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Biomedical subjects

K Sethi

Publications and source records attributed to K Sethi.

17 recordsLinked to original sources

Clinico-immunologic aspects of botulinum toxin type B treatment of cervical dystonia.

In this multicenter study of 100 patients with cervical dystonia, we examined the immunogenicity of botulinum toxin type B (BTX-B) and correlated the clinical response with the presence of blocking antibodies (Abs) using a novel mouse protection assay. One-third of the patients who were negative for BTX-B Abs at baseline became positive for BTX-B Abs at last visit. Thus, the high antigenicity of BTX-B limits its long-term efficacy.

Botulinum Toxins↗

In vivo expression of myosin essential light chain using plasmid expression vectors in regenerating frog skeletal muscle.

It is well established that mutations in specific structural elements of the motor protein myosin are directly linked to debilitating diseases involving malfunctioning striated muscle cells. A potential way to study the relationship between myosin structure and function is to express exogenous myosin in vivo and determine contractile properties of the transgenic muscle cells. However, in vivo expression of functional levels of contractile proteins using transient transgenesis in skeletal muscle has not been demonstrated. Presently, we used in vivo gene transfer to express high levels of full-length myosin light chain (MLC) in skeletal muscle fibers of Rana pipiens. Anterior tibialis (AT) muscles were injected with cardiotoxin to cause degeneration and then injected at various stages of regeneration with plasmid expression vectors encoding full-length MLC1(f). In fibers from the most robustly transfected muscles 3 weeks after plasmid injections, trans-MLC1(f) expression averaged 22-43% of the endogenous MLC1(f). Trans-MLC1(f) expression was the same whether a small epitope tag was placed on the C- or N-terminus and was highly variable along individual fibers. Confocal microscopy of skinned fibers showed correct sarcomeric incorporation of trans-MLC1(f). The expression profile of myosin heavy chain isoforms 21 days after transfection was similar to normal AT muscle. These data demonstrate the feasibility of using in vivo gene transfer to probe the structural basis of contractile protein function in skeletal muscle. Based on these promising results, we discuss how further improvements in the level and consistency of myosin transgene expression may be achieved in future studies, and the therapeutic potential of plasmid gene transfer in regenerating muscle.

Animals↗

Ropinirole for restless legs syndrome: a placebo-controlled crossover trial.

The authors performed a double-blind, placebo-controlled, crossover study of ropinirole (0.5 to 6.0 mg/day) for restless legs syndrome (RLS). The RLS Rating Scale score improved (p < 0.001) from a mean (SD) of 25 (7) during placebo treatment to 13 (12) during ropinirole treatment. Eight of the 22 patients had complete resolution of symptoms on ropinirole. Adverse events included nausea and dizziness. Ropinirole was effective and well tolerated for treating the symptoms of RLS.

Adult↗

British-Asian women's views on and attitudes towards menopause and hormone replacement therapy.

OBJECTIVE: To establish an understanding of the views and values of Asian women living in the UK but of Indian subcontinent origin, in relation to the menopause and hormone replacement therapy (HRT): hopefully this will allow the development of strategies for increasing HRT uptake and long-term adherence. METHOD: This was a postal, structured questionnaire survey, completed anonymously by British-Asian women who expressed their opinions and knowledge about the menopause and HRT, including their views on service provision. RESULTS: Some 70% of women were in the age range 40-59 years; 74.5% had some education. In all 82% declared that they understood the menopause, and 77% thought that the menopause was a natural phenomenon. Over 75% were interested in seeking a medical opinion for management of the menopause. Of the women surveyed, 33% (n = 88) felt happy about and 46% (n = 123) felt frightened by the menopause. CONCLUSIONS: The results suggest an overwhelming demand for information and the need for special clinics run by female doctors who can communicate in the women's own language. Fears and concerns are similar to those of the Caucasian population.

Adult↗

Verapamil for severe hyperkinetic movement disorders.

The use of verapamil in three cases of severe hyperkinetic movement disorders resulted in dramatic improvement in patients who had been refractory to many other treatments over a prolonged period. A videotape illustration of one of the patients is provided. The mechanism of action and evidence of efficacy of calcium-channel blockers for abnormal movements are discussed.

Adult↗

Antimicrobial susceptibility and plasmid profile of Neisseria gonorrhoeae in India (New Delhi).

OBJECTIVES: To determine the antibiotic susceptibility and plasmid profile of all Neisseria gonorrhoeae strains (PPNG and non-PPNG) isolated from May 1995 to March 1996 in Lok Nayak Hospital, New Delhi, India. METHODS: The agar plate dilution method was used to determine the minimum inhibitory concentration of five antimicrobials including norfloxacin and ceftriaxone which are most commonly used for treatment of gonorrhoea in Delhi. Isolates were screened for production of penicillinase by paper acidometric method and plasmid analysis of PPNG and non-PPNG was carried out by agarose gel electrophoresis. RESULTS: 50 consecutive isolates of N gonorrhoeae were studied, 8% among them were found to be PPNG while 28% were highly resistant to tetracycline (TRNG). Reduced susceptibility to norfloxacin (MIC > or = 1 microgram/ml) was observed in 12% of all isolates. All PPNG harboured the 4.4 MDa beta lactamase plasmid along with the 25.2 MDa tetracycline resistance plasmid. Norfloxacin resistance (MIC > or = 1 microgram/ml) was present in 28.5% of TRNG but only in 5.5% of the other gonococcal isolates. CONCLUSIONS: Results of this study clearly demonstrate that antibiotic resistant gonococcal strains of different clones are frequently found in New Delhi. Continued surveillance of susceptibility to currently prescribed antimicrobials and epidemiological studies are essential to prevent treatment failures leading to further spread of resistant strains.

Adolescent↗

A multicenter trial of ropinirole as adjunct treatment for Parkinson's disease. Ropinirole Study Group.

OBJECTIVE: To evaluate the nonergot dopamine agonist ropinirole as an adjunct to L-dopa in a randomized, double-blind trial in PD patients with motor fluctuations. BACKGROUND: L-dopa in the treatment of PD is associated with motor fluctuations, dyskinesia, and other adverse effects. The use of dopamine agonists in the treatment of PD delays recourse to L-dopa and thus delays the possibility of adverse effect onset. METHODS: Ropinirole (n = 95) or placebo (n = 54) was added to L-dopa, and L-dopa was then reduced in a planned manner during the 6-month trial. RESULTS: A significantly greater number of ropinirole patients were able to achieve a 20% or greater reduction in both L-dopa dose and in percent time spent "off" compared with placebo (35.0% versus 13.0%; p = 0.003). The mean daily L-dopa dose was reduced significantly with ropinirole treatment (242 mg versus 51 mg; p < 0.001) as was the percent awake time spent "off" (11.7% versus 5.1%; p = 0.039). There was no difference in the percent of patients who withdrew because of adverse effects (15.8% on ropinirole versus 16.7% on placebo). CONCLUSIONS: Ropinirole permits a reduction in L-dopa dose with enhanced clinical benefit for PD patients with motor fluctuations.

Antiparkinson Agents↗

Thrombotic thrombocytopenic purpura in systemic lupus erythematosus and antiphospholipid antibodies: effective treatment with plasma exchange and immunosuppression.

We describe 2 patients with systemic lupus erythematosus (SLE) with neurological complications and thrombocytopenia, who, upon further investigation, were found to have thrombotic thrombocytopenic purpura. While neither patient responded to treatment with corticosteroids, both responded to plasma exchange and intravenous cyclophosphamide. This highlights the need to carefully consider this diagnosis in patients with SLE presenting with neurological complications and thrombocytopenia.

Adult↗

Aminoglycoside nephrotoxicity and its predictability.

Nephrotoxicity was evaluated in 37 patients receiving aminoglycosides by serial urinary measurements of the low-molecular weight protein beta 2-microglobulin (beta 2m) and the proximal tubular enzymes N-acetyl-glucosaminidase and beta-glucuronidase. Clinical nephrotoxicity, with a rise in serum creatinine greater than 20% of the baseline value, was diagnosed in 15 of 30 evaluable patients. The laboratory diagnosis of nephrotoxicity, defined as a two-fold increase in beta 2m, N-acetylglucosaminidase and beta-glucuronidase, was confirmed in 11/15 patients. Additionally, there were 3 patients in whom there was definitive laboratory nephrotoxicity in the absence of a rise in serum creatinine. The laboratory diagnosis of nephrotoxicity could be made 4.1--5.5 days prior to significant elevation in serum creatinine. The data suggest that beta 2m and enzyme studies are predictors of nephrotoxicity.

Acetylglucosaminidase↗

Proteinuria following renal transplantation.

Proteinuria was studied in ten renal allograft recipients; it was defined as: (a) glomerular--characterized by predominant albumin excretion; (b) tubular--significant excretion of both albumin and low molecular weight (LMW) proteins; and (c) glomerulo-tubular or mixed type, a combination of the two. LMW protein and albumin were quantitated by polyacrylamide gel electrophoresis with sodium dodecyl sulfate. In the immediate posttransplant period, LMW protein and albumin excretion, expressed as a percentage of creatinine clearance, were high, revealing a mixed pattern, and excretion of both protein classes was higher than during both acute tubular necrosis and acute rejection crisis. Tubular proteinuria was observed in acute tubular necrosis; a glomerulo-tubular or mixed pattern of protein excretion in acute rejection crises.

Adolescent↗

beta2 microglobulinuria in a patient with nephrotoxicity secondary to mercuric chloride ingestion.

A case of mercuric chloride intoxication is reported in which protein excretion was measured. Urinary albumin and low molecular weight proteins, including beta2 microglobulin, were greatly elevated following ingestion, reaching maximal values on the second day. The increased excretion of both albumin and beta2 microglobulin indicated the presence of both tubular and glomerular lesions. Data obtained on this patient suggest that the determination of beta2 microglobulin may be useful guide for the evaluation of renal tubular function.

Adolescent↗

Method for measuring the concentration of urinary proteins according to their molecular size category.

We combined the use of a concentrating device (Minicon) and polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate to semi-quantitate the concentration of (a) the collective low-molecular-weight proteins and (b) of albumin excreted in the urine of patients after renal transplantation. Analytical recovery of many serum proteins from samples concentrated 100-fold in the Minicon apparatus was about 70%. It was possible to examine many urine samples by polyacrylamide gel electrophoresis after concentration with this device. The reproducibility (CV) of the technique was on the order of 20% when albumin and low-molecular-weight protein were in about equal concentration. The method was adequate to differntiate glomerular and tubular proteinuria, because in glomerular proteinuria the ratio of albumin to low-molecular-weight proteins is about 20/1, whereas in tubular proteinuria the ratio is about 1/1.

Electrophoresis, Polyacrylamide Gel↗

IgG ratios and oligoclonal IgG in multiple sclerosis and other neurological disorders.

The findings are reported of various CSF abnormalities, including IgG indices and oligoclonal IgG, in 160 patients with multiple sclerosis of differing diagnostic certainty and 146 patients with other neurological disorders. An abnormal IgG index, defined as the ratio of IgG/albumin in CSF to that in serum, has been found in 77.7% of definite MS cases, falling to a figure of 32.1% in the single lesion group. A tendency, reported previously, for IgG levels to be higher in disabled patients, particularly those with a short history or early onset, has been confirmed. Oligoclonal IgG, on the other hand, has been found in 56% of definite MS cases, less frequently than in most other reported series. Analysis of the literature suggests considerable variability in the finding of oligoclonal IgG in other than definite MS, and in other neurological disorders. The possibility that subjective factors are partly responsible for this variability, rather than discrepancies in patient selection requires consideration, and suggests that CSF electrophoresis and IgG estimations are complementary aids in the diagnosis of multiple sclerosis. Differences have been expressed regarding the relationship of oligoclonal IgG to clinical parameters of the disease. Further sequential analysis of the development and variability of the oligoclonal pattern in MS is required.

Adult↗

Does balance control deficit account for walking difficulty in Parkinson's disease?

Patients with Parkinson's disease (PD) walk slowly, in part to compensate for their balance control deficit. We tested the effect of balance support to determine if walking performance in PD patients would improve. The sample consisted of unmedicated older adults with idiopathic Parkinson's disease who had poor balance control but no stooped posture, arthritis or muscle weakness. There was no difference in walking speed between unsupported and supported walking. The speeds were between those reported for disease-free older adults and older adults with muscle weakness and a history of falling. PD patients' walking difficulties, even while using a balance aid, may be partly explained by their set-changing problems. They frequently hold the cane off the ground when walking, suggesting their set-changing difficulty may be severe enough that using it aggravates their walking difficulty. Treatment of walking difficulty in PD patients should consider interventions other than those dealing only with balance control.

Adult↗