Analysis of Determinants for Suture-mediated Closure Device Failure During EVAR Procedures.

OBJECTIVE: Endovascular aortic repair (EVAR) for elective and emergency infrarenal aortic pathologies is the primary approach for treatment nowadays. During such procedure, the suture-mediated closure device (SMCD) (Perclose ProGlideTM, Abbott Laboratories, Chicago, IL, USA) is commonly used. This study aimed to identify potential contributors for SMCD failure in a patient cohort of elective and emergency EVAR. METHODS: Archived medical records from patients who underwent EVAR for aortic pathologies in elective and emergency setting at the University Hospital Düsseldorf, Germany were included. Patient's co-morbidities, access vessel morphologies and hemostasis-related blood parameters were evaluated on their association with SMCD failure applying different statistical methods. RESULTS: A total of 71 patients (139 femoral accesses) was included. The mean age was 73.5 ± 8.4 years. Overall SMCD failure rate was 4.3%, 4.1% for elective and 5.9% for emergency cases, respectively. Total procedure time was longer for the SMCD failure group (323 ± 117.8 min vs 171 ± 43.7 min). The calcification status of the common femoral artery (CFA), the diameter of the aortic bifurcation, and dual anti-platelet therapy (DAPT) on the medication plan prior to the procedure were associated with SMCD failure. Univariate binary logistic regression analysis nominated several potentially relevant predictors for SMCD failure who underwent subsequent multivariable binary logistic regression analysis. Here, DAPT on the medication plan was identified as being promising in predicting SMCD failure (OR 30.5), while anterior plaque formation in the CFA maintained as only statistically relevant determinant (OR 44.9). CONCLUSIONS: This study confirms the CFA calcification status to be associated with SMCD failure. Although discontinued prior to endovascular treatment, DAPT was also found to be associated with SMCD failure. Our results may advocate to perform obligatory platelet testing prior to EVAR to maximize patient safety.

Expression of gastrin-releasing peptide receptor in patients with cutaneous malignant melanoma.

BACKGROUND: Gastrin-releasing peptide (GRP) is a neuroendocrine peptide shown to possess growth-stimulatory effects in many types of human cancers. High levels of GRP receptors have been found in various types of human cancers, and preclinical studies exploring the therapeutic use of GRP receptor (GRPR) antagonists have been reported, with promising results. Data on GRPR expression in human malignant melanoma (MM) are scanty. AIM: To determine GRPR expression in biopsy material obtained from patients diagnosed with cutaneous MM. METHODS: Immunohistochemistry was performed on formalin-fixed, paraffin wax-embedded tissue samples obtained from 51 patients with cutaneous MM. The relationship between GRPR expression and the clinicopathological features was analysed using the Fisher exact test. RESULTS: GRPR immunoexpression was found in 42/51 cutaneous melanoma samples (82.4%). It was strongly expressed in 30 cases (58.9%). There was no significant difference in the levels of GRPR expression between primary or metastatic lesions. We correlated the GRPR expression score with pathological features associated with prognosis in cutaneous MM. There was no significant difference in GRPR expression in relation to Clark level (CL; P = 0.35) or Breslow Index (BI; P = 0.17). CONCLUSIONS: GRPR expression levels were high in tissue specimens of MM (82.4%), but did not correlate with pathological features related to prognosis, such as CL or BI. Further studies, preferably in a larger patient population, are warranted.

Protective effect of RC-3095, an antagonist of the gastrin-releasing peptide receptor, in experimental arthritis.

OBJECTIVE: To evaluate the antiinflammatory effects of RC-3095 in 2 experimental models of arthritis, collagen-induced arthritis (CIA) and antigen-induced arthritis (AIA), and to determine the mechanisms of action involved. METHODS: RC-3095 was administered daily to mice with CIA and mice with AIA, after induction of disease with methylated bovine serum albumin. Disease incidence and severity were assessed using a clinical index and evaluation of histologic features, respectively. In mice with CIA, gastrin-releasing peptide receptor (GRPR) was detected by immunohistochemical analysis, while in mice with AIA, migration of neutrophils, presence of glycosaminoglycans, and lymphocyte proliferation, determined using the MTT assay, were assessed. Expression of cytokines interleukin-17 (IL-17), IL-1ß, and tumor necrosis factor α (TNFα) was evaluated in all mouse knees using enzyme-linked immunosorbent assay. Treg cell production was assessed by flow cytometry in the joints of mice with AIA. RESULTS: In mice with AIA, administration of RC-3095 reduced neutrophil migration, mechanical hypernociception, and proteoglycan loss. These findings were associated with inhibition of the levels of all 3 proinflammatory cytokines, decreased lymphocyte proliferation, and increased Treg cell numbers. In the CIA model, treatment with RC-3095 led to a significant reduction in arthritis clinical scores and the severity of disease determined histologically. Synovial inflammation, synovial hyperplasia, pannus formation, and extensive erosive changes were all dramatically reduced in the arthritic mice treated with RC-3095. Furthermore, arthritic mice treated with RC-3095 showed a significant reduction in the concentrations of IL-17, IL-1ß, and TNFα, and showed a diminished expression of GRPR. CONCLUSION: These findings suggest that the GRP pathway has a significant role in chronic arthritis, and its inhibition can be explored as a possible therapeutic strategy in rheumatoid arthritis.

P53 and Ki-67 overexpression in gastroesophageal reflux disease--Barrett's esophagus and adenocarcinoma sequence.

Gastroesophageal reflux disease (GERD) is a major risk factor for the development of esophageal adenocarcinoma (ACE). Many molecular alterations occur in esophageal carcinogenesis, yet the exact mechanism of ACE development remains unknown. This study aims to determine p53 protein and Ki-67 expression in esophageal mucosa of patients with GERD and study the correlation between these markers and the progression from normal squamous epithelium to esophagitis, columnar epithelium with or without intestinal metaplasia and ACE. We analyzed p53 protein and Ki-67 expression in biopsies of 200 patients with GERD and 35 patients with ACE. Those biopsies were classified into five groups: (i) G1 normal squamous epithelium (58); (ii) G2 esophagitis (80); (iii) G3 columnar epitheliums without intestinal metaplasia (30); (iv) G4, columnar epitheliums with intestinal metaplasia (32); and (v) G5 ACEs (35). p53 protein overexpression was found in 7% (4) of G1, 37.5% (30) of G2, 30% (9) of G3, 62.5% (20) of G4, and 71.4% (25) of G5 (p < 0.001). Ki-67 index increased according to the severity of histopathological diagnoses. Ki67 index was 21.3 +/- 19.5% in G1, 38.8 +/- 24.9% in G2, 37.7 +/- 26.3% in G3, 52.8 +/- 24.6% in G4, and 57.1 +/- 25.1% in G5 (P < 0.001). Linear correlation between p53/Ki67 expression and the multistep progression from squamous epithelium to ACE was observed (P < 0.001 and P < 0.05). Our results indicate that overexpression of p53 and increased Ki-67 could be associated with the development and progression to ACE in patients with GERD.

Do interventions to limit sedentary behaviours change behaviour and reduce childhood obesity? A critical review of the literature.

We sought to determine whether interventions that emphasize decreasing sedentary behaviours in children and adolescents result in behaviour change and weight control. A comprehensive literature search was conducted to identify all comparative studies of interventions to reduce sedentary behaviour among children, alone or in combination with other health messages. Two investigators evaluated articles for eligibility and validity. As methods, settings and interventions differ across studies, results were synthesized narratively. Twelve studies met the inclusion criteria and provided relevant data. Six targeted clinic-based populations that were overweight or at risk of overweight, and six were population-based prevention studies. Approaches varied, but all reduced sedentary behaviour and improved weight indices. An emphasis on decreasing sedentary behaviours is an effective intervention to decrease sedentary behaviours and control weight in children and adolescents.

Subcutaneous inflammation (panniculitis) in tibio-tarsal joint of rats inoculated with complete Freund's adjuvant.

Complete Freund's adjuvant (CFA)-induced arthritis in rats, which presents similar features to rheumatoid arthritis, is a model widely used in aetiopathogenetic and investigational drug studies. In this model, arthritis is induced by intradermal injection of Mycobacterium tuberculosis suspended in mineral oil in the hind footpad. Although the histopathology findings in the joint are well described, the marked subcutaneous features of panniculitis that concomitantly occur in this model have received no attention. The objective of this paper is to describe the subcutaneous histopathological features in 8 Wistar rats after intraplantar injection of CFA. We studied the subcutaneous histopathological features in 8 Wistar rats after intraplantar injection of CFA in the left hind paw. The levels of subcutaneous inflammation of the animals in this study were evaluated for the histological characteristics present in the tissue and scored with 4 parameters (acute inflammation, chronic inflammation with fibrosis, subcutaneous and profound soft tissue necrosis, and the presence of giant cells, neutrophils, macrophages and lymphocytes) on days 4, 7, 11 and 15 after induction. All animals developed intense subcutaneous inflammation characteristic of panniculitis, with predominance of acute changes in the initial period, with progression to a self-perpetuating chronic fibrotic process on day 15. These observations precede the joint changes. Besides being an interesting model for better studying diseases with panniculitis, our observations bring up issues concerning the possible relations between subcutaneous and joint inflammatory changes.

An alternative protocol for DNA extraction from formalin fixed and paraffin wax embedded tissue.

BACKGROUND: DNA extraction from paraffin wax embedded tissue requires special protocols, and most described methods report an amplification success rate of 60-80%. AIMS: To propose a simple and inexpensive protocol consisting of xylene/ethanol dewaxing, followed by a kit based extraction. METHOD: Xylene/ethanol dewaxing was followed by a long rehydration step and a kit based DNA extraction step. RESULTS: This method produced a 100% amplification success rate for fragments of 121 to 227 bp for tamponated formalin fixed paraffin wax embedded tissue. CONCLUSION: This cost effective and non-laborious protocol can successfully extract DNA from tamponated formalin fixed paraffin wax embedded tissue and should facilitate the molecular analysis of a large number of archival specimens in retrospective studies.

Synthesis and hypoglycemic activity of substituted 8-(1-piperazinyl)imidazo[1,2-a]pyrazines.

A series of alkyl- and halo-substituted 8-(1-piperazinyl)imidazo[1,2-a]pyrazines were prepared using two approaches, the condensation of alpha-halocarbonyl derivatives with an aminopyrazine or the oxidation-dehydration of a [(beta-hydroxyalkyl)amino]pyrazine. These imidazo[1,2-a]pyrazines were evaluated for their binding affinity to the alpha 1, alpha 2, beta 1, and beta 2 adrenergic receptors as well as their ability to lower blood glucose in insulin resistant hyperglycemic ob/ob mice. Modifications on 8-(1-piperazinyl)imidazo[1,2-a]pyrazine (4) reduced alpha 2 binding, lowered hypoglycemic potency, and showed variations in binding to the alpha 1, beta 1, and beta 2 adrenergic receptors. In addition to 4, the 2-methyl, 3-methyl, and 5-methyl 8-(1-piperazinyl)imidazo[1,2-a]pyrazines (16k, 25m, and 16f, respectively) displayed high affinity for the alpha 2 receptor and were potent hypoglycemic agents when compared to 2-amino-7,8-dihydro-4-(1-piperazinyl)-6H-thiopyrano[3,2- d]pyrimidine (MTP-1403, 2). Receptor binding was modified by use of a 4-methylpiperazine moiety which reduced alpha 1 and beta 1 binding while retaining some hypoglycemic activity. The structure-activity relationship for heterocyclic alkyl and halo substitution on biological activity is discussed.

Synthesis and antiherpetic activity of (+/-)-9-[[(Z)-2-(hydroxymethyl)cyclopropyl]methyl]guanine and related compounds.

A series of analogues of acyclovir and ganciclovir were prepared in which conformational constraints were imposed by incorporation of a cyclopropane ring or unsaturation into the side chain. In addition, several related base-modified compounds were synthesized. These acyclonucleosides were evaluated for enzymatic phosphorylation and DNA polymerase inhibition in a staggered assay and for inhibitory activity against herpes simplex virus types 1 and 2 in vitro. Certain of the guanine or 8-azaguanine derivatives were good substrates for the viral thymidine kinase and were further converted to triphosphate, but none was a potent inhibitor of the viral DNA polymerase. Nevertheless, one member of this group, (+/-)-9-[[(Z)-2-(hydroxymethyl)cyclopropyl]methyl]guanine (3a), displayed significant antiherpetic activity in vitro, superior to that of the corresponding cis olefin 4a. Another group, typified by (+/-)-9-[[(E)-2-(hydroxymethyl)cyclopropyl]methyl]adenine (17b), possessed modest antiviral activity despite an apparent inability to be enzymatically phosphorylated. The relationship of side-chain conformation and flexibility to biological activity in this series is discussed.

Renin inhibitors containing C-termini derived from mercaptoheterocycles.

A series of transition-state analogues having heterocyclythio C-termini has been synthesized and evaluated for inhibition of human renin. Addition of mercaptoheterocycles to a chiral Boc-amino epoxide intermediate led, after several steps, to the target [(2R,3S)-3-(BocPheHis-amino)-4-cyclohexyl-2-hydroxy-1-butyl]thio derivatives. Oxidation of the thioether to sulfone was also investigated. Several of the compounds, especially those derived from N1-substituted-5-mercaptotetrazoles or N4-substituted-3-mercapto-5-(trifluoromethyl)-1,2,4-triazoles, were moderately potent inhibitors of human plasma renin, having IC50 values of 30-40 nM. When selected compounds were administered intravenously to sodium-deficient rhesus monkeys at 0.3-1.2 mg/kg, they reduced plasma renin activity by 75-98%. However, this inhibition and the accompanying drop in blood pressure were of short duration.

Influence of medical school curriculum on primary care specialty choice: analysis and synthesis of the literature.

There is a growing consensus that the proportion of primary care physicians in the United States is inadequate to meet health care needs. Many graduating medical students continue to choose to subspecialize. The literature on curriculum and specialty choice is fraught with confounders and a lack of randomized trials, and recommendations for strategies to increase the production of generalists have not been based on clear evidence that the interventions will be effective, thus making it difficult for medical schools to react responsibly to these recommendations. To assist educators and policymakers in their efforts to produce more generalists, the author critically reviewed the literature on curriculum and primary care specialty choice from 1982 through April 1993. A literature search was conducted using the MEDLINE, Educational Resources Information Center, and PsychInfo databases. Of more than 150 studies found in the search, 31 were determined to be relevant and to meet inclusion criteria. The results confirm that the determinants of specialty choice are multifactorial and that there are many weaknesses in the published literature, making interpretation difficult. Important trends did emerge, however, providing direction for intervention and recommendations for further investigation. The evidence suggests that three types of curricular experiences may increase interest in primary care: third-year required family medicine clerkships (especially those that are six, rather than four, weeks long), continuity experiences in primary care settings, and, most promising of all, primary care tracks.

Determinants of primary care specialty choice: a non-statistical meta-analysis of the literature.

This paper analyzes and synthesizes the literature on primary care specialty choice from 1987 through 1993. To improve the validity and usefulness of the conclusions drawn from the literature, the authors developed a model of medical student specialty choice to guide the synthesis, and used only high-quality research (a final total of 73 articles). They found that students predominantly enter medical school with a preference for primary care careers, but that this preference diminishes over time (particularly over the clinical clerkship years). Student characteristics associated with primary care career choice are: being female, older, and married; having a broad undergraduate background; having non-physician parents; having relatively low income expectations; being interested in diverse patients and health problems; and having less interest in prestige, high technology, and surgery. Other traits, such as value orientation, personality, or life situation, yet to be reliably measured, may actually be responsible for some of these associations. Two curricular experiences are associated with increases in the numbers of students choosing primary care: required family practice clerkships and longitudinal primary care experiences. Overall, the number of required weeks in family practice shows the strongest association. Students are influenced by the cultures of the institutions in which they train, and an important factor in this influence is the relative representation of academically credible, full-time primary care faculty within each institution's governance and everyday operation. In turn, the institutional culture and faculty composition are largely determined by each school's mission and funding sources--explaining, perhaps, the strong and consistent association frequently found between public schools and a greater output of primary care physicians. Factors that do not influence primary care specialty choice include early exposure to family practice faculty or to family practitioners in their own clinics, having a high family medicine faculty-to-student ratio, and student debt level, unless exceptionally high. Also, students view a lack of understanding of the specialties as a major impediment to their career decisions, and it appears they acquire distorted images of the primary care specialties as they learn within major academic settings. Strikingly few schools produce a majority of primary care graduates who enter family practice, general internal medicine, or general practice residencies or who actually practice as generalists. Even specially designed tracks seldom produce more than 60% primary care graduates. Twelve recommendations for strategies to increase the proportion of primary care physicians are provided.

A systematic approach to conducting a non-statistical meta-analysis of research literature.

Literature analyses and syntheses are becoming increasingly important as a means of periodically bringing coherence to a research area, contributing new knowledge revealed by integrating single studies, and quickly informing scientists of the state of the field. As a result, there is a need for approaches that can provide replicable, reliable, and trustworthy results. Over the last decade many researchers have begun using the statistical meta-analysis approach to integrate studies. However, the single studies conducted in many areas are not of the type amenable to statistical meta-analysis but are more appropriate for non-statistical analysis and synthesis. The present paper describes (1) a rigorous approach to conducting a non-statistical meta-analysis of research literature and (2) an example of how this approach was applied to the literature of determinants of primary care specialty choice published between 1987 and 1993. This approach includes model development, literature retrieval, literature coding, rating references for quality, annotating high-quality references, and synthesizing only the subset of the literature found of sufficient quality to be considered. Also, the basic results of each included study are reported in the synthesis so that readers have before them all the "data points" used in the synthesis. Thus, readers can draw their own interpretations without having to re-collect the data, just as they would be able to do in any single study that presents original data as well as conclusions and discussion.

The state of the literature on primary care specialty choice: where do we go from here?

A large body of research on medical students' choice of primary care specialties has been published. However, the literature is difficult to interpret because of multiple biases, design weaknesses, small numbers of subjects, inconsistencies in both dependent and independent variables, and conflicting results. These weaknesses have been noted by authors who have reviewed the work in this area, but the authors have given little direction for ways to improve and build upon the current state of the literature. This paper provides a quantitative description of the content of the specialty choice literature. As part of a larger project that included an exhaustive literature analysis, all research on primary care specialty choice published between 1987 and 1993 was collected and summarized according to study questions, designs, data sources, samples, theory, and outcome variables. Portions of this information were used to rate the quality of each study, yielding a score from zero to 100 that indicated the trustworthiness of the study's conclusions. Overall, the studies examined were found to use predominantly cross-sectional designs and to lack theoretical basis. Special curricular tracks, student personality, and self-reported influences were the most frequently studied determinants of primary care specialty choices. The results confirm previous qualitative descriptions of the state of the literature on specialty choice, and lead to recommendations for approaches to improve the quality of further work in this area. The research agenda that emerged from the larger project is also presented.

Understanding the careers of physician educators in family medicine.

PURPOSE: Little is known about what contributes to the career decisions of physician educators in family medicine. This study sought to understand the variables that influence these decisions and to identify key sources of vitality for physician educators in family medicine. METHOD: A national sample of randomly selected physician educators in family medicine responded to a postcard survey regarding their contribution(s) to education and career satisfaction. A series of exclusion criteria were applied to 399 useable responses, yielding 24 physician educators who participated in a semi-structured telephone interview focusing on their careers. Using qualitative research methods, themes were identified and categorized from the transcribed interviews and investigators' field notes. RESULTS: The career decisions and actions of physician educators in family medicine emanated from an underlying set of values and beliefs associated with "making the world better." Participants sought challenging, diverse, and stimulating positions from which they could have an impact in ways that were consistent with their values. Three major sources of vitality (learners, colleagues, and patients) complemented the desire for challenging positions. Physician educators in family medicine, however, continually struggled to balance their personal and professional lives. CONCLUSION: The study results highlight the key variables that draw faculty into education and sustain their vitality, and the professional and personal challenges that can derail or support their careers. This information can be used to recruit, develop, and retain successful and productive physician educators in family medicine.

A profile of family medicine scholarship 1978-1995: an analysis of national presentations.

BACKGROUND AND OBJECTIVES: Presentations at the annual meetings of the Society of Teachers of Family Medicine were analyzed to determine trends in the content of the work and the types of work represented. METHODS: All program presentations from 1979, 1986, and 1993-1995 were analyzed. Content classifications were based on historic analyses of family medicine literature. Classifications of types of scholarship came from a 1990 Carnegie Foundation report, Scholarship Reconsidered: Priorities of the Professoriate. RESULTS: Results showed that a wide variety of scholarly activities were presented, but application of educational work was predominant. Many presentations crossed interdisciplinary boundaries, including behavioral science, faculty development, and health services. CONCLUSIONS: Contributions of family medicine scholarship may be applicable to other medical fields. The variety of family medicine scholarship may warrant a redefinition of reward systems for faculty.

Published literature on faculty development programs.

BACKGROUND AND OBJECTIVES: Published faculty development program evaluation articles often leave the program description incomplete, making it difficult for new program planners to build on previous work. Using a model based on the work of Stuffelbeam, we examined faculty development literature for the inclusion of important program elements. We found that many important program components, including local needs assessment, leadership and resource support, stakeholder input, implementation barriers, participant attendance, and cost were each discussed in fewer than 30% of published articles. The context, input, process, and product framework is proposed as a guiding model for future program reports.

Self-rated health status: a new vital sign for primary care?

Self-reported health status ratings depend on whether one references health problems or health behaviors. Pessimistic health perceptions may indicate underlying emotional distress or predict mortality. This study explores the association between a single-item health status question and self-reported health problems or behaviors among women in a Wisconsin family medicine clinic. All women who present for health maintenance complete a health history form that includes a single item health status rating. Health status ratings from 251 randomly selected records were compared with certain reported demographics, health behaviors (e.g. smoking, exercise), health concerns, depression and anxiety symptoms, vital signs and body mass index. Health status ratings of fair or poor were found to be associated with race, marital and employment status, obesity, exercise, and depressive symptoms. Smokers were 4.22 times more likely to report a less favorable health category than non-smokers. Implications for future research are discussed.

Bacterial vaginosis in pregnancy and the risk of prematurity: a meta-analysis.

OBJECTIVE: We conducted this meta-analysis to determine the magnitude of risk conferred by bacterial vaginosis during pregnancy on preterm delivery. SEARCH STRATEGY: We selected articles from a combination of the results of a MEDLINE search (1966-1996), a manual search of bibliographies, and contact with leading researchers. SELECTION CRITERIA: We included case control and cohort studies evaluating the risk of preterm delivery, low birth weight, preterm premature rupture of membranes, or preterm labor for pregnant women who had bacterial vaginosis and those who did not. DATA COLLECTION AND ANALYSIS. Two investigators independently conducted literature searches, applied inclusion criteria, performed data extraction, and critically appraised included studies. Summary estimates of risk were calculated as odds ratios (ORs) using the fixed and random effects models. MAIN RESULTS: We included 19 studies in the final analysis. Bacterial vaginosis during pregnancy was associated with a statistically significant increased risk for all outcomes evaluated. In the subanalyses for preterm delivery, bacterial vaginosis remained a significant risk factor. Pooling adjusted ORs yielded a 60% increased risk of preterm delivery given the presence of bacterial vaginosis. CONCLUSIONS: Bacterial vaginosis is an important risk factor for prematurity and pregnancy morbidity. Further studies will help clarify the benefits of treating bacterial vaginosis and the potential role of screening during pregnancy.

p16 INK4a and Ki67 expression in normal, dysplastic and neoplastic uterine cervical epithelium and human papillomavirus (HPV) infection.

Cellular cycle proteins like the p16(INK4a) and the Ki67 proliferation nuclear antigen have been used as oncogenicity cellular markers. The E6 and E7 oncoproteins interact with tumor suppressor genes p53 and pRb, culminating with the p16(INK4a) overexpression. The objective of this study was to evaluate the presence of HPV-DNA in 174 cervical biopsies and correlate the different histological grades with the p16(INK4a) and Ki67 immunohistochemical expression (IHC). A cross-sectional study that enrolled a total of 174 women who underwent uterine cervical biopsies between February 2003 and December 2006, in southern Brazil, was performed. Cervical smear samples were analyzed for the presence of HPV-DNA through polymerase chain reaction (PCR), and biopsy samples were examined for p16(INK4A) and Ki67 expression through IHC techniques. The presence of HPV-DNA was observed in 89% of the tested patients, among which 52% were positive for high-risk (HR) viral types [16, 18 and 31]. Regarding p16(INK4a), an expression of 69% was observed, being expressed in 100% of the high-grade squamous lesions (HSIL) and HR-HPV-DNA positives. Ki67 expression was associated with the lesion grade, being more expressive in the most severe lesions (p<0.001). p16(INK4A) and Ki67 markers coexpression was present in 86% of the samples (p<0.001), being 100% among those positive to HR-HPV-DNA with HSIL (p<0.001). The results suggest an association between the presence of HR-HPV infection and the p16(INK4a) and Ki67 expression and which is even stronger among women with HSIL.