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Biomedical subjects

D Kenigsberg

Publications and source records attributed to D Kenigsberg.

16 recordsLinked to original sources
PubMed1989

Treatment of familial male precocious puberty with spironolactone and testolactone.

Because the pubertal growth spurt in boys appears to be mediated by both androgens and estrogens, we hypothesized that blockade of both androgen action and estrogen synthesis would normalize the growth of boys with familial male precocious puberty. To test this hypothesis, we studied nine boys (age range, 3.3 to 7.7 years) during treatment with an antiandrogen (spironolactone) or an inhibitor of androgen-to-estrogen conversion (testolactone), followed by treatment with both agents. After six months of observation without treatment, the first four boys received spironolactone for six months, followed by spironolactone and testolactone. The next five boys received testolactone for six months, followed by spironolactone and testolactone. Neither spironolactone nor testolactone, given alone, was satisfactory as a treatment for this condition. However, a combination of spironolactone and testolactone, given for at least six months, restored both the growth rate and the rate of bone maturation to normal prepubertal levels and controlled acne, spontaneous erections, and aggressive behavior. The combined therapy was associated with a significantly lower growth rate than testolactone alone (P less than 0.05) and a significantly lower rate of bone maturation than spironolactone alone (P less than 0.05). No important adverse effects were observed during combined treatment. Six of the nine boys continued to receive the combined therapy for an additional 12 months and maintained normal prepubertal rates of growth and bone maturation. The mean predicted height (+/- SEM) increased progressively during the combined treatment although the difference between the pretreatment and post-treatment predictions was not significant (169.5 +/- 2.8 at the end of treatment vs. 166.2 +/- 4.5 cm before treatment; P = 0.29). We conclude that blockade of both androgen action and estrogen synthesis with the combination of spironolactone and testolactone is an effective short-term treatment for familial male precocious puberty. Further study will be required, however, to assess the long-term outcome in boys who receive this treatment.

Aggression↗
PubMed1989

New tests for the prediction of ovulation.

With improvements in basic science understanding and technology, it is predictable that within the next decade, more reliable and accurate methods of ovulation prediction will be available. The former may result from the exploration of gonadal peptides and their measurement whereas the latter may result from the ever-increasing resolution of ultrasonographic imaging. The current state of the art in predicting ovulation involves the combination of several of the described techniques (cervical mucus, urinary LH, ultrasonography). Used skillfully together they serve the infertility specialist well.

Body Temperature↗
PubMed1987

Cumulative ovulation rate in human menopausal/human chorionic gonadotropin-treated monkeys: "step-up" versus "step-down" dose regimens.

Cumulative ovulation rates in monkeys given human menopausal gonadotropin/human chorionic gonadotropin (hMG/hCG) on menstrual cycle days 3 to 9 in a "step-up" versus "step-down" protocol were compared with those achieved by hMG only. Using direct ovarian observation to detect sites of follicular rupture, retrograde tubal irrigation to collect eggs or embryos, and serum estradiol and progesterone levels to infer changes in ovarian status, we counted the number of ovulations at intervals of 24, 48, 72, 96, and 120 hours after hCG or comparable intervals without hCG. The data indicate (1) whereas most ovulations occurred on or before day 3 after hCG treatment, when the "step-up" dose regimen was employed additional follicles had ruptured on days 4 and 5; (2) a "step-down" protocol for hMG therapy may better synchronize follicular rupture and reduce susceptibility to delayed ovulations compared with a "step-up" dose regimen; and (3) under hMG stimulation, few follicles would rupture spontaneously (without hCG or luteinizing hormone treatment).

Animals↗
PubMed1986

The NIH experience with precocious puberty: diagnostic subgroups and response to short-term luteinizing hormone releasing hormone analogue therapy.

Between 1979 and 1983, 129 children (95 girls) with precocious puberty were referred to the National Institutes of Health and received treatment for at least 6 months with the long-acting LHRH analogue D-Trp6-Pro9-NEt-LHRH. The majority (107 of 129) of the children had central precocious puberty mediated by activation of the hypothalamic-pituitary-gonadal axis in association with hypothalamic hamartomas (24 of 107) or other central nervous system lesions (21 of 107), or idiopathic precocious puberty (62 of 107). Hypothalamic hamartomas or other central nervous system lesions were a frequent cause of central precocious puberty in girls (27 of 87), but idiopathic precocious puberty was still the most frequent diagnosis (63%). Idiopathic precocious puberty was uncommon in boys (6%). The patients with peripheral precocious puberty included six girls with McCune-Albright syndrome and six boys with familial male precocious puberty. These children had peripheral sex steroid secretion in the absence of hypothalamic-pituitary-gonadal axis maturation. The children with combined peripheral and central precocious puberty included nine children with congenital adrenal hyperplasia and one girl with a virilizing adrenal tumor. In the patients with central precocious puberty or combined peripheral and central precocious puberty, LHRHa therapy caused suppression of gonadotropin and sex steroid levels (P less than 0.001), stabilization or regression of secondary sexual characteristics, and decreases in growth rate and in the rate of bone age maturation (P less than 0.005). Patients with peripheral precocious puberty, however, had no significant change in gonadotropin or sex steroid levels, growth rate, or the rate of bone age maturation, and no improvement in secondary sexual characteristics. Thus, LHRHa is an effective treatment of central precocious puberty and combined peripheral and central precocious puberty, but is ineffective in the therapy of peripheral precocious puberty.

Adrenal Hyperplasia, Congenital↗
PubMed1986

Ovulation inhibition by administration of weekly gonadotropin-releasing hormone antagonist.

To test the feasibility of administering the GnRH antagonist [(Ac-pClPhe1,pClPhe2,DTrp3,DArg6,DAla10) GnRH] intermittently to inhibit ovulation, this agent was given to normal ovulatory cynomolgus monkeys once weekly for 4 weeks. Ovulation was blocked in all females (eight of eight) throughout the 32 study weeks and resumed within 14.3 +/- 3.8 (+/- SEM) days in six of eight primates. Interestingly, mean tonic serum estradiol levels were not significantly reduced during treatment. Conversely, although midcycle levels of estradiol were not found, moderate estradiol levels occurred but they did not elicit preovulatory LH surges during the week after GnRH antagonist injection. In a second study directed at clarifying the mechanism(s) by which estrogen-induced LH surges were blocked, monkeys received GnRH antagonist in the early through the midfollicular phase of the menstrual cycle during which an estrogen (n = 3) or a GnRH (n = 4) challenge test was given on cycle day 6. Among monkeys receiving estradiol benzoate or a bolus dose of GnRH during the GnRH antagonist regimen, only those given GnRH (four of four monkeys) had increased LH secretion. These responses were similar to those of control monkeys (n = 3). Indeed, the pituitary was refractory (three of three monkeys) to estrogen-positive feedback for the LH surge. These findings indicate the potential utility of intermittent GnRH antagonist treatment to achieve contraception by ovulation inhibition, without creating a severely hypoestrogenic milieu attendant with the risks of negative sequelae effecting bone calcium loss, hot flushes, and atrophy of estrogen-dependent genital tissues.

Animals↗
PubMed1986

Endometrial immunofluorescence associated with endometriosis and pelvic inflammatory disease.

Anti-immunoglobulin G (anti-IgG) staining in the endometrium by immunofluorescence has been associated with endometriosis. To investigate this phenomenon further, we took endometrial samples from 42 patients who underwent laparoscopy or laparotomy, which were tested for immunofluorescence. Fluorescein-labeled anti-IgG was incubated with tissue samples. Of 18 patients with documented endometriosis, 16 had positive immunofluorescence (89% sensitivity). Of 24 patients with no evidence of endometriosis, 9 had false-positive immunofluorescence and 15 had negative immunofluorescence. Of the 9 false-positive samples, 8 had evidence of old pelvic inflammatory disease. In the absence of this condition, there was only one false-positive study for immunofluorescence. The implications of these findings in terms of the pathophysiology of endometriosis-associated infertility is that it may be an immune-mediated process. With regard to diagnosis, the high predictive value of endometrial immunofluorescent IgG may be a useful tool in indicating early laparoscopic examination of the infertile period.

Antibodies, Anti-Idiotypic↗
PubMed1984

Medical hypophysectomy: I. Dose-response using a gonadotropin-releasing hormone antagonist.

The hypothalamic-pituitary-ovarian axis can be "dissected" in a nonsurgical and reversible fashion by the administration of a potent gonadotropin-releasing hormone (GnRH) antagonist. We created a transient, functional lesion at the level of the pituitary gonadotrope by using a potent GnRH antagonist ([ Ac- pClPhe1 , pClDPhe2 , DTrp3 , DArg6 , DAla10 ]-GnRH). In long-term castrate cynomolgus monkeys, doses of 0.05 to 2.0 mg/kg/day intramuscularly were administered for a total of 32 days. At doses up to 0.2 mg/kg/day, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in circulation were only moderately suppressed; these subjects responded to an estradiol challenge by manifesting an LH elevation or surge within 48 hours. At doses of 0.5 to 1.0 mg/kg/day, FSH and LH secretion was suppressed to or below the limits of assay detection within 7 days, remaining in a severely hypogonadotropic state for the remainder of the treatment interval. Using 2 mg/kg/day, estradiol-positive feedback for midcycle-like LH/FSH surges was fully inhibited. This suppression of gonadotropin secretion was rapidly reversible, in that circulating gonadotropin levels had returned to pretreatment castrate levels within 60 days after termination of GnRH antagonist treatments. These findings suggest that potent GnRH antagonists can effectively create a hypogonadotropic milieu without the initial enhancement of gonadotropin secretion that occurs during initiation of GnRH agonist therapy. "Medical hypophysectomy" through GnRH antagonist administration may permit a more direct and controlled approach to gonadal therapies such as ovulation induction.

Animals↗
PubMed1984

Medical hypophysectomy: II. Variability of ovarian response to gonadotropin therapy.

In an attempt to control individual variability of ovarian response to gonadotropin therapy, ovulatory monkeys received either "pure" follicle-stimulating hormone (FSH) or human menopausal gonadotropin (hMG), with or without gonadotropin-releasing hormone (GnRH) antagonist administration. Among females that responded to gonadotropin therapy, the GnRH antagonist reduced (P less than 0.05) the variability of serum estradiol patterns. Surprisingly, after pretreatment and concurrent administration of the GnRH antagonist, FSH alone was as effective as the FSH/luteinizing hormone (LH) mixture (hMG) in stimulating follicular maturation, even when serum LH levels were at or below the limits of detection. The results indicate that in a rapidly reversible hypogonadotropic state approaching a "medical hypophysectomy," concurrent gonadotropin therapy produces a less varied ovarian response. The relative (un)importance of LH in the primate ovarian cycle seems diminished in the face of evidence that FSH alone, or in the presence of vanishingly small amounts of LH, supports follicular maturation and dynamic estrogen biosynthesis.

Animals↗
PubMed1984

Ocular findings in Turner syndrome. A prospective study.

We performed complete ophthalmological examinations of 30 consecutive patients with Turner syndrome. Twenty-three had 45XO and 7 had 45XO/46XX karyotypes (mosaicism). Non-familial strabismus was the most prominent ocular abnormality and was present in 33% of the patients. Other eye findings included ptosis (16%), hypertelorism (10%), epicanthus (10%), and antimongoloid slants (10%). Red-green color deficiency was found in 10% of the patients. One patient had congenital periodic alternating nystagmus.

Adolescent↗
PubMedDate not supplied

Polar body-based preimplantation diagnosis for X-linked disorders.

Preimplantation diagnosis for X-linked disorders has been performed predominantly by gender determination, which, however, leads to the discarding of 50% unaffected male embryos. In an attempt to identify X-linked mutation-free embryos for transfer, the present authors introduced preimplantation genetic diagnosis (PGD), using a sequential first and second polar body analysis, as an alternative to gender determination. This method was offered to eight couples at risk for having children with X-linked disorders, including haemophilia B, fragile-X syndrome (FMR1), myotubular myotonic dystrophy (MTMD), ornithine transcarbamylase (OTC) deficiency and X-linked hydrocephalus. The first and second polar bodies were removed following maturation and fertilization of oocytes in a standard IVF protocol and analysed using a multiplex nested polymerase chain reaction (PCR), involving testing for mutations simultaneously with linked markers. Overall, 13 PGD cycles were performed, resulting in the detection of 25 embryos with the predicted mutation-free maternal contribution; these embryos were transferred back to the patients in all cycles, yielding four clinical pregnancies. Four children were born following these pregnancies, including three unaffected and one with misdiagnosis as a result of allele dropout (ADO), which was predictable in the case of FMR1. Presented results demonstrate the clinical usefulness of the specific polar body testing for X-linked disorders as an alternative to PGD by gender determination.

Female↗