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Biomedical subjects

F Schaffner

Publications and source records attributed to F Schaffner.

At least 19 recordsLinked to original sources

Mapping of resistance to vegetable polyphenols among Aedes taxa (Diptera, Culicidae) on a molecular phylogeny.

To recover some evolutionary aspects of the interaction between culicine larvae and dietary polyphenols of the vegetation surrounding mosquito breeding sites, we constructed a phylogeny of the most common French Aedes species, chosen as reference species. We also evaluated the differential resistance of these larval taxa to the polyphenols of leaf litter from the riparian vegetation used as a food source. Mitochondrial DNA sequence analysis was performed among 14 different taxa and ecotypes (Aedes aegypti, Ae. albopictus, Ae. cantans, Ae. caspius, Ae. cataphylla, Ae. cinereus, Ae. detritus, Ae. geniculatus, Ae. mariae, Ae. pullatus, Ae. punctor, Ae. rusticus, Ae. sticticus, and Ae. vexans) through direct sequencing of a 763-base segment of the cytochrome oxidase subunit I gene. Phylogenetic analysis, based on nucleotide and amino acid sequences, was conducted by means of parsimony and distance methods. The differential tolerance of larvae to vegetable leaf litter was comparatively tested by use of 10-month-old alder leaf litter as an experimental standard. The absence of correlation between resistance to polyphenols and molecular phylogeny suggests that larval adaptation to polyphenol-rich vegetable breeding sites is a labile character. The acquisition of such resistance appears not to be ancestrally inherited, but rather to be a dynamic adaptation to the environment. Molecular data also support the classical morphological classification within the Aedes genus.

Aedes↗

Metabolic correlates of eating behavior in severe obesity.

BACKGROUND: The benefit of spreading energy intake over many small meals ('nibbling') rather than few large ones ('gorging') for control of blood glucose, serum lipids and body fat accretion has been known for 60 y, but the mechanisms are poorly understood. Men exhibit more of a gorging eating pattern than women and are also more prone to the metabolic complications of obesity, as are women with a 'male', central distribution of adipose tissue. We have shown correlations between central fat distribution, and other components of the metabolic 'Syndrome X' and fatty infiltration of the liver. Here we study relationships between eating rate and fat distribution and test the hypothesis that gorging might be associated with fatty liver. SUBJECTS AND METHODS: In 30 non-alcoholic, non-diabetic, severely obese women (body mass index, BMI=47+/-1 kg/m(2); mean+/-s.e.m.) with a mean age of 36+/-1 y and 16 men (BMI: 52+/-3) age 38+/-2 y, who were candidates for anti-obesity surgery, we measured eating rate using an eating monitor, and fat distribution by the waist-hip circumference ratio (WHR). In addition in the 17 women and 11 men who had surgery, serum lipids were analyzed and routine liver biopsies were evaluated for steatosis by a pathologist blinded to the conditions of the study. RESULTS: Men ate significantly faster than women (188+/-28 vs 123+/-9 g/min; P<0.01), and had more liver fat (score: 2.7+/-03 vs 1.5+/-0.3; P<0.01), with no statistically significant sex differences in s-cholesterol or s-triglycerides. Eating rate correlated with WHR (r=0.46; P<0.01, n=46), liver fat (r=0.55; P<0.01), and s-triglycerides (r=0.42; P<0.05) adjusting for sex. Liver fat correlated with WHR (r=0.50; P<0.05), s-triglycerides (r=0.70; P<0.01) and s-cholesterol (r=0.50; P<0.05), while there were no significant correlations with BMI or body weight. In multivariate analysis eating rate (32%), meal size (8%) and WHR (6%) contributed 46% of the variance in liver fat. CONCLUSION: We showed increased eating rates in severely obese men and women with central fat distribution. Furthermore, increased eating rates were associated with fatty liver and elevated serum lipids. Eating rate in severely obese women and men may be a determinant of the metabolic syndrome.

Adipose Tissue↗

[First report of Aedes albopictus (Skuse, 1984) in metropolitan France].

The first record of Aedes albopictus in metropolitan France has been made in a village of Orne (Basse-Normandie). A few larvae were collected in October 1999, in the used tire stock of an important tire recycling company, importing in particular from the USA and Japan. Reproduction of the species has taken place in France, and the environmental conditions make the implantation of the species probable.

Aedes↗

Genetic differentiation of Anopheles claviger s.s. in France and neighbouring countries.

An investigation of polymorphism of 11 autosomal and one sex-linked allozyme loci was made on 18 samples of Anopheles claviger Meigen (Diptera: Culicidae) from localities across France and neighbouring sites in Germany and Switzerland, plus one sample of Anopheles petragnani Del Vecchio from the French Pyrénées. Genetic differentiation between these two sibling species was confirmed (Nei genetic distance 0.33-0.44) and two genetically distinct groups of populations were identified within An. claviger. These two forms of An. claviger showed contiguous geographical distributions, Group I found across western and Central France, Group II in eastern France and nearby parts of Germany and Switzerland. The two groups were in contact in a region near the Rhone Valley where two intermediate samples were found. The taxonomic significance of this finding is discussed in the context of the recent climatic history of Europe and in relation to the vector potential of each member of the An. claviger complex.

Animals↗

The history of liver disease at The Mount Sinai Hospital.

Diseases of the liver and biliary tract interested the physicians of The Mount Sinai Hospital from the time the hospital started until the present. Indeed, the institution has become a well-recognized center for the study of the liver and its diseases. During the first 75 years of the hospital, there were many admissions for hepatobiliary diseases, resulting in many case reports. The evolution of the hospital into a teaching hospital brought with it a more systematic method of studying diseases, not only in Pathology under Paul Klemperer, but in clinical chemistry and microbiology as well. Liver biopsy was also attempted. With the arrival of Hans Popper in 1957, the emphasis shifted to coordinated studies of structure and function under normal circumstances and in diseases as they progressed. Soon, Liver Diseases (Hepatology) were split from Gastroenterology, with Fenton Schaffner as the first chief. Over the next 30 years, more than 1000 papers, chapters and books were published. The main areas of research were fibrosis, cholestasis (especially morphology and bile salt metabolism), toxic liver injury, metabolic transformations and carcinogenesis. Primary biliary cirrhosis and viral hepatitis were and continue to be special interests. Fellows from all over the world were trained and many moved on to leadership positions. Although he was active in the development of the liver transplant program, Popper did not live to see its start. A new generation of hepatologists maintains the interest and position of The Mount Sinai Hospital in this important field of medicine.

History, 19th Century↗

The histologic effects of low-dose methotrexate therapy for primary biliary cirrhosis.

OBJECTIVE: Primary biliary cirrhosis is a progressive liver disease that is believed to be autoimmune in nature. Treatment, at best, may slow the progression of the disease, although no therapy has been able to halt its progression. Preliminary data suggest a beneficial effect of methotrexate in the treatment of primary biliary cirrhosis. We evaluated the histologic effect of 2 years of treatment with methotrexate. DESIGN: Liver biopsies were obtained before methotrexate was started and after 2 years of therapy. Ninety-six paired biopsies from 48 patients with primary biliary cirrhosis were reviewed by a pathologist who was blinded to all clinical history and sequence of the biopsies. Variables examined included stage of the disease, degree of portal fibrosis, portal inflammation and piecemeal necrosis, bile duct injury or loss, bile ductular proliferation, lobular inflammation and necrosis, steatosis, granulomas, cholestasis, and nuclear pleomorphism of hepatocytes. RESULTS: In most categories, pretreatment and posttreatment biopsies did not reflect a change over the 2-year period of treatment. There was a trend toward progression of the stage of the disease, portal fibrosis, bile duct loss, fat, and pleomorphism over the 2 years and toward regression in piecemeal necrosis, bile duct injury, ductular proliferation, granulomas, and lobular inflammation and necrosis. CONCLUSION: After 2 years of treatment with methotrexate, the stage of disease and fibrosis of primary biliary cirrhosis continue to progress, although overall, inflammation and bile duct injury decrease with methotrexate treatment.

Biopsy↗

Autoantibodies against integral membrane proteins of the nuclear envelope in patients with primary biliary cirrhosis.

BACKGROUND/AIMS: Autoantibodies against nuclear membrane proteins have been identified in patients with primary biliary cirrhosis (PBC). The aim of the present study was to determine the incidence of these autoantibodies in patients with PBC and examine their significance. METHODS: An assay using recombinant polypeptides was designed to unequivocally detect autoantibodies against gp210 and the lamin B receptor, integral proteins of the nuclear membranes. RESULTS: Autoantibodies against gp210 were detected in 15 of 159 patients with PBC and 0 of 46 controls. Autoantibodies against lamin B receptor were detected in 2 patients with PBC and 0 controls. The presence of these autoantibodies had a sensitivity of 11% and specificity of 100% for the diagnosis of PBC. Autoantibodies against gp210 were present in 4 of 19 (21%) patients with PBC who did not have detectable antimitochondrial antibodies. Patients with PBC and gp210 autoantibodies had a higher incidence of associated arthritis. CONCLUSIONS: Autoantibodies against gp210 and the lamin B receptor are present in approximately 10% of patients with PBC. These autoantibodies are highly specific for the diagnosis of PBC and may be useful in diagnosing individuals without antimitochondrial antibodies and in identifying a subgroup of patients with an increased incidence of associated arthritis.

Autoantibodies↗

Familial primary biliary cirrhosis.

To estimate the prevalence of primary biliary cirrhosis in family members with this disease and determine if a family history of primary biliary cirrhosis predisposes to the development of this disease, we performed a retrospective review of charts and a prospective mail survey of patients with primary biliary cirrhosis. Prevalence of primary biliary cirrhosis in family members of 405 patients with disease was compared to known prevalence of disease in the general population. Twenty-six patients with primary biliary cirrhosis had at least one family member with primary biliary cirrhosis. The estimated prevalence per 100,000 was 6420 or 6.4%. Exclusion of family members with primary biliary cirrhosis who were patients in our practice, in order to avoid duplication, changed the prevalence to 4282 per 100,000 or 4.3%. Affected family members included mothers, daughters, sisters, brothers, aunts and cousins. Estimates of prevalence of primary biliary cirrhosis are between 0.7 and 7.5 cases per 100,000. Therefore, compared to estimates in the general population, the prevalence of primary biliary cirrhosis in family members of patients with this disease is markedly increased. A family history of primary biliary cirrhosis is therefore a predisposing factor for the development of this disease.

Causality↗

Body fat topography as an independent predictor of fatty liver.

Abdominal (truncal) fat distribution reflected by an elevated waist to hip ratio (WHR) predicts metabolic abnormalities such as diabetes and dyslipidemia as well as hypertension and stroke, all of which are associated with obesity. The pathogenesis is not known, although elevated splanchnic serum free fatty acid levels and reduced hepatic insulin clearance have been implicated. WHR and body fat (BF) by 40K-counting and 3H2O were measured before liver biopsy during antiobesity surgery in 68 severely obese women (body mass index [BMI], 48.9 +/- 1.1 SEM) and 15 men (BMI, 49.0 +/- 3.1) without histories of liver disease, diabetes, or hepatotoxic exposure. Biopsies were graded for fat content semiquantitatively (0 to 4+) by the hepatologist who was blinded to the patients' clinical characteristics. All 15 men had fatty infiltration (score, 2.5 +/- 0.3 v 1.4 +/- 0.1 in women; P < .001). The correlation between WHR and liver fat was .44 (P < .0005), while BF (-.16), weight (.15), or BMI (.04) did not correlate significantly with steatosis (all NS). As expected, percentage body fat (BF%) was greater in women than in men (40.3 +/- 0.8 kg v 33.9 +/- 2.0, P < .007), and accordingly liver fat was inversely related to BF% (r = -.32, P < .002). Steatosis was significantly greater in 14 men (2.5 +/- 0.3) than in 20 women (1.7 +/- 0.3, P < .04) matched for BF%. In multiple regression analysis R2 = .49, P < .0001), WHR and sex accounted for the variance in liver fat content without any further contribution from weight, BMI, BF, or BF%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗

HLA-DR expression in bile duct damage in hepatitis C.

Several investigations have demonstrated aberrant expression of HLA-DR on damaged bile duct epithelium of patients with primary biliary cirrhosis, liver allograft rejection, graft versus host disease, and AIDS. Since bile duct damage is a prominent feature of chronic hepatitis C, it may also be associated with HLA-DR induction. Therefore, we examined the expression of HLA-DR antigen in formalin-fixed, paraffin-embedded liver biopsy sections of 30 patients with chronic hepatitis C by the avidin-biotin peroxidase complex method using a monoclonal antibody to HLA-DR. HLA-DR was not detected on bile duct epithelium in any of the cases, although bile duct damage of varying degree was observed in 90% of the cases. HLA-DR was expressed by Kupffer cells; inflammatory infiltrates in portal tracts, and in areas of piecemeal necrosis and lobular necrosis; dendritic cells in portal and periportal areas; and occasionally hepatocytes. These observations suggest that the mechanism of bile duct injury in chronic hepatitis C may be different from that of other conditions such as primary biliary cirrhosis, liver allograft rejection, and graft versus host disease.

Antibodies, Monoclonal↗

The histological features of chronic hepatitis C and autoimmune chronic hepatitis: a comparative analysis.

Before the availability of serological markers for hepatitis C, the morphological features of this diagnosis, which represents most non-A, non-B hepatitis, could not be confirmed. We examined biopsy specimens from 50 patients with chronic hepatitis C and 21 patients with autoimmune chronic hepatitis. Each biopsy specimen was graded on 19 different histological features. The results indicated that at the time of biopsy, the average age of patients with chronic hepatitis C was 46 yr vs. 36 yr for autoimmune chronic hepatitis. Cirrhosis was seen more frequently in autoimmune chronic hepatitis (90%) than in hepatitis C (58%). Features more commonly observed in chronic hepatitis C were bile duct damage (91% vs. 40%), bile duct loss (91% vs. 20%), steatosis (72% vs. 19%) and lymphoid cell aggregation (follicles) within portal tracts (49% vs. 10%). Severe lobular necrosis and inflammation (76% vs. 38%), piecemeal necrosis (81% vs. 10%), multinucleated hepatocytes (29% vs. 6%) and broad areas of parenchymal collapse (76% vs. 6%) were seen more often in autoimmune chronic hepatitis. Exclusion of five patients with autoimmune chronic hepatitis who received immunosuppression before biopsy accentuated these differences. In conclusion, morphological criteria, in addition to serological data, may be useful for differentiating chronic hepatitis C from autoimmune chronic hepatitis, which histologically is a more aggressive disease.

Adult↗

Prediction of survival of patients with primary biliary cirrhosis. Examination of the Mayo Clinic model on a group of patients with known endpoint.

Increasing use of liver transplantation and new treatment regimens necessitate an accurate estimate of prognosis in primary biliary cirrhosis. To test the usefulness of the Mayo model for this purpose, the R value of the model was calculated for a group of 28 patients after each patient encounter and plotted against time. The data were best described by two linear regressions. For the period 10-2 years before death, the average increase in R value was 0.23 annually [R = 7.1-0.23 x time (in years)]. In the last 2 years of life, the average increase in R value was 1.4. This period could be fit by the expression R = 8.2-1.4 x time (in years). The increase in R value represents the natural progression of primary biliary cirrhosis and can be used for evaluating treatment of patients.

Forecasting↗

Hepatic histopathology in the acquired immunodeficiency syndrome.

Involvement of the liver with the same opportunistic organisms and neoplasms affecting other organs has been recognized since the beginning of the AIDS epidemic. In this overview of hepatic histopathologic features in AIDS, we review the range of opportunistic infections and neoplasms accompanying HIV infection. Hepatic disease may result from viral, bacterial, protozoal, or fungal infection, or secondary to drugs and neoplasms. Liver involvement in AIDS usually reflects disseminated rather than primary disease. CMV and mycobacteria are the most common organisms in liver identified in biopsy and autopsy studies. A variety of nonspecific features, including steatosis, granulomas, and sinusoidal abnormalities may also be seen. HIV-1 itself was recently identified in the liver. Speculation regarding the significance of this finding has been discussed in this review. Hepatitis B, C, and D may also complicate the course of disease in patients with AIDS. Hepatitis B behaves differently in the population with AIDS than in immunocompetent patients. We concluded our review with a discussion of the present recommendations regarding the use of liver biopsies in these patients. This topic continues to be widely debated in the literature.

Acquired Immunodeficiency Syndrome↗

Structural and functional aspects of regeneration of human liver.

Regeneration of human liver was long suspected to occur. It was proven in animals 100 years ago but could not be demonstrated in man until liver biopsy and modern hepatic tests became available. Structural changes in the regenerating liver mainly concern the arrangement of liver cell plates and the size and appearance of hepatocytic nuclei. A return to normalcy in test results depends on the factors responsible for regeneration since various test results change at different rates. Mass, estimated by imaging procedures, is restored parallel with the return of function. Shape is not restored but the pressure of neighboring organs and structures molds the growing remnant so that it almost resembles the original. Factors regulating regeneration in man are beginning to be recognized as they have been in animals. The hope is that regeneration can be accelerated or that cells can be transplanted to replace those lost.

Hepatectomy↗