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Biomedical subjects

N Gonzalez

Publications and source records attributed to N Gonzalez.

At least 37 records · Page 2Linked to original sources
PubMed1999

Association of the serotonin transporter gene with serum cholesterol levels and heart disease.

In a study of a group of elderly athletes we observed an unexpected association between serum cholesterol levels and the HTTLPR insertion/deletion polymorphism of the promoter region of the serotonin transporter gene (HTT, SLC6A4). As a follow-up we examined the potential association of this polymorphism with cholesterol and triglyceride levels, or heart disease, in two other groups of subjects. We examined the possible association between cholesterol levels and heart disease and genotypes of the HTTLPR insertion/deletion polymorphism of the promoter region of the HTT gene, in three independent study populations ranging from 42 to 90 years of age. For subjects 55 to 70 years of age in Group 1, cholesterol levels were significantly greater in the LS heterozygotes than either LL or SS homozygotes, indicating a heterosis effect (P </= 0.0001). This was replicated in Group 2 (P </= 0.015). Triglyceride levels were also significantly elevated in the LS subjects (P </= 0.001). In Groups 1 and 3 there was a significant association between LS heterozygosity and heart disease, angina, and heart attacks in subjects 70 years of age or less. All of these associations were absent in subjects >70 years of age. While these studies are preliminary and exploratory, they are consistent with a relationship of the HTT gene in cholesterol levels and a risk for heart disease. Replication of these findings in independent, epidemiologically based studies is required.

Adult↗
PubMed1999

Additive effect of three noradrenergic genes (ADRA2a, ADRA2C, DBH) on attention-deficit hyperactivity disorder and learning disabilities in Tourette syndrome subjects.

Halperin et al. (Halperin JM. Newcorn JH, Koda VH, Pick L, McKay KE, Knott P. Noradrenergic mechanisms in ADHD children with and without reading disabilities: a replication and extension. J Am Acad Child Adolesc Psychiatry 1997: 36: 1688 1696) reported a significant increase in plasma norepinephrine (NE) in attention-deficit hyperactivity disorder (ADHD) children with reading and other cognitive disabilities compared to ADHD children without learning disabilities (LD). We examined the hypothesis that ADHD + LD was associated with NE dysfunction at a molecular genetic level by testing for associations and additive effects between polymorphisms at three noradrenergic genes the adrenergic alpha2A receptor (ADRA2A), adrenergic alpha2C receptor (ADRA2C), and dopamine beta-hydroxylase (DBH) genes. A total of 336 subjects consisting of 274 individuals with Tourette syndrome (TS) and 62 normal controls were genotyped. Regression analysis showed a significant correlation between scores for ADHD, a history of LD, and poor grade-school academic performance that was greatest for the additive effect of all three genes. Combined, these three genes accounted for 3.5% of the variance of the ADHD score (p = 0.0005). There was a significant increase in the number of variant NE genes progressing from subjects without ADHD (A-) or learning disorders (LD-) to A + LD - to A - LD + to A + LD + (p = 0.0017), but no comparable effect for dopamine genes. These data support an association between NE genes and ADHD, especially in ADHD + LD subjects.

Adolescent↗
PubMed1999

Homozygosity at the dopamine DRD3 receptor gene in cocaine dependence.

We examined the hypothesis that the dopamine D3 receptor gene (DRD3) is a susceptibility factor for cocaine dependence. The MscI/BalI polymorphism of the DRD3 gene was examined in 47 Caucasian subjects with cocaine dependence and 305 Caucasian controls. Based on prior studies with a range of psychiatric disorders we hypothesized there would be a decrease in the frequency of the 12 genotype in the patient sample (increased homozygosity). We observed a significant decrease in the frequency of 12 heterozygotes in subjects with cocaine dependence (29.8%) vs controls (46.9%) (P </= 0.028). This percentage was still lower in those who had chronically used cocaine for more than 10 years (25%), or more than 15 years (21.5%). The DRD3 gene accounted for 1.64% of the variance of cocaine dependence. The DRD2 gene had an independent and additive effect on cocaine dependence. These findings support a modest role of the DRD3 gene in susceptibility to cocaine dependence.

Adult↗
PubMed1999

Acute Chagas' disease in western Venezuela: a clinical, seroparasitologic, and epidemiologic study.

A clinical, parasitologic, and serologic study carried out between 1988 and 1996 on 59 acute-phase patients in areas of western Venezuela where Chagas' disease is endemic showed 19 symptomatic patterns or groups of symptoms appearing in combination with different frequencies. The symptomatic pattern with the highest frequency was that showing simultaneously fever, myalgia, headache, and Romaña's sign, which was detected in 20% of the acute-phase patients. Asymptomatic individuals and patients with fever as the only sign of the disease made up 15% and 11.9% of the total acute cases, respectively. Statistical correlation analysis revealed that xenodiagnosis and hemoculture were the most reliable and concordant of the five parasitologic methods used; these two methods also showed the highest proportions in detecting any clinical symptomatic pattern in acute-phase patients. A similar high reliability and concordance was obtained with a direct agglutination test, an indirect immunofluorescent antibody test, and an ELISA as serologic tests, which also showed a higher proportion of positive detection of clinical patterns than parasitologic methods (P < 0.001). It is recommended that individuals coming from endemic areas showing mild and/or severe clinical manifestations should be suspected of being in contact or having been in contact with Trypanosoma cruzi, be referred for parasitologic and serologic evaluations to confirm the presumptive clinical diagnosis of acute Chagas' disease, and start specific treatment. The epidemiologic implications of the present findings are discussed and the use of similar methodology to evaluate other areas where Chagas' disease is endemic is suggested.

Acute Disease↗
PubMed1999

Myocardial parasite persistence in chronic chagasic patients.

The persistence of Trypanosoma cruzi tissue forms was detected in the myocardium of seropositive individuals clinically diagnosed as chronic chagasic patients following endomyocardial biopsies (EMBs) processed by immunohistochemical (peroxidase-anti-peroxidase [PAP] staining) and molecular (polymerase chain reaction [PCR]) techniques. An indirect immunofluorescent technique revealed antigenic deposits in the cardiac tissue in 24 (88.9%) of 27 patients. Persistent T. cruzi amastigotes were detected by PAP staining in the myocardium of 22 (84.6%) of 26 patients. This finding was confirmed with a PCR assay specific for T. cruzi in 21 (91.3%) of 23 biopsy specimens from the same patients. Statistical analysis revealed substantial agreement between PCR and PAP techniques (k = 0.68) and the PCR and any serologic test (k = 0.77). The histopathologic study of EMB specimens from these patients revealed necrosis, inflammatory infiltrates, and fibrosis, and made it possible to detect heart abnormalities not detected by electrocardiogram and/or cineventriculogram. These indications of myocarditis were supported by the detection of T. cruzi amastigotes by the PAP technique or its genome by PCR. They suggest that although the number of parasites is low in patients with chronic Chagas' disease, their potential for heart damage may be comparable with those present during the acute phase. The urgent necessity for testing new drugs with long-term effects on T. cruzi is discussed in the context of the present results.

Adult↗
PubMed1999

99mTc-labeled antihuman epidermal growth factor receptor antibody in patients with tumors of epithelial origin: Part III. Clinical trials safety and diagnostic efficacy.

UNLABELLED: Monoclonal antibody (moAb) ior egf/r3 is an IgG2a that recognizes the epidermal growth factor receptor (EGF-R). The aim of this study was to evaluate the diagnostic efficacy of the 99mTc-labeled moAb ior egf/r3 for the detection of epithelial-derived tumors, their metastases and recurrences. METHODS: One hundred forty-eight adult patients (51 women, 97 men; mean age 53 +/- 13 y) who were suspected of having cancer of epithelial origin were administered 3 mg/50 mCi (1.85 GBq) 99mTc-labeled moAb ior egf/r3 by intravenous bolus injection. Planar anterior and posterior images of the lesion sites and suspected metastases were acquired at 2, 4, 6 and 24 h after injection, and SPECT images were scanned at 5 h postinjection, using a 360 degrees circular orbit with 64 images. The backprojection method was used for image reconstruction with a Hamming-Hann filter. RESULTS: Labeling efficiency was always greater than 98.5% +/- 2.1 %. No adverse reactions or side effects were observed. Results of the biopsy specimens showed that 85.1% (126/148) of the patients had tumors of epithelial origin, 14.2% (21/148) were negative and 0.7% (1/148) had non-Hodgkin's lymphoma. The sensitivity rate by organ was as follows: brain (8/8, 100%), digestive tract (10/11, 90.9%), head and neck (17/23, 73.9%), lung (52/62, 83.9%) and breast (16/18, 88.9%). Overall sensitivity, specificity, accuracy, and positive and negative predictive values of the immunoscintigraphic imaging were 84.2% (106/126), 100.0% (22/22), 86.5% (128/148), 100% (106/106) and 52.4% (22/42), respectively. New metastases not identified previously by other diagnostic methods were detected in the 50% of the patients. CONCLUSION: Immunoscintigraphy with 99mTc-labeled moAb ior egf/r3 could be a useful procedure for the diagnosis and follow-up of the patients with tumors of epithelial origin.

Animals↗
PubMed1998

Influence of long-term, low-dose, diuretic-based, antihypertensive therapy on glucose, lipid, uric acid, and potassium levels in older men and women with isolated systolic hypertension: The Systolic Hypertension in the Elderly Program. SHEP Cooperative Research Group.

BACKGROUND: Previous studies often of short duration have raised concerns that antihypertensive therapy with diuretics and beta-blockers adversely alters levels of other cardiovascular disease risk factors. METHODS: The Systolic Hypertension in the Elderly Program was a community-based, multicenter, randomized, double-blind, placebo-controlled clinical trial of treatment of isolated systolic hypertension in men and women aged 60 years and older. This retrospective analysis evaluated development of diabetes mellitus in all 4736 participants in the Systolic Hypertension in the Elderly Program, including changes in serum chemistry test results in a subgroup for 3 years. Patients were randomized to receive placebo or treatment with active drugs, with the dose increased in stepwise fashion if blood pressure control goals were not attained: step 1, 12.5 mg of chlorthalidone or 25.0 mg of chlorthalidone; and step 2, the addition of 25 mg of atenolol or 50 mg of atenolol or reserpine or matching placebo. RESULTS: After 3 years, the active treatment group had a 13/4 mm Hg greater reduction in systolic and diastolic blood pressure than the placebo group (both groups, P<.001). New cases of diabetes were reported by 8.6% of the participants in the active treatment group and 7.5% of the participants in the placebo group (P=.25). Small effects of active treatment compared with placebo were observed with fasting levels of glucose (+0.20 mmol/L [+3.6 mg/dL]; P<.01), total cholesterol (+0.09 mmol/L [+3.5 mg/dL]; P<.01), high-density lipoprotein cholesterol (-0.02 mmol/L [-0.77 mg/dL]; P<.01) and creatinine (+2.8 micromol/L [+0.03 mg/dL]; P<.001). Larger effects were seen with fasting levels of triglycerides (+0.9 mmol/L [+17 mg/dL]; P<.001), uric acid (+35 micromol/L [+.06 mg/dL]; P<.001), and potassium (-0.3 mmol/L; P<.001). No evidence was found for a subgroup at higher risk of risk factor changes with active treatment. CONCLUSIONS: Antihypertensive therapy with low-dose chlorthalidone (supplemented if necessary) for isolated systolic hypertension lowers blood pressure and its cardiovascular disease complications and has relatively mild effects on other cardiovascular disease risk factor levels.

Aged↗
PubMed1997

HLA class I and class II alleles and haplotypes in Mexican mestizos established from serological typing of 50 families.

We describe new information on the frequency and association of class II antigens (HLA-DR and HLA-DQ) of the major histocompatibility complex (MHC) in Mexicans. The study includes HLA-B typing and its association with the HLA-DR antigens determined in 50 families, which included 100 individuals. This family study allowed the establishment of the precise composition of the 200 HLA haplotypes, which cannot be obtained from unrelated individuals. The predominant antigens in decreasing order of frequency were B35, B39, and B61 at the B locus; DR4, DR5, and DR8 at the DR locus; and DQ3 at the DQ locus. The most common HLA-B,HLA-DR haplotype (considering broad specificities) was B16,DR4, with a frequency of 8.0%. Five HLA-B,HLA-DR haplotypes showed significant delta values (observed vs. expected frequencies) after correcting for the number of comparisons. On the other hand, the most common HLA-DR,HLA-DQ haplotypes were DR4,DQ3 and DR5,DQ3 with a frequency higher than 10%. Ten of the 17 HLA-DR,HLA-DQ haplotypes had significant postcorrection delta values.

Ethnicity↗
PubMed1996

Effect of diuretic-based antihypertensive treatment on cardiovascular disease risk in older diabetic patients with isolated systolic hypertension. Systolic Hypertension in the Elderly Program Cooperative Research Group.

OBJECTIVE: To assess the effect of low-dose, diuretic-based antihypertensive treatment on major cardiovascular disease (CVD) event rates in older, non-insulin-treated diabetic patients with isolated systolic hypertension (ISH), compared with nondiabetic patients. DESIGN: Double-blind, randomized, placebo-controlled trial: the Systolic Hypertension in the Elderly Program (SHEP). SETTING: Multiple clinical and support centers in the United States. PARTICIPANTS: A total of 4736 men and women aged 60 years and older at baseline with ISH (systolic blood pressure [BP], > or = 160 mm Hg; diastolic BP, <90 mm Hg) at baseline, 583 non-insulin-dependent diabetic patients and 4149 nondiabetic patients (4 additional patients not so classifiable were randomized but not included in these analyses). Diabetes mellitus defined as physician diagnosis, taking oral hypoglycemic drugs, fasting glucose level of 7.8 mmol/L or more (> or = 140 mg/dL), or any combination of these characteristics. INTERVENTION: The active treatment group received a low dose of chlorthalidone (12.5-25.0 mg/d) with a step-up to atenolol (25.0-50.0 mg/d) or reserpine (0.05-0.10 mg/d) if needed. The placebo group received placebo and any active antihypertensive drugs prescribed by patient's private physician for persistently high BP. MAIN OUTCOME MEASURES: The 5-year rates of major CVD events, nonfatal plus fatal stroke, nonfatal myocardial infarction (MI) and fatal coronary heart disease (CHD), major CHD events, and all-cause mortality. RESULTS: The SHEP antihypertensive drug regimen lowered BP of both diabetic and nondiabetic patients, with few adverse effects. For both diabetic and nondiabetic patients, all outcome rates were lower for participants randomized to the active treatment group than for those randomized to the placebo group. Thus, 5-year major CVD rate was lower by 34% for active treatment compared with placebo, both for diabetic patients (95% confidence interval [CI], 6%-54%) and nondiabetic patients (95% CI, 21%-45%). Absolute risk reduction with active treatment compared with placebo was twice as great for diabetic vs nondiabetic patients (101/1000 vs 51/1000 randomized participants at the 5-year follow-up), reflecting the higher risk of diabetic patients. CONCLUSION: Low-dose diuretic-based (chlorthalidone) treatment is effective in preventing major CVD events, cerebral and cardiac, in both non-insulin-treated diabetic and nondiabetic older patients with ISH.

Adrenergic beta-Antagonists↗
PubMed1996

International comparison of hip fracture rates in 1988-89.

A comparison of hip fracture rates among nine countries (Canada, Chile, Finland, Hong Kong, Scotland, Sweden, Switzerland, the United States and Venezuela) was made using national hospital discharge data for the same time interval. The rates increased by age and were higher for females than males in all nine countries. When based on overall discharge rates, the incidence of hip fracture appeared high in three European countries (Finland, Scotland and Sweden) relative to the other countries. However, when transfer cases were removed and adjustments made for differences in case definition, the risk of hip fracture for both men and women was much similar among the four European and two North American countries, but higher than in Hong Kong. Rates of fracture were lowest in Venezuela and Chile, varying from three to 11 times less than for residents of the other seven countries. Although there are limitations in using hospital discharge data as a measure of incidence, the wide variation in the risk of hip fracture across the nine countries appears real but differences between North American and north European countries may not be as great as previously reported. Such cross-national comparisons may help clarify different etiologic hypotheses.

Age Factors↗
PubMed1994

Presence of Leishmania braziliensis in blood samples from cured patients or at different stages of immunotherapy.

By using a PCR assay specific for Leishmania braziliensis in blood samples, we detected this parasite in patients cured by immunotherapy or at different stages of treatment. We also found the parasite in subjects who had never suffered leishmaniasis but who had lived in endemic areas and migrated to nonendemic ones many years ago. These results suggest that L. braziliensis infections are difficult to eradicate and that a clinical cure but rarely a complete elimination of the parasite is generally accomplished.

Animals↗
PubMed1994

Influenza virus-infected dendritic cells stimulate strong proliferative and cytolytic responses from human CD8+ T cells.

Antigen-specific, CD8+, cytolytic T lymphocytes (CTLs) could potentially provide resistance to several infectious and malignant diseases. However, the cellular requirements for the generation of specific CTLs in human lymphocyte cultures are not well defined, and repetitive stimulation with antigen is often required. We find that strong CD8+ CTL responses to influenza virus can be generated from freshly isolated blood T cells, as long as dendritic cells are used as antigen presenting cells (APCs). Small numbers of dendritic cells (APC:T cell ratio of 1:50-1:100) induce these CTL responses from most donors in 7 d of culture, but monocytes are weak or inactive. Whereas both dendritic cells and monocytes are infected with influenza virus, the former serve as effective APCs for the induction of CD8+ T cells while the latter act as targets for the CTLs that are induced. The strong CD8+ response to influenza virus-infected dendritic cells is accompanied by extensive proliferation of the CD8+ T cells, but the response can develop in the apparent absence of CD4+ helpers or exogenous lymphokines. CD4+ influenza virus-specific CTLs can also be induced by dendritic cells, but the cultures initially must be depleted of CD8+ cells. These findings should make it possible to use dendritic cells to generate human, antigen-specific, CD8+ CTLs to other targets. The results illustrate the principle that efficient T cell-mediated responses develop in two stages: an afferent limb in which dendritic cells are specialized APCs and an efferent limb in which the primed T cells carry out an immune response to many types of presenting cells.

Antigen-Presenting Cells↗
PubMed1991

Sodium chloride raises blood pressure in normotensive subjects. The study of sodium and blood pressure.

The effects of dietary sodium on blood pressure in normotensive adults is not well characterized. The Study of Sodium and Blood Pressure (SNaP) is a randomized, double-blind crossover trial using a placebo or 96 meq sodium in 4-week treatment periods separated by a 2-week washout period. Before capsule treatment periods, participants were instructed in a low sodium diet for 10 weeks to reduce urinary sodium excretion to less than 35 meq/8 hr. The low sodium diet was continued throughout the capsule treatment periods. Participants (n = 48; 47 white, 1 black) were 79% male and had an average age of 52 years, a body mass index of 27.6, and a baseline blood pressure of 131/84 mm Hg. Baseline overnight urinary sodium excretion was 51 meq/8 hr and 19 meq/8 hr after the low sodium diet run-in period, before the capsule treatment periods began. Resting, seated blood pressure was measured twice at each visit in a standard fashion. Differences between sodium and placebo treatment periods were as follows: systolic blood pressure, 123.9 versus 120.3 mm Hg, respectively (p less than 0.001); diastolic blood pressure, 78.7 versus 76.4 mm Hg, respectively (p = 0.005); and sodium excretion, 51.3 versus 30.9 meq/8 hr, respectively (p less than 0.001). Both systolic and diastolic blood pressures increased significant amounts in normotensive adults on a low sodium diet supplemented with 96 meq/day sodium. Long-term effects and dose-response relations need further study.

Adult↗
PubMed1984

Complications associated with intra-arterial BCNU administered in combination with vincristine and procarbazine for the treatment of malignant brain tumors.

We have used intra-arterial (i.a.) 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) either alone or as part of adjuvant chemotherapy in patients with malignant brain tumors over a 3 year period (1979-1982). The i.a. BCNU technique was used 111 times to infuse 134 arteries in 37 patients. These patients, 28 cases with glial tumor and 9 cases with brain metastasis, received i.a. BCNU in combination with Vincristine and Procarbazine every 6 weeks. Complications encountered were transient and included: periorbital erythralgia or occipital-nuchal pain in 23 (62%), mild confusion and disorientation in 14 (38%), and ipsilateral conjunctival edema in 10 (27%). Reversible myelosuppression was not found. Our findings suggest that BCNU (100 mg/M2) may be given by i.a. infusion in combination chemotherapy without persistent severe untoward effects with a cumulative dose of 700 mg/M2.

Adolescent↗