Clinical features of multiple lacunar and small deep infarcts.
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Biomedical subjects
Publications and source records attributed to M Hommel.
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A total of 160 adult Malawians with epigastric pain for longer than 2 weeks was investigated by endoscopy and serologically for evidence of infection with Helicobacter pylori. The organism was demonstrated histologically and/or by culture in 141 (88%) patients. With histological means and/or culture as the 'gold standard', the histological technique was 100% sensitive while culture was only 81% sensitive. All isolates tested were sensitive to amoxycillin and tetracycline; 74% were resistant to metronidazole. Endoscopic findings were normal in 104 (65%) patients (86.5% H. pylori positive). Evidence of duodenal ulcer was found in 41 (25%) patients (95% H. pylori positive). Histologically, gastritis was common, severe gastritis being associated with increased colonisation by H. pylori. Two kinds of urease test were found to be 100% specific for the presence of H. pylori. The sensitivity of the serological test (Helico-G test) was 98% but its specificity was only 27%. These results provide important background information for planned therapeutic studies in patients with upper gastro-intestinal disease in Malawi.
We observed considerable diversity in the cytoadherence of Plasmodium falciparum isolates from Malawi to melanoma cells, U937 cells and human peripheral monocytes. Each isolate exhibited a unique cytoadherence profile for the three human cell types. These isolates generally adhered well to U937 cells and fresh monocytes, moderately to melanoma cells and poorly to TE 671, MIA-Pa-Ca, WI 38, PLC/PRF/5 and HeLa cells. An antimalarial immunoglobulin pool inhibited binding to melanoma cells by 50% or more and to U937 cells by 25% or less. There was no correlation between in vitro cytoadherence to the three cells and clinical disease. These results suggest that malarial adherence ligands exposed on the surface of infected erythrocytes vary from one isolate to another.
Hyperimmune globulin can inhibit and reverse the cytoadherence between Plasmodium falciparum-infected erythrocytes and melanoma cells in vitro. Cytoadherence is believed to mediate disease in cerebral malaria. Therefore we studied the efficacy of i.v. immunoglobulin, purified from the plasma of local semi-immune blood donors, as an adjunct to standard treatment for cerebral malaria in Malawian children. The immunoglobulin preparation (IFAT antimalarial antibody titre 1:5120) recognized erythrocyte-associated antigens of each of 22 Malawian P. falciparum isolates studied, and reversed binding of Malawian isolates to melanoma cells. Immunoglobulin did not reverse binding to human monocytes or to cells of the human histiocytic lymphoma cell line U937. Thirty-one children with P. falciparum parasitaemia and unrousable coma were enrolled. All were treated with i.v. quinine dihydrochloride; in addition patients were randomized to receive either immunoglobulin (400 mg/kg by i.v. infusion over 3 h) or placebo (albumen and sucrose by similar infusion) in a double blind trial with sequential analysis. Of 16 patients receiving immunoglobulin, five (31%) died and five survivors had neurological sequelae. Of 15 patients receiving placebo, one (7%) died and two had sequelae. Parasite clearance, fever clearance and coma resolution times in survivors were similar in the two groups. Although the difference in outcome between the two groups was not significant, the trial was stopped because immunoglobulin was demonstrated not to be superior to placebo.
Antileishmanial chemotherapy is hampered by the location of the parasite within the phagolysosome of the macrophage, which restricts the bioavailability of many potentially useful antileishmanial drugs. In this study, the possibility of using antileishmanial drugs targeted to the infected macrophages by means of a chemical linkage to a neutral mannose-substituted poly-L-lysine carrier molecule was explored. The study was performed in an in vitro model with Leishmania donovani-infected murine macrophages. The antileishmanial activities of various synthetic constructs were compared with those of the free drugs and the pentavalent antimonial Pentostam, which was used as the positive control. The 50% effective dose of allopurinol riboside linked to the mannosylated poly-L-lysine was below 7.5 x 10(-6) M, while it was up to 3 x 10(-4) M for the free drug, indicating that the drug bound to the polymer was 50 times more active than the free drug. Control experiments with other constructs (e.g., allopurinol riboside linked to the mannose-free polymer) confirmed that the enhancement of activity was indeed achieved by means of the mannose homing device.
Thirty patients with Parkinson's disease were studied for the purpose of investigation relations between motor symptoms and cerebral atrophy evaluated by magnetic resonance imaging (MRI). Axial symptoms (gait disorder, postural instability and difficulty in arising from a chair), assessed at the time of maximum clinical improvement, were significantly correlated with frontal atrophy, while no correlation was found between the basal parkinsonian disability score and cerebral atrophy. It is suggested that frontal atrophy observed by MRI is linked with axial motor symptoms resulting from non-dopaminergic lesions. The origin of this atrophy is unknown.
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The sequestration of Plasmodium falciparum-infected erythrocytes to the endothelial cells of brain capillaries is believed to represent one of the determining factors in the pathogenesis of cerebral malaria. In vitro studies of cytoadherence provide an experimental approach to understand the mechanism of sequestration and the respective roles played by parasite and host components in this interaction. This paper critically reviews current studies on cytoadherence, with particular emphasis on the nature of the information provided by such studies and their limitations. The paper also describes how cytoadherence studies using the patient's own monocytes can provide original information on the level of receptor up-regulation in the course of malarial infection.
A PEG-ELISA was used to demonstrate parasite specific immune complexes in a significant proportion (25/26) of Onchocerca volvulus infection sera from Sierra Leone. The parasite antigen was detected using a peroxidase-conjugated rabbit serum raised to the bovine parasite O. gibsoni. Controls including European control serum, endemic control serum and Rh+ sera gave consistently low readings. Characterization of the parasite component in the immune complexes by Western blotting demonstrated a heat stable antigen of M(r) 46,000. This antigen was not present in the circulating immune complexes (CIC) prepared from patients with Wuchereria bancrofti infection, but a cross-reactive molecule of the same size was weakly recognized in the CIC of Loa loa and Mansonella perstans infected patients. No association between the level of parasite specific CIC and clinical disease was observed in the O. volvulus patients.
Spasticity following upper motor neuron lesion can be alleviated by few treatments such as physiotherapy, drugs and neurosurgery. However, they all have side effects, limitations or lack of selectivity. We tentatively used the paralyzing effects of botulinum toxin. Since the late 1970's the use of this toxin has increased and it has been extended to numerous muscles and diseases of various causes. In this pilot and open study we use botulinum toxin in spasticity. Eight patients (7 stroke, 1 head injury) with longstanding severe spasticity (minimum: 12 months, maximum: 15 years) were included. Spasticity greatly interfered with their activity in daily life and was resistant to oral antispastic medications. Six patients suffered from pain and 4 had cutaneous lesions especially maceration of the palm of the hand. A-botulinum toxin was injected with a 30-gauged needle. The sites chosen for injection were the following muscles: biceps brachii, brachioradialis, flexor digitorum, flexor carpi, tibialis anterior, flexor digitorum longus. Altogether 41 injections were performed. There were no side effects. Spasticity was improved in all patients. Five patients reported significant pain relief on a visual analogical scale. Most of them reported a benefit in their limb tone and referred to subjective improvement in the activity of daily life and nursing. The beneficial effects of one injection lasted more than 5 months. Seven patients received a second course of treatment. A double-blind study of botulinum toxin in spasticity is to be undertaken to assess its effectiveness and safety when prescribed in the required dose to treat this condition.
A dipstick colloidal dye immunoassay (DIA) for multiple antigen detection is described. The test combines the concepts of double antibody (Ab) sandwich ELISA, dot blotting, and colloidal particle-linked Abs to produce a dipstick test for multiple antigen (Ag) detection. Dipsticks prepared from Ab coated nitrocellulose membrane mounted on acetate strips served as the assay capture matrix. Abs absorbed to colored dye particles from a family of commercially available textile dyes (Dye/Ab reagent) served as Ag detecting reagents. DIA and enzyme labelled dot blot assays showed similar Ag detection limits down to a sensitivity of 10 ng/ml. In a pilot study, an assay designed to detect species-specific IgG for use in mosquito bloodmeal identification demonstrated the feasibility of the technique. Experiments comparing bloodmeal analysis of mosquitoes using DIA and ELISA methods showed 100% agreement. This DIA method provides an inexpensive, simple, robust test for multiple Ag detection without instrumentation suitable for a wide variety of field applications.
The usefulness of high-frequency stimulation of the ventral intermediate nucleus (Vim) as the first neurosurgical procedure in disabling tremor was assessed in 26 patients with Parkinson's disease and 6 with essential tremor. 7 of these patients had already undergone thalamotomy contralateral to the stimulated side, and 11 others had bilateral Vim stimulation at the same time. Chronic stimulating electrodes connected to a pulse generator were implanted in the Vim. Tremor amplitude at rest, during posture holding, and during action and intention manoeuvres was assessed by means of accelerometry. Of the 43 thalami stimulated, 27 showed complete relief from tremor and 11 major improvement (88%). The improvement was maintained for up to 29 months (mean follow-up 13 [SD 9] months). Adverse effects were mild and could be eradicated by reduction or cessation of stimulation. This reversibility and adaptability, allowing control of side-effects, make thalamic stimulation preferable to thalamotomy, especially when treatment of both sides of the brain is needed.
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Ten variant populations derived from the Indochina-1 strain of Plasmodium falciparum were analyzed by using (i) hyperimmune serum raised against some of these populations in squirrel monkeys and (ii) an oligonucleotide probe based on the rep-20 sequence, which had previously been shown to be a useful marker of diversity. Although all 10 subpopulations had an identical fingerprint pattern on Southern blots probed with the oligonucleotide, thus demonstrating a homogeneous genetic makeup, they all had a different phenotype for erythrocyte-associated antigens, thus confirming serological variant-specific differences. Antibodies to erythrocyte-associated antigens were measured with a new technique including immunogold and silver enhancement. The results of this study indicate that antigenic variation can occur without major genomic reorganization.
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A single unilateral lesion, near the midline, may interrupt the pathways involved in vertical gaze just before and after they decussate, inducing an anatomically unilateral, but functionally bilateral, lesion. We report 11 patients with supranuclear vertical gaze palsies (two with conjugate upgaze palsy, four with combined up- and downgaze palsies, two with monocular elevation palsy, and three with vertical "one-and-a-half" syndrome) due to unilateral midbrain strokes.
Cerebrovascular accidents (CVA's) of the brain stem have the same causes and physiopathological mechanisms as CVA's of the hemispheres, but they are ten times less frequent. They correspond to ischaemic or haemorrhagic lesions in the territories of the vertebral arteries and the basilar artery, including their collateral, circumferential and perforating branches. Clinically, CVA's of the brain stem are characterized by the association of unilateral motor and/or somatosensory symptoms on the side opposite the lesion, and by involvement of the ipsilateral cranial nerves, which helps in evaluating the level of the CVA. Motor or somatosensory symptoms may be bilateral or on alternate sides. The complexity of these CVA's reflects the rich anatomical organization of the brain stem. Their severity in case of extensive lesions is due to the fact that they affect structures that are vital to consciousness and cardiorespiratory regulation. Patients with CVA's of the brain stem must be hospitalized in neurology departments.