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Biomedical subjects

A C Anand

Publications and source records attributed to A C Anand.

At least 55 records · Page 3Linked to original sources

Prescribing drugs for patients with liver disease.

BACKGROUND: Adverse reactions to prescribed drugs are a common cause of morbidity in patients receiving medical care. Pre-existing or underlying liver dysfunction is one of the commonest factors that enhance the risk of such adverse events in medical practice. Most textbooks of medicine contain no guidelines on special precautions to be taken in prescribing to a patient with pre-existing liver disease. METHODS: To provide a ready reckoner for modifying drug dosage in liver diseases, a literature search was carried out. All papers related to human studies were reviewed and relevant material extracted for preparing the guidelines. RESULTS: Most adverse drug reactions in the presence of liver disease are related to altered pharmacokinetics, pharmacodynamics and susceptibility to drugs. The influence of hepatic disease on various drugs is highly variable. However, many such adverse events are predictable and preventable. Ideally, drug dosage should be modified with the help of serum drug concentrations, which unfortunately, are not available in most Indian hospitals. Hence, some broad guidelines are presented to assist the treating physician to be aware of the risk of adverse drug reactions and modify drug dosage empirically to avoid such events. CONCLUSION: The altered metabolism of pharmacological agents in patients with liver disease may induce several undesirable effects. A large number of adverse drug reactions can be prevented by modifying drug prescribing habits for patients who have pre-existing liver disease.

Chronic Disease↗

Cytokines and inflammatory bowel disease.

Cytokines are the key mediators of inflammation in the IBD and are focus of renewed interest to plan therapeutic strategies against this disease. However, there are gaps in our knowledge at present and a lot of questions need clear answers. Even with a therapy as specific as anti-TNF antibody, it is not clear if the benefit is attributable to simple binding and clearance of TNF-alpha or to binding on the cell surface and subsequent deletion of the activated macrophage. When a drug appears to be less effective than pre-clinical models suggest, can failures in effectiveness from delivery or dosing the differentiated? The disappointing results of clinical trials with IL-10 is at odds with the prediction of benefit from animal models. It even brings into question the validity of those models as well as the soundness of design of the clinical trials on which efficacy of IL-10 is assessed. Other exciting new methods to treat IBD could be use of monoclonal antibodies to effector T cell molecules (such as CD4 or CD44v7) removal of such cytokine secreting cells (apheresis), antibodies to proinflammatory cytokines (such as TNF-alpha, IFN-alpha, IFN-gamma, and IL-12) or administration of anti-inflammatory cytokines (such as IL-10, IL-11). Challenges in developing new therapeutic strategies include not only identifying novel agents, but also improving the definitions of clinical endpoints and defining efficacy at the biologic level. There is also need to further refine our knowledge about genetic elements and environment initiators to comprehensively manage IBD.

Cytokines↗

Bio-artificial liver from cultured human foetal hepatocytes: feasibility and prospects.

BACKGROUND: Conventional therapy for acute liver failure has not been able to improve survival beyond 40%. Apart from liver transplantation, the most promising development in this field is the utilization of cultured hepatocytes to make 'bio-artificial liver support systems' as a 'bridge to transplantation' or ideally as a 'bridge to total recovery'. This study examines the feasibility of culturing foetal hepatocytes without the use of growth factors and formulating a bio-artificial liver support device in our set-up. METHODS: Foetal hepatocytes were harvested from the liver obtained from mid trimester abortions at Armed Forces Medical College and Command Hospital (SC), Pune. The liver was perfused with Phosphate Buffered Saline (PBS) and collagenase type IV and was cut with a pair of sterile scissors into tiny pieces. Cells so separated, were washed with PBS plus foetal calf serum and stirred to disperse the cell aggregates. Filtered cell suspensions were inoculated in polystyrene flasks containing hepatocyte culture medium (MEM E: 75%, M199: 25%, BSA: 0.1%, Bovine Insulin 5 micrograms/ml, FCS: 10%, Penicillin: 10 i.u., Streptomycin 50 micrograms/ml, Hydrocortisone 5 micrograms/ml and incubated at 37 degrees C. The functional capabilities of the cultured hepatocytes were analyzed by studying production of albumin and a foetoprotein. Structural integrity of hepatocytes was assessed by light and electron microscopy. RESULTS: The hepatocyte yield varied from 2 to 60 x 10(6) cells/L with an average of 38 x 10(6) cells/L in the eight consecutive experiments. Initial hepatocyte viability varied from 25% to 90% with an average of 61%. The yield and the viability of hepatocytes were adversely affected by the condition of foetus at birth and use of intra-amniotic injections for inducing abortions. Hepatocyte monolayers and colonies formed in 75% experiments. The cultures could be maintained in incubation without the use of epidermal or hepatocyte growth factors for 2-25 days with a mean survival of 8.9 days. The cells in culture were found to be structurally normal and functionally active and could be cryo-preserved. These hepatocytes were inoculated into a hollow fiber module to formulate bio-artificial liver support device. The cultures ultimately developed either cellular disintegration or bacterial infections despite use of antibiotics in the culture medium. CONCLUSIONS: We conclude that it is feasible to maintain foetal hepatocyte cultures without the use of expensive growth factors for over 8 days. Bio-artificial liver formulated with cultured foetal hepatocytes is now a step closer to clinical trials.

Artificial Organs↗

Hepatopulmonary syndrome: prevalence and clinical profile.

BACKGROUND: The hepatopulmonary syndrome (HPS) is defined as a triad of liver dysfunction, intrapulmonary vascular dilatations (IPVD) and arterial hypoxemia. There is paucity of Indian studies regarding the prevalence of IPVD and arterial hypoxemia particularly amongst patients with non-cirrhotic portal fibrosis (NCPF) and extrahepatic portal vein obstruction (EHPVO), where liver dysfunction is not a feature. METHODS: All patients with portal hypertension and esophageal varices seen at a tertiary care hospital during 1995-98 were studied. Ultrasonography of abdomen, contrast-enhanced echocardiography (CEE), arterial blood gas analysis and assessment of alveolar-arterial oxygen gradient were done. RESULTS: Of 138 patients with portal hypertension seen during the study period, 88 fulfilled the inclusion and exclusion criteria. These included 63 with cirrhosis, 15 with NCPF and 10 with EHPVO. CEE showed IPVD in 17 (27%) patients with cirrhosis, of which 11 (17.5%) fulfilled the criteria for HPS. IPVD were also noted in 4 (26.6%) cases of NCPF and 3 (30%) of EHPVO, though only 2 (13.3%) and 1 (10%) respectively had elevated alveolar-arterial gradient and liver dysfunction in addition. Age and sex distribution and duration of symptoms were not different in patients with HPS. Patients with HPS had higher incidence of dyspnea, platypnea, clubbing and spider nevi. CONCLUSIONS: Hepatopulmonary syndrome is present in 17.5% of cirrhotics, 13.3% of patients with NCPF and 10% with EHPVO. Patients with HPS had significantly higher incidence of dyspnea, platypnea, clubbing and spider nevi.

Adolescent↗

Kerala pesticide tragedy.

Explore the source record for details and available documents.

Abnormalities, Drug-Induced↗

Thrombosis as a complication of extended stay at high altitude.

BACKGROUND: There is limited knowledge about the medical problems of long term stay at high (> 3000 m) and extreme (> 5000 m) altitudes, as these areas are generally considered uninhabitable. METHODS: Prospectively collected clinical records of all patients hospitalized at Command Hospital, Western Command between November 1998 and February 2000 were reviewed to identify thrombotic complications among patients from high and extreme altitude areas as well as those from non-high altitude areas who were < 45 years of age. RESULTS: Of 20,257 hospital admissions during the study period, 1692 were from high and extreme altitude areas. Forty-six patients from these areas had thrombosis-related diseases compared to 17 from non-high altitude areas (odds ratio: 30.49; 95% CI: 17.06-51.67; p < 0.001). The mean (SD) age of all patients with thrombotic complications was 32 (8) years and all were men. The mean duration of stay at high and extreme altitudes of such patients was 10.2 (5.6) months. Only 25 were smokers (mean 5.2 pack-years) and 39 consumed alcohol (mean 54 ml/day). Apart from frostbite in 5, no other medical condition was noted in these patients. The vascular events were deep vein thrombosis (20), pulmonary thromboembolism (6), stroke (15), thrombosis of the abdominal veins (8), and retinal artery and peripheral arterial thrombosis (1 each). The presenting complaint in all patients with thrombosis of the abdominal veins was poorly localized pain in the upper abdomen followed by ascites (6/8). Five of these patients also had a large spontaneous splenic haematoma. None of the patients investigated was found to have a procoagulant disorder. CONCLUSION: Long term stay at high and extreme altitudes is associated with a 30 times higher risk of spontaneous vascular thrombosis. Veins are common sites of such thrombotic events. We also encountered thrombosis of the portal, splenic and superior mesenteric veins in our patients who had stayed at high and extreme altitudes.

Adult↗

Massive lower intestinal bleeding--a decade of experience.

BACKGROUND: Lower gastrointestinal bleeding is defined as hemorrhage orginating distal to the ligament of Treitz. Its diagnosis is difficult, often requiring endoscopy, angiography and isotope scans. METHODS: All patients with massive lower gastrointestinal bleeding seen in three gastroenterology centers of Armed Forces during an 11 year period between 1988 and 1999 were retrospectively analysed. RESULTS: A total of 91 patients with massive lower gastro intestinal bleeding were seen during 11 years. The mean age of the patients was 38.9 years and 64 were males. Aetiological diagnosis was: Non-specific ulcers--11, Ileal tuberculosis--8, NSAID enteropathy--8, Enteric fever--7, Meckel's diverticulum--7, Polyps--6, Ulcerative colitis--5, Carcinoma colon--5, Colonic diverticulosis--5, No cause found--5, Polyposis coli--5, Jejunal diverticulae--3, Angiodysplasia colon--3, Radiation colitis--3, Ischaemic colitis--3, Ileal tumor--2, Ileal angiodysplasia--2, Intestinal Lymphoma--2, Bechet's syndrome--1. Bleeding stopped on conservative therapy in 18 patients (including 5 where no diagnosis could be made). Diagnosis was made in 36 patients on fiber-optic colonoscopy done during active bleeding. Remaining patients were subjected to emergency laparotomy and diagnosis was obvious on inspection of abdominal contents in 25 cases. The diagnosis was finally made in remaining 12 cases by intraoperative endoscopic examination through an ileotomy. Four patients died, only one of them due to rebleed after surgery from an additional lesion. CONCLUSIONS: Compared with experience in Western countries, massive lower gastro-intestinal hemorrhage in India affects younger patients, has different causes and carries a lower mortality. Colonoscopy is useful in making diagnosis during active lower intestinal bleeding in about one-third cases. Exploratory laparotomy and Intra-operative endoscopy are complimentary to above examination and can make the diagnosis in most of the remaining cases.

Adolescent↗

Portal system thrombosis: a complication of long-term residence at extreme altitude.

BACKGROUND: With induction of the Indian Army to heights over 5,000 meters above sea level, complications of long-term stay at extreme altitude have come to light. We describe our experience with patients developing portal system thrombosis. METHODS: Clinical data were collected over 2 years on patients hospitalized for thrombotic complications from high-altitude (HAA) and non-high altitude (non-HAA) areas. Site of thrombosis was confirmed by imaging or at surgery. Patients were investigated for conditions that predispose to venous thrombosis. RESULTS: Ten cases of portal system thrombosis were seen during the period; of these, 9 (mean age 28 [SD 3.9] years; all men) were from HAA. Mean duration of residence in HAA was 12.4 (4.9) months; two were smokers and six drank 7-22 g alcohol/day at least 5 times a week. The first symptom was abdominal pain; this was later complicated by gastrointestinal bleeding (n=5), fever (7), vomiting (7), and weight loss (5). Average time between onset of first symptom and reaching a tertiary-care hospital was 9.5 (4.7) days. Clinical examination showed ascites (8 cases), splenomegaly (7), and hepatomegaly (6). Mean hemoglobin level at admission was 15.8 (3.4) g/dL. Ascites was hemorrhagic; five cases also had large splenic hematoma. The site of thrombosis was splenic vein (7 cases), portal vein (6), and superior (4) and inferior (1) mesenteric vein. None of 5 patients investigated had any prothrombotic condition. Endoscopic/ sonographic evidence of development of collaterals appeared as early as 12-20 days after onset of symptoms. CONCLUSION: Residence in HAA for extended periods is a risk factor for development of portal system thrombosis. Persistent pain in abdomen in such individuals should raise the possibility of portal system thrombosis.

Adult↗

Malarial hepatitis: a heterogeneous syndrome?

BACKGROUND: The incidence of malarial hepatitis in patients with Plasmodium falciparum infection and jaundice is not known and it is not clear whether the condition is a single entity or a heterogeneous syndrome. METHODS: We prospectively studied the natural history of all patients with falciparum malaria and jaundice admitted to military hospitals in Northeast India from 1988 to 1991. A possible drug or viral cause for the hepatitis was excluded by the history, serological tests and liver histology. RESULTS: Of the 732 patients admitted with falciparum malaria, 39 had jaundice but only 18 had malarial hepatitis indicated by a rise in their serum glutamate pyruvate transaminase levels to more than three times the upper limit of normal and an absence of clinical or serological evidence to suggest drug or viral hepatitis. The liver in these patients was always enlarged. Their mean age was 27.6 years and 85% were males. The mean serum bilirubin was 12.7 +/- 10.3 mg/dl, serum glutamate oxaloacetate transaminase was 212.8 +/- 144.9 IU, serum glutamate pyruvate transaminase was 287.1 +/- 206.2 IU and the serum alkaline phosphatase was 20.4 +/- 10.1 KA. Clinically, 2 groups of patients were seen. Thirteen patients who presented with a severe form of disease had coma, deep jaundice and renal failure. The other 5 patients had a relatively mild illness with only fever, headache and vomiting for 2 days. Four patients with severe disease died. Liver histology (studied in 5 patients) showed Kupffer cell hyperplasia and deposition of malarial pigment. Plasmodium falciparum was demonstrated in sinusoidal red blood cells in only 2 cases. CONCLUSIONS: Malarial hepatitis occurred in 18 out of 39 patients with jaundice and falciparum malaria. It is a heterogeneous syndrome with at least two clinical subsets and the severe disease should not be mistaken for fulminant hepatic failure as there is a better response to therapy.

Adult↗