Small bowel transplantation in the rat: impact of various immunosuppressive regimens on graft-versus-host reaction.

The effect of ciclosporin (CS) and methotrexate (MTX) on the development of graft-versus-host (GvH) disease was examined after small bowel allotransplantation in the rat. The drugs were tested either alone or in combination. Lewis small bowel allografts were transplantated into Brown Norway recipients in a heterotopic position. The native small bowel, spleen, liver, skin, mesenteric lymph nodes and the kidney of the recipients were examined histologically 5, 10 and 20 days after allotransplantation. Intraepithelial lymphocyte numbers were determined quantitatively in the native small bowel. The relative spleen weight of the host was determined after sacrifice for estimation of the severity of GvH disease. Grade I GvH reaction of the native small bowel occurred in the animals without immunosuppression, but graft rejection predominated in this group. Treatment with CS was effective in the early postoperative periods; after 10 and 20 days GvH lesions in the native small bowel were comparable to those observed in the allogeneic combinations. MTX had a detrimental effect on the allografts and the GvH reaction was augmented. When CS and MTX were combined, GvH lesions were comparable to those in the animals treated solely with CS. Animals, however, suffered from heavy side effects. The spleen, liver, lymph nodes and kidney exhibited only unspecific histologic changes, which could not unequivocally be recognized as a GvH reaction. This was true for all groups. As a conclusion it can be said that GvH reaction occurs in the early postoperative period in a fully allogeneic model and cannot be prevented by CS in the dosae used. MTX was not seen to be of any value in this regard.     

Nitric oxide synthesis in the in vivo allograft response: a possible regulatory mechanism.

Activated macrophages are known to oxidatively metabolize L-arginine to nitric oxide and citrulline. We have recently shown that nitric oxide is a potent inhibitory molecule in the in vitro rat mixed-splenocyte culture, resulting in inhibition of proliferation and cytolytic T-cell induction. We undertook this study using the sponge matrix allograft model in the rat to determine whether nitric oxide plays a role in an in vivo allograft response. Our experiments showed that on day 6 after grafting, when cytolytic activity of allograft-infiltrating cells is first detected, allogeneic graft fluid contains higher levels of NO2-/NO3- (the stable endproducts of nitric oxide metabolism) than syngeneic graft fluid. Furthermore, evaluation of the supernatants of cultured graft-infiltrating cells revealed that allogeneic graft-infiltrating cells spontaneously produce higher amounts of nitric oxide than syngeneic graft-infiltrating cells. The nitric oxide production was inhibited in the presence of NG-monomethyl-L-arginine (NMA), the competitive inhibitor of nitric oxide production. Most of the nitric oxide production was observed in the adherent macrophage fraction of the allograft-infiltrating cells. When allograft-infiltrating cells were cultured in the presence of NMA, donor-specific cytolytic activity was observed, whereas allograft-infiltrating cells cultured in the absence of NMA showed no cytolytic activity. These data show that nitric oxide production may play an important regulatory role in the allograft response.     

The prediction of outcome in schizophrenia. IV: Eleven-year follow-up of the Washington IPSS cohort

Two- and five-year follow-up observations of the International Pilot Study of Schizophrenia's Washington cohort provided data bearing on several controversial issues regarding the course of schizophrenia. Forty schizophrenic patients have now been observed 11 years after their index admission. Social, occupational, hospital utilization, and symptom areas of functioning continue to be only modestly correlated with one another and do not become increasingly uniform over time. Initial prognostic variables continue to be more predictive of long-term outcome than are cross-sectional symptom manifestations. Restricted affect at the initial evaluation had been a predictor of 5-year outcome, but it was not a significant predictor of outcome at 11 years. While serious long-term consequences of illness are observed, the follow-up data suggest that the illness tends to reach a plateau of psychopathology early in the course, with as many patients tending to improve in the long-term as those who tend to show further deterioration.     

Efficacy of cefcanel on staphylocci

The minimum inhibitory concentration (MIC) of cefcanel, a new oral cephalosporin, has been tested against 153 staphylococci subdivided into the species Staphylococcus aureus. S. epidermidis sensu lato and S. saprophyticus, with and without beta-lactamase production. The concentration inhibiting 50% of the strains was 0.5 mg/l for all three species while the corresponding values for 90% of the strains were 1, 2 and 1 mg/l, respectively. These values apply to all the strains. The MICs of the non-beta-lactamase-producing strains were identical to the MICs of the beta-lactamase-producing strains for S. aureus, three twofold steps lower for S. epidermidis and one step higher for S. saprophyticus. Consequently, beta-lactamase production had no consistent consequences for the activity of cefcanel against S. aureus and S. saprophyticus. In contrast, the beta-lactamase production of S. epidermidis did influence the activity of cefcanel. Among the tested cephalosporins, cefcanel had the highest antistaphylococcal activity, and no strain was resistant to this new cephalosporin.     

The effect of cephalothin prophylaxis on postoperative ventriculoperitoneal shunt infections.

Postoperative infection is an important complication after insertion of a ventriculoperitoneal (VP) shunt in children with hydrocephalus. A randomized double-blind placebo-controlled study was performed to determine the efficacy of cephalothin in preventing postoperative shunt infection. Sixty-three children who presented for elective VP shunt insertion between January 1982 and December 1985 and who did not have a history of shunt infections were randomly assigned to receive four doses of prophylactic cephalothin, 25 mg/kg (32 patients), or of a multivitamin placebo (31 patients). Postoperative infection developed in 6% of the treatment group, compared with 10% of the placebo group, a difference that was not statistically significant, although a clinical significance may have been masked by the small sample size. A large multicentre trial is needed to determine the efficacy of antibiotic prophylaxis in reducing the incidence of postoperative VP shunt infections.     

Acute effects of nitroglycerin on the energetics of the human left ventricular myocardium

We analyzed performance and efficiency of the left ventricular myocardium on the basis of two new energetic parameters. The myocardial energy consumed during one cardiac cycle is related to performed work on the one hand (E1) and to the stress-time-integral on the other (E2). E1 was obtained by analysis of the pressure-volume integral divided by left ventricular muscle mass. E2 was obtained as follows: the stress-time integral was analyzed from pressure-volume data and wall thickness using an ellipsoidal calculation model. In order to transfer the stress-time integral into energy units, the value was multiplied by a constant factor which was obtained in experimental myothermal studies. In ten patients with coronary heart disease undergoing diagnostic heart catheterization, angiocardiography was performed before and after oral administration of nitroglycerin (1.6 mg). Total energy consumption (2E1 + E2) per gram myocardium per beat decreased from 6.1 +/- 1.3 mcal/g to 4.7 +/- 1.4 mcal/g (P less than 0.01), and myocardial efficiency (E1/[2E1 + E2]) increased from 27.0 +/- 3.1% to 28.4 +/- 4.3% (N.S.) on the average. This analysis explains quantitatively the beneficial effect of nitro-preparations on myocardial function and energetics.     

A primary lung carcinoma producing alpha-fetoprotein, carcinoembryonic antigen, and human chorionic gonadotropin. Immunohistochemical and biochemical studies

This article documents a patient with lung carcinoma that produced three oncofetal antigens including alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), and human chorionic gonadotropin (hCG). Serum AFP, CEA, and hCG-beta-subunit were extremely high--118,000 ng/ml, 133 ng/ml and 0.9 ng/ml, respectively. Immunohistochemical staining of these tumor markers revealed that these proteins were present in different cells. The pattern of lectin affinity electrophoresis of AFP resembled that of hepatocellular carcinoma. Also investigated was the reactivity of serum CEA to monoclonal antibodies against peptide or sugar moieties. Serum CEA values measured by antipeptide monoclonal antibodies were higher than those measured by antisugar monoclonal antibodies. The demonstration of AFP, CEA, and hCG in different tumor cells suggests that three genomes were not reactivated together in a cell, and the lung carcinoma probably consisted of at least three clones of cancer cells with different phenotypes.