Why we prefer the thin layer technique to conventional Pap smears. A double-blind study of 473 specimens

The study evaluated the feasibility of a thinlayer technique on a routine basis for cervical smears and compared 473 ThinPrep preparations to the matched conventional Papsmears. The interpretation was double-blind and performed according to the Bethesda system. A consensus was established in discordant cases. The technique was easily mastered by gynecologists and technicians. Main advantages of the thinlayer technique were: a low number (1%) of unsatisfactory samples; a constant quality; homogeneity of cell distribution; the disappearance of problems of interpretation due to fixation or smear artifacts, red cells, polymorphs; a more precise interpretation, a firmer diagnosis; less visual fatigue; a shorter time of interpretation; the possibility of preparing more slides and performing special techniques on the same specimen. Main disadvantages were a higher cost and a necessary period of learning for cytologists.     

alpha(v)beta(3) Integrin in central nervous system tumors

alpha(v)beta(3) Is an integrin specifically expressed in endothelial cells of newly forming blood vessels. Integrin-mediated angiogenesis is hypothesized to play a central role in the development and the progression of central nervous system neoplasms. Accordingly, it is considered a potential target for antiangiogenic therapy. In the current study, we compare the expression of alpha(v)beta(3) in ependymomas, oligodendrogliomas, pilocytic astrocytomas, medulloblastomas, and vestibular schwannomas (acoustic neuromas). Samples of 5 tumors of each of the 5 tumor types were harvested surgically and frozen. After the pathological diagnosis was confirmed, immunohistochemistry was performed using an anti- alpha(v)beta(3) monoclonal antibody (LM609). The expression of alpha(v)beta(3) was assessed using a 4-tiered (0-3) grading scheme reflecting the percentage of positively staining vessels. All vestibular schwannomas demonstrated strong (grade 3) alpha(v)beta(3) expression. The expression was uniformly prominent in Antoni B regions of the tumors. Of 5 ependymomas, 4 demonstrated uniformly strong alpha(v)beta(3). Oligodendrogliomas, medulloblastomas, and pilocytic astrocytomas demonstrated more variable alpha(v)beta(3). alpha(v)beta(3) may contribute significantly to angiogenesis in vestibular schwannomas and ependymomas. Despite the high vascular density of oligodendrogliomas, pilocytic astrocytomas, and medulloblastomas, these tumors had variable moderate alpha(v)beta(3) expression. This discrepancy suggests temporal and/or regional variability in the angiogenesis in these types of tumor. This study provides the first demonstration of alpha(v)beta(3) expression in vestibular schwannomas, medulloblastomas, and pilocytic astrocytomas.     

A retrospective study of 230 consecutive patients hospitalized for presumed travel-related illness (2000–2006)

A good knowledge of morbidity profiles among ill-returned travelers is necessary in order to guide their management. We reviewed the medical charts of 230 patients hospitalized in one infectious diseases department in France for presumed travel-related illnesses. The male-to-female ratio was 1.6 and the median age was 33 years (interquartile range [IQR], 25–50). Most patients (70.9%) were returning from sub-Saharan Africa. The median duration of travel was 28 days (IQR, 15–60) and the median time from return of travel to hospitalization was 13 days (IQR, 7–21). Malaria was the most frequent diagnosis (49.1%), which was especially encountered in patients returning from sub-Saharan Africa (95.6%), without adequate chemoprophylaxis (78.2%). Imported diseases at risk of secondary transmission were also diagnosed, including pulmonary tuberculosis (n = 8), viral hepatitis (n = 8), typhoid fever (n = 6), human immunodeficiency virus (HIV) (six new diagnosis), non-typhoid salmonellosis (n = 5), severe acute respiratory syndrome, and Crimean-Congo hemorrhagic fever. This study underlines the need to maintain tropical expertise for infectious diseases physicians, even in Europe.     

Simultaneous evaluation of lymphocyte subpopulations in the liver and in peripheral blood mononuclear cells of HCV-infected patients: relationship with histological lesions

Intrahepatic lymphocytes are believed to be involved in the immunopathogenesis of hepatitis C virus (HCV) infection and the evolution of HCV-induced hepatitis. In the present study, we examined the three main intrahepatic lymphocyte subsets, namely CD3+CD56- conventional T lymphocytes, CD3+CD56+ natural T (NT) lymphocytes and CD3-CD56+ natural killer (NK) lymphocytes in HCV-infected patients. The proportion of each lymphocyte subset was evaluated both in liver biopsies and in samples of peripheral blood lymphocytes (PBL) by flow cytometry in 21 patients with histologically proven chronic hepatitis C. Simultaneously, alanine aminotransferase (ALT) levels, viral load and histological lesions were assessed. Neither NT nor NK populations correlated with any biochemical, viral or histological parameters. Furthermore, Valpha24+ NT lymphocytes showed no preferential enrichment in the liver of HCV-infected patients. Regarding conventional T lymphocytes, a highly significant linear correlation was found between intrahepatic CD3+CD56- T lymphocytes and the Knodell score, a numerical score for assessing histological activity and fibrosis (r = 0.715, P < 0.0001) and more specifically with the periportal necrosis parameter, which is the main lesion of chronic hepatitis C. In addition, analysis of the peripheral compartment revealed a high correlation between values of CD3+CD56- lymphocytes and both Knodell score (r = 0.624, P = 0.003) and serum ALT levels and again with periportal necrosis. The strong correlation between the proportion of peripheral CD3+CD56- conventional T lymphocytes and the severity of hepatic lesions leads us to propose that evaluation of this accessible peripheral population could be used as an indicator test for the severity of histological lesions in chronic hepatitis C. Abbreviations:     

Mutational analysis of the SOX9 gene in campomelic dysplasia and autosomal sex reversal: lack of genotype/phenotype correlations

It has previously been shown that, in the heterozygous state, mutations in the SOX9 gene cause campomelic dysplasia (CD) and the often associated autosomal XY sex reversal. In 12 CD patients, 10 novel mutations and one recurrent mutation were characterized in one SOX9 allele each, and in one case, no mutation was found. Four missense mutations are all located within the high mobility group (HMG) domain. They either reduce or abolish the DNA-binding ability of the mutant SOX9 proteins. Among the five nonsense and three frameshift mutations identified, two leave the C-terminal transactivation (TA) domain encompassing residues 402-509 of SOX9 partly or almost completely intact. When tested in cell transfection experiments, the recurrent nonsense mutation Y440X, found in two patients who survived for four and more than 9 years, respectively, exhibits some residual transactivation ability. In contrast, a frameshift mutation extending the protein by 70 residues at codon 507, found in a patient who died shortly after birth, showed no transactivation. This is apparently due to instability of the mutant SOX9 protein as demonstrated by Western blotting. Amino acid substitutions and nonsense mutations are found in patients with and without XY sex reversal, indicating that sex reversal in CD is subject to variable penetrance. Finally, none of 18 female patients with XY gonadal dysgenesis (Swyer syndrome) showed an altered SOX9 banding pattern in SSCP assays, providing evidence that SOX9 mutations do not usually result in XY sex reversal without skeletal malformations.      

Immunohistochemical detection of Fas and Fas ligand in sarcomatoid renal cell carcinoma

Sarcomatoid renal cell carcinomas (SRC) are rare neoplasms associated with a very poor prognosis. The aim of this study was to evaluate biomarker expression and clinical significance in this uncommon renal cancer. Cytokeratin, epithelial membrane antigen, vimentin, desmin, smooth muscle actin, CD34, S-100 protein, MIB 1, p53, Fas and Fas ligand immunohistochemical expression was investigated in seven renal cell carcinomas with sarcomatoid changes. No significant difference between sarcomatoid and nonsarcomatoid areas was observed with the different biomarkers, excepted for Fas ligand. Fas expression was diffuse in sarcomatoid and nonsarcomatoid areas. However, Fas ligand had a higher expression in sarcomatoid in comparison to nonsarcomatoid areas. Our results showed that Fas and Fas ligand are both expressed in renal cancer. We suggest that the aggressive behavior of sarcomatoid carcinoma may be related to a higher expression of Fas ligand by tumor sarcomatoid cells. These findings may indicate that Fas ligand is a possible therapeutic molecular target for treatment of SRC.     

Systems biology: integrating technology,biology, and computation

The Human Genome Project has changed the worlds of biology and medicine-helping to catalyze two major paradigm changes: systems biology and predictive, preventive and personalized medicine. These two themes will dominate 21st century biology and medicine. I will discuss these changes and indicate how they may interface with with the process of aging.     

Cytogenetic analysis of a mesenchymal hamartoma of the liver

Cytogenetic analysis of a mesenchymal hamartoma of the liver in a 3-year-old child revealed a balanced translocation between chromosomes 15 and 19 as the sole chromosome change.     

Potential Association between Zika Infection and Microcephaly during 2007 Fever Outbreak,Gabon

Although Zika virus (ZIKV) circulates in sub-Saharan Africa, no case of ZIKV-associated microcephaly has thus far been reported. Here, we report evidence of a possible association between a 2007 outbreak of febrile illness and an increase in microcephaly and possibly ZIKV infection in Gabon.     

Dose dependency of antibody response in infants and children to pneumococcal polysaccharides conjugated to tetanus toxoid.

Three injections of tetravalent pneumococcal polysaccharide-tetanus toxoid conjugate vaccine (PncT) were given to infants at 2, 4 and 6 months of age simultaneously with diphtheria-tetanus-pertussis and Haemophilus influenzae type b-tetanus toxoid conjugate vaccines. Three doses (1, 3 or 10 microg) of polysaccharides were used. Children were boosted with unconjugated polysaccharide vaccine at 14 months of age. No dose dependency was seen after primary immunization. However, booster response to three vaccine serotypes was highest in the group primed with the lowest dose of conjugate vaccine. As the magnitude of the response to booster may be related to the number of polysaccharide-specific memory B cells, we hypothesize that the 10 microg dose of the tetravalent conjugate vaccine is too high for optimal induction of immunologic memory.