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Current status of treatment of gestational trophoblastic disease.

A brief summary is given of the developments leading to the current status of treatment of gestational trophoblastic neoplasms, both nonmetastatic and metastatic. Hydatidiform mole has been identified as the precursor type of pregnancy in approximately 50% of those women developing metastatic disease. The other half developed this as consequences of either a full-term delivery or some type of abortion. Sensitive assays for human chorionic gonadotropin (HCG) are needed in the diagnosis, management, and follow-up of these patients. Current therapy is outlined: nonmetastatic disease receives single agent chemotherapy with methotrexate or actinomycin D, with approximately 100% cure and 90% retention of reproductive function; metastatic disease, "low risk", receives single agent chemotherapy with the same drugs, with an expected cure rate of 95-100%; metastatic disease, "high risk", receives initial therapy with multiple agent chemotherapy, with a cure rate of approximately 75%. Current unresolved questions are discussed briefly.

Choriocarcinoma↗

Conservative surgery for stage I ovarian carcinoma in women of childbearing age.

OBJECTIVE: To assess the results of a policy of tailored conservative surgical management for young women with stage I ovarian carcinomas. DESIGN: Retrospective study. PARTICIPANTS: Ninety-nine women aged 40 years or younger who underwent either primary surgery in our department or were referred after primary surgery performed elsewhere. METHODS: Of the 99 women in our study, 56 underwent fertility-sparing surgery and 43 more radical surgery. Minimal requirements for conservative management were adequate staging and complete information about the therapeutic options. Factors important in the choice of the treatment were, age, wish to preserve fertility, histologic type and grade, and the stage of the tumour. RESULTS: Conservative treatment was conducted in 84% of nulliparous and in 33% of parous women; 62% of grade 1 tumours, 48% of grade 2, and 50% of grade 3 were treated conservatively. With a median follow up of seven years, we observed five recurrences (9%) of carcinoma in women treated conservatively and five (12%) in those treated more radically. Two women (one in each treatment arm) were saved after recurrence. Two recurrences after conservative surgery involved the residual ovary (3.6%). Two women developed borderline tumour in the contralateral ovary and both were treated by surgery. CONCLUSION: After adequate staging and accurate information is given to the patient, conservative treatment may be safe in some women with early ovarian cancer. The risk of recurrence in the contralateral ovary is low. Conservative surgery may be also considered in some Stage I grade 3 tumours and in some women with stage JC tumours.

Adolescent↗

Respiratory system loop gain in normal men and women measured with proportional-assist ventilation.

We hypothesized that increased chemical control instability (CCI) in men could partially explain the male predominance in obstructive sleep apnea (OSA). CCI was assessed by sequentially increasing respiratory control system loop gain (LG) with proportional-assist ventilation (PAV) in 10 men (age 24-48 yr) and 9 women (age 22-36 yr) until periodic breathing or awakening occurred. Women were studied in both the follicular and luteal phases of the menstrual cycle. The amount by which PAV amplified LG was quantified from the tidal volume amplification factor [(VtAF) assisted tidal volume/unassisted tidal volume]. LG was calculated as the inverse of the VtAF occurring at the assist level immediately preceding the emergence of periodic breathing (when LG x VtAF = 1). Only 1 of 10 men and 2 of 9 women developed periodic breathing with PAV. The rest were resistant to periodic breathing despite moderately high levels of PAV amplification. We conclude that LG is low in the majority of normal men and women and that higher volume amplification factors are needed to determine whether gender differences exist in this low range.

Adult↗

Sex differences in chronic cor pulmonale in delhi.

Chronic cor pulmonale is more prevalent in northern India than in the south. It is equally common in men and in women and accounts for 20% of all admissions for heart disorder in Delhi. In a study of 766 patients (239 men and 527 women) carried out over a 15-year period there were some striking sex differences. Some 75% of men and 10% of women smoked. The women came from the poorest class and all of them cooked from an early age over smoky and primitive fireplaces in ill-ventilated huts, while only 7% of the men cooked their own food. Chronic bronchitis and bronchiectasis were the commonest associated lung disorders in both sexes. The women developed heart failure 10-15 years earlier and showed more severe congestive failure with larger hearts and greater derangement of pulmonary function. It is concluded that the cause of chronic cor pulmonale in women in Delhi was damage to the lungs from exposure to smoky cooking fuels from girlhood onwards, followed by repeated chest infections.

Adult↗

Endometrial Resection and Late Reoperation in the Treatment of Menorrhagia

We evaluated the effectiveness of transcervical resection of the endometrium (TCRE) and the indications of late reoperations in 250 women with dysfunctional bleeding. The women were questioned about symptoms and levels of satisfaction 3, 12, 24, 36, and 48 months after the procedure. Average follow-up was 24 months (range 4-48 mo). Repeat resection was performed in 8 women (3.2%) and hysterectomy in 13 (5.2%). Seven women (2.8%) had reoperation because of recurrent unacceptable vaginal bleeding. Late onset of pain occurred in 14 (5.6%). The success rate at 3 months as measured by patient satisfaction was 97% and at 4 to 45 months 91%. A definite subgroup of women developed late onset of pain with or without bleeding after endometrial resection. Results at 3 months did not necessarily correlate with longer-term outcomes. Provided that the surgeon has extensive training, few women will be dissatisfied with the procedure.

Journal Article↗

Factor V Leiden as a risk factor for miscarriage and reduced fertility.

The Leiden mutation is a recent discovery. It is the main cause of inherited thrombophilia and has been found in 20-60% of deep vein thrombosis cases. More recently it has been found in a significant number of cases of obstetric complications attributable to placental thrombosis. Current patient management practice for dealing with the Leiden mutation is based mainly on information about deep vein thrombosis because there is little information on pregnancy complications. There are no prospective studies examining the risk of developing pregnancy complications for Leiden mutation carriers. The aim of this study is to do that by comparing the frequency of unfavourable pregnancy outcomes among carriers with those among controls. The number of women developing miscarriages, intrauterine deaths, or infertility problems among 128 Leiden mutation carriers was compared with the number among 461 controls. The risk of having at least one miscarriage or infertility problems was 1.5 times greater for Leiden mutation carriers than controls. This result was statistically significant (95% CI 1.2, 2.7). The risk of having at least two miscarriages or infertility problems was 2.5 times greater for Leiden mutation carriers than controls. This was also statistically significant (95% CI 1.2, 5.13).

Abortion, Spontaneous↗

Myocardial infarction in women.

The leading cause of death in the United States is cardiovascular disease, regardless of gender. Women will more often have angina preceding their first myocardial infarct, but have more unrecognized infarctions than men. Women will be older, have more concomitant disease and present later in the course of their acute myocardial infarction. Although myocardial infarction may have similar clinical presentations in men and women, there are some important differences such as an increased incidence of non Q-wave myocardial infarctions in women, and the higher rate of complication and immortality from a myocardial infarct. Women develop less collateral cardiac vessels, which may explain the increased rate of hemodynamic complications after a myocardial infarct. Both early and late survival rates are also affected by the advanced mean age of women when they do present with a myocardial infarct. There is less data regarding treatment modalities based upon gender differences but in general, it appears that women benefit from established treatment modalities in the acute setting and subsequent to the event. It has been determined that there are epidemiologic differences, but pathophysiologic and clinical factors specific to women in this setting have yet to be determined.

Female↗

Decreased inhibin B secretion is associated with the monotropic FSH rise in older, ovulatory women: a study of serum and follicular fluid levels of dimeric inhibin A and B in spontaneous menstrual cycles.

UNLABELLED: This study sought to compare circulating and follicular fluid (FF) concentrations of dimeric inhibin A and B utilizing specific two-site ELISAs for these hormones in normal older and younger ovulatory women. METHODS. Normally ovulating women age 40-45 (n = 10) and 20-25 (n = 13) were studied throughout the follicular phase with daily blood sampling, transvaginal ultrasound examinations, and dominant follicle aspiration. When the dominant follicle reached a mean diameter of 16 mm or serum estradiol (E2) was > or = 550 pmol/L, 10,000 IU of hCG was administered intramuscularly followed 32 hours later by transvaginal follicle aspiration. Serum and FF samples were analyzed for E2, FSH, and inhibin A and B. Daily hormone levels were compared by ANOVA, and mean results were compared using t-tests. RESULTS: Older women developed a dominant follicle sooner, meeting criteria for hCG cycle day 10.6 +/- 0.4 vs. 14.5 +/- 1.0 p < 0.001. As expected, the older group had higher maximal serum FSH concentrations compared to the younger women (11.4 +/- 0.5 vs. 8.0 +/- 0.4 IU/L, p < 0.001). We compared hormone concentrations from days-1 to 3 (where day 0 = day of maximal FSH concentration). E2 concentration was higher in the older women (p = 0.002), and there was no significant difference in inhibin A secretion (p = 0.61). In contrast, mean inhibin B concentration was significantly lower in the older women (p = 0.04). On the day of aspiration of the dominant follicle, serum inhibin B was decreased in the older subjects (42.6 +/- 6.5 vs. 153.1 +/- 53 pg/ml, p = 0.02), whereas older subjects had higher levels of inhibin A (106 +/- 16 vs. 60.4 +/- 9.4 pg/ml, p = 0.04) and similar E2 levels (665 +/- 35.2 vs. 687 +/- 92 pmol/L, p = 0.83). There were no differences in FF concentrations of inhibin B (164 +/- 31 vs. 174 +/- 37 ng/ml, p = 0.85), inhibin A (317.7 +/- 38 vs. 248 +/- 57 ng/ml, p = 0.16), or E2 (2074 +/- 294 vs. 2474 +/- 338 nmol/L, p = 0.82) in the older and younger women. CONCLUSION. Follicular phase inhibin B secretion is decreased in older ovulatory women who demonstrate a monotropic FSH rise, whereas inhibin A secretion is similar to that in younger women. The dominant follicle in these older women appears to be normal in terms of FF E2 and inhibin content. We speculate that decreased inhibin B secretion most likely reflects a diminished follicular pool in older women and may be an important regulator of the monotropic FSH rise.

Adult↗

Early coping strategies do not influence the prognosis after whiplash injuries.

This is a 1-year prospective study to investigate the prognostic value of coping strategies such as catastrophising for persistent pain after a whiplash injury. A consecutive series of 96 patients who were seen in the emergency room in the acute phase after the injury were followed prospectively for 1 year. Age, gender and whether or not pain in the neck preceded the accident was recorded. Cases involving fractures or dislocations of the cervical spine, head trauma or pre-existing neurological disorders were not included. The mean interval between the accident and the initial examination was 3+/-2(S.D.) days. Coping was measured using the Coping Strategies Questionnaire (CSQ). The outcome parameter was self-reported neck pain at 1 year after the motor vehicle accident. At 1 year, 34% of the patients had neck pain. Women developed chronic neck pain more often than men (71% versus 29%); they also had significantly higher coping activity, such as diverting attention, praying or hoping (p<0.05), catastrophising and increasing behavioural activities (p<0.0001). Women reported pain in the neck or shoulder more often before the accident and this was the only statistically significant predictor of chronic symptoms when analysed by logistic regression (odds ratio 4.5). To conclude, we found no evidence that the different coping patterns during the early phase after a whiplash injury influenced the prognosis.

Acute Disease↗

Pituitary function in prolactinoma. Effect of surgery and postoperative bromocriptine therapy.

Forty-five women and fifteen men with prolactinomas have been treated surgically. Patients with large tumours received pituitary irradiation and postoperative hyperprolactinaemia was treated with bromocriptine. The patients have been followed-up for 6-36 months following the operation. The tumours were larger and the levels of production higher in men as compared with women. All women had amenorrhoea. Galactorrhoea was present in forty-three women but not in the men. After surgery serum prolactin levels fell significantly in all women but remained above normal in thirty-six; prolactin remained high in twelve men. Bromocriptine effectively decreased the postoperative hyperprolactinaemia. The surgical complications were oculomotor nerve paresis in one woman and one man. After surgery six (23%) women developed impaired GH secretion, six (15%) impaired thyroid function, eight (18%) impaired cortisol secretion and five (17%) impaired LH secretion in isolation or combination which had not been present preoperatively. Three patients relapsed. Fifteen women menstruated after surgery and ten began to do so during the subsequent bromocriptine treatment. Thus, menstruation was restored in all six women with microadenomas in sixteen of twenty patients with intrasellar macroadenomas and three of nineteen patients with suprasellar adenomas. The preoperative LH-reserve proved to be an important prognostic indicator. Nine patients, i.e. 50% of patients desiring fertility became pregnant. In the men gonadal function deteriorated in four patients and did not improve in any without testosterone treatment.

Adenoma↗

Type and intensity of activity and risk of mobility limitation: the mediating role of muscle parameters.

OBJECTIVES: To investigate the association between different types of physical activity behavior and incident mobility limitation in older men and women and to examine whether muscle parameters mediate these associations. DESIGN: Cohort study with 4.5-year follow-up. SETTING: Metropolitan areas surrounding Pittsburgh, Pennsylvania, and Memphis, Tennessee. A random sample of white Medicare beneficiaries and all age-eligible blacks. PARTICIPANTS: Three thousand seventy-five black and white men and women aged 70 to 79 with no self-reported difficulty walking one-quarter of a mile or climbing 10 steps, enrolled in the Health, Aging and Body Composition (Health ABC) Study. MEASUREMENTS: Participants were classified as exercisers (reporting > or = 1,000 kcal/wk of exercise activity), lifestyle active (reporting < 1,000 kcal/wk of exercise activity and > or = 2,719 kcal/wk of total physical activity), or inactive (reporting < 1,000 kcal/wk of exercise activity and < 2,719 kcal/wk of total physical activity). The study outcome, incident mobility limitation, was defined as two consecutive, semiannual self-reports of any difficulty walking one quarter of a mile or climbing 10 steps. Thigh muscle area, thigh muscle attenuation (a marker of fat infiltration in muscle), appendicular lean soft tissue mass, and isokinetic knee extensor strength were examined as potential mediators. RESULTS: Over 4.5 years, 34.3% of men and 47.4% of women developed mobility limitation. Inactive persons had twice the risk of incident mobility limitation as exercisers (hazard ratio (HR)=2.08, 95% confidence interval (CI)=1.60-2.70, for men, HR=1.98, 95% CI=1.51-2.60, for women). Lifestyle-active men and women had an intermediate risk (HR=1.47 and 1.44, respectively). For the lifestyle active and inactive, absence of walking activity conferred an additional risk of mobility limitation. Muscle parameters did not mediate the relationship between physical activity and mobility limitation, except for knee extensor strength in men. CONCLUSION: Exercise and an active lifestyle that includes walking protect against mobility loss in older men and women. Activity effects on muscle parameters do not explain this association.

Activities of Daily Living↗

A randomized trial for the treatment of mild iodine deficiency during pregnancy: maternal and neonatal effects.

One hundred and eighty euthyroid pregnant women were selected at the end of the first trimester of gestation on the basis of biochemical criteria of excessive thyroid stimulation, defined as supranormal serum thyroglobulin (TG > 20 micrograms/L) associated with a low normal free T4 index (< 1.23) and/or an increased T3/T4 ratio (> 25 x 10(-3)). Women were randomized in a double blind protocol into three groups and treated until term with a placebo, 100 micrograms potassium iodide (KI)/day, or 100 micrograms iodide plus 100 micrograms L-T4/day. Parameters of thyroid function, urinary iodine excretion, and thyroid volume were monitored sequentially. Neonatal thyroid parameters, including thyroid volume by echography, were also assessed in the newborns from mothers of the three groups. In women receiving a placebo, the indices of excessive thyroid stimulation worsened as gestation progressed, with low free T4 levels, markedly increased serum TG and T3/T4 ratio. Serum TSH doubled, on the average, and was supranormal in 20% of the cases at term. Urinary iodine excretion levels were low, around 30 micrograms/L at term. The thyroid volume increased, on the average, by 30%, and 16% of the women developed a goiter, confirming the goitrogenic stimulus associated with pregnancy. Moreover, the newborns of these mothers had significantly larger thyroid volumes at birth as well as elevated serum TG levels. In both groups of women receiving an active treatment, the alterations in thyroid function associated with pregnancy were markedly improved. The increase in serum TSH was almost suppressed, serum TG decreased significantly, and changes in thyroid volume were minimized (group receiving KI) or almost suppressed (group receiving KI combined with L-T4). Moreover, in the newborns of the mothers in the two groups receiving an active treatment, serum TG was significantly lower, and thyroid volume at birth was normal. The effects of therapy were clearly more rapid and more marked in the group receiving a combination of T4 and KI than in the women receiving KI alone. The differences could be partly attributed to the slightly higher amount of iodine received by women in the combined treatment. However, the main benefits of the combined treatment were almost certainly attributable to the hormonal effects of the addition of L-T4. Furthermore, the study demonstrated that the administration of T4 did not hamper the beneficial effect of iodine supplementation. In conclusion, the present work emphasizes the potential risk of goitrogenic stimulation in both mother and newborn in the presence of mild iodine deficiency.(ABSTRACT TRUNCATED AT 400 WORDS)

Double-Blind Method↗

Ultrasound-guided puncture of cystic tumors in the lower pelvis of young women.

During the period from 1984 through 1986, 72 ultrasound-guided cyst punctures were performed in 60 young women (less than or equal to 40 years). Thirty-one punctures were performed using the transabdominal route and 41 punctures under the guidance of endovaginal scanning. General or local anesthesia were used in 97% of the transabdominal punctures while the corresponding figure for the endovaginal technique was 49%. Seventy-seven percent (46/60) of the women developed no new cysts within one year of the last puncture. Thirteen percent (8/60) had to be punctured twice and 3% (2/60) three times. No complications occurred in any of the 72 punctures. Of those women with cyst relapses and/or persistent abdominal pain, 7 were subjected to laparotomy and 5 to laparoscopy. Ultrasound-guided puncture of cystic tumors in the lower pelvis of young women seems to be an alternative to laparoscopically guided puncture or laparotomy. As compared to surgery, the ultrasound-guided technique may mean less risk for pelvic adhesions in young women with unproven fertility.

Adolescent↗

Trunk muscle co-ordination during gait: relationship between muscle function and acute low back pain.

Low back pain costs billions of Euros annually in all industrialized countries. Often radiological diagnosis fails to give evidence of the pathogenesis of low back pain. Although psychophysiological characteristics have an influence, it seems that insufficient muscular spinal stabilization may play the major role in the development of low back pain. Assessment of trunk muscle stabilization activity during everyday activities is rare. Therefore, in this study healthy persons were investigated during walking on a treadmill at a speed of 4 km/h. Women (n = 16) with no history of back pain were investigated before and after a static loading situation of the spine, i.e. while wearing a waistcoat. After this loading situation four women developed pain (pain subjects). Surface EMG (SEMG) was taken from five trunk muscles of both sides. Grand averaged amplitude curves over stride, amplitude normalized curves and variation between all included strides were calculated for all muscles and subjects, respectively. The normal range of all calculated parameters was defined within the span between the 5th and the 95th percentiles of all pain free subjects. Data were evaluated according to deviations from the normal range. Already before the load situation, pain subjects showed considerable deviations from the normal range, mainly of their abdominal muscles. There was no relationship between magnitude of deviation and pain intensity, but perceived exertion was highest in those subjects who showed the most symptoms in terms of number of muscles being identified as considerably deviating from the normal range. No specific "dysfunction pattern" could be identified, which argues for highly individual mechanisms instead of a single target muscle. The results suggest cumulative effects of different disturbance levels resulting in acute back pain. Since deviations could be identified already before the pain occurred, disturbed muscle function seems to be a risk factor for developing back pain. Further investigations aimed at clear identification of and, as a second step, correction of muscle function are necessary.

Journal Article↗

Excellent survival, cancer type, and Nottingham grade after atypical lobular hyperplasia on initial breast biopsy.

BACKGROUND: Atypical lobular hyperplasia (ALH) is associated with a 10% to 20% risk of subsequent invasive carcinoma, primarily in the ipsilateral breast. Nottingham grading, special tumor types, and survival after invasive cancer diagnosis were analyzed consistently for the first time. METHODS: A longitudinal follow-up study of 252 women who underwent 261 benign surgical biopsies between 1950 and 1985 with a diagnosis of ALH was undertaken. Subsequent invasive breast cancers were graded and subtyped based on histologic features and the cohort assessed for cancer survival. RESULTS: Forty-eight (19%) women developed invasive breast cancer at an average of 15.1 years. Twenty (42%) of the tumors were special subtype tumors with good prognosis. By an average of 13 years after invasive cancer diagnosis, 2 (10%) of 20 women with special type and variant tumors had died of breast cancer, compared with 9 (32%) of 28 women with tumors of no special type (24 tumors) or an unknown type (4 tumors). Only 1 patient with a tumor of low Nottingham grade died of breast cancer. CONCLUSIONS: ALH is a nonobligate cancer precursor associated with a moderate risk of breast cancer and predicts that later cancers are associated with overall excellent survival. Nearly half of the subsequent cancers show classic or variant patterns of special types with a good prognosis and the majority are of low or intermediate combined histologic grade. Treatment of women with ALH should be influenced by their modest elevation in breast cancer risk and the good prognosis and low mortality of many of these cancers.

Biopsy↗

The Royal Women's Hospital Family Birth Centre: the first 10 years reviewed.

In reviewing the first 10 years experience of the Royal Women's Hospital Family Birth Centre (FBC), we examined the outcomes of pregnancy and labour in a group of women who requested alternative birthing care and who were identified antenatally as being a 'low-risk' population. This study is a retrospective analysis of 5,365 women booked with the birth centre between 1980 and 1989. Over 16% of women developed antenatal complications precluding further care there, while a further 16% developed complications in labour requiring transfer out to conventional labour wards. Thus 67% of those originally booked delivered in the FBC. The instrumental delivery rate was 11%, and the Caesarean section rate was 4%. Of the women who delivered in the FBC, 3.1% had a postpartum haemorrhage and 1.8% required manual removal of placenta. Approximately 4% of babies born in the FBC required some resuscitation, and 0.8% needed admission to the neonatal nursery. Two perinatal deaths occurred in women admitted in labour to the FBC with a live baby, whilst 2 other women presented in labour with a fetal death in utero (perinatal mortality 0.89 per 1,000).

Birthing Centers↗

Leg mass and lower body negative pressure tolerance in men and women.

To explore the hypothesis that lower body muscle mass correlates with orthostatic tolerance, 18 healthy volunteers (age 18-48 yr; 10 men, 8 women) underwent a graded lower body negative pressure (LBNP) protocol consisting of six, 5-min stages of suction up to 60 mmHg in 10-mmHg increments. Forearm blood flow, heart rate, and blood pressure were measured, and forearm vascular resistance was calculated. Leg muscle mass was assessed by dual-energy X-ray absorptiometry. All subjects received standard intravenous hydration for at least 8 h before the study. Six men and four women completed all stages of LBNP. Four men and four women developed presyncopal symptoms, including marked bradycardia and/or hypotension, at LBNP levels of 30 mmHg (n = 2;1 man, 1 woman), 40 mmHg (n = 2;1 man, 1 woman), and 50 mmHg (n = 4;2 men, 2 women). The presyncopal subjects had leg muscle masses ranging from 19.5 to 25.2 kg in men and from 11.7 to 16.6 kg in women. In subjects who completed all stages of LBNP, leg muscle mass ranged from 17.5 to 24.1 kg in men and from 10.4 to 18.0 kg in women. Leg muscle mass did not differ between presyncopal subjects and those who completed the protocol. Furthermore, there were no differences in the hemodynamic responses to LBNP between subjects with low vs. high leg mass. These data suggest that leg muscle mass is not a critical determinant of LBNP tolerance in otherwise healthy men and women.

Absorptiometry, Photon↗

HLA-DR factors associated with postpartum hypothyroidism: an early manifestation of Hashimoto's thyroiditis?

Thirty-three Danish women selected from a prospective study of postpartum thyroiditis were HLA-DR typed. All women had positive titers of antimicrosomal antibodies, and 20 women developed thyroid dysfunction after delivery. DR5 and the phenotype 4.5 were significantly increased in the whole group (p less than 0.001) and strongly associated to hypothyroidism (p less than 0.01), whereas DR3 was insignificantly increased in thyrotoxic women. It is concluded that postpartum hypothyroidism is an autoimmune disorder and may be an early manifestation of Hashimoto's thyroiditis.

Female↗