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Biomedical subjects

Baljinder Singh

Publications and source records attributed to Baljinder Singh.

11 recordsLinked to original sources

A Kv4.2 truncation mutation in a patient with temporal lobe epilepsy.

Temporal lobe epilepsy (TLE) has a multifactorial etiology involving developmental, environmental, and genetic components. Here, we report a voltage-gated potassium channel gene mutation found in a TLE patient, namely a Kv4.2 truncation mutation. Kv4.2 channels, encoded by the KCND2 gene, mediate A currents in the brain. The identified mutation corresponds to an N587fsX1 amino acid change, predicted to produce a truncated Kv4.2 protein lacking the last 44 amino acids in the carboxyl terminal. Electrophysiological analysis indicates attenuated K+ current density in cells expressing this Kv4.2-N587fsX1 mutant channel, which is consistent with a model of aberrant neuronal excitability characteristic of TLE. Our observations, together with other lines of evidence, raise the intriguing possibility of a role for KCND2 in the etiology of TLE.

Action Potentials↗

Stress degradation studies on ezetimibe and development of a validated stability-indicating HPLC assay.

Ezetimibe was subjected to different ICH prescribed stress conditions. Degradation was found to occur in hydrolytic and to some extent in photolytic conditions, while the drug was stable to oxidative and thermal stress. The drug was particularly labile under neutral and alkaline hydrolytic conditions. A stability-indicating HPLC method was developed for analysis of the drug in the presence of the degradation products. It involved a C-8 column and a mobile phase composed of ammonium acetate buffer (0.02 M, pH adjusted to 7.0 with ammonium hydroxide) and acetonitrile, which was pushed through the column in a gradient mode. The detection was carried out at 250 nm. The method was validated for linearity, range, precision, accuracy, specificity, selectivity and intermediate precision.

Azetidines↗

Terlipressin versus albumin in paracentesis-induced circulatory dysfunction in cirrhosis: a randomized study.

BACKGROUND: Therapeutic paracentesis in patients with cirrhosis induces arterial vasodilatation, causes a decrease in effective arterial blood volume and leads to circulatory dysfunction, which can be prevented by intravenous albumin. However, the use of albumin, being a blood product, is controversial. Recently, terlipressin, a vasoconstrictor, has been successfully used to combat this adverse effect of therapeutic paracentesis. Therefore, the aim of the present study was to investigate the preventive effect of terlipressin on paracentesis-induced circulatory dysfunction in patients with cirrhosis after therapeutic paracentesis and compared with that of intravenous albumin. METHODS: Forty patients with cirrhosis and tense ascites underwent therapeutic paracentesis with albumin or terlipressin in a randomized pilot study at a tertiary center. Effective arterial blood volume was assessed by measuring plasma renin activity at baseline and at 4-6 days after treatment. RESULTS: Effective arterial blood volumes as indicated by plasma renin activity before and 4-6 days after paracentesis did not differ in the two groups (19.15 +/- 12.1 to 20.33 +/- 12.8 ng/mL per h, P = 0.46 in the albumin group; and 20.11 +/- 10.6 to 21.08 +/- 10.52 ng/mL per h, P = 0.44 in the terlipressin group). Plasma aldosterone concentrations before and 4-6 days after paracentesis were also similar in both groups (1334.75 +/- 1058 to 1440.0 +/- 1161 pg/mL, P = 0.06 in the albumin group; and 1473.0 +/- 1168 to 1572.29 +/- 1182 pg/mL, P = 0.24 in the terlipressin group). Both terlipressin and albumin prevented paracentesis-induced renal impairment in these patients. CONCLUSIONS: Terlipressin may be as effective as intravenous albumin in preventing paracentesis-induced circulatory dysfunction in patients with cirrhosis after therapeutic paracentesis.

Albumins↗

Progressive cerebral disease in lymphomatoid granulomatosis causes anterograde amnesia and neuropsychiatric disorder.

The authors report neuropsychological (NP) and serial quantitative magnetic resonance imaging (MRI) findings of a 29-year-old woman with lymphomatoid granulomatosis (LG). Disease course was characterized by acute psychosis, tremor, fever, seizures, and progressive cognitive impairment. At the time of symptom onset, brain MRI revealed mild lesion volume and normal parenchymal volume. This was followed by dramatic progression of brain lesions and atrophy over 2 years, at which point the patient expired. Atrophy was most prominent in the mesial temporal lobes. NP testing revealed marked amnesia and mild impairments in other cognitive domains. To our knowledge, this is the first recorded case of LG in which bilateral temporal lobe atrophy is evident and accompanied by anterograde amnesia. We speculate that temporal lobe atrophy was influenced by the established susceptibility of this region in various neurological diseases.

Adult↗

A magnetization transfer MRI study of deep gray matter involvement in multiple sclerosis.

BACKGROUND/PURPOSE: Gray matter involvement in multiple sclerosis (MS) is of growing interest with respect to disease pathogenesis. Magnetization transfer imaging (MTI), an advanced MRI technique, is sensitive to disease in normal appearing white matter (NAWM) in patients with MS. DESIGN/METHODS: We tested if MTI detected subcortical (deep) gray matter abnormalities in patients with MS (n= 60) vs. age-matched normal controls (NL, n= 20). Magnetization transfer ratio (MTR) maps were produced from axial proton density, conventional spin-echo, 5 mm gapless slices covering the whole brain. Region-of-interest-derived MTR histograms for the caudate, putamen, globus pallidus, thalamus, and NAWM were obtained. Whole brain MTR was also measured. RESULTS: Mean whole brain MTR and the peak position of the NAWM MTR histogram were lower in patients with MS than NL (P < .001) and mean whole brain MTR was lower in secondary progressive (SP, n= 10) than relapsing-remitting (RR, n= 50, P < .001) patients. However, none of the subcortical gray matter nuclei showed MTR differences in MS vs. NL, RR vs. SP, or SP vs. NL. CONCLUSIONS: The MTI technique used in this cohort was relatively insensitive to disease in the deep gray matter nuclei despite showing sensitivity for whole brain disease in MS. It remains to be determined if other MRI techniques are more sensitive than MTI for detecting pathology in these areas.

Adult↗

Validated specific HPLC method for determination of zidovudine during stability studies.

The objective of the current study was to develop a validated stability-indicating assay method (SIAM) for zidovudine (3'-azido-3'-deoxythymidine) after subjecting it to forced decomposition under hydrolysis, oxidation, photolysis and thermal stress conditions. The drug decomposed under hydrolytic stress upon refluxing, and also on exposure to light. It was stable to oxidation and thermal stress. The same major decomposition product could be seen in all the decomposed solutions, which was identified as thymine through comparison with the standard. Separation of drug from major and minor degradation products was successfully achieved on a C-18 column utilising water-methanol in the ratio of 77:23. The detection wavelength was 265 nm. The method was validated and response was found to be linear in the drug concentration range of 25-500 microg ml(-1). The mean values (+/-R.S.D.) of slope and correlation coefficient were 21,859 (+/-0.213) and 0.9995 (+/-0.00578), respectively. The R.S.D. values for intra- and inter-day precision were <0.9 and <1.6%, respectively. The method was established to have sufficient intermediate precision as similar separation was achieved on another instrument handled by a different operator. The recovery of the drug from a mixture of degraded samples ranged between 100.6 and 100.9%. PDA peak purity test confirmed the specificity of the method. The method was also successful in analysis of drug in marketed tablets subjected to stability testing under accelerated conditions of temperature, humidity, and to thermal and photolytic stress.

Chromatography, High Pressure Liquid↗

Establishment of inherent stability of stavudine and development of a validated stability-indicating HPLC assay method.

The present study describes degradation of stavudine under different stress conditions (hydrolysis, oxidation, photolysis and thermal stress), and establishment of a stability-indicating reversed-phase HPLC assay method. The drug was found to hydrolyse in acidic, neutral and alkaline conditions and also under oxidative stress. The major degradation product formed under various conditions was thymine, as evidenced through comparison with the standard and spectral studies (NMR, IR and MS) on the isolated product. Separation of drug, thymine and another minor degradation product was successfully achieved on a C-18 column utilising water-methanol in the ratio of 90:10. The detection wavelength was 265 nm. The method was validated with respect to linearity, precision (including intermediate precision), accuracy and specificity. The response was linear in the drug concentration range of 25-500 microg ml(-1). The mean values (+/-R.S.D.) of slope and correlation coefficient were 24256 (+/-0.679) and 0.9994 (+/-0.0265), respectively. The R.S.D. values for intra- and inter-day precision studies were <0.210 and <1%, respectively. The recovery of the drug ranged between 99.7 and 101.5% from a mixture of degraded samples. The method even proved to be affective on application to a stressed marketed capsule formulation.

Chromatography, High Pressure Liquid↗

Lung scintigraphy in the diagnosis and follow-up of pulmonary thromboembolism in children with nephrotic syndrome.

Thromboembolic phenomenon and pulmonary embolism is quite frequent in children with nephrotic syndrome (NS). The incidence of pulmonary thromboembolism in children with NS is as common as in adults, and severity is also reported to be relatively high. The mortality rate in NS with thromboembolic complications may be significantly increased if not diagnosed and treated well in time. For establishing the diagnosis of pulmonary embolism, although the combined use of magnetic resonance venography and CT angiography has been proposed, V/Q scan is still the best modality. We performed serial lung perfusion scans in two young patients with NS who developed sudden onset tachypnea during their stay in the hospital. Initial lung perfusion scans showing marked perfusion defects and normal chest X-rays indicated a high probability for pulmonary embolism. The patients were treated with streptokinase, and the study was repeated. Marked improvement was seen in lung perfusion, thereby highlighting the importance of lung perfusion scan in the follow-up of such patients.

Child, Preschool↗

Comparison of left ventricular functional parameters measured by gated single photon emission tomography and by two-dimensional echocardiography.

The aim of the present study was to evaluate the correlation amongst left ventricular (LV) functional parameters estimated by gated single photon emission tomography (GSPET) and two-dimensional (2D) M-mode, echocardiography (ECHOC). GSPET was performed in a single day stress/rest protocol by using either technetium-99m methoxy-isobutyl-isonitrile ((99m)Tc-MIBI) or technetium-99m tetrofosmin ((99m)Tc-myoview) in 36 consecutive patients, 21 males and 15 females; mean age 57.6+/-11.8 y, range 32-82 y. The various LV parameters studied were: ejection fraction (EF), end systolic volume (ESV), end diastolic volume (EDV), stroke volume (SV) and LV mass (LVM). The GSPET data were reconstructed using an automatic algorithm employing filtered back projection (FBP) and further analyzed by Emory cardiac (EC) toolbox versions EO-00369 and EO-00733 for the quantitative determinations of these parameters. All patients underwent ECHOC within 1-2 h of the post-stress data acquisition of GSPET. Our results showed that the LV volumes and the LVM showed good correlation (r=0.749 to 0.952, P=0.01). These values could thus be used interchangeably. The assessment of these parameters by GSPET therefore does not seem to be affected by the dose of the radioactivity administered as the dose of the (99m)Tc-labeled myocardial agents for acquiring rest study was approximately four times higher than that for the stress study. Our results also showed that the mean +/- SD values of the volumes and the EF of the LV evaluated by the two techniques, differed significantly except significant correlations for ESV, EDV and LVEF were observed between the two methods: r=0.574 to 0.954; 0.347 to 0.952 and 0.516 to 0.876 respectively. On the other hand, a wide disagreement was observed in estimating the LVM by the two techniques. The LVM measurements by 2D ECHOC were approximately double the values estimated by GSPET. Despite the large disagreement, a small correlation (r=0.33, P=0.05) was observed for LVM between the two techniques. In conclusion, although we observed a good correlation for LV volumes and LVM between the GSPET and the ECHOC techniques, yet these two techniques cannot be used interchangeably.

Adult↗