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Biomedical subjects

V Shane Pankratz

Publications and source records attributed to V Shane Pankratz.

At least 19 recordsLinked to original sources

Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer's disease.

We sought to identify new susceptibility loci for Alzheimer's disease through a staged association study (GERAD+) and by testing suggestive loci reported by the Alzheimer's Disease Genetic Consortium (ADGC) in a companion paper. We undertook a combined analysis of four genome-wide association datasets (stage 1) and identified ten newly associated variants with P ≤ 1 × 10(-5). We tested these variants for association in an independent sample (stage 2). Three SNPs at two loci replicated and showed evidence for association in a further sample (stage 3). Meta-analyses of all data provided compelling evidence that ABCA7 (rs3764650, meta P = 4.5 × 10(-17); including ADGC data, meta P = 5.0 × 10(-21)) and the MS4A gene cluster (rs610932, meta P = 1.8 × 10(-14); including ADGC data, meta P = 1.2 × 10(-16)) are new Alzheimer's disease susceptibility loci. We also found independent evidence for association for three loci reported by the ADGC, which, when combined, showed genome-wide significance: CD2AP (GERAD+, P = 8.0 × 10(-4); including ADGC data, meta P = 8.6 × 10(-9)), CD33 (GERAD+, P = 2.2 × 10(-4); including ADGC data, meta P = 1.6 × 10(-9)) and EPHA1 (GERAD+, P = 3.4 × 10(-4); including ADGC data, meta P = 6.0 × 10(-10)).

ATP-Binding Cassette Transporters↗

The association of class I HLA alleles and antibody levels after a single dose of measles vaccine.

Despite the success of the current measles vaccine in controlling disease in industrialized countries, the importance of vaccine failure has become increasingly apparent. Our objective was to determine if associations exist between seronegativity after measles vaccination and class I human leukocyte antigen (HLA) alleles. We undertook a cross-sectional observational study in Rochester, Minnesota, with 242 school-age children previously recruited from a communitywide seroprevalence study. We studied two groups of subjects: 72 were seronegative (EIA < or =0.8 after a single dose of measles vaccine) and 170 were seropositive (enzyme immunoassy [EIA] > or =1.0 after one dose). We used the resources of Mayo Clinic's tissue typing laboratory for serotyping class I HLA-A and HLA-B alleles via microlymphocytotoxicity assays. We found no statistically significant associations with class I HLA-A but did find associations with class I HLA-B, which includes alleles associated with seronegativity (B8, B13, and B44) and those associated with seropositivity (B7 and B51). Elucidation of the specific peptide-HLA complex interactions that lead to varying or failed immune responses may provide fertile groundwork for improved vaccines that can overcome limitations of the current live, attenuated measles vaccine.

Alleles↗

Prospective evaluation of a screen for complex discharge planning in hospitalized adults.

OBJECTIVES: To test the predictive ability of the Probability of Repeated Admission (PRA) screen for nonroutine discharge planning (requiring new referrals for formal services). DESIGN: Prospective cohort. SETTING: Two hospitals within a large Midwestern, tertiary care, referral-based system. PARTICIPANTS: Nine hundred ninety-one hospitalized adults identified using a systematic sampling strategy. MEASUREMENTS: The PRA screen was administered, and use of nonroutine discharge planning resources and nonroutine discharge disposition were determined using observation and open record review. Prolonged length of stay was determined by comparing the actual length of stay with the combined average length of stay for diagnosis-related groupings. RESULTS: Significant differences in PRA scores existed in two of three endpoints, but the differences were small, and the ranges of scores overlapped almost completely. Using, logistic regression, items predicting use of nonroutine discharge-planning resources were self-rated health, caregiver availability, age, and sex (chi-square (chi2) = 105.7, df = 9, P <.001), accounting for 17.9% of the variability and area under receiver operating characteristic curve (AUC) of 0.74. Self-rated health and sex predicted prolonged length of stay (chi2 = 15.3, df = 5, P =.009), but only explained 2.2% of the variability, with an AUC of 0.58. The predictors of nonroutine discharge disposition were self-rated health, caregiver availability, age, sex, and diabetes mellitus (chi2 = 125.8, df = 11, P <.001), accounting for 23.0% of the variability, with an AUC of 0.79. CONCLUSION: The clinical utility of using the PRA as a screen for early identification of persons who use nonroutine discharge planning is limited, although certain individual items may be useful.

Aged↗

Evaluating an instrument for the peer review of inpatient teaching.

The purpose of this study was to assess an instrument for the peer review of inpatient teaching at Mayo. The Mayo Teaching Evaluation Form (MTEF) is an instrument, based on the Stanford seven-category educational framework, which was developed for the peer review of inpatient teaching. The MTEF has 28 Likert-scaled items derived from the Stanford Faculty Development Program form (SFDP-26), the Mayo electronic evaluation form and three additional items. In this study three physician-evaluators used the MTEF to evaluate 10 attending physicians on the Mayo general internal medicine hospital services. Cronbach's alphas were used to assess the internal consistency of the MTEF, and Kendall's coefficient of concordance was used to summarize the inter-rater reliability. Results of this study reveal that the MTEF is internally consistent, based on average ratings across all evaluators (Cronbach's alpha=0.894). Stanford categories with the highest alphas are Self-Directed Learning, Learning Climate, Communication of Goals, and Evaluation. Categories with lower alphas are Feedback, Understanding and Retention, and Control of Teaching Session. Additionally, the majority of items on the MTEF show significant agreement across all evaluators, and teacher enthusiasm was among the most reliable items. In conclusion, the MTEF is overall internally consistent for the peer review of inpatient teaching at Mayo. Hence, the MTEF may be a useful element in the peer evaluation of teaching at our institution.

Education, Medical↗

Decisional capacity of severely depressed patients requiring electroconvulsive therapy.

OBJECTIVE: The decisional capacity of severely depressed people frequently comes into question. The ability to improve this decisional capacity through educational efforts alone is not known. Our study aimed to determine the decisional capacity of severely depressed people requiring electroconvulsive therapy (ECT), and whether educational interventions improve their ability to provide informed consent for ECT. MATERIALS AND METHODS: Forty subjects with severe depression were recruited. Using the MacArthur Competence Assessment Tool for Treatment instrument, decisional capacity was assessed at baseline and reassessed after education. All of the subjects received standard education. Additionally, half were blindly randomized to receive an experimental educational intervention. RESULT: SAt baseline, there was no statistical difference in the decisional capacity between the standard and experimental intervention groups. After educational interventions, all four areas of decisional capacity improved for both groups (understanding p < 0.001, reasoning p < 0.001, appreciation p = 0.031, choice p = 0.006). However, there was no measurable additional improvement in scores for those randomized to receive additional education. CONCLUSION: Our findings indicate that this group of severely depressed people had good decisional capacities to give informed consent. Education improved their decisional capacity. There is an endpoint beyond which additional educational intervention does not result in measurable improvement in decisional capacity.

Adult↗

Lymphocyte-rich gastric cancer: associations with Epstein-Barr virus, microsatellite instability, histology, and survival.

Lymphocyte-rich gastric carcinomas may have a better prognosis than cancers without a pronounced host inflammatory response. Two subsets of gastric cancer-Epstein-Barr virus-positive and microsatellite instability high-have been associated with a lymphocyte-rich phenotype. We assessed relationships between tumor-infiltrating lymphocytes, Epstein-Barr virus status, microsatellite instability status, and cancer-specific survival in 110 resected gastric cancers. Seven patients had Epstein-Barr virus-positive cancer, including 4 (3.7%) of 107 consecutive patients. Tumors from 17 patients (16%) were designated microsatellite instability high on the basis of negative immunohistochemical staining for MLH1; all tumors had intact expression of MSH2 and MSH6. Epstein-Barr virus-positive cancers had increased tumor-infiltrating lymphocytes compared with Epstein-Barr virus-negative cancers (median 450/10 HPF versus 21/10 HPF, P <.001). Microsatellite instability-high cancers also had increased tumor-infiltrating lymphocytes compared with non-microsatellite instability-high cancers (median 150/10 HPF versus 20/HPF, P <.001). Microsatellite instability-high cancers affected older patients and were more likely to be intestinal in the Lauren classification and expanding in the Ming classification. By univariate analysis, decreased risk of death from gastric cancer was significantly associated with low tumor stage, expanding growth pattern, increasing tumor-infiltrating lymphocyte count, and microsatellite instability-high status. High tumor-infiltrating lymphocyte count and microsatellite instability-high status retained statistical significance as favorable prognostic factors after adjustment for tumor stage in multivariate analysis. Tumor-infiltrating lymphocyte count retained statistical significance as a favorable prognostic factor after adjustment for microsatellite instability-high status; but microsatellite instability-high status did not remain a significant independent prognosticator after adjustment for tumor-infiltrating lymphocyte count. The association between microsatellite instability-high cancers and high tumor-infiltrating lymphocyte counts may account for the association of microsatellite instability-high gastric cancers with improved survival.

Adenocarcinoma↗

Evolutionary pressure of a receptor competitor selects different subgroup a avian leukosis virus escape variants with altered receptor interactions.

A complex interaction between the retroviral envelope glycoproteins and a specific cell surface protein initiates viral entry into cells. The avian leukosis-sarcoma virus (ALV) group of retroviruses provides a useful experimental system for studying the retroviral entry process and the evolution of receptor usage. In this study, we demonstrate that evolutionary pressure on subgroup A ALV [ALV(A)] entry exerted by the presence of a competitive inhibitor, a soluble form of the ALV(A) Tva receptor linked to a mouse immunoglobulin G tag (quail sTva-mIgG), can select different populations of escape variants. This escape population contained three abundant ALV(A) variant viruses, all with mutations in the surface glycoprotein hypervariable regions: a previously identified variant containing the Y142N mutation in the hr1 region; a new variant with two mutations, W141G in hr1 and K261E in vr3; and another new variant with two mutations, W145R in hr1 and K261E. The W141G K261E and W145R K261E viruses escape primarily by lowering their binding affinities for the quail Tva receptor competitive inhibitor while retaining wild-type levels of binding affinity for the chicken Tva receptor. A secondary phenotype of the new variants was an alteration in receptor interference patterns from that of wild-type ALV(A), indicating that the mutant glycoproteins are possibly interacting with other cellular proteins. One result of these altered interactions was that the variants caused a transient period of cytotoxicity. We could also directly demonstrate that the W141G K261E variant glycoproteins bound significant levels of a soluble form of the Tvb(S3) ALV receptor in a binding assay. Alterations in the normally extreme specificity of the ALV(A) glycoproteins for Tva may represent an evolutionary first step toward expanding viral receptor usage in response to inefficient viral entry.

Amino Acid Sequence↗

A multidimensional workshop using human cadavers to teach bedside procedures.

BACKGROUND: Internal medicine residents should be able to perform bedside procedures safely and efficiently. DESCRIPTION: We developed a human cadaver workshop for teaching internal medicine residents bedside procedures. The workshop consisted of lectures and hands-on experiences with cadavers covering thoracentesis, paracentesis, lumbar puncture, arthrocentesis, and bone marrow biopsy. A Web site was developed to provide technical support to residents on the medical wards after completion of the workshop. EVALUATION: We successfully developed and implemented a procedure workshop for residents using human cadavers. The workshop improved mean scores on knowledge and procedure comfort level assessments. Residents demonstrated the skills required to safely complete each procedure. CONCLUSIONS: Our multidimensional educational intervention may be an effective tool for improving the knowledge, skills, and attitudes required for performing bedside procedures. More research needs to be done to determine if this workshop increases the number and proficiency of bedside diagnostic procedures performed by residents.

Attitude of Health Personnel↗

Search for neuron-specific and nonneuron-specific antibodies in narcoleptic patients with and without HLA DQB1*0602.

STUDY OBJECTIVES: Narcolepsy is strongly associated with the presence of HLA DQB1*0602. This and other evidence suggests that human narcolepsy is an autoimmune disease. This is in distinction to that found in canine models where hypocretin receptor 2 mutations are etiologic. We decided to test for the presence of several neuron-specific and organ-specific autoantibodies to see if they were present in HLA DQB1*0602-associated or cataplexy-associated narcolepsy or could serve as a serologic marker of the illness. DESIGN: We tested for N-type and P/Q-type voltage-gated calcium-channel antibodies, neuronal nicotinic acetylcholine receptor alpha3 subunit, acetylcholine receptor-binding antibodies, striated muscle antibodies, Type 1 Purkinje cell cytoplasmic antibodies, types 1 and 2 antineuronal nuclear antibodies and amphiphysin antibodies, GAD-65 antibody, and thyroid microsomal and thyroglobulin antibodies in the serum of 43 patients with or without cataplexy, 41 with known HLA status. SETTING: Narcoleptic subjects were recruited from the Mayo Sleep Disorders Center. PARTICIPANTS: N/A. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: No antibody test yielded significantly positive results for the group as a whole or for subgroups of patients with cataplexy or positive HLA DQB1*0602 status. CONCLUSIONS: These results do not support the hypothesis that narcolepsy is an autoimmune disease. However, it is possible that the autoimmune attack is very selective and does not involve the epitopes measured in this study. Recent findings that the hypocretin neurotransmission system is involved in animal models of narcolepsy should lead to research to look for antibodies directed against components of the hypocretin neurotransmission system in narcolepsy.

Adult↗

Hypocretin (orexin) levels in cerebrospinal fluid of patients with narcolepsy: relationship to cataplexy and HLA DQB1*0602 status.

STUDY OBJECTIVES: Hypocretin (orexin) deficiency (< 40 pg/ml) is highly associated with narcolepsy with cataplexy (89.5%) and more specifically with patients with cataplexy who are HLA DQB1*0602 positive (95.7%). The relationship between hypocretin-1 levels and narcolepsy without cataplexy or the DQB1*0602 allele is less clear. METHODS/DESIGN: This study compared cerebrospinal (CSF) hypocretin-1 in 13 patients with HLA DQB1*0602 allele and cataplexy to 4 HLA negative patients with cataplexy, 3 HLA positive patients without cataplexy, and 6 HLA negative patients without cataplexy, plus 15 neurologic controls. SETTING: Data were collected at a sleep disorders center. PATIENTS/PARTICIPANTS: Twenty-six patients with narcolepsy, with and without HLA DQB1*0602 and with and without cataplexy, as well as 15 neurologic controls. INTERVENTIONS: N/A. MEASUREMENT & RESULTS: Using analysis of variance techniques, statistically significant differences were found between the CSF hypocretin-1 levels in HLA positive patients and all other groups (P < 0.01). Although the sample size was small, subjects with the DQB1*0602 allele without cataplexy had lower hypocretin-1 levels than did other groups (other than the HLA and cataplexy positive group). Hypocretin-1 levels were not associated with age at diagnosis, age at lumbar puncture, body mass index at time of diagnosis, or body mass index at time of lumbar puncture. CONCLUSION: This data confirms the previous finding that undetectable hypocretin-1 levels are highly specific for HLA positive narcolepsy with cataplexy. The data suggests that the pathophysiology and, by extension, etiology of this disorder are distinctly different from the other conditions studied. The relationship of the DQB1*0602 allele and reduced hypocretin-1 levels needs further study.

Adolescent↗

Metastatic prostate carcinoma to bone: clinical and pathologic features associated with cancer-specific survival.

BACKGROUND: The objective of this study was to examine the clinical and pathologic features of metastatic prostate carcinoma to bone in a large cohort of men, and the associations of these features with outcome. METHODS: Sixty-eight men who underwent surgery for metastatic prostate carcinoma to bone for stabilization of a pathologic fracture or impending fracture were studied. Clinical characteristics included the type of treatment for the primary and metastatic prostate carcinoma, age and serum prostate specific antigen (PSA) at the diagnosis of the metastatic prostate carcinoma, radiographic findings of the metastasis (osteoblastic, osteolytic, or mixed), and the number of metastatic sites at the time of the surgery for the metastasis. Pathologic features examined included Gleason score of the metastatic prostate carcinoma. Immunohistochemical stains for MIB-1, cytokeratin, PSA, synaptophysin, chromogranin A, serotonin, estrogen receptor, progesterone receptor, and androgen receptor were performed for all cases. The Kaplan-Meier method was used to estimate cancer-specific survival. The duration of follow-up was defined as the interval from the date of surgery for the metastasis to the date of death or last follow-up. Univariate and multivariate Cox proportional hazards models were fit to assess the features that were associated with death from prostate carcinoma. RESULTS: The average (standard deviation) time from the surgery for the metastasis to death from prostate carcinoma was 1.5 (1.9) years, ranging from 0 days to 10 years, with a median of 1 year. The estimated cancer-specific survival rates at 1 year, 2 years, and 3 years were 54.3%, 28.8%, and 22.9%, respectively. Median cancer-specific survival occurred at 1.1 years. After 4 years of follow-up, there were only seven patients left at risk for death from prostate carcinoma. Features that were found to be significantly associated with death from prostate carcinoma univariately included the interval between the diagnosis of metastasis and the surgery for metastasis (P < 0.001), androgen deprivation therapy before surgery for the metastasis (P = 0.002), presentation with metastasis (P = 0.003), the number of metastatic sites (P = 0.034), Gleason score of the metastasis (P = 0.002), and tumor positivity for chromogranin A (P = 0.041). On multivariate analysis, the interval between the diagnosis of metastasis and the surgery for metastasis (P < 0.001), Gleason score of the metastasis (P < 0.001), and tumor positivity for chromogranin A (P = 0.009) were associated significantly with death from prostate carcinoma. CONCLUSIONS: Although cancer-specific survival for patients after surgery for prostate carcinoma metastatic to bone is poor, assessments of tumor differentiation of the metastasis and chromogranin A positivity provide prognostic information.

Aged↗

Associations between human leukocyte antigen homozygosity and antibody levels to measles vaccine.

The association between human leukocyte antigen (HLA) homozygosity and measles antibody levels was assessed in a volunteer group of 242 children. Serum samples were tested for measles IgG antibodies, class I and class II HLA alleles were typed, and associations were examined between HLA homozygosity and antibody levels. Children who were homozygous for at least 1 locus were twice as likely to be seronegative (odds ratio, 1.97; 95% confidence interval, 1.08-3.61). Children who were homozygous at >/=1 loci were increasingly likely to be seronegative (chi(2) test for trend; P=.02). When serum antibody levels were examined as continuous variables, children who were homozygous at certain loci tended to have lower mean antibody levels. These results suggest that lack of HLA diversity may limit the range of peptides that can be presented to antibody-producing cells, potentially resulting in a decreased immune response to viral infections.

Adolescent↗

The epidemiology of narcolepsy in Olmsted County, Minnesota: a population-based study.

STUDY OBJECTIVES: To determine the age- and sex-specific incidence rates and prevalence of narcolepsy in a United States community. DESIGN: The records-linkage system of the Rochester Epidemiology Project was utilized to ascertain all patients with narcolepsy seen in Olmsted County, Minnesota between 1960 and 1989. Age- and sex-specific incidence rates were calculated, using census data. Prevalence of narcolepsy on January 1,1985 was calculated. SETTING: N/A. PATIENTS OR PARTICIPANTS: Community patients diagnosed with narcolepsy by a validated set of diagnostic criteria. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: The incidence rate per 100,000 persons per year was 1.37 (1.72 for men and 1.05 for women). The incidence rate was highest in the 2nd decade, followed in descending order by the 3rd, 4th and 1st decades. The prevalence on January 1, 1985 was 56.3 per 100,000 persons. Approximately 36% of prevalence cases did not have cataplexy. CONCLUSIONS: Narcolepsy is not a rare disorder. It appears to be commoner in men. It originates most commonly in the 2nd decade. Narcolepsy without cataplexy is an important subgroup, warranting further study.

Adolescent↗

Interaction of waist/hip ratio and family history on the risk of hormone receptor-defined breast cancer in a prospective study of postmenopausal women.

The authors previously reported an interaction of waist/hip ratio and family history on the risk of breast cancer in the Iowa Women's Health Study. Here they reexamine this association based on 9 additional years of follow-up, stratifying on tumor receptors for estrogen and progesterone. Data on risk factors and family history of breast cancer were ascertained in 1986. The occurrences of breast cancer and estrogen receptor/progesterone receptor were determined through the Iowa Surveillance, Epidemiology, and End Results' registry. Rate ratios were elevated with increasing weight and body mass index and decreasing body mass index at age 18 years, but they did not vary by family history. There was no association with height, waist circumference, or waist/hip ratio. A linear trend of increasing risk with increasing waist/hip ratio was observed among family history-positive women (p = 0.06) but not among family history-negative women (p = 0.87). This apparent interaction (p = 0.09) was examined by estrogen receptor or progesterone receptor status. When stratified on family history and estrogen receptor, no clear patterns were evident. In contrast, family history-positive women in the upper quintile of the waist/hip ratio were at 2.2-fold greater risk of progesterone receptor-negative tumors compared with those in the lowest quintile (95% confidence interval: 0.9, 5.8). Thus, the previously reported interaction between family history and waist/hip ratio is still (weakly) evident and appears to reflect risk for progesterone receptor-negative tumors.

Abdomen↗

How common is attention-deficit/hyperactivity disorder? Incidence in a population-based birth cohort in Rochester, Minn.

CONTEXT: The frequency of occurrence of attention-deficit/hyperactivity disorder (AD/HD) is in dispute. This uncertainty has contributed to the concern that too many children in the United States are being treated with stimulant medication. OBJECTIVES: To determine the cumulative incidence of AD/HD in a population-based birth cohort and to estimate the prevalence of pharmacologic treatment for children who fulfill research criteria for AD/HD. DESIGN: Population-based birth cohort study. SETTING AND SUBJECTS: All children born between 1976 and 1982 in Rochester, Minn, who remained in the community after age 5 years (N = 5718). MAIN OUTCOME MEASURES: Medical and school records were reviewed for clinical diagnoses of AD/HD and supporting documentation (symptoms consistent with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria and positive results for AD/HD-related questionnaires). Research-identified cases were defined as: (1) "definite" AD/HD (clinical diagnosis and at least one type of supporting documentation); (2) "probable" AD/HD (clinical diagnosis but no supporting documentation or no clinical diagnosis but both types of supporting documentation); (3) "questionable" AD/HD (no clinical diagnosis, but at least one type of supporting documentation); and (4) "not AD/HD" (all other subjects). Information about pharmacologic treatment for AD/HD was abstracted for all subjects. RESULTS: The highest estimate of the cumulative incidence at age 19 years (with 95% confidence interval) of AD/HD (definite plus probable plus questionable AD/HD) was 16.0% (14.7-17.3). The lowest estimate (definite AD/HD only) was 7.4% (6.5-8.4). Prevalence of treatment with stimulant medication was 86.5% for definite AD/HD, 40.0% for probable AD/HD, 6.6% for questionable AD/HD, and 0.2% for not AD/HD. CONCLUSIONS: These results provide insight into the apparent discrepancies in estimates of the occurrence of AD/HD, with less stringent criteria resulting in higher cumulative incidence. Children who met the most stringent criteria for AD/HD were most likely to receive pharmacologic treatment.

Adolescent↗

Intraoperative transesophageal echocardiography during surgery for congenital heart defects.

OBJECTIVE: This study was undertaken to further define the impact of intraoperative transesophageal echocardiography during surgery for congenital heart disease and to determine appropriate indications. METHODS: The impact of transesophageal echocardiography on patient care was assessed in 1002 patients who underwent this procedure during surgery for congenital heart defects. It had major impact when new information altered the planned procedure or led to a revision of the initial repair. The safety of intraoperative transesophageal echocardiography was evaluated by review of the prospective data sheets and the medical record. A simple relative cost analysis was also performed. RESULTS: Patient median age was 9.9 years (range 2 days to 85 years). Transesophageal echocardiography had prebypass or postbypass major impact in 13.8% of cases (n = 138/1002). Major impact was more frequent during reoperations (P <.03). Procedures that benefited most from the additional information were valve repairs (aortic or atrioventricular) and complex outflow tract reconstructions. Partial anomalous pulmonary venous connection, tricuspid valve repair (other than of Ebstein anomaly), simple atrioventricular discordance, aortic arch anomalies, and secundum atrial septal defects had major impact rates less than 5%. No major complications occurred. Minor complications occurred in 1% of patients and were most often observed in infants smaller than 4 kg. Routine use of transesophageal echocardiography for all patients with congenital heart defects proved cost-effective. CONCLUSIONS: On the combined basis of the observed rates of major impact, the minimal complications, and the relative cost advantage, we believe that routine use of transesophageal echocardiography during most intracardiac repairs of congenital heart defects is justified, particularly for patients undergoing repeat operations for congenital cardiac malformations.

Child↗

Perineural invasion and MIB-1 positivity in addition to Gleason score are significant preoperative predictors of progression after radical retropubic prostatectomy for prostate cancer.

We assessed the use of clinical stage, serum prostate specific antigen, DNA ploidy, proliferation, and traditional histologic findings from the biopsy to predict prostate cancer progression after radical retropubic prostatectomy. Between 1995 and 1998, 454 consecutive patients with cancer on biopsy were treated by radical retropubic prostatectomy. Preoperative serum prostate specific antigen, clinical stage, Gleason score, percentage of cores and surface area positive for cancer, perineural invasion, and DNA ploidy and MIB-1 immunostain quantitation by image analysis were evaluated in a multivariate Cox proportional hazards regression model to predict cancer progression. Cancer progression was defined as a postoperative serum prostate specific antigen level of > or = 0.4 ng/mL, local recurrence, or systemic progression. Mean follow-up was 3.4 years (range 17 days to 5.8 years). Cancer progression was observed in 73 patients with a mean time to progression of 2.1 years (range 33 days to 5.1 years). Gleason score (p <0.001), MIB-1 cancer proliferation (p = 0.008), and perineural invasion (p = 0.008) were significantly associated with progression. Patients with cancer Gleason scores of 7 and >7 had a 2.5-fold and nearly 4-fold increased risk, respectively, of cancer progression compared with patients with cancer Gleason scores of < or = 6. Patients with perineural invasion at biopsy were twice as likely to progress compared with patients without perineural invasion. Each 1-unit increase in MIB-1 on the natural logarithmic scale increased the risk of cancer progression by 64%. Cancer progression models that include serum prostate specific antigen and clinical stage may require revision to incorporate perineural invasion and MIB-1 proliferative activity in addition to Gleason score.

Adult↗