cerebrovascular, and renal events if the disease goes untreated or is poorly treated. Thus, the high incidence of hypertension coupled with its poor control make it imperative that more effective and well-tolerated treatments that exhibit target-organ protection be developed. Vasopeptidase inhibitors are a new class of cardiovascular agents that simultaneously inhibit neutral endopeptidase and angiotensin converting enzyme. They enhance peptides with vasodilatory and possibly organ-protective properties and also inhibit the production of the vasoconstrictor angiotensin II. In preclinical studies, omapatrilat has shown blood pressure-lowering effects independent of renin status and has increased survival in an animal model of congestive heart failure. Human studies with omapatrilat, the most clinically advanced vasopeptidase inhibitor, administered orally once daily have demonstrated powerful dose-dependent reduction of systolic and diastolic blood pressures, regardless of age, race, or gender. Omapatrilat is particularly effective in lowering systolic blood pressure; this article summarizes data from recent clinical trials. This drug is well tolerated, with adverse effects comparable to those of currently available antihypertensive agents. Omapatrilat and other vasopeptidase inhibitors have potential applications in the treatment of hypertension, heart failure, and other cardiac and vascular disorders.

Angiotensin II↗
PubMed1999

A 1-year study of antibiotic resistance among paediatric pneumococcal isolates in 1995 from four regions of France.

The main object of this study was to describe the features of antibiotic resistance in pneumococci from children in four regions of France in 1995. Despite the high prevalence (40%) of pneumococci with diminished susceptibilty to penicillin (PDSP), resistance to amoxycillin (0.8%) and cefotaxime (0.4%) was rare; 16% of pneumococci were resistant to penicillin G (PRP, MIC > 1 mg/l). PDSP showed the expected resistance to macrolides (67%) and cotrimoxazole (57%) and were predominantly serotypes 23F, 14, 9 and 6. This study by the Regional Pneumococcal Observatories confirms the high prevalence and the main characteristics of antibiotic resistance among pneumococci isolated from children. Nevertheless, the resistance to all antibiotics was lower than that found in French multicentre, nationwide surveys, possibly because of differences in the mode of strain collection and geographic origin.

Adolescent↗
PubMed1999

Molecular epidemiology of respiratory syncytial virus in The Gambia.

Respiratory syncytial virus (RSV) infection in The Gambia occurs seasonally in association with the rainy season. This study examined the genetic variability of RSV isolates from four consecutive epidemics from 1993-6. Each epidemic was made up of a number of variants which were replaced in subsequent epidemics. Analysis of attachment (G) protein gene sequences showed that isolates were closely related to those observed in the rest of the world. However, many isolates from 1993 and 1994 were unlike other isolates observed in the developed world during this period and were more similar to isolates from 1984 in Europe. In addition, the most commonly observed genotype in the UK in the 1990s was not detected in The Gambia during this period.

Amino Acid Sequence↗
PubMed1999

Activated polyamidoamine dendrimers, a non-viral vector for gene transfer to the corneal endothelium.

We investigated the efficiency of activated polyamidoamine dendrimers, a new class of nonviral vectors, to transfect rabbit and human corneas in ex vivo culture. In addition to assessing the expression of a marker gene we have demonstrated that this approach can be used to induce the production of TNF receptor fusion protein (TNFR-Ig), a protein with therapeutic potential. Whole thickness rabbit or human corneas were transfected ex vivo with complexes consisting of dendrimers and plasmids containing lacZ or TNFR-Ig genes. Following optimisation 6-10% of the corneal endothelial cells expressed the marker gene. Expression was restricted to the endothelium and was maximal after transfection with 18:1 (w/w) activated dendrimer:plasmid DNA ratio and culture for 3 days. The supernatant of corneas transfected with TNFR-Ig plasmid contained TNFR-Ig protein which was able to inhibit TNF-mediated cytotoxicity in a bioassay. We have therefore shown that activated dendrimers are an efficient nonviral vector capable of transducing corneal endothelial cells ex vivo. They may have applications in gene-based approaches aimed at prevention of corneal allograft rejection or in treatment of other disorders of corneal endothelium.

Animals↗
PubMed1999

A 24-month, double-blind, placebo-controlled multicentre pilot study of the efficacy and safety of nicergoline 60 mg per day in elderly hypertensive patients with leukoaraiosis.

In this pilot study, 72 non-demented and non-depressive elderly hypertensive patients with evidence of leukoaraiosis on cerebral computed tomography scan (Rezek score: > 16) were randomly assigned to receive either nicergoline 30 mg b.i.d. (n = 36) or a placebo (n = 36) for 24 months. All patients received antihypertensives and their hypertension was controlled under treatment. They were evaluated by nine neuropsychological tests exploring memory, concentration, verbal and motor performances, administered at baseline and at every six-month interval during the study period. At baseline, the two groups were comparable for all demographic and clinical characteristics, including cognitive functions, except for the delayed recall of the Auditory Verbal Learning Test (AVLT), which was better in the placebo group (P = 0.04). Changes in scores over time were compared between the two groups. At the last visit, patients on nicergoline (n = 31) were found to have deteriorated less or to have improved more on test scores than the patients on placebo (n = 30). Significant differences were observed for memory function (AVLT short term recall, P = 0.026; AVLT delayed recall, P = 0.013; and, Benton Visual Retention Test, P = 0.002) and attention and concentration (Letter Cancellation Test, P = 0.043; and, WAIS-R Digit Symbol subtest, P = 0.006). The Rezek score remained unchanged in the two groups. Tolerance of nicergoline was similar to that of placebo. In conclusion, this study shows that nicergoline 30 mg b.i. d. administered over a 24-month period attenuates the deterioration in cognitive functions in elderly hypertensive patients with leukoaraiosis. Whether these effects were specific for this type of white matter changes could not be determined in the context of this pilot study.

Aged↗
PubMed1999

T cells and T cell-derived cytokines as pathogenic factors in the nonallergic form of atopic dermatitis.

A subgroup of patients with atopic dermatitis are known to have normal serum total immunoglobulin E levels, undetectable specific immunoglobulin E, and negative skin prick tests towards allergens. This form of the disease has been termed nonallergic atopic dermatitis. In this study, we found that, among 1151 chronic atopic dermatitis patients, about 10% had normal serum immunoglobulin E levels with no evidence for immunoglobulin E sensitization. We investigated immunologic mechanisms of patients with "allergic" and "nonallergic" atopic dermatitis using peripheral blood and skin biopsy samples. Our data suggest that T cells are likely involved in the pathogenesis of both forms of atopic dermatitis. Skin T cells equally responded to superantigen, staphylococcal enterotoxin B, and produced interleukin-2, interleukin-5, interleukin-13, and interferon-gamma in both forms of the disease. Interleukin-4, however, was not detectable in the skin biopsies of both atopic dermatitis types and was secreted in very low amounts by T cells cultured from the skin biopsies. Moreover, skin T cells from nonallergic atopic dermatitis patients expressed lower interleukin-5 and interleukin-13 levels compared with allergic atopic dermatitis patients. Accordingly, T cells isolated from skin biopsies of atopic dermatitis, but not from the nonallergic atopic dermatitis, induced high immunoglobulin E production in cocultures with normal B cells that was mediated by interleukin-13. In addition, B cell activation with high CD23 expression was observed in the peripheral blood of atopic dermatitis, but not nonallergic atopic dermatitis patients. These data suggest, although high numbers of T cells are present in lesional skin of both types, a lack of interleukin-13-induced B cell activation and consequent immunoglobulin E production in nonallergic atopic dermatitis.

Adult↗