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Biomedical subjects

D Lapierre

Publications and source records attributed to D Lapierre.

8 recordsLinked to original sources
PubMed2001

Synthesis and evaluation of novel dipeptide-bound 1,2,4-thiadiazoles as irreversible inhibitors of guinea pig liver transglutaminase.

Herein we report the synthesis and evaluation of 14 novel peptides as potential irreversible inactivators of guinea pig liver transglutaminase (TGase). These peptides were designed to resemble Cbz-L-Gln-Gly, known to be a good TGase substrate, and to include a 1,2,4-thiadiazole group. The side chain length of the amino acid residue bearing the inhibitor group was also varied in order to permit investigation of this effect. Their inactivation rate constants were measured using a direct continuous spectrophotometric method and were found to vary between 0.330 to 0.89 microM(-1) min(-1).

Animals↗
PubMed1996

Atovaquone as long-term suppressive therapy for toxoplasmic encephalitis in patients with AIDS and multiple drug intolerance. Atovaquone Expanded Access Group.

OBJECTIVE: To evaluate the efficacy and tolerance of atovaquone used as long-term maintenance therapy in patients with toxoplasmic encephalitis and intolerant of conventional anti-Toxoplasma therapies. DESIGN: Uncontrolled open-label study of atovaquone given through an expanded access programme; statistical analysis was performed on an intent-to-treat basis. PATIENTS: Sixty-five patients intolerant of conventional toxoplasmic encephalitis therapies-pyrimethamine, sulphadiazine or clindamycin-received atovaquone as maintenance therapy after resolution of an acute episode of toxoplasmic encephalitis. Patients were clinically and neurologically evaluated monthly. Toxoplasmic encephalitis relapse was defined as the occurrence of neurological abnormalities, except in the case of a proven alternative diagnosis. RESULTS: Sixty-five patients were treated with atovaquone 750 mg four times daily and followed up for a mean period of 1 year. Mean CD4 lymphocytes count was 29 x 10(6)/l. Prior to starting atovaquone, patients had experienced a total of 129 episodes of intolerance to conventional anti-Toxoplasma drugs. Atovaquone was used as a single anti-toxoplasmic agent in 75% of the cases. Seventeen patients (26%) experienced a toxoplasmic encephalitis relapse. Sixty-three patients (97%) were able to tolerate and continued taking atovaquone. Two patients had to discontinue therapy because of side-effects. In a multivariate analysis, only the duration of pyrimethamine-sulphadiazine therapy during the acute therapy phase of toxoplasmic encephalitis was significantly associated with a decreased risk of toxoplasmic encephalitis relapse during maintenance therapy [relative risk, 0.64 for each week of pyrimethamine-sulphadiazine; 95% confidence interval (CI), 0.42-0.96; P = 0.03]. The survival probability was 70% at 1 year after the episode of toxoplasmic encephalitis (95% CI, 57-83). CONCLUSION: These results suggest that atovaquone is a well-tolerated alternative anti-Toxoplasma treatment for maintenance therapy in patients who are intolerant to conventional anti-Toxoplasma drugs.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Ventral frontal deficits in psychopathy: neuropsychological test findings.

The hypothesis of prefrontal dysfunction in psychopathy has been pursued for many years, without convincing results. It is proposed here that this approach in previous studies was far too global. The present investigation was carried out in order to test a more specific hypothesis of orbitofrontal and/or frontal ventromedial deficits in psychopathy. Psychopathic criminals were compared to non-psychopathic criminals with measures related to orbitofrontal or frontal ventromedial functioning, as well as with control measures more associated with frontodorsolateral and posterorolandic functions. All subjects provided urine samples for drug assay. It was found that, while the two groups performed similarly on all the control measures, including the drug tests, the psychopaths were significantly impaired on all the orbitofrontal-ventromedial tasks. The psychopaths were significantly impulsive on several tests as well as significantly dysosmic [corrected]. The latter finding is particularly important in the sense that it cannot readily be explained socioculturally, thus presenting a new and convincing argument for brain-based etiology of this disorder. The results are discussed in relation to other psychiatric disorders characterized by impulse dyscontrol as well as in relation to other putative neurobiological etiological factors in psychopathy.

Adult↗
PubMed1995

Neuropsychological correlates of violence in schizophrenia.

Thirty-one outpatient men with schizophrenia were assessed with various measures of lifelong history of physical violence as well as psychopathology, neuropsychological performance, and neurological intactness. Most of the results consisted of nonsignificant positive relationships between physical aggression and neuropsychological performance in these schizophrenia subjects. Some neuropsychological test performances did show significant positive correlations with levels of aggressivity. In contrast with previous studies that have established a relation between neuropsychological impairment (as opposed to performance) and violence in schizophrenia, subjects of the present study were high-functioning outpatients who may not have attained a level of neurological impairment inducing constant uncontrollable outbursts of irritative aggression in their daily living. The importance of defining in detail the clinical characteristics of the subjects studied and the type of violence assessed is discussed, and an ecological interpretation of these counterintuitive results is provided.

Activities of Daily Living↗
PubMed1995

Neurological soft signs in schizophrenia: are they related to negative or positive symptoms, neuropsychological performance, and violence?

This investigation was carried out on 31 unemployed schizophrenic outpatient men. The general purpose was to explore new aspects of neurological soft signs in schizophrenia. A 108-item version of the Nathan Kline Institute scale of soft signs, the Schedule for Affective Disorders and Schizophrenia psychiatric interview, the negative and positive symptom scale (PANSS), a comprehensive scale of life-time history of violence, and a large set of neuropsychological tests were administered. It was found that "motor" soft signs were significantly more prevalent than "sensory-perceptual" signs, but that each body side manifested equal numbers of neurological signs. Before and after statistical correction for age, education, alcoholism, drug abuse disorder, and daily and cumulative neuroleptic dosage, orbitofrontal-type neuropsychological tasks measuring "impulsivity" related very robustly to the soft signs. Furthermore, before and after the same statistical corrections, right body-side signs correlated significantly with the same neuropsychological tests, whereas left body-side signs did not. The PANSS scores and levels of lifetime violence generally did not correlate significantly with neurological soft signs. The latter negative findings, we think relate to the fact that these were relatively high-functioning (i.e., outpatient) schizophrenics. Overall, the results support notions of frontal lobe and left hemisphere involvement in schizophrenia, these two dysfunctional systems being apparently linked at the level of the orbitofrontal area of the brain.

Journal Article↗
PubMed1993

Antibody avidity measurement and immune complex dissociation for serological diagnosis of vertically acquired HIV-1 infection.

Differences in avidity between HIV-1 antibodies transmitted passively and antibodies synthesized by children born to HIV-1-positive mothers can be measured using a commercially available competitive enzyme immunoassay kit. The avidity determination method is based on the competition between an anti-HIV-1-peroxidase-labeled antibody at a stable and known concentration and the anti-HIV-1 antibodies (IgA, IgG, IgM) present in the child's serum at various and increasing dilutions. The shift in the competition/dilution curves between serum samples taken at the third and the sixth month of the child's life showed either the loss or the synthesis of anti-HIV-1 antibodies. The antibody avidity determination combined with a test detecting free or complexed p24 antigen is a workable and inexpensive serological method for the follow-up of children born to seropositive mothers. Combining these two complementary methods, HIV-1 infection has been established at 6 months of age in 13 of 13 infants, and positive results were confirmed by coculture and by PCR. An HIV-1 infection was excluded at 6 months of age in 17 of 17 infants, results otherwise confirmed by virological and clinical follow-up. These new and convenient approaches to the diagnosis of vertically acquired HIV-1 could be used worldwide, including in developing countries.

AIDS Serodiagnosis↗
PubMed1989

Electrocardiographic aspects of skin diving.

Electrocardiographic (ECG) aspects of skin diving were monitored by means of continuous ECG recording in a pool 15 m deep. Ten regularly trained divers with different levels of experience divid a minimum of three consecutive times, holding their beath, reaching depths of 6 m, 9 m, and 12 or 15 m. The water temperature was 28 degrees C. During the ascending part of these dives, bradycardia was observed in all skin-divers. Minimal heart rate correlated negatively with the diver's experience (number of dives previously performed). In six divers cardiac arrhythmia was observed. Atrial arrhythmias were sometimes isolated occurrences, but more frequently they were multiple. Ventricular arrhythmias tended to be bigeminal. Apparently, forced expiration through the snorkel when surfacing precipitated these rhythmic disorders.

Adult↗