Graeme Catto

Death during the first 90 days of dialysis: A case control study☆

Comparison of survival data among centers may be used to assess performance, but may be influenced by the number of patients who die during the first 90 days of renal replacement therapy (RRT). Data published by registries in Europe do not detail these deaths, and US data generally exclude them from analysis for financial reasons. To study factors influencing such deaths we compared 42 patients who died within 90 days of first commencing RRT in one Scottish renal unit (group A) between 1971 and 1992 with 42 age- and sex-matched controls who started RRT over the same period and survived longer (group B). Patients who died within 90 days of RRT ranged in age from 25.3 to 83.7 years and had a mean age of 65.2 (SEM, 1.6; 95% confidence interval, 61.9 to 68.4). The proportion of patients who died during the first 90 days of RRT increased from 2% of all patients treated before 1981 to 12% in subsequent years. Thirty-three patients in group A received emergency dialysis via temporary venous access compared with only nine in group B (P < 0.055). There were more patients in group A with a diagnosis of arteriosclerotic renal artery stenosis (14 v 1) and with a history of smoking (15 v 2) than in group B (P < 0.0005). Median renal or nonrenal follow-up before RRT was 1.1 month in group A and 10.6 months in group B (P < 0.0001). Fewer patients in group A had no coexisting disease (1 v 17; P < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Membranous nephropathy and granulomatous interstitial nephritis in sarcoidosis.

A 56-year-old woman developed nephrotic syndrome in association with pulmonary sarcoidosis. Renal biopsy revealed both granulomatous interstitial nephritis and membranous nephropathy. Treatment with steroids resulted in a decrease in proteinuria and there was no deterioration in renal function over a subsequent period of 10 months. This case provides further evidence that secondary membranous nephropathy associated with sarcoidosis should be treated with steroids.

Diagnostic value of urinary N-acetyl-β-d-glucosaminidase, its isoenzymes and the fractional excretion of sodium following renal transplantation

Daily total urine N-acetyl-beta-D-glucosaminidase activity, isoenzyme profile and fractional excretion of sodium were measured in 13 consecutive renal transplant patients. Rejection episodes were clinically diagnosed in 12 patients, 11 of whom (92%) showed an increased enzymuria either before or during the onset of clinical signs. The ratio of the two major isoenzymes (A/B) fell during 10 episodes (83%) and in six of these (50%) increased levels of the minor isoenzyme forms were observed. Increased fractional excretion of sodium was associated with nine (75%) of the episodes. Increased fractional excretion of sodium with a raised total enzymuria accompanied by a reduced A/B ratio and an increased proportion of the minor isoenzyme forms occurred in eight (67%) of the rejection episodes. The use of these measurements in the diagnosis of episodes of acute rejection in renal transplantation is discussed.

Noncytotoxic antibodies to paternal antigens in maternal sera and placental eluates.

Noncytotoxic antibodies were detected in sera from 6 of 7 primigravid women during the first trimester of pregnancy. Such antibodies directed to antigens expressed on paternal B lymphocytes were detectable within the first 4–5 weeks of gestation. Antibody activity toward paternal B lymphocytes was also detected in 6 of 10 placental eluates, and in 3 of 10 predelivery and 2 of 10 postdelivery maternal serum samples. When B lymphocytes from umbilical cord blood were used as target cells, antibodies were detected in 5 of 7 placental eluates, and in 3 of 7 predelivery and 2 of 7 postdelivery serum samples. These antibodies also reacted with selected members of a normal B lymphocyte panel. The concept of an immunological enhancing mechanism in normal pregnancy is supported by these data.

Richter's hernia: an unrecognised complication of chronic ambulatory peritoneal dialysis.

returning to work after a holiday in England he was repatriated severely ill. He had had a progressive dry cough, drowsiness, anorexia, weight loss, and recurring fevers. Examination showed drowsiness and confusion, tachypnoea, tachycardia, and fever of 40°C. Apart from mild oral candidiasis examination showed no abnormality and there was no lymphadenopathy or splenomegaly. He underwent full investigations with negative results apart from a mild leucopenia (white cell count 3-8 x 109/1 with 93 % neutrophils, 7 %/o lymphocytes). Chest radiography showed slight diffuse upper-zone infiltration. Immunoglobulin and immune complex concentrations, T-cell assays, and repeated marrow biopsy specimens were all normal. Appearances at fibreoptic bronchoscopy were normal, but transbronchial biopsy disclosed cysts of P carinii. He was treated with co-trimoxazole without therapeutic response and on the 12th day developed profound pancytopenia necessitating a change to pentamidine. Again there was no response and he gradually deteriorated and died a week later. At necropsy there was confluent consolidation of the left lung and patchy consolidation in all the lobes of the right. The reticuloendothelial system was normal macroscopically, with no enlargement of glands or the spleen. Microscopy confirmed P carinii to be the infective agent in the lungs, and examination of the spleen and lymph nodes showed a histiocytic medullary reticulosis.

Maternal alloantibody responses during early pregnancy detected by a cellular enzyme-linked immunospecific assay

Using a cellular enzyme-linked immunospecific assay (CELISA), we have examined sera from nulliparous women and women in the first trimester of a first or subsequent pregnancy for the presence of antibodies directed to surface determinants on peripheral blood lymphocytes from unrelated donors. Maternal antibody activity was found in sera from 1/13 nulliparae, 19/37 primigravidae, and 8/12 multigravidae. Cytotoxic antibody activity was present in 3/12 multigravidae but in no other group. Absorption with packed, pooled platelets did not remove the antibody activity from three of the primigravid sera; unabsorbed sera, however, bound equally well to T and B lymphocytes. These data suggest that the antibody detected by CELISA is not directed to any of the classical HLA antigen series (-A, -B, -C, or -DR) but may be directed to the HLA linked non-class I HT antigen system.

Interface between university and medical school: the way ahead?

Editorial by Goldbeck-Wood Education and debate pp 630, 636 In the midst of the very public debate on health, the interface between university and medical school remains largely hidden. It is, however, an important influence not only on academic activity and resources but increasingly on commercial interests. The changing roles and responsibilities of medical schools affect many aspects of health, education, and regional development. The ways in which medical schools respond to different challenges should be understood if there is to be agreement on the opportunities and threats facing modern medical education. #### Summary points Medical education comprises a decreasing proportion of the workload of medical schools Medical schools have close links with the health departments, but links with the funding councils and departments of education may be less robust, and funding streams are complex and poorly understood Research interests of medical schools and their parent university may take precedence over teaching commitments and clinical duties Curricular reform has been stimulated by the General Medical Council since graduation is linked to provisional GMC registration, and the public and profession must agree on standards expected at graduation We all know what they are, but a succinct definition is now elusive. Of course, a medical school educates undergraduate medical students, but that role is decreasing as medical education moves with patients to the community and primary care. Indeed, colleagues in the NHS now undertake at least 70% of the clinical teaching and increasingly participate in planning the curriculum and assessment. Given the considerable diversity of arrangements adopted by different universities, the only other features medical schools have in common are a robust research base, clinical academic staff, and public interest. Many have substantial numbers of undergraduate and postgraduate students in disciplines other than medicine. A medical school is an integral part of its parent …

Drug Hypersensitivity Causing Granulomatous Interstitial Nephritis

In association with treatment for pharyngitis, a 47-year-old white man developed a systemic illness with fever, myalgia, episcleritis, hemoptysis, pleurisy, eosinophilia, and renal impairment. Renal biopsy revealed granulomatous interstitial nephritis, which resolved due to no specific treatment other than withdrawing all medication. Both the severe systemic manifestations and spontaneous recovery are unusual in association with drug-induced granulomatous nephritis. The drugs that may have caused the reaction included dihydrocodeine, phenylpropanolamine, erythromycin, and amoxycillin. Although the latter three drugs have been previously implicated in the development of interstitial nephritis, there have been no previous reports of granulomatous interstitial nephritis with any of these drugs.

The effects of rapamycin on humoral immunity in vivo : suppression of primary responses but not of ongoing alloantibody synthesis or memory responses

The effect of rapamycin on primary and secondary alloantibody responses to major histocompatibility complex class I antigens was investigated in inbred rat strains. Primary anti—MHC class I alloantibody responses, detected by indirect hemagglutination and complement-dependent cytotoxicity assays, were abrogated in high-responder WAG (RT1U) recipients of DA (RTla) blood transfusions, given on days 0 and 7 of a 14-day course of rapamycin (3 mg/kg/day). Antibody class studies showed that both IgM and IgG responses were equally effectively inhibited. Moreover, when these animals were rechallenged with DA transfusions, 28 days after drug withdrawal, they exhibited donor-specific humoral unresponsiveness. Similar results were observed in cyclosporine-treated rats. In preimmunized high-responder LEW (RTl1) rats with high titer anti-DA class I alloantibodies, a 35-day course of rapamycin (3 mg/kg/day) had no significant suppressive effect on serum alloantibody levels when compared with untreated preimmunized control animals. WAG rats were immunized by DA transfusions and serum antibody levels then allowed to decay over 16 weeks. The animals were then challenged with a further DA transfusion given on the second day of a 14-day course of rapamycin (3 mg/kg/day). Alloantibody responses to the challenge transfusion in this group were not, however, significantly suppressed when compared with a non-drug-treated control group. The results of this study indicate that rapamycin is a potent inhibitor of primary alloantibody synthesis in high-responder rat strains, but does not significantly

FK506--its influence on anti-class 1 MHC alloantibody responses to blood transfusions.

The influence of FK506 on in vivo alloantibody responses to major histocompatability class 1 antigens was investigated in inbred rat strains, and compared with the effect of cyclosporine. AO rats received transfusions of DA blood on days 0 and 7. From days 0 to 14 the rats also received, daily, either FK506 0.3 mg/kg suspended in saline or dissolved in olive oil, or CsA 10 mg/kg. The administration of FK506 suspended in saline at the time of blood transfusion completely abrogated the development of anti-MHC class 1 alloantibodies as detected by indirect hemagglutination (IHA)* and 51Cr release complement dependent cytotoxicity assays (CDC). Isotyping studies showed that FK506 suspended in saline suppressed IgM production and inhibited the switch to IgG production. Similar responses were seen in CsA-treated animals. In contrast, rats treated with FK506 dissolved in olive oil developed high titers of anti-class 1 alloantibodies. On days 49 and 56 the rats were challenged with further DA blood transfusions given without immunosuppression. In the groups given FK506 suspended in saline or CsA, cytotoxic antibodies did not develop; low titer antibodies were, however, detected by IHA in the animals that had previously received FK506 suspended in saline. The results indicate that FK506, in common with CsA, inhibits anti-class 1 MHC alloantibody production, and at the same time enables the development of tolerance. The vehicle in which FK506 is administered is, however, critical to its efficacy at the low doses used. These results may be of relevance to clinical transplantation as similar antibodies mediate hyperacute renal allograft rejection in man.