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Biomedical subjects

M Hommel

Publications and source records attributed to M Hommel.

At least 19 recordsLinked to original sources

The AMPA antagonist ZK 200775 in patients with acute ischaemic stroke: a double-blind, multicentre, placebo-controlled safety and tolerability study.

BACKGROUND AND PURPOSE: ZK 200775 is a selective competitive AMPA receptor antagonist. It has demonstrated neuroprotective efficacy in experimental models of stroke and tolerability in healthy volunteers. We tested the safety and tolerability of ZK 200775 in patients with acute ischaemic stroke. METHODS: In a multicentre double-blind, randomised, placebo-controlled phase II trial, 61 ischaemic stroke patients were treated with either placebo or active drug in a dose finding design. Twenty-five patients received placebo, 12 patients received a total dose of 262.5 mg in 48 h (group 1) and 13 patients received a total dose of 525 mg in 48 h (group 2), and 11 patients received a total dose of 105 mg over a period of 6 h (group 3). We studied the pharmacokinetics of the compound and the effect of the infusion on the neurologic and haemodynamic parameters of the patients. The study was not powered to detect neuroprotective efficacy. RESULTS: In group 2 there was a significant transient worsening in the mean NIH stroke scale score 14- 18 h after the start of treatment. This was due to reduction of consciousness (stupor and coma) in 8 out of 13 patients. Level of consciousness improved approximately 6 h after cessation of infusion. No significant haemodynamic responses were observed. Even after reduction of the administered dose and duration of infusion to 6 h (group 3), 2 patients experienced a reduction in level of consciousness. The effect of ZK 200775 on level of consciousness gave cause for concern and the trial was stopped prematurely for safety reasons. CONCLUSIONS: The AMPA antagonist ZK 200775 reversibly worsened the neurological condition in patients with acute ischaemic stroke. Our results suggest that ZK 200775 exerts significant sedative effects in patients with acute stroke which preclude its further development as a neuroprotective agent in this indication.

Acute Disease↗

[Readability of informed consent forms for subjects participating in biomedical research: updating is required].

OBJECTIVE: We compared informed consent forms of subjects participating in biomedical research with those of references texts in order to determine the factors that influence readability. METHODS: We assessed the readability of 73 informed consent forms of research protocols conducted in the clinical investigation centres in the Rhone-Alpes area, and then compared them with 33 reference texts corresponding to 5 French school grades (first year infant, primary school, GCS level, high school, and classics aggregation), using the Flesch test and Cordial" analyser. RESULTS: Median Flesch scores were 66 for the first year infant level, 62 for the primary school level, 58 for the GCS level, 42 for the high school level, and 43 for the aggregation level. It was 22 for the informed consent forms. Median Cordial scores were 86 for the first year infant level, 77 for the second, 74 for the third, 49 for the fourth, 43 for the fifth. It was 1 for the informed consent forms. No methodological factor correlated with Flesch and Cordial" results. CONCLUSION: The quantitative readability scores for informed consent forms for subjects participating in biomedical research are low, lower than those proposed to aggregation candidates, whatever the type of protocol. Some thought must be given to the impact of the reduced readability on patients' understanding, and steps should be taken to improve the readability of the forms.

Adolescent↗

[Epidemiology of athrotherombotic lower limb arterial disease].

Chronic occlusive arterial disease of the lower limbs is a common presentation of atherothrombotic disease. This systematic review of the literature analyses the natural history of this condition and the prevalence of asymptomatic lesions of other arterial localisations requiring specific treatment. The Medline database was researched and completed by a bibliography of the principal articles selected, Internet sites and their publication reviews and also the Cochrane database. The incidence of systemic complications has been assessed in many good quality epidemiological study. It increases with the severity of lower limb arterial disease, but in asymptomatic patients defined by a pathological systolic pressure index (< 0.90) the cardiovascular mortality is already 2% per year, the incidence of myocardial infarction 3% per year and that of cerebrovascular accidents 1 to 2% per year. The prevalence of asymptomatic lesions in other arterial sites is less well documented, the evaluations varying according to the population studied and criteria of significant lesions: 21 to 69% for coronary artery disease, 12 to 59% for carotid artery stenosis, 14 to 40% for renal artery stenosis and 6 to 14% for abdominal aortic aneurysms. Despite the uncertainty of these estimations, the prevalence of asymptomatic atherothrombotic lesions is high in all arterial networks and justifies the setting up of studies to assess the clinical benefits of their systematic diagnostic investigations.

Arteriosclerosis↗

[Diffusion-weighted magnetic resonance imaging in hypoglycemic coma].

Hypoglycemia is a classic cause of coma and can result in irreversible neuronal loss. Until now, the main prognostic factors were depth of hypoglycemia and duration of coma. We report the case of a 55-Year-old woman who suffered severe hypoglycemic coma with abnormal cortico- subcortical diffusion weighted MR images. These MRI abnormalities preceded severe atrophy of these cerebral areas. This findings suggests that diffusion abnormalities in hypoglycemic coma may be related to neuronal loss and may thus have prognostic value.

Alcoholism↗

Evaluation of a urinary antigen-based latex agglutination test in the diagnosis of kala-azar in eastern Nepal.

BACKGROUND: We evaluated the diagnostic accuracy as well as the reproducibility of the urine latex agglutination test 'KAtex' in the diagnosis of kala-azar in patients recruited at a tertiary care centre in Dharan, Nepal, between November 2000 and January 2002. METHODS: All patients presenting with fever of 2 weeks or more and splenomegaly were consecutively enrolled. Bone marrow and--if negative--spleen aspirates were examined for Leishmania donovani. Serum and urine samples were taken in duplicate for the Direct Agglutination Test (DAT) and KAtex. The reference laboratory determined sensitivity and specificity of KAtex. Reproducibility between both laboratories was assessed. RESULTS: KAtex was performed on urine from 155 parasitologically confirmed kala-azar and 77 non-kala-azar cases (parasitology and DAT-negative). KAtex showed a sensitivity of 47.7% (74/155, 95% CI: 39.7-55.9) and a specificity of 98.7% (76/77, 95% CI: 93.0-100.0). Reproducibility of KAtex showed a kappa of 0.684 (P < 0.001, n = 232). CONCLUSION: KAtex evaluation showed high specificity, low sensitivity and moderate reproducibility. A urine test for kala-azar could become a real breakthrough in kala-azar management if its reproducibility and sensitivity could be further improved.

Adult↗

Detection of Cryptosporidium amongst diarrhoeic and asymptomatic children in Jeddah, Saudi Arabia.

Between the March and May of 2000, stool specimens were collected from children aged <5 in six pre-school crèches and clinics in the Jeddah area of Saudi Arabia. Sixty-three (25%) of the children had diarrhoeal disease but the other 190 were asymptomatic. When the stool samples were stained and examined for the oocysts of Cryptosporidium spp. and other enteric protozoa, 20 (32%) of the symptomatic children but only nine (4.7%) of the asymptomatic were found to be excreting Cryptosporidium oocysts. Similarly, Cyclospora cayetanensis was found, always as a co-infection with Cryptosporidium sp., in seven (11%) of the children with diarrhoeal disease but only eight (4.2%) of the asymptomatics. One asymptomatic child was found to be co-infected with Isospora belli and Cryptosporidium. Giardia intestinalis and cysts of Entamoeba histolytica/dispar were detected in 18 (29%) and nine (14%) of the children with diarrhoeal disease and in eight (4.2%) and 13 (6.8%) of the asymptomatic children, respectively. This appears to be the first report of Cy. cayetanensis from Saudi Arabia and the highest prevalence of Cryptosporidium infection ever described.

Animals↗

Field evaluation of latex agglutination test for detecting urinary antigens in visceral leishmaniasis in Sudan.

A latex agglutination test to detect urinary antigens for visceral leishmaniasis (VL) was studied. In 204 patients with suspected VL, KAtex had a sensitivity of 95.2% with good agreement with microscopy smears but poor agreement with 4 different serology tests. It was also positive in 2 confirmed VL cases co-infected with HIV. In all K4tex-positive confirmed cases actively followed up after treatment, the test became negative 1 month after completion of treatment. While IC4tex had a specificity of 100% in healthy endemic and non-endemic controls, the direct agglutination test (DAT) was positive in 14% of the KAtex-negative healthy endemic controls. KAtex is a simple addition to the diagnostics of VL particularly at field level and as a complementary test for the diagnosis of VL in smear-negative cases with positive DAT results.

Adolescent↗

The impact on Parkinson's disease of electrical parameter settings in STN stimulation.

BACKGROUND: The main advantage of deep brain stimulation (DBS) in the treatment of PD is that the electrical settings can be adjusted to optimize benefits and minimize adverse effects. The main objective of this study was to discover how varying these electrical parameters impacted on parkinsonian motor signs. METHODS: Twelve patients with PD with chronic bilateral subthalamic nucleus (STN) stimulation were selected. The authors evaluated the effects of a variation in the voltages, frequencies, and pulse widths on tremor, bradykinesia, and rigidity using two different paradigms: one in which the total electrical energy delivered was held constant, and one in which this was varied. Up to 26 parameter conditions were tested under double blind randomized conditions. RESULTS: Voltages >or=3 V and frequencies >or=130 Hz led to the greatest improvement in all three parkinsonian signs. A rate of 5 Hz significantly worsened akinesia. The combination of the highest voltage with the narrowest pulse width was most effective. CONCLUSIONS: This study confirms that the most beneficial effects induced by STN stimulation are obtained at high frequencies and that voltage is the most critical factor to obtain adequate alteration in STN activity. The mechanisms by which STN DBS improves parkinsonism remain speculative.

Adult↗

Alternative polymerase chain reaction method to identify Plasmodium species in human blood samples: the semi-nested multiplex malaria PCR (SnM-PCR).

A simplified protocol for the identification of Plasmodium species by semi-nested multiplex polymerase chain reaction (SnM-PCR) in human blood samples is compared with microscopical examination of thin and thick blood films in 2 field trials in Côte d'Ivoire and Cameroon. Also, dried blood spots or liquid blood collected from Dutch soldiers returning from Goma, Zaire (n = 141), Angola (n = 40), and from Marechaussee (Dutch border police) returning from various parts of the world (n = 161) were examined, together with miscellaneous other material obtained from laboratories and hospitals. The method is based on features of the small subunit nuclear ribosomal ribonucleic acid (RNA) gene (ssrDNA), a multicopy gene which possesses both highly conserved domains and domains characteristic for each of the 4 human malaria parasites. The first reaction of the SnM-PCR includes a universal reverse primer with 2 forward primers specific for Plasmodium and mammals, respectively. The mammalian-specific primer was included as a positive control to distinguish uninfected cases from simple PCR failures. The second PCR reaction includes a Plasmodium-specific forward primer plus species-specific reverse primers for P. vivax, P. ovale, P. falciparum and P. malariae. The technique worked better with samples collected in the field as dried blood spots on filter paper and heparinized blood rather than with frozen pelleted blood; it was more sensitive and more specific than the standard microscopical examination.

Animals↗

Latex agglutination test for the detection of urinary antigens in visceral leishmaniasis.

This paper describes a new latex agglutination test ('KATEX') for the detection of leishmanial antigen in the urine of patients with visceral leishmaniasis. In preliminary laboratory trials, using urine collected from well-defined cases and controls from Brazil, Yemen and Nepal, the test had 100% specificity and a sensitivity between 68 and 100%. When used in a time-course experiment in cotton rats infected with Leishmania donovani, the test became positive 1 week after inoculation and antigen levels in urine declined rapidly after chemotherapy (the test was negative before the end of the course of treatment). Finally, in an integrated study performed in Sudan, KATEX was compared to microscopy and four different serological tests in a group of 73 patients having presented with clinical manifestations suggestive of visceral leishmaniasis. Compared to microscopy, KATEX performed better than any single serological test in predicting positivity and a particularly good result was obtained by combining KATEX and the direct agglutination test (DAT).

Animals↗

Addition of hypoxanthine to culture media allows in vitro cultivation of Babesia bovis and B. bigemina at reduced serum concentrations.

The microaerophilous stationary phase system (MASP) was introduced in 1980 and successfully used as a standard technique for Babesia bovis and B. bigemina in vitro culture. The percentage of serum in the medium and the dependence on specific serum donors have been recognized as important constraints both for immunochemical studies and for the logistics of culture routine. In the present study the supplementation of RPMI 1640 with hypoxanthine at a concentration between 50 and 200 microM has enabled patterns of growth of B. bovis and B. bigemina to be achieved comparable to the standard technique with a simultaneous reduction of serum concentration from 40% to 5%. With hypoxanthine-supplemented medium it was possible to either replace the bovine serum from a specific donor with horse serum or use commercial adult bovine serum or foetal calf serum at 10%. When the serum replacement media Albumax II and GF21 were used, the growth of both B. bovis and B. bigemina markedly decreased after 3 x 72 h cycles. However, when these species were cultivated in culture flasks previously coated with cells from a murine peritoneal lavage, continuous parasite growth was achieved.

Animals↗

Expression of intercellular adhesion molecule 1 (ICAM-1) in Plasmodium falciparum-infected placenta.

We investigated the expression of intercellular adhesion molecule 1 (ICAM-1) in malarial placenta and related histological changes. Thirty-two malarial and 40 control term placentae were collected at Tanga, Tanzania and examined histologically and immunohistochemically. Malaria infected placentae were further divided into acute (15) and chronic (17) cases according to the presence of malarial pigment. The expression of ICAM-1 on monocyte, syncytio- and cytotrophoblasts, endothelial and stromal cells was assessed. Birthweight was lower and leukocyte counts higher in placentae with chronic infection. Many monocytes were present within the intervillous spaces, especially in placentae with chronic infection, and aggregated with parasitized erythrocytes. Some monocytes were adhesive to the surface of fibrinoid deposits. ICAM-1 expression on monocytes of malarial placentae was significantly conspicuous and correlated to the degree of intervillous leukocyte infiltration. Syncytiotrophoblasts often did not show ICAM-1, even though ICAM-1 was expressed by endothelium and weakly by cytotrophoblasts and stromal cells in both infected and control placentae. These results suggest that the expression of ICAM-1 on monocytes contributes to sequestration of infected erythrocytes within the intervillous spaces and their adhesion to fibrin masses and that ICAM-1 is unlikely to be associated with the direct adhesion of infected erythrocytes to the syncytiotrophoblasts.

Birth Weight↗

Brachiofacial pure motor stroke.

Pure motor stroke is the commonest lacunar syndrome, but it may be associated with nonlacunar mechanisms of infarction. Pure motor brachiofacial weakness has been considered as a partial syndrome depending on a lacunar mechanism. We studied the correlations between stroke type, topography of infarction and etiology in 22 patients with pure motor brachiofacial weakness who were consecutively admitted to our stroke unit during a 10-year period. Seventeen patients had a small deep infarct, 4 had a cortical infarct in the superficial MCA territory and 1 had no specific lesion. The part of the cardiovascular risk factors was about 36% for smoking, 13% for diabetes mellitus, 60% for dyslipidemia and 40% for heart disease. Hypertension was present in 75% of our cases. None of the patients had a large artery stenosis on Doppler ultrasonography. We concluded that brachiofacial pure motor stroke is not always correlated to lacunar infarcts and may be due to a cortical infarct. MRI should be performed when brain CT is normal because of the implications it may have in management and therapy.

Aged↗

[Katex for the diagnosis of human visceral leishmaniasis].

Katex is a latex agglutination test allowing highly specific detection Leishmania antigen in urine of patients with visceral leishmaniasis. A multicentric study of this new diagnostic tool which is also effective in patients co-infected by leishmaniasis and HIV is currently in progress in Sudan, India, Nepal, Brazil and Spain. The authors describe the utility of this technique in comparison with other routine diagnostic procedures such as microscopic examination and serological tests. Preliminary results suggest that it could be used to confirm infection in the field and to monitor treatment efficacy.

Antigens, Protozoan↗