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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

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↗

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↗

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↗

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↗

Employee Retirement Income Security Act and managed care: current issues and their impact on medical practice.

BACKGROUND: Managed care organizations (MCOs) routinely make decisions regarding utilization of health services, with an expectation of protection from liability through the Employee Retirement Income Security Act of 1974 (ERISA). An MCO decision to deny services to a patient may expose the physician to liability, while ERISA often shields the MCO from liability. A recent United States Supreme Court decision, New York State Conference of Blue Cross and Blue Shield Plans v Travelers, as well as legislation on the state and federal levels, may resolve this area of friction between physicians and MCOs. METHODS: We reviewed federal and state laws, as well as relevant case law and legal commentaries. RESULTS: The Travelers decision raised the threshold for ERISA preemption, decreasing the protection once afforded to MCOs. The American Medical Association, many state legislatures, and some members of Congress have recognized ERISA preemption and its protection of MCOs as a source of potential risk to patient care and increased liability for physicians. CONCLUSION: The problems created by the interaction of ERISA and managed care appear headed for a legislative resolution on the federal and state levels. This will significantly affect the interaction of MCOs with patients and physicians.

Employee Retirement Income Security Act↗

Pneumonia acquired in the community through drug-resistant Streptococcus pneumoniae.

The aim of the study was to determine the incidence of and risk factors for drug resistance of Streptococcus pneumoniae, and its impact on the outcome among hospitalized patients of pneumococcal pneumonia acquired in the community. Consecutive patients with culture-proven pneumococcal pneumonia were prospectively studied with regard to the incidence of pneumococcal drug resistance, potential risk factors, and in-hospital outcome variables. A total of 101 patients were studied. Drug resistance to penicillin, cephalosporin, or a macrolide drug was found in pneumococci from 52 of the 101 (52%) patients; 49% of these isolates were resistant to penicillin (16% intermediate resistance, 33% high resistance), 31% to cephalosporin (22% intermediate and 9% high resistance), and 27% to a macrolide drug. In immunocompetent patients, age > 65 yr was significantly associated with resistance to cephalosporin (odds ratio [OR]: 5.0; 95% confidence interval [CI]: 1.3 to 18.8, p = 0. 01), and with the presence of > 2 comorbidities with resistance to penicillin (OR: 4.7; 95% CI: 1.2 to 19.1; p < 0.05). In immunosuppressed patients, bacteremia was inversely associated with resistance to penicillin and cephalosporin (OR: 0.04; 95% CI: 0.003 to 0.45; p < 0.005; and OR: 0.46; 95% CI: 0.23 to 0.93; p < 0.05, respectively). Length of hospital stay, severity of pneumonia, and complications were not significantly affected by drug resistance. Mortality was 15% in patients with any drug resistance, as compared with 6% in those without resistance. However, any drug resistance was not significantly associated with death (relative risk [RR]: 2. 5; 95% CI: 0.7 to 8.9; p = 0.14). Moreover, attributable mortality in the presence of discordant antimicrobial treatment was 12%, as compared with 10% (RR: 1.2; 95% CI: 0.3 to 5.3; p = 0.67) in the absence of such treatment. We conclude that the incidence of drug-resistant pneumococci was high. Risk factors for drug resistance included advanced age, comorbidity, and (inversely) bacteremia. Outcome was not significantly affected by drug resistance.

Adult↗

Etiology of community-acquired pneumonia: impact of age, comorbidity, and severity.

The aim of this study was to determine the etiology of community-acquired pneumonia (CAP) and the impact of age, comorbidity, and severity on microbial etiologies of such pneumonia. Overall, 395 consecutive patients with CAP were studied prospectively during a 15-mo period. Regular microbial investigation included examination of sputum, blood culture, and serology. Sampling of pleural fluid, transthoracic puncture, tracheobronchial aspiration, and protected specimen brush (PSB) sampling were performed in selected patients. The microbial etiology was determined in 182 of 395 (46%) cases, and 227 pathogens were detected. The five most frequent pathogens were Streptococcus pneumoniae (65 patients [29%]), Haemophilus influenzae (25 patients [11%]), Influenza virus A and B (23 patients [10%]), Legionella sp. (17 patients [8%]), and Chlamydia pneumoniae (15 patients [7%]). Gram-negative enteric bacilli (GNEB) accounted for 13 cases (6%) and Pseudomonas aeruginosa for 12 cases of pneumonia (5%). Patients aged < 60 yr were at risk for an "atypical" bacterial etiology (odds ratio [OR]: 2.3; 95% confidence interval [CI]: 1.2 to 4.5), especially Mycoplasma pneumoniae (OR: 5.3; 95% CI: 1.7 to 16.8). Comorbid pulmonary, hepatic, and central nervous illnesses, as well as current cigarette smoking and alcohol abuse, were all associated with distinct etiologic patterns. Pneumonia requiring admission to the intensive care unit was independently associated with the pathogens S. pneumoniae (OR: 2.5; 95% CI: 1.3 to 4.7), gram-negative enteric bacilli, and P. aeruginosa (OR: 2.5; 95% CI: 0.99 to 6.5). Clinical and radiographic features of "typical" pneumonia were neither sensitive nor specific for the differentiation of pneumococcal and nonpneumococcal etiologies. These results support a management approach based on the associations between etiology and age, comorbidity, and severity, instead of the traditional syndromic approach to CAP.

Adult↗

Severe community-acquired pneumonia. Risk factors and follow-up epidemiology.

The aim of the study was to determine risk factors for severe community-acquired pneumonia (CAP) as well as to compare microbial patterns of severe CAP to a previous study from our respiratory intensive care unit (ICU) originating from 1984 to 1987. Patients admitted to the ICU according to clinical judgment were defined as having severe CAP. For the study of risk factors, a hospital-based case-control design was used, matching each patient with severe CAP to a patient hospitalized with CAP but not requiring ICU admission. Microbial investigation included noninvasive and invasive techniques. Overall, 89 patients with severe CAP were successfully matched to a control patient. The presence of an alcohol ingestion of >/= 80 g/d (odds ratio [OR] 3.9, 95% confidence interval [CI] 1.4 to 10.6, p = 0.008) was found to be an independent risk factor for severe CAP and prior ambulatory antimicrobial treatment (OR 0.37, 95% CI 0.17 to 0.79, p = 0.009) to be protective. Streptococcus pneumoniae (24%) continued to be the most frequent pathogen; however, 48% of strains were drug-resistant. "Atypical" bacterial pathogens were significantly more common (17% versus 6%, p = 0.006) and Legionella spp. less common (2% versus 14%, p = 0.004) than in our previous study, whereas gram-negative enteric bacilli (GNEB) and Pseudomonas aeruginosa continued to represent important pathogens (6% and 5%, respectively). Our findings provide additional evidence for the importance of the initiation of early empiric antimicrobial treatment for a favorable outcome of CAP. Variations of microbial patterns are only in part due to different epidemiological settings. Therefore, initial empiric antimicrobial treatment will also have to take into account local trends of changing microbial patterns.

Adolescent↗

Fixing EMTALA: what's wrong with the Patient Transfer Act.

Congress primarily enacted the Emergency Medical Treatment and Active Labor Act (EMTALA) in 1986 to prevent the denial of care to uninsured patients in emergency departments. The final version of EMTALA lacks specific protection for indigent patients and saddles hospitals and physicians with more liability than Congress initially intended. Loopholes in the law allow denial of care to patients when temporarily stabilized. Congress should ameliorate these problems through amendment of the law.

Emergency Treatment↗

Erx, a novel retina-specific homeodomain transcription factor, can interact with Ret 1/PCEI sites.

Our previous studies on the transcriptional regulation of rod opsin gene expression had defined a strikingly conserved element, Ret 1/PCEI, present in the upstream regulatory regions of opsin and other photoreceptor-specific genes. This element interacts with a 40 kDa, developmentally regulated, retina-specific protein. In this study we report the cloning of the novel retina-specific homeodomain protein Erx. Erx contains a homeodomain that is 79% homologous to that of Drosophila empty spiracles. This 40 kDa protein can interact with the Ret 1 element in electrophoretic mobility shift assays. Mutation of key residues in Ret 1 eliminates all Erx binding. Transient transfection of Y79 retinobalstoma cells with Erx leads to significant transcriptional activation of a reporter gene via Ret 1 elements. We conclude that Erx is the Ret 1 binding activity. This is the first example of a Q50 homeodomain protein expressed in retinal photoreceptors.

Amino Acid Sequence↗

Leptin gene transfer into muscle increases lipolysis and oxygen consumption in white fat tissue in ob/ob mice.

The effects of leptin production in ob/ob mice injected with a plasmid expression vector containing mouse leptin cDNA in the tibialis anterior muscle were investigated. A significant reduction in food intake (-18%, p < 0.01) along the experimental period was found after DNA injection, while differences in body weight gain were only significant (-41%, p < 0.05) when determined between days 2.9 of the study. Concerning adipocytes metabolism, there was a significant increase in oxygen consumption in vitro (+34%, p < 0.05) and in basal lipolysis (+151%, p < 0.05) in DNA-injected mice compared to PBS-injected animals. Our results confirm that functional leptin can be produced in muscle and released into the blood stream and give new support to the fact that leptin may have direct auto- or paracrine effects on adipocytes, possible contributing to the weight- and fat-reducing effects of leptin in ob/ob mice.

Adipose Tissue↗

ICV administration of CRF blocker (CRF9-41 delta helical) reduces morphine withdrawal in rats.

1. The effects of CRF9-41 delta helical on morphine withdrawal signs in rats were studied. 2. Intracerebroventricular administration of CRF9-41 delta helical 5 at 10 micrograms/kg reduced central and peripheral symptoms of the withdrawal syndrome, such as ptosis, jumping, wet dog shakes and teeth chattering; other signs remained unchanged. The effect were not dose dependent. 3. The hypothermi characteristic of the Withdrawal syndrome was reduced by CRF9-41 delta helical. 4. These results suggest that the hypothalamo pituitary adrenal(HPA) axis play an important role in the morphine withdrawal syndrome in rats.

Animals↗

Racial differences in renal kallikrein excretion: effect of the ovulatory cycle.

BACKGROUND: Renal kallikrein excretion is diminished in essential hypertension, especially in African-Americans, and evidence exists for a major gene effect on the kallikrein phenotype. In addition, urinary kallikrein excretion differs by gender, with ovulating females having greater kallikrein excretion than males or postmenopausal females. Recent studies have shown that renal kallikrein excretion varies in females during the ovulatory cycle, with levels rising during the luteal phase and returning during the follicular phase to levels that are similar to those of males. In family studies, gender differences in urinary kallikrein excretion were present in white subjects, but not black subjects. We therefore hypothesized dysregulation of kallikrein biosynthetic responses in African-Americans. METHODS: We determined urinary kallikrein activity [chromogenic substrate S2266 (D-val-leu-arg-paranitroanilide) assay; in microU/mg creatinine] in white (N = 15) and black (N = 11) ovulating females during the ovulatory cycle. Serum progesterone, estrogen, plasma renin activity as well as urinary aldosterone, and urinary electrolytes were determined to investigate changes between mid-follicular and mid-luteal phases in the two groups. RESULTS: White and black groups were matched for age, body mass index, blood pressure, heart rate and renal function. Ovulatory cycle phases were confirmed by serum progesterone determinations, which increased significantly in whites and blacks to a comparable degree [0.84 +/- 0.14 nmol/liter (mid-follicular) to 29.77 +/- 4.70 nmol/liter (mid-luteal) in whites, 0.67 +/- 0.08 nmol/liter (mid-follicular) to 28.62 +/- 5.83 nmol/liter (mid-luteal) in blacks; P < 0.001 for cycle effect, P = NS for race effect and race X cycle interaction]. Urinary kallikrein activity increased from 623 +/- 86 microU/mg creatinine (mid-follicular) to 948 +/- 142 microU/mg creatinine (mid-luteal) in whites, but did not change in blacks during the ovulatory cycle [239 +/- 73 microU/mg creatinine (mid-follicular] to 244 +/- 41 microU/mg creatinine (mid-luteal)]. Two-way ANOVA revealed significant effects on urinary kallikrein for race (P < 0.001), cycle (P < 0.05), and race X cycle interaction (P < 0.05). Thus, white females had higher urinary kallikrein than black females, and demonstrated a significant increase in urinary kallikrein excretion during the ovulatory cycle, whereas no significant change in urinary kallikrein activity was seen in the black group. Enzyme kinetic studies and mixing studies demonstrated that these racial differences in renal kallikrein excretion were quantitative, rather than due to qualitative differences in the renal kallikrein enzyme or due to the presence of a kallikrein inhibitor. CONCLUSIONS: These results suggest pronounced blunting of menstrual cycle changes in urinary kallikrein excretion in black females. Blunted urinary kallikrein responses during the ovulatory cycle are consistent with dysregulation of renal kallikrein biosynthetic responses in African-Americans, a group at increased risk for hypertension.

Adult↗

Severe community-acquired pneumonia. Assessment of severity criteria.

The purpose of the study was to validate the criteria used in the guidelines of the American Thoracic Society (ATS) for severe community-acquired pneumonia (CAP). Severe pneumonia was defined as admission to the intensive care unit (ICU). Overall 331 nonsevere (84%) and 64 severe cases (16%) of CAP were prospectively studied. Mortality was 19 of 395 (5%) and 19 of 64 (30%), respectively. Single severity criteria as well as the ATS definition of severe pneumonia were assessed calculating the operative indices. A modified prediction rule including minor (baseline) and major (baseline or evolutionary) criteria was derived. Single minor criteria at admission had a low sensitivity and positive predictive value. Defining severe pneumonia according to the ATS guidelines had a high sensitivity (98%). However, specificity and positive predictive value were low (32% and 24%, respectively). A modified prediction rule (presence of two or three minor criteria [systolic blood pressure < 90 mm Hg, multilobar involvement, PaO2/FIO2 < 250] or one of two major criteria [requirement of mechanical ventilation, presence of septic shock]) had a sensitivity of 78%, a specificity of 94%, a positive predictive value of 75%, and a negative predictive value of 95%. The ATS definition of severe pneumonia was highly sensitive but insufficiently specific and had a low positive predictive value. Our suggested modified rule had a more balanced performance and, if validated in an independent population, may represent a more accurate definition of severe CAP.

APACHE↗