[Insulinoma with hyperproinsulinemia: a two cases report]. / Insulinome à proinsuline.

We report two cases of insulinoma with increased serum proinsulin levels and with normal insulin levels.Clinically, the two patients show typical symptoms of insulinoma, but serum insulin levels are normal. Only high levels of serum proinsulin allow us to retain the diagnosis of insulinoma. The new insulin assays using monoclonal antibodies are very specific for insulin and though can not detect isolated high proinsulin levels. So proinsulin assay is useful when diagnosing insulinoma.

[Complete supernumerary breast on the thigh in a male patient]. / Sein surnuméraire complet de la cuisse chez un homme.

BACKGROUND: Supernumerary nipples are not rare but the developement of a complete supernumerary breast is exceptional. CASE REPORT: A 59-year-old man presented a progressively increasing ancient right- groin-masse. The histopathologic examination of the lesion confirmed the diagnostic of polymastia. DISCUSSION: The interest of this observation results from the very unusual occurence of polymastia (less than 1 p. 100 of supernumerary nipples), especially for a caucasian man. The prevalence appears to be higher in women and oriental people. Diagnostic of supernumerary nipple is difficult because of its atypical appearance and ectopic location. However, this diagnostic is important because ectopic breast tissue is subject to the same pathologic changes that occur in normally positioned breasts and it can be a marker for associated diseases such as urologic malformations or urogenital malignancies.

Macrophage activation in type 1 diabetic patients with catheter obstruction during peritoneal insulin delivery with an implantable pump.

OBJECTIVE: The purpose of this study was to evaluate the activation of macrophages in type 1 diabetic patients during peritoneal insulin delivery with an implantable pump against two types of insulin: that which was collected from the pump reservoir and that which came straight fromn the bottle (i.e., vial insltlin). Macrophage activation was studied in patients with and without cathcter obstruction and compared with activation in healthy subjects. RESEARCH DESIGN AND METHODS: Human insulin (21 PH, 400 U/ml; Hoescht) was collected from the pump reservoir (Minimed) of diabetic patients with (n = 3) or without (n = 7) catheter obstruction, as assessed by histological examination of the catheter tip. Monocytes were obtained from venous blood samples from both kinds of diabetic patients and from healthy subjects (n = 5) and were differentiated into monocyte-derived macrophages in culture. Their chemotaxis and tumor necrosis factor-alpha (TNF-alpha) release were studied with respect to both types of insulin, as previously stated. Formyl-methionyl-leucyl-phenylalanine (fMLP) and lipopolysaccharide (LPS) were used as controls. RESULTS: Neither insulin recovered from the pump reservoir nor vial insulin proved chemotactic to macrophages from either healthy subjects or those diabetic patients with and without catheter obstruction. The migration toward fMLP of macrophages from patients presenting a catheter obstruction was significantly higher than that observed with macrophages from either diabetic patients without obstruction or healthy subjects, the chemotactic index (mean +/- SD) was 3.81 +/- 0.36 vs. 2.30 +/- 0.89 and 2.60 +/- 0.80, respectively (P < 0.05). LPS significantly stimulated the TNF-alpha secretion of macrophages from diabetic subjects with a catheter obstruction, whereas both native and reservoir-recovered insulin had no effect on this release (144.83 +/- 67.25 vs. 5.15 +/- 2.93 and 5.27 +/- 2.43 pg/ml, P < 0.001). CONCLUSIONS: The human insulin used in implantable pumps, regardless of how long it had remained in the pump reservoir, did not induce macrophage activation in diabetic patients treated through intraperitoneal insulin delivery. In some of these diabetic patients, catheter obstruction could be explained by their high capacity of macrophage chemotaxis.

p53 gene mutation pattern in rat liver tumors induced by vinyl chloride.

Vinyl chloride (VC) induces angiosarcomas of the liver (ASL) and hepatocellular carcinomas (HCCs) in humans and rodents. We examined the presence of p53 gene mutations in ASL and HCC induced by VC in Sprague Dawley rats; 25 ASL and eight HCCs were analyzed for point mutations in exons 5-8, using PCR amplification, single-strand conformation polymorphism analysis, and direct DNA sequencing. Mutations were found in 11 (44%) of the ASL and in 1 HCC. A 12-base pair deletion was found in one tumor; all others were base pair substitutions. Nine of the point mutations were observed at A:T base pairs (5 A:T --> T:A; 2 A:T --> G:C, and 2 A:T --> C:G), and of three G:C --> A:T transitions, only one was at a CpG site. In ASL, four mutations were found in exon 5, two in exon 6, and six in exon 7; the base pair substitution found in one HCC was in exon 8. One ASL exhibited two point mutations, including a silent one. Two ASL exhibited the same mutation in codon 203 and two other samples in codon 253. Codon 235 was found to be mutated in three ASL. These data show that p53 is often mutated in ASL induced by VC in rats and, as observed in ASL in humans exposed to VC, the majority of the missense mutations involved A:T base pairs. The characteristic patterns of mutations found suggest that a common mechanism operates in VC-induced p53 mutagenesis in both species, and these mutations are consistent with the formation of DNA etheno adducts by VC in the liver. The A:T --> T:A transversion observed in the first nucleotide of codon 253 in two rat ASL is equivalent to the A:T --> T:A transversion characterized previously in codon 255 in one human ASL associated with VC exposure.

[Granulosis rubra nasi and pheochromocytoma]. / Granulosis rubra nasi et phéochromocytome.

INTRODUCTION: Granulosis rubra nasi, a papular red lesion of the nose associated with hypersudation is an uncommon dermatosis usually seen in children. CASE REPORT: A noradrenalin secreting pheochromocytoma was found in 19-year-old girl with hyperhidrosis, granulosis rubra nasi and tachycardia. Surgical exeresis of the pheochromocytoma was followed by involution of the hyperhidrosis, regression of the nasal dermatosis and normalization of urinary catecholamines. DISCUSSION: The diagnosis of pheochromocytoma should be entertained in patients with hypersudation and tachycardia. Granulosis rubra nasi could be a complication of hyperhidrosis.

Mutagenesis of ras proto-oncogenes in rat liver tumors induced by vinyl chloride.

Vinyl chloride is a DNA-damaging carcinogen which induces liver angiosarcomas in humans and animals. Activation of the Ki-ras 2 gene by a GC-->AT transition at the second base of codon 13 in human liver angiosarcomas associated with occupational exposure to vinyl chloride has been reported recently. In order to compare the molecular pathways of carcinogenesis in humans and animals, Sprague-Dawley rats were exposed to vinyl chloride and hepatic tumors, including two hepatocellular carcinomas and five liver angiosarcomas, were investigated for mutations at codons 12, 13 and 61 of the Ha-ras, Ki-ras and N-ras genes. High molecular weight DNA was amplified by the polymerase chain reaction and point mutations were analyzed by allele specific oligonucleotide hybridization, direct sequencing of polymerase chain reaction products and sequencing after cloning. None of the tumors exhibited a mutation in codons 12, 13 and 61 of the Ki-ras gene, nor in codons 12 of the Ha-ras gene or 61 of the N-ras gene. However, an activating AT-->TA transversion at base 2 of codon 61 of the Ha-ras gene was detected in the two hepatocellular carcinomas. Mutations involving codon 13 (GGC-->GAC) and codon 36 (ATA-->CTA) of the N-ras A gene were detected in two liver angiosarcomas, suggesting that the nature of the ras gene affected by a given carcinogen depends on host factors specific to cell types. Several additional base pair substitutions were found in exon 1 of the N-ras B and C sequences. NIH 3T3 transfection assays and Southern blot analysis of DNA from transformed NIH 3T3 cells confirmed the presence of a dominant activated N-ras gene. These results emphasize the differences in the molecular pathways leading to tumors in humans and rats and within a given species between different cell types.