Carboplatin-radiation interaction in squamous cell carcinoma cell lines.

Chemoradiotherapy has been considered one of the most promising improvements in the treatment of advanced head and neck cancer. This article describes in vitro chemosensitivity to carboplatin in five squamous cell carcinoma cell lines established from head and neck cancers and in one vulvar squamous cell carcinoma cell line. Sensitivity to carboplatin was found to vary markedly when using the 96-well plate clonogenic assay and continuous drug exposure. The difference in carboplatin response between the most sensitive and the most resistant cell lines was fourfold. No cross-resistance was observed between inherent radiosensitivity and chemosensitivity. Effects of concomitant use of carboplatin and radiation were further investigated in the two cell lines that were found to be most sensitive to carboplatin. The drug was administered 1 hour before acute radiation doses, and an additive effect was observed in both cell lines.     

Natural history of oral papillomavirus infections in spouses: a prospective Finnish HPV Family Study.

BACKGROUND: The natural history of genital human papillomavirus infection is well known, but nearly nothing is known about the outcome of oral HPV-infection. OBJECTIVES AND STUDY DESIGN: To study natural history of oral HPV in spouses during the follow-up 331 women (mean 25.5+/-3.4 years) and 131 men (mean 28.8+/-5.0 years) were recruited from maternity unit. Scrapings from healthy oral mucosa of spouses at baseline, 2, 6, 12 and 24 months and genital samples were taken for HPV testing. HPV DNA was detected by nested PCR and confirmed by hybridization using a cocktail of 12 high-risk (HR) oligoprobes. RESULTS: The detection rate of HR HPVs varied from 15% to 27%. Baseline oral HPV status between the spouses was closely related (odds ratio 4.3; 95% confidence interval 1.6-12.0; P=0.006). Persistent oral infection in one spouse was a significant risk factor (odds ratio 10.0; 95% confidence interval 1.5-68.7; P=0.005) for oral HR HPV persistence in the other partner. Cumulative incidence of new HR HPV infections was identical in both spouses, while men seemed to clear their infection more rapidly. In univariate survival analysis, the partner's oral or genital HPV status, oral sex habits or age did not predict clearance or acquisition of oral HR HPV. CONCLUSION: Natural history of HPV infection in oral mucosa mimics that of genital HPV infection. Oral sex had no association to oral HPV infection, but a persistent oral HPV infection of the spouse increased the risk of persistent oral HPV infection 10-fold in the other spouse.     

Immunohistochemical localization of syndecan-1 in normal and pathological human uterine cervix

Expression of syndecan-1, a cell surface proteoglycan that binds growth factors and extracellular matrix components, was studied in normal and pathological human uterine cervix using immunohistochemical methods. Normal cervical squamous epithelium showed positive staining for syndecan-1 in all cell layers, except the basal cell layer, whereas endocervical columnar epithelium stained weakly. In non-neoplastic reactive lesions, metaplastic squamous cells were positive for syndecan-1, whereas columnar cells showed weak or negative staining. In cervical condylomas, cells showing koilocytotic atypia were positive for syndecan-1. The progression of cervical intraepithelial neoplasia (CIN) grade I to grade III was associated with reduced syndecan-1 expression and localization of syndecan-1 to more superficial cell layers. In squamous cell carcinomas (SCCs), syndecan-1 expression correlated with histological differentiation, being absent from most poorly differentiated tumours. The results suggest that loss of syndecan-1 from atypical cells is an early event during cervical carcinogenesis and show a close association of syndecan-1 expression with preserved epithelial morphology and differentiation.     

Testing the reliability of a new measure of life events and experiences in childhood: The Psychosocial Assessment of Childhood Experiences (PACE)

There are few well validated instruments for measuring the impact of life events and experiences in childhood and adolescence. This study examines the reliability of a new instrument, the Psychosocial Assessment of Childhood Experiences of PACE. Fifteen children and parents were interviewed on two cassions ten days apart for the main test-retest reliability study. About half of the events recorded were reported on both occasions (0.45% and 0.55% concordance). When the impact of specific events was examined much higher levels of agreement were found. Inter-rater reliability tests also yielded higher rate (Kappa 0.74 and above). Possible reasons for these important differences are discussed and the inherent methodological difficulties considered.

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Zusammenfassung Es existieren nur wenige gut validierte Meßinstrumente zur Erfassung von Lebensereignissen und Erfahrungen im Kindes- und Jugendalter. Diese Studie untersucht die Reliabilität eines neuen Verfahrens, des Psychosocial Assessment of Childhood Experiences oder PACE. 15 Kinder und Elternteile wurden zweimal im Abstand von 10 Tagen für die Überprüfung der Haupttest-Retest-Reliabilität interviewt. Ca. die Hälfte aller Ereignisse, die beim Interview berichtet wurden, wurdem beim Zweitinterview ebenfalls angegeben (Konkordanzen 0,45 und 0.55). Deutlich höhere Übereinstimmungen fanden sich bei Untersuchung der Auswirkungen spezifischer Ereignisse. Die Inter-Rater-Reliabilitätstests ergaben ebenfalls höhere Werte (Kappa 0.74). Mögliche Ursachen dieser wichtigen Unterschiede werden unter Berücksichtigung der inhärenten methodischen Schwierigkeiten diskutiert.

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Résumé II y a peu d'instruments correctement validés de mesures de l'impact des événements de vie des expériences dans l'enfance et l'adolescence. Cette étude examine la fiabilité d'un nouvel instrument, l'évaluation psycho-sociale des expériences infantiles (Psychosocial Assessment of Childhood Experiences ou PACE). 15 enfants et parents furent interrogés à deux reprises à 10 jours d'intervalle pour evaluer la fiabilité test-retest. Environ la moitié des événements rapportés le furent dans les deux occasions (0.45% et 0.55% de concordance). Quand l'impact des événements déviés spécifiques fut étudié un niveau plus élevé de concordance fut trouvé. La fidélité inter-cotateurs des tests obtinet également des taux plus élevés (kappa 0.74 et audessus). Les raisons possibles de ces différences sont discutées et les difficultés méthodologiques inhérentes prises en compte.

     

p53Mutations and Presence of HPV DNA Do Not Correlate with Radiosensitivity of Gynecological Cancer Cell Lines

Objective.The correlation betweenp53tumor suppressor gene mutations and the presence of high-risk human papillomavirus (HPV) DNA with thein vitroradiosensitivity of gynecological malignancies was studied in 26 cell lines derived from gynecological cancers of 23 patients.Methods.Comparison of the intrinsic radiosensitivity was performed with mean inactivation dose (D?) determined with the 96-well plate clonogenic assay.p53mutations were investigated with polymerase chain reaction and single-strand conformation polymorphism (PCR–SSCP) analysis and direct DNA sequencing, and the presence of HPV DNA was studied with PCR using HPV consensus primers.Results. p53mutations were found in 6 of 10 vulvar squamous cell carcinoma (SCC) lines. Nine vulvar and 1 vaginal SCC cell lines were HPV DNA negative and 1 vulvar cell line was HPV 16 positive. All 4 cervical SCC lines were HPV positive and possessed the wild-typep53.Three cell lines expressed HPV 16 and 1 HPV 68. Among 10 endometrial cancer cell lines, 2 cell lines with mutantp53and 1 HPV 16 positive cell line were found. No correlation could be demonstrated between inactivation of thep53gene and radiosensitivityin vitro;the cell lines were evaluated as one group or according to their anatomical origin or histology.Conclusion.Our results indicate that inactivation of thep53gene through mutation or binding with HPV DNA does not increase the resistance of gynecological malignancies to ionizing radiationin vitro.     

Evaluation of current care effectiveness: a survey of hypertension guideline implementation in Finnish health centres

OBJECTIVE: To assess the extent and style of implementation of the Hypertension Guideline (HT Guideline) in Finnish primary health centres, and to identify a scale of contrasting implementation styles in the health centres (with the two ends of the scale being referred to as information implementers or disseminators respectively). DESIGN: A cross-sectional study. Development of a questionnaire and criteria for assessing the extent and style of implementation of the HT Guideline. SETTING: Primary healthcare. SUBJECTS: All head physicians and senior nursing officers in Finnish health centres (n =290). MAIN OUTCOME MEASURES: The extent of adoption of the HT Guideline in health centres and the characteristics associated with the implementation style. RESULTS: Responses were received from 410 senior medical staff (246 senior nursing officers and 164 head physicians) representing altogether 264 health centres (91%) in Finland. The HT Guideline had been introduced into clinical practice in most health centres (89%). The style of implementation varied widely between health centres: at opposite ends of the implementation scale were 21 implementer health centres, which used multiple implementation channels, and 23 disseminator health centres, which used few or no implementation channels. The implementers had typically larger population bases and had organized services around the family doctor system, while the disseminators were smaller and had organized services according to a traditional model (appointments could be with any doctor in the surgery). CONCLUSION: The Finnish HT Guideline has become well known in most health centres since being introduced into clinical practice. However, the style of implementation varies markedly between health centres.     

Nurses’ experiences of guideline implementation: a focus group study

Aims. The aim of the study was to address the following questions: What kind of experiences do primary care nurses have of guideline implementation? What do nurses think are the most important factors affecting the adoption of guidelines? Background. The implementation of clinical guidelines seems to be dependent on multiple context‐specific factors. This study sets out to explore the experiences of primary care nurses concerning guideline implementation. Design. Qualitative interview. Methods. Data were generated by four focus group interviews involving nurses working in out‐patient services in primary health centres in Finland. Purposive sampling was used to select health centres. Inductive content analysis was used to identify themes emerging from the data. Results. Four main groups of factors were identified from the analysis of data: (i) factors related to the organisation, (ii) factors related to nurses, (iii) factors related to the anticipated consequences and (iv) factors related to the patient group. Nurses’ awareness and acceptance of guidelines and the anticipated positive consequences facilitate the implementation of guidelines. Organisational support, especially the adapting of guidelines to local circumstances, seems to be crucial for successful implementation. Conclusions. Clinical guidelines can be promising tools in enhancing evidence‐based nursing practice, as nurses see them as practical work tools in patient care and so are willing to adopt them. However, support from management and physicians is needed to ensure the successful implementation of guidelines into nursing practices. Relevance to clinical practice. Based on the findings of this study and previous knowledge of guideline implementation some practical recommendations are suggested. Select the most relevant guidelines to clinical practice, organise the adaptation of guidelines to local circumstances, inform all practitioners involved in treatment and give clear instructions for the adoption of the guidelines.     

Epidural and paracervical blockades in obstetrics. Catecholamines, arginine vasopressin and analgesic effect

A comparative study of analgesic and endocrinologic effects of obstetrical epidural anesthesia (EA, n = 23) and paracervical block (PCB, n = 39) was performed. Pain intensity was assessed on a horizontal linear scale. Simultaneously, blood samples for the determination of concentrations of norepinephrine (NE), epinephrine (E) and arginine vasopressin (AVP) were obtained. NE and AVP levels did not bear any relationship to pain scores. Instead, the average plasma E profile during labor was practically identical with the profile of pain scores. Plasma levels of E decreased significantly after EA. A similar but short-lived effect was observed also after PCB. When comparable doses of bupivacaine were used (30 mg in the EA group and 25 mg in the PCB group); initial pain relief after EA and PCB was similar, though after 30 min the pain score increased for patients who received the PCB, while patients who received EA had continued pain relief. Faster absorption of bupivacaine was observed after paracervical than epidural injection. Decreased variability was seen in the fetal cardiograms in 25% after EA and in 33% after PCB. Transient bradycardia was observed in 2 cases after paracervical injection.