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Biomedical subjects

M Bhatia

Publications and source records attributed to M Bhatia.

At least 19 recordsLinked to original sources

Hematopoietic capacity of adult human skeletal muscle is negligible.

Using experimental mouse models, hematopoietic potential has been shown to exist within skeletal muscle. In humans, the clinical utility of using muscle-derived hematopoietic progenitors remains uncertain. Here, we evaluate the hematopoietic potential of human skeletal muscle. De novo adult muscle contained markedly reduced levels of hematopoietic colony-forming units (hCFU) and negligible responsiveness to hematopoietic ex vivo culture conditions that augment hematopoietic activity of fetal muscle. Neither fetal nor adult muscle yielded significant engraftment in transplanted immune-deficient mice. Although adult muscle possessed 1.5+/-0.9 hCFU/g, similar hematopoietic activity (2.3+/-0.17 hCFU) could also be demonstrated from as little as 3-10 microl of contaminating peripheral blood. We suggest that the clinical utility of adult skeletal muscle as an alternative source of hematopoietic cells in humans appears limited due to the low yield of blood-forming precursors and their lack of responsiveness to ex vivo expansion.

Adult↗

Unidirectional whole body turning: a new lateralising sign in complex partial seizures.

BACKGROUND: The lateralising significance of unidirectional whole body turning in patients with complex partial seizures (CPS) arising from the temporal lobe was evaluated. METHODS: A total of 330 patients undergoing long term video-EEG study were included. "Unidirectional whole body turning" was defined as rotation of the trunk, head, and limbs by >90 degrees and lasting >10 s. EEG correlates, MRI, and SPECT findings were compared and outcome after surgery was noted for patients with follow up data for >1 year. RESULTS: Unidirectional whole body turning was observed in 13 patients with a mean age of 18+/-8 years. Concordance of the side of whole body turning with the EEG focus and MRI findings was observed in 11 of the 13 patients (84.7%) and in 26 of 28 seizures (92.8%). The six patients who underwent temporal lobectomy or resection of lesion, opposite to the direction of body turning, had good seizure outcome. CONCLUSION: Unidirectional whole body turning is a new lateralising sign in temporal lobe CPS with good predictive value for epileptogenic focus contralateral to the direction of turning.

Adolescent↗

Inflammatory response on the pancreatic acinar cell injury.

Acute pancreatitis is an inflammatory disorder, and inflammation not only affects the pathogenesis but also the course of the disease. Acinar cell injury early in acute pancreatitis leads to a local inflammatory reaction; if marked this leads to a systemic inflammatory response syndrome (SIRS). An excessive SIRS leads to distant organ damage and multiple organ dysfunction syndrome (MODS). MODS associated with acute pancreatitis is the primary cause of morbidity and mortality in this condition. Recent studies by us and other investigators have established the critical role played by inflammatory mediators such as TNF-alpha, IL-1beta, IL-6, IL-8, CINC/GRO-alpha, MCP-1, PAF, IL-10, CD40L, C5a, ICAM-1, MIP1-alpha, RANTES, substance P, and hydrogen sulfide in acute pancreatitis and the resultant MODS. This review intends to present an overview of the inflammatory response that takes place following pancreatic acinar cell injury.

Acute Disease↗

Seizures among families of Indian probands with different epileptic syndromes.

OBJECTIVES: To investigate the contribution of hereditary factors in the causation of different epilepsy syndromes. MATERIAL AND METHODS: Occurrence of seizures among first- and second-degree relatives of 5628 Indian probands with epilepsy, and 3357 probands with non-epilepsy neurological disorders (who acted as control population) was documented. Syndromic concordance between epilepsy probands and affected relatives was investigated. RESULTS: Twenty percent epilepsy probands (1129) had affected relatives. Relatives of epilepsy probands were more often affected compared with relatives of non-epilepsy probands (OR: 3.4). Probands with some epilepsy syndromes more often had a positive family history. Relatives of younger probands were at greater risk of having epilepsy. Sibs were more often affected compared with other first- and second-degree relatives (OR: 1.3 and 4.6). Sibs having generalized epilepsies and syndromes and febrile convulsions (FC) were at greater odds of syndromic concordance with probands compared with second-degree relatives. Sibs and second-degree relatives having idiopathic/cryptogenic epilepsy had greater odds for concordance compared with those with symptomatic epilepsies. CONCLUSIONS: One-fifth of probands with all types of epileptic syndromes have family history of seizures. Familial risk of epilepsy correlated with the epilepsy syndrome among probands and their age at presentation. Risk of relatives being affected varied as a function of the relation with probands. Concordance of epilepsy syndromes varied both as a function of the epilepsy syndrome and relation with the probands.

Adolescent↗

Threshold intensity and central motor conduction time in patients with monomelic amyotrophy: a transcranial magnetic stimulation evaluation.

OBJECTIVE: To determine the Cortical threshold intensity (TI) and central motor conduction time (CMCT) in patients with monomelic amyotrophy (MMA). METHODS: TI and CMCT were evaluated by means of transcranial magnetic stimulation in 18 patients of MMA and 12 healthy controls at the clinical neurophysiology laboratory, department of neurology, All India Institute of Medical Sciences, New Delhi. RESULTS: The mean age of patients was 23.6 (SD 6. 7) years and of controls was 24.3 (SD 3.2) years (p > 0. 05). The mean TI in patients was 60.83% (SD 11.28) on ipsilateral and 60% (11.5%) on contralateral cortex stimulation. In controls, the mean TI was 66.67% (SD 11.5) on one side and 65% (11.87%) on contralateral cortex stimulation. There was no significant difference in the TI between these two groups (p > 0.05). The mean CMCT in patients was 8.3 (SD 1. 7) ms on ipsilateral and 9.4 (SD 1.6) ms on contralateral cortex stimulation (p > 0.05). In controls CMCT was 8.3 (SD 1.8) ms on one side and 8.6 (SD 1.4) ms on contralateral cortex stimulation. Upper limit of normal CMCT was 12.7 ms. CONCLUSIONS: As compared to controls there was no significant abnormality in TI and CMCT was normal in all except two patients where it was marginally prolonged. This could be because of excessive loss of anterior horn cells.

Adolescent↗

Inter-observer and intra-observer reliability of a sleep questionnaire in Indian population.

UNLABELLED: Sleep disorders are a cause of significant morbidity and mortality. These are however still not widely detected/treated. Though various questionnaires have been designed for screening purposes, none are available in India. AIM: To construct a questionnaire for detection of sleep disorders and determine its reliability and validity. MATERIAL AND METHOD: The questionnaire was prepared from the Case Western Health Research Questionnaire, translated into Hindi and then back into English, prior to its use. This was administered to 20 subjects at an interval of 2 weeks by the same observer to determine the intra-observer reliability. For estimation of validity, 275 subjects were evaluated by a trained health worker and a specialist in sleep disorders. The specialist's opinion was taken as the 'gold standard' to calculate sensitivity and specificity. RESULTS: The kappa statistic was 0.94 for intra-observer reliability. The sensitivity and specificity were calculated for the question, presence/absence of sleep disorders and for all the other questions also. The sensitivity ranged from 70-91% and specificity 80-100%. CONCLUSION: This questionnaire is simple to use, reliable and has good sensitivity and specificity. It can be used in epidemiological community surveys.

Adult↗

Treatment with Met-RANTES reduces lung injury in caerulein-induced pancreatitis.

BACKGROUND: Severe acute pancreatitis leads to a systemic inflammatory response characterized by widespread leucocyte activation and, as a consequence, distant lung injury. In CC chemokines the first two cysteine residues are adjacent to each other. The aim of this study was to evaluate the effect of Met-RANTES, a CC chemokine receptor antagonist, on pancreatic inflammation and lung injury in caerulein-induced acute pancreatitis in mice. METHODS: Acute pancreatitis was induced in mice by hourly intraperitoneal injection of caerulein. Met-RANTES was administered either 30 min before or 1 h after starting caerulein injections, and pancreatic inflammation and lung injury were assessed. There were five groups of eight mice each including controls. RESULTS: Treatment with Met-RANTES had little effect on caerulein-induced pancreatic damage. Met-RANTES, however, reduced lung injury when given either before administration of caerulein (mean(s.e.m.) lung myeloperoxidase (MPO) 1.47(0.19) versus 3.70(0.86)-fold increase over control, P = 0.024; mean(s.e.m.) microvascular permeability 1.15(0.05) versus 3.57(0.63) lavage to plasma fluorescein isothiocyanate-labelled albumin fluorescence ratio (L/P) per cent, P = 0.002) or after caerulein administration (lung MPO 1.96(0.27) versus 3.65(0.63)-fold increase over control, P = 0.029; microvascular permeability 0.94(0.04) versus 2.85(0.34) L/P per cent, P < 0.001). CONCLUSION: Treatment with Met-RANTES reduces lung damage associated with caerulein-induced pancreatitis in mice. Chemokine receptor antagonists may be of use for the treatment of the systemic complications of acute pancreatitis.

Acute Disease↗

Excessive daytime sleepiness in Parkinson's disease as assessed by Epworth Sleepiness Scale (ESS).

OBJECTIVE: To assess daytime sleepiness in patients with Parkinson's disease (PD) using the Epworth Sleepiness Scale (ESS). MATERIAL AND METHODS: One hundred and forty-nine patients with PD (126 men, 23 women) and 115 age matched controls recruited from relatives of medical staff or spouses and other family members accompanying patients to the Movement Disorder Clinic of the All India Institute of Medical Sciences in New Delhi were included in the study. An ESS score of > or =8 was considered abnormal. Data obtained were analyzed using Chi square test for categorical variables and Student's t-test for continuous variables. RESULTS: The mean age of patients with PD was 58.37 (S.D.=10.45) years, and that of controls 56.50 (S.D.=11.45) years, with a mean duration of disease of 5.68 (S.D.=3.85) years. The mean ESS score was 4.9 (S.D.=3.63) and 2.17 (S.D.=2.54) in PD patients and controls, respectively (P<0.05). Thirty-two patients with PD (21%) had an ESS score of >8 whereas only 3% of controls scored > or =8 on the ESS (P<0.05). Higher ESS scores were associated with a higher Hoehn and Yahr (H&Y) stage of disease and higher Unified Parkinson's Disease Rating Scale (UPDRS) (part I, III and total) scores (P<0.019, P<0.013 and P<0.011, respectively). CONCLUSION: Excessive daytime sleepiness was more common in PD patients as compared to controls. Higher ESS scores correlated significantly with higher H&Y stage and higher UPDRS (part I, III and total) scores.

Aged↗

A study of nonepileptic seizures in an Indian population.

OBJECTIVE: The goal of this study was to evaluate the background and the clinical profile of nonepileptic seizures (NESs) confirmed by short-term video encephalography (ST-VEEG) recording in an Indian population. METHODS: Seventy-one patients with NESs were enrolled. A complete history was taken and the recorded event was reviewed to define the ictal events. Patients were divided into two groups, Group 1 with a paucity of movements and Group 2 with an excess of movement, and results were analyzed. RESULTS: The mean age was 22.9 (9.6); there were 15 males (21.1%) and 56 females (78.9%). Twenty-four patients (33.8%) were receiving antiepileptic drugs. The majority of the patients (42, 59.1%) were students. All patients were amnesic for the event and were unresponsive during the event. The other characteristics were similar events in 98.6%, hyperventilation in 58 (81.7%). Forty-two patients (59.2%) were in Group 1 and 29 patients (40.8%) were in Group 2. CONCLUSION: NES is a disease of the young and can affect the student or professional. A wrong diagnosis can result in inappropriate treatment. Awareness of this entity is critical to ensuring prompt diagnosis and early intervention.

Adult↗

Differential response of primitive human CD34- and CD34+ hematopoietic cells to the Notch ligand Jagged-1.

Recent reports indicate that activation of the Notch signaling pathway delays the differentiation of hematopoietic progenitors, suggesting that Notch may be used to develop novel ex vivo culture conditions for the expansion of primitive cells to be used in clinical transplantation. Here, we compare Notch expression and the effects of Jagged-1 treatment on highly purified subfractions of primitive CD34+ and CD34- human hematopoietic cells. Unlike response of cultured CD34+ cells, Jagged-1 treatment did not enhance the proliferation of CD34- cells, or promote differentiation of CD34- cells into CD34+ cells. While CD34+ and AC133-CD34- cells were shown to express all known forms of Notch receptors, Notch-3 and Notch-4 were not detected in AC133+CD34- cells. Similarly, CD34+ progeny of differentiated CD34- cells did not upregulate Notch-3 or Notch-4 upon differentiation, although transcripts for these genes were expressed in CD34+ arising from CD34+ CD38- parents, suggesting that the Notch receptor expression is tightly and differentially controlled. Fringe, known to inhibit Notch signaling in response to specific Notch ligands, was expressed in parent CD34- and CD34+ cells as well as their CD34+ progeny. We suggest that the inability of primitive CD34- cells to positively respond to Jagged-1 may be due in part to the absence of Notch-3 and Notch-4. Taken together, our study illustrates functional distinctiveness of the primitive CD34- subsets to CD34+ counterparts in relation to Jagged-1 response, and represents the first demonstration of a molecular difference among de novo isolated CD34+ compared to in vitro generated CD34+ cells arising from primitive CD34- or CD34+ parents.

Antigens, CD34↗

Coculture and transplant of purified CD34(+)Lin(-) and CD34(-)Lin(-) cells reveals functional interaction between repopulating hematopoietic stem cells.

The human hematopoietic stem cell compartment is comprised of repopulating CD34(+) and CD34(-) cells. The interaction between these subsets with respect to their reconstitution capacity in vivo remains to be characterized. Here, lineage-depleted (Lin(-)) human CD34(+) and CD34(-) hematopoietic cells were isolated from human male and female umbilical cord blood (CB) and transplanted into immune-deficient NOD/SCID EMV(null) mice, thereby allowing the use of human and Y-chromosome-specific DNA sequences to discriminate human reconstitution contributed by CD34(+) vs CD34(-) repopulating stem cells. Although cultured human CB CD34(-)Lin(-) cells transplanted alone possessed only minimal repopulating capacity, with 15% of mice achieving low levels of engraftment, transplantation of cocultured male CD34(-)Lin(-) cells with female CD34(+)Lin(-) cells demonstrated human repopulation with a contribution from CD34(-)Lin(-)-derived progeny in 80% of the recipients. After coculture and transplantation, male CD34(-)Lin(-) cells gave rise to primitive CD34(+)CD38(-) cells isolated in vivo, which demonstrated clonogenic progenitor function into multiple lineages. Taken together, our study indicates that the presence of CD34(+)Lin(-) cells in coculture enhanced the low repopulating function of human CD34(-)Lin(-) cells in vivo. We propose that CD34(+)Lin and CD34(-)Lin cells represent phenotypically distinct, but related cell types that exhibit unique and previously unappreciated functional interaction.

Animals↗

An audit of the out-patient follow-up of hip and knee replacements.

Medical records of 100 consecutive patients who underwent hip and knee replacements (56 hips and 44 knees) in 1997-1998 were studied. Particular attention was paid to the out-patient follow-up appointments with regard to any postoperative complication and intervention based on the clinical and radiological assessment conducted during the follow-up visit. The average period of follow-up was 845 days. During this period, these patients had 304 out-patient visits. Twenty-two patients had a problem during this period of whom 10 needed an intervention. Of the 10 patients who needed an intervention, 3 were identified during the routine out-patient visits whereas 7 were either by general practitioner referral or were seen in the accident and emergency department. At these appointments, 187 radiographs were taken. Of these, 8 (4.3%) showed some abnormality. The minimum cost for these follow-up appointments was estimated to be 23,297 pounds sterling. We recommend that the postoperative out-patient appointment of the patients with hip and knee replacements should be restricted to a visit at 6-12 weeks followed by discharge if no problems are anticipated.

Ambulatory Care↗

Increased cortical excitability with longer duration of Parkinson's disease as evaluated by transcranial magnetic stimulation.

Transcranial Magnetic Stimulation (TMS) was used to evaluate the cortical excitability and central motor pathways in Parkinson's disease (PD) and correlate with severity and duration of disease. 19 cases of PD and 13 controls were enrolled. The threshold intensity (TI), cortical latency (CL), central conduction time (CCT), motor evoked potential amplitude (MEP) obtained with TMS were correlated with Hoehn and Yahr and duration of disease. The threshold intensity (TI) was significantly lower in patients of PD than controls. The TI in patients with PD was 53.16-/+8.4% patients and 67.1-/+21.6% in controls (p<0.05). This strongly correlated with duration of disease, TI being lower in patients with disease duration more than 5 years. There was no difference in the other TMS parameters - CL, CCT, MEP between patients and controls. Our study revealed increased excitability in PD which was related to longer duration of disease.

Aged↗

Cortical silent period in essential tremor.

BACKGROUND: Pathophysiology of essential tremor (ET) is controversial, current evidence indicating its genesis through a central oscillator and modulation by a peripheral component. Since transcranial magnetic stimulation induced silent period (SP) has been attributed mainly to intracortical inhibitory mechanisms, it has been found useful in assessing central motor disturbances. AIMS AND OBJECTIVES: To assess if the cortically induced SP was different in ET patients as compared to age matched healthy controls. MATERIAL AND METHODS: Twenty-four patients of ET (mean age 45.4 +/- 14.9 years) diagnosed according to criteria of Louis et al (1998) and an equal number of healthy controls (mean age 36.2 +/- 15.7 years) were recruited in the study. Cortically induced (magnetic) SP were recorded according to the standard methods described. Student's "t" test and Wilcoxon sign rank test were used for statistical analysis. RESULTS: The mean +/- SD cortical SP in ET patients (180.75 +/- 57.11 msec) in ET patients and in controls (163.83 +/- 35.65 msec) were statistically similar (p = 0.22). CONCLUSION: Our study shows that there is no significant difference in mean cortical SPs in patients with ET as compared to controls.

Adult↗

Restless legs syndrome: diagnosis and treatment.

AIM: To describe clinical, biochemical and electrophysiological profile in Indian patients with Restless Legs Syndrome. MATERIAL AND METHODS: A total of 84 patients with sleep disorders were evaluated. Eight patients were diagnosed to have RLS. All underwent series of hematological, biochemical investigations and electrophysiological studies. Severity was assessed before and after specific treatment RESULTS: Eight patients presenting with clinical features of RLS formed the study group. The mean age was 51.6 +/- 13.8 years. The male : female ratio was 7:1. Six cases were primary and two were of secondary type of RLS. Seven patients reported significant improvement in symptoms after treatment CONCLUSION: RLS can be diagnosed purely on clinical criteria; and appropriate treatment results in significant relief. Thus, the recognition of this entity is essential.

Adult↗

Obstructive sleep apnoea: a case-control study.

INTRODUCTION: Obstructive sleep apnoea (OSA), is characterized by loud snoring and excessive daytime sleepiness. Though the gold standard for diagnosis is overnight polysomnography (PSG), sleep questionnaires have also been used to diagnose this with good predictive value. MATERIAL AND METHODS: A pre-designed proforma with clinical details, symptom-specific questions for diagnosis of OSA, and Epworth Sleepiness Scale (ESS) was administered to 20 patients presenting to the Sleep Disorder Clinic of our hospital and to 40 age and sex-matched relatives (control group). The students 't-test' and chi-square were used as the statistical tests. RESULTS: There were 20 patients with a mean age of 41+/- 8 years, and 40 controls with a mean age of 41 +/- 6 years (P=>0.05). Seven had family history of snoring in the study group and 3 in the control group (P=0.02). Four had met with road traffic accidents in the study group and none in the control group (P=0.001). The body mass index (BMI) was 29.9 (SD 4.4) in the study group and 24.5 (SD3.5) in the controls (P=0.001). The mean ESS was 13.3 +/- 6 in the patients and 4.2+ 4 in the controls (P=0.001). A larger number of patients with OSA had hypertension: 5/20 vs. 3/40 (P=0.01). CONCLUSION: Patients with OSA had significantly higher BMI and ESS score, and were more likely to have hypertension and road traffic accidents. Increased awareness of this entity is essential.

Adult↗