Direct observations of submarine melt and subsurface geometry at a tidewater glacier.

Ice loss from the world's glaciers and ice sheets contributes to sea level rise, influences ocean circulation, and affects ecosystem productivity. Ongoing changes in glaciers and ice sheets are driven by submarine melting and iceberg calving from tidewater glacier margins. However, predictions of glacier change largely rest on unconstrained theory for submarine melting. Here, we use repeat multibeam sonar surveys to image a subsurface tidewater glacier face and document a time-variable, three-dimensional geometry linked to melting and calving patterns. Submarine melt rates are high across the entire ice face over both seasons surveyed and increase from spring to summer. The observed melt rates are up to two orders of magnitude greater than predicted by theory, challenging current simulations of ice loss from tidewater glaciers.

Self-organized criticality in geophysical turbulence.

Turbulence in geophysical flows tends to organize itself so that the mean flow remains close to a stability boundary in parameter space. That characteristic suggests self-organized criticality (SOC), a statistical property that has been identified in a range of complex phenomena including earthquakes, forest fires and solar flares. This note explores the relationship between the properties of forced, sheared, stratified turbulence (as found in oceans, atmospheres and other geophysical fluids) and those of SOC. Self-organization to the critical state is demonstrated in a wide range of cases drawn mostly (but not entirely) from in situ observations of ocean turbulence. Turbulent events in the ocean also exhibit a second characteristic associated with SOC: their sizes follow a power-law distribution indicating self-similarity. These results suggest SOC as a new conceptual foundation for the study of geophysical turbulence, an explanation for the mixing efficiency of ocean turbulence and a potential for cross-fertilization with other areas of geophysics.

Healthy People 2020: assessment of pharmacists' priorities.

OBJECTIVE: The purpose of this study was to assess perceptions of pharmacy educators on the priorities and roles of pharmacists in meeting the Healthy People 2020 objectives. STUDY DESIGN: Cross-sectional, qualitative online national survey. METHODS: A comprehensive literature review identified documented roles and responsibilities of pharmacists in addressing the 42 topic areas in Healthy People 2020. From this, a 14-item survey was developed to identify priorities of categories to improve the health of the nation and importance of the pharmacist role to achieve the objectives. The survey was sent electronically to the members of the Public Health Special Interest Group of the American Association of Colleges of Pharmacy in May and June 2014. RESULTS: Participants identified the following Healthy People 2020 categories as most important in improving the health of the nation: chronic diseases, health care services, lifestyle, prevention/well-being, and environmental factors. They identified the following Healthy People 2020 categories as possessing the most important roles for pharmacists in working to improve the health of the nation: chronic diseases, health care services, lifestyle, prevention/well-being, and infectious disease. CONCLUSIONS: There exists great congruence between top categories of importance and those that the pharmacist can impact to improve the health of the nation. The results of this study can guide efforts to educate and activate pharmacists as interprofessional team members improving health locally and globally.

Vulvar cancer.

Historically, nearly all vulvar cancer is managed by ultraradical surgery. Currently, individualized and more surgically conservative approaches achieve equivalent outcomes with far less morbidity and cosmetic disfiguration. Microinvasive disease can be cured with local excision only. Lateral lesions are usually managed with local excision and ipsilateral groin node dissection only. Advanced disease responds remarkably to chemoradiation.

Abnormal expression of the retinoblastoma gene in ovarian neoplasms and correlation to p53 and K-ras mutations.

We analyzed the expression of the retinoblastoma (Rb) gene in a group of ovarian neoplasms previously characterized for mutations in the p53 suppressor gene and the Ki-ras oncogene. Using immunohistochemical techniques, a total of 59 ovarian neoplasms spanning the histiologic spectrum from benign to malignant were examined for the expression of the Rb protein. All benign cystic adenomas and low malignant potential tumors exhibited normal expression of the Rb protein. Abnormalities in Rb protein staining were noted in 3 of 22 (14%) ovarian carcinomas. The staining patterns included tumors that were totally or focally negative for Rb protein. One tumor focally expressed Rb. This tumor demonstrated a direct juxtaposition of sections of Rb expressing and nonexpressing malignant epithelial cells. Two of the three tumors with abnormal Rb expression also had p53 mutations and staining on serial sections demonstrated that selected ovarian cancer cells possessed mutations in both oncogenes. These data suggest that the loss of Rb gene expression may play a role in the pathogenesis of a small number of invasive ovarian malignancies, but not in noninvasive ovarian neoplasms.

The molecular genetics of gyn malignancies.

Gynecologic malignancies, representing 13% of all cancers affecting women, have a major impact on women's health. Cervical, endometrial, and ovarian cancers comprise the majority of these tumors and contribute significant morbidity and mortality to the female population. While cervical and endometrial cancers can be detected early in their development, sadly, many patients present with advanced disease, as do the majority of patients with ovarian cancer. Unfortunately, advanced cases of these malignancies are usually lethal despite modern therapeutic modalities. In order to impact upon these grim statistics, gynecologic researchers have turned to molecular biology in an attempt to elucidate the etiology of these cancers. Recent research describing dominant oncogene and tumor suppressor gene mutations common to these malignancies is providing a basis for the molecular genesis of these cancers. This information should offer new avenues for the development of early detection and chemoprevention, as well as novel treatment strategies.

p53 and Ki-ras gene mutations in epithelial ovarian neoplasms.

In an effort to define the pathogenic relationship between ovarian neoplasms spanning the clinicopathological spectrum from benign to malignant, the incidence of Ki-ras and p53 mutations was determined in 20 ovarian cystadenomas, 20 low malignant potential (LMP) tumors of the ovary, and 23 ovarian carcinomas. Using DNA extracted from paraffin embedded tissue, polymerase chain reaction amplification, designed restriction fragment length polymorphism analysis, and DNA sequencing, 1 cystadenoma (5%), 6 LMP tumors (30%), and 1 ovarian carcinoma (4%) demonstrated an activated Ki-ras gene. All of the Ki-ras mutations identified except one were GGT to GAT transversions at codon 12. One LMP tumor demonstrated a CAA to CAC transversion at codon 61. Using polymerase chain reaction/single strand conformational polymorphism, DNA sequencing, and immunohistochemistry, 11 ovarian carcinomas (48%) demonstrated a p53 mutation. These mutations included 5 missense, 2 nonsense, and 1 frameshift mutation located within exons 6-8 and 3 mutations that were identified only by immunohistochemical staining. No p53 mutations could be identified in cystadenomas or LMP tumors. Clinically, the presence of either a Ki-ras or p53 mutation was associated with advanced stage disease. The pattern of Ki-ras and p53 mutations appears to distinguish LMP tumors from invasive carcinomas and suggests that they may be separate biological entities.

Atypical cervical cytology. Colposcopic follow-up using the Bethesda System.

Patients with a cytologic diagnosis of either atypical squamous cells of undetermined significance (squamous ACUS) (191), atypical squamous cells suggestive of papillomavirus (ACPV) (79), low grade squamous intraepithelial lesion (LSIL) (184) or atypical glandular cells of undetermined significance (glandular ACUS) (30) obtained over an 18-month period were evaluated colposcopically at the National Naval Medical Center. The diagnosis of squamous atypia rendered using the Bethesda System was reduced when compared to the diagnosis of atypia rendered using traditional cytologic terms (1.9% versus 7.2%). Results from colposcopic evaluations of patients with squamous ACUS demonstrated similar rates of underlying dysplasia as in studies using older terminology (low grade dysplasia in 14% and high grade in 6% of the referrals). Colposcopic evaluation of patients with a referral diagnosis of squamous ACPV demonstrated rates of underlying low grade dysplasia double that of the diagnosis of squamous ACUS but half that of a diagnosis of LSIL (25% versus 14%, and 48%, respectively). Colposcopic evaluation of glandular ACUS rendered a diagnosis of high grade dysplasia more than three times (20%) as often as of squamous ACUS (6%). While the Bethesda System reduces inconsistencies in the diagnosis of atypical cytologic changes, a separate category (ACUS) appears to be useful in identifying underlying, unsuspected low grade dysplasias in our laboratory. In addition, glandular atypias herald a significant rate of underlying high grade dysplasias and warrant immediate colposcopic investigation.

The postmenopausal palpable ovary syndrome. A retrospective review with histopathologic correlates.

Since its introduction in 1971 and based on experience with three patients, the postmenopausal palpable ovary (PMPO) syndrome has been widely accepted as appropriate justification for exploratory celiotomy to rule out ovarian malignancy. However, reports on only two small series have been published that address the incidence of malignancy in these patients. From March 1982 to June 1986, 20 patients underwent surgical exploration at the Naval Hospital, Bethesda, to evaluate an asymptomatic PMPO. Thirteen patients (60%) were found to have an ovarian neoplastic process. Three of the neoplasms were malignant or of borderline malignant potential, resulting in an overall malignancy rate of 15% for the PMPO syndrome. In comparing the PMPO groups, patients in the malignancy group had a statistically significant lower mean parity and greater mean number of postmenopausal years (P = .02 and .03, respectively). When the PMPO group was compared to patients with adnexal masses larger than 5 cm, there were no significant differences in the malignancy rates (15% versus 25%, P = .26), but the power was low. The data suggest that the PMPO syndrome may be clinically important. Additional studies to compare ultrasound, CA-125 and pelvic examination are indicated.

Gynecologic malignancies.

The combination of cisplatin and cyclophosphamide remains the preferred regimen for the primary treatment of advanced stage epithelial ovarian cancer. Maximal dose intensity, particularly that of cisplatin, is generally accepted as critical for optimal results, but the concept has not yet been rigorously validated by prospective, randomized trials. Since higher doses of cisplatin are associated with renal and neurologic toxicity, the accumulating evidence of equivalent response rates with the less toxic platinum analogue, carboplatin, is encouraging. Salvage chemotherapy remains unsatisfactory, although the remarkable responses observed this year in heavily pre-treated and platinum-resistant patients with the novel new agent taxol is promising. Further trials with this unique drug in combination with other agents in previously untreated patients, as well as in salvage settings, is eagerly anticipated. Although experience with intraperitoneal therapy is rapidly accumulating, the precise role for this route of delivery has yet to be demonstrated in prospective trials. The management of early stage ovarian cancer has become increasingly clarified. Several trials have now demonstrated that a subgroup of patients at low risk for recurrence do well with surgery alone, while a high-risk subgroup clearly benefits from adjuvant therapy. The identification of optimal regimens awaits further trials. In cervical carcinoma, trials utilizing a variety of radiation-sensitizing agents have failed to demonstrate superiority over that of hydroxyurea, which has been shown to improve survival in advanced disease. Preliminary experience with neo-adjuvant regimens administered prior to surgery or radiation therapy is promising, but survival advantages utilizing this approach have yet to be demonstrated. In endometrial cancer, cisplatin was shown to achieve response rates similar to those attainable with single agent doxorubicin, and in uterine mixed mesodermal tumors, ifosfamide was found to have significant activity.

Estrogen and anti-estrogen effects on the growth of human epithelial ovarian cancer in vitro.

An epithelial ovarian cancer cell line, PE04, has been shown to contain high levels of cytosolic estrogen receptor-like binding. Analysis of PE04 cytosol on low-salt sucrose density gradients demonstrated 7-9S binding of [3H]17 beta-estradiol, with specificity consistent with that of an estrogen receptor. When compared with the proliferation of cells grown in monolayer without steroids, a 50% increase in growth rate of the cell line was observed by treatment with 17 beta-estradiol (E2). Growth stimulation was dose-dependent and maximal at 10(-10) M. The E2 effect on substrate-independent growth was more striking; 3 x 10(-9) M produced a 30-fold increase in cloning efficiency. Treatment with 4-hydroxytamoxifen resulted in a dose-dependent inhibition (maximal at 3 x 10(-9) M) of cell growth, which was reversible by E2. Although treatment with estrogen in systems containing functional estrogen receptor commonly results in progesterone receptor synthesis, E2 induction of progesterone receptor could not be demonstrated in this cell line. The endocrine characteristics of PE04 contrast with those of another ovarian cancer cell line, NIH:OVCAR-3, in which E2 induces progesterone receptor but does not stimulate cell proliferation. This is the first report of an ovarian cancer cell line in which the clinically important end-effect of estrogen, cell growth, has been observed. Furthermore, retention of a mitogenic response to estrogen in the apparent absence of progesterone receptor induction has not been described previously in model systems.(ABSTRACT TRUNCATED AT 250 WORDS)

Diagnosis of recurrent gynecologic malignancy with fine-needle aspiration cytology.

Between 1980-1985, 177 fine-needle aspirations were performed on 139 patients suspected of having recurrent gynecologic malignancy. Suspected sites of recurrence included a pelvic mass (122), peripheral lymph node (39), and a variety of other locations (16). There were 69 positives, 79 negatives, eight suspicious specimens, and 21 specimens inadequate for interpretation. Excluding suspicious or inadequate specimens, the results of the remaining 148 evaluable aspirations were confirmed by histopathologic correlation (35) or subsequent clinical course (113). Because there were no false positives, the specificity of the technique was 100%. The sensitivity was 68%, with an associated false-negative rate of 32%. The predictive value of a positive was 100%; that of a negative was 57%. An analysis of the false-negative results failed to show a correlation with cell type, lesion location, previous radiotherapy, or previous chemotherapy. The complication rate was less than 1%. These data support the conclusion that fine-needle aspiration cytology is a safe, highly specific method for diagnosing recurrent gynecologic malignancy. However, in patients with negative fine-needle aspiration cytology and suspected recurrent disease, it would appear that further evaluation is indicated.

Evaluation of the scalene lymph nodes in primary and recurrent cervical carcinoma.

Open biopsy of the left scalene lymph nodes has been utilized to identify distant spread of cervical carcinoma in selected groups of patients who do not have other clinical evidence of disseminated disease. Twenty-one patients with primary cervical carcinoma and histologically proven para-aortic lymph node metastases and 10 patients with centrally recurrent tumors underwent scalene lymph node biopsy at Walter Reed Army Medical Center or the Naval Hospital, Bethesda, Maryland, between July 1, 1979 and June 30, 1985. All patients undergoing scalene node biopsy had clinically negative physical examinations. There were no surgical complications. All 31 biopsies were negative for metastatic tumor. Combined with previously reported data from this institution, 3 of 28 patients (11%) with primary cervical carcinoma and involved para-aortic nodes, and 6 of 35 patients (17%) with centrally recurrent disease had subclinical scalene node metastases. Patients with clinically suspicious scalene lymphadenopathy had fine needle aspiration cytology performed to document metastatic disease. The success of this technique has eliminated the need for open biopsy in these patients. Scalene node biopsy provides valuable prognostic information in patients with cervical cancer who have positive para-aortic lymph nodes. It also obviates surgical exploration in some patients felt to have resectable recurrent disease who actually have subclinical distant spread.

End colostomy using the end-to-end anastomosis instrument.

Gastrointestinal stapling instruments have achieved wide-spread application in intestinal surgery. Reported advantages of stapled bowel procedures compared to classic hand-sutured procedures include reduced tissue trauma, shorter operating time, and improved blood supply to the stapled bowel segment. A technique for creation of an end colostomy using the end-to-end anastomosis stapler (EEA instrument) is described. This technique was used in 11 gynecologic oncology patients who required colostomy. Postoperative stomal function was normal in all cases. No patient developed stomal necrosis, peristomal hematoma, or abscess. No delayed complications have been observed. Colostomy creation with the EEA instrument is a safe, simple and rapid procedure. Possible advantages of the stapled colostomy are enhanced blood flow to the stomal site, reduced incidence of peristomal infection, and improved appliance fit.

Biologic course of cervical human papillomavirus infection.

To determine the natural course of cervical human papillomavirus infection, we prospectively studied all new patients referred to the colposcopy clinic at the Naval Hospital Bethesda, from April 1981 to August 1983, whose screening cervical cytology demonstrated features consistent with human papillomavirus infection as the only abnormality. Histologic confirmation of human papillomavirus infection was required for entry into the study. All patients were evaluated by repeat cytology, colposcopy, endocervical curettage, and colposcopically directed biopsy as indicated at intervals of three to six months. Patients who developed classic features of cervical intraepithelial neoplasia were treated by standard modalities, whereas patients with evidence of human papillomavirus infection without associated cervical intraepithelial neoplasia were not treated. Confirmation of the resolution of human papillomavirus infection required negative cytology and colposcopy on two consecutive evaluations. Of the 45 patients for whom complete follow-up data are available, five (11.1%) had cervical intraepithelial neoplasia at the time of their initial evaluation, 15 (33.3%) progressed to cervical intraepithelial neoplasia over an average of 10.9 months, 18 (40%) resolved over an average of 13.7 months, and seven (15.6%) persisted with neither progression nor resolution for an average of 21 months. These data suggest that about one-third of patients who have histologically confirmed human papillomavirus cervical infection can be expected to develop cervical intraepithelial neoplasia within a year.