Biomedical subjects

J Verhaeghe

Publications and source records attributed to J Verhaeghe.

At least 19 recordsLinked to original sources

PubMed2001

Insulin-like growth factor-binding protein-1 in umbilical artery and vein of term fetuses with signs suggestive of distress during labor.

Insulin-like growth factor-binding protein-1 (IGFBP-1) is believed to be an inhibitory factor for fetal growth. The regulation of IGFBP-1 secretion in the fetus is uncertain, although insulin and oxygen tension (PO2) and saturation are thought to play a role. We studied IGFBP-1 levels in umbilical cord artery (UA) and vein (UV) of 98 singleton fetuses at term with clinical signs of distress during labor, i.e. meconium-stained liquor or/and an abnormal fetal heart rate tracing. Blood gas values and serum C-peptide and IGFBP-1 concentrations were measured in both UA and UV. Twenty-five fetuses had an UA pH<7.20. The concentrations of IGFBP-1 were similar in UA and UV and were highly correlated (r=0.98). IGFBP-1 levels were inversely correlated with birth weight, with increased concentrations in small-for-gestational age fetuses (< or =10th weight percentile). IGFBP-1 levels were negatively correlated with C-peptide concentrations, and remained so after correction for birth weight (r=-0.37 for both UA and UV; P<0.001); more specifically, IGFBP-1 levels were increased in the lowest C-peptide quartile (<0.23 nmol/l) compared with the other quartiles. In addition, IGFBP-1 levels were inversely correlated with PO(2) values (r=-0.39 in UA and r=-0.34 in UV; P<0.001); quartiles of UA and UV PO2 showed a gradual increase in IGFBP-1 concentrations with lower PO2 values. A regression model with C-peptide and PO2 values as independent variables predicted IGFBP-1 concentrations (R2 of model was 0.25 and 0.22 for UA and UV respectively; P<0.001). Other blood gas values (pH, PCO2, HCO3- and base deficit) did not correlate with IGFBP-1 levels. The data of this study indicate that serum IGFBP-1 levels in term fetuses are determined by both insulin and PO2 levels, and suggest that acute hypoxemia stimulates IGFBP-1 secretion in the fetus.

Analysis of Variance↗

PubMed2000

Effects of exercise and disuse on bone remodeling, bone mass, and biomechanical competence in spontaneously diabetic female rats.

Diabetes is associated with low bone formation. In this study we investigate the effect of additional or reduced mechanical loading on indices of bone formation and resorption, bone mass, and biomechanical properties in spontaneously diabetic BB rats. Female diabetic (mean age 13 weeks) and age-matched control rats were each allocated to three experimental groups: no-intervention; supervised running exercise program (Ex); and unloading induced by unilateral sciatic neurectomy (USN). The study period was 8 weeks. We measured biochemical parameters of bone formation (plasma osteocalcin) and resorption (urinary deoxypyridinoline [Dpd]); bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA) at middiaphyseal and metaphyseal regions of the femur; histomorphometry of the proximal tibial metaphysis (PTM); and biomechanical properties of the femur (neck, diaphysis, and metaphysis) and lumbar vertebra (L-5). In nondiabetic rats, Ex did not affect parameters of bone formation/resorption and BMD, and had little effect on biomechanical properties. USN increased Dpd excretion, whereas there was a decreased trabecular bone formation rate (BFR) on morphometry of PTM in both paralyzed and intact limbs. Compared with intact limbs, paralyzed limbs of USN rats showed decreased trabecular bone volume at the PTM, and decreased BMD and biomechanical properties at the distal femoral metaphysis (DFM) and, to a lesser extent, femoral neck. Diabetic rats of the three experimental groups had low plasma osteocalcin levels and Dpd excretion, as well as low BFR on morphometry. The BMD and biomechanical properties of both femur and L-5 were unchanged in diabetic rats. Diabetic Ex rats, however, showed a lower maximum load and stress at DFM than control Ex rats. Diabetic USN rats showed no increase in Dpd excretion; their paralyzed limbs showed decreased maximum load at DFM, but there was no significant decrease in trabecular bone volume at PTM or BMD at DFM. Thus, the running exercise does not affect low bone formation in diabetic rats; however, trabecular bone loss caused by disuse is less pronounced in diabetic rats, probably as a result of low bone resorption.

Absorptiometry, Photon↗

PubMed2000

Placental growth hormone and IGF-I in a pregnant woman with Pit-1 deficiency.

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.

Adult↗

PubMed2000

Does local anesthesia at mid-trimester amniocentesis decrease pain experience? A randomized trial in 220 patients.

OBJECTIVES: To evaluate whether local anesthesia decreases patients' pain experience during mid-trimester amniocentesis. METHODS: In a randomized trial, one group did not receive local anesthesia while, in another group, lignocaine 1% was injected subcutaneously prior to amniocentesis. Five different scoring systems were used to evaluate patients' pain experience. RESULTS: 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. CONCLUSIONS: Mid-trimester amniocentesis is not a painful procedure. Local anesthesia does not affect pain experience during amniocentesis.

Adult↗

PubMed2000

Dietary calcium and phosphate restriction in guinea-pigs during pregnancy: fetal mineralization induces maternal hypocalcaemia despite increased 1 alpha,25-dihydroxycholecalciferol concentrations.

Guinea-pig fetuses at term are mineralized to a degree comparable with human fetuses, which makes the guinea-pig an attractive animal model to study maternal-fetal interactions with regard to Ca and phosphate (P) homeostasis. We studied non-pregnant and pregnant (day 57) vitamin D-replete guinea-pigs, fed either a normal guinea-pig chow with 9.6 g Ca/kg and 4.9 g P/kg or a study diet with 2 g Ca/kg and 1 g P/kg (low-Ca-P diet) for 7-8 weeks. Both pregnancy and the low-Ca-P diet decreased plasma concentrations of 25-hydroxycholecalciferol (25(OH)D3), but increased total and free 1 alpha,25-dihydroxycholecalciferol (1,25(OH)2D3), strongly suggesting an additive stimulation of 1 alpha-hydroxylase activity. Maternal and fetal 25(OH)D3 and 1,25(OH)2D3 levels were highly correlated (r 0.82 and 0.92 respectively, P < 0.001). Dual-energy absorption X-ray absorptiometry (DXA) showed that both pregnancy and the low-Ca-P diet decreased bone mineral density (BMD) of the maternal femur, particularly at the distal metaphysis. Despite higher 1,25(OH)2D3 concentrations and lower BMD, pregnant animals on the low-Ca-P diet were hypocalcaemic; blood Ca2+ levels were inversely correlated with the number of fetuses in this group (r -0.93, P < 0.001). Fetal growth as well as mineralization (assessed by whole-body and femoral DXA, bone histomorphometry and plasma-bone osteocalcin measurements) were unaltered in the low-Ca-P group. In conclusion, fetal mineralization proceeds normally but induces maternal hypocalcaemia in guinea-pigs with dietary restriction of Ca and P.

Absorptiometry, Photon↗

PubMed1999

Management of severe neonatal anemia due to fetomaternal transfusion.

Three cases of severe neonatal anemia due to fetomaternal transfusion are reported. The key features that lead to early diagnosis were the maternal history, fetal monitoring, the clinical and laboratory findings of anemia, and a negative Coombs test. Diagnosis was confirmed by a rapid Kleihauer-Betke test. A partial exchange transfusion was performed in two of the three neonates with rapid clinical and hematological improvement. As two patients showed signs of heart decompensation, a partial exchange transfusion was performed with good success. In patients presenting with severe subacute or chronic anemia and heart failure, a partial exchange transfusion may be preferable to that of simple transfusion associated with diuretics.

Adult↗

PubMed1999

Pathogenesis of fetal hypomineralization in diabetic rats: evidence for delayed bone maturation.

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.

Animals↗

PubMed1999

IGF-I, IGF-II, IGF binding protein 1, and C-peptide in second trimester amniotic fluid are dependent on gestational age but do not predict weight at birth.

Previous data suggested that small for gestational age newborns have increased levels of IGF binding protein 1 (IGFBPI) in amniotic fluid (AF) at 15-16 wk of pregnancy. In this study, we developed an RIA for IGFBP1 and measured IGFBP1 concentrations in 209 AF samples with normal fetal karyotype between 14 and 20 wk; we measured IGF-I, IGF-II, and C-peptide in the same samples. Concentrations of these growth-modulating factors were all positively correlated with gestational age at sampling (p < 0.0001). After correcting for gestational age, AF IGFBP1 remained strongly correlated with IGF-I and IGF-II (both p < 0.0001); their concentrations were many times higher in AF than in cord serum during the third trimester. None of the growth-modulating factors in AF correlated with birth weight, after correction for gestational age; birth weight percentile distribution was comparable in two groups of newborns who had AF values of IGF-I, IGF-II, IGFBP1, or C-peptide that were either less than or equal to the 50th percentile or more than the 50th percentile at sampling. However, placenta weight and the placenta weight to birth weight percentage were negatively correlated with AF IGF-I, IGF-II, and IGFBP1; placenta weight to birth weight percentage was lower in pregnancies with IGFBP1 values more than the 50th percentile compared with those less than or equal to the 50th percentile at sampling. In conclusion, AF concentrations of IGFBP 1 increase gradually between 14 and 20 wk gestational age and correlate with IGF-I and IGF-II levels; high IGFBP1 levels do not predict small for gestational age newborns, but are associated with lower placenta weight.

Adult↗

PubMed1999

Calciotrophic hormones during experimental hypocalcaemia and hypercalcaemia in spontaneously diabetic rats.

1,25-Dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) concentrations have been found to be decreased in diabetic humans and rats. To investigate further the regulation of plasma Ca in diabetes, first we measured Ca(2+), P, Mg, parathyroid hormone(1-34) (PTH), and total and free 1,25(OH)(2)D(3) in male spontaneously diabetic rats 7 and 28 days after the onset of glycosuria. Secondly, we studied changes in the levels of PTH and 1,25(OH)(2)D(3) in response to hypocalcaemia induced by an i.v. infusion of EGTA (2.5%, wt/vol.) for 24 h, and changes in the levels of 1,25(OH)(2)D(3) in response to an i.v. infusion of rat PTH (10 microgram over 24 h) without or with concomitant EGTA infusion (producing hypercalcaemia or normo/hypocalcaemia respectively), in diabetic and control rats. Ca(2+), P, Mg and PTH concentrations remained within the control ranges after 7 and 28 days of glycosuria; 1,25(OH)(2)D(3) concentrations were decreased after 7, but not after 28, days of glycosuria. PTH concentrations showed a similar rise during EGTA-induced hypocalcaemia in control and diabetic rats compared with saline-infused rats, whereas 1,25(OH)(2)D(3) concentrations were unchanged in both groups. Total and free 1,25(OH)(2)D(3) levels were comparably (about 3-fold) increased during PTH, but not during combined PTH and EGTA infusion in control and diabetic rats. Total 1, 25(OH)(2)D(3) concentrations were lower in the diabetic groups infused with saline or PTH than in their respective controls, and there was a similar trend in the PTH+EGTA-infused group; free 1, 25(OH)(2)D(3) levels, however, were normal or increased in the diabetic groups, confirming our previous data. The novel finding of this study is that, despite severe insulin deficiency and altered 1, 25(OH)(2)D(3) levels, the in vivo response of PTH levels to hypocalcaemia and the in vivo response of 1,25(OH)(2)D(3) levels to PTH in diabetic rats are comparable with those found in nondiabetic rats.

Animals↗

PubMed1999

Treatment for postdural puncture headache associated with late postpartum eclampsia.

Postdural puncture headache (PDPH) is the most common complication of accidental or deliberate dural puncture. It also occurs after epidural or spinal analgesia for labor and delivery. Treatment may be conservative with analgesics and/or caffeine. Definitive treatment can be accomplished with an epidural blood patch (EBP). We present a case of postpartum convulsions which were temporally related to a caffeine infusion and an EBP.

Acetaminophen↗

PubMed1998

Recombinant human interleukin-11 does not modify biochemical parameters of bone remodeling and bone mineral density in adult ovariectomized rats.

Interleukin (IL)-11 stimulates osteoclast formation and inhibits osteoblast function in vitro and has been implicated in estrogen deficiency-induced bone loss. Herein we report the in vivo effect of recombinant human IL-11 (rHU-IL-11), administered s.c. in doses between 10 and 200 microg/kg/day for 6 weeks into 6-month-old rats after ovariectomy. There was no difference between vehicle-treated and rHu-IL-11 treated rats in the ovariectomy-induced increase in the urinary excretion of pyridinoline and deoxypyridinoline. Neither was there a significant effect of rHu-IL-11 on the plasma concentrations of osteocalcin and on bone mineral density (BMD) measured at a metaphyseal area of the distal femur after 6 weeks. At all dosages tested, rHu-IL-11 increased the femoral diaphyseal area. In conclusion, IL-11 has no deleterious in vivo effect on biochemical parameters of bone remodeling and BMD in estrogen-deficient rats.

Amino Acids↗

PubMed1997

Decreased osteoblast activity in spontaneously diabetic rats. In vivo studies on the pathogenesis.

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 i.v. infusion of glucose (30%, 4 d) did not change OC; s.c. 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 micrograms/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.

Adrenalectomy↗

PubMed1997

Effects of long-term diabetes and/or high-dose 17 beta-estradiol on bone formation, bone mineral density, and strength in ovariectomized rats.

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 high-dose 17 beta-estradiol (E2), 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 E2 (30 micrograms/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 E2 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 (R2 = 0.55; p < 0.0001). E2 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 E2-treated 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.

Animals↗

PubMed1997

Maternal semistarvation and streptozotocin-diabetes in rats have different effects on the in vivo glucose uptake by peripheral tissues in their female adult offspring.

Previous work in humans and rats has revealed a link between perinatal growth retardation and glucose intolerance in adulthood. Both maternal semistarvation and severe diabetes are accompanied by perinatal growth retardation in rats. In this study, we compared the effect of these conditions on tissue glucose uptake in their female offspring. Glucose uptake was measured as glucose metabolic index (GMI), using 2-deoxy-[1-3H]-glucose, in the postabsorptive state and during euglycemic hyperinsulinemia. The GMI was measured in insulin-sensitive tissues (5 skeletal muscles, diaphragm and white adipose tissue) and in two noninsulin-sensitive tissues (duodenum and brain) of adult offspring of normal dams, dams rendered diabetic with streptozotocin on d 11 of pregnancy, and dams fed half normal rations from d 11 of pregnancy. Whole-body insulin resistance, measured by decreased glucose infusion rate during hyperinsulinemia, was milder in offspring of semistarved rats (O-SR) than in offspring of diabetic rats (O-DR). The basal GMI did not differ among the three groups in any tissue except tibialis anterior; during hyperinsulinemia, GMI was significantly greater in the insulin-sensitive tissues of all three groups. GMI of skeletal muscles and adipose tissue during hyperinsulinemia did not differ between control rats and O-SR; in contrast, the GMI was 25-50% lower in skeletal muscles of O-DR during hyperinsulinemia than in those of control rats or O-SR. Thus, maternal semistarvation and diabetes have dissimilar effects on peripheral insulin sensitivity of the adult female offspring. Because both conditions are associated with perinatal growth retardation and fetal hypoinsulinemia, other mechanisms must be identified to explain impaired glucose uptake by skeletal muscles in the offspring of diabetic rats.

Adipose Tissue↗

PubMed1997

Intrauterine tracheal obstruction, a new treatment for congenital diaphragmatic hernia, decreases amniotic fluid sodium and chloride concentrations in the fetal lamb.

OBJECTIVE: To evaluate the effect of fetal tracheal occlusion on sodium and chloride concentrations in amniotic and tracheal fluid. SUMMARY BACKGROUND DATA: Intrauterine tracheal occlusion has been proposed to reverse pulmonary hypoplasia, an important prognostic factor in congenital diaphragmatic hernia. In early human trials, technical failure of the obstructive device has been reported. METHODS: Eight fetal lambs (gestational age = 95 days) were subjected to fetal tracheoscopy, and amniotic and tracheal fluid samples were taken. In multiple pregnancies (n = 6), amniotic fluid was also sampled from the contralateral amniotic sac and used as a control. Subsequently, endotracheal obstruction, using a detachable balloon, was performed. After 14 days, all fetuses were delivered, and sodium and chloride concentrations in amniotic and tracheal fluid were measured again. Statistical analysis was done using a two-tailed Student's t test, paired or unpaired as appropriate. RESULTS: In controls, between 95 and 109 days gestational age, no significant changes occurred in sodium or chloride concentrations in amniotic or tracheal fluid. After 2 weeks of tracheal obstruction, however, chloride and sodium concentrations in amniotic fluid decreased (chloride = 76.7 mEq/L vs. 107.6 mEq/L, p = 0.0003; sodium = 109.6 mEq/L vs. 125.9 +/- 5.2 mEq/L, p = 0.019). A concomitant increase in chloride and sodium concentration was observed in tracheal fluid (chloride = 145.4 mEq/L vs. 130.0 mEq/L, p = 0.047; sodium = 153.1 mEq/L vs. 142.9 mEq/L, p = 0.051). When comparing groups at 109 days, chloride and sodium concentrations in amniotic fluid were markedly lower in the treated group versus controls (p = 0.0004 and p = 0.05 for chloride and sodium, respectively). CONCLUSION: Complete tracheal occlusion in ovine fetuses results in a significant decrease of amniotic fluid sodium and chloride concentrations.

Amniotic Fluid↗

PubMed1996

Effects of recombinant human growth hormone and insulin-like growth factor-I, with or without 17 beta-estradiol, on bone and mineral homeostasis of aged ovariectomized rats.

This study aimed to evaluate whether recombinant human growth hormone (rhGH) or insulin-like growth factor-I (rhIGF-I) can reverse or prevent further bone loss in aged osteopenic ovariectomized (OVX) rats and to compare their effects with those of 17 beta-estradiol (E2). Twelve-month-old rats were OVX, remained untreated for 8 weeks, and subsequently received daily subcutaneous (SC) injections of rhGH (75 micrograms/day), rhIGF-I (250 micrograms/day), E2 (1.5 micrograms/day), and their respective combinations during 8 weeks, and were then compared with sham-operated, pretreatment OVX, and saline-treated OVX rats. A single sc injection of rhGH resulted in peak hGH concentrations after 90 minutes, with a half-life of 124 minutes; the highest plasma IGF-I concentrations were reached 45 minutes after rhIGF-I injection (+57% vs. baseline) with a gradual decline thereafter. Measurements included: biochemical parameters of bone remodeling (plasma osteocalcin and urinary pyridinolines); histomorphometry of proximal tibial metaphysis; DXA of femur; biomechanical analysis of femur and fifth lumbar vertebra (L5); plasma 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), and calbindin-D9K in duodenal mucosa. Whereas all E2-treated OVX rats had much suppressed bone remodeling, rhGH or rhIGF-I had no effect on any biochemical or histomorphometrical parameter of remodeling. The bone mineral density (BMD) at the distal femoral metaphysis as well as parameters of strength at L5 were maintained at pretreatment values in OVX rats treated with E2, GH, or IGF-I, but not in saline-treated OVX rats; their effects were not additive, however. Trabecular bone volume in the tibial metaphysis was also higher in rats treated with these agents than in saline-treated rats, but this was more apparent at the primary than at the secondary spongiosa, suggesting that their mechanism of action is on primary spongiosa formation or breakdown. E2 alone was ineffective to augment the BMD at the femoral diaphysis; however, the diaphyseal BMD was 12-14% higher (p < 0.01) after 8 weeks of GH treatment than in pretreatment or saline-treated OVX rats and sham-operated rats, while IGF-I was less effective than GH, GH or IGF-I treatment had no effect on plasma 1,25(OH)2D3 or duodenal calbindin-D9K concentrations, but the combination of GH or IGF-I with E2 potentiated the effect of E2 to stimulate calbindin-D9K concentrations and urinary calcium excretion, indicating "hyperabsorption hypercalciuria." In conclusion, the administration of rhGH and rhIGF-I, like that of E2, into aged OVX rats prevents further loss of bone mass and strength at sites containing trabecular bone. In addition, rhGH increases cortical bone mass above pretreatment values.

Absorptiometry, Photon↗

PubMed1996

Combined surgery and brachytherapy in the treatment of some cancers of the bladder (partial cystectomy and interstitial iridium-192).

Eighty-five bladder cancers were treated at the Urology Clinic of Nancy and the Centre Alexis Vautrin from 1975 to 1992 with short course preoperative radiation therapy (3 x 3.5 Gy), conservative surgery and brachytherapy by iridium-192. The tumours were classified according to the 1979 UICC pTNM classification. There were 27 pT1, 31 pT2 and 22 pT3, two pT4 and three pTx. The pT1-pT2 cases received only one brachytherapy (50 Gy at least) after the short course preoperative irradiation. The pT3 cases received only 30 Gy of brachytherapy and an external irradiation boost (generally 40 Gy to the node areas and 30 Gy to the tumour, but the dose varied during the time course). Surgery was often preceded by an endoscopic resection consisting of a tumoral resection or a partial cystectomy according to the localisation. The plastic vector tubes were put into place at the time of partial cystectomy. Until 1983 the radioactive wires were loaded into the vector tubes on the day following surgery, thereafter it was done one week later. The 85 patients were classified into two groups: 63 patients who were untreated previously and 22 patients who had received one or more endoscopic resections for recurrences. The median follow-up was 84 months. The local controls at 5 years were 78% in the first group versus 56% in the second group (p = 0.005) with an overall survival of 73 and 65%, respectively. The local control did not vary according to the differentiation (grade 1/2 vs. grade 3). The local control for pT1, pT2, pT3 was 85, 64 and 70% with a specific survival of 85, 76 and 72%, and an overall survival of 78, 66 and 66%. Among early complications, delay in healing of the bladder wall with subsequent vesico-cutaneous fistula depends mainly on the loading time of radioactive wires after surgery and is rare if the loading is delayed by one week. The late complications depend mostly on dosimetric factors. We found 24 grade 1, three grade 2, four grade 3 and one grade 4. The following factors are significant: the surface treated (> 14 cm2), a distance between the sources of more than 2 cm and, especially, activity of the wires of more than 2 mCi/cm (this factor was found in the five complications of grade 3 and 4), the other factors were not significant in univariate analyses.

Brachytherapy↗

PubMed1996

C-peptide, insulin-like growth factors I and II, and insulin-like growth factor binding protein-1 in cord serum of twins: genetic versus environmental regulation.

OBJECTIVE: Our purpose was to examine the regulation of fetal serum concentrations of insulin (C-peptide), insulin-like growth factor-I, insulin-like growth factor-II, and insulin-like growth factor binding protein-1, which are growth-regulating factors in the fetus, in monozygotic and dizygotic twin pairs. STUDY DESIGN: Cord serum samples were collected from 110 twin pairs and compared with 178 nonsibling singleton pairs with the same gestational age. Five twin pairs were excluded from the statistical analyses because of severe intrauterine growth restriction and placental abnormalities in one. Zygosity was assigned by histologic examination of the placenta and by a questionnaire sent to the mother when the twins were > or = 6 months old. Analyses included the calculation of correlation coefficients, between-pair variation, and univariate genetic analysis. RESULTS: Cord serum C-peptide concentrations were highly correlated in monozygotic (r = 0.94) and dizygotic twins (r = 0.79) but not in singleton pairs (r = -0.05); the between-pair variation was also smaller in twins than in singletons. Genetic analysis demonstrated a large contribution of the common environment to the variance in C-peptide concentrations (80%) and a smaller genetic contribution (12%). Insulin-like growth factor-I concentrations were better correlated in monozygotic (r = 0.82) than in dizygotic twins (r = 0.42), with a smaller between-pair variation in the former group (22% +/- 4% vs 51% +/- 5%). Univariate genetic analysis indicated that insulin-like growth factor-I levels were regulated predominantly by genetic mechanisms (93% in boys and 77% in girls). The regulation of insulin-like growth factor-II was more complex, with a gender-specific genetic contribution (50% for both sexes combined, 63% for girls but only 5% for boys). Insulin-like growth factor binding protein-1 was regulated by genetic mechanisms (41%) and the common environment (32%) but also by the specific or unique environment of each fetus (27%). In all five twins with intrauterine growth restriction of one member insulin-like growth factor binding protein-1 concentrations were markedly higher in the growth-restricted fetus. CONCLUSIONS: Insulin secretion in twin fetuses is determined primarily by their common, probably maternal, environment, whereas insulin-like growth factor-I production is predominantly genetically regulated. Insulin-like growth factor-II and insulin-like growth factor binding protein-1 are regulated by both genetic and environmental factors. Of these growth-regulating factors, insulin-like growth factor binding protein-1 appears to be the best marker of intrauterine growth restriction in the individual case.

C-Peptide↗