Laying the Groundwork: A Pilot Study Exploring Improved Endometriosis Management Strategies in Primary Healthcare.

Objective: To evaluate if a brief educational intervention for primary health care staff regarding endometriosis gives sustainable knowledge of endometriosis symptoms and if a brief questionnaire for women seeking care for common symptoms is feasible in the Swedish primary care context. Design: Pilot study. Setting: 3 primary care centres (PCCs) in Sweden. Exploring knowledge among staff about endometriosis at baseline and 3 months after an information workshop. Evaluation of feasibility of a brief questionnaire for women seeking care for common symptoms For PCC personnel: knowledge about endometriosis at baseline and after 3 months. For patient questionnaire: whether adequate, understandable, acceptable, and feasible. Participants: Females in primary care centre waiting room, and staff members at participating PCCs. Results: The knowledge level of endometriosis was improved or sustained after 3 months compared to baseline among staff at PCCs. Over 90% of the patients stated that the questionnaire was adequate, understandable, acceptable, and feasible. Conclusion: We found that an educational programme improved the staff's knowledge about endometriosis. The programme together with the patient questionnaire could be a way to enhance knowledge about endometriosis among PCCs. This combined effort might facilitate earlier detection and treatment of women with endometriosis.

Side-to-side differences in knee laxity and side hop test may predispose an anterior cruciate ligament reinjury in competitive adolescent alpine skiers.

An anterior cruciate ligament (ACL) injury is a common, severe injury in alpine skiing, and anterior cruciate ligament reconstruction (ACLR) is frequently performed in competitive alpine skiers younger than 20 years old. To reduce the reinjury rate, both intrinsic and extrinsic risk factors should be examined. The aim of this study was to investigate possible intrinsic risk factors for an ACL reinjury in competitive alpine skiers. A cohort of 384 alpine skiers (191 males/193 females) from the Swedish ski high schools were prospectively followed during their high school years. The students were clinically examined and physically tested prior to each ski season. In addition, the RAND 36-Item health survey 1.0 (SF-36, Copyright 1994 Medical Outcome Trust, distributed by RAND Corporation) and injuries were prospectively registered. Thirty-one of the skiers (five males/26 females) had undergone an ACLR before entering the ski high school. This cohort was analyzed with respect to the occurrence of, and possible risk factors for an ACL reinjury (including ipsilateral and contralateral ACL injuries). Skiers who sustained an ACL reinjury were called the "ACL reinjury group," and those who did not sustain an ACL reinjury were called the "ACL injury group." Notably, 12 of the 31 students (39%), ten female and two male skiers, aged 16.5 (SD 0.5) years, sustained an ACL reinjury during the two first years at the ski high school. In addition, 10 of the 12 ACL reinjuries occurred within 10-23 months from the first injury [m 14.8 (SD4.7)] and two ACL reinjuries occurred at 29 and 47 months, respectively, from the first injury. It is noted that eight of the ACL reinjuries were to the ipsilateral knee and four to the contralateral knee. There were no differences between the groups with respect to muscle flexibility in the lower extremity, Beighton score, and one leg hop for distance or square hop test. Side-to-side differences were found with respect to knee joint laxity, >3 mm, measured with KT-1000 arthrometer (p = 0.02), and the side hop test (p = 0.04). RAND 36-Item health survey did not predict an ACL reinjury. In conclusion, a side-to-side difference in the side hop test and knee joint laxity (KT-1000) may predispose an ACL reinjury in competitive adolescent alpine skiers.

A screening instrument for side dominance in competitive adolescent alpine skiers.

Previous research has shown that high school ski students injure their left anterior cruciate ligament (ACL) more often than their right ACL, and that a prevention program focusing on equal load to the right and left ski turns prevents ACL injuries. Whether the injuries were in the dominant or non-dominant side of ski students was not determined but may be important knowledge to ski coaches for future design of ski-specific training programs. There is no gold standard on how to investigate the dominant side of alpine skiers. Therefore, the aim of this study was to develop a screening instrument consisting of five questions for identifying side dominance and to evaluate side dominance in competitive adolescent alpine skiers. First, 121 competitive adolescent alpine skiers answered the questions on side dominance using a test-retest design. The questions were: which hand/arm (left/right) or foot/leg (left/right) one uses as the first choice when writing, throwing, kicking a ball, jumping over a fence and stair-climbing. A question about safer/better ski turn to the left or to the right was also added. Second, 274 skiers answered the questions at one occasion. A very good agreement was shown in writing and throwing and kicking a ball, and a fair agreement was shown in jumping over a fence and stair climbing. A total of 243 skiers reported right-sided dominance, and seven skiers reported left-sided dominance. One hundred and nineteen of the 121 skiers who took part in the test-retest design answered the question safer/better ski turn, and of those 70 (59%) reported that they had a safer/better ski turn to one side than to the other side. However, the side was not consistent between the two test occasions, and the question did not correlate with side dominance. A combination of the three questions "What hand/arm do you use as first choice when writing?" "What hand/arm do you use as first choice when throwing?" and "What foot/leg do you use as first choice when kicking a ball?", may be used to decide side dominance in adolescent alpine skiers. Most adolescent alpine skiers reported right-sided dominance.

Prevention of Anterior Cruciate Ligament Injuries in Competitive Adolescent Alpine Skiers.

Anterior cruciate ligament (ACL) injury is one of the most serious injuries among Swedish alpine ski high school students. An ACL injury forces the skier to stop skiing for several months, and some skiers even have to give up their skiing career. Therefore, an ACL injury prevention program might play an important role for alpine skiers. In the present study ski high school students have been followed in terms of ACL injuries during 1-2 ski seasons between 2006/2007 and 2012/2013. Alpine skiers studying at the Swedish ski high schools during the ski seasons 2011/2012 and 2012/2013 received a specific ACL injury prevention program (n = 305), while alpine skiers who attended a Swedish ski high school between the ski seasons 2006/2007 and 2010/2011 served as controls (n = 431). The prevention program was based on earlier studies and included indoor and outdoor exercises on snow focusing on core stability and neuromuscular control. Alpine skiing is an equilateral sport. Therefore, the goal of the prevention was to encourage the skiers to practice these exercises in order to perform equally good on both legs. The outcome measure consisted of the number and incidence of ACL injuries. The 2 years of prevention resulted in 12 ACL injuries (3.9%) compared with 35 ACL injuries during the control period (8.1%). The absolute risk rate showed a decreased incidence rate of -0.216 [CI -0.001-(-0.432)]/100 months attending a ski high school in favor of the intervention group. A prevention program focusing on the skier's ability to perform neuromuscular exercises equally good on both legs led to a reduction of ACL injuries.

Tumoral and stromal expression of MMP-2, MMP-9, MMP-14, TIMP-1, TIMP-2, and VEGF-A in cervical cancer patient survival: a competing risk analysis.

BACKGROUND: Expression of matrix metalloproteases 2, 9 and 14 (MMP-2, MMP-9, MMP-14), tissue inhibitors of metalloprotease 1 and 2 (TIMP-1, TIMP-2) and vascular endothelial growth factor A (VEGF-A) is involved in tumor invasion and metastasis via extracellular matrix degradation and angiogenesis. This study aimed to assess whether the expression of MMP-2, MMP-9, MMP-14, TIMP-1, and TIMP-2 in tumors and in the adjacent stroma is associated with cervical cancer prognosis. METHODS: This study analyzed a retrospective cohort of 64 patients. Protein expression was previously obtained by immunohistochemistry from biopsies containing both tumor and stroma. The expression and percentage of stained cells were categorized as high or low according to the cutoff points by using ROC curves. The follow-up data was collected from diagnosis to the last clinical visit. Clinical status categorized as alive without disease, alive with disease, death due to other causes, and death from the disease. The relative risk of death from the disease was evaluated according to the proteins expression using a cause-specific Cox regression model with a 95% confidence interval (95%CI). For the significant associations (p < 0.05), survival curves of patients with low and high expression were plotted for the competing risk survival curve analyses. RESULTS: High expression levels of stromal MMP-2 (RR; 95%CI: 3.91; 1.17-13.02) and stromal TIMP-2 (RR, 95%CI: 8.67; 1.15-65.27) were associated with a greater relative risk of death from the disease and with lower survival (p = 0.03; p = 0.04) than lower expression levels. Low expression levels of stromal MMP-9 (RR, 95%CI: 0.19; 0.05-0.65) and tumoral MMP-9 (HR, 95%CI: 0.19; 0.04-0.90) were protective factors against death from the disease and were associated with poorer survival. CONCLUSIONS: High expression levels of MMP-2 and TIMP-2 in the stroma were significantly associated with poor survival in cervical cancer patients. High expression of MMP-9 was associated with a favorable cervical cancer prognosis.

Risk Factors for Anterior Cruciate Ligament Injury in Competitive Adolescent Alpine Skiers.

BACKGROUND: There is a high risk for anterior cruciate ligament (ACL) injuries in alpine skiers. To reduce or try to prevent these injuries, intrinsic and extrinsic risk factors need to be identified. PURPOSE: To identify possible intrinsic and extrinsic ACL injury risk factors among competitive adolescent alpine skiers. STUDY DESIGN: Case-control study; Level of evidence, 3. METHODS: Between 2006 and 2009, a cohort of 339 alpine ski students (176 male, 163 female) from Swedish ski high schools were prospectively observed in terms of ACL injuries. First-time ACL injuries were recorded. In September, prior to each ski season, the skiers were clinically examined according to a specific knee protocol. RESULTS: Overall, 11 male and 14 female skiers sustained a total of 25 first-episode ACL injuries. The majority of injuries occurred in the left knee (P < .05). Skiers who had participated in alpine skiing for >13 years (hazard ratio, 0.83; 95% CI, 0.68-1.00; P < .05) had a reduced risk of sustaining an ACL injury. Eighteen ACL injuries occurred during training, 12 in the technical discipline of giant slalom, and 8 in slalom. Fourteen skiers reported not to be fatigued at all at the time of injury, and 8 skiers reported that they were somewhat fatigued. CONCLUSION: ACL injuries occurred more often in the left knee than the right. This should be taken into consideration in the design of ACL injury prevention programs. Those who reported a higher number of active years in alpine skiing showed a reduced risk of sustaining an ACL injury. No other factor among those studied could be identified as an independent risk factor for ACL injury.

Mutations in the genes for keratin-4 and keratin-13 in Swedish patients with white sponge nevus.

BACKGROUND: White sponge nevus is a rare autosomal dominant disorder that affects the non-keratinised stratified squamous epithelium. Mutations in the genes that encode mucosa-specific keratin-4 and keratin-13 are strongly linked to the manifestation of white sponge nevus. This study involved mutational analysis of the genes encoding keratin-4 and keratin-13 in two Swedish families with white sponge nevus. METHODS: The diagnosis of white sponge nevus was based on disease history, clinical characteristics of the lesions and, in the majority of the cases, histopathological examination. Samples were collected from the affected buccal mucosa using buccal swabs. DNA was subsequently extracted and amplified using touchdown-PCR. The keratin-4 and keratin-13 genes were sequenced, and a genetic analysis was performed. RESULTS: A novel heterozygous missense mutation was identified in exon 1A of the keratin-4 gene in Family 2. In addition, previously reported heterozygous missense mutations were identified in the keratin-4 (E449K, A72V, Q156R, R208H) and keratin-13 (L115P) genes in both families. CONCLUSION: We describe a novel heterozygous missense mutation in the keratin-4 gene of a Swedish family with white sponge nevus. Our results support the notion that mutations in keratin-4 and keratin-13 are the underlying cause of white sponge nevus.

The correlation between anterior cruciate ligament injury in elite alpine skiers and their parents.

PURPOSE: The aim of this study was to investigate whether a familiar correlation with anterior cruciate ligament (ACL) injury exists between competitive alpine skiers and their parents. METHODS: All 593 (293 males, 300 females) elite alpine skiers who have studied at a Swedish alpine Ski High School during 2006 and 2012 answered a questionnaire whether they or their parents had suffered an ACL injury. A total of 418 skiers (70%) answered the questionnaire. RESULTS: Twenty-nine per cent (n = 19) out of the 65 ACL-injured skiers reported that they had a parent (mother or father) who have had an ACL injury. In skiers without an ACL injury (n = 353), the result was 18% (n = 64). An odds ratio of 1.95 (95% confidence interval 1.04-3.65) was found to suffer an ACL injury if you have a parent who has had an ACL injury compared with if you have a parent without any ACL injury. CONCLUSION: The findings of the current study demonstrated a family history to tear the ACL between alpine skiers who had studied at a Swedish Ski High School and ACL injuries of their parents. LEVEL OF EVIDENCE: III.

Primary prevention of childhood obesity through counselling sessions at Swedish child health centres: design, methods and baseline sample characteristics of the PRIMROSE cluster-randomised trial.

BACKGROUND: Childhood obesity is a growing concern in Sweden. Children with overweight and obesity run a high risk of becoming obese as adults, and are likely to develop comorbidities. Despite the immense demand, there is still a lack of evidence-based comprehensive prevention programmes targeting pre-school children and their families in primary health care settings. The aims are to describe the design and methodology of the PRIMROSE cluster-randomised controlled trial, assess the relative validity of a food frequency questionnaire, and describe the baseline characteristics of the eligible young children and their mothers. METHODS/DESIGN: The PRIMROSE trial targets first-time parents and their children at Swedish child health centres (CHC) in eight counties in Sweden. Randomisation is conducted at the CHC unit level. CHC nurses employed at the participating CHC received training in carrying out the intervention alongside their provision of regular services. The intervention programme, starting when the child is 8-9 months of age and ending at age 4, is based on social cognitive theory and employs motivational interviewing. Primary outcomes are children's body mass index and waist circumference at four years. Secondary outcomes are children's and mothers' eating habits (assessed by a food frequency questionnaire), and children's and mothers' physical activity (measured by accelerometer and a validated questionnaire), and mothers' body mass index and waist circumference. DISCUSSION: The on-going population-based PRIMROSE trial, which targets childhood obesity, is embedded in the regular national (routine) preventive child health services that are available free-of-charge to all young families in Sweden. Of the participants (n = 1369), 489 intervention and 550 control mothers (75.9%) responded to the validated physical activity and food frequency questionnaire at baseline (i.e., before the first intervention session, or, for children in the control group, before they reached 10 months of age). The food frequency questionnaire showed acceptable relative validity when compared with an 8-day food diary. We are not aware of any previous RCT, concerned with the primary prevention of childhood obesity through sessions at CHC that addresses healthy eating habits and physical activity in the context of a routine child health services programme. TRIAL REGISTRATION: ISRCTN16991919.

Experiences of returning to elite alpine skiing after ACL injury and ACL reconstruction.

AIM: To explore the experiences of alpine skiing at the elite level after anterior cruciate ligament (ACL) injury and reconstruction. DESIGN: A qualitative approach where semi-structured interviews were conducted, and an analysis of the manifest content was performed. PARTICIPANTS: Five ski high school students, two male and three female skiers, who had suffered ACL injuries and undergone ACL reconstructions. RESULTS: Seven categories were identified. The participants described their perceived opportunities with regard to returning to alpine skiing after ACL injury and reconstruction as something positive to do with self-belief, being mentally and physically prepared, regaining confidence in their own ability, being given time and using active strategies. In contrast, perceived barriers to a return to elite alpine skiing gave rise to negative feelings, for example, fear, disheartenment, a total lack of or ambivalent confidence in their own ability and the use of passive strategies. CONCLUSION: The two male skiers returned to alpine skiing. They reported confidence in their own ability, active strategies and support on all levels, as well as enhanced physical ability. The female skiers did not return to their pre-injury level of competitive alpine skiing. They stated a lack of support on all levels, deterioration in their physical ability and two out of three reported passive strategies and no or ambivalent confidence in their own ability. The most important factors were family support, support on all levels, access to a physiotherapist and time given.

High-grade squamous intraepithelial lesion in women aged <30 years has a prevalence pattern resembling low-grade squamous intraepithelial lesion.

BACKGROUND: Cervical cytology is the cervical cancer screening test for women aged <30 years because of the low specificity of human papillomavirus tests in this age group. The Bethesda System classifies cervical intraepithelial neoplasia grade 2 (CIN 2) and grade 3 (CIN 3) as high-grade intraepithelial lesions (HSIL). In this study, the authors subclassified cytologic HSIL as suggestive of CIN 2 (HSIL-CIN 2) or CIN 3 (HSIL-CIN 3) and evaluated whether there was a correlation between these findings and age for screened and unscreened women. METHODS: The study included 2,002,472 cervical smears collected from women who had at least 1 previous test (screened) and 217,826 previously untested women (unscreened). The laboratory has been using the Bethesda System since 1998 with the subcategorization of HSIL-CIN 2 and HSIL-CIN 3. RESULTS: For unscreened women, the prevalence of low-grade intraepithelial lesion (LSIL) and HSIL-CIN 2 decreased with age, whereas the prevalence of HSIL-CIN 3 increased. The prevalence of HSIL-CIN 2 was greater than that of HSIL-CIN 3 for women up to age 29 years (prevalence ratio [PR], 4.73; 95% confidence interval [CI], 3.90-5.75) and lower for the groups ages 30 to 49 years (PR, 0.66; 95% CI, 0.50-0.87) and ≥ 50 years (PR, 0.21; 95% CI, 0.12-0.36). For screened women, the prevalence of HSIL-CIN 2 also was greater in the group aged ≤ 29 years (PR, 2.72; 95% CI, 2.49-2.97). CONCLUSIONS: The prevalence pattern of HSIL suggestive of CIN 2 resembled the pattern observed in LSIL and was more prevalent than HSIL suggestive of CIN 3 in younger women. The impact of screening was less evident when HSIL was suggestive of CIN 2. A conservative approach for younger women who have HSIL is important for management guidance.

Psychological treatment of dental anxiety among adults: a systematic review.

The aim was to investigate the efficacy of behavioural interventions as treatment of dental anxiety/phobia in adults, by conducting a systematic review of randomized controlled trials (RCTs). The inclusion criteria were defined according to the Patients, Interventions, Controls, Outcome (PICO) methodology. The study samples had documented dental anxiety, measured using validated scales [the Dental Anxiety Scale (DAS) or the Dental Fear Survey (DFS)], or fulfilled the psychiatric criteria for dental phobia. Behavioural interventions included were based on cognitive behavioural therapy (CBT)/behavioural therapy (BT), and control conditions were defined as information, sedation, general anaesthesia, and placebo/no treatment. The outcome variables were level of dental anxiety, acceptance of conventional dental treatment, dental treatability ratings, quality of life and oral health-related quality of life, and complications. This systematic review identified 10 RCT publications. Cognitive behavioural therapy/behavioural therapy resulted in a significant reduction in dental anxiety, as measured using the DAS (mean difference = -2.7), but the results were based on low quality of evidence. There was also some support that CBT/BT improves the patients' acceptance of dental treatment more than general anaesthesia does (low quality of evidence). Thus, there is evidence that behavioural interventions can help adults with dental anxiety/phobia; however, it is clear that more well-designed studies on the subject are needed.

Injury profile of competitive alpine skiers: a five-year cohort study.

PURPOSE: The aim of this study was to make a survey of injuries in young elite alpine skiers. METHODS: During 5 years, all students at the Swedish Ski High schools were prospectively followed regarding injuries, time of exposure, injury location, type of injury, injury severity and gender. Four hundred and thirty-one skiers, 215 males and 216 females completed the entire study. RESULTS: Of 431 skiers, 193 (91 males, 102 females) sustained 312 injuries during the 5-year study period. The injury incidence for males was 1.62 injuries/1,000 ski hours or 2.97 injuries/100 months at a Ski High school, and the corresponding values for females were 1.77 and 3.25, respectively. Forty-one percent of the injuries involved the knee, 69% were ligament injuries, and 49% were classified as severe injuries. Of 190 injured skiers, 120 injured their left leg (P = 0.0097). This was their first time injury. The risk of sustaining a re-injury or a new injury increased the sooner the first time injury occurred (P = 0.001). CONCLUSION: There was a high risk for alpine ski students to sustain an injury during their education at the Swedish Ski High schools. Most injuries, especially ligament injuries, occurred in the knee joint in both males and females. Both genders were more likely to sustain injuries to the left than to the right leg. Nearly 50% of the injuries were classified as severe. LEVEL OF EVIDENCE: II.

Value of HPV-DNA test in women with cytological diagnosis of atypical glandular cells (AGC).

OBJECTIVE: This study analyzed whether HPV (human papillomavirus) testing contributes towards defining histological abnormalities in women with atypical glandular cells (AGC) diagnosed at cervical cytology. STUDY DESIGN: One hundred and eight women with conventional cervical cancer screening smears suggestive of AGC not otherwise specified (AGC-NOS) and favor neoplastic (AGC-FN) were consecutively enrolled. All women underwent colposcopic examinations and biopsy was performed according to the cytopathologic and/or colposcopic abnormalities present. All specimens were tested for high risk HPV genotypes by Roche's polymerase chain reaction reverse line blot assay. The chi-square test was used to evaluate the association between HPV findings and a diagnosis of high-grade pre-invasive or invasive disease (CIN 2 or worse) taking negative tests or CIN 1 as a reference. Odds ratios (OR) with their respective 95% confidence intervals (95%CI) were used to evaluate the magnitude of the association between HPV testing and CIN 2 or worse. Sensitivity, specificity and their respective 95% confidence intervals (95%CI), positive predictive values (PPV) and negative predictive values (NPV) were also calculated. RESULTS: Final diagnosis revealed a negative outcome in 80 cases (74%), cervical epithelial neoplasia 1 (CIN 1) in 13 cases (12%), CIN 2 or worse in 12 cases (11%) and glandular neoplasia in 3 (3%) cases. The overall detection rate of HPV was 21% (23/108). Neoplasia was significantly associated with positive HPV-DNA in women with AGC-NOS (OR=15.21; 95%CI: 2.64-87.50); however, there was no significant association between a histological diagnosis of neoplasia and HPV positivity in women with AGC-FN (OR=3.00; 95%CI: 0.36-24.92). The sensitivity, specificity, positive predictive value and negative predictive value of HPV-DNA testing for the detection of CIN 2 or worse in women with AGC-NOS were 71%, 86%, 29% and 97%, respectively. In women with AGC-FN, these values were 50%, 75%, 66% and 60%, respectively. CONCLUSIONS: HPV testing at the time of colposcopy for patients with AGC in whom no colposcopic abnormality is found may be a powerful ancillary tool for identifying women at a high risk of underlying significant cervical lesions.

Outcome of expectant management of cervical intraepithelial neoplasia grade 2 in women followed for 12 months.

OBJECTIVE: To evaluate the outcome of CIN 2 diagnosed by colposcopy-directed biopsy in women followed without treatment for 12 months and to verify whether the regression and progression of this lesion are associated with the woman's age at diagnosis and age at first sexual intercourse. STUDY DESIGN: Women diagnosed with CIN 2 by biopsy and with previous cervical smear showing LSIL were included in this cohort study and followed up for one year with cervical smear and colposcopy every three months. The rates of progression, persistence and regression of the CIN 2 were evaluated. The Kruskal-Wallis test was used to analyze the woman's age at diagnosis, age at first sexual intercourse and interval since the first sexual intercourse according to the CIN 2 outcome, assuming a significance level of 5%. RESULTS: At the end of 12 months of follow-up the CIN 2 regression rate was 74% (31/42), progression rate to CIN 3 was 24% (10/42) and in one case CIN 2 persisted (2%). Among women who had regression, this event was detected in the first six months of follow-up in 26 of the 31 cases. There was no statistically significant association between the evolution of CIN 2 and the woman's age at diagnosis, age at first sexual intercourse and interval since first sexual intercourse. Women whose lesions were restricted to one quadrant were more likely to have CIN 2 regression at three-month follow-up compared with women with a lesion extending to one or more quadrants (OR: 6.50; 95% CI: 1.20-35.23). CONCLUSIONS: The results of this study indicate that the majority of CIN 2 diagnosed by biopsy in women with previous Pap smear showing LSIL will regress in 12 months and therefore an expectant approach could be considered in these cases, not only for young women. Nevertheless these findings are not conclusive, and larger studies are required in order to certify when it is safe to adopt expectant management for CIN 2.

Cytomorphological criteria, subclassifications of endocervical glandular cell abnormalities, and histopathological outcome: a frequency study.

The objective of this study was to evaluate the frequency and the significance of cytomorphological criteria defined in studies as being predictive of neoplasia in cervical smears of women with a cytological diagnosis of atypical glandular cells (AGC) or adenocarcinoma in situ (AIS). Women (n = 103) with cytological findings suggestive of AGC or AIS, whose diagnoses were later established by histopathology, were included in the study. The criteria analyzed and classified as present or absent in cervical smears previously classified as AGC-NOS (not otherwise specified), AGC-FN (favor neoplasia), or AIS were as follows: irregular nuclear membranes; scanty cytoplasm; dyskeratotic cells; increased nuclear/cytoplasmic ratio; nucleoli; overlapping; papillary clusters, feathering; loss of polarity; nuclear enlargement; coarsely granular chromatin; and pseudostratified strips. Histopathology resulted in neoplastic diagnoses in 55 cases (53.3%) and nonneoplastic diagnoses in 48 cases (46.6%). Coarsely granular chromatin was observed in 62.5% of cases with a diagnosis of neoplasia. Feathering was present in 80% of cases of histopathological AIS. Loss of polarity and coarsely granular chromatin were significantly associated with neoplastic diagnosis considering all subcategories of glandular abnormalities diagnosis. In AGC-SOE subclassification, coarsely granular chromatin was significantly associated with neoplastic diagnosis. The presence of nucleoli was significantly associated with neoplastic diagnosis in cervical smears qualified as AGC-FN and AIS. Nuclear enlargement, increased nuclear/cytoplasmic ratio, coarsely granular chromatin and overlapping cells were found in all the subclassifications of glandular cell abnormalities irrespective of the histopathological results. Chromatin aspects, polarity, and presence of nucleoli can predict neoplasia.

Human papillomavirus-specific genotypes in cervical lesions of women referred for smears with atypical glandular cells or adenocarcinoma in situ.

This study was designed to analyze whether specific human papillomavirus (HPV) genotypes may predict histologic outcomes in women with glandular abnormalities in their cervical smears. Of the 160 women included, 111 were diagnosed with atypical glandular cells, 35 had both atypical glandular cells and high-grade squamous intraepithelial lesions, whereas 14 women had AIS, in 1 case associated with high-grade squamous intraepithelial lesions. All women underwent colposcopic examinations and biopsy was performed in 129/160 (80.6%). Thirty-one women (19.3%) were considered negative for neoplasia and scheduled for follow-up. All specimens were tested for 27 HPV genotypes by Roche's polymerase chain reaction-reverse line blot assay. Histologic diagnoses were either cervical intraepithelial neoplasia or invasive carcinoma in 75 (58%) women, and negative for neoplasia in 54 (42%). The overall prevalence of HPV was 43%. HPV 16 was the most prevalent type followed by HPV 18. HPV 16 was significantly associated with squamous and glandular neoplasia and HPV 18 with glandular neoplasia. In women with cervical intraepithelial neoplasia 2 or 3, 11 different HPV genotypes were found, whereas in those who had invasive glandular or invasive carcinoma HPV 16 and HPV 18 were found predominantly. The detection of HPV 16 in women with glandular abnormalities in cervical smears did not help differentiating squamous from glandular lesions. However, the detection of HPV 53 in abnormal smears can predict squamous neoplasia, whereas HPV 18 can predict glandular neoplasia as histologic diagnoses.

Atypical glandular cells and adenocarcinoma in situ according to the Bethesda 2001 classification: cytohistological correlation and clinical implications.

BACKGROUND: The objective of this study was to evaluate the correlation between the 2001 Bethesda classification of endocervical glandular abnormalities and histological diagnosis. STUDY DESIGN: A series of 155 women with endocervical glandular abnormalities on cervical smears were included: 91 with atypical glandular cells (AGC) not otherwise specified (NOS), 15 with AGC-favor neoplastic (FN); 35 with AGC associated with high-grade squamous intraepithelial lesion (HSIL) as combined diagnosis and 14 with adenocarcinoma in situ (AIS). RESULTS: Histological outcome of squamous neoplasias (CIN 2 or worse) and adenocarcinoma were significantly associated with AGC-FN and AIS, taking as reference AGC-NOS, and more associated with AIS than AGC-FN. Similar associations were observed for histological outcome of adenocarcinoma, but no association was observed for only squamous neoplasia. Histological outcome of CIN2 or worse was strongly associated with AGC when HSIL was also present, but no association was observed with only for adenocarcinoma histological outcome. CONCLUSIONS: AGC-NOS, AGC-FN and AIS cytological diagnosis represent a progressively increasing association with neoplastic diagnosis, due to progressively increasing association with adenocarcinoma. Histological outcome of squamous neoplasia is frequent but does not differ with these cytological interpretations. The presence of HSIL associated with AGC represents greater probability of squamous neoplasia but not adenocarcinoma.

Peroxisomes contain a specific phytanoyl-CoA/pristanoyl-CoA thioesterase acting as a novel auxiliary enzyme in alpha- and beta-oxidation of methyl-branched fatty acids in mouse.

Phytanic acid and pristanic acid are derived from phytol, which enter the body via the diet. Phytanic acid contains a methyl group in position three and, therefore, cannot undergo beta-oxidation directly but instead must first undergo alpha-oxidation to pristanic acid, which then enters beta-oxidation. Both these pathways occur in peroxisomes, and in this study we have identified a novel peroxisomal acyl-CoA thioesterase named ACOT6, which we show is specifically involved in phytanic acid and pristanic acid metabolism. Sequence analysis of ACOT6 revealed a putative peroxisomal targeting signal at the C-terminal end, and cellular localization experiments verified it as a peroxisomal enzyme. Subcellular fractionation experiments showed that peroxisomes contain by far the highest phytanoyl-CoA/pristanoyl-CoA thioesterase activity in the cell, which could be almost completely immunoprecipitated using an ACOT6 antibody. Acot6 mRNA was mainly expressed in white adipose tissue and was co-expressed in tissues with Acox3 (the pristanoyl-CoA oxidase). Furthermore, Acot6 was identified as a target gene of the peroxisome proliferator-activated receptor alpha (PPARalpha) and is up-regulated in mouse liver in a PPARalpha-dependent manner.

The impact of a community intervention to improve cervical cancer screening uptake in the Amazon region of Brazil.

CONTEXT AND OBJECTIVE: In the northern region of Brazil, cervical cancer is the most important cause of cancer-related deaths among women. There is considerable likelihood, however, that official incidence and mortality figures are greatly underestimated. The aim of this study was to estimate the repercussions from improvement in cervical cancer screening programs on the incidence of pre-invasive and invasive cervical lesions in a municipality in this region. DESIGN AND SETTING: This was a quasi-experimental study that assessed process dimensions relevant to the program objectives. The study comprised a sample of 2,226 women seen at primary healthcare units in Cruzeiro do Sul, a small city in the Brazilian Amazon region, from April 2003 to July 2004. METHODS: Women were recruited through local radio advertisements and by oral communication from the investigators. The women answered a structured questionnaire and underwent pelvic examination, which included Papanicolaou (Pap) smears and naked-eye inspection of the cervix after applying diluted acetic acid. Women with positive Pap smears or abnormal gynecological examination were referred for colposcopy and possible biopsy, diathermic large loop excision of the transformation zone or conization. RESULTS: The results obtained were compared with historical official data retrieved from the Brazilian Ministry of Health's database. Intervention resulted in a 40% increase in positive Pap smears and detection of cancer was nine times higher than had been observed in routine screening. CONCLUSIONS: Detection of pre-invasive and invasive cervical lesions in the intervention group was remarkably higher than among women seen during routine screening.