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Biomedical subjects

T May

Publications and source records attributed to T May.

At least 109 records · Page 6Linked to original sources

Amnesia of the epileptic aura.

In a prospective study lasting 6 months, we recorded on video 108 seizures with aura of 23 patients in an attempt to evaluate the mechanisms involved in the encoding of memories. In 88 of those seizures, we also recorded an EEG. The percentage of auras remembered decreased significantly with increasing severity of the seizures. The recollection of auras was also significantly dependent on the ictal EEG changes during the aura. Ninety-seven percent of the auras without EEG changes, 94% of the auras with unilateral EEG changes, and 73% of the auras with bilateral EEG changes during the aura were remembered. The spread of the ictal EEG pattern during the aura also showed a significant correlation with the severity of the ensuing seizure. Three patients with bitemporal epilepsy made up a considerable proportion of those who never remembered their aura before secondary generalized tonic-clonic seizures (2 of 3) and of those who had a transient postictal amnesia of their aura (2 of 3). The only patient who failed to remember a previously documented isolated aura also suffered from bitemporal epilepsy. During the second part of the study, we questioned whether information provided during the history could be helpful in defining the type of epilepsy syndrome or localizing the EEG seizure pattern of the 80 patients who had been admitted for presurgical epilepsy diagnosis. Localized (regional, unilateral, and independent left and right lateral) EEG seizure patterns occurred in 82% of the 51 patients with auras in their history as compared with 24% of the 17 patients who did not have auras in their history (p < 0.01).

Amnesia↗

[Isolation of an acid-alcohol resistant bacillus (BAAR) in the febrile HIV infected patients: Mycobacterium tuberculosis (MT) or Mycobacterium avium complex (MAC)?].

The detection of BAAR in HIV infected patients with CD4 < 100/mm3 and with an infectious syndrome urge on beginning an effective treatment against Mycobacterium tuberculosis and/or Mycobacterium avium Complex, before the results of the culture are known. Our purpose was to search clinical and biological features to angle directly the diagnosis towards a tuberculosis or not, and to start the most suitable treatment. This retrospective study, from 1986 to 1993, stated on 54 patients who had at least one sample with positive BAAR (blood, marrow, stools, sputum or urine cultures). From these cultures, MAC was isolated on 37 patients and BK on 17. The both groups were similar for age, sex, risk factor, number of opportunistic infections, delay between the date of AIDS and the discovery of a positive BAAR, and Ag p24. However, a significant difference in favor of a MAC disease exists regarding about: disseminated infections (92% vs 53%), digestive troubles (57% vs 23.5%), anterior or concomitant CMV infection (49% vs 9%), isolation of BAAR in blood culture (54% vs 20%) or in stools culture (76% vs 33%), leucopenia (2850/mm3 +/- 1520 vs 4124/mm3 +/- 2232), anémia (Hb 9.1 g/dl +/- 1.5 vs 10.1 g/dl +/- 1.6). The univariated analysis of results allowed us to conclude that the presence of one among those parameters must induce the prescription of a suitable treatment against MAC.

AIDS-Related Opportunistic Infections↗

Striatal dopamine receptors and adenylyl cyclase activity in a rat model of alcohol addiction: effects of ethanol and lisuride treatment.

In this report a novel animal model of spontaneous development of alcohol and drug addiction was used. Addiction to ethanol was induced in male Wistar rats (free choice between ethanol solutions and water for 11 mo). After 36 wk of alcohol deprivation these rats (series A) had ingested 3.4 +/- 0.4 g ethanol/kg/day. Age-matched, "controlled" alcohol consumers (series C: free choice for 8 wk) had ingested only 1.6 +/- 0.4 g/kg/day (P < .001). Two additional series of addicted (AL) and controlled alcohol-consuming rats (CL) received lisuride (90 micrograms/kg/day) for 8 wk concomitantly with the self-administered ethanol and again during the last week before death. Ethanol intake was increased by lisuride treatment in both groups (AL: 4.1 +/- 0.3 g/kg/day; CL: 2.7 +/- 0.4 g/kg/day; P < .05). Four months before death the alcohol was withdrawn. After this period of abstinence the in vitro dose-response curves for striatal dopamine D-1 receptor-stimulated adenylyl cyclase activity were determined (with eight concentrations of dopamine between 50 nM and 30 microM). Both lisuride-treated (AL) and untreated ethanol-addicted rats (A) displayed a significant (P < .01) increase in the effective concentration required to induce 50% of the response (EC50) as compared with controlled drinkers (C: 720 +/- 150 nM; A: 1820 +/- 390 nM; CL: 590 +/- 110 nM; AL: 1050 +/- 160 nM). Lisuride treatment increased forskolin- (10 microM) stimulated adenylyl cyclase activity and the Bmax of high-affinity [3H]DA binding to the D-1 site.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylyl Cyclases↗

Changes of G-protein levels in platelet membranes from alcoholics during short-term and long-term abstinence.

The levels of G alpha i2-protein and the G beta gamma-heterodimer were measured in platelet membranes of non-alcoholics, non-alcoholics after an ethanol load (1 g/kg body weight) and of alcoholics under various conditions. The findings were correlated with the activation of the adenylyl cyclase (AC) by various agents. The activation of AC was facilitated by acute ingestion of ethanol. This could not be explained by changes of the G-proteins determined because the levels of the G alpha i2-protein increased, whereas those of the G beta gamma-proteins remained in the control range. The alcoholics were divided into two groups on the day of admission: those with ethanol still present in the blood (intoxicated alcoholics) and those acutely withdrawn within the last 48 h (ethanol absent from the blood). The intoxicated alcoholics had elevated G alpha i2-protein levels in contrast to the acutely withdrawn patients, who did not. This observation suggests rapid changes of the G-protein levels. By analysing the inhibitory efficacy of the G-proteins on AC, it was found that the concentration of the G beta gamma-heterodimer, but not that of the G alpha i2-proteins, correlated with the inhibitory efficacy. The basal activity of the AC was reduced as well as the activation by some compounds. Eight days later (short-term withdrawal) both the levels of G alpha i2 and G beta gamma were elevated. Again, the inhibitory efficacy of the G-proteins correlated with the G beta gamma-heterodimer levels but not with those of the G alpha i2-protein. Furthermore, the changes of the G beta gamma-protein levels between the first and the eighth day correlated with the changes of the inhibiting efficacy. Only a trend was observed with respect to a lowered basal activity if compared with the intoxicated non-alcoholics. The activation of AC by guanylylimidyldiphosphate [Gpp(NH)p] and Gpp(NH)p + ethanol (200 mM in vitro) was still reduced. Observations after 3 and 6 months of abstinence demonstrated elevated G alpha i2- and G beta gamma-protein levels. This suggests residual marker properties of the G-proteins whereby the activity of AC was normal. Only the reduced stimulation by Gpp(NH)p + ethanol in vitro (200 mM), compared with the respective stimulation of AC of intoxicated non-alcoholics, suggested some residual disturbances of the signal transduction during long-term abstinence.

Adenylyl Cyclases↗

[Value of the stool bacteriological test in Mycobacterium avium complex infections in AIDS].

Incidence of Mycobacterium avium complex (MAC) infection has increased in HIV infected patients. We report a retrospective study of 25 cases of MAC infection occurring in HIV patients. Stools examination was performed in 5 (31%) of the patients without digestive symptoms and in the 9 (100%) patients presenting with diarrhoea. The stools culture are positive in 79% of cases (11/14). In all the patients with diarrhoea, direct examination of the stools gave the diagnosis of MAC infection. All the patients had profound immunodepression with CD4+ cell count < 5/mm3. The mean survival time from mycobacteriosis diagnosis was 122 +/- 90 days despite antimycobacteriosis therapy.

AIDS-Related Opportunistic Infections↗

Harman (1-methyl-beta-carboline) is a natural inhibitor of monoamine oxidase type A in rats.

Harman (1-methyl-beta-carboline) displaces [3H]pargyline in vitro from high affinity binding sites on membranes from cerebral cortex, provided that experimental conditions are chosen under which [3H]pargyline labels selectively monoamine oxidase type A. Norharman (beta-carboline) is a much weaker displacing compound. It is well known that the type A enzyme can be blocked irreversibly in vivo by treatment of rats with clorgyline. Under these conditions no specific binding of [3H]harman and [3H]pargyline to monoamine oxidase type A was detected in brain, whereas the specific binding was reduced to 5% in liver tissue. The in vitro and ex vivo experiments suggest that there is a specific binding site for harman on monoamine oxidase type A, thereby extending earlier in vitro findings. It has been postulated that harman operates as a natural inhibitor of monoamine oxidase type A in mammals. The present study demonstrates that harman and norharman occur in rat brain, blood plasma, heart, kidney and liver. It further shows that pretreatment with clorgyline induces a time-dependent increase in the blood plasma levels of harman, suggesting the displacement of harman from the enzyme in tissue with its subsequent delivery into the blood. These findings strongly support the hypothesis based on in vitro experiments, that harman binds reversibly to the active site of monoamine oxidase type A in vivo. Dietary sources for mammalian harman play probably only a minor role, because the concentrations in beer and wine as well as other foodstuffs are too low to contribute substantially to endogenous levels of harman.

Animals↗

Monoamine oxidase (MAO; E.C. 1.4.3.4) characteristics of platelets influenced by in vitro and in vivo ethanol on alcoholics and on control subjects.

Ethanol (ETOH) in vitro displays a competitive inhibition of human platelet MAO-B with a Ki of 270 +/- 30 mM. Lineweaver-Burk analyses with 6 substrate concentrations (5-160 microM kynuramine) in the presence or absence of 200 mM ETOH were performed with platelets of alcoholics before withdrawal (Alc day 1), one week (Alc day 8) and 3 months (Alc mon 3) after withdrawal as well as in control subjects without and after ETOH intake. In all groups the Km increases highly significantly (p < 0.001) but the Vmax is unchanged by the presence of ETOH in vitro supporting the view of a competitive inhibition in each group. The Vmax of Alc day 1 is significantly 25% decreased, of Alc day 8 unchanged and of Alc mon 3 nonsignificantly 19% decreased in comparison with the controls. The increase of the Km in the presence of 200 mM ETOH is significantly 15% reduced in Alc day 1 and 9% in Alc day 8 but unchanged in Alc mon 3 compared with the controls.

Alcoholism↗

Comparison of the in vitro binding characteristics of the beta-carbolines harman and norharman in rat brain and liver and in bovine adrenal medulla.

The in vitro binding of the naturally occurring beta-carbolines harman and norharman in their tritium-labelled forms to cell membranes from the rat brain and liver and from bovine adrenal medulla was investigated. Displacement of the specific [3H]harman binding in bovine adrenal medulla and rat liver by several beta-carbolines and monoamine oxidase (MAO) inhibitors revealed the pharmacological profile of a single, high-affinity binding site (KD 4.92 +/- 0.43 nmol/l, Bmax 8.47 +/- 0.17 pmol/mg protein; adrenal medulla) which corresponded to the active site of MAO type A (MAO-A). Similar characteristics have previously been found for brain tissue from rat, marmoset and pig. In order to determine the temperature dependence of the [3H]harman binding, the KD and Bmax values for rat cerebral cortex were calculated from the results of saturation experiments at 5 temperatures (range: 0 degree C-37 degrees C). Whereas the Bmax values under all conditions were approximately 4 pmol/mg protein, the KD values, with increasing temperature, ranged from approximately 3 nmol/l to 30 nmol/l. The calculated linear van't Hoff plot (-ln KD against 1/T) suggested an enthalpy-driven binding of [3H]harman to MAO-A. At least three different [3H]norharman-binding sites were detected. In the rat forebrain, approximately 85% of the specific binding (at about 2 nmol/l of [3H]norharman) can be attributed to a MAO binding site of type B: the binding is displaceable, in nmol/l concentrations by the potent and selective MAO-B inhibitors MDL 72,974 A, R(-)-deprenyl and pargyline and, in mumol/l concentrations, by S(+)-deprenyl and the potent and selective MAO-A inhibitors clorgyline, harmine, harman, harmaline, brofaromine 5-F-alpha-methyltryptamine. After suppression of the MAO binding sites with 1 mumol/l clorgyline and 1 mumol/l R(-)-deprenyl, a second binding site was found. However, the binding at this site was biphasically displaceable by harman and norharman (Hill-slopes about 0.5 and 0.6, curvilinear Rosenthal plots) suggesting the presence of negative co-operativity or of two binding sites (states). A similar clorgyline/R(-)-deprenyl resistant single (Hill-slopes of displacement by norharman, harman and 6-hydroxy-beta-carboline about unity; linear Rosenthal plots) high affinity binding sites (KD 7.5 +/- 2 nmol/l, Bmax 130+/- 30 fmol/mg protein) was found in bovine adrenal medullary cell membranes. A third quite different clorgyline/R(-)-deprenyl resistant high-affinity (KD approximately 14 nmol/l) and high-density (Bmax 10-30 pmol/mg protein) binding site was detected in the liver.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenal Medulla↗

Extracerebral toxoplasmosis in patients infected with HIV. A French National Survey.

A French nationwide survey of extracerebral toxoplasmosis (ECT) in HIV-infected patients was performed between January 1990 and September 1992. All French hospitals were surveyed, and all but a few responded. Data collected included epidemiologic, clinical, and biologic features; therapy; and outcome. During the 33-month survey, 199 cases were collected. The prevalence of ECT in patients with AIDS can be estimated at 1.5%-2%. Age, sex, and HIV risk factors were similar to those of the general AIDS population in France. Extracerebral toxoplasmosis appeared mainly in HIV-infected patients with advanced immunosuppression: the mean CD4+ lymphocyte count was 57/mm3(+/- 99). The localizations observed were: eyes (50% of patients); lung (26%); disseminated (at least 2 extracerebral visceral localizations) (11.5%); peripheral blood (acute febrile syndrome with isolated positive parasitemia) (3%); heart (3%); bone marrow (3%); bladder (1%); and isolated cases of rhinopharynx, skin, liver, lymph nodes, conus medullaris, and pericardium. In this survey, muscular and pancreatic localizations were always associated with other extracerebral localizations. A cerebral localization was diagnosed in 41% of cases. Serologic data provided little information. Ocular fundus examination, bronchoalveolar lavage, tissue biopsy, and search for parasitemia were the main diagnostic procedures. Treatment was the same as for cerebral toxoplasmosis. A clinical response was observed in 64% of cases; 19% relapsed. Death occurred in 106 (53%) cases and was related to ECT in 34% of cases.(ABSTRACT TRUNCATED AT 250 WORDS)

AIDS-Related Opportunistic Infections↗

Longitudinal observations of monoamine oxidase B in alcoholics: differentiation of marker characteristics.

The marker characteristics of monoamine oxidase B (MAO B) in human platelets were investigated in a clinical study of 59 alcoholics (diagnosed according to the criteria of ICD-10) observed over a period of 6 months. Demographic and family history were obtained by a structured interview, including the substance abuse section of CIDI (Composite International Diagnostic Interview). The patient's personality was assessed by Cloninger's Tridimensional Personality Questionnaire (TPQ). Blood samples were first drawn during chronic intoxication (day of admission to the hospital for detoxication), after short-term abstinence (8 days later), medium-term (3 months later), and long-term abstinence (6 months later). A group of 22 matched healthy nonalcoholics served as controls studied under sober conditions and during acute intoxication (4 hr after ingestion of 1 g ethanol/kg body weight). All platelet samples were investigated with 6 kynuramine concentrations as substrate (fluorometric assay) in the absence and presence of 200 mM ethanol (ETOH) in vitro. MAO B activity was significantly reduced in alcoholics during chronic intoxication (Vmax: 2.70 +/- 0.15 nmol/mg protein) compared with sober (Vmax: 3.25 +/- 0.23 nmol/min/mg protein) and acutely intoxicated controls that turned to normal during abstinence. However, MAO B activity obtained during medium- and long-term abstinence was significantly lowered in patients with high novelty-seeking and impulsiveness scores in the TPQ, a history of suicide attempts, or an alcoholic mother. The affinity of MAO B (Km values) was unchanged in alcoholics at any time investigated. Addition of ETOH in vitro reduced the affinity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Cerebellar atrophy does not increase susceptibility to carbamazepine toxicity.

Cerebellar atrophy (CA) is a frequent finding in patients with chronic epilepsy. To find out whether the existence of CA has an influence on the tolerance of high-dose monotherapy with carbamazepine, we compared the lowest individual toxic serum levels in patients with complex focal seizures, with CA (n = 27) and without CA (n = 20) in computerized tomography (CT). There was no statistical difference between the groups, even after separating patients with mild CA (n = 20) from those with more severe damage (n = 7). In addition, other clinical, EEG and CT data also seemed to have no influence on the individual toxic threshold serum levels of carbamazepine.

Adolescent↗

Synergistic effects of parathyroid hormone and 1,25-dihydroxyvitamin D3 on proliferation and vitamin D receptor expression of rat growth cartilage cells.

We investigated possible interaction of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] and PTH on: 1) proliferation (monolayer culture) and colony formation (agarose stabilized suspension cultures); 2) expression of 1,25-(OH)2D3 receptor (VDR); and 3) cAMP response to PTH, using primary cultures of chondrocytes from rat tibia proximal epiphysis. 1 alpha,25-(OH)2D3 stereospecifically stimulated DNA synthesis, cell counts, and colony formation at low concentration (10(-12) M). Within 6 h bovine PTH (bPTH)(1-34), human PTH (hPTH)(28-48) (10(-10) M), (Bu)2cAMP (1-2 mM), and 12-O-tetradecanoyl-13-acetate (10(-8) M) increased [3H]thymidine incorporation in the absence and presence of 1,25-(OH)2D3. Both PTH fragments also stimulated chondrocyte growth and colony formation in a Ca-dependent fashion. Prolonged exposure to bPTH(1-34) or hPTH(28-48) did not affect baseline DNA synthesis but increased the stimulatory effect of 1,25-(OH)2D3. This increase was inhibited in the presence of H7 (inhibition of PKC) or the monoclonal hPTH(1-38) antibody A1-70. In subconfluent chondrocyte cultures VDR was up-regulated by bPTH(1-34) and hPTH(28-48) (10(-10) M) or activators of protein kinase C (PKC), but not by (Bu)2cAMP. It was blocked by cycloheximide and actinomycin D and persisted in the presence of Ca-channel blockers. Inhibition of PKC by H7 also blocked the effect of bPTH(1-34) on VDR. The cAMP response to bPTH(1-34) was not affected by 1,25-(OH)2D3. We conclude that: 1) DNA synthesis, cell proliferation, and colony formation in chondrocyte monolayer or suspension cultures is increased by aminoterminal and midregional PTH fragments and by cAMP analogs in a Ca- dependent fashion; 2) bPTH(1-34) and hPTH(28-48) up-regulate VDR by cAMP-independent, PKC-dependent steps requiring transcriptional and translational processes; both PTH fragments also amplify the effect of 1,25-(OH)2D3 on DNA synthesis; and 3) no difference is found between the bPTH(1-34) and hPTH(28-48) fragments with respect to chondrocyte proliferation and VDR up-regulation, although the two differ with respect to stimulation of cAMP production.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Effect of fiber source on short-chain fatty acid production and on the growth and toxin production by Clostridium difficile.

BACKGROUND: Fermentable fiber promotes the growth of resident gut microbes, which modify the environment of the gastrointestinal tract and thus prevent colonization by Clostridium difficile. METHODS: An in vitro system with pigs as fecal inoculum donors was used to estimate fiber fermentability and changes in intestinal microbiota. RESULTS: Acetate and propionate production (mumol/mg substrate fermented/day) was greatest for gum arabic (1013.4 and 704.1, respectively); butyrate production was greatest for xylo-oligosaccharide (345.6). Growth of total anaerobes and clostridia was greatest for gum arabic (21.2 and 16.2 x 10(8) counts/ml, respectively) and xylo-oligosaccharides (21.0 and 19.6 x 10(8) respectively); growth of acidogenic bacteria was greatest with fructo-oligosaccharide (6.7 x 10(8) counts/ml). No culturable counts of C. difficile were obtained, nor was toxin A detected. CONCLUSIONS: Fermentable fibers support the growth of indigenous intestinal bacteria, particularly acidogenic bacteria, and yield large amounts of short-chain fatty acids with decreased gut pH. These factors contribute to the prevention of growth and toxin elaboration by C. difficile.

Animals↗

[Changes in drug therapy and in seizure frequency in an institution for epilepsy patients between 1971 and 1986].

Trends in treatment of epilepsy in an institution for handicapped patients with epilepsy were investigated in a retrospective longitudinal study. Medications and seizure frequencies in the period 1971 to 1986 were compared in 663 patients living in the institution at least since 1971. The results show that the majority of patients were on polytherapy, being treated on average with 2.95 (1971) to 2.60 (1986) anticonvulsants. The use of phenytoin, primidone and the succinimides clearly declined; the use of phenobarbitol declined slightly. The use of carbamazepine and valproic acid and their mean doses increased. The mean serum concentration of most of the anticonvulsants studied tended to move into the "therapeutic" range. The primidone and phenytoin concentrations remained rather low. The frequency of seizures, in particular of grand mal seizures, decreased between 1971 and 1981; from 1981 to 1986, no clear trend could be established. The results are compared with those of studies carried out in various other countries. It is discussed whether special antiepileptic therapy is required for the treatment of handicapped patients.

Aged↗

[Pulmonary involvement with a favorable course during Loa loa filariasis].

We report a case of pulmonary infiltrate in filariasis due to Loa loa in a 52 years old patient, living in Cameroon. Antifilarial treatment with ivermectin then diethylcarbamazine led to a rapid resoluting of the pulmonary abnormalities. It is the fifth case of lung disease during filariasis Loa loa.

Cameroon↗

Trimethoprim-sulfamethoxazole versus aerosolized pentamidine for primary prophylaxis of Pneumocystis carinii pneumonia: a prospective, randomized, controlled clinical trial. LFPMI Study Group. Ligue Française de Prévention des Maladies Infectieuses.

The objective was to compare the efficacy and tolerance of monthly aerosolized pentamidine versus trimethoprim-sulfamethoxazole (TMP-SMX) to prevent the first episode of Pneumocystis carinii pneumonia (PCP) in human immunodeficiency virus (HIV)-infected patients. In an open, prospective, randomized multicentric clinical trial, HIV-infected patients (n = 214) with CD4 cell counts < 200/mm3 or 20% without a history of PCP or cerebral toxoplasmosis were randomized to receive for at least 2 years aerosolized pentamidine (300 mg monthly) or low-dose daily TMP-SMX (400-80 mg). The mean follow-up was 578 days. The two groups (except for gender) were homogeneous for age, risk group for HIV infection, initial CD4+ lymphocyte count, and mean follow-up. The PCP rate per year of observation using an intent-to-treat analysis was 3.1% and 1.3% in the groups treated with pentamidine and TMP-SMX, respectively (p > 0.05). Moderate or severe clinical and biological side effects were observed in five patients on pentamidine and 33 on TMP-SMX (p < 0.05). Nineteen episodes of cerebral toxoplasmosis were diagnosed during the study. The analysis showed no significant difference in time of development of toxoplasmosis, but only one patient was actually treated with TMP-SMX. Survival was not significantly different in the two groups. Low-dose daily TMP-SMX or monthly aerosolized pentamidine effectively prevented a first episode of PCP in HIV-infected patients, but aerosolized pentamidine was better tolerated. However, TMP-SMX is less costly and should have a preventive effect for toxoplasmosis.

AIDS-Related Opportunistic Infections↗