Outcome of bought living non-related donor kidneys followed up at a single centre.

Between October 1985 and November 1991, 16 dialysis patients travelled to Bombay and bought kidneys from living non-related Indian donors for U.S. $7,372. One patient died peri-operatively; one contracted HIV and another hepatitis B virus infections. Six patients are presently positive for hepatitis C virus antibody compared to two cadaver graft recipients (P = 0.03); two of the six patients have chronic active hepatitis. Five-year patient and graft survival rates (75% and 43%, respectively) were similar to those of recipients of 24 cadaver grafts obtained in the United States (67% and 55%, respectively), as was graft function during the first 5 years of follow-up. Graft survival may have improved following commercial kidney transplantation in Bombay, but this practise still poses a risk of dangerous infections and exploitation of donors and recipients. The establishment of a centralized programme of anonymous "rewarded gifting" in countries that cannot eradicate rampant organ commerce may help to expunge exploitation and to ensure uniform, acceptable clinical standards and the safety of patients.

High incidence of post-transplant diabetes mellitus in a single-centre study.

Twelve of 29 Saudi patients (41.4%) developed diabetes mellitus following renal transplantation. Post-transplant diabetes mellitus occurred within the first 2 months in eight patients; two others presented with diabetic ketoacidosis associated with severe infections. The diabetic and non-diabetic patients had received similar doses of prednisolone and cyclosporin (CsA) during the initial 2 months post-transplantation, and their mean CsA blood values at 3 months were not significantly different. Increasing patient age (over 40 years), but not sex, donor source, or body mass index, was associated with an increased risk for developing diabetes mellitus. Post-transplant diabetes mellitus was controlled with oral hypoglycaemic agents in most patients, but one-third required insulin. Patients who developed diabetes had significantly decreased mean creatinine clearance/1.73 m2 at a mean graft age of 3.4 years (P less than 0.001). Diabetes mellitus after transplantation may be more common among Saudi patients than elsewhere, especially those aged over 40 years. It develops rapidly, may present with ketosis, and is associated with graft dysfunction.

Untreated tuberculosis may be associated with lymphopoenia, not lymphocytosis.

Initial full blood counts were compared in 25 consecutive adult patients admitted with active tuberculosis and 25 matched, healthy controls and, if available, repeated at 6 and 12 months during treatment. Patients with tuberculosis had significant lymphopoenia associated with anaemia, neutrophil leucocytosis and monocytosis. None of these derangements correlated with radiological extent of lung disease or cutaneous tuberculin reactivity. Lymphocyte counts returned to normal within 2 weeks of initiating chemotherapy in all lymphopoenic patients and normal ranges for all blood counts were restored by 6 months in all the patients studied. In a smear-negative patient, a clinical diagnosis of tuberculosis would be supported by the finding of lymphopoenia, not lymphocytosis.

Paratyphoid fever presenting with renal failure and nephrotic syndrome.

A previously healthy 39-year-old woman had a short, febrile illness that culminated in severe, acute renal failure in association with features of the nephrotic syndrome. Salmonella paratyphi B was isolated from her blood and stool. Treatment with chloramphenicol, dialysis, heparin and steroids was followed by gradual but complete recovery. Paratyphoid is usually more benign than typhoid fever, but is not without danger and may be complicated by potentially fatal renal disease.

Successful peritoneal dialysis using 0.9% sodium chloride with modified M/6 sodium lactate solution and recycled catheters.

Acute peritoneal dialysis (PD) was carried out in 8 patients with renal failure (5 acute, 3 chronic) using 2.076-litre cycles of 0.9% sodium chloride (1,250 ml) plus M/6 sodium lactate (600 ml) to which 5% dextrose (170 ml), 50% dextrose (40 ml) and 10% calcium gluconate (16 ml) were added. Two acute catheters were recycled amongst all the patients after sterilisation in 5% formaldehyde. In all 8 patients, there was progressive clinical and biochemical improvement during 12-88 cycles of PD performed over 0.5-35 days. 2 patients with acute renal failure recovered completely. Another patient had prostatectomy for obstruction and a 4th subsequently received a successful kidney transplant abroad. 3 patients died, 2 of them after discharge from hospital, and 1 defaulted from follow-up. Peritonitis occurred in 2 patients. No side effects attributable to the dialysis solution were observed. However, repeated chemical treatment resulted in catheter opacification and blockage of perforations, but reperforation using a sterile needle usually restored good drainage. In poor countries with limited dialysis facilities, the use of 0.9% sodium chloride with modified M/6 sodium lactate solutions for PD and reuse of acute PD catheters are effective, safe and cost-saving.

Deaths from AIDS-like illnesses in west Africans.

PIP: 2 cases are reported from Nigeria of patients with illnesses compatible with a diagnosis of AIDS, but whose serum was HIV-negative. The 1st patient had Kaposi's sarcoma and cervical lymphadenopathy. The 2nd patient had lymph node tuberculosis and generalized lymphadenopathy. The 1st patient had had intramuscular injections for malaria at a local pharmacy, and the 2nd patient had received a blood transfusion after an appendectomy. They may have been infected with HIV-related but antigenically distinct retroviruses.^ieng

Immune status in tuberculosis and response to treatment.

Thirty hospitalized patients with newly diagnosed tuberculosis were studied prospectively with a range of in vitro and in vivo tests of immune function. Responses were compared with those of healthy controls matched for age, sex, ethnic group and diet. A series of metabolic and immunologic abnormalities was found, including evidence of undernutrition, anaemia, neutrophil leucocytosis, monocytosis, lymphopenia, hyperglobulinaemia and raised erythrocyte sedimentation rate. Some patients had accelerated, others diminished, cutaneous tuberculin hypersensitivity, and some had diminished mononuclear cell proliferative and lymphokine responses to tuberculin (purified protein derivative, PPD). The patients were not uniform in their responsiveness, but could be arranged within a spectrum which showed a relationship to crude bacillary excretion and response to treatment. 27% of patients were characterized by hypersensitivity, with normal in vitro cellular responses and skin tests to PPD, scanty bacillary excretion and rapid bacteriologic sputum conversion to negative cultures with treatment. In contrast, 30% of patients were relatively anergic with negative skin tests, reduced or absent in vitro cellular reactivity to PPD, moderate or heavy bacillary excretion and later (greater than 4 weeks) bacteriologic sputum conversion. The remainder of the patients fell between these two groups. There were no correlations between cellular immunity on the one hand, and radiological extent of disease, levels of serum immunoglobulins, peripheral white cell counts or ESR on the other. In those patients followed throughout treatment, all the abnormalities with the exceptions of arm muscle circumference and serum albumin, reverted to the normal ranges established in the control group.

Malnutrition among tuberculosis patients in Harrow, England.

Nutritional assessment was performed on 30 patients, aged 19-61 years, admitted to the Lister Unit of Northwick Park Hospital, Harrow, with active tuberculosis. Nutritional measurements were related to the duration and extent of disease, and also compared with those obtained in healthy age-, sex- and ethnic-matched controls before and during treatment of patients. Tuberculosis patients had significant reductions in body mass index (weight/height2) (P = 0.001), triceps skinfold thickness (P = 0.01), arm muscle circumference (P = 0.002), serum albumin (P less than 0.0001), iron (P less than 0.0001) and total iron binding capacity (P less than 0.001). Chemotherapy was associated with progressive nutritional recovery and restoration of nutrition-related indices. However, mean arm muscle circumference and serum albumin levels of the patients remained subnormal at 12 months, suggesting that body protein reserves may not be fully repleted during treatment. Active tuberculosis is associated with profound protein-energy undernutrition which improves during treatment. Further study is required to determine whether dietary protein supplementation may accelerate recovery from tuberculosis.

Fulminant hepatic failure in nephrotic syndrome related to withdrawal of immunosuppressive therapy.

Two patients with nephrotic syndrome developed fatal fulminant hepatitis B following withdrawal of prednisolone or cyclophosphamide. Immunosuppressive therapy probably enhanced hepatitis B virus (HBV) replication and widespread infection of hepatocytes; its withdrawal permitted a return of immune competence resulting in massive destruction of infected hepatocytes. Prior screening of all patients for hepatitis B surface antigen, gradual withdrawal of immunosuppressive drugs with careful monitoring, and prompt intervention with corticosteroids at the first clinical or biochemical signs of liver cell damage may prevent this complication.

Haemoglobinuric renal failure and typhoid fever.

Three patients with typhoid fever, initially misdiagnosed, developed intravascular haemolysis, disseminated intravascular coagulation, haemoglobinuria and acute renal failure. 2 of the patients were deficient in erythrocyte glucose-6-phosphate dehydrogenase; Plasmodium falciparum was present in the blood of the third. Among the indigenous population of endemic areas, typhoid fever is the likely diagnosis in any pyrexial illness associated with haemoglobinuric renal failure.

Measurement of aflatoxin in Nigerian sera by enzyme-linked immunosorbent assay.

Sera from 78 healthy men donating blood in Enugu, Nigeria were examined for aflatoxin by enzyme-linked immunosorbent assay (ELISA). Levels varied from less than 20 pg/ml to 3.1 ng/ml. The ELISA method is simple, sensitive and specific, and therefore well suited to the low-resource tropical environment. Aflatoxin is ingested in considerable amounts in Nigeria and many contribute, with hepatitis B, to the development of hepatocellular carcinoma.

Defective monocyte chemotactic responsiveness in patients with active tuberculosis.

Monocyte migration was studied in 15 patients with newly diagnosed tuberculosis and 17 healthy control subjects matched for age, sex and ethnic group, using a raft modification of the Boyden chamber. Compared with matched controls, patients with tuberculosis exhibited impaired in vitro monocyte random locomotion and directional locomotion (chemotaxis) in response to 2% casein. However, no correlation was found between in vitro monocyte migration and monocyte count, radiological extent of disease or in vitro dermal reactivity to tuberculin-PPD. The observed defects were corrected during the course of chemotherapy.

Reduced in vitro tuberculin reactivity of lymphocytes from patients with tuberculosis.

29 patients with newly diagnosed tuberculosis, and matched healthy controls, were studied on the basis of 3H-thymidine incorporation of peripheral blood mononuclear cells (PBMC) induced in vitro by staphylococcal enterotoxin A plus tetrahydrophorbyl acetate (SEA+TPA) or tuberculin purified protein derivative (PPD). PBMC from patients had normal SEA+TPA-induced, but depressed spontaneous (p less than 0.01) and PPD-induced (p less than 0.01) 3H-thymidine uptake. Their peak responses tended to occur later (p = 0.007) and with larger doses of the antigen (p = 0.02). The group of patients with low in vitro PBMC responses to PPD were not clinically distinguishable with respect to the extent of pulmonary tuberculosis, cutaneous reactivity to PPD, nutritional status, bacillary content of sputum or time to sputum sterilization during treatment. Evidence for a plasma factor blocking lymphocyte proliferation was not found in 15 patients tested. Chemotherapy was associated with restoration of normal PPD-induced 3H-thymidine uptake, concomitant with clinical improvement and recovery of nutritional abnormalities.

T4 lymphopenia in human tuberculosis.

Lymphocyte subpopulations in vitro in 13 patients with bacteriologically-proven tuberculosis and 12 matched controls, by immunofluorescence using monoclonal antibodies have been studied. Active tuberculosis was associated with significant reductions in absolute numbers of total T (Leu 4 or 1+), T4 (Leu 3a+) and B (Leu 12+) lymphocytes, but there were no significant differences in total T8 (Leu 2a+) counts. In two patients, T4-lymphopenia was sufficiently profound to cause reversal of T4: T8 ratio (less than 1.2). These changes were not related to the radiological extent of the disease or size of the Mantoux reaction. Normal ranges for the different classes of lymphocytes were readily restored by chemotherapy.

Tuberculin sensitivity in tuberculosis.

Seven of twenty-eight (25%) patients with untreated tuberculosis had skin induration of less than 6 mm to one tuberculin unit (TU), and 3 (11%) to 10 TU PPD. Among twenty-four patients with lung disease, there were no detectable differences in radiological extent of disease between reactors and non-reactors to low-dose tuberculin. However, non-reactors were significantly more malnourished (P less than 0.02), excreted more bacilli (P less than 0.02) and took longer for sputum sterilization during chemotherapy (P less than 0.01). Early skin reactions (6-8 h) occurred in fourteen of twenty-four (58%) patients, but in none of twenty-four matched healthy controls (P less than 0.0001); the proportions giving delayed (48-72 h) reactions were similar. Although the patients had larger delayed reactions as a group (P = 0.04), this would not have been of value in making the diagnosis. Repeat tuberculin testing of subjects had a booster effect, but did not induce hypersensitivity in initially healthy non-reactors. All nutritional abnoalities observed in the patients, except arm muscle circumference and serum albumin, reverted to normal during chemotherapy, concomitant with clinical improvement and an increase in dermal reactivity to tuberculin. Antigen overload may lead to both skin anergy and undernutrition. The accelerated tuberculin skin reaction could offer a practical and specific, although not particularly sensitive, method of aiding the diagnosis of active tuberculosis.

Acute respiratory distress related to chemotherapy of advanced pulmonary tuberculosis: a study of two cases and review of the literature.

Two patients with non-miliary pulmonary tuberculosis developed a syndrome resembling adult respiratory distress following initiation of drug treatment. They were studied clinically and with a representative range of in vitro and in vivo tests of immune function. Both were alcoholic, malnourished and presented with radiologically widespread, smear-positive disease and lymphocytopenia. One had cutaneous anergy in vivo and profound reduction on mononuclear cell proliferative and interferon responses to tuberculoprotein (PPD) in vitro; the other patient, who died two weeks after starting treatment, had relatively normal values for these measures of cell-mediated immunity. In both cases there was a progressive increase during treatment, in peripheral blood lymphocyte counts, skin reactions and in vitro cellular responses to PPD, and a sudden rise in ESR at the time of their deterioration. We propose that the reactions may represent local manifestations of heightened delayed hypersensitivity, mounted by increasing numbers of 'resuscitated' lymphocytes against immunogenic cell wall substances released from dying tubercle bacilli in patients whose level of cellular immunity is being enhanced as a result of chemotherapy. The likelihood of an acute respiratory reaction during treatment may therefore depend on the bacillary load, the extent of lung disease present, and its severity may be related to the pre-treatment immune status of the patient.

Tolerance of one-month intranasal interferon.

Under double-blind conditions, groups of volunteers (68 in total) were allocated at random to take intranasal solutions of placebo or one of three doses of highly purified leucocyte interferon by intranasal spray twice a day for 28 days. The highest dose would have been expected to protect against experimental colds. Treatment was discontinued because of upper respiratory symptoms as often in each of the interferon groups as in the placebo group. However, it was possible to distinguish clinically between "colds" on placebo and low-dose interferon and "reactions to treatment" on high-dose interferon. The features of the reactions to treatment were a protracted build-up of local symptoms and minor epistaxis. None of the volunteers on the high-dose interferon were thought to have a definite cold, but viruses were isolated from four out of six volunteers on low-dose interferon who had definite colds. Previous experiments had also shown this dose to be insufficient to protect against experimental rhinovirus challenge. The dose of interferon that appeared to protect against virus infection caused significant unwanted effects. It is essential to find interferon preparations with less inflammatory activity before interferon can be considered for use as a long-term prophylactic against the common cold.

Deficient immune interferon production in tuberculosis.

Production of interferon (IFN)-alpha and -gamma by peripheral blood mononuclear cells (PBMC) were studied in 28 patients with active tuberculosis and 28 healthy control subjects matched for age, sex, ethnic origin and diet. No significant differences were found between patients and matched controls in mean titres of IFN-alpha induced by Newcastle disease virus, IFN-gamma induced by staphylococcal enterotoxin A with tetrahydrophorbyl acetate, and IFN-gamma induced by purified protein derivative (PPD). However, a subset of nine out of 25 tuberculosis patients tested produced low titres (less than 100 u/ml) of IFN-gamma in response to PBMC stimulation with PPD. In comparison to other patients, this group was characterized by lower IFN-alpha and IFN-gamma responses to virus and mitogens respectively, relative anergy to tuberculin skin testing, depressed in vitro PBMC proliferative responses to PPD, and neutrophil leucocytosis. In all nine patients effective chemotherapy restored cutaneous reactivity, PBMC proliferative responses, neutrophil counts and IFN-alpha responses to virus by 6 months, and also IFN-gamma responses to PPD in one patient re-tested.

Natural killer cell activity in tuberculosis.

Natural killer (NK) cell activity was studied in 27 patients with active tuberculosis and 27 healthy controls matched for age, sex, ethnic origin and diet. Spontaneous and interferon (IFN)-augmented NK cytotoxicity against K562 target cells were measured, using a 4-hour 51Cr-release assay. There were no differences between the patients and their matched controls in mean spontaneous and IFN-augmented cytotoxicity before and during antituberculosis chemotherapy. However, one malnourished alcoholic patient with extensive non-reactive multibacillary disease had depressed NK cell activity which was not significantly enhanced by in vitro pretreatment with leucocyte IFN. We conclude that the NK system is not of prime importance in host defence against human tuberculosis, although advanced disease may be associated with deficient NK activity, as part of generalized anergy.