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Biomedical subjects

A Dhawan

Publications and source records attributed to A Dhawan.

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

Lumbar sagittal contour after posterior interbody fusion: threaded devices alone versus vertical cages plus posterior instrumentation.

STUDY DESIGN: An observational radiographic study examining lumbar sagittal contour of patients undergoing posterior interbody arthrodesis. OBJECTIVES: To compare operative alterations of lumbar sagittal contour after posterior interbody fusion using threaded interbody devices alone versus vertical cages combined with posterior compression instrumentation. SUMMARY OF BACKGROUND DATA: Technique-related alterations of lumbar sagittal contour during interbody arthrodesis have received little attention in the spinal literature. METHODS: Standing lumbar radiographs were measured for preoperative and postoperative segmental lordosis at levels undergoing posterior interbody arthrodesis using either stand-alone side-by-side threaded devices or vertical cages combined with posterior transpedicular compression instrumentation. Sagittal plane segmental correction (or loss of correction) was calculated and statistically compared. RESULTS: The radiographs of 30 patients (34 spinal segments) undergoing lumbar or lumbosacral arthrodesis were compared. Seventeen patients (18 segments) had undergone interbody fusion using threaded cages,whereas 13 patients (16 segments) underwent fusion using vertically oriented mesh cages combined with posterior compression instrumentation. Preoperative segmental lordosis averaged 8 degrees for both groups. For patients undergoing fusion with threaded cages, there was a mean lordotic loss of 3 degrees/segment. For patients undergoing fusion with vertically oriented mesh cages combined with posterior compression instrumentation,there was a mean lordotic gain of 5 degrees/segment. This difference in segmental sagittal plane contour was highly significant (P = 0.00). CONCLUSION: Threaded fusion devices placed under interbody distraction with the endplates parallel fail to preserve or reestablish segmental lordosis. Vertical cages, however, when combined with posterior compression instrumentation, not only maintain segmental lordosis, but also can correct sagittal plane deformity.

Humans↗
PubMed2001

Induction of rat brain cytochrome P450s (P450s) by deltamethrin: regional specificity and correlation with neurobehavioral toxicity.

Oral administration of 5 mg/kg body weight of deltamethrin, an alpha-cyano type II pyrethroid insecticide once a day for 1, 7, 15 and 21 consecutive days to young Druckerey rats (6- 8 weeks old) produced a time dependent increase in the activity of cytochrome P450 (P450) dependent 7-ethoxyresorufin-O-deethylase (EROD) and 7-pentoxyresorufin-O-dealkylase (PROD) in rat brain microsomes. A significant induction was observed on prolonged exposure of deltamethrin for 15 or 21 days. The induction in the activity of cerebral P450 enzymes was associated with the time dependent increase in the spontaneous locomotor activity indicating accumulation of deltamethrin or its metabolites in brain with the increase in the duration of exposure. Administration of deltamethrin (5 mg/kg) for 21 days produced region specific changes in the dealkylation of ethoxyresorufin and pentoxyresorufin in rat brain with significant induction occurring in the activity of P450 1A1/2 dependent EROD in cerebellum, hippocampus, hypothalamus and medulla-pons and that of P450 2B1/2 mediated PROD in hippocampus, hypothalamus, corpus striatum and mid brain. The data suggests that the differences in the induction of individual P450 isoenzymes in diverse brain regions could play a role in regulating the response of brain to pyrethroid insecticides by modulating their concentration per se or their active metabolites at the target site(s).

Journal Article↗
PubMed2001

Serum hyaluronic acid as an early prognostic marker in biliary atresia.

PURPOSE: The aim of this study was to assess whether serum concentrations of hyaluronic acid (HA), measured at diagnosis is an early biochemical marker of prognosis in biliary atresia. METHODS: Serum HA was measured at diagnosis using a radiometric assay in 84 infants with biliary atresia (BA), and related to outcome by 5 years of age. RESULTS: Serum HA was higher in the 29 patients who died or required liver transplant by 5 years of age compared with the 56 who survived to 5 years without transplant (490 +/- 216 microg/L v 262 +/- 163 microg/L; P <.001, 95% confidence intervals of the difference 145 to 311 microg/L). CONCLUSION: High serum concentrations of HA at diagnosis may help to identify at an early stage those patients with BA who have a poor prognosis and will require liver transplant by 5 years of age.

Actuarial Analysis↗
PubMed2001

Glycopeptide-resistant Enterococcus faecium infections in paediatric liver transplant recipients: safety and clinical efficacy of quinupristin/dalfopristin.

We describe our experience of quinupristin/dalfopristin for glycopeptide-resistant Enterococcus faecium (GREF) infections in 19 paediatric liver transplant recipients. The median patient age was 2 years and all were receiving immunosuppressive regimens. Quinupristin/dalfopristin was well tolerated and complete resolution of infection was seen in 74% of patients. Side-effects included reversible elevation of serum alkaline phosphatase, skin rash, itching, diarrhoea and vomiting, but therapy was not withdrawn from any patient. Quinupristin/dalfopristin appears safe and efficacious in critically ill immunocompromised children with renal or hepatic impairment.

Adolescent↗
PubMed2001

Temporal changes in brain volume and cognition in a randomized treatment trial of vascular dementia.

OBJECTIVE: To measure changes in brain and ischemic volume over time by magnetic resonance imaging (MRI) as part of a randomized treatment trial of vascular dementia. METHODS: Participants who met criteria for vascular dementia underwent comprehensive neurological and neuropsychological testing on entrance, during, and at completion of the 1-year study. For those centers who had easily available MRI, MRI of the brain was to be performed on entry and completion of the study. Image analysis was performed on all balanced and T2-weighted MR films to determine ventricular, sulcal, ischemic, and hemispheric brain volumes. RESULTS: Of the 105 patients who met the criteria for vascular dementia, 40 had a baseline MRI study that met protocol requirements and was of excellent image quality. The baseline ventricular volume in these 40 patients with high-quality MR correlated with most measures of cognitive and behavioral function, including the total Alzheimer's Disease Assessment Score (ADAS) (r = 0.51, P = .0024), as well as activities of daily living (r = 0.61, P = .0002). The baseline ischemic brain volume correlated well only with the gait and postural stability scale (r = 0.74, P = .009). Of the 40 participants, 25 had MRI studies at baseline and at completion of the study that were comparable and of excellent image quality. For these 25 patients, the mean ventricular volumes increased by 9% over the study year (P = .001) and the mean ischemic brain volume increased by 18% (P = .01). Temporal changes in the sulcal and nonischemic brain volume did not reach significance. None of the 14 clinical score measures changed significantly between baseline and completion of the study in these 25 patients. CONCLUSION: In summary, ventricular volume correlated well with cognitive measures in patients with vascular dementia and was a more sensitive marker for change during the study year than the clinical scales used in this study. This study also points out the practical limitations of brain imaging as a surrogate measure of clinical outcome in multicenter randomized treatment trials of brain disease.

Activities of Daily Living↗
PubMed2001

Effect of antioxidant flavonoids and a food mutagen on lymphocytes of a thalassemia patient without chelation therapy in the Comet assay.

Thalassemia remains a significant health problem in Europe, the Middle East, and Asia. In such patients, generally high iron levels make free oxygen radicals accessible, for example, through Fenton-type chemistry, and generate superoxide and hydroxyl radicals. Increased oxygen radical capacity is known to be associated with cancer and ageing. It was shown in previous studies that peripheral blood lymphocytes from a sickle/beta thal double heterozygote-sickle phenotype, thalassemia patient, not yet on chelation therapy, were more sensitive to the effects of oxygen radicals and iron salts than lymphocytes from normal controls. Iron overload in thalassemia patients can result from dietary absorption. It was considered that with other dietary agents, such as food mutagens and flavonoids, the thalassemia patient might also show increased sensitivity to the effects of these agents. The present study, therefore, compared the effects of the food mutagen/carcinogen, 3-amino-1-methyl-5H-pyrido(4,3-b)indole (Trp-P-2), in fresh or frozen normal human peripheral lymphocytes with frozen lymphocytes from the same thalassemia patient. The lymphocytes from the thalassemia patient showed an approximately two-fold increase in sensitivity. When a combination of Tryp-P-2, with either quercitin or kaempferol, was compared in frozen lymphocytes and lymphocytes from the thalassemia patient, a two-fold increase in sensitivity was also maintained. Responses to Trp-P-2 were reduced to untreated control levels at the highest doses of quercitin and kaempferol, and were highly significantly different by comparison with Trp-P-2 alone (P<0.001). The flavonoids acted in an antigenotoxic/antioxidant manner. Sensitivity was slightly increased with kaempferol by comparison with quercitin. At low concentrations of the flavonoids there was some evidence of an exacerbation of response, perhaps due to a switch to pro-oxidant status. This exacerbation of response at low doses of flavonoids has been seen in earlier studies with normal lymphocytes. Teratogenesis Carcinog. Mutagen. 21:165-174, 2001.

Carbolines↗
PubMed2001

An experimental study of tolerance among alcohol dependent individuals.

BACKGROUND & OBJECTIVES: Continued alcohol use leads to tolerance, however, some dependent individuals lose tolerance despite continued alcohol consumption. The exact mechanism for this is not known. This study evaluated tolerance in alcohol dependent patients in a treatment centre using multiple measures. METHODS: Male patients with alcohol dependence (DSM III R criteria) were chosen and detoxified in an inpatient setting. On day 14 of detoxification, each subject was given ethanol (0.75 g/kg body wt) mixed in an equal amount of placebo (cola) drink once and an equivalent amount of placebo (cola) during the other occasion in a single blind, randomised, cross over manner. Assessment of each subject was made using multiple measures (clinical, neuro-psychological tests, scales for subjective effect and blood alcohol levels), 30 min after intake of each drink. RESULTS: The subjects (n = 26) did not very under the two conditions (alcohol/placebo) as regards subjective effects, tests on logical memory and Bender Gestalt test (BGT). Cognitive screening scores though different under the two conditions, were within the normative range. Of these 26 subjects, 50 per cent showed clinical signs of intoxication after consumption of alcohol. These two groups (impaired vs unimpaired) were comparable on all base-line clinical parameters, assessment of euphoria and sedation, and various neuropsychological tests except BGT under the two conditions (placebo/alcohol). The non-tolerant (impaired) group scored significantly (P < 0.05) worse on BGT after alcohol consumption. INTERPRETATION & CONCLUSIONS: The study suggests that clinical tests were more sensitive in detecting intoxication. Further studies are needed to understand the mechanism of loss of tolerance.

Adolescent↗
PubMed2000

Response to varicella immunization in pediatric liver transplant recipients.

BACKGROUND: Individuals undergoing therapeutic immunosuppression are at risk of severe varicella-zoster virus (VZV) infection, particularly those without evidence of previous infection. METHODS: Eleven children, median age 10 months (range 5.5 months to 7 years and 9 months) received one dose of varicella vaccine (Varilrix, SmithKline Beecham plc, UK) before liver transplantation (median interval 95 days, range 40-289 days). The serological response to varicella vaccine was evaluated retrospectively and matched with the outcome and management of any subsequent exposures to VZV. RESULTS: Three children responded postimmunization, six children showed no response, and in two children the outcome was difficult to interpret having received blood products. Four children required varicella-zoster immunoglobulin prophylaxis posttransplantation, two of whom developed mild chickenpox. CONCLUSIONS: Only 3 of 11 children developed a clear antibody response to varicella vaccine. Administration of varicella vaccine did not affect the management of subsequent VZV exposures.

Antibody Formation↗
PubMed2000

Recurrence of Langerhans cell histiocytosis in the graft after pediatric liver transplantation.

Two girls were diagnosed with Langerhans cell histiocytosis (LCH) at the age of 16 and 7 months and developed end stage chronic liver disease related to LCH-induced sclerosing cholangitis at 28 and 8 months, respectively. They received liver transplants at 34 and 14 months of age. Five months post-orthotopic liver transplantation (OLT) one of the patients developed posttransplant lymphoproliferative disease, successfully treated with a combination of surgery and reduction of immunosuppression. Fourteen months post-OLT she developed diabetes insipidus, bilateral ear discharge, and new osteolytic lesions. After transplantation both girls had mild skin reactivations of LCH, requiring minimal steroid increments. At 60 and 5 months post-OLT intrahepatic LCH recurrence was diagnosed on the basis of abnormal biliary enzymes and presence of Langerhans cells in the grafts. Initial cholangiography in both patients was unremarkable. LCH activity was controlled by maintenance chemotherapy with vinblastine, etoposide, and prednisolone. Ten months after reappearance of LCH in the liver graft a follow-up cholangiography in one of the girls demonstrated a low grade cholangiopathy. Residual elevation of liver enzymes probably represents an ongoing pathogenic process.

Cholangiography↗
PubMed2000

Isolated liver transplant and sequential small bowel transplantation for intestinal failure and related liver disease in children.

Liver dysfunction is a well-recognized complication of intestinal failure in children. Advances in total parenteral nutrition (TPN) have allowed these children to survive while their intestinal tract gradually adapts. Unfortunately TPN may lead to cholestatic liver disease particularly in the young children. Progression of liver disease is associated with a poor prognosis and is an indication for small bowel transplantation. We report our experience of orthotopic liver transplantation in four children with short gut and sequential liver and small bowel transplantation in one child. All children had TPN-related liver failure. Causes of intestinal failure included necrotising enterocolitis (n=2), gastroschisis (n=1), intestinal atresia (n=1), and megacystic, microcolon syndrome (n=1). At the time of liver transplantation the children's mean age was 10.9 months (2.5-24) and weight 6.7 kg (4.8-10.1). The mean serum bilirubin was 522 micromol/liter (299-823), aspartate transaminase 423 IU/liter (49-1024) and international normalized ratio 2.8 (2-3.9). There were two deaths both from respiratory failure secondary to adenovirus pneumonia including the child who received a sequential small bowel transplant. Three children with isolated liver grafts are alive and off TPN at 20 months (mean) follow up (range 6-35). Isolated orthotopic liver transplantation has a role in selected children with intestinal failure, particularly those with short but normally functioning gut and progressing with satisfactory intestinal adaptation but developing liver disease. Those children with TPN-related liver disease and unadapted gut or irreversible intestinal disease need combined liver and small bowel transplantation. Sequential small bowel transplantation is feasible after orthotopic liver transplantation and may provide an option for the child with terminal liver and small bowel failure.

Adolescent↗
PubMed2000

Size reduction of small bowels from adult cadaveric donors to alleviate the scarcity of pediatric size-matched organs: an anatomical and feasibility study.

BACKGROUND: Small bowel transplantation in children weighing less than 10 kg is hindered by the lack of size-matched donors. The ability to create reduced size small bowel grafts from adult cadaveric donors suitable for use in young children has been studied. METHODS: Volumetric assessment of computed tomography scans were used to evaluate abdominal cavity and small bowel volumes in children. Small bowels were retrieved from adult cadaveric donors and reduced in size. RESULTS: Computed tomography studies of the abdominal cavity showed that the mean volume available for a small bowel graft was 260 ml in children less than 5 kg (n = 5) and 460 ml in children weighing 5-10 kg (n = 5). Fifteen small bowels were successfully reduced to provide an ileal graft of one meter while keeping the whole length of the superior mesenteric artery and vein after their dissection in the proximal part of the mesentery. The mean volume of the grafts created was 270 ml in seven thin patients (body mass index [BMI] <25), 390 ml in five preobese patients (25< BMI<30), and 490 ml in three obese patients (BMI>30). Mesenteric transillumination in thin donors allowed safe dissection and complete hemostasis. No diameter reduction was required. Technical modifications permitted the creation of two grafts, one ileal and the other jejunal from a single donor. Volumetric and surgical data show that implantation of up to two meters of ileum from a thin adult weighing up to 80 kg is feasible in children weighing less than 10 kg. CONCLUSION: Size reduction of adult cadaveric small bowels can provide suitable grafts for children of less than 10 kg and could expand the potential pool of donors for these patients.

Adult↗
PubMed2000

Liver transplantation for alpha-1-antitrypsin deficiency in children.

Alpha-1-antitrypsin (a1-AT) deficiency is an inborn error of metabolism, which can cause liver disease. The condition is one of the most common genetic disorders in the Caucasian population. Here we review our experience with 21 children suffering from end-stage liver disease due to a1-AT deficiency. All children are PIZZ homozygotes. Nineteen of them initially presented with neonatal jaundice and two with hepatosplenomegaly in childhood. Twenty-five liver transplantations were performed. All children are currently alive at a median followup of 40 months. Liver replacement provides the only definite treatment for children with end-stage liver disease associated with a1-AT deficiency. Excellent results can be achieved by reducing waiting time for transplantation and by early referral to a liver transplant centre.

Adolescent↗
PubMed2000

Inhibition by human embryos of mouse granulosa cell progesterone production: development of a sensitive bioassay.

Reproduction technologies could be improved by the development of methods to evaluate oocyte or embryo quality in a non-invasive, quantitative manner. Since human embryos secrete a factor that inhibits granulosa cell progesterone production, an interspecies bioassay was established to investigate whether the presence of this progesterone-inhibitory factor (PIF) in human embryo-conditioned (HEC) media is related to the health and developmental capacity of the embryos. Oocytes were microsurgically removed from oocyte-cumulus complexes isolated from superovulated mouse ovaries, and the oocytectomized complexes were cultured in HEC media in the presence of follicle stimulating hormone and testosterone. Progesterone accumulation in the media was determined by radioimmunoassay. Despite the potential limitations of very small volumes of HEC media to evaluate, and the need to freeze these media at the source, the bioassay was able to detect PIF activity in HEC media. Most embryos produced PIF activity, but the degree of inhibition was not correlated with the ability of oocytes to be fertilized, nor with embryo morphology or ability to cleave and develop after transfer. These results demonstrate that secretion of PIF by human embryos can be measured by this bioassay and that human PIF can inhibit murine granulosa cell steroidogenesis; however, PIF activity is not correlated with human embryo quality or developmental competence.

Animals↗
PubMed2000

Bone marrow failure in children with acute liver failure.

BACKGROUND: Aplastic anemia is a rare but well-recognized complication of acute hepatitis and acute liver failure. The cause is unknown, and the condition is fatal without bone marrow recovery. Treatment includes immunosuppression regimens or bone marrow transplantation. The purpose of this study was to investigate the incidence, cause, treatment, and outcomes of this disorder in children. METHODS: Retrospective chart review of 75 patients with acute liver failure in a major pediatric liver center. RESULTS: Eight patients had evidence of bone marrow failure. Of those, six had aplastic anemia, and two had transient bone marrow suppression. There were five boys, median age 57 months (range, 36-132 months). Two had parvovirus B19, six had non-A, non-B, non-C hepatitis. Five underwent liver transplantation: auxiliary in one, orthotopic in four. The interval between initial symptoms and development of aplastic anemia and/or bone marrow suppression was 21 to 99 days (median, 39 days). Four patients with aplastic anemia received intravenous antithymocyte globulin (ATG) or antilymphocyte globulin (ALG). Median recovery period of granulopoiesis was 62 days (range, 27-115 days). Two made a full recovery, one had myelodysplasia, and one with unresponsive disease died of septic complications. Four did not receive ATG/ALG, two had aplastic anemia, and two had bone marrow suppression. Three underwent liver transplantation, and all four resumed granulopoiesis. One child who underwent liver transplantation died of sepsis with chronic rejection. Median recovery of granulopoiesis was 99 days (range, 20-153 days). CONCLUSIONS: Bone marrow failure occurs in 10.7% of children with acute liver failure. It sometimes occurs in association with non-A, non-B, non-C hepatitis and parvovirus B19 infection. Treatment with ATG/ALG is successful and is well tolerated in most cases.

Adolescent↗
PubMed2000

Mycobacterium tuberculosis infection in pediatric liver transplant recipients.

OBJECTIVES: To study the incidence, clinical presentation, management, complications and outcome of tuberculosis in pediatric liver transplant recipients. METHODS: A retrospective review of the medical records of children who underwent liver transplantation between 1991 and 1998. RESULTS: Mycobacterium tuberculosis infection occurred in 6 of 254 (2.4%) children undergoing liver transplantation between 1991 and 1998. Cough, pyrexia and poor appetite were common presentations; one-half had normal chest radiographs. The median time to confirmation of diagnosis was 8 months (range, 1 to 17 months). Tests contributing to diagnosis included: Ziehl-Neelsen (ZN) stain (2 patients), M. tuberculosis polymerase chain reaction (1 patient), Mantoux test (1 patient) and histopathology (4 patients). Family health screening was productive for 4 patients. Duration of treatment varied from 9 to 18 months. Isoniazid-induced hepatitis was observed in 2 patients but resolved with dose reduction. Two patients died while receiving treatment, one of Klebsiella spp. septicemia and the other of pulmonary hemorrhage. CONCLUSIONS: Tuberculosis after liver transplantation has a significant morbidity and mortality. Pretransplantation a personal and family history of tuberculosis must be sought, and screening of patients and their families should be considered. Standard regimens incorporating isoniazid and rifampin are effective, but regular monitoring of liver function is essential to detect drug-induced hepatotoxicity.

Adolescent↗