Biomedical subjects
Publications and source records attributed to G Offermann.
The simultaneous administration of the calcium channel blocker diltiazem and cyclosporin results in a significant increase of RIA cyclosporin blood levels. The HPLC cyclosporin levels are not influenced.
During the last 4 years we observed four cases of neonatal rickets. The mothers of the infants suffered from osteomalacia for 1-3 years prior to its diagnosis shortly after the birth of their children. All four infants were born with craniotabes, and one infant had, in addition, a radial fracture. The diagnoses were confirmed by radiological and laboratory tests which revealed a rarefied bone structure, decreased serum 25-hydroxy-vitamin D and increased alkaline phosphatase levels in all patients. The disorder regressed under low-dose vitamin D3 therapy. As osteomalacia seems to be predominant in oriental women living in Berlin, it is necessary to consider vitamin D deficiency when clinical symptoms of this disease arise and to treat these women at least during pregnancy.
In patients with normal renal function, defined peak (5-10 mg/L) and trough levels (less than 2 mg/L) for gentamicin, tobramicin, and netilmicin are considered therapeutic. Netilmicin peak and trough levels were investigated in 50 patients requiring hemodialysis due to acute (70%) or permanent (30%) renal failure. Netilmicin was given at a dosage interval of 24 h, with a loading dose on the first day (1.5 mg/kg) and a reduced daily maintenance dose (0.5 mg/kg) supplemented to the posthemodialysis dosage (1.3 mg/kg) after each hemodialysis. As compared with studies on patients not requiring hemodialysis, mortality (44%) was higher, mainly due to uncontrolled infection, whereas ototoxicity (17%) was not. Peak (5.9 +/- 1.7 mg/L) and trough plasma levels (3.0 +/- 0.9 mg/L) were significantly lower in patients who did not respond and died than were peak (8.2 +/- 2.5 mg/L) and trough (3.8 +/- 1.2 mg/L) levels in patients responding to aminoglycoside treatment. In renal failure patients, there is obviously not only the risk of overdosing and toxic side effects but also the risk of insufficient bactericidal effect as a result of underdosing. Consequently, by use of an aminoglycoside dosage similar to the present schedule, peak levels (5-10 mg/L) as desired in normal subjects but trough levels (2.5-5 mg/L) that are considerably higher than in normal subjects should be the target concentrations for patients with advanced renal failure.
The human immunodeficiency virus (HIV) is reportedly transmitted by sexual contact, sharing of infected needles among intravenous drug abusers, blood and blood products, artificial insemination, and kidney transplantation. This study reports on cornea and kidney recipients of two HIV-infected donors. HIV was transmitted to two kidney recipients who developed symptoms of acute HIV infection (i.e., fever, leukopenia, mild thrombopenia, splenomegaly) starting 12 days after transplantation. These signs of acute infection ended with seroconversion of HIV antibodies on approximately the 56th day after transplantation. The three cornea recipients showed no signs of acute infection and no HIV antibodies were detected up to three years after transplantation. The nontransmission observed in our cases, however, may not be representative of cornea transplantations in general. HIV is neurotropic in the later stages of the disease, and transmission of other neurotropic viruses like rabies and Creutzfeldt-Jakob disease by cornea transplantation has been reported. All tissue and organ donors should be tested for anti-HIV prior to donation.
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It is well-known that plasma aluminium in haemodialysis patients increases with the amount of aluminium hydroxide consumption. In a cross-sectional study at our haemodialysis centre we found that mean plasma aluminium levels are significantly higher in haemodialysis patients with analgesic-associated nephropathy (AAN) than in haemodialysis patients with other kidney diseases (controls) (logarithmic mean +/- SD = 1.93 +/- antilog 0.32 versus 1.21 +/- antilog 0.31 mumol/l; p = 0.001). AAN patients consume a significantly higher amount of aluminium-containing phosphate binders than the controls (21 +/- antilog 0.3 versus 13 +/- antilog 0.4 g/kg body weight/year; p = 0.007). These findings may be explained by the higher incidence of peptic ulcer disease in AAN patients, since hyperacidity decreases the phosphate-binding effect. Analgesic patients also need more aluminium-containing stomach medication than do patients with other kidney diseases (0.21 +/- antilog 1.15 versus 0.03 +/- antilog 0.87 g/kg body weight/year; p = 0.0001). A statistically significant correlation was obtained between bone aluminium and duration of phosphate binder consumption (r = 0.6459; n = 14; p less than 0.05). There was no correlation between plasma aluminium and bone aluminium. Anaemia was more pronounced in the AAN patients than in the others (mean haemoglobin 8.4 +/- 1.9 vs. 9.2 +/- 2.0 g%; p less than 0.02). Dialysis dementia was observed in 4 AAN patients. We conclude that the higher plasma aluminium levels in AAN patients represent a higher aluminium load which may be followed by higher aluminium toxicity.
Sera of 1046 patients undergoing haemodialysis for terminal renal failure or after renal transplantation were tested with the ELISA screening test for anti-LAV/HTLV-III and, if positive, the Western blot and ELAVIA tests. Four patients (0,38%) had "true" antibodies against LAV/HTLV-III, confirmed by the Western blot and ELAVIA tests. These patients had definite signs of cellular immune defects. They had received transplants from drug addict donors. Such kidneys should therefore no longer be used for transplantation. In addition, 29 patients (2.8%) had "false-positive" antibodies against LAV/HTLV-III in the ELISA test, unconfirmed in the Western blot and ELAVIA tests. The "false-positive" result was presumably due to cross-reaction with HLA antibodies. Sera of dialysis and transplantation patients who had received many blood transfusions should therefore be especially carefully tested before a diagnosis of infection with LAV/HTLV-III is made.
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Antibiotic prophylaxis in kidney transplantation is controversial. In a prospective controlled study, 34 cadaveric kidney transplant recipients were investigated. Antibiotic prophylaxis was given in a random order to 16 patients whereas 18 without prophylaxis served as controlls. In 4 of 20 investigated clinical parameters statistically significant differences were found between both groups: the controlls happened to have better initial conditions; perioperative and postoperative better initial conditions; perioperative and postoperative infections were less frequent in the prophylaxis group and more antibiotics postoperatively were needed in the controlls. These findings indicate that antibiotic prophylaxis has a beneficial effect in kidney transplantation.
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The diagnosis of analgesic-associated nephropathy (AAN) may be missed because of the patients denial or regular analgesic intake. We therefore performed a cross-sectional study of the 144 patients of our hemodialysis center to investigate differences between the 48 patients with AAN (33%) and patients with other kidney diseases who served as controls. The aim was to find other attributes of analgesic users relating to social history, habits and morbidity. Dialysis patients with AAN were significantly older (60 +/- 10 versus 52 +/- 15 years) and more frequently women (65% versus 37%) compared with controls; they often had a family history of analgesic abuse. Comparison with an age-matched control group of hemodialysis patients with other kidney diseases showed that AAN patients smoked, used hypnotics and laxatives, and required prescriptions significantly more frequently; they were less frequently willing to undergo renal transplantation. With regard to accompanying diseases, they suffered significantly more often than the age-matched controls from anemia, renal osteodystrophy, peptic ulcer disease, diverticulosis, hemorrhoids, atrial fibrillation, coronary heart disease, hyperlipidemia, carpal tunnel syndrome, and urinary tract infections. The characteristic pattern of habits, social history and accompanying diseases may facilitate the diagnosis of AAN even in cases where analgesic consumption is denied.
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Cyclosporin A trough blood levels were unusually low during rifampin treatment in a kidney transplant patient. Simultaneously, acute graft rejection occurred. Pharmacokinetic investigation revealed a rapid turnover of cyclosporin A leading to low blood levels. Cessation of rifampin therapy reversed these changes. Rifampin substantially reduces the bioavailability of cyclosporin A and should not be used in transplant recipients on cyclosporin A.
Antimicrobial therapy in hemodialysis patients is made possible by pharmacokinetic dosage modifications. The problem is that overdosage produces side effects whereas therapeutic drug action is missed by underdosage. The dose should be calculated to achieve identical peak levels (for bactericidal drugs) as in normal renal function or identity of AUC (for bacteriostatic drugs). Antimicrobial therapy is started with a loading dose which usually equals the dose in patients with normal renal function. The maintenance dose is reduced in renal failure and adjusted to the increase in the dominant elimination half-life. The effect of hemodialysis must be taken into account and replacement of the removed fraction by a supplementary dose is needed to assure therapeutic drug action.
Prevailing reports on psychological prediction of renal graft integration are rare, mostly based on case studies. Focusing on patients' expectations from the transplantation process before grafting, we investigate the influence of psychological data and statements on the final transplantation results. In the whole group (n = 83) the attitude toward transplantation was very optimistic. Comparing the features of patients with successful graft outcome (n = 23) and graft failure or patient's death (n = 10) the latter group shows: lower scale values of optimistic attitude toward transplantation outcome, higher level of fear concerning surgical treatment, less willingness to agree preoperatively to second transplantation in case of first graft failure. Psychological data indicate a greater tendency toward more submissive, rigid, and depressive behavior. It is assumed that the patient's attitude and expectation on grafting is a part of the conditions influencing the final transplantation result. Further studies should prove this concept.
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Out of 80 kidney graft recipients treated with cyclosporin A and low dose steroids 19 (23.8%) developed herpes virus infection and from these 15 (18.8%) herpetic stomatitis. Evaluation of enhancing factors for herpetic stomatitis suggested a role of cyclosporin A rather than of steroids and a probable relation to preceding CMV infection. Acyclovir treatment was effective on the course of stomatitis and pain in 12 of the 15 patients. No serious side effects were observed. Leukopenia as a possible hazard was discussed.