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Biomedical subjects

S Arora

Publications and source records attributed to S Arora.

At least 37 records · Page 2Linked to original sources
PubMed2001

Increase in mortality rates from intrahepatic cholangiocarcinoma in England and Wales 1968-1998.

BACKGROUND: The age standardised mortality rate per 100 000 population for all causes of liver tumours (International Classification of Disease 9 (ICD-9) 155) has almost doubled in England and Wales during the period 1979-1996. We further analysed the mortality statistics to determine which anatomical subcategories were involved. METHODS: Mortality statistics for liver tumours of ICD-9 155, 156, and subcategories, and for tumours of the pancreas (ICD-9 157), in England and Wales were investigated from the Office for National Statistics, London, from 1968 to 1996 inclusive. Data for 1997 and 1998 were also available on intrahepatic cholangiocarcinomas. RESULTS: There has been a marked rise in age standardised mortality rates for intrahepatic cholangiocarcinoma. Since 1993, it represents the commonest recorded cause of liver tumour related death in England and Wales. This is evident in age groups older than 45 years. In contrast, mortality trends from other primary liver tumours, including hepatocellular carcinoma, were unremarkable. CONCLUSIONS: The observed increase in mortality from intrahepatic cholangiocarcinoma may represent better case ascertainment and diagnosis due to improved diagnostic imaging, use of image guided biopsies, or increased use of ERCP. However, the trend started before ERCP was introduced nationally, mortality rates have continued to increase steadily thereafter, and there is no clear evidence that diagnostic transfers easily explains the findings. Alternatively, these observations may represent a true increase in intrahepatic bile duct tumours. Epidemiological studies are required to determine whether there is any geographical clustering of cases around the UK.

Adult↗
PubMed2001

Steady-state pharmacokinetics and tolerability of modafinil given alone or in combination with methylphenidate in healthy volunteers.

The potential for a pharmacokinetic (PK) drug-drug interaction between modafinil and methylphenidate, each at steady state, was investigated in an open-label, randomized, single-period study in 32 healthy male and female volunteers. All subjects received modafinil once daily orally for 28 days (200 mg on Days 1-7 and 400 mg on Days 8-28). On Days 22 to 28, half of the subjects also received 20 mg of methylphenidate orally 8 hours after their modafinil dose. PK profiles of modafinil were obtained on Days 21 and 28 and compared between the two groups. There were no statistically significant differences between the treatment groups in the mean changes in PK parameters for modafinil. Parameters for its metabolites were also similar between the groups, and all treatments were well tolerated. The results indicate that administration of low-dose methylphenidate 8 hours after treatment with modafinil does not appear to alter the steady-state pharmacokinetics of modafinil in healthy volunteers.

Adult↗
PubMed2001

Suppression of beta 2 microglobulin by pentoxiphylline therapy in asymptomatic HIV infected individuals.

Pentoxiphylline, an inhibitor of tumor necrosis factor-alpha (TNF-alpha) has been used in the treatment of human immunodeficiency virus (HIV) infection. The inhibition of TNF-alpha results in decreased immune activation. Beta 2 microglobulin (beta 2 M) has been used as a surrogate marker to study the progression of HIV infection. The objective of this study was to see if use of pentoxiphylline resulted in any decline in beta 2 M levels. Twenty patients with HIV infection who were free of opportunistic infections at the time of inclusion in the study and 18 age and sex matched controls were studied. beta 2 M was measured using an enzyme immunoassay before and four weeks after the start of treatment with pentoxiphylline. Mean levels of beta 2 M before therapy were 1.51 +/- 0.77 mg/l (range 0.78-3.8 mg/l) and were significantly higher (P < 0.001) than the levels among controls [0.72 +/- 0.06 mg/l (range 0.46-0.88 mg/l)]. beta 2 M levels in patients declined to 0.85 +/- 0.22 mg/l (range 0.72-1.0 mg/l) after four weeks of therapy and this was statistically significant (P < 0.001). Use of pentoxiphylline for four weeks results in a significant decline in the levels of beta 2 M suggesting that the level of immune activation is reduced with the therapy.

Adult↗
PubMed2001

Spectrum of floppy children in Indian scenario.

OBJECTIVE: To study the clinical profile of paralytic floppy infants undertaking available investigations and detect the frequency of exon7 of survival motor neuron (SMNT) gene deletion among the spinal muscular atrophy (SMA) cases. DESIGN: Descriptive study. SETTING: Tertiary care teaching hospital. SUBJECTS: 70 paralytic floppy infants (40 males/30 females) with age less than 13 years were included in the study. Exclusion criteria included central hypotonia of any cause. Detailed clinical evaluation was done followed by serum creatine phosphokinase levels, electrophysiological studies, muscle biopsy including immunohistochemistry and electron microscopy. Exon7 of SMNT gene deletion studies was done by PCR. RESULTS: Final diagnosis of SMA was assigned to 37 patients followed by congenital myopathy (n = 7), cogenital muscular dystrophy (n = 5), mitochondrial myopathy (n = 4), neuropathies (n = 5) and diaphragmatic SMA (n = 1). Only 15.7% of cases remained unclassified. When EMG was correlated with final diagnosis, it was 80.6% and 75% sensitive and 68.8% and 87.5% specific for neurogenic and muscle disease, respectively. Muscle biopsy revealed neurogenic atrophy in 47.8% cases followed by normal in 37.3% and myopathic pattern in 14.97% cases. Exon7 of SMNT gene was deleted in only 50% of SMA cases. CONCLUSIONS: Spinal muscular atrophy was the commonest cause of floppy children. The low rate of SMNT gene deletion detected needs confirmation with further studies.

Child↗
PubMed2000

Circulating p53 antibodies, p53 gene mutational profile and product accumulation in esophageal squamous-cell carcinoma in India.

Esophageal cancer (EC) in the Indian population presents in advanced stages with poor prognosis and warrants the identification of a non-invasive marker for early detection and better prognostic assessment. We have previously reported high prevalence of p53 protein accumulation in esophageal squamous-cell carcinomas (ESCCs). The present study was designed to determine (i) if esophageal cancer patients elicit a humoral immune response to intra-tumoral p53 protein accumulation and (ii) their relationship with p53 gene mutations. The goal was to compare the cellular events, p53 protein accumulation and gene mutations with the presence of serum anti-p53 antibodies (p53-Abs) and to assess the utility of serological p53-Ab analysis as a surrogate marker for p53 alterations in esophageal cancer. A high prevalence of circulating p53-Abs was observed in 36 of 60 (60%) ESCC patients. In a subset of 44 ESCCs, exons 5-9 of the p53 gene were examined for mutations by PCR and direct sequencing of PCR products. Mutational data have been correlated with p53-Abs and p53 protein accumulation in ESCCs. Circulating p53-Abs in ESCC patients were significantly associated with intra-tumoral p53 protein accumulation (p=0.0005). A strong correlation observed between humoral immune response against p53 protein, missense gene mutations and protein accumulation warrants the application of serological p53-Abs as a non-invasive surrogate marker in screening high-risk populations for early detection of malignancy.

Adult↗
PubMed2000

Novel polymorphism in p21(waf1/cip1) cyclin dependent kinase inhibitor gene: association with human esophageal cancer.

p21(waf1/cip1), an important regulator of the cell cycle, binds to PCNA and acts as a mediator of the growth suppressing and apoptosis promoting functions of p53. We report a hitherto unobserved polymorphism in the carboxy terminal domain (codon 149) of p21(waf1/cip1) gene, the domain encoding the PCNA binding motif. The codon 149 polymorphism (GAT-->GGT) was observed in 42 of 50 (84%) esophageal squamous cell carcinomas (ESCCs) and eight of 50 (16%) normal individuals. The resultant amino acid substitution from aspartate to glycine may have vital implication in PCNA mediated cell cycle regulation by p21(waf1/cip1). The second polymorphism at codon 31, involving a C-->A transversion at nucleotide 168 (AGC-->AGA) changing the amino acid from serine to arginine, was observed in 2/50 (4%) ESCCs at a relatively lower frequency in the Indian population than that reported in the West. No significant association was observed between p21(wap1/cip1) polymorphism at codon 149 and p21(wap1/cip1) protein expression in ESCC in this cohort of patients. Interestingly, the frequency of p21(wap1/cip1) variants (codon 149) in ESCCs (18 of 19 cases) with wild-type p53 was significantly higher than in tumors with p53 mutations, suggesting that this polymorphism affects the p53 pathway and may play an important role in esophageal tumorigenesis. Analysis of p21(waf1/cip1) expression in relation to p53 gene and protein status revealed its induction by p53-dependent as well as independent pathways in esophageal tumorigenesis.

Carcinoma, Squamous Cell↗
PubMed2000

Frequent alterations in the expression of tumor suppressor genes p16INK4A and pRb in esophageal squamous cell carcinoma in the Indian population.

PURPOSE: Alterations in the cell cycle regulatory p16INK4a/Cyclin D1/pRb pathway play a pivotal role in tumorigenesis. Knowledge of alterations in the tumor suppressor protein pRb and its negative regulator, p16CDKN2/MTS1/INK4a in esophageal squamous cell carcinoma (ESCC) from the Indian subcontinent is meager. To gain insight into the mechanisms underlying tumorigenesis and to search for diagnostic molecular markers for ESCC, we analyzed the expression of p16INK4a and pRb in ESCCs in the Indian population. METHODS: Immunohistochemical analysis of pRb and p16INK4a proteins was carried out in paraffin-embedded sections from 61 surgically resected ESCCs and matched normal tissues, and the results correlated with clinicopathological parameters using chi square and Fisher's exact tests. Dual immunohistochemical analysis has been carried out to demonstrate the concomitant loss of expression of p16INK4a and pRb. RESULTS: Fifty-nine of 61 (97%) cases showed aberration(s) in either or both of these proteins confirming their critical role in esophageal tumorigenesis. Loss of pRb was observed in 51 of the 61 (84%) and loss of p16INK4a was observed in 35 of 61 (57%) cases. Loss of pRb showed significant association with dedifferentiation of the tumor (P = 0.004). p16-/pRb-, and p16+/pRb- phenotypes were significantly associated with nodal metastasis (P = 0.017 and 0.027, respectively), while p16-/pRb+ phenotype was associated with dedifferentiation of the tumor (P = 0.012). CONCLUSION: pRb/p16INK4a pathway plays a critical role in esophageal tumorigenesis in the Indian population. The dual hits (concomitant loss) of pRb and p16INK4a expression suggest that these two components are not mutually exclusive, and can both be altered in a significant proportion of primary ESCCs serving as putative diagnostic markers for esophageal cancer. However, the impact of dual hit on tumor behavior and disease prognosis remains to be determined.

Adult↗
PubMed2000

Thiamine (Vitamin B1) protects against glucose- and insulin-mediated proliferation of human infragenicular arterial smooth muscle cells.

Accelerated proliferation of arterial smooth muscle cells (ASMC) plays an important role in the development of atherosclerosis, which preferentially affects the infragenicular vasculature in patients with diabetes mellitus. High insulin and glucose levels, which are present in patients with type II diabetes, have an additive effect in infragenicular ASMC proliferation in vitro. Thiamine is a coenzyme important in intracellular glucose metabolism. The objective of this study is to determine the effect of thiamine on human infragenicular ASMC proliferation induced by high glucose and insulin levels in vitro. Human infragenicular ASMC isolated from diabetic patients undergoing lower extremity amputation were used. Cells were cultured at 37 degrees C in 5% CO(2). Cells were identified as ASMC by immunohistochemical analysis. Cells from passages 3-5 were exposed to glucose concentrations of 0.1 and 0.2% with and without insulin concentrations of 100 ng/mL and 1000 ng/mL, in the presence or absence of 200 microM of thiamine. Standard hemocytometry and (3)H-thymidine incorporation quantified cell proliferation after incubation for 6 days and 24 hr, respectively. The data suggest that thiamine inhibits human infragenicular ASMC proliferation induced by high glucose and insulin. Vitamin B1 intake may prove important in delaying the atherosclerotic complications of diabetes.

Aged↗
PubMed2000

Abdominoperineal electrical injury involving urogenital organs.

Although the incidence of electrical burns is not very high this incidence is rising in India. The residual effects of electrical burns are sometimes very severe and long lasting, if not managed properly. This case report is of a patient who sustained severe electrical burns over his left arm, lower abdomen and perineal area. The injuries were so severe that life-saving disarticulation of the limb together with excision of the involved pubic bone and genitalia and suprapubic urinary diversion was done. During follow up an unusual finding was noticed. There was a peritubal leak with no drainage from the catheter and on removal of the catheter, a manual examination of the urinary bladder revealed a stone which was removed at the same time. Following removal of the stone two ureteric openings with the trigone were seen and it was concluded that the granulating tissue was actually the posterior wall of the bladder. This was then mobilized and reposited into the abdomen. The deficient lower abdomen was reconstructed with a tensor fascia lata flap. A penile reconstruction for the patient is under consideration.

Abdominal Injuries↗
PubMed2000

The use of arm vein in lower-extremity revascularization: results of 520 procedures performed in eight years.

PURPOSE: The absence of an adequate ipsilateral saphenous vein in patients requiring lower-extremity revascularization poses a difficult clinical dilemma. This study examined the results of the use of autogenous arm vein bypass grafts in these patients. METHODS: Five hundred twenty lower-extremity revascularization procedures performed between 1990 and 1998 were followed prospectively with a computerized vascular registry. The arm vein conduit was prepared by using intraoperative angioscopy for valve lysis and identification of luminal abnormalities in 44.8% of cases. RESULTS: Seventy-two (13. 8%) femoropopliteal, 174 (33.5%) femorotibial, 29 (5.6%) femoropedal, 101 (19.4%) popliteo-tibial/pedal, and 144 (27.7%) extension "jump" graft bypass procedures were performed for limb salvage (98.2%) or disabling claudication (1.8%). The average age of patients was 68.5 years (range, 32 to 91 years); 63.1% of patients were men, and 36.9% of patients were women. Eighty-five percent of patients had diabetes mellitus, and 77% of patients had a recent history of smoking. The grafts were composed of a single arm vein segment in 363 cases (69. 8%) and of spliced composite vein with venovenostomy in 157 cases (30.2%). The mean follow-up period was 24.9 months (range, 1 month to 7.4 years). Overall patency and limb salvage rates for all graft types were: primary patency, 30-day = 97.0% +/- 0.7%, 1-year = 80.2% +/- 2.1%, 3-year = 68.9% +/- 3.6%, 5-year = 54.5% +/- 6.6%; secondary patency, 30-day = 97.0% +/- 0.7%, 1-year = 80.7% +/- 2.1%, 3-year = 70.3% +/- 3.4%, 5-year = 57.5% +/- 6.2%; limb salvage, 30-day = 97.6% +/- 0.7%, 1-year = 89.8% +/- 1.7%, 3-year = 82.1% +/- 3.3%, 5-year = 71.5% +/- 6.9%. Secondary patency and limb salvage rates were greatest at 5 years for femoropopliteal grafts (69.8% +/- 12.8%, 80.7% +/- 11.8%), as compared with femorotibial (59.6% +/- 10. 3%, 72.7% +/- 10.5%), femoropedal (54.9% +/- 25.7%, 56.8% +/- 26.9%, ) and popliteo-tibial/pedal grafts (39.0% +/- 7.3%, 47.6% +/- 15.4%). The patency rate of composite vein grafts was equal to that of single-vein conduits. The overall survival rate was 54% at 4 years. CONCLUSION: Autogenous arm vein has been used successfully in a wide variety of lower-extremity revascularization procedures and has achieved excellent long- and short-term patency and limb salvage rates, higher than those generally reported for prosthetic or cryopreserved grafts. Its durability and easy accessibility make it an alternative conduit of choice when an adequate saphenous vein is not available.

Adult↗
PubMed2000

Arm vein conduit is superior to composite prosthetic-autogenous grafts in lower extremity revascularization.

PURPOSE: Various alternative conduits have been used for lower extremity revascularization when an adequate ipsilateral greater saphenous vein is absent. This study compared the effectiveness of all-autogenous multisegment arm vein bypass grafts with that of composite grafts composed of combined prosthetic and autogenous conduits. METHODS: One hundred fifty-three lower extremity revascularization procedures performed between 1990 and 1998 were followed up prospectively using a computerized vascular registry. The grafts were composed of spliced arm vein segments with venovenostomy in 122 and of composite prosthetic-autogenous conduit in 31. Arm vein conduit was prepared by means of intraoperative angioscopy for valve lysis and identification of luminal abnormalities in 47.7% of cases. RESULTS: Bypass graft configurations were as follows: femoropopliteal (12 arm vein, 2 composite); femorotibial (75 arm vein, 23 composite); femoropedal (14 arm vein, 6 composite), and popliteo-tibial/pedal (21 arm vein, 0 composite). The indication for surgery was limb salvage in 98% and disabling claudication in 2% of cases. The mean follow-up was 25.1 months (range, 1 month to 7.9 years). Overall survival at 4 years was 51%. Overall patency and limb salvage rates were as follows: primary patency, at 1 year-arm vein, 76.9% +/- 4.8%; composite, 59. 5% +/- 9.6% (P =.02); at 3 years-arm vein, 70.0% +/- 8.0%; composite, 43.7% +/- 12.4% (P <.01); and at 5 years-arm vein, 53.8% +/- 8.7%; composite, 0%; secondary patency, at 1 year-arm vein, 77.5% +/- 4. 6%; composite, 59.8% +/- 9.5% (P =.02); at 3 years-arm vein, 70.7% +/- 7.5%, composite, 44.9% +/- 13.1% (P <.01); at 5 years-arm vein, 57.7% +/- 8.0%; composite, 0%; limb salvage, at 1 year-arm vein, 89. 3% +/- 3.7%; composite, 73.9% +/- 8.9% (P <.01); at 3 years-arm vein, 80.5% +/- 7.0%; composite, 49.6% +/- 14.3% (P <.01); at 5 years-arm vein, 76.3% +/- 9.9%; composite, 0%. CONCLUSION: In this study, multisegment autogenous arm vein was used successfully in a wide variety of lower extremity revascularization procedures and achieved good long-term patency and limb salvage rates, well in excess of those achieved with composite prosthetic-autogenous grafts. The use of autogenous conduit appears to offer superior results to composite conduit in lower extremity revascularization. The superior durability of arm vein makes it one of the alternative conduits of choice when an adequate greater saphenous vein is not available.

Aged↗
PubMed2000

A comparative study of alternative conduits for lower extremity revascularization: all-autogenous conduit versus prosthetic grafts.

PURPOSE: In the absence of an adequate ipsilateral greater saphenous vein, various alternative conduits have been used for the performance of lower extremity revascularization. In this study we compared the effectiveness of all-autogenous arm vein bypass grafts with that of prosthetic grafts. METHODS: Seven hundred forty lower extremity revascularization procedures (506 arm vein, 234 prosthetic) performed between 1990 and 1999 were followed prospectively by means of a computerized vascular registry. RESULTS: Bypass graft configurations were femoro-above-knee-popliteal (26 arm vein, 100 prosthetic); femoro-below-knee-popliteal (38 arm vein, 29 prosthetic); femorotibial (174 arm vein, 55 prosthetic); femoropedal (23 arm vein, 2 prosthetic); popliteotibial/pedal (101 arm vein, 1 prosthetic); and extension "jump" grafts (144 arm vein, 47 prosthetic). The indications for surgery were limb salvage (98.0% arm vein, 89.7% prosthetic) and disabling claudication (2.0% arm vein, 10.3% prosthetic). The mean follow-up was 23.4 months (range, 1 month-7.4 years). Overall patient survival at 4 years was 54% (arm vein) and 69% (prosthetic). Cumulative patency varied with graft configuration. The 1-year primary patency rates for femorotibial grafts were 81.6% +/- 3.6% (arm vein) and 58.0% +/- 8.4% (prosthetic); the 3-year rates were 68.3% +/- 6.1% (arm vein) and 41.1% +/- 9.8% (prosthetic) (P<.01). The 1-year limb salvage rates for femorotibial grafts were 91.1% +/- 2.8% (arm vein) and 69.1% +/- 8. 8% (prosthetic); the 3-year rates were 81.4% +/- 5.6% (arm vein) and 63.2% +/- 10.3% (prosthetic) (P =.02). The 1-year primary patency rates for femoro-below-knee-popliteal grafts were 92.9% +/- 5.1% (arm vein) and 83.4% +/- 8.0% (prosthetic); the 3-year rates were 72.8% +/- 10.1% (arm vein) and 55.5% +/- 12.1% (prosthetic) (P=.05). The 1-year limb salvage rates for femoro-below-knee-popliteal grafts were 100% (arm vein) and 91.3% +/- 7.0% (prosthetic); the 3-year rates were 94.7% +/- 7.3% (arm vein) and 75.3% +/- 14.6% (prosthetic) (P = NS). CONCLUSION: In this study autogenous arm vein grafts demonstrated increased patency and limb salvage, compared with prosthetic grafts. These increases achieved statistical significance in the femoro-below-knee-popliteal and femorotibial configurations. An effort to use an all-autogenous vein conduit is justified on the basis of these results; however, if no autogenous vein is available, prosthetic grafts provide a reasonable alternative to primary amputation.

Aged↗
PubMed2000

A novel insulin mimetic without a proliferative effect on vascular smooth muscle cells.

BACKGROUND: Insulin induces vascular smooth muscle cell (VSMC) proliferation, which is an important step in the atherosclerotic process. Recently, a nonpeptidyl fungal metabolite originally referred to as L-783,281, but also known as demethylasterriquinone B-1 (DMAQB-1), was found to have hypoglycemic activity in diabetic mice through interaction with the intracellular beta subunit of the insulin receptor. This study was designed to determine whether DMAQB-1 has an insulin-like proliferative effect on human infragenicular VSMCs. METHODS: Human infragenicular VSMCs were isolated from diabetic patients undergoing amputations. DMAQB-1 cell culture dose response was measured in both serum-free media and media with 1% fetal bovine serum (FBS). A working concentration of DMAQB-1 that ranged from 0.5 to 500 nmol/L was studied in the presence of varying concentrations of glucose and insulin. The ability of DMAQB-1 to stimulate glucose transport at less than or equal to 100 nmol/L was determined by [(14)C]-2-deoxyglucose uptake. DNA synthesis was used as the marker for proliferative stimulus and detected by [(3)H]-thymidine uptake measured at 24 hours. Analysis of variance was used to compare the results among the groups; a P value less than.05 was considered significant. Polynomial regression was used to calculate the median lethal dose. RESULTS: In normal glucose media (100 mg/dL), various concentrations of DMAQB-1 demonstrated a small but statistically significant decrease in DNA synthesis at 0.5 nmol/L in serum-free media and at 5 nmol/L in media supplemented with 1% FBS. The corresponding median lethal dose was 107 nmol/L in serum-free media and 650 nmol/L in media supplemented with 1% FBS. A DMAQB-1 concentration of 5 nmol/L induced glucose transport that was equivalent to an insulin concentration of 100 microU/mL. In serum-free, high glucose media (200 mg/dL), DMAQB-1 concentrations up to 500 nmol/L did not cause a statistically significant change in DNA synthesis. When serum-free, high glucose media was combined with mild (100 microU/mL) or moderate (250 microU/mL) concentrations of insulin, DMAQB-1 caused no statistically significant increase in DNA synthesis. CONCLUSION: Nontoxic doses of DMAQB-1 can induce glucose transport equivalent to insulin in the physiologic range. However, DMAQB-1 does not have an insulin-like proliferative effect on human VSMCs in normal-glucose, high-glucose, or high-insulin environments.

Analysis of Variance↗