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Biomedical subjects

G Offermann

Publications and source records attributed to G Offermann.

At least 37 records · Page 2Linked to original sources
PubMed1991

Plasma exchange and hemoperfusion in iodine-induced thyrotoxicosis.

Iodine-induced thyrotoxicosis is a life-threatening disease. Plasma exchange and hemoperfusion are the available means of detoxication. Both methods were applied repeatedly to 4 patients with iodine-induced thyrotoxicosis, and the efficacy of these treatment methods was compared. Thyroxine plasma levels were decreased by 33%, while the calculated body stores were reduced by 18% during plasma exchange. Hemoperfusion was less effective. With both methods, a rebound of plasma levels was seen. Improvement of the clinical condition was delayed for 1 week after discontinuation of treatment. One patient died, probably because detoxication was discontinued too soon after the thyroid hormone levels had normalized. Plasma exchange by using albumin (120 g/4,000 ml = 30 g/l) as replacement fluid is superior to that by using fresh-frozen plasma (2,000 ml/4,000 ml), since less thyroxine is administered (19 vs. 160 nmol).

Aged↗
PubMed1990

Risk factors of system clotting in heparin-free haemodialysis.

Heparin-free haemodialysis must be considered for all dialysis patients with a risk of haemorrhage. This technique is associated with increased danger of system coagulation with a blood loss of up to 250 ml. In 84 patients with a risk of haemorrhage, 296 heparin-free haemodialyses were recorded prospectively. First signs of coagulation were found very much more frequently in the venous airtrap than in the dialyser (146 vs 42). System coagulation occurred in 13 of the 296 dialyses (4%) and was prevented by prophylactic switching of the system and dialyser in 140 dialyses (47%). The time of system coagulation was on average 1.8 hours (+/- 0.2) after the beginning of dialysis. The 13 patients with system coagulation had a reduced blood flow on dialysis (217 +/- 52 vs 240 +/- 36 ml/min). Their initially normal clotting time (12 +/- 5 vs 14 +/- 4 min) was more significantly shortened after 2 h (4 +/- 3 vs 8 +/- 3 min). The activities of antithrombin III (87 +/- 34% vs 88 +/- 39%) and protein C (66 +/- 45% vs 59 +/- 37%) do not differ from those of 47 other patients, even at the time of system coagulation, as measured in five patients (92 +/- 34% for antithrombin III, 51 +/- 29% for protein C). System coagulation and shortening of clotting time thus cannot be regarded as a consequence of absorption of these inhibitory factors of plasmatic coagulation. The danger of system coagulation in heparin-free haemodialysis could probably be further reduced by an improvement of the biocompatibility of systems (airtrap) and dialysers (less activation of thrombocytes).

Bleeding Time↗
PubMed1990

Soluble interleukin 2 receptor and tissue polypeptide antigen serum concentrations in end-stage renal failure.

Serum concentrations of soluble interleukin 2 receptor (IL-2R) were measured in 65 hemodialysis patients and compared with serum levels of beta 2-microglobulin and tissue polypeptide antigen (TPA). Elevated IL-2R levels, found in 85% of examined patients, correlated with elevated TPA serum concentrations (p less than 0.05). Patients with high IL-2R levels were significantly younger (p less than 0.05) than patients with low levels. Primary renal disease and residual renal function had no significant influence on TPA or IL-2R serum concentrations. In 16 patients with carpal tunnel syndrome, increased serum concentrations of IL-2R (p less than 0.005) and TPA (p less than 0.001) were found. We conclude that a non-specific dialysis-induced activation of epithelial and lymphoid cells rather than a specific immune response could explain the concomitant elevation of IL-2R and TPA serum concentrations in hemodialyzed patients. Patients with pronounced cell turnover, reflected by elevated IL-2R and TPA levels, may show an increased susceptibility to dialysis-associated amyloidosis.

Aged↗
PubMed1990

Cancer incidence in patients on chronic dialysis and in renal transplant recipients.

A markedly increased incidence of cancer in renal transplant recipients is now recognized; to determine if immunosuppression alone may be responsible for this increase in risk, cancer incidence was compared in 709 renal transplant recipients and 317 dialysis patients. Malignancy developed in 19 transplant recipients (2.7%) and in 33 patients on chronic dialysis (10.4%). In our report an excess of skin cancer was observed in the transplant series while tumors of the urinary tract were seen more frequently in patients on dialysis. Transplantation and consecutive immunosuppression does not appear to constitute an additional cancer risk for the uremic patient who is faced with the alternative to undergo chronic dialysis or renal transplantation.

Adult↗
PubMed1990

Slow accumulation of cyclosporin metabolites as measured by specific and nonspecific cyclosporin RIA.

Blood cyclosporin concentrations were measured by radioimmunoassay (RIA) using nonspecific polyclonal and specific monoclonal antibodies in 32 kidney transplant patients. Kinetics of cyclosporin concentrations after transplantation (day 0-2) and after long-term dosage (day 7-month 6) were evaluated by nonlinear regression analysis. Elimination and accumulation kinetics were linear and in agreement with one- or two-compartment kinetics. Only in 3 cases were saturable Michaelis-Menten kinetics observed (Vm = 23 ng/ml h-1, Km = 636 ng/ml). Bioavailability was 0.72 as estimated from first-pass extraction. The median values (5-95% CI) for the elimination half-life of nonspecific RIA concentrations increased from 5 h (2.5-6.2) on day 2 after transplantation to 10 h (9.2-11) after long-term dosage. The specific monoclonal antibody data revealed an elimination half-life of 6.4 h (5.6-7.7) for parent cyclosporin, which was unchanged after multiple dosing. After month 6, the elimination half-life of specific monoclonal antibody data was significantly shorter (p = 0.03) than elimination half-life of nonspecific RIA concentrations (6.6 vs 9.1 h). In relation to blood concentrations measured by nonspecific polyclonal antibody RIA, the fraction of parent cyclosporin significantly decreased from 84 percent (49-90) to 30 percent (24-52) after long-term dosage as measured by specific monoclonal antibody (p = 0.01). It is concluded that metabolites of cyclosporin accumulate in a slow compartment and, after long-term cyclosporin administration, nonspecific RIA blood concentrations are mainly contributed by cyclosporin metabolites.

Adult↗
PubMed1989

[Advantages and risks of kidney transplantation from related donors].

Living related kidney transplantation must offer the recipient distinct advantages over cadaveric grafting in order to justify the health risk undertaken by the donor. At Steglitz Medical Center in Berlin from 1970 to 1987 30 such transplantations were performed (5% of all kidney transplantations) where the donor was a relative of the recipient. In cases of haploidentity and positive mixed lymphocyte culture, the recipients were pretreated with donor-specific transfusions. The posttransplantation graft function rate was higher in the group where the donated kidney came from a relative than where it did not (after 2 years under cyclosporin: 92% vs 73%, P = 0.04), and corticosteroid treatment could be terminated more frequently under cyclosporin (95% vs 51%, P = 0.001). Transplantations from living related donors were performed more often in foreigners (43% vs 20%, P = 0.01) and children (19% vs 4%, P = 0.0001). Perioperative complications in the donor nephrectomy occurred in 63% of the cases, severe ones in 13% (bleeding, pneumonia, and late abscess). Late sequelae were not observed. The short waiting time, the high graft function rate, and the low steroid requirement justify kidney transplantation from living related donors providing strict indicational criteria are observed.

Berlin↗
PubMed1989

Cyclosporin drug monitoring: comparison of four immunoassays and HPLC.

Cyclosporin blood trough levels were measured with four different immunoassays and high-performance liquid chromatography in 12 patients receiving low-dose steroids and CsA after kidney transplantation. These patients represent a selection with an uncomplicated posttransplant course and received no drugs with a known influence on CsA pharmacokinetics. The use of specific antibodies against the parent drug yielded levels comparable to those detected by HPLC. CsA levels measured with nonspecific antibodies exceeded those measured with specific ones by a factor of two to three. All immunoassay-detected CsA levels correlated significantly with the HPLC-determined CsA levels. In addition, blood levels of the CsA metabolites 1, 17, 18, and 21 were determined by HPLC. In one additional patient, who was under tuberculostatic treatment and had a transitory deterioration of liver function, levels of nonspecific-antibody-determined CsA rose, as confirmed by rising levels of metabolite 17, while those of the parent drug fell. We conclude that routine drug monitoring should include at least one immunoassay with a specific antibody detecting the unchanged CsA, and a supplementary immunoassay with a nonspecific antibody detecting a composition of cross-reacting metabolites plus the unchanged substance. If available, HPLC should be used to confirm levels of CsA and its metabolites in patients with suspected alteration of their CsA metabolism.

Administration, Oral↗
PubMed1989

Saturable first-pass kinetics of propranolol.

Reduced bioavailability (F) due to hepatic first-pass extraction of an oral dose (D) is a well-known pharmacokinetic phenomenon. An integrated solution for Michaelis-Menten kinetics of the first-pass effect is derived from the maximal metabolic rate (Vm), volume of distribution (Vd), first order absorption rate constant (ka), Michaelis constant (Km), and liver blood flow (Q). F = 1 - VmVd/kaD ln (1 + kaD/QKm) This equation for single dosage can also be extended to steady state kinetics after multiple dosing in which the amount of a drug present in the hepatic circulation is considered. According to the literature, the bioavailability of a single 80 mg oral dose of propranolol (F = 0.22) increases after multiple doses Fss = 0.36). Based on the first pass equations for single dosage and multiple dosing, the maximal metabolic rate (Vm = 0.043 mg l-1 h-1) corresponding to 310 mg per day and the Michaelis constant (Km = 0.10 mg/l) were calculated for propranolol. Incorporation of nonlinear plasma protein binding in this concept may explain the lack of threshold phenomenon for a single dose of less than 40 mg propranolol. Zero order absorption kinetics could explain why cumulation kinetics seem linear even at an excessive dosage of 960 mg propranolol per day. From these derivations it may be concluded that multiple dosing, increase in plasma protein binding, high absorption rate, and increased portal venous blood flow will increase bioavailability, whereas slow release formulations, fractional drug dosage, and saturable absorption kinetics will decrease bioavailability of first-pass drugs like propranolol.

Absorption↗
PubMed1989

Late conversion from steroids to azathioprine in cyclosporin-treated renal graft recipients.

In renal graft recipients primarily treated with cyclosporin and low-dose methylprednisolone, withdrawal of the long-term steroid medication increases the likelihood of developing rejection episodes. In order to determine the predictive value of clinical parameters and routine prewithdrawal graft biopsies for the risk of rejection, the authors studied 141 kidney recipients from whom steroids were withdrawn 7-9 months after transplantation in a clinically stable situation. Both the quality of the HLA-match and the results of prospective graft biopsies were found to correlate significantly to the occurrence of acute rejection. In order to investigate the influence of additional azathioprine medication on the incidence of acute rejections in recipients not receiving steroids, immunosuppression was continued with cyclosporin monotherapy in 88 patients and with cyclosporin plus azathioprine in 53 patients. The risk of developing rejection episodes was significantly reduced from 48% after 1 year on monotherapy to 28% after the addition of azathioprine medication.

Azathioprine↗
PubMed1989

Factors influencing the response to hepatitis B vaccination of hemodialysis patients.

The response rate and HBsAG antibody concentrations were examined after hepatitis B vaccination in 78 hemodialysis patients aged between 29 and 79 years. The values were related to age, duration of hemodialysis, body weight, creatinine, urea nitrogen, serum concentrations of beta 2-microglobulin and soluble interleukin-2 receptor (IL-2R). Patients with low anti-HBsAG antibody concentrations (10-100 mU/ml) had significantly higher IL-2R serum concentrations than those with high anti-HBsAG antibody concentrations (greater than 3,000 mU/ml; p less than 0.05). Discriminant multivariate analysis (p = 0.032) revealed the influence (62%) of IL-2R on the response rate while other factors were similar in all patient groups. It is concluded that preactivation of T cells with an increased release of IL-2R may contribute to impaired immune response after hepatitis B vaccination.

Adult↗
PubMed1989

Progression of renal failure in analgesic-associated nephropathy.

The factors that influence the progression of renal failure in analgesic-associated nephropathy (AAN) still remain to be clarified. In this study, the actual analgesic intake (N-acetyl-p-aminophenol, NAPAP, i.e. acetaminophen in urine) and progression of renal failure (1/crea method) in 127 outpatients with various renal diseases were investigated over a period of 7-150 months. AAN was diagnosed in 57 of the 127 patients (44%). The NAPAP test was positive in 21% of the 57 AAN patients and in 3% of the 70 control patients with other renal diseases (p = 0.0001). The AAN patients presented with more advanced renal insufficiency, lost more weight, and had more severe hypertension as well as a higher mortality rate than the control patients (univariate analysis). Progression of renal insufficiency, as measured by regression analysis of the reciprocal of serum creatinine versus time and expressed as clearance loss per year, was more rapid in the AAN patients who were found positive for NAPAP (6.9 +/- 5.5 ml/min/year) than in the AAN patients who were found negative (4.1 +/- 11.0 ml/min/year) or in control patients with other renal diseases (5.1 +/- 14.9 ml/min/year). Multivariate analysis showed the more rapid clearance loss to be the most discriminating factor between the AAN patients who continued analgesic abuse of phenacetin-or acetaminophen-containing drugs and AAN patients who stopped. We therefore conclude that continued analgesic abuse promotes renal insufficiency in AAN. The progression of renal failure in AAN patients who stopped abusing analgesics, however, cannot be explained within the parameters investigated, i.e. urinary tract infection, hypertension, hyperalimentation, or papillary necrosis.

Acetaminophen↗
PubMed1989

Multivariate analysis of aminoglycoside levels in hemodialysis patients.

Multivariate discriminant analysis was performed on data for 50 consecutive hemodialysis patients who had received aminoglycoside treatment because of severe bacterial infections. The 10 of the 60 clinical parameters considered to be most important were survival of patients (28/50 patients), success of treatment (27/50 patients), acute or chronic renal failure (15 vs. 35), age (54 +/- 17 years), creatinine level (675 +/- 298 mumol/l), artificial ventilation (21/50 patients), need for catecholamines (19/50 patients), continuous arteriovenous hemofiltration (9/50 patients), duration of therapy (12 +/- 8 days) as well as aminoglycoside peak (7.5 +/- 2.7 mg/l) and trough levels (3.6 +/- 1.3 mg/l). The 4 of the 10 parameters investigated by multivariate analysis significantly contributing to survival of patients were clinical success of aminoglycoside treatment (p = 0.0001), no need for catecholamines (p = 0.0001), duration of dosage (p = 0.003) and aminoglycoside peak levels (p = 0.009).

Adolescent↗
PubMed1989

The influence of renal insufficiency on caesium metabolism in man and rat (with a note on the Cs content of some biological standard materials).

Caesium was measured by instrumental neutron activation analysis in blood plasma and erythrocytes of persons suffering from renal disorders and in age-and sex-matched controls. The disease was at an early stage of development, the patients having creatinine plasma values below 1000 mumol/l. None of them had been dialysed. In a group of 5 patients with plasma creatinine below 250 mumol/l no changes in the blood caesium contents could be observed, but in a group of 17 with plasma creatinine between 250 and 1000 mumol/l the caesium level in the plasma was increased by 70% and in the erythrocytes by 50%, compared to the controls. An effect of renal insufficiency on the caesium metabolism was also observed in rats, in which 5/6-nephrectomy led to increases in the caesium tissue levels (muscle 30%; spleen 25%; pancreas 100%). However, as in the animals the element content in blood plasma and erythrocytes remained unchanged, it is not clear to what extent the nephrectomized rat can be used as a model in the investigation of relations between chronic uraemia and caesium metabolism. It can therefore not yet be decided whether the changes in the blood caesium levels in the patients are due to a decrease in renal excretion or are only a secondary effect of unnoticed changes in dietary habits. The increase in caesium levels suggests, however, that in the first stages of the disease the patients may receive higher radiation doses from the radioisotopes of caesium than the normal population does in the case of environmental or industrial exposure.

Animals↗