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M Castellano

Publications and source records attributed to M Castellano.

At least 55 records · Page 3Linked to original sources
PubMed1997

CDKN2A/p16 is inactivated in most melanoma cell lines.

The CDKN2A gene maps to chromosome 9p21-22 and is responsible for melanoma susceptibility in some families. Its product, p16, binds specifically to CDK4 and CDK6 in vitro and in vivo, inhibiting their kinase activity. CDKN2A is homozygously deleted or mutated in a large proportion of tumor cell lines and some primary tumors, including melanomas. The aim of this study was to investigate the involvement of CDKN2A and elucidate the mechanisms of p16 inactivation in a panel of 60 cell lines derived from sporadic melanomas. Twenty-six (43%) of the melanoma lines were homozygously deleted for CDKN2A, and an additional 15 (25%) lines carried missense, nonsense, or frameshift mutations. All but one of the latter group were shown by microsatellite analysis to be hemizygous for the region of 9p surrounding CDKN2A. p16 was detected by Western blotting in only five of the cell lines carrying mutations. Immunoprecipitation of p16 in these lines, followed by Western blotting to detect the coprecipitation of CDK4 and CDK6, revealed that p16 was functionally compromised in all cell lines but the one that carried a heterozygous CDKN2A mutation. In the remaining 19 lines that carried wild-type CDKN2A alleles, Western blot analysis and immunoprecipitation indicated that 11 cell lines expressed a wild-type protein. Northern blotting was performed on the remaining eight cell lines and revealed that one cell line carried an aberrantly sized RNA transcript, and two other cell lines failed to express RNA. The promoter was found to be methylated in five cell lines that expressed CDKN2A transcript but not p16. Presumably, the message seen by Northern blotting in these cell lines is the result of cross-hybridization of the total cDNA probe with the exon 1beta transcript. Microsatellite analysis revealed that the majority of these cell lines were hemi/homozygous for the region surrounding CDKN2A, indicating that the wild-type allele had been lost. In the 11 cell lines that expressed functional p16, microsatellite analysis revealed loss of heterozygosity at the markers immediately surrounding CDKN2A in five cases, and the previously characterized R24C mutation of CDK4 was identified in one of the remaining 6 lines. These data indicate that 55 of 60 (92%) melanoma cell lines demonstrated some aberration of CDKN2A or CDK4, thus suggesting that this pathway is a primary genetic target in melanoma development.

Blotting, Western↗
PubMed1997

Characterization of the promoter for the human long pentraxin PTX3. Role of NF-kappaB in tumor necrosis factor-alpha and interleukin-1beta regulation.

The "long pentraxins" are an emerging family of genes that have conserved in their carboxy-terminal halves a pentraxin domain homologous to the prototypical acute phase protein pentraxins (C-reactive protein and serum amyloid P component) and acquired novel amino-terminal domains. In this report, a genomic fragment of 1371 nucleotides from the human "long pentraxin" gene PTX3 is characterized as a promoter on tumor necrosis factor-alpha (TNFalpha) and interleukin (IL)-1beta exposure in transfected 8387 human fibroblasts by chloramphenicol acetyltransferase and RNase protection assays. In the same cells, the PTX3 promoter does not respond to IL-6 stimulation. Furthermore, IL-1beta and TNFalpha responsiveness is not seen in the Hep 3B hepatoma cell line. The minimal promoter contains one NF-kappaB element which is shown to be necessary for induction and able to bind p50 homodimers and p65 heterodimers but not c-Rel. Mutants in this site lose the ability to bind NF-kappaB proteins and to respond to TNFalpha and IL-1beta in functional assays. Sp1- and AP-1 binding sites lying in proximity to the NF-kappaB site do not seem to play a major role for cytokine responsiveness. Finally, cotransfection experiments with expression vectors validate that the natural promoter contains a functional NF-kappaB site.

Animals↗
PubMed1997

Frequencies of the five PCR-based genetic markers LDLR, GYPA, HBGG, D7S8 and GC in the population of Asturias (North Spain).

Allele and genotype frequencies of the loci LDLR, GYPA, HBGG, D7S8 and GC (PM loci) were investigated in a population sample of 215 unrelated individuals from Asturias (North Spain). Multiplex amplification and simultaneous typing of the five loci was carried out using the polymarker PCR amplification and typing kit. All loci met Hardy-Weinberg expectations. The Asturian sample does not differ significantly from other Caucasians, but significant differences were observed between this population and SW Hispanic, Afro-american and Korean populations.

Alleles↗
PubMed1997

Increased potency of neuropeptide Y to antagonize alpha2-adrenoceptor function in the nucleus tractus solitarii of the spontaneously hypertensive rat.

The regulation by neuropeptide Y of alpha2-adrenoceptors in the nucleus tractus solitarii was evaluated in the adult normotensive Wistar Kyoto rat and the adult spontaneously hypertensive rat. The microinjection of a submaximal dose of l-noradrenaline (800 pmol in 50 nl) alone into the nucleus tractus solitarii produced a significant reduction in the mean arterial blood pressure in either strain. The threshold dose (1 pmol in 50 nl) of neuropeptide Y(1-36) for the vasodepressor response in the Wistar Kyoto rat was five times higher than that (0.2 pmol in 50 nl) in the spontaneously hypertensive rat. Furthermore, neuropeptide Y(1-36) at 0.2 pmol in 50 nl could significantly counteract the vasodepressor response to l-noradrenaline (800 pmol in 50 nl) in the spontaneously hypertensive rat, but not in the Wistar Kyoto rat, in which 1 pmol in 50 nl of neuropeptide Y(1-36) must be employed to counteract the vasodepressor response to l-noradrenaline (800 pmol in 50 nl), although the vasodepressor responses are of a similar magnitude. The in situ hybridization and quantitative receptor autoradiographical experiments showed that the alpha2A-adrenoceptor messenger RNA levels and the B(max) value of the alpha2-adrenoceptor agonist [3H]p-aminoclonidine binding sites measured in the nucleus tractus solitarii of the spontaneously hypertensive rat were substantially lower than those in the Wistar Kyoto rat. The quantitative receptor autoradiographical results were consistent with the cardiovascular results and showed that in the spontaneously hypertensive rat, neuropeptide Y(1-36) at 1 nM led to a significant increase in the K(d) value of [3H]p-aminoclonidine binding sites. In the Wistar Kyoto rat, neuropeptide Y(1-36) produced this effect only at 10 nM. The present study provides evidence for an increase of the potency of neuropeptide Y(1-36) to antagonistically modulate alpha2-adrenoceptors in the nucleus tractus solitarii of the spontaneously hypertensive rat. This enhanced antagonistic action may partly be related to a reduction in the number of alpha2A-adrenoceptors in the nucleus tractus solitarii of the spontaneously hypertensive rat, since a decrease has been observed in the alpha2A-adrenoceptor messenger RNA levels and the alpha2-adrenoceptor binding sites in the spontaneously hypertensive rat. This increased potency of neuropeptide Y(1-36) to antagonize alpha2-adrenoceptor function in the nucleus tractus solitarii of the spontaneously hypertensive rat may contribute to the development of high blood pressure in this hypertensive strain.

Adrenergic alpha-2 Receptor Agonists↗
PubMed1997

Prolonged effects of short-term fosinopril on blood pressure and vascular morphology and function in rats.

The aim of this study was to evaluate the delayed effects of an angiotensin converting enzyme (ACE) inhibitor on blood pressure and on structural and functional alterations in mesenteric small resistance arteries of spontaneously hypertensive rats (SHR). The ACE inhibitor fosinopril (25 mg/kg/day) was administered according to three different schedules: in one group of SHR from 4 to 8 weeks of age (n = 12), in a second group from 8 to 12 weeks of age (n = 15), and in a third group from 4 to 12 weeks of age (n = 12). Eighteen untreated SHR and 18 untreated Wistar-Kyoto rats served as controls. About half the animals in each group were killed at 13 weeks of age, and the remaining were killed at 38 weeks of age. After death, relative left ventricular mass (left ventricular weight/body weight) was calculated. Vascular morphology (media:lumen ratio) and function (responses to norepinephrine and acetylcholine) in mesenteric small resistance arteries were then assessed using a micromyographic technique. Short-term fosinopril, given either before or after the development of hypertension, persistently reduced (but did not normalize) systolic blood pressure, vascular structural alterations, and reactivity to norepinephrine in mesenteric resistance arteries in SHR. These favorable effects were maintained at least for 26 to 30 weeks after treatment withdrawal. The endothelium-dependent vasodilator response to acetylcholine was improved at 13 but not at 38 weeks of age, in treated SHR. Therefore, the vascular response to norepinephrine seems to be dependent mainly on the structure of the vessels, whereas endothelial function is probably more linked to the hemodynamic load.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1997

Effects of long-term antihypertensive treatment with lisinopril on resistance arteries in hypertensive patients with left ventricular hypertrophy.

OBJECTIVE: To evaluate the effects of long-term antihypertensive therapy with the angiotensin converting enzyme inhibitor lisinopril on structural alterations and the endothelial function of small resistance arteries in hypertensive patients with left ventricular hypertrophy. METHODS: Fourteen patients with left ventricular hypertrophy were treated for 3 years with a lisinopril-based regimen. Patients underwent an echocardiographic evaluation of left ventricular mass index at baseline, during the first and third years of treatment. At the end of the treatment period, subcutaneous small resistance arteries (obtained by biopsy of the subcutaneous fat from the gluteal region) were dissected and mounted on a micromyograph (Mulvany's technique); the media : lumen ratio was then calculated. Data obtained were compared with those observed for 14 untreated essential hypertensive patients and 14 normotensive subjects, age- and sex-matched. RESULTS: In the present study, a significantly lower media : lumen ratio was observed in treated compared with untreated hypertensive patients, although it remained significantly higher than that in normotensive subjects. In treated hypertensive patients a significant reduction in clinic blood pressure was observed. However, their blood pressure remained significantly higher than that in normotensive subjects. Significant correlations between the media : lumen ratio and blood pressure, left ventricular mass index or changes in left ventricular mass index during treatment were observed. The response to acetylcholine administration was reduced in untreated hypertensives compared with that in normotensives. In patients treated with lisinopril, the vasodilatation obtained with the two higher doses of acetylcholine was greater than that in untreated hypertensives, thus suggesting an improvement of endothelial function. CONCLUSIONS: Long-term therapy based on lisinopril was associated with a smaller media : lumen ratio in the subcutaneous small resistance arteries of hypertensive patients with left ventricular hypertrophy. Our retrospective study confirms previous findings obtained in prospective studies with other angiotensin converting enzyme inhibitors. Endothelial function was probably improved by lisinopril therapy.

Aged↗
PubMed1997

Structural changes of small resistance arteries in spontaneously hypertensive rats after treatment with various doses of lacidipine.

OBJECTIVE: To evaluate the modifications of the morphology of mesenteric small resistance vessels in spontaneously hypertensive rats (SHR) induced by lacidipine treatment. METHODS: Lacidipine was administered at three different dosages, 20, 10, and 0.3 mg/kg per day. Fifty rats were studied. Nine SHR and 11 Wistar-Kyoto (WKY) rats were not treated. Each lacidipine dose was administered to 10 SHR. The drug and the placebo were administered by gavage from age 4 to age 12 weeks. The blood pressure was measured noninvasively every week. The animals were killed when they were aged 13 weeks, and the relative left ventricular mass (left ventricular weight plus septum weight/body weight) was calculated. Small mesenteric resistance vessels were dissected and mounted on a micromyograph (Mulvany's technique), and morphological parameters of the vessels were studied (media thickness and media: lumen ratio). RESULTS: The systolic blood pressure of SHR administered 20 and 10 mg/kg lacidipine per day was reduced significantly during the treatment period, whereas that of rats treated with 0.3 mg/kg lacidipine per day did not change. A significant reduction in media: lumen ratio was observed for all three groups of treated rats, including those to which 0.3 mg/kg lacidipine per day had been administered, and no reduction in systolic blood pressure could be detected. The relative left ventricular mass was reduced significantly only in rats to which 20 and 10 mg/kg lacidipine per day had been administered. CONCLUSION: A significant reduction in magnitude of vascular structural alternations was observed even in SHR treated with a low, nonhypotensive dose of lacidipine.

Animals↗
PubMed1997

The vasoconstriction induced by endothelin-1 is mediated only by ET(A) receptors in mesenteric small resistance arteries of spontaneously hypertensive rats and Wistar Kyoto rats.

OBJECTIVE: To evaluate the functional responses of mesenteric small resistance arteries of spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rat controls to endothelin-1 (ET-1), in the presence and absence of an ET(A) receptor antagonist drug as well as to an ET(B) receptor agonist. METHODS: Twenty rats aged 12 weeks were studied. They were 10 SHR and 10 WKY rats. Mesenteric small resistance arteries (relaxed diameter 100-180 microm) were dissected and mounted on a micromyograph (Mulvany's technique). A dose-response curve for response to ET-1 was plotted for cumulative concentrations (from 10(-11) to 10(-8) mol/l) in the presence and absence of 10(-6) mol/l FR 139317 (a selective antagonist of ET(A) receptors). In addition, the effects of 10(-7) mol/l N-succinyl-[Glu9, Ala11,15]-endothelin 1 fragment 8-21 (IRL 1620, a selective agonist of ET(B) receptors) were evaluated. RESULTS: The response of ET-1 was greater in WKY rats than it was in SHR. Almost all the vasoconstrictor effect of ET-1 could be prevented by addition of FR 139317, whereas the agonist of ET(B) receptors had no effect (no change in active force). CONCLUSIONS: The contractile effects of ET-1 on mesenteric small resistance arteries of SHR and WKY rats are mediated mostly by ET(A) receptors, whereas ET(B) receptors play a minor role, if any. It is possible, however, that a vasoconstrictor effect of ET(B) receptors on the smooth muscle could be masked by the concomitant stimulation of endothelial ET(B) vasodilator receptors.

Animals↗
PubMed1997

Alpha-adducin gene polymorphism and cardiovascular phenotypes in a general population.

BACKGROUND: Previous studies have shown that molecular variants of the cytoskeletal protein adducin may be involved in regulation of blood pressure both in genetic rat hypertension and in human essential hypertension. OBJECTIVE: To investigate the relationship of genetic polymorphism of alpha-adducin with blood pressure, cardiovascular structure, and some biochemical indexes of cardiovascular risk in a sample of general population. DESIGN AND METHODS: A sample of 246 subjects (124 men and 122 women, aged 57.7+/-3.7 years) was randomly chosen from a middle-aged population. Twenty-four-hour ambulatory blood pressure, as well as left ventricular mass (by echocardiographic methods) and carotid wall thickness (by B-mode ultrasound methods) were measured. DNA was extracted from peripheral blood samples; the Gly460Trp diallelic variant of human alpha-adducin was genotyped by polymerase chain reaction amplification and then allele-specific oligo hybridization. RESULTS: A trend toward higher 24 h ambulatory blood pressure values in subjects not treated with antihypertensive drugs was observed among carriers of Trp460 allele, although the differences did not attain statistical significance (at closest, P = 0.066 for a dominant effect of Trp460 on systolic blood pressure). When blood pressure was considered a dichotomous variable, allowing the inclusion of treated hypertensives), a higher prevalence of Trp460 allele among hypertensives was observed (0.188 versus 0.106 among normotensives, P= 0.02). There was no evidence of association either of left ventricular mass or of common carotid wall thickness with Gly460Trp polymorphism. CONCLUSIONS: In this sample of a general population, the relationship of a genetic polymorphism of alpha-adducin with blood pressure values was rather weak. However, a population-based case-control analysis indicated that there was an association between Trp460 allele and hypertension, with a relative risk for subjects carrying at least one Trp460 allele of approximately 1.6. Further investigation of larger and different population samples in order to assess the role of adducin gene polymorphism as a marker of genetic predisposition to the development of hypertension is warranted.

Aged↗
PubMed1997

Restoration of CDKN2A into melanoma cells induces morphologic changes and reduction in growth rate but not anchorage-independent growth reversal.

CDKN2A is a melanoma susceptibility gene that is mutated and/or deleted in familial and sporadic melanoma as well as in a range of other tumors. It encodes a cell cycle regulator, p16, whose function is to inhibit activity of cyclin-dependent kinases 4 and 6. We set out to investigate the effect of reintroducing CDKN2A into MM96L, a melanoma cell line that does not express p16, by electroporation of wt CDKN2A cDNA. Our results show that transfection of the CDKN2A cDNA has a dramatic effect on cell morphology, inducing a more dendritic phenotype resembling that of adult melanocytes. This effect on cell morphology was not cell line specific because it was reproduced in another melanoma line (SK-MEL-13), which has a homozygous deletion of CDKN2A. It was abolished by mutations that abrogate p16 function, as shown by transfection of a Pro81Leu p16 variant. Reintroduction of levels of p16 protein similar to those of cultured neonatal foreskin melanocytes decreased the growth rate of the transfected clones. Surprisingly, we did not see any effect on anchorage-independent growth or on the following melanoma markers tested by western blotting: p21/WAF1, tyrosinase-related antigen 1, HMB45, and intermediate filament antigen. These data indicate that reintroduction into melanoma cells of wild type p16 at levels similar to cultured melanocytes can induce morphologic changes and suppress growth but is not sufficient to affect anchorage-independent growth.

Aged↗
PubMed1997

The cardiac beta-adrenoceptor-mediated signaling pathway and its alterations in hypertensive heart disease.

Hypertension-induced cardiac hypertrophy is a predictor of the development of cardiac failure. It is unknown which cellular markers contribute to the progression from compensated hypertrophy to failure. In heart failure, several signal transduction defects leading to adenylate cyclase desensitization have been demonstrated, such as beta-adrenoceptor downregulation, increase of inhibitory G protein expression, and uncoupling of beta-adrenergic receptors, presumably by an increase of receptor kinase activity. In hypertensive heart disease, most studies have been performed in rat models of hypertension. As in heart failure, heterologous adenylyl cyclase desensitization occurs. The mechanisms are often different between the heterogeneous models for acquired and genetic hypertension, but Gi protein alterations and beta-adrenoceptor downregulation have been observed frequently. The underlying mechanism for desensitization is most likely a sympathetic activation in established hypertension rather than genetic alterations of signal transduction proteins. The data available suggest that beta-adrenergic desensitization could represent a mechanism that contributes to the progression from hypertrophy to failure. The key question remains whether those hypertensive patients who develop heart failure are more prone to beta-adrenergic desensitization or whether early intervention to reduce sympathetic activity is more effective in preventing or delaying the transition from compensated hypertrophy to overt failure.

Adenylyl Cyclases↗
PubMed1997

Distribution of types for six PCR-based loci; LDLR, GYPA, HBGG, D7S8, GC and HLA-DQA1 in central Pyrenees and Teruel (Spain).

The PCR-based DNA loci LDLR, GYPA, HBGG, D7S8, GC and HLA DQA1 are widely used in forensic casework analyses. Population data on the distribution of allele frequencies are desired to estimate the rarity of a DNA profile. We studied the allele distributions at these forensically important DNA markers in two Spanish populations (Central Pyrenees and Teruel). Results were in agreement with Hardy-Weinberg expectations. Furthermore, there was little evidence for departures from expectation of independence between loci within the two sample populations. Tests for homogeneity were carried out between the two Spanish populations and a U.S. Caucasian population.

Alleles↗
PubMed1996

Distribution of HLA DQ A1 alleles and genotypes in two Spanish populations (Aragon and Asturias).

HLA DQ A1 is probably one of the PCR-based genetic marker systems most widely used in actual forensic casework analyses. As accurate data about the distribution of the alleles is one of the most important prerequisites for the application in forensic biology, we studied the allele distribution in two relevant Spanish populations (Aragonese and Asturian). Results were in good agreement with the Hardy-Weinberg law in both Aragonese and Asturian populations. The power of discrimination was 0.92 in the Aragonese and 0.93 in Asturian sample. A test for homogeneity of the HLA DQ A1 population data based on alelle frequency counts for 12 European samples was performed and no significant differences were found (P = 0.831).

Alleles↗
PubMed1996

Cloning of mouse ptx3, a new member of the pentraxin gene family expressed at extrahepatic sites.

Pentraxins, which include C reactive protein (CRP) and serum amyloid P component (SAP), are prototypic acute phase reactants that serve as indicators of inflammatory reactions. Here we report genomic and cDNA cloning of mouse ptx3 (mptx3), a member of the pentraxin gene family and characterize its extrahepatic expression in vitro and in vivo. mptx3 is organized into three exons on chromosome 3: the first (43 aa) and second exon (175 aa) code for the signal peptide and for a protein portion with no high similarity to known sequences the third (203 aa) for a domain related to classical pentraxins, which contains the "pentraxin family signature." Analysis of the N terminal portion predicts a predominantly alpha helical structure, while the pentraxin domain of ptx3 is accommodated comfortably in the tertiary structure fold of SAP. Normal and transformed fibroblasts, undifferentiated and differentiated myoblasts, normal endothelial cells, and mononuclear phagocytes express mptx3 mRNA and release the protein in vitro on exposure to interleukin-1beta (IL-1beta) and tumor necrosis factor (TNF)alpha. mptx3 was induced by bacterial lipopolysaccharide in vivo in a variety of organs and, most strongly, in the vascular endothelium of skeletal muscle and heart. Thus, mptx3 shows a distinct pattern of in vivo expression indicative of a significant role in cardiovascular and inflammatory pathology.

3T3 Cells↗
PubMed1996

Human T-cell lymphotropic virus type-I infection in the severe combined immunodeficiency mouse.

Human T-cell lymphotropic virus type-I (HTLV-I) is the etiologic agent of HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and adult T-cell leukemia (ATL). HAM/TSP and ATL occur infrequently among HTLV-I-infected individuals, and rarely develop in the same individual. To study host and viral factors involved in the induction, tissue tropism, as well as pathogenesis of HAM/TSP, peripheral blood lymphocytes (PBL) from 14 patients with HAM/TSP and from 9 controls were introduced into severe combined immunodeficiency (SCID) mice by intraperitoneal injection. Mice were followed for up to 26 weeks. Human IgG was produced from 2 to 14 weeks after reconstitution in all animals. Thirty-two of 44 mice (72%) showed circulating human antibody against the major viral protein products of HTLV-I. Analysis of viral sequences by polymerase chain reaction (PCR) demonstrated HTLV-I sequences in 21/38 (55%) brains and in 7/17 (41%) spinal cords from HTLV-I-hu SCID mice. No animal had clinical evidence of neurological impairment or pathological findings similar to those seen in HAM/TSP. Seven mice who received PBL from Epstein Barr virus (EBV)-seropositive patients developed an intraperitoneal lymphoma. In 2 mice an infiltration of brain by a lymphoblastic tumor of B/T cell type was observed. By PCR, all the tumors were EBV-positive; HTLV-I sequences were detected in 5 of them. Our study suggests that the HTLV-I-hu-SCID mouse provides a potentially valuable system for studying the production, kinetics, and pathogenicity of anti-HTLV-I antibody, and may help clarify the interaction of EBV and retroviruses in the development of disease.

Adult↗
PubMed1996

Thyroid function and serum thyroid binding proteins in prepubertal and pubertal children with chronic renal insufficiency receiving conservative treatment, undergoing hemodialysis, or receiving care after renal transplantation.

OBJECTIVE: The abnormalities reported in some thyroid function tests in children with renal disease could be adaptive phenomena, shared by a variety of other nonthyroidal illnesses, or could reflect hypothyroidism. STUDY DESIGN: To answer this question, we studied thyroid function and serum thyroid binding proteins in 36 prepubertal and 23 pubertal patients with renal disease receiving three different therapies: conservative treatment, hemodialysis, and care after renal transplantation. RESULTS: During prepuberty, the serum concentration thyroxine binding globulin (mean +/- SE) in the three groups of patients (294 +/- 18, 303 +/- 18, and 323 +/- 16 nmol/L, respectively) was significantly lower than in prepubertal control subjects (451 +/- 71 nmol/L). Only in prepubertal patients after renal transplantation (3583 +/- 573 nmol/L) were serum thyroxine binding prealbumin values lower than in respective control subjects (5999 +/- 908 nmol/L). The serum total thyroxine concentration in the three groups of patients (108 +/- 41.9, 121 +/- 5.7, and 123 +/- 5.5 nmol/L, respectively) was significantly lower than in prepubertal control subjects (149 +/- 10 nmol/L), whereas serum free thyroxine and serum albumin-bound thyroxine concentrations were similar to those in control subjects. The serum total triiodothyronine level in the three groups of patients (2.29 +/- 0.82, 2.13 +/- 0.13, and 2.01 +/- 0.20 nmol/L respectively) was significantly lower than in prepubertal control subjects (3.04 +/- 0.24 nmol/L), whereas serum levels of free triiodothyronine and serum albumin-bound triiodothyronine were similar to those in prepubertal control subjects. During puberty, serum thyroxine binding globulin and serum thyroxine binding prealbumin levels in the three groups of patients were not statistically different from those in pubertal control subjects (309 +/- 47 and 4950 +/- 1230 nmol/L, respectively). Serum levels of total thyroxine, free thyroxine, albumin-bound thyroxine, total triiodothyronine, free triiodothyronine, and albumin-bound triiodothyronine were similar to those in pubertal control subjects except for pubertal patients undergoing hemodialysis. In all clinical groups the basal serum thyrotropin concentration was similar to those in respective control subjects. The frequency of goiter was increased in patients undergoing hemodialysis, probably as a result of iodide washout with dialysis. CONCLUSION: Children and adolescents with chronic renal insufficiency or endstage renal disease or after renal transplantation do not have a primary abnormality of thyroid function and therefore are not candidates for thyroid hormone treatment.

Adolescent↗
PubMed1996

Cardiac and vascular structural changes. Prevalence and relation to ambulatory blood pressure in a middle-aged general population in northern Italy: the Vobarno Study.

The aims of this study were to determine the prevalence of structural changes in the carotid arteries and heart and the correlation between these changes and the commonly recognized cardiovascular risk factors in the general population. Structural changes in the carotid arteries were defined as the intima-media thickness of the artery measured by B-mode ultrasound. Changes in the heart were defined as left ventricular mass index (LVMI) measured by echocardiography. LVMI values greater than 134 g/m2 in men and greater than 110 g/m2 in women were considered abnormal, indicating the presence of left ventricular hypertrophy. Blood pressure (BP) was measured in the clinic setting with a mercury sphygmomanometer and by 24-hour noninvasive ambulatory monitoring. Hypertension was defined as a sustained systolic BP greater than or equal to 160 mm Hg and/or diastolic BP increase greater than or equal to 95 mm Hg. The study population consisted of 225 subjects (107 women and 118 men) 48 to 64 years old. Prevalence of intima-media thickening (intima-media thickness > 1 mm) was 11% in normotensive subjects and 44% in hypertensive subjects. The presence of plaque (wall thickening with either mineralization or focal protrusion in the lumen at least 50% greater than the surrounding wall, usually > 2 mm) was observed in 35% of normotensive subjects and 44% of hypertensive subjects. The prevalence of left ventricular hypertrophy was 13% in normotensive subjects and 19% in hypertensive subjects. Intima-media thickness in the common and bifurcation segments of carotid arteries correlated well with LVMI (r = .20 and r = .19, respectively; P < .01). Intima-media thickness and LVMI were both positively related to 24-hour monitored BP (P < .01). However, in the multivariate analysis, body mass index (P = .027), sex (P < .001), and 24-hour mean BP (P = .025) were the most significant determinants of LVMI, whereas carotid artery intima-media thickness was found to be associated best with age (P < .001), cigarette smoking (P = .009), serum cholesterol (P = .025), serum glucose (P = .038), and nighttime systolic BP (P = .006). Logistic regression analysis confirmed the association between the presence of plaque and age (P < .001), nighttime systolic BP (P < .05), and cigarette smoking (P < .05); a negative association between plaque and the decrease in mean systolic BP daytime to nighttime was also observed (P < .001). In conclusion, in a general population of unselected middle-aged subjects, carotid wall thickness and LVMI were associated with each other and related to 24-hour BP levels although the major determinants of carotid wall and cardiac structure were different.

Aged↗