[Changes in the incidence and mortality rates of malignant melanoma in the Seine-Maritime region over a 20-year period]. / Évolution de l'incidence et de la mortalité du mélanome en Seine-Maritime sur une période de 20ans.

BACKGROUND: The aim of this study was to assess changes in the incidence and mortality rates of malignant melanoma (MM) over a 20-year period in a region without a cancer registry. METHODS: All cases of MM studied were collected retrospectively from the databases of six private and three hospital-based histopathology laboratories in the Seine-Maritime region covering three 24-month periods each 10years apart: 1988-1989, 1998-1999 and 2008-2009, The incidence and mortality rates were estimated based on data provided by French National Institute for Statistics and Economic Studies (Insee) and French National Institute of Health and Medical Research (Inserm). RESULTS: Over the 20-year period, the incidence of MM increased from 8.6 to 21.2/100,000inhabitants per year (+147%, P<0.0001) while the mortality rate rose from 1.3 to 2.8/100,000inhabitants per year (+115%, P=0.0003). The incidence of invasive MM increased by +110%, while the incidence of MM in situ increased by +456%. The incidence and overall mortality rate of invasive MM increased particularly during the first 10-year period: +62% (P<0.0001) and +77% (P=0.01) respectively, and to a much lesser extent during the last 10-year period: +30% (P=0.0007) and +22% (P=0.22) respectively. This slowdown in the incidence of invasive MM and in overall mortality rates was even more pronounced in women over the last 10years (+17 and +9%), whereas these rates continued to increase in men (+49% and +35%, respectively). In contrast, the incidence of MM in situ increased above all during this same period (+257%). CONCLUSION: This study shows that while the incidence and mortality rate of invasive MM has increased little over the last 10years in the Seine-Maritime region, the incidence of MM in situ continues to rise sharply.

[Liver lipogranulomas with log-term fever caused by paraffin oil]. / Lipogranulomes hépatiques à l'huile de paraffine responsables d'une fièvre au long cours.

In hepatic granuloma, identification of lipogranulomas generally leads to etiological diagnosis. The case reported here was granulomatosis due to mineral oil ingestion, revealed by prolonged fever. In the literature lipogranulomas are generally asymptomatic and diagnosed at autopsy.

Description of two different patients with abetalipoproteinemia: synthesis of a normal-sized apolipoprotein B-48 in intestinal organ culture.

We describe here two patients, M. P. and S. L., with recessive abetalipoproteinemia. Analysis of restriction fragments of DNA from both patients using cDNA probes spanning the entire apolipoprotein B gene revealed no major insertions or deletions. Further, as defined by restriction fragment length polymorphism, abetalipoproteinemia, in these patients, did not appear associated with particular alleles of apolipoprotein B. Northern and dot blot analysis of intestinal mRNA of one patient (M. P.) revealed a normal-sized apolipoprotein B mRNA which was present in slightly reduced amounts. At the cellular level apolipoprotein B was detected in both intestinal and hepatic biopsies, of one patient (S. L.), by immunoenzymatic techniques using polyclonal and monoclonal antibodies to apolipoprotein B-48 and/or B-100. The level of apolipoprotein B-48 appeared to increase in the intestine after a fatty meal. In the other patient (M. P.), although no apolipoprotein B was detected in the enterocytes using similar immunoenzymatic techniques, organ culture experiments using [35S]methionine demonstrated the synthesis of a normal-sized apolipoprotein B-48 which appeared to be normally glycosylated. The glycosylation and processing of two intestinal membrane enzymes, sucrase-isomaltase and aminopeptidase N, were also normal. Although lipids and apolipoprotein B-48 were present intracellularly, no lipoprotein-like particles were observed by electron microscopy in the endoplasmic reticulum, the Golgi apparatus, or in the intercellular spaces of intestinal biopsies obtained in the fasted (M. P. and S. L.) or fed state (S. L.). The defect in these cases of abetalipoproteinemia, therefore, does not appear to involve the apolipoprotein B gene nor the synthesis or the glycosylation of the apolipoprotein but instead appears to involve some aspect of lipoprotein assembly or secretion.

Selective reinnervation of the abductor and adductor muscles of the canine larynx after recurrent nerve paralysis.

Functional rehabilitation of the larynx after unilateral vocal cord paralysis was attempted in the dog by selective reinnervation of the laryngeal muscles. The intralaryngeal branches of the right recurrent nerve were dissected. The adductor branch was anastomosed with the ansa cervicalis; the abductor branch was anastomosed with the trunk of the phrenic nerve either within the larynx or through the recurrent nerve, the adductor branch of which was sectioned. Results could be analyzed in seven dogs: mobility of the vocal cord was checked, and electromyography, stimulation of the nerves, and histologic studies were performed. Functional reinnervation of both the adductor and abductor muscles was obtained in only one case, with good abduction. Adduction was recorded in five cases. False-positive results emphasize the necessity of collecting several types of data before concluding that functional reinnervation has been accomplished. The reliability of the procedure can and must be improved.

[Morphometric study of variations related to human aging in pulp unmyelinated and myelinated axons]. / Etude morphométrique des variations liées au vieillissement humain des populations d'axones amyéliniques et myéliniques pulpaires.

The evolution of myelinated and unmyelinated axon population in dental pulps during human aging was followed by electron microscopy and morphometry. A total of 2684 nerve fibers were measured in 16 subjects aged 10 to 72 years. The total distribution is bimodal with a recovering zone of 9.8% between unmyelinated and myelinated fibers. The mean diameter of A delta fibers was 1.96 mu and that of C fibers was 0.52 micron. The old pulps showed a loss of A delta fibers of small sizes (0.35-2 micron), the presence of numerous unmyelinated C fibers of very small diameters (0.1-0.25 micron) and a decrease of unmyelinated fibers of 0.5 to 1 micron comparative to young pulps. The logarithms of the diameters unmyelinated axons varied linearly with that of the subjects ages (CR = 0.63; p = 8, 8.10(-3]. The older the patients, the more the fiber C diameters were reduced. The decrease in numbers of A delta fibers could result from a local reduction of pulpal volume related to age or a response to a more general aging process of cerebral origin. The decrease in diameter of unmyelinated fibers in aging pulps would be a reduction of metabolic energy.

CCNU-adriamycin association induces earlier and more severe nephropathy in rats.

Adriamycin (ADR) has a broad spectrum of antitumoral activity but is ineffective against human brain tumors. However, such tumors can be sensitive to a combination of adriamycin and lipophilic antineoplastic agents such as the nitrosoureas. CCNU, a nitrosourea, induces cholestasis in the rat and ADR is predominantly excreted via the biliary route. We decided to investigate the effect of CCNU on the nephrotic syndrome induced by ADR. Female Wistar rats were injected with a single dose of 10 mg/kg ADR and 24 h later were force fed 20 mg/kg CCNU in a single dose. Animals were sacrificed 4, 8, 15, 21, 28 or 60 days after the injection of ADR. A high rate of fatality (60%) occurred after the 21st day of treatment. Biological changes (alkaline phosphatase, SGPT, bilirubin) and ultrastructural studies showed that CCNU and CCNU + ADR induced the same degree of cholestasis. With the administered dose, CCNU is not nephrotoxic, ADR induces a nephrotic syndrome and ADR + CCNU appeared more nephrotoxic. With ADR, visceral epithelial foot process fusion was seen on day 15 and tubulo-interstitial lesions and glomerulosclerosis on day 60. With ADR + CCNU fusion of the foot process was seen on day 4, glomerular vacuolation on day 8, tubulo-interstitial alterations on day 15 and glomerulosclerosis on day 60. For both ADR and ADR + CCNU wrinkling and thickening of the basement membrane of proximal tubular cells were seen on day 60. Lipid mesangial overload was seen with ADR and was more intense with ADR + CCNU on day 60. CCNU hepatoxicity modifies the excretion of ADR and the predominantly renal excretion of ADR seems to induce earlier renal alterations in ADR + CCNU-treated rats. This study supports the concept that lipid mesangial overload may play an important role in chronic progressive glomerulosclerosis and thus the ADR + CCNU combination appears to be an interesting model in which to study these relationships.

Renal toxicity of the antitumor drug N2-methyl-9-hydroxyellipticinium acetate in the Wistar rat.

Celiptium (N2-methyl-9-hydroxy-ellipticinium) is an antitumoral agent used to treat bone metastases from breast carcinomas. This new drug appeared to be of great interest because of the absence of hepato- or myelotoxicity. Three different investigators recently mentioned cases of celiptium-induced renal failure. We therefore undertook a study of renal function and morphology in female Wistar rats. Two single i.v. doses (10 or 20 mg/kg) were administered and animals were sacrificed 4, 8, 15, 28 and 60 days after injection. One group of rats received multiple doses, 5 mg/kg/week for 8 weeks. No mortality was observed. With the 10 mg/kg single dose creatinine clearance (Ccr) and urinary enzymes did not change, and tubular lesions were rare. With the 20 mg/kg single dose CCr decreased on day 4 and returned to normal on day 28. Urinary enzyme excretion (AAP, NAG, gamma GT) increased. Renal lesions were diffuse with tubular necrosis, luminal dilation and later (day 28) interstitial cellular infiltration. These lesions persisted on day 60 and appeared to be irreversible. Ultrastructural studies showed numerous large fat droplets in proximal tubular cells. Glycerol concentrations in renal cortex homogenates were increased while phospholipids are slightly decreased. With 5 mg/kg every week (multiple doses) Ccr decreased and tubular lesions similar to the observed with the 20 mg/kg single dose were seen. Thus celiptium induced dose-dependent nephrotoxicity in rats with prolonged tubular alterations.(ABSTRACT TRUNCATED AT 250 WORDS)

The hepatotoxicity of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) in rats. Ultrastructural evidence of a delayed microtubular toxicity.

A few cases of liver involvement have been reported in patients receiving treatment with the antineoplastic nitrosourea CCNU. A single oral dose of 20 or 50 mg/kg CCNU in female Wistar rats induced an important increase in transaminases between day 2 and day 6, followed by a second, moderate increase between day 21 and day 28. Alkaline phosphatases and conjugated hyperbilirubinemia (threefold-increase) were noted for the two doses and were greater for the highest dose. Histological and ultrastructural studies disclosed hepatic lesions of two types: during the first phase of transaminase increase, inflammation of the portal tracts; during the second phase marked dilation of bile canaliculi and numerous filamentous bundles distributed at random throughout the liver cell cytoplasm like normal microtubules. Thus, CCNU induced pericholangitis and intrahepatic cholestasis with microtubular abnormalities. The long-term evolution of hepatic alterations revealed that in the 3rd month after a single oral dose of 20 mg/kg CCNU, lesions were persistent but stable; no reversibility was observed in the 3rd month after 50 mg/kg CCNU, and evolution towards cholangiolysis and biliary cirrhosis was noted. We suggest that CCNU causes a bimodal hepatotoxicity in rats: an early and prolonged ductal injury and a delayed anti-liver cell microtubule toxicity.

[Bone lymphomas]. / Les lymphomes osseux.

Non-hodgkin's lymphomas have benefitted from recent progresses in pathology and from new classifications having a prognostic value. In reference to a case of primary osseous lymphoma, we mention their definition and main characteristics. We stress the good sensitivity of the osseous scintigraphy to detect the osseous localizations of lymphomas. These secondary osseous lymphomas have a poor prognosis. The difficulties of the pathological diagnosis are frequent, but should decrease with the wider use of immunohistochemical marking of the bone or node biopsies.

[Hepatopathy with a progressive course after one-time administration of (chloro-2-ethyl)-1-cyclohexyl-3-nitroso-1-uréa (CCNU) in rats]. / Hépatopathie d'évolution progressive après une seule administration de (chloro-2-éthyl)-1-cyclohexyl-3-nitroso-1-urée (CCNU) chez le rat.

A few cases of liver involvement have been reported in patients receiving treatment with CCNU. Nitrosourea CCNU is an antitumoral agent largely used in the treatment of some types of leukemia, Hodgkin's disease, bronchial or cerebral tumors. It was shown that CCNU induced pericholangitis and intra-hepatic cholestasis in rat: moderate after 20 mg/kg CCNU, these hepatic lesions were maximal on day 8. In the present report we were interested in the evolution of hepatic alterations a long time after cessation of drug administration. So we studied hepatic ultrastructure three months after a unique 20 mg/kg or 50 mg/kg CCNU administration. Lesions were stable after 20 mg/kg CCNU and no reversibility was observed 3 months after 50 mg/kg CCNU: evolution to cholangiolysis, to adenomatous transformation of parenchyma or biliary cirrhosis were noted.

[Acute systemic lupus erythematosus after thymectomy for myasthenia. Sequential study of lymphocyte subpopulations]. / Lupus érythémateux aigu disséminé survenu après thymectomie pour myasthénie. Etude séquentielle des sous-populations lymphocytaires.

A 35 year-old woman developed severe systemic lupus erythematosus 9 years after thymectomy for myasthenia gravis. "Seric Thymic Factor" (STF) was low; T helpers subset, T helpers/T suppressors ratio and to a lesser extent T suppressors subset were decreased. Suppressor cell function investigated by Concanavaline A lymphocyte reactivity was low. Under cyclophosphamide, plasmapheresis and steroids all clinical and biological symptoms improved but STF remained low; T helpers, T suppressors subsets and T helpers/T suppressors ratio increased but did not reach the normal range. Statistical and immunological arguments suggest that the association between systemic lupus erythematosus and myasthenia gravis did not occur only by chance. Moreover, thymectomy might have played a role by decreasing the number and function of some subpopulations of lymphocytes.

[Anorectal stenosis caused by suppositories of dextropropoxyphene and paracetamol (Diantalvic)]. / Sténose anorectale par suppositoires de dextropropoxyphène et paracétamol (Diantalvic).

Occasionally, administration of medical substances per annum may result in serious local lesions. The authors report the case of a 58 year-old woman presenting ulcerative and stenosing lesions of the anal canal which led to abdominoperineal resection. History revealed the administration of two suppositories daily, each containing an association of dextropropoxyphene and paracetamol, during seven years because of a cervical pain. Fourteen similar cases have been found in the literature, underlining the difficulties in clinical and pathological diagnosis. The exact mechanism of these lesions remains unknown.

[Hereditary visceral myopathy: an entity in idiopathic intestinal pseudo-obstruction]. / Myopathie viscérale héréditaire: une entité au sein des pseudo-obstructions intestinales idiopathiques.

A 17 year-old girl with chronic idiopathic intestinal pseudo-obstruction is reported. Abnormalities of smooth intestinal muscle were shown on light and electron microscopic studies of the excised small intestine and led to the diagnosis of visceral myopathy based on the following features: vacuolar degeneration of intestinal smooth muscle cells with replacement by fibrous preferential involvement of the external longitudinal muscle layer normal myenteric plexus. For the first time similar ultrastructural changes were found on histological study of the colon. Manometric studies revealed a diffuse disease involving the esophagus, small bowel, and bladder. Anorectal abnormalities, never described before, were reported. Family involvement was shown by abnormal esophageal and anorectal manometries in the patient's brother and by paternal history of fatal small intestine occlusion without mechanical obstruction. The prognosis of severe forms of visceral myopathy is generally poor because of the inefficiency of drugs. In this case, after a long period of parenteral nutrition with maintenance of a good nutritional status, a terminal ileostomy (with a special procedure to avoid evagination) associated with a second stage total colectomy allowed to stop parenteral nutrition.

[Morphometric analysis of human pulp myelinated fibers during aging]. / Analyse morphométrique des fibres myéliniques pulpaires humaines au cours du vieillissement.

In view of the considerable variations in contour shapes noted in transverse sections of myelinated axons from dental pulps a morphometric method involving image analysis (TAS Leitz) was used to calculate directly the surfaces of the nerves in sections of human root pulp using the Bodian stain. The sample studies consisted of 26 patients aged 10.5 to 72 years. The variation in numbers of myelinated pulpal nerves was analysed by age. Of 3606 myelinated fibres measured, 95% had a diameter less than 5 microns (A delta fibres) and about 0.5% had a diameter greater that 7 microns (A beta fibres). The mean diameter of these myelinated fibres was 2.90 microns. The statistical analysis clearly showed a difference in distribution between these fibres in young and very old subjects. The total number of pulpar myelinated fibres decreased with age particularly at the expense of a A delta fibres. The A beta fibres remained constant. This decrease of A delta fibres with age may be related to a reduced sensitivity to the perception of dental pain transmitted by these fast-conducting A delta fibres.

[Hepatotoxicity of (chloro-2-ethyl)-1-cyclohexyl-3-nitroso-1-urea (CCNU) in the rat]. / Hépatotoxicité du (chloro-2-éthyl)-1-cyclohexyl-3-nitroso-1-urée ou CCNU chez le rat.

Few cases of liver involvement have been reported in patients receiving treatment with CCNU. CCNU is an anti-tumoral agent used in the treatment of leukemia, Hodgkin's disease and bronchial or cerebral tumors. A single daily dose of 20 or 50 mg/kg CCNU in female Wistar rats induces an important increase of transaminases, reaching 10 times initial level between day 2 and day 6, followed by a second and moderate increase between day 21 and day 28. Three-fold increased alkaline phosphatases and conjugated hyperbilirubinemia were noted for the two doses, and was greater for the higher dose. Histological and ultrastructural studies showed two types of lesions: during the first phase of transaminase elevation, edema and inflammatory infiltration of the portal spaces; during the second phase of transaminases elevation, numerous bundles of pericanalicular microfilaments and severe dilation of the biliary tract. Hepatic cells had few alterations although some necrotic foci were observed, particularly at the higher dose. So CCNU induced an intrahepatic cholestasis with pericholangitis in the rat.