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Biomedical subjects

J A Martinez

Publications and source records attributed to J A Martinez.

At least 19 recordsLinked to original sources

Decreased invasive capacity of quinolone-resistant Escherichia coli in patients with urinary tract infections.

Quinolone-resistant (QR) Escherichia coli may have lower invasive capacity than does quinolone-susceptible E. coli. To evaluate this, we prospectively collected data regarding all cases of E. coli invasive urinary tract infections (IUTI) in 669 adults admitted to the Infectious Diseases Unit of our hospital during a 3-year period, as well as 10,950 patients with cystitis or asymptomatic bacteriuria who presented to the outpatient clinic during a 1-year period. QR E. coli was isolated in 20% of patients with cystitis, compared with 8% of those with IUTI (P<.05). The proportion of E. coli isolates that were quinolone resistant was similar in patients with bacteremic and nonbacteremic IUTI. The factors of urinary manipulation and structural abnormalities were independently associated with the presence of quinolone resistance. Old age was the only variable independently associated with blood invasion. QR E. coli is less likely to produce invasive disease (pyelonephritis and prostatitis) than is quinolone-susceptible E. coli. However, once pyelonephritis or prostatitis have developed, there is no difference in the incidence of bacteremia.

4-Quinolones↗

Up-regulation of a thermogenesis-related gene (UCP1) and down-regulation of PPARgamma and aP2 genes in adipose tissue: possible features of the antiobesity effects of a beta3-adrenergic agonist.

A number of experiments have demonstrated the antiobesity effects of beta(3)-adrenergic receptor stimulation by promoting thermogenesis and/or lipolysis. While many studies have been performed in order to develop beta(3)-adrenergic agonists as a novel strategy in the management of obesity, more information is needed about the mechanisms involved in thermogenesis and the actions of these drugs on adipocyte differentiation. To address this, the possible thermogenic and antiadipogenic properties of Tertatolol, a beta(3)-adrenergic agonist, in a diet-induced obesity model has been tested. Animals fed on a high-fat diet gained more weight and fat mass as compared with control and high-fat fed animals treated with Tertatolol. A RT-PCR was carried out in white adipose tissue specific genes involved in thermogenesis such as uncoupling proteins (UCPs) and adipogenesis such as peroxisome proliferator-activated receptor (PPARgamma2), retinoid receptors (RXRalpha/RARalpha), and fatty acid binding protein (aP2). Levels of UCP1 mRNA were augmented in the Tertatolol-treated group as compared to non-treated high-fat fed animals, while the beta(3)-adrenergic agonist treatment significantly decreased the expression levels of aP2 and transcription factors such as PPARgamma2 and the ratio RXRalpha/RARalpha as compared to obese rats. Altogether these data suggest that the antiobesity effects of beta(3)-adrenergic agonists are not limited to the promotion of thermogenesis and/or lipolysis and support the implication that these beta(3)-adrenergic agonists also affect fat deposition by impairing adipogenesis in white adipose tissue (WAT).

Adaptor Protein Complex 2↗

Elevation of soluble interleukin-2 receptor levels in the bronchoalveolar lavage from patients with systemic sclerosis.

This study was designed to investigate the levels of IL-2 and its soluble receptor (sIL-2R) in bronchoalveolar lavage fluid (BALF) from patients with systemic sclerosis (SSc). We studied 18 patients with SSc and 10 healthy volunteers. Based on high-resolution computed tomography lung scans the patients were divided into two groups, those with (SSc-ILD group, n= 10) and those without (SSc group, n = 8) evidence of interstitial lung disease (ILD). Both groups showed significantly higher total cell and neutrophil counts in the BALF than controls. The SSc group also showed significantly higher levels of lymphocytes than controls. IL-2 was not detectable in BALF. The patients showed significantly higher levels of sIL-2R than controls (77.8% vs 20%, P=0.005). The median sIL-2R levels detected did not differ between the two patient groups (SSc-ILD 270 pg/ml, SSc 232 pg/ml). This study suggests that SSc patients with or without ILD have elevated levels of sIL-2R in BALF and that in some of these patients this finding could be explained by subclinical pulmonary inflammation.

Adult↗

Pulmonary embolism with ST segment elevation in leads V1 to V4: case report and review of the literature regarding electrocardiographic changes in acute pulmonary embolism.

A 62-year-old man presented to the Emergency Department (ED) after having three short syncopal episodes earlier that day soon after experiencing acute onset of shortness of breath. He had no significant past medical history and was a nonsmoker. Initially in the Emergency Department he was without any complaints, but then became acutely short of breath and hemodynamically unstable and died despite resuscitative efforts. His electrocardiogram showed ST segment elevations in leads V1 to V4, which is consistent with an anteroseptal myocardial infarction. Autopsy revealed that this patient did not have a myocardial infarction, but rather died of a pulmonary embolism (PE). This case demonstrates how a PE can mimic an anteroseptal myocardial infarction on electrocardiogram. This patient's lack of risk factors for PE also makes this case unusual.

Electrocardiography↗

UCP2 muscle gene transfer modifies mitochondrial membrane potential.

OBJECTIVE: The aim of this work was to evaluate the effect of uncoupling protein 2 (UCP2) muscle gene transfer on mitochondrial activity. DESIGN: Five week-old male Wistar rats received an intramuscular injection of plasmid pXU1 containing UCP2 cDNA in the right tibialis anterior muscles. Left tibialis anterior muscles were injected with vehicle as control. Ten days after DNA injection, tibialis anterior muscles were dissected and muscle mitochondria isolated and analyzed. RESULTS: There were two mitochondrial populations in the muscle after UCP2 gene transfer, one of low fluorescence and complexity and the other, showing high fluorescence and complexity. UCP2 gene transfer resulted in a 3.6 fold increase in muscle UCP2 protein levels compared to control muscles assessed by Western blotting. Furthermore, a significant reduction in mitochondria membrane potential assessed by spectrofluorometry and flow cytometry was observed. The mitochondria membrane potential reduction might account for a decrease in fluorescence of the low fluorescence mitochondrial subpopulation. CONCLUSION: It has been demonstrated that UCP2 muscle gene transfer in vivo is associated with a lower mitochondria membrane potential. Our results suggest the potential involvement of UCP2 in uncoupling respiration. International Journal of Obesity (2001) 25, 68-74

Animals↗

Early alteration in glomerular reserve in humans at genetic risk of essential hypertension: mechanisms and consequences.

Essential hypertension has a familial predisposition, but the phenotype of elevated blood pressure has delayed penetrance. Because the kidney is a crucial determinant of blood pressure homeostasis, we studied early glomerular alterations in still-normotensive young subjects at genetic risk of hypertension. Thirty-nine normotensive adults (mean age 29 to 31 years), stratified by genetic risk (parental family history [FH]) of hypertension (26 with positive FH [FH+], 13 with negative FH [FH-]), underwent intravenous infusion of mixed amino acids. Before and during amino acid administration, we measured glomerular filtration rate (GFR), putative second messengers of amino acids (nitric oxide [NO.] metabolites and cGMP), serum insulin and amino acid concentrations, and the FE(Li)+ as an index of renal proximal tubular reabsorption. The FH+ group had a blunted GFR rise in response to amino acids (2.43+/-8.16% versus 31.0+/-13.4% rise, P:=0.0126). The amino acid-induced change in GFR correlated (r=0.786, P:<0.01) with the change in urinary NO. metabolite excretion; a diminished rise in urinary NO. metabolite excretion in the FH+ group (P:=0.0105) suggested a biochemical mechanism for the different GFR responses between FH groups: a relative inability to convert arginine to NO. The FH+ group had a far lower initial cGMP excretion at baseline (261+/-21.1 versus 579+/-84.9 nmol. h(-1)/1.73 m(2), P:=0.001), although cGMP did not change during the amino acid infusion (P:=0.703). FH status, baseline GFR, and baseline serum insulin jointly predicted GFR response to amino acids (P:=0.0013), accounting for approximately 45% of the variance in GFR response. Decline in FE(Li)+, an inverse index of proximal tubular reabsorption, paralleled increase in GFR (r=-0.506, P:=0.01), suggesting differences in proximal tubular reabsorption during amino acids between the FH groups. GFR response to amino acid infusion was blunted in the FH+ group despite significantly higher serum concentrations of 6 amino acids (arginine, isoleucine, leucine, methionine, phenylalanine, and valine) in the FH+ group, suggesting a novel form of insulin resistance (to the amino acid-translocating action of insulin) in FH+ subjects. We conclude that blunted glomerular filtration reserve in response to amino acids is an early-penetrance phenotype seen even in still-normotensive subjects at genetic risk of hypertension and is linked to impaired formation of NO. in the kidney. Corresponding changes in GFR and fractional excretion of Li(+) suggest that altered proximal tubular reabsorption after amino acids is an early pathophysiologic mechanism. Resistance to the amino acid-translocating actions of insulin may play a role in the biological response to amino acids in this setting. This glomerular reserve phenotype may be useful in genetic studies of renal traits preceding or predisposing to hypertension.

Adult↗

Increased exhalation of hydrogen peroxide in healthy subjects following cigarette consumption.

CONTEXT: Increased hydrogen peroxide has been described in the expired breath condensate (H2O2-E) of several lung conditions, such as acute respiratory distress syndrome, chronic obstructive pulmonary disease and asthma. This technique has been advocated as being a simple method for documenting airway inflammation. OBJECTIVE: To evaluate H2O2-E in healthy cigarette smokers, and to determine the acute effects of the consumption of one cigarette on H2O2-E levels. TYPE OF STUDY: Prospective, controlled trial. SETTING: A pulmonary function laboratory in a University Hospital. PARTICIPANTS: Two groups of healthy volunteers: individuals who had never smoked (NS; n=10; 4 men; age = 30.6 +/- 6.2 years) and current cigarette smokers (S; n=12; 7 men; age = 38.7 +/- 9.8). None of the volunteers had respiratory symptoms and all showed normal spirometric tests. INTERVENTION: Expired air was collected from all volunteers through a face mask and a plastic collecting system leading into a flask with dry ice and pure ethanol. Samples from the group S were collected twice, before and half an hour after the combustion of one cigarette. MAIN MEASUREMENTS: Expired hydrogen peroxide using the Gallati and Pracht method. RESULTS: The S and NS groups showed comparable levels of H2O2-E at basal conditions [NS = 0.74 microM (DP 0.24) vs. S = 0.75 microM (DP 0.31)]. The smokers showed a significant increase in H2O2-E levels half an hour after the consumption of only one cigarette [0.75 microM (DP 0.31) vs. 0. 95 microM (DP 0.22)]. CONCLUSION: The present results are consistent with the concept that smokers increase oxidative stress with elevated production of reactive oxygen species, contributing to the development of smoking-related disorders.

Adult↗

The subcellular localization of Otx2 is cell-type specific and developmentally regulated in the mouse retina.

Recent evidence implicates homeodomain-containing proteins in the specification of cell fates in the central nervous system. Here we report that in the embryonic mouse eye Otx2, a paired homeodomain transcription factor, was found in retinal pigment epithelial cells and a restricted subset of retinal neurons, including ganglion cells. In the postnatal and adult eye, however, both the cellular and subcellular distribution of the Otx2 protein were cell type-specific. Otx2 was detected only in the nuclei of retinal pigment epithelial and bipolar cells, but was present in the cytoplasm of rod photoreceptors. Immunohistochemical studies of retinal explants and transfected cell lines both suggested that the retention of Otx2 in the cytoplasm of immature rods is a developmentally regulated process. The differential distribution of Otx2 in the cytoplasm of rods and the nucleus of other cell types, suggests that subcellular localization of this transcription factor may participate cell fate determination during specific phases of retinal development.

3T3 Cells↗

Body-weight regulation: causes of obesity.

The aetiology and treatment of obesity have been fraught with disappointment for researchers, because the mechanisms that control fuel homeostasis and adiposity are incompletely understood. It is assumed that regulatory processes match the dietary fuel supply with energy requirements in order to maintain a stable body mass and adiposity. In this context several theories have been proposed to explain the laws of thermodynamics describing the conservation and transformation of energy in living organisms. In the light of new evidence it can now be hypothesized that the control of body weight and composition depends on an axis with three interrelated and self-controlled components: (1) food intake; (2) nutrient turnover and thermogenesis; (3) body fat stores. Complex feedback mechanisms underlie all these components. The major factors involved in obesity seem to be dietary and physical activity habits. These factors are affected by susceptibility genes that in turn may influence energy expenditure, fuel metabolism, muscle fibre function and appetite or food preferences. However, the increasing rates of obesity cannot be explained exclusively by changes in the gene pool, although genetic variants that were previously 'silent' are now being triggered by the high availability of energy- and fat-dense foods, and by the increasingly sedentary lifestyle of modern societies. The study of factors such as genetics and lifestyle implicated in weight gain and obesity is crucial for predictions about the future impact of the global epidemic of obesity, and provides a unique opportunity for the implementation of preventive action.

Body Weight↗

Methodological approaches to assess body-weight regulation and aetiology of obesity.

Obesity, which is becoming one of the major health hazards in developed and developing societies, results from a long-term positive energy balance. Body-weight regulation and stability depend on an axis with three interrelated components: food intake, energy expenditure and adipogenesis, although there are still many unknown features concerning fuel homeostasis and energy balance. Biochemical processes are interconnected, and a separate consideration of each component is often useful for methodological purposes and to achieve a better understanding of the whole system. Thus, many different experimental approaches can be applied by using laboratory animals, cell culture or human subjects to unravel the molecular mechanisms which participate in body-weight regulation. Thus, both in vitro (cellular and subcellular models) and in vivo methods have dramatically increased our knowledge of weight control. Several strategies in obesity research are reported here, exploiting the opportunities of the molecular era as well as novel whole-body approaches, which will impact on the development of new targets for obesity management and prevention.

Animals↗

Renal kallikrein excretion: role of ethnicity, gender, environment, and genetic risk of hypertension.

BACKGROUND AND OBJECTIVE: Alterations in renal kallikrein excretion are well-described in hypertension, and kallikrein excretion may predict risk of developing hypertension, but kallikrein excretion has not been directly compared across several ethnic strata, nor have the effects of ethnicity, gender, environment, and genetic risk of hypertension been simultaneously considered as determinants of kallikrein. METHODS: We investigated determinants of kallikrein excretion in a cross-section of n = 204 normotensive subjects stratified by ethnicity (119 Caucasian, 33 African-American, 52 Asian), gender (109 men, 95 women), environment (spontaneous electrolyte intake/excretion), and heredity (genetic risk (family history) of hypertension). Results were interpreted by analysis of variance (with Bonferroni post hoc comparison corrections), analysis of covariance, multiple linear regression, and maximum likelihood. RESULTS: Urinary kallikrein activity varied substantially (F = 5.30, P = 0.006) across the three ethnic groups, with African-American values approximately 50% lower than Caucasian (P = 0.005) or Asian (P = 0.02). Ethnicity and gender (T = 3.24, P = 0.001) had independent effects on kallikrein, with women excreting approximately 50% more kallikrein than men, regardless of ethnicity. Subjects at genetic risk of hypertension were over-represented (P = 0.048) in the lower stratum of a bimodal distribution of kallikrein excretion (chi-square = 29.6, P < 0.001). Potassium excretion was diminished in African-Americans (P < 0.001 to P = 0.002), and in a multivariate analysis, potassium excretion was the strongest correlate of kallikrein excretion (T = 4.10, P = 0.0001). In a subset of Caucasian and African-American individuals, African-Americans exhibited diminished excretion of not only kallikrein and potassium, but also aldosterone (P = 0.003), suggesting a mechanistic link between potassium and kallikrein excretion in their ethnic variations. CONCLUSIONS: Kallikrein excretion is influenced by several independent determinants, both hereditary (gender, ethnicity, and genetic risk of hypertension) and environmental (potassium intake and excretion). Ethnicity and environment may interact uniquely to influence kallikrein, as demonstrated by the case of African-Americans with diminutions of both kallikrein and potassium excretion. These results suggest a mechanism whereby kallikrein excretion is diminished in African-Americans, as well as therapeutic strategies to correct this deficiency. Finally, the identified determinants of kallikrein excretion will require analytic adjustment during genetic studies of this 'intermediate phenotype' in hypertension. Journal of Human Hypertension (2000) 14, 461-468

Adult↗

Diffuse panbronchiolitis in Latin America.

Diffuse panbronchiolitis (DPB) is a unusual form of bronchiolar disease that has been reported almost exclusively in Asians. We describe DPB in a non-Asian Brazilian citizen who has never traveled outside the country. The clinical, radiographic, and histologic features of this case resemble those described in Japanese patients. The present case shows that DPB, although rare in Western countries, is not a disease restricted to Asia. It always should be considered in the differential diagnosis of nodular radiographic opacities associated with airflow limitation, especially in non-smokers with a history of chronic sinusitis.

Adult↗

Dyspnea scales in the assessment of illiterate patients with chronic obstructive pulmonary disease.

BACKGROUND: Multiple physiological, psychological, social and environmental factors may affect the perception of dyspnea. Although different scales have been used to record the severity of dyspnea in subjects with chronic obstructive pulmonary disease (COPD), none has reported evaluating the properties of such tools in illiterate patients. The objective of this study was to evaluate the reliability and features of concurrent validity of 4 dyspnea scales in illiterate (IL) subjects with COPD. METHODS: One hundred COPD patients submitted to spirometry and were asked to score their breathlessness using a visual analogue scale (VAS), a numerical rating scale (NRS), the Borg scale (BS), and the basal dyspnea index (BDI). Each scale was presented to the patients before and after they had performed spirometry and measurement of residual volume. The obtained scores were analyzed according to the literacy status of the patients. RESULTS: Thirty-three patients were classified as IL and 67 as literate (L). Both groups showed similar respiratory impairment and median scores of dyspnea (VAS, L = 45.0, IL = 49.0; NRS, L = 5.0, IL = 5.0; BS, L = 3.0, IL = 3.0; BDI, L = 5.0, IL = 4.0). No significant differences were found between the dyspnea scores obtained before and after spirometry for all scales in both groups. The degree of correlation between forced expiratory volume in 1 second (FEV1) and usual dyspnea evaluated by BDI did not show a statistical difference between the two groups (L, r = 0.37; IL, r = 0.51). CONCLUSION: The employed dyspnea scales showed comparable reliability in both L and IL COPD subjects.

Adult↗

Antimicrobial treatment failures in patients with community-acquired pneumonia: causes and prognostic implications.

The aim of the study was to determine the causes and prognostic implications of antimicrobial treatment failures in patients with nonresponding and progressive life-threatening, community-acquired pneumonia. Forty-nine patients hospitalized with a presumptive diagnosis of community-acquired pneumonia during a 16-mo period, failure to respond to antimicrobial treatment, and documented repeated microbial investigation >/= 72 h after initiation of in-hospital antimicrobial treatment were recorded. A definite etiology of treatment failure could be established in 32 of 49 (65%) patients, and nine additional patients (18%) had a probable etiology. Treatment failures were mainly infectious in origin and included primary, persistent, and nosocomial infections (n = 10 [19%], 13 [24%], and 11 [20%] of causes, respectively). Definite but not probable persistent infections were mostly due to microbial resistance to the administered initial empiric antimicrobial treatment. Nosocomial infections were particularly frequent in patients with progressive pneumonia. Definite persistent infections and nosocomial infections had the highest associated mortality rates (75 and 88%, respectively). Nosocomial pneumonia was the only cause of treatment failure independently associated with death in multivariate analysis (RR, 16.7; 95% CI, 1.4 to 194.9; p = 0.03). We conclude that the detection of microbial resistance and the diagnosis of nosocomial pneumonia are the two major challenges in hospitalized patients with community-acquired pneumonia who do not respond to initial antimicrobial treatment. In order to establish these potentially life-threatening etiologies, a regular microbial reinvestigation seems mandatory for all patients presenting with antimicrobial treatment failures.

Community-Acquired Infections↗

Evaluation of the short-form 36-item questionnaire to measure health-related quality of life in patients with idiopathic pulmonary fibrosis.

OBJECTIVE: To validate the use of the 36-item short-form questionnaire (SF-36) for measuring health-related quality of life (HRQL) in patients with idiopathic pulmonary fibrosis (IPF). DESIGN: : Observational data at a single point in time. SETTING: : A specialized outpatient respiratory clinic. PARTICIPANTS: Thirty-four patients (mean +/- SE age, 58.29 +/- 1.87 years) with IPF and no significant comorbidity. A matched control group for HRQL measurements was composed of 34 normal subjects (mean age, 58.00 +/- 1.89 years). MEASUREMENTS AND RESULTS: Dyspnea was measured by the baseline dyspnea index (BDI). Respiratory function evaluation included FVC, FEV(1), and resting arterial blood gases. IPF patients showed a mean BDI score of 5.21 +/- 0.46. The mean FVC and FEV(1) values were 62.41 +/- 2.96% and 66.41 +/- 3.33%, respectively. The mean PaO(2) was 67 +/- 2.51 mm Hg, and the mean PaCO(2) was 37 +/- 1. 05 mm Hg. Patients scored significantly worse than control subjects with respect to the SF-36 domains of physical functioning, physical role, general health perceptions, vitality, social functioning, emotional role, and mental health index. BDI scores were significantly correlated with five SF-36 components, and FVC and FEV(1) were significantly correlated with two SF-36 components. Significant negative correlations were found between arterial pH and four SF-36 domains. CONCLUSIONS: Patients with IPF have a significant impairment of HRQL in both physical and psychological functioning. Dyspnea is the most important factor influencing the quality of life in these subjects. The SF-36 questionnaire is a valid instrument to evaluate HRQL in IPF patients.

Adaptation, Psychological↗

Electrical injuries.

Electrical injuries may occur from high or low voltage contact. Low voltage injuries usually occur in the home, tetany may lead to sustained contact, and dangerous cardiac disturbances often result. High voltage injuries are usually work related and result from brief contact but may cause serious tissue destruction and secondary injuries. Both forms may be fatal. Electrical injury more closely resembles a crush injury than a thermal injury and is managed accordingly. External manifestations often belie the severity of deeper wounds.

Accidents, Home↗

Panic induced by carbon dioxide inhalation and lack of hypothalamic-pituitary-adrenal axis activation.

It has been hypothesized that spontaneous panic is distinct from anticipatory anxiety, which activates the hypothalamic-pituitary-adrenal (HPA) axis. Panic attacks characterized by prominent respiratory symptoms, such as those induced by sodium lactate, are not associated with increases in cortisol. We examined blood cortisol responses to CO2-induced panic. Cortisol levels did not increase and actually decreased significantly in 10 panicking subjects with panic disorder. No reductions were noted after 20 min of CO2 inhalation in either eight normal comparison subjects or six non-panicking panic disorder patients. These results lend support to the hypothesis that the pathophysiological mechanism underlying CO2-induced panic is different from that underlying general or anticipatory anxiety.

Adult↗