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Biomedical subjects

G Klintmalm

Publications and source records attributed to G Klintmalm.

At least 73 records · Page 4Linked to original sources
PubMed1987

Development of chronic renal cyclosporin-A toxicity.

Treatment with cyclosporine in renal transplantation causes an increased incidence of interstitial fibrosis. The degree of interstitial fibrosis seems to be correlated with high cyclosporine consumption and episodes of acute CyA nephrotoxicity. The cause of acute CyA nephrotoxicity seems to be hemodynamic alterations. Whether this is the cause for the chronic nephrotoxicity has still not been shown.

Azathioprine↗
PubMed1987

Liver transplantation in patients with patent splenorenal shunts.

Patent distal splenorenal shunts (Warren shunt) have been reported to cause decreases in the portal perfusion pressure and the total hepatic blood flow. Such hemodynamic alterations could have adverse effects on the transplanted liver. The experience with hepatic replacement in four patients with patent Warren shunts is reported. Operative findings were phlebosclerotic portal veins of small size and diminished portal blood flows. Hepatofugal collateral channels created by the construction of the Warren shunt were eliminated by division of the shunt and splenectomy in three patients and splenectomy alone in the other. All patients recovered; thus the presence of a patent Warren shunt should not be a contraindication for hepatic transplantation.

Adult↗
PubMed1986

HLA-matching and pretransplant blood transfusions in cadaveric renal transplantation--a changing picture with cyclosporin.

613 patients were included in a study to assess the extent to which HLA-matching and pretransplant blood transfusions affect the outcome of cadaveric renal transplantation in patients treated with cyclosporin and low doses of prednisolone. Matching for the HLA-DR-antigens significantly reduced the frequency of rejection episodes, but neither HLA-matching nor pretransplant blood transfusions influenced the patient and graft survival rates.

Analysis of Variance↗
PubMed1986

Pharmacokinetics, safety and preliminary clinical experiences using foscarnet in the treatment of cytomegalovirus infections in bone marrow and renal transplant recipients.

Fifty seven episodes of severe cytomegalovirus (CMV) infection were treated with iv foscarnet in 13 bone marrow and 33 renal graft recipients. The ranges of the daily dose, duration, average steady state level and total dose were 23-268 mg/kg, 2-46 days, 42-400 mg/l and 2-399 g, respectively. Adverse effects, such as decreased haemoglobin, decreased renal function and increased serum calcium, were observed in a few patients only. Increased liver enzymes, hallucinations and tremor were seen in one uraemic patient and coincided with foscarnet plasma concentrations above 400 mg/l. Among 25 patients evaluated for clinical efficacy, 12 died. Improvements, such as eradication of CMV (8/14 assessable patients), resolution of fever (11/22), and improved laboratory values (13/23) were noted in 17/24 (70%). Controlled trials are warranted on the basis of this study.

Adult↗
PubMed1986

HLA-matching in cyclosporine treated renal transplant recipients: a prospective Swedish-Norwegian multicenter study.

1. In this prospective study of 613 CD and 205 one haplotype mismatched LRD transplant recipients treated with CyA, there was no influence of HLA-matching (A, B, DR or combinations) on graft survival rate at one and two years. 2. Patients who successfully received HLA-DR-matched kidneys (CD or LRD) had fewer rejection episodes during the first six months after transplantation. 3. Three factors significantly reduced the cadaveric graft survival rate: (a) presence of panel reactive T-cell antibodies in a current recipient serum, (b) cold ischemia time beyond 27 hours, and (c) recipient age above 55 years. 4. The survival rate of one haplotype mismatched LRD kidneys was excellent and is considered to be the optimal treatment for uremia also in CyA-treated patients. 5. Based on this study, exchange of well HLA-matched CD kidneys to non-sensitized patients has been terminated provisionally in Scandia-transplant. Exchange of HLA-A, B-matched kidneys will be maintained, however, for sensitized patients inasmuch as this will increase the chance of obtaining a negative cross-match and possibly improve graft survival in this high-risk patient group.

Cyclosporins↗
PubMed1986

Gingival enlargement. A comparison between cyclosporine and azathioprine treated renal allograft recipients.

The immunosuppressive drug cyclosporine (CsA) which is used to facilitate renal transplantations, has shown several side effects. Gingival hyperplasia has been demonstrated in animal experiments and also during treatment of humans. In the present study the prevalence of gingival enlargement was investigated in a group of patients treated with CsA. The results were compared with those obtained from a time matched control group of patients treated with azathioprine. The CsA treated patients showed a high prevalence of gingival enlargement, while the azathioprine treated patients showed none. Edentulous patients showed no gingival enlargement. The gingival enlargement was confined to the free gingiva and the interdental papilla, and had a rough surface, with small fissures. It was extremely fragile and bled on probing. Oral hygiene measures showed a slight reduction of the size of the gingival enlargement.

Adult↗
PubMed1985

Cyclosporine plasma levels in renal transplant patients. Association with renal toxicity and allograft rejection.

In 69 renal allograft recipients the highest-tolerated dose was given with respect to clinical events but without respect to the CsA plasma level (CsA-PL). The CsA dose was gradually decreased during the first 6-12 months after transplantation, and in some patients even later. The CsA dose after 12 months was 5-8 mg/kg/day and after 18 months 4-6 mg/kg/day, resulting in CsA-PL of 85-140 ng/ml and less than 50-110 ng/ml, respectively. CsA side-effects were usually seen in patients with high CsA-PL, but they were also encountered at levels normally seen in patients without toxicity. In the individual patient, acute CsA nephrotoxicity was associated with a significant rise in CsA-PL. In patients with acute nephrotoxicity a reduction of the CsA dose (mean 24%) was necessary to regain satisfactory renal function. All patients with several consecutive CsA-PL above 1000 ng/ml had hepatotoxicity or nephrotoxicity, or both, associated with severe morbidity and mortality. No difference was found between CsA-PL during acute rejection and during good renal function. The percentage of CsA determinations resulting in plasma levels below 50 ng/ml (the limit of detection) increased with the time of therapy and constituted 22% of all CsA-PL after 6 months of therapy. No rejections were seen later than 5 months after transplantation despite the low CsA-PL in many long-term treated patients. Treatment with high doses of methylprednisolone increased CsA-PL by 223%. Trimethoprimsulphamethoxazole in CsA-treated patients caused increases in serum creatinine levels. Monitoring of trough CsA plasma levels is recommended as a complement to clinical judgment. To avoid most nephrotoxicity and hepatotoxicity we have decided to keep the CsA-PL below 500 ng/ml during the first month, below 250 ng/ml the second month after transplantation, and below 200 ng/ml the third month after transplantation--and in long-term treated patients we now keep the CsA-PL between less than 50 and 150 ng/ml.

Adolescent↗
PubMed1985

Intravenous foscarnet for the treatment of severe cytomegalovirus infection in allograft recipients.

Foscarnet, trisodium phosphonoformate, was administered intravenously to 6 immunosuppressed patients with life-threatening cytomegalovirus infection. Three of the patients were recipients of a kidney and 3 of a bone-marrow transplant. Favourable clinical responses were seen in 5 of the patients, 2 of whom were still in good health 5 and 8 months after the infection had cleared up. No toxic effect of the drug was detected. The results seem to justify further trials, in which foscarnet should be introduced at an earlier stage of the disease.

Adult↗
PubMed1984

Interstitial fibrosis in renal allografts after 12 to 46 months of cyclosporin treatment: beneficial effect of low doses in early post-transplantation period.

To investigate whether cyclosporin (CsA) causes chronic renal damage 38 renal allograft biopsies were performed 1 to 4 years after transplantation in 28 CsA-treated patients, in the absence of rejection or acute CsA nephrotoxicity. Blind, semi-quantitative light microscopic examination showed that interstitial fibrosis plus tubular atrophy occurred more often in CsA-treated patients than in patients treated with azathioprine. The degree of interstitial fibrosis correlated with high cumulative CsA dose during the first 6 months of treatment, as well as with the number of acute CsA nephrotoxic episodes, which suggests that the findings are an effect of chronic CsA nephrotoxicity. Maintenance doses of CsA (2.3-10.7 mg/kg/day) seemed to contribute little to the renal damage. The pathogenesis of the observed lesions is not known. A high trough CsA level at the time of biopsy correlated with the degree of interstitial mononuclear cell infiltrate in the renal tissue. The results thus demonstrate chronic morphological changes in renal allografts from CsA-treated patients. Avoiding high CsA doses may be a way of preventing this side-effect. Until this has been confirmed, the risk of chronic renal damage must be taken into consideration when new clinical trials of CsA are being planned.

Acute Disease↗
PubMed1984

Deterioration in glucose metabolism in pancreatic transplant recipients after conversion from azathioprine to cyclosporine.

Six recipients of combined pancreas and kidney transplants displayed a deterioration in glucose tolerance when the immunosuppressive therapy was changed from azathioprine-prednisolone to cyclosporine-prednisolone. Because at the same time the plasma C-peptide level increased it seems that insulin resistance, rather than reduced insulin secretion, caused the impairment in glucose tolerance. The condition was found to be reversible.

Adult↗
PubMed1984

Optimal cyclosporine plasma levels decline with time of therapy.

To avoid nephrotoxicity and hepatotoxicity the CsA-PL should be kept at less than 500 ng/mL during the first month after transplantation and less than 200 ng/mL after four months. After ten months most patients in this study had a CsA-PL of less than 150 ng/mL and many had levels of less than 50 ng/mL with an apparently good immunosuppressive effect. Rejections showed no correlation with high or low CsA-PL. Continuous monitoring of CsA-PL is recommended for the management of renal allograft recipients.

Adolescent↗