bluuebunny/crossref_metadata_2025 huggingface dataset:
Oncogenic osteomalacia: is there a new phosphate regulating hormone?
Authors: Nelson Anne E. , Robinson Bruce G. , Mason Rebecca S.
Published: November 2003

Oncogenic osteomalacia is a syndrome associated with rare, usually mesenchymal tumours, which is characterized by hypophosphataemia, phosphaturia and low concentrations of 1,25‐dihydroxyvitamin D. The reversal of clinical and biochemical abnormalities following removal of the tumour, indicates it is the source of a humoral factor that is responsible for these abnormalities. It has been demonstrated that the humoral factor inhibits renal phosphate uptake and reduces 1,25‐dihydroxyvitamin D production. Although there is evidence that it may act via parathyroid hormone/parathyroid hormone‐related peptide receptors and may be a peptide, the factor has not yet been identified, nor has its relationship to factors involved in X‐linked hypophosphataemic rickets been established. We propose unifying hypotheses for the pathogenesis of oncogenic osteomalacia and X‐linked hypophosphataemic rickets which involve defects in the PEX gene. These hypotheses do not fully explain all the available data and it remains possible that hormone(s) with little or no role in X‐linked hypophosphataemic rickets may be responsible for oncogenic osteomalacia.
Frequency of a polymorphism in the regulatory region of the 17α‐hydroxylase‐17,20‐lyase (CYP17) gene in hyperandrogenic states
Authors: Techatraisak K. , Conway G. S. , Rumsby G.
Published: November 2003

OBJECTIVE Dysregulation of 17α‐hydroxylase (CYP17) has been proposed as a cause of hyperandrogenism. We have determined the prevalence of a polymorphic allele in the CYP17 gene in sporadic patients with polycystic ovaries (PCOS) compared to a reference population, and to a group of hyperandrogenic individuals, to assess its significance to androgen production.

PATIENTS AND DESIGN DNA was isolated from EDTA blood samples from 69 patients with PCOS, 63 patients with congenital adrenal hyperplasia secondary to 21‐hydroxylase deficiency and 124 consecutive patients attending for a full blood examination. The thymine (T) to cytosine (C) polymorphism at −34 base pairs (bp), denoted alleles A1 and A2 respectively, was detected by amplification of DNA followed by restriction enzyme digestion.

MEASUREMENTS Testosterone and LH. The frequency of alleles A1 and A2 in each of the subject groups was determined.

RESULTS The prevalences of the A1 and A2 alleles were 75 and 25% respectively in the PCOS group which was not significantly different from that in either the hyperandrogenic or the reference group. Neither allele segregated with hyperandrogenism.

CONCLUSION The polymorphism plays no apparent role in the dysregulation of CYP17.
Improved glucose tolerance after effective lipid‐lowering therapy with bezafibrate in a patient with lipoatrophic diabetes mellitus: a putative role for Randle’s cycle in its pathogenesis?
Authors: Panz V. R. , Wing J. R. , Raal F. J. , Kedda M.‐A. , Joffe B. I.
Published: November 2003

This report describes a patient with lipoatrophic diabetes mellitus (LDM), which is a rare clinical syndrome characterized by lipoatrophy and severe insulin resistance. Although a genetic abnormality is suspected in the development of LDM, no functional mutations in key domains of the insulin receptor gene were detected. Therapy was directed primarily at decreasing the availability of non‐esterified fatty acids (NEFA), and thereby improving glucose tolerance (Randle’s cycle), by the administration of a lipid‐lowering drug, bezafibrate. Serial changes in fasting levels of the hormones of glucose homeostasis and lipids were measured, as well as glucose and insulin responses to a 75‐g oral glucose challenge at onset and following 3 and 6 months of fibrate therapy. Progressive reductions in the patient’s levels of triglycerides and NEFA were paralleled by an improvement in β‐cell function, a decrease in insulin resistance, and the attainment of normal glucose homeostasis. We conclude that the pathogenesis of LDM may be related primarily to abnormal regulation of lipid, rather than glucose, metabolism.
Vitamin D receptor gene polymorphism in men and its effect on bone density and calcium absorption
Authors: Francis R. M. , Harrington F. , Turner E. , Papiha S. S. , Datta H. K.
Published: November 2003

OBJECTIVE Previous studies have suggested that polymorphism of the alleles of the vitamin D receptor (VDR) gene may account for the major part of the heritable component of bone density in women, possibly mediated in part by impaired calcium absorption from the bowel. In view of the increasing importance of osteoporosis in men, we have now investigated the association between common allelic variations in the vitamin D receptor gene, calcium absorption and bone density in men.

SUBJECTS  Forty‐eight men (median age 64, range 27–77) with a wide range of bone density measurements, comprising 20 men with vertebral crush fractures and 28 male control subjects.

MEASUREMENTS Analysis of the VDR gene polymorphism and measurement of fractional radiocalcium absorption and bone mineral density was performed in all subjects.

RESULTS The distribution of the three genotypes (TT, tt, Tt) was comparable to that reported previously. There was no significant difference in femoral neck bone density Z‐scores between the three genotypes (mean±SD TT −0.31±1.19, tt −0.08±001.28 and Tt −0.37±1.17). There were also no significant differences in mean femoral neck bone density T‐scores or lumbar spine bone density Z or T‐scores between the three genotypes. Fractional radiocalcium absorption was 0.59±0.27 for TT, 0.69±0.30 for tt and 0.60±0.30 for Tt, showing no significant difference between the genotypes.

CONCLUSIONS This study shows no association between vitamin D receptor gene polymorphism and bone density or fractional calcium absorption in a group of men with a range of bone density values. We conclude that the vitamin D receptor gene alleles probably account at most for only a small part of the genetic component of bone density in men.
Intracellular calcium ion responses to somatostatin in cells from human somatotroph adenomas
Authors: Chen Zhen‐Ping , Xu Su , Lightman Stafford L. , Hall Len , Levy Andrew
Published: November 2003

OBJECTIVE Various GH secretory responses to long‐acting somatostatin (SRIH) analogues have been observed during the treatment of acromegalic patients. The effects of SRIH on intracellular Ca2+ homeostasis in human somatotroph adenoma cells has not been examined in detail, and the underlying mechanisms therefore remain to be determined. Using isolated cells from human somatotroph adenomas, we have investigated the SRIH‐induced intracellular Ca2+ responses at a single‐cell level with computerized real time intracellular calcium ion (Ca2+i) imaging.

PATIENTS Adenoma specimens were obtained from 4 male and 11 female acromegalic patients (mean age 56, range 26–72 years) undergoing transsphenoidal hypophysectomy.

METHODS The identity of the biopsy material obtained was confirmed by immunocytochemistry for hGH and in situ hybridization histochemistry using a 35S end‐labelled hGH oligodeoxynucleotide probe and probes complementary to proopiomelanocortin and prolactin. Genomic DNA coding for somatostatin receptor (SSTR2) from each adenoma was PCR amplified and sequenced. Cells cultured from these adenoma were subject to computerized real time intracellular Ca2+i imaging at a single cell level.

RESULTS In cells from 11 of the 15 adenomas, SRIH produced a reversible, dose‐independent reduction in [Ca2+]i from the mean of 167±11 to 43±3 nM within 51±1.8s, and blocked the growth hormone releasing hormone (GRH)‐induced increase in [Ca2+]i as expected. In the same adenomas, withdrawal of SRIH after a 30 second exposure produced a small but significant increase in resting [Ca2+]i. Pretreatment with pertussis toxin abolished the SRIH‐induced inhibition of [Ca2+]i and prevented the SRIH‐induced inhibition of the effect of GRH on [Ca2+]i. One of the remaining 4 adenomas was completely unresponsive to SRIH despite responding vigorously to other ligands and immunostaining strongly for GH. Surprisingly, cells from 3 adenomas showed a paradoxical increase in [Ca2+]i in response to SRIH in some or, in one case, all of the cells examined. In all adenomas the sequence of SSTR2 corresponded to wild‐type.

CONCLUSIONS In the majority of cells derived from human somatotrophic adenomas, SRIH caused a reduction in baseline [Ca2+]i and inhibition of GRH‐induced [Ca2+]i increase, as observed in somatotrophs of other species. In addition, SRIH was found either to induce a paradoxical increase in [Ca2+]i or to have no effect on [Ca2+]i in a small proportion of somatotroph adenomas examined. This finding corroborates the clinical observation that the response to SRIH analogues varies markedly between somatotroph adenoma patients. There was no evidence of SSTR2 mutations in any of the adenomas examined.
Changes in dimeric inhibin A and B during normal early puberty in boys and girls
Authors: Crofton P. M. , Illingworth P. J. , Groome N. P. , Stirling H. F. , Swanston I. , Gow S. , Wu F. C. W. , McNeilly A. , Kelnar C. J. H.
Published: November 2003

OBJECTIVE Although recently developed specific and sensitive assays of bioactive dimeric inhibin A and B have given new insights into the pituitary‐gonadal axis in adult men and during the adult female menstrual cycle, there have been no reports on circulating inhibin A and B during normal human puberty. The aim of this study was to assess the relationship of dimeric inhibin A and B to pubertal stage, FSH and testosterone or oestradiol in late prepuberty and in early puberty.

STUDY DESIGN AND SUBJECTS Serial samples were collected during a prospective longitudinal trial of GH treatment in short normal children. Seven boys were studied from late prepuberty to genital stage 3, and six pre‐menarche girls from late prepuberty to breast stage 4.

MEASUREMENTS Dimeric inhibin A (girls only) and inhibin B (boys and girls) were measured by highly specific and sensitive two‐site ELISAs, FSH by IRMA, testosterone and oestradiol by RIA.

RESULTS In boys, inhibin B increased progressively from pubertal stages 1 to 3 (ANOVA P<0.0001) and correlated strongly with mean testicular volume (r=0.72, P=0.0005). Prepubertal boys showed a positive correlation between inhibin B and FSH (r=0.65, P=0.056), whereas pubertal boys gave a strong negative correlation (r=0.75, P=0.012). In both prepubertal and pubertal boys positive correlations were observed between inhibin B (y) and testosterone (x) (r=0.81, P=0.008 and r=0.62, P=0.054 respectively), but the slope of the regression line between the two was much steeper before than after the onset of clinical puberty. In girls, both inhibin A and B increased through pubertal stages 1–4 (ANOVA P=0.01 and P=0.047 respectively). Both showed strong positive correlations with oestradiol (r=0.80 and 0.79, P=0.001) and with FSH (r=0.83, P=0.0004 and r=0.80, P=0.001). Inhibin A and B were also strongly correlated with each other (r=0.92, P=0.0001).

CONCLUSIONS In boys, testicular production of inhibin B increases as puberty progresses. Our results show for the first time that the initiation of puberty is accompanied by a dramatic switch from a positive to a negative relation between inhibin B and FSH as inhibin B begins to exert the expected negative feedback on FSH. The results in girls suggest that, prior to menarche, the ovarian follicles produce inhibin A and B in strict proportion, and in progressively greater amounts as puberty proceeds. Measurement of dimeric inhibin A and B may provide a sensitive new tool for determining gonadal maturity in late prepuberty and early puberty.
Influence of exercise training on heart rate variability in post‐menopausal women with elevated arterial blood pressure
Authors: Davy K. P. , Willis W. L. , Seals D. R.
Published: November 2003

Low heart rate variability (HRV) has been reported to be an independent risk factor for the development of coronary heart disease in women and has recently been identified as a risk factor for cardiac sudden death and all‐cause mortality. We have recently demonstrated that endurance‐trained post‐menopausal women demonstrate higher levels of HRV than sedentary control subjects. The purpose of the present study was to test the hypothesis that 12 weeks of regular aerobic exercise would increase HRV in sedentary post‐menopausal women with elevated arterial blood pressure (BP) (i.e. either high normal BP or stage I hypertension). A secondary aim was to test the hypothesis that the increase in HRV with exercise training, if observed, would be associated with an increase in spontaneous cardiac baroreflex sensitivity (SBRS), an important physiological determinant of HRV. To accomplish these aims, we studied eight sedentary post‐menopausal women (age=54·5±1·3 years) before and after 12 weeks of aerobic exercise training (3·3±0·3 days per week at 70%±2% of maximal heart rate for 43±3 min per day). Maximal oxygen uptake and body weight did not change (P>0·05) with training, but percentage fat (35·5±2·6% vs. 34·5±2·3%, P<0·05) decreased and treadmill time to exhaustion increased (9·8±0·5 vs. 11·3±0·5 min, P<0·05). Supine resting levels of heart rate, RR interval and the standard deviation of the RR interval (time domain measure of HRV) were unchanged (all P>0·05) from baseline levels after 12 weeks of aerobic training. Similarly, the high‐frequency, low‐frequency and total power of HRV (frequency domain measures) were also unchanged from baseline (all P>0·05). SBRS was also not different before and after aerobic exercise training (1062 vs. 1363 ms mmHg−1 respectively, P>0·05). In contrast, systolic and diastolic BP were reduced approximately 8 and approximately 5 mmHg with training (both P<0·05) respectively. These results indicate that 12 weeks of moderate‐intensity aerobic exercise training does not increase HRV or SBRS, despite producing a clinically significant reduction in BP at rest in post‐menopausal women with elevated BP. Considered together with our previous findings in female master endurance athletes, these findings suggest that more intense and prolonged exercise training may be required to produce increases in HRV and SBRS in sedentary post‐menopausal women.
Skin temperature changes and changes in skin blood flow monitored with laser Doppler flowmetry and imaging: a methodological study in normal humans
Authors: Bornmyr S. , Svensson H. , Lilja B. , Sundkvist G.
Published: November 2003

The aim of the present study was to elucidate the interrelation between changes in skin temperature and changes in skin blood flow, as measured by laser Doppler techniques. Therefore, 17 healthy volunteers were studied upon immersion of both feet in water of 15°C for 10 min followed by body warming for 30 min. Measure‐ments using laser Doppler flowmetry (LDF) were performed from the nailfold of the big toe, while measurements using laser Doppler imaging (LDI) were performed from the dorsum of the foot. Temperatures were recorded simultaneously from the toe tip and the dorsal foot skin. Temperatures at the toe tip were significantly lower than at the dorsal foot skin. Cooling caused decreased values in all parameters, with restitution during indirect heating. There was an exponential interrelation between LDF and temperature readings from the toe owing to very high LDF values at the end of indirect heating. On the dorsum of the foot, relative changes in LDI and temperature showed a linear relationship (rs=0·65), although LDI values were consistently higher than tem‐peratures. It is concluded that temperature readings constitute an ambiguous measure of skin blood flow. On the toe tip, blood flow through opened arteriovenous shunts during indirect heating does not correlate with temperature. Cooling of the foot decreases skin temperature, mainly by heat conduction, whereas skin blood flow is only slightly reduced.
Cerebral and circulatory haemodynamics before vasovagal syncope induced by orthostatic stress
Authors: Collier W. N. J. M. , Binkhorst R. A. , Hopman M T. E. , Oeseburg B.
Published: November 2003

Vasovagal syncope is usually described as a sudden and transient loss of consciousness that resolves spontaneously. Cardiocirculatory changes are well described during and before syncope. However, changes in the cerebral oxygenation are not well defined. In this study, near‐infrared spectroscopy (NIRS) was used to assess the cerebral oxygenation directly during 80° head‐up (HU) tilt. To simulate central hypovolaemia, 500 ml of blood was drawn from each of 10 healthy subjects. Oxygenation index (OI) was defined as the difference between oxy‐ and deoxyhaemoglobin concentration. Blood pressure, heart rate and cardiac output were monitored using a finger plethysmographic device. The protocol was divided into two stages, each consisting of a 15‐min stabilization period in the supine (SUP) position, 15 min in HU position and another 10 min in SUP position. Between both stages, blood was drawn from the subject. Haemoglobin concentration and haematocrit were measured before and 30 min after withdrawal of blood. No compensatory haemodilution was observed. During HU position in the second stage, six subjects showed signs of presyncope (F) and four did not (NF). A significant difference between F and NF was found in the observation that, before fainting, the OI of F showed a steady and significant (P=0·02) decrease (−1·460·5 μM min−1) compared with NF (−0·18±0·16 μM min−1). This indicates that the onset of (pre)syncope is preceded by a mismatch between oxygen demand and oxygen supply in the cerebrum. Using NIRS enabled us to monitor this mismatch and to predict the onset of a syncope before clear signs in cardiocirculatory variables were visible.
Effects of compression bandaging on leg pulsatile blood flow
Authors: Mayrovitz H. N. , Larsen P. B.
Published: November 2003

Leg external compression bandaging is the mainstay of venous ulcer treat‐ment, yet little is known about the impact of therapeutic compression levels on arterial haemodynamics. In this study, the effect of foot‐to‐knee, four‐layer compression bandaging on below‐knee arterial pulsatile blood flow was assessed by nuclear magnetic resonance flowmetry. In 14 healthy supine subjects, bilateral flow measurements at five below‐knee sites without compression, and after compressing one leg to an average malleolar sub‐bandage pressure of 40·7±4·0 mmHg, revealed a potentially important new phenomenon. The forefoot‐to‐knee compression bandaging caused a highly significant (P<0·001) increase in the bandaged leg pulsatile blood flow owing to increases in both peak flow and pulse width. It is hypothesized that arteriolar vasodilatation, induced either myogenically by reduced transmural pressure or by vasodilatory substance release triggered by increased venous shear stress, produce the observed compression‐related phenomenon. Whatever the mechanism(s), the finding of a compression‐associated pulsatile flow increase suggests a previously undiscovered arterial linkage, which may play a role in the well‐documented beneficial effects of compression bandaging in venous ulcer treatment. A possible impact of the arterial flow–pulse increase is speculated to effect venous ulcer outcome via a decrease in leucocyte effects in the distal microvasculature, as a consequence of the more vigorous haemodynamic state.
Exercise increases insulin clearance in healthy man and insulin‐dependent diabetes mellitus patients
Authors: Tuominen J. A. , Ebeling P. , Koivisto V. A.
Published: November 2003

Exercise is known to decrease insulin secretion, but the effect on insulin clearance is unclear. We examined the effect of exercise on insulin clearance with euglycaemic insulin clamp in 28 healthy men either 12 h after a marathon run (n=14) or 44 h after a 2‐h treadmill exercise (n=14), and in seven insulin‐dependent diabetes mellitus (IDDM) patients 12 h after a marathon run, and after a resting, control day. During the post‐exercise insulin infusion, steady‐state plasma insulin concentration was reduced by 9% in healthy men after both types of exercise, and by 16% in the diabetic subjects compared with the control study (P<0·05 in all). In healthy men, C‐peptide concentrations were more than one‐third lower during insulin infusion, both after the marathon run (P<0·001) or treadmill exercise (P<0·02) compared with the control study. Insulin clearance was significantly increased by exercise both in healthy men (9%, P<0·05) and in IDDM subjects (15%, P<0·05). After exercise, endogenous insulin secretion in healthy men is reduced and insulin clearance is enhanced both in healthy men and in IDDM patients. Decreased insulin availability may allow enhanced muscle lipid utilization and spare glucose after long‐term exercise.
Physiological characteristics and hormonal profile of young normotensive men with exaggerated blood pressure response to exercise
Authors: Nazar K. , Kaciuba‐Uscilko H. , Ziemba W. , Krysztofiak H. , Wójcik‐Ziólkowska E. , Niewiadomski W. , Chwalbinska‐Moneta J. , Bicz B. , Stupnicka E. , Okinczyc A.
Published: November 2003

Exaggerated blood pressure (BP) response to exercise in normotensive subjects is considered as a predictor of future hypertension. The aim of the study was to find out whether elevated BP response to exercise is associated with any other haemody‐namic, metabolic or hormonal abnormalities. Abnormal BP response to exercise, i.e. systolic BP (SBP)>200 mmHg at 150 W or lower workload, was found in 37 out of 180 normotensive, male students, aged 20–24 years. Fifteen students with elevated exercise BP (group E) volunteered for further examinations. Their resting and ambulatory BP showed high normal values. Eight of them had a family history of hypertension. Four subjects met the criteria of cardiac hypertrophy. Significant correlations were found between exercise SBP and left ventricular mass index, average 24 h and daytime SBP recordings. In comparison with normal subjects of the same age (group N, n=13), those from group E did not differ in body mass index, plasma lipid profile, fasting glucose, insulin and catecholamine (CA) concentrations, but had increased erythrocyte sodium content, slightly elevated plasma renin activity and cortisol level. During exercise, E subjects showed greater cardiac output (CO) increases with normal heart rate, total peripheral resistance (TPR) and plasma CA. There were no significant differences between groups in haemodynamic and plasma CA responses to posture change from supine to standing. Glucose ingestion (75 g) caused smaller increases in CO and smaller decreases in TPR in E than in N subjects without differences in BP, blood glucose, plasma insulin and CA. It is concluded that young normotensive men with exaggerated BP response to exercise show some other characteristics that may be considered as markers of predisposition to hypertension or factors promoting the development of hypertension.
Haemodynamic changes during vasodepressor syncope in children and autonomic function
Authors: Tanaka H. , Yamaguchi H. , Tamai H. , Mino M. , Konishi K. , Thulesius O.
Published: November 2003

We investigated postural haemodynamic changes in 24 boys and 30 girls, aged 8–16 years, with orthostatic intolerance. During the orthostatic test, nine boys and seven girls (30%) developed a vasodepressor attack (orthostatic‐positive group). The orthostatic‐positive group had a more marked increase in heart rate (HR) with slightly lower systolic blood pressure than the orthostatic‐negative group during standing, with no significant difference in cardiac output (CO). The shift of blood volume from the intrathoracic region to the lower part of the body determined by electrical impedance and plasma catecholamines on rising were identical in the two groups. At the onset of the vasodepressor attack, CO did not change significantly, indicating that sudden arterial vasodilatation was the cause. In a pharmacological study on autonomic function, higher sensitivity of α‐adrenoceptor in the resistance vessels was found in the orthostatic‐positive group, but there was no significant difference in the basal level of cardiac vagal and sympathetic activity and in cardiac β‐adrenoceptor sensitivity between the two groups. The stepwise regression analysis showed that the magnitude of HR increment during standing was the most useful indicator in predicting the occurrence of a vasodepressor attack. These results suggest that low sympathetic activity in the resistance vessels together with an exaggerated rise in HR during upright posture is strongly associated with vasovagal and vasodepressor attacks in children.
Differences in lung function and chest dimensions in school‐age girls and boys
Authors: Kivastik J. , Kingisepp P.‐H.
Published: November 2003

The present analysis was undertaken to find out whether differences in the performance of the lungs of boys and girls of the same height are explicable by differences in thoracic size. We measured forced vital capacity (FVC), peak expiratory flow (PEF) and forced expiratory flows (FEFs), when 50% and 75% of FVC had been exhaled (FEF50, FEF75), and standing height, chest width and depth and biacromial diameter in 1187 schoolchildren aged 6–18 years. Thoracic dimensions were usually greater in boys than in girls of the same height, except for the height range of 150·0–164·9 cm. For this height range, the pulmonary function variables (PEF, FEF50, FEF75 and PEF/FVC) were significantly higher in girls, and for FVC almost as high as the male values. For FEF50/FVC and FEF75/FVC, the female values were larger over the whole height range (115·0–184·9 cm), but even for these parameters the differences were greatest for the height range 150·0–164·9 cm. In conclusion, very similar growth patterns of lung function and thoracic parameters can suggest that differences in the lung function parameters of boys and girls of the same height may be explained by differences in the thorax size.
Artery blood pressure oscillation after active standing up: an indicator of sympathetic function in diabetic patients
Authors: Lindqvist A. , Toffvit O. , Rittner R. , Agardh C.‐D. , Pahlm O.
Published: November 2003

Dynamic artery blood pressure (Finapres) response to active standing up, normally consisting of initial rise, fall and recovery above the baseline (overshoot), was compared with the early steady‐state artery blood pressure level to measure sympathetic vasomotor function in healthy subjects (n=23, age 35±9 years; mean±SD) and in type I diabetic patients without autonomic neuropathy (AN) (group 1: n=18, 38±13 years), with AN but no cardiovascular drugs (group 2a: n=7, 44±11 years) and with both AN and cardiovascular drugs (group 2b: n=10, 47±7 years). Systolic and diastolic overshoot were similar in the control (15±13/15±11 mmHg) and group 1 subjects. Systolic overshoot disappeared in 57% of patients in group 2a (−1±9 mmHg; P<0·03), whereas artery blood pressure still overshot in diastole (8±7 mmHg; NS). Systolic overshoot disappeared in all patients in group 2b (−22±22 mmHg; P<0·0006) and diastolic overshoot disappeared in 60% of these patients (−6±16 mmHg; P=0·0006). Systolic early steady‐state level was not lower in group 2a than in group 1 (NS), but it was impaired in group 2b (P<0·006), in which six diabetic patients had a pathological response beyond the age‐related reference values. There was a strong association between the overshoot and steady‐state levels (P for χ2<0·001, n=58). Overshoot of the control subjects and patients in group 2b correlated to their respective steady‐state blood pressure levels (r≥0·76; P≤0·001). In conclusion, baroreceptor reflex‐dependent over‐shoot of the artery blood pressure after active standing up diminishes with the development of AN and it is associated with the early steady‐state level of the artery blood pressure.
Pulmonary clearance of [99mTc]DTPA and [99mTc]albumin in smokers
Authors: Nilsson K. , Evander E. , Wollmer P.
Published: November 2003

We measured the pulmonary clearance of [99mTc]DTPA and [99mTc]albumin for 3 h in 10 non‐smokers and 10 healthy smokers. Seven of the non‐smokers had a monoexponential clearance of [99mTc]DTPA with a mean half‐life of 66±18 min. The other three had a biexponential clearance of [99mTc]DTPA with a fraction of radioactivity clearing rapidly (fF) of 14±4%. Eight smokers had biexponential clearance of [99mTc]DTPA. The half‐life of the fast and slow clearance components was 1265 and 62611 min respectively. The fF was 56±25%. Two of the smokers showed a monoexponential clearance of [99mTc]DTPA with a half‐life of 72 and 55 min. All non‐smokers had monoexponential clearance curves for [99mTc]albumin, compared with seven smokers. The half‐life was 279±43 min in non‐smokers and 236±64 min in smokers. The difference in half‐life was not significant. In three smokers, the clearance curves of [99mTc]albumin were significantly better described by a bi‐exponential equation. The fF was 22±9%. The effects of smoking on the clearance of [99mTc]albumin appear to be qualitatively similar to those on the clearance of [99mTc]DTPA. Clearance of [99mTc]albumin seems less sensitive to the effects of smoking than clearance of [99mTc]DTPA.
The non‐invasive acetylene rebreathing method for estimation of cardiac output: influence of breath‐by‐breath variation
Authors: Hansen S. , Wendelboe O. , Christensen P.
Published: November 2003

The inert gas rebreathing method enables non‐invasive estimation of pulmonary capillary blood flow, lung tissue volume, transfer factor and functional residual capacity. In the present study, we have examined the influence of breathing pattern during the rebreathing manoeuvre on the precision of the rebreathing method, both theoretically and experimentally. We examined whether the precision of the method could be improved by the guidance and training of the subjects doing the rebreathing manoeuvre. The results of the theoretical study showed that the precision and accuracy of the rebreathing method are practically insensitive to random variation in the breathing pattern. Simulated breath‐by‐breath variations up to ±50% of the average 3·0 l VT resulted in coefficients of variation of about 3% for QC and about 5% for VTC. Simulated breath‐by‐breath variations indicate that with mean tidal volume or rebreathing bag volume lower than 1·0 l the precision will worsen, and with tidal volume lower than 1·5 l the accuracy will worsen. The experimental results showed no significant improvement in the precision of the rebreathing method by visual guiding and training of the subjects to optimize the breathing pattern during the rebreathing manoeuvre.
Haematocrit, plasma volume and noradrenaline in humans during simulated weightlessness for 42 days
Authors: Johansen L. B. , Gharib C. , Allevard A.‐M. , Sigaudo D. , Christensen N. J. , Drummer C. , Norsk P.
Published: November 2003

Previous results from our laboratory demonstrate that changes in haematocrit (Hct) and haemoglobin concentration (Hb) underestimate the relative (%) change in plasma volume (PV) in seated subjects during simulation of weightlessness by water immersion. Therefore, we examined whether changes in Hct and Hb would accurately reflect the changes in PV in seven subjects during simulation of weightlessness by another model, 6° head‐down tilted bed rest (HDBR), for 42 days. Since we have previously observed unexpectedly high plasma levels of noradrenaline (NA) in astronauts during space flight, we also took the opportunity to measure this variable. The measurements were compared with those of the supine horizontal position before and after HDBR. During HDBR, PV measured by the Evans blue dye dilution technique decreased by 6·1±2·8% (P<0·05) on day 2 and 9·6±2·2% (P<0·05) on the 42nd day compared with that of the supine, horizontal position. Based on changes in Hct and Hb, PV decreased similarly by 8·3±2·8 and 10·2±3·2% (P<0·05) respectively. There were no differences comparing the results of the two methods (P>0·05). Forearm venous plasma NA was unchanged during the whole course of HDBR compared with that of the pre‐HDBR supine position. It is concluded that changes in Hct and Hb reliably reflect the changes in PV comparing prolonged HDBR with the pre‐ and post‐HDBR horizontal, supine position. Thus, changes in Hct and Hb might accurately reflect the change in PV during weightlessness in humans provided that the horizontal supine position is used as the ground‐based reference. Furthermore, the results of this study, as well as of previous studies from space, confirm that NA release is unchanged or even increased during weightlessness.
Effects of swim training on body weight, carbohydrate metabolism,lipid and lipoprotein profile
Authors: Tanaka H. , Bassett, Jr. D. R. , Howley E. T.
Published: November 2003

The beneficial effects of regularexercise are primarily based on data using land‐based exercise. Currently, no data exist thatdemonstrate the efficacy of swimming exercise for the treatment of obesity and cardiovascularrisk factors, despite the fact that swimming is a widely recommended exercise mode. Eighteenpreviously sedentary obese individuals were divided into a swim‐training group and a non‐exercising control group. The training group swam at 60% of maximal heart rate reservefor 45 min per day for 3 days per week for 10 weeks, whereas the control group remainedsedentary. The swim‐training programme produced significant cardiovascular training effects,as evidenced by reductions (P<0·05) in resting and submaximal heartrate values in the training group. Significant reductions (P<0·05) werealso observed in the rating of perceived exertion and blood lactate concentrations during fixedsubmaximal exercise on an arm cycle ergometer. Caloric and macronutrient intake estimatedfrom the dietary records stayed constant before and after training. Body mass, body fatpercentage (36±2% vs. 35±2%) and body mass index, as well asregional adiposity, showed no statistically significant changes. Neither the training nor thecontrol groups experienced significant changes in fasting serum glucose and insulinconcentrations and glucose–insulin ratio during the study. Total, high‐densitylipoprotein (HDL)‐ and low‐density lipoprotein (LDL)‐cholesterol did not change significantlyin either group. It was concluded that swim training of the duration, frequency and intensityused in the present study failed to elicit favourable modifications in these traditionalcardiovascular risk factors.
Cardiac secretion of atrial and brain natriuretic peptides in acuteischaemic heart failure in pigs: effect of angiotensin II receptor antagonism
Authors: Klinge P. , Djøseland O. , Karlberg B. E. , Hall C.
Published: November 2003

In amodel of acute ischaemic left ventricular failure in pigs, we compared the plasma levels andcardiac secretion of the three atrial peptides, atrial natriuretic factor (ANF), N‐terminalproatrial natriuretic factor (N‐terminal proANF) and brain natriuretic peptide (BNP). Acuteischaemic left ventricular failure was induced by embolization of the left coronary artery withplastic microspheres. Thereafter, treatment was given by an intravenous injection of theangiotensin II receptor (AT1) antagonist losartan. Effects of failure induction and treatmentwere documented by measurement of haemodynamic parameters and plasma concentrations ofcatecholamines, plasma renin activity, angiotensin II and aldosterone. Acute left ventricularfailure was accompanied by significant increases in cardiac secretion and plasma levels of allthree atrial peptides, which was considerably more pronounced for ANF and N‐terminalproANF than for BNP. Treatment with losartan resulted in significant decreases in plasma ANFand N‐terminal proANF, whereas BNP did not change. These findings indicate that ANF andN‐terminal proANF may be better suited than BNP as markers of cardiac preload during thedevelopment and treatment of acute heart failure.
How well does journal impact work in the assessment of papers onclinical physiology and nuclear medicine?
Authors: Hansen H. B. , Henrikson J. H.
Published: November 2003

This study reports a citation analysis of 217scientific papers on clinical physiology and nuclear medicine published in 69 different journalsduring the years 1985–92. The actual citation frequency was compared with the journal‘impact factor’ (i.e. the average number of times a paper is cited in a particularjournal in the year of publication and the subsequent year). The average impact factor per paperwas 1·96 and per journal 1·92 (range 0·0–22·8). Adirect relation was found between the journal impact factor and the citation factor (i.e. theactual citations in the year of publication and the subsequent year) (journals with five or morepapers R=0·69, P<0·01; all journals R=0·40, P<0·001). However, the citation factor wassignificantly below the journal impact factor (P<0·0001). An almostlinear relation was found between cumulated citations and time (R=0·99, P<0·02–0·0001), but an initial phase of nocitation was identified, and the number of citations per year reached a maximum or plateau3–7 years after publication, which was later than the general maximum of 2–3years for all medical specialities. In a sample of 200 known autocitations, 75% of thepapers had full recovery, 3% mixed recovery and 22% no recovery, giving anoverall recovery of 70%. In conclusion, although a phase of no citation was identified,which gave a lower citation factor than the journal impact factor, the citation frequencyincreased over time, and altogether there seems to be a good agreement between journalimpact factor and overall citation frequency of papers on clinical physiology and nuclearmedicine.
Effects of strength and endurance training on muscle fibrecharacteristics in elderly women
Authors: Sipilä S. , Elorinne M. , Alen M. , Suominen H. , Kovanen V.
Published: November 2003

The effects of 18weeks’ intensive strength and endurance training on fibre characteristics of the vastuslateralis muscle were studied in 76‐ to 78‐year‐old women. Type I and type IIa fibresconstituted over 90% of the cell population and were almost equally represented. Nochanges were observed in the proportions of the different fibre types. When comparing thebaseline and the 18‐week measurements within the groups, the strength group showed a meanincrease of 34% (P=0·028) in mean type I fibre area. Thefrequency histograms showed an increased proportion of larger type I fibres after strengthtraining and a decreased proportion of smaller type IIa fibres after endurance training. In thecontrol subjects, the proportion of smaller type I and type IIa fibres increased during theexperimental period. The results indicate that intensive strength training induces type I fibrehypertrophy, whereas the effects of endurance training are less evident. The considerablevariation found in the change in muscle fibre cross‐sectional areas is also noteworthy.
Ventilatory response to CO2 in patients with snoring, obstructivehypopnoea and obstructive apnoea
Authors: Appelberg J. , Sundström G.
Published: November 2003

Obstructive sleep apnoea (OSA) is caused by an obstruction of the upper airway. Sufficientsensitivity to CO2 in the respiratory centre is known to be a critical factor for adequatetone in the upper airway muscles. The hypothesis of this study is, therefore, that the ventilatoryresponse to CO2 is reduced in patients with OSA. Twenty‐six patients who sufferedfrom snoring, 19 snoring patients with obstructive hypopnoea (OH) and 33 snoring patients withobstructive apnoea (OA), were studied. The control group consisted of 25 subjects from a randomsample with no history of snoring or daytime sleepiness. Tests of the hyperoxic and hypoxicventilatory response to CO2 were performed, as well as static and dynamic spirometry.Subjects in the OA group displayed a higher hyperoxic (EE/FetCO2hy=12·6 l min−1/%) and hypoxic (EE/FetCO2ho=15·7 l min−1/%) ventilatory responseto CO2 than patients with obstructive hypopnoea(EE/FetCO2hy=8middot;6 l min−1/%; EE/FetCO2ho=15·2 l min−1/%), snorers(EE/FetCO2hy=8·4 l min−1/%;EE/FetCO2ho=12·7 l min−1/%) and non‐snorers(EE /FetCO2hy=7·6 l min−1/%;EE/FetCOho=9·6 l min−1/%). Multiple regression analysis revealsthat neck circumference, apnoea index, oxygen desaturation index, PCO2 and sex (male gender) are correlated with EE/FetCO2hy (R2=0·43).Multiple regression analysis also reveals that ERV (expiratory reserve volume) and sex (malegender) are correlated with EE/FetCO2ho ((R2=0·21). Arguing against thehypothesis, patients with OSA displayed an increased hyperoxic and hypoxic ventilatory responseto CO2 . Nocturnal apnoea frequency and the obesity factor in OSA may havecontributed to these results.
The effect of flumazenil on subclinical psychometric orneurophysiological alterations in cirrhotic patients: a double‐blind placebo‐controlled study
Authors: Amodio P. , Marchetti P. , Del Piccolo F. , Beghi A. , Comacchio F. , Carraro P. , Campo G. , Baruzzo L. , Marchiori C. , Gatta A.
Published: November 2003

It is not yet clear if benzodiazepine receptor ligands,implicated in the pathophysiology of hepatic coma, also have a role in subclinical cognitive orneurophysiological alterations in cirrhotic patients. Therefore, we carried out a double‐blind,placebo‐controlled study to evaluate the effectiveness of flumazenil, a benzodiazepine antagonist,on brainstem auditory evoked responses and on the number connection test in cirrhotic patientswith subclinical neurophysiological or cognitive alterations. Thirteen cirrhotic subjects withsubclinical neurophysiological or cognitive alterations were studied. A total of 3 mg of flumazenilor saline was infused intravenously. Before and after the infusion, the number connection test wasadministered and brainstem auditory evoked responses recorded. After 72 h, patients werecrossed over. Flumazenil did not influence brainstem auditory evoked responses or the numberconnection test. A screening test for benzodiazepines was negative in all subjects. We concludethat benzodiazepine receptor ligands have a negligible role, if any, in the pathophysiology of sub‐clinical neurophysiological or cognitive alterations of cirrhotic patients.
Effects of low‐dose transdermal scopolamine on autonomic cardiovascular control in healthy young subjects
Authors: Vesalainen R. K. , Tahvanainen K. U. O. , Kaila T. J. , Kantola I. M. , Kuusela T. A. , Eckberg D. L.
Published: November 2003

We studied how posture influences the effects of transdermal scopolamine on autonomic cardiovascular regulation in a randomized, double‐blind, placebo‐controlled crossover study of 10 healthy young volunteers. We recorded the electrocardiogram and auscultatory sphygmomanometric and continuous non‐invasive finger arterial pressure (Finapres device) to obtain signals for the beat‐by‐beat R–R interval and systolic, mean and diastolic pressures. R–R interval and arterial pressure variabilities were characterized by power spectral analysis. Scopolamine increased the mean R–R intervals and reduced arterial pressure in both the supine and the standing positions, but did not affect blood pressure variability. Scopolamine increased the total variability of R–R interval and its mid‐ (0·07–0·15 Hz) and high‐ (0·15–0·40 Hz) frequency band power in the standing position during controlled breathing at 0·25 Hz. In the supine position, scopolamine did not affect R–R interval variability. In the deep breathing test, scopolamine increased the maximal expiratory–inspiratory R–R interval ratio. This study showed that low‐dose scopolamine increases vagal cardiac inhibition in both supine and standing positions in healthy volunteers. However, scopolamine increases heart rate variability only in the standing position during partial vagal withdrawal. The study also demonstrates that transdermal scopolamine decreases blood pressure in healthy young subjects.
Histological examination of clots from cytological specimens: is this a worthwhile procedure?
Authors: ADDEY A. , RACHEL J. , CODLING B. W. , D. N. POLLER
Published: November 2003

A comparison of conventional cytology and clot histology was made on 174 serous fluids, fine needle aspirates (FNA) and other non‐gynaecological specimens. In eight cases (4.5%) this clot material contained malignant cells or cells suspicious of malignancy despite the absence of suspicious or malignant cells in conventionally prepared smears from the same specimen. In 11 cases (6.3%) the clot was negative, although conventional smears contained malignant or suspicious cells. A χ2 test showed that there was no statistically significant difference between the number of positive diagnostic scores in each group with χ2 of 0.223 (degrees of freedom=1), P=0.637. Examination of clot material from serous fluids and FNA aspirates is as effective as examination of conventional cytological preparations. Processing of clots from cytological aspirates for histological examination should be more widely adopted, and is applicable in all cytopathology laboratories.
Fine needle aspiration (FNA) cytology of pilomatrixoma
Authors: KUMAR N. , VERMA K.
Published: November 2003

FNA smears from five histologically confirmed cases of pilomatrixoma were reviewed to delineate the cytological features helpful in diagnosis. A combination of basaloid cells, ghost cells and foreign body giant cells appeared to be necessary in FNA smear for a confident cytodiagnosis of pilomatrixoma. Presence of naked nuclei, nucleated squamous cells and calcification were additional features in favour of the diagnosis. Another 10 cases with initial cytodiagnosis of pilomatrixoma or benign skin appendage tumour were reviewed. Using the above criteria, diagnosis of pilomatrixoma was easy in five cases. One case was problematical due to presence of atypical squamous cells. Initially the cytological features were most commonly confused with epidermal inclusion cyst, giant cell lesion or a squamous cell carcinoma. The main reasons for erroneous diagnosis were lack of awareness of cytological features, predominance of one component over the others, and non‐representative FNA smears. Atypia in nucleated squamous cells, and misinterpretation of basaloid cells as malignant can lead to diagnostic dilemma. Adequate clinical data are also necessary.
The Yorkshire slide exchange external quality assessment (EQA) scheme
Authors: BOON A. P. , WILLIAMSON P. , BROWN J. M. , THOMAS G. D. H.
Published: November 2003

A slide circulation scheme measuring cervical screening performance of individual cytologists in 15 laboratories in Yorkshire Regional Health Authority is described. The advantages and disadvantages are compared with the current National Proficiency Testing (NPT) scheme. The results indicate that a slide circulation scheme can be successfully used in cervical cytology external quality assessment (EQA). Levels of participation are better than those currently achieved by regional variations of the NPT scheme, and the use of laboratory consensus in the selection of scoring slides appears to be no less valid than the use of a pre‐selected slide pool assembled by an expert panel. The volume of data accumulated in one round is considerably greater than that achieved by proficiency testing and the educational value is regarded as high. However, the scheme is very time consuming for participants and consequently expensive for laboratories. The lack of external supervision increases the risk of unfair practices within individual laboratories. Because of these problems, Yorkshire has now switched to an NPT scheme.