Search PubMed⌕ Search

Biomedical subjects

G Offermann

Publications and source records attributed to G Offermann.

At least 55 records · Page 3Linked to original sources
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↗
PubMed1989

Long-term treatment and prognosis of rapidly progressive glomerulonephritis.

Short-term prognosis of rapidly progressive glomerulonephritis (RPGN) has improved since immunosuppressive therapy was introduced. The long-term course of the disease was investigated in 46 consecutive and unselected patients over a period of 15 years (1970-1986) with a mean observation time of five years (+/- 45 months). Most of the 46 patients had idiopathic RPGN (61%). Initially, hemodialysis needed 25 of the 46 patients (54%). Immunosuppressive therapy (plasma exchange, methylprednisolone pulses, steroids, cyclophosphamide, azathioprine) was administered in 36 of the 46 patients (78%). A remission was achieved in only 19 of the 36 patients who received immunosuppression (53%) and no spontaneous improvement was seen. Factors indicating poor prognosis were initial high serum creatinine, high percentage of crescents in glomeruli, glomerular sclerosis, and immunohistologic staining of the IgG at the tubuli. In 11 patients with remission, immunosuppression was discontinued and 6 had a relapse. Long-term immunosuppression was given to 8 patients with remission. Their renal function was not normal (creatinine 240 +/- 77 mumol/l), but none had a relapse (p = 0.01). It is concluded that the treatment of RPGN requires long-term attendance and repeated immunosuppression comparable to a systemic immune disease.

Adult↗
PubMed1988

[Cumulative functional rates of orthoptic dialysis fistulas and interposition grafts].

The function of 221 dialysis shunts was investigated retrospectively in 111 patients of an outpatient haemodialysis centre. The mean age of the patients was 58 years. Of 221 recorded shunts, 171 were direct arteriovenous fistulas, while 50 were interposition grafts. The longest observation period was almost 20 years (227 months). The cumulative function rate was evaluated by the life table method; primary patency (until first revision) was differentiated from total function (revisions included). The direct fistulas as compared to the grafts had a significantly (P less than 0.05) higher primary function rate (median 35 vs. 13 months) and after 36 months also a significantly longer total function (median 76 vs. 28 months). Complications were significantly (P less than 0.05) more frequent in grafts than in fistulas (61/50 vs 120/171). Surgical revisions of fistulas failed significantly more often (P less than 0.05) than revisions of grafts (137/171 versus 26/50). Grafts on the forearm had significantly worse results as compared to grafts or fistulas on the upper arm (P = 0.03). In contrast to age, sex and underlying disease of patients a blood pressure less than 130/70 mmHg was a significant risk factor for shunt failure (P = 0.002). Analysis of primary function shows (clearer than the total patency rate) that a direct fistula is a better vascular access in haemodialysis patients than a graft.

Actuarial Analysis↗
PubMed1988

Transplantation of a horseshoe kidney en bloc: report of a case.

Transplantation of a horseshoe kidney rarely has been reported. We report a case of successful en bloc transplantation of a horseshoe kidney. The kidney could not be divided because of a complex vascular situation in the isthmus region. The recipient was discharged from our hospital with normal kidney function 12 days postoperatively. We recommend the use of kidneys with anatomical malformations for transplantation.

Adult↗
PubMed1988

Elevated tumor markers in hemodialysis patients.

The incidence of elevated tumor markers without clinical signs of malignant disease was examined in 93 patients between the age of 29 and 79 years and on chronic dialysis for 3-240 months. Tissue polypeptide antigen was found to be elevated in 92.5%, carcinoembryonic antigen in 29.8, and alpha-fetoprotein in 6.5%. High levels of tissue polypeptide antigen were accompanied by high levels of beta 2-microglobulin (p less than 0.005). This indicates that tumor markers, and tissue polypeptide antigen in particular, may be unreliable for monitoring malignant disease in patients on hemodialysis.

Adult↗
PubMed1988

Granulomatous interstitial nephritis after nonsteroidal anti-inflammatory drugs.

Electrolyte and renal hemodynamic imbalance, acute interstitial nephritis with nephrotic-range proteinuria, papillary necrosis, tubular necrosis, and vasculitis are complications after intake of nonsteroidal anti-inflammatory drugs (NSAID). We report on 2 cases of biopsy-proven granulomatous interstitial nephritis with rapidly progressing renal insufficiency. Patient 1 was on ketoprofen for 7 months and indomethacin for 10 weeks before admission to hospital. The medication was not discontinued and renal insufficiency progressed to end-stage renal failure. Renal function did not respond to steroid and tuberculostatic treatment. Patient 2 was on diclofenac for 6 months and indomethacin for 7 weeks before admission to hospital. These drugs were withdrawn at diagnosis and renal function rapidly improved. We conclude that granulomatous interstitial nephritis may be a complication of NSAID medication indicating a cell-mediated immunologic disorder. False diagnosis (sarcoidosis, tuberculosis) may lead to end-stage renal disease (case 1). Discontinuation of medication obviates further therapy (case 2).

Adult↗
PubMed1988

Increased procollagen III production in patients with kidney disease.

Measurements of elevated procollagen III peptide (PIIIP) levels are used to monitor fibrosing activity in hepatic and various other diseases. Elevated PIIIP levels have also been reported in renal failure patients without such diseases. Therefore, the serum levels and renal clearance of PIIIP were investigated in 17 healthy volunteers and 100 patients with different types of acute (n = 15) and chronic (n = 85) kidney disease. PIIIP was measured by conventional and Fab radioimmunoassays. Median PIIIP levels in serum (18, range 5-55 ng/ml) and urine (34, range 1-110 micrograms/day) were significantly higher in kidney patients than serum (9, range 6-14 ng/ml) and urine levels (17, range 6-24 micrograms/day) in normal volunteers (p = 0.01). No significant differences (Kruskal-Wallis H test) were found, however, within the different kidney disease groups (acute, chronic/glomerulonephritis, interstitial nephritis). Median renal clearance of PIIIP-related peptides in kidney patients (1.5, range 0.5-2.4 ml/min) did not differ significantly (Wilcoxon U test) from that in normal volunteers (1.3, range 0.4-2.2 ml/min). These findings indicate that PIIIP elimination does not depend on renal function. PIIIP-related peptides in serum and urine, however, increase with renal failure irrespective of the activity or type of renal disease. This can be explained most probably by enhanced turnover of collagen type III by the affected kidney itself.

Adult↗