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Biomedical subjects

N S Panesar

Publications and source records attributed to N S Panesar.

At least 37 records · Page 2Linked to original sources

Increased bone resorption and decreased bone formation in Chinese patients with hip fracture.

Biochemical markers of bone formation (bone-specific alkaline phosphatase and osteocalcin) and bone resorption (hydroxyproline excretion and bone isoenzyme of acid phosphatase) were measured in 30 patients (15 M and 15 F) with hip fracture and 30 healthy subjects matched for age and sex. Bone isoenzyme of tartrate-resistant acid phosphatase (TRACP) was measured by a recently developed specific immunoassay. Serum osteocalcin concentration and bone-specific alkaline phosphatase activity were significantly lower and serum TRACP concentration and urinary hydroxyproline excretion were elevated in patients compared with healthy subjects. We suggest that there is reduced bone formation and increased bone resorption in patients with hip fracture.

Acid Phosphatase↗

Immunoassay of a tartrate-resistant acid phosphatase in serum.

A tartrate-resistant acid phosphatase (TRACP) was purified from cord plasma by use of cation-exchange chromatography (carboxymethyl Sepharose), gel-filtration chromatography (Sephacryl S-200), and preparative isoelectric focusing. After raising polyclonal antibodies to the purified TRACP in rabbit, we used the antiserum to develop an ELISA. The antiserum cross-reacted with an extract of bone, but not with extracts of spleen, erythrocytes, platelets, or osteoblasts or with prostatic acid phosphatase. With this ELISA we determined the concentration of serum TRACP in healthy men to be 197 (61-301) micrograms/L (median and range). Serum TRACP concentrations were significantly higher in children and postmenopausal women and in patients with chronic renal failure, hyperparathyroidism, or hyperthyroidism. Estrogen replacement therapy of postmenopausal women for 3-6.5 months decreased their serum TRACP concentration by 70%.

Acid Phosphatase↗

Bufalin radioimmunoassays: in search of the endogenous digitalis-like substance.

The existence of a mammalian natriuretic substance similar to plant digitalis, which inhibits Na,K-ATPase, has been speculated about, but as yet no definite substance has been found. Digoxin-like immunoreactive substance (DLIS) has been reported in various clinical states including new born infants. Using bufalin (a cardioactive substance of animal origin) as antigen, four polyclonal antisera have been produced from 2 separate rabbits and characterised for cross-reactivity with 32 compounds. One antiserum showed a marked change in its cross-reactivity after resting the animal for a year. Of the endogenous substances tested, progesterone was found to be the most cross-reactive. Radioimmunoassay of foetal cord sera with different antisera, gave different levels of bufalin-like immunoactivity. However, after a novel "affinity-immunoassay" procedure, this apparent bufalin-like immunoactivity disappeared. It is concluded that bufalin-like immunoactivity in the cord blood is caused by the cross-reaction of endogenous steroids with bufalin antiserum, and the same may be true for DLIS.

Animals↗

Thyrotropin stimulation of the lutropin/choriogonadotropin receptor: different sites mediate agonist activity and high affinity binding.

Surprisingly, thyrotropin (TSH) can increase cAMP and inositol phosphate (IP) levels in Cos-7 cells transfected with the lutropin (LH)/choriogonadotropin (CG) receptor (LH/CGR) as well as LH or CG, as evidenced by similar EC50 and maximal stimulation values. Additionally surprising, TSH activation is evident, despite markedly reduced levels of high affinity TSH binding by comparison to CG (Hidaka A, et al. 1993 Biochem Biophys Res Commun 196:187-195). In this report, we questioned whether the unusual TSH activity, as well as the discrepancy between TSH activity and binding, might reflect the existence of distinct agonist and binding sites on the LH/CGR extracellular domain and the ability of TSH to interact with the former despite a minimal interaction with the latter. We evaluated this possibility by using two chimeras spanning the extracellular domain of the TSHR and the LH/CGR:Mc1 + 2, where residues 8-165 of the TSHR are substituted, and Mc2 + 3 + 4, where residues 90-370 are replaced with the corresponding peptide segment from the LH/CGR. After transfection in Cos-7 cells, Mc2 + 3 + 4 exhibits higher affinity for CG than wild-type LH/CGR, but has no CG agonist response in assays measuring cAMP or inositol phosphate (IP) levels. Conversely, the Mc1 + 2 chimera exhibits significantly decreased affinity for CG, but CG agonist activity is comparable to wild-type LH/CGR in cAMP and IP assays. These data show that the extracellular domain of the LH/CGR does have distinct sites for CG binding and agonist activity: the C-terminus in Mc2 + 3 + 4 is important for high affinity CG binding, whereas the N-terminus in Mc1 + 2 is able to exhibit a CG agonist response, despite low affinity binding. When evaluated using TSH, Mc1 + 2, with the C-terminus of the TSHR present, exhibits high affinity TSH binding comparable to wild-type TSHR. Unexpectedly, Mc1 + 2, with the substitution of the N-terminus of the extracellular domain of the LH/CGR, exhibits even better TSH agonist activity than wild-type TSHR, not a loss of activity. Thus, the N-terminus of the extracellular domain of the LH/CGR can couple TSH binding to signal transduction events even better than the N-terminus of the TSHR. This may, in part, explain why TSH has an unusual agonist activity in cells transfected with LH/CGR, despite relatively low affinity binding. Although distinct agonist and binding sites exist in the linear sequence of the extracellular domain, the activity of the two sites is interdependent.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

17 alpha-Hydroxylase deficiency with persistence of müllerian ducts in a genotypic male and paradoxical aldosterone secretion.

We report a case of congenital adrenal hyperplasia due to 17 alpha-hydroxylase deficiency in a Chinese genotypic male patient. Despite the male genotype, normal female external genitalia were present and with the introduction of cyclical oestrogen therapy withdrawal bleeding occurred, confirming the presence of functional endometrial tissue. We believe this to be the first report of persistent Mullerian duct structures in a genotypic male with 17 alpha-hydroxylase deficiency. It could be explained by either impaired secretion or impaired action of anti-Mullerian hormone. Further, contrary to the usual finding of suppressed aldosterone secretion, this patient had measurable levels of plasma aldosterone.

Adolescent↗

Transient neonatal hyperthyrotropinaemia.

Of 48 consecutive newborns with elevated umbilical venous plasma thyrotropin (TSH) concentration, only two (4%) were subsequently proved to have congenital hypothyroidism, while the other 46 had transient elevation of TSH. Compared with matched controls, these 46 newborns were all delivered vaginally (P less than 0.0003) and had a longer second stage of labour (P less than 0.002), together with higher incidences of nuchal encirclement of the cord (P less than 0.05) as well as female babies (P less than 0.05). There was no difference in the incidence of antenatal complications, mean gestational age, birth weight, or birth asphyxia. There were no small-for-gestational age infants in the study group, while four were found in the controls. The results indicate that elevated umbilical cord plasma TSH concentration may represent a response to the stress of difficult or complicated delivery in the healthy appropriate- or large-for-gestational age newborn who does not have congenital hypothyroidism.

Delivery, Obstetric↗

The contribution of steroids to digoxin-like immunoreactivity in cord blood.

Samples of cord serum from 29 healthy neonates were analysed for digoxin-like immunoreactive substance (DLIS), cortisol, 17 beta-oestradiol, progesterone, dehydroepiandrosterone-sulphate (DHEAS), 17 alpha-hydroxyprogesterone (17OHP), androstenedione, oestriol and ouabain-like activity (OLA; by inhibition of Na+, K+ATPase activity). The mean serum concentration of DLIS was 0.91 (SD = 0.19) nmol/L and the mean OLA was 26.1 (SD = 11.5) nmol/L. There was no correlation between DLIS and OLA. DLIS correlated significantly with oestriol (r = 0.521), progesterone (r = 0.534) and 17OHP (r = 0.43). Stepwise multiple regression analysis showed that 17 beta-oestradiol, progesterone and androstenedione contributed to DLIS and the intercept was 0.64 (SD = 0.127). The concentrations of steroids (17 beta-oestradiol, progesterone, androstenedione) required to displace digoxin by 50% in the digoxin immunoassay and inhibit Na+,K+ATPase in the OLA assay were 10(3)-10(4)-fold higher than those found in cord serum. We conclude that the contribution of these steroids to DLIS is small and that DLIS and OLA measure different compounds.

Cross Reactions↗

Nephrogenous cyclic AMP in primary hepatocellular carcinoma patients with or without hypercalcaemia.

OBJECTIVE: To study the relationship between the excretion of nephrogenous cyclic AMP (NcAMP) and other blood and urine parameters as an index of PTH-like activity in patients with primary hepatocellular carcinoma. DESIGN: After overnight fast, a double voided urine and a blood sample were collected from each subject for determination of various analytes and results compared between various groups. PATIENTS: Fifty-five consecutive untreated patients with primary hepatocellular carcinoma, 14 healthy controls and eight patients with cirrhosis only. MEASUREMENTS: Serum calcium, phosphate, alkaline phosphatase, albumin, creatinine and urinary calcium, creatinine and hydroxyproline were measured by routine methods. cAMP was measured in plasma and urine by a radioimmunoassay (Diagnostic Products Corporation) and PTH measured in serum by an immunoradiometric assay (Nichols Institute). TmP/GFR, NcAMP etc. were calculated according to various published methods. RESULTS: Four out of 55 patients (7%) with primary hepatocellular carcinoma had hypercalcaemia. These four patients had significantly lower (P less than 0.05) phosphate, PTH and TmP/GFR and elevated NcAMP (P less than 0.001) compared with normocalcaemic hepatocellular carcinoma and cirrhotic patients, and healthy controls. The excretion of hydroxyproline and calcium was significantly elevated (P less than 0.001) in the hypercalcaemic patients. Bone resorption was found to be the major cause of hypercalcaemia in three of the four hypercalcaemic patients. Fifteen hepatocellular carcinoma patients (29%) with normocalcaemia had suppressed PTH. CONCLUSION: We conclude that a PTH-like humoral factor such as PTH related peptide is the cause of hypercalcaemia in patients with primary hepatocellular carcinoma, and that in some normocalcaemic patients with this tumour PTH is suppressed.

Adult↗

Salivary oestradiol and progesterone after in vitro fertilization and embryo transfer using different luteal support regimens.

Salivary oestradiol (E2) and progesterone (P) levels have been shown to reflect the biologically active fractions in the serum. The luteal-phase status of stimulated cycles was investigated after in vitro fertilization and embryo transfer (IVF-ET). Thirty patients were randomly allocated to one of three luteal therapy groups: group A had no support, group B had intramuscular P and group C had intramuscular P and human chorionic gonadotrophin (hCG). One pregnancy was achieved in group A, two in group B and three in group C. Significant correlations between salivary and serum levels of E2 and of P in matched samples during luteal phase were found. Salivary E2 levels from luteal day 8 through day 14 and P levels from day 3 through day 14 were significantly higher in the pregnant than in the nonpregnant cycles. Among the nonpregnant cycles, salivary E2 and P levels were significantly higher in group C than in group A or B. These findings suggest that, in stimulated cycles for IVF-ET, determination of salivary E2 and P levels may be used as reliable alternatives to serum concentrations for assessing the luteal phase. Also, the additional hCG has an enhanced luteotrophic effect, as reflected by the higher salivary E2 and P levels, which may lead to a better pregnancy rate.

Chorionic Gonadotropin↗

Paediatric glucose homeostasis during anaesthesia.

The perioperative blood glucose regulatory response was compared in 20 healthy children (aged 1-5 yr) presenting for minor surgery and allocated randomly to either a fasted or a glucose group. All children received a milk feed at midnight. The fasted group received no oral intake thereafter, whereas the glucose group received 5% dextrose water 10 ml kg-1 orally about 4 h before operation. The mean plasma glucose concentrations in the two groups were similar before operation and were within normal limits. The pattern of change in the concentrations of plasma glucose, insulin, cortisol, growth hormone and glucagon were also similar between the two groups. Ten percent of patients in the fasted group and 33% in the glucose group had gastric aspirates in excess of 0.4 ml kg-1. The pH of all gastric samples was less than 2.5. The results suggest that healthy preschool children were able to maintain glucose homeostasis after 8 h of fasting. Feeding within 4-6 h before surgery may increase the risk of pulmonary aspiration.

Anesthesia, Inhalation↗

Controlled ovarian hyperstimulation for in vitro fertilization using buserelin and gonadotropin in patients with previous failed cycles.

Fifteen patients who had had previous unsuccessful in vitro fertilization and embryo transfer (IVF) cycles were treated with intranasal buserelin, a gonadotropin releasing hormone agonist (GnRH-a), commencing in the mid-luteal phase prior to ovarian stimulation in the next cycle. The use of buserelin was associated with the suppression of spontaneous luteinizing hormone (LH) surges (nil versus 6), an increase in gonadotropin requirements (27.3 versus 13.7 ampoules), higher serum estradiol peak levels (8, 154 versus 4,446 pmol/l), more oocytes retrieved (87 versus 20) as well as more embryos being transferred (28 versus 7). In buserelin-treated cycles, 2 pregnancies resulted but no oocyte was recovered in 2 of the 3 poor responders.

Adult↗

The effect of labour on prolactin and cortisol concentrations in the mother and the fetus.

Concentrations of prolactin and cortisol were determined in maternal and umbilical cord serum of women delivered by elective Caesarean section and by vaginal delivery. There was no difference in the concentration of prolactin in the two groups of women. Similarly, cord blood prolactin concentrations were not significantly different in the two groups. Cortisol concentrations in the women undergoing Caesarean section were similar to the vaginal delivery group before the onset of labour. However, there was a significant increase in cortisol concentration at delivery following labour. The cord blood cortisol concentration was significantly higher in the neonates delivered vaginally, and it correlated with the maternal cortisol concentration at delivery. The relevance of these findings is discussed.

Cesarean Section↗

Neonatal thyrotrophin and mode of delivery.

This study was performed to assess the association between labour and the mode of delivery with the umbilical cord plasma thyroxine (T4) and thyroid-stimulating hormone (TSH) concentrations in full-term uncomplicated pregnancies delivered in our hospital. Babies born vaginally had statistically significantly higher umbilical cord plasma TSH but similar T4 concentrations than babies born by caesarean section. Labour was not associated with either higher TSH or T4 concentrations. All the babies with an elevated TSH concentration (greater than 20 miu/l) were born vaginally. Our findings indicate that the mode of delivery should be taken into consideration in the interpretation of umbilical cord plasma TSH results.

Birth Weight↗

Birth weight and thyroxine-binding globulin in pre-eclampsia.

Plasma concentrations of thyroxine (T4) and thyroxine-binding globulin (TBG) as well as triiodothyronine uptake (T3U) were measured in 32 proteinuric pre-eclamptic patients and 24 normotensive pregnant women at similar gestations in the third trimester. The pre-eclamptic patients had slightly lower TBG, and significantly lower T4, concentrations, which were significantly correlated. They also had significantly lower infant birth weight which was correlated to the TBG and T3U values. There was no correlation between T4 and TBG or between birth weight and TBG or T3U in the normotensive women. It is likely that the correlation between TBG and birth weight in the pre-eclamptic patients reflects the severity of proteinuria in pre-eclampsia.

Alpha-Globulins↗

Thyroid function in hyperemesis gravidarum.

Plasma total T4 (TT4), T3 (TT3), free T4 (FT4), free T3 (FT3), thyroxine binding globulin, hCG, and erythrocyte zinc content were measured in 43 women with uncomplicated pregnancy and in 71 patients admitted with hyperemesis gravidarum. Plasma concentration of thyroid hormones in hyperemesis subjects showed wide variability and 32% of subjects had high TT4 (higher than mean +2 SD of normal pregnant subjects), 33% had high FT4, 20% had high TT3, and 20% had high FT3. Red cell zinc content, a tissue marker of thyroid status, in the hyperthyroxinemic subjects was not different from that of normothyroxinemic hyperemesis subjects or of subjects with uncomplicated pregnancy. The elevated TT4 concentration decreased spontaneously in all but two of the hyperemesis subjects to normal pregnant levels. The plasma FT4 concentration at presentation correlated with plasma hCG in hyperemesis gravidarum (partial correlation coefficient r = 0.411, P less than 0.01), but not in normal pregnancy (partial correlation coefficient r = 0.043) after allowing for the effect of gestational age. We conclude that approximately one third of hyperemesis subjects show transient hyperthyroxinemia and suggest that hCG or a molecular variant of hCG may stimulate the thyroid gland.

Adult↗