Experience with knee synovectomy in Norwich, 1964-1973

Thirty-six patients (43 knees) who underwent anterior synovectomy for rheumatoid disease between 1964 and 1973 have been personaly reviewed. The notes and X-rays of a further seven patients (10 knees) have been examined. Twenty-five per cent of the knees were failures at the time of review, but only two were failures from the outset. The indications for the operation and also the contraindications are described and evaluated. It is concluded that: 1. In the rheumatoid knee, anterior synovectomy is a pain relieving operation. 2. The indications are wider than classically stated, and can include knees with full thickness cartilage destruction, and flexion deformities up to 20 degrees. 3. The majority of knees fail because of secondary degenerative change, and this is manifested by pain rather than stiffness. 4. Postoperative manipulation does not prejudice the final result. 5. Associated popliteal cysts (five in this series) can be cured by anterior synovectomy.     

Early diagnosis of necrotizing enterocolitis

This study demonstrates that the diagnosis of necrotizing enterocolitis can sometimes be made before the full-blown clinical and radiographic findings are manifest. Of 12 infants with films available prior to diagnosis of the disease, nine had early selective dilatation of small bowel and little or no air in the colon. Necrotizing enterocolitis should be foremost in the differential diagnosis when this finding is coupled with signs such as abdominal distention, acidosis, and diarrhea.     

Increased nerve-growth-factor beta-chain cross-reacting material in familial dysautonomia

To determine whether dysautonomia arises from alteration in nerve-growth factor (NGF), we measured serum levels of NGF subunits in normal and dysautonomic subjects using a biologic assay based on neurite outgrowth from chick ganglions, a binding assay based on displacement of radiolabeled betaNGF from rabbit-ganglion microsomes, and radioimmunoassays of chi, gamma and betaNGF subunits via antiserum to mouse NGF polypeptides. A threefold increase (P less than 0.001) in serum antigen levels of the biologically active subunit (betaNGF) was found for dysautonomic as compared with normal subjects. By all other assays, the groups were alike. The marked discrepancy in betaNGF levels between antigenic and functional (biologic and binding) measurements suggests a qualitative abnormaltiy of betaNGF in dysautonomia. Alternatively, elevation of betaNGF antigen can be regarded as secondary to disease. This alternative seems less likely since we must then suppose that the normalcy of functional assays in spurious.     

Uterine pressure-flow relationships during early gestation

Placental and myoendometrial pressure-flow relationships were determined in 17 gravid ewes between 29 and 110 gestational days with the use of radioactive-labeled microsphere injections under flow meter guidance. Myoendometrial relationships were consistently curvilinear with convexity toward the flow axis. From 29 to 40 days, caruncular-cotyledonary relationships were similar to myoendometrial ones. After 50 days, the relationship was slightly but significantly curvilinear with convexity toward the pressure axis. From 42 to 50 days, responses were intermediate. The changes in caruncle-cotyledon vascular reactivity correlated with the onset and maturation of interdigitation of fetal and maternal tissues during definitive placentation. A hypothesis for these changes in vascular reactivity is presented.     

Further characterization of rat liver mitochondrial fractions. Lipid composition and synthesis, and protein profiles

Although large hemoglobin inclusions are observed in intraerythrocytic Babesia microti parasites, they are absent from parasites freed of hamster red cells by immune lysis with anti-hamster erythrocyte serum. Babesia microti has no cytostome. This parasite, therefore, does not appear to feed by phagocytosis of large boluses of hemoglobin, as does Plasmodium. To determine whether Babesia can pinocytose protein, free parasites were fed ferritin in an in vitro system. Ferritin was taken up from the entire cell surface into narrow channels within 15 min at 37 C. Only merozoites, with their pellicular complex, failed to take up the protein. By 60 min, the ferritin was highly concentrated in many channels and vesicles, which formed interconnecting stacks. The ferritin-containing channels became associated with membrane whorls of the multimembranous structure. Membrane whorls were also observed in the process of extrusion in samples incubated for longer times. These events may represent steps in the digestion and excretion of the pinocytosed protein. Empty channels formed when Babesia was fed albumin. The diaminobenzidine reaction for hemoprotein was positive for the channels in both free and intraerythrocytic babesias. The staining reaction was completely inhibited by cyanide, but not at all by aminotriazole. These results further suggest that Babesia pinocytoses hemoglobin in vivo. Plasmodium lophurae parasites freed of red cells by immune lysis are surrounded by 2 membranes and apparently can ingest ferritin only through the cytostome. Extracellular cytostomal feeding involves both membranes, as it does in vivo. Ferritin was found in food vacuoles, some of which contained hemoglobin ingested before parasite isolation, connected to or near the cytostome. In both Plasmodium and Babesia low temperature inhibited ferritin uptake.     

Hepatic uptake and biliary excretion of d-tubocurarine and trimethyltubocurarine in the rat in vivo and in isolated perfused rat livers

The clearance from perfusion medium and the biliary excretion of d-tubocurarine (d-TC) and trimethyltubocurarine (tMeTC) was studied in isolated perfused rat livers. Despite the related structure, d-TC exhibited considerably higher lipophilicity and plasma protein binding than its trimethyl derivative. Significant differences in hepatic disposition of the two agents were found. The clearance constant of elimination from the perfusate for d-TC was 2.00 and 0.41 ml/min for tMeTC. Fifty-one percent of the administered d-TC was excreted in the bile during 2 hours of perfusion. For tMeTC this amounted to only 16%. Bile/plasma concentration ratios of d-TC were 10 times those of tMeTC. There was no evidence for biotransformation of the substances. The unequal biliary output cannot be explained by differences in subcellular distribution. After injection into rats in vivo, the major part of drug in the liver is confined to the particulate fractions. Subfractionation studies indicate binding to lysosomes. The hepatocyte cytosol concentrations of d-TC and tMeTC are in the same order and are lower than the concomitant plasma concentrations. Both bile/liver and liver/plasms concentration ratios were higher for d-TC. The results support the idea that the balance of hydrophilic and hydrophobic properties is an important factor determining hepatic transport of organic compounds.     

Renal failure after open heart surgery

One hundred fifty of 490 patients undergoing open heart surgery had renal failure attributable to cardiopulmonary bypass. In 69, serum creatinine concentrations did not exceed 2 mg/dl and returned to normal by the fourth postoperative day. In 60 patients, serum creatinine attained levels between 2 and 5 mg/dl, oliguria did not develop, and recovery of renal function occurred within 4 to 37 days. Serum creatinine increased to levels exceeding 5 mg/dl in 21 patients, 11 of whom were oliguric. Despite dialysis, 14 of these patients died from cardiac causes or sepsis. Prolonged cardiopulmonary bypass time, hypotension, oliguria, low output syndrome, and hemoglobinemia during open heart surgery correlated with the development of renal failure postoperatively. Although severe renal failure was an uncommon complication after open heart surgery, its occurrence carried a grave prognosis.     

The cofactors required by C3 nephritic factor to generate a C3 convertase in vitro

The mechanisms by which a C3 convertase is generated by C3 nephritic factor (NeF) were investigated using purified NeF, C3, C3b, factor B and factor D of the alternative pathway of complement activation. NeF could generate a C3 convertase with C3 and B in the absence of D, and without cleavage of B. At lower concentrations of NeF the addition of D was required to generate a C3 convertase, and B cleavage now occurred. The generation of both the D-independent and D-dependent C3 convertases with NeF was inhibited by preincubation of the C3 source with C3b inactivator (KAF); isolated C3b was more efficient than the C3 preparations used in generating the D-independent C3 convertase with NeF. These experiments indicate that C3b is required for the formation of both convertases, and that the reaction occurring with apparently native C3 is due to trace amounts of C3b. It is concluded that the C3 convertase generated by NeF in the absence of D is C3bB (NeF), and that generated in the presence of D is the feedback convertase C3bBb. The relevance of these experiments to reactions which may occur in vivo is discussed.     

The Case for Fairness of Trust Management

All trust management systems must take into account the possibility of error: of misplaced trust. Therefore, regardless of whether it uses reputation or not, is centralized or distributed, a trust management system must be evaluated with consideration for the consequences of misplaced or abused trust. Thus, the issue of fairness has always been implicitly considered in the design and evaluation of trust management systems. This paper attempts to show that an implicit consideration, using the utilitarian paradigm of maximizing the sum of agents' utilities, is insufficient. Two case studies presented in the paper concern the design of a new reputation systems that uses implicit and emphasized negative feedbacks, and the evaluation of reputation systems' robustness to discrimination. The case studies demonstrate that considering fairness explicitly leads to different trust management system design and evaluation. Trust management systems can realize a goal of system fairness, identified with distributional fairness of agents' utilities. The realization of this goal can be achieved in a laboratory setting when all other factors that affect utilities can be excluded, and where the system can be tested using modeled adversaries. Taking the fairness of agent behavior explicitly into account when building trust or distrust can help to realize the goal of fairness of trust management systems.