Diarrhea in liver transplant recipients: etiology and management.

Diarrhea is common after liver transplantation (LT). The true incidence of diarrhea in liver transplant recipients is unknown but possibly ranges from 10% to 43% based on a few published studies in other solid organ and bone marrow transplantation. Infectious etiologies, including cytomegalovirus (CMV), Clostridium difficile, and occasional atypical intestinal infections, are the most common causes. Diarrhea is also a frequent side effect of immunosuppressive medications. To variable extents, mycophenolate mofetil (MMF), cyclosporine A (CSA), tacrolimus, and sirolimus are all known to be associated with diarrhea. Rarely, graft-versus-host disease (GVHD), lymphoproliferative disorder, de novo inflammatory bowel disease (IBD), or colon cancer may present as diarrhea. Flare-up of preexisting IBD is also not uncommon after LT. However, the cause of acute diarrhea remains unidentified in 1 of 3 patients. This review summarizes the literature and provides recommendations on the management of acute diarrhea after LT. Although our focus is on LT, the etiology and management recommendations apply to most transplant recipients.     

King syndrome: a genetically heterogenous phenotype due to congenital myopathies.

We report on a patient with myopathy, kyphoscoliosis, joint contractures, and a facial appearance consistent with King syndrome. Unlike other reported cases, our patient had hyperextensible joints, normal stature, and pectus excavatum. The cardiac ventricles, aorta, and pulmonary artery were dilated. Malignant hyperthermia did not occur under anaesthesia although there was a transient increase in CK levels. Muscle bulk and tone were significantly decreased but collagen and elastin fibres were normal. The variable clinical presentation of King syndrome suggests that the manifestations are caused by different congenital myopathies and in all cases there is probably an increased risk of malignant hyperthermia.     

Polyl-histidine

Poly-l-histidine (PHSTD) of molecular weight 26,000 induced the generation of large amounts of Superoxide (O ₂ ^– ) and hydrogen peroxide (H₂O₂) in human neutrophils (PMNs). Despite its low solubility at neutral pH, PHSTD was bound very rapidly to the PMN surfaces. Maximal generation of O ₂ ^– took place with 4–5 ×10^–6 M of PHSTD, starting after a lag of about 25 sec and proceeding for 15–17 min at a rate of 150 nmol/10⁷ PMNs/min, suggesting that this polycation is one of the most potent stimulators of O ₂ ^– generation known, PHSTD was found to be non-toxic for PMNs even at millimolar concentrations. Generation of O ₂ ^– by PHSTD depended on extracellular calcium; it was inhibited by calcium channel blockers and by trifluoperazine, and it triggered a sharp rise in intracellular calcium as determined by the Quin 2 fluorescence technique. The generation of both O ₂ ^– and H₂O₂ by PHSTD was partially inhibited by cytochalasin B or (CYB, CYE). On the other hand, CYB markedly enhanced the generation of both O ₂ ^– and H₂O₂ following stimulation of PMNs either by PHSTD, polyarginine, histone, or by antibody-opsonized group A streptococci. Electron microscopic analysis and NBT reduction tests revealed that both PHSTD and PHSTD-opsonized streptococci were avidly phagocytosed by PMNs. Since CYB totally inhibited internalization of both PHSTD and the PHSTD-opsonized streptococci, it was suggested that these agents stimulated oxygen radical generation mainly on the leukocyte surfaces. Complexes (CX) formed between PHSTD and polyanethole sulfonate (a strong polyanion) or between histone and the polyanion mimicked immune CX in their ability to trigger the generation of large amounts of O ₂ ^– which were inhibited by CYB. Generation of O ₂ ^– and chemiluminescence either by PHSTD or by PHSTD-opsonized streptococci were markedly inhibited by poly-l-glutamate, suggesting that PHSTD acted as a cationic agent which interacted via electrostatic forces with some negatively charged sites in the leukocyte membrane. Generation of H₂O₂ by PHSTD was also markedly inhibited by deoxyglucose, KCN, DASA, as well as by the lipoxygenase inhibitors nordihydroguaiaretic acid, phenidone, and propylgallate. On the other hand, cyclooxygenase inhibitors such as aspirin, indomethacin, and piroxicam were inactive, suggesting that arachidonic acid metabolism via lipoxygenase pathway might have been involved in the activation by PHSTD of the NADPH oxidase in PMNs. PHSTD may mimic the effects of antibodies both as an opsonin and as a potent stimulator of the respiratory burst in PMNs and may thus serve as a model for further study of leukocyte-bacteria interactions in infectious and inflammatory sites and of the pathogenicity of immune complexes.Supported by a research grant from Dr. S. M. Robbins of Cleveland, Ohio.