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Biomedical subjects

G Martinez

Publications and source records attributed to G Martinez.

At least 55 records · Page 3Linked to original sources
PubMed1999

Hepatopulmonary syndrome associated with cardiorespiratory disease.

BACKGROUND/AIMS: Hepatopulmonary syndrome is defined as a clinical triad including chronic liver disease, abnormal pulmonary gas exchange resulting ultimately in profound arterial hypoxaemia, and evidence of intrapulmonary vascular dilatations. We report five patients with liver cirrhosis diagnosed with hepatopulmonary syndrome who had associated chronic obstructive or restrictive respiratory diseases. METHODS: Clinical, radiographic and constrast-enhanced echocardiographic findings, and systemic and pulmonary haemodynamic and gas exchange, including ventilation-perfusion distributions, measurements were assessed in all five patients. RESULTS: Echocardiography was consistent with the presence of intrapulmonary vasodilation without intracardiac abnormalities, and high resolution computed tomographic scan features were compatible with clinical (3 cases) or histopathological diagnoses (2 cases) of associated respiratory disorders. The most common prominent functional findings were moderate to severe arterial hypoxaemia, caused by moderately to severely increased intrapulmonary shunting and/or mild to moderate low ventilation-perfusion areas, and hypocarbia along with an increased cardiac output and a low pulmonary artery pressure and vascular resistance. CONCLUSIONS: These functional characteristics, classically reported in the setting of clinically stable, uncomplicated hepatopulmonary syndrome, conform to a distinctively unique, chronic gas exchange pattern. Equally important, these pulmonary haemodynamic-gas exchange hallmarks are not influenced by the co-existence of chronic cardiorespiratory disease states. These data may have clinical relevance for elective indication of hepatic transplantation in patients with life-threatening hepatopulmonary syndrome.

Adult↗
PubMed1999

DNA restriction patterns produced by pulsed-field gel electrophoresis in Moraxella catarrhalis isolated from different geographical areas.

Pulsed field gel electrophoresis (PFGE) of the genomic DNA of Moraxella catarrhalis was done in 172 strains isolated from sputum of patients with respiratory infections in Nagasaki (130 strains), Europe (14 strains), Thailand (6 strains), Uganda (3 strains), Bangladesh (5 strains) and Kuwait (14 strains). Restriction endonuclease with SmaI generated 4-16 DNA fragments ranging from 1000 kb to 24.25 kb and was classified into 31 major groups. It was found that there were wide variations of DNA restriction patterns of strains isolated from the same and different geographical areas. DNA restriction patterns of strains isolated in Nagasaki during the last 12 years showed dynamic changes of the predominant strains in each time period. We conclude from this study that PFGE is a suitable method to document interstrain variation in M. catarrhalis.

Adult↗
PubMed1999

Detection of loss of heterozygosity at RAD51, RAD52, RAD54 and BRCA1 and BRCA2 loci in breast cancer: pathological correlations.

Loss of heterozygosity (LOH) in loci of the 15q15.1, 12p13, 1p32, 17q21 and 13q12-13 regions may collaborate in the inactivation of RAD51, RAD52, RAD54, BRCA1, BRCA2 and possibly other genes implicated in the repair of double-stranded DNA and in DNA recombination. We investigate allelic losses in microsatellites of the RAD51, RAD52, RAD54, BRCA1 and BRCA2 regions, and their correlations with nine pathologic parameters in 127 breast carcinomas. The LOH analysis was performed by amplifying DNA by PCR, using 15 markers of the 15q15.1, 12p13.3, 1p32, 17q21 and 13q12-13 regions. LOH was found in the RAD51 region in 32% of tumours, in the RAD52 region in 16%, in RAD54 in 20% and in the BRCA1 and BRCA2 regions in 49% and 44% respectively. Significant correlations between one or more regions with concomitant LOH and pathologic parameters were observed with respect to age (P = 0.008), oestrogen receptor content (P = 0.03), progesterone receptors (P = 0.003), higher grade (P = 0.001), more advanced stage (P = 0.004) and peritumoural vessel involvement (P < 0.0001). The number of cases in which LOH was observed simultaneously in two or more regions was always higher than expected on the basis of their statistical probability, and curiously, the three patients with LOH at five regions concomitantly were under the age of 30 years. These results suggest that LOH at these regions could be related to breast cancer, and probably to a poor tumour prognosis.

Age Factors↗
PubMed1999

Intraoperative respiratory failure in a patient after treatment with bleomycin: previous and current intraoperative exposure to 50% oxygen.

Patients treated with bleomycin (BLM) are at risk of developing acute respiratory distress syndrome (ARDS) post-operatively, and this has been associated with high intraoperative concentrations of oxygen. We report progressive arterial desaturation noticeable 2 h after the start of a 4-h radical neck dissection for which the anaesthesia included 50% O2 in N2O. The patient had received two courses of bleomycin within the previous 2 months and had undergone an uneventful right hemiglossectomy under shorter but otherwise similar anaesthesia 4 weeks previously. His pulmonary function tests before the second procedure showed a slight depression of diffusing capacity (DLco) to 80% of predicted and minimal airway obstruction consistent with his history of smoking. The pulse oximetric reading during his second procedure reached 75%, but rose to 95% after treatment with methylprednisolone salbutamol and inspired O2 concentrations between 80% and 100%. By the end of the procedure, he satisfied the criteria for ARDS and was transferred to the ICU, where he developed bilateral pneumonia, deteriorated and died of multiple organ failure. This case suggests that the risk of hyperoxic pulmonary damage in patients exposed to bleomycin may increase not only with the degree and duration of hyperoxia in a given exposure, but also with the latent effects of recent previous exposure. Near normality of pulmonary function tests cannot be taken as reassurance, and small changes may have more adverse prognostic significance than in patients who have not been exposed to bleomycin.

Anesthesia, Inhalation↗
PubMed1999

The effects of S-carboxymethylcysteine and N-acetylcysteine on the adherence of Moraxella catarrhalis to human pharyngeal epithelial cells.

We investigated the effects of two mucoregulating drugs, S-carboxymethylcysteine (S-CMC) and N-acetylcysteine (NAC), on the attachment of Moraxella catarrhalis (M. catarrhalis) to pharyngeal epithelial cells. The attachment of M. catarrhalis decreased (33-57%) significantly (P<0.01) in a dose-dependent manner in cells treated with mucoregulating drugs as compared to the control. There was a significant (P<0.01) decrease (35-45%) in the attachment of M. catarrhalis to pharyngeal cells after oral administration of S-CMC. By electron microscopic observation, it was found that there was a fine, granular, electron-dense, ruthenium red-positive layer on the surface of pharyngeal epithelial cells; this layer was absent on cell surfaces treated with mucoregulating drugs. Possibly, this layer contained the portion of M. catarrhalis receptor which is responsible for the attachment of this bacteria to pharyngeal epithelial cells. From the above results, it may be concluded that one of the mechanisms of mucoregulating drugs to decrease the episode of respiratory infections in patients with chronic respiratory diseases is by inhibiting the attachment of bacteria to the upper respiratory tract.

Acetylcysteine↗
PubMed1999

Age, renal perfusion and function in island-dwelling indigenous Kuna Amerinds of Panama.

BACKGROUND/AIMS: Among possible contributors to a progressive fall in renal perfusion and function with increasing age, some hypotheses have invoked the rise in blood pressure that occurs with age, and a high-protein diet typical of urban cultures. Kuna Amerinds residing in isolated islands off the Panamanian Coast have a very low protein intake and show no tendency for blood pressure to rise with age, thus providing an opportunity to test these hypotheses. METHODS: We measured renal plasma flow and glomerular filtration rate (PAH and inulin clearance) in 16 Kuna Indians ranging in age from 18 to 86 years (51 +/- 6 years) who have resided on Ailigandi, an isolated Panamanian island for all of their lives. Inulin and PAH were infused with a battery-driven pump for 60 min, and a metabolic clearance rate used to calculate inulin and PAH clearance. For comparison, we employed identical techniques in 29 residents of Boston, ranging in age from 19 to 79 years (52 +/- 4 years), all normotensive and free of disease or medication use. Twenty-four were Caucasian. RESULTS: The Bostonian controls showed the anticipated fall in PAH clearance with age (y = 806 - 4.9 x; r = -0.82; f = 38.0; p < 0.0001). Our hypothesis was that the absence of a blood pressure rise with age and the low protein intake would flatten the slope relating renal perfusion to Kuna age. Our finding was a numerically steeper slope relating age and renal plasma flow in the Kuna (y = 936 - 6.48x; r = -0.81; p < 0.001). Filtration fraction rose with age in both populations, and again the rise was steeper in the Kuna. GFR in the Kuna, on the other hand, was very much higher at any age (139 +/- 4 ml/min/1.73 m2) than in Bostonians (112 +/- 3 ml/min/1.73 m2; p < 0.001). CONCLUSION: The findings are not in accord with the hypothesis that age-related changes in renal perfusion and glomerular filtration rate reflect an important contribution from blood pressure rise and a high protein intake, typical of modern, urban life.

Adolescent↗
PubMed1999

Increased serum levels of interferon-gamma and interleukin-12 during human brucellosis.

Brucellosis is a zoonotic disease that often becomes chronic with a high rate of recurrence. To understand the cytokines induced during this infection we determined the levels of interleukin (IL)-1beta, IL-2, IL-4, IL-8, IL-12, tumor necrosis factor-of (TNF-alpha) and interferon-gamma (IFN-gamma) in serum of patients with brucellosis and compared with those without brucellosis and controls. Control sera were taken from healthy persons residing in an area that was not endemic for brucellosis. The levels of IL-1, IL-2, IL-4, and TNF-alpha were not detectable in all the sera from patients. There was no difference in the level of IL-8 in patients with brucellosis and those without this disease. However, IL-8 was significantly higher in these two groups of patients compared with the controls. Significantly higher levels of IL-12 and IFN-alpha were found in the serum of patients with brucellosis compared with patients without brucellosis and controls. These data indicate that there is induction of Thl type cytokines during human brucellosis.

Adolescent↗
PubMed1999

Mediation of attachment of Burkholderia pseudomallei to human pharyngeal epithelial cells by the asialoganglioside GM1-GM2 receptor complex.

Melioidosis is the term given to any infection caused by Burkholderia pseudomallei. This bacteria is one of the important causative agents of life-threatening pulmonary infections in the tropical and subtropical areas. The initiation of respiratory infections is attachment of this bacteria to pharyngeal cells. The precise mechanism of attachment of B. pseudomallei is not known. In this study, we found that asialoganglioside GM1 at concentrations of 25, 12.5, and 5 microg/ml significantly decreased the attachment of B. pseudomallei strain Sp-186 in a dose-dependent manner. On the other hand, asialoganglioside GM2 decreased the attachment of B. pseudomallei, but only at a concentration of 25 microg/ml. At a concentration of 1 mg/ml, glucose, N-acetyl-galactosamine, and galactose caused a significant decrease in attachment. However, at concentrations of 250 microg/ml, no decrease in attachment was observed in B. pseudomallei treated with these carbohydrates. Mannose and fucose at concentrations of 1 mg/ml had no effects on the inhibition of attachment of B. pseudomallei. Four other isolates of B. pseudomallei showed a significant decrease in attachment after treatment with asialoganglioside GM1. We conclude that asialogangliosides GM1 and GM2 are part of the receptor complex for B. pseudomallei on human pharyngeal epithelial cells.

Bacterial Adhesion↗
PubMed1998

Bone mineral density in children and adolescents with diabetes mellitus type 1 of recent onset.

There is still controversy over the impact of diabetes control and duration on bone mass and growth parameters in children and adolescents with insulin-dependent diabetes mellitus (IDDM). The aim of this study was to assess bone mineral density (BMD) at axial and appendicular sites, in children with noncomplicated IDDM of recent onset, and its relation to metabolic control and auxological parameters (weight, height, and puberal stage). Fifty-five young Spanish IDDM, otherwise healthy patients (26 males, aged (SD 9.7 +/- 4.3 years) and 29 females, aged (SD 11.2 +/- 3.8 years) were studied. Duration of diabetes was 1-13.8 years. Two hundred eighty-two age-matched, healthy, Spanish children served as controls. HbA1 was assayed by high pressure liquid chromatography (HPLC) and BMD was measured using dual X-ray absorptiometry (DXA) densitometry at the spine and forearm. Results showed a Gaussian BMD distribution of patients according to sex and age, without sexual-stage differences. There was no correlation between BMD and glycated hemoglobin (average life disease or last HbA1 values) or duration of the disease; moreover, no differences in bone mass were found between <3 and >/=3 years of disease duration. Diabetes impact index (mean HbA1 x duration of disease in months) showed no significant influence of diabetes control on BMD. We could not demonstrate any impact of diabetes on BMD and growth parameters in children with IDDM of short duration.

Absorptiometry, Photon↗
PubMed1998

Mild or absent clinical signs in twin sisters with short-chain acyl-CoA dehydrogenase deficiency.

UNLABELLED: Two HLA-identical twin sisters are reported, of whom one has remained essentially asymptomatic, and an episode of hypotonia and decreased level of conciousness being the only relevant clinical finding in the other. Organic acid-analysis revealed that ethylmalonate was constantly, although sometimes only slightly, increased. No abnormal acylglycines or acylcarnitines could be detected. Enzyme assay in cultured skin fibroblasts confirmed short-chain acyl-CoA dehydrogenase deficiency. CONCLUSION: The lack of appropriate biochemical markers for this deficiency makes the diagnosis difficult and consequently, the low number of patients described may be the result of underdiagnosis.

Acyl-CoA Dehydrogenase↗
PubMed1998

GFAP, S-100 and vimentin proteins in rat after cerebral post-ischemic reperfusion.

In the present study astrocytes reactivity during cerebral post-ischemic reperfusion was evaluated immunocytochemically by using antibodies to vimentin, glial fibrillary acidic protein (GFAP) and S-100 protein. At the 7th day of post-ischemic reperfusion few GFAP-positive cells were observed in the hippocampus and cerebellum, the number of GFAP-positive cells increased slightly after 20 days of reperfusion. This poor GFAP-positivity may be due to the inhibition of GFAP polymerization by S-100; in fact, S-100 immuno-reactivity was already evident from the 7th day. Vimentin immuno-staining was evident both at the 7th and 20th day of reperfusion in microglial cells and in oligodendrocytes, suggesting that these cells are involved in the recovery of neurons following brain injury.

Animals↗
PubMed1998

Effects of glutathione depletors on post-ischemic reperfusion in rat brain.

The present paper reports the effects of GSH depletion (diethylmaleate induced) on partial cerebral ischemia and reperfusion for 7 and 20 days. Our results confirm that there is a paradoxical protective effect of the GSH-depletor and suggest an improved neuronal trophism induced by diethylmaleate treatment.

Animals↗
PubMed1998

Identification of four new mutations in the short-chain acyl-CoA dehydrogenase (SCAD) gene in two patients: one of the variant alleles, 511C-->T, is present at an unexpectedly high frequency in the general population, as was the case for 625G-->A, together conferring susceptibility to ethylmalonic aciduria.

We have shown previously that a variant allele of the short-chain acyl-CoA dehydrogenase ( SCAD ) gene, 625G-->A, is present in homozygous form in 7% of control individuals and in 60% of 135 patients with elevated urinary excretion of ethylmalonic acid (EMA). We have now characterized three disease-causing mutations (confirmed by lack of enzyme activity after expression in COS-7 cells) and a new susceptibility variant in the SCAD gene of two patients with SCAD deficiency, and investigated their frequency in patients with elevated EMA excretion. The first SCAD-deficient patient was a compound heterozygote for two mutations, 274G-->T and 529T-->C. These mutations were not present in 98 normal control alleles, but the 529T-->C mutation was found in one allele among 133 patients with elevated EMA excretion. The second patient carried a 1147C-->T mutation and the 625G-->A polymorphism in one allele, and a single point mutation, 511C-->T, in the other. The 1147C-->T mutation was not present in 98 normal alleles, but was detected in three alleles of 133 patients with elevated EMA excretion, consistently as a 625A-1147T allele. On the other hand, the 511C-->T mutation was present in 13 of 130 and 15 of 67 625G alleles, respectively, of normal controls and patients with elevated EMA excretion, and was never associated with the 625A variant allele. This over-representation of the haplotype 511T-625G among the common 625G alleles in patients compared with controls was significant ( P < 0.02), suggesting that the allele 511T-625G-like 511C-625A-confers susceptibility to ethylmalonic aciduria. Expression of the variant R147W SCAD protein, encoded by the 511T-625G allele, in COS-7 cells showed 45% activity at 37 degrees C in comparison with the wild-type protein, comparable levels of activity at 26 degrees C, and 13% activity when incubated at 41 degrees C. This temperature profile is different from that observed for the variant G185S SCAD protein, encoded by the 511C-625A allele, where higher than normal activity was found at 26 and 37 degrees C, and 58% activity was present at 41 degrees C. These results corroborate the notion that the 511C-625A variant allele is one of the possible underlying causes of ethylmalonic aciduria, and suggest that the 511C-->T mutation represents a second susceptibility variation in the SCAD gene. We conclude that ethylmalonic aciduria, a commonly detected biochemical phenotype, is a complex multifactorial/polygenic condition where, in addition to the emerging role of SCAD susceptibility alleles, other genetic and environmental factors are involved.

Acyl-CoA Dehydrogenase↗
PubMed1998

High risk of medium chain acyl-coenzyme A dehydrogenase deficiency among gypsies.

Medium chain acyl-CoA dehydrogenase (MCAD) deficiency is recognized as the most common hereditary defect of fatty acid oxidation in humans. Death is the outcome of the first attack in about 25% of cases. A point mutation (A to G [corrected] at position 985) of the MCAD gene represents more than 90% of alleles causing MCAD deficiency. The frequency of this allelic variant exhibits considerable geographical variations. In Spain, where the few diagnosed patients are mostly of Gypsy origin, the frequency is low as occurs in other Southern European countries (1 heterozygote among 200 individuals). Here we have analyzed the frequency of the G985 allele among Spanish gypsies. Heterozygotes were detected at a frequency of 1/17, with a 95% confidence interval ranging from 1/11 to 1/39. This represents the highest G985 rate described so far and calls for preventive measures, such as selective screening in this population.

Acyl-CoA Dehydrogenase↗
PubMed1998

Elevated hepatitis A and E seroprevalence rates in a Texas/Mexico border community.

Two seroprevalence studies of viral hepatitis A and hepatitis E were conducted in El Paso, Tex, and Cd Juárez, Mexico. Subjects were randomly selected, low-income pregnant women. Blood from 557 women in El Paso and 307 women in Cd Juárez, obtained from routine prenatal testing, was analyzed for antibodies to hepatitis A and hepatitis E. Women from both cities showed high seroprevalence rates of hepatitis A (75.8% in El Paso and 96.1% in Cd Juárez). Rates increased significantly by age, with 100% of women in Cd Juárez older than 28 years testing positive. Nationality and ethnicity were significantly associated with hepatitis A seroprevalence: Mexican nationals, 96.1%; US Hispanics, 78.8%; and US Caucasians, 36.4% (P < .001). With respect to hepatitis E, 0.4% of women in El Paso and 1.6% of women in Cd Juárez tested positive for anti-HEV. The rate of hepatitis A seroprevalence was higher for women with lower educational levels and for women residing in crowded households, but these findings were not statistically significant.

Adolescent↗
PubMed1997

Catecholamine modulatory effects of nepicastat (RS-25560-197), a novel, potent and selective inhibitor of dopamine-beta-hydroxylase.

1. Inhibitory modulation of sympathetic nerve function may have a favourable impact on the progression of congestive heart failure. Nepicastat is a novel inhibitor of dopamine-beta-hydroxylase, the enzyme which catalyses the conversion of dopamine to noradrenaline in sympathetic nerves. The in vitro pharmacology and in vivo catecholamine modulatory effects of nepicastat were investigated in the present study. 2. Nepicastat produced concentration-dependent inhibition of bovine (IC50 = 8.5 +/- 0.8 nM) and human (IC50 = 9.0 +/- 0.8 nM) dopamine-beta-hydroxylase. The corresponding R-enantiomer (RS-25560-198) was approximately 2-3 fold less potent than nepicastat. Nepicastat had negligible affinity (> 10 microM) for twelve other enzymes and thirteen neurotransmitter receptors. 3. Administration of nepicastat to spontaneously hypertensive rats (SHRs) (three consecutive doses of either 3, 10, 30 or 100 mg kg-1, p.o.; 12 h apart) or beagle dogs (0.05, 0.5, 1.5 or 5 mg kg-1, p.o.; b.i.d., for 5 days) produced dose-dependent decreases in noradrenaline content, increases in dopamine content and increases in dopamine/noradrenaline ratio in the artery (mesenteric or renal), left ventricle and cerebral cortex. At the highest dose studied, the decreases in tissue noadrenaline were 47%, 35% and 42% (in SHRs) and 88%, 91% and 96% (in dogs) in the artery, left ventricle and cerebral cortex, respectively. When tested at 30 mg kg-1, p.o., in SHRs, nepicastat produced significantly greater changes in noradrenaline and dopamine content, as compared to the R-enantiomer (RS-25560-198), in the mesenteric artery and left ventricle. 4. Administration of nepicastat (2 mg kg-1, b.i.d, p.o.) to beagle dogs for 15 days produced significant decreases in plasma concentrations of noradrenaline and increases in plasma concentrations of dopamine and dopamine/noradrenaline ratio. The peak reduction (52%) in plasma concentration of noradrenaline and the peak increase (646%) in plasma concentration of dopamine were observed on day-6 and day-7 of dosing, respectively. 5. The findings of this study suggest that nepicastat is a potent, selective and orally active inhibitor of dopamine-beta-hydroxylase which produces gradual modulation of the sympathetic nervous system by inhibiting the biosynthesis of noradrenaline. This drug may, therefore, be of value in the treatment of cardiovascular disorders associated with over-activation of the sympathetic nervous system, such as congestive heart failure.

Animals↗
PubMed1997

MAP2, synaptophysin immunostaining in rat brain and behavioral modifications after cerebral postischemic reperfusion.

Plasticity in the central nervous system after cerebral ischemia is a controversial issue; focal cerebral ischemia produces an area of infarction that is surrounded by neurons that may respond to nearby damage by creating new synapses. In the present study the expression of the postsynaptic microtubule-associated protein 2 (MAP2) and the presynaptic marker protein, synaptophysin, was investigated by immunocytochemical techniques in the CA1 sector of hippocampus and in cerebellum of rats made ischemic by bilateral clamping of common carotid arteries and reperfused for 7 and 30 days. In addition, ischemia-induced behavioral alterations were also evaluated after 7 and 30 days of reperfusion. The present study demonstrates a decreased postsynaptic MAP2 immunoreactivity, representative of neuronal loss, particularly in CA1 sector of hippocampus and in cerebellum of ischemic rats reperfused for 7 days. After 30 days of reperfusion, MAP2 immunostaining was similar to control. In the same brain sections an increased presynaptic synaptophysin immunoreactivity has been observed only after 30 days of reperfusion. These data suggest compensatory regenerative changes associated with synaptic remodelling and are supported by behavioral recovery observed under the same experimental conditions.

Animals↗