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Biomedical subjects

P Martin

Publications and source records attributed to P Martin.

At least 487 records · Page 27Linked to original sources
PubMed1995

High-dose cyclophosphamide, carmustine, and etoposide followed by allogeneic bone marrow transplantation in patients with lymphoid malignancies who had received prior dose-limiting radiation therapy.

PURPOSE: To evaluate a high-dose chemotherapy regimen without total-body irradiation (TBI) followed by allogeneic (allo) bone marrow transplantation (BMT) in patients with lymphoid malignancies who had received prior dose-limiting radiotherapy. PATIENTS AND METHODS: Fifty-six patients with non-Hodgkin's lymphoma (NHL, n = 26), Hodgkin's disease (HD, n = 17), or acute lymphoblastic leukemia (ALL, n = 13) with a history of previous radiation therapy were treated with cyclophosphamide (7.2 g/m2), carmustine (300 mg/m2 or 600 mg/m2), and etoposide (2,400 mg/m2; CBV) followed by allo BMT. RESULTS: Nine of 56 patients are alive and disease-free a median of 1,091 (range, 512 to 1,784) days post-transplant. The probabilities of transplant-related mortality, relapse, and event-free survival at 2 years for the entire group of 56 patients were .62, .59, and .17, respectively. Patients who received 600 mg/m2 of carmustine had a higher incidence of grade 3 or 4 regimen-related toxicities (RRTs) (14 of 22) than did patients who received 300 mg/m2 (12 of 33; P < .04), whereas there was no difference in relapse (.34 and .53, respectively, P = .73). Fourteen of 16 patients who received allo BMT for advanced disease (n = 12) or less-advanced disease (n = 4) but who were also eligible for auto BMT relapsed (n = 4) or died of transplant-related complications (n = 10). CONCLUSIONS: Allo BMT following a high-dose CBV regimen resulted in long-term disease-free survival in 17% of patients with lymphoid malignancies who had received prior dose-limiting radiotherapy. A high incidence of transplant-related complications, especially fatal idiopathic pneumonia syndrome (IPS) and a high relapse rate limited success. Morbidity and mortality associated with carmustine 600 mg/m2 were high and were not associated with a decrease in relapse. The number of patients in this study eligible for either allo or auto BMT was limited and precluded meaningful analysis of relative effectiveness.

Adolescent↗
PubMed1995

Effects of racist provocation and social support on cardiovascular reactivity in African American women.

It has been speculated that exposure to the chronic stress of racism contributes to the high rates of hypertension among African Americans. Social support may buffer the effects of stress on cardiovascular (CV) health by attenuating stress-induced CV responses that have been linked to hypertension. In this study we investigated the effects of racism and social support on CV reactivity in African American women. Participants showed greater increases in CV and emotional responses while responding and listening to racist provocation. Augmented blood pressure (BP) persisted through recovery following racial stress. Participants receiving no support showed the greatest increases in anger during racist provocation. No significant effects were seen for support on CV reactivity. These results provide some of the first evidence that interactive confrontation with racism elicits significant increases in CV reactivity and emotional distress. Furthermore, individuals receiving less support may be at greater risk for the potentially health-damaging effects of racial stress. These findings may have significant implications for the health of African Americans.

Journal Article↗
PubMed1995

Transformation of the germ line into muscle in mes-1 mutant embryos of C. elegans.

Mutations in the maternal-effect sterile gene mes-1 cause the offspring of homozygous mutant mothers to develop into sterile adults. Lineage analysis revealed that mutant offspring are sterile because they fail to form primordial germ cells during embryogenesis. In wild-type embryos, the primordial germ cell P4 is generated via a series of four unequal stem-cell divisions of the zygote. mes-1 embryos display a premature and progressive loss of polarity in these divisions: P0 and P1 undergo apparently normal unequal divisions and cytoplasmic partitioning, but P2 (in some embryos) and P3 (in most embryos) display defects in cleavage asymmetry and fail to partition lineage-specific components to only one daughter cell. As an apparent consequence of these defects, P4 is transformed into a muscle precursor, like its somatic sister cell D, and generates up to 20 body muscle cells instead of germ cells. Our results show that the wild-type mes-1 gene participates in promoting unequal germ-line divisions and asymmetric partitioning events and thus the determination of cell fate in early C. elegans embryos.

Animals↗
PubMed1995

Centenarians: their memories and future ambitions.

Research investigating how the recall of one's past functions in maintaining psychological well-being and/or adaptation to the aging process is widely scattered and generally inconclusive with regard to significant findings. One way to address the lack of a systematic research thrust is to replicate previous work. The purpose of the study reported herein was to replicate Costa and Kastenbaum's 1967 study of the relationship between past memories and future ambitions of centenarians using data from the Georgia Centenarian Study. Ninety-seven centenarians and 189 eighty- and sixty-year-olds were asked the same four questions as found in the Costa and Kastenbaum study. Contrary to Costa and Kastenbaum's results, no significant relationship was found between the ability to recall three types of past events and being able to conceive of the future in the Georgia study. Other similarities and differences in findings between the two studies are discussed.

Adaptation, Psychological↗
PubMed1995

Cerebral blood flow in just detoxified alcohol dependent patients. A 99 m Tc-HMPAO-SPECT study.

Chronic alcohol abuse is responsible for several organic brain disorders. However, even the most characteristic of them are largely underdiagnosed by routine procedures. Therefore, there is need for sensitive, noninvasive and low-cost diagnostic procedures. 99m-Tc-HMPAO-SPECT could be an interesting candidate in this indication, because it estimates the distribution of the cerebral blood flow and the metabolic activity of the brain with a good resolution. We used this technique in 17 healthy volunteers and in a sample of 50 patients dependent on alcohol, without other major physical or mental disorder. SPECT was performed during the attendance of these patients in an inpatient detoxification program. We observed abnormal SPECT in 34 patients, but only in 2 volunteers (p < 0.001). The main abnormality was heterogeneity of the distribution of the tracer. SPECT abnormalities appear to be due nor to withdrawal syndrome, nor to medication. On the contrary, they are correlated with stigmata of heavy alcoholism. Furthermore, a genetic vulnerability to alcohol was suspected because SPECT abnormalities are more frequent in patients with an history of drinking problems in their relatives.

Adult↗
PubMed1995

1994 Consensus Conference on Acute GVHD Grading.

Grading acute graft-versus-host disease (GVHD) is usually based on quantification of rash, serum bilirubin and diarrhea. Standard criteria have been developed and used for > 20 years by most transplant centers. However, neither the standard GVHD grading system nor any of several revisions has been validated in the context of GVHD prophylaxis with cyclosporine. The 1994 Consensus Conference on Acute GVHD Grading held in Keystone in January 1994 provided an opportunity to: (1) review data regarding these standard criteria; (2) determine if there are sufficient data to revise these criteria; and (3) develop recommendations for reporting results of GVHD prevention trials. Data were provided for 8249 patients from 12 large transplant centers and 2 transplant registries. Standard GVHD grading criteria were found to distinguish different mortality risks and treatment response rates. Analysis of new data suggested that persistent nausea with histologic evidence of GVHD but no diarrhea be included as stage 1 gastrointestinal GVHD. Additional studies were recommended to evaluate heterogeneity of outcome within GVHD grades prior to making further revisions. To improve comparability between publications, reports of GVHD prevention trials should include an accurate description of the grading system used and should report actuarial rates of grades II-IV and III-IV GVHD corrected for graft failure and potential interventions for early relapse. Additional information should include indications for therapy of GVHD and response.

Acute Disease↗
PubMed1995

[Medical economic impact of schizophrenia].

In common with other chronic illness, schizophrenia places a major economic burden on society, in terms of direct costs (in and outpatient care, residential care, drug therapy, etc.) and indirect costs (lost activity and earnings due to illness) and intangible costs (e.g. suffering experienced by the patient and family). Of the psychiatric illness, schizophrenia is by far the most costly: it develops early in life, results in high morbidity, is associated with a high suicide rate, and lacks a standard effective treatment. Analysis of worldwide epidemiological studies published during the last 30 years indicates that the prevalence of schizophrenia ranges from 0.6 to 9 cases per 1,000 population. The prevalence of treatment-resistant schizophrenia ranges from 5 to 30% patients. In other hand, clinical options for the management of treatment-resistant schizophrenia appears to be limited. Clozapine, an antipsychotic agent with relatively weak central antidopaminergic activity, displays atypical pharmacological and clinical properties towards the standard antipsychotics. Furthermore, clozapine is effective in a substantial proportion of patients who are refractory therapy. Although the acquisition cost of clozapine is high in comparison with that of standard antipsychotics, preliminary cost-effectiveness estimates in patients with treatment-resistant schizophrenia suggest that the clinical benefits of the drug (viz improved psychopathology; social functioning and quality of life) may confer medium to long term economic benefits, primarily by reducing the need for psychiatric hospital service.

Adult↗
PubMed1995

Bupropion: a review of its mechanism of antidepressant activity.

BACKGROUND: The mechanism of action of the novel antidepressant bupropion remains unclear after many years of study. A review of the relevant biochemical, in vivo brain microdialysis, electrophysiologic, behavioral, and clinical data clarifies what is known about this unique compound and suggests possible modes of action. METHOD: A panel of 11 experts was convened for a conference to discuss bupropion's mechanism of antidepressant activity. Four of the panelists presented current research findings, followed by a discussion. RESULTS: (1) Biochemical studies suggest down-regulation of postsynaptic beta-adrenoceptors and desensitization of the norepinephrine-stimulated adenylate cyclase in the rat cortex occur only after chronic administration of very high doses of bupropion. (2) In vivo brain microdialysis studies demonstrate that, after chronic administration, there is an enhancement of bupropion-induced increases in extracellular dopamine in the nucleus accumbens. (3) Electrophysiologic data show that with acute dosing, bupropion reduces the firing rates of noradrenergic neurons in the locus ceruleus. The firing rates of dopaminergic neurons are reduced by bupropion in the A9 and A10 areas of the brain, but only at very high doses, and bupropion does not alter the firing rates of serotonergic neurons in the dorsal raphe. (4) Behavioral studies show that the most active metabolite of bupropion, hydroxybupropion (306U73), appears to be responsible for a large part of the compound's effects in animal models of antidepressant activity. (5) Clinical studies indicate that bupropion enhances noradrenergic functional activity as reflected by an increased excretion of the hydroxy metabolite of melatonin, while at the same time producing a presumably compensatory decrease in norepinephrine turnover. In one study, bupropion elevated plasma levels of the dopamine metabolite homovanillic acid in nonresponders, but not in responders. CONCLUSION: The mechanism of action of bupropion appears to have an unusual, not fully understood, noradrenergic link. The bupropion metabolite hydroxybupropion probably plays a critical role in bupropion's antidepressant activity, which appears to be predominantly associated with long-term noradrenergic effects. The mild central nervous system activating effects of bupropion appear to be due to weak dopaminergic mechanisms. There is some evidence that dopamine may contribute to bupropion's antidepressant properties. Antidepressant effects of bupropion are not serotonergically mediated.

Animals↗
PubMed1995

Ultrastructural and morphometric analysis of capillaries surrounding regenerating muscle fibers in rats.

A study was made of the characteristics of the capillaries surrounding regenerating muscle fibers at three different stages of their development. Mepivacaine was injected in the anterior tibial muscles of Wistar rats in order to obtain muscle and capillary degeneration which was followed by muscle and capillary regeneration. Muscles were examined at 4, 8 and 30 days post-injection. Capillaries were subjected to quantitative and qualitative examination using electron microscopy. Results showed the morphological and morphometrical variations taking place in capillaries as the regenerative fiber matures. Changes were most evident in the capillaries surrounding the most immature fibers. It was concluded that although capillary morphology suggests that the supply of blood to regenerative fibers may be hindered, morphometric data appear to indicate no such obstacle.

Animals↗
PubMed1995

Hepatotoxicity of anesthetics and other central nervous system drugs.

A large number of anesthetics, tranquilizers, hypnotic sedatives, and anticonvulsants are used clinically. Although these agents are generally well tolerated, liver injury of differing patterns is well recognized with their use. Knowledge of the likelihood of hepatotoxicity and the characteristic clinical features with these compounds is important as fatal outcomes due to liver failure have been reported with several of these agents. This article describes the potential mechanisms and clinical features of drug hepatotoxicity associated with these compounds.

Anesthetics↗
PubMed1995

Nuclear localization signals, DNA binding, and transactivation properties of quail Pax-6 (Pax-QNR) isoforms.

We reported previously the characterization of Pax-QNR/Pax-6 products expressed in the avian neuroretina. Five proteins (48, 46, 43, 33, and 32 kDa) were characterized, among which the 33 and 32 kDa proteins are devoid of the paired domain. In contrast to the 48-kDa (containing an alternative paired exon 4a) and 46-kDa proteins exclusively located in the nucleus, the 43- (in which the paired exon 5 is spliced out), 33-, and 32-kDa proteins were also found in the cytoplasmic compartment. We report the identification of two nuclear targeting sequences: the basic LKRKLQR region (amino acids 206-212) located in the NH2 terminus of the homeodomain used by the p43 and 33/32 kDa proteins; and the paired exon 5 sequence. A case of human aniridia, where arginine 208 of LKRKLQR is mutated into a tryptophan, has been reported recently. We introduced this mutation into the Pax-QNR p46, p43, and p33/32 proteins. No effect on the nuclear localization or in transactivation potential of the proteins could be observed. Among the several Pax-QNR isoforms characterized, only p46 exhibited DNA-binding and transactivating properties on the Pax-QNR promoter. Deletions of parts of the protein showed that the Pax-6 transactivation domain is located in the carboxyl terminus of the protein.

Amino Acid Sequence↗
PubMed1994

[Bacterial epidemiology of pharyngitis in pediatric private practice].

OBJECTIVES: While viruses are usually the causal agents of common sore throat in children, bacterial infections cannot be distinguished solely on the basis of clinical presentation. Thus most physicians in France prefer to prescribe antibiotics in order to prevent rheumatismal complications of group A streptococcal infections. We updated current epidemiological data on bacterial pharyngitis in paediatric out-patient clinics. METHODS: A prospective study was conducted from March 1 to June 1, 1992 by 9 physicians. Throat swabs were obtained from 102 controls and from 307 patients with acute pharyngitis. Samples were transferred to the same bacteriology laboratory for examination. RESULTS: The mean age of the children was 6.1 years for patients and 7.2 years for controls. Throat swabs were inoculated for culture within a mean delay of 22.6 hours. Cultures were performed on Columbia blood medium with nalidixic acid and colistin then incubated in CO2 enriched atmosphere and on trypticase blood soy medium + 3.5% NaCl. Group A streptococcal strains were identified by search for beta-haemolysis and latex characterisation of group A polyosides. Group A streptococcal strains were found in 8.8% of the controls and 36.8% of the patients. Groups B, C or G streptococci were found in 10.8 et 11.4% of the controls and patients respectively (NS). Arcanobacterium haemolyticum was never isolated. Clinical association of sore throat, erythematous pharyngitis, fever > 38 degrees C and cervical lymph nodes was found in only 33.63% of the sore throat cases with group A streptococcal infection and in 7.73% of those without group A streptococcal infection (p < 0.0001, sensitivity 33%, specificity 92%). CONCLUSION: These results emphasize the necessity either to treat all pharyngitis or to do throat swabs or rapid group A streptococcal tests for diagnosis.

Age Factors↗
PubMed1994

Occurrence of a LINE sequence in the 3' UTR of the goat alpha s1-casein E-encoding allele associated with reduced protein synthesis level.

The E allele of the alpha s1-casein (alpha s1-Cas)-encoding gene is associated with a reduced casein content in milk. Structural analysis of mRNA and sequencing of amplified genomic DNA fragments, have revealed that this allele contains a 457-bp insertion within exon 19 (last untranslated exon). This insert is a truncated long interspersed repeated element (LINE) containing part of the ORF-2, the 3' UTR and the poly(A) tail of the original retroposon. This LINE sequence was found to be highly repeated in the goat genome. The threefold reduction in the amount of alpha s1-CasE mRNA in the total, as well as in the polysomal fractions, as compared with its A counterpart, leads one to suppose either a reduced transcriptional rate of allele E or/and a decreased stability of the relevant mRNA. Northern blot and PCR experiments suggested the setting up of highly stable secondary structures involving the 3' UTR of the alpha s1-CasE transcript. The mRNA folding calculations support such an hypothesis, by base-pairing interactions between the E allele messenger poly(A) tail and a long poly(U)-stretch occurring at the 5' end of the insertion. In addition, since A+U-rich motifs are also present in the truncated LINE insertion, we propose that this extra sequence might be responsible for the lower milk alpha s1-Cas content by reducing the allele E mRNA stability.

Alleles↗
PubMed1994

Characterization of the goat lactoferrin cDNA: assignment of the relevant locus to bovine U12 synteny group.

Lactoferrin (LTF), which is the major iron-binding protein in milk and physiological fluids, belongs to the transferrin family. We report here the sequence of a caprine LTF cDNA, 2411 bp in length, encoding the pre-protein (709 amino acid residues). Sequence comparisons reveal that structural features, including iron-binding sites, cysteine residues involved in disulphide bonds are remarkably conserved between LTF proteins from various species. Of the 5 potential glycosylation sites identified, only one site appears to be conserved between artiodactyls, rodents and humans. Using a somatic cell hybrid panel, the LTF locus was assigned to the bovine U12 syntenic group. This assignment and the localization of the LTF gene on bovine chromosome 22 (BTA 22) by Schwerin et al. (1) using fluorescent in situ hybridization achieves an additional analogy between a synteny group and a chromosome in cattle. Since serum transferrin (STF) had been previously mapped on BTA 1, in cattle LTF and STF loci are not localized on the same chromosome, conversely to the situation observed in humans (HSA 3) and mice (MMU 9).

Amino Acid Sequence↗