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Biomedical subjects

R Kumar

Publications and source records attributed to R Kumar.

At least 649 records · Page 36Linked to original sources

Treatment of putative immune-mediated and idiopathic cervical dystonia with intravenous methylprednisolone.

A young pregnant woman developed a persistent dystonic head tremor a few days after Rho (D) immune globulin administration; further deterioration occurred after a second administration of Rh(o) (D) immune globulin with the development of marked retrocollis. This persisted and she was treated 2 months later with a 5-day course of intravenous (1 g daily) methylprednisolone (IVMP) with resolution of her condition. We proceeded to treat similarly the next four patients with idiopathic cervical dystonia who were seen in our practice and who had current symptoms of less than 6 months duration. One also experienced persistent resolution and another had a marked, but transient, improvement after each of two separate courses of IVMP. The other two patients did not have improvement. This suggests a possible autoimmune pathogenesis for a limited subset of cervical dystonia. However, identifying which cases of recent-onset cervical dystonia will respond to IVMP therapy has yet to be determined.

Adult↗

Coexistence of tics and parkinsonism: evidence for non-dopaminergic mechanisms in tic pathogenesis.

We report four patients with tics since childhood who presented with typical Parkinson's disease (PD). No alteration in tics occurred before or during the development of symptoms. L-Dopa/carbidopa therapy in three patients improved parkinsonism without worsening tics over 3 months to 11 years of follow-up. Our experience fails to support hypotheses exclusively emphasizing overactivity of dopaminergic function underlying tics that would predict that PD would reduce and L-dopa exacerbate tics. This emphasizes the role of other neurotransmitter systems in the pathophysiology of tics.

Aged↗

Vascular expression of polycystin.

Autosomal dominant polycystic kidney disease (AD-PKD) is predominantly caused by mutations of the gene PKD1, which encodes a large protein, polycystin, of unknown function. A variety of arterial abnormalities occur with increased prevalence in ADPKD patients. Using an antiserum against the nonduplicated region of the polycystin protein, immunostaining of vascular smooth muscle cells was detected in normal adult elastic arteries. Partial digestion of tissue slices with nonspecific proteases greatly enhanced this staining. Similar enhancement was seen with specific elastase digestion. Immunostaining for smooth muscle actin was not affected by elastase. Antiserum preadsorbed with peptide antigen gave no staining. In specimens of intracranial aneurysms, aortic dissections, and dolichoectatic arteries from thirteen patients with ADPKD, immunostaining of variable intensity for polycystin was demonstrated in arterial smooth muscle cells and myofibroblasts, along with disruption of elastic laminae. Further elastase digestion did not significantly alter staining patterns. Intracranial aneurysms from patients without ADPKD also showed a variable degree of immunostaining with polycystin antisera in the same distribution. The expression of polycystin in arterial smooth muscle suggests a direct pathogenic role for ADPKD-related mutations in the arterial complications of this disease.

Adolescent↗

Changes in myosin heavy chain (MHC) expression during pregnancy in rat uterus.

Expression of myosin heavy chain (MHC) was investigated in rat uterus during pregnancy. Two MHC isoforms, SM MHCI (204 kDa) and SM MHCII (200 kDa), were resolved following the analysis of Guba Straub extract of non-pregnant and pregnant uterus using sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Whereas SM MHCI showed an increase from 69.26 +/- 3.26% in nonpregnant uterus to 81.40 +/- 5.36% in pregnant uterus, the SM MHCII exhibited a corresponding decline from 30.73 +/- 3.29 to 18.59 +/- 5.36%. The native myosin separated under non-dissociating conditions and subsequently analyzed in denaturing SDS-PAGE also demonstrated two MHC isoforms with identical electrophoretic mobilities. A SDS-PAGE analysis of native myosin from pregnant rats extracted at room temperature and in the absence of proteolytic inhibitors revealed a characteristically increased proteolysis of MHC into two peptide products of 153 and 140 kDa during pregnancy. Such a proteolysis of MHC, but in very low proportions, was noticed in nonpregnant uterus too.

Animals↗

Smoking in pregnancy: a study of psychosocial and reproductive risk factors.

Smoking during pregnancy is a well-recognized public health problem and several associated variables to smoking have been identified such as low socioeconomic status, low educational attainment, low social support, younger age and unplanned pregnancy. The purpose of this research was to further examine possible risk factors associated with smoking in pregnancy. One hundred and nineteen pregnant women who were having their first babies had been recruited in early pregnancy from a General Hospital Obstetric Service and were followed up throughout the pregnancy and then until 4 years after the birth of the baby. The findings of this longitudinal study have already been reported in relation to maternal postnatal depression and to child development and in the analyses of smoking behavior which are reported here, it was possible to control for several confounding variables in the search for possible risk factors. Women who smoked during pregnancy were more likely to have had previous miscarriages and terminations and to have taken longer to conceive this pregnancy. They were also more likely to report marital difficulties and more likely to physically discipline their 1-year-old infants. These results point to a possible different perspective in trying to understand this intransigent unhealthy behavior.

Adult↗

Quantification of behaviour in social colonies of rhesus monkey.

It is necessary to use experimental animals with behavioural, physiological and disease susceptibility pattern similar to man so that the results have a clinical predictive value. For such studies the non-human primate is the animal of choice. Rhesus monkey is a good choice for this purpose but information about its behaviour is fragmentary. In order to obtain a quantitative baseline data for psychopharmacological studies, a protocol has been developed to score various social and solitary behaviours in adult male and female rhesus monkeys. The study was conducted on rhesus monkeys in a social colony of one male and seven female living in a semi-restricted environment. The behavioural patterns were quantitated so as to compare effect on various components of behaviour. Aggressiveness and vigilance were prominent in the male while social affiliative behaviour was dominant in the female. Other behavioural responses were of similar magnitude in both sexes. It is however necessary to have data with some standard CNS active agents on these behavioural protocol. Therefore, initially the behavioural effects of amphetamine and haloperidol were studied. Significant effects observed following d-amphetamine (1-4 mg/kg, im); it induced dose dependent suppression of social behaviour (approach, contact, grooming), feeding, hypervigilance, stereotypy and oral hyperkinesia. On the other hand haloperidol (0.01-0.04 mg/kg, im) produced decrease in social and solitary behaviour and marked cataleptic posture. It is possible to quantitate drug effects on various aspects of behaviour of the rhesus monkey and to develop neuropsychitric models with the help of this protocol for use in study of drug effects on behaviour.

Aggression↗

Heterotopic ossification after total knee arthroplasty.

Heterotopic ossification (HO) is a rare complication following total knee arthroplasty (TKA). In the case report presented, a 52-year-old man who had previously undergone TKA for osteoarthritis noticed painful limitation of range of motion (ROM) in spite of active participation in physical therapy and the use of a continuous passive motion machine. A plain radiograph 1 month after surgery revealed HO anterior to the distal femoral shaft in the quadriceps expansion. Ambulation for this patient was limited to short distances because of severe pain and limitation in ROM. The patient underwent manipulation under general anesthesia 2 months after the TKA. Range of motion in flexion improved from 50 degrees to 110 degrees, and the patient became ambulatory without assistive devices. However, the flexion range deteriorated to 50 degrees over a period of 4 months, and ambulation again became significantly limited. The patient underwent resection of HO 6 months after manipulation and regained his ROM to 110 degrees in flexion. He was prescribed indomethacin after surgery for 2 months to prevent recurrence of HO. Follow-up radiographs 3 months after surgery revealed minimal recurrence of HO. The patient's ROM did not deteriorate, and he remained ambulatory. Heterotopic ossification should be suspected in post-TKA patients if ROM does not improve. Physical therapy including ROM exercises remains an essential component in the treatment of HO. Manipulation under general anesthesia or surgical resection of HO may be inevitable in certain patients whose ambulation is significantly limited.

Humans↗

Reversion of uroepithelial cell tumorigenesis by the ectopic expression of human wnt-5a.

Wnt gene family members are thought to play an important role in cell growth and differentiation. When normal wnt gene expression is disrupted, there is the potential for cell transformation. We have found previously that a strong correlation exists between the loss of normal wnt-5a gene expression and cell transformation (Olson and Papkoff, Cell Growth & Differ., 5: 197-206, 1994). Recently, this has been tested directly using antisense wnt-5a, which, when expressed in mouse mammary cells, results in cell transformation (Olson and Gibo, Antisense wnt-5a transforms C57MG mouse mammary epithelial cells, manuscript in preparation). We hypothesize that wnt-5a is a growth-regulating gene, the disruption of which could result in tumorigenesis. The multistage progression of many human cancers involves the loss of normal tumor suppressor gene(s) activity. Several tumor suppressor genes are thought to map to chromosome 3p11-p25. We have studied the ectopic expression of human wnt-5a (3p14-p21) in a tumorigenic uroepithelial cell line with deletion of chromosome 3p13-p21.2. This results in loss of tumorigenicity in athymic nude mice and suppresses anchorage-independent cell growth in soft agar. This suggests that human wnt-5a is a novel tumor suppressor gene in uroepithelial cell carcinoma and may be one of the suppressor genes deleted or rearranged on chromosome 3p.

Animals↗

Comparative evaluation of two indigenously developed tests for rapid detection of group-A streptococci directly from throat swabs.

The efficacy of two indigenously developed rapid tests, latex agglutination and antibody capture assay (a colour immunochromatographic assay) to detect group A Streptococcus pyogenes (GAS) was evaluated in comparison with the traditional culture method ('Gold Standard') in both asymptomatic children (1500) and symptomatic patients (233). Throat swabs were taken in duplicate and rapid tests performed on one swab and culture on the other. Both latex agglutination and antibody capture assays showed a sensitivity of 100 per cent and specificity of > 98 per cent as compared to culture and isolation in symptomatic patients. However, among asymptomatic carriers sensitivity of 100 per cent and 87.5 per cent and specificity > 95 per cent were observed for latex agglutination and antibody capture assays respectively. Latex agglutination showed no false negative results and sensitivity was not affected by low beta-haemolytic counts in asymptomatic children. The rapid tests described here will help in the detection and thereby the management of GAS infection.

Adolescent↗

Reproductive tract infections--and associated difficulties.

In addition to financial constraints there are significant social, educational, moral and religious barriers to the prevention and treatment of reproductive tract infections in rural India. A pilot project aimed at achieving progress in this field is reported below.

Adult↗

Clinical global measures of dementia. Position paper from the International Working Group on Harmonization of Dementia Drug Guidelines.

Following is the report of the committee working on clinical global measures for antidementia drug guidelines. The concepts involved in global scales, the distinctions between change and severity scales, advantages and disadvantages of structured interviews, and anchoring of change scores are discussed, and selected existing clinical global scales are described. In addition, the committee assessed the utility of global scales in clinical trials for antidementia drugs. There was a consensus among the members of the working group on the following: (1) Clinical global scales are interview based; in most cases, they include information obtained from caregivers as well as directly from patients, but they can rely on information from the subject only. (2) Clinicians' global ratings are intended to assess clinically meaningful change based on multidimensional clinical assessment and take into account the clinical heterogeneity of dementia by assessing at least cognition, behavior, and functioning. (3) There are two distinct types of clinical global measures: (a) clinicians' interview-based global severity scales, which generally incorporate classification by stage or severity of illness and (b) clinicians' interview-based global change scales, which incorporate global assessment ratings of clinical change. The committee could not reach a consensus on whether global scales should be required in phase II and phase III clinical trials, or whether other specific assessments such as well-designed activities of daily living, cognition, and behavior measures could, when used in appropriate combinations, replace the global as assessments of clinical meaningfulness.

Activities of Daily Living↗

Isolation of a fluoroquinolone resistant Shigella dysenteriae 1 strain from Calcutta.

Fourteen strains of Shigella spp. were isolated from patients aged 5-12 yr, hospitalized with dysentery during 1995-1996. The strains isolated were Shigella dysenteriae 1, S. flexneri and S.sonnei. All but one of the 14 strains were sensitive to ciprofloxacin and norfloxacin. The MIC of both the fluoroquinolones was 15 micrograms/ml for the resistant S.dysenteriae 1 strain (NRM4). Therefore, the careful use of antimicrobials is required for therapy of Shigellosis.

Anti-Infective Agents↗

Changes in uterine myosin isozymes from goat during early pregnancy.

Changes in the expression of native myosin, myosin heavy chains (MHCs) and myosin light chains (MLCs) were investigated in goat uterus during early pregnancy. Electrophoresis of native myosin under non dissociating conditions displayed two isozymes differing in their proportions during gestation. Three MHC isoforms were obtained following sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE). Whereas 204 kDa (a smooth muscle MHC) and 196 kDa (a non muscle MHC) were recorded in uterus from non pregnant goat, uterus of pregnant goat displayed a third 200 kDa smooth muscle MHC. Two conspicuous proteins (154 and 140 kDa respectively) in addition to MHCs were also obtained when the myofibrillar extracts were analysed either in the presence or absence of proteolytic inhibitors. Non pregnant goat uterus showed a basal level (ca.5%) of phosphorylation of regulatory myosin light chain. Uterine myosin from pregnant goat was recorded in a completely dephosphorylated state.

Animals↗

Impact of health centre availability on utilisation of maternity care and pregnancy outcome in a rural area of Haryana.

Six hundred married women of 15-45 years age group were interviewed in 4 villages of the district Ambala in Haryana. Impact of health centre (HC) availability on the knowledge, opinion and practices related to maternity care and pregnancy outcome was assessed after adjusting the effect of socio-economic status. Except 17 women (2.8%), everyone knew at least one correct purpose of antenatal care (ANC) and 98.2% women had contacted health staff for ANC. However, knowledge of the respondents about the components of ANC was found to be poor in study villages. Traditional birth attendants (TBAs) conducted delivery in 76.1% cases in sub-centre (SC), 75.6% in villages without a HC compared to 49.8% in primary health centre (PHC) village. However, preference for TBAs in PHC village was 14.9%, in SC village 33.5%, and in villages without HC 36.3% (p < 0.001). Among respondents having better awareness about ANC components, preference and utilisation of modern delivery attendants was found to be higher. For maternity illnesses, consultation rate of government functionaries was 67.9% in PHC village, 52.2% in SC village and 55.8% in villages without a HC. Perinatal mortality rate of 76.0/1000 births in villages without HC was not significantly different from the rate of 87.4/1000 in SC village but rate of 38.9/1000 in the PHC village was significantly lower (p < 0.01). Awareness and availability of modern maternity services were found to have significant influence on the health seeking behaviour and pregnancy outcome.

Adolescent↗