Cardiac structural and functional abnormalities in primary hyperparathyroidism.

PURPOSE: Studies on cardiac structural and functional abnormalities in primary hyperparathyroidism (PHPT) have yielded conflicting and inconsistent results. In this prospective case-control study, we sought to compare cardiac structure and function in symptomatic PHPT patients and controls. METHODS: One hundred consecutive symptomatic PHPT patients and 113 matched controls underwent echocardiographic evaluation by the same operator. RESULTS: Left ventricular mass index (LVMI) was significantly higher in patients as compared to controls, (median of 90.95 g/m2 vs 86.5 g/m2, p = 0.041). Patients had significantly lower early trans-mitral diastolic flow (E velocity) as compared to controls (57.13 ± 14.88 vs 64.76 ± 15.45 cm/s, p < 0.001). Patients also had significantly lower early to late mitral annular velocity (E/A) as compared to controls (0.98 ± 0.37 vs 1.10 ± 0.34, p 0.013). Patients had higher frequency of aortic valve calcification (29% vs 2.65%, p < 0.001), mitral annular calcification (23% vs. 4.42%, p < 0.001), myocardial and septal calcifications (25% vs none, p < 0.001) as compared to controls. Serum PTH, calcium and uric acid significantly correlated with calcifications. Serum calcium showed a negative correlation with E/A ratio. CONCLUSIONS: Symptomatic patients with PHPT have substantial cardiac structural and functional abnormalities. These abnormalities include elevated LVMI, diastolic dysfunction, and aortic valve, mitral annular, septal and myocardial calcifications. We strongly suggest and conclude that the evaluation of PHPT patients should not only include traditional end organs like bones and kidneys but also the cardiovascular system in the form of echocardiography to detect subclinical cardiac dysfunction so that the cardiovascular health of such patients can be optimized.

A High Energy X-ray Diffraction Study of Amorphous Indomethacin.

Amorphous pharmaceuticals often possess a wide range of molecular conformations and bonding arrangements. The x-ray pair distribution function (PDF) method is a powerful technique for the characterization of variations in both intra-molecular and inter-molecular packing arrangements. Here, the x-ray PDF of amorphous Indomethacin is shown to be particularly sensitive to the preferred orientations of the chlorobenzyl ring found in isomers in the crystalline state. In some cases, the chlorobenzyl ring has no preferred torsional angle in the amorphous form, while in others evidence of distinct isomer orientations are observed. Amorphous samples with no preferred torsion angles of the chlorobenzyl ring are found to favor enhanced inter-molecular hydrogen bonding, and this is reflected in the intensity of the first sharp diffraction peak. These significant variations in structure rule out amorphous Indomethacin as a possible standard for x-ray PDF measurements. At high humidity, time resolved PDF's for >40 h reveal water molecules forming hydrogen bonds with Indomethacin molecules. A simple linear hydrogen bond model indicates that water molecules in the wet amorphous form have similar hydrogen bond strengths to those found between Indomethacin dimers or chains in the dry amorphous form.

Primary hyperparathyroidism and pancreatitis.

PURPOSE: The true association between primary hyperparathyroidism (PHPT) and pancreatitis continues to be controversial. In this study, we present clinical data, investigative profile, management and follow-up of PHPT patients with pancreatitis and compare this group with PHPT patients without pancreatitis. METHODS: Records of 242 patients with PHPT managed at our center over 24 years were retrospectively analyzed for demographic and laboratory data. The diagnosis of pancreatitis was entertained in the presence of at least two of the three following features: abdominal pain, levels of serum amylase greater than three times the normal or characteristic features at imaging. RESULTS: Fifteen (6.19%) of the 242 consecutive patients with PHPT had had pancreatitis. Fourteen patients (93.3%) had acute pancreatitis (AP), while one patient had chronic calcific pancreatitis. Over half (8 of 14) of the patients with AP had at least two episodes of pancreatitis. Pancreatitis was the presenting symptom in 14 (93.3%) patients. None of the pancreatitis cases had additional risk factors for pancreatitis. PHPT patients with pancreatitis had significantly higher serum calcium and ALP than PHPT patients without pancreatitis. After successful parathyroidectomy, 14 patients had no further attacks of pancreatitis during a median follow-up of 16 months (range 2-41 months), while recurrence of pancreatitis was seen in one patient. CONCLUSIONS: We conclude that pancreatitis can be the only presenting complaint of PHPT. Our study highlights the importance of fully investigating for PHPT in any pancreatitis patient with high normal or raised serum calcium level, especially in the absence of other common causes of pancreatitis.

Comparison of efficiency of in vitro cloned sheep embryo production by conventional somatic cell nuclear transfer and handmade cloning technique.

Conventional somatic cell nuclear transfer (SCNT) technique of in vitro production of cloned embryos involves use of costly and complicated micromanipulators. Handmade cloning (HMC) technique has been applied as efficient and cost-effective alternative in many livestock species. The aim of the present study was to compare the efficiency of in vitro production and in vitro development of cloned sheep embryos by the two techniques. Cloned embryos were produced by conventional SCNT using micromanipulator apparatus and by HMC technique. Enucleation efficiency and efficiency of fusion with somatic cell (nucleus donor) were compared. Cleavage percentage was observed on day 2 of in vitro culture (IVC), and morula and blastocyst percentages were calculated on day 7 of IVC. Higher enucleation efficiency (96.98 ± 1.01 vs. 93.62 ± 1.03; p > .05) as well as fusion efficiency was obtained with HMC technique than with conventional SCNT (96.26 ± 1.34 vs. 92.63 ± 0.70, p < .05); 181 cloned sheep embryos were produced in vitro by conventional SCNT and 92 by HMC. Cleavage percentage observed on day 2 of in vitro culture was higher in HMC than SCNT (66.92 ± 3.72 vs. 55.97 ± 2.5, respectively, p < .05). Morula percentage obtained was higher in SCNT than HMC (44.12 ± 2.93 vs. 30.43 ± 6.79, respectively, p < .05), whereas blastocyst percentage obtained by HMC was higher (12.46 ± 4.96) than SCNT (5.31 ± 2.25; p > .05). It was inferred that HMC technique provides a cost-effective and efficient method of in vitro production of cloned sheep embryos with a comparatively simpler technique with a possibility of automation. Efficiency of cloned embryo production could be improved further by propagating and standardizing this technique.

Molecular characterization of RNA binding motif protein 3 (RBM3) gene from Pashmina goat.

Pashmina goat inhabits the high altitude cold arid desert of Ladakh, India. This goat is known for its finest and costliest under fiber. Though the under fiber may be a part of its complex thermoregulation mechanism, the genetics of its adaptability under cold conditions is not known. As an attempt to understand its adaptive genetics, and the role of RNA-binding proteins at the cellular response, this study was conducted to characterize the RBM3 gene in Pashmina goat and its expression during hypothermia. The ORF of Pashmina RBM3 gene was 273 bp. Phylogenetic analysis revealed that Pashmina RBM3 is closely related to Bos taurus RBM3. Pashmina RBM3 was characterized by comparative modeling studies. The final 3-D model contained two α-helices and four ß-sheets. qRT-PCR data showed that Pashmina RBM3 gene expression was significantly higher (P < 0.05) at moderate (30 °C) hypothermic stress conditions as compared with deep (15 °C) hypothermia.

Open pulled straw vitrification and slow freezing of sheep IVF embryos using different cryoprotectants.

The aim of the present study was to evaluate the post-thaw survival and hatching rates of sheep blastocysts using different cryoprotectants. In Experiment 1, Day 6 sheep embryos were cryopreserved by a slow freezing protocol using 10% ethylene glycol (EG), 10% dimethyl sulfoxide (DMSO) or a mixture of 5% EG and 5% DMSO. Hatching rates were higher in the 10% EG group than in the 10% DMSO or EG + DMSO groups (30% vs 18% and 20%, respectively). In Experiment 2, embryos were cryopreserved by open pulled straw (OPS) vitrification using either 33% EG, 33% DMSO or a mixture of 16.5% EG + 16.5% DMSO. Re-expansion and hatching rates in the EG + DMSO group (79.16% and 52.74%, respectively) were higher than those in the EG group (64.28% and 30.02%, respectively), whereas the outcomes for the DMSO group were the lowest (45.18% and 8.6%, respectively). In Experiment 3, embryos were cryopreserved by OPS vitrification using either 40% EG, 40% DMSO or a mixture of 20% EG + 20% DMSO. Re-expansion and hatching rates were highest in the EG group than in the EG + DMSO and DMSO groups (92.16% vs 76.30% and 55.84% re-expansion, respectively; and 65.78% vs 45.55% and 14.46% hatching, respectively). In conclusion, OPS vitrification was found to be more efficient for cryopreservation of in vitro-developed sheep embryos than traditional freezing.

Comparison of slow freezing and vitrification on ovine immature oocytes.

BACKGROUND: Immature oocytes are more sensitive to cold injury than mature oocytes. OBJECTIVE: The study was to evaluate the post thaw normal oocytes, cleavage and blastocyst rates of ovine cumulus oocyte complexes (COC's) using different cryoprotectants by slow freezing and Open pulled straw (OPS) vitrification. METHODS: In five replicates, abattoir derived COC's were collected and distributed into three groups. In Experiment 1, COC's were cryopreserved by a slow freezing protocol using 10% concentration of ethylene glycol (EG), 10% dimethyl sulphoxide (DMSO) or 5% EG and 5% DMSO mixture. In Experiment 2 and 3 embryos were cryopreserved by OPS vitrification using either 33% or 40% (EG, DMSO or an equal mixture of EG and DMSO mixture. Normal oocytes post thaw were in vitro matured and parthenogenetically activated. RESULTS: Although, there was no difference in the number of post thaw normal oocytes between the groups, cleavage and blastocyst rates were higher in 10% slow freezing group than any of the vitrified groups. CONCLUSION: The study demonstrates better cryopreservation of ovine COC's by controlled slow freezing than OPS vitrification.

In vitro development of goat-sheep and goat-goat zona-free cloned embryos in different culture media.

The gradual decline in the genetic diversity of farm animals has threatened their survival and risk of their extinction has increased many fold in the recent past. Endangered species could be rescued using interspecies embryo production. The objective of this study was to investigate the effect of three different culture media on the development of Handmade cloned intraspecies (goat-goat) and interspecies (goat-sheep) embryo reconstructs. Research vitro cleave media (RVCL) yielded higher cleavage and morula-blastocyst development in intraspecies and interspecies nuclear transfer groups compared with G1.G2 and modified synthetic oviductal fluid (mSOFaaci). Cleavage frequency of intraspecies cloned embryos in RVCL, mSOFaaci, and G1.G2 did not differ significantly (87.12%, 82.45%, and 92.52%, respectively). However, the morula/blastocyst frequency in RVCL was greater in mSOFaaci and G1.G2 (51.18% vs. 38.28% vs. 36.50%, respectively). Cleavage and morula/blastocyst frequency in interspecies cloned embryos was greater in RVCL than in mSOFaaci and G1.G2 (76.14% and 42.3% vs. 65.9% and 38.3% vs. 58.56% and 33.1%, respectively). Goat oocytes were parthenogenetically activated and cultured in RVCL, mSOFaaci, and G1.G2 and kept as control. Cleavage and morula/blastocyst frequency in this group was greater in RVCL than in mSOFaaci and G1.G2 (89.66% and 65.26% vs. 85.44% and 48.05% vs. 86.58% and 42.06%, respectively). Conclusively, the results suggest that not only can the interspecies embryos of goat be produced using sheep oocytes as donor cytoplast but also the percentages can be improved by using RVCL media for culturing of the embryos.

Rational use of glucocorticoid during pituitary surgery--a pilot study.

BACKGROUND & OBJECTIVE: The conventionally used perioperative glucocorticoid replacement protocol in patients with pituitary tumours is far from optimal. In this study we evaluated the validity of a modified protocol for perioperative glucocorticoid replacement in non-functioning pituitary macroadenomas. METHODS: A total of 24 consecutive patients with non functioning pituitary macroadenomas were included in this interventional study. Patients with a pre-operative 0800 h cortisol of > or = 350 nmol/l (> or = 12.6 microg/dl) did not receive glucocorticoid replacement during perioperative (d(0)-d-(2)) period, while those with < or = 100 nmol/l (< or = 3.6 microg/dl) received glucocorticoid replacement. Those patients with 0800 h cortisol value between > 100-349 nmol/l (> 3.6-12.6 microg/dl) required them to undergo an insulin induced hypoglycaemia (IIH). In response to IIH, patients with a peak cortisol of < 550 nmol/l (< 19.8 microg/dl) received glucocorticoid replacement. Post-operatively, patients on day 3 with 0800 h cortisol of < or = 100 nmol/l (< or = 3.6 microg/dl) received hydrocortisone 10 mg/m(2) per day; those between > 100-449 nmol/l (> 3.6-16 microg/dl) received hydrocortisone replacement only if they had symptoms of adrenal insufficiency (AI) or during stress; while patients with > or = 450 nmol/l (> or = 16.0 microg/dl) did not receive any glucocorticoid replacement. Retesting was done at 12 wk in 23 subjects based on the algorithm. RESULTS: Pre-operatively, 8 (35%) patients were hypocortisolic and received glucocorticoid supplementation, thereby sparing 15 (65%) subjects from glucocorticoid replacement. On d(3) of surgery, 13 (57%) patients were hypocortisolic, but only 6 with serum cortisol of < or = 100 nmol/l (< or = 3.6 microg/dl), had symptoms and were substituted with glucocorticoid. Remaining seven patients, with serum cortisol between >100-349 nmol/l (> 3.6-12.6 microg/dl), were asymptomatic and advised glucocorticoid support only during stress but none required. Overall, 17 (74%) patients were spared from unnecessary glucocorticoid support. At 12 wk, 13 (57%) patients were hypocortisolic and only 6 either with serum cortisol level of < or = 100 nmol/l (< or = 3.6 microg/dl) or symptomatic for AI received glucocorticoids. Post-operative complications including diabetes insipidus and CSF leak remarkably decreased. INTERPRETATION & CONCLUSION: The protocol used was safe and spared unnecessary use of glucocorticoids peri- and post-operatively. However, more number of patients are to be studied to substantiate the validity of this protocol.

Vitrification of a monatomic metallic liquid.

Although the majority of glasses in use in technology are complex mixtures of oxides or chalcogenides, there are numerous examples of pure substances-'glassformers'-that also fail to crystallize during cooling. Most glassformers are organic molecular systems, but there are important inorganic examples too, such as silicon dioxide and elemental selenium (the latter being polymeric). Bulk metallic glasses can now be made; but, with the exception of Zr50Cu50 (ref. 4), they require multiple components to avoid crystallization during normal liquid cooling. Two-component 'metglasses' can often be achieved by hyperquenching, but this has not hitherto been achieved with a single-component system. Glasses form when crystal nucleation rates are slow, although the factors that create the slow nucleation conditions are not well understood. Here we apply the insights gained in a recent molecular dynamics simulation study to create conditions for successful vitrification of metallic liquid germanium. Our results also provide micrographic evidence for a rare polyamorphic transition preceding crystallization of the diamond cubic phase.

Hyperthyroidism with fibrous dysplasia: an unusual presentation of McCune-Albright syndrome.

McCune-Albright Syndrome (MAS) is a sporadic disorder characterized by a triad of poly/monostotic fibrous dysplasia, café-au-lait macules, and hyperfunctioning endocrinopathies. Hyperthyroidism as a manifestation of endocrine hyperfunction in MAS is uncommon. We report a patient who had polyostotic fibrous dysplasia with multiple pathological fractures and hyperthyroidism. She underwent surgery for hyperthyroidism and received pamidronate therapy with remarkable relief in bone pains and without any new fractures during her subsequent follow up of 3 years.

Presentation and outcome of emphysematous renal tract disease in patients with diabetes mellitus.

BACKGROUND: Emphysematous renal tract disease (ERTD) is a rare necrotizing infection of the renal parenchyma and urinary tract caused by gas-producing organisms. ERTD deserves special attention because of its life-threatening potential. OBJECTIVES: To study the clinical features, radiological classification and prognostic factors of ERTD; and to compare the modalities of management and the outcome among the various radiological classes of ERTD. PATIENTS AND METHODS: Twenty consecutive patients with diabetes and ERTD, seen over last 3 years in a tertiary care institute of north India, were included in the study. All patients were subjected to computerized tomography (CT) after initial diagnosis by ultrasonography. They were classified into 5 classes as previously described. All patients included in the study were conservatively managed with appropriate antibiotics and/or percutaneous drainage or surgery if required. RESULT: Mean age (+/- SD) of these subjects was 54.4 +/- 20.6 years; duration of diabetes mellitus 8.6 +/- 5.8 years, and duration of symptoms related with ERTD ranged from 3 days to 3 months. Two patients had isolated emphysematous cystitis, 13 patients had emphysematous pyelonephritis (EPN), 3 had both EPN and cystitis, and 1 patient had EPN with cholecystitis, and 1 patient had EPN with pyomyositis. Only 7 (35%) patients had a history of pneumaturia. Escherichia coli was the commonest microorganism. The radiological distribution in 18 (2 had isolated cystitis) patients with EPN was: 2 patients had class 1; 1 had class 2; 2 had class 3A; 11 had class 3B, and 2 had class 4. Of 20 patients 11 (55%) survived. However, those patients who died had severe EPN based on radiological class (6 had class 3B and 1 had class 4). There was no significant difference between the survivor and non-survivor groups with respect to age, gender, duration of diabetes mellitus, duration of symptoms, serum creatinine level, total leukocyte count, hemoglobin, platelet count and culture positivity. CONCLUSION: Computerized tomographic class 3B or 4 is the most reliable predictor of outcome in patients with ERTD.

Hypomagnesaemia masquerading as hypoparathyroidism.

Magnesium deficiency is a common clinical problem. Dietary malabsorption and renal wasting are the commonest causes. Hypomagnesemia induces a state of functional hypoparathyroidism due to decreased secretion of parathormone (PTH) as well as resistance to its action. Contrary to typical autoimmune hypoparathyroidism, it is associated with decreased levels of serum phosphate. We report a patient who presented with hypocalcemic tetany associated with hypomagnesaemia due to renal wasting. Subsequently, he improved with magnesium supplementation of therapy.

Clinical and etiological profile of hyperprolactinemia--data from a tertiary care centre.

OBJECTIVE: To study the clinical presentation and etiology of hyperprolactinemia, a common disorder encountered in endocrine practice. METHODS: We analyzed the clinical data, hormone profile and imaging reports of 187 females with documented hyperprolactinemia, over a period of 6 years (5 years retrospective analysis and one year prospective study). RESULTS: Majority of the 187 subjects studied presented in 3rd or 4th decade. Galactorrhoea was the commonest presenting symptom occurring in 159 subjects (85%), followed by amenorrhea in 68.9%; both amenorrhea and galactorrhea were seen in 45.4%. A microprolactinoma was demonstrated in 67 patients (35.8%), a nonfunctioning pituitary macroadenoma with stalk hyperprolactinemia occurred in 30 patients (16%) and polycystic ovarian disease was documented in 24 (12.8%). In 52 patients (27.8%) no apparent cause could be ascertained. CONCLUSIONS: Syndrome of amenorrhea and/or galactorrhea is the commonest presentation in hyperprolactinemia. Microprolactinoma was the most frequent identifiable etiology followed by idiopathic and stalk hyperprolactinemia in our series.

Diffuse abdominal lipomatosis.

We report a 22-year male who developed progressive distension of abdomen, clinically diagnosed as ascites. A diagnosis of abdominal lipomatosis was made on the basis of CT evidence of excessive fatty tissue in abdominal cavity which was confirmed on laparotomy.

Clinical and aetiological profile of early onset diabetes mellitus: data from a tertiary care centre in the Indian subcontinent.

BACKGROUND: Type 2 diabetes mellitus (DM) in youth is emerging as a serious clinical entity and its incidence has increased over the years. AIM: To analyse the causes of DM in the age group of <40 years of age. SETTINGS AND DESIGN: Tertiary care centre; retrospective analysis of data from January 1990 to December 1999. SUBJECTS AND MATERIAL: Analysis of data of all the subjects of DM in whom disease started before the 40th birthday. RESULTS: 724 subjects were detected to have diabetes mellitus before their 40th birthday. Of these, 205 had Type 1, 174 had Type 2 and 48 had fibrocalculous pancreatic diabetes. Males outnumbered in Type 1 and fibrocalculous pancreatic diabetes while as females in Type 2 diabetes mellitus. Chronic complications were more common in Type 2 diabetes mellitus. CONCLUSION: Type 2 diabetes mellitus is becoming an important cause of diabetes in subjects with onset of disease at younger age.

Puerperal alactogenesis with normal prolactin dynamics: is prolactin resistance the cause?

OBJECTIVE: To determine the cause of puerperal alactogenesis in a young woman. DESIGN: After proper clinical assessment, a definitive investigative protocol was followed to determine the cause of alactogenesis. SETTING: Tertiary care medical center in Kashmir, India. PATIENT(S): A young married woman with three full-term deliveries, all characterized by puerperal alactogenesis. INTERVENTION(S): An investigative protocol to document prolactin reserve and mammography to demonstrate presence of normal breast tissue. MAIN OUTCOME MEASURE(S): Prolactin secretory reserve. RESULT(S): The patient had normal breast development and an adequate pituitary prolactin reserve. CONCLUSION(S): Prolactin resistance may have caused alactogenesis.

The foam mattress-back syndrome.

BACKGROUND: Many medical residents used to sleeping on cotton mattresses at home complain of mild to moderate back pain after sleeping on foam mattresses provided in the hospital and hostel rooms. OBJECTIVE: To determine the relationship of sleeping on foam mattress with the appearance of back pain in a 500 bedded multispecialty tertiary care hospital. METHODS: One hundred medical residents were interviewed for the appearance of backache after sleeping on 10 cm thick foam mattress provided to them in the hostels. Pain was scored over a visual analog scale of 10 cm. Effect of sleeping on a regular cotton mattress was assessed. RESULTS: Sixty-three (5 female residents) developed back pain on the morning of a night of sleep over the foam mattress. The pain was mostly of lower back and was not associated with any objective neurodeficit. Four residents on account of the backache reported thirteen episodes of absenteeism. Sixty-one residents had a relief of the pain on going home where they would sleep on regular cotton mattresses, only to recur after sleeping again on the foam mattress in the hospital/hostel. CONCLUSION: Sleeping on foam mattress is associated with the appearance of backache in medical residents which is reproducible and gets relieved after using regular cotton mattresses.