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Biomedical subjects

V Sharma

Publications and source records attributed to V Sharma.

At least 253 records · Page 14Linked to original sources

Reduced circulating placental protein concentrations during the first trimester are associated with preterm labour and low birth weight.

Serum concentrations of human chorionic gonadotrophin (HCG), Schwangerschaftsprotein 1 (SP-1), pregnancy-associated plasma protein A (PAPP-A), progesterone and oestradiol were measured at weekly intervals between the fifth (embryo transfer plus 3 weeks) and 13th week of gestation during the first trimester of pregnancies achieved following in-vitro fertilization (IVF) and embryo transfer in a group of women who delivered before (n = 8) or at term (n = 52). Those women who had a preterm delivery had significantly lower concentrations of PAPP-A (weeks 7-13; P = 0.0001-0.028) and SP-1 (weeks 6-8 and 10-12; P = 0.004-0.04). After correction of birth weight for sex and gestational age at delivery, preterm delivery was found not to be associated with growth retardation. However, comparison of the circulating concentrations of the substances analysed in mothers who delivered babies of < 85% of the 50th centile of the normal range of birth weight for a given gestational age and sex, with those who delivered babies of > 85% revealed that the concentrations of HCG (P = 0.012-0.04 on weeks 6-9) and SP-1 (P = 0.003-0.03 on weeks 7, 9-13) were significantly lower in the former group. Weak, inconsistent associations were found between the circulating concentrations of HCG, SP-1 and PAPP-A and both corrected birth weight and gestational age at delivery. Thus, both the gestational age at delivery and low birth weight may be related to impaired placental development/function during the first trimester.

Chorionic Gonadotropin↗

Endocrinology of in-vitro fertilization pregnancies during the first trimester.

The endocrine function of the corpus luteum and placenta and the inter-relationships between ovarian steroids and the placental proteins in pregnancies achieved following ovarian stimulation, in-vitro fertilization and embryo transfer (IVF-ET) have been investigated. The serum concentrations of human chorionic gonadotrophin (HCG), Schwangerschaft protein-1 (SP-1), pregnancy-associated plasma protein A (PAPP-A), progesterone and oestradiol were measured at weekly intervals between the 4th (ET plus 2 weeks) and 14th week of gestation in 86 pregnancies. The mean concentrations of the placental proteins and oestradiol were significantly higher in twin than in singleton pregnancies from as early as 5 weeks gestation, but the mean concentrations of progesterone were significantly higher only at the end of the first trimester. Ranking, as demonstrated by the presence of statistically significant correlations between serum levels of each substance analysed in week 13 with those of preceding weeks, was established for progesterone and SP-1 from the 5th week, for oestradiol and PAPP-A from the 7th week and for HCG from the 8th week of gestation. The presence of statistically significant correlations between each substance analysed suggests that the placenta becomes the dominant source of oestradiol from 8 weeks gestation and of progesterone not until 12 weeks gestation, and that the placental synthesis of HCG, SP-1, PAPP-A, oestradiol and progesterone appear to be linked. There were no statistically significant correlations between the serum concentrations of HCG and either progesterone or oestradiol until the production of each had become predominantly placental.

Adult↗

Corpus luteum failure in ectopic pregnancy.

The endocrinology of ectopic pregnancy was studied in order to investigate the origin of the discordance in the circulating amounts of human chorionic gonadotrophin (HCG) and those of oestradiol and progesterone. Serial maternal blood samples were obtained at 4-9 weeks gestation from 93 patients who became pregnant following in-vitro fertilization and embryo transfer including 10 ectopic, 21 anembryonic and 62 normal singleton pregnancies. The samples were analysed for HCG, Schwangerschaft protein-1 (SP-1), pregnancy-associated plasma protein-A (PAPP-A), progesterone and oestradiol. In ectopic pregnancies, concentrations of all substances analysed were significantly reduced compared to singleton pregnancies from 5 weeks gestation (P < 0.05-0.001) but they were not significantly different from those of anembryonic pregnancies. In ectopic pregnancies, associations were found between the concentration of both HCG and SP-1 and those of progesterone and oestradiol. No associations were found between PAPP-A and any other substances analysed. This may be due to insensitivity of the PAPP-A assay; alternatively PAPP-A concentrations may be differentially reduced in ectopic pregnancy. These findings suggest that progesterone and oestradiol are derived from the corpus luteum in early ectopic pregnancy but that the corpus luteum fails rapidly and the dominant source of both hormones becomes the trophoblast as early as 5 weeks.

Chorionic Gonadotropin↗

Interactions between the embryo and corpus luteum.

A total of 102 patients who had become pregnant following in-vitro fertilization (IVF) and embryo transfer were studied at weekly intervals between 4 and 14 weeks gestation. The pregnancies were classified as follows: (i) normal singleton, n = 52; (ii) normal twin, n = 24; (iii) heterotopic, n = 4 (weeks 4-8 only); and (iv) anembryonic with a viable intra-uterine singleton, n = 22. The serum concentrations of human chorionic gonadotrophin (hCG), Schwangerschaft protein-1 (SP-1) and pregnancy-associated plasma protein-A (PAPP-A), oestradiol and progesterone were measured. The mean serum concentrations of HCG, SP-1 and PAPP-A were significantly less in heterotopic than in singleton, singleton/anembryonic or twin pregnancies (P < 0.01-0.05), while those of progesterone and oestradiol were not different at any time. There were no significant differences between the serum concentrations of any of the substances analysed in singleton/anembryonic and singleton pregnancies, but the concentrations of all the substances analysed were significantly greater in twin pregnancies from as early as 7 weeks (P < 0.01-0.05). These data show that in heterotopic pregnancies trophoblast function is reduced, as suggested by the lower concentrations of the placental proteins. Despite this the concentrations of oestradiol and progesterone, derived predominantly from the corpus luteum between 4 and 8 weeks, are equivalent to those found in twin pregnancies, and greater than those found in singleton and singleton/anembryonic pregnancies. These findings support the notion that although HCG may rescue the corpus luteum it does not subsequently have a direct effect on its function, and suggest that the embryo may influence corpus luteum function.

Chorionic Gonadotropin↗

Discriminant validity of attention-deficit hyperactivity disorder.

OBJECTIVE: The primary purpose of this study was to assess the discriminant validity of attention-deficit hyperactivity disorder (ADHD) relative to well-defined groups of children with other psychiatric disorders. METHOD: Clinic-referred patients diagnosed as having ADHD without any other comorbid diagnosis (N = 13), were compared with patients with only anxiety disorders (N = 20), disruptive disorders other than ADHD (N = 15), and nonreferred controls (N = 18) on measures of cognitive and academic functioning, as well as on objective measures of attention, impulse control, and activity level. RESULTS: All three patient groups were found to have cognitive and academic achievement difficulties relative to controls. However, the ADHD group was found to be inattentive and impulsive relative to the other patient groups and the nonreferred controls. Objective measurement of activity level distinguished the ADHD group from controls but not from the other two patient groups. CONCLUSIONS: These data support the diagnostic validity of a small subgroup of ADHD children (i.e., those without comorbid diagnoses) and demonstrates, that as a group, these children can be distinguished from patients with anxiety as well as other disruptive disorders on objective test measures.

Adolescent↗

The role of trophoblast dysfunction in the aetiology of miscarriage.

OBJECTIVE: To investigate the endocrine changes associated with spontaneous miscarriage after fetal heart activity has been demonstrated. DESIGN: Prospective study during the first trimester of pregnancy comparing the circulating levels of human chorionic gonadotrophin (hCG), Schwangerschaft protein 1 (SP-1), pregnancy-associated plasma protein A (PAPP-A), oestradiol (E2), and progesterone (P), and fetal growth (crown-rump length [CRL] and gestational sac volume [GSV]) in women who miscarried after the identification of fetal heart activity with those of normal singleton and twin pregnancies achieved following in vitro fertilisation (IVF) and embryo transfer (ET). SETTING: The Assisted Conception Unit of King's College Hospital, London. SUBJECTS: Nine women who miscarried after demonstration of fetal heart activity, 52 normal singleton and 22 normal twin pregnancies. INTERVENTIONS: Weekly blood tests and ultrasound assessments of CRL and GSV. RESULTS: Four fetuses (all singleton) died between 9 and 12 weeks gestation (Group 1), and seven (three singleton and two twin) died between 16 and 20 weeks gestation (Group 2). In Group 1, both fetal growth and placental function, as assessed by serial measurements of CRL and GSV, and of serum levels of PAPP-A, SP-1 and hCG respectively, were reduced before fetal death. In Group 2, while fetal growth was maintained in all but one case, placental function was reduced in 4 of 5 women. CONCLUSION: These findings suggest that there may be a relationship between trophoblast dysfunction and some forms of miscarriage. Furthermore, the pattern of the reduction in the circulating levels of the placental proteins in later miscarriages suggests that the function of specific cell types may be impaired.

Abortion, Spontaneous↗

Prospective data on the prevalence of abnormal involuntary movements among elderly people living in the community.

Trained raters from the Liverpool Continuing Health in the Community study interviewed 1070 people over the age of 65 in 1982-1983 using the Geriatric Mental State (GMS) examination. Three years later the cohort was re-interviewed, this time by psychiatrists trained in the GMS, who used the GMS and the History and Aetiology Schedule (HAS). The cohort had fallen in size to 875, because of mortality; 701 were re-interviewed. The cohort was followed up again 6 years after the first interview by trained nurse raters using the GMS (A3) and the Mini-Mental State Examination. Cases of mental disorder identified by the computer diagnostic program AGECAT were re-interviewed by psychiatrists along with a number of controls using the GMS and the HAS on the remaining 450 individuals. Observational behavioural ratings from the GMS and summary sheets were analysed along with AGECAT diagnoses and data on medication gained at the 3 assessments. The community prevalence of tardive dyskinesia and other movement disorders in elderly people over a 6-year follow-up appears to be very low (the community prevalence of tardive dyskinesia being 0.22% and akathisia 1.57%), is usually associated with organic mental disorder (and consequently higher mortality) and is furthermore not usually associated with antipsychotic medication.

Aged↗

Menaquinone (vitamin K2) biosynthesis: cloning, nucleotide sequence, and expression of the menC gene from Escherichia coli.

The benzenoid aromatic compound o-succinylbenzoic acid is formed by dehydration of the prearomatic compound 2-succinyl-6-hydroxy-2,4-cyclohexadiene-1-carboxylic acid by the enzyme o-succinylbenzoate synthase, encoded by the menC gene. A 1.3-kb PstI-PvuII fragment was found to complement the menC mutation. The complete nucleotide sequence of this fragment revealed a single open reading frame of 954 bp capable of encoding a 35-kDa protein. A consensus sequence for a ribosomal binding site but no promoter consensus sequences were found. However, the first base of the initiating codon of this open reading frame overlaps the upstream menB gene termination codon, suggesting an operon-like organization for these genes. Consistent with this suggestion, the menB promoter can initiate transcription of the menC gene.

Amino Acid Sequence↗

Genetic and molecular analyses of the C-terminal region of the recE gene from the Rac prophage of Escherichia coli K-12 reveal the recT gene.

The nucleotide sequence of the C-terminal region of the recE gene of the Rac prophage of Escherichia coli K-12 reveals the presence of a partially overlapping reading frame we call recT. Deletion mutations show that recT is required for the RecE pathway of conjugational recombination. By cloning recT with a plasmid vector compatible with pBR322, we showed by cis-trans tests that the portion of the recE gene encoding ExoVIII DNA nuclease activity is also required for RecE pathway conjugational recombination. The recT gene can replace the redB gene of lambda for recA-independent plasmid recombination. A Tn10 insertion mutation previously thought to be in recE is located in recT and is renamed recT101::Tn10. Discrepancies between the molecular mass estimates of wild-type ExoVIII protein determined from mobility in sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and calculated from the predicted amino acid sequence are discussed. The hypothesis that wild-type ExoVIII protein results from fusion of RecE and RecT proteins is disproved genetically, thus supporting a previous hypothesis that the discrepancies are due to abnormal protein mobility in SDS-PAGE. A computer-performed scan of the bacteriophage nucleotide sequence data base of GenBank revealed substantial similarity between most of recE and a 2.5-kb portion of the b2 region of lambda. This suggests interesting speculations concerning the evolutionary relationship of lambda and Rac prophages.

Amino Acid Sequence↗

Treatment of rapid cycling bipolar disorder with combination therapy of valproate and lithium.

Over the past two decades there has been a great deal of interest in the use of anticonvulsants to treat a variety of primary psychiatric disorders. Valproate, one such anticonvulsant, has been found to be effective in the treatment of acute mania, mixed states and rapid cycling disorders. This paper presents the results of an open study with combination therapy of valproate and lithium in a series of nine patients (mean age = 50 years). These patients had previously been treated with various psychotropic agents, including a combination of carbamazepine and lithium. All but one patient showed marked or moderate improvement in their condition. Of particular interest was the observation that in three patients there was evidence of augmentation between valproate and lithium during the depressed phase of their illness. There was significant improvement in their depression within 24 to 48 hours of the addition of lithium to valproate. The combination therapy was very well-tolerated. It is concluded that valproate and lithium combination therapy provides a safe and effective alternative for the treatment of rapid cycling variant of bipolar illness.

Adult↗

A study of disposal of hospital wastes in a rural teaching hospital.

The present study was carried out in order to observe and analyse the waste disposal patterns in a 500 bedded, multidisciplinary hospital located in a rural area. The hospital under study is a teaching hospital attached to a Medical college and has been functioning for over ten years. Data were collected by means of pre-structured interviews and on-the-spot observations of the various stages in the waste disposal chain. It was observed that the hospital does not have a documented wastes management and disposal policy. The disposal of wastes is not properly supervised and is exclusively entrusted to the junior most staff from the house keeping department. The disposal of all categories of hospital wastes, in general, leaves much to be desired and even pathological wastes were observed to be disposed off, on the open ground with scant regard to aesthetic considerations. Both the internal as well as external transportation of hospital wastes were found to be far from satisfactory.

Data Collection↗

Steroid withdrawal, rejection and the mixed lymphocyte reaction in children after renal transplantation.

With improved long-term graft survival after renal transplantation, cardiovascular mortality is emerging as the leading cause of death in adults and is also being reported in children. Chronic corticosteroid therapy is thought to be an important cause of post-transplant hyperlipidemia and hypertension. This study describes a steroid withdrawal protocol initiated to reduced cardiovascular risk factors in pediatric renal allograft recipients, reports on the rate of rejection observed and the use of an in vitro method to measure immunoresponsiveness and identify those patients who have not experienced a rejection episode. Thirty-six of 67 patients were able to discontinue prednisone and were maintained on cyclosporine alone. Twenty-two of the 36 patients experienced an acute rejection episode a mean of 14 months (range 1.5 to 36 months) after completion of the steroid taper. Ten of the 22 rejections occurred within 12 months after completion of the taper. Fourteen patients remain rejection free to date for a mean of 70.3 months (range 19 to 111 months) after withdrawal. Using the mixed lymphocyte culture reaction, we tested the hypothesis that steroid dependent recipients (SDR) will express donor antigen specific responsiveness and steroid independent recipients (SIR) will exhibit donor antigen-specific tolerance. Four of seven SDR were tolerant to donor specific antigens but responsive to unrelated controls, while five of six SIR were responsive to donor specific antigens. These unanticipated results highlight the complexity of allograft tolerance.

Child, Preschool↗

Late radiation induced laryngeal oedema in the treatment of vocal cord cancer: analysis using the linear quadratic model.

The incidence of late complications for different size of dose per fraction is analysed in 208 cases with squamous cell carcinoma of the vocal cord. The series comprised 156 cases with T1 and 52 cases with T2 lesions. Radical radiotherapy was given with three different regimens having dose per fraction as 3.33, 2.5 and 2.25 Gy. There were 46 cases with persisting radiation induced laryngeal oedema. Using two different statistical methods, an alpha/beta value of 2.38 Gy of linear quadratic model was estimated for late complications of vocal cord. The analysis indicate the increased incidence of late complications with size of dose per fraction. Relevance of linear quadratic model for the prediction of late complication is demonstrated in the present study.

Carcinoma, Squamous Cell↗

Brofaromine in depression: a Canadian multicenter placebo trial and a review of standard drug comparative studies.

Brofaromine is a new, reversible, and selective type-A monoamine oxidase inhibitor (MAOI) that also has serotonin reuptake inhibitory properties. Its dual pharmacologic effects offer promise in the treatment of a wide spectrum of depressed patients while producing less severe anticholinergic side effects in comparison with standard drugs. A multicenter, double-blind, placebo-controlled study including 220 patients was undertaken to evaluate the efficacy and safety of brofaromine in major depression. This study of a fixed-dose design and 6 weeks' duration found that brofaromine was significantly better than placebo on the Overall Evaluation of Efficacy, Beck self-rating scale, HAM-D Bech subscale, HAM-D total 14 items (minus the three sleep items), HAM-D depressed mood item and retardation factor, and worse than placebo on the insomnia items of HAM-D. Significantly more patients on placebo than on brofaromine did not complete the trial due to lack of efficacy. In comparative controlled studies (n = 899), brofaromine was found to be at least as efficacious as tricyclic antidepressants (imipramine) and standard MAOIs (tranylcypromine and phenelzine). Reductions of at least 50% in the HAM-D total score were seen in 58-66% of patients treated with either brofaromine or imipramine (n = 609). Brofaromine also was found to be of comparable efficacy to tranylcypromine in two clinical trials (n = 132), one of which included patients considered to have a treatment-resistant depression (n = 39). In another double-blind study that compared brofaromine (150 mg/day) to phenelzine (45 mg/day) (n = 158), there was no difference between brofaromine and phenelzine.

Adolescent↗