Search PubMed⌕ Search

Biomedical subjects

C Gonzales

Publications and source records attributed to C Gonzales.

At least 37 records · Page 2Linked to original sources

Clinical observations of axillary involvement for tubular, lobular, and ductal carcinomas of the breast.

BACKGROUND AND OBJECTIVES: Recently, there has been much interest in identifying primary breast cancer characteristics which have predictive value for axillary metastases. We studied breast cancer patients to determine variables associated with the incidence/extent of axillary involvement and to construct a modeled analysis. METHODS: Patients with invasive ductal, lobular, and tubular breast cancer (group 1, n = 15,719) were analyzed by tumor size and histology for the probability/extent of axillary metastases. A subgroup of patients was analyzed separately for any association of axillary involvement and other variables (group 2). RESULTS: In group 1, the incidence and extent (number of positive lymph nodes) of axillary metastases correlated significantly with histology and increasing tumor size of ductal and lobular histologies. Significant associations for < or = 10% axillary involvement in group 2 were age and S phase for tubular histology and differentiation for ductal histology. In a multivariate analysis, increasing tumor size was the only statistically significant correlate for axillary involvement (group 2) and for increasing number of positive nodes (group 1). CONCLUSIONS: A multivariate model of tumor size and age combined with staging techniques can successfully confirm or assess extent of axillary metastases in breast carcinoma.

Adenocarcinoma↗

Hemoglobin concentration of high-altitude Tibetans and Bolivian Aymara.

Elevated hemoglobin concentrations have been reported for high-altitude sojourners and Andean high-altitude natives since early in the 20th century. Thus, reports that have appeared since the 1970s describing relatively low hemoglobin concentration among Tibetan high-altitude natives were unexpected. These suggested a hypothesis of population differences in hematological response to high-altitude hypoxia. A case of quantitatively different responses to one environmental stress would offer an opportunity to study the broad evolutionary question of the origin of adaptations. However, many factors may confound population comparisons. The present study was designed to test the null hypothesis of no difference in mean hemoglobin concentration of Tibetan and Aymara native residents at 3,800-4,065 meters by using healthy samples that were screened for iron deficiency, abnormal hemoglobins, and thalassemias, recruited and assessed using the same techniques. The hypothesis was rejected, because Tibetan males had a significantly lower mean hemoglobin concentration of 15.6 gm/dl compared with 19.2 gm/dl for Aymara males, and Tibetan females had a mean hemoglobin concentration of 14.2 gm/dl compared with 17.8 gm/dl for Aymara females. The Tibetan hemoglobin distribution closely resembled that from a comparable, sea-level sample from the United States, whereas the Aymara distribution was shifted toward 3-4 gm/dl higher values. Genetic factors accounted for a very high proportion of the phenotypic variance in hemoglobin concentration in both samples (0.86 in the Tibetan sample and 0.87 in the Aymara sample). The presence of significant genetic variance means that there is the potential for natural selection and genetic adaptation of hemoglobin concentration in Tibetan and Aymara high-altitude populations.

Adaptation, Physiological↗

Ventilation and hypoxic ventilatory response of Tibetan and Aymara high altitude natives.

Newcomers acclimatizing to high altitude and adult male Tibetan high altitude natives have increased ventilation relative to sea level natives at sea level. However, Andean and Rocky Mountain high altitude natives have an intermediate level of ventilation lower than that of newcomers and Tibetan high altitude natives although generally higher than that of sea level natives at sea level. Because the reason for the relative hypoventilation of some high altitude native populations was unknown, a study was designed to describe ventilation from adolescence through old age in samples of Tibetan and Andean high altitude natives and to estimate the relative genetic and environmental influences. This paper compares resting ventilation and hypoxic ventilatory response (HVR) of 320 Tibetans 9-82 years of age and 542 Bolivian Aymara 13-94 years of age, native residents at 3,800-4,065 m. Tibetan resting ventilation was roughly 1.5 times higher and Tibetan HVR was roughly double that of Aymara. Greater duration of hypoxia (older age) was not an important source of variation in resting ventilation or HVR in either sample. That is, contrary to previous studies, neither sample acquired hypoventilation in the age ranges under study. Within populations, greater severity of hypoxia (lower percent of oxygen saturation of arterial hemoglobin) was associated with slightly higher resting ventilation among Tibetans and lower resting ventilation and HVR among Aymara women, although the associations accounted for just 2-7% of the variation. Between populations, the Tibetan sample was more hypoxic and had higher resting ventilation and HVR. Other systematic environmental contrasts did not appear to elevate Tibetan or depress Aymara ventilation. There was more intrapopulation genetic variation in these traits in the Tibetan than the Aymara sample. Thirty-five percent of the Tibetan, but none of the Aymara, resting ventilation variance was due to genetic differences among individuals. Thirty-one percent of the Tibetan HVR, but just 21% of the Aymara, HVR variance was due to genetic differences among individuals. Thus there is greater potential for evolutionary change in these traits in the Tibetans. Presently, there are two different ventilation phenotypes among high altitude natives as compared with sea level populations at sea level: lifelong sustained high resting ventilation and a moderate HVR among Tibetans in contrast with a slightly elevated resting ventilation and a low HVR among Aymara.

Acclimatization↗

Genital infections in the aetiology of late fetal death: an incident case-referent study.

Women with prelabour fetal death in the third trimester were recruited in order to study the association between intra-uterine death and maternal genital colonization of bacteria. Fifty-eight women with verified fetal death were compared with a group of 58 women matched for age, parity and gestational length (the first referent group) and with women delivering liveborn neonates (second referent group). Cultures from the vagina, the endocervix, the amniotic fluid, the placenta, the conjunctivae of the newborn and the secretion of gastric aspirate of the newborn were carried out. Blood was taken for haemoglobin, thick film (malaria) and syphilis and HIV serology. Cases were more affected by previous stillbirths than first referents (OR = 11.88). Preterm delivery was significantly more common in cases than in second referents (OR = 57.70). Cases had significantly more often < 3 ANC visits (OR = 2.81). Cases had a lower body mass index than first referents (OR = 2.38). Temperature > or = 37 degrees C was 12 times more frequent in cases than in first referents (OR = 21.20) and four times more frequent than in second referents (OR = 6.60). Average birth weight among stillborns was 1954 g and in liveborns 3223 g (P = 0.001). The corresponding prevalence of LBW was 78% in cases and 0% among second referents (P < 0.001). Histological chorioamnionitis was significantly prevalent in cases than in second referents (OR = 4.97). Syphilis was significantly more common in cases than in first (OR = 7.71) and in second referents (OR = 5.30).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Pharmacokinetics and pharmacodynamics in copper deficiency. I. Antiinflammatory activity of aspirin.

The effect of nutritional copper (Cu) deficiency on the antiinflammatory activity and pharmacokinetics of aspirin (ASA) was investigated in rats. Male, weanling Sprague-Dawley rats were fed either a Cu-deficient (CuD) or Cu-sufficient (CuS) diet for 49-50 d. The antiinflammatory activity of ASA was studied using the carrageenan-induced paw edema (CPE) test. ANOVA analyses of edema volumes at 2, 3, 4, 5, and 21 h postcarrageenan indicated significant differences between groups. The percent inhibition of edema due to ASA treatment in CuS was lower than that in CuD rats at 5 h, AUC5h, and AUC21h. ASA was found to be significantly more effective in inhibiting the CPE in CuD rats when compared to the CuS rats. Thus, we hypothesized that the increase in ASA's antiinflammatory activity in CuD rats was a result of a decrement in its elimination during nutritional Cu deficiency. The elimination of ASA in CuD and CuS rats was studied using an iv dose of 200 mg/kg. Concentrations of ASA and salicylic acid (SA) were determined in blood; whereas the concentrations of SA, salicylic phenol-glucuronide (SPG), and salicyluric acid (SUA) were determined in urine by HPLC. The results of the pharmacokinetic analyses from blood and urinary data indicated no significant differences in the disposition of ASA between CuD and CuS rats. For instance, the total body clearance for ASA (mean +/- SD, mL/min/kg) was 37.9 +/- 9.4 and 38.5 +/- 13.9 (p > 0.05); and the volume of distribution (Vd) for ASA (mean +/- SD, mL/kg) was 385.5 +/- 110.3 and 397.1.1 +/- 137.9 (p > 0.05) for CuD and CuS groups, respectively. Thus, contrary to our hypothesis, the enhanced antiinflammatory activity of ASA in CuD rats does not appear to be mediated via a decrement in the elimination of the drug. In addition, plasma ASA-esterase activity was found to be independent of Cu nutritional status.

Analysis of Variance↗

Pattern of expression of highly polysialylated neural cell adhesion molecule in the developing and adult rat striatum.

In rats, morphological and synaptic maturation of the striatum, a brain area involved in the control of movement and in cognitive behaviour, proceeds for several weeks postnatally. Little is known, however, about the molecular events associated with the final maturation of the striatum. In particular, there is little information on molecules playing a role in cell adhesion, a phenomenon of particular importance for neuronal development. We have examined the time course and topography of expression of the highly polysialylated form of the neural cell adhesion molecule in the rat striatum during postnatal development and in the adult, and compared it to growth-associated protein-43, a marker of axonal growth. As earlier during development [Aaron L. I. and Chesselet M.-F. (1989) Neuroscience 28, 701-710], immunolabelling for polysialylated neural cell adhesion molecule was very intense in the entire striatum at postnatal days 17-19. At postnatal days 21 and 22, loss of polysialylated neural cell adhesion molecule immunoreactivity in the caudal part of the striatum contrasted with the persistence of immunoreactivity at more rostral levels. Most of the striatum was devoid of polysialylated neural cell adhesion molecule immunoreactivity by postnatal day 25. At this age, as well as in the striatum of adult rats, immunolabelling was only observed along the ventricular edge of the striatum. In contrast to polysialylated neural cell adhesion molecule immunoreactivity, immunolabelling for growth-associated protein-43 had reached its adult pattern by postnatal day 17, indicating that polysialylated neural cell adhesion molecule persists beyond the period of major axonal growth. In the adult, an area of stronger growth associated protein-43 immunoreactivity overlapped with the region which retained immunoreactivity to polysialylated neural cell adhesion molecule. The results indicate that, in the developing rat striatum, the neural cell adhesion molecule remains highly sialylated not only during the ingrowth of cortical and nigral inputs but also during the formation of dendritic spine and synaptogenesis. Loss of polysialyated neural cell adhesion molecule occurs at the time of emerging spontaneous activity in cerebral cortex, and precedes the development of mature responses to cortical stimulation and adult membrane properties in a majority of striatal neurons.

Animals↗

Anthropometry and lung function of 10- to 12-year-old Bolivian boys.

Anthropometric measurements of 23 HAHSES, 44 HALSES, 43 LAHSES, and 28 LALSES boys (see Introduction to this Supplement) are presented here. They include body height (H), body weight (BW), upper arm circumference (UAC), and skinfold thickness taken at four locations. From these measurements, body fat, lean body mass, and body mass index (BMI = BW/H2) were calculated. The degree of maturation was assessed according to Tanner, orchidometry, and by quantification of testosterone in saliva. Lung function data include: vital capacity (VC), forced expired volume per 1 s (FEV1), functional residual capacity (FRC), residual volume (RV), and total lung capacity (TLC). The results show enhanced lung volumes in both HA groups in comparison to LA groups, with HALSES boys having the greatest increase, even though the LSES boys were significantly smaller compared to the HSES boys at both altitudes and their growth was delayed by approximately 2 years. From the anthropometric data it appears that physical growth of prepubertal boys is dependent on SES but not on high-altitude exposure. We tentatively conclude that chronic hypoxia per se does not affect physical growth in prepubertal boys in an Andean environment and that development of lung function is accelerated in relation to linear growth as has been suggested by other authors (15).

Altitude↗

[Results of unilateral adrenalectomy for primary hyperaldosteronism].

From 1970 to 1992, 57 patients underwent unilateral adrenalectomy for primary hyperaldosteronism. All were hypertensive and the biochemical profile was diagnosed in all cases but two. 44 out of 57 were operated on using to the posterior Young Mayor approach. The present series included 44 macroadenomas > or = 1 cm in diameter (21 > 2 cm; 23 < or = 2 cm), 7 microadenomas (< 1 cm), 3 associations of macro and microadenomas and 3 cases of unilateral hyperplasia. All were biochemically cured. 4/57 patients remained hypertensive postoperatively (3/44 macroadenomas and 1/3 unilateral hyperplasia). There were two late recurrences, which were both clinical and biochemical (2 macroadenomas < or = 2 cm), and one of these was reoperated on for contralateral multiple "adenomas". Pathological background was defined by preoperative imaging studies with a sensitivity of 100% for MRI (23 cases), 96% for CT-scan (52 cases), 73% for NP 59 scanning (15 cases), 38% for sonography (16 cases) and 85% for venous sampling (7 cases). Cure of hyperaldosteronism or hypertension after unilateral adrenalectomy was therefore not predictable by the pathological background. If a firm diagnosis of primary hyperaldosteronism has been made and the unilaterality of the disease has been established, the patient should be operated. Even adrenalectomy for unilateral hyperplasia can lead to cure, and the syndrome can recur after removal of a solitary macroadenoma.

Adrenalectomy↗

Is microalbuminuria part of the prediabetic state? The Mexico City Diabetes Study.

Microalbuminuria is associated with increased cardiovascular mortality in both diabetic and non-diabetic subjects. A number of studies have indicated that insulin resistance, increased blood pressure and dyslipidaemia precede the onset of clinical diabetes. We examined various correlates of microalbuminuria in 1,298 non-diabetic subjects who participated in the Mexico City Diabetes Study, a population-based study of diabetes and cardiovascular risk factors. Both parental history of diabetes and impaired glucose tolerance were significantly associated with microalbuminuria. These results were not explained by differences in age or blood pressure between subjects with or without a parental history of diabetes or impaired glucose tolerance. In addition, subjects with microalbuminuria had increased 2-h insulin and triglyceride concentrations, a higher prevalence of hypertension, and decreased high density lipoprotein cholesterol concentrations relative to subjects without microalbuminuria. These results that microalbuminuria may be a feature of the prediabetic state.

Albuminuria↗

Messenger RNAs encoding glutamate-decarboxylases are differentially affected by nigrostriatal lesions in subpopulations of striatal neurons.

Dopaminergic nigrostriatal neurons constitute one of the major inputs to the striatum, and play a role in the regulation of gamma-aminobutyric acid (GABA) and glutamic acid decarboxylase (GAD), the GABA-synthesizing enzyme, in striatal neurons. The effect of nigrostriatal lesions on the level of expression of messenger RNAs encoding two distinct isoforms of glutamate decarboxylase was examined at the single cell level with in situ hybridization histochemistry. Rats received a unilateral injection of the neurotoxin 6-hydroxydopamine in the substantia nigra and were sacrificed 2 or 3 weeks later. Sections of the striatum were processed for in situ hybridization histochemistry with radiolabeled RNA probes selective for mRNAs encoding glutamate decarboxylase with molecular weights of 65,000 and 67,000, respectively. In addition, immunohistochemistry with a monospecific antibody for the latter glutamate decarboxylase isoform was performed. In agreement with previous reports, we observed increased labeling for the messenger RNA encoding glutamate decarboxylase (M(r) 67,000) in a population of medium-sized striatal efferent neurons normally expressing low levels of this messenger RNA. We now show that this effect occurred in two striatal compartments, the striosomes and the extrastriosomal matrix, and was accompanied by increased immunostaining for the corresponding protein with a monospecific antibody. In contrast, labeling for messenger RNA encoding GAD (M(r) 67,000) was decreased in a population of medium-sized neurons normally expressing high levels of this messenger RNA and corresponding to GABAergic interneurons. Labeling for messenger RNA encoding glutamate decarboxylase (M(r) 65,000) was not modified in the dopamine-depleted striatum. The results show that dopamine depletion differentially affects gene expression for different isoforms of glutamate decarboxylase in distinct subpopulations of striatal neurons in rat.

Animals↗

Relative sparing of GABAergic interneurons in the striatum of gerbils with ischemia-induced lesions.

Striatal gamma-aminobutyric acid (GABA)ergic interneurons express intense immunoreactivity to glutamic acid decarboxylase (GAD), GABA and parvalbumin. The distribution of these cells in the striatum of gerbils was examined 2-90 days after transient occlusion of the common carotid, a procedure which results in a zone of profound neuronal loss in the dorso-lateral sector of the head of the caudate-putamen (striatum), with relative sparing of somatostatinergic and cholinergic interneurons. Despite a marked decrease in GAD immunoreactivity corresponding to the loss of striatal efferent neurons in this area, isolated neurons expressing intense immunoreactivity to GAD and parvalbumin were still observed in the lesioned area, suggesting that striatal GABAergic interneurons are also relatively spared by ischemic insult in the adult gerbil.

Animals↗

Neuropsychological and structural brain lesions in multiple sclerosis: a regional analysis.

Quantified lesion scores derived from MRI correlate significantly with neuropsychological testing in patients with multiple sclerosis (MS). Variables used to reflect disease severity include total lesion area (TLA), ventricular-brain ratio, and size of the corpus callosum. We used these general measures of cerebral lesion involvement as well as specific ratings of lesion involvement by frontal, temporal, and parieto-occipital regions to quantify the topographic distribution of lesions and consequent effects upon cognitive function. Lesions were heavily distributed in the parieto-occipital regions bilaterally. Neuropsychological tests were highly related to all generalized measures of cerebral involvement, with TLA being the best predictor of neuropsychological deficit. Mean TLA for the cognitively impaired group was 28.30 cm2 versus 7.41 cm2 for the cognitively intact group (p less than 0.0001). Multiple regression analyses revealed that left frontal lobe involvement best predicted impaired abstract problem solving, memory, and word fluency. Left parieto-occipital lesion involvement best predicted deficits in verbal learning and complex visual-integrative skills. Analysis of regional cerebral lesion load may assist in understanding the particular pattern and course of cognitive deficits in MS.

Adult↗

Distribution of glutamic acid decarboxylase (Mr 67,000) in the basal ganglia of the rat: an immunohistochemical study with a selective cDNA-generated polyclonal antibody.

Distinct isoforms of glutamic acid decarboxylase, the synthetic enzyme for GABA, exist in brain. Their distribution at the cellular level is not known, because previous studies have been confounded by the lack of monospecificity of available antibodies. We have examined the distribution of glutamic acid decarboxylase (Mr 67,000; GAD67) in the basal ganglia of the rat with a polyclonal antibody generated against the protein expressed in bacteria transformed with the corresponding cDNA. This antibody, which is directed against a portion of GAD67 non homologous to other known glutamic acid decarboxylase isoforms, selectively recognizes GAD67 on western blots. We show that GAD67 is present to various degree in all types of GABAergic neurons previously described in these regions. In contrast with results obtained with non-selective antibodies for glutamic acid decarboxylase, GAD67-positive neuronal cell bodies were readily detected in sections of the striatum, pallidum and substantia nigra in the absence of colchicine treatment. Modifications in the immunohistochemical procedure favoured staining of glutamic acid decarboxylase-positive fibres with the same antibody, indicating that GAD67 is also present in axon terminals of GABAergic neurons. The results suggest that GAD67 may be involved in GABA synthesis in both cell bodies and axon terminals of all GABAergic neurons of the basal ganglia, but is particularly abundant or accessible in their cell bodies.

Animals↗