Primary HPV DNA screening with cytology triage is more sensitive than conventional screening. Among women aged 35 years or older, primary HPV DNA screening with cytology triage is also more specific than conventional screening and decreases colposcopy referrals and follow-up tests.

We studied subcellular localization of saccharide moieties in cultured normal and malignant cells fixed in paraformaldehyde and treated with a nonionic detergent, using lectins specific for various sugar residues as probes in fluorescence microscopy. In normal cells, concanavalin A and Lens culinaris agglutinin, specific for mannose-rich carbohydrate cores in glycoproteins, labeled the endoplasmic reticulum as a wide perinuclear region . Other lectins, on the other hand, stained the Golgi apparatus as a juxtanuclear reticular structure . A similar compartmentalization was also seen in all malignant cells studied, although the Golgi apparatus in these cells was distinctly vesicular in appearance . Our results indicate that saccharide moieties in both normal and malignant cells are similarly compartmentalized, and thus speak in favor of a unidirectional subcellular flow for both membrane and secreted glycoconjugates .

The gene encoding alpha 6(IV) collagen, COL4A6, was identified on the human X chromosome in a head-to-head arrangement and within 452 base pairs of the alpha 5(IV) collagen gene, COL4A5. In earlier studies, intragenic deletions of COL4A5 were detected in a subset of patients with Alport syndrome (AS), a hereditary defect of basement membranes. In some families, AS cosegregates with diffuse leiomyomatosis (DL), a benign smooth muscle tumor diathesis. Here it is shown that patients with AS-DL harbor deletions that disrupt both COL4A5 and COL4A6. Thus, type IV collagen may regulate smooth muscle differentiation and morphogenesis.

Objective To assess the performance and impact of primary human papillomavirus (HPV) DNA screening with cytology triage compared with conventional cytology on cervical cancer and severe pre-cancerous lesions. Design Randomised trial. Setting Population based screening programme for cervical cancer in southern Finland in 2003-5. Participants 58 076 women, aged 30-60, invited to the routine population based screening programme for cervical cancer. Interventions Primary HPV DNA test (hybrid capture II) with cytology triage if the result was positive or conventional cytological screening (reference). Main outcome measures Rate of cervical cancer, cervical intraepithelial neoplasia (CIN) grade III, and adenocarcinoma in situ (as a composite outcome referred to as CIN III+) during 2003-7 through record linkage between files from the screening registry and the national cancer registry. Results In the HPV and conventional arms there were 95 600 and 95 700 woman years of follow-up and 76 and 53 cases of CIN III+, respectively (of which six and eight were cervical cancers). The relative rate of CIN III+ in the HPV arm versus the conventional arm was 1.44 (95% confidence interval 1.01 to 2.05) among all women invited for screening and 1.77 (1.16 to 2.74) among those who attended. Among women with a normal or negative test result, the relative rate of subsequent CIN III+ was 0.28 (0.04 to 1.17). The rate of cervical cancer between arms was 0.75 (0.25 to 2.16) among women invited for screening and 1.98 (0.52 to 9.38) among those who attended. Conclusions When incorporated into a well established organised screening programme, primary HPV screening with cytology triage was more sensitive than conventional cytology in detecting CIN III+ lesions. The number of cases of cervical cancer was small, but considering the high probability of progression of CIN III the findings are of importance regarding cancer prevention.Trial registration Current Controlled Trials ISRCTN23885553.

Epidermal growth factor is an important modulator of cell growth, and its role in normal wound healing is well documented. Epidermal growth factor receptors have been identified in tympanic membranes of different animals. The ability of epidermal growth factor to promote healing of tympanic membrane perforations has recently been shown in experimental animals. We performed a double-blind, placebo-controlled study of the effect of epidermal growth factor applied locally on the tympanic membrane for 1 week in patients with chronic perforations. Seventeen adult patients took part in the study, eight in the epidermal growth factor group and nine in the placebo group. Three placebo-treated patients were later treated with epidermal growth factor, and five patients received repeated epidermal growth factor treatment. Perforation size was measured as a percentage of the tympanic membrane area before and at least 1 month (mean, 2.6 months) after treatment. One perforation in the placebo group healed completely, but none of the epidermal growth factor-treated perforations closed. Perforations became slightly smaller in both groups (mean decrease, 0.3% and 2.7% for epidermal growth factor and placebo, respectively), but these changes in size were not statistically significant for either group. At otomicroscopy, a proliferation reaction with thickening of the tympanic membrane and pseudomembrane formation at the perforation edge could be seen in some ears. Histologically, a sample from one epidermal growth factor-treated ear demonstrated signs of hypertrophic epithelium when compared with the morphology of a placebo-treated tympanic membrane. The only complications were two mild infections in the placebo group. Hearing remained stable after epidermal growth factor treatment.

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Nonionic detergent (NP40) treatment of paraformaldehyde-fixed normal and SV40-transformed human fibroblasts resulted in intracellular penetration of two chosen fluorescent antibodies and Concanavalin A (Con A). After the detergent treatment nuclear SV40 T antigen, cytoplasmic fibronectin glycoprotein and Con A binding sites could be visualized in fluorescence microscopy. The lowest NP40 concentration which made fixed cells permeable was 0.05%. The morphology of cells was preserved better by this new method than by conventional fixation methods, such as acetone treatment. In scanning electron microscopy the surface of the fixed NP40-treated cells had only small rugosities and fine pores. The subsurface cytoskeleton especially was well preserved and had a more distinct fine structure. The improved morphology made it possible to detect a similar distribution of fibronectin and Con A binding sites in the perinuclear endoplasmic reticulum regions.

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