Search PubMed⌕ Search

Biomedical subjects

U Frei

Publications and source records attributed to U Frei.

At least 127 records · Page 7Linked to original sources
PubMed1993

COL4A5 splice site mutation and alpha 5(IV) collagen mRNA in Alport syndrome.

Mutations affecting the COL4A5 gene encoding the alpha 5 chain of type IV collagen, are involved in the pathogenesis of X-linked Alport syndrome. We used denaturing gradient gel electrophoresis (DGGE) to screen PCR amplified exons of COL4A5 for point mutations in a set of 18 Alport patients previously characterized by Southern blotting. One sequence variant was identified in the exon 38 region of a male Alport patient. Sequence analysis revealed a G to C transversion in the 5' intron splice donor site downstream from exon 38 (GT to CT). To determine the effect of the mutation on mRNA splicing, alpha 5(IV) cDNA was generated from total RNA of peripheral blood lymphocytes. Subsequent cDNA PCR yielded a product 81 base pairs shorter in the affected Alport patient, compared to normal controls. The absence of exon 38 from the alpha 5(IV) cDNA was confirmed by sequence analysis. The results demonstrated that the mutation leads to skipping of exon 38 in the processing of alpha 5(IV) pre-mRNA. The shortened transcript lacked 27 codons encoding a Gly-X-Y-repeat sequence with a preserved reading frame, enabling the translation of codons further downstream. Clinically, the patient presented with juvenile onset Alport syndrome, end-stage renal failure, and deafness. He had no ocular lesions. Typical ultrastructural changes of the glomerular basement membrane (GBM) were shown on electron microscopy. The patient developed anti-GBM antibodies after renal transplantation, however, renal function deteriorated only moderately.

Adult↗
PubMed1993

Total hepatectomy and liver transplantation as two-stage procedure.

OBJECTIVE: This article describes the experience with a bridging procedure for a prolonged anhepatic period during clinical liver transplantation in case of special emergency situations. SUMMARY BACKGROUND DATA: Hepatic necrosis due to fulminant hepatitis or acute graft failure, as well as severe liver trauma are well-known and accepted indications for urgent liver transplantation. Prerequisite is the allocation of a suitable donor organ. If no allograft is available in time, patients with "toxic liver syndrome" or exsanguinating hemorrhage have been shown to benefit from advanced total hepatectomy. METHODS: As a modification of the standard one-stage procedure, recipient hepatectomy and subsequent liver transplantation are performed in two separate operations. To bridge the prolonged anhepatic period and to allow decompression and return of venous blood, an end-to-side portocaval shunt is constructed temporarily. RESULTS: Thirteen of thirty-two patients underwent hepatectomy but not transplantation subsequently, and died within 34 hours after progressive deterioration. In 19 of 32 patients, transplantation was realized 6-41 hours after hepatectomy; 9 of 19 patients died, mostly from sepsis. Ten of nineteen liver recipients survived the procedure including three unrelated late deaths; presently, seven patients are alive with a follow-up of 3 to 46 months. CONCLUSIONS: Two-stage total hepatectomy with temporary portocaval shunt, and subsequent liver transplantation can be a life-saving approach in patients most likely to die of the sequelae of advanced liver or graft necrosis or exsanguination that cannot be controlled by conventional treatment or immediate liver transplantation.

Adolescent↗
PubMed1993

Antibody-based immunoadsorption as a therapeutic means.

Polyclonal antibodies against human low-density lipoprotein (LDL), covalently coupled to Sepharose CL-4B, are used to remove LDL from the plasma of familial hypercholesterolemic patients. During a single treatment LDL-cholesterol is lowered by more than 60%, and plasma viscosity is decreased by 10%. The usual treatment frequency is once a week. The possible development of human antisheep antibodies was followed for up to 5 years. The ELISA signal rose slightly above baseline reaching a plateau within the first year. Clinically, there have been no signs of column-related adverse reactions. Due to the versatility of immunoapheresis it is also applicable to deplete IgG by coupling antihuman IgG antibodies. These columns might be indicated for patients with high panel reactivity to enable organ transplantation and for patients with autoimmune disease. In vitro tests with plasma from high-panel-reactive dialysis patients have shown that IgG could be depleted by 95% across all subclasses and that panel reactivity could be reduced from 91 to 25%.

Animals↗
PubMed1992

Influence of antihypertensive therapy on renal function.

Antihypertensive therapy influences kidney function by different mechanisms depending on the mode of action of the drug used. The GFR is improved by calcium entry blockers and ACE inhibitors, unaffected by vasodilators, alpha-blockers and centrally acting sympatholytics and impaired by beta-blockers. The same is true for renal blood flow and is due to changes of renal vascular resistance. Renal sodium excretion is impaired mostly by vasodilators, by alpha-blockers, sympatholytics and beta-blockers; in contrast, calcium entry blockers and ACE inhibitors acutely induce natriuresis. The RAAS is stimulated by vasodilators, unaffected by alpha-blockers and sympatholytics and suppressed by beta-blockers. Plasma catecholamines are stimulated by vasodilators and suppressed by centrally acting sympatholytics and unaffected by the others. Induction of acute renal functional impairment is reported for ACE inhibitors under conditions of compromised renal perfusion pressure such as in renal artery stenosis. These data from the literature reviewed are supported by our own experimental data on sodium balance under different drugs and micropuncture data in experimental renal artery stenosis. To achieve effective antihypertensive treatment with a low profile of side effects, careful monitoring of renal function seems to be mandatory.

Animals↗
PubMed1992

Present status of kidney transplantation.

Kidney transplantation today is the method of choice to treat end-stage renal disease (ESRD) in more than 50% of the ESRD-population. Due to major improvements in surgical handling, immunosuppressive therapy, and infection control, the one-year survival for patients and first grafts has reached nearly 90% in the recent years. In contrast no comparable achievements have been made in long-term graft survival. A constant number of grafts is lost yearly after the first postoperative year. In addition an increasing number of well functioning grafts is lost due to the death of the recipients caused mainly by cardiovascular and malignant disorders. The extension of kidney transplantation to all suitable recipients is nearly exclusively hampered by the organ shortage, which is further enhanced by failing grafts. This urges us to further improve the prognosis for patient and graft. This must include organ sharing on the basis of improved HLA-typing to achieve highly compatible grafts. The tools for differential diagnosis of acute and chronic graft dysfunction have to be improved. New immunosuppressive agents with higher immunosuppressive power and specificity but fewer nephrotoxic, metabolic and hemodynamic side effects are required at least for chronic rejection. The risk of infectious and malignant complications must be limited.

Cadaver↗
PubMed1992

Kidney transplantation in Alport's syndrome: long-term outcome and allograft anti-GBM nephritis.

Anti-glomerular basement membrane (anti-GBM) nephritis occurring in kidneys transplanted in patients with Alport's syndrome (AS) has been reported repeatedly. Therefore, we studied graft survival and course of renal function in all 30 AS patients grafted at Hannover Medical School and compared them with non-diabetic, age and sex matched patients, transplanted on the date closest to the transplantation of the AS patient. Serum creatinine, proteinuria, urinary sediment and anti-GBM antibodies were examined in all AS patients with functioning grafts. Cases of patient or graft loss in the AS group were analyzed retrospectively. One- and five-year patient survival was 100 and 91% in AS and 89 and 78% in controls (p > 0.05, respectively). One- and five-year first graft survival was 79 and 66% in both groups. Graft histology was available in 34 biopsies obtained from 21 kidneys in 15 AS patients. Anti-GBM nephritis was not detected in any of the biopsies. No graft was lost due to anti-GBM nephritis. Anti-GBM antibodies were detectable temporarily only in one AS patient. He also had linear IgG staining in his graft GBM, but no other signs of anti-GBM nephritis. We conclude that patient survival and graft survival in AS patients following kidney transplantation is not different from non-AS patients. Allograft anti-GBM nephritis is a rare complication in patients with Alport's syndrome.

Adult↗
PubMed1992

Glomerular hemodynamics of the clipped kidney: effects of captopril and diltiazem.

Glomerular hemodynamics of the clipped kidney in two kidney-one clip Goldblatt-hypertensive rats were studied by micropuncture techniques after administration of either captopril (20 mg/kg of b.wt./day p.o.) or diltiazem (3 mg/kg of b.wt./hr i.v.). Both drugs decreased mean arterial and poststenotic renal arterial pressure to comparable levels. Total kidney glomerular filtration rate was not significantly different in the three groups (0.78 +/- 0.09 in hypertensive controls, 0.62 +/- 0.11 after captopril and 0.74 +/- 0.07 ml/min/g of kidney weight after diltiazem). Glomerular capillary pressure fell significantly in both treated groups but was lower in captopril-treated animals (60 +/- 2 in hypertensive controls, 45 +/- 2 after captopril and 53 +/- 1 mm Hg after diltiazem, both P < .05 vs. hypertensive controls). Afferent arteriolar resistance was lowered in both treatment groups to the same extent, whereas only captopril decreased efferent arteriolar resistance. Single nephron filtration rate of cortical nephrons was not altered significantly by captopril due to a 96% increase in the ultrafiltration coefficient and a 58% rise in glomerular plasma flow, whereas diltiazem increased ultrafiltration coefficient by 62% but did not affect glomerular plasma flow. These studies indicate that, despite of decreased effective filtration pressure, glomerular filtration rate is well preserved after converting enzyme inhibition. Captopril and diltiazem have different effects on glomerular hemodynamics within the stenosed kidney.

Angiotensin II↗
PubMed1991

Impact of long-term immunosuppression with cyclosporin A on serum lipids in stable renal transplant recipients.

To determine the impact of long-term immunosuppression on serum lipids in stable renal graft recipients we measured serum lipids and apolipoprotein B concentrations in 20 patients receiving therapy with cyclosporin (CsA) and low-dose prednisolone (CsA/P) and in 18 patients on therapy with azathioprine and maintenance steroids (Aza/P). The patients were matched for age, body mass index, primary renal disease and dose of prednisolone, but not for the duration in transplantation and serum creatinine concentration. Triglyceride concentrations were significantly higher in the CsA/P group than in Aza/P-treated patients: 2.62 +/- 0.35 vs 1.62 +/- 0.23 mmol/l (P less than 0.05). Similarly, total cholesterol (C) levels were significantly more elevated in the CsA/P recipients than in the other group: 7.44 +/- 0.32 vs 5.84 +/- 0.25 (P less than 0.02). CsA/P patients had higher serum levels of LDL-C (4.79 +/- 0.20 vs 3.43 +/- 0.19 mmol/l (P less than 0.001) and apolipoprotein B concentrations (191 +/- 13 vs 128 +/- 9 mg/dl: P less than 0.001). CsA/P and Aza/P recipients had similar concentrations of HDL-C (1.73 +/- 0.13 vs 1.52 +/- 0.09 mmol/l: NS). We conclude that in stable renal graft recipients with good transplant function long-term immunosuppression with CsA/P is associated with a more atherogenic lipid status than therapy with Aza/P.

Adult↗
PubMed1991

Cyclophosphamide pulse therapy in Wegener's granulomatosis.

Twenty-three patients with Wegener's granulomatosis, 15 with daily oral cyclophosphamide therapy and eight with intravenous cyclophosphamide pulse therapy, were studied retrospectively. All patients had involvement of the kidneys and systemic symptoms. Mean monthly cyclophosphamide dose was 1.0 g in the pulse group and 2.7 g in the daily treated group. In all patients remission could be achieved. During 207.5 months of daily oral therapy the following complications were observed: leukopenia, necessitating dose reduction in seven patients, severe infection in one patient, relapses in three patients. During 103 months of intravenous pulse therapy one patient developed leukopenia. No patient had a severe infection. Two relapses were seen. Our data suggest that cyclophosphamide pulse therapy is an effective treatment strategy in patients with Wegener's granulomatosis and kidney involvement. It offers the chance of bladder protection and marked total dose reduction, possibly decreasing the risk of malignancies.

Administration, Oral↗
PubMed1991

Improved physical performance after treatment of renal anemia with recombinant human erythropoietin.

The physical performance of 12 anemic patients on renal dialysis was investigated following treatment of renal anemia with recombinant human erythropoietin (rhEPO; 40-120 U/kg, 3 times a week). Exercise intensity at a heart rate of 130 beats/min (PWC130) on a bicycle ergometer was assessed before rhEPO treatment, after reaching the target hematocrit (73 +/- 18 days), and in the maintenance phase (211 +/- 53 days). Hemoglobin concentrations measured at these time points were 7.3 +/- 1.2, 11.9 +/- 1.5, and 12.1 +/- 1.4 g/dl, respectively. PWC130 rose from 77 +/- 27 to 104 +/- 37 and 104 +/- 51 W, respectively. Aerobic threshold (i.e. blood lactic acid concentration of 2 mmol/l) shifted to higher workloads indicating improved muscle oxygen supply.

Adult↗
PubMed1991

Hypertension as a possible complication of recombinant human erythropoietin therapy.

The analysis of the hemodynamics accompanying correction of renal anemia by rhEPO shows that--although they behave qualitatively as in nonuremic anemic patients--cardiac output and peripheral resistance may change inadequately and thereby cause a rise of blood pressure. The underlying mechanisms are not yet fully understood but to a great part may be related to preexisting pathology due to a history of longlasting hypertension. In some patients the development of hypertension may only represent a temporary phenomenon of hemodynamic dysregulation. To avoid cardiovascular complications the following should be considered: Patients with a history of hypertension, even if they are normotensive in the anemic state, are at a higher risk of developing hypertension during therapy with rhEPO. Hypertensive complications may be rare events when anemia is corrected slowly. In case of the development or aggravation of hypertension a reduction of the target hematocrit is indicated.

Anemia↗
PubMed1991

[Pregnancy following organ transplantation].

Pregnancies following organ transplantation are high-risk pregnancies for mother and fetus. There are many reports concerning pregnancies following renal transplantation whereas only few reports are published about pregnancies in recipients of liver, heart and bone marrow transplants. During the pregnancy after kidney transplantation pregnancy-induced hypertension can develop or the renal function can decrease. Risks for the fetus are prematurity, growth retardation and prenatal infections. A higher incidence of complications for mother and fetus is observed in patients with renal insufficiency or severe hypertension prior to conception. The risks can be reduced by an intradisciplinary cooperation of gynecologist, transplant specialist and paediatrician. The paediatrician. The experiences with pregnancies in women after organ transplantations in the Medical School of Hannover are analyzed and compared with the reports in the literature. The management of these patients is described on current state of knowledge.

Female↗