Body Mass Index and Glomerular Hyperfiltration in Renal Transplant Recipients: Cross-Sectional Analysis and Long-Term Impact

Obesity is a risk factor for renal graft loss. Higher body mass index (BMI) in native kidneys is associated with glomerular hyperfiltration. Whether higher BMI in renal transplants is associated with hyperfiltration is unknown. We investigated the impact of BMI on renal hemodynamics 1 year post-transplant. We analyzed glomerular filtration rate (GFR, (125)I-iothalamate) and effective renal plasma flow (ERPF, (131)I-hippurate) in 838 kidney transplants. Data were analyzed for all patients and for the subpopulation without diabetes. Long-term impact of BMI and renal hemodynamics were explored by Cox-regression. With higher BMI GFR and filtration fraction (FF) increased significantly. Multivariate analysis supported impact of BMI on GFR (adjusted r(2) of the model 0.275) and FF (adjusted r(2) of the model 0.158). This association was not explained by diabetes mellitus. On Cox-regression analysis, lower GFR and higher FF were independent determinants of overall graft loss and graft loss by patient mortality. Lower GFR and higher BMI were determinants of death-censored graft loss, with borderline contribution of higher FF. In renal transplants higher BMI is independently associated with higher GFR and FF one year posttransplant, suggesting glomerular hyperfiltration with altered afferent-efferent balance. Mechanisms underlying the long-term prognostic impact of hyperfiltration deserve further exploration.     

To what extent does IQ 'explain' socio-economic variations in function?

Background  

The aims of this study were to examine the extent to which higher intellectual abilities protect higher socio-economic groups from functional decline and to examine whether the contribution of intellectual abilities is independent of childhood deprivation and low birth weight and other socio-economic and developmental factors in early life.     

Cancer pain control by infusion techniques in the home situation in the Northern Netherlands: an innovative project on the use of medical technology in the home situation

Since 1982, 229 terminally ill cancer pain patients were treated by the administration of epidural opioids. An adequate level of aid was provided by the coordinated efforts of the patients' general practitioner, the district nurse, and the anesthesiologist. Based on 9 yr of experience with this model, a project on quality improvement and organization of cancer pain control by infusion techniques in the home situation was proposed. The purpose of the study is to create a nationwide organization for cancer pain control for terminal patients on a home-care basis. Specially trained ambulatory field teams will be set up to collect and process the information necessary to make protocols and instructions.     

Immunohistochemical localization of pepsinogen A and C containing cells in Barrett's oesophagus

Summary No data are available on the localization of Pepsinogen A (PGA=PG I) and Pepsinogen C (PGC=PG II) positive cells in Barrett's epithelium. Endoscopic biopsy specimens were taken from the columnar epithelium from 23 patients (n=93), and in addition from the cardia from eight healthy control subjects (n=38). The tissue was stained by the immunoperoxidase technique with specific anti-pepsinogen antisera, and double immunostained for PGA and PGC. In the Barrett's epithelium PGA was found in 28 out of 93 biopsy specimens (30.1%) and PGC in 55 out of 93 (59.1%). Chief cells always stained both for PGA and PGC, while clear mucous cells were often PGA– and PGC+. PGA+ and PGC+ cells were found each in 100% of the biopsy specimens with fundic type epithelium, in 21.7% and 70.7% of biopsy specimens with junctional type, in 0% and 26.1% of biopsy specimens with specialized epithelium and in 12.5% and 43.5% of biopsy specimens with mixed junctional/specialized features respectively. Dysplastic epithelium stained always negatively with both anti-pepsinogen antisera. In most control cardia biopsy specimens PGA as well as PGC were demonstrable; occasionally clear mucous glands were PGA– and PGC+.It is concluded that pepsinogen-containing cells can be accurately identified in the Barrett's epithelium; their presence seems related to the histological cell type. Identification of pepsinogen positive cells may contribute to a more accurate morphological classification of the Barrett's epithelium.Presented in part at the Annual Meeting of the American Gastroenterological Association, San Francisco, May 1986     

Differential expression of pepsinogen isozymogens in a patient with Barrett esophagus

The pepsinogen A (PGA) isozymogens in the gastric mucosa and Barrett epithelium of a female patient with Barrett esophagus were studied on different occasions during a 3-year period by electrophoretic analysis of in vivo steady-state pepsinogen in biopsies by activity staining in combination with variant specific monoclonal antibodies and of de novo synthesized pepsinogen by autoradiography. In Barrett epithelium only one (Pg3) or two (Pg3 and Pg5) primary PGA gene products were detected, whereas in gastric mucosal biopsies three (Pg3, Pg4 and Pg5) primary gene products were demonstrated on all occasions. These differences strongly suggest differential expression/activation of individual gene numbers in the PGA gene cluster in Barrett esophagus and are in line with the preneoplastic nature of this condition. The mechanism behind this deregulation is currently under investigation by cell biology and molecular genetic techniques.     

Clones producing antibodies of more than one class

Clones producing antibodies directed against oligo-D-alanine (D-ala) determinants have been demonstrated in X-irradiated recipient mice after transfer of limited numbers of spleen and thymus cells. Seven out of eighty-one recipients were found to have donor allotype clones, all of which produced IgG1 antibodies to D-ala; two of these clones also produced small quantities of IgG2a antibodies. In addition, each of the seven responder mice contained IgM antibodies to D-ala. Isoelectric focusing (IEF) patterns of anti-D-ala antibodies from each of the seven responder mice were restricted and compatible with one to three antibody types. Most of these IEF patterns were significiantly different from each other. Five mice have been used for a comparison of IgM and IgG1 combining sites by affinity and specifity measurements. In each case affinity and specificity of IgM and IgG1 antibodies were alike. No similarity was found when comparing IgM from one clone with IgG1 from another one. These data led us to conclude that a single precursor cell can give rise to a clone producing antibodies of the IgM class and different IgG subclasses all of which share combininig sites.     

A dinucleotide mutation in the endothelin-B receptor gene is associated with lethal white foal syndrome (LWFS); a horse variant of Hirschsprung disease

Lethal white foal syndrome (LWFS) is a congenital anomaly of horses characterized by a white coat colour and aganglionosis of the bowel, which is similar to Hirschsprung disease (HSCR). We decided to investigate possible mutations of the endothelin-B receptor gene ( EDNRB ) in LWFS as recent studies in mutant rodents and some patients have demonstrated EDNRB defects. First, we identified a full-length cDNA for horse EDNRB . This cDNA fragment contained a 1329 bp open reading frame which encoded 443 amino acid residues. The predicted amino acid sequence was 89, 91 and 85% identical to human, bovine and mouse as well as rat EDNRB respectively, but only 55% identical to the human, bovine and rat endothelin A receptor (EDNRA). Secondly, sequence analysis, together with allele-specific PCR and the amplification- created restriction site (ACRS) technique, revealed a dinucleotide TC-- >AG mutation, which changed isoleucine to lysine in the predicted first transmembrane domain of the EDNRB protein. This was associated with LWFS when homozygous and with the overo phenotype when heterozygous.      

Prevention of immunoglobulin production by allotype-dependent T cells.

Adoptive lymphocyte transfers between Iga, Igb and Igd allotype-congenic mouse strains revealed host barriers against the production of certain donor allotypes. First, as recipients of Igb cells, Iga and Igd mice permitted the production of donor Ig-4b but not that of Ig-1 b. The apparent mediators of this Ig-1 b barrier were T cells specific for Ig- 1 b determinants on B cells. Additional cell transfers showed Iga mice to have a second barrier against allotype production by Igd donor cells. Reciprocal cell transfers showed Igb and Igd mice to have comparatively weak barriers against Iga-producing cells. As host barriers were absent in mice deficient for T cells (athymic nude mice), it appears that they are T cell-mediated. Further, the allotype-dependence of such barriers means that the antigens responsible must be under the control of allotype-linked genes. The regulatory implications of this for the immune system are discussed.