Complex wavelet filter improves FLIM phasors for photon starved imaging experiments.

Fluorescence lifetime imaging microscopy (FLIM) with phasor analysis provides easy visualization and analysis of fluorophores' lifetimes which is valuable for multiple applications including metabolic imaging, STED imaging, FRET imaging and functional imaging. However, FLIM imaging typically suffers from low photon budgets, leading to unfavorable signal to noise ratios which in many cases prevent extraction of information from the data. Traditionally, median filters are applied in phasor analysis to tackle this problem. This unfortunately degrades high spatial frequency FLIM information in the phasor analysis. These high spatial frequency components are typically edges of features and puncta, which applies to membranes, mitochondria, granules and small organelles in a biological sample. To tackle this problem, we propose a filtering strategy with complex wavelet filtering and Anscombe transform for FLIM phasor analysis. This filtering strategy preserves fine structures and reports accurate lifetimes in photon starved FLIM imaging. Moreover, this filter outperforms median filters and makes FLIM imaging with lower laser power and faster imaging possible.

Incidence of cervical dysplasia and cervical cancer in women living with HIV in Denmark: comparison with the general population.

OBJECTIVES: Women living with HIV (WLWH) are reportedly at increased risk of invasive cervical cancer (ICC). A recent publication found that WLWH in Denmark attend the national ICC screening programme less often than women in the general population. We aimed to estimate the incidence of cervical dysplasia and ICC in WLWH in Denmark compared with that in women in the general population. METHODS: We studied a nationwide cohort of WLWH and a cohort of 15 age-matched women per WLWH from the general population for the period 1999-2010. Pathology samples were obtained from The Danish Pathology Data Bank, which contains nationwide records of all pathology specimens. The cumulative incidence and hazard ratios (HRs) for time from inclusion to first cervical intraepithelial neoplasia (CIN)/ICC and time from first normal cervical cytology result to first CIN/ICC were estimated. Sensitivity analyses were performed to include prior screening outcome, screening intensity and treatment of CIN/ICC in the interpretation of results. RESULTS: We followed 1140 WLWH and 17 046 controls with no prior history of ICC or hysterectomy for 9491 and 156 865 person-years, respectively. Compared with controls, the overall incidences of CIN1 or worse (CIN1+), CIN2+ and CIN3+, but not ICC, were higher in WLWH and predicted by young age and a CD4 count < 200 cells/µL. In women with normal baseline cytology, incidences of CIN1+ and CIN2+ were higher in WLWH. However, when we compared subgroups of WLWH and controls where women in both groups were adherent to the national ICC screening programme and had a normal baseline cytology, incidences of CIN and ICC were comparable. CONCLUSIONS: Overall, WLWH developed more cervical disease than controls. Yet, in WLWH and controls adherent to the national ICC screening programme and with normal baseline cytology, incidences of CIN and ICC were comparable.

HPV16 is associated with younger age in women with cervical intraepithelial neoplasia grade 2 and 3.

OBJECTIVE: To evaluate if women with HPV16 positive CIN2 and CIN3 are diagnosed at a younger age. METHODS: We conducted a population-based cohort study including more than 40,000 women having a liquid based cervical cytology sample taken as part of routine screening. HPV analysis was performed using Hybrid Capture 2 and LiPAv2. The study population was linked to the Danish Pathology Data Bank to retrieve information on subsequent cervical histology. We included HR HPV positive CIN2/3 samples, comprising 173 CIN2 and 467 CIN3 lesions. Due to a high number of multiple concurrent HPV infections, the causative HPV type was assigned to a hierarchically group. RESULTS: In CIN3, the estimated proportion of lesions positive for HPV16 was 68.1% among women aged 20 years and decreased to 38.9% among women aged 50 years. A decrease in HPV16 positivity with increasing age was also observed in CIN2. In a multinomial logistic regression analysis, young age was strongly associated with HPV16 positivity in CIN3 lesions (OR=0.46 per 10 year increase in age, 95% CI: 0.32-0.65). The proportion of HPV16 and/or 18 positive lesions among women diagnosed with CIN2 and CIN3 below 30 years of age was 44% and 75%, respectively. CONCLUSIONS: HPV16 positivity was significantly associated with younger age at diagnosis of CIN3. In a population vaccinated against HPV16 and 18, we will experience a shift to older ages in cervical precancerous lesions. These findings may imply that cervical cancer screening programs could start at an older age in HPV vaccinated populations.

Comparison of conventional Papanicolaou smear and SurePath liquid-based cytology in the Copenhagen population screening programme for cervical cancer.

OBJECTIVE: To compare diagnostic performance of conventional Papanicolaou smear with SurePath liquid-based cytology in a population screening programme. METHODS: A retrospective comparison was performed on data from two 18-month periods of the screening programme for cervical cancer in the municipality of Copenhagen with conventional Papanicolaou technique (n = 82,116) and liquid-based cytology (n = 84,414). RESULTS: After the conversion to liquid-based cytology the percentage of unsatisfactory samples decreased from 2.3% to 0.3% (P < 0.001), whereas the number of normal cervical samples lacking an endocervical component increased from 8.5% to 8.9% (P < 0.005). The percentage of samples with atypical cells and cells suspicious for malignancy increased from 3% to 4.2% (P < 0.001) and from 1.9% to 2.4% (P < 0.001), respectively. The subsequent histological follow-up showed normal findings decreased from 70.5% to 68.9% and from 28.0% to 26.1%, respectively. However, in relation to the entire screening populations, there was an increase of normal findings from 2.12% to 2.89% after primary atypical diagnosis and from 0.53% to 0.62% after diagnosis of suspicious cells after conversion to the liquid-based technique. CONCLUSIONS: This study showed the number of unsatisfactory samples to be significantly reduced with the liquid-based technique. The data suggest that there is an increased detection rate of cervical precancerous lesions with liquid-based cytology, but the number of false positive tests is still high. The specificity of the two tests seems similar, but this cannot be ascertained exactly, because of the fact that follow-up of negative cases is unavailable.

Anxious and depressive symptoms in adolescents: epidemiological data of a large scale study in Dresden.

OBJECTIVES: The present large scale epidemiological study was designed to assess the prevalence of mental disorders in adolescents. METHODS: Two cross-sectional studies have been performed in adolescents in Dresden and the results of the examination of 627 high school and 485 secondary school students (mean age 15.5 years) are presented. Self rating procedures like the Beck Depression inventory (BDI) and clinical interviews have been used to enhance validity. RESULTS: The results underline the high prevalence rates of anxiety and depression in adolescents. Up to 30% of the 9th and 10th grades students suffer from mental disorders or are at risk for the development of mental disorders. CONCLUSIONS: Therefore primary prevention of mental disorders is desirable.

Prognostic markers of short-term mortality in AIDS-associated Pneumocystis carinii pneumonia.

BACKGROUND: Since 1990, corticosteroids have been recommended as adjunctive therapy for patients with AIDS-associated Pneumocystis carinii pneumonia (PCP) and respiratory failure. We hypothesized that the natural course of AIDS-associated PCP has changed in the era of adjunctive corticosteroid therapy. OBJECTIVE: To study variables obtained on hospital admission for possible prognostic value of short-term (3-month) outcome of PCP. DESIGN AND PATIENTS: Prospective observational study of 176 consecutive HIV-1-infected individuals with PCP between 1990 and 1999. METHOD: Cox proportional-hazards regression models. RESULTS: Univariate analysis showed that age, one or more prior episodes of PCP, use of antimicrobial therapy other than trimethoprim-sulfamethoxazole (TMP-SMZ), use of PCP prophylaxis at diagnosis, and culture of cytomegalovirus (CMV) in BAL predicted progression to death within 3 months. After adjustment, age (relative risk [RR], 4.1; 95% confidence interval [CI], 1.8 to 9.3), initial antimicrobial therapy other than TMP-SMZ (RR, 3.1; 95% CI, 1.2 to 8.5), use of PCP prophylaxis (RR, 5.6; 95% CI, 2.2 to 14.4), and culture of CMV in BAL fluid (RR, 2.7; 95% CI, 1.3 to 5.6) remained independent predictors of a poor outcome. In contrast, neither PO(2) nor serum lactate dehydrogenase, which in earlier studies were identified as prognostic markers, were predictors of mortality. CONCLUSION: Age, initial anti-PCP therapy, use of PCP prophylaxis, and BAL CMV status may be useful predictors of outcome of PCP in patients treated in the era of adjunctive corticosteroid therapy.

[Anxiety and depression in students. A study in Dresden middle schools and high schools]. / Angst und Depression bei Schülern. Eine Untersuchung an Dresdner Mittelschulen und Gymnasien.

OBJECTIVES: Recent investigations by the WHO have shown once again the high prevalence of mental disorders in European countries. Mainly in the field of mental disorders considerable deficits exist particularly with regard to primary prevention. METHODS: Although there is no doubt as to the importance of primary prevention within the scope of Public Health, there are deficits in this branch in Germany. This is unfortunate, considering that the proof of successful interventions is evidence for causal risk models. The current investigation is part of a study focusing upon the development, implementation and evaluation of a prevention program for anxiety and depression in adolescents and young adults. RESULTS: Presented here are the prevalence rates of anxiety disorders and depression ascertained in the first cross-sectional study carried out in secondary schools and high schools. A total of 627 high school students and 485 secondary school students in grades nine and ten in Dresden were examined.

Loop diathermy or laser excisional conization for cervical intraepithelial neoplasia.

BACKGROUND: Cervical intraepithelial neoplasia (CIN) can be managed by ablative or excisional procedures. We have compared the excision time, effectiveness, and safety of loop diathermy (loop) against laser conization. METHODS: In a prospective study in two hospital departments 222 women were randomized to loop or laser conization. Data were collected by questionnaires after operation and at two follow-up examinations. RESULTS: At department A (122 women), two physicians performed 27% of the loop and 35% of the laser excisions; at department B (100 women), the corresponding figures were 69% and 59%. Loop was quicker than laser conization in both departments (median 3-4 min versus 10-20 min), while laser conization was more time consuming in department A (median A/B = 20/10 min). Peroperative bleeding dominated during the laser procedure in both departments and complicated the loop procedure more frequently in department A. Postoperative bleeding occurred with equal frequency in the four groups (41.8%, 52.7%, 59.2%, 64.7%). At both departments, bleeding for more than two weeks was reported twice as often after laser conization (A:13.8%, B:24.2%), when compared to loop excision (A:7.1%, B:13.7%). Residual CIN was found in all of three re-conizations and in one of eight hysterectomy specimens. CONCLUSIONS: Loop was quicker than laser excision, per- and postoperative bleeding diminished, and the success rates were comparable. Physicians mastered Loop excision after a few attempts. However, the results improved, when performed by a restricted number of physicians. Histological incomplete excision indicates close colposcopic and cytologic follow-up to identify residual CIN.

Changes in gastric intramucosal pH following mesenteric traction in patients undergoing pancreas surgery.

BACKGROUND/AIM: During major abdominal surgery, mesenteric traction (MT) may result in hemodynamic instability mainly due to endogenous prostacyclin release. Gastric intramucosal pH (pHi) and PiCO2 are indicators of splanchnic tissue perfusion with a predictive value for the postoperative outcome. We investigated the influence of MT on gastric pHi and on postoperative outcome in patients undergoing pancreas surgery. METHODS: Forty-six consecutive patients scheduled for pancreas surgery were investigated. We registered hemodynamics and pHi by gastric tonometry and documented postoperative outcome (complications, hospital stay). Baseline data (T0) were recorded after skin incision. Further assessments followed 30, 60 and 120 min after intentional MT (T1-3) and at the end of surgery (T4). RESULTS: Thirty-three patients demonstrated a decrease in mean arterial pressure (MAP) following MT, whereas 13 patients showed entirely stable hemodynamics. The significant reduction in MAP in patients with an MT response was not associated with changes in pHi as compared to patients with no response (stable MAP) (T0 7.34 +/- 0.08 vs. 7.35 +/- 0.06; T1 7.34 +/- 0.05 vs. 7.32 +/- 0.07; T2 7.32 +/- 0. 05 vs. 7.31 +/- 0.08; T3 7.32 +/- 0.05 vs. 7.32 +/- 0.07; T4 7.26 +/- 0.1 vs. 7.27 +/- 0.08; mean +/- SD, MT response vs. no response). Neither MT response nor gastric intramucosal acidosis as evidenced by a pHi <7.32 at the end of surgery predicted postoperative complications or longer hospital stay. CONCLUSION: No deterioration of gastric pHi was found, which could reflect acceptable splanchnic perfusion and oxygenation despite systemic blood pressure reactions in patients experiencing an MT response.

Thermal balloon endometrial ablation: safety aspects evaluated by serosal temperature, light microscopy and electron microscopy.

OBJECTIVES: Thermal balloon endometrial ablation is a new method for treating menorrhagia. The technique appears to be less difficult compared to standard hysteroscopic ablation techniques and to be significantly safer. The influence into the uterine wall of the thermal balloon ablation procedure was investigated with special reference to the ability of total destruction of the endometrium and the thermal action on the myometrium and the serosa. STUDY DESIGN: Temperatures were measured at the uterine serosal surface during thermal balloon endometrial ablation for 8-16 min in eight patients. After subsequent hysterectomy the extent of thermal damage into the myometrium was assessed by light and electron microscopy. RESULTS: The highest temperature measured on the uterine serosa was 39.1 degrees C. Coagulation of the myometrium adjacent to the endometrium could be demonstrated by light microscopy in all patients, with a maximum depth of 11.5 mm. By electron microscopy no influence of heat could be demonstrated beyond 15 mm from the endometrial surface. CONCLUSION: Up to 16 min of thermal balloon endometrial ablation therapy can destroy the endometrium and the submucosal layers. The myometrium is only coagulated to a depth where full thickness necrosis or injury is unlikely.

Plasma YKL-40: a new potential marker of fibrosis in patients with alcoholic cirrhosis?

BACKGROUND: YKL-40 (human cartilage glycoprotein-39, or 38-kDa heparin-binding glycoprotein) is a mammalian member of a protein family that includes bacterial chitinases. YKL-40 mRNA is expressed by human liver and may play a role in tissue remodelling. The aims were to assess whether circulating YKL-40 is released or extracted in the hepatosplanchnic system and to localize YKL-40 in liver tissue. METHODS: Plasma YKL-40 was determined by radioimmunoassay in 25 patients with liver diseases (alcoholic cirrhosis (n = 20), chronic active hepatitis (n = 2), cirrhosis of unknown aetiology (n = 2), and fatty liver (n = 1) and in 18 subjects with normal liver function during a haemodynamic investigation with catheterization of liver vein and the femoral artery. Immunohistochemical studies of the localization of YKL-40 in cryostal liver biopsy specimens were obtained from eight other patients with alcoholic liver disease. RESULTS: Plasma YKL-40 was significantly increased in patients with alcoholic cirrhosis (median, 523 micrograms/l; P < 0.001) compared with controls (106 micrograms/l), and plasma YKL-40 in the hepatic vein was higher (P < 0.01) than that of the artery in both the patients and controls, showing release of YKL-40 from the hepatosplanchnic area. The release rate of YKL-40 from the hepatosplanchnic area was higher in patients with liver disease than in controls (11.0 versus 2.1 micrograms/min, P < 0.05). Furthermore, the highest plasma YKL-40 levels were found in patients with a moderate or severe degree of liver fibrosis, and immunohistochemical studies showed positive staining for YKL-40 antigen in areas of the liver biopsy with fibrosis. CONCLUSIONS: The increased plasma YKL-40 in patients with alcoholic cirrhosis may reflect the remodelling of liver fibrosis.

Alveolar damage in AIDS-related Pneumocystis carinii pneumonia.

OBJECTIVE: Pneumocystis carinii pneumonia is the most common and serious of the pulmonary complications of AIDS. Despite this, many basic aspects in the pathogenesis of HIV-associated P carinii pneumonia are unknown. We therefore undertook a light and electron microscopic study of transbronchial biopsy specimens to compare pathologic features of P carinii pneumonia and other HIV-related lung diseases. DESIGN AND PATIENTS: Thirty-seven consecutive HIV-infected patients undergoing a diagnostic bronchoscopy. RESULTS: P carinii pneumonia was characterized by an increase in inflammation, edema, exudate, fibrosts, type II pneumocyte proliferation, and cellular infiltration of the alveolar wall when compared with other lung diseases (all p < 0.05). Electron microscopy showed apposition of the trophozoite to the type I pneumocyte. Erosion of type I pneumocytes was observed in 13 of 15 patients with P carinii pneumonia, whereas none without P carinii pneumonia had this finding (p < 0.05). Erosion of the type II pneumocyte was not observed. CONCLUSION: Inflammation, interstitial fibrosis, and alveolar epithelial erosion are characteristic features of P carinii pneumonia. The changes may form the pathologic basis for the respiratory failure seen in patients with P carinii pneumonia. Electron microscopy did not show any diagnostie advantage over conventional light microscopy using routine stains.

Prognosis of vulvar dysplasia and carcinoma in situ with special reference to histology and types of human papillomavirus (HPV).

Sixty-one women with vulvar dysplasia or carcinoma in situ were treated with local laser excision of the initial lesion and of the recurrences, and followed at intervals of from 3 increasing to 12 months. Recurrences were observed in 16 (26%) patients. No case of invasive carcinoma was seen. Patients with recurrences were significantly younger than those without (P < 0.02, median age 42.5 and 54 years, respectively). The resection borders were significantly more often involved in the initial lesions in the group with recurrences (36%) than in the group without (9%) (P < 0.014). All lesions were classified according to the WHO (mild, moderate, severe dysplasia or carcinoma in situ) and Toki et al. (1991) (warty, basaloid, combined warty/basaloid or mixed (warty, basaloid and simple). No pure types of Toki (1991) could be demonstrated. There were no differences regarding recurrences in any of these groups. HPV DNA was detected in the initial lesions by PCR in 50/56 (89%) (44 with HPV type 16 and 6 with HPV type 33) and by ISH in 23/61 (38%). The same type of HPV could be demonstrated in all first recurrences except in two, where HPV types 33 was shown in specimens harboring HPV type 16 in the initial lesions. In one of these cases, HPV type 16 could again be demonstrated in the second and final recurrence. In no specimen was more than one type of HPV detected. The results indicate that the most important parameter in predicting the recurrence of vulvar dysplasia or carcinoma in situ is the involvement of the resection borders. The location of the lesion, the degree and type of dysplasia, and the type of HPV seem to play a minor role. Local excision and subsequent intensive control with removal of any visible new lesion probably prevents development of vulvar invasive carcinoma.

Human papillomaviruses and multifocal genital neoplasia.

In 143 patients with vulvar carcinoma (76 cases) or vulvar intraepithelial neoplasia (VIN III, 67 cases), cervical cancer or cervical intraepithelial neoplasia CIN III lesions developed in 39 patients (27%) at some time during their life. In patients with classic keratinizing squamous cell carcinoma (KSC) of the vulva, cervical neoplasia developed in only one of 51 (2%), whereas the frequency was 10 of 25 (40%) in patients with vulvar carcinoma of the basaloid or warty type and 28 of 67 (42%) in patients with VIN III lesions. The original, paraffin-embedded surgical specimens were examined by polymerase chain reaction and type-specific molecular hybridization for human papillomavirus (HPV) DNA of the types 6, 11, 16, 18, and 33. DNA of the oncogenic types HPV 16 or HPV 33 was found in 4% of the KSCs, in 84% of the basaloid or warty carcinomas, in 90% of VIN III lesions, and in 89% of the cervical lesions. The same HPV type was found in both lesions in 81% of the patients with double primary tumors. The results support the concept that VIN III and a subgroup of vulvar carcinomas are HPV-related lesions, that they are frequently associated with another HPV-related genital primary tumor, and that these multiprimary tumors are secondary to an HPV infection involving the entire genital tract.

[Prognostic value of interleukin-8 in AIDS-related Pneumocystis carinii pneumonia]. / Prognostisk vaerdi af interleukin-8 ved AIDS-relateret Pneumocystis carinii-pneumoni.

UNLABELLED: We evaluated the significance of interleukin-8 (IL-8) in Pneumocystis carinii pneumonia (PCP). Bronchoalveolar lavage (BAL) fluid and serum was prospectively collected in 76 consecutive HIV-infected patients with a primary episode of PCP, as well as in ten healthy control subjects. Patients were found to have elevated levels of IL-8 in BAL fluid compared to control subjects (p < 0.01). Nine patients died during the course of PCP. Non-survivors had significantly higher IL-8 levels in BAL fluid than survivors (p < 0.05). Furthermore patients with levels of IL-8 in BAL greater then 90 pg/ml (i.e. greater than control subjects) had significantly worse vital prognosis (log rank test, p < 0.05). Thirteen patients required mechanical ventilation (MV), and these patients had significantly elevated levels of IL-8 compared with patients not requiring MV (p < 0.05). IN CONCLUSION: i) IL-8 in BAL fluid correlates to the clinical severity of the pneumonia, and ii) is a predictor of mortality and severe respiratory compromise.

Pituitary adenylate cyclase activating polypeptide (PACAP): occurrence and vasodilatory effect in the human uteroplacental unit.

UNLABELLED: Pituitary adenylate cyclase activating polypeptide (PACAP) is a neuropeptide which was originally isolated from ovine hypothalamus. PACAP exists in at least two biologically active forms, PACAP-38 and PACAP-27. The aim of this study was to establish the distribution, localization and smooth muscle effects of PACAP-38 and PACAP-27 in the human uteroplacental unit. For this purpose we used radioimmunoassay, immunocytochemistry and in vitro studies of the effect of the peptides on smooth muscle activity. RESULTS: By radioimmunoassay both peptides were detected throughout the uteroplacental unit. The concentrations of PACAP-27 were in general low, ranging from 1/6-1/25 of the corresponding PACAP-38 concentrations. PACAP-immunoreactivity was localized in nerve fibres of the lower segment of the pregnant uterus, but the number of PACAP-immunoreactive nerves was very clearly reduced compared to the corresponding isthmic region of non-pregnant myometrial tissue. PACAP-immunoreactive fibres were not observed in placenta or in the umbilical cord. Both PACAP-38 and PACAP-27 caused a concentration-dependent relaxation on stem villous arteries and on the intramyometrial arteries. Neither of the peptides displayed any effect on non-vascular smooth muscle specimens from the term pregnant myometrium. In conclusion the findings suggest a vasoregulator role of PACAP in the human uteroplacental unit.

Management of low-grade CIN: follow-up or treatment?

OBJECTIVE: To examine whether low-grade cervical dysplasia carries a higher risk of progression when associated with the cancer-related human papillomavirus types 16, 18, 31 or 33. STUDY DESIGN: Retrospective, with PCR-based HPV diagnosis on the original cervical biopsies from 71 patients with CIN I and II. CIN III developed in 34 lesions, and 37 showed complete regression during non-invasive follow-up. RESULTS: Progression occurred in 15/41 CIN I and in 19/30 CIN II lesions (P = 0.03). HPV DNA was detected in 43 specimens. CIN III developed in 25% of HPV-negative lesions, in 48% of HPV-positive CIN I lesions, and in 77% of HPV-positive CIN II lesions. CONCLUSION: Low-grade lesions are at higher risk of progression when associated with HPV types 16, 18, 31 or 33 (P = 0.002). HPV diagnosis can be useful in the triage of patients with low-grade CIN.

Pituitary adenylate cyclase-activating polypeptide: occurrence and relaxant effect in female genital tract.

The distribution, localization, and smooth muscle effects of pituitary adenylate cyclase-activating polypeptide (PACAP) were studied in the human female genital tract. The concentrations of PACAP-38 and PACAP-27 were measured by radioimmunoassays, and both peptides were found throughout the genital tract. The highest concentrations of PACAP-38 were detected in the ovary, the upper part of vagina, and the perineum. The concentrations of PACAP-27 were generally low, in some regions below the detection limit and in other regions 1 to 5% of the PACAP-38 concentrations. Immunocytochemistry revealed that PACAP was located in delicate varicose nerve fibers that were most abundant in the internal cervical os, where they mainly seemed to innervate blood vessels and smooth muscle cells. PACAP-38 and PACAP-27 (10(-10)-10(-6) M) caused a concentration-dependent relaxation of the spontaneous activity of the nonvascular smooth muscle strips from fallopian tube and myometrium in vitro. Likewise, both peptides (10(-10)-10(-6) M) caused relaxation of nonrepinephrine (10(-6) M)-precontracted intramyometrial arteries. No effect of the PACAP sequences, PACAP-(6-27), PACAP-(16-38), and PACAP-(18-27), on fallopian tube was observed. The findings suggest a smooth muscle regulatory role of PACAP in the human female reproductive tract.

Human papillomavirus (HPV) in vulvar dysplasia and carcinoma in situ.

Surgical specimens from 62 patients with vulvar dysplasia and carcinoma in situ were morphologically investigated. Lesions were classified according to WHO (mild, moderate, severe dysplasia and carcinoma in situ) and according to Toki et al. (1991) (warty, basaloid, combined warty/basaloid or basaloid/warty types or mixed (warty, basaloid and simple) forms). Following the WHO classification, moderate dysplasia was shown in 4 cases, severe dysplasia in 47 and carcinoma in situ in 11 cases. Pure warty type was shown in 2 cases (both biopsy specimens). One case revealed pure simple dysplasia whereas no case of pure basaloid type was found. Various combinations of warty and basaloid types were shown in 52 cases and mixed forms in 7 cases. The results indicate that pure forms of warty and basaloid types probably do not exist. HPV DNA was detected by PCR in 51/58 cases (88%) (45 with HPV type 16 and 6 with HPV type 33) evenly distributed in all age groups and in all types of lesions (WHO and Toki et al. 1991). By ISH HPV was detected in 24/62 cases (39%) (21 with HPV type 16/18 and 3 with HPV type 31/33), nearly always in warty areas. All these cases were positive for the same virus type by PCR. No case revealed more than one type of HPV. HPV type 6, 11, 18, and 31 were not detected by PCR. The results indicate a correlation between HPV type 16 and 33 and dysplasia/carcinoma in situ in the vulva.

Analgesic and hemodynamic effects of epidural clonidine, clonidine/morphine, and morphine after pancreatic surgery--a double-blind study.

This study characterizes analgesia an hemodynamics after epidural clonidine 8 micrograms/kg (Group C) or clonidine 4 micrograms/kg+morphine 2 mg (Group CM) in comparison to epidural morphine 50 micrograms/kg (Group M). Forty-five patients scheduled for pancreatectomy in combined general/epidural anesthesia were studied. The study drugs were administered 75 min postoperatively and for 10 h pain intensity (visual analog scale [VAS]), heart rate (HR), mean arterial pressure (MAP), and cardiac output (CO) were measured; filling pressures were kept > 5 mm Hg. Adequate analgesia could be achieved within 1 h in all patients of Groups C and CM, but only in six patients of Group M (P < 0.001). Quality of analgesia was comparable in all groups (VAS reduction 82% +/- 20%, mean +/- SD) but duration of analgesic action was longer in Groups CM (586 +/- 217 min) and M (775 +/- 378 min) compared to Group C (336 +/- 119 min) (P < 0.001). In Group M, no hemodynamic alterations occurred. In Groups C and CM, HR, CO, and MAP were reduced significantly compared to baseline within the first 15-90 min, while stroke volume and systemic vascular resistance remained stable. We conclude, that hemodynamic alteration after epidural clonidine under conditions of stable filling pressures is caused mainly by a decrease in HR. It is not an effect of analgesia but of the intrinsic antihypertensive action of clonidine.