Admixture between historically isolated mitochondrial lineages in captive Western gorillas: recommendations for future management.

Although captive populations of western gorilla have been maintained in the United States for over a century, little is known about the geographic origins and genetic composition of the current zoo population. Furthermore, although previous mitochondrial analyses have shown that free-range gorilla populations exhibit substantial regional differentiation, nothing is known of the extent to which this variation has been preserved in captive populations. To address these questions, we combined 379 pedigree records with data from 52 mitochondrial sequences to infer individual haplogroup affiliations, geographical origin of wild founders and instances of inter-breeding between haplogroups in the United States captive gorilla population. We show that the current captive population contains all major mitochondrial lineages found within wild western lowland gorillas. Levels of haplotype diversity are also comparable to those found in wild populations. However, the majority of captive gorilla matings have occurred between individuals with different haplogroup affiliations. Although restricting crosses to individuals within the same haplogroup would preserve the phylogeographic structure present in the wild, careful management of captive populations is required to minimize the risk of drift and inbreeding. However, when captive animals are released back into the wild, we recommend that efforts should be made to preserve natural phylogeographic structure.

Complete mitochondrial genome sequence of the Eastern gorilla (Gorilla beringei) and implications for african ape biogeography.

The Western and Eastern species of gorillas (Gorilla gorilla and Gorilla beringei) began diverging in the mid-Pleistocene, but in a complex pattern with ongoing gene flow following their initial split. We sequenced the complete mitochondrial genomes of 1 Eastern and 1 Western gorilla to provide the most accurate date for their mitochondrial divergence, and to analyze patterns of nucleotide substitutions. The most recent common ancestor of these genomes existed about 1.9 million years ago, slightly more recent than that of chimpanzee and bonobo. We in turn use this date as a calibration to reanalyze sequences from the Eastern lowland and mountain gorilla subspecies to estimate their mitochondrial divergence at approximately 380000 years ago. These dates help frame a hypothesis whereby populations became isolated nearly 2 million years ago with restricted maternal gene flow, followed by ongoing male migration until the recent past. This process of divergence with prolonged hybridization occurred against the backdrop of the African Pleistocene, characterized by intense fluctuations in temperature and aridity, while at the same time experiencing tectonic uplifting and consequent shifts in the drainage of major river systems. Interestingly, this same pattern of introgression following divergence and discrepancies between mitochondrial and nuclear loci is seen in fossil hominins from Eurasia, suggesting that such processes may be common in hominids and that living gorillas may provide a useful model for understanding isolation and migration in our extinct relatives.

A cohort study of topical vaginal estrogen therapy in women previously treated for breast cancer.

OBJECTIVE: To estimate the risk of recurrence of breast cancer associated with the use of topical vaginal estrogen therapy in the management of vaginal atrophy in women previously treated for breast cancer. METHODS: The study group comprised 1472 women with histologically confirmed breast cancer. In 69 of these subjects (4.7%) their only bothersome menopausal problems were vaginal symptoms. In these women, poorly absorbed topical vaginal estrogen cream or tablets were used. The response of these patients was compared with that of the rest of the database. A Cox regression analysis was performed using sex hormone usage after diagnosis as a time-dependent covariate. Disease-free interval was the outcome measured. Results are expressed as a hazard ratio with 95% confidence intervals. The hazard rate is defined as the probability of disease recurrence or of a subject dying from breast cancer over the study period. A second analysis was performed adjusting for factors known to affect breast cancer prognosis. RESULTS: Hormone usage was entered as a time-dependent covariate with disease-free interval as the outcome. Subjects who used a topical estrogen alone for menopausal symptoms had an uncorrected hazard ratio of 0.30 (95% confidence interval (CI) 0.11-0.80, p = 0.02). The corrected hazard ratio was 0.57 (95% CI 0.20-1.58, p = 0.28). The hazard rate for a subject dying was not analyzed, as there were too few numbers. CONCLUSIONS: Although the small numbers of this study preclude a definitive result, topical estrogen usage does not appear to be associated with an increased risk of recurrence of breast cancer.

Tamoxifen, hormone receptors and hormone replacement therapy in women previously treated for breast cancer: a cohort study.

OBJECTIVE: To determine the risk of recurrence of breast cancer associated with the use of hormone replacement therapy (HRT) in the management of menopausal symptoms in women previously treated for breast cancer who were taking concurrent tamoxifen or who were estrogen receptor-positive. METHODS: The study group comprised 1472 women with histologically confirmed breast cancer, of whom 342 subjects (23.2%) elected to use hormonal therapy in the management of their menopausal symptoms. Women were not excluded from treatment with hormonal therapy if they were taking adjuvant tamoxifen or if they had receptor-positive breast cancer. The response of these patients was compared with that of the rest of the database. A Cox regression analysis was performed with sex hormone usage as time-dependent covariate. Disease-free interval was the outcome measured. RESULTS: Subjects who took concurrent tamoxifen with combined continuous estrogen-progestogen therapy had a hazard ratio of 0.67 (95% confidence interval (CI) 0.14-3.24, p = 0.62), while concurrent tamoxifen and topical vaginal estrogen users had a hazard ratio of 0.31 (95% CI 0.10-2.57, p = 0.28). The hazard ratio for the estrogen-progestogen users who were estrogen receptor-positive was 0.24 (95% CI 0.10-1.49, p = 0.14). CONCLUSIONS: The use of HRT was not associated with an increased risk of recurrence of breast cancer in women taking concurrent tamoxifen or who were estrogen receptor-positive.

The significance of pelvic ultrasound abnormalities detected on routine ultrasound scanning prior to assisted reproduction.

OBJECTIVE: To determine the benefit of screening patients with pelvic ultrasound before commencing treatment with in vitro fertilization or gamete intra-fallopian transfer, as well as before each subsequent treatment cycle was performed. SUBJECTS AND SETTING: Seven hundred and seventy-nine patients who were enrolled in the Royal Hospital for Women Fertility Group assisted reproduction program. METHOD: A retrospective analysis was performed. RESULTS: It was found that the majority of abnormalities were detected by the initial ultrasound. However, ultrasound contributed little to their diagnosis and management. CONCLUSION: As a result of this review of pelvic ultrasound examinations performed, the policy of screening prior to the initial cycle of treatment will be continued to exclude significant ovarian tumors and to identify patients with polycystic ovaries, who are more likely to be stimulated to levels at which there is a risk of ovarian hyperstimulation syndrome. The policy of screening before each subsequent treatment cycle has been discontinued, since few additional abnormalities were detected.

The influence of advanced age on the outcome of assisted reproduction.

PURPOSE: Our purpose was to determine the influence of age on the outcome of assisted reproduction, with particular interest in women aged 40 years or older. METHODS: A retrospective review of the 779 patients enrolled in the Royal Hospital for Women Fertility Group fertility program between 1987 and 1994 was performed. The results for women aged 40 years or older were compared with those for women between 36 and 39 years and those younger than 36 years. The main outcome measures were pregnancy rate, pregnancy outcome, fertilization rate, and ovarian response. RESULTS: Compared with those in younger women, pregnancy rate, pregnancy outcome, fertilization rate, and ovarian response to controlled ovarian stimulation were significantly worse in women aged 40 years or older. CONCLUSIONS: The outcome of assisted reproduction in women of 40 years of age or older was extremely poor. Compared with those in younger women, pregnancy outcome and ovarian response to controlled ovarian stimulation were significantly worse in women of 40 years or more.

A cohort study of hormone replacement therapy given to women previously treated for breast cancer.

UNLABELLED: Women who have been previously treated for breast cancer are usually advised to avoid hormone therapy for fear of increasing their risk of tumor recurrence. However, for some women, menopausal symptoms are so severe that their quality of life is poor. Because ethic committees are reticent to permit a double-blind randomized trial, we performed a cohort study of hormone therapy after breast cancer. METHODS: The study group comprised 1472 women with breast cancer. A total of 167 subjects had used an oral or transdermal estrogen after their treatment for breast cancer. Amongst these estrogen users, 152 (91%) had also used a progestin. In total, 106 other women had used a progestin alone as a treatment for menopausal flushes and not as a treatment for breast cancer. Cox regression analysis was performed using estrogen as a time-dependent covariate with disease-free interval as the outcome. RESULTS: The uncorrected hazard ratio for the estrogen-progestin users was 0.67 (95% confidence interval (CI) 0.38-1.16) and for the progestin alone users was 0.85 (95% CI 0.44-1.65). CONCLUSIONS: This study was unable to demonstrate a significant increase in risk of breast cancer recurrence for women who used HRT and suggests that the time is now appropriate for a randomized prospective trial of hormone therapy after breast cancer.

The significance of mild squamous atypia on cytology.

Between January, 1991 and February, 1993 inclusive, 396 Papanicolaou smears were reported to show Mild Squamous Atypia with or without Human Papilloma Virus (MSA +/- HPV). All women with MSA +/- HPV smears were routinely recalled for colposcopy. To determine the significance of MSA +/- HPV on routine smear screening, the records of all patients were reviewed. Three hundred and thirty-seven women (85.1%) attended the colposcopy clinic and are the subjects analyzed for this report. The remaining 59 (14.9%) failed to attend. Intraepithelial neoplasia was found in 61 patients (18.1%), of whom 27 (8.0%) had a high grade lesion (CIN 2 or 3 or GIN 2). No patient had invasive cancer of the cervix. Only 1 of the 45 pregnant women had a significant lesion. It is concluded that all asymptomatic women with MSA +/- HPV on cervical smear may be managed in accordance with the current NH and MRC recommendations (1) and have a repeat smear in 6 months and colposcopy if the abnormality persists at 12 months.

Gynaecological complications of women treated with tamoxifen for breast cancer.

We present 6 cases illustrating some of the gynaecological complications associated with tamoxifen treatment of women with breast cancer. The first 2 represent cases of myometrial hypertrophy secondary to tamoxifen use, a postmenopausal woman and a premenopausal women with recurrent carcinoma of the breast. The third is a case of probable ovulation induction in a perimenopausal women with recurrent breast cancer who was commenced on tamoxifen 20 mg daily. The other 3 cases illustrate some of the endometrial effects associated with tamoxifen therapy in women with a history of breast cancer, namely cystic glandular hyperplasia, endometrial polyps and endometrial cancer.

An adult developmental study of the encoding of spatial location.

The present study was designed to test the hypothesis that there is a differential deficit in the ability to encode contextual information with increasing age. Young, middle-aged, and elderly adults were shown target words in various quadrants of a computer screen (contexts) and were told to either (a) remember the words and their locations, (b) remember the words, or (c) tell whether the words referred to something that was alive or not. Following presentation of the words, subjects were given a recognition test for the words and were asked to identify the quadrant in which each word had been presented. If older adults have a contextual encoding deficit, than an interaction between age and instruction condition would be expected in memory for quadrants. Older adults would be expected to perform better relative to younger adults when the locations were target information (intentionally learned) than when they were contextual (not intentionally learned). Since such an interaction was not obtained, the results provide no support for the hypothesis that the elderly have an encoding deficit that is specific to contextual information.

Glutathione decreases the pulmonary reimplantation response in canine lung autotransplants.

The pulmonary reimplantation response (PRR) is a form of membrane permeability pulmonary edema occurring in lung transplants. The severity of the PRR reflects the quality and duration of lung graft preservation. Free radicals formed during ischemia with reperfusion in the autotransplanted dog lung may play a role in producing PRR. We hypothesized that the addition of reduced glutathione (GSH) to the preservative solution could decrease PRR if hydroperoxides are being formed. Six dogs underwent left lung autotransplantation after the lung was flushed with Euro-Collins solution (EC). These dogs demonstrated radiographic and histopathologic evidence of bilateral pulmonary edema, greatest in the transplanted left lung. They also had increases in lung wet to dry weight (W/D) ratios in both lungs (left, 12.0 +/- 0.9; right, 10.1 +/- 0.8) as compared with a group of five unmanipulated control animals (left, 6.0 +/- 0.5; right, 7.0 +/- 0.4). Malondialdehyde (MDA) concentrations were significantly increased in the transplanted left lungs (14 +/- 4) from this group as compared with the controls (5 +/- 7). Five additional dogs underwent left lung autotransplantation with GSH added to the EC cryopreservation fluid. These animals did not develop histologic or radiographic evidence of pulmonary edema, and W/D ratios as well as MDA concentrations were not different from those in controls. To evaluate the effect of ischemia alone on changes in lung GSH concentrations, ten additional dogs underwent left pneumonectomy. Left lungs were cryopreserved in EC + GSH. In five of the animals, the right lung was removed and preserved in EC alone. In the other five animals, the right lung remained in vivo for 3 h and was then removed. Lung GSH concentrations were doubled after 3 h of ischemia when incubated in EC + GSH compared to in vivo controls and to EC-treated lungs. These data suggest that GSH added to the preservation fluid prevents PRR following transplantation and that lung GSH concentrations actually increase during preservation prior to reimplantation and reperfusion if the lung graft is exposed to GSH in the preservation fluid.

An adult development study of contextual memory.

This study tested the hypothesis that there is a relatively greater decrease in memory for contextual features than in memory for target information with increasing age. Young, middle-aged, and elderly adults were presented with a number of slides, each of which contained a word centered on a background composed of either a landscape/cityscape or a border design. One third of the subjects were told to remember the words, one third were told to remember the backgrounds, and one third were told to remember the word-and-background pairs. Recognition memory for both words, backgrounds, and word-and-background pairings was tested in all subjects. The interaction between age, instruction condition, and type of information tested was not significant. Thus, there was no support for the hypothesis that older adults have a greater deficit in contextual memory than in memory for target information when compared to younger adults.

Utility of the Wang 18-gauge transbronchial histology needle in the staging of bronchogenic carcinoma.

Use of the Wang 18-gauge histology needle in TBNA was employed as a staging procedure in 29 patients with bronchogenic carcinoma and mediastinal adenopathy demonstrated on chest CT. Twenty patients had malignant aspirates; 12 had both histologic and cytologic specimens demonstrating malignancy; six patients had malignant histologic specimens; two had cancerous cytologic specimens as their only evidence of mediastinal disease. Of the nine negative aspirates, four were true negative at surgery. Five patients had false-negative aspirates. Overall sensitivity of the Wang 18-gauge histology needle in the mediastinal staging of patients with bronchogenic carcinoma was 80 percent. When patients with small cell carcinoma were excluded, sensitivity was 82 percent. The enhanced yield of the 18-gauge histology needle warrants its use in mediastinal staging of bronchogenic carcinoma. We conclude that all patients with bronchogenic carcinoma and mediastinal adenopathy demonstrated on chest CT accessible via TBNA should undergo histology needle aspiration as an initial staging procedure.

Optic nerve decompression in osteopetrosis.

Osteopetrosis is a rare disorder characterized by generalized increased skeletal density with abnormalities of bone modeling. The skull base is usually involved. Loss of vision with optic nerve atrophy is the most common neurological finding and is traditionally believed to be the result of optic nerve compression within the compromised optic canal. However, retinal degeneration has recently been described and is hypothesized to be the etiology of the visual loss (thus challenging the value of surgical decompression). The authors report their experience with six children suffering from osteopetrosis and severe visual loss. All six patients underwent bilateral microsurgical optic nerve decompression through a supraorbital craniotomy. Improvement in visual acuity occurred postoperatively in five patients, and none had complications. Two technical points are emphasized: 1) optic nerve decompression should be wide and include not only unroofing of the canal but also drilling along both sides of the optic nerve, and 2) the thick, irregular, and highly domed orbital roof should be smoothed down by high-speed drilling to facilitate surgical exposure with minimal retraction of the frontal lobe.

Amniocentesis carried out for neural tube indications in South Wales 1973-1981: outcome of pregnancies and findings in the malformed abortuses.

The 2872 second trimester amniocentesis followed by amniotic alphafetoprotein (AFP) estimations carried out in South Wales between 1973 and 1981 on women known to be at increased risk for neural tube defect (NTD) and those who had a raised serum AFP level in an NTD screening programme led to the identification of 78 pregnancies of a fetus with anencephalus, 61 with 'open' spina bifida, 8 with gastroschisis, 3 with exomphalos, 2 with encephalocele and 6 with chromosome abnormality. Pregnancies of fetuses having 4 potentially identifiable NTDs were missed because of an equivocal AFP level and there were two false positive results leading to the termination of one normal fetus. It is emphasized that both the latter problems of one normal fetus. It is emphasized that both the latter problems would not have occurred had gel-electrophoresis for isoenzymes of acetyl cholinesterase been available. Follow-up of pregnancies showed that 7 children with 'closed' NTD and 3 with congenital hydrocephalus were born. The anencephalic and the 'open' spina bifida had a more florid lesion than is usual at term. Nearly all the spina bifida were associated with hydrocephalus, often severe and with an obvious Arnold-Chiari malformation. All but 13 had leg or back deformation or malformations in other systems, mostly in the renal tract.