Johan Verhaeghe - Academia.edu (original) (raw)

Papers by Johan Verhaeghe

Journal of Family Planning and Reproductive Health Care, 2010

American Journal of Obstetrics and Gynecology, 1996

OBJECTIVE: Our purpose was to determine the correlation between birth weight and hormones or grow... more OBJECTIVE: Our purpose was to determine the correlation between birth weight and hormones or growth factors believed to be involved in fetal growth: insulin, insulin-like growth factors I and II, and insulin-like growth factor binding protein-1. STUDY DESIGN: Five hundred thirty-eight cord serum samples were analyzed for insulin-like growth factor-I, insulin-like growth factor-II, C-peptide, and insulin-like growth factor binding protein-1 by immunoassay. Samples included all gestational ages in the third trimester and a large range of birth weights. RESULTS: Cord serum insulin-like growth factor-I concentrations increased until 39 weeks (+ 84% from 28 to 29 weeks), followed by a 21 % decline at 41 weeks. Insulin-like growth factor-I levels were decreased by 40% in small-for-gestational-age « 10th percentile) newborns and were increased by 28% in large-for-gestational-age (> 90th percentile) newborns in the absence of diabetes. Insulin-like growth factor-I levels were best correlated with birth weight (R = 0.48, P < 0.001). Cord serum insulin-like growth factor-II concentrations were sixfold to tenfold higher than those of insulin-like growth factor-I and were 8% to 10% (p < 0.001) higher in large-for-gestational-age than in average-weight and small-for-gestational-age newborns. Cord serum C-peptide concentrations were 28% and 34% higher in large-for-gestational-age than in average-for-gestational-age and small-for-gestational-age newborns, respectively. Insulin-like growth factor binding protein-1 levels were increased in preterm average-for-gestational-age and in term small-for-gestational-age newborns compared with term average-for-gestational-age newborns and showed a negative correlation with birth weight (R = -0.43, n = 131, P < 0.001). Insulin-like growth factor binding protein-1 was not correlated with C-peptide concentrations. CONCLUSIONS: Insulin-like growth factors I and II and insulin are all related to fetal growth and weight gain, and insulin-like growth factor-I correlates best with birth weight. Insulin is mainly related to fetal overgrowth (macrosomia). Insulin-like growth factor binding protein-1 may be a growth inhibitor in the fetus. (AM J OBSTET GVNECOL 1993;169:89-97.) Key words: Birth weight, insulin-like growth factor-I, insulin-like growth factor-II, C-peptide, insulin-like growth factor binding protein-l There is extensive, although largely indirect, evidence that insulin and the insulin-like growth factors I (IGF-I) and II (IGF-II) have a role in the regulation of fetal growth and weight gain. Insulin is secreted by fetal pancreatic B-cells primarily during the second half of gestation and is believed to primarily stimulate somatic growth and adiposity through classic endocrine modes From the Department of Obstetrics and Gynecology, a and the Laboratorium voor Experimentele Geneeskunde en Endocrinologie, b Katholieke Universiteit Leuven.

Journal of Steroid Biochemistry and Molecular Biology, 1992

This review summarizes the reported effects of the menstrual cycle, pregnancy and lactation on se... more This review summarizes the reported effects of the menstrual cycle, pregnancy and lactation on serum concentration of the calciotropic hormones PTH and 1,25(OH)~D. A midcycle rise in PTH and 1,25(OH)2 D has been observed, but in the majority of studies there was no change in PTH and 1,25(OH)2 D concentrations throughout the menstrual cycle. Both total and free 1,25(OH):D levels are increased during pregnancy. The renal 1,25(OH)2 D production is stimulated, and there is some evidence of 1,25(OH)2 D production by decidua/ placenta and fetal kidney in vitro; the decidual/placental production should not be overestimated in vivo. The increased renal l~t-hydroxylase activity is possibly mediated by estrogens and PTH, although the effect of pregnancy on PTH remains uncertain. Increased serum 1,25(OH)2D concentrations probably result in a rise of intestinal calcium absorption during pregnancy. There is a postdelivery drop in PTH and 1,25(OH)2D levels, but they are increased when lactation is prolonged, or in mothers nursing twins. The l~-hydroxylase activity during lactation may be stimulated by PTH, but also by prolactin.

Bone, 1997

Long-term diabetes in female rats preserves the bone mineral density (BMD) but impairs the streng... more Long-term diabetes in female rats preserves the bone mineral density (BMD) but impairs the strength of the femur. In this study, we have compared the effects of diabetes and highdose 171~-estradiol (Ez), two conditions of low bone formation, in ovariectomized (ovx) rats. Spontaneously diabetic BB rats were ovx 0-3 days after onset, and nondiabetic ovx littermates were used as controls; the rats were either untreated or treated with E 2 (30 ixg/day, subcutaneously), for 6 or 12 weeks (n = 9 in each of the eight groups). Analysis included: plasma 1,25-dihydroxyvitamin D3, insulin-like growth factor-I (IGF-I), and osteocalcin concentrations; histomorphometry of the proximal tibial metaphysis (PTM); and DXA and biomechanical testing of the femur. Both E 2 treatment and diabetes markedly lowered plasma IGF-I and osteocalcin concentrations, as well as dynamic morphometric parameters of bone formation in the PTM. Plasma IGF-I and osteocalcin were correlated (R 2 = 0.55; p < 0.0001). E 2 treatment in both control and diabetic ovx rats increased the trabecular bone volume in the PTM and the BMD in the metaphysis of the distal femur; there was no difference between control and diabetic rats, however. The diaphyseal area and BMC were decreased in E2-treated or/and diabetic ovx rats, but the diaphyseal BMD remained unchanged compared with untreated ovx rats. The biomechanical properties of the whole femur (strength, angular deformation, and stiffness) were decreased in E2-treated and diabetic E 2treated ovx rats after 12 weeks. The data indicate that in situations of chronic low bone formation, whole bone strength does not reflect total BMD but correlates better with bone size and bone mineral content measurements. (Bone 20: 421-428; 1997) © 1997 by Elsevier Science Inc. All rights reserved. E 2 had been administered. Although diabetic rats weigh less than nondiabetic ones, we used the same dose of E 2 (30 ~g/day) because diabetic rats have been shown to have increased metabolic clearance rate of E2. 6

Bone and Mineral, 1994

Bone loss during androgen deficiency has been associated with accelerated bone turnover and imbal... more Bone loss during androgen deficiency has been associated with accelerated bone turnover and imbalance between bone formation and resorption but the relative increase of both phenomena is not well described. Serum osteocalcin as marker of bone formation and urinary excretion of pyridinoline (PYD) and deoxypyridinoline (DPD) as markers of bone resorption were measured in both orchidectomized (ORCH, n = 8) and sham-operated (SHAM, n = 8) aged (12-month-old) male rats from 2 days before until 66 days after surgery. PYD and DPD were significantly higher in the ORCH group compared to the SHAM group starting from 21 days after surgery until the end of the experiment. Serum osteocalcin was only significantly increased in the ORCH group at 30 and 40 days. The maximal increase of serum osteocalcin was also smaller than the increase in PYD and DPD (30% versus 74% and 112%, respectively). The two markers of bone resorption were correlated with osteocalcin (r = 0.63 for PYD and r = 0.71 for DPD). Based on these results, we conclude that (1) bone resorption, as measured by PYD and DPD, increased during androgen deficiency; (2) moreover, the increase of bone resorption, as measured by DPD and PYD, was followed by a more moderate increase in bone formation as measured by serum osteocalcin, supporting the hypothesis that androgen deficiency causes accelerated bone turnover and imbalance between bone resorption and bone formation.

Diabetes, 1990

The effect of long-term diabetes mellitus on bone and mineral metabolism was studied in BB rats. ... more The effect of long-term diabetes mellitus on bone and mineral metabolism was studied in BB rats. Diabetic rats were treated with 1 U of long-acting insulin every other day for 12 wk and compared with nondiabetic littermates. Urinary calcium excretion was increased greater than 10-fold, but serum total and diffusible calcium remained normal. Serum concentrations of both 1 alpha, 25-dihydroxyvitamin D3 and vitamin D-binding protein were significantly decreased in diabetic rats. The intestinal calbindin-D 9K concentration was decreased by nearly 50%, and active duodenal calcium absorption was totally abolished. Trabecular bone volume measured in the tibial metaphysis was decreased by 44%, and the osteoblast and osteoid surfaces were less than 10% of values observed in control rats, whereas the osteoclast surface was unchanged by diabetes. The daily bone formation (bone mineral apposition rate) measured by labeling twice with calcein was decreased by 86% in diabetic rats. The serum concentration of osteocalcin, a biochemical marker of osteoblast function, was similarly decreased (mean +/- SE 23 +/- 3 and 62 +/- 4 micrograms/L in diabetic [n = 15] and nondiabetic [n = 15] rats, respectively). Serum osteocalcin was significantly correlated with the serum concentration of insulinlike growth factor I (r = 0.89, P less than 0.001). Bone strength measured as the energy needed to fracture the femur was markedly decreased (5.3 +/- 1.4 and 8.4 +/- 1.3 N.m.degree in diabetic and nondiabetic rats, respectively; P less than 0.01). These histological, chemical, and biomechanical data clearly indicate that long-standing diabetes in BB rats results in severe low-turnover osteoporosis probably related to decreased osteoblast recruitment and/or function.

Metabolism-clinical and Experimental, 2007

Exposure to a dysmetabolic in utero environment may be one of the mechanisms to explain why indiv... more Exposure to a dysmetabolic in utero environment may be one of the mechanisms to explain why individuals with high birth weight are more likely to remain overweight. We explored this hypothesis in an animal model of diet-induced obesity (DIO). We studied adipose tissue development and glucose tolerance in the offspring of rat dams fed a diet rich in milk and sugar from early adulthood until day (d) 2 postpartum. This diet promoted body weight (BW) gain and was previously shown to produce insulin resistance and gestational glucose intolerance. The DIO offspring showed a higher BW in early life (between d7 and d35), with a maximum of 1 SD above the mean BW of controls; however, BW in DIO offspring after d35 was comparable with that of controls. Neonatal DIO offspring also showed larger fat depots, adipocyte hypertrophy (P ≤ .001), and more than 2-fold increased tumor necrosis factor α messenger RNA levels in subcutaneous adipose tissue (P b .05). In addition, they displayed a higher peak glucose response to a glucose challenge (P b .05). In postpubertal (d56) and adult (d98) offspring, we found differences in fat mass and distribution and glucose tolerance relating to the offspring's sex but not the maternal diet. In conclusion, DIO during pregnancy results in hyperadiposity and reduced glucose tolerance only in their neonatal/weanling but not postpubertal offspring. Future research should disclose whether these early-life effects are reactivated in conditions of heightened insulin resistance.

Journal of Endocrinology, 1989

Concentrations of osteocalcin were measured in plasma and bone of normal and diabetic rats during... more Concentrations of osteocalcin were measured in plasma and bone of normal and diabetic rats during the reproductive cycle and compared with plasma 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) concentrations. The age-dependence of osteocalcin was also examined. Plasma concentrations of osteocalcin levels were low but detectable in 21-day-old fetuses (3.7 +/- 0.3 nmol/l); osteocalcin concentrations were highest in weaning rats (104 +/- 9 nmol/l) and decreased thereafter. In adult rats, plasma concentrations of both osteocalcin and 1,25-(OH)2D3 increased during the last days of normal pregnancy, and even more so in rats fed a diet low in calcium and phosphate. After an early post-partum decline, osteocalcin concentrations in plasma remained at non-pregnant levels in lactating rats fed a high calcium/phosphate diet while their 1,25-(OH)2D3 concentrations were higher than in non-pregnant rats; however, lactating rats fed a low calcium/phosphate diet showed increasing osteocalcin concentrations. In spontaneously diabetic BB rats, plasma osteocalcin concentrations were severely decreased compared with those in non-diabetic rats, more than would have been expected from their decreased 1,25-(OH)2D3 concentrations. Moreover, plasma osteocalcin did not increase during pregnancy or lactation in diabetic rats, even when fed a low calcium/phosphate diet. Fetuses of diabetic rats also had lower plasma osteocalcin levels than fetuses from non-diabetic rats or than weight-matched fetuses from semistarved rats. In contrast to plasma osteocalcin concentrations, bone osteocalcin concentrations and content were not altered by pregnancy, lactation, low calcium/phosphate diet or diabetes.(ABSTRACT TRUNCATED AT 250 WORDS)

Endocrinology, 1989

Calcium homeostasis was investigated in male BB rats with a diabetes duration of 3-4 weeks and co... more Calcium homeostasis was investigated in male BB rats with a diabetes duration of 3-4 weeks and compared with that in nondiabetic littermates either fed ad libitum or receiving selective semistarvation or an oral Ca supplement to obtain additional weight-matched and Ca intake-matched control groups. Diabetic rats had markedly increased food and Ca intake, so that their net Ca balance remained positive despite a 13-fold increase in urinary Ca excretion and a disappearance of active duodenal Ca absorption. Decreased duodenal Ca uptake correlated with decreased 1,25-(OH)2D3 levels (89 +/- 15 vs. 160 +/- 13 pg/ml in nondiabetic rats), decreased duodenal 9K Ca-binding protein concentrations (10 +/- 1 vs. 21 +/- 2 micrograms/mg protein), and decreased number of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3]-binding sites in duodenum, although the binding affinity was above normal. Nondiabetic Ca-supplemented rats exhibited a similar response: decreased 1,25-(OH)2D3 (95 +/- 8 pg/ml) and 9K Ca-binding protein (7 +/- 0.5 micrograms/mg protein) concentrations, decreased active duodenal Ca uptake, increased urinary Ca excretion, and a normal net Ca balance. Plasma vitamin D-binding protein levels were decreased by 62% in diabetic rats, due to a marked decrease in production rate, while the plasma half-time remained normal. The free 1,25-(OH)2D3 index was highest in diabetic rats, suggesting partial vitamin D resistance at the duodenal level. In semistarved rats, 1,25-(OH)2D3 levels and active Ca uptake remained normal, and the free 1,25-(OH)2D3 index was increased, together with suppressed vitamin D-binding protein levels. These studies indicate that nutritional abnormalities may contribute to but cannot totally explain the disturbances in vitamin D metabolism, transport, or action at the intestinal level.

Ultrasound in Obstetrics & Gynecology, 2000

ObjectivesTo evaluate whether local anesthesia decreases patients' pain experience during mid-tri... more ObjectivesTo evaluate whether local anesthesia decreases patients' pain experience during mid-trimester amniocentesis.To evaluate whether local anesthesia decreases patients' pain experience during mid-trimester amniocentesis.MethodsIn a randomized trial, one group did not receive local anesthesia while, in another group, lignocaine 1% was injected subcutanously prior to amniocentesis. Five different scoring systems were used to evaluate patients' pain experience.In a randomized trial, one group did not receive local anesthesia while, in another group, lignocaine 1% was injected subcutanously prior to amniocentesis. Five different scoring systems were used to evaluate patients' pain experience.ResultsTwo hundred and twenty women entered the study: 114 received local anesthesia, while 106 did not. The mean (SD) Visual Analog Scale was 1.4 (1.5) on a 0–10 scale (range 0–7.6). Some 97% of patients described the procedure as not painful or bearable, 79% had expected the procedure to be more painful and 59% reported the amniocentesis to have a comparable discomfort as venous blood sampling; 98% of women declared they would undergo an amniocentesis again if indicated. There were no statistical differences between both randomization groups.Two hundred and twenty women entered the study: 114 received local anesthesia, while 106 did not. The mean (SD) Visual Analog Scale was 1.4 (1.5) on a 0–10 scale (range 0–7.6). Some 97% of patients described the procedure as not painful or bearable, 79% had expected the procedure to be more painful and 59% reported the amniocentesis to have a comparable discomfort as venous blood sampling; 98% of women declared they would undergo an amniocentesis again if indicated. There were no statistical differences between both randomization groups.ConclusionsMid-trimester amniocentesis is not a painful procedure. Local anesthesia does not affect pain experience during amniocentesis. Copyright © 2000 International Society of Ultrasound in Obstetrics and GynecologyMid-trimester amniocentesis is not a painful procedure. Local anesthesia does not affect pain experience during amniocentesis. Copyright © 2000 International Society of Ultrasound in Obstetrics and Gynecology

Pediatric Research, 1999

There is some evidence that fetuses of diabetic rats (FDR) are hypomineralized. To explore the pa... more There is some evidence that fetuses of diabetic rats (FDR) are hypomineralized. To explore the pathogenic role of decreased maternal duodenal Ca absorption, fetal hypotrophy, and decreased placental calbindin-D9K, respectively, spontaneously diabetic rats fed a 1.0% Ca diet were compared with diabetic rats treated with 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] (15 ng/ 100 g) during week 3 of pregnancy, which restored duodenal calbindin-D9K concentrations to normal; with nondiabetic rats semistarved during week 3, which resulted in similar fetal hypotrophy; and with nondiabetic rats fed high cation diets (1.5% Ca-1.5% Sr and 1.5% Ca-3.5% Sr) during week 3, the latter of which repressed duodenal and placental calbindin-D9K toward concentrations measured in diabetic rats. In addition, fetal tibiae were studied histologically. Ca content was lower in 21.5-d-old FDR than in control fetuses. FDR had lower plasma osteocalcin (OC) levels and, on histomorphometry, increased hypertrophic cartilage width, indicating retarded bone maturation. Maternal 1,25(OH)2D3 treatment did not change Ca content and hypertrophic cartilage width in FDR. Fetuses of semistarved rats had plasma OC levels and hypertrophic cartilage width comparable to those of control fetuses. Fetuses of rats fed the 1.5% Ca-3.5% Sr diet were more severely hypomineralized than FDR but had higher plasma OC than both FDR and control fetuses, compatible with fetal Ca deficiency. Whereas diabetic placentas showed weak but homogeneous staining of calbindin-D9K in the labyrinth on immunohistology, degenerative zones were present in placentas of rats fed the 1.5% Ca-3.5% Sr diet. Thus, there is no mineralization defect in FDR caused by disturbed maternal duodenal Ca absorption or transplacental Ca transport, but a delay in bone maturation that is unexplained by their lower body weight.

Diabetes, 1993

Adult offspring of diabetic rats or SDF rats are characterized by insulin resistance in the liver... more Adult offspring of diabetic rats or SDF rats are characterized by insulin resistance in the liver and extrahepatic tissues; this insulin resistance does not worsen during pregnancy. In this study, we determined the glucose metabolic index in tissues of anesthetized virgin and pregnant control and SDF rats in basal conditions and during a euglycemic hyperinsulinemic clamp. Tissues comprised insulin-sensitive tissues (five skeletal muscles, diaphragm, and periovarian white adipose tissue) and control tissues (duodenum and cerebrum). In addition, this study measured the GMI of placenta and fetuses. In basal conditions, SDF rats showed a slight decrease (9-29%) in the GMI of skeletal muscles compared with control rats; it was not altered by pregnancy in any of the tissues. During physiological hyperinsulinemia, virgin SDF rats exhibited a 25-70% decrease in the GMI of skeletal muscles compared with control rats; this decrease was not observed in diaphragm, or in adipose tissue in which the GMI was found to be increased. During pregnancy, SDF rats did not show an additional drop in the GMI of skeletal muscles, whereas the GMI of both skeletal muscles and adipose tissue was clearly diminished (25-60%) in control rats. The GMI of skeletal muscles was therefore comparable in pregnant control rats and SDF rats. The placental, but not fetal, GMI was increased by 24% during hyperinsulinemia in control rats; the placental and fetal GMIs, in basal and hyperinsulinemic conditions, were similar in control rats and SDF rats. In conclusion, skeletal muscles, but not white adipose tissue, are involved in the peripheral insulin resistance of the SDF rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical Endocrinology, 2000

The respective contributions of pituitary and placental GH to circulating IGF-I in pregnant women... more The respective contributions of pituitary and placental GH to circulating IGF-I in pregnant women have not been well established. We measured the serum concentrations of placental growth hormone (PGH) and IGF-I in a woman with pit-1 deficiency before, during and after pregnancy, resulting in the birth of a healthy child (not pit-1 deficient). Both PGH and IGF-I concentrations were below the assay detection limit before and after pregnancy. During pregnancy, PGH and IGF-I levels increased steadily; the concentrations of PGH and IGF-I in late pregnancy were comparable with levels previously measured in normal pregnancies. PGH and IGF-I concentrations were strongly correlated throughout pregnancy (r = 0.90; P = 0.002). PGH was undetectable in cord serum, whilst the IGF-I concentration was within the normal range. The findings of this case study corroborate the notion that PGH is the prime regulator of maternal serum IGF-I during pregnancy.

Endocrine, 1997

Diabetes in both humans and rats is accompanied by low bone formation, which is presumably caused... more Diabetes in both humans and rats is accompanied by low bone formation, which is presumably caused by serum-borne factors. To explore its pathogenesis, we carried out experiments in diabetic and nondiabetic BB rats, using plasma osteocalcin concentrations (OC) as a marker for osteoblast activity. In nondiabetic rats, the iv infusion of glucose (30%, 4 d) did not change OC; sc insulin infusion (4 U/d, 14 d) reduced OC by 27% (p<0.01). In diabetic rats, OC were decreased from the first day of glycosuria (71±5% of paired controls), declining exponentially to 24±3% after 5 wk. Insulin infusion (1,2, and 3 U/d, 14 d) produced gradual restoration of OC. OC were better correlated with insulin-like growth factor-I (IGF-I) than with insulin levels in these experiments. OC were dramatically increased 4 d after adrenalectomy (ADX) in all diabetic rats (73±8 vs 22±4 μg/L before ADX;p<0.001), but not if corticosterone was administered. Ligand blotting of IGF binding proteins showed a marked decrease in two bands (44–49 and 32–35 kDa) 10–14 d after diabetes onset; the density of these bands was increased, but not normalized after ADX. Thus, decreased osteoblast activity is present from the onset of diabetes, is dependent on endogenous corticosterone, and cannot be reproduced by hyperglycemia in nondiabetic rats.

Journal of The Society for Gynecologic Investigation, 1996

The purpose of the present study was to investigate insulin sensitivity in adult rats after perin... more The purpose of the present study was to investigate insulin sensitivity in adult rats after perinatal malnutrition. Wistar rats were food-restricted (about 50% of normal food intake) during pregnancy (group A) or during pregnancy and lactation (group B) and compared with rats fed ad libitum during pregnancy and lactation (group C). The insulin sensitivity in the adult female offspring was assessed with the hyperinsulinemic euglycemic clamp technique in combination with isotopic measurement of glucose turnover. Hepatic and peripheral insulin sensitivities were determined in the basal state and after 3, 10, or 50 mU/kg/minute insulin. Group A and group B rats had lower non-fasting plasma insulin levels (0.15 +/- 0.07 and 0.15 +/- 0.01 nmol/L, respectively) than group C rats (0.26 +/- 0.03 nmol/L) (P < .001). During hyperinsulinemia, the steady-state glucose infusion rate was lower in groups A and B, with 10 and 50 mU/kg/minute insulin, indicating insulin resistance. Hepatic glucose production in the basal state was normal, but its suppression by 10 and 50 mU/kg/minute insulin was dampened in group A and B rats, indicating decreased insulin responsiveness of the liver. Peripheral glucose utilization, however, in the basal state and during hyperinsulinemia remained normal in groups A and B. After perinatal malnutrition, adult rats have decreased plasma insulin concentrations and exhibit insulin resistance, with decreased insulin responsiveness of the liver.

Hormone and Metabolic Research, 1993

Breast Cancer Research and Treatment, 2007

Objective Arthralgia, skeletal and muscle pain have been reported in postmenopausal women under t... more Objective Arthralgia, skeletal and muscle pain have been reported in postmenopausal women under treatment with third generation aromatase inhibitors (AIs). However, the pathogenesis and anatomic correlate of musculoskeletal pains have not been thoroughly evaluated. Moreover, the impact of AI-induced musculoskeletal symptoms on normal daily functioning needs to be further explored. Patients and methods We examined 12 consecutive non-metastatic breast cancer patients who reported severe musculoskeletal pain under a third generation AI; 11 were on letrozole and 1 on exemestane. Clinical rheumatological examination and serum biochemistry were performed. Radiological evaluation of the hand/wrist joints were performed using ultrasound (US) and/or magnetic resonance imaging (MRI). Results The most common reported symptom was severe early morning stiffness and hand/wrist pain causing impaired ability to completely close/stretch the hand/fingers and to perform daily activities and work-related skills. Six patients had to discontinue treatment due to severe symptoms. Trigger finger and carpal tunnel syndrome were the most frequently reported clinical signs. US showed fluid in the tendon sheath surrounding the digital flexor tendons. On MRI, an enhancement and thickening of the tendon sheath was a constant finding in all 12 patients. Conclusions Musculoskeletal pains in breast cancer patients under third generation AIs can be severe, debilitating, and can limit compliance. Characteristic tenosynovial, and in some patients joint changes on US and MRI were observed in this series and have not been reported before.

Journal of Endocrinology, 1992

Spontaneously diabetic BB rats have a markedly depressed longitudinal bone growth and bone format... more Spontaneously diabetic BB rats have a markedly depressed longitudinal bone growth and bone formation/turnover. In this study, male diabetic BB rats were infused intraperitoneally or subcutaneously for 2 weeks with hormones that are believed to stimulate skeletal growth and/or trabecular bone formation: insulin (3 or 4 U/day), human GH (hGH; 400 mU/day), recombinant human insulin-like growth factor-I (rhIGF-I; 300 or 600 micrograms/day) and testosterone (80 micrograms/100 g body weight per day). Saline-treated diabetic BB rats had decreased plasma concentrations of IGF-I and osteocalcin (OC) (OC, 3.7 +/- 0.3 vs 13.1 +/- 0.8 (S.E.M.) nmol/l in controls); bone histomorphometry showed decreased epiphyseal width, osteoblast surface (0.04 +/- 0.04 vs 1.5 +/- 0.3%) and osteoid surface, and mineral apposition rate (MAR) (1.8 +/- 0.5 vs 7.9 +/- 0.6 microns/day). Testosterone and hGH infusions had no effect on weight loss or on decreased skeletal growth and bone formation of diabetic rats, nor did they increase plasma IGF-I concentrations. Insulin infusions into diabetic rats resulted in hyperinsulinaemia and accelerated weight gain. The epiphyseal width, osteoblast/osteoid surfaces and OC levels of insulin-treated rats were normalized or stimulated well above control values (osteoblast surface, 4.3 +/- 0.8%; plasma OC, 16.1 +/- 1.4 nmol/l); the MAR (4.0 +/- 0.9 microns/day) was only partly corrected after the 2-week infusion. Infusions of rhIGF-I into diabetic rats doubled but did not restore plasma IGF-I levels to normal; weight gain, however, was similar to that in control rats. IGF-I treatment had no effect on epiphyseal width, osteoblast/osteoid surfaces and OC concentrations, but improved the decreased MAR (4.6 +/- 1.2 microns/day).(ABSTRACT TRUNCATED AT 250 WORDS)

American Journal of Physiology-endocrinology and Metabolism, 2006

Gravidas with obesity and diabetes (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;... more Gravidas with obesity and diabetes (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;diabesity&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;) may transmit this syndrome to their children through genetic and nongenetic mechanisms. Here, we used the Lepr(db/+) diabese mouse to examine the magnitude of these transmission modes, focusing on adipose tissue (AT). We compared the following six groups: wild-type (+/+) offspring from +/+ or db/+ dams (different early life environment) and db/+ offspring from db/+ dams, fed a standard or high-fat diet. Weight gain (0-8 wk) was higher in +/+ offspring from db/+ vs. +/+ mothers, and even higher in db/+ vs. +/+ offspring from db/+ mothers. In addition, we observed a stepwise increase in AT and adipocyte size in +/+ from +/+ mice, +/+ from db/+ mice, and db/+ mice at 8 wk. Differences in weight and adiposity between +/+ offspring from db/+ vs. +/+ dams were more pronounced in males than in females. Leptin and apelin mRNA levels in white and brown AT were higher in +/+ offspring from db/+ vs. +/+ dams; however, leptin, apelin, and tumor necrosis factor-alpha expression were boosted more robustly in db/+ offspring. The high-fat diet amplified AT differences between db/+ vs. +/+ offspring from db/+ dams, but not between +/+ offspring from db/+ vs. +/+ dams. Moreover, db/+ but not +/+ offspring from db/+ mothers were insulin-resistant and hyperinsulinemic after a glucose challenge. In conclusion, the genetic transmission of the diabesity phenotype clearly prevailed, but the early-life diabesity environment had discernible effects on postnatal weight gain as well as on adipocyte size and adipokine expression at a postpubertal age.