bluuebunny/crossref_metadata_2025_split huggingface dataset:
Normal VLDL metabolism despite altered lipoprotein composition in type 1 diabetes mellitus
Authors: Christ E. R. , Carroll P. V. , Albany E. , Umpleby A. M. , Lumb P. J. , Wierzbicki A. S. , Simpson H. L. , Sönksen P. H. , Russell‐Jones D. L. 
Published: March 2003

OBJECTIVES Patients with type 1 diabetes are at increased risk of cardiovascular disease, which may be related to abnormal lipid metabolism. Secretion and clearance of VLDL apolipoprotein B100 (apoB) are important determinants of plasma lipid concentrations and are known to be influenced by hormones, including insulin and growth hormone.PATIENTS This study examined overnight VLDL apoB metabolism and VLDL composition in six lean patients with type 1 diabetes during euglycaemia (controlled by a varying insulin infusion) and in six age‐, sex‐ and BMI‐matched control subjects.METHODS VLDL apoB kinetics were determined using a primed constant 1–13C leucine infusion, and VLDL apoB enrichment was measured by gas‐chromatography mass‐spectrometry. Fasting lipid profile, IGF‐I, IGFBP‐3, overnight GH profiles and free insulin concentrations were also assessed.RESULTS Fasting concentrations of triglycerides (TG), total cholesterol (TC), HDL‐cholesterol (HDL‐C) and LDL‐cholesterol (LDL‐C) were similar in both groups. The VLDL apoB secretion and metabolic clearance rates were not significantly different between the two groups, but the VLDL‐TG/VLDL apoB and the VLDL‐C/VLDL apoB ratios were significantly increased in those with diabetes (P < 0·02 and P < 0·03, respectively). Total IGF‐I concentrations were similar between the two groups; however, the GH area under the curve and free insulin concentrations were increased in patients with type 1 diabetes (GH: diabetes: 94·8 ± 15·1 vs. controls: 45·6 ± 10·6, mU/L/h, P < 0·04; free insulin: diabetes: 78·4 ± 5·0 vs. controls: 28·3 ± 3·26, pmol/l, P < 0·001). IGFBP‐3 concentrations were lower in diabetic patients (diabetes: 2454·2 ± 68·7 vs. controls: 3219·4 ± 76·4, ng/ml, P < 0·001). In the control group overnight GH secretion correlated negatively with fasting TC (P < 0·01) and LDL‐C (P < 0·03) concentrations, whereas free insulin concentrations correlated positively with fasting TG concentrations (P < 0·009). No significant correlations were found in the patients with diabetes.CONCLUSION This study suggests that in euglycaemic conditions patients with type 1 diabetes mellitus have normal VLDL apoB kinetics but altered VLDL composition. The altered VLDL composition may be associated with accelerated atherogenesis. We speculate that the disrupted hormonal balance and, in particular, the increased GH secretion might be responsible for the compositional changes of VLDL particles in type 1 diabetes mellitus.
HLA‐DRB3 *0101 is associated with Graves' disease in Jamaicans
Authors: Smikle Monica Fisher , Pascoe Rosemarie Wright , Barton Everard , Morgan Owen , Christian Nicole , Dowe Gwendolyn , Roye‐Green Karen , Bailey Valerie , James Owen 
Published: March 2003

OBJECTIVES Graves' disease is associated with different human leucocyte antigen (HLA) genes in different populations. This study was designed to examine the HLA class II associations with Graves' disease in Jamaicans.PATIENTS One hundred and six Jamaicans with Graves' disease and 104 controls.DESIGN Oligotyping for HLA‐DRB1, DRB3, DQA1 and DQB1 alleles was performed using the polymerase chain reaction sequence specific oligonucleotide probe (PCR‐SSOP) technique.RESULTS The frequency of HLA‐DRB3 *0101 was increased significantly in the patients compared to controls (38·7% vs. 19·2%; RR = 2·72; Pc < 0·015). The protective alleles for Graves' disease were DRB1 *0901 (0·9% vs. 20·2%; RR = 0·04; Pc < 0·001), DRB1*1001 (0·0% vs. 11%; RR = 0·0%; Pc < 0·01) and DRB4 *0101 (0·0% vs. 12·5%; RR = 0·0; Pc < 0·05). A high female to male ratio of Graves' disease, 25 : 1, was observed. Other associated autoimmune diseases were rare and no significant HLA class II associations were found with clinical markers of disease.CONCLUSIONS Jamaican patients with Graves' disease share the DRB3 *0101 susceptible allele and the DRB4 *01 protective allele but not the susceptible haplotype DRB1 *0301, DRB3 *0101, DQA1 *0501 with Caucasians.
The neuro‐cardio‐endocrine response to acute subarachnoid haemorrhage
Authors: Espiner Eric A. , Leikis Robert , Ferch Richard D. , MacFarlane Martin R. , Bonkowski Janusz A. , Frampton Christopher M. , Richards A. Mark 
Published: March 2003

Summaryobjective Whereas cardiac hormones increase after subarachnoid haemorrhage (SAH), and may contribute to sodium wastage and hyponatraemia, there is controversy concerning the relative roles of atrial natriuretic peptide (ANP) vs. brain natriuretic peptide (BNP) and the factors initiating their secretion. Noting previous work linking stress hormone responses with cardiac injury after SAH, we have studied responses in stress hormones, markers of cardiac injury and the temporal changes in ANP and BNP and related them to changes in sodium status post ictus and during recovery from acute SAH.design, patients, measurements Eighteen patients with verified SAH of variable severity were studied in a single unit for a 14‐day period post ictus under controlled conditions of sodium and fluid intake. All received a standardized protocol of daily dexamethasone and nimodipine throughout the study. Severity was graded using criteria of Hess and Hunt at admission. Stress hormones (AVP, catecholamines and admission plasma cortisol), markers of cardiac injury (ECG and daily plasma troponin T) and cardiac hormones (ANP and BNP) were measured daily and related to severity, plasma sodium and renin–aldosterone activity. Hormone levels (ANP, BNP and endothelin) in cerebrospinal fluid (CSF) were also measured in nine patients.results Intense neurohormonal activation (AVP, cortisol and catecholamines) at admission was associated with increased levels of both plasma ANP and BNP whereas levels in CSF were unaffected. In individual patients plasma levels of ANP and BNP were strongly correlated (P < 0·001). Cardiac events (abnormal ECG and/or elevated troponin) occurred in six of seven patients graded severe but neither stress hormones nor cardiac peptides differed significantly in patients with mild (n = 11) vs. severe (n = 7) SAH. During the course of a progressive fall in plasma sodium concentration (P = 0·001), there was a delayed activation of renin–aldosterone which was inversely correlated with declining levels of plasma ANP/BNP (P < 0·002).conclusions Excessive secretion of both ANP and BNP occurs in all patients after acute subarachnoid haemorrhage and is unrelated to severity, stress hormone activation or markers of cardiac injury. Inhibition of renin–aldosterone by cardiac hormones may impair renal sodium conservation and contribute to developing hyponatraemia. In the absence of evidence for activation of natriuretic peptides within the brain, the prompt and consistent increase in both ANP and BNP strongly supports the view that the heart is the source of increased natriuretic peptide secretion after acute subarachnoid haemorrhage.
Poor uterine development in Turner syndrome with oral oestrogen therapy
Authors: Paterson Wendy F. , Hollman Anne S. , Donaldson Malcolm D. C. 
Published: March 2003

SummaryOBJECTIVE To evaluate uterine development in Turner syndrome (TS) patients in relation to treatment with oral ethinyl oestradiol (E2) for pubertal induction.DESIGN AND PATIENTS Pelvic ultrasound data for 96 TS patients scanned since 1989 were analysed. Patients were classified into three groups: (1) untreated (n = 48); (2) complete spontaneous puberty (n = 10); and (3) treated with ethinyl oestradiol (n = 38). Uterine development was described in the three groups and compared with the normal data.MEASUREMENTS Uterine length, fundal‐cervical ratio (FCR) and shape were recorded, and presence or absence of ovaries noted. In the treated group, cross‐sectional and longitudinal data were combined to compare uterine development with Tanner breast stage.RESULTS In untreated girls up to age 10 years there was a variable distribution of uterine length and FCR about the mean. Thereafter, the uterus failed to grow and mature normally. Girls with complete spontaneous puberty had morphologically normal ovaries and uteri, but of 7 girls who attained menarche, 3 subsequently developed secondary oligomenorrhoea or amenorrhoea. In the treated group, in general, breast development and uterine length progressed with increasing E2 dose. However, only 50% of girls with complete secondary sexual development had a mature heart‐shaped uterine configuration.CONCLUSIONS Our current E2 treatment regimen for TS girls gives rise to satisfactory pubertal induction and maintenance, but failed to induce a fully mature uterus in half the cohort. In view of the high risk of miscarriage in TS in both spontaneous and assisted pregnancies, the effect of more physiological methods of E2 replacement on uterine development should be investigated.
Mutational analysis of Portuguese families with multiple endocrine neoplasia type 1 reveals large germline deletions
Authors: Cavaco B. M. , Domingues R. , Bacelar M. C. , Cardoso H. , Barros L. , Gomes L. , Ruas M. M. A. , Agapito A. , Garrão A. , Pannett A. A. J. , Silva J. L. , Sobrinho L. G. , Thakker R. V. , Leite V. 
Published: March 2003

Summaryobjective To determine the spectrum of MEN1 mutations in Portuguese kindreds, and identify mutation‐carriers.patients, design and results Six unrelated MEN1 families were studied for MEN1 gene mutations by single‐strand conformational polymorphism (SSCP) and DNA sequence analysis of the coding region and exon‐intron boundaries of the MEN1 gene. These methods identified 4 different heterozygous mutations in four families: two mutations are novel (mt 1539 delG and mt 655 ims 11 bp) and two have been previously observed (mt 735 del 46p and mt 1656 del C) all resulting in a premature stop codon. In the remaining two families, in whom no mutations or abnormal MEN1 transcripts were detected, segregation studies of the 5′ intragenic marker D11S4946 and codon 418 polymorphism in exon 9 revealed two large germline deletions of the MEN1 gene. Southern blot and tumour loss of heterozygosity analysis confirmed and refined the limits of these deletions, which spanned the MEN1 gene at least from: exon 7 to the 3′ untranslated region, in one family, and the 5′ polymorphic site D11S4946 to exon 9 (obliterating the initiation codon), in the other family. Twenty‐six mutant‐gene carriers were identified, 6 of which were asymptomatic.conclusions These results emphasize the importance of the detection of MEN1 germline deletions in patients who do not have mutations of the coding region. Important clues indicating the presence of such deletions may be obtained by segregation studies using the intragenic polymorphisms D11S4946 and at codon 418. The detection of these mutations will help in the genetic counselling of clinical management of the MEN1 families in Portugal.
FSH and ovarian response: spontaneous recovery of pituitary–ovarian activity during the pill‐free period vs. exogenous recombinant FSH during high‐dose combined oral contraceptives
Authors: Van Heusden A. M. , Coelingh Bennink H. J. T. , Fauser B. C. J. M. 
Published: March 2003

Summaryojbective Compare spontaneous recovery of pituitary–ovarian activity during the pill‐free period following the correct use of low‐dose oral contraceptives and subsequent ovarian function during the administration of exogenous recombinant FSH (recFSH) after switching to continued Lyndiol® (2·5 mg lynestrenol + 0·05 mg ethinyl‐oestradiol) medication.design Prospective, randomized, group‐comparative, single‐centre study. Following the monitoring of the pill‐free period (week 1) and subsequent treatment with Lyndiol® (for a total of 5 weeks), all subjects were randomly allocated to one of four groups receiving daily FSH injections for 1 week [75, 150, 225 IU recFSH or 150 IU purified urinary FSH (uFSH)] during the fourth week of Lyndiol® use.patients Thirty‐six healthy volunteers aged 18–39 years, prestudy oral contraceptive use for at least 3 months, cycle length between 24 and 35 days.measurements Serum FSH, LH and oestradiol (E2) concentrations as well as transvaginal ultrasound assessment of the number and diameter of follicles > 2 mm were used to monitor pituitary ovarian function.results At the start of the pill‐free period following the prestudy contraceptive medication, 67% of the women presented with LH and FSH levels < 1 IU/l and only one follicle > 10 mm was observed. Initial levels of LH and FSH correlated (P < 0·05) with the extent of pituitary–ovarian activity during the pill‐free period. At the end of the pill‐free period a follicle > 10 mm had emerged in one subject only. During the first 3 days of Lyndiol® use, seven women (19%) eventually showed at least one follicle > 10 mm. During combined exogenous FSH and Lyndiol® administration, LH levels remained completely suppressed (≤ 0·5 IU/l) in all women studied. FSH levels and number and size of follicles increased with increasing doses of exogenous FSH in a dose‐dependent manner. E2 levels remained low in all groups (< 150 pmol/l). During the week following FSH administration, FSH levels and E2 levels decreased gradually while the number of follicles > 10 mm still increased.conclusions We have confirmed that dominant follicles > 10 mm are present at the end of the pill‐free period and during the first days after resumption of pill intake. Once follicles > 10 mm arose at the end of the pill‐free period, continued use of Lyndiol® did not reduce follicle diameters. One week of Lyndiol® reduces pituitary–ovarian activity to levels observed after 3 weeks of low‐dose pills. FSH administration during Lyndiol® resulted in dose‐dependent follicle growth despite extremely low LH levels. E2 secretion (56 ± 51 pmol/l) occurred to a limited and variable extent along with extremely low serum LH concentrations. Recovery of pituitary–ovarian activity at the end of the pill‐free period is comparable to FSH levels and follicle dynamics following 7 days of 75–150 IU/l recFSH.
Submandibular salivary gland volume is increased in patients with acromegaly
Authors: Manetti Luca , Bogazzi Fausto , Brogioni Sandra , Grasso Lucia , Lupi Isabella , Genovesi Maura , Cecconi Elisabetta , Gasperi Maurizio , Martino Enio 
Published: March 2003

Summaryobjective Acromegaly is characterized by an enlargement of various organs. The aim of the present study was to evaluate whether acromegalic patients have an increased volume of submandibular salivary glands.design and subjects Prospective study on 40 consecutive acromegalic patients (18 male, 22 female; mean age ± SD, 50 ± 13 years, range 22–74 years) submitted to submandibular salivary gland ultrasound. Among acromegalic patients, 15 had active and untreated disease (Acro‐U), 13 were under long‐acting somatostatin analogue therapy (Acro‐SA), 12 were in remission after surgery (Acro‐R). Two hundred subjects (90 male, 110 female, mean age ± SD, 50 ± 11 years, range 23–74 years) matched for age, sex and body mass index served as controls.measurements Submandibular salivary gland volume was measured in all acromegalic patients and normal subjects by ultrasound and calculated by the ellipsoid model. Serum GH and IGF‐I concentrations were measured in all subjects.results Acro‐U patients had higher serum IGF‐I levels (691 ± 235 µg/l) than Acro‐R (174 ± 74 µg/l), Acro‐SA (436 ± 239 µg/l) or controls (151 ± 66 µg/l) (P < 0·0001, P = 0·008, P < 0·0001, respectively). The mean submandibular salivary gland volume was higher in acromegalic patients than in controls: Acro‐U 18·1 ± 3·3 ml, Acro‐SA 16·2 ± 3·3 ml, Acro‐R 15·7 ± 3·0 ml and controls 8·2 ± 2·4 ml (P < 0·0001). Differences among subgroups of Acro patients were not significant. Enlargement of the submandibular salivary glands was present in 35/40 (87·5%) acromegalic patients. A positive correlation between serum IGF‐I (P < 0·0001), GH (P < 0·0001) and submandibular salivary gland volume was found.conclusions Acromegalic patients have an increased volume of submandibular salivary glands, independently of the activity of disease.
Pancreatic lesions in von Hippel–Lindau disease
Authors: Mukhopadhyay B. , Sahdev A. , Monson J. P. , Besser G. M. , Reznek R. H. , Chew S. L. 
Published: March 2003

Summaryobjective Von Hippel–Lindau disease is an inherited neoplasia syndrome. The main endocrine manifestations are phaeochromocytoma and paraganglioma. The presence of pancreatic disease has also been variably reported. This study was undertaken to describe the prevalence, nature, natural history and clinical associations of pancreatic lesions in von Hippel–Lindau disease.patients and design A retrospective analysis of the case notes of 17 consecutive patients. Average duration of follow‐up was 5·5 years. Clinical, biochemical, genetic and radiological testing was routinely performed.results Eleven (64·7%) patients had pancreatic lesions either on computed tomography or magnetic resonance imaging. Serous microcystic adenomas and multiple cysts were the commonest findings, but solid lesions were also found. The commonest clinical association was diabetes mellitus in patients with extensive serous microcystic adenomas. None of the pancreatic lesions showed evidence of biochemical function. All patients with pancreatic lesions also had renal lesions. Mutations were found at several points in the gene and there was no apparent association between pancreatic lesions and a particular mutation.conclusions Pancreatic lesions are very common in von Hippel–Lindau disease and all patients had coexisting renal lesions. The main clinical correlate was diabetes mellitus, but otherwise the lesions were clinically and biochemically silent.
IGF‐I in a normal population: relation to psychosocial factors
Authors: Unden Anna‐Lena , Elofsson Stig , Knox Sarah , Lewitt Moira S. , Brismar Kerstin 
Published: March 2003

SummaryObjectiveIGF‐I has important actions on cell division, apoptosis, differentiation and metabolism, as well as on cell proliferation in vascular smooth muscle. Deficiency of GH, an important regulator of IGF‐I, is associated with reduced well‐being. IGF‐I levels have been related to cognitive function in older individuals. The aim of the present study was to investigate the IGF‐I concentrations in a normal population of men and women aged 20–74 years and to determine the influence of a variety of behavioural and psychosocial factors as well as metabolic factors on these concentrations.DesignCross‐sectional study.PatientsThe study group consisted of 408 randomly selected people who had answered a questionnaire concerning health care utilization and quality of life that was administered to a random sample of 4200 people over age 17 from the northwestern region of greater Stockholm in 1995. Thirty‐four men and 34 women were randomly selected from the age group 20–24 and from each 10‐year age group between the ages of 25–75 years. Seventy‐one per cent of the 408 people invited to come in for an examination agreed to attend, making a total sample size of 288 people.MeasurementsA medical examination was performed and blood drawn in the morning after subjects had been fasting overnight. Before the examination, they were asked to fill out a questionnaire concerning lifestyle and psychosocial factors.ResultsThe distribution of IGF‐I was positively skewed, but using logarithmically transformed IGF‐I, a more symmetrical distribution was obtained. A linear inverse correlation was found between logarithmically transformed IGF‐I levels and age which explained more than 40% of the variation in men and women. Linear correlation analysis between IGF‐I and different parameters of health and disease, lifestyle and psychosocial factors, resulted in several significant correlations most of which disappeared after controlling for age. In the younger age group (20–44) there were positive correlations between IGF‐I and psychosocial factors representing quality of life and psychological well‐being. In the middle age group (45–59) higher IGF‐I levels were related to better physical health, higher education and higher concentrations of lipoprotein Lp(a). In the older age group (over 59 years) higher levels of low‐density lipoprotein‐cholesterol (LDL‐C) and lower levels of SHBG were associated with higher IGF‐I levels.ConclusionIn a randomly selected (nondisease) population, IGF‐I concentrations show a consistent decrease with age in both men and women, accompanied by different association patterns relevant to disease risk. Levels are related to psychosocial parameters in the younger age group and metabolic impairment associated with increased cardiovascular risk in the older age groups. We speculate on the relative roles of age and cohort differences in rearing conditions in determining these differences.
Testicular dose and fertility in men following I131 therapy for thyroid cancer
Authors: Hyer Stephen , Vini Louiza , O'Connell Mary , Pratt Brenda , Harmer Clive 
Published: March 2003

Summaryobjective Young adults with differentiated thyroid cancer are treated with high doses of radioiodine and have an excellent long‐term prognosis. However, there is limited information on the effects of this treatment on the gonads and fertility in male patients. We have reviewed the outcome of treatment in our centre with respect to male fertility. We have also assessed directly the radiation dose received by the testes.design Retrospective analysis of males attending the thyroid clinic at the Royal Marsden Hospital for treatment of differentiated thyroid cancer. A prospective study was also performed to assess radiation dose to testes in 14 consecutive patients attending for thyroid cancer treatment.patients Males under the age of 40 years at the time of treatment with a minimum of 3 years follow‐up.measurements Number of children fathered by patients and number of congenital malformations. For the prospective study: gonadal function assessed by serum FSH, LH and testosterone measurements; radiation dose to the testes (Gy) measured by thermoluminescent dosimetry.results Fertility was assessed in 122 men with a median follow‐up of 21 years (range 3–39) of whom 93 were under active follow‐up. One hundred and six children were fathered by 59 patients; the remainder had no wish to have children. No major malformations were reported. Of these 59 patients, 12 had received a single 3GBq ablation dose, 19 had been treated with up to 14 GBq radioiodine and 28 had received up to 44 GBq. In 14 patients followed prospectively, the median estimated radiation dose to each testis was 6·4 cGy following 3 GBq, 14·1 cGy following 5·5 GBq and 21·2 cGy following 9·2 GBq. There was a transient elevation in serum FSH after radioiodine which normalized within 9 months from the last administration.conclusions Radioiodine treatment for thyroid cancer may result in transient impairment of gonadal function. The radiation dose absorbed by the testis after a single ablative dose of radioiodine is well below that associated with permanent damage to germinal epithelium and the risk of infertility in these patients is minimal. Patients requiring multiple administrations for persistent or metastatic thyroid cancer may be at greater risk of gonadal damage although even in this group, we found no evidence of infertility.