AlleleRetain: a program to assess management options for conserving allelic diversity in small, isolated populations.

Preserving genetic health is an important aspect of species conservation. Allelic diversity is particularly important to conserve, as it provides capacity for adaptation and thus enables long-term population viability. Allele retention is difficult to predict beyond one generation for real populations with complex demography and life-history traits, so we developed a computer model to simulate allele retention in small populations. AlleleRetain is an individual-based model implemented in r and can be applied to assess management options for conserving allelic diversity in small populations of animals with overlapping generations. AlleleRetain remedies the limitations of similar existing software, and its source code is freely available for further modification. AlleleRetain and its supporting materials can be downloaded from https://sites.google.com/site/alleleretain/ or CRAN (http://cran.r-project.org).

The functions of internet use and their social and psychological consequences.

Although the Internet has spawned significant changes in communication and interpersonal behavior, the data concerning the social and psychological effects of its use are equivocal. Drawing on the uses and gratifications model of communications media, it was hypothesized that the social and psychological effects of Internet use depend primarily on the user's reasons and goals for using the technology. That is, the Internet's social and psychological effects depend upon the functions it serves for users. A theoretical model involving the functions of Internet use, dimensions of social integration, and dimensions of psychological well-being was examined. In study 1, participants indicated the primary reasons for which they use the Internet. Principle components analyses indicated that these reasons fell under two empirically robust dimensions accounting for about half of the total variance in Internet use. These dimensions, or functions, were labeled Socio-Affective Regulation (SAR) and Goods-and-Information Acquisition (GIA); SAR may be conceptualized as a social or an affiliative orientation toward Internet use, whereas GIA may be conceptualized as a utilitarian or practical orientation toward Internet use. In study 2, structural equation modeling revealed that Internet use driven by SAR negatively influences psychological well-being by first reducing social integration. However, Internet use motivated principally by GIA appears to have a favorable effect on psychological well-being by first increasing social integration. Implications of these results and directions for future research are discussed.

Reduced hepatic growth hormone (GH) receptor gene expression and increased plasma GH binding protein in experimental uremia.

In uremia, reduced longitudinal growth and decreased hepatic insulin-like growth factor-I (IGF-I) secretion despite elevated GH serum levels point to an insensitivity to the action of GH. The molecular basis that accounts for this insensitivity could comprise decreased GH receptor expression in the target organs for GH or binding of GH in the circulation to substances that compete with the receptor. To address this hypothesis, the abundance of hepatic GH receptor mRNA was measured by solution hybridization RNase protection assay in uremic female Sprague-Dawley rats, following two-stage 5/6 nephrectomy, and in pair-fed and in ad libitum-fed sham-operated controls; rat GH binding protein (GHBP) plasma concentration was measured by a sensitive direct RIA. Uremia was associated with a 50% decrease of hepatic GH receptor expression compared to pair-fed controls, which themselves showed a 25% reduction of hepatic GH receptor mRNA abundance when compared to ad libitum-fed controls. Plasma GHBP levels in uremia were markedly higher than in both control groups. Treatment with recombinant human GH (rhGH) (10 IU/kg body wt per day s.c. for 10 days) led to a comparable induction of IGF-I plasma levels and weight gain in uremia and pair-fed controls, indicating that the insensitivity to GH in uremia can be overcome by large rhGH doses. Subcutaneous rhGH injections did not significantly alter the hepatic GH receptor transcript abundance or plasma GHBP levels in any of the groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Surgery for vulvar cancer.

In recent years, data have been accumulated regarding risk factors for metastatic potential and have improved the understanding of the pathways and frequency of lymphatic dissemination. Proper application of this information allows individualization of treatment to obtain optimal cure rates with minimum morbidity in patients with vulvar malignancy.

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.

Pulmonary embolization of a vascular ligature clip as a complication of para-aortic lymph node sampling.

A case is reported of a 57-year-old woman who underwent cytoreductive surgery for stage III, grade 2 endometrioid cystadenocarcinoma of the ovary. During para-aortic lymph node sampling, hemostasis was achieved with medium and small metallic ligature clips. The immediate postoperative period was uneventful and the chest radiograph was unchanged from preoperative film. On the sixth postoperative day a chest radiograph showed a radio-opaque object consistent with a metallic ligature clip in the peripheral left middle lung field. The remaining postoperative course was uncomplicated and the patient is well 14 months postoperatively; the ligature clip is unchanged in position. This is an interesting and previously unreported complication of para-aortic lymph node sampling. The means by which the clip entered the vascular system is unknown. Nonsurgical removal of the clip was not feasible due to its peripheral location. No studies exist as to the long-term outcome of foreign bodies embolized to the peripheral lung.

Perineal leiomyosarcoma.

Perineal leiomyosarcomas are rare aggressive tumors for which the therapy remains to be defined. These tumors may be extensively infiltrating and therapy may require radical surgery. The problems encountered in treating these tumors are similar to those for retroperitoneal sarcomas. Namely, delay in diagnosis, lack of distinct anatomic boundaries, and close proximity to and encroachment on multiple organs prevents resection with adequate surgical margins. We discuss the current literature and present our management of perineal leiomyosarcomas.

Intraoperative evaluation of depth of myometrial invasion in stage I endometrial adenocarcinoma.

In patients with stage I endometrial adenocarcinoma, the incidence of pelvic and para-aortic lymph node metastasis is related to the grade of the tumor and the depth of myometrial invasion. Although the grade of the tumor may be predicted preoperatively by endometrial sampling, the depth of myometrial invasion cannot be determined until after the uterus has been removed. Although complications have been attributed to lymph node sampling, failure to perform the procedure in patients at risk for nodal metastasis may result in underdiagnosis of extrauterine disease, leading to inadequate therapy. Gross visual examination of the cut surface of the tumor at the time of hysterectomy accurately determined the depth of myometrial invasion in 135 of 148 prospectively studied patients (91%) (P less than .001). The sensitivity of the test was 0.71, the specificity was 0.96, and the positive predictive value was 0.80. Intraoperative assessment of the depth of myometrial invasion is a simple, inexpensive, and useful technique for selecting those patients with stage I endometrial adenocarcinoma who might benefit from selective para-aortic lymphadenectomy.

Extraperitoneal versus transperitoneal selective paraaortic lymphadenectomy in the pretreatment surgical staging of advanced cervical carcinoma (a Gynecologic Oncology Group study).

Two-hundred and eighty-eight patients with predominately stage IIB or IIIB cervical carcinoma underwent pretreatment surgical staging including selective paraaortic lymphadenectomy (SPAL), followed by pelvic irradiation with or without paraaortic irradiation (RT). Four patients were excluded from analysis (two received no RT and two were insufficiently documented). Of the remaining 284 patients, 128 underwent extraperitoneal (EP) SPAL and 156 transperitoneal (TP) SPAL procedures. Age, race, and stage (clinical and surgical), cell type, paraaortic nodal status, and peritoneal cytology findings were similar in both groups. Complications presumed to arise from operative staging were infection, which was similar for both groups, and vascular injury, which was higher in the TP group, although not statistically significant. Complications subsequent to RT fell into two categories: local-pelvic necrosis, vesicovaginal and rectovaginal fistulas, proctitis, etc., and regional-enterovaginal fistula, bowel obstruction, enteritis, bowel perforation, etc. The frequency of local complications was similar for both EP and TP patients. Utilizing univariant analysis, among regional complications, both bowel obstruction and nonobstructive enteric injuries were observed significantly more often in TP patients than in EP patients (11.5% vs 3.9%, P = 0.03, for both types). Multivariant analysis confirmed these observations. This report supports the conclusions that in advanced cervical carcinoma (1) EP- and TP-SPAL are of similar sensitivity in detecting nodal spread, (2) no significant differences in the frequency of surgical complications could be detected between EP- and TP-SPAL groups, and (3) TP-SPAL is associated with a higher frequency of certain postirradiation regional enteric complications.

Determinants of survival of patients with epithelial ovarian carcinoma following whole abdomen irradiation (WAR).

In an attempt to identify those parameters which represent predictors of clinical outcome, a retrospective review of patients with epithelial ovarian carcinoma who were primarily treated with whole abdominal irradiation (WAR) following staging laparotomy was performed. Complete records with extensive long-term follow-up were available on 102 patients treated from 1962 through 1974. Histopathologic review excluded 18 patients with lesions of low malignant potential. Of the remaining 84 cases there were 12 Stage I (14%), 23 Stage II (27%), 45 Stage III (54%), and 4 Stage IV (5%). Measure of completeness of surgical resection was expressed as the largest diameter of residual gross tumor. Following primary surgical debulking Stages II and III patients, 24 patients had no gross residual disease, 24 patients had less than 2 cm of residual disease, and 20 patients had greater than 2 cm of residual disease. For Stages II and III patients together, 5- and 10-year actuarial survivals were: No gross residual, 69% and 59%; less than 2 cm, 48% and 42%; and greater than 2 cm, 15% and 10%. The technique of administration of WAR did not appear to influence survival. The results of this review support the concept that in selecting WAR for primary treatment of ovarian carcinoma, completeness of cytoreductive surgery should be considered. These data justify a prospective randomized study in patients with minimal residual disease following staging laparotomy comparing WAR with current first-line combination chemotherapy.

Nonsquamous cancer of the vagina.

This report retrospectively analyzes 48 cases of primary vaginal cancer treated at Walter Reed Army Medical Center and the Naval Hospital, Bethesda, from 1962 through 1983. There was an unusually high number of uncommon histologic types. Nine patients had an adenocarcinoma, 5 had a sarcoma, 3 had a melanoma, 2 had an adenosquamous carcinoma, 1 had a lymphoma, and 1 had a carcinoid tumor. The remaining 27 patients had a squamous cell carcinoma. This represents a 43% prevalence of nonsquamous lesions. Nonsquamous cancer of the vagina occurred in patients at an earlier age than squamous cell carcinoma. Presenting symptoms, the location of the tumor within the vagina, and survival rates were similar for both groups. The clinical characteristics and treatment of the patients with nonsquamous tumors are discussed.

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.

Radical hysterectomy and pelvic lymphadenectomy for stage IB carcinoma of the cervix: 21 years experience.

From September 1971 through December 1982, 153 patients with Stage IB carcinoma of the cervix underwent radical hysterectomy and pelvic lymphadenectomy at two of the teaching hospitals of the Uniformed Services University of the Health Sciences. Records were retrospectively analyzed and independent pathologic review was performed. All surgical procedures were performed by fellows or senior residents under the direct supervision of the gynecologic oncology staff of the Walter Reed Army Medical Center or the Naval Hospital, Bethesda, Maryland. In this series, IB carcinoma was defined as squamous carcinoma clinically confined to the cervix with invasion greater than 5 mm from the basement membrane or any adenocarcinoma confined to the cervix. The average age of the patients was 38.3 years. The histologic types were squamous in 72%, adenocarcinoma in 16%, and adenosquamous in 10.5%. The mean operating time was 5 hr and 40 min with an average blood loss of 1800 cc. There were two ureterovaginal and two vesicovaginal fistulae for an overall fistula rate of 2.6%. Actuarial survival for these 153 patients is 84%. This extends the previous series of R. C. Park, W. E. Patow, R. E. Rogers, and E. A. Zimmerman, Obstet. Gynecol. 41, 117-122 (1973) of 122 cases collected from 1961 to September 1971 to 275 cases. In comparing the two time periods, no significant differences were found in operative technique or complications, but there was a change in the incidence of adenocarcinoma and mixed cell types and a difference in survival. A relatively higher incidence of more aggressive tumors may indicate the need for different therapeutic approaches in the future.

The treatment of retroperitoneal fibromatosis with medroxyprogesterone acetate.

Wide excision is the recommended primary therapy for retroperitoneal fibromatosis. Radiation therapy and a variety of medications have been used to treat patients with recurrent tumors, but the response to these agents has not been uniform. The patient presented was successfully treated with medroxyprogesterone acetate for recurrent retroperitoneal fibromatosis that was refractory to multiple operative resections and radiation therapy.

Clinical patterns of tumor recurrence after radical hysterectomy in stage IB cervical carcinoma.

We reviewed the cases of 31 patients with International Federation of Gynecology and Obstetrics (FIGO) stage IB cervical carcinoma who developed recurrent disease after radical hysterectomy and pelvic lymphadenectomy between 1961 and 1982. The overall incidence of recurrence was 11.3%. Recurrence was significantly more common in patients with adenocarcinoma or adenosquamous carcinoma (17.4%) than in those with pure squamous tumors (9.2%). The median time from operation to recurrence was eight months. The median survival of patients dying of disease was 18 months. Sites of recurrence were categorized as central pelvic in 35% of cases, pelvic sidewall in 39%, and distant in 26%. Patients treated with postoperative pelvic radiotherapy for positive pelvic nodes or surgical margin involvement were more likely to develop distant recurrence. Various therapeutic modalities were used to treat recurrent disease. Twenty-two of 23 patients with central pelvic or sidewall recurrence failed radiation therapy. None of four patients with central recurrence treated by pelvic exenteration survived. No patient treated with chemotherapy survived. Overall survival for patients with recurrence was 3.2%. The dismal prognosis for this group of patients warrants evaluation of alternative treatment modalities.

Prognostic factors associated with radical hysterectomy failure.

Two hundred seventy-five patients who underwent radical hysterectomy and pelvic lymphadenectomy for FIGO stage IB carcinoma of the cervix between 1961 and 1982 were retrospectively analyzed to identify specific risk factors associated with treatment failure. Patients were classified as high or low risk on the basis of tumor spread to pelvic lymph nodes or surgical margins. Thirty-eight patients had tumor involvement of pelvic nodes or surgical margins. Despite postoperative whole pelvis radiation therapy in 88% of patients, 13 (34.2%) developed recurrence. All patients with involved nodes or margins who recurred died of disease. Patients with pelvic lymph node or surgical margin involvement clearly constitute a high risk group and should be considered candidates for some form of adjuvant therapy. Two hundred thirty-seven patients had negative nodes and clear surgical margins. There were 18 recurrences (7.6%) in this group. Pathologic specimens were reviewed to evaluate additional histologic criteria which might identify those patients at greatest risk for tumor recurrence in this low risk group. Patients whose tumors contained vascular-lymphatic space invasion or adenomatous histologic components recurred more frequently than patients whose tumors did not (P less than 0.05). Eighty-three percent of low risk patients who recurred had tumors with at least one of these features. Degree of differentiation and depth of invasion did not correlate with risk of recurrence. Prospective randomized trials are needed to determine the effectiveness of postoperative adjuvant therapy for patients at risk for recurrent disease.

Right hemicolectomy and ileal resection with primary reanastomosis for irradiation injury of the terminal ileum.

Injury to the small intestine from pelvic irradiation increases in frequency when extended treatment fields are utilized and when radiation therapy follows a major abdominal operation. Recommended surgical correction of such injury has been intestinal bypass to avoid the excessive morbidity and mortality from anastamotic leaks associated with primary resection and anastomosis. Since 1980, eight patients with extensive ileal injury secondary to irradiation have been seen at the Naval Hospital Bethesda, Maryland. All patients had previously undergone an abdominal operation and three patients had irradiation utilizing extended fields. In all cases, right hemicolectomy and extended ileal resection were performed with primary anastamosis of the ileum to the ascending colon or the transverse colon. Operating time averaged 4 1/2 hr utilizing hand closure anastomoses and 2 1/2 hr with stapled anastomoses. All patients received postoperative hyperalimentation and six of eight patients received preoperative hyperalimentation. One operative death occurred in a patient with intestinal perforation who required multiple resections. The remaining seven patients experienced no serious complications and had rapid return of bowel function. Our experience indicates that wide ileal resection with right hemicolectomy and primary reanastomosis is an acceptable alternative to intestinal bypass for the treatment of severe irradiation injury, especially when performed with gastrointestinal stapling devices.

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.

Cardiotoxic effects of the venom of the burrowing asp, Atractaspis engaddensis (Atractaspididae, Ophidia).

The venom from the snake Atractaspis engaddensis has a very high lethal potency, with an i.v. LD50 of 0.06-0.075 micrograms per g body weight in mice. The action of the venom is rapid and death results from seemingly neurotoxic effects. However, even at high concentrations, the venom does not block contractions of skeletal muscles that are directly or indirectly stimulated. The most prominent action of the venom is seen in the function of the heart in anesthetized mice, with or without artificial respiration. The changes observed in the ECG are similar to those recorded in human victims and are the result of an A-V block that is caused by an apparent direct action of the venom on the heart.