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Biomedical subjects

L Herranz

Publications and source records attributed to L Herranz.

At least 19 recordsLinked to original sources

What is the relative contribution of blood glucose levels at different time points of the day to HbA1c in Type 1 diabetes?

AIMS: To evaluate the relative contribution of blood glucose levels at different time points of the day to HbA(1c) in Type 1 diabetes. METHODS: Consecutive home blood glucose records (n = 146) from 71 Type 1 diabetic patients who were on an intensive diabetes therapy programme were examined. Each home blood glucose record included six daily blood glucose profiles over 2 months. The relationship between glycaemic values at each time point and HbA(1c) measured at the end of each record period was analysed. RESULTS: Significant linear correlations were found between HbA(1c) and glycaemia at each time point of the day (ranged from 0.413 to 0.593), the strongest being with predinner glycaemia (r = 0.593; P = 0.000). Total daily glycaemia, mean preprandial and mean postprandial glycaemia were also significant and linearly correlated with HbA(1c) (r = 0.701; r = 0.686; r = 0.620, respectively; P < 0.0001). Multiple linear regression analysis showed that predinner, prebreakfast and post-breakfast glycaemia correlated significantly and independently with HbA(1c). The model accounted for 47.8% of the variance in HbA(1c). CONCLUSIONS: Our study shows that among individual time points, prebreakfast and predinner are those with more influence on HbA(1c) in Type 1 diabetes and, to a lesser extent, post breakfast. It also confirms that preprandial glycaemia better predicts overall glycaemic control in Type 1 diabetes than postprandial glycaemia.

Blood Glucose↗

[Effect of preconceptional metabolic control in the course of pregnancy in diabetic patients].

BACKGROUND: We analysed the relationship between metabolic control parameters during the preconception stage and pregnancy outcome in diabetic patients. PATIENTS AND METHOD: We examined 69 diabetic patients who underwent a preconception control at the Diabetes and Pregnancy Unit between 1992-1998. At the end of the preconception care period, 50 women (72.6%) became pregnant. Eight out of them (16%) had an abortion. RESULTS: Women who had an abortion did not differ from those who had not an abortion with regard to HbA1c levels at the end of the preconception period, age, duration of diabetes, age at diagnosis,anti-thyroid antibodies or microvascular disease. Among 41 single age stations, fetal macrosomia was observed in 36.6% cases, neonatal hypoglycemia in 19.5% and major congenital malformations in one case. Average level of HbA1c was 7.6 +/- 1.3%and 6.5 +/- 0.7 at the beginning and at the end of the preconception period, respectively (p < 0.001). In the group with macrosomia,average HbA1c at the end of the preconception period was 6.8 +/- 0.66% as opposed to 6.3 +/- 0.7% for the non-macrosomic group (p < 0.05). A linear correlation was seen between HbA1c levels at the end of the preconception period and infant weight (r = 0,432; p = 0,014), birth weight ratio (r = 0,450; p = 0,009), and a morbidity score (r = 0,458;p = 0,007). CONCLUSIONS: A better metabolic control during the preconception period may contribute to lessen the risk of fetal macrosomia and neonatal morbidity.

Adult↗

Early postpartum metabolic assessment in women with prior gestational diabetes.

OBJECTIVE: To present the results of early postpartum metabolic assessment in women with gestational diabetes mellitus (GDM), to determine predictive factors for subsequent diabetes, and to investigate the association of postpartum glucose tolerance with other components of the metabolic syndrome. RESEARCH DESIGN AND METHODS: A total of 788 women were evaluated 3-6 months after a GDM pregnancy. A 75-g oral glucose tolerance test (OGTT) was performed. Cholesterol, HDL cholesterol, triglycerides, blood pressure, BMI, and body fat distribution were assessed. Clinical and obstetric history, baseline variables at the diagnosis of GDM, metabolic control during pregnancy, and index pregnancy outcome were compared in women with diabetes and women without diabetes (American Diabetes Association [ADA] criteria) after pregnancy. Multivariate logistic regression analysis was used to ascertain independent predictors of subsequent diabetes. Correlation coefficients were assessed between postpartum glucose tolerance and lipid levels, blood pressure, BMI, and body fat distribution. RESULTS: According to ADA criteria, 588 (74.6%) women were normal, 46 (5.8%) had impaired fasting glucose, 82 (10.4%) had impaired glucose tolerance, 29 (3.7%) had both impaired fasting glucose and impaired glucose tolerance, and 43 (5.4%) had diabetes. Prepregnancy obesity, recurrence of GDM, gestational age at diagnosis of GDM, glucose values in the 100-g OGTT, number of abnormal values in the 100-g OGTT, fasting C-peptide levels in pregnancy, C-peptide/glucose score in pregnancy, insulin requirement in pregnancy, 3rd trimester HbA1c levels, and macrosomia differed significantly in women with subsequent diabetes. Independent predictors of postpartum diabetes were prepregnancy obesity, C-peptide/glucose score during pregnancy, and the number of abnormal values in the 100-g diagnostic OGTT. The area under the postpartum glucose curve was positively associated with BMI, waist circumference, waist-to-hip ratio, triglycerides, and systolic and diastolic blood pressures. CONCLUSIONS: Low C-peptide/glucose score during pregnancy together with prepregnancy obesity and severity of GDM (number of abnormal values in the 100-g diagnostic OGTT) are independent predictors of subsequent diabetes. Our data suggest that regardless of obesity and severity of GDM, a beta-cell defect increases the risk of postpartum diabetes. The association of postpartum glucose tolerance with triglyceride levels, blood pressure, obesity, and regional distribution of body fat suggests that postpartum glucose intolerance anticipates a high-risk cardiovascular profile that comprises other risk factors besides diabetes.

Adult↗

Efficacy of octreotide in the regression of a metastatic carcinoid tumour despite negative imaging with In-111-pentetreotide (Octreoscan).

We present the case of a 52-year old patient diagnosed with carcinoid tumour of the rectum with liver metastases in which treatment with somatostatin analogues (octreotide) proved very effective in the disappearance of the symptomatology and dramatic efficacy in the regression of the tumour. Imaging by octreoscan was always negative. The role of octreotide in the treatment of carcinoid tumour and the usefulness of In-111-pentetreotide (octreoscan) in the localization and prediction of the response to treatment with octreotide is discussed. We conclude that the negative result of the scintigraphic image with octreoscan does not necessarily suppose the inefficacy of octreotide treatment. We believe that this may constitute an important issue since some patients may be denied octreotide treatment in the absence of a positive octreoscan result.

Antineoplastic Agents, Hormonal↗

Body fat distribution, insulin mediated suppression of non-esterified fatty acids and plasma triglycerides in obese subjects.

Triglyceride levels and free fatty acid metabolism are influenced by body fat distribution. To test whether the pattern of fat distribution in obese subjects results in distinct insulin mediated suppression of non-esterified fatty acids which could account for differences in plasma triglycerides, we studied 59 obese subjects who were classified according to waist-to-hip ratio. Non-esterified fatty acids and insulin response to a 75 g oral glucose tolerance test were higher in abdominal obesity. Total non-esterified fatty acids response, after adjustment for sex, showed a positive association with waist-to hip ratio (r = 0.292; p < 0.05). The abdominal obese group had higher fasting triglycerides (1.74+/-0.83 versus 1.11+/-0.71 mmol/L; p = 0.003) and lower glucose/insulin ratio (5.2+/-2.3 versus 7.1+/-2.4; p = 0.003). Stepwise multiple regression analysis showed that triglyceride levels are explained by fasting and 120 min non-esterified fatty acids and by glucose/insulin ratio. We conclude that abdominal obesity is associated with a higher resistance to insulin mediated suppression of non-esterified fatty acids in obese subjects. Variation of triglyceride concentrations in obesity is dependent on both fasting and 120 min non-esterified fatty acids as well as on insulin sensitivity to glucose utilization.

Adolescent↗

Hürthle cell tumors.

OBJECTIVES: a) To provide a clinicopathological profile of Hürthle cell neoplasms (HCT) in our experience. b) To evaluate if there are any differences in the clinical or morphological features between three HCT categories: benign, malignant and indeterminate. c) To examine the role of the clinical and morphological features in predicting the behavior of these neoplasms. METHODS: We reviewed the clinical reports of all patients with a histological diagnosis of HCT at our Hospital between 1981 and 1996. The final study group consisted of 25 cases. The neoplasms were divided into three categories on the basis of presence and degree of capsular and vascular invasion, marked nuclear atypia, tumour necrosis and pattern of growth. A series of clinical parameters were evaluated. RESULTS: Of the 25 tumors, 52% were morphologically classified as benign, 8% as indeterminate and 40% as malignant. Follow-up ranged from 10 months to 14.8 years or until death (average 3.8 years). There were four local recurrences (20%), three in the malignant group (30%) and one in the benign group (7.6%) (p = 0.15). One patient presented metastases and died because of tumor during the follow-up. Apart from capsular and vascular invasion and some aspects of therapy, no significant differences were found in the clinical and histological parameters analyzed between the three histological groups or between the groups with or without recurrence. CONCLUSION: We did not find any clinical or morphological parameter which can predict recurrence among these tumors. Our study further establishes the controversial issues surrounding the biological behavior of Hürthle cell neoplasms.

Adenoma, Oxyphilic↗

Leuprolide suppression of androgen secretion by hilus cell hyperplasia within the wall of an ovarian cyst.

Androgenic manifestations coexisting with hilus cell hyperplasia adjacent to a tumour or an ovarian cyst are extremely rare. We report the case of a post-menopausal woman with hirsutism associated with hilus cell hyperplasia within the wall of an ovarian cyst. The pattern of steroid secretion revealed increased testosterone release. Suppression of testosterone to 'normal range' was seen in response to leuprolide administration. This new approach demonstrates gonadotrophin dependence of hilus cell hyperplasia within an ovarian cyst.

Androstenedione↗

Dehydroepiandrosterone sulphate, body fat distribution and insulin in obese men.

Sex steroid hormones may be involved in determining body fat distribution in men. Recent evidence suggests that insulin may be an important regulator of sex hormones metabolism in men. Few data, however, are available on the relationship of dehydroepiandrosterone sulphate (DHEA-SO4), a major secretory product of the adrenal gland, to regional distribution of body fat or to insulin levels in men. We therefore examined the association of DHEA-SO4, total testosterone and free testosterone to waist-to-hip ratio (WHR) and to subscapular-to-triceps ratio (STR) in 34 obese, otherwise healthy men. In addition, we examined the relation between these sex steroid hormones and insulin response to an oral glucose tolerance test. DHEA-SO4 was significantly positively related to STR and significantly negatively related to insulin area. These associations remained significant after adjustment for age and obesity. Using multiple linear regression, DHEA-SO4 was independently related to both STR and insulin area. Without claiming any causality in the observed associations, we conclude that, in obese men, high DHEA-SO4 levels are related to centralized adiposity, while low DHEA-SO4 levels are related to hyperinsulinemia.

Adipose Tissue↗

RNA-mediated specificity of DNA packaging into hybrid lambda/phi 29 proheads.

A small RNA (pRNA, 174 nt) is known to be essential for DNA packaging in bacteriophage phi 29. However, in an in vitro DNA packaging system based on hybrid lambda/phi 29 proheads (made up of head proteins from phage lambda and connectors from phage phi 29), the specificity of DNA packaging is lost, and different RNA molecules fulfil the requirements for DNA packaging, albeit with less efficiency than phi 29 pRNA. Competition assays with RNAs from different sources have shown that phi 29 connectors bind preferentially pRNA. An increase in the efficiency of phi 29 DNA packaging into hybrid proheads induced by phi 29 pRNA is observed because, when phi 29 pRNA is incubated with hybrid proheads, phi 29 DNA is packaged more efficiently than other DNAs of similar length. Furthermore, when hybrid proheads carrying phi 29 pRNA are incubated with a mixture of DNAs from different sources, phi 29 DNA is selectively packaged, thus indicating that phi 29 pRNA determines the specificity of DNA packaging.

Amino Acid Sequence↗

Protein intake during aggressive calorie restriction in obesity determines growth hormone response to growth hormone-releasing hormone after weight loss.

OBJECTIVE: We evaluated the influence of two types of calorie restriction, total fast or very low calorie diet, on GH responsiveness to GHRH in severely obese patients. DESIGN: Twenty patients with massive obesity underwent one of two types of calorie restriction, total fast (10 patients) or very low calorie diet (10 patients). MEASUREMENTS: Fasting GH, IGF-I, glucose, insulin and GH secretion after GHRH (100 ug i.v.) were assessed in all patients before and after diet therapy. RESULTS: Both types of diet produced similar weight reduction (total fast, 5.6 +/- 1.6 kg/m2 vs very low calorie diet, 5.6 +/- 1.5 kg/m2 mean +/- SD). A significant increase in the integrated GH secretion was observed after weight loss with very low calorie diet (17 +/- 9 vs 27 +/- 12 mU/l min; P < 0.05). However, no change was found in GH response after weight loss with total fast (13 +/- 5 vs 15 +/- 7 mU/l min). Glucose, insulin and IGF-I levels showed a significant decrease with weight reduction which was similar for both groups. CONCLUSION: These findings suggest that the type of dietary manipulation during calorie restriction in obese patients may influence the changes in GH response to GHRH after weight loss.

Adult↗

DNA conformational change induced by the bacteriophage phi 29 connector.

Translocation of viral DNA inwards and outwards of the capsid of double-stranded DNA bacteriophages occurs through the connector, a key viral structure that is known to interact with DNA. It is shown here that phage phi 29 connector binds both linear and circular double-stranded DNA. However, DNA-mediated protection of phi 29 connectors against Staphylococcus aureus endoprotease V8 digestion suggests that binding to linear DNA is more stable than to circular DNA. Endoprotease V8-protection assays also suggest that the length of the linear DNA required to produce a stable phi 29 connector-DNA interaction is, at least, twice longer than the phi 29 connector channel. This result is confirmed by experiments of phi 29 connector-protection of DNA against DNase I digestion. Furthermore, DNA circularization assays indicate that phi 29 connectors restrain negative supercoiling when bound to linear DNA. This DNA conformational change is not observed upon binding to circular DNA and it could reflect the existence of some left-handed DNA coiling or DNA untwisting inside of the phi 29 connector channel.

Bacillus Phages↗

Autoimmune insulin syndrome in a patient with progressive systemic sclerosis receiving penicillamine.

The case of a patient with progressive systemic sclerosis, who developed hypoglycaemia and insulin autoantibodies, is described. Repeated blood glucose measurements showed levels less than 2.8 mmol/l. High immunoreactive insulin levels, with undetectable free insulin, led to the discovery of anti-insulin antibodies in the patient's serum. He had no history of exogenous insulin use and was receiving penicillamine treatment. A double mechanism for the autoimmune insulin syndrome in this case is proposed: acting in a patient with increased humoral immunoresponsiveness, penicillamine might have induced the development of insulin autoantibodies.

Adult↗

Conformational changes in bacteriophage phi 29 connector prevents DNA-binding activity.

In vitro DNA packaging activity in a defined system derived from bacteriophage phi 29 depends upon the chemical integrity of the connector protein p10. Proteolytic cleavage of p10 rendered the proheads inactive for DNA packaging. A similar treatment on isolated connectors abolished the DNA-binding activity of the native p10, but the general shape and size of the connector was not changed as revealed by electron microscopy. Analytical ultracentrifugation showed that the proteolyzed connectors had a smaller sedimentation coefficient, while amino acid analysis after dialysis of the proteolyzed p10 confirmed the loss of 16 and 19 amino acids from the amino and carboxy termini, respectively. Low angle X-ray scattering revealed that proteolysis was followed by a small decrease in the radius of gyration and a reorganization of the distal domain of the cylindrical inner part of the connector. Characterization of the cleavage sites in the primary sequence allowed us to propose the location of the DNA-binding domain in the connector model.

Amino Acid Sequence↗

Bacteriophage T3 connector: three-dimensional structure and comparison with other viral head-tail connecting regions.

The bacteriophage T3 connector, which consists of 12 copies of protein gp8, has been studied by image processing of electron micrographs from negatively stained ordered aggregates. A three-dimensional reconstruction of T3 connectors was obtained by collection of tilted views and using the direct Fourier method, up to 2.3 nm resolution. The reconstructed unit cell contains two connectors whose main structural features are essentially identical, but facing in opposite directions. The T3 connector has a height of about 10.9 nm, with two clearly defined domains: a wider one 14.4 nm in diameter, with 12 morphological units in the periphery, and a narrower one, 9.7 nm in diameter. There is a channel clearly defined in the narrower domain that almost closes along the wider domain. Comparison of the three-dimensional structure obtained for the connector of phages T3 and phi 29, and that of the neck extracted from phage phi 29 particles, reveals striking similarities and significant differences. A model for a general connector to account for the common functions carried out by these viral assemblies is discussed together with the possible role of the channel for DNA translocation.

Computer Graphics↗

Three-dimensional reconstruction of the connector of bacteriophage phi 29 at 1.8 nm resolution.

The three-dimensional reconstruction of the connector of bacteriophage phi 29 has been obtained from tilt series of negatively stained tetragonal ordered aggregates under low-dose conditions and up to a resolution of (1/1.8) nm-1. These connectors are built up as dodecamers of only one structural polypeptide (p10). Two connectors form the crystal unit cell, each one facing in the opposite direction with respect to the plane of the crystal and partially overlapping. The main features of the two connectors that build the unit cell were essentially the same, although they were negatively stained in slightly different ways, probably due to their situations with respect to the carbon-coated support grid. The main features of the phi 29 connector structure revealed by this three-dimensional reconstruction are: the existence of two clearly defined domains, one with a diameter of around 14 nm and the other narrower (diameter approximately equal to 7.5 nm); an inner hole running all along the structure (around 7 to 8 nm in height) with a cylindrical profile and an average diameter of 4 nm; a general 6-fold symmetry along the whole structure and a 12-fold one in the wider domain; a clockwise twist of the more contrasted regions of both domains from the narrower towards the wider domain (the direction of DNA encapsidation). These features are compatible with an active role for the connector in the process of DNA packaging.

Bacteriophages↗