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Introduction: The lesser trochanter profile (LTP) method is an intraoperative fluoroscopic technique that can assess the femoral version and limit malrotation. The purpose of this study was to directly assess the accuracy and reliability of the LTP method, as well as determine the incidence of malrotation produced by this technique. Methods: Three groups of observers (fellowship-trained orthopedic surgeons, orthopedic residents, and medical students) utilized the LTP method to replicate pre-imaged rotation angles on a cadaveric femur bone. Recorded outcomes include rotational error and number of attempts. Accuracy and interobserver reliability were assessed by rotational error and the interclass correlation coefficient (ICC), respectively. Results: Accuracy was within 3° for all three groups. ICC between each group was greater than 0.99. There was no statistical difference between the accuracy of fellowship-trained surgeons, orthopedic residents, and medical students. Medical students on average required more attempts to obtain their final image compared to fellowship-trained surgeons. There was no statistical difference in the number of attempts between residents and fellowship-trained surgeons. Conclusion: None of the LTP measurements were greater than 15°, the clinical threshold for malrotation. The average error of the observers was less than 3°, demonstrating that the LTP is an effective method of assessing the femoral version. There was no statistically significant difference between the observers, indicating that this technique is reliable and easy to use. Ultimately, the LTP method is easily reproducible for surgeons to avoid femoral malrotation.

The development of next-generation polymers necessitates optimizing several key properties simultaneously, a task that is expensive and infeasible using traditional trial-and-error experimental approaches. A promising alternative is employing a combination of machine learning and physics-based tools to rapidly screen the polymer design space and provide suggestions of new polymers that meet the critical properties required for industrial applications. In this study, we introduce a comprehensive workflow that utilizes machine learning and molecular modeling approaches to design new polymers with the focus on improving five polymer properties: (1) glass transition temperature, (2) dielectric constant, (3) refractive index, (4) stress optic coefficient, and (5) linear coefficient of thermal expansion. Using a small dataset ( $ \lt$ 200 unique polymers), we developed quantitative structure-property relationships (QSPRs) models to accurately predict the experimental polymer properties for both homo- and co-polymer systems. We tested several ML algorithms and identified the best models for predicting these polymer properties, achieving test set R ^2 greater than 0.77 across all properties. We then explored new polymers by creating a library of over ∼10 000 homopolymers using R-group enumeration tools and applied the trained QSPR models to rapidly predict the five polymer properties. The predictions of QSPR models were used to create a multi-parameter optimization score, which helped downselect the large polymer space to ∼10 promising candidates. The properties of these selected polymer candidates were subsequently validated with classical molecular dynamics simulations and density functional theory, revealing a strong correlation with the QSPR model predictions. Finally, one of the top candidates was validated by experiments, which showed good agreement against QSPR and physics-based models. Our workflow underscores the power of combining data-driven and theoretical methods in the polymer design process given a small dataset size, offering a valuable resource for experimentalists looking to leverage computer-aided strategies in materials innovation.

Introduction: The purpose of this study is to report on infection with anterior subcutaneous internal pelvic fixation (INFIX) for pelvic ring injuries and the outcomes of treatment. Methods: An IRB-approved retrospective study was performed using trauma databases of a level one and level two trauma center from 2012–2018. Infection after the INFIX procedure was diagnosed in 10 of 179 cases. Treatment included formal irrigation and debridement, removal of the hardware, and culture-specific antibiotics. Patients were followed for a minimum of 12 months. Recorded outcomes include X-rays, Majeed scores, and the presence of any loss of reduction using reduction parameters. Results: Time to detect the infection was 54.2 ± 24.3 days (range 24–90, median 56 days). Staphylococcus aureus was the most common bacteria isolated. The average follow-up was 830 ± 170 days (range 575–1088 days). All patients went on to the radiographic union. There were no recurrent infections or osteomyelitis at the latest follow-up. Patients maintained their reduction after INFIX removal (KI), and Majeed scores ranged from 72 to 96 (seven good, three excellent). Discussion: Infections after using the INFIX procedure were dealt with by irrigating and debriding the wounds, removing the INFIX with culture-specific antibiotics for 2–6 weeks. Implants were maintained for at least 25 days, and there was no loss of reduction. There were no long-term sequelae noted in this small series or the literature review included in this paper.

The placement of anterior column screws is a useful procedure and has standard views when placing this screw in the supine position. Feng et al. described an acetabular anterior column axial view for patients in the supine position for a placement of a retrograde anterior column screw [J Orthop Surg (Hong Kong) 25, 2309499016685012]. However, many acetabular fracture surgeries are performed in the lateral decubitus position due to a variety of reasons. Placing an antegrade anterior column screw in this position is difficult due to an unfamiliarity of the optimal fluoroscopic images. The purpose of this article is to describe a novel technique to obtain appropriate imaging to safely place an anterior column screw while the patient is in the lateral decubitus position.

Introduction: Locked intramedullary nailing (IMN) is the standard treatment for femoral shaft fractures in adults with high rates of union and relatively low rates of complications. Leg length discrepancy (LLD) after IMN of femoral shaft fractures is common, and is reported in 20–43% of cases. A known surgical challenge when trying to obtain equal leg lengths is comminuted fracture, which results in a loss of bony landmarks that guide reduction. The purpose of this study was to assess the effect of inherent tibial asymmetry on LLD measurements after IMN. Methods: Postoperative CT scanograms were performed on 79 consecutive patients after locked IMN for comminuted femoral shaft fracture. Leg lengths were determined by measurements taken from the scout view of a CT scanogram. Calculations of discrepancy were made for both femurs, tibias, and total leg length. Assessment was also made on the frequency wherein the tibial discrepancy compounded the femoral discrepancy. In situations where a limb segment was exactly symmetric to the contralateral side, the total leg was not regarded as a having compounded asymmetry. Results: Notable discrepancies were found in tibial length that significantly departed from the null of symmetry (p < 0.0001). Forty-two patients (53.2%) were found to have a tibial asymmetry of 3 mm or more, and 20 patients (25.3%) were found to exhibit a difference of 6.3 mm or more. Median femoral discrepancy was 5.3 mm and median tibial discrepancy was 3.0 mm. Seven patients were found to be asymmetric in total leg length as a consequence of underlying tibial asymmetry. Conversely, 11 patients benefited from their tibial asymmetry, which compensated for femoral asymmetry after IMN. Conclusion: Tibial symmetry cannot be assumed. If not accounted for, inherent tibial asymmetry may influence LLD after IMN of femur fractures.

Abstract Background We have recently developed a subcutaneous anterior pelvic fixation technique (INFIX). This internal fixator permits patients to sit, roll over in bed and lie on their sides without the cumbersome external appliances or their complications. The purpose of this study was to evaluate the biomechanical stability of this novel supraacetabular pedicle screw internal fixation construct (INFIX) and compare it to standard internal fixation and external fixation techniques in a single stance pelvic fracture model. Methods Nine synthetic pelves with a simulated anterior posterior compression type III injury were placed into three groups (External Fixator, INFIX and Internal Fixation). Displacement, total axial stiffness, and the stiffness at the pubic symphysis and SI joint were calculated. Displacement and stiffness were compared by ANOVA with a Bonferroni adjustment for multiple comparisons Results The mean displacement at the pubic symphysis was 20, 9 and 0.8 mm for external fixation, INFIX and internal fixation, respectively. Plate fixation was significantly stiffer than the INFIX and external Fixator (P = 0.01) at the symphysis pubis. The INFIX device was significantly stiffer than external fixation (P = 0.017) at the symphysis pubis. There was no significant difference in SI joint displacement between any of the groups. Conclusions Anterior plate fixation is stiffer than both the INFIX and external fixation in single stance pelvic fracture model. The INFIX was stiffer than external fixation for both overall axial stiffness, and stiffness at the pubic symphysis. Combined with the presumed benefit of minimizing the complications associated with external fixation, the INFIX may be a more preferable option for temporary anterior pelvic fixation in situations where external fixation may have otherwise been used.

Introduction: Hyperinsulinemia in the absence of impaired glucose tolerance and normal HbA1c is considered indicative of pre-diabetes. Very few Indian studies have focused on hyperinsulinemia particularly in young adults. The present study aimed to determine whether hyperinsulinemia may be present despite HbA1c being normal., Methods: This was a cross-sectional study conducted on adolescents and young adults aged 16-25 years living in Mumbai, India. The participants attended various academic institutions and were those who underwent screening as the first step of a clinical trial for studying the efficacy of almond intake in prediabetes., Results: Among this young population (n=1313), 4.2% (n=55) of the participants were found to be prediabetic (ADA criteria) and 19.7% of them had HbA1c levels between 5.7%-6.4%. However, almost, 30.5% had hyperinsulinemia inspite of normal blood glucose levels and normal HbA1c. Among those with HbA1c<5.7 (n=533), 10.5% (n=56) participants had fasting insulin>15 mIU/L and a higher percentage (39.4%, n=260) had stimulated insulin above 80 mIU/L. These participants had higher mean anthropometric markers than those with normal fasting and/or stimulated insulin., Conclusion: Hyperinsulinaemia in the absence of impaired glucose tolerance and normal HbA1c may provide a much earlier indicator of detection for risk of metabolic disease and progression to metabolic syndrome and diabetes mellitus., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Vaidya, Desai, Moitra, Salis, Agashe, Battalwar, Mehta, Madan, Kalita, Udipi and Vaidya.)

Background & Objectives: Polycystic Ovary Syndrome (PCOS) is becoming an area of global and national health concern. It requires a life cycle approach from adolescence to menopause. To comprehensively address the wide spectrum of this disorder, a multidisciplinary model of care was established for women with PCOS in a government setting in India with an objective to screen and manage multifaceted manifestations of PCOS and to diagnose and treat associated comorbidities such as metabolic syndrome, dermatologic manifestations and psychological issues., Methods: A model of integrated multidisciplinary PCOS clinic was implemented for services and research at ICMR-National Institute for Research in Reproductive and Child Health (NIRRCH), Mumbai Maharashtra, India. This is a one-stop holistic centre for managing menstrual, cosmetic, infertility, obesity, metabolic and psychological concerns of women affected with PCOS. Two hundred and twenty six women diagnosed with PCOS using the Rotterdam criteria were screened for metabolic comorbidities with anthropometry, ultrasonography, hormonal and biochemical tests and for psychological problems. Analysis was performed using SPSS version 19.0., Results: Mean body mass index (BMI) was 26.1 kg/m 2 , higher for Asians. Hirsutism was observed in 53.6 per cent of women. Metabolic syndrome was seen among 35.3 per cent and non-alcoholic fatty liver in 18.3 per cent. Psychological issues such as anxiety and depression were identified in majority of the women 31.4 per cent of women could achieve pregnancy at the end of one year of multidisciplinary management., Interpretation & Conclusions: The results of the present study suggest that an integrated multidisciplinary approach led to the early identification and treatment of comorbidities of PCOS, especially metabolic syndrome. There is hence an urgent need to implement multidisciplinary PCOS clinics in government health facilities.

Context: Dalbergia sissoo had shown anti-osteoporotic and fracture-healing activities in animal models of postmenopausal osteoporosis (PMO). Standardized extract of leaves of D. sissoo (SEL-Ds) was clinically evaluated for osteoporosis., Aims: To investigate the anti-osteoporotic activity of D. sissoo in PMO by dual-energy X-ray absorptiometry (DXA), biochemical markers, and effect on clinical profile. Tolerability was assessed by organ function tests and adverse events., Settings and Design: An open-labeled prospective clinical study in ambulant settings was conducted at the menopausal health-care facility of a women's hospital., Materials and Methods: Thirty women (45-69 years) were enrolled for this 1-year study. Evaluations were basally, fortnightly twice, and three monthly four times. SEL-Ds (300 mg) twice daily was administered orally. Calcium (250 mg) and Vitamin D (200 IU) were given twice a day. The efficacy of SEL-Ds was assessed by DXA-scan (spine, femur), by biochemical markers, alkaline phosphatase (ALP), tumor necrosis factor-alpha (TNF-α), and anti-inflammatory marker high-sensitivity C-reactive protein (hs-CRP). Baseline symptom changes and adverse events were carefully recorded., Statistical Analysis: Summary statistics (n, mean, standard deviation, median, and maximum and minimum values) of changes from baseline values and Student's "t-" test for P values were used., Results and Discussion: SEL-Ds was well tolerated at given dose for 1 year. Anti-osteoporotic and anti-inflammatory activities of SEL-Ds were demonstrated by reduction in TNF-α (12.04 ± 2.81-2.35 ± 1.08 pg/ml), ALP (208.75 ± 45.88-154.52 ± 37.25 IU/L), and hs-CRP (6.1 ± 0.77-3.9 ± 0.47 mg/L). BMD-score on DXA-scan also remained unchanged at majority of the bone locations (increased 13/75, unchanged 51/75, and decreased 08/75)., Conclusions: D. sissoo has demonstrated anti-osteoporotic and anti-inflammatory activities as indicated by decline in circulating TNF-α along with concurrent reduction in ALP. The nondecline in BMD index in the majority confirms the anti-osteoporotic activity., Competing Interests: Dr Ashwinikumar Raut has been a consultant to Pharmanza Herbal Pvt. Ltd.

Thyroid hormone is classically known to play a crucial role in neurodevelopment. The potent effects that thyroid hormone exerts on the adult mammalian brain have been uncovered relatively recently, including an important role in the modulation of progenitor development in adult neurogenic niches. This chapter extensively reviews the current understanding of the influence of thyroid hormone on distinct stages of adult progenitor development in the subgranular zone (SGZ) of the hippocampus and subventricular zone (SVZ) that lines the lateral ventricles. We discuss the role of specific thyroid hormone receptor isoforms, in particular TRα1, which modulates cell cycle exit in neural stem cells, progenitor survival, and cell fate choice, with both a discrete and overlapping nature of regulation noted in SGZ and SVZ progenitors. The balance between liganded and unliganded TRα1 can evoke differing consequences for adult progenitor development, and the relevance of this to conditions such as adult-onset hypothyroidism, wherein unliganded thyroid hormone receptors (TRs) dominate, is also a focus of discussion. Although a detailed molecular understanding of the specific thyroid hormone target genes that contribute to the neurogenic actions of thyroid hormone is currently lacking, we highlight the current state of knowledge and discuss avenues for future investigation. The goal of this chapter is to provide a comprehensive and detailed analysis of the effects of thyroid hormone on adult neurogenesis, to discuss putative molecular mechanisms that mediate these effects, and the behavioral, functional, and clinical implications of the neurogenic actions of thyroid hormone., (© 2018 Elsevier Inc. All rights reserved.)

Macrophage activation plays a significant role in homeostasis of organisms. Various internal and external stress factors may affect their function, leading to adverse effects on the body. ‘In vitro macrophage activation techniques provide us with a window to understand the mechanisms of inflammation and response of macrophages to the modulating interventions. Apart from infectious diseases, inflammation is also the major culprit in pathogenesis of many noncommunicable diseases such as arthritis, obesity, metabolic syndrome, diabetes, cancer, cardiovascular disease etc. In vitro macrophage activation allows us to study the role of polarized macrophages in the process of pathogenesis. This emerging technique leads to newer diagnostics, understanding pathophysiological mechanism/s, drug development and management of chronic inflammatory diseases. We, at MRC-KHS, use this technique for screening of medicinal plant-derived phytomolecules for their anti-inflammatory, immunomodulatory and anticancer activities. This review briefly outlines the different experimental models of in vitro macrophage activation and their applications for understanding the pathophysiological mechanisms of underlying chronic inflammation and screening of therapeutic activity of plant-based phytomolecules.

Background: An unceasing threat of drug resistance continuously poses demand for new antimalarial drugs. A scientific assessment of traditionally used antimalarial plants through reverse pharmacology is crucial for a fast track drug discovery. An Ayurvedic plant Nyctanthes arbor-tristis Linn. - (Parijat) is being used in clinical practice and had shown antimalarial activity, with a parasite clearance in 76.6% of 120 patients, in an earlier clinical study., Objective: To further explore antimalarial potential of the plant through additional objective markers., Materials and Methods: An open-labelled observational study was conducted at M.A. Podar Hospital - Ayurveda (MAPH-A) after ethics committee approval. Administration of a paste of 5 fresh leaves, thrice a day for a week was a standard practice for management of malaria at MAPH-A. Clinical activity of N. arbor-tristis was evaluated by monitoring pyrexia, parasitemia and morbidity score (MS) in twenty patients. In addition, immune and biochemical markers and organ functions were monitored for objective markers of response. Student's paired-'t' test was applied to assess statistical significance., Results: Ten out of 20 patients showed both fever and parasite clearance, which was confirmed by polymerase chain reaction. Remaining ten patients had persistent but decreasing parasitemia. Four of them needed chloroquine as a fail-safe procedure. Irrespective of the degree of parasitemia all the patients showed decrease in MS. There was also an increase in platelet count and normalization of plasma lactic acid. There was a good clinical tolerability and an improvement in organ function. The inflammatory cytokines showed a reduction; particularly in TNF-α within a day., Conclusions: At the given dosage, N. arbor-tristis showed disease-modifying activity; early clinical recovery with a decline of TNF-α and a gradual parasite clearance. Further studies with a standardised formulation for dose-searching and optimizing the treatment schedule are needed in a larger sample size., Clinical Trial Registration No: The process of trial registration had not begun when the study was conducted in 2000., (Copyright © 2016 Transdisciplinary University, Bangalore and World Ayurveda Foundation. Published by Elsevier B.V. All rights reserved.)

Cytokine research is currently at the forefront in cancer research. Deciphering the functions of these multiple small molecules, discovered within the cell and in intercellular spaces, with their abundance and pleotrophism, was initially a great challenge. Advances in analytical chemistry and molecular biology have made it possible to unravel the pathophysiological functions of these polypeptides/proteins which are called interleukins, chemokines, monokines, lymphokines and growth factors. With more than 5 million women contracting cervical cancer every year this cancer is a major cause of mortality and morbidity the world over, particularly in the developing countries. In more than 95% of cases it is associated with human papilloma virus (HPV) infection which is persistent, particularly in those with a defective immune system. Although preventable, the mere magnitude of prevalence of HPV in the world population makes it a dominating current health hazard. The discovery of cytokine dysregulation in cervical cancer has spurted investigation into the possibility of using them as biomarkers in the early diagnosis of cases at high risk of developing cancer. Their critical role in carcinogenesis and progression of cervical cancer is now being revealed to a great extent. From diagnostics to prognosis, and now with a possible role in therapeutics and prevention of cervical cancer, the cytokines are being evaluated in all anticancer approaches. This review endeavours to capture the essence of the astonishing journey of cytokine research in cervical neoplasia.

Ashwagandha (Withania somnifera) (WS), a "rasayana" drug, is recommended for balavardhan and mamsavardhan. The study was intended to evaluate dose-related tolerability, safety, and activity of WS formulation in normal individuals. The design was prospective, open-labeled, variable doses in volunteers. Eighteen apparently healthy volunteers (12M:6F, age:18-30 years, and BMI: 19-30) were enrolled. After baseline investigations, they received WS capsules (Rx) (aqueous extract, 8:1) daily in two divided doses with increase in daily dosage every 10 days for 30 days (750 mg/day ×10 days, 1 000 mg/day × 10 days, 1 250 mg/day × 10 days). Volunteers were assessed for symptoms/signs, vital functions, hematological and biochemical organ function tests. Muscle activity was measured by hand grip strength, quadriceps strength, and back extensor force. Exercise tolerance was determined using cycle ergometry. Lean body weight and fat% were computed from skin fold thickness measurement. Adverse events were recorded, as volunteered by the subjects. Repeated measures ANOVA, McNemar's test, and paired t test were employed. All but one volunteer tolerated WS without any adverse event. One volunteer showed increased appetite, libido, and hallucinogenic effects with vertigo at the lowest dose and was withdrawn from study. In six subjects, improvement in quality of sleep was found. Organ function tests were in normal range before and after the intervention. Reduction in total- and LDL- cholesterol and increase of strength in muscle activity was significant. Total body fat percentage showed a reduction trend. WS, in escalated dose, was tolerated well. The formulation appeared safe and strengthened muscle activity. In view of its traditional Rasayana use, further studies are planned to evaluate potential of this drug in patients of sarcopenia.

A 61 year old male, with a bilateral persistent and recurrent pleural effusion, had undergone frequent tapping over a period of eight months, prior to the referral. The patient was treated earlier to the referral empirically for pulmonary tuberculosis with no response to the treatment. Malignancy was suspected and ruled out. A detailed examination showed that he also had atrophic nails with yellow discoloration and lymphedema of feet. Yellow nail syndrome was diagnosed on the basis of the clinical findings of the triad viz. yellow atrophic nails, lymphedema and bilateral pleural effusions. Pathogenesis still remains elusive for the syndrome. Pleurodesis provided both symptomatic relief and a respite from repeated tapping. The case is presented as a rare condition, which was missed for diagnosis, for quite some time by several specialists.

Objective: To assess serum IL-6 in women with or without low-grade squamous intraepithelial lesions (LSILs) in Pap smears and correlate with the nucleo/cytoplasmic (N/C) ratio., Methods: Manual micrometry was carried out on Pap smears for N/C ratios: Group A, negative findings (N=15); Group B, inflammation without abnormality (N=14); Group C, LSIL with inflammation (N=13). Serum IL-6 was measured in Groups B and C after treatment of nonviral genital infections. Women with pelvic inflammatory or systemic diseases were excluded., Results: The N/C ratio was significantly higher in Group C vs Group B, both before and after treatment of nonviral infections and also vs group A (p<0.001, Students t test). After treatment for non-viral infections serum IL-6 levels were >50 pg/ml in 5/13 cases of Group C and significantly higher than levels in Group B (p<0.05), correlating positively with the N/C ratio in the 13 cases of LSIL (Pearson's coefficient r=0.659, p<0.05)., Conclusions: High peripheral circulating level of IL-6, despite prior treatment of nonviral infections, was observed in more than one third of women with persistent LSIL in Pap smears, and may serve as an additional biomarker for early cervical neoplasia. Long term follow up is indicated.

Background & Objective: Soy isoflavones are being used as therapy for menopausal syndrome in many countries. Marketed preparations show variability in bioavailability and there are variations in kinetics due to ethnicity and diet. Inspite of soy isoflavone being available in the Indian market there are no studies to show whether the preparation is likely to be effective in women. This study was carried out to determine circulating levels of genistein, a bioactive soy isoflavone, in Indian women after a single dose of soy extract., Methods: Six healthy vegetarian women volunteers, between 36 and 62 yr and with a mean body mass index (BMI) 25.01+/-2.02 (kg/m2), were enrolled after an informed consent. Women with antibiotic or Soy food intake within 1 month of study were excluded. A single dose of standardized soy extract capsule containing 64.12 mg of total isoflavones (genistein content equivalent to 31.76 mg) was ingested under supervised fasting condition and multiple blood samples were collected at 0, 1, 2, 4, 6, 8 and 24 h. Genistein levels were measured by high performance liquid chromatography (HPLC) method with a detection level of 2.5 ng/100 microl of injection volume. The intra- and inter-assay coefficients of variation were < 5.32 per cent., Results: Genistein was detected (10.3 to 16.2 ng/ml) in 3 volunteers in baseline samples. Within one hour genistein levels rose from 42 ng to 215 ng/ml with a maximum concentration of 117 to 380 ng/ml at 4 to 8 h. A secondary peak suggestive of enterohepatic circulation was seen between 4 and 6 h in 2 out of 6 volunteers. The mean Cmax was 315.5 +/- 57.1 ng/ml. All women had detectable levels from 25.2 to 109.3 ng/ml at 24 h., Interpretation & Conclusion: Our study showed adequate circulating levels of genistein in Indian vegetarian women after a single dose of soy extract. Variability in plasma levels of the soy isoflavones may explain differences in responses to therapy.

Objective: To assess Homocysteine (Hcy), vitamin B12 and folic acid (FA) concentrations in resident Indian women and to study their correlation with traditional risk factors for coronary artery disease., Material and Methods: The study included 137 consecutive women who attended a health care program (HCP) for women at and above 40 years of age (MAITREYI's HCP). Fasting blood samples for Hcy, B12 and folate were collected on ice, centrifuged within 1/2 hour and stored at -70 degrees C till assayed using a chemiluminescence method. All women underwent a screening for their general health profile including cardiovascular health., Results: Of the 137 women screened 21 were excluded because of presence of factors known to affect Hcy levels (history of existing CAD had hypothyroidism or were on multivitamin supplements). The median Hcy, folic acid and vitamin B12 levels were 9 pmol/L (range 4.2-38.6), 8.8 ng/ml (2.3-31.6 range) and 214 pg/ml (100-2400 range) respectively. The prevalence of hyperhomocysteinemia (>15 pmol/L) was 24.2%. Correlation for continuous variables using spearman's test and for categorical variables with chi-square test showed a highly significant negative correlation with vitamin B12 (p < 0.001) and FA (p<0.002). Both systolic (p < 0.05) and diastolic (p < 0.02) and diastolic blood pressure also showed a significant correlation. However, no correlation was found between plasma Hcy and blood sugars, lipids, age, body mass index and menopausal status. The CAD risk was assessed using Framingham risk scores and this too did not show a correlation with plasma Hcy., Conclusions: A large number of women from the present study had hyperhomocysteinemia and were deficient in vitamin B12. A significant negative correlation between vitamin B12 and plasma Hcy levels was foundin these older women. Most Indian studies including the present one do not show a positive correlation between elevated Hcy levels and CAD in spite of a large percentage of persons showing elevated homocysteine levels. Since high Hcy levels are recognized as an independent risk factor for CAD, these findings of absence of correlation between Hcy and CAD as reported in various Indian studies need to be explored and explained.

Familial Partial Lipodystrophy, Dunnigan type (FPLD), is characterised by loss of subcutaneous fat from the limbs and an excessive accumulation of fat on the neck, shoulder girdle and face. Affected individuals have insulin resistance, dyslipidaemia and early cardiovascular events. Body composition (BC) with details of adipose tissue distribution were studied by Dual-Energy X-ray Absorptiometry (DEXA) and Magnetic Resonance Imaging (MRI) ina heterozygote for the FPLD mutation LMNA R482W, and in an age, sex and body mass index (BMI) matched normal control. DEXA revealed a marked decrease in total as well as regional fat percentage in the patient compared to a normal control. Marked reductions in subcutaneous fat in the extremities with substantial lipodeposition in the nape of the neck were confirmed with. MRI. The importance of increased perinephric, retroperitoneal and intermuscular fat in the thighs found in this patient, needs to be explored vis-à-vis the pathogenesis of insulin resistance found in FPLD.

We have examined the influence of thyroid hormone on adult hippocampal neurogenesis, which encompasses the proliferation, survival and differentiation of dentate granule cell progenitors. Using bromodeoxyuridine (BrdU), we demonstrate that adult-onset hypothyroidism significantly decreases hippocampal neurogenesis. This decline is predominantly the consequence of a significant decrease in the survival and neuronal differentiation of BrdU-positive cells. Both the decreased survival and neuronal differentiation of hippocampal progenitors could be rescued by restored euthyroid status. Adult-onset hyperthyroidism did not influence hippocampal neurogenesis, suggesting that the effects of thyroid hormone may be optimally permissive at euthyroid levels. Our in vivo and in vitro results revealed that adult hippocampal progenitors express thyroid receptor isoforms. The in vitro studies demonstrate that adult hippocampal progenitors exhibit enhanced proliferation, survival and glial differentiation in response to thyroid hormone. These results support a role for thyroid hormone in the regulation of adult hippocampal neurogenesis and raise the possibility that altered neurogenesis may contribute to the cognitive and behavioral deficits associated with adult-onset hypothyroidism.

Prader Willi syndrome (PWS) is a rare endocrine-metabolic disorder that is characterised by neonatal hypotonia, hyperphagia, marked obesity, short stature, hypogonadism and behavioural problems. 7-20% percent of these children develop diabetes mellitus. A large number of individuals with PWS show growth hormone (GH) deficiency. Recent studies indicate beneficial effects of GH replacement therapy not only for their linear growth but also for correction of metabolic dysfunction. In the present communication this article details about the therapeutic outcome in a girl with PWS who received recombinant growth hormone (rGH), Genotropin. Some carry-over therapeutic benefits have been observed even after discontinuation of rGH.

Objective: To study clinical, endocrine and metabolic profiles in the kindred of subjects with familial partial lipodystrophy (FPLD, Dunnigan type)., Material and Methods: Twenty two relatives (10 males, 12 females), from an extended family with FPLD, were assessed for the phenotypic features, impaired glucose tolerance (IGT)/diabetes mellitus (DM), dyslipidemia and the presence of insulin resistance. Plasma glucose and serum lipids were measured using glucose oxidase and standard colorimetric methods. Serum insulin was estimated by radioimmunoassay., Results: The age was 12 to 67 years, two being adolescents. Two of the 20 adults were overweight and eight were underweight; BMI (adults) was 15.5 to 28.5. Features of FPLD were evident among eight out of 12 women. This typical phenotype was not obvious in all 10 male members. Varying degree of Hirsuitism was observed in four of 12 women, acanthosis nigricans in 11 out of 22 members and skin tags were present in only eight of 22; hypertension in six members and diabetes in four. Eleven members had either impaired glucose tolerance (IGT) (n=7), or DM (n=4). Ten of 20 members showed hyperinsulinemic response on oral glucose tolerance test (OGTT). Dyslipidemia was present in 13 family members., Conclusion: The majority (2/3rd) of female members showed typical phenotypic features of FPLD, with a clustering of cardiovascular risk factors and insulin resistance syndrome. More than half the men without phenotypic features of FPLD had either IGT/DM, dyslipidemia, hypertension or cardiovascular disease.

Background: The availability of sensitive and specific assays for evaluation of the thyroid axis has allowed definition of thyroid disorders at subclinical stage. This has almost obviated the use of thyrothrophin releasing hormone (TRH) study. We describe here a group of patients with minimal signs of hypothyroidism having normal thyroid function tests (T3, T4, thyroid stimulating hormone (TSH)) and have shown exaggerated TSH response to TRH., Material and Methods: Total 82 subjects were studied. Of these, 11 were age and sex matched controls, and 71 were patients. In all subjects TSH and other thyroid assays (T3, T4, FT4) were done by immunoradiometric assay (IRMA), and radioimmunoassay (RIA) respectively. Thyroid antibody was carried out by haemagglutination method. Results were compared to age and sex related normal ranges. To further investigate the status of thyroid axis, TRH study was carried out using standard protocol., Results: Based on TRH study patients were grouped in three categories. Group 1 included 29 patients whose TSH response to TRH was normal. Group 2 included 20 patients with normal baseline TSH and exaggerated TSH response to TRH and Group 3 included 18 patients with baseline TSH in the range of 5 to 10 mu IU/ml and exaggerated TSH response to TRH. There was a significant difference to total T3 between group 1 and 3 (p < 0.05) but mean values were within normal limits. While no significant difference was observed in total T4 between controls and patient's group. Serum TSH values were high in group 3 as compared to controls and Group 1 and 2 (p < 0.0001). For Free T4 no statistical significance was observed between Group 1, 2 and 3. Thyroid antibodies were positive in 22.7% of patients in Group 2 and 33.33% in Group 3., Conclusion: We conclude from the present study that even with sensitive TSH assays TRH study still has a role to mark the early stage of hypothyroidism. Those with a normal or upper normal TSH with exaggerated response to TRH are termed as sub-biochemical hypothyroidism and can be considered for thyroid replacement therapy.

An open comparative trial was conducted in 58 adult obese patients (Body Mass Index > or = 25 kg/square metre). Group I (n = 27), non-drug, was advised diet (1200-1600 cals) and a brisk walk for 30 minutes. Group II, in addition, received Guggulu (Medohar) 1.5-3 gms/day for 30 days. Mean difference in weight loss between Guggulu and non-drug group was 0.32 kg (ns) on day 15 and 0.58 kg on day 30 (ns). The mean weight reduction in patients (> 90 kgs) was 1.92 kg (ns) and 2.25 kg (ns) higher in Guggulu group. All patients weighing > 90 kg lost weight in Guggulu group whilst 3 in non-drug group did not lose weight. Guggulu was tolerated well. The data from this pilot study suggest a synergistic diet-Guggulu interaction over 30 days in patients weighing > 90 kgs which needs to be confirmed in a large placebo controlled study.

The widespread use of hormonal contraceptives for a prolonged time in women during the child-bearing period necessitates that appropriate precautions be taken to ensure safety for the patient as well as for her progeny. Hormonal administration during or prior to pregnancy may be potentially teratogenic. Although there have been many reports during the last decade, it has been very difficult to document conclusively such a relationship. Over-all, it seems that hormonal use prior to pregnancy does not lead to an increase in the frequency of chromosomal aberrations or of congenital malformations. The use of certain hormones during pregnancy, on the other hand, may lead to an increase in the incidence of congenital malformations, probably in the genetically predisposed fetus. In view of this concept hormonal contraceptives should not be used to treat threatened abortion, and their use as a pregnancy test should be abandoned. Since the question of the safety of the inadvertent administration of pills during early pregnancy has not been resolved, the mother should be informed of the potential risks.

Laparoscopically directed ovarian biopsy has been evaluated in 39 cases of secondary amenorrhea. The definite diagnosis was achieved in 29 cases. In 10 cases, ovarian histopathology alone was insufficient, and the estimations of gonadotropins were essential for the final diagnosis. The scope and limitations of this procedure for the differential diagnosis of premature ovarian failure and hypothalamic-pituitary lesions are discussed.

Two patients with galactorrhea-amenorrhea and bilateral visual field defects were studied. Routine radiologic examination of each patient revealed a normal sella turcica and no demineralization of the posterior clinoid process. Serum prolactin levels were elevated (patient V. G., 80 ng/ml; patient S. R., 204 ng/ml). Within 2 months of bromocriptine therapy, the serum prolactin levels were normal (patient V. G., 12.21 ng/ml; patient S. R., 8.25 ng/ml) and the bilateral visual field defects were corrected. Bromocriptine has been shown to control prolactin secretion in patients with prolactin-secreting pituitary tumors. Normalization of restricted visual fields following bromocriptine therapy indicates the possibility of an anatomical regression of pituitary hyperplasia or an underlying prolactin-producing microadenoma. It is speculated that the modality of functional galactorrhea reflects hyperplasia of the lactotrophs preceding a nodular and ultimately an adenomatous change. The continuous and prolonged administration of bromocriptine may prevent such a progressive sequence. Further experience is required to validate this possibility.

Elevation of serum luteinizing hormone levels was observed in five normal male volunteers while they were taking Centchroman. This effect resembles that of clomiphene and suggests a new biologic potential of Centchroman.

C57BL/6 inbred female mice preimmunized by serial injections of isogeneic male spleen cells were mated and the effects of the circulating anti H-Y antibodies on the fetal gonads and on their fertility were studied. Female mice receiving injections of saline formed one control group and those given female spleen cells a second control group. The experiment was carried out three times and since observations were similar and reproducible the data of all three sets were pooled. There was no significant change in the birth weights of newborns, total number of conceptions or sex ratio in the study group compared to either of the controls. There was no difference in the mean live birth rate between the study group and both the controls. Although the incidence of stillbirths in the study group was higher than that in both controls the difference was not statistically significant. In the study group there were no histopathological changes in the gonads from female pups compared to ovaries from the controls. In contrast, the gonads of male pups showed mild to severe structural disorganization in the study group, but not in the female spleen cell injected group. In spite of the morphological changes in the testes, the newborn male pups had a normal anogenital distance and testicular descent suggesting that Leydig cell function was normal.