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Biomedical subjects

M T Muñoz

Publications and source records attributed to M T Muñoz.

At least 19 recordsLinked to original sources

A variation in Bone Alkaline Phosphatase levels that correlates positively with bone loss and normal levels of aminoterminal propeptide of collagen I in girls with anorexia nervosa.

Anorexia nervosa (AN) is a very extended pathology among adolescent girls nowadays. These patients show a high degree of osteopenia; hence, study of their bone remodelling is of great interest. Serum bone alkaline phosphatase (bAP) and aminoterminal propeptide of procollagen I (PINP) provide good sensitivity in the analysis of bone alterations in postmenopausal osteoporosis. The aim of this study was to compare the usefulness of bAP and PINP in the study of bone remodelling in AN, and their possible correlation with the degree of osteopenia in this pathology. In order to help in the interpretation of the results, levels of the beta-isomer of urinary carboxyterminal propeptide of collagen I (beta-CTX) have also been included. Serum bAP (IRMA) Tandem R-Ostase, Hybritech), PINP (RIA, Orion Diagnostica) and CTX (CrossLaps ELISA, Osteometer) were determined in 41 girls with AN, aged 18.5+/-2.2 years (mean+/-SD) and in 31 healthy control women, aged 19+/-2.3 years. Bone mineral density (BMD) in lumbar spine was measured by DEXA in the AN group. We found that 41 of the 43 patients had BMD z-scores under -2. No significant differences were found in the levels of serum bAP nor in PINP and beta-CTX levels between controls and patients, although values in the AN group were highly variable. All the BMD z-score values were negative, and their absolute value correlates positively with bAP (P = 0.0279) and almost with beta-CTX (P = 0.0921) but not with PINP (P = 0.4627). Bone AP correlates with PINP in control girls (P = 0.017), but not in the AN group (P = 0.3573). Patients with AN were divided into three groups according to their levels of bAP: low (I), normal (II) or high (III). Patients with the highest bAP levels also presented the highest increase in bone resorption, according to their beta-CTX levels, and the highest degree of osteopenia. However, values of PINP were similar in the three groups of patients. The bAP/beta-CTX ratios in subgroups I, II and III of AN patients were 0.035, 0.065 and 0.073, a finding that suggests that bAP is not indicating the real degree of bone mineralization in these patients, because it is a contradiction that the formation/resorption ratio should be higher in the patients who have the highest bone loss. These results could suggest that bone loss in AN is produced by an increase in bone resorption (beta-CTX), without variations in bone matrix formation (PINP); bAP levels are a good marker in the follow-up of osteopenia degree, but not a real indicator of bone mineralization, a similar situation to that of osteomalacia.

Adolescent

Collagenous gastrobulbitis and collagenous colitis. Case report and review of the literature.

A case is reported of collagenous gastrobulbitis on collagenous colitis in a 57-year-old woman with a 6-month history of watery diarrhea. Low serum levels of total proteins and albumin and increased fecal elimination of alpha1-antitrypsin were the only abnormal laboratory test results. Biopsy specimens from the colon, rectum, antrum, fundus, and duodenal bulb showed a thick subepithelial band composed of ultrastructurally normal collagen immunohistochemically negative for collagen IV and laminin. The diarrhea resolved with prednisone and responded to this treatment after a relapse 6 months later. One year later the patient developed severe alimentary intolerance and secondary weight loss. This symptom also responded to the same treatment. However, the collagen deposition did not disappear in the second biopsy samples of colonic and gastric mucosa. Only six cases have been previously reported with gastric and/or duodenal subepithelial collagenous deposition. Four were associated with collagenous colitis. One of these presented a subepithelial collagenous band in the terminal ileum. All these features suggest that this collagen deposition may affect the entire digestive tract with variable intensity, extension, and symptoms.

Colitis

Disturbances in the growth hormone-insulin-like growth factor axis in children and adolescents with different eating disorders.

Numerous endocrine abnormalities of the growth hormone (GH)-insulin-like growth factor axis have been described in patients with both anorexia nervosa and obesity during childhood and adolescence. These alterations include changes in the levels of 24-hour spontaneous GH secretion, high-affinity, low-capacity GH binding protein (GHBP), IGF-I, IGF-II and the IGF binding proteins (IGFBPs). However, the existing information is sometimes confusing and contradictory. Furthermore, little or no data in these pathologies are available concerning IGFBP-2 or free IGF-I. We have analysed the GH-IGF axis in large populations of adolescents with anorexia nervosa and prepubertal children with exogenous obesity. These patients were studied at the time of diagnosis and at two timepoints during nutritional therapy and normal weight recovery. The results of these studies using age- and sex-matched controls are described here.

Adolescent

Human papillomavirus DNA and antibodies to human papillomaviruses 16 E2, L2, and E7 peptides as predictors of survival in patients with squamous cell cervical cancer.

PURPOSE: To assess whether human papillomavirus (HPV) DNA detection in cervical cancer specimens, or antibodies to selected HPV 16 peptides are predictors of tumor recurrence and long-term survival in patients with squamous cell invasive cervical cancer. SUBJECTS AND METHODS: Four hundred seventy-one cases included in two population-based case-control studies underwent follow-up evaluation. The survival and cause of death were ascertained for 410 cases (87%), with a median follow-up time of 4.6 years after diagnosis. HPV DNA was assessed using an L1 polymerase chain reaction (PCR)-based system and Southern hybridization (SH) on scraped cytologic specimens or biopsies. HPV 16 antibodies to E2, L2, and E7 peptides were detected with enzyme-linked immunosorbent assay (ELISA). RESULTS: Clinical stage was the only independent prognostic factor for recurrence or survival. Although seropositivity to HPV 16 E7/3 peptide predicted a twofold excess risk of mortality (adjusted hazards ratio [HRa] = 2.0; 95% confidence interval [CI], 1.2 to 3.3), the association was restricted to stage I (HRa = 6.6; 95% CI, 1.2 to 37.6) and II (HRa = 5.9; 95% CI, 2.1 to 16.5) patients. The presence of HPV DNA (HRa = 0.9; 95% CI, 0.5 to 1.5), different estimates of the HPV viral load and the HPV type identified were not predictors of tumor recurrence or survival. CONCLUSION: The presence of antibodies to HPV 16 E7 proteins is of prognostic value in early-stage cervical cancer. Our results provide strong evidence that detection and typing of HPV DNA in cervical cells or tissues is not a prognostic factor for recurrence or survival.

Adult

Multiple endocrine abnormalities of the growth hormone and insulin-like growth factor axis in prepubertal children with exogenous obesity: effect of short- and long-term weight reduction.

We have studied the GH-insulin-like growth factor (IGF) axis in prepubertal children with exogenous obesity at the time of clinical diagnosis and at two time points during weight reduction on a calorie-restricted diet. Spontaneous GH secretion, IGF-I, free IGF-I (fIGF-I), IGF-II, their binding proteins (IGFBP-1, IGFBP-2, and IGFBP-3), and GH-binding protein (GHBP) values at the time of clinical diagnosis (n = 65), after a 25% decrease in the body mass index (BMI) expressed as the SD score (BMI SD score; n = 29), and after a diminution of at least 50% of the initial BMI SD score (n = 9) are reported. GH secretion was significantly reduced at diagnosis, and after a decrease of at least 25% in the initial BMI SD score, it returned to normal in all patients. Total IGF-I levels were not significantly different from those in controls at any point. In contrast, fIGF-1 and IGF-II levels were significantly increased, both at diagnosis and after BMI SD score reduction. Obese patients were hyperinsulinemic at diagnosis and remained so even after a 50% reduction of their BMI SD score. Serum IGFBP-1 and IGFBP-2 levels were significantly decreased at diagnosis and at the two points studied during weight reduction. Serum IGFBP-3 and GHBP levels were increased significantly at diagnosis and returned to normal levels after a reduction in the BMI SD score. A positive correlation between serum GHBP levels and BMI was found in both controls and obese patients. Serum IGFBP-3 levels correlated positively with IGF-I, fIGF-I, and IGF-II in all groups, but these correlations were weaker in the obese patients at diagnosis. IGFBP-2 correlated significantly with IGF-II only in the obese group at diagnosis (r = -0.760; P < 0.0001), but with fIGF-I in all groups. IGFBP-1 was negatively correlated with IGF-I and fIGF-I in all groups. In conclusion, the GH-IGF axis is dramatically altered in patients with exogenous obesity. However, most changes in the peripheral IGF system appear to be independent of the modifications in GH secretion. In addition, in contrast to current thought, not all of the observed abnormalities are reversed with a significant reduction in the BMI SD score.

Body Mass Index

Multiple endocrine abnormalities of the growth hormone and insulin-like growth factor axis in patients with anorexia nervosa: effect of short- and long-term weight recuperation.

We have studied the GH-insulin-like growth factor (IGF) axis in patients with anorexia nervosa at the time of diagnosis and at two points during weight recuperation. We report their spontaneous GH secretion and IGF-I, free IGF-I (fIGF-I), IGF-II, the IGF-binding proteins (IGFBP-1, IGFBP-2, and IGFBP-3), and GH-binding protein (GHBP) levels at the time of the clinical diagnosis (n = 50) and after recuperation of between 6-8% (n = 42) and 10% or less of the initial weight (n = 20). Two distinct groups were seen, those who significantly hypersecreted GH and those whose GH secretion was reduced significantly. After recuperation of 10% or more of their initial weight, all patients had a normal GH pattern. Independently of GH secretory dynamics, IGF-1, IGFBP-3, and GHBP serum levels were all significantly decreased at diagnosis, and only GHBP returned to normal after weight recuperation. Serum IGFBP-1 and IGFBP-2 levels were significantly increased at the time of diagnosis and decreased after weight recuperation. The body mass index (BMI) correlated positively with fIGF-I levels and negatively with IGFBP-1 and IGFBP-2 levels, but only after weight recuperation in all cases. Contrary to what is seen in normal individuals, no correlation was found between BMI and serum GHBP levels in anorexia nervosa patients. Serum IGFBP-2 levels had a strong negative correlation with fIGF-I, IGF-II, and the sum of IGF-I and IGF-II, but only at the time of diagnosis. In conclusion, the GH-IGF axis is dramatically altered in patients with anorexia nervosa. Changes in the peripheral IGF system however, appear to be independent of modifications in GH secretion and, in contrast to current thought, not all of the observed abnormalities are rapidly reversed with weight recuperation.

Adolescent

Serological response to HPV16 in CIN-III and cervical cancer patients. Case-control studies in Spain and Colombia.

This study evaluates the association of antibodies against HPV-16-derived peptides with cervical cancer and estimates the sensitivity and specificity of the serological assays in relation to HPV DNA detection in cervical cells by PCR. Study subjects were derived from 4 case-control studies carried out in Spain and Colombia. Sera from 544 cases of CIN III and invasive cancer and of 543 age-matched controls were tested for antibodies to 5 peptides derived from E2, E7 (3 partially overlapping frames of HPV 16 denoted E7/ 1, E7/2, E7/3) and L2 open reading frames of HPV 16. HPV DNA was detected using a L1-PCR based method. Among cancer controls, antibody response to E2 and E7/1, E7/2, E7/3 was higher in Colombia (22.5%,7.2%,11.7%,12.6% respectively) than in Spain (17.1 %, 4.7%, 5.9%, 5.9%). E7 antibodies were related to stage, particularly in CIN III vs. invasive stages and less markedly within invasive stages. Detection of antibodies to the E7/1 was associated to CIN III (OR = 1.8). The risk of invasive cervical cancer was increased among those with antibodies to E2 (OR = 2.2), to E7/1 (OR = 4.2), to E7/2 (OR = 4.3), and to E7/3 (OR = 2.5). Presence of antibodies to all the 3 E7 peptides increased the risk of CIN III (OR = 5.6) and that of invasive cancer (OR = 17.5). High levels of antibodies to E7/1 or E7/2 or E7/3 increased the risk of invasive cervical cancer (OR for high levels of antibodies vs. negatives to E7/1 OR = 22.6; E7/2 OR = 7.5, E7/3 OR = 3.4). In the present analysis, antibodies to L2 were not associated with either CIN III or cervical cancer. Serological markers of HPV 16 detected less than half of the HPV-16-DNA-positive cases. It is concluded that antibodies to E2 and particularly E7 antigens are strongly associated with cervical cancer. Antibodies to E7 seem to be a moderate marker of tumor burden.

Adult

Insulin-like growth factor I, insulin-like growth factor binding proteins, and growth hormone binding protein in Spanish premature and full-term newborns.

The normal values of insulin-like growth factor I (IGF-I), IGF-binding proteins 1 and 3 (IGFBP-1 and IGFBP-3), and the high-affinity growth hormone binding protein (GHBP) are not well established in large series of healthy fullterm newborns. We report the normative data for IGF-I, IGFBP-I, IGFBP-3, and GHBP in 271 normal Spanish full-term newborns, born between 37 and 42 weeks of gestation, and compare these results with the same parameters studied in 39 premature infants. Furthermore, we report the relationship between results found in the normal full-term newborns and those of 252 healthy prepubertal (Tanner stage I) Spanish children. Serum GHBP, IGF-I, and IGFBP-3 levels are very low in the premature infant and show a significant increase in full-term newborns, and continue to decline during childhood (p < 0.001; analysis of variance). A positive correlation between GHBP, IGF-I, and IGFBP-3 versus gestational age was observed. In contrast, we found a negative correlation between IGFBP-I and gestational age. There is a direct relationship between the ponderal index and IGF-I and IGFBP-3. When the group of premature newborns was divided into infants born before or after 32 weeks of gestation, we found higher levels of IGF-I and IGFBP-3 (p < 0.01 and p < 0.05, respectively, by Student's test) in the group with the higher gestational age; however, the IGFBP-I level was lower in this group (p < 0.001 by Student's t test), with no differences seen in serum GHBP concentrations. The presence of IGFBPs in the premature infant suggests that they are important modulators of IGF-I action during fetal growth and development.

Carrier Proteins

Insulin-like growth factor I, its binding proteins 1 and 3, and growth hormone-binding protein in children and adolescents with insulin-dependent diabetes mellitus: clinical implications.

Values of IGF-I after extraction, its binding proteins, and the high affinity GH-binding protein (BP) are not well established in pediatric patients with insulin-dependent diabetes mellitus (IDDM). We report data for IGF-I, IGFBP-1, and -3, and GHBP in 92 Spanish children with IDDM, separated according to pubertal stage: prepubertal (n = 49); pubertal onset (n = 17); mid-puberty (n = 17), and complete puberty (n = 9), as well as to metabolic control (HbA1 < 9% or > or = 9%). IGF-I levels in IDDM patients increased throughout development (p < 0.001), but were diminished at every developmental stage when compared with marched control subjects. IGF-I concentrations showed a negative correlation with the degree of metabolic control, in particular during the prepubertal stage of development. A negative correlation (r = -0.22; p < 0.005) between IGF-I concentrations and HbA1 was found. Serum IGFBP-I levels diminish during maturation in diabetic patients (p < 0.001). However, IDDM patients have significantly higher levels of IGFBP-1 than control subjects at every stage of development, and IDDM patients with inadequate metabolic control exhibit even greater differences when compared with matched control subjects. A positive correlation (r = 0.22; p < 0.005) between IGFBP-1 concentrations and HbA1 was found. IGFBP-3 serum levels were similar to those observed in normal subjects, and no correlation was observed in relation to the metabolic control. In IDDM patients, GHBP levels change significantly during maturation, as they do in normal control subjects; however, significantly lower GHBP levels were found in prepubertal and pubertal IDDM patients. GHBP levels were independent of metabolic control, although a tendency toward lower levels of GHBP was seen when HbA1 levels increased. We suggest that a partial GH resistance syndrome exists in IDDM patients, and this may be related to the metabolic control. Hence, the biochemical markers measured here may be of value in evaluating the smaller pubertal growth spurt in diabetic patients.

Adolescent

Socioeconomic differences in cervical cancer: two case-control studies in Colombia and Spain.

OBJECTIVES: This study examined the causes of socioeconomic differences in invasive cervical cancer in two countries that differ substantially in cervical cancer incidence and economic development. METHODS: Data were derived from two case-control studies carried out in Spain and Colombia; there were 373 case subjects, 387 control subjects, and 425 husbands interviewed with a structured questionnaire. Exfoliated cells were obtained from cervical or penile scrapes and tested for human papillomavirus (HPV) DNA. RESULTS: Relative to better educated women, women with low educational levels in both countries reported fewer Pap smears and had a higher prevalence of HPV DNA. The prevalence ratio of HPV DNA across educational strata was twofold in Spain and fourfold in Colombia. In both countries, husbands of poorly educated women reported higher use of prostitutes than husbands of better educated women. In Colombia, 30% of husbands of poorly educated women harbored HPV DNA, compared with 10% of husbands of better educated women. CONCLUSIONS: Socioeconomic differences in invasive cervical cancer could be partly explained by differences in the prevalence of HPV DNA and by a lower use of preventive care.

Adult

Growth hormone secretion in children with normal variants of short stature.

Pulsatile growth hormone (GH) secretion plays a central role in human growth during the prepubertal period of life. In order to investigate whether or not short stature in prepubertal children with normal variants of short stature (NVSS) may be explained, at least in part, by the presence of abnormalities in the pulsatile pattern of GH secretion, we have studied the spontaneous secretion of GH/24 h in 139 prepubertal children with short stature (< or = -2 SD) and normal growth velocity (> -1 SD) and in 37 prepubertal children with normal height and growth velocity. All of the subjects included in this study exhibited a body mass index (BMI) lower than 1 SD. The patients with short stature were divided into three groups according to their bone age and the existence of familial antecedents of short stature. These groups were: (1) familial short stature without bone age retardation (FSS-1); (2) constitutional, nonfamilial short stature, with bone age retardation suggesting further delay of puberty (possible constitutional delay of growth and puberty), and (3) familial short stature with bone age retardation (FSS-2). Spontaneous GH secretion was analyzed by using a computerized mathematical algorithm of pulsatility (Cluster). In addition, in all of the patients with short stature, the GH secretory response to three different pharmacological stimuli was evaluated, including: clonidine, growth hormone-releasing hormone (GHRH) and hypoglycemia after insulin administration. The mean values of GH/24 h exhibited a wide range of distribution (1.4-7.8ng/ml).(ABSTRACT TRUNCATED AT 250 WORDS)

Body Height

Normative data for insulin-like growth factors (IGFs), IGF-binding proteins, and growth hormone-binding protein in a healthy Spanish pediatric population: age- and sex-related changes.

The normal values of insulin-like growth factors (IGFs) after extraction, their binding proteins, and the high affinity GH-binding protein are not well established in infancy or childhood. We report the relationship between serum IGF-I, IGF-II, their binding proteins IGFBP-1 and IGFBP-3, and GH-binding protein in 600 normal Spanish children who were divided into 5 groups according to Tanner stage: I, 150 males and 102 females; II, 40 males and 42 females; III, 45 males and 45 females; IV, 42 males and 55 females; and V, 23 males and 56 females. Serum IGF-I levels increase slowly during childhood in both sexes, exhibiting a dramatic increase during puberty and a significant decline [P < 0.001, by analysis of variance (ANOVA)] during adulthood. The pubertal peak occurs approximately 2 yr earlier in girls than in boys. In contrast, serum IGF-II levels remain stable throughout childhood, showing no pubertal peak. In boys, there is a significant decline in IGF-II levels during adulthood (P < 0.001). Serum IGFBP-3 levels show a pattern similar to that of IGF-I, with a significant increase during childhood and a significant decline during adulthood (P < 0.001, ANOVA) in both males and females. In contrast, serum IGFBP-1 levels decrease dramatically during childhood in both boys and girls (P < 0.001 and P < 0.005, respectively, by ANOVA). A significant decline in serum GH-binding protein levels is observed between prepubertal and pubertal children of both sexes (P < 0.001). There is a close linear correlation between the sum of serum IGF-I plus IGF-II levels vs. serum IGFBP-3 (r = 0.724; P < 0.0001). In contrast, there is a nonlinear correlation between serum IGF-I vs. serum IGFBP-3 (concave curve) as well as between serum IGF-II and serum IGFBP-3 (convex curve). A negative correlation was found between serum IGF-I vs. IGFBP-1 (r = -0.51; P < 0.0001) as well as between the sum of serum IGF-I plus IGF-II vs. IGFBP-1 (r = -0.47; P < 0.0001), but not between serum IGF-II and IGFBP-1. These data emphasize that when these tests are performed in the clinic, their interpretation should be based upon age- and sex-specific criteria.

Adolescent

[Diagnostic value of the hepatic echo-histogram in chronic hepatopathy].

The aim of this study was to determine the histogram patterns and the diagnostic efficacy of liver echohistogram in chronic diffuse liver diseases. Abdominal ultrasound and liver echo-histogram were prospectively and blindly performed on 21 healthy controls, 24 patients with chronic hepatitis, 26 patients with liver cirrhosis, and 22 patients with fatty liver disease. Maximum liver echo intensity and echogenicity were decreased in chronic hepatitis. Increased anterior maximum liver echo intensity and echogenicity, decreased posterior maximum liver echo intensity and echogenicity, and reduced posterior/anterior maximum liver echogenicity ratio were found in fatty liver disease. The diagnostic efficacy indexes of abdominal ultrasound were enhanced by some echo-histogram data: anterior maximum echo intensity of the liver less than 20.52 decibels for chronic hepatitis and posterior/anterior maximum liver echogenicity ratio less than 0.231 for fatty liver disease. In liver cirrhosis, echohistogram showed a high dispersion of values and not enhanced the abdominal ultrasound diagnostic efficacy. In fatty liver disease, a positive correlation was found between percentage of hepatocytes with fatty change and anterior maximum echo intensity of the liver (rs = 0.47, p < 0.05), as well as between percentage of hepatocytes with fatty change and anterior maximum echogenicity of the liver (rs = 0.68, p < 0.01). These findings indicate that the liver echo-histogram improves the diagnostic efficacy of abdominal ultrasound in chronic hepatitis and fatty liver disease. We suggest that combined abdominal ultrasound and liver echo-histogram should be performed in the investigation of chronic diffuse liver diseases.

Adult

Rhabdomyolysis and cutaneous necrosis following intravenous vasopressin infusion.

A continuous IV infusion of vasopressin was administrated to a patient with cirrhosis of the liver and acute gastrointestinal bleeding from esophageal varices. In the first 24 hours, the patient developed rhabdomyolysis and cutaneous necrosis. Stopping vasopressin infusion resulted in relief of these lesions. The rarity of these complications suggests an idiosyncratic reaction of susceptible individuals that may be related to previous vascular disease or a failure in baroreceptor regulation.

Aged

[Fuenlabrada study: lipid and lipoprotein levels in children and adolescents associated with ischemic cardiopathy prevalence among their relatives].

The prevalence of coronary heart disease (CHD) was studied in parents and grandparents of 2,419 children surveyed for lipid levels. Children and their families were divided into 3 groups depending on the level of each lipid and lipoprotein studied in children: high greater than or equal to 95 percentile (p), medium 5-95 p, and low less than 5 p. Total cholesterol (Chol) and triglycerides (TG) were determined by enzymatic techniques in autoanalyzer. C-HDL was determined by precipitation method. C-LDL and C-VLDL were obtained by Friedewald-Fredrickson's equation. The prevalence of CHD in parents and grandparents was ascertained from clinical history. Fathers of children in the high groups of Chol, TG, C-LDL/C-HDL, and low group of C-HDL had increased prevalence of CHD compared with those of the low groups of Chol, TG, C-LDL, C-LDL/C-HDL and high group of C-HDL. The strongest association was with C-HDL. Maternal and paternal grandfathers of children in the high groups of Chol had also increased prevalence of CHD compared with those of low group of Chol. There was no association with any other variable. The association was not significant neither in mothers nor in maternal and paternal grandmothers. Childhood lipid and lipoprotein levels could identify families at elevated risk for CHD.

Adolescent