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New Jersey health care providers face the need to change dramatically the way health care is delivered as it enters a new era of managed care. This year, more than 24% of New Jersey's total population is enrolled in commercial managed care plans (New Jersey Department of Insurance, 1996). In addition, the state's Medicaid agency took steps to improve the delivery of health services to recipients by initiating implementation activities to transition from the traditional Medicaid program to a managed care model. Eighty-two percent of New Jersey's Aid to Families with Dependent Children (AFDC) and related populations have already been enrolled in managed care. The state plans to expand enrollment in managed care to the remaining 400,000 Medicaid beneficiaries. Communities with high Medicaid populations are challenged with the need to move through the managed care evolution at an accelerated rate.

To study the interrelationships of steroids within the follicle, combined 6-h infusions of [3H]dehydroepiandrosterone sulfate and [14C] testosterone ([14C]T) were performed in four normal women treated with menotropins who were undergoing medically indicated surgery. The concentrations of tracer and/or nonisotopic dehydroepiandrosterone sulfate, androst-5-ene-3 beta,17 beta-diol sulfate, androst-5-ene-3 beta,17 beta-diol, dehydroepiandrosterone, androstenedione, T, dihydrotestosterone, estrone (E1), and estradiol (E2) were determined in arterial and venous blood and follicular fluid. The log-transformed product/precursor ratio of [3H]dihydrotestosterone/[3H]T in follicular fluid was negatively correlated with the log-transformed follicular concentrations of E1 (P = 0.01) and E2 (P = 0.02), suggesting a reciprocal relationship between 5 alpha-reductase and follicular E1 and E2. E2 and T were positively correlated in follicular fluid (r = 0.84; P = 0.0003), suggesting a stimulatory action of follicular T on aromatase. These findings along with extensive published data suggest that follicular T functions as a follicular regulator, enhancing follicular aromatase activity when adequate amounts of FSH are available. These conclusions have important implications with regard to mechanisms for selecting the dominant follicle and producing atresia in the remaining cohort of follicles, and they describe a final common path in the pathophysiology of anovulation.

In this prospective, randomized clinical trial, we tested the hypothesis that a needle-free CO 2 injection system (Biojector 2000) would be better tolerated by patients when compared with traditional sharp needles used for gonadotropin injections during stimulation for IVF. As measured by our questionnaire, the needle-free CO 2 injection system was not better tolerated by patients, even though it was equally effective clinically.

At the time of surgery, women were infused with [3H]dehydroepiandrosterone sulfate ([3H]DS)/[14C]testosterone ([14C]T) for 6 h; blood samples were obtained from an artery the ovarian veins, and a peripheral vein; and fluid was obtained from ovarian follicles. Both blood and follicular fluid samples were analyzed for radioactivity as DS, dehydroepiandrosterone (D), androstenedione (delta 4A). T, and dihydrotestosterone (DHT), and the blood was also analyzed for the concentration of nonisotopic DS by RIA. In other subjects the concentrations of D and DS were measured in paired samples of blood and follicular fluid. From these data, values of 13.6 +/- 0.69 L/day four (mean +/- SE; n = 4) for MCRDS, 607 +/- 90 L/day (n = 3) for MCRT, and 0.0190 +/- 0.0089 (n = 3) for [p]DS-T (fraction of plasma DS metabolized to plasma T) were obtained. The ratio of the concentration of the tracer-labeled steroid in the follicular fluid to the concentration in the arterial plasma sample was elevated significantly above 1 for three 3H-labeled and three [14C-labeled metabolites: [3H]D (21-fold; P less than 0.001), [3H]T (81-fold; P less than 0.001), [3H]DHT (19-fold; P less than 0.001), [14C]T (4-fold; P less than 0.025), [14C]DHT (21-fold; P less than 0.01), and [14C]delta 4A (50-fold; P less than 0.001). The estimated concentrations of steroids in follicular fluid derived from DS based on specific activity calculations were as follows: [geometric mean (95% confidence limits; n)]: DS, 5600 (4800-6500 nmol/L; 12); D, 370 (88-1500 nmol/L; 10); delta 4 A, 120 (67-220 nmol/L; 12); T, 130 (39-450 nmol/L; 10); and DHT, 64 (35-120 nmol/L; 8). Comparison of these data to known follicular fluid steroid concentrations shows that DS from the intravascular pool can be used as an ovarian prehormone.

The HFE gene and its mutations C282Y and H63D cause hereditary haemochromatosis (HH). Among 54 affected individuals from North-East Scotland, 91% were homozygous for C282Y and 5.5% were compound heterozygotes for C282Y and H63D. The general population allele frequencies were high (8% and 15.7% for C282Y and H63D respectively). Although it is likely that HH is under diagnosed, these figures suggest that disease expression is variable, and many of those with the genetic predisposition HH will never develop the clinical consequences of iron overload. This has implications for diagnosis and predictive testing.

We report an instance of critical ovarian hyperstimulation syndrome in a highly responsive in-vitro fertilization patient despite the preventive measure of a 4 day 'coast' interval during which no gonadotrophins were administered while gonadotrophin-releasing hormone agonist therapy continued until serum oestradiol concentrations fell below 3000 pg/ml.

Topotecan, a semisynthetic water-soluble analogue of camptothecin, inhibits human topoisomerase I (topo I). We performed a Phase I clinical and plasma pharmacological study of topotecan administered by 24-h continuous infusion without and with granulocyte colony-stimulating factor (G-CSF). We also measured topo I-DNA complexes in peripheral blood mononuclear cells (PBMCs) in an attempt to correlate formation of topo I-DNA complexes in patients treated with topotecan with toxicity and/or response. One hundred four courses of topotecan at doses of 2.5-15.0 mg/m2 were administered to 44 patients with solid tumors. The maximum tolerated dose without G-CSF was 10.0 mg/m2; granulocytopenia was the dose-limiting toxic effect. The maximum tolerated dose could not be increased with G-CSF because of severe thrombocytopenia. Plasma pharmacology was obtained in 11 patients treated at 12.5 mg/m2 and 15.0 mg/m2. The topotecan lactone end-infusion plasma levels correlated strongly with the area under the curve. Lactone elimination was biexponential with a mean t1/2alpha of 28 min and a t1/2beta of 3.8 h at 12.5 mg/m2. Topo I-DNA complexes were measured before and after treatment in PBMCs from seven patients. Pretopotecan topo I-DNA complexes were available on two additional patients treated at 15 mg/m2. The mean increase in topo I-DNA complexes at the end of the topotecan infusion was 1.25 times the pretreatment value. There was a statistically significant relationship (P = 0.02) between lack of disease progression and the level of topo I-DNA complexes measured in PBMCs before therapy. For Phase II studies of minimally treated adults with solid tumors, the recommended topotecan starting dose administered by 24-h continuous infusion is 10 mg/m2 without G-CSF.

Circulating GH and insulin-like growth factor-I (IGF-I) levels in adults generally fall with age. Studies in aging women have rarely controlled for menstrual cycle stage or status or body mass index. We hypothesized that GH and IGF-I levels in reproductive-aged women fall with age despite the stimulatory effects of endogenous estradiol (E2). Eight older reproductive-aged women (aged 42-46 yr) with regular menses, of normal weight, and in good health were compared to a group of eight young control subjects (aged 19-34 yr). Daytime frequent blood sampling was performed in the early follicular phase of the menstrual cycle to characterize pulsatile GH and LH concentrations. Pooled samples were also analyzed for IGF-I, E2, progesterone, and FSH levels. Older reproductive-aged women had lower 12-h integrated daytime GH concentrations (mean +/- SE, 171 +/- 35 vs. 427 +/- 130 micrograms min/L; P = 0.036) than younger controls and a strong trend for lower IGF-I levels (22.7 +/- 2.1 vs. 31.3 +/- 3.5 nmol/L; P = 0.055) than younger controls despite having higher circulating E2 on the day of sampling (368 +/- 51 vs. 167 +/- 20 pmol/L; P = 0.002). We conclude that older reproductive-aged women have lower daytime GH concentrations than younger controls despite having higher E2 levels on the day of sampling and overall normal gonadal hormone parameters.

Evidence has suggested that dehydroepiandrosterone sulfate (DS) is a prehormone for ovarian steroidogenesis. To study this hypothesis, combined 6-h infusions of [3H]dehydroepiandrosterone sulfate and [14C]testosterone ([14C]T) were performed in four normal women treated with menotropins who were undergoing medically indicated surgery, and the data were compared to those from nine normal women. The concentrations of tracer and nonisotopic DS, androst-5-ene-3 beta,17 beta-diol sulfate (delta 5diolS), androst-5-ene-3 beta,17 beta-diol (delta 5diol), dehydroepiandrosterone (D), androstenedione (delta 4A), and T were determined in arterial and venous blood and in follicular fluid. From these data, the concentrations and fractions of steroids in the follicular fluid that were derived from DS were calculated from the specific activity of intravascular DS and the concentrations of follicular fluid tracer steroids and their specific activities. The fractions of T (0.48), delta 5diol (0.31), delta 5diolS (0.42), and D (0.25) in follicular fluid arising from circulating DS were similar and were not significantly different from that of follicular DS arising from circulating DS (0.32). However, the fraction of follicular fluid delta 4A (0.041) was significantly less (P < 0.01), and the fractions of intrafollicular estrone and estradiol arising from DS were both less than 0.04. The mean MCR of DS in the women treated with menotropins of 22.0 +/- 3.5 L/day (mean +/- SE) was significantly higher than the normal control value. These findings elucidate an important mechanism of adrenal/ovarian interaction at the level of steroidogenesis; circulating DS serves as a prehormone for the production of intrafollicular delta 5diolS, delta 5 diol, D, and T.

Summary Compartment syndrome occurred after a tubal anastomosis in a prolonged lithotomy position. Thissyndrome carries the risk of permanent neuromuscular and kidney damage. The pathophysiologic features of the syndrome are reviewed. Specific guidelines for the prevention and management of this syndrome in patients undergoing gynecologic procedures are presented

The present experiments were designed to study male and female luteinizing hormone (LH) secretory patterns following pulsatile or continuous LH-releasing hormone (LHRH) administration using a perifused dispersed rat anterior pituitary cell culture system. In male cells, consistent LH responses were elicited by hourly LHRH pulses (30 pmol), whereas in the female cells (proestrus or diestrus I), a statistically significant (P less than or equal to 0.01) decrease in the LH secretion occurred with successive LHRH pulses. Proestrous cells secreted significantly (P less than or equal to 0.01) more LH than diestrous cells during the first 24 h but not after 48 h in culture. When exposed to a 6-h continuous infusion of LHRH (10 nM), male cells released LH in a single phase and female cells secreted LH in a biphasic pattern. These data suggest that significant sex differences exist in the rat LH secretory pattern elicited by LHRH in vitro.

Recent evidence suggests that a group of children exists in whom premature sexual maturation occurs in the absence of pubertal levels of gonadotropins; that is, they have gonadotropin-independent precocious puberty. We compared six boys and one girl with this disorder with four boys and five girls with central precocious puberty, in which there is a pubertal pattern of gonadotropin release. The two groups were similar in age of onset, degree of sexual development, growth velocity, and rate of skeletal maturation. A family history of precocity was noted in four of the boys with gonadotropin-independent precocity, and the girl had McCune-Albright syndrome. Children with central precocious puberty demonstrated a pulsatile release of gonadotropins, pubertal responses to luteinizing hormone-releasing hormone, and complete suppression of gonadarche after exposure to an analogue of luteinizing hormone-releasing hormone (LHRHa). In contrast, children with gonadotropin-independent precocity demonstrated an absence of gonadotropin pulsations, variable responses to luteinizing hormone-releasing hormone, lack of suppression of puberty in response to LHRHa, and cyclic steroidogenesis. Tissue from testicular biopsies performed in five of six boys with gonadotropin-independent precocity showed a range from incipient pubertal development of the tubules with proliferation of Leydig cells to the appearance of normal adult testes. We conclude that gonadotropin-independent precocious puberty is a distinct syndrome, of unknown cause, that may be familial and may have been responsible for many previously reported cases of precocious puberty.

Uterine leiomyoma is the most common solid tumor of the female genital tract and may cause heavy menometrorrhagia and infertility. Uterine myomectomy is not always feasible and total hysterectomy may be necessaryin young women who have not yet completed their families. Herein we report the regression of a presumed uterine leiomyoma induced by long-term treatment with a long-acting luteinizing hormone-releasing hormone (LHRH) agonist, which was administered to suppress ovarian estrogen secretion. sent from the patient. Metrorrhagia subsided within 48 hours from the initiation of treatment, at the time of the rapidly rising estradiol levels that characterize the agonist phase of LHRH, administration (Fig. 2). Another episode of uterine bleeding occurred 13 days after the beginning of therapy, coincident with suppression of serum estradiol to prepubertal levels. During the first 2 months of therapy the patient reported only minor episodes of vagina1 bleeding, usually lasting no longer than 1 day. No further bleeding occurred after the eighth week of therapy, and the hemoglobin level rose steadily from a pretherapy value of 7.4 gm/dl to 12.8 gmldl within 60 days. Plasma estradiol levels became undetectable (~20 pg/mI) during the third week (Fig. 2) and the patient noted the onset of hot flashes shortly thereafter. At 8 weeks of treatment the leiomyoma had decreased to 5 by 5 by 4 cm according to ultrasound examination and a further reduction to 4 by 4 by 4 cm had occurred by the twelfth week (Fig. 1, B). At 15 weeks the size of the mass was noted to be unchanged at 4by4by4cm.

The gonadotropin-releasing hormone-like agonist D-Trp6-Pro9-NEt-LHRH (LHRHa) has been shown to induce a reversible short-term suppression of gonadotropins and gonadal steroids in patients with central precocious puberty. Since accelerated statural growth and bone maturation are clinical features of precocity not well controlled by conventional therapies, we examined the effects of prolonged LHRHa therapy for 18 consecutive months on growth and skeletal maturation in nine girls with neurogenic or idiopathic precocious puberty. Suppression of gonadotropin pulsations and gonadal steroids was maintained in all subjects. Growth velocity fell from a mean rate (+/- S.E.M.) of 9.35 +/- 0.64 cm per year during the 19 months before treatment to 4.58 +/- 0.60 cm per year during treatment (P less than 0.001). Bone age advanced a mean of 9.4 +/- 2.3 months during treatment. These changes resulted in a mean increase of 3.3 cm in predicted height (P less than 0.01). Complete suppression of the pituitary-gonadal axis can be maintained by LHRHa therapy, resulting in slowing of excessively rapid growth and skeletal maturation and in increased predicted adult height in girls with precocious puberty.