Stereotactic core biopsy of breast microcalcifications: comparison of film versus digital mammography, both using an add-on unit.

OBJECTIVE: The goal of this study was to assess the accuracy of an add-on stereotactic unit for core biopsy of indeterminate breast microcalcifications and to compare digital with conventional stereotactic guidance. MATERIALS AND METHODS: We conducted a retrospective review of 232 lesions with indeterminate microcalcifications in 218 women who underwent stereotactically guided breast biopsies. All biopsies were performed using a standard mammography machine with an add-on unit, 121 with conventional and 111 with digital stereotactic guidance. Successful sampling of the lesion was determined by the detection of microcalcifications on specimen radiography or at pathology. RESULTS: Using the add-on unit, 219 (94.4%) of the 232 targeted lesions were successfully sampled. The size, location, number of cores per lesion, and histology of the lesions were not different between the conventional and digital stereotactic biopsy groups (p > 0.1). Indeterminate microcalcifications were missed on biopsy in nine (7.4%) of 121 cases using conventional radiography and in only four (3.6%) of 111 cases using digital imaging. Digital stereotactic guidance allowed sampling of lesions with fewer calcifications per square centimeter (p < 0.001). CONCLUSION: Sampling of indeterminate microcalcifications using a standard mammography machine and an add-on unit has a high accuracy, similar to rates reported for dedicated prone biopsy tables. An add-on unit offers the advantage of considerable cost and space savings. Relative to conventional radiography, digital stereotactic guidance allows lesions with fewer calcifications to be sampled and achieves a greater biopsy success rate. Immediate digital images in the biopsy room also permit rapid adjustment of alignment and minimize patient movement.

A collaborative clerkship with a focus on rural community health.

The Deans' Rural Primary Care Clerkship was developed through the collaborative efforts of South Carolina's two medical schools. The clerkship provides students an innovative learning experience in rural community medicine through the unique combination of learning opportunities with community-oriented primary care, continuous quality improvement, interdisciplinary health care teams, and cultural competency. Much of students' learning addresses current directives for population health training. The positive experience students are having in these rural, underserved South Carolina communities will help them better understand the rewards and challenges of rural, community-responsive health care.

Implementation of a college-wide GME core curriculum.

As health care delivery and its associated costs have been scrutinized carefully over the past decade, educational institutions have been expected to demonstrate how a particular educational requirement such as residency training brings benefit to the purchasers and users of their health care services. As part of this trend, the Accreditation Council for Graduate Medical Education recently enacted new accreditation standards mandating the inclusion of curricular elements that expose residents to basic concepts and principles of the non-technical areas of health care across a variety of topics, including ethics, cost containment, socioeconomics, medical-legal issues, communication skills, research design, statistics, and critical review of the medical literature. The authors report the efforts at the Medical University of South Carolina to overcome obstacles and successfully implement an institution-wide core curriculum program, dealing with the kinds of topics mentioned above, across 47 specialty and subspecialty programs with over 500 residents and fellows. The seminal events and critical strategies are described, along with lessons learned along the way. The following were key elements to success: (1) adhering to a strategic plan assigning oversight of residency education to the graduate medical education (GME) office; (2) gaining strong support from the dean and other college officials; (3) creating a stepwise centralization of residencies in college via the GME committee; (5) making the first core curriculum element one that had an excellent chance to succeed; (6) having core curriculum sessions begin in evenings and weekends to not interfere with regular curriculum, but later, when the value of the curriculum became evident to departments, moving the sessions to be within the week; (7) having the philosophy of the GME office be to maintain a flexible approach and serve departments.

Ventriculitis due to Cryptococcus uniguttulatus.

Infections due to non-neoformans cryptococci are rare. We report the first case of a human infection caused by Cryptococcus uniguttulatus. Ventriculitis caused by this organism developed in a 65-year-old woman who had had repair of an internal carotid aneurysm. In vitro sensitivity testing showed the Cryptococcus species sensitive to amphotericin B and itraconazole. Treatment with amphotericin led to resolution of the infection.

Body mass, age, and the APC I1307K allele in Ashkenazi Jewish prostate cancer patients.

The I1307K mutation of the adenopolyposis coli gene (APC), located on chromosome 5q21-q22, is associated with an increased risk of cancer in Ashkenazi Jews. In the present study, we analyzed age and body mass of Ashkenazi Jewish prostate cancer patients, with and without the APC I1307K mutation. Participants in our study were found through urology and radiation oncology clinics, and all eligible patients were asked to take part. A familial history was obtained by interview or self-report questionnaire. Histological confirmation of diagnosis was obtained for all subjects. The I1307K allele of the APC gene was detected by amplification of lymphocyte DNA from peripheral blood according to standard polymerase chain reaction (PCR) and dot blot procedures. We studied 135 Ashkenazi Jewish men with prostate cancer. The youngest was 49, the oldest 80, average age 68 +/- 6.88 (mean +/- SD). The older patients carrying the wild type APC allele tended to have a lower body mass than the younger ones (r = -.27, P =.002). Of 71 patients under 70 years old, 65 carried the wild type APC allele, and had a body mass index of 28. 7 +/- 4.23 kg/m(2). The six men under age 70 carrying the I1307K APC allele had a body mass index of 26.87 +/- 1.44 kg/m(2). The difference in body mass index of the two groups is significant (P =. 032, t test for unequal variance). Increased body mass is a prostate cancer risk factor, and hereditary prostate cancer is associated with younger patients. Therefore, our finding, that patients under age 70 carrying the I1307K allele are significantly thinner than those carrying the wild type allele, suggests that the APC I1307K allele is also a prostate cancer risk factor. Our results are in accord with other studies indicating that APC mutations increase the risk of prostate cancer.

Founder BRCA 1 and 2 mutations among a consecutive series of Ashkenazi Jewish ovarian cancer patients.

OBJECTIVE: The purpose of this study was to describe the incidence of the three Ashkenazi Jewish founder genetic BRCA 1 and 2 mutations among an unselected, consecutive group of Ashkenazi Jewish ovarian cancer patients. MATERIALS AND METHODS: From 7/30/96 to 4/12/99, 92 Ashkenazi Jewish patients with histologically confirmed epithelial ovarian cancer had surgery. All of these patients had DNA extracted from 5-microm sections of their paraffin-embedded surgical specimen tissue blocks using the Qiagen QIAamp tissue extraction kit. A multiplex (triplex) polymerase chain reaction was performed to amplify fragments for the 185delAG, 5382insC, and 6174delT mutations. The products were hybridized with normal and mutant probes for each of the three mutations. All clinical data were collected retrospectively and statistical significance was evaluated using the chi(2) test or a two-tailed Fisher's exact test, depending on the sample size. RESULTS: There were 23 patients positive for one of the three founder BRCA mutations. Fourteen patients were positive for the 185delAG mutation, 2 patients were positive for the 5382insC mutation, and 7 patients were positive for the 6174 delT mutation (61, 9, and 30%, respectively). This represented a 25% incidence (95% CI: 16-34%) of one of the three founder BRCA mutations among our 92 Ashkenazi Jewish ovarian cancer patients. None of the patients was positive for more than one mutation. There was no statistically significant difference in parity, histology, grade, or stage between the BRCA founder mutation positive and negative patients. The difference between the percentage of mutation carriers among patients with one affected first-degree relative (13/22 or 59%) compared to those without at least one affected first-degree relative (10/70 or 14%) was highly significant (P = 0.001). CONCLUSIONS: Ashkenazi Jewish ovarian cancer patients represent a group with a high likelihood of being carriers of BRCA 1 and 2 genetic mutations, regardless of family history. As a result, all ovarian cancer patients who are of Ashkenazi Jewish descent should be counseled regarding BRCA 1 and 2 genetic screening, as well as the potential implications of these results for the patient as well as her relatives in terms of prognosis, screening, chemoprevention, and consideration of prophylactic surgical procedures.

Stereotaxic core needle biopsy of breast microcalcifications obtained using a standard mammography table with an add-on unit.

OBJECTIVE: To demonstrate the reliability of stereotaxic biopsy of indeterminate microcalcifications using a standard mammography table with an add-on unit. METHODS: In 121 cases of indeterminate microcalcifications, core biopsy was performed using a standard mammography table with an add-on stereotaxic unit. Microcalcifications were identified on radiography of core specimens. RESULTS: Microcalcifications and a definitive histologic diagnosis were obtained in 112 core biopsies (92.6%), with no significant complications. In 23 lesions frank malignancy was diagnosed, and all of these diagnoses were confirmed on surgery. Pathologic examination suggested carcinoma in 4 lesions, and open biopsy confirmed malignancy in 3 of these cases. Four lesions showed atypical ductal hyperplasia. Benign disease was diagnosed in 81 lesions, of which 78 remained stable on mammographic follow-up (mean 16 months later) and 3 were subjected to surgical biopsy (of which 1 was malignant and 2 were benign). Nine cases were technically unsatisfactory because microcalcifications were not sampled. CONCLUSION: Stereotaxic core biopsy performed with an add-on unit is a safe and reliable technique for biopsy of indeterminate microcalcifications. For successful biopsy, microcalcifications must be harvested. Pathologic results should be correlated with mammographic findings. The accuracy rate compares favourably with results reported using prone biopsy tables. In an era of cost containment, this alternative to prone biopsy tables could result in significant savings in terms of capital investment and use of hospital rooms. In this study, surgical biopsy could have been avoided in 64.5% of cases.

Curricular renewal for the new millennium at the Medical University of South Carolina College of Medicine.

The MUSC College of Medicine is engaged in a curricular renewal process that emphasizes increased integration of the basic and clinical sciences throughout all four years of the curriculum, more self-directed learning, and earlier patient contact for students. Several basic science courses have been modified and a new "Doctoring Curriculum" has been introduced to develop students' clinical skills and preparation for medical practice. Changes to the third year of the curriculum include the new Deans' Rural Primary Care Clerkship. Other third-year curricular changes include small-group case discussion sessions that emphasize the integration of basic and clinical sciences in medical practice, and the incorporation of nutrition throughout all fours of the curriculum. The changes described in this manuscript are designed to address a wide range of educational needs of future physicians, including the acquisition of the attributes endorsed by the AAMC MSOP--altruism, knowledge, skillfulness and dutifulness. This new curriculum will evolve over time and the goal remains to help equip future physicians with the requisite knowledge, skills and attitudes for medical practice in the new millennium.

D1S80 allele frequencies in Hasidic and non-Hasidic New York City Jewish populations.

Allele frequencies were determined for the VNTR locus D1S80 in Hasidic and non-Hasidic Ashkenazi New York City Jewish subpopulations. Samples were amplified via the polymerase chain reaction and underwent genotyping using polyacrylamide gel electrophoresis. In the Hasidic population 14 alleles were observed as opposed to 19 alleles in the non-Hasidic community. Both populations were tested for Hardy-Weinberg equilibrium. The frequency data obtained can be used for comparison to other populations and for allele and genotype frequency estimates in genetic marker profiling of evidentiary specimens.

Frequency and carrier risk associated with common BRCA1 and BRCA2 mutations in Ashkenazi Jewish breast cancer patients.

Based on breast cancer families with multiple and/or early-onset cases, estimates of the lifetime risk of breast cancer in carriers of BRCA1 or BRCA2 mutations may be as high as 85%. The risk for individuals not selected for family history or other risk factors is uncertain. We determined the frequency of the common BRCA1 (185delAG and 5382insC) and BRCA2 (6174delT) mutations in a series of 268 anonymous Ashkenazi Jewish women with breast cancer, regardless of family history or age at onset. DNA was analyzed for the three mutations by allele-specific oligonucleotide hybridization. Eight patients (3.0%, 95% confidence interval [CI] 1.5%-5.8%) were heterozygous for the 185delAG mutation, two (0.75%, 95% CI 0.20-2.7) for the 5382insC mutation, and eight (3.0%, 95% CI 1.5-5.8) for the 6174delT mutation. The lifetime risk for breast cancer in Ashkenazi Jewish carriers of the BRCA1 185delAG or BRCA2 6174delT mutations was calculated to be 36%, approximately three times the overall risk for the general population (relative risk 2.9, 95% CI 1.5-5.8). For the 5382insC mutation, because of the low number of carriers found, further studies are necessary. The results differ markedly from previous estimates based on high-risk breast cancer families and are consistent with lower estimates derived from a recent population-based study in the Baltimore area. Thus, presymptomatic screening and counseling for these common mutations in Ashkenazi Jewish women not selected for family history of breast cancer should be reconsidered until the risk associated with these mutations is firmly established, especially since early diagnostic and preventive-treatment modalities are limited.

HLA-DQA1 and polymarker allele frequencies in two New York City Jewish populations.

Allele and genotype frequencies were determined for the HLA-DQA1 and Amplitype Polymarker loci (low density lipoprotein receptor (LDLR), glycophorin A (GYPA), hemoglobin G gammaglobin (HBGG), D7S8, and group-specific component (Gc)) in Hasidic and non-Hasidic Ashkenazi New York City Jewish subpopulations. For all loci tested, except HBGG, the 2 subpopulations meet the assumption of Hardy-Weinberg equilibrium. Comparison of various allele and genotype frequencies for the Hasidic and the non-Hasidic groups showed no significant differences. Comparison of the various allele frequencies in the two subpopulations to another Caucasian group revealed significant differences at the HLA-DQA1 and D7S8 loci in the Hasidic group. These frequency data can be used for comparison to other populations and for frequency estimates in DNA profiling.

Prenatal detection and molecular characterization of a de novo duplication of the distal long arm of chromosome 19.

A tandem duplication of the distal long arm of chromosome 19 was identified in a 10 week fetus by analysis of chorionic villi. The fetal karyotype from two primary cultures was 46,XY,dir dup(19)(q13.2q13.4). The origin of the extra material was confirmed by fluorescence in situ hybridization using a chromosome 19 whole chromosome probe. Parental chromosomes were normal, indicating a de novo origin of the extra chromosome material. This is the first case of dup(19q) detected by prenatal diagnosis. Molecular studies demonstrated that the duplication involved a maternal chromosome 19.

Paternal uniparental disomy for chromosome 14: a case report and review.

Uniparental disomy (UPD) for several chromosomes has been associated with disease phenotypes. Maternal UPD for chromosome 14 has been described and has a characteristic abnormal phenotype. Paternal UPD14 is rare and only three previous cases have been reported. We describe a new case of paternal UPD for chromosome 14 in an infant with a 45,XX,der(13q;14q) karyotype, which was confirmed by molecular analysis. The proposita had findings similar to those of the previous cases of patUPD14 and we conclude that there is a characteristic patUPD14 syndrome most likely due to imprinting effects. Couples with Robertsonian translocations involving chromosome 14 should be counseled as to the possibility of UPD14 and the option of prenatal diagnosis when indicated.

Homozygosity for pericentric inversions of chromosome 9. Prenatal diagnosis of two cases.

The finding of homozygosity for a pericentric inversion of chromosome 9 [inv(9)] is rare, and previously has not been reported at prenatal diagnosis. We describe two unrelated cases of homozygosity for inv(9) identified in amniocytes. In each case, both parents were heterozygotes for the inv(9); 46,XX,inv(9)(p11q13) and 46,XY,inv(9) (p11q13). Case 1 resulted in a normal term infant who at age 5 years was phenotypically and developmentally normal. Case 2 was referred for severe intrauterine growth retardation (IUGR) and oligohydramnios, and subsequently expired in utero. Even though inv(9) is a normal chromosome variant with a frequency of 1 to 3% in the general population, the finding of homozygosity for inv(9) and IUGR in this fetus suggested the possibility of uniparental disomy (UPD). Molecular studies confirmed the presence of both parental inv(9) chromosomes, excluding the possibility of chromosome 9 UPD as the cause of IUGR in this fetus. Presumably, inv(9) homozygosity results from the high frequency of inv(9) heterozygosity, and is a normal variant. However, until the effects of UPD for chromosome 9 are established, parental karyo types and, where appropriate, molecular studies should be performed to exclude UPD. In addition, more reports of inv(9) homozygosity detected prenatally are needed to assess its frequency and outcome.

Mosaic trisomy 14 with hepatic involvement.

Mosaic trisomy 14 in liveborns is rare and may be accompanied by uniparental disomy in the euploid cell line. We report the case of a 6 month old male with growth failure, microcephaly, macroglossia, developmental delay, hypotonia, congenital heart disease, neonatal hepatitis, cryptorchidism, talipes equinovarus, limb length asymmetry, bilateral overriding of 1st by 2nd toe, and extended abnormal pigmentation in a linear-whorl distribution. The proband's karyotype in peripheral lymphocytes and skin fibroblasts was mos47,XY,+14/46,XY. Parental blood chromosomes were normal. Molecular analysis excluded uniparental disomy in the euploid cell line of the proband.

Fulfilling the social contract between medical schools and the public.

To gain a better understanding of the effects of medical schools related to transformations in medical practice, science, and public expectations, the Association of American Medical Colleges (AAMC) established the Advisory Panel on the Mission and Organization of Medical Schools (APMOMS) in 1994. Recognizing the privileges academic medicine enjoys as well as the power of and the strain on its special relationship with the American public, APMOMS formed the Working Group on Fulfilling the Social Contract. That group focused on the question: What are the roles and responsibilities involved in the social contract between medical schools and various interested communities and constituencies? This article reports the working group's findings. The group describes the historical and philosophical reasons supporting the concept of a social contract and asserts that medical schools have individual and collective social contracts with various subsets of the public, referred to as "stakeholders." Obligations derive implicitly from the generous public funding and other benefits medical school receive. Schools' primary obligation is to improve the nation's health. This obligation is carried out most directly by educating the next generation of physicians and biomedical scientists in a manner that instills appropriate professional attitudes, values, and skills. Group members identified 27 core stakeholders (e.g., government, patients, local residents, etc.) and outlined the expectations those stakeholders have of medical schools and the expectations medical schools have of those stakeholders. The group conducted a survey to test how leaders at medical schools responded to the notion of a social contract, to gather data on school leaders' perceptions of what groups they considered their schools' most important stakeholders, and to determine how likely it was that the schools' and the stakeholders expectations of each other were being met. Responses from 69 deans suggested that the survey provoked thinking about the broad issue of the social contract and stakeholders. Leaders on the same campuses disagreed about what groups were the most important stakeholders. Similarly, the responses revealed a lack of national consensus about the most important stakeholders, although certain groups were consistently included in the responses. The group concludes that medical school leaders should examine their assumptions and perspectives about their institutions' stakeholders and consider the interests of the stakeholders in activities such as strategic planning, policymaking, and program development.