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Biomedical subjects

W D Fraser

Publications and source records attributed to W D Fraser.

At least 37 records · Page 2Linked to original sources
PubMed2004

Gender variation in PTH sensitivity and rhythmicity following growth hormone replacement in adult growth hormone-deficient patients.

BACKGROUND: Adult GH deficiency (AGHD) is associated with osteoporosis and reduced bone turnover; factors improved by GH replacement (GHR), with men gaining greater benefit than women. Reduction in sensitivity of bone and kidney to the effects of PTH may underlie AGHD changes in bone turnover. We determined the gender difference in PTH target-organ sensitivity following GHR in AGHD patients. DESIGN, PATIENTS AND MEASUREMENTS: Twenty AGHD patients (10 men) were admitted to hospital before and after GHR initiation. Half-hourly blood samples were collected for PTH, calcium, nephrogenous cyclic AMP (NcAMP, marker of PTH activity), type-I collagen C-telopeptide (CTX, bone resorption marker) and procollagen type-I amino-terminal propeptide (PINP, bone formation marker). RESULTS: The 24-h mean PTH concentration decreased in both genders (P < 0.001), with maximal changes seen 6 and 12 months following GHR in men and women, respectively. Increases in 24-h mean NcAMP (P < 0.05), calcium (P < 0.001) and bone turnover markers (P < 0.001) occurred in both genders following GHR, with maximal changes at 1 month in men, but at 3 months for NcAMP, calcium and CTX and 12 months for PINP in women. Maximal NcAMP increase was higher in men (P = 0.009). CONCLUSIONS: Following GHR, PTH target-organ sensitivity increased in both genders, demonstrated by simultaneous reduction in PTH concentration and increase in NcAMP, calcium and bone turnover. In women, improvement in renal PTH sensitivity was delayed and reduced, and changes in bone turnover were delayed, with increase in bone resorption preceding bone formation. Both factors may contribute to the reduced bone mineral density (BMD) response to GHR observed in women.

Adult↗
PubMed2003

Mathematical study of the role of non-linear venous compliance in the cranial volume-pressure test.

The role of the cerebral venous bed in the cranial volume-pressure test was examined by means of a mathematical model. The cerebral vascular bed was represented by a single arterial compartment and two venous compartments in series. The lumped-parameter formulation for the vascular compartments was derived from a one-dimensional theory of flow in collapsible tubes. It was assumed in the model that the cranial volume is constant. The results show that most of the additional volume of cerebrospinal fluid (deltaV(CSF)) was accommodated by collapse of the cerebral venous bed. This profoundly altered the venous haemodynamics and was reflected in the cranial pressure P(CSF). The cranial volume-pressure curve obtained from the model was consistent with experimental data; the curve was flat for 0 < or = deltaV(CSF) < or = 20 ml and 35 < or = deltaV(CSF) < or = 40 ml, and steep for 20 < or = deltaV(CSF) < or = 35 ml and deltaV(CSF) > or = 40 ml. For deltaV(CSF) > 25 ml and P(CSF) > 5.3 kPa (40 mmHg), cerebral blood flow dropped. When P(CSF) was greater than the mean arterial pressure, all the veins collapsed. The conclusion of the study was that the shape of the cranial volume-pressure curve can be explained by changes in the venous bed caused by various degrees of collapse and/or distension.

Cerebral Veins↗
PubMed2003

Anemia during pregnancy in a Chinese population.

OBJECTIVES: To study prevalence, risk factors, and birth outcomes of women with anemia during pregnancy in a Chinese population. METHODS: A retrospective cohort study was performed based on 16936 pregnancies delivered between January 1989 and December 1990 in Suzhou, China. Anemia was defined as hemoglobin less than 10 g/dl. Multivariate logistic regression was used to estimate odds ratio, 95% confidence interval, and to control for confounding variables. RESULTS: The prevalence of anemia was 10.3% at the first trimester, 18.9% at the third trimester. Overall, 26.2% pregnant women experienced anemia in pregnancy. Anemia during early pregnancy was not associated with increased risk of adverse perinatal outcomes. However, anemia in later pregnancy was inversely associated with preterm birth and low birth weight. CONCLUSIONS: Anemia during pregnancy does not increase the risk of poor birth outcomes.

Adult↗
PubMed2003

Parathyroid hormone secretory pattern, circulating activity, and effect on bone turnover in adult growth hormone deficiency.

Adult growth hormone deficiency (AGHD) is associated with osteoporosis. Reports have associated parathyroid hormone (PTH) circadian rhythm abnormalities with osteoporosis. Furthermore, there is evidence of relative PTH insensitivity in AGHD patients. Factors regulating PTH circadian rhythm are not fully understood. There is evidence that serum phosphate is a likely determinant of PTH rhythm. The aim of this study was to investigate PTH circadian rhythm and its circulating activity and association with bone turnover in untreated AGHD patients compared to healthy individuals. We sampled peripheral venous blood at 30-min and urine at 3-h intervals during the day over a 24-h period from 1400 h in 14 untreated AGHD patients (7 M, 7 W; mean age, 49.5 +/- 10.7 years) and 14 age (48.6 +/- 11.4 years; P = NS) and gender-matched controls. Cosinor analysis was performed to analyze rhythm parameters. Cross-correlational analysis was used to determine the relationship between variables. Serum PTH (1-84), phosphate, total calcium, urea, creatinine, albumin, type I collagen C-telopeptides (CT(x)), a bone resorption marker, and procollagen type I amino-terminal propeptide (PINP), a bone formation marker, were measured on all samples. Nephrogenous cyclic adenosine monophosphate (NcAMP), which reflects the renal activity of PTH, was calculated from plasma and urinary cAMP. Urinary calcium and phosphate were measured on all urine samples. Significant circadian rhythms were observed for serum PTH, phosphate, CT(x), and PINP in AGHD and healthy subjects (P < 0.001). No significant rhythm was observed for serum-adjusted calcium. PTH MESOR (rhythm-adjusted mean) was significantly higher (P < 0.05), whereas the MESOR values for phosphate, CT(x) (P < 0.05), and PINP (P < 0.001) were lower in AGHD patients than in controls. AGHD patients had significantly lower 24-h NcAMP (P < 0.001) and higher urinary calcium excretion (P < 0.05). Maximum cross-correlation between PTH and phosphate (r = 0.75) was observed when PTH was lagged by 1.5 h in healthy individuals, suggesting that changes in phosphate precede changes in PTH concentration. PTH/CT(x) and PTH/PINP showed maximum correlation when CT(x) (r = 0.68) and PINP (r = 0.71) were lagged by 3 h. In AGHD patients, compared to controls the maximum correlation between PTH/phosphate (r = 0.88, P = 0.007), PTH/CTx (r = 0.61, P = 0.027), and PTH/PINP (r = 0.65, P = 0.028) was observed when the lag time was reduced by 1.5 h in all variables, with changes in PTH and phosphate occurring at concurrent time points. Our data suggest decreased end-organ sensitivity to the effects of PTH in AGHD patients, resulting in a significantly lower NcAMP, low bone turnover, and higher calcium excretion in the presence of significantly higher PTH concentrations. We have also demonstrated that changes in serum phosphate precede those of PTH, which in turn precede changes in bone resorption and formation in healthy individuals. This relationship was altered in AGHD patients. These results suggest a possible role for GH in regulating PTH secretion and the bone remodeling process.

Adult↗
PubMed2003

Gender variation in leptin circadian rhythm and pulsatility in adult growth hormone deficiency: effects of growth hormone replacement.

OBJECTIVES: Adult growth hormone deficiency (AGHD) is characterized by obesity and associated with increased leptin concentration and decreased leptin pulsatility. Growth hormone replacement (GHR) results in a decrease in leptin concentration and increase in leptin pulsatility, followed by reduction in body fat mass (BFM). In both health and AGHD, women exhibit relatively higher leptin concentrations compared to men. The effect of gender on leptin rhythm and pulse parameters in AGHD is yet to be defined and the gender difference in the response of leptin secretory pattern to GHR has not been determined. Therefore the aim of this study was to evaluate the effect of gender on circadian and pulse parameters of leptin secretion in AGHD, and examine the gender variation in response of these parameters to GHR. STUDY DESIGN: A prospective, open treatment design study to determine the effect of gender on leptin rhythm and pulse parameters in untreated and treated AGHD. GH was commenced at a daily dose of 0.5 IU, and titrated up by increments of 0.25 IU at 2-weekly intervals to achieve and maintain IGF-I SDs between the median and upper end of the age-related reference range. PATIENTS: Twelve patients (six men, six women) with severe AGHD following pituitary surgery, defined as peak GH response < 9 mU/l to provocative testing were studied. All patients required additional pituitary replacement hormones following pituitary surgery and were on optimal doses at recruitment. MEASUREMENTS: Plasma leptin was measured at half-hourly intervals for 24 h, before and 1 month after initiation of GHR. Cosinor analysis was used to determine the circadian rhythm parameters: MESOR (rhythm-adjusted mean), acrophase and amplitude; and ULTRA algorithm used for pulse analysis. Body composition was measured using bioelectrical impedance. RESULTS: BFM was higher in women than men at both visits (P < 0.05), but there was no significant change in BFM in either gender following 1 month of GHR. Women had a higher mean 24-h leptin concentration, MESOR, circadian amplitude and pulse amplitude, both before and after GHR (P < 0.05). Following treatment, mean leptin concentration and MESOR decreased significantly in both men and women (P < 0.05), with no significant difference in percentage change between the genders. Pulse frequency increased and duration decreased significantly after GHR in both groups, without any significant gender difference. IGF-I and IGF SDs were similar in both genders at baseline (P = 0.93). However, after 1 month GHR, the increase in both measurements was greater in men than women (P = 0.005) and men had significantly higher IGF-I and IGF SDs than women (P = 0.01). CONCLUSIONS: As in healthy individuals, leptin levels were higher in women with AGHD than men, both prior to and after GHR. Decline in leptin concentrations and increase in leptin pulsatility following 1 month of GH treatment were similar in both genders. Changes in leptin secretory parameters appeared to occur without any significant decrease in BFM, suggesting a regulatory role for GH. Additionally, the action of GH on leptin secretory pattern does not appear to be mediated by IGF-I. Our data suggest that changes in leptin concentration and rhythm parameters following GHR are independent of gender.

Adult↗
PubMed2003

Effect of pregnancy on bone mineral density and biochemical markers of bone turnover in a patient with juvenile idiopathic osteoporosis.

Juvenile idiopathic osteoporosis (JIO) is rare, presenting with vertebral fractures in the immediate prepubertal years; however, recovery is normally observed. We report the case of a 19-year-old pregnant woman previously diagnosed with JIO. She experienced three vertebral fractures in the third trimester of pregnancy. She delivered by caesarean section at 38 weeks gestation. Spinal bone mineral density decreased by 25%, hip bone mineral density by 10%, and forearm bone mineral density by 3% during pregnancy. Bone resorption markers, free pyridinoline and deoxypyridinoline (fPYD and fDPD), were elevated at baseline and markedly increased during pregnancy (fPYD/fDPD at 0, 10, 15, 20, and 28 weeks and immediately postpartum: 36.2/11.5, 52.9/15.8, 54.3/13.3, 51.1/13.3, 90/21.8, and 95.6/22.7 nmol/mmol creatinine, respectively) The bone formation marker, bone-specific alkaline phosphatase (BSAP), was within the reference range at baseline and increased in the third trimester. (BSAP at 0, 10, 15, 20, and 28 weeks and immediately postpartum: 20.5, 18.3, 17.7, 19.8, 26.9, and 30.0 U/liter, respectively). Parathyroid hormone (PTH) was measured by two methods to assess the possible effect of PTH fragments. PTH(1-84) (Roche) showed little change during the pregnancy, whereas the Nichols assay [(1-84) and(7-84) PTH fragment], revealed increases paralleling the changes in bone resorption. This young woman's bone turnover showed an exaggerated response to pregnancy, with bone resorption predominating over formation. PTH fragments may have partially mediated this effect.

Adult↗
PubMed2002

The management of primary hyperparathyroidism.

Recent improvements in parathyroid imaging have led to renewed interest in the criteria for, and the surgical approach to, parathyroidectomy. It therefore seemed appropriate to review current evidence relating to the evaluation and management of primary hyperparathyroidism for those working within a general endocrine service. The recommendations are based on an electronic search spanning the past decade using the search terms hyperparathyroidism, management and parathyroidectomy/surgery, but we have also included key publications outside this period. The findings have been graded systematically (Appendix), according to the quality of the information available, to indicate the level of evidence on which they are based.

Bone Density↗
PubMed2002

Myositis in children with meningococcal disease: a role for tumour necrosis factor-alpha and interleukin-8?

OBJECTIVES: Myalgia is under-recognized in meningococcal disease (MCD). In septic shock, myositis is thought to be mediated by pro-inflammatory cytokines such as tumour necrosis factor-alpha (TNF-alpha), interleukin-8 (IL-8) and interleukin-6 (IL-6) but this has never previously been studied in MCD. We aimed to demonstrate whether muscle damage mediated via TNF-alpha and other pro-inflammatory cytokines occurs in MCD, as estimated by creatine kinase skeletal muscle isoenzyme (CK-MM) and cardiac isoenzyme (CK-MB) concentrations. METHODS: A total of 68 children, median age 2.7 years, with a diagnosis of MCD were prospectively studied. Severity of disease was measured using the Glasgow Meningococcal Septicaemia Prognostic Score (GMSPS). Severe disease was defined as a GMSPS of > or =8. TNF-alpha, IL-8, IL-6 and IL-1Ra concentrations were determined on samples taken on admission. RESULTS: CK-MM correlated significantly with TNF-alpha, IL-8 and GMSPS. There was no significant correlation between CK-MB and TNF-alpha or IL-6, but CK-MB correlated with GMSPS and IL-8. Fifty-six percent of children with MCD had evidence of muscle damage as manifested by elevated CK-MM. CONCLUSIONS: TNF-alpha and IL-8 may be potential mediators in the pathophysiology of skeletal muscle damage in MCD.

Adolescent↗
PubMed2002

Presentation of a PTHrP-secreting pancreatic neuroendocrine tumour, with hypercalcaemic crisis, pre-eclampsia, and renal failure.

Severe hypercalcaemia during pregnancy is rare and most cases are secondary to hyperparathyroidism. This is the first report of a parathyroid hormone related protein (PTHrP) secreting neuroendocrine tumour of the pancreas manifesting with severe hypercalcaemia during pregnancy. Measurement of PTHrP was useful in both the diagnosis and follow up of our patient and should be considered in the diagnostic workup of patients with unexplained hypercalcaemia. A raised PTHrP concentration is a strong indicator of malignancy.

Acute Kidney Injury↗
PubMed2002

Comparison of the humoral markers of bone turnover and bone mineral density in patients on haemodialysis and continuous ambulatory peritoneal dialysis.

Renal osteodystrophy is an important complication in patients with end-stage renal disease on maintenance dialysis. The aim of this study was to compare the biochemical markers of bone formation (serum collagen type I C-terminal propeptide) and resorption (serum deoxypyridinoline - DPD - and pyridinoline - PYR) with the bone mineral density (BMD) at lumbar spine, femoral neck, and forearm in patients with end-stage renal disease on haemodialysis (HD) versus continuous ambulatory peritoneal dialysis (CAPD). Fifty-nine adult patients, 45 on CAPD (18 females, 27 males) and 14 on HD (2 females, 12 males), were studied. The mean age was 44 +/- SEM 1.6 and 54.4 +/- 4.8 years, respectively. No significant differences in serum calcium, phosphorus, creatinine, and parathyroid hormone were found between patients on HD and CAPD in predialysis samples. Serum urea was significantly lower (p = 0.02) in the CAPD group. Serum PYR (nmol/l) and DPD (nmol/l) were significantly higher in patients on HD as compared with those on CAPD: 105 +/- 23.3 versus 43.7 +/- 3.47 (p = 0.007) and 31.0 +/- 2.4 versus 24.4 +/- 1.4 (p = 0.027), respectively. The results were still significantly higher in the HD patients following correction for serum creatinine and body mass index. There was a close correlation between dialysate DPD and creatinine in both dialysis modalities (HD r = 0.9, CAPD r = 0.76). The clearance of DPD did not differ significantly between the CAPD membrane and the HD membrane (p = 0.22). Serum collagen type I C-terminal propeptide was not significantly different between the HD and CAPD patients. The results were unaffected following correction for age and gender. The BMD was measured in 38 (65%) of the patients (HD n = 8, CAPD n = 30) by dual-energy X-ray absorptiometry and expressed as 'Z' scores. This was reduced at all sites in the patients with end-stage renal disease. The BMD was significantly lower at the ultradistal forearm (mostly trabecular bone) in HD patients as compared with CAPD patients (n = 0.02). A similar trend was observed at the lumbar spine, although the results failed to reach significance. In the whole population (n = 38), linear regression analysis revealed a significant negative correlation between BMD at the ultradistal forearm and serum PYR (r = -0.35, p = 0.04) and DPD (r = -0.33, p = 0.049). Combined measurements of BMD and biochemical markers of bone resorption may have potential in the identification of patients at high risk of bone loss who may require further evaluation of bone remodeling by bone histomorphometry.

Adult↗
PubMed2001

Pitfalls in the use of thyrotropin concentration as a first-line thyroid-function test.

Measurement of thyrotropin concentration alone as a first-line thyroid-function test fails to indicate hypopituitarism in a number of patients. Using a combination of thyrotropin and thyroxine assays, we analysed 56,000 tests for a population of 471,000 over 12 months. 15 patients with clinically unsuspected hypopituitarism were detected, indicating that the occurrence of hypopituitarism might be underestimated.

Aged↗
PubMed2001

Recurrent cleft lip and palate in siblings of a patient with malabsorption syndrome, probably caused by hypovitaminosis a associated with folic acid and vitamin B(2) deficiencies.

We present a woman with metabolic disorders secondary to malabsorption and renal disease who gave birth to a stillborn male fetus with left unilateral cleft lip and palate and a live born infant with left unilateral cleft lip and palate. We discuss potential cofactors that could be implicated in the abnormal embryonic process.

Adult↗
PubMed2001

Body composition and quality of life in adults with growth hormone deficiency; effects of low-dose growth hormone replacement.

OBJECTIVE: Adult growth hormone deficiency (AGHD) is characterized by abnormalities in body composition and a poor perceived quality of life (QoL). Weight-based high-dose growth hormone replacement (GHR) results in improvements in body composition and QoL in AGHD. However, a high patient percentage reported side-effects on high-dose GHR resulting in a high rate of patient withdrawal from growth hormone (GH) treatment. High-dose GH therapy also leads to supraphysiological serum insulin-like growth factor-I (IGF-I) concentrations that have been associated with breast and prostate cancer, raising major concerns over the use of such high-dose GH regimen in AGHD. The aim of this study was to assess the effects of low-dose growth hormone replacement (GHR) on body composition and QoL as early as 1 and 3 months. STUDY DESIGN: A prospective, open treatment design study to determine the early effects of low-dose GH administration on body composition and QoL. GH was initiated at a daily dose of 0.4-0.5 IU, and titrated up to achieve and maintain IGF-I standard deviation score (IGF-I SDS) between the median and upper end of the age-related reference range. PATIENTS: Forty-six, post-pituitary surgery, severe AGHD patients (22 women), defined as peak GH response < 9 mU/l to provocative testing. The mean age was 50.4 years (range 26-72). Forty-three patients required additional pituitary replacement hormones following pituitary surgery and were on optimal doses at recruitment. MEASUREMENTS: Body composition and QoL were assessed prior to GHR and subsequently at 1 and 3 months after initiating GHR. Body mass index (BMI) and waist hip ratio (WHR) were calculated from measurements of height, weight, and waist and hip circumference, respectively. Bioelectrical impedance analysis (BIA) was used to determine body fat and lean body mass. QoL was assessed using the disease-specific 'QoL-assessment of growth hormone deficiency in adults (QoL-AGHDA)' questionnaire. Serum IGF-I was measured at each visit to assess the adequacy of GHR. RESULTS: IGF-I and IGF-I SDS increased significantly at 1 and 3 months (P < 0.001) after commencing GHR. The increase in IGF-I (P < 0.05) and IGF-I SDS (P < 0.01) was significant between 1 and 3 months in the absence of any significant increase in GH dose (P = ns) during this period. Eighty-five per cent of patients achieved IGF-I SDS levels between median and upper end of the age-related reference range after 3 months of GHR, and no side-effects were reported during this period. There was a significant reduction in body fat percentage (BFP) from 36.1 +/- 9.1% at baseline to 34.9 +/- 9.3% (P < 0.01) at 1 month and 34.1 +/- 9.2% (P < 0.001) at 3 months. Body fat mass (BFM) reduced from 32.8 +/- 13.6 kg at baseline to 31.9 +/- 13.9 kg at 1 month (P < 0.05) and 31.1 +/- 13.6 kg at 3 months (P < 0.001). These changes in BFP and BFM occurred in the absence of any significant change in BMI and WHR (P = ns). Lean body mass (LBM) was 55.9 +/- 11.1 kg at baseline and increased to 57.1 +/- 11.3 kg after 1 month (P < 0.01) and to 57.6 +/- 11.5 kg (P < 0.001) after 3 months of GHR. Significant improvement was observed in the perceived QoL with the AGHD assessment scores reducing from 13.3 +/- 6.4 to 11.5 +/- 6.6 within 1 month (P < 0.01) and 10.0 +/- 6.6 at 3 months (P < 0.001). There was no significant correlation between improvement in QoL and changes in body fat percentage (r = 0.01 at 1 month and r = 0.12 at 3 months, P = ns) or IGF-I levels (r = 0.04 and r = 0.003, P = ns at 1 and 3 months, respectively). The improvement in body composition and QoL was significant between 1 and 3 months. CONCLUSIONS: Low-dose GHR improves body composition and QoL as early as 1 month after commencement and the beneficial effects continue at 3 months. Most importantly, these changes occur in the absence of side-effects. We therefore suggest the use of low-dose GH therapy, maintaining IGF-I between the median and upper end of the age-related reference range, for the treatment of AGHD.

Adult↗
PubMed2001

Bone status in cystic fibrosis.

AIM: To investigate bone mineral status of children with cystic fibrosis (CF). METHODS: In 29 children with CF and 49 matched controls, bone mineral content (BMC), projected bone area (BA), and areal bone mineral density (BMD) of the whole body, total hip, and lumbar spine (L1-L4) were measured using dual energy x ray absorptiometry. The BMC values at each site were adjusted for BA, height, and weight. At the lumbar spine, the bone mineral apparent density (BMAD) was calculated by dividing the BMC by the estimated volume, derived from BA. Vertebral (T12-L3) trabecular bone mineral density (vTBMD) was measured using quantitative computed tomography in children with CF. Calcaneal broadband ultrasound attenuation (BUA) was measured in CF patients and controls using quantitative ultrasound. The disease severity of CF children was evaluated by the Shwachman-Kulczycki (SK) score. RESULTS: The mean BUA, whole body and regional BA, adjusted BMC, and areal BMD of children with CF were not different from those of controls. The mean BMAD of the lumbar spine was reduced in CF patients compared with controls, whereas the mean vTBMD standard deviation scores were significantly higher in CF patients. The median SK score of the CF group was 81 (range 42-100), indicating that as a group our CF patient population had relatively mild disease. CONCLUSION: The normal vertebral BMC, decreased BMAD, and higher vTBMD suggests that the vertebral cortical thickness or density might be reduced in CF subjects. The overall bone mineral status of CF children with relatively mild disease was not different from size matched controls.

Absorptiometry, Photon↗
PubMed2001

Analysis of the contribution of dydrogesterone to bone turnover changes in postmenopausal women commencing hormone replacement therapy.

Although gestagens have been reported to influence bone metabolism, whether these contribute to the beneficial effects of hormone replacement therapy (HRT) on the skeleton of postmenopausal women is currently unclear. To address this question, we compared changes in bone turnover markers after commencing HRT in 26 postmenopausal women randomized to receive 8 weeks of treatment with 2 mg estradiol daily or 2 mg estradiol plus 10 mg dydrogesterone daily. Serum and second morning void urine samples were obtained at baseline (twice) and after 1, 2, 4, and 8 weeks. Serum estradiol was measured by RIA, urinary total deoxypyridinoline (DPD) excretion by high pressure liquid chromatography, and serum osteocalcin and C-terminal procollagen peptide by enzyme-linked immunosorbent assay. The increase in serum estradiol after treatment with estradiol alone was slightly, but significantly, greater than that in the combination group (P = 0.04). Although estradiol suppressed urinary DPD excretion to a greater extent when given alone (P = 0.02), osteocalcin levels were significantly higher in this group than in women receiving combination therapy (P = 0.04). To assess the effect of dydrogesterone on the balance between formation and resorption in more detail, we subsequently compared the ratio between formation and resorption markers in the two treatment groups. We found that osteocalcin/DPD and C-terminal procollagen peptide/DPD ratios were significantly higher in women treated with estradiol alone (P < 0.0001 and P = 0.002, respectively), suggesting that dydrogesterone may reduce formation relative to resorption. These results suggest that gestagens may reduce estrogen's beneficial effects on the skeleton of postmenopausal women, as assessed over the first 8 weeks of replacement therapy.

Amino Acids↗
PubMed2001

Circadian and ultradian rhythm and leptin pulsatility in adult GH deficiency: effects of GH replacement.

Leptin contributes to the regulation of body weight in healthy individuals and is secreted by adipocytes in a diurnal pattern, with superimposed pulsatility. The circulating leptin concentration is increased in both normally obese and untreated adult GH deficiency, a syndrome characterized by increased adiposity. Leptin circadian rhythm is preserved in adult GH deficiency patients; however, an ultradian rhythm and pulsatility has previously not been reported. Alterations in plasma leptin concentration in obese individuals and adult GH deficiency patients after GH replacement have been attributed to changes in body fat mass. In our present study leptin circadian and ultradian rhythm, leptin pulsatility and its relationship with body fat mass were examined in 12 adult GH deficiency patients (6 men) before and 1 month after GH replacement. All subjects with adult GH deficiency had hypopituitarism subsequent to pituitary surgery and were stabilized on conventional pituitary hormone replacement. Plasma leptin was measured over 24 h at 30-min intervals, and changes in body composition were recorded using bioelectrical impedance. The 24-h mean leptin concentration decreased from 2.04 +/- 0.04 nmol/liter in untreated adult GH deficiency patients to 1.64 +/- 0.03 nmol/liter after 1 month of GH replacement (P < 0.0001). Before GH replacement, patients demonstrated a significant mean leptin circadian rhythm (P < 0.001), with a mesor of 2.05 +/- 0.03 nmol/liter and a superimposed ultradian frequency of 2.0 +/- 0.1 cycles/d. After GH replacement, the circadian rhythm was preserved (P < 0.001), but mesor decreased to 1.65 +/- 0.01 nmol/liter (P < 0.0001), and leptin ultradian frequency increased to 16.0 +/-0.2 cycles/d (P < 0.0001). Pulse analysis (ULTRA) revealed 3.1 +/- 0.9 pulses/24 h in untreated adult GH deficiency patients, which significantly increased to 9.9 +/- 2.2 pulses/24 h after 1 month of GH replacement (P < 0.001). There was no significant change in body mass index or body fat mass after 1 month of GH replacement. The body fat percentage significantly reduced from 36.5 +/- 2.8% to 35.5 +/- 2.7% after 1 month of GH replacement (P < 0.05). This change in body fat percentage was explained by a significant increase in lean body mass, from 56.2 +/- 2.8 kg at baseline to 57.4 +/- 2.7 kg after 1 month (P < 0.05). A significant correlation was observed between plasma leptin and body fat percentage at baseline and 1 month after GH replacement (both, r = 0.7; P < 0.01) in the absence of a significant correlation between leptin and body fat mass before and after GH replacement (P = 0.13 and P = 0.11, respectively). Thus, untreated adult GH deficiency is associated with elevated 24-h leptin concentration, preserved circadian rhythm, and decreased pulsatility. The secretory pattern is restored after GH replacement, with a significant reduction in the 24-h mean leptin concentration, maintenance of circadian rhythm, and increased pulsatility. This GH-induced change in the leptin secretory pattern precedes significant changes in body fat mass and may therefore be independent of changes in adipose tissue. Restoration of leptin pulsatility may be of clinical benefit, and our data could lead to novel approaches for leptin manipulation in the future.

Activity Cycles↗
PubMed2001

A mechanical model of cerebral circulation during sustained acceleration.

BACKGROUND: High positive Gz may result in inadequate blood supply to the brain even if the central blood pressures are maintained at normal levels. We use a mechanical model to simulate the influence of sustained +Gz on cerebral circulation. METHODS: The model consists of ascending and descending tubes representing the extracranial arteries and veins, respectively, and a cranium in which the tubes are enclosed within water-filled rigid container to account for the skull and the cerebrospinal fluid. A thick-walled Tygon tube and a thin-walled surgical drain tube were used for the arteries and veins, respectively. The flow of water was driven by a pressure difference at the model ends, and the change in the gravitational vector was accomplished by tilting the model. RESULTS: The flow drops with an increasing tilt angle only if the descending arm collapses. However, when the pressures at the model ends are sufficiently elevated, the flow is restored to normal value. In the cranium model, the pressure in the water surrounding the tubes always stays close to the pressure in the surgical tubing. Consequently, the tubes in the container do not collapse. CONCLUSIONS: The principal effect of Gz on flow through the model occurs via changes in the resistance of the collapsed descending arm. As the pressures at the model ends are elevated, the descending arm opens and the flow increases. The pressure in the cranium model is dictated by the condition that the volume of the container has to remain constant.

Acceleration↗