Gene/Protein Disease Symptom Drug Enzyme Compound
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Seventy-two and 34 consecutive HLA-identical sibling renal transplant recipients were treated with azathioprine/prednisone (AZA; follow-up, 5.0 years) and cyclosporine/prednisone (CSA; mean follow-up, 2.9 years), respectively. Both groups were similar in age, sex, race, and number of transplants, but there were more diabetics in the CSA group (34% v 8%). Actual patient survival at 1 year and actuarial patient survival at 5 years were 100% and 96%, respectively in the CSA group compared with an actual patient survival of 91% and 82% at 1 and 5 years, respectively, in the AZA group. Actual graft survival at 1 year improved from 85% in the AZA group to 97% in the CSA-treated recipients (P less than 0.05). Mean serum creatinine at 5 years remained stable in the AZA group at a mean of 123 mumol/L (1.4 mg/dL) compared with a progressive increase in this parameter to a mean of 212 mumol/L (2.4 mg/dL) after the same time interval in the CSA patients. Furthermore, the slopes of the serum creatinine against time were significantly different between the two groups (P less than 0.01). Mean daily CSA dose averaged 4 mg/kg 12 months following transplantation, with a decrease to 2.4 mg/kg by the fifth year. Causes of death in the AZA group were cardiovascular (eight), sepsis (three), cancer (one); and in the CSA group, Kaposi's sarcoma (one). Causes of graft failure in the AZA group were immunological (six), sepsis (three), technical (two), recurrence of disease (one), and patient death with a functioning graft (five). Technical (one), noncompliance (two), recurrence of disease (one), and patient death with a functioning kidney (one) caused graft failure in the CSA group. No difference in posttransplantation serum cholesterol or incidence of new onset diabetes was observed between the two groups, but hypertension was significantly more frequent (51% v 21%, P less than 0.01) when CSA was used. In conclusion, intermediate-term results of CSA-treated HLA-identical transplant recipients showed improved patient and graft survival with less complications apart from hypertension. However, the slow, but relentless, increase in serum creatinine in the CSA-treated patients compared with those treated with AZA is of concern.
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PMID:HLA-identical renal transplants: impact of cyclosporine on intermediate-term survival and renal function. 223 30

The problem of illegal drug abuse and extremity loss was identified in 27 patients-22 men and 5 women, with a mean age of 26 years. Associated medical problems included: smoking in 27, cardiac disease in 2, diabetes in 3, and hypertension in 3. Six femoral pseudoaneurysms, 2 with distal emboli and all with sepsis and thrombosis, directly contributed to limb loss along with 2 patients with progressive phlegmasia dolens. There were 3 below-the-elbow, 7 above-the-knee, 11 below-the-knee, and 6 transmetatarsal amputations. Eight patients received prostheses; 8 patients subsequently died in follow-up.
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PMID:Parenteral illegal drug use and limb loss. 226 3

A preventive effect of dietary marine n-3 fatty acids on early delivery and toxaemia has recently been hypothesized. In only one published controlled trial fish oil has been given to pregnant women, namely in that conducted during 1938-9 in London by the People's League of Health with a dietary supplement containing vitamins, minerals, and halibut liver oil. Although it was of high quality and its findings are hitherto unexplained, neglect and misinterpretation of the trial seem to occur commonly in reviews. Of the 5644 women who were enrolled the 622 withdrawals were independent of treatment. Alternate allocation to treatment was used, producing two groups that were well balanced as to age and parity. The supplement was given from about week 20. The control group did not receive any supplement. Reductions of 20.4% (95% confidence interval 9-30%, P = 0.00083) and 31.5% (95% confidence interval 11-47%, P = 0.0047) were seen in odds of delivering before 40 weeks of gestation and pre-eclampsia respectively. No significant effects were seen on perinatal mortality, average birth weight, deliveries after 40 weeks, hypertension in the absence of oedema and proteinuria, duration of labour, sepsis or breast-feeding occurrence. Later controlled trials with vitamins or minerals given in the same amounts as in this trial have largely failed to show convincing effects as seen here. A controlled trial assessing the isolated effects of fish oil in pregnancy is warranted.
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PMID:A possible preventive effect of low-dose fish oil on early delivery and pre-eclampsia: indications from a 50-year-old controlled trial. 226 75

Despite great improvement in patient and graft survival, the long-term morbidity and mortality in renal transplant recipients are still significant. Cardiovascular disease accounts for much of the mortality in long-term survivors; screening before the transplant procedure and adequate control of hypertension should help improve patient survival. Many of the gastrointestinal complications are due to overimmunosuppression and sepsis. Adequate management must include withdrawal of all immunosuppressive medications in order to save the patient's life. Liver disease is usually of viral origin; patients with chronic active hepatitis or cirrhosis should remain on dialysis. Chronic rejection is the major cause of graft loss in long-term survivors; it is unresponsive to antirejection treatment and its progression may be mediated by nonimmunologic mechanisms. Correctable problems such as renal artery stenosis and ureteral obstruction should be ruled out before a late deterioration in graft function is disregarded as chronic rejection. Post-transplant diabetes, osteonecrosis, cataracts, and nephrotoxicity are directly related to the various immunosuppressive drugs currently used. The lowest dose compatible with graft acceptance should help reduce the incidence of these nonfatal but significant complications. Recurrence of disease is a common histologic finding in many transplant recipients but, except for a few diseases such as HUS, FSGS, and oxalosis, it usually does not lead to graft failure. Successful transplantation restores fertility in many uremic patients. Adequate counseling on contraception is imperative in order to avoid unwanted pregnancies and to delay parenthood for at least 1 year. Current immunosuppressive agents are not teratogenic, no dose adjustments are necessary, and an ill-advised decrease in medication may precipitate a rejection episode. Premature delivery is the major problem in these patients and can be avoided by maintaining adequate graft function and controlling hypertension and infections. It is evident from this review that most of the long-term morbidity and mortality seen in renal allograft recipients are due to overimmunosuppression with sepsis or to side effects of the individual drugs, steroids being a common denominator in almost all cases. New immunosuppressive protocols must aim not only to improve patient and graft survival but also to avoid the many complications that limit the full rehabilitation of these patients.
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PMID:Problems in the long-term renal allograft recipient. 226 90

Multiple levels of aortoileofemoral occlusive disease may necessitate profundoplasty or extension of the outflow anastomosis to insure pelvic and distal arterial perfusion. During the period 1978 through 1988, 1637 patients underwent elective aortic reconstruction for aneurysmal or occlusive disease. One hundred forty-five had profundoplasty performed to ensure adequate outflow. Associated disease was common with 88 (60%) patients having arteriosclerotic heart disease and chronic obstructive pulmonary disease (COPD) present in 89 (61%) patients. Hypertension and extracranial occlusive disease was found in 68 (46%) and 56 (38%) patients, respectively. The superficial femoral artery was occluded in 108 (74%) patients, while in 17 (12%) the profunda femoris was the only patent artery in the groin. Death occurred in nine patients (6.2%). Three were due to arrhythmias or myocardial infarction and ischemic colitis was the cause of death in two. Renal failure, sepsis, aspiration and cerebral anoxia, and disseminated intravascular coagulopathy accounted for one each. Five graft limbs failed. Amputation was required in one patient, while thrombectomy or distal bypass restored flow in four patients. Seventeen graft limbs in 136 patients occluded during the follow-up period. Distal bypass was successful in four and amputation was required in the fifth patient. Extension of the profundoplasty restored flow in nine limbs, while thrombectomy alone was successful in one. Bilateral amputation was required in one patient with poor run off and insufficient autogenus venous tissue. One hundred fourteen (78.6%) of the 145 patients survived 10 years with patency in 268 of the original 290 limbs at risk (92.4%). Profundoplasty in these patients with multilevel disease seems to extend the long-term patency of aortofemoral grafts and allows return to a normal life-style.
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PMID:Extended profundoplasty to minimize pelvic and distal tissue loss. 235 32

Seventy-seven very low birthweight (VLBW) infants (mean birthweight 891 +/- 209 g) with a diagnosis of bronchopulmonary dysplasia (BPD) were treated with a steroid (dexamethasone) in an attempt to wean them from mechanical ventilation. Seventeen of 77 (22%) treated infants died. Death from respiratory failure occurred in 13 infants; sepsis occurred in six infants (7.8%) and contributed to death in one. During steroid therapy systemic hypertension occurred in 18 surviving infants (30%), glucose intolerance occurred in 29 infants (38%), and marked irritability occurred in three infants (3.8%). Elevated blood pressure returned to normal and glucose intolerance resolved in all infants following discontinuation of therapy. Fifty infants were available for follow-up at a mean corrected age of 14.9 +/- 9.8 months. Twenty-two percent required rehospitalization in the first year of life for respiratory illnesses. Results of testing by Bayley Scales of Infant Development were normal in 60% of infants. Fifty percent were considered normal based on both developmental testing and physical examination. Twenty-eight percent had mild to moderate abnormalities, and 22% were severely handicapped. These follow-up results are statistically similar to those recorded in LBW infants with BPD not treated with steroids who were hospitalized during the same period. We conclude that the side effects of steroid therapy for BPD consist primarily of blood pressure elevation, glucose intolerance, and irritability. Causes of death are unchanged by steroids. The incidence of severe infection and the long-term neurologic outcome of high-risk infants with BPD are not appreciably compromised by this therapy. These data suggest that concern for steroid side effects should not prevent additional prospective investigation to determine the role of steroid therapy in the overall management of BPD.
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PMID:Side effects and long-term follow-up of corticosteroid therapy in very low birthweight infants with bronchopulmonary dysplasia. 235 96

The Dialysis Centre at the Lagos University Teaching Hospital became operational in November 1981 and caters for acute haemodialysis, chronic maintenance haemodialysis and continuous arteriovenous haemofiltration. In the past 5 years, over 600 patients had presented out of whom 245 could be accommodated within the realities of available facilities and patients' financial status. Of the 245 patients, 25 were discharged against medical advice and five were transferred to hospitals abroad but did not survive. There were 117 patients in end-stage renal failure (ESRF), 75 males, 42 females, ratio M:F 1.8:1, age range 13-69 years, mean 37.5. There were 51 males and 47 females in acute renal failure (ARF), ratio 1.1:1, age range 13-76 years, mean age 32.3 (Table 1). All patients in ESRF had moderate to severe hypertension (diastolic pressure of greater than or equal to 120 mmHg or 22.1 kPa) and a creatinine clearance of less than or equal to 5 ml/min and about 75% had established cardiac decompensation. Full pertinent investigations were precluded or contra-indicated in most patients in ESRF because of late presentation. In only 13 patients was renal biopsy performed and the pathohistologies were end stage renal disease (8), chronic glomerulonephritis (4) and glomerulosclerosis (1). In ARF the cause of the renal damage was multifactorial in 66.7%, with sepsis being the direct cause of death in 60.0%. The commonest conditions were septicaemia (61.4%), nephrotoxin (17.2%), trauma (31.3%), septic abortion (33.3%) and toxaemia of pregnancy (29.0%) (Table 2). The dialysis associated complications which were encountered included shunt infection (7%), burst membrane (9%), suspected pyrogen reaction (5.6%) and femoral vein perforation (0.9%).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Five years experience of haemodialysis at the Lagos University Teaching Hospital--November 1981 to November 1986. 255 Nov 60

Of 400 patients with acute, chronic or chronic relapsing pancreatitis surveyed in the present study, only 54 had had ECG in their files. Among these, 80% showed ECG alterations, mostly sinus tachycardia and diffuse disturbances of ventricular repolarization. The causes of these alterations are, as yet controversial. Some explanations for these alterations are hypovolemia, sepsis and acute inflammatory state. Other important findings in the patients were bundle branch block, not encountered either before the pancreatic crisis or after its resolution, nor was dielectric effect and lesion current observed in either the acute and chronic forms. The possibility of the presence of previous cardiopathy in patients with high alcoholic intake, Chagas' disease, high blood pressure or diabetes, which are quite likely in these patients, should be recalled as important factors: marked electrolytes disorders were not frequent and did not correlate with ECG findings. The aim of this study is to highlight the importance of ECG during systematic search in the follow-up of patients with pancreatitis, in order to better understand associated cardiac disorders and to improve diagnosis, prevention and treatment.
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PMID:[Electrocardiographic changes in pancreatitis]. 260 72

Recent improvements in the results of orthotopic liver transplantation (OLT) have made this a well-accepted treatment for patients with severe hepatic failure. Current problems encountered following OLT are discussed. Immediate complications comprise surgical bleeding, primary graft non-function, and graft failure due to hepatic artery occlusion. Secondary complications are frequent. Surgical ones include biliary and vascular (hepatic artery thrombosis most often) problems, as well as intra-abdominal abscesses associated with gastrointestinal perforation, biliary leak, graft ischaemia or an infected haematoma. 40% of patients having undergone OLT will be reoperated on, 2/3 of them within 3 months. Non-surgical complications are mostly pulmonary. The risk of pneumonitis is increased by prolonged mechanical ventilation; it is always potentially disastrous in the immunosuppressed, transplanted patient. Hypertension is also often seen in the early postoperative period; it requires prompt treatment. Early renal impairment after OLT is common, and of better prognosis than late onset renal failure, which is generally associated with shock, graft failure, sepsis or use of nephrotoxic agents. Seizures, usually only one, occur in about 10% of patients; recovery is complete. Encephalopathy with intracranial oedema related to fulminant hepatitis has a worse prognosis, but survival figures are quite encouraging. Three type of rejection are described after OLT: 1) severe accelerated rejection (very rare), 2) acute rejection encountered in about 70% of patients over the first 3 months, and 3) late rejection, which can lead to the vanishing bile duct syndrome (VBDS). Diagnosis of rejection is made by liver biopsy. Prophylactic immunosuppression includes cyclosporin, methylprednisolone and azathioprine. Cyclosporin toxicity and drug interactions are reviewed. Treatment of acute rejection episodes comprises an initial bolus of high doses of corticoid drugs; if there is no response, antilymphocyte globulin or monoclonal antibodies may have to be used. Infection is the main cause of death following OLT. Early infections, mostly intra-abdominal and pulmonary, are bacterial or fungal. Vital (especially CMV) and other opportunistic infections occur generally after the second week. Retransplantation, carried out in 10 to 25% of patients, may be urgent in case of primary graft failure, or hepatic artery thrombosis associated with graft failure, or hepatic artery thrombosis associated with graft failure. Other indications are early graft rejection with severe hepatic dysfunction, chronic rejection with severe VBDS, and recurrence of the initial disease.
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PMID:[Liver transplantation in adults: postoperative management and development during the first months]. 262 46

A boy, aged 14 1/2 years, presented with Burkitt leukemia. His renal status was normal before treatment. Chemotherapy (SFOP LMB 86 protocol) was begun Oct. 9, 1986. After the first 2 courses of chemotherapy, the patient had Gram negative sepsis treated with cefotaxime, netilmycine, Vancomycin and ornidazole. During sepsis, nephrotic syndrome developed (albumin 25 g/l, non selective proteinuria 15 g/24 h), with moderately high blood pressure, functional renal failure (creatinine 141 mumols/l, U/P urea = 20), polyuria and tubular damage. Kidney ultrasonography was normal. Needle biopsy showed minimal glomerular lesions, acute tubular lesions, and no deposits in immunofluorescence. The nephrotic syndrome disappeared within 3 weeks, with treatment of leukemia. He is at present in complete remission with a follow-up of 25 months.
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PMID:[Nephrotic syndrome and B leukemia]. 262 44


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