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Biomedical subjects

M Hommel

Publications and source records attributed to M Hommel.

At least 55 records · Page 3Linked to original sources

Modulation of host cell receptors: a mechanism for the survival of malaria parasites.

Intra-erythrocytic stages of malaria parasites can alter the surface of their host cells and release toxins which induce the production of cytokines, which in turn can up- or down-regulate the expression of adhesion receptors on the surface of microvascular endothelial cells. New adhesion receptors on endothelial cells provide the parasite with increased chances of survival despite an increasing level of host immunity. In order to take advantage of these new opportunities for survival, the parasite itself needs to make best use of its considerable ability to vary its surface antigens and adherent molecules. The paper describes the various players in this survival game and articulates a working hypothesis to explain how it may all fit together.

Animals↗

The direct agglutination test: a non-specific test specific for the diagnosis of visceral leishmaniasis?

Serology has an important role to play in the diagnosis of the severe clinical syndrome of visceral leishmaniasis (VL). The direct agglutination test (DAT), a simple agglutination test which requires no laboratory facilities, has become the preferred test, particularly for field studies. The nature of the antigens responsible for the agglutination of leishmanial promastigotes by the serum of VL patients is not known. A series of experiments which provide some clues to the molecular basis for the test and which indicate that there might be more in DAT than meets the eye is reported.

Agglutination Tests↗

High levels of parasite-specific IgG1 correlate with the amicrofilaremic state in Loa loa infection.

To investigate the mechanisms of protective immunity operating in Loa loa infection, 56 persons from a L. ioa-endemic village in southeast Gabon were examined over a 7-year period. The level of L. loa-specific IgG subclasses in defined parasitologic groups was compared by use of ELISA with either adult, microfilarial, or third-stage larval (L3) antigens of L. loa. With all antigen preparations, IgG1 levels were significantly higher in amicrofilaremic persons than in persons with high or low levels of microfilariae. Moreover, there was a significant negative correlation between IgG1 levels to L3 antigen and the density of microfilariae (Spearman's r(s) = -.701; P < .01). There was no correlation between density of microfilariae and levels of other IgG subclasses or of IgE. These data indicate that IgG1 may play a role in the effector mechanism(s) involved in resistance against L. loa and suggest that L3 antigens may be important in eliciting protective responses.

Adult↗

Atherosclerotic disease of the aortic arch as a risk factor for recurrent ischemic stroke.

BACKGROUND: Atherosclerotic disease of the aortic arch is found in 60 percent of patients 60 years of age or older who have had brain infarction. The aim of this study was to determine whether atherosclerotic plaques in the aortic arch are a risk factor for recurrent brain infarction and for vascular events in general (i.e., brain infarction, myocardial infarction, peripheral embolism, and death from vascular causes). METHODS: For a period of two to four years, we followed a cohort of 331 patients 60 years of age or older who were consecutively admitted to the hospital with brain infarction (a total of 788 person-years of follow up). All patients underwent transesophageal echocardiography to determine whether atherosclerotic plaques were present in the aortic arch proximal to the ostium of the left subclavian artery. The patients were divided into three groups according to the thickness of the wall of the aortic arch ( < 1 mm, 1 to 3.9 mm, and > or = 4 mm). RESULTS: The incidence of recurrent brain infarction was 11.9 per 100 person-years in patients with an aortic-wall thickness of > or = 4 mm, as compared with 3.5 per 100 person-years in patients with a wall thickness of 1 to 3.9 mm and 2.8 per 100 person-years in patients with a wall thickness of < 1 mm (P < 0.001). The overall incidence of vascular events was 26.0, 9.1, and 5.9 per 100 person-years of follow-up in the respective groups (P < 0.001). After adjustment for the presence of carotid stenosis, atrial fibrillation, peripheral arterial disease, and other risk factors, aortic plaques > or = 4 mm thick (including the thickness of the aortic wall) were found to be independent predictors of recurrent brain infarction (relative risk, 3.8; 95 percent confidence interval, 1.8 to 7.8; P = 0.0012) and of all vascular events (relative risk, 3.5; 95 percent confidence interval, 2.1 to 5.9; P < 0.001). CONCLUSIONS: Atherosclerotic plaques > or = 4 mm thick in the aortic arch are significant predictors of recurrent brain infarction and other vascular events.

Aged↗

[Physiopathology of symptoms of malaria. Role of cytokines, cytoadherence and premunition].

Clinical symptoms of malaria are caused by a cascade of events triggered by the release of parasite "toxins" at the time of schizont rupture. The production of cytokines, particularly TNF alpha, plays a central role in this cascade. In addition to TNF, the pathogenesis of cerebral malaria (the most severe form of the disease) also requires the existence of cytoadherence of infected erythrocytes in cerebral capillaries and the intensity of this cytoadherence is controlled by a mixture of host and parasite features. Finally, anti-parasite and anti-toxic immunity (or "premunition") play a role in the reduction of pathology in individuals living in endemic areas.

Cell Adhesion↗

Synthetic peptide-based enzyme-linked immunosorbent assay for serodiagnosis of visceral leishmaniasis.

Synthetic peptides, derived from the amino acid sequence of a Leishmania donovani clone, were used to develop an enzyme-linked immunosorbent assay (ELISA) for detecting antibodies against L. donovani. For this purpose, five peptides were conjugated to a protein carrier, human serum albumin (HSA), by using a heterobifunctional reagent, epsilon-maleimidocaproic acid N-hydroxysuccinimide ester, to obtain a well-defined product. The sensitivity and the specificity of the peptide-specific ELISA were determined with a panel of 106 serum samples from individuals living in areas where visceral leishmaniasis is endemic; sera from post-kala azar dermal leishmaniasis-infected patients and from individuals suffering from other infectious diseases were also included. ELISAs were performed with either a single peptide-HSA conjugate or a mixture of two peptide-HSA conjugates. Ninety-seven percent of the serum samples from patients with visceral leishmaniasis had detectable antibodies to one or more of the single synthetic peptides. ELISA with a single peptide-HSA conjugate proved to be less sensitive (less than 71%) but more specific (up to 93%) than ELISA with crude promastigote antigens (80% sensitivity and 79% specificity); when a combination of two different peptide-HSA conjugates was used, the test increased both in sensitivity and in specificity. Chemically defined peptide-protein conjugates improve the reproducibility and reliability of ELISA for the serodiagnosis of L. donovani infection.

Amino Acid Sequence↗

[Physiopathology of protozoan infections].

The pathophysiology of diseases produced by protozoal infections is caused not only by a direct effect of the parasites on their host (e.g. host cell lysis or parasite adherence), but also by indirect effects, where molecules of parasite origin exert an effect on host cells, which in turn produces a cascade of events (including the secretion of inflammatory cytokines, prostaglandins and nitric oxide) responsible for the symptomatology observed. The role of the host itself in the pathogenic events is not negligeable and its genetic background, nutritional and immunological status will influence the outcome of the infection (which will result in asymptomatic infections in some individuals and severe disease in others). The general and specific features of a variety of protozoal infections of medical and veterinary importance (including malaria, babesiosis, trypanosomiasis, toxoplasmosis, cryptosporidiosis, amoebiasis, giardiasis and trichomoniasis) are discussed in this review and a number of common patterns are identified.

Animals↗

[Thrombolytic therapy in ischemic cerebrovascular accidents].

Thrombolysis together with neuroprotective agents the two most important recent advances in the treatment of acute ischemic stroke. This update summarizes the recent randomized clinical trials and emphasizes the question of risk versus benefit of this potentially useful but dangerous treatment.

Anistreplase↗

Experimental models for leishmaniasis and for testing anti-leishmanial vaccines.

In public health terms, leishmaniases are diseases of humans and dogs, whereas, in epidemiological terms, Leishmania spp. are considered to represent infections of a wide variety of animals, which represent the natural reservoirs of the various parasite species involved. Humans and dogs (which may be considered secondary or 'accidental' hosts in the leishmanial life-cycle) often exhibit severe clinical signs and symptoms when infected, whereas reservoir hosts generally show a few, minor or no signs. This situation makes the definition of a suitable laboratory model a difficult one, since the various experimental hosts may behave either like a reservoir or an accidental host. This review discusses the concept of animal models for leishmaniases and provides a critical evaluation of the most common experimental models and their respective advantages and disadvantages. In this state-of-the-art review, particular emphasis is given to the value of using mouse, hamster, cotton-rat, dog and primate models, especially in the context of testing potential anti-leishmanial vaccines.

Animals↗

Vertebrobasilar infarcts in patients with dolichoectatic basilar artery.

We reported 18 patients who had stroke in the posterior circulation with dolichoectatic basilar artery. TIAs preceded posterior circulation infarct in 5 patients. Strokes involved medulla oblongata (3), pons (4), cerebellum (4), mesencephalon (4), thalamus or occipital lobe (3). Dolichoectatic basilar artery also produced hydrocephalus in one patient. The mechanism of stroke may be due to penetrating artery occlusion, basilar artery thrombosis or an embolism from the abnormal basilar artery. Short-term prognosis was poor seeing that 4 patients died within 12 days of stroke.

Adult↗

Postpartum cerebral angiopathy possibly due to bromocriptine therapy.

BACKGROUND: Eight cases of benign angiopathy of the postpartum period have been reported previously, none of which involved the administration of bromocriptine. CASE DESCRIPTION: We describe a case of benign cerebral angiopathy in a 20-year-old woman in the postpartum period occurring after bromocriptine therapy prescribed to suppress lactation. CONCLUSIONS: Other adverse effects due to vasoconstriction have been reported during bromocriptine therapy, such as myocardial infarction and arterial hypertension. This case suggests that a similar mechanism may be possible in cerebral arteries, although the cause of vasoconstriction remains uncertain.

Adult↗

Prevalence of stroke at high altitude (3380 m) in Cuzco, a town of Peru. A population-based study.

BACKGROUND AND PURPOSE: We carried out a door-to-door survey on stroke prevalence at high altitude in Cuzco City, a town in the Peruvian Andes located 3380 m above sea level. METHODS AND RESULTS: Among the 3246 screened individuals over 15 years old, there were 21 cases of first-ever completed stroke, yielding a crude prevalence ratio of 6.47 per 1000 (95% confidence interval [CI], 3.71 to 8.93 per 1000). The age-adjusted to WHO population point prevalence ratio was 5.74 per 1000 (95% CI, 3.14 to 8.35 per 1000), and the age-adjusted to North American US population point prevalence ratio was 8.58 per 1000 (95% CI, 5.44 to 11.75 per 1000). Multivariate logistic regression analysis suggested that age, polycythemia, high consumption of alcohol, and area of residence were associated with stroke prevalence. Our results suggest that the stroke prevalence in the central areas of Cuzco with sedentary people having a relatively high standard of living was higher than that in the peripheral areas with people with a relatively lower standard of living and less sedentary activities (odds ratio, 5.8; 95% CI, 1.4 to 23). CONCLUSIONS: The prevalence of stroke suggests that stroke may be a public health problem in developing countries. This study suggests the importance of environmental factors such as altitude and lifestyle in stroke occurrence. The role of these factors should be confirmed and taken into account in future stroke prevalence studies.

Adolescent↗

Is it clinically possible to distinguish nonhemorrhagic infarct from hemorrhagic stroke?

BACKGROUND AND PURPOSE: Diagnosis of the nonhemorrhagic ischemic type of stroke by analysis of patients' clinical features is considered unreliable because no clinical feature is specific. The diagnosis is so difficult to establish that we cannot hope to use the same method to make a reliable diagnosis in all stroke cases. In this study, we propose a simple scoring system with a positive predictive value of close to 100% to distinguish nonhemorrhagic infarct from hemorrhagic stroke. This scoring is available for all physicians in bedside diagnosis even if this score can be applied to a subgroup of patients. METHODS: Twenty-six clinical variables that might potentially distinguish cerebral hemorrhage from infarction were recorded in patients consecutively admitted to our stroke unit for stroke lasting more than 24 hours with at least unilateral motor weakness affecting face and/or arm and/or leg (internal validity study). Patients previously receiving anticoagulant therapy were excluded. We used CT scan as the gold standard. We used multivariate logistic regression to establish a clinical score from which we derived the classification rule. This rule was validated with data from the next 200 consecutive patients hospitalized in the stroke unit (external validity study). RESULTS: Three hundred sixty-eight patients were enrolled in the internal study. The obtained score was (2 x alcohol consumption) + (1.5 x plantar response) + (3 x headache) + (3 x history of hypertension)--(5 x history of transient neurological deficit)--(2 x peripheral arterial disease)--(1.5 x history of hyperlipidemia)--(2.5 x atrial fibrillation on admission). All patients with a score less than 1 (n = 123) had a nonhemorrhagic infarct (ie, 40% of the 305 patients with a nonhemorrhagic infarct). No threshold was found to diagnose cerebral hemorrhage with a sufficiently high positive predictive value. Among the 200 patients enrolled in the external validity study, 72 patients with a score below 1 had a nonhemorrhagic infarct (ie, 43% of patients with a nonhemorrhagic infarct). CONCLUSIONS: Diagnosis of nonhemorrhagic infarct can be made in 36% (95% confidence interval [CI], 29 to 43) of patients with a high level of accuracy (100% in the external validity study, which gives a 95% CI of 93 to 100). Thus, 43% (95% CI, 36 to 50) of patients with a nonhemorrhagic infarct could receive a bedside diagnosis. The score is simple and can be calculated from information available to all physicians.

Adult↗

[Malaria vaccines: why, who and how?].

Although the search for a malaria vaccine has much progressed in recent years, all of the many vaccine candidates have still a long way to go before becoming available for clinical use. This paper reexamines the rationale of using a vaccine as an intervention tool against malaria, reviews the results recently obtained and discusses current trends of malaria vaccine research.

Animals↗

Atherosclerotic disease of the aortic arch and the risk of ischemic stroke.

BACKGROUND: Atherosclerotic disease of the aortic arch has been suspected to be a potential source of cerebral emboli. We conducted a study to quantify the risk of ischemic stroke associated with atherosclerotic disease of the aortic arch. METHODS: Using transesophageal echocardiography, we performed a prospective case-control study of the frequency and thickness of atherosclerotic plaques in the ascending aorta and proximal arch in 250 consecutive patients admitted to the hospital with ischemic stroke and 250 consecutive controls, all over the age of 60 years. RESULTS: Atherosclerotic plaques > or = mm in thickness were found in 14.4 percent of the patients but in only 2 percent of the controls. After adjustment for atherosclerotic risk factors, the odds ratio for ischemic stroke among patients with such plaques was 9.1 (95 percent confidence interval, 3.3 to 25.2; P < 0.001). Among the 78 patients who had brain infarcts with no obvious cause, 28.2 percent had plaques > or = 4 mm in thickness, as compared with 8.1 percent of the 172 patients who had infarcts whose possible or likely causes were known (odds ratio, 4.7; 95 percent confidence interval, 2.2 to 10.1; P < 0.001). Plaques of > or = 4 mm in the aortic arch were not associated with the presence of atrial fibrillation or stenosis of the extracranial internal carotid artery. In contrast, plaques that were 1 to 3.9 mm thick were frequently associated with carotid stenosis of > or = 70 percent. CONCLUSIONS: These results indicate a strong, independent association between atherosclerotic disease of the aortic arch and the risk of ischemic stroke. The association was particularly strong with thick plaques. Atherosclerotic disease of the aortic arch should be regarded as a risk factor for ischemic stroke and as a possible source of cerebral emboli.

Aged↗