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Biomedical subjects

A Dhawan

Publications and source records attributed to A Dhawan.

At least 73 records · Page 4Linked to original sources
PubMed1997

Local delivery of interleukin 4 by retrovirus-transduced T lymphocytes ameliorates experimental autoimmune encephalomyelitis.

Experimental autoimmune encephalomyelitis (EAE) is an inflammatory autoimmune disease of the central nervous system which serves as a model for the human disease multiple sclerosis. We demonstrate here that encephalitogenic T cells, transduced with a retroviral gene, construct to express interleukin 4, and can delay the onset and reduce the severity of EAE when adoptively transferred to myelin basic protein-immunized mice. Thus, T lymphocytes transduced with retroviral vectors can deliver "regulatory cytokines" in a site-specific manner and may represent a viable therapeutic strategy for the treatment of autoimmune disease.

Animals↗
PubMed1997

Posttransplant eosinophilic gastroenteritis in children.

The cause of eosinophilic gastroenteropathy in older children and adults is unknown. In this report, two post-liver transplantation children treated with low-dose cyclosporine A and alternate-day low-dose prednisone are described who were administered a single bolus administration of a lympholytic dose of corticosteroids without taper and who developed intestinal symptomatology several weeks later. Histologic examination of mucosal biopsy specimens from various regions of the gastrointestinal tract showed an intense eosinophilic infiltration of the mucosa and lamina propria. The patients recovered after corticosteroid administration was tapered. Post-transplant gastroenteric eosinophilic inflammation may need to be considered in patients on immunomodulatory medications who have chronic intestinal symptomatology.

Anti-Inflammatory Agents↗
PubMed1997

Tacrolimus (FK506) malabsorption: management with fluconazole coadministration.

We report the use of fluconazole to control primary immunosuppressive management with tacrolimus in a 9-year-old liver transplant recipient. Progressive increases in the doses of both cyclosporin (up to 20 mg/kg/day) and, subsequently, tacrolimus (up to 60 mg/day) failed to maintain immunosuppressive levels of both agents. After excluding poor compliance, drug interactions and analytical problems and identifying poor bioavailability (< 2.6%) and rapid clearance (4.2 l/h), fluconazole (100 mg/day) was initiated to inhibit tacrolimus metabolism and consistent therapeutic blood levels of tacrolimus were achieved. However, graft function had deteriorated irrevocably and retransplantation was performed. Simultaneous use of tacrolimus (5 mg/day) and fluconazole (100 mg/day) maintained immunosuppression after transplantation. Three weeks later, obstruction of the Roux loop caused deteriorating liver function and tacrolimus blood levels fell. After correction at laparotomy, stabilisation was achieved and discharge was possible on 5 mg tacrolimus b.i.d. plus fluconazole (100 mg).

Absorption↗
PubMed1996

Liver transplantation for Langerhans' cell histiocytosis--a case report and literature review.

Langerhans' cell histiocytosis (LCH) is a rare disorder of unknown etiology and pathogenesis. End-stage chronic liver disease is one presentation and orthotopic liver transplantation (OLT) has been reported in 17 cases, with variable resolution of LCH lesions postoperatively. We report a case of multisystem LCH with end-stage liver disease treated by OLT and review the overall results of OLT for children with LCH.

Child, Preschool↗
PubMed1996

An investigation of bone marrow and testicular cells in vivo using the comet assay.

The effects of the mutagens, cyclophosphamide (CP), ethyl methanesulphonate (EMS), bleomycin (BLM) and the testicular toxin ethylene glycol monomethyl ether (EGME) in bone marrow and testicular cells have been compared in the alkaline COMET assay. Sprague-Dawley rats were administered by gavage with 50, 100 and 150 mg/kg body weight (bw) of CP; 100, 200 and 300 mg/kg bw EMS; 50, 100 and 150 mg/kg bw BLM and 500, 1000 and 1500 mg/kg bw EGME. Effects were examined at week 2 after treatment for CP, EMS BLM and EGME and at weeks 5 and 6 for EGME. Bone marrow cells were removed and separated by aspiration of the femur and testicular cells by decapsulation of the testis, treating with collagenase followed by trypsin. Various statistical methods were used to analyse the data. For CP there was an increase in damage above control values for bone marrow at 50 mg/kg bw which decreased at 100 mg/kg bw, and there was mortality of the animals at 150 mg/kg bw. A similar response was found in the testicular cells. For EMS and BLM, there were only occasional slight increases in damage in bone marrow and testicular cells. Two studies were conducted with EGME. In the first, where effects were examined at week 2 after treatment, there was an increase in damage in bone marrow cells, but a larger response was observed in testicular cells. In the second study where effects were examined at weeks 5 and 6 after treatment, bone marrow and testicular cells were not affected. The overall results showed that damage persisted for 2 weeks after treatment with CP and EGME but not in weeks 5 and 6 for EGME. Various statistical methods were used to analyse the data. Statistically significant responses were produced after treatment with CP and EGME and were dose-related for EGME, but after treatment with EMS and BLM statistical increases were sporadic. These results suggest that the assay is useful for measuring DNA damage and its persistence, and for comparing the sensitivity of different target organs in vivo.

Animals↗
PubMed1995

The incidence and management of biliary complications following liver transplantation in children.

Biliary complications following liver transplantation are a cause of significant morbidity and mortality. During the period 1988-1993 ten cases of biliary complications occurred after 98 transplantations in 78 children. The complications were four bile leaks, three intrahepatic biliary strictures (one with recurrent cholangitis), two anastomotic biliary strictures (one with recurrent cholangitis) and one recurrent cholangitis. All leaks occurred within 6 weeks of transplantation whereas all strictures and cholangitic episodes occurred after 3 months. Two biliary complications (20%) - one intrahepatic and one anastomotic stricture - developed secondary to hepatic artery thrombosis. The incidence of biliary complications was 13.2% with whole liver grafts as compared to 6.7% with partial liver grafts and it was 4.3% with duct-to-duct anastomosis as compared to 12.0% with Roux-en-Y hepatico-jejunostomy. Seven children required intervention for management of biliary complications and three were managed conservatively. There were no deaths related to the biliary complications.

Adolescent↗
PubMed1995

Choledochal cysts: lessons from a 20 year experience.

Cystic dilatation of the biliary tree is a rare congenital anomaly. To determine mode of presentation, diagnostic pitfalls, and long term outcome after surgery, 78 children (57 girls, 21 boys) with choledochal cyst treated between 1974 and 1994 were reviewed. Anatomical types were: Ic (n = 44), If (n = 28), IVa (n = 4), and V (n = 2); a common pancreaticobiliary channel was identified in 76% patients. Age at presentation ranged from 0-16 (median 2.2) years, six patients being diagnosed by prenatal ultrasonography. Of the 72 patients diagnosed postnatally, 50 (69%) presented with jaundice, associated with abdominal pain in 25 or a palpable mass in three, 13 (18%) presented with pain alone, and two (3%) with a palpable mass. The classic triad of jaundice, pain, and a right hypochondrial mass was present in only four (6%). Four children presented acutely after spontaneous perforation of a choledochal cyst, two presented with ascites and one cyst was discovered incidentally. Plasma and/or biliary amylase values were raised in 30 of 31 patients investigated for abdominal pain; seven had evidence of pancreatitis at operation. In 35 of 67 (52%) patients referred without previous surgery, symptoms had been present for more than one month, and in 14 of them for more than one year, before diagnosis. Delayed referral was due to misdiagnosis as hepatitis (n = 12), incomplete investigation of abdominal pain (n = 6), and failure to note the significance of ultrasonographic findings (n = 10). Two patients referred late died from liver failure. Of the 76 patients with type I or IV cysts, 59 underwent radical cyst excision and hepaticojejunostomy as a primary procedure and 10 as a secondary operation after previously unsuccessful surgery. Sixteen patients have been lost to follow up but most of the remainder are well after a mean period of 4.1 (0.1-13) years. Choledochal cysts are often misdiagnosed, but prognosis is excellent if radical excision is performed.

Adolescent↗
PubMed1995

Prognostic value of serum hyaluronic acid and type I and III procollagen propeptides in extrahepatic biliary atresia.

Although portoenterostomy has greatly improved the prognosis of extrahepatic biliary atresia (EHBA), 10-20% of patients still die before 5 y of age, and the only treatment option is liver transplantation (LT). To investigate whether these patients may be identified at an early stage, when the changes of successful LT are optimal, we have measured serum concentrations of hyaluronic acid (HA), the amino-terminal propeptide of type III procollagen (PIIINP) and the carboxy-terminal and amino-terminal propeptides of type I procollagen (PICP, PINP) in 24 selected patients with EHBA, both before portoenterostomy and then every 6 mo until death (n = 10, age at death = 7-20 mo), LT (n = 6, age at LT = 1.1-4.8 y) or 5 y of age (n = 8). Raised serum HA above 200 micrograms/L before portoenterostomy identified those patients who would die or require LT in the first 5 y of life with a positive predictive value of 88%; after portoenterostomy, longitudinal changes in HA reflected clinical status in each patient. None of the other three markers was of prognostic value, and only PIIINP showed any relationship with clinical status, and then only up to 1.5 y. Interestingly, PINP (but not PICP) tended to be low in all patients before portoenterostomy and may reflect impaired bone collagen metabolism during early skeletal changes in EHBA. This study therefore suggests that measurement of serum HA may be a useful complementary test in EHBA, particularly in identifying, at an early stage, those patients who should be considered for LT.

Age Factors↗
PubMed1995

University of Nebraska Medical Center Liver Transplant Program.

The field of liver transplantation has evolved slowly over the past 5 years. The most important new additions to this field include new immunosuppressive agents and greatly broadened recipient selection criteria. The most compelling problem in transplantation today remains the lack of suitable donors. Innovative surgical techniques, such as auxiliary liver transplantation, extracorporeal support and living-related donation, represent new and important additions to the approach to patients with liver disease.

Academic Medical Centers↗
PubMed1994

Validity of clinical signs for the identification of pneumonia in children.

In a prospective study to determine simplified clinical signs predictive of pneumonia in children between 2 months and 5 years of age, and to test the validity of the signs recommended by the World Health Organization, clinical findings were correlated with X-ray evidence of pneumonia in 854 children, 400 with pneumonia and 454 with upper respiratory infections (no pneumonia). A respiratory rate of > or = 50/min in infants 2-6 months of age, > or = 40/min in children 7-35 months, and > or = 35/min in children > or = 36 months was the best discriminator of radiological evidence of pneumonia. Use of a respiratory rate of > or = 50/min instead of > or = 40/min resulted in a 14%, 19% and 32% loss of sensitivity with little gain in specificity in the age groups 7-11 months, 12-35 months and > or = 36 months, respectively. The age-specific respiratory rate (recommended by WHO) and/or chest indrawing, history of rapid or difficult breathing and/or chest indrawing, and nasal flaring were also sensitive and specific indicators of pneumonia in almost all the age groups studied.

Age Factors↗
PubMed1994

Clinical signs of pneumonia in infants under 2 months.

To determine clinical signs that can predict pneumonia (confirmed by radiography) in infants under 2 months of age, 101 infants with pneumonia and 150 with an upper respiratory infection (but not pneumonia) were studied. Ten infants with pneumonia and 15 with an upper respiratory infection did not have the cough and/or difficult (or rapid) breathing that are recommended as 'entry criteria' by the World Health Organisation (WHO). The remaining infants met WHO entry criteria; in them sensitivity and specificity of respiratory rate > or = 60/min and/or severe chest indrawing to diagnose pneumonia was 85% and 97% respectively. Addition of four non-specific signs (stopped feeding well, looked sick, temperature < or = 38 degrees C, and abdominal distension) to respiratory rate > or = 60/min and/or chest indrawing for case identification resulted in a 7% gain in sensitivity but 22% loss of specificity. Addition of nasal flaring improved the sensitivity by 6% without loss of specificity. However, the non-specific signs were the only clue to diagnosis in five infants weighing < or = 2500 g. At age < 7 days, a weight < or = 2500 g and cyanosis were associated with significantly higher risk of mortality. These findings support the use of a respiratory rate > or = 60/min and/or chest indrawing for identification of pneumonia, and suggest addition of nasal flaring to the criteria for case identification in infants under 2 months with cough and/or difficult or rapid breathing.

Body Weight↗