bluuebunny/crossref_metadata_2025 huggingface dataset:
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

objective 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

OBJECTIVE 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

objective 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

ojbective 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

objective 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

objective 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

ObjectiveIGF‐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

objective 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.
Tibolone lowers high density lipoprotein cholesterol by increasing hepatic lipase activity but does not impair cholesterol efflux
Authors: Von Eckardstein Arnold , Crook David , Elbers Jolanda , Ragoobir Jennifer , Ezeh Benjamin , Helmond Frans , Miller Norman , Dieplinger Hans , Bennink Herjan Coelingh , Assmann Gerd
Published: March 2003

objective Androgens and other drugs that reduce plasma concentrations of high density lipoprotein (HDL) cholesterol are often considered to be pro‐atherogenic. Tibolone lowers HDL‐cholesterol by 20% but the clinical significance of this effect is unknown.

methods In a randomized, double‐blind study, 34 women received 2·5 mg tibolone daily and 34 women received placebo. Serum concentrations of lipids, lipoprotein subclasses and apolipoproteins, together with plasma activities of lipid transfer proteins and lipolytic enzymes and the capacity of plasma to induce cholesterol efflux from cultured cells, were measured.

results Compared to placebo, tibolone reduced serum concentrations of HDL‐cholesterol (−14%), HDL phosphatidylcholine (−14%), apolipoprotein (apo)A‐I (−12%), HDL subclasses lipoprotein (Lp)A‐I (−20%), HDL‐apoE (−16%), preβ‐LpA‐I (−10%) and α‐LpA‐I (−12%) and increased hepatic lipase activity (+25%) and HDL sphingomyelin : phosphatidylcholine ratio (10·5%), but did not alter serum concentrations of HDL sphingomyelin, apoA‐IV and LpA‐I/A‐II, lipoprotein lipase, the plasma activities of lecithin : cholesterol acyl transferase, cholesteryl ester transfer protein, phospholipid transfer protein or the plasma capacity to release cholesterol from cultured fibroblasts or Fu5AH hepatocytes.

conclusions Tibolone lowers HDL‐cholesterol in part by increasing hepatic lipase activity. Conservation of sphingomyelin and apoA‐II in HDL, as well as cholesteryl ester transfer protein activity, preserves the capacity of plasma to release cholesterol, despite the lower concentrations of HDL‐cholesterol. This may have important implications for the use of steroid effects on HDL concentrations as surrogates for atherosclerosis.
Prolonged high‐dose phosphate treatment: a risk factor for tertiary hyperparathyroidism in X‐linked hypophosphatemic rickets
Authors: Mäkitie Outi , Kooh Sang Whay , Sochett Etienne
Published: March 2003

objective X‐linked hypophosphatemic rickets is characterized by renal phosphate wasting, hypophosphatemia and defective bone mineralization. Treatment with oral phosphate (Pi) and calcitriol improves skeletal changes but associates with secondary hyperparathyroidism and nephrocalcinosis. Tertiary hyperparathyroidism is a rare complication of the treatment. The aim of the present study was to identify treatment‐related factors that might be associated with the transition of secondary hyperparathyroidism to tertiary hyperparathyroidism in patients with X‐linked hypophosphatemic rickets.

design Thirteen patients with X‐linked hypophosphatemic rickets and secondary or tertiary hyperparathyroidism were included in the study. Their hospital records were reviewed and compared for onset, duration and dosage of treatment, and for age of diagnosis and degree of secondary hyperparathyroidism.

results Two patients developed tertiary hyperparathyroidism and 11 patients secondary hyperparathyroidism during the treatment. Patients with tertiary hyperparathyroidism had, on average, earlier onset and longer duration of treatment, higher dose of Pi and longer duration of treatment with very high Pi doses (> 100 mg/kg/day) compared to the 11 patients with secondary hyperparathyroidism. However, variation of all parameters was great with considerable overlap. Very high S‐PTH levels ≥ 42 pmol/l were observed in those who later developed tertiary hyperparathyroidism.

conclusions Prolonged very high dose oral Pi treatment is a major risk factor for the development of tertiary hyperparathyroidism in X‐linked hypophosphatemic rickets.
Relationship between plasma insulin and left ventricular mass in normotensive participants of the Gubbio Study
Authors: Vaccaro Olga , Cardoni Ondina , Cuomo Vincenzo , Panarelli Walter , Laurenzi Martino , Mancini Mario , Riccardi Gabriele , Zanchetti Alberto
Published: March 2003

background There is substantial but not conclusive evidence that insulin resistance is related to left ventricular mass (LVM) in hypertensive individuals. To what extent this association is mediated by the relationship between plasma insulin and body size and build is still debated, and is poorly explored in nonhypertensive people.

objective To explore the relationship between insulin or insulin resistance and LVM in a population‐based sample of nonhypertensive participants of the Gubbio Study.

method Echocardiographic LVM was determined in 91 nondiabetic, nonhypertensive individuals aged 45–54 years, participating in a population‐based screening. LVM normalized for height2·7 was used in the analyses; LV hypertrophy was defined as a value of ≥ 50 g/m2·7 in men or ≥ 47 g/m2·7 in women. Fasting plasma insulin and glucose were measured and the Homeostasis Model Assessment (HOMA) index was used as a measure of insulin resistance.

results LVM was positively and significantly correlated with body mass index (BMI) (P < 0·01), waist circumference (P < 0·01) and HOMA index (P < 0·05), whereas correlations with plasma glucose and triglycerides did not reach statistical significance (P = 0·07 for both); all correlations were offset after adjusting for BMI. Fasting plasma insulin and HOMA index were not significantly different in subjects with or without LV hypertrophy (70·8 ± 27·8 vs. 77·7 ± 29·6 pmol/l and 2·2 ± 1·0 vs. 2·6 ± 1·4, respectively). Bivariate analysis performed stratifying participants above or below the 75th percentile of the sex‐specific distribution for BMI (29·1 and 29·4 kg/m2 for males and females, respectively) and plasma insulin (84 pmol/l for either gender), did not result in appreciable differences in LVM due to insulin levels. Similar results were obtained replacing the HOMA index for insulin in the analysis.

conclusion In nonhypertensive individuals left ventricular mass is not associated with plasma insulin independently of body mass index.
A relationship between serum ferritin and the insulin resistance syndrome is present in non‐diabetic women but not in non‐diabetic men
Authors: Sheu Wayne Huey‐Herng , Chen Ying‐Tsung , Lee Wen‐Jane , Wang Chen‐Wen , Lin Lih‐Yuan
Published: March 2003

background Previous studies have suggested that serum ferritin is one of the components of the insulin resistance syndrome in Caucasians. Because serum ferritin levels differ significantly between men and women, variation in the role of ferritin in insulin resistance between the sexes, particularly in Asian populations, is still unknown.

objective To examine whether the association between serum ferritin and insulin resistance differs between men and women in randomly selected non‐diabetic Chinese subjects.

design A retrospective study.

patients Four hundred and seventeen non‐diabetic Chinese subjects (140 men and 277 women) were studied.

measurements Fasting plasma glucose, insulin, lipoproteins and serum ferritin concentrations, as well as plasma glucose and insulin responses to a 75‐g oral glucose test (n = 219), were determined.

results Fasting serum ferritin concentrations (mean ± SEM) were significantly higher in men than in women (504 ± 33 vs. 242 ± 18 pmol/l, P < 0·001). In women, fasting serum ferritin concentrations correlated significantly with age, body mass index (BMI), amount of body fat, fasting plasma glucose, insulin, cholesterol, triglyceride concentrations, glucose response to an oral glucose load, and homeostasis model assessment (HOMA) of insulin resistance but not with blood pressure, high density lipoprotein (HDL) cholesterol levels and insulin response to oral glucose. On the contrary, none of the above anthropometric and metabolic variables was related to fasting serum ferritin levels in men. HOMA insulin resistance increased progressively across three different tertiles for measured serum ferritin concentrations in women (P < 0·003). In men, HOMA insulin resistance levels were not different among three differing measured serum ferritin levels (P = 0·424). Adjustment for age, BMI and menopause status did not change the significant relationship between HOMA insulin resistance and serum ferritin in women.

conclusions We observed that a relationship between serum ferritin levels and insulin resistance exists in women but not in men. This sexual dimorphism merits further investigation.
Effect of the H1 blocker d‐chlorpheniramine on cerebral blood flow in the conscious dog during normocapnic hypoxia
Authors: Audibert  , Siat  , Müller  , Hartemann  , Naja  , Saunier  , Laxenaire
Published: March 2003

The mechanism causing cerebral vasodilatation during hypoxia remains unclear. A role for histamine is suspected because H2 receptor‐blocking drugs blunt the hypoxia‐induced increase in cerebral blood flow (CBF). Moreover, in vitro blockade of H1 receptors by chlorpheniramine decreases the vasodilatation of cerebral arteries that is induced by histamine. The present study tested the hypothesis that an H1 receptor blocker (d‐chlorpheniramine) would have a similar effect in vivo during hypoxia. Isocapnic hypoxia (inspired oxygen fraction, FIO2 = 0·10; inspired carbon dioxide fraction, FICO2 = 0·035) was induced in 16 conscious dogs randomly divided into two groups: eight dogs received saline intravenously (controls) at time 0 (normoxia) and after 2 h and 4 h hypoxia, and the other eight dogs received d‐chlorpheniramine intravenously (0·5 mg kg−1) to block the H1 receptors. Regional CBF was measured by the radioactive microspheres technique 15 min after each injection of d‐chlorpheniramine or saline. In the control group, CBF increased during hypoxia in all regions of the brain. In the d‐chlorpheniramine group, total CBF increased similarly after 2 h of hypoxia. After 4 h of hypoxia, the increase was limited, especially in the pons, cerebral peduncles, hippocampus, hypothalamus, thalamus, and occipital lobes (six out of 12 studied regions). It is concluded that the H1 blocker d‐chlorpheniramine did not strongly inhibit the increase in CBF during hypoxia. After cumulative doses, however, as in the fourth hour of hypoxia, the increase in total CBF was limited.
Cardiovascular effects of ephedrine, caffeine and yohimbine measured by thoracic electrical bioimpedance in obese women
Authors: Waluga  , Janusz  , Karpel  , Hartleb  , Nowak
Published: March 2003

Low caloric diet is a commonly accepted treatment in obesity. However, owing to moderate results, a pharmacological support has been proposed. As some efficacious drugs activate overall sympathetic activity, they might modify functions of the cardiovascular system. Three groups of subjects were studied: (1) nine obese women receiving only a standard hypocaloric diet; (2) nine obese women receiving a standard hypocaloric diet and ephedrine (2 × 25 mg) with caffeine (2 × 200 mg); (3) nine obese women receiving a standard hypocaloric diet and ephedrine (2 × 25 mg) with caffeine (2 × 200 mg) and yohimbine (2 × 5 mg). The cardiovascular state was evaluated by thoracic electrical bioimpedance, automatic sphygmomanometry and continuous ECG recording. In each patient, the haemodynamic study was performed twice: at rest, i.e. before treatment; and after 10 days of treatment. On the same days in each patient, the haemodynamic tests were performed during physical exercises (handgrip stress and cycloergometer exercise). Caffeine and ephedrine had no haemodynamic effect in resting patients. These two drugs led to an increase in ejection fraction during cycloergometer exercise. Addition of yohimbine increased diastolic pressure and heart rate but decreased ejection fraction and stroke index during rest. We also observed that addition of yohimbine decreased ejection fraction during the handgrip and cycloergometer exercise and increased cardiac load during dynamic exercise. Pharmacological supplement of ephedrine and caffeine to a low caloric diet modified the cardiovascular system weakly, but the addition of yohimbine to this regimen attenuated cardiac performance during rest and handgrip and increased cardiac work during dynamic exercise.
Reduced left ventricular relaxation velocity after acute myocardial infarction
Authors: Bojö  , Wandt  , Ahlin
Published: March 2003

Diastolic left ventricular function is usually described using Doppler recording of the early to atrial (E/A) ratio. However, because of pseudonormalization in patients with moderately impaired diastolic function, the E/A ratio does not allow a meaningful comparison between a group of patients with varying degrees of dysfunction, e.g. after acute myocardial infarction (AMI), and a group of healthy control subjects. In this study, diastolic function was assessed using the E/A ratio, deceleration time of early mitral inflow and maximal longitudinal relaxation velocity. The relaxation velocity was measured using echocardiographic M‐mode recording of mitral annulus motion. Mitral annulus motion was recorded in four‐ and two‐chamber views. Relaxation velocities were measured in the septal, lateral, anterior and posterior parts of the mitral annulus and the mean value (RVm) was calculated. Twenty‐two consecutive patients were investigated 3–21 days after first transmural AMI. Twenty‐two healthy subjects of similar age served as a control group. The group of patients with AMI had an RVm of 40·9 ± 15·4 mm s−1 compared with 68·5 ± 12·4 mm s−1 in the control group (P<0·0001). In contrast, the E/A ratio, deceleration time and heart rate did not differ significantly between the two groups. The results suggest that maximal longitudinal relaxation velocity is a simple and appropriate measure of diastolic function in patients with transmural AMI.
Exaggerated blood pressure response to exercise: importance of resting blood pressure
Authors: Bassett D. R. , Duey W. J. , Walker A. J. , Torok D. J. , Howley E. T. , Tanaka H.
Published: March 2003

Normotensive individuals who exhibit an exaggerated blood pressure (BP) response to exercise have an increased risk of future hypertension. However, previous studies failed to control for resting BP despite the fact that an elevated resting BP in the normotensive range is also a strong predictor of future hypertension. Therefore, we determined whether maximal systolic BP is associated with resting BP. Resting BP was measured in 68 healthy normotensive men on three separate days. The subjects then performed a graded, maximal exercise test on a Monark cycle ergometer. Maximal systolic BP was strongly correlated with resting systolic BP (r = 0·64, P<0·0001). Subjects with elevations in systolic BP during maximal exercise (>220 mmHg) also had higher (P<0·005) resting BP than those without (<220 mmHg). When stepwise regression analyses were performed, systolic BP at rest was a significant independent predictor of maximal systolic BP, explaining over 40% of the variability. These results suggest that exaggerated BP response as a predictor of future hypertension reported in previous studies may be little more than a simple reflection of elevated resting BP. Specifically, these studies should not be interpreted as demonstrating that exercise BP is a better predictor of future hypertension than resting BP alone. In the future, defining the BP `response' to exercise as a change score (i.e. maximal BP minus resting BP) may be advantageous as it permits the effects of exercise to be examined independently of the level of resting BP.
Left ventricular geometry and function are related to electrocardiographic characteristics and diagnoses
Authors: Sundström J. , Lind L. , Andrén B. , Lithell H.
Published: March 2003

We investigated the relationships between echocardiographic indices of left ventricular geometry and function and major electrocardiographic (ECG) abnormalities in 540 elderly (69–74 years old) male participants of a health survey conducted in Uppsala county, Sweden. Comparing men with major ECG abnormalities that were present or absent in various hierarchic mutually exclusive categories, left ventricular mass indexed to body surface area (LVMI) was significantly increased with major Q‐waves (P = 0·0002), ST or T‐wave abnormalities (P = 0·005), left bundle‐branch block (P = 0·005) and also with atrioventricular block type 1 (P = 0·008) and frequent premature beats (P = 0·02). The left atrial diameter was also significantly increased with most ECG abnormalities. The increased LVMI was in left bundle‐branch block mainly due to an increased left ventricular diameter, whereas left ventricular wall thickness was increased with frequent premature beats, atrioventricular block type 1 and ST or T‐wave abnormalities. The prevalence of Q‐waves was highest in eccentric left ventricular hypertrophy, whereas the prevalence of ST or T‐wave abnormalities and atrioventricular block type 1 was highest in concentric left ventricular hypertrophy. Both left ventricular systolic (ejection fraction) and diastolic function (E/A ratio) were inversely related to Sokolow–Lyon QRS amplitude (r = −0·25, P < 0·02 and r = −0·22, P < 0·03 respectively). In conclusion, LVMI was increased in subjects with ECG signs of coronary artery disease as well as in subjects with several other ECG diagnoses. Furthermore, both left ventricular systolic and diastolic dysfunction were related to increased QRS amplitudes. Thus, the finding of ECG abnormalities in elderly men should raise the suspicion of structural and/or functional left ventricular abnormality.
Respiratory‐like periodicities in slow eye movements during sleep onset
Authors: Rittweger J. , Pöpel A.
Published: March 2003

Slow eye movements (SEMs) during sleep onset and their relationship to vegetative rhythms were investigated in six healthy, sleep‐deprived subjects, yielding 143−289 SEMs in an epoch of 31·5−56 min per experiment. Exclusively, sleep in stages I and II was recorded. From the bandpass‐filtered electro‐oculogram (EOG) signal (cut‐off frequencies 0·05 and 1 Hz), turning points of the gaze were detected and compared with the start of inspiration, which was discriminated from the abdominal respiratory excursions. SEM cycle times varied considerably more than respiratory cycle times (P < 0·05 in Levene's test). Both were preferentially of equal length, or, in some subjects, in 2:1 co‐ordination. Cross‐correlation histograms yielded that inspiration and SEMs were also temporally co‐ordinated. Thus, there is a temporal coherence regarding the occurrence, the cycle time and the phase between SEMs and a respiratory‐like rhythm. Our findings show that it is not exactly the respiratory rhythm that is mirrored in the SEMs. Rather, we favour the interpretation of an autorhythmicity that is temporarily connected to the common brainstem system in the reticular formation of the brainstem.
Leptin: physiology and pathophysiology
Authors: Frühbeck G. , Jebb S. A. , Prentice A. M.
Published: March 2003

The identification and sequencing of the ob gene and its product, leptin, in late 1994 opened new insights in the study of the mechanisms controlling body weight and led to a surge of research activity. During this time, a considerable body of knowledge regarding leptin's actions has been accumulated and the field continues to expand rapidly. Currently there is particular interest in the interaction of leptin with other peripheral and neural mechanisms to regulate body weight, reproduction and immunological response. In this review, we attempt to place the current state of knowledge about leptin in the broader perspective of physiology, including its structural characteristics, receptors, binding proteins, signalling pathways, regulation of adipose tissue expression and production, secretion patterns, clearance mechanisms and functional effects. In addition, leptin's involvement in the pathophysiology of obesity, anorexia nervosa, diabetes mellitus, polycystic ovary syndrome, acquired immunodeficiency syndrome, cancer, nephropathy, thyroid disease, Cushing's syndrome and growth hormone deficiency will be reviewed.
Twenty‐four‐hour cortisol response to multiple daily exercise sessions of moderate and high intensity
Authors: Hackney  , Viru
Published: March 2003

The aim of this study was to characterize and describe the cortisol responses in athletes over a 24‐h period on different days involving multiple exercise sessions of varied intensity. Seventeen endurance athletes volunteered to undergo three experimental treatment conditions: (a) a control day involving no exercise; (b) an exercise day with two sessions of high‐intensity exercise; and (c) an exercise day with two sessions of moderate‐intensity exercise. Significant changes (P<0·01) were found owing to the influence of both types of exercise during the daytime (high‐intensity exercise producing a greater cortisol response than moderate intensity). At night after the moderate‐intensity exercise (at selected times), cortisol response was significantly less than during the control condition at corresponding times (P<0·05). After high‐intensity exercise (at selected times), cortisol levels were significantly less (P<0·05) than in the control condition at corresponding times. Additionally, certain night‐time responses after the high‐intensity exercise were significantly less than the moderate‐intensity exercise responses at similar time points. The results indicate that daytime multiple exercise sessions produce suppressed cortisol levels at night, and the magnitude of this effect is dependent upon the intensity at which the daytime exercise is performed. The physiological mechanism inducing this effect upon cortisol levels at night is unclear from the present data.
Different plasma levels of nitric oxide in arterial and venous blood
Authors: Cicinelli Ettore , Ignarro Louis J. , Schonauer Luca M. , Matteo Maria G. , Galantino Pietro , Falco Nunziata
Published: March 2003

Experimental investigations suggest that a basal release of nitric oxide (NO) occurs in arterial but not in venous endothelium. We therefore decided to compare plasma levels of NO in the arterial and venous circulation. Parallel blood samples were drawn from the radial artery and brachial vein in 15 healthy drug‐free women. Nitric oxide levels were assessed by measuring plasma levels of nitrite and nitrate, the two stable oxidation products of NO metabolism. Plasma levels of NO metabolites in arterial blood were significantly higher than in the paired venous blood samples (45·1 ± 17·7 versus 22·5 ± 8·5 μmol l−1, respectively, mean ± SD). The results of this preliminary study strongly suggest that the endothelial release of NO is probably different in arteries and veins in vivo; this is also consistent with previous literature indicating that basal release of NO occurs mainly from the endothelium of arteries but not from that of veins.
Simplified scintigraphic methods for measuring gastrointestinal transit times
Authors: Graff  , Brinch  , Madsen
Published: March 2003

To investigate whether simple transit measurements based on scintigraphy performed only 0, 2, 4 and 24 h after intake of a radiolabelled meal can be used to predict the mean transit time values for the stomach, the small intestine, and the colon, a study was conducted in 16 healthy volunteers. After ingestion of a meal containing 111indium‐labelled water and 99mtechnetium‐labelled omelette, imaging was performed at intervals of 30 min until all radioactivity was located in the colon and henceforth at intervals of 24 h until all radioactivity had cleared from the colon. Gastric, small intestinal and colonic mean transit times were calculated for both markers and compared with fractional gastric emptying at 2 h, fractional colonic filling at 4 h, and geometric centre of colonic content at 24 h, respectively. Highly significant correlations were found between gastric mean transit time and fractional gastric emptying at 2 h (111In: r=0·95, P<0·00001; 99mTc: r=0·96, P<0·00001), between small intestinal mean transit time and fractional colonic filling at 4 h (111In: r=−0·97, P<0·00001; 99mTc: r=−0·89, P<0·00001), and between colonic mean transit time and geometric centre of colonic content at 24 h (111In: r=− 0·88, P<0·00001). We therefore conclude that reliable regional gastrointestinal transit times can be estimated from scintigraphic images taken 0, 2, 4 and 24 h after intake of radiolabelled markers.
Effects of low‐dose adrenomedullin on cardiac function and systemic haemodynamics in man
Authors: Bene R. Del , Lazzeri C. , Barletta G. , Vecchiarino S. , Guerra C. T. , Franchi F. , La Villa G.
Published: March 2003

The cardiovascular effects of low‐dose adrenomedullin (ADM, 1, 2 and 3 pmol kg−1 min−1 for 30 min each) were evaluated in six healthy subjects in a placebo controlled, cross‐over study by determining cardiac volumes, systolic and diastolic function (echocardiography) and systemic haemodynamics before, during and after ADM or placebo. High‐resolution ultrasound was used to evaluate changes in carotid artery distension. ADM caused a +85% increment in its plasma levels and significantly increased plasma cyclic adenyl monophosphate (cAMP). Compared with placebo, ADM induced significant decrements in left ventricular (LV) systolic diameter and systemic vascular resistance, and increments in LV posterior wall thickening, ejection fraction and cardiac index. Right and left atrial emptying fraction and carotid artery distention increased. LV diastolic function, heart rate, and plasma renin activity did not change, whereas packed cell volume increased. These results indicate that ADM influences cardiovascular function and systemic haemodynamics at physiological plasma levels in man mainly because of its vasodilating activity, leading to reduced afterload.
Factors influencing 133‐xenon washout in a nose‐sinus model
Authors: Paulsson Bo , Dolata Jan , Lindberg Sven , Ohlin Per
Published: March 2003

The 133‐xenon washout technique is a non‐invasive method for the evaluation of ventilation of the paranasal sinuses. The half‐time of 133‐xenon washout (T½) is considered to reflect sinus ostial function and sinus ventilation. However, it is not known how morphological and physiological factors affect the washout from the paranasal sinuses. The aim of the present study was to evaluate how sinus volume, ostial diameter and nasal ventilation influence 133‐xenon washout in a nose‐sinus model. This is important for the interpretation of measurements of 133‐xenon washout from paranasal sinuses in healthy subjects and in subjects with sinus disease. The 133‐xenon washout was measured with a scintillation camera. The statistical analysis of the results showed that the logarithm (to the base 10) of the half‐time of 133‐xenon washout is linearly related to the ostial diameter, the sinus volume and the nasal ventilation in the model. In a multiple linear regression model, the most important factor contributing to 133‐xenon washout was found to be the ostial diameter, which explained 76% of the variation in log T½. In the same statistical model the sinus volume explained 7·5% and the ventilation 5·3% of the variation in log T½. Calculations of the functional ostial diameter in healthy subjects were made, based on the results of the model study. The mean functional ostial diameter was found to be 3·5 mm (range 0·5–7·5 mm). The results obtained with the present model experiments may be of importance for the correct interpretation of the results of measurements of 133‐xenon washout in healthy subjects and patients.