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Biomedical subjects

P Pfeffer

Publications and source records attributed to P Pfeffer.

At least 19 recordsLinked to original sources
PubMed2000

Are heart transplant recipients more likely to develop skin cancer than kidney transplant recipients?

Non-melanoma skin cancer is frequent in organ transplant recipients. The risk of posttransplant cutaneous squamous cell carcinoma in Norwegian heart transplant recipients (n = 148) and kidney transplant recipients (n = 1020) on triple immunosuppressive therapy with cyclosporine, azathioprine, and prednisolone, transplanted between 1983 and 1992, were studied. After adjustment for age at transplantation in multivariable Cox models, heart transplant recipients had a significantly 2.8-times higher risk of developing squamous cell carcinoma relative to kidney transplant recipients. The risk relative to the general population (standardized incidence ratio) was higher in heart transplant recipients than in kidney transplant recipients. The results indicate that heart transplant recipients are more likely to be diagnosed with skin cancer than kidney transplant recipients, probably due to the higher doses of cyclosporine and azathioprine after heart transplantation used at our center in the study period.

Azathioprine↗
PubMed2000

Functional equivalence of the transcription factors Pax2 and Pax5 in mouse development.

Pax2 and Pax5 arose by gene duplication at the onset of vertebrate evolution and have since diverged in their developmental expression patterns. They are expressed in different organs of the mouse embryo except for their coexpression at the midbrain-hindbrain boundary (MHB), which functions as an organizing center to control midbrain and cerebellum development. During MHB development, Pax2 expression is initiated prior to Pax5 transcription, and Pax2(-/-) embryos fail to generate the posterior midbrain and cerebellum, whereas Pax5(-/-) mice exhibit only minor patterning defects in the same brain regions. To investigate whether these contrasting phenotypes are caused by differences in the temporal expression or biochemical activity of these two transcription factors, we have generated a knock-in (ki) mouse, which expresses a Pax5 minigene under the control of the Pax2 locus. Midbrain and cerebellum development was entirely rescued in Pax2(5ki/5ki) embryos. Pax5 could furthermore completely substitute for the Pax2 function during morphogenesis of the inner ear and genital tracts, despite the fact that the Pax5 transcript of the Pax2(5ki )allele was expressed only at a fivefold lower level than the wild-type Pax2 mRNA. As a consequence, the Pax2(5ki )allele was able to rescue most but not all Pax2 mutant defects in the developing eye and kidney, both of which are known to be highly sensitive to Pax2 protein dosage. Together these data demonstrate that the transcription factors Pax2 and Pax5 have maintained equivalent biochemical functions since their divergence early in vertebrate evolution.

Alleles↗
PubMed1999

Molecular cloning and expression of the human and mouse homologues of the Drosophila dachshund gene.

Recent genetic analysis of the Drosophila dachshund (dac) gene has established that dac encodes a novel nuclear protein that is involved in both eye and leg development. In the Drosophila eye, dac expression appears to be controlled by the product of the eyeless/Pax6 gene. In order to analyze the Pax6 pathway in vertebrates we have isolated and characterized the cDNA and genomic clones corresponding to the human and mouse homologues of Drosophila dac. A full-length human cDNA encoding dachshund (DACH) encodes the 706 amino acids protein with predicted molecular weight of 73 kDa. A 109 amino acid domain located at the N-terminus of the DACH showed significant sequence and secondary structure homologies to the ski/sno oncogene products. Northern blot analysis found human DACH predominantly in adult kidney, heart, and placenta, with less expression detected in the brain, lung, skeletal muscle and pancreas. A panel of human cell lines was studied and most notably a large proportion of neuroblastomas expressed DACH mRNA. Mouse Dach encodes a protein of 751 amino acids with predicted molecular weight of 78 kDa that is 95% identical to the human DACH. RNase protection analysis showed the highest Dach mRNA expression in the adult mouse kidney and lung, whereas lower expression was detected in the brain and testis. RT/PCR analysis readily detected Dach mRNA in the adult mouse cornea and retina. Dach mRNA expression in the mouse E11.5 embryo was observed primarily in the fore and hind limbs, as well as in the somites.

Adult↗
PubMed1999

Skin cancer in kidney and heart transplant recipients and different long-term immunosuppressive therapy regimens.

BACKGROUND: Nonmelanoma skin cancer occurs frequently in organ transplant recipients, but the relative importance of different immunosuppressive therapy regimens is unclear. OBJECTIVE: We studied the risk of skin cancer in the complete, single-center Norwegian cohort of kidney and heart transplant recipients (n = 2561). METHODS: We determined cancer risk estimation by means of standardized incidence ratios and multivariate Cox regression. RESULTS: Transplant recipients had an increased risk of cutaneous squamous cell carcinoma (SCC) (65-fold), malignant melanoma (3-fold), and Kaposi's sarcoma (84-fold), and of lip SCC (20-fold), compared with the general population. After adjustment for age, kidney transplant recipients receiving cyclosporine, azathioprine, and prednisolone had a significantly (2.8 times) higher risk of cutaneous SCC relative to those receiving azathioprine and prednisolone. After adjustment for age and type of immunosuppressive regimen, heart transplant recipients had a significantly (2.9 times) higher risk than kidney transplant recipients. CONCLUSION: The risk of cutaneous SCC, malignant melanoma, Kaposi's sarcoma, and lip SCC is increased in kidney and heart transplant recipients. The risk of posttransplant cutaneous SCC is related to the degree of immunosuppression caused by long-term immunosuppressive therapy.

Adolescent↗
PubMed1998

Unrelated living donors in 141 kidney transplantations: a one-center study.

BACKGROUND: Kidney transplantation is the optimal treatment for the majority of patients with end-stage renal disease. However, the shortage of kidneys for transplantation is a global problem, and any attempt to improve the donor situation would be of benefit to the growing number of patients on transplant waiting lists. PATIENTS AND METHODS: Since 1984, we have transplanted 141 kidneys from genetically unrelated living donors. Donors were most often spouses and were accepted regardless of HLA match grade. Preemptive transplantation was performed in 39% of the patients. Standard triple-drug immunosuppression with prednisolone, cyclosporine, and azathioprine was used. The patients were followed from 6 months to 13 years. RESULTS: The incidence of acute rejection during the first 3 months after transplantation was higher in recipients of grafts from unrelated donors than in recipients of grafts from related living donors or cadaveric donors. However, unrelated living donor grafts survived significantly better than did cadaveric grafts (P < 0.02) and had a survival rate similar to that of living-related donor grafts mismatched for one or both HLA haplotypes. The perioperative complication rate for the donor was low. CONCLUSION: We consider unrelated living donors an excellent source for alleviating the shortage of donor kidneys.

Adult↗
PubMed1998

The national kidney transplant program in Norway still results in unchanged waiting lists.

1. Of 2,670 patients starting renal replacement therapy for end-stage renal disease in Norway from 1989-1997, 76% were candidates for transplantation. The annual need for transplantations increased from 47 to 64 grafts PMP as the number of elderly patients increased. The national waiting list has remained almost stable during the period from 1989-1997 at levels of 25-30 PMP, but the dialysis population has increased from 57-105 PMP. 2. A total of 1,681 transplants was performed at an annual rate varying between 38 and 46 grafts PMP. The grafts were procured from LDs in 41% and CDs in 59% of cases. Totally 69% of all patients in need were transplanted and 54% of all patients requiring replacement therapy for end-stage renal disease received a transplant. 3. Graft survival rates in recipients of first LD grafts (n = 641) were 91% and 77% at one and 5 years, respectively. One-year graft survival was 97% in HLA-identical grafts (n = 71), 92% in haploidentical grafts (n = 419), 88% in 2 haplotype-mismatched related grafts (n = 43), and 87% in spousal donor grafts (n = 108). 4. Graft survival rates in recipients of first CD grafts (n = 801) were 84% and 65% at one and 5 years, respectively. The rates were 86% and 74% in younger (n = 557) versus 78% and 46% in older (> 65 years) (n = 244) patients. Death with a functioning graft caused approximately 45% and 75% of all graft losses in younger and older patients, respectively. Cardiovascular disease was the major cause of death. 5. A significant beneficial effect of HLA-DR matching was observed in CD grafts performed after 1989, in particular in patients older than age 65.

Adolescent↗
PubMed1997

[Scintigraphic localization of ectopic parathyroid tissue].

Ectopic parathyroid adenomas and hyperplastic glands are difficult to locate during surgical exploration. Failure to find and remove them is the most usual cause of surgical failure in the treatment of hyperparathyroidism. Earlier methods of preoperative localization of pathological parathyroid tissue had low sensitivity and were not generally recommended. Recent advances in parathyroid scintigraphy have improved this technique; the sensitivity is now as high as 95% for parathyroid adenomas. In the present study, ectopic parathyroid adenomas and hyperplasia were correctly localized by scintigraphy and were verified surgically in seven patients. Six of the patients had previously undergone ten unsuccessful operations altogether. Preoperative parathyroid scintigraphy might have saved these failed surgical explorations. In a pregnant woman, a mediastinal parathyroid adenoma was correctly localized by preoperative parathyroid scintigraphy. This patient was successfully operated by a sternotomy, and she was the only one of five patients with a mediastinal parathyroid adenoma who escaped unnecessary neck exploration. Preoperative parathyroid scintigraphy may reduce the number of surgical failures in hyperparathyroidism and shorten the operation time by less extensive exploration and thus fewer complications.

Adenoma↗
PubMed1996

Deregulation of PAX-5 by translocation of the Emu enhancer of the IgH locus adjacent to two alternative PAX-5 promoters in a diffuse large-cell lymphoma.

Analyses of the human PAX-5 locus and of the 5' region of the mouse Pax-5 gene revealed that transcription from two distinct promoters results in splicing of two alternative 5' exons to the common coding sequences of exons 2-10. Transcription from the upstream promoter initiates downstream of a TATA box and occurs predominantly in B-lymphocytes, whereas the TATA-less downstream promoter is active in all Pax-5-expressing tissues. The human PAX-5 gene is located on chromosome 9 in region p13, which is involved in t(9;14)(pl3;q32) translocations recurring in small lymphocytic lymphomas of the plasmacytoid subtype and in derived large-cell lymphomas. A previous molecular analysis of a t(9;14) breakpoint from a diffuse large-cell lymphoma (KIS-1) demonstrated that the immunoglobulin heavy-chain (IgH) locus on 14q32 was juxtaposed to chromosome 9p13 sequences of unknown function [Ohno, H., Furukawa, T., Fukuhara, S., Zong, S. Q., Kamesaki, H., Shows, T. B., Le Beau, M. M., McKeithan, T. W., Kawakami, T. & Honjo, T. (1990) Proc. Natl. Acad. Sci. USA 87,628-632]. Here we show that the KIS-1 translocation breakpoint is located 1807 base pairs upstream of exon 1A of PAX-5, thus bringing the potent Emu enhancer of the IgH gene into close proximity of the PAX-5 promoters. These data suggest that deregulation of PAX-5 gene transcription by the t(9;14)(pl3;q32) translocation contributes to the pathogenesis of small lymphocytic lymphomas with plasmacytoid differentiation.

Amino Acid Sequence↗
PubMed1996

Five-level k

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Journal Article↗
PubMed1995

[Pancreas transplantation. A 10-year material].

A programme for pancreas transplantation was initiated in Oslo in 1983. Of a total of 100 transplants so far, 14 were performed as pancreas transplantation alone (PTA) in non-uremic diabetics (n = 9), or as pancreas after kidney (PAK), i.e. in diabetic patients with a functioning renal transplant (n = 5). Duct occluded segmental grafts were used until 1988, when the pancreaticoduodenal technique with bladder drainage was introduced. Since 1991, owing to a low graft survival rate in PAK and PTA cases, all pancreas transplantations have been performed simultaneously with a renal transplant, giving a one-year survival of 82%, 83% and 93% for kidney, pancreas and patient respectively. The authors give a brief overview of the experience gained during ten years, with a pancreas transplant rate of ten/year.

Adult↗
PubMed1993

Aortoiliac reconstruction in preparation for renal transplantation.

Aortoiliac angiography has always been an integral part of the pretransplantation work-up of renal transplant candidates in Norway. The present study was undertaken to investigate the value of this routine. Based on the angiograms of approximately 1400 patients evaluated for renal transplantation during the 7-year period 1984-1991, 26 were found to have aortic and/or iliac atherosclerosis requiring pretransplant vascular reconstruction. Fifteen of the 26 patients had aneurysm of the abdominal aorta and 11 had extensive aortoiliac occlusive disease. A prosthetic graft was inserted in 25 patients and endarterectomy of the aortic bifurcation was performed in one. The cause of death was coronary heart disease in four of six patients who died before, and in one patient who died after, transplantation. Sixteen patients received a renal transplant while four patients are still on the waiting list. Fifteen of the recipients are alive, 14 with functioning renal transplants. The low yield of patients below 40 years of age requiring vascular reconstruction calls into question the routine use of angiographic investigation of renal transplant candidates below this age. However, we recommend this routine for the higher age groups because it often provides the surgeon performing the transplantation with valuable information. Aortoiliac reconstruction as preparation for renal transplantation is advocated when atherosclerosis of a degree that may preclude transplantation is found. Because of the high risk of myocardial infarction in these patients, one must be especially aware of coronary atherosclerosis when evaluating patients for this procedure.

Adult↗