Interstitial nephritis associated with perianeurysmal retroperitoneal fibrosis.

Renal failure in retroperitoneal fibrosis is usually secondary to ureteric obstruction. We report a patient whose renal failure did not improve following relief of obstruction. Renal biopsy showed an interstitial nephritis, and function improved with steroid therapy. We suggest that renal biopsy should be considered in cases of renal failure associated with retroperitoneal fibrosis that do not respond to the relief of ureteric obstruction.

Effects of type 2 cytokines on glomerular epithelial cells.

Visceral glomerular epithelial cells (GECs) are involved in the maintenance of the filtration barrier and may play a role in immune responses. Cytokines may act on GECs and we wished to test this in vitro. Vascular endothelial growth factor (VEGF) is a specific product of the GEC that may play a role in glomerular permeability. We have investigated whether GECs in culture express receptors for interleukin (IL)-4, 10 and 13 (often grouped together as type 2 cytokines) and whether these cytokines alter GEC VEGF production. Type 2 cytokines were compared to transforming growth factor-beta (TGF-beta) and IL-1beta which are known to upregulate VEGF production. GECs were grown from human nephrectomy specimens and cultured with and without the addition of exogenous cytokines. Messenger RNA data demonstrated the presence of IL-4 receptor alpha, IL-10 receptor 1 and 2, and IL-13 receptors alpha1 and alpha2. However, at the protein level by flow cytometry, only IL-13 alpha2 could be consistently demonstrated. IL-4, IL-10 and IL-13 inhibited production of VEGF but did not affect the pattern of isoform expression. In contrast, TBF-beta and IL-1beta caused an increase in VEGF production. These effects were not explained by effects on proliferation. Our data provide evidence that GECs express receptors for type 2 cytokines and that these cytokines can act directly on GECs, to decrease VEGF production.

Dinucleotide repeat polymorphisms within the Flt-1 gene in minimal change nephropathy.

Dysregulation of Flt-1, a major receptor for vascular permeability factor (VPF), may provide a mechanism for the development of proteinuria in minimal change nephropathy (MCN). The gene for Flt-1 has a polymorphic dinucleotide repeat. We have demonstrated an 88% predominance of one allele and an 80% rate of homozygosity for this polymorphism with no association with MCN.

Interleukin-4 and interleukin-4 receptor polymorphisms in minimal change nephropathy.

Minimal change nephropathy (MCN) is an important cause of nephrotic syndrome, especially in children, that is strongly associated with atopy and IgE production. The immunogenetics of MCN are poorly understood. Interleukin-4 (IL-4) is the critical cytokine involved in the development of atopy. Polymorphic regions in the genes encoding IL-4 itself and the IL-4 receptor have been demonstrated that may predispose to increased activity. We have analysed these polymorphisms in 149 patients with MCN and 73 controls to test the hypothesis that these loci are involved in genetic predisposition to MCN. In our populations there were no polymorphisms in the IL-4 promoter. We did confirm allelic variation in a dinucleotide repeat in the second intron of the IL-4 gene, but there was no significant difference between allele distributions in MCN and controls. Similarly, allele frequencies for the IL-4 receptor alpha chain polymorphism were similar in patients and controls. Genetic loci which are believed to influence IL-4 responsiveness and to predispose to atopy do not appear to be associated with susceptibility to MCN.

Serum leptin correlates with fat mass but not dietary energy intake in continuous ambulatory peritoneal dialysis patients.

OBJECTIVES: In view of previous studies demonstrating hyperleptinemia in uremic and hemodialysis patients, the aims of the present study were to determine whether serum leptin levels are elevated in peritoneal dialysis (PD) patients, to establish whether leptin is significantly removed by PD, and to elucidate the relationship of plasma leptin to body composition, dietary intake, nutritional indices, and dialysis adequacy. DESIGN: Cross-sectional analysis of PD patients and matched healthy controls. SETTING: Tertiary-care institutional dialysis center. PARTICIPANTS: The study included 49 PD patients [35 women and 14 men; median age 63 years, interquartile range (IQR) 49.5-68.5 yr; body mass index (BMI) 25.5 +/- 0.8] and 27 controls (11 men and 16 women; median age 42 years, IQR 34.8-51; BMI 27.2 +/- 0.9). For evaluation of leptin clearance, 8 patients receiving nocturnal intermittent PD were also evaluated. MAIN OUTCOME MEASURES: The primary outcome measure was plasma leptin concentration. Dialysate leptin concentration was also measured in 7 patients. RESULTS: Serum leptin levels were significantly higher (p < 0.01) in patients (males: median 11 ng/mL, IQR 9-19 ng/mL; females: 53 ng/mL, 19.5-128 ng/mL) compared with controls (males: 5.5 ng/mL, 4-9.5 ng/mL; females: 12 ng/mL, 9.8-17.3 ng/mL). Leptin levels in both groups correlated positively with BMI (r = 0.64 and 0.60, respectively; p < 0.0001) and with percentage body fat determined by dual-energy x-ray absorptiometry (r = 0.86 and 0.82, respectively; p < 0.01). Dialysis patients exhibited a greater increase in serum leptin for any given increase in BMI. No significant correlation was observed between leptin concentration and residual renal function, dialysis adequacy (Kt/V), dietary protein or caloric intake, or serum levels of albumin, prealbumin, C-reactive protein, glucose, and insulin-like growth factor-I. Although leptin was detectable in peritoneal dialysate after a 6-hour dwell (median 4.2 ng/mL, IQR 1.1-8.5 ng/mL, n = 8), serum leptin levels were not appreciably lowered following intermittent PD via an automated cycler (63.9 +/- 19.3 ng/mL vs 57.6 +/- 20.5 ng/mL, p = NS, n = 8). CONCLUSIONS: Serum leptin levels are elevated in PD patients and are not appreciably cleared by PD. Although hyperleptinemia correlates poorly with dialysis adequacy and protein intake, a strong and significant relationship was maintained between serum leptin and fat mass. Serum leptin could therefore serve as a useful clinical marker of body fat content in PD patients.

Chondrolaryngoplasty for appearance.

Prominent thyroid cartilage (pomus Adamus) is frequently a constant embarrassment to the male transsexual as well as to the asthenic male. The demand for reduction and contouring of the pomus Adamus continues to increase in our societies today. Since our first presentation of this procedure, we have been able to follow 31 patients over a 17-year period. We present a review of our technique of chondrolaryngoplasty, with anatomic details and a follow-up of 31 patients ranging from 4 months to 17 years. The results are effective and satisfying, with few complications. Those which do occur tend to be transient, with the most frequent being a temporary mild voice weakness. We believe this operation has a place among the techniques of plastic surgeons.

When is there nipple involvement in carcinoma of the breast?

Two hundred cases of carcinoma of the breast were examined to determine the extent of nipple involvement. Carcinoma was present in 8 percent of the specimens. Fourteen of the 16 nipples which contained tumor were macroscopically abnormal in reappearance--being either ulcerated, retracted, or attached to an underlying indurated mass. Clinically normal niples are not likely to contain carcinoma. A frozen section across the nipple base should also be used as a safeguard if the nipple is to be used in reconstruction.