Campath IH allows low-dose cyclosporine monotherapy in 31 cadaveric renal allograft recipients

BACKGROUND: Campath 1H is a depleting, humanized anti-CD52 monoclonal antibody that has now been used in 31 renal allograft recipients. The results have been very encouraging and are presented herein. METHODS: Campath 1H was administered, intravenously, in a dose of 20 mg, on day 0 and day 1 after renal transplant. Low-dose cyclosporine (Neoral) was then initiated at 72 hr after transplant. These patients were maintained on low-dose monotherapy with cyclosporine. RESULTS: At present, the mean follow-up is 21 months (range: 15-28 months). All but one patient are alive and 29 have intact functioning grafts. There have been six separate episodes of steroid-responsive rejection. One patient has had a recurrence of her original disease. Two patients have suffered from opportunistic infections, which responded to therapy. One patient has died secondary to ischemic cardiac failure. CONCLUSIONS: Campath 1H has resulted in acceptable outcomes in this group of renal allograft recipients. This novel therapy is of equal efficacy compared to conventional triple therapy, but allows the patient to be steroid-free and to be maintained on very-low-dose immunosuppressive monotherapy.     

Anti-inflammatory activity of c(ILDV-NH(CH2)5CO), a novel, selective, cyclic peptide inhibitor of VLA-4-mediated cell adhesion.

1. Small, N- to C-terminal cyclized peptides containing the leucyl-aspartyl-valine (LDV) motif from fibronectin connecting segment-1 (CS-1) have been investigated for their effects on the adhesion of human T-lymphoblastic leukaemia cells (MOLT-4) to human plasma fibronectin in vitro mediated by the integrin Very Late Antigen (VLA)-4 (alpha4beta1, CD49d/CD29). 2. Cyclo(-isoleucyl-leucyl-aspartyl-valyl-aminohexanoyl-) (c(ILDV-NH(CH2)5CO)) was approximately 5 fold more potent (IC50 3.6+/-0.44 microM) than the 25-amino acid linear CS-1 peptide. Cyclic peptides containing two more or one less methylene groups had similar potency to c(ILDV-NH(CH2)5CO) while a compound containing three less methylene groups, c(ILDV-NH(CH2)2CO), was inactive at 100 microM. 3. c(ILDV-NH(CH2)5CO) had little effect on cell adhesion mediated by two other integrins, VLA-5 (alpha5,beta1, CD49e/CD29) (K562 cell adhesion to fibronectin) or Leukocyte Function Associated molecule-1 (LFA-1, alphabeta2, CD11a/CD18) (U937 cell adhesion to Chinese hamster ovary cells transfected with intercellular adhesion molecule-1) at concentrations up to 300 microM. 4. c(ILDV-NH(CH2)5CO) inhibited ovalbumin delayed-type hypersensitivity or oxazolone contact hypersensitivity in Balb/c mice when dosed continuously from subcutaneous osmotic mini-pumps (0.1-10 mg kg(-1) day(-1)). Maximum inhibition (approximately 40%) was similar to that caused by the monoclonal antibody PS/2 (7.5 mg kg(-1) i.v.) directed against the alpha4 integrin subunit. 5. c(ILDV-NH(CH2)5CO) also inhibited oxazolone contact hypersensitivity when dosed intravenously 20 h after oxazolone challenge (1-10 mg kg(-1)). Ear swelling was reduced at 3 h and 4 h but not at 1 h and 2 h post-dose (10 mg kg(-1)). 6. Small molecule VLA-4 inhibitors derived from c(ILDV-NH(CH2)5CO) may be useful as anti-inflammatory agents.     

High resolution CT of the lungs in acute disseminated tuberculosis and a pediatric radiology perspective of the term “miliary”

High resolution CT (HRCT) of the lungs in six children with acute disseminated tuberculosis was evaluated. There was a wide variation in the HRCT appearances. This covered differences in size, distribution and concentration of nodular opacities. Coalescence of nodules and the presence of intestitial thickening was variable. The recognition of acute disseminated tuberculosis is important for diagnosis and has prognostic implications. The use of the term acute disseminated tuberculosis rather than miliary tuberculosis is advocated.     

Rapid diagnosis of glucocorticoid suppressible hyperaldosteronism in infants and adolescents

Glucocorticoid suppressible hyperaldosteronism (GSH) is an uncommon form of dominantly inherited hypertension. Presentation with hypertension and complications such as stroke in early life are well recognised. The use of a simple genetic test carried out on blood or placenta facilitates the detection of infants and children with GSH before the development of hypertension, allowing prompt treatment of hypertension if it occurs, and an opportunity to study the effects of growth and environmental influences on the progression of the condition.     

THE ACTION OF DIGITALIS IN PNEUMONIA

We have shown in a series of 105 cases of pneumonia, 95 of which we have selected as available for statistical study, that digitalis given by mouth has an action on the heart. We have judged this action to be present because changes occurred in the auriculoventricular conduction time and in the form of the T wave of the electrocardiogram, just as they do in the non-febrile heart. This conclusion is strengthened by finding that the pulse rate in fibrillating and fluttering cases fell in the presence of fever, exactly as it does in non-febrile cases. The dose and the time required to produce these effects are given and are the same as in the non-febrile cases. When there was a difference in the amount necessary to produce one or the other of the changes, it was found that the T wave is more often and more readily affected than the conduction interval. We have shown that the intoxication due to pneumonia is probably not responsible for the changes found, both from a study of the statistics and because in the control cases reverse tendencies were often found (that is, decrease in conduction time and increase in the size of the T wave). We have shown that the method of selection in consequence of which we treated a large number of severe cases did not prejudice our results, because it could be demonstrated that the proximity of death, whether in control or treated cases, was not necessarily associated with the changes we are describing. We have also, by referring to the literature of the subject, brought evidence to show that heart muscle does not undergo those changes in pneumonia, as it does in other infectious diseases, which would lead one to expect changes in conduction found in other diseases. The changes in conduction which have been reported by others were almost entirely associated with the giving of digitalis.     

Peripancreatic Fat Invasion Is an Independent Predictor of Poor Outcome Following Pancreaticoduodenectomy for Pancreatic Ductal Adenocarcinoma

Background  

Following pancreaticoduodenectomy for pancreatic ductal adenocarcinoma (PDAC), identification of peripancreatic fat tumor invasion promotes a tumor to stage T3. We sought to understand better the impact of histological peripancreatic fat invasion on prognosis and site of recurrence in a cohort of patients with PDAC.