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Biomedical subjects

T May

Publications and source records attributed to T May.

At least 55 records · Page 3Linked to original sources
PubMed2000

[Mycobacterium avium complex disease in HIV seropositive patients: incidence and risk factors before and after the introduction of highly active antiretroviral treatments. Clinical Epidemiology Group of the Information and Care Center for Human Immunodeficiency].

The objective of this study was to determine the risk factors of the first occurrence of Mycobacterium avium complex disease (MAC) infection among human immunodeficiency virus (HIV)-infected subjects during two different time periods: before and after the introduction of protease inhibitor (respectively, period 1: 1 January 1992 to 31 December 1995, and period 2: 1 January 1996 to 30 June 1998). This study was performed using the French Hospital Database on HIV (FHDH). Subjects were included when their CD4+ cell count was less than 100/mm3. If they did not die or develop MAC within the first 6 months after the inclusion, their follow-up had to be longer than 6 months to be included. Cox's model was used to calculated the relative hazards (RH) of MAC occurrence according to the age and time-dependent variables, such as CD4+ below 50/mm3, previous occurrence of tuberculosis, cytomegalovirus (CMV) infection and other acquired immunodeficiency syndrome (AIDS)-defining disease, nature of antiretroviral treatment and MAC prophylaxis. Among the 14,779 subjects followed during period 1, 1,710 (11.6%) had a diagnosis of MAC infection during their follow-up (incidence: 8.4 +/- 0.2 for 100 persons per year), while only 453 (4.4%) among 10,239 subjects presented this infection during period 2 (2.8 +/- 0.1 for 100 persons per year). Rifabutin regular prescription was a protective factor of MAC occurrence during period 1 (RH = 0.51 95% confidence interval (CI) = [0.37-0.69]), whereas this protective effect was not observed during period 2 (RH = 1.05 CI = [0.63-1.67]). Thus, during the HAART period, the results that we present do not indicate an interest into continuing MAC prophylaxis.

Adult↗
PubMed2000

Pregnancy-associated invasive squamous cell carcinoma of the vulva in a 28-year-old, HIV-negative woman. A case report.

BACKGROUND: The incidence of invasive squamous cell carcinoma of the vulva in women under 40 years of age has been increasing, particularly in association with human papillomavirus. Invasive vulvar carcinoma is rare in women under 30, as is an association with pregnancy. We report on a 28-year-old woman who was diagnosed with invasive squamous cell carcinoma of the vulva during pregnancy. CASE: The patient, gravida 5, para 4105, HIV negative, presented to the emergency room with vulvar pain. She had delivered a term infant three months earlier at another institution and was diagnosed with squamous cell carcinoma of the vulva at that time. At this admission, a 4.0-cm, ulcerated lesion involving the left labium minus was noted. The patient underwent examination under anesthesia with bilateral inguinal lymph node dissection, cone biopsy, radical vulvectomy and excision of perianal lesions. CONCLUSION: This case demonstrates the need to biopsy all suspicious vulvar lesions, even in young and pregnant women.

Adult↗
PubMed2000

Poisoning due to eating fungi in Victoria.

OBJECTIVES: To determine the range of fungi eaten in Victoria and the incidence and severity of associated illness. METHOD: From May 1997 to April 1999, 174 callers to the Victorian Poisons Information Centre who had eaten fungi posted samples for identification and 170 completed a questionnaire. The study was suspended for three months from 1 November 1997 to 10 January 1998 and for four months from 1 July 1998 to 30 October 1998. RESULTS: Species categorised as: 'poisonous', 'possibly poisonous', 'hallucinogenic', 'possibly hallucinogenic' and 'coprine containing' or 'possibly coprine containing' were identified in 87/174 (50%) samples. Accidental ingestions: 55 types of fungus were identified in the 126 ingestions; Coprinus species were the most common (24/126 [19%]). Illness 'likely' or 'possibly' due to the fungi was reported in 13/126 (10%) of these ingestions. Deliberate ingestions: The fungi were eaten for food in 46/47 of these cases; 41 of these (89%) were Agaricus xanthodermus or other Agaricus species. Illness 'likely' or 'possibly' due to the fungi was reported in 40/47 (85%) deliberate ingestions. In one case the reason for ingestion was unknown. CONCLUSIONS: A large range of fungi was eaten in the accidental ingestions; the incidence of illness was low. A small range of fungi was eaten deliberately. The predominant species was Agaricus xanthodermus, which was probably confused with other edible Agaricus species. The incidence of associated gastrointestinal irritation was high; it was of limited duration and mild severity.

Adolescent↗
PubMed2000

The VIRGO study: nevirapine, didanosine and stavudine combination therapy in antiretroviral-naive HIV-1-infected adults.

The virological and immunological efficacy of the triple regimen containing nevirapine (once or twice daily), didanosine (once daily) and stavudine, in antiretroviral-naive patients infected with HIV-1, was evaluated in an open-label, prospective, non-randomized, multi-centre, 52-week study. The first 60 patients (VIRGO I) received nevirapine as the standard dose, 200 mg twice daily; the subsequent 40 patients (VIRGO II) received nevirapine at a dose of 400 mg once daily. All patients received 400 mg of didanosine once daily and 40 mg of stavudine twice daily, adjusted for body weight. At baseline, the median CD4 cell count and plasma viral load (pVL) were 414 cells/mm3 and 4.59 log10 copies/ml in VIRGO I, and 412 cells/mm3 and 4.87 log10 copies/ml in VIRGO II. Using an intent-to-treat, 'non-completer equals failure', analysis, 78% (95% CI, 68-88%) of patients in VIRGO I and 68% (95% CI, 53-83%) of those in VIRGO II had a pVL <500 copies/ml at 24 weeks; the proportions achieving a pVL of <50 copies/ml were 62% (95% CI, 50-74%) and 50% (95% CI, 35-65%), respectively. The week 24 median CD4 cell count increase was 168 cells/mm3 (VIRGO I) and 139 cells/mm3 (VIRGO II). At week 52, 39/45 (87%) of VIRGO I patients had pVL <500 copies/ml and 30/45 (67%) <50 copies/ml. Of the 100 patients, 44 experienced grade 2 to 4 adverse events; 20 permanently discontinued study medication because of an adverse event. Combination therapy with the three reverse transcriptase (RT) inhibitors stavudine, once-daily didanosine and either once- or twice-daily nevirapine could be considered as an alternative option for first-line antiretroviral therapy.

Adult↗
PubMed1999

Effects of etonitazene consumption and abstinence on the signal transmission of mu-opioid receptors in brain membranes of rats.

Rats, for 8 weeks consuming the mu-opioid agonist etonitazene (forced and free choice conditions yielding high and low drug-consumers), were sacrificed after 2 days or 6 weeks lasting drug deprivation. Binding characteristics of membranes from the parieto-occipital cortex of these four groups were compared with those of drug-naive controls. In all five groups, 1 microM of the mu-opioid receptor agonist [D-Ala2,N-MePhe4,Gly5-ol]enkephalin (DAMGO) increased the guanosine-5'-O([35S]3'thio)triphosphate ([35S]GTPgammaS) binding activity on guanine nucleotide-binding (G) proteins, and 500 nM of GTPgammaS decreased the [3H]DAMGO binding affinity. During acute withdrawal, both opioid consuming groups displayed a higher maximum efficacy (Emax) in basal [35S]GTPgammaS binding (34 and 31%, each P < 0.01), but only the forced group showed a 58% higher net DAMGO-stimulated binding density Bmax (P < 0.01) and 53% more activated G proteins per mu-opioid receptor (P < 0.05). In the presence of GTPgammaS both groups revealed a higher affinity in [3H]DAMGO binding (each 25%, P < 0.01). The long-term drug-deprived groups displayed no differences in their binding characteristics.

Animals↗
PubMed1999

Chloroplast precursor protein translocon.

Chloroplasts are believed to have originated from a photosynthetic, prokaryotic ancestor. As the result of endosymbiotic evolution, most of the genes of the endocytobiont were displaced to the host nucleus. Today's chloroplasts must import most of their proteins from the cytosol as precursors. Oligomeric protein complexes in the chloroplast outer and inner envelope membranes are responsible for the specific recognition and membrane translocation of precursor proteins. The translocon at the outer membrane of chloroplasts and the inner membrane of chloroplasts act jointly during the import process. Several translocon subunits have been partially characterized in their molecular structure and function. Initial evidence indicates the prokaryotic origin of some chloroplast translocon components.

Biological Transport↗
PubMed1999

Characterization of protein Ser/Thr phosphatases of the malaria parasite, Plasmodium falciparum: inhibition of the parasitic calcineurin by cyclophilin-cyclosporin complex.

Two major protein phosphatase (PP) activities were purified from cytosolic extracts of the erythrocytic stage of the malaria parasite, Plasmodium falciparum. Both enzymes were specific for phosphoserine and phosphothreonine residues with very little activity against phosphotyrosine residues. The biochemical properties of the enzymes suggested their strong similarity with eukaryotic PP2A and PP2B protein phosphatases. Both enzymes preferentially dephosphorylated the alpha subunit of phosphorylase kinase, and were resistant to inhibitor-1. The PP2A-like enzyme required Mn2+ for activity and was inhibited by nanomolar concentrations of okadaic acid (OA). The cDNA sequence of the PP2A-like enzyme was identified through a match of its predicted amino acid sequence with the N-terminal sequence of the catalytic subunit. The PP2B-like (calcineurin) enzyme was stimulated by calmodulin and Ca2+ or Ni2+, but was resistant to OA. Malarial calcineurin was strongly and specifically inhibited by cyclosporin A (CsA) only in the presence of wild type P. falciparum cyclophilin but not a mutant cyclophilin. The inhibition was noncompetitive, and provides a potential explanation for the cyclosporin-sensitivity of the parasite. There was no significant quantitative difference in the total protein Ser/Thr phosphatase activity among the ring, trophozoite, and schizont stages.

Amino Acid Sequence↗
PubMed1999

Comparison between premortem and postmortem serum concentrations of phenobarbital, phenytoin, carbamazepine and its 10,11-epoxide metabolite in institutionalized patients with epilepsy.

The last premortem serum concentrations of phenobarbital (PB), phenytoin (PHT), carbamazepine (CBZ) and its CBZ-10,11-epoxide metabolite (CE) were compared with the corresponding postmortem serum concentrations in 16 adult patients of an epilepsy centre. Based on complete postmortem examinations, 12 individuals showed a known cause of death (KCD) and four patients succumbed from sudden unexplained death (SUD). The last premortem and the postmortem serum levels of PB (r = 0.991), PHT (r = 0.986), CBZ (r = 0.985) and CE (r = 0.936) were highly correlated. However, the regression analysis indicated that, except for CE, the premortem concentrations were significantly higher than the postmortem concentrations, i.e. 65% for PB, 34% for PHT, and 16% for CBZ. Varying time lapses (4-62 h) between death and serum sampling during autopsy did not significantly influence the ratio of premortem to postmortem serum levels for PB, PHT, CBZ, and CE (p > 0.1). Furthermore we found no significant differences between the premortem and the postmortem serum concentration ratios CE/CBZ. Considering the above variables, the data of SUD and KCD patients were comparable. Postmortem decrease in anticonvulsant serum concentrations, especially for PB and PHT, should be considered in order to avoid misinterpretation in respect to so-called 'subtherapeutic' serum levels and noncompliance in context with SUD or fatal intoxication.

Adult↗
PubMed1999

Bioethics in a liberal society--political, not moral.

This paper argues for the importance of the political context of a society for bioethics. In particular, I argue that in a liberal constitutional society, such as the one we find ourselves in, no particular moral perspective is granted a privileged position. Rather, individuals are allowed to live their lives according to values they adopt for themselves, and the rights granted to protect this ability "trump" social consensus, and place boundaries on the social application of personal moral beliefs and values.

Bioethical Issues↗
PubMed1999

[Disseminated infestation of Enterocytozooon bieneusi a an HIV-infected patient].

An HIV-positive patient developed disseminated Enterocytozoon bieneusi infection. The parasite was identified in stool, duodenal biopsy, nasal discharge, and sputum specimens using transmission electron microscopy. Albendazole therapy failed to improve the symptoms or eradicate the parasite. The patient survived for nine months after the diagnosis of E. bieneusi infection.

AIDS-Related Opportunistic Infections↗
PubMed1998

A protein import receptor in pea chloroplasts, Toc86, is only a proteolytic fragment of a larger polypeptide.

The protein import complex of the chloroplastic outer envelope (Toc-complex) contains a prominent subunit of 86 kDa molecular weight (Toc86). Toc86 was identified as a putative precursor receptor. The Arabidopsis genome sequencing project indicates that Toc86 represents only a proteolytic fragment of a larger polypeptide of 160 kDa. The 160-kDa protein, which we name Toc160, is only present in significant amounts in pea chloroplasts isolated under stringent conditions. The capacity of chloroplasts to import an in vitro translated precursor protein correlates well with the integrity of Toc160. We conclude that Toc160 is still a bonafide subunit of the protein import machinery of chloroplasts.

Amino Acid Sequence↗
PubMed1998

Efficacy and safety of stavudine and didanosine combination therapy in antiretroviral-experienced patients.

OBJECTIVES: To assess the efficacy, tolerance, and safety of combination antiretroviral therapy with didanosine and stavudine in HIV-infected patients with CD4+ cell counts > 100 x 10(6)/l and HIV plasma RNA > 10(4) copies/ml previously treated with other antiretroviral agents for at least 3 months. DESIGN: In this open, multicentre, non-randomized, Phase II pilot study, adult patients were administered didanosine (200 mg twice daily) plus stavudine (40 mg twice daily) for 6 months. Patients for whom the first regimen had led to undetectable HIV RNA levels were offered a second 6-month course of treatment; those who had achieved insufficient immunological and virological gains in the first 6 months were given a new combination. METHODS: Primary evaluation of efficacy was based on viral load measured by branched DNA second-generation testing (lower limit of detection, 500 copies/ml) and CD4+ cell counts; secondary evaluations included AIDS-defining events and clinical side-effects. RESULTS: Sixty-five patients with median prior antiretroviral therapy of 24 months (65 with zidovudine, 29 with zalcitabine) were included in the study. At baseline, median CD4+ cell count was 198 x 10(6)/l and median plasma HIV RNA was 80000 copies/ml (4.9 log10 copies/ml). In this heavily pretreated population, an increase in the mean CD4+ cell count was observed (+70 x 10(6)/l at 24 weeks). In addition, rapid and prolonged antiviral activity was seen, with a mean maximal decrease of 1.1 log10 copies/ml at week 4, a mean decrease of 0.89 log10 copies/ml at week 24, and a plasma RNA viraemia < 500 copies/ml achieved in 14% of patients at week 24. CONCLUSIONS: Combination therapy with stavudine and didanosine is safe and leads to a sustained antiviral effect, even in patients with prolonged prior antiretroviral exposure and low CD4+ cell counts.

Adult↗
PubMed1998

Positive charges determine the topology and functionality of the transmembrane domain in the chloroplastic outer envelope protein Toc34.

The chloroplastic outer envelope protein Toc34 is inserted into the membrane by a COOH-terminal membrane anchor domain in the orientation Ncyto-Cin. The insertion is independent of ATP and a cleavable transit sequence. The cytosolic domain of Toc34 does not influence the insertion process and can be replaced by a different hydrophilic reporter peptide. Inversion of the COOH-terminal, 45-residue segment, including the membrane anchor domain (Toc34Cinv), resulted in an inverted topology of the protein, i.e., Nin-Ccyto. A mutual exchange of the charged amino acid residues NH2- and COOH-proximal of the hydrophobic alpha-helix indicates that a double-positive charge at the cytosolic side of the transmembrane alpha-helix is the sole determinant for its topology. When the inverted COOH-terminal segment was fused to the chloroplastic precursor of the ribulose-1,5-bisphosphate carboxylase small subunit (pS34Cinv), it engaged the transit sequence-dependent import pathway. The inverted peptide domain of Toc34 functions as a stop transfer signal and is released out of the outer envelope protein translocation machinery into the lipid phase. Simultaneously, the NH2-terminal part of the hybrid precursor remained engaged in the inner envelope protein translocon, which could be reversed by the removal of ATP, demonstrating that only an energy-dependent force but no further ionic interactions kept the precursor in the import machinery.

Adenosine Triphosphate↗
PubMed1998

Long-lasting effects of chronic mu-opioid intake on the signal transmission via dopamine D1 receptors in the limbic forebrain of drug deprived rats.

Rats orally self-administered the potent and selective mu-opioid receptor agonist etonitazene for 8 weeks (free choice between three opioid solutions and water resulting in low drug intake, or forced intake of a single drug solution resulting in high opioid consumption). The signal transmission in membranes of the limbic forebrain (nucleus accumbens and olfactory tubercle) was studied during acute withdrawal (2 days of abstinence) and after 6 weeks of drug deprivation. Binding experiments with the dopamine (DA) D1 receptor antagonist [3H]SCH23390 revealed in the high consuming rats an increased binding density (Bmax) by 19% during withdrawal and a decreased Bmax by 17% after long-term abstinence compared with drug-naive controls (each P < 0.05). The addition of 500 nM DA reduced the [3H]SCH23390 binding affinity (Kd increased by 60-105%) and density (by 15-23%) in each of the five groups (P < 0.001). During acute withdrawal, the portion of Bmax inhibited by DA increased by 83% in the high consuming rats vs. the controls (P < 0.05). Full concentration-response curves of adenylyl cyclase (AC) stimulation by the DA D1 receptor agonist dihydrexidine and of inhibition of forskolin stimulated AC activity by the GTP analogue guanosine-5'-O-(3-thio)triphosphate (GTPgammaS) were performed: the former revealed a reduced maximum efficacy (Emax decreased by 23-37%), P < 0.001), the latter a reduced effective concentration (EC50 decreased by 60-103%, P < 0.05), in each etonitazene-experienced group vs. the controls.

Adenylyl Cyclase Inhibitors↗
PubMed1998

Enterocytozoon bieneusi multiorgan microsporidiosis in a HIV-infected patient.

Multiorgan microsporidiosis due to Enterocytozoon bieneusi was diagnosed in an HIV-infected patient. The parasite was found and identified as E. bieneusi by transmission electron microscopy in stools, duodenal biopsy, nasal discharge and sputum. No clinical improvement or parasite eradication was obtained after albendazole therapy, but the patient remained alive 9 months after diagnosis.

AIDS-Related Opportunistic Infections↗