European consensus-based (S2k) Guideline on the Management of Herpes Zoster - guided by the European Dermatology Forum (EDF) in cooperation with the European Academy of Dermatology and Venereology (EADV), Part 1: Diagnosis.

Herpes zoster (HZ, shingles) is a frequent medical condition which may severely impact the quality of life of affected patients. Different therapeutic approaches to treat acute HZ are available. The aim of this European project was the elaboration of a consensus-based guideline on the management of patients who present with HZ, considering different patient populations and different localizations. This interdisciplinary guideline aims at an improvement of the outcomes of the acute HZ management concerning disease duration, acute pain and quality of life of the affected patients and at a reduction of the incidence of postherpetic neuralgia and other complications. The guideline development followed a structured and predefined process, considering the quality criteria for guidelines development as suggested by the AGREE II instrument. The steering group was responsible for the planning and the organization of the guideline development process (Division of Evidence based Medicine, dEBM). The expert panel was nominated by virtue of clinical expertise and/or scientific experience and included experts from the fields of dermatology, virology/infectiology, ophthalmology, otolaryngology, neurology and anaesthesiology. Recommendations for clinical practice were formally consented during the consensus conference, explicitly considering different relevant aspects. The guideline was approved by the commissioning societies after an extensive internal and external review process. In this first part of the guideline, diagnostic means have been evaluated. The expert panel formally consented recommendations for the management of patients with (suspected) HZ, referring to the assessment of HZ patients, considering various specific clinical situations. Users of the guideline must carefully check whether the recommendations are appropriate for the context of intended application. In the setting of an international guideline, it is generally important to consider different national approaches and legal circumstances with regard to the regulatory approval, availability and reimbursement of diagnostic and therapeutic interventions.

European consensus-based (S2k) Guideline on the Management of Herpes Zoster - guided by the European Dermatology Forum (EDF) in cooperation with the European Academy of Dermatology and Venereology (EADV), Part 2: Treatment.

Herpes zoster (HZ, shingles) is a frequent medical condition which may severely impact the quality of life of affected patients. Different therapeutic approaches to treat acute HZ are available. The aim of this European project was the elaboration of a consensus-based guideline on the management of patients who present with HZ, considering different patient populations and different localizations. This interdisciplinary guideline aims at an improvement of the outcomes of the acute HZ management concerning disease duration, acute pain and quality of life of the affected patients and at a reduction in the incidence of postherpetic neuralgia (PHN) and other complications. The guideline development followed a structured and pre-defined process, considering the quality criteria for guidelines development as suggested by the AGREE II instrument. The steering group was responsible for the planning and the organization of the guideline development process (Division of Evidence-Based Medicine, dEBM). The expert panel was nominated by virtue of clinical expertise and/or scientific experience and included experts from the fields of dermatology, virology/infectiology, ophthalmology, otolaryngology, neurology and anaesthesiology. Recommendations for clinical practice were formally consented during the consensus conference, explicitly considering different relevant aspects. The guideline was approved by the commissioning societies after an extensive internal and external review process. In this second part of the guideline, therapeutic interventions have been evaluated. The expert panel formally consented recommendations for the treatment of patients with HZ (antiviral medication, pain management, local therapy), considering various clinical situations. Users of the guideline must carefully check whether the recommendations are appropriate for the context of intended application. In the setting of an international guideline, it is generally important to consider different national approaches and legal circumstances with regard to the regulatory approval, availability and reimbursement of diagnostic and therapeutic interventions.

Perturbation by insulin of human breast cancer cell cycle kinetics.

The growth of cultured human breast cancer cells is sensitive to physiological concentrations of insulin suggesting that it may regulate breast cancer growth in vivo. The mechanisms for the growth effects of insulin are poorly defined. In the present study, we examine the effects of insulin on the cell cycle kinetics of asynchronous MCF-7 human breast cancer cells growing in serum-free medium. When the [3H]thymidine labeling index is used to estimate the S-phase fraction, insulin added to asynchronously growing cells results in a time-dependent increase in the proportion of cells engaged in DNA synthesis. Computer analysis of DNA histograms obtained by flow cytometry of mithramycin-stained cells also shows a time-dependent progression of cells into and through the S-phase compartment. Sixteen hr after adding insulin to asynchronous cells, 66% of cells are in S-phase compared to 37% in controls. The effect of insulin on the cell cycle progression of MCF-7 cells is also dose dependent. Stimulation is observed with physiological insulin concentrations of 0.1 to 1.0 nM; maximal effects are observed with 1.0 to 10 nM insulin. Various insulin analogues enhance the progression of cells into S phase in proportion to their ability to bind to the insulin receptor in MCF-7 cells (porcine greater than or equal to chicken greater than guinea pig greater than deoctapeptide insulin), while unrelated peptide hormones have no effect on the cell cycle kinetics. Cell cycle analysis after the addition of colchicine to prevent mitosis and the reentry of cells into G1 demonstrates a shortened G1 in response to insulin. Continuous [3H]thymidine-labeling studies after the addition of colchicine suggest that the growth fraction is about 88% with or without insulin. In summary, insulin causes a marked perturbation of the cell cycle kinetics of MCF-7 human breast cancer cells by facilitating the transit of cells through G1. The data also suggest that this effect is mediated via the insulin receptor.

Multiple progesterone receptor assays in human breast cancer.

A review of assay results from more than 5500 patients revealed 283 patients in whom multiple breast cancer specimens were analyzed for progesterone receptor (PGR). All assays were performed in a single laboratory between 1975 and 1982 using the sucrose gradient technique. We considered only the 8S fraction of PGR. Simultaneous assays in 109 patients yielded 14% discordance [one assay with greater than 10 fmol/mg cytosol protein (PGR+) and one assay with less than 5 fmol/mg protein (PGR-)]. Among 161 sequential assays, there was an overall discordance of 19%: 8% (nine of 106) when the initial assay was PGR-, but 44% (24 of 55) when the initial assay was PGR+. Among PGR+ patients initially assayed at the time of diagnosis, there was a tendency to greater receptor loss in patients with positive axillary lymph nodes (44 versus 11%). The length of time between biopsies did not increase the discordance, but endocrine therapy within this interval did increase it (56% of initially PGR+ patients who received interim endocrine therapy were PGR- at second biopsy). to evaluate the significance of interval loss of PGR, we compared survival from first biopsy in initially PGR+ patients who subsequently lost their receptor versus those whose receptor persisted. The latter group experienced a significantly longer survival (p less than 0.02). In summary, we observed an ominous loss of PGR in sequential biopsies, particularly with intervening endocrine therapy, and those patients whose tumor cells lost PGR experienced poorer survival than did patients retaining PGR. Therefore, patients with PGR+ primary tumors require repeat biopsy for PGR upon disease recurrence for optimal treatment planning.

Novel human papillomavirus (HPV) DNA sequences from recurrent cutaneous and mucosal lesions of a stoma-carrier.

Recent studies have demonstrated a high prevalence of human papillomavirus (HPV) types originally believed to be restricted to patients with epidermodysplasia verruciformis (EV) in benign and malignant skin tumors of the general population. Other groups detected typical mucosal HPV in skin tumors. We have investigated recurrent leukoplakial cutaneous and mucosal lesions located around the ileostoma of a woman with ulcerative colitis for the presence of HPV. Cutaneous, mucocutaneous, and mucosal ileostoma-biopsies were analyzed by three different polymerase chain reaction protocols for genital, cutaneous, and cutaneous EV-associated HPV types. Polymerase chain reaction products were cloned, sequenced, and submitted to phylogenetic analyses. HPV-DNA sequences of the EV-HPV group could be detected in all biopsies, whereas genital/mucosal or cutaneous HPV types were not found. HPV types detected comprised HPV20, HPV23, HPV38, and four putatively novel HPV types that belong to different clusters of the EV-HPV group B1. Different HPV types prevailed in cutaneous, mucocutaneous, and mucosal lesions and the number of HPV sequences found per lesion varied between one and three. Our data show the association of recurrent lesions around a stoma and at the ileum with known and novel EV-HPV types. These results emphasize the plurality of HPV and yield data for the possible transmission of cutaneous HPV to mucosal areas of the intestine.

[Current developments in anogenital HPV infections]. / Neuere Entwicklungen bei den anogenitalen HPV-Infektionen.

Human papillomaviruses are found with increasing frequency in malignant epithelial tumours of the skin and the mucosae, especially in the anogenital region. Clinical dermatology and venereology have focused much interest on papillomaviruses, because these agents are responsible for the most frequently diagnosed sexually transmitted diseases. Early diagnosis using colposcopy, peniscopy and acetic-acid testing are helpful in preventing the further dissemination of HPV and associated diseases. In general, preventive diagnosis, improved treatment combining conventional methods and immunotherapy and regular follow-up examinations should be coordinated among dermatovenerologists, gynaecologists and urologists.

The role of the tumor board in a community hospital.

A hospital tumor board is a multidisciplinary group of physicians that meets on a regular basis to review cancer cases. Through regular meetings, the tumor board will improve the quality of cancer care, provide educational opportunities for participants, and become an asset to the hospital and to the community. The use of multidisciplinary tumor-board consultations can ensure that the cancer patient has access to the best current thinking about cancer management. This structure provides the individual practitioner and his hospital with the educational, quality assurance, and legal mechanisms to deliver state-of-the-art care.

[Herpesvirus infections--indications for chemotherapy in dermato-venereology]. / Herpesvirus-Infektionen--Indikationen zur Chemotherapie in der Dermatovenerologie.

Specific antivirals like acyclovir have ameliorated the outcome of severe herpesvirus infections, especially in immunocompromised patients. Varicella can be prevented in high-risk patients after exposure by therapy with varicella-zoster immunoglobulin. Despite this favorable development, there are many unresolved problems in the management of herpesvirus infections, such as the use of acyclovir during pregnancy, the treatment of both motoric neuropathy and postherpetic neuralgia. Chemotherapy-resistant herpesvirus may cause severe syndromes in patients suffering from HIV infection or from iatrogenic immunosuppression. Isolation of resistant viruses provides the stimulus to establish tests of viral resistance and to use antiviral drugs more carefully.

Duplication of enhancer sequences in human papillomavirus 6 from condylomas of the mamilla.

Human papillomavirus (HPV) 6 usually induces tumors of the genital, oral, or laryngeal mucosa. An HPV 6-related DNA of 8.2 kb was detected in an extrachromosomal state in atypically located condylomas of the mamilla and was molecularly cloned. The identity of the cloned HPV DNA and the viral DNA in the biopsy was confirmed by comparative Pstl cleavage analysis, which showed typical HPV 6 DNA fragment patterns except for 0.2-kb larger B fragments. Sequencing revealed an exact 236-bp duplication encompassing nucleotides 7681 to 7896 of HPV 6b. This tandem repeat is just upstream from the putative early promoter and contains a 20-bp insertion at position 7720, which constitutes an enhancer element described by R. F. Rando, W. D. Lancaster, P. Han, and C. Lopez (Virology 155, 545-556, 1986). A Hinfl-Pstl fragment containing the whole duplication was cloned into an enhancer-dependent CAT expression vector and led to three- to sevenfold increased CAT activity when compared with the monomeric sequence in C127 cells and BPV1 transformed C127 cells. This indicates that the duplication within the HPV 6 isolate from the mamilla may influence early gene expression and possibly tissue tropism.

Papilloma virus particles in a fibroma of the tongue.

Papilloma virus particles could be identified in material from a fibroma of the tongue. Histology revealed an irritated fibroma with a very high degree of intranuclear and cytoplasmic vacuolization.