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Biomedical subjects

G Thiel

Publications and source records attributed to G Thiel.

At least 181 records · Page 10Linked to original sources
PubMed1989

[HIV infection caused by kidney transplant: case report and review of 18 published cases].

Since 1985 organ donors are routinely tested for the presence of HIV-antibodies, but prior to that time several patients acquired HIV-infection from grafts. In May 1984 a 65-year-old woman on hemodialysis received a cadaver kidney graft from a young iv drug addict. The transplant functioned perfectly with cyclosporin A immunosuppression. Retrospectively, 22 days after surgery HIV antigen was detected. At this time only a faint band of anti-p24 antibodies was found in the Western blot. Two years after surgery splenomegaly was found in the apparently healthy patient. During the third year thrombocytes fell and she developed lymphadenopathy and constitutional symptoms. Up to this time the immunological parameters were in the range of 10 healthy renal transplant patients with cyclosporin A treatment. In the 4th year T-lymphocytes dropped to values below 200 and the patient developed Pneumocystis carinii pneumonia. A few months later a pulmonary node, which later proved to be a B-cell lymphoma, appeared. Slightly less than 5 years after transplantation the patient died from clinically diagnosed pulmonary embolism. The progression of the HIV-Infection in this patient and in one of 18 patients in published reports show that the incubation period is several years shorter in renal transplant patients than in those who acquire HIV from blood products.

AIDS Serodiagnosis↗
PubMed1989

Cyclosporin A: action and side-effects.

Cyclosporin A (CSA) is a new, potent immunosuppressive agent which is of proven value in organ transplantation. The use of CSA is associated with numerous side-effects, of which a dose-dependent nephrotoxicity is the most serious. CSA nephrotoxicity can be divided into two major groups: (i) functional toxicity without significant morphological lesions and (ii) morphological forms of toxicity with tubular and/or vascular-interstitial lesions. Vascular-interstitial toxicity is the most serious form because the renal lesions are irreversible.

Acute Kidney Injury↗
PubMed1989

Long-term enalapril and verapamil in rats with reduced renal mass.

The effect of long-term treatment with either enalapril or high dose verapamil on survival, proteinuria, blood pressure and renal morphology was studied in female Wistar rats with markedly reduced renal mass. Four weeks were allowed for remnant kidney hypertrophy before determining the response to renal ablation of individual animals regarding proteinuria and hypertension. At this time, five groups of 18 rats were formed with equal levels of proteinuria and hypertension. Groups E1 and E2 were treated with enalapril, groups V1 and V2 with verapamil, and one group served as control. The daily food allowance was 14 g/rat of a standard rat diet, containing 30% protein and 100 mmol NaCl/kg food in groups E1 and V1. NaCl content was reduced to 20 mmol/kg food in groups E2, V2 and control. The drugs were added to the drinking water, enalapril at a dose of 0.1 g/liter, verapamil at 0.5 to 0.7 g/liter. Drug intake thus amounted to 10 to 25 mg/kg for enalapril and 50 to 140 mg/kg for verapamil. Treatment was continued for 15 weeks. Three of the 18 control rats did not survive up to 15 weeks. Mortality was lower in the enalapril treated groups with a single nonsurvivor in group E1. In contrast, mortality was higher in the verapamil treated animals with seven nonsurvivors in group V1 and eight in group V2. Blood pressure control was excellent in both enalapril treated groups. and proteinuria decreased in most animals of group E1 and all of group 22. Glomerulosclerosis did not develop in the majority of the enalapril treated animals. Despite the high dose, verapamil barely lowered blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Incidence of arrhythmias and myocardial ischaemia during haemodialysis and haemofiltration.

Thirty-two patients (10 male, 22 female; age 37-82 years) undergoing maintenance haemodialysis or haemofiltration were studied by means of Holter device capable of simultaneously analysing rhythm and ST-changes in three leads. Twenty-five patients were on haemodialysis, seven on haemofiltration, mean duration of haemodialysis/haemofiltration being 3.4 +/- 3 years. Incidence of ventricular tachycardia was low, being detected only in 1 of 32 patients. Ventricular premature beats in excess of 10/h during a period of 2 h were found in 8 of 32 patients and 100 supraventricular premature beats for 2 h or more in 4 of 32 patients. Both ventricular premature beats and supraventricular premature beats were most frequently recorded during the last hour of haemodialysis/haemofiltration. ECG signs of ischaemia were detected in eight patients, four of whom were asymptomatic. Ischaemia also occurred predominantly during the last hour of haemodialysis/haemofiltration. Two symptomatic patients displayed neither arrhythmias nor ST-changes while being monitored. The study shows that silent ischaemia and arrhythmias in patients undergoing chronic haemodialysis/haemofiltration may not be infrequent. Recognition of these events could be of importance in the management of these patients.

Adult↗
PubMed1989

[Transplantation of kidneys of relatives].

In the last few decades kidney transplants have shown an increasing survival rate of about 85% after one year. The growing demand for transplants is limited by the insufficient availability of kidneys and the living donor represents a possible means of reducing the discrepancy between supply and demand. We report here results of 41 transplantations from related, living donors. The overall transplant survival rate at one year was 91% and at 5 years 71%. In the group treated with cyclosporine the survival rate was 92% at 5 years. The mean serum creatinine levels at the latest follow-up was 115 mumol/l, while the mean blood pressure was 139/82 mmHg. Donor nephrectomy resulted neither in morbidity nor mortality. An extensive follow-up study of 8 donors revealed normal values for both blood pressure and serum creatinine. Careful donor selection is crucial in order to guarantee the voluntary nature of donation and, thus, to avoid the risk of commercialism.

Follow-Up Studies↗
PubMed1988

cAMP-dependent protein phosphorylation of membrane proteins in the parotid gland, platelets and liver. Comparison of a 22-kDa phosphoprotein from rat parotid microsomes (protein III) with phosphoproteins of similar molecular size from platelet and liver membranes.

Stimulation of secretion in exocrine secretory glands leads to the phosphorylation of a 22-kDa membrane protein (protein III) whose function is still unknown [Jahn et al. (1980) Eur. J. Biochem. 112, 345-352; Jahn & Söling (1980) Proc. Natl Acad. Sci. USA 78, 6903-6906]. This report describes the comparison of this protein with phosphorylated membrane proteins of similar molecular mass in platelets and liver. Incubation of platelets with agents which raise the intracellular cAMP concentration results in the phosphorylation of a 22-kDa protein which is also phosphorylated in membrane preparations by endogenous kinases or by exogenous cAMP-dependent protein kinase. It is shown that this protein is distinct from protein III although both proteins have the same molecular mass and are substrates of cAMP-dependent protein kinase. In contrast to platelets, protein III could be demonstrated in liver microsomes. This indicates that the function of protein III is not exclusively linked to the stimulus-secretion coupling in exocrine cells.

Animals↗
PubMed1988

[Hereditary Poland syndrome with megacalycosis of the right kidney].

Poland's syndrome is characterized by congenital aplasia of the sternocostal head of the pectoralis major muscle associated with ipsilateral hand deformities (most often synbrachydactylia). 20% of patients have rib cage abnormalities, some with herniation of the lung. In some cases other associated ipsilateral anomalies (hypoplasia or absence of the nipple and/or the breast, defects of the vertebrae, dextrocardia, renal aplasia of hypoplasia, undescended testes, Möbius syndrome) have been described. We describe a patient with right-sided Poland's syndrome, the first published case associated with megacalycosis of the ipsilateral kidney. It is also the first publication of a familial case with this renal anomaly, since a brother has megacalycosis of the right kidney without Poland's syndrome. The majority of cases of Poland's syndrome are sporadic. The incidence has been estimated at between 1:30,000 and 1:80,000 of live births. The great uncle of our patient had a short forearm and only rudimentary fingers. The etiology of the syndrome is unknown. Toxic effects early in fetal life or effects on primary asymmetrical blood vessels, e.g. the subclavian artery, followed by uneven growth, are discussed as possible causes of Poland's syndrome.

Abnormalities, Multiple↗
PubMed1988

[Phase contrast microscopy demonstration of glomerular erythrocytes in urine: practicable in ambulatory practice?].

The use of phase-contrast microscopy in microhematuria, as proposed in 1979 by Birch and Fairley, renders morphological changes in red cells easily detectable and makes it possible to distinguish glomerular from non-glomerular bleeding. The aim of this study was to evaluate the practicability of this method as a routine laboratory test in ambulatory care. 60 patients with asymptomatic microhematuria (greater than or equal to 2 erythrocytes per high power field) were followed up over a one-year period. All patients were investigated by intravenous pyelography, ultrasound of urinary tract and three cytological examinations of the urine. The description of urine samples was done with phase-contrast microscopy by a first investigator at the beginning of the study and by a second after 12.8 months, blinded to clinical results and previous examinations. In 21 patients a definitive diagnosis was possible. In 18 patients the morphologic descriptions of the two investigators correlated with the clinical results. Only in two patients with established diagnosis there were differences between the urine description of the two investigators, and in one patient the interpretations of both investigators were wrong. These incorrect descriptions concerned patients with low-grade microhematuria. Thus, phase-contrast microscopy is a practicable method for the practitioner's use as a routine laboratory investigation. In low-grade microhematuria the method seems to be of minor value.

Ambulatory Care↗
PubMed1988

The angiotensin converting enzyme inhibitor enalapril in acute ischemic renal failure in rats.

The influence of the renin-angiotensin system on renal hemodynamics, tubular pressure and tubulo-glomerular feedback was investigated with the angiotensin converting enzyme inhibitor MK 421 (enalapril), in uninephrectomized rats with and without ischemia-induced acute renal failure. In animals with normal renal function proximal tubular pressure and tubulo-glomerular feedback response were lowered by enalapril long-term treatment, whereas glomerular filtration rate and renal blood flow were not influenced by the drug. After 45 and 70 minutes ischemia there was no difference between treated and untreated animals in the severely impaired glomerular filtration rate. Renal blood flow remained unaffected by the treatment. The histological damage due to ischemia (tubular casts, tubular necrosis and medullary capillary congestion) was not influenced by enalapril. As tubulo-glomerular feedback had been significantly inhibited during renin-angiotensin inhibition, its importance in mediating acute renal failure remains doubtful; other factors such as tubular obstruction and medullary congestion may be crucial.

Acute Kidney Injury↗
PubMed1988

Purification and characterization of a 22-kDa microsomal protein from rat parotid gland which is phosphorylated following stimulation by agonists involving cAMP as second messenger.

Stimulation of secretion in exocrine glands by agonists involving cAMP as second messenger leads to the phosphorylation of the ribosomal protein S6 (protein I) and two other particulate proteins with apparent molecular masses of 24 kDa (protein II) and 22 kDa (protein III) [Jahn, R., Unger, C. & Söling, H. D. (1980) Eur. J. Biochem. 112, 345-352]. This report describes the purification and characterization of protein III. Solubilization studies indicate that protein III is an intrinsic membrane protein. It could be extracted from the endoplasmic reticulum membrane only with Triton X-100, SDS or concentrated formic or acetic acid. The purification of this protein involved extraction of the microsomes with Triton X-100, removal of the detergent by acetone precipitation, extraction of water-soluble proteins, lipids and lipoproteins, and preparative SDS polyacrylamide gel electrophoresis. The protein has a basic pI (greater than 8.7). For determination of the amino acid composition of protein III and for sequencing of its amino-terminal portion, the protein was electroeluted out off the gel, the detergent removed and the protein finally purified by reversed-phase HPLC. Protein III could be phosphorylated in vitro by the catalytic subunit of the cAMP-dependent protein kinase to a degree of approximately 0.14 mol phosphate/mol protein. The only phosphopeptide obtained after in vitro phosphorylation and subsequent tryptic or chymotryptic digestion was identical with the phosphopeptide obtained after stimulation of intact rat parotid gland lobules with isoproterenol. The sequence of this peptide was Lys-Leu-Ser(P)-Glu-Ala-Asp-Asn-Arg. It was confirmed by an analysis of the synthetic peptide following in vitro phosphorylation with cAMP-dependent protein kinase. The first 41 N-terminal residues of protein III were sequenced. So far no sequence homology with other known peptides or proteins could be found.

Amino Acids↗
PubMed1988

Ca2+/calmodulin-dependent protein kinase II: identification of threonine-286 as the autophosphorylation site in the alpha subunit associated with the generation of Ca2+-independent activity.

Autophosphorylation of Ca2+/calmodulin-dependent protein kinase II converts the enzyme to a Ca2+-independent form. The time course for this conversion correlates with the autophosphorylation of a threonine residue located within a thermolytic phosphopeptide common to the alpha and beta/beta' subunits. In the present study, this site was identified in the alpha subunit. After autophosphorylation under conditions that produced near-maximal Ca2+-independent activity, the alpha and beta/beta' subunits were separated by NaDodSO4/PAGE, and the alpha subunit was cleaved with cyanogen bromide. The major phosphopeptide (CB-1), containing phosphothreonine as the only radiolabeled amino acid, was purified by reverse-phase high performance liquid chromatography and subjected to automated gas-phase Edman degradation. The sequence obtained, Xaa-Arg-Gln-Glu-Thr-Val-Asp-Xaa-Leu-Lys-Lys-Phe-Asn-Ala-Arg-Arg-Lys-Leu, represented the NH2-terminal 18 residues (residues 282-299) of a 26-amino acid cyanogen bromide peptide predicted from the deduced primary structure of the alpha subunit and contained a consensus sequence for Ca2+/calmodulin-dependent kinase II phosphorylation that included Thr-286. The sequences obtained for two phosphopeptides derived from secondary chymotryptic digestion of CB-1 confirmed that Thr-286 was the phosphorylated residue.

Amino Acid Sequence↗
PubMed1988

Pharmacokinetics of cyclosporine G in patients with renal failure.

The pharmacokinetics of the cyclosporine A (CsA, Sandimmune) analogue Nva2-cyclosporine, or cyclosporine G (CsG) was investigated in 6 patients with terminal renal failure after a 4-hr intravenous infusion (3.5 mg/kg) and after oral administration (600 mg) of the drug. Blood samples were collected up to 38 hr and CsG concentrations were measured by radioimmunoassay and high-performance liquid chromatography. The resulting pharmacokinetic parameters of CsG were similar to those described for CsA in the same patient population. Based on HPLC determinations, a mean terminal elimination half-life of 18.9 hr was calculated. The total body clearance was 0.55 L/hr/kg, the volume of the central compartment was 0.32 L/kg, and the steady-state volume of distribution was 5.97 L/kg. After oral administration maximum CsG concentrations in blood were reached between 2.5 and 3 hr, and the bioavailability was in the range of 24-55% (mean 36%). The ratios between the polyvalent RIA and HPLC determinations were considerably larger after oral dosing than after i.v. infusion. The blood-to-plasma ratio was 1.23, which is smaller than that observed for CsA. These results suggest that in patients undergoing renal transplantation the same dosing strategies can be applied for CsG as have been established for CsA.

Adult↗
PubMed1988

Cytomegalovirus and kidney.

This study was conceived to identify specific morphological characteristics associated with cytomegalovirus (CMV) infection of the kidney. 33 patients with manifest CMV infection at autopsy and 32 biopsies of kidney transplants with active or inactive CMV infection were studied. In 8 patients of the autopsy group a CMV infection of the kidney was detected (CMV cells in 3 cases, positive viral tissue culture in 4 cases, positive in-situ hybridization in one case), which was associated with severe dissemination into different organs. In situ hybridization was not superior to ordinary light microscopy in the detection of CMV cells. The biopsies were screened for the presence of glomerulopathy. No association of glomerulopathy with CMV could be found by light microscopy, whereas a significant correlation of glomerulopathy with vascular rejection was demonstrated. No differences as to the incidence of glomerulopathy were found, when non-transplant patients with manifest CMV infection at autopsy were compared with matched controls. With active infection electron microscopy revealed no osmiophilic deposits, but in immunofluorescence tiny IgG deposits were identified within the glomeruli (p less than 0.01). IgM or C3 deposition in the glomeruli was not specifically associated with either CMV infection or vascular rejection. Thus morphological identification of CMV infection of the kidney is difficult, necessitating the detection of CMV cells, positive viral tissue culture or positive in-situ hybridization. Glomerulopathy in light microscopy is associated with vascular rejection and is therefore termed transplant glomerulitis. Tiny IgG deposits may be indicative of CMV infection, although these are not always present.

Autopsy↗
PubMed1988

The influence of HLA antigens on progression of alcoholic liver disease.

The aim of our study was to elucidate further possible genetic influences on the incidence and progression of alcoholic liver disease. We determined HLA A, B and DR antigens in a well-controlled group of chronic alcoholics with and without liver disease, in repeated liver biopsies over period of 8.1 years (+/- 0.4 SEM). Patients with the antigen B 35 had an increased incidence of alcoholic liver cirrhosis, and especially a more rapid progression to cirrhosis (p less than 0.01). Increased susceptibility of these patients was shown by a more rapid progression of liver disease, despite the consumation of less alcohol over a shorter period. Results of this long-term study suggest that there is a sub-group of alcoholics genetically predisposed to higher susceptibility with more rapid deterioration of alcohol-induced liver disease.

Adult↗