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Biomedical subjects

Jorge L Gross

Publications and source records attributed to Jorge L Gross.

At least 19 recordsLinked to original sources

The effect of aspirin and vitamins C and E on HbA1c assays.

BACKGROUND: Aspirin (ASA) and vitamins C and E may inhibit non-enzymatic glycation in vivo and may also interfere with HbA(1c) assays, masking true results. We investigated the effect of usual doses of ASA, vitamin C and E on HbA1c levels in a group of non-diabetic volunteers. METHODS: A randomized clinical trial was performed with 28 healthy non-diabetic individuals. Subjects were allocated to take ASA 200 mg/day, vitamin C 1 g/day, vitamin E 400 mg/day, or to a control group, for a period of 4 months. Blood samples were collected at baseline and at monthly intervals for HbA1c analysis by HPLC Variant II (BioRad), HPLC L-9100 (Merck - Hitachi) and Tina Quant HbA(1c) II immunoassay (Roche). RESULTS: HbA(1c) levels of the control, vitamin C and E groups did not change throughout the study, independently of the method used. HbA(1c) measured by Hitachi L-9100 HPLC increased significantly (P=0.033) at 4 months after ASA intake, although this increase was of only 0.17%. CONCLUSIONS: Treatment with vitamins C and E in pharmacological doses does not have any impact on HbA1c measurements in non-diabetic patients with the three methods employed. ASA induces a modest, not clinically relevant, increase in HbA1c levels with one of the methods.

Ascorbic Acid↗

Value of diagnostic tools for myocardial ischemia used in routine clinical practice to predict cardiac events in patients with type 2 diabetes mellitus: a prospective study.

OBJECTIVE: To analyze tests used in routine clinical practice for the diagnosis of myocardial ischemia to predict the development of cardiac events in type 2 diabetic patients. METHODS: The occurrence of cardiac events (new myocardial infarct, myocardial re-vascularization procedures, congestive heart failure, acute pulmonary edema, sudden death, and death after myocardial infarction or pulmonary edema) were prospectively assessed in a cohort of 135 type 2 diabetic patients after up to seven years of follow-up. At baseline, coronary artery disease was assessed by the WHO cardiovascular questionnaire, resting electrocardiogram, and stress myocardial scintigraphy. RESULTS: Forty-eight cardiac events were observed in 41 patients (10.5 events/100 patients-year). In a Cox's proportional-hazard model only the presence of symptoms of coronary artery disease on the WHO cardiovascular questionnaire alone (RR = 2.13, 95% CI 1.11-4.07, P= 0.022) or in combination with abnormalities on resting ECG (RR= 2.03, 95% CI 1.05-3.92, P= 0.034) or on myocardial scintigraphy (RR= 1.89, 95% CI 1.001-3.57, P= 0.050) predicted cardiac events, adjusted for fasting plasma glucose, mean blood pressure, body mass index, peripheral vascular disease and diabetic nephropathy. CONCLUSION: The WHO cardiovascular questionnaire, a simple tool for the diagnosis of coronary artery disease, is a significant predictor of cardiac events in type 2 diabetic patients.

Cohort Studies↗

A simplified protocol to screen for distal polyneuropathy in type 2 diabetic patients.

To test a simplified protocol to screen type 2 diabetic patients (DM2) for distal polyneuropathy (DPN), 80 outpatients and 45 controls answered a symptom questionnaire, underwent a directed examination (pin-prick, tuning fork, monofilament, ankle jerk, cold spatula and walking on heels), autonomic tests, and an electroneurophysiological study (EMG). Symptoms were also analysed as scores. DPN was diagnosed in the presence of abnormal EMG (or autonomic neuropathy), plus one symptom or one abnormal objective finding. Symptoms were equally frequent in patients (56%) and controls (35%, P=0.20). Objective findings were more frequent in patients (62/80 versus 11/45; P<0.05). The 60 DM2 patients with DPN were older, with longer diabetes duration and more often hypertensive than those without DPN. The 15 patients unable to walk on heels had DPN (sensitivity 20.8%, specificity 100%, positive predictive value 100% and negative predictive value 12.3%). The 12 patients able to walk on heels but with three or more abnormal tests had DPN (sensitivity 21.1%, specificity 100%, positive predictive value 100% and negative predictive value 15.1%). Isolated signs and symptoms do not identify patients with DPN. Patients with higher degrees of impairment can be identified by six simple ambulatory tests, reducing in one-third the need for EMG.

Aged↗

[Blood pressure homeostasis and microvascular complications in diabetic patients].

The retinopathy and nephropathy are among the most prevalent and disabling complications associated to microvascular damage in diabetes mellitus. The severity of hyperglycaemia and the presence of arterial systemic hypertension are among the main risk factors for these complications. The ambulatory blood pressure provided a better understanding of patterns of blood pressure in diabetic patients. There is a growing number of evidence relating diabetic patients with abnormal 24 h blood pressure patterns. Even subtle modifications of these patterns, frequently shown by patients diagnosed as normotensives in office blood pressure measurings, may be implicated in an increased risk of microvascular complications. Hyperglycaemia and these abnormal pressure patterns appear to have a synergistic effect on promoting and aggravating diabetic retinopathy. Impairment of the normal retinal autoregulation is one of the implicated physiopathological mechanisms. Probably, ABP may be useful in predicting an increased risk of microvascular complications on diabetic normotensive patients. The objective of this paper is to provide an updated and clinically oriented review in blood pressure homeostasis and diabetes mellitus.

Albuminuria↗

Withdrawal of red meat from the usual diet reduces albuminuria and improves serum fatty acid profile in type 2 diabetes patients with macroalbuminuria.

BACKGROUND: Replacement of red meat in the diet with chicken has reduced the urinary albumin excretion rate (UAER) and serum cholesterol in microalbuminuric type 2 diabetes patients. The effects of withdrawing red meat are unknown in the more advanced stages of diabetic nephropathy. OBJECTIVE: Our objective was to assess the effects of replacing red meat in the usual diet (UD) with chicken (CD) and of consuming a lactovegetarian low-protein diet (LPD) on renal function, fatty acid, and lipid profile in macroalbuminuric type 2 diabetes patients. DESIGN: A crossover controlled trial was conducted in 17 type 2 diabetes patients with macroalbuminuria (24-h UAER > or = 200 microg/min). Each patient followed the UD, CD, and LPD in a random order for 4 wk. After each diet, glomerular filtration rate, UAER, serum fatty acid, lipid profile, glycemic control, anthropometric indexes, and blood pressure were measured. RESULTS: UAER [median CD: 269.4 (range: 111-1128) microg/min; LPD: 229.3 (76.6-999.3) microg/min; UD: 312.8 (223.7-1223.7) microg/min; P < 0.01] and mean (+/-SD) non-HDL cholesterol (CD: 3.92 +/- 0.99 mmol/L; LPD: 3.92 +/- 0.93 mmol/L; UD: 4.23 +/- 1.06 mmol/L; P = 0.042) were lower after CD and LPD than after UD. Compared with the UD, an increase in serum total polyunsaturated fatty acids was also observed (CD: 39.8 +/- 2.6%; LPD: 39.7 +/- 4.4%; UD: 37.3 +/- 3.1%; P = 0.029). CONCLUSION: In macroalbuminuric patients with type 2 diabetes, withdrawing red meat from the diet reduces the UAER.

Aged↗

Familial history of type 2 diabetes in patients from Southern Brazil and its influence on the clinical characteristics of this disease.

OBJECTIVE: To investigate the presence of maternal and paternal history of type 2 diabetes mellitus (DM) in relatives of 644 type 2 diabetic patients from Southern Brazil, and also to evaluate its influence on the clinical characteristics of this disease. PATIENTS AND METHODS: Familial history of type 2 DM was investigated by a questionnaire. The maternal and paternal history was investigated over two generations. Complete data sets on familial history were obtained from 396 patients. RESULTS: In general, 76.6% of the patients reported at least one first-degree affected relative. Besides, 31.6% of the patients reported a maternal history of type 2 DM and 12.6% reported a paternal history. Patients with maternal and/or paternal history presented a lower age at type 2 DM diagnosis when compared to patients without familial history. In addition, patients with only paternal history presented a higher frequency of hypertension than patients with no familial history. CONCLUSIONS: This study suggests that there is a significant maternal effect in the transmission of type 2 DM in Southern Brazil, and that most of the clinical characteristics of this disease do not differ between patients with or without familial history of type 2 DM.

Adult↗

Aspirin therapy is still underutilized among patients with type 2 diabetes.

The daily use of aspirin in patients with type 2 diabetes mellitus (DM2) reduces significantly cardiovascular events (CVE). In the absence of contraindications, American Diabetes Association (ADA) recommends the use of aspirin to all DM2 patients older than 40 years of age. To evaluate aspirin use among 636 out patients with DM2 who participate in a regional multicenter study in Southern Brazil, a standard questionnaire was used. Patients also underwent a physical examination and laboratorial tests. All patients were older than 40 years (mean 58 +/- 11 years old; 42% male) and by ADA guidelines most of them should be using aspirin. However, only 177 (27.5%) were on this medication. The use of aspirin was higher when any CVE were present. However, the percentage of users was still below the expected, not even reaching 50%. In conclusion, even though the use of aspirin is greater in patients with CVE, and its benefits are well documented, it is still underutilized. Strategies to enhance the use of aspirin should be developed to reduce the morbidity and mortality from cardiovascular diseases in patients with DM2.

Adult↗

[Pituitary abscess simulating apoplexy].

A pituitary abscess is a rare pathology, but it must be considered when evaluating sellar masses, since its prognosis depends on surgical drainage and on the use of specific antibiotics. The main clinical manifestation is chronic headache, and it is not always associated with the identification of a site of infection, which diminishes the probability of including it in diagnostic hypotheses. The case is presented of a patient with a pituitary abscess and a previous history of adenoma that had been operated on, recent onset headache and acquired hypopituitarism whose initial diagnosis was pituitary apoplexy.

Adenoma↗

[The role of the diet as a risk factor for the development and progression of diabetic nephropathy].

Diabetic nephropathy (DN) is the leading cause of kidney disease in patients starting renal replacement therapy, and affects up to 40% of type 1 and type 2 diabetic patients. Diet seems to play an important role in the development of the disease. There are evidences supporting the concept that not only the amount but also the origin of dietary protein are associated with DN. Few studies analyzed the role of dietary lipids. A low-protein diet slows down the decline of renal function and ameliorates the DN prognosis and death in patients with type 1 diabetes with micro- and macroalbuminuria. Studies in type 2 diabetic patients are scanty but short-term studies suggest that this approach decreases albuminuria. However, the use of low-protein diet for long periods is compromised by poor compliance and its long-term safety is not firmly established. Enthusiastic results come up when comparing the effect of different sources of animal protein on renal function and lipid profile in patients with DN, which may represent an alternative strategy for low-protein diet on medical nutritional therapy in patients with DN and in cardiovascular risk factors and endothelial function.

Albuminuria↗

The type 2 deiodinase A/G (Thr92Ala) polymorphism is associated with decreased enzyme velocity and increased insulin resistance in patients with type 2 diabetes mellitus.

The single-nucleotide polymorphism A/G in the type 2 deiodinase (D2) gene predicts a threonine (Thr) to alanine (Ala) substitution at codon 92 (D2 Thr92Ala) and is associated with insulin resistance in obese patients. Here, this association was investigated in 183 patients with type 2 diabetes mellitus, using homeostasis model assessment. The median fasting plasma insulin in Ala/Ala individuals was significantly higher than in patients with Ala/Thr or Thr/Thr genotypes (19.6 vs. 12.0 vs. 14.8 mIU/ml, respectively; P = 0.004). Assuming a recessive model, the homeostasis model assessment index was higher in the Ala/Ala group when compared with Ala/Thr-Thr/Thr group (8.50 vs. 4.85, P = 0.003). Although this polymorphism has not been associated with changes in D2 kinetics as measured in HEK-293 cells transiently expressing D2 Thr92Ala, we investigated whether such association could be detected in human tissue samples. Remarkably, in thyroid and skeletal muscle samples from subjects homozygous for the Ala allele, D2 velocity was significantly lower than in subjects with Ala/Thr-Thr/Thr genotypes (P = 0.05 and 0.04, respectively). In conclusion, the A/G polymorphism is associated with greater insulin resistance in type 2 diabetes mellitus patients and with lower D2 velocity in tissue samples. These findings suggest that the D2-generated T(3) in skeletal muscle plays a role in insulin resistance.

Alanine↗

The fatty acid-binding protein-2 A54T polymorphism is associated with renal disease in patients with type 2 diabetes.

The intestinal fatty-acid binding protein-2 (FABP2) gene codes a protein responsible for the absorption of long-chain fatty acids. To test whether FABP2 is a candidate gene for renal disease in patients with type 2 diabetes, a functional A54T polymorphism was genotyped in 1,042 Brazilians with type 2 diabetes. Patients were classified as having normoalbuminuria (urinary albumin excretion [UAE] <20 microg/min; n = 529), microalbuminuria (UAE 20-199 microg/min; n = 217), or proteinuria (UAE >199 microg/min; n = 160). Patients with end-stage renal disease (ESRD) (n = 136) were also included. The prevalence of the TT genotype was higher in patients with renal involvement compared with those with normoalbuminuria (odds ratio [95% CI] 2.4 [1.1-5.4]) following adjustment for type 2 diabetes duration, BMI, hypertension, A1C, and cholesterol levels. The risk was similar considering different stages of renal involvement. In a second independent patient sample (483 type 2 diabetic Caucasians residing in Massachusetts), a significant association was also observed between the TT genotype and proteinuria or ESRD (2.7 [1.0-7.3]; P = 0.048). This study thus provides evidence that FABP2 confers susceptibility to renal disease in type 2 diabetic patients.

Brazil↗

Diabetic nephropathy: diagnosis, prevention, and treatment.

Diabetic nephropathy is the leading cause of kidney disease in patients starting renal replacement therapy and affects approximately 40% of type 1 and type 2 diabetic patients. It increases the risk of death, mainly from cardiovascular causes, and is defined by increased urinary albumin excretion (UAE) in the absence of other renal diseases. Diabetic nephropathy is categorized into stages: microalbuminuria (UAE >20 microg/min and < or =199 microg/min) and macroalbuminuria (UAE > or =200 microg/min). Hyperglycemia, increased blood pressure levels, and genetic predisposition are the main risk factors for the development of diabetic nephropathy. Elevated serum lipids, smoking habits, and the amount and origin of dietary protein also seem to play a role as risk factors. Screening for microalbuminuria should be performed yearly, starting 5 years after diagnosis in type 1 diabetes or earlier in the presence of puberty or poor metabolic control. In patients with type 2 diabetes, screening should be performed at diagnosis and yearly thereafter. Patients with micro- and macroalbuminuria should undergo an evaluation regarding the presence of comorbid associations, especially retinopathy and macrovascular disease. Achieving the best metabolic control (A1c <7%), treating hypertension (<130/80 mmHg or <125/75 mmHg if proteinuria >1.0 g/24 h and increased serum creatinine), using drugs with blockade effect on the renin-angiotensin-aldosterone system, and treating dyslipidemia (LDL cholesterol <100 mg/dl) are effective strategies for preventing the development of microalbuminuria, in delaying the progression to more advanced stages of nephropathy and in reducing cardiovascular mortality in patients with type 1 and type 2 diabetes.

Albuminuria↗

Urinary albumin excretion rate is associated with increased ambulatory blood pressure in normoalbuminuric type 2 diabetic patients.

OBJECTIVE: To evaluate the 24-h blood pressure profile in normoalbuminuric type 2 diabetic patients. RESEARCH DESIGN AND METHODS: A cross-sectional study was conducted in 90 type 2 diabetic patients with a urinary albumin excretion rate (UAER) <20 microg/min on two occasions, 6 months apart (immunoturbidimetry). Patients underwent clinical and laboratory evaluations. Ambulatory blood pressure monitoring and echocardiograms were also performed. RESULTS: UAER was found to correlate positively with systolic doctor's office blood pressure measurements (r = 0.243, P = 0.021) and ambulatory blood pressure (24 h: r = 0.280, P = 0.008) and left ventricular posterior wall thickness (r = 0.359, P = 0.010). Patients were divided into four groups according to UAER (<5, > or =5-10, > or =10-15, and > or =15-20 microg/min). Systolic blood pressure parameters for the 1st, 2nd, 3rd, and 4th groups, respectively, were 123.0 +/- 10.6, 132.5 +/- 15.0, 139.0 +/- 23.4, and 130.7 +/- 8.0 mmHg for 24-h blood pressure (ANOVA P = 0.004) and 48.4 +/- 6.0, 54.5 +/- 11.2, 58.8 +/- 15.6, and 57.6 +/- 8.0 mmHg for 24-h pulse pressure (ANOVA P = 0.003). A progressive increase in the prevalence of diabetic retinopathy was observed from the 1st to the 4th UAER group: 27.3, 43.8, 45.5, and 66.7% (P = 0.029 for trend). CONCLUSIONS: In type 2 diabetic patients, UAER in the normoalbuminuric range is positively associated with systolic ambulatory blood pressure indexes, left ventricular posterior wall thickness, and diabetic retinopathy, suggesting that intensive blood pressure treatment may prevent diabetes complications in these patients.

Albuminuria↗

Effect of pre-analytical variables on glycohemoglobin measurements in routine clinical care.

OBJECTIVES: To analyze the contribution of the labile A1C fraction (L-A1C) and sample storage conditions on GHb measurements. DESIGN AND METHODS: L-A1C separation (HPLC Hitachi L-9100) was evaluated before and after sample treatment by four different methods for L-A1C removal. Different sample storage conditions were analyzed. RESULTS: L-A1C may overestimate up to 1.64% total A1C if not properly separated. Samples were stable for up to 10, <1, and at least 100 days for whole blood stored at 4, -20, and -80 degrees C, respectively. CONCLUSIONS: The presence of L-A1C may overestimate GHb results. Samples may be kept under refrigeration up to 10 days and at -80 degrees C if long-term storage is required.

Analysis of Variance↗

Serum thyrotropin-receptor autoantibodies levels after I therapy in Graves' patients: effect of pretreatment with methimazole evaluated by a prospective, randomized study.

OBJECTIVE: Radioiodine therapy (131I) in hyperthyroid Graves' disease is generally followed by a transitory increase in levels of thyrotropin receptors antibodies (TRAb). Immunosuppressive effects of antithyroid drugs are still a matter of debate. In this study we evaluated the effect of methimazole pretreatment on the TRAb boost induced by 131I. DESIGN: A randomized, prospective clinical trial. METHODS: 61 patients were randomly assigned to receive 131I alone (32 patients) or 131I plus pretreatment with methimazole (30 mg/day; 29 patients). Serum TRAb levels were measured on the day of 131I dosing (D0), and at 1, 3, 6 and 12 months after 131I administration. RESULTS: The mean serum TRAb levels decreased significantly from baseline to D0 in patients treated with methimazole (80.8 vs 48.8 U/l; P<0.05). After 131I treatment, TRAb levels increased at 3 months (48.8 to 60 U/l; 19%) and they were still elevated at 6 months compared with D0 values (99.9 U/l; 105%). Thereafter, TRAb levels decreased to baseline values (47.8 U/l) at 12 months. In hyperthyroid patients, TRAb levels increased significantly from D0 to 1 month (45.0 to 78 U/l; 73%) reaching their highest levels at 3 months (225 U/l; 400%). After this, we observed a progressive decrease to the baseline levels at 12 months (40.0 U/l). The course of TRAb levels after 131I treatment was significantly different between the two groups (P<0.05). Multiple regression analysis identified serum TRAb levels on D0 as independent predictors of TRAb increment after 131I therapy (r2=0.34; P=0.001). A higher increment in serum TRAb levels was associated with hypothyroidism after 1 year of follow-up. CONCLUSION: Methimazole pretreatment attenuates the 131I-induced rise in serum TRAb levels. The effects of methimazole could be attributed to a direct immunomodulatory action or may be due to its effects on the control of hyperthyroidism, which is a known cause of immune dysregulation.

Adult↗

RET codon 634 mutations in multiple endocrine neoplasia type 2: variable clinical features and clinical outcome.

Since the establishment of a protocol for molecular analysis of hereditary medullary thyroid carcinoma (MTC) in southern Brazil, in 1997, 17 independent families with RET germline mutation have been identified. Because neither molecular diagnosis nor the pentagastrin test were available before the establishment of this protocol, we had the opportunity to observe a large number of patients in whom the disease has evolved naturally without medical intervention, namely prophylactic thyroidectomy. We observed a wide spectrum in terms of clinical presentation and natural course of the disease even among genetically related individuals. Sixty-nine individuals from 12 different families presented a codon 634 mutation, the most prevailing missense mutation in our series. The specific mutations identified were C634Y (n = 49), C634R (n = 13), and C634W (n = 7). Individuals with the C634R mutation presented significantly more distant metastases at diagnosis than subjects with the C634Y or C634W mutations (54.5% vs. 19.4% vs. 14.3%, respectively, P = 0.03). Further analysis of the estimated cumulative frequency of lymph node and/or distant metastases by Kaplan-Meier curves showed that the appearance of lymph nodes and metastases occurred later in patients with C634Y than in those with C634R (P = 0.001). Our results suggest that specific nucleotide and amino acid exchanges at codon 634 might have a direct impact on tumor aggressiveness in MEN 2A syndrome.

Adult↗