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Biomedical subjects

R Kumar

Publications and source records attributed to R Kumar.

At least 91 records · Page 5Linked to original sources

Emergence of restless legs syndrome during subthalamic stimulation for Parkinson disease.

The authors systematically studied the emergence of restless legs syndrome (RLS) after subthalamic nucleus (STN) deep brain stimulation (DBS) for Parkinson disease (PD). Postoperatively, 11 of 195 patients with STN DBS reported new problematic symptoms of RLS. The mean reduction in antiparkinsonian medication was 74%. The mean RLS score at diagnosis was 15 (+/-5.9) of a possible 24 points and after symptomatic drug therapy 4.3 (+/-3.1) points. Reduction of antiparkinsonian medication during STN DBS may unmask symptoms of RLS and complicate therapy of both RLS and PD.

Adult↗

Antitumour efficacy of VEGFR2 tyrosine kinase inhibitor correlates with expression of VEGF and its receptor VEGFR2 in tumour models.

During the development of indazolylpyrimidines as novel and potent inhibitors of vascular endothelial growth factor (VEGF) receptor-2 (VEGFR2) tyrosine kinase, we observed that some human tumour xenografts are more sensitive to VEGFR2 kinase inhibitors than others. A better understanding of the basis for this differential response may help to identify a predictive marker that would greatly aid in the identification of a suitable patient population for treatment. One representative compound from the indazolylpyrimidine series is GW654652 that inhibited all three VEGFRs with similar potency. The inhibition of VEGFR2 kinase by GW654652 was about 150 to >8800 more potent than the inhibition of eight other kinases tested. GW654652 inhibited VEGF- and bFGF-induced proliferation in endothelial cells with an IC(50) of 110 and 1980 nM, respectively, and has good pharmacokinetic profile in mouse and dog. We investigated the association between VEGF and VEGFR2 expression and the antitumour efficacy of GW654652, in various xenograft models. Statistically significant associations were observed between the antitumour efficacy of GW654652 in xenografts and VEGF protein (P=0.005) and VEGFR2 expression (P=0.041). The oral dose of GW654652 producing 50% inhibition of tumour growth (ED(50)) decreased with increasing levels of VEGF (r=-0.94); and, in contrast, the ED(50) increased with the increased expression of VEGFR2 (r=0.82). These results are consistent with the observed inverse correlation between VEGF and VEGFR2 expression in tumours. These findings support the hypothesis that VEGF and VEGFR2 expression by tumours may predict the therapeutic outcome of VEGFR kinase inhibitors.

Animals↗

Partial androgen insensitivity syndrome and t(X;5): are there upstream regulatory elements of the androgen receptor gene?

BACKGROUND/AIMS: Two half-brothers with similar malformed genitals, who both inherited a maternally derived t(X;5)(q13;p15) translocation, have a phenotype consistent with partial androgen sensitivity syndrome. The aim was to identify the gene disrupted by the X chromosome breakpoint. METHODS: The breakpoint was localized using fluorescence in situ hybridization to metaphase spreads of the translocation. RESULTS: The breakpoint on the X chromosome of the X;5 translocation was localized to a 30-kb region. This region does not contain any identified genes or transcripts. However, the breakpoint is approximately 134 kb from the 5' end of the androgen receptor (AR) gene. CONCLUSIONS: Genetic defects of the AR gene are collectively called androgen insensitivity syndrome and include a range of phenotypes from normal males, often with associated sterility, to XY females. The phenotype seen in the males with the t(X;5) is consistent with this syndrome. The analysis of the chromosomal abnormality suggests that this translocation may remove one or more upstream regulatory elements of the AR gene that are essential for its normal expression and its role in typical external masculinization.

Androgen-Insensitivity Syndrome↗

The antifilarial activity of a marine red alga, Botryocladia leptopoda, against experimental infections with animal and human filariae.

The antifilarial activity of the marine red alga Botryocladia leptopoda against rodent and human lymphatic filarial parasites is described. The animal filarial species included Litomosoides sigmodontis and Acanthocheilonema viteae maintained in cotton rats and Mastomys coucha, respectively, while a subperiodic strain of the human lymphatic filarial parasite Brugia malayi was maintained in M. coucha. The crude extract and its hexane fraction brought about a marked reduction in the peripheral microfilarial level in both of the rodent filarial parasites L. sigmodontis and A. viteae. The microfilaricidal effect began slowly from day 8 or 15 after initiation of treatment and increased with time with a very high efficacy at the end of the observation period against both rodent filariids. The microfilaricidal efficacy was, however, not as prominent in the case of B. malayi. The antifilarial activity, which occurred in the hexane fraction, exerted action at a much lower dose. The product killed a significant proportion of A. viteae and L. sigmodontis adult parasites. In the case of B. malayi, although the macrofilaricidal efficacy was much less than that of the rodent parasites, it (hexane fraction) caused sterilization of a significant proportion of the surviving female parasites. The present findings indicate the possibility of developing an adulticidal and female sterilizing agent against filarial parasites from a marine red alga.

Animals↗

Early versus delayed laparoscopic cholecystectomy for acute cholecystitis: a prospective randomized trial.

BACKGROUND: The role of laparoscopic cholecystectomy for acute cholecystitis is not yet clearly established. The aim of this prospective randomized study was to evaluate the safety and feasibility of laparoscopic cholecystectomy for acute cholecystitis and to compare the results with delayed cholecystectomy. METHODS: Between January 2001 and November 2002, 40 patients with a diagnosis of acute cholecystitis were assigned randomly to early laparoscopic cholecystectomy within 24 h of admission (early group, n = 20) or to initial conservative treatment followed by delayed laparoscopic cholecystectomy, 6 to 12 weeks later (delayed group, n = 20). RESULTS: There was no significant difference in the conversion rates (early, 25% vs delayed, 25%), operating times (early, 104 min vs delayed, 93 min), postoperative analgesia requirements (early, 5.3 days vs delayed, 4.8 days), or postoperative complications (early, 15% vs delayed, 20%). However, the early group had significantly more blood loss (228 vs 114 ml) and shorter hospital stay (4.1 vs 10.1 days). CONCLUSIONS: Early laparoscopic cholecystectomy for acute cholecystitis is safe and feasible, offering the additional benefit of a shorter hospital stay. It should be offered to patients with acute cholecystitis, provided the surgery is performed within 72 to 96 h of the onset of symptoms.

Acute Disease↗

Temperature driven morphological changes of chemically precipitated hydroxyapatite nanoparticles.

Hydroxyapatite (HA) is synthesized by a wet chemical route using calcium hydroxide and ortho-phosphoric acid at various temperatures (40, 80, and 100 degrees C). X-ray diffraction of the precipitate particles revealed HA as the predominant phase (>99%) with a small amount of beta-tricalcium phosphate. Fourier transform infrared spectroscopy indicated the presence of carbonate substitution, which decreased with increasing temperature. Transmission electron microscopy observations revealed needle-shaped particles with a high aspect ratio at 40 degrees C, which changed to spheroidal when the precipitation temperature was increased to 100 degrees C. The changes in the morphology with temperature were analyzed taking into account the driving force for the HA precipitation and the supersaturation level of Ca2+ and PO4(3-) ions with respect to HA. The analysis indicated that the supersaturation level of the reactants, especially the concentration of Ca2+ ions, played a predominant role on the precipitate morphology for this classical acid-base reaction.

Chemical Precipitation↗

Persistent activity of moxidectin long-acting injectable formulations against natural and experimentally enhanced populations of lice infesting cattle.

A study was conducted under a common protocol in Wisconsin and Wyoming, USA, to evaluate therapeutic and persistent efficacy of two long-acting injectable formulations of moxidectin against lice populations infesting cattle. At each site, 30 beef calves were blocked into groups of three based on naturally acquired Linognathus vituli populations, then randomly assigned to treatments within blocks. Treatments, injected subcutaneously into the proximal third of the ear on Day 0, included saline, a long-acting oil-based formulation containing 10% moxidectin given at the rate of 1 mg moxidectin/kg body weight (M10/1.0), or a long-acting oil-based formulation containing 15% moxidectin given at the rate of 0.75 mg moxidectin/kg b.w. (M15/0.75). Species of sucking and chewing lice were quantified on nine predilection sites before treatment, then 28, 63, 98, 133 and 168 days after treatment. During intervals between lice counts after Day 28, study animals from the three treatment groups were commingled for 32 days with two lice-free sentinels plus four to six seeder calves with infestations of both sucking and chewing lice. Following each 32-day commingling interval, seeder and sentinel animals were removed, and principal animals were sorted into pens by treatment. Lice were quantified on sentinel animals on the day of removal, and lice were quantified on principal study animals 3 days after removal of sentinel and seeders. Moxidectin was generally not efficacious against Bovicola bovis in the injectable formulations tested, whereas Haematopinus eurysternus infestations were inadequate to judge product effectiveness. Based on geometric means, both M15/0.75 and M10/1.0 provided statistically significant therapeutic efficacy against existing infestations of L. vituli and Solenopotes capillatus (100% efficacy on Day 28), and provided persistent protection against reinfestation with L. vituli and S. capillatus (efficacy >97%) for at least 133 days following treatment.

Animals↗

Novel estrogen receptor coregulators and signaling molecules in human diseases.

The steroid hormone estrogen and signaling from its receptors are increasingly recognized as critical mediators of a variety of organ-specific biological processes. Recent advances in the identification and functional characterization of novel estrogen receptor interacting proteins clearly show the complexity of hormonal signaling regulation, but may also contribute to our understanding of the roles of estrogen signaling in normal physiology and the pathobiology of human disease.

Bone and Bones↗

Spheroidization of glass powders for glass ionomer cements.

Commercial angular glass powders were spheroidized using both the flame spraying and inductively coupled radio frequency plasma spraying techniques. Spherical powders with different particle size distributions were obtained after spheroidization. The effects of spherical glass powders on the mechanical properties of glass ionomer cements (GICs) were investigated. Results showed that the particle size distribution of the glass powders had a significant influence on the mechanical properties of GICs. Powders with a bimodal particle size distribution ensured a high packing density of glass ionomer cements, giving relatively high mechanical properties of GICs. GICs prepared by flame-spheroidized powders showed low strength values due to the loss of fine particles during flame spraying, leading to a low packing density and few metal ions reacting with polyacrylic acid to form cross-linking. GICs prepared by the nano-sized powders showed low strength because of the low bulk density of the nano-sized powders and hence low powder/liquid ratio of GICs.

Compressive Strength↗

Metabolite pattern of Cysticercus cellulosae metacestode from different predilection sites of swine using proton magnetic resonance spectroscopy.

Cysticercosis due to Taenia solium is one of the most common public health problems in various regions of the world. We have performed prolon magnetic resonance spectroscopy (1H MRS) experiments of the fluid aspirated from cysticerci excised from skeletal muscle (n = 16) and brain (n = 9) of infected swine to compare the metabolite pattern of cysticerci in different predilection sites. Perchloric acid extract of cysticercus cysts excised from skeletal muscles (n = 16) was also prepared to ascertain water-soluble, low molecular weight metabolites using 1H MRS. Absolute quantification and statistical analysis of different metabolites was done to look for any significant differences in different locations of cysts. The metabolite pattern of cysticerci was found to be similar in the various predilection sites. Metabolites observed were leucine, valine, alanine, lysine, glycine, lipid contents, lactate, glutamate, acetate, succinate, creatine, choline, and glucose. Concentration of creatine in cysticercus fluid of cysts removed from the muscle was found to be significantly higher (p = 0.001) than the cysts located in the brain. We conclude that the metabolite pattern in the cysticerci is not influenced by the surrounding tissue location; however concentration of certain metabolites may depend upon the tissue location.

Animals↗

Role of skeletal scintigraphy in advanced retinoblastomas.

PURPOSE: To document the incidence of skeletal metastases exclusively in advanced cases of retinoblastoma and to rationalize the use of preoperative skeletal scintigraphy in such patients. MATERIAL AND METHODS: Preoperative bone scans of 36 consecutive patients with advanced retinoblastoma who underwent skeletal scintigraphy during 1998 to 2003 were analyzed retrospectively. Bone scans were classified as: Grade 1 (high probability scan for skeletal metastases), Grade 2 (equivocal malignant or benign abnormalities), or Grade 3 (normal or certainly benign lesions). RESULTS: Grade 1 scan was found in 3 (8.33%) patients; bone metastases were confirmed by additional investigations. Grade 2 scan was found in 5 (13.88%) patients; bone metastases were excluded in all by additional investigations. Grade 3 scan was found in the remaining 28 (77.77%) patients. Extraorbital extension of disease was demonstrated by fine needle aspiration of lymph nodes in five patients, which included all three patients with Grade 1 scan. In addition to lymph node metastases, two patients had intracranial extension of the disease; demonstrated by contrast-enhanced magnetic resonance imaging of the head. One patient had liver metastases detected on abdominal ultrasound. None of the patients had skeletal metastases only. CONCLUSION: Routine preoperative bone scan is not justified in patients with locally advanced retinoblastoma. Bone scan should only be performed in patients with documented extraocular metastatic disease.

Adolescent↗

Role of Tc-glucoheptonic acid brain single photon emission computed tomography in differentiation of recurrent brain tumour and post-radiation gliosis.

Blood-brain barrier imaging of brain tumours is fast attracting interest now that it has been demonstrated that disruption of the blood-brain barrier is essential for uptake of all tumour-seeking agents. The aim of the present study was to differentiate recurrent tumour from post-radiation gliosis using (99m)technetium-glucoheptonate ((99m)Tc-GHA) as a tumour-seeking agent. Brain single photon emission computed tomography (SPECT) with (99m)Tc-GHA was performed in 73 patients with primary malignant brain tumours after radiotherapy, and the results were correlated with the clinical behaviour of the disease on follow up. The SPECT was suggestive of recurrent tumour in 55 patients. The clinical course was consistent with recurrence in 51 of the 55 patients. The clinical course was consistent with radiation necrosis in the remaining 21 patients, which included 17 patients with a negative SPECT and four patients with a positive SPECT study. Mean GHA index in recurrent tumour and post-radiation gliosis was 7.04 +/- 4.35 and 1.88 +/- 1.70, respectively (P = 0.0001). Mean GHA index in high-grade and low-grade glioma was 7.78 +/- 4.73 and 3.15 +/- 2.44, respectively (P = 0.001). (99m)Technetium-glucoheptonate brain SPECT is a sensitive and reliable diagnostic modality to differentiate recurrent tumour from post-radiation gliosis.

Adolescent↗

Pathological and immunohistochemical study of experimental peste des petits ruminants virus infection in goats.

Peste des petits ruminants (PPR) is an emerging, economically important viral disease of goats and sheep in the Indian subcontinent. In the present investigation, 15 hill goats were experimentally infected with 2 ml of 10% splenic suspension of a virulent isolate of PPR virus (PPR/Izatnagar/94) that had caused heavy mortality (>75%) in goats during 1994 outbreaks in northern India. More than 86% (13 of 15) animals died between 9 and 13 days post inoculation at the height of temperature or when temperatures were declining. Necropsy findings included congestion of gastrointestinal tract (GIT), nasal sinuses, consolidation of antero-ventral lobes of lungs, engorged spleen, and occasionally oedematous lymph nodes. Histopathological examination of major organs of GIT revealed degeneration and necrosis of labial mucosa, severe mucosal and submucosal congestion, degeneration and necrosis of intestinal epithelium and lymphoid cell depletion from Peyer's patches along with presence of syncytia at times. Lungs showed broncho-interstitial changes and presence of intracytoplasmic and intranuclear eosinophilic inclusions in alveolar macrophages and syncytial cells. These changes in lungs were frequently complicated with serofibrinous pneumonia (57%, eight of 14). Lymphocytolysis and occasional syncytia formation were evident in the lymphoid tissues. Immunohistochemical (IHC) findings included presence of PPR virus antigen in the labial, intestinal, and bronchiolar epithelial cells, pneumocytes, macrophages and syncytial cells in lungs, and lymphoid (intact and necrotic) and reticular cells in lymphoid organs. The findings of the study indicated the highly virulent nature of the PPR virus isolate (PPR/Izatnagar/94), causing 100% mortality and characteristic pathological changes in the target organs such as lungs, intestines and lymphoid tissues. The results of the IHC study suggested that indirect immunoperoxidase could be an alternative method in the absence of more sophisticated methods of laboratory diagnosis of PPR virus infection in goats.

Animals↗

Molecular heterogeneity among north Indian isolates of Group A Streptococcus.

AIM: To monitor molecular heterogeneity among the clinical isolates of group A Streptococcus (GAS) from north India by Vir and emm typing. METHODS AND RESULTS: GAS isolates, 31 from pharyngitis and nine from rheumatic fever (RF)/rheumatic heart disease (RHD) patients were differentiated into 16 Vir types (VT). These isolates were further discriminated into 23 emm types. Most of emm types were Vir type specific, except few (7.5%), which revealed different Vir types within same emm type. The most prevalent emm type found was emm 49 (15%) followed by 7.5% of emm 69, emm 71 and emm 75 which were different from emm type distribution reported from south India. CONCLUSIONS: Analysis of data revealed 40% heterogeneity by Vir typing and 57.5% by emm typing among GAS isolates which is significant in view of small number of isolates studied. SIGNIFICANCE OF IMPACT OF THE STUDY: The molecular study for the first time demonstrates different emm types prevalent and circulating in northern region of India and such data may help in selection of types for vaccine development.

Adolescent↗

Prevalence of anemia in adult rural population of north India.

OBJECTIVES: To find the prevalence of anemia in adult males and non-pregnant females of rural north Indian population. METHODS: During an epidemiological survey on hypertension in rural population of north India (n=2559), a random sample of 215 individuals underwent blood investigations including hemoglobin estimation. RESULTS: The overall prevalence of anemia in 16-70 years of age group was 47.9% (n=215), being 50% (n= 136) among females and 44.3% (n=78) among males. Low socioeconomic status, illiteracy and lower body mass index, were associated with higher prevalence of anemia. CONCLUSIONS: The finding of higher prevalence of anemia in adult males need further investigation and corroboration in other studies. The intervention for anemia should be directed on the community as a whole.

Adolescent↗