Does body growth impair immune function in a large herbivore?

According to the principle of allocation, trade-offs are inevitable when resources allocated to one biological function are no longer available for other functions. Growth, and to a lesser extent, immunity are energetically costly functions that may compete with allocation to reproductive success and survival. However, whether high allocation to growth impairs immune system development during the growing period or immune system performance during adulthood is currently unknown in wild mammals. Using three roe deer (Capreolus capreolus) populations experiencing contrasting environmental conditions, we tested for potential costs of growth on immune phenotype over both the short-term (during growth), and the long-term (during adulthood) over the course of an individuals' life. We investigated potential costs on a set of 12 immune traits that reflect both innate and adaptive responses, and compared them between sexes and populations. Although fast growth tended to be associated with low levels of some humoral traits (globulins) during the growing period and some cellular immune traits (i.e. eosinophil and neutrophil counts) during adulthood, evidence for a trade-off between growth and other immune components was limited. Unexpectedly, no detectable growth costs on immunity were found in females from the population experiencing the least favourable environment. We discuss our findings in the light of the complex interplay between resource allocation strategies among reproduction, maintenance and immunity, in relation to local environmental conditions experienced by roe deer.

Cervical cancer screening in France.

In France, as in other European countries the incidence and mortality rates of carcinoma of the cervix uteri indicate a clear decrease in invasive cancers. Opportunistic screening has spread and, presently, approximately 60% of the female population undergo a regular cytological test. This rate increases up to 80% in the younger age groups and decreases to 20% after the age of 60 years. In 1990, intervention procedures were defined at a consensus conference; the major recommendations were to screen all women exclusively by cervical smears, for ages 25-65 years over a 3-year period. Guidelines on the quality control of cervical smear taking and reading were published by the national agency of evaluation of health intervention (ANAES). Since 1990, four population-based, organised pilot programmes, have been implemented in Isère. Doubs, Bas-Rhin and Martinique. These programmes evaluate the participation rate (from approximately 20-80% depending upon the age and the geographical area), the rate of abnormal tests (0.2-3%), according to the laboratories, the cancer detection rate (0.04%-0.15%) and some other quality indicators. Recently (November 1998) a law was passed stipulating that the screening test will be free of charge when performed in agreement with the national recommendations. A specific organisation for cytological quality control will be implemented. An effort to better identify and to include the screening process the women in the population who are not yet participating has to be made.

Effects of cyclosporin A on the course of murine alveolar echinococcosis and on specific cellular and humoral immune responses against Echinococcus multilocularis.

The effects of cyclosporin A (CsA) on Echinococcus multilocularis (E. multilocularis) metacestode growth, and on the specific immune responses of the hosts, were examined in AKR mice. Mice were intra-peritoneally infected with a metacestode homogenate. CsA (40 mg kg(-1) day(-1)) was injected subcutaneously from the 45th day after infection (Group 1), and from the day before infection (Group 2) until the day of autopsy (days 125 and 80, respectively). Results showed that unlike ths situation with some other helminthiases, CsA had no antiparasitic effect, although it lengthened the maturation time of protoscoleces in Group 1. The parasitic burden, unmodified in Group 1, was significantly enhanced in Group 2. This enhancement was associated with a decrease in antibody levels, whereas the delayed-type hypersensitivity was decreased in the two groups. These results confirm the role of cellular immunity in controlling the first stages of the larval development of E. multilocularis and indicate the necessity for a careful follow-up of any recurrence of alveolar echinococcosis in patients treated with CsA after liver transplantation.

T cell-depleted allogeneic bone marrow transplantation in a case of childhood idiopathic myelofibrosis.

An 11-year-old boy developed primary myelofibrosis. Nine months after diagnosis he received high-dose chemoradiotherapy followed by T cell-depleted allogeneic bone marrow transplantation as primary therapy. Sixteen months after grafting the patient is well, with reversal of the marrow sclerosis and no evidence of chronic graft-versus-host disease.

Evaluation of Biohit HPV Screening and Typing kits in detection of human papillomavirus DNA from lesions of anogenital tract.

The Biohit HPV Screening and Typing kits for in situ hybridization of human papillomavirus (HPV) DNA are now commercially available. The HPV Screening kit contains a cocktail of HPV probes, and the Typing kit contains separated hybridization probes for HPV 6, 11, 16, 18, 31, and 33. They were evaluated by comparison with an in situ hybridization (ISH) method, using the Pathogene HPV probes 6/11, 16/18, 31/33/51. One hundred anogenital biopsies from 78 women and 22 men were tested. Among them, 43% showed normal or inflammatory mucosa, 44%, koilocytosis or mild dysplasia, and 13%, moderate to severe dysplasia. Altogether, 60 specimens were positive with the ISH reference method: 17 with the HPV 6/11 probe, 12 with the HPV 16/18 probe, 16 with the HPV 31/33/51 probe, and 15 had mixed infections. The agreement between the Screening test and the homemade ISH is 91%. The Screening test has a sensitivity of 93% and a specificity of 87%. As for the Biohit Typing test, four false-negative samples, and partial or total discordance in nine and four samples, respectively, were observed when compared to our reference method. Thus the agreement between both typing ISH tests is 92%. The sensitivity of the Biohit Typing test is 93%, and the specificity, 91%. The sensitivity decreases to 72% when the 31 and 33 probes are evaluated separately. The Biohit Screening assay is simple, reliable, reproducible, and suitable for rapid routine screening. The Biohit Typing test allows the detection of a specific type of HPV DNA and also permits, in mixed HPV infection, definition of the type of associated HPV DNA.(ABSTRACT TRUNCATED AT 250 WORDS)

Genital human papillomavirus infection among women recruited for routine cervical cancer screening or for colposcopy determined by Hybrid Capture II and polymerase chain reaction.

The purpose of this study was to evaluate the clinical use of the Hybrid Capture (HC)-II system for the detection of human papillomavirus (HPV) DNA to identify women at risk of progression to high grade squamous intraepithelial lesions (HGSIL) and carcinomas by differentiating low risk (LR) HPV types (6, 11, 42, 43, 44) and high/intermediate risk (HR) HPV types (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68). Five hundred and ninety-six women were enrolled in the study. Among them, 466 attended the hospital for routine cytologic screening and 130 were referred for colposcopy because of an abnormal Pap smear. The presence of HPV DNA was tested in cervical samples collected with the Digene Cervical Sampler in Digene Specimen Transport Medium (Digene Corporation, Silver Spring, MD, U.S.A.) using the HC-II assay. Results were compared with those obtained by polymerase chain reaction (PCR) using the MY09-MY11 primers followed by several hybridizations with specific probes. The overall HPV positivity was 32.9% by HC-II and 37.8% by PCR. Among cytologically normal smears, 19.5% were positive by HC-II (14.3% HR) and 25.1% by PCR. Of the atypical squamous cells of undetermined significance samples, 52.9% were positive by HC-II (41.1% HR) and 55.9% by PCR. Of the low grade SIL, 64.5% were positive by HC-II (59.4% HR) and 68.7% by PCR. The HPV positivity rate was found identical by both techniques in high grade smears (81.6%) and squamous cervical carcinomas (100%). By using PCR as the reference method, the sensitivity of HC-II was higher among women with abnormal cytology than with normal cytology (87.3% vs. 70%). Specificity was 80.8% and 97.5%, respectively. In summary, these results indicate that the HC-II method and MY-PCR identified nearly equivalent prevalences of HPV in cervical smear specimens.

Pattern of chromosomal imbalances in non-B virus related hepatocellular carcinoma detected by comparative genomic hybridization.

Only limited data are available on comparative genomic hybridization (CGH) in hepatocellular carcinoma (HCC). They concern mainly B virus related HCC. Therefore, we used CGH to detect chromosomal imbalances in 16 non-B virus related HCC in alcoholic cirrhosis in 7 cases (HA1 to HA7), in C virus cirrhosis in 7 cases (HC1 to HC7), in non-cirrhotic liver in 2 cases (NC1, NC2), and in 9 non-malignant cirrhotic tissues. The most frequent imbalances in HCC were gains of whole chromosomes or chromosomal regions 7 or 7q (10/16, 62%), 1q (9/16, 56%), 5 or 5q (9/16, 56%), 8q (8/16, 50%), 6p (6/16, 37%), 15q (5/16, 31%), 20 or 20q (5/16, 31%), and losses of 17p (6/16, 37%), and 8p (5/16, 31%). High-level gains were identified in HCC on 1q (2/16), 3q (1/16), 7q (1/16), and 8q (3/16). No chromosomal imbalances were detected in any of the cirrhotic tissues. Most of the gains, losses, and amplifications detected in this CGH study corresponded well to those identified in previous studies, except for gains of whole chromosome 5 or 7 and/or of chromosome arms 5q or 7q and losses on 4q. Our results suggest that other chromosomal regions are involved in hepatocarcinogenesis.

Influence of cigarette smoking on P53 gene mutations in bladder carcinomas.

BACKGROUND: The aim of this study was to analyse the influence of cigarette smoking on bladder carcinomas. PATIENTS AND METHODS: 98 cases of bladder cancers were examined by single strand conformation polymorphism analysis of exons 5 to 9, followed by DNA direct sequencing. RESULTS: The incidence of p53 gene mutations was not significantly influenced by habitual smoking. However, the p53 mutation spectrum of current smokers differed significantly from the pattern for non-smokers and ex-smokers. Differences between the two populations included multiple mutations in the current-smokers and an absence in non- and ex-smokers (p<0.01), with the predominance of G:C to A:T transitions at CpG sites in non-smokers (60.0%) in comparison with current smokers (7.6%) (p<0.02). Moreover, G:C to T:A and G:C to C:G transversions were found solely in current smokers. CONCLUSION: It would appear that, in current-smokers, the spectrum of p53 gene mutations is related to tobacco-smoke carcinogens and that the habit of smoking increases the extent of DNA damage.

Treatment of mild chronic hepatitis C with interferon alpha-2b: results of a multi-centre randomized study in 80 patients.

OBJECTIVE: The natural history of mild chronic hepatitis C is not well-known and the benefit of treating this form of the disease is not well-defined. We conducted a pilot study to answer this question. DESIGN: Mild chronic hepatitis C was defined by positivity for anti-HCV antibodies, detectable serum HCV RNA by PCR, and a Knodell score < or = 5 on a liver biopsy performed within the previous 6 months. Eighty patients from six centres were randomized into two groups receiving interferon alpha-2b, 3 MU three times a week for 6 months (group 1, n = 39) or no treatment (group 2, n = 41). Sustained response was defined by the loss of detectable serum HCV RNA at 6 months after therapy. RESULTS: The two groups were not different at entry with respect to age, sex ratio, source of infection, disease duration, genotype, viral load and Knodell score. One patient (group 1) was excluded from the study, while two patients in group 1 (5%) and seven in group 2 (17.1 %) did not complete the trial. A sustained response was observed in seven patients (18%) in group 1 versus none in group 2 (P < 0.01). The difference in mean Knodell score remained non-statistically significant between the two groups at the end of the study. Reduction or interruption of interferon was necessary in eight patients (24.2%). CONCLUSIONS: This first randomized controlled study in mild chronic hepatitis C shows a proportion of sustained responders to interferon alpha-2b similar to that observed in active chronic hepatitis C.

[News from the French cancer registry of Doubs (author's transl)]. / Registre des tumeurs du Doubs: application pratique.

Cancer Registry of Doubs (471 845 h, 5 260 km2), an area located in east part of France close the Swiss frontier, gave cancer rates in 1977 and 1978, for male and female, for urban and rural areas, with interesting comparisons with death in the period. Histological information was available in a percentage of 0.88, cases variable with different locations. It is possible to analyse the different histological sub types and grading among some cancer sites (gastric, large bowel, bronchus). Different modalities of treatment (surgery, radiotherapy, hormono and immunotherapy) applied to the 2 783 cases of cancer are analysed.

[Obliterative arteriopathy in chronic rejection after hepatic transplantation. Search of cytomegalovirus genome by in situ hybridization and viral antigens by immunohistochemistry]. / Artériopathie oblitérante du rejet chronique après transplantation hépatique. Recherche du génome du cytomégalovirus par hybridation in situ et des antigènes viraux par immunohistochimie.

OBJECTIVES: This study was performed to assess the role of cytomegalovirus in the parietal infection of intrahepatic arteries in the pathogenesis of obliterative arteriopathy from chronic rejection after orthotopic liver transplantation. METHODS: We studied two groups of liver transplants by in situ hybridization and immunohistochemistry: group 1, including 10 liver grafts with obliterating arteriopathy, and group 2 including 7 liver grafts without any arterial disorders. The results were correlated with clinical data (cytomegalovirus infection and acute rejection). RESULTS: By in situ hybridization, cytomegalovirus DNA was identified in the media in 70% of transplants in group 1 and 42% in group 2. Detection of immediate early and late antigens by immunohistochemistry was negative. Cytomegalovirus infections were often associated with acute rejection. CONCLUSION: These results suggest that cytomegalovirus detected in arteries is latent, and that cytomegalovirus probably does not play a role in the pathogenesis of chronic rejection obliterative arteriopathy.

[Acute cytolytic hepatitis caused by coumarin. 2 cases]. / Hépatite aiguë cytolytique à la coumarine. Deux cas.

Coumarin is a drug which is extensively used to treat lymphedema. We report two cases of acute hepatitis probably due to coumarin. Two women, 40 year and 45 year-old, were treated with 90 mg/d of coumarin for 5 months. Clinical features included jaundice, pruritus, and diarrhea. A marked increase in serum aminotransferases was observed (ALT: 30 and 100 times the upper limit of normal, respectively). Coumarin withdrawal was rapidly followed by a favorable outcome in both cases. Rechallenge in one case induced a relapse of symptoms and liver test abnormalities. Coumarin can induce acute cytolytic hepatitis.

[Hepatotoxicity of isaxonine phosphate: 4 cases of severe subacute hepatitis]. / Hépatotoxicité du phosphate d'isaxonine: quatre observations d'hépatites subaiguës sévères.

Isaxonine phosphate is known to induce acute hepatitis which in most cases is reversible after withdrawal of the drug. The authors describe 4 new cases of hepatitis which differ from those previously reported by their evolutive and pathological features. In 3 cases, the outcome was fatal within a delay of 15-40 days despite discontinuation of the drug, and was associated with hepatic encephalopathy and ascites. In the 4 cases plasma concentration of alanine- and aspartate-aminotransferases were initially increased (up to 33 X upper normal range) and decreased to normal values in 2 cases. Plasma bilirubin levels were also elevated at first and continued to increase during the first 15 days of evolution. Pathological examination of the liver showed mild necrosis, sometimes with a piecemeal or a bridging aspect, marked fibrosis infiltrated with mononuclear and neutrophil polymorphonuclear cells and a conspicuous biliary neogenesis. In these particular cases of hepatitis due to isaxonine phosphate, occurrence in women, increased serum immunoglobulin levels, presence of autoantibodies, clinical and pathological aspects resembling those observed in iproniazid hepatitis may be suggestive of an immunological, or even autoimmune, mechanism.

[Amyloid goiter. Report of two cases]. / Le goitre amyloïde. A propos de deux observations.

We report two cases of amyloid goiter which clinical appearance had evoked a neoplastic lesion. The diagnosis was made by histologic examination. The nature of the amyloid precursor, determined by immunohistochemistry, has allowed to evoke primitive amyloidosis in one case and to attribute amyloid goiter to renal insufficiency in the second case.

[Solid cell nests and thyroid pathologies. Retrospective study of 1,390 thyroids]. / <> et pathologies thyroïdiennes. Etude retrospective de 1,390 thyroïdes.

Solid Cell Nests (SCN) of the thyroid gland were considered as embryonic remnants or as squamous metaplasia of follicular epithelium. In a retrospective study of 1 390 thyroids, SCN were found in 9.7 % of thyroids (16 % men and 8 % women, chi(2) : p <0, 01). The number of SCN rises with increasing number of sections examined. No statistical differences were found with age or thyroid disorders and presence of SCN, excluding the metaplastic theory. SCN contained in 38 % of cases, neuroendocrine cells (calcitonin and/or calcitonin gene related peptide, chromogranin A) and thyroglobulin cells was observed in 78.3 % of SCN. The different cell types of SCN fitted with the ultimobranchial remnant theory. Thus, some rare carcinomas (like mixed medullary and vesicular carcinoma or mucoepidermoid carcinoma) might originate from SCN.

[Preservation of human corneas in an enriched culture medium at +37 degrees Centigrade: histological and biochemical analyses]. / Conservation des cornées humaines en milieu de culture enrichi à +37 degr'es C: analyses histologiques et biochimiques.

Using the methods of Doughman, Sperling and Pels 66 human corneas were preserved up to five weeks in a modified tissue culture medium at +37 degrees C. The organ culture medium consisted of the following ingredients: Dulbecco Iscov's medium, 2% fetal calf serum, penicillin 100 IU/ml, Streptomycin 0.5 mg/ml, and fungizone 5 mg/ml. After culture the corneal endothelium was examined by light microscopy after staining with trypan blue 0.3% and alizarin red 1%. The number of dead cells was counted and the morphological alterations were described at 7, 14, 21 and 35 days. Biochemical analysis of the medium (pH, lactate, glucose) during storage has allowed the comparison of three kinds of storage: 50 ml, 20 ml, and 20 ml with 10 ml substitution weekly. After culture the number of dead cells did not exceed 1% at each period indicating that no dead cell was present at that time. Alteration of the cell shape and formation of rosette and joint meetings of 5 to 8 cells were the dominating morphological changes of the endothelial cells. The endothelial layer was intact and coherent on to 35 days culture. Endothelial cells loses during culture were not determined. The biochemical studies have shown the better quality (pH stability, anaerobic ratio) of storage in 50 ml medium or 20 ml 50% weekly substitution medium. This last kind of storage has given the best metabolic conditions for the preserved corneas. However for long period of storage up to 3-4 weeks, renewing 50% of the medium is found appropriate. At the end of this study a clinical trial is proposed.

[Corneal cryopreservation in man: a proposal for an original technic]. / La cryoconservation cornéenne chez l'homme: proposition technique originale.

Using the method of Capella and Kaufman, the authors propose an original cryopreservation technique of human corneas. Sixty biomicroscopically normal corneas were obtained from cadavers (50-70 years) within six hours after death. Initial protocol involves four phases: 1) cryoprotection is carried out in three baths of three minutes each with human plasma and DMSO (dimethylsulfoxide) at 2-4-7%; 2) freezing is performed with 10 ml of the final cryoprotective fluid in a controlled rate freezer, the "Minicool" (CFPO). The cornea is cooled at a rate of 2 degrees C/min from + 6 degrees C down - 40 degrees C then at 5 degrees C/min down - 140 degrees C; 3) a tank containing liquid nitrogen at - 150 degrees C is used for a long term storage; 4) thawing is carried out in a water-bath at 37 degrees C for one minute, then in serum albumin 25% for three minutes and in M-K medium for thirty minutes. Effects of three cryobiological parameters are studied: cryoprotection: DMSO is diluted with human plasma at the following increasing concentrations: 2-4-7% or 4-6-10%; freezing medium: the cornea is frozen with or without the final cryoprotective bath. Thus freezing is carried out either in dry or liquid phase; thawing: initial temperature and the osmolar decrease of the dilution are modified in order to obtain four protocols: n degrees 1, initial protocol; n degree 2, an additional step using Hanks 5% - SA 25% for three minutes (1 000 mosm); n degree 3, after initial step reheating the cornea is directly placed in M-K medium; n degree 4, temperature of 50 degrees C for ten seconds precedes the initial protocol. For each protocol change, the endothelial viability is controlled by histological and/or SEM studies results: For each protocol change, the endothelial viability is controlled by histological and/or SEM studies results: cellular osmotic lesions are greater for DMSO concentrations of 10%; dry phase freezing induces more intense and more diffuse nuclear damage than in liquid phase; thawing under protocols 4 and 2 cause a high degree of nuclear damage associated with diffuse cytoplasmic vacuole formation. Histological and SEM studies clearly show endothelial cell lesions due to the cryoconservation. The human cornea endothelium is affected by any modification of the cryobiological parameters.(ABSTRACT TRUNCATED AT 400 WORDS)

[Ultrastructural study of human cornea preserved in organ culture media at +31 degrees C]. / Etude ultrastructurale des cornées humaines conservées en milieu de culture d'organe à +31 degrees C.

Organ culture becomes a standard method of corneal graft preservation. The aim of the study was to evaluate the preservation injuries induced by organ culture. We examined 12 organ cultured human corneas. Corneas were preserved in the medium for 2 to 21 days. Corneas showed some abnormalities: numerous light vacuoles, mitochondrial swelling and increased cell thickness in all cells of the cornea, sloughing of the external and medium epithelial cell layers. We observed normal endoplasmic reticulum, Golgi apparatus and nucleus. These preservation injuries are moderate and reversible.

[Value of histologic examination of the interamniotic membrane in the twin placenta for confirmation of chorionicity diagnosis]. / Intérêt de l'examen histologique de la membrane interamniotique du placenta gémellaire pour confirmation du diagnostic de chorionicité.

The interest of twin chorionocity and zygosity diagnosis is unquestioned. Indeed, in many medical situations, the knowledge of zygosity is an important fact for management of twins. Prenatal echographia is not a perfect tool to characterize chorionicity, and so postnatal examination of the placenta is always necessary. But macroscopic examination is also not relevant, and competent midwives can make many mistakes. Considering that biological postnatal diagnosis of twin zygosity is difficult and costly, we believe that microscopic chorionicity confirmation is required for identical twins.

[Participation of women in cervical cancer screening. Results of the first 5 years of a pilot program in the province of Doubs]. / Participation féminine au dépistage des cancers du col de l'utérus. Résultats des 5 premières années du programme pilote du département du Doubs.

OBJECTIVE: To analyze women participation and test results during the 1993 to 1997 screening cycle. METHODS: The program was managed by a multidisciplinary health professional committee who determined the screening policy according to the recommendations of the French consensus (Lille 1990). All smears and cervical histological tests taken from women living in the area were collected by centralizing data from cytopathological laboratories. RESULTS: Within five years, 71% of women in the 20-65 years age group had at least one smear. After the age of 29, participation rate decreased with age. The prevalence of unsatisfactory smears was 1.4/1000 and 3% of screened women had an abnormal smear (squamous intraepithelial lesion or carcinoma). A follow-up test was registered for 83% of women with an abnormal smear. Lesions were confirmed by histology in 77% of women with a histological test. CONCLUSION: In the context of initiating a national screening program, our study shows that implementing women invitation and follow-up and quality control procedures are necessary to improve the results of ongoing cervical cancer screening.