[Echographic images of fetal visceral atony: limits between dysmorphism and dysfunction].
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Dilatation, Pathologic↗
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[On variations of the tonicity of the small bowel in connection with dysfunction of the secretion by the stomach (author's transl)].
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Adult↗
Orthotopic liver transplantation for bone-marrow transplant-associated veno-occlusive disease and graft-versus-host disease of the liver.
Bone marrow transplantation (BMT) is a highly successful and curative therapy for many primary hematologic malignancies. However, hepatic dysfunction and failure are important causes of morbidity and mortality in this patient group after BMT. Hepatic failure can occur as a result of involvement by graft-versus-host disease (GVHD) or as a result of veno-occlusive disease (VOD). Therapies for these complications are often ineffective, especially for VOD, as approximately one fourth of patients develop irreversible liver disease and die of multiorgan failure. Accordingly, we have reviewed our center's experience with orthotopic liver transplantation (OLT) to manage the hepatic complications of BMT. We describe two patients who were treated with OLT after developing hepatic failure post-BMT. One patient had VOD with mild cutaneous and gastrointestinal GVHD; in the other patient, the pathophysiologic process affecting the liver was severe GVHD. Based on our center's experience and review of the literature, we believe OLT should be considered in patients with severe hepatic dysfunction post-BMT.
Adult↗
Mycophenolatemofetil for immunosuppression after liver transplantation: a follow-up study of 191 patients.
BACKGROUND: Mycophenolatemofetil (MMF) combined with calcineurin inhibitors (CNIs) as immunosuppression after orthotopic liver transplantation (OLT) is still under discussion. We retrospectively investigated the immunosuppressive potency of MMF for treatment of steroid-resistant acute rejection (AR) or chronic rejection (CR), chronic graft dysfunction, and CNI-induced toxicity in patients after OLT. METHODS: Between 1988 and 2001 we performed 1386 OLTs in 1258 patients. Since 1995, 191 patients have received MMF after OLT for steroid-resistant AR or CR, chronic graft dysfunction (115 patients), and CNI-induced toxicity (76 patients). The mean follow-up time was 56 months. RESULTS: Of 47 patients with steroid-resistant AR, 12 had been treated with OKT3, without resolving the rejection. Overall, bilirubin and transaminases decreased significantly within 2 weeks after the addition of MMF, and liver function normalized in 38 patients. Five of eight patients with CR demonstrated stable liver function after a follow-up of 55+/-8 months; 52 of 60 patients with chronic graft dysfunction improved within 3 months; and 46 of 59 patients with CNI-induced nephrotoxicity improved after MMF treatment and a reduction of CNIs (with a significant decrease in serum creatinine within 2 weeks and an increase of creatinine clearance within 3 months). Clinical symptoms improved in 10 of 12 patients with neurotoxicity and four of five patients with hepatotoxicity. Side effects of MMF, such as gastrointestinal disorders or bone marrow toxicity, occurred in 60 patients (31.4%). The incidence of infections did not increase. Patient survival was 93%, and graft survival was 88.2%. CONCLUSIONS: MMF is a potent and safe immunosuppressive agent in OLT recipients for rescue therapy in AR, CR, or chronic graft dysfunction and helps to reduce the serious toxic side effects of CNIs.
Adult↗
Stimulatory effect of metoclopramide on the esophagus and lower esophageal sphincter of patients of patients with PSS.
Metoclopramide has been shown to stimulate motility of the gastrointestinal tract, including the esophagus. The authors therefore tested the effect of intravenous injections of metoclopramide on the sphincteric pressure and esophageal motility in 14 patients with esophageal dysfunction due to progressive systemic sclerosis (PSS). Isotonic saline similarly injected in a control period in 7 of the patients showed no effect. None of the 14 patients had a detectable pressure zone at the sphincteric area in basal conditions, but following the injection of metoclopramide, one appeared in 7 patients. Metoclopramide also caused the appearance of pressure waves in 5 of 11 patients who had aperistalsis, and caused up to a three fold increase in the amplitude of the pressure waves in the 3 patients who had hypomotility of the esophagus.
Adult↗
A cystic fibrosis allele encoding missense mutations in both nucleotide binding folds of the cystic fibrosis transmembrane conductance regulator.
German cystic fibrosis (CF) chromosomes were screened for molecular lesions in exon 20 of the cystic fibrosis transmembrane conductance regulator (CFTR) gene by chemical cleavage of mismatch. An 3884G-to-A transition was detected in two patients which leads to an exchange of a serine by an asparagine in the Walker motif A of the second nucleotide binding fold. The affected serine residue is evolutionarily strongly conserved among the pro- and eukaryotic members of the protein superfamily of traffic ATPases. The two S1251N alleles were linked to the benign missense mutation F508C which is located in another conserved region of CFTR, the center region of the first nucleotide binding fold. Both patients with the complex allele F508C-S1251N are carrying delta F508 on the other CF chromosome and are suffering from severe pulmonary and gastrointestinal CF disease. Although F508C has been classified as a neutral sequence variation because of its discovery in healthy delta F508 gene carriers, it may nevertheless influence CFTR dysfunction caused by the S1251N mutation.
Adolescent↗
An assessment of the physiological significance of cimetidine interactions with copper and zinc in biofluids as based on the computer-simulated distribution of the involved complexes at therapeutic levels of the drug.
The hypothesis was formerly put forward that the main therapeutic action of cimetidine (the histamine H2-receptor antagonist marketed as Tagamet) as well as some of its side effects might be mediated by its interactions with essential metal ions. The present paper reports the potentiometric study of the coordination of the drug with copper(II) and zinc(II) in NaCl 0.15 mol dm-3 at 37 degrees C. Special attention was paid to copper complexes, due to (i) the involvement of cimetidine in rheumatoid arthritis evolution which could be related to the well-established role of copper against this disease, (ii) the anti-ulcer and anti-inflammatory properties of copper. In particular, the copper-cimetidine-histamine and copper-cimetidine-histidine ternary systems were investigated. Computer simulations of the distribution of cimetidine, zinc and copper in blood plasma were performed at therapeutic levels of the drug. No influence can be expected from cimetidine on the bioavailability of these metal ions, the opposite being also true. The mediation of copper in the action of cimetidine on rheumatoid arthritis should thus be ruled out, the influence of the drug being rather interpretable in terms of reduction of histamine release. Similarly, the sexual dysfunctions due to cimetidine administration are unlikely to arise from the interactions of drug with zinc in blood plasma. The possible involvement of copper and zinc in cimetidine gastrointestinal absorption is also discussed.
Cimetidine↗
[Doxycycline--the forgotten antibiotic].
BACKGROUND: Doxycycline is an broad-spectrum antimicrobial agent, it remains an inexpensive alternative for the treatment of community-acquired respiratory infections and urinary tract infections. Despite these clinical data the use of doxycycline has decreased during the last years. PHARMACOLOGY: Adverse effects and resistance to therapy are infrequent and not different to fluoroquinolones and macrolide antibiotics. Gastrointestinal and phototoxic side effects are of importance. After oral administration 75% will be absorbed and largely eliminated by the hepatic and intestinal way. Contraindications are severe liver dysfunction and treatment in childhood. CLINICAL INDICATIONS: Bacterial resistance to doxycycline has a low incidence in Germany. A therapeutic success can be expected in respiratory and urinary tract infections in about 80%. Doxycycline is the drug of choice for treating infections caused by Rickettsia, Borrelia, Ehrlichia. It shows good activity against Plasmodium falciparum as one part in a combination therapy. Daily costs of therapy are low, in oral administration DM 0.80 per day, in i.v. administration DM 22,-per day. CONCLUSION: Despite competition from new antibiotics, doxycycline can retain an important place in the treatment of many infectious diseases.
Bacterial Infections↗
Portal vein aneurysm as late complication of liver transplantation: a case report.
OBJECTIVE: A case of intrahepatic portal vein aneurysm in the late postoperative period after liver transplantation, as well its complications, is reported. CASE REPORT: A 59-year-old man underwent orthotopic liver transplantation in 1996 for treatment of hepatitis C virus cirrhosis. The patient received a graft from a 10-year-old child. During the follow-up from 1996 to 1998, the patient did not show any alterations. In 1999, during an annual routine exam, a portal vein aneurysm was identified; however, it had no impact on graft function. In November 2002, the patient developed jaundice and serious graft dysfunction requiring hospital admission. Helicoidal CT scan showed an intrahepatic image compatible with a portal vein aneurysm without biliary tract dilatation. During the same hospitalization, he developed upper gastrointestinal bleeding due to variceal rupture as well as kidney and liver failure, and expired on December 31, 2002. The necropsy demonstrated an intrahepatic portal vein aneurysm with portal vein thrombosis and chronic liver disease. The evolution in this case suggests that if there is an intrahepatic portal vein aneurysm after liver transplantation, the patient is likely to experience an eventual recurrence of portal hypertension; retransplant may be an alternative.
Aneurysm↗
Combined abdominoperineal resection.
Abdominoperineal resection has long been recognized as a procedure with formidable morbidity. Through meticulous dissection, use of proper tissue planes, attention to location of urologic and neurologic structure, careful hemostasis, and appropriate postoperative measures, most of the complications outlined in this article can be avoided. Should a complication develop, close surveillance and early recognition coupled with the appropriate management can still offer the patient a satisfactory recovery.
Abdomen↗
Ten-year experience in porto-caval hemitransposition for liver transplantation in the presence of portal vein thrombosis.
Porto-caval hemitransposition (PCH) in liver transplantation allows revascularization of the liver when the porto-mesenteric axis is thrombosed. We, here, review our experience over an 11-year period. A total of 23 patients underwent liver transplantation using PCH. Immunosuppression was based on tacrolimus, with sirolimus used in case of renal insufficiency. Most common diagnoses were hepatitis C, Laennec's, Budd-Chiari and cryptogenic cirrhosis. Six patients needed splenectomy prior to transplant, 5 during transplant, 1 post-transplant, 11 had no splenectomy. Overall survival was 60% at 1 year and 38% at 3 years, with 10 of 23 patients currently alive and the longest survivor at 9.3 years. Most common cause of death was sepsis/multisystem organ failure, followed by pulmonary embolism. A total of 7/23 patients experienced post-operative gastrointestinal bleeding episodes, 6/23 patients developed thrombosis of the vena cava (median 162 days post-op). Post-operative ascites was noted in almost all patients. Renal dysfunction was commonly seen even after the first month post-transplant. PCH offers a feasible option for liver transplantation in those patients with complex thrombosis of the mesenteric and portal circulation.
Adult↗
Acute hyperglycaemia affects anorectal motor and sensory function in normal subjects.
BACKGROUND: The pathogenesis of anorectal dysfunction, which occurs frequently in patients with diabetes mellitus, is poorly defined. Recent studies indicate that changes in the blood glucose concentration have a major reversible effect on gastrointestinal motor function. AIMS: To determine the effects of physiological changes in blood glucose and hyperglycaemia on anorectal motor and sensory function in normal subjects. SUBJECTS: In eight normal subjects measurements of anorectal motility and sensation were performed on separate days while blood glucose concentrations were stabilised at 4, 8, and 12 mmol/l. METHODS: Anorectal motor and sensory function was measured using a sleeve/sidehole catheter incorporating a balloon, and electromyography. RESULTS: The number of spontaneous anal relaxations was greater at 12 mmol/l than at 8 and 4 mmol/l glucose (p < 0.05 for both). Anal squeeze pressures were less at a blood glucose of 12 mmol/l when compared with 8 and 4 mmol/l (p < 0.05 for both). During rectal distension, residual anal pressures were not significantly different between the three blood glucose concentrations. Rectal compliance was greater (p < 0.05) at a blood glucose of 12 mmol/l when compared with 4 mmol/l. The threshold volume for initial perception of rectal distension was less at 12 mmol/l when compared with 4 mmol/l (40 (20-100) ml versus 10 (10-150) ml, p < 0.05). CONCLUSIONS: An acute elevation of blood glucose to 12 mmol/l inhibits internal and external anal sphincter function and increases rectal sensitivity in normal subjects. In contrast, physiological changes in blood glucose do not have a significant effect on anorectal motor and sensory function.
Acute Disease↗
Update on gastroesophageal reflux and respiratory disease in children.
Pediatric respiratory diseases have been linked to gastroesophageal reflux disease (GERD), but evidence regarding the association and its potential mechanisms continues to accumulate, and important aspects remain to be determined. Evidence for the association in two common pediatric respiratory disorders - infantile apnea and asthma in older children - and difficult clinical issues associated with the diagnosis and treatment of these two disorders are reviewed. The provocative embryological and physiological connections between the upper gastrointestinal tract and the respiratory tract, and recent understanding of the compensatory anatomy and physiology that protect the normal individual from respiratory manifestations of GERD are also explored. Dysfunctions of these protections likely underlie the pathophysiology of these disorders.
Child↗
Clinical pharmacokinetics of metronidazole and other nitroimidazole anti-infectives.
Metronidazole was first introduced for the treatment of trichomoniasis. Its therapeutic use has subsequently been expanded to include amoebiasis, giardiasis and, more recently, anaerobic infections. Most of the early pharmacokinetic studies employed nonspecific assays such as microbiological and chemical assays. These assays were not able to differentiate the parent drug from the metabolites or other interfering substances. Pharmacokinetic data obtained through the use of specific chromatographic techniques provide the basis for this review of recent pharmacokinetic findings concerning metronidazole and other nitroimidazole antibiotics. When given intravenously or orally at usual recommended doses, metronidazole attains concentrations well above the minimum inhibitory concentrations for most susceptible micro-organisms. The drug has an oral bioavailability approaching 100%. Rectal and vaginal administration results in a smaller amount of drug absorption and lower serum concentrations. Metronidazole has limited plasma protein binding but can attain very favourable tissue distribution, including into the central nervous system. The drug is extensively metabolised by the liver to form 2 primary oxidative metabolites: the hydroxy and acetic acid metabolites. The kidney is responsible for the elimination of only a small amount of the parent drug; however, normal excretion of the 2 metabolites is dependent on the integrity of kidney function. The metabolism of metronidazole was found to vary among patient groups. Preterm and term infants have lower total body clearance (CL) and prolonged elimination half-lives. However, children older than 4 years old were observed to have pharmacokinetic parameters similar to those in adults. Reduced CL was also observed in children who are malnourished. Elderly patients have reduced renal excretion of both the parent drug and hydroxy metabolite. Pharmacokinetic parameters in pregnant patients were not significantly different from those in nonpregnant women; however, the drug is distributed into breastmilk and the infant will be exposed to the drug through the nursing mother. Patients undergoing gastrointestinal surgery or having enteric diseases and those who are hospitalised or critically ill also have altered pharmacokinetics. Metabolism of the drug is reduced in patients with liver dysfunction, giving delayed production of metabolites. In contrast, renal failure has little effect on the elimination of the parent drug, but affects the excretion of the metabolites more significantly. Haemodialysis was found to remove a substantial amount of the metronidazole while the effect of peritoneal dialysis was more limited. Energy and protein deficient diets as well as occupational exposure to gasoline did not alter metronidazole pharmacokinetics. However, the effect of alcohol consumption on metronidazole CL requires further study.(ABSTRACT TRUNCATED AT 400 WORDS)
Aged↗
A prostaglandin E1 analog, OP-1206, alleviates 5-fluorouracil-induced injury of rat small intestine.
5-Fluorouracil (5-FU) often causes the gastrointestinal toxicity, including enterocolitis. We investigated effects of OP-1206 (17S, 20-dimethyl-trans-delta2-prostaglandin E1) on 5-FU-induced leukocyte infiltration and epithelial barrier dysfunction of rat small intestine. Myeloperoxidase (MPO) activity of the small intestine was assayed as an index of leukocyte infiltration. Intestinal epithelial permeability was determined by the small intestinal absorption of a paracellular permeation marker, fluorescein isothiocyanate-labeled dextran (molecular weight; 4,400) (FD-4) using the in situ closed intestinal loop technique. The MPO activity and FD-4 permeation were significantly increased by the administration of 5-FU to rats for 4 days, while on the coadministration of 5-FU and OP-1206, they were similar to those of control rats treated with saline solution alone, respectively. These observations indicate that OP-1206 reduced the leukocyte infiltration and the change in epithelial permeability of rat small intestine induced by 5-FU.
Alprostadil↗
[Desmopressin in the treatment of hemorrhagic diathesis].
Over the past several years, the use of 1-deamino-8-D-arginine vasopressin (DDAVP), a synthetic analogue of vasopressin, has been found to be useful in the treatment of patients with abnormal bleeding tendency. This article is a review of inherited and acquired disorders with prolonged bleeding time in which DDAVP is supposed to shorten the bleeding time. DDAVP is established as effective therapy of the abnormal haemostasis in mild or moderate haemophilia A and von Willebrand's disease. Frequently, DDAVP infusions are used to control bleeding in patients with uraemia. Bleeding time is also significantly shortened in patients with liver cirrhosis, although randomized trials of DDAVP therapy of gastrointestinal bleeding in this group of patients are still needed. Shortening or normalization of the bleeding time with DDAVP has also been observed in patients with inherited platelet dysfunctions, acquired disorders of haemostasis and abnormal haemostasis in chronic myeloproliferative diseases. In addition, preoperative treatment with DDAVP seems to reduce blood loss during surgery.
Deamino Arginine Vasopressin↗
Cogan's syndrome: a systemic vasculitis.
Nonsyphilitic interstitial keratitis with vestibuloauditory dysfunction (Cogan's syndrome) is a rare clinical entity. We have reviewed 53 cases (including one of our own) of this disease. In 72 per cent of the affected patients there was an underlying systemic process, often a vasculitis. Ten per cent had fatal or near fatal aortic valvular disease, which has been shown to be amenable to surgical intervention. Other systemic manifestations have included congestive heart failure, gastrointestinal hemorrhage, adenopathy, splenomegaly, hypertension, musculoskeletal involvement and eosinophilia. The clinical course is extremely variable, ranging from months to over 15 years with a minimal five year survival of 28 per cent. Medical therapy with corticosteroids has been beneficial but has only limited effect on symptoms of vestibuloauditory dysfunction. Cogan's syndrome appears to be a manifestation of a systemic disorder which is often apparent only after long-term follow-up.
Adolescent↗
Administration of oral charcoal adsorbent (AST-120) suppresses low-turnover bone progression in uraemic rats.
BACKGROUND: Using a rat model of renal failure with normal parathyroid hormone levels, we had demonstrated previously that bone formation decreased depending on the degree of renal dysfunction, and hypothesized that uraemic toxins (UTx) are associated with the development of low-turnover bone development, complicating renal failure. In this study, focusing on indoxyl sulphate (IS) as a representative UTx, we analysed the effect of an oral charcoal adsorbent AST-120, which removes uraemic toxins and their precursors from the gastrointestinal tract, on bone turnover. METHODS: AST-120 or vehicle was administered orally to model rats with uraemia and low turnover bone. Bone turnover was analysed by histomorphometry. Expression of osteoblast-related genes and oat-3 gene was analysed by reverse transcription polymerase chain reaction. RESULTS: In rats treated with vehicle, serum IS level increased with time after renal dysfunction, while bone formation decreased accompanied by down-regulation of the parathyroid/parathyroid-related peptide hormone receptor, alkaline phosphatase and osteocalcin genes. Administration of AST-120 inhibited the accumulation of IS in blood and ameliorated bone formation. Bone formation rate was 2.4 +/- 1.7 microm(3)/m(2)/year in controls given vehicle and was 11.7 +/- 2.4 microm(3)/m(2)/year in rats administered with AST-120 (P < 0.05). AST-120 treatment also reversed the down-regulation of osteoblast-related genes. Gene expression of oat-3 was detected in the tibia of rats. CONCLUSION: Administration of the oral charcoal adsorbent AST-120 decreases the osteoblast cytotoxicity of UTx including IS, and suppresses progression of low bone turnover in uraemic rats.
Administration, Oral↗