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M Martinez

Publications and source records attributed to M Martinez.

At least 127 records · Page 7Linked to original sources

Patterns of parental transmission and familial aggregation models in bipolar affective disorder.

Two recent studies [McMahon et al., 1995: Am J Hum Genet 56:1277-1286; Gershon et al., 1996: Am J Med Genet (Neuropsychiatr Genet) 67:202-207] reported an excess of maternal transmission in bipolar affective disorder in multiply affected families. In a sample of 130 families ascertained through a bipolar proband without regard to psychiatric family history we analysed the frequency of maternal (MAT) and paternal (PAT) transmissions, the morbid risk (MR) in relatives of transmitting mothers and fathers and the inheritance patterns in families with MAT vs. PAT transmission of the disease. In the total sample of 130 families we identified 39 families where the disease was transmitted from the paternal side (PAT families) and 35 families where the disease was transmitted from the maternal side (MAT families). Counting PAT and MAT transmissions in these unilineal families we found nearly equal numbers for both transmission types under a narrow (BP: bipolar disorder, schizoaffective-bipolar type disorder) and a broad definition (AFF: BP, recurrent unipolar depression) of the phenotype. The MRs for narrow and broad phenotypes were not significantly different in any type of PAT relative in PAT families vs. MAT relatives in MAT families. However, in PAT families there were two times more affected females than males with both disease models, while in MAT families there was no MR difference by relatives' sex. The transmission of BP was compatible with the Mendelian major gene model in PAT families and with the multifactorial model in MAT families. Extension of the relatives' phenotype led to borderline non-Mendelian major effects in PAT families and reproduced the multifactorial model in MAT families.

Bipolar Disorder↗

New susceptibility locus for rheumatoid arthritis suggested by a genome-wide linkage study.

Rheumatoid arthritis (RA), the most common autoimmune disease, is associated in families with other autoimmune diseases, including insulin-dependent diabetes mellitus (IDDM). Its genetic component has been suggested by familial aggregation (lambdas = 5), twin studies, and segregation analysis. HLA, which is the only susceptibility locus known, has been estimated to account for one-third of this component. The aim of this paper was to identify new RA loci. A genome scan was performed with 114 European Caucasian RA sib pairs from 97 nuclear families. Linkage was significant only for HLA (P < 2.5.10(-5)) and nominal for 19 markers in 14 other regions (P < 0.05). Four of the loci implicated in IDDM potentially overlap with these regions: the putative IDDM6, IDDM9, IDDM13, and DXS998 loci. The first two of these candidate regions, defined in the RA genome scan by the markers D18S68-D18S61-D18S469 (18q22-23) and D3S1267 (3q13), respectively, were studied in 194 additional RA sib pairs from 164 nuclear families. Support for linkage to chromosome 3 only was extended significantly (P = 0.002). The analysis of all 261 families provided a linkage evidence of P = 0. 001 and suggested an interaction between this putative RA locus and HLA. This locus could account for 16% of the genetic component of RA. Candidate genes include those coding for CD80 and CD86, molecules involved in antigen-specific T cell recognition. In conclusion, this first genome scan in RA Caucasian families revealed 14 candidate regions, one of which was supported further by the study of a second set of families.

Arthritis, Rheumatoid↗

Anticipation in schizophrenia: no evidence of expanded CAG/CTG repeat sequences in French families and sporadic cases.

A decrease in age of onset of schizophrenia through consecutive family generations (anticipation) has been found in several studies. Anticipation is known to result from expansion of CAG repeats in genes that determine several neurodegenerative disorders. In a previous study we analysed 26 unilineal two-generation French pedigrees and found clinical evidence of anticipation. A 10-year mean reduction in age of onset of schizophrenia was found in the second generation compared with the parental generation. The repeat expansion detection method was used to screen for CAG expansion in 21 of the 26 families with evidence of anticipation for the disease and in 59 sporadic schizophrenics and 59 controls. Comparison of the frequency distributions of CAG/CTG repeat size observed in schizophrenics and controls showed no significant difference, even when we considered familial (P = 0.23) and sporadic (P = 0.25) affected individuals separately. These results do not support the association between long CAG repeats and schizophrenia. However, the possibility that expansions with fewer than 40 repeats are involved in schizophrenia cannot be excluded.

Adult↗

ACTH and beta-endorphin in transcendental meditation.

We have evaluated the effect of Transcendental Meditation (TM) on the hypothalamo-hypophyseal-adrenal axis diurnal rhythms through the determination of hormone levels. Blood samples were taken at 0900 hours. and at 2000 hours. These samples were taken from 18 healthy volunteers who regularly practice TM and from nine healthy non-meditators. Cortisol, beta-endorphin, and adrenocorticotropic hormone (ACTH) were measured at both hours. TM practitioners showed no diurnal rhythm for ACTH and for beta-endorphin (ACTH, pg/mL, mean +/- SE; 13.8+/-1.2 - 12.1+/-1.5/beta-endorphin, pg/mL; 14.4+/-1.5 - 17.2+/-1.9, at 0900 hours and 2000 hours, respectively), in contrast to control subjects, who showed normal diurnal rhythm for these hormones and for cortisol (ACTH, pg/mL; 19.4+/-1.9 - 11.9+/-2.2/beta-endorphin, pg/mL; 25.4+/-1.7 - 17.7+/-1.1/Cortisol, ng/mL; 201.4+/-13.2 - 71.3+/-6.5, at 0900-2000 hours, respectively, p < 0.01 in the three cases). Practitioners of TM with similar anxiety levels to those of the control group showed a different pattern in the daytime secretion of pituitary hormones. TM thus appears to have a significant effect on the neuroendocrine axis. Because cortisol levels had a normal pattern in the TM group, these results may be due to a change in feedback sensitivity caused by this mental technique.

Adrenocorticotropic Hormone↗

Apolipoprotein E epsilon4 allele and familial aggregation of Alzheimer disease.

OBJECTIVE: To investigate the relationship among risk for Alzheimer disease (AD), familial aggregation of AD, and the apolipoprotein E (apoE) epsilon4 allele in first-degree relatives of probands with AD and known apoE genotype. PATIENTS: Two hundred ninety subjects fulfilling the criteria of the National Institute of Neurological Communicative Disease and Stroke-Alzheimer's Disease and Related Disorders Association for probable AD were ascertained from March 1, 1992, to December 31, 1996, through consecutive admissions in several university hospitals. DESIGN AND METHODS: Family data were collected on 1176 first-degree relatives (parents and siblings), aged 40 to 90 years. Most living relatives underwent a clinical examination, whereas we relied on family history for clinical data for deceased or unavailable relatives. First, we conducted standard survival analyses to estimate cumulative lifetime risk (LTR) for AD among relatives and to investigate for sex and apoE genotype effects on LTR. Then, we assessed to what extent clustering of secondary AD could be explained by the apoE epsilon4 allele by deriving the expected proportions of relatives with 0, 1, or 2 apoE epsilon4 alleles conditionally on the proband's genotype. RESULTS: Cumulative LTR for AD among first-degree relatives increased significantly with the number of epsilon4 alleles present in the proband. By 90 years of age, LTRs in relatives of probands with epsilon3/epsilon3, epsilon3/epsilon4, and epsilon4/epsilon4 genotypes were 29.2%, 46.1%, and 61.4%, respectively. Significant sex-by-apoE genotype interaction effects on LTR were observed. Women had about a 2-fold higher risk for AD than men among relatives of epsilon4 carriers but not among relatives of non-epsilon4 carriers. The predicted proportion of epsilon4 carriers in relatives of probands with epsilon3/epsilon3 genotype remains about 50% lower than the corresponding LTR for AD, indicating that familial clustering of AD is largely due to other factors than the apoE epsilon4 allele. Although aggregation of AD in families of probands with the epsilon4 allele is more prominent, we estimated that AD would not develop in about 30% of female and up to 60% of male relatives carrying at least 1 epsilon4 allele, even by 90 years of age. CONCLUSION: Our results support the hypothesis that the apoE epsilon4 allele enhances AD susceptibility, but putative factors enhancing risk for AD remain to be found.

Adult↗

Clinical approach to inherited peroxisomal disorders: a series of 27 patients.

To illustrate the clinical and biochemical heterogeneity of peroxisomal disorders, we report our experience with 27 patients seen personally between 1982 and 1997. Twenty patients presented with a phenotype corresponding either to Zellweger syndrome, neonatal adrenoleukodystrophy, or infantile Refsum disease, 3 of whom had a peroxisomal disorder due to a single enzyme defect. One patient had a mild form of rhizomelic chondrodysplasia punctata, 1 had classic Refsum disease. Finally, 5 patients presented with clinical manifestations that were either unusually mild or completely atypical, and initially did not arouse suspicion of a peroxisomal disorder. They showed multiple defects of peroxisomal functions with one or several functions remaining intact, suggesting a peroxisome biogenesis disorder. The defect in peroxisome biogenesis was further characterized by variable expression in different tissues and/or individual cells in 5 patients. Studies restricted to fibroblasts failed to identify abnormalities in this group. We demonstrate that clinical manifestations of peroxisomal disorders may be very mild or completely atypical, and therefore, peroxisomal disorders should be considered in a variety of clinical settings. Furthermore, we suggest performing extensive peroxisomal investigations in every patient suspected of suffering from a peroxisomal disorder, even when the clinical presentation is typical.

Adult↗

Prenatal care in cocaine-exposed pregnancies.

OBJECTIVE: To examine the effect of prenatal care with and without drug rehabilitation on perinatal outcome in cocaine-using women. METHODS: Cocaine-exposed pregnancies of 905 human immunodeficiency virus (HIV)-negative women were frequency matched (ratio 6:1) and compared with 150 nonusers. Cocaine subgroups consisted of 278 women who received prenatal care and drug rehabilitation ("comprehensive care"), 206 women who received prenatal care only, and 421 who received neither. Maternal and fetal complications, drug screening, and attendance were recorded. Pregnancy rates and HIV seroconversion were determined over the year following delivery. RESULTS: The groups were similar in age, race, education and poverty level. Linear trends of increasing incidence of maternal complications were seen across the four groups. Comparing nonusers with cocaine users, the odds ratios, with 95% confidence intervals were: 28.0 (4.2, 103.2) for both anemia and weight under 100 lb; 2.4 (1.8, 5.0) for urinary tract infections; 15 (4.6, 36.1) for syphilis; and 11.2 (4.0, 35.8) for other sexually transmitted diseases. Perinatal outcome measures were similar for nonusers and "comprehensive care" groups but significantly worse for the other two groups. Four maternal deaths and two myocardial infarctions occurred with no care. Positive toxicology at delivery was 1.5 and 4.3 times more likely for the two groups without drug treatment, than for "comprehensive care." Congenital anomalies and HIV seroconversion increased in cocaine users. Repeat pregnancy was less likely and more often drug free with "comprehensive care." CONCLUSION: "Comprehensive care" of the cocaine-using gravida increases the likelihood of carrying to term, having fewer complications, being drug free at delivery, and having fewer exposed repeat pregnancies.

Adult↗

Adaptation in patterns of c-fos expression in the brain associated with exposure to either single or repeated social stress in male rats.

Intraspecific confrontation between male rats represents a biologically relevant form of social stress. C-fos expression has been used to map the pattern of neural activation following either a single (acute) or repeated (10 times) exposure of an intruder male to a larger male in the latter's home cage. These conditions induce high levels of aggressive interaction. Sixty minutes after a single defeat, there was intense c-fos expression (quantified using image analysis) in restricted areas of the basal forebrain (including lateral septum, bed nucleus of stria terminalis, lateral preoptic area, lateral hypothalamic area, paraventricular nucleus, and medial and central amygdala) as well as in the autonomic and monoaminergic nuclei of the brainstem (central grey, dorsal and median raphe, locus coeruleus and nucleus of the solitary tract). After the tenth defeat, this pattern was modified despite persistently high levels of aggression. Some areas in the forebrain (bed nucleus of stria terminalis, paraventricular nucleus and medial amygdala) continued to express increased c-fos; others (the septum, lateral hypothalamic area, lateral preoptic area and central amygdala) no longer expressed c-fos. The brainstem response was equally varied: the central grey and the raphe nuclei continued to respond after repeated defeat, whereas the solitary nucleus and locus coeruleus did not. On the other hand, there was no change in the behaviour of intruder rats after repeated defeat. This study shows the pattern of adaptation at a cellular level in the basal forebrain and brainstem to repeated defeat. As in our previous studies of repeated restraint, modulation in the expression of c-fos following repeated stress is highly regionally specific, suggesting that differential neural processing is involved in adaptation to social stress.

Adaptation, Psychological↗

Light and scanning electron microscopic study of the palatine mucosa of nine-banded armadillo (Dasypus novemcinctus).

The three-dimensional structure of the lamina propria of the hard and soft palatine mucosa of the nine-banded armadillo was observed by scanning electron microscopy. Sodium hydroxide cell maceration method was applied to demonstrate the architecture of the connective tissue papillae. The palatine mucosa of the armadillo had a triangular shape and measured appr. 6.5 cm length. The hard palate showed 9 transverse palatine plicae while the soft palate was smooth. In the 10% NaOH treated specimens, the lamina propria of the hard palatine mucosa showed numerous connective tissue papillae with a general finger-like shape. These structures were composed by a meshwork of collagen fibers arranged in several directions. On the other hand, the connective tissue papillae of the soft palate mucosa were scattered and small. Numerous openings of glandular ducts with circular or elliptical shape were located in the interplicae area and in the soft palate.

Animals↗

Scintigraphic evaluation of malignant melanoma lesions with Tc-99m tetrofosmin.

Two cases of malignant melanoma (primary and metastatic lesions) imaged with Tc-99m tetrofosmin are reported. One patient showed intense uptake in a primary skin lesion of the thorax, and the other patient had accumulation in skin, cerebellum, breast, and lymph node metastases. Like Tc-99m MIBI, Tc-99m tetrofosmin imaging may be of clinical relevance in the evaluation of suspicious skin lesions and in patients with known cutaneous malignant melanoma in the assessment of recurrent disease during follow-up evaluation.

Adult↗

Reasons for dissatisfaction: a survey of relatives of intensive care patients who died.

OBJECTIVE: To describe the reasons for eventual dissatisfaction among the families of patients who died in the intensive care unit (ICU), regarding both the assistance offered during the patient's stay in the hospital and the information received from the medical staff. DESIGN: Cross-sectional descriptive study, which was conducted after a survey using a questionnaire. SETTING: Interdisciplinary ICU (n = 8 beds) at San Giovanni Hospital in Bellinzona (CH). SUBJECTS: Three-hundred ninety families of patients who died in the ICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A postal questionnaire (n = 43 questions) was sent to the families of 390 patients who died in the ICU during 8 yrs (1981 to 1989). The results referred to 123 replies: a) 82.6% of the respondents expressed no criticism of the patient's hospital stay; b) 90% considered the patient's treatment was adequate; c) 17% felt that the information received concerning diagnosis was insufficient or unclear; and d) 30% (particularly close relatives and those relatives who were informed of the death by telephone and not in person) expressed dissatisfaction regarding the information received on the cause of death. CONCLUSIONS: Our survey found that the relatives of patients who died were most dissatisfied with the care received according to: a) the type of death (e.g., sudden death vs. death preceded by a gradual deterioration in the patient's condition); and b) the manner in which the relatives were notified of the death (in person vs. by telephone). The personal characteristics of the people interviewed, such as gender and the closeness of their relationship to the deceased, also seem to have some bearing on the opinions expressed. A high percentage of respondents were satisfied with the treatment received by their dying relative and the information conveyed by caregivers. Nevertheless, the dissatisfaction expressed by some respondents indicates a need for improvement, especially in communicating information to the relatives of these patients.

Adult↗

Detection of recurrent malignant melanoma with 99mTc-MIBI scintigraphy.

Initial reports suggest that 99mTc-methoxyisobutylisonitrile (MIBI) scanning may be of clinical value in staging patients with malignant melanoma. We carried out a study to evaluate the potential of this technique in the detection of recurrent disease. Whole-body 99mTC-MIBI scans were performed in 81 patients with a history of a surgically excised MM: 28 with known recurrent lesions and 53 during follow-up without evidence of disease. Images started 10 min post-injection, using a dose of 740 MBq. Diagnoses were confirmed by cytological/histological examination or at least one conventional imaging modality. Blinded interpretations of the MIBI scans were performed. Whole-body MIBI scanning correctly detected 68 (92%) of 74 metastatic lesions in the following sites: regional lymph nodes (n=23), non-regional lymph nodes (n=10), skin (n=16), brain/cerebellum (n=6), lung (n=8), bone (n=4) and breast (n=1). The technique failed to detect three subcutaneous regressive lesions (< 1 cm), one liver metastasis, one spleen metastasis and a case of multiple small lesions of the duodenal mucous membrane. In 14 patients the procedure detected previously unknown metastatic lesions. These results suggest that 99mTc-MIBI scanning is an effective imaging modality for whole-body screening of metastatic disease in malignant melanoma patients with the potential to influence treatment planning.

Adult↗

Elevated concentrations of eotaxin and interleukin-5 in human neurocysticercosis.

Symptomatic neurocysticercosis, a major cause of epilepsy worldwide, results from inflammation around Taenia solium larvae, but the mechanisms are unknown. Eotaxin, not previously reported in cases of human infection, and interleukin-5 (IL-5) but not IL-8 concentrations were elevated in patient serum, and IL-5 levels were also elevated in cerebrospinal fluid (CSF). Eosinophil-selective mediators may be involved in the pathogenesis of cysticercosis. IL-6 concentrations were also elevated in patient CSF, possibly indicative of an acute-phase response.

Adult↗

First pass metabolism of ethanol is strikingly influenced by the speed of gastric emptying.

BACKGROUND: Ethanol undergoes a first pass metabolism (FPM) in the stomach and liver. Gastric FPM of ethanol primarily depends on the activity of gastric alcohol dehydrogenase (ADH). In addition, the speed of gastric emptying (GE) may modulate both gastric and hepatic FPM of ethanol. AIMS: To study the effect of modulation of GE on FPM of ethanol in the stomach and liver. METHODS: Sixteen volunteers (eight men and eight women) received ethanol (0.225 g/kg body weight) orally and intravenously, and the areas under the ethanol concentration time curves were determined to calculate FPM of ethanol. In seven of these subjects, FPM of ethanol was measured after the intravenous administration of 10 mg metoclopramide (MCP) and 20 mg N-butylscopolamine (NBS) in separate experiments to either accelerate or delay GE. GE was monitored sonographically by integration of the antral area of the stomach every five minutes for 90 minutes after oral ethanol intake. In addition, gastric biopsy specimens were taken to determine ADH activity and phenotype, as well as to evaluate gastric histology. Blood was also drawn for ADH genotyping. RESULTS: GE time was significantly delayed by the administration of NBS as compared with controls (p<0.0001) and as compared with the administration of MCP (p<0.0001). This was associated with a significantly enhanced FPM of ethanol with NBS compared with MCP (p = 0.0004). A significant correlation was noted between GE time and FPM of ethanol (r = 0.43, p = 0.0407). Gastric ADH activity did not significantly correlate with FPM of ethanol. CONCLUSION: FPM of ethanol is strikingly modulated by the speed of GE. Delayed GE increases the time of exposure of ethanol to gastric ADH and may therefore increase gastric FPM of ethanol. In addition, hepatic FPM of ethanol may also be enhanced as the result of slower absorption of ethanol from the small intestine. Thus a knowledge of GE time is a major prerequisite for studying FPM of ethanol in humans.

Administration, Oral↗