Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0024523 (malabsorption)
 7,319 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It has been suggested that cyclosporin A might be of some benefit to patients with Crohn's disease. The clinical response and side-effects of cyclosporin A in Crohn's disease are described in a series of 13 adults. The majority of patients had ileal disease and all but one were started on an initial oral dose of 15 mg/kg per day. Duration of treatment ranged from 3 to 42 weeks. Of the 13 patients, 6 showed a response to therapy; the remainder showed no response or deteriorated. The commonest side-effect was hyperaesthesia, but one patient developed nephrotoxicity and one developed hepatotoxicity. Significant drug malabsorption occurred in one case. The side-effects were dose dependent and reversible. Cyclosporin A may have a part to play in the treatment of resistant Crohn's disease, and in our hands has been associated with a 46 per cent response rate; however, the precise role of cyclosporin A in the management of Crohn's disease awaits further study.
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PMID:Treatment of Crohn's disease in relapse with cyclosporin A. 306 76

Pairs of mongrel dogs received orthotopic total small bowel allografts. Half were treated with the immunosuppressive agent cyclosporin A and the other half were not. Ten untreated dogs survived a mean of 12.5 days (range from 7 to 25 days). They lost up to 30% of their initial body weight and rejection with hemorrhagic necrosis was usually the cause of graft failure. The mean survival of 11 dogs treated with cyclosporin A was 90.6 days (range 9 to 286 days) with early deaths being due to pneumonia or volvulus. Intestinal mucosa appeared normal, but there was some smooth muscle hypertrophy. Reconnection of lymph vessels was complete in all dogs examined more than 21 days after allografting. Two dogs survived for 203 and 221 days, respectively, and one dog remains alive and well 287 days after operation. The long-term survivors remained healthy, with steady body weights, formed stools, normal plasma protein values and xylose absorption curves that did not differ from those of autografted dogs. Roentgenography after a barium meal and follow-through study showed normal mucosa. The transit time was around 60 minutes (normal 150 minutes). Late, acute episodes of rejection occurred in two dogs, when blood levels of cyclosporin A were low (less than 400 ng/ml). Bowel mucosa showed ulceration and villous atrophy, with lymphoid infiltration, leading to malabsorption as a terminal event. Cyclosporin A is effective in increasing the duration of survival in dogs with small bowel allografts while maintaining essentially normal bowel structure and good function.
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PMID:Structure and function of small bowel allografts in the dog: immunosuppression with cyclosporin A. 705 64

Patients with malabsorption and histological findings consistent with celiac disease, who are unresponsive to gluten free diet, and in whom other causes of flat mucosa have been excluded, are considered to suffer from so called unclassified or refractory sprue. Although the true nature of this condition needs to be further elucidated, it is known to represent a difficult therapeutical problem with potentially fatal course. Herein, we report a patient with refractory sprue-like disease who after failing to respond to corticosteroids and TPN was in a critical condition. He responded promptly to cyclosporine and made a remarkable recovery. In contrast to previous reports, the cyclosporine treatment in this patient was pursued only for 1 month, whereupon the patient turned responsive to steroids. Subsequent treatment with azathioprine allowed corticosteroids to be reduced to a low maintenance dose and eventually all drugs could be discontinued without reappearance of symptoms. Cyclosporine therapy might be lifesaving in occasional patients with refractory sprue-like disease and it may result in reversal of steroid resistance. Moreover, azathioprine seems to have a steroid sparing effect in this setting. Short term immunosuppressive treatment may have an advantage of lower risk for drug related side effects.
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PMID:Role of immunosuppressive therapy in refractory sprue-like disease. 993 59

Cyclosporine (Sandimmune; Novartis Pharmaceuticals UK Ltd) is an effective immunosuppressive drug, but its lipid formulation and variable absorption may expose children to the risk of rejection during episodes of gastroenteritis after liver transplantation. Neoral (Novartis) is a microemulsified form of cyclosporine that may be better absorbed. In this study, the pharmacokinetic profiles of Neoral and Sandimmune were compared in stable children after liver transplantation to evaluate whether Neoral is more predictably absorbed. Eight children, 6 boys and 2 girls, with a mean age of 4.5 years (range, 1.2-12) were studied between 4 and 12 months after liver transplantation. Pharmacokinetic profiles were performed on each child by using the same dose (mg/kg) of Neoral or Sandimmune. Tmax, Cmax, Ctrough, and the area under the curve (AUC) were calculated and side effects were documented in children taking either drug for more than 3 months. Mean peak cyclosporine levels were higher and were achieved significantly sooner with Neoral (Cmax 790.5 +/- 216.5 ng/mL, P =.06; Tmax 1.8 +/- 1.0 hr, P =.01) than with Sandimmune (Cmax 589.4 +/- 313 ng/mL, Tmax 2.5 +/- 1.7 hr), implying more rapid and better absorption. There was no significant difference in overall drug exposure (AUC) and 12-hour trough levels between the two formulations (P >.05). Children with Roux-en-Y loop biliary anastomosis taking Neoral, however, showed greater increases in AUC (mean increase = 37%) than those with duct-to-duct anastomosis (mean increase = 16%). There was no correlation between 12-hour trough level and AUC for either Neoral (r2 = 0.48) or Sandimmune (r2 = -0.08); however, for both drugs, AUC correlated very well with the 2-hour post-dose level (r2 = 0.68 and 0.7, respectively). Hirsutism was reported in 4 of 6 children on Neoral and may be associated with higher peak levels. Neoral is more consistently absorbed than Sandimmune in children after liver transplantation and may be more effective prophylaxis against rejection. Because of the increased peak levels and drug exposure, which may influence side effects, particularly in children with Sandimmune malabsorption, we recommend a 1:0.75 dose conversion ratio in patients being converted from Sandimmune to Neoral.
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PMID:Comparison of pharmacokinetics of Neoral and Sandimmune in stable pediatric liver transplant recipients. 1007 49