The wreathing protocol: the imbrication of hypnosis and EMDR in the treatment of dissociative identity disorder and other dissociative responses. Eye Movement Desensitization Reprocessing.

Dissociative Identity Disorder (DID), a chronic childhood onset posttraumatic stress disorder, is currently recognized as a treatable condition. It is considered the paradigmatic dissociative condition and carries with it extreme posttraumatic symptomatology. Therapists skilled in the treatment of DID are typically fluent in the uses of hypnosis for stabilization, affect management, building a safe place and grounding to name of few. EMDR, which has come to the forefront of clinical awareness in the last ten years, seems aptly suited for the treatment of trauma, but can be destabilizing. This paper proposes a protocol, called Wreathing Protocol, for the imbricated use of EMDR and hypnosis in the treatment of not only DID (though this will be the primary focus of the paper), but also Dissociative Disorder Not Otherwise Specified (DDNOS) and chronic Posttraumatic Stress Disorder (PTSD). This protocol is useful to advanced clinicians skilled in both modalities independently. The sequential steps of the Wreathing Protocol will be described and illustrated by a clinical vignette on DID. The clinical implications of the use of the Wreathing Protocol will be discussed in DID as well as the chronic post traumatic spectrum.

Repetitive responses to clomiphene citrate in normal women of late reproductive age.

The hormonal response to clomiphene citrate (CC) has been used to evaluate ovarian reserve. In the current study, we tested the reproducibility of response to 100 mg of CC administered for 5 days in a group of 20 women, 35 to 40 years of age, with regular menstrual cycles who completed 57 cycles during the study. Individual hormonal responses to repeated stimulation were not identical. When ovarian responsiveness to CC was categorized as "low" (E(2) and E(2)/FSH ratios =200 pg/mL and =20, respectively) or "high" (E(2) =400 pg/mL and E(2 /FSH ) =61), however, responses of individual subjects seldom spanned both categories. Specifically, only 3 of 20 subjects had both low and high E(2) and low and high E(2/FSH ) ratios (P<0.001). In addition, seven subjects were identified as FSH hyperresponsive in at least one cycle (post-CC FSH =10 IU/L). Only 2 of 21 cycles in these seven subjects had post-CC E(2)/FSH ratios =61, in comparison with 20 of 36 cycles in the other 13 subjects (P<0.01). Thus, despite the cycle-to-cycle variations, the hormonal response of an individual subject could usually be categorized as occurring at one or the other end of the spectrum of ovarian function, these two extremes probably signifying good and poor ovarian reserve. This prediction is further strengthened by the observation of a significant negative correlation between the FSH and E(2) responses after administration of CC (P=0.05).

Ascorbic acid stimulation of gonadotropin release from hamster anterior pituitary gland is not mediated through cyclic nucleotide system.

Ascorbic acid (AA) can transiently stimulate LH and FSH release from superfused male hamster anterior pituitary glands. The effective concentration is 1 mM or higher. Since 8-Br-cAMP or 8-Br-cGMP can not mimic the AA stimulation pattern, the action mechanism is not mediated through cyclic nucleotide system.

Serum androgens in hyperinsulinemic Pima Indian and obese Caucasian women and their response to short-term insulin infusion.

Insulin resistance and its attendant hyperinsulinemia has been linked with hyperandrogenism. Insulin resistance is characteristic of the Pima Indians of the Gila River Indian community in central Arizona. Serum androgens, testosterone and dehydroepiandrosterone sulfate (DHEA-S) were quantitated at baseline and in response to low- and high-dose insulin infusion in 11 obese, hyperinsulinemic Pima Indian and 10 obese, hyperinsulinemic Caucasian women and were compared with baseline androgens in 16 nonobese Caucasian women. While there was no significant testosterone or DHEA-S response to short-term insulin infusion in either Pimas or obese Caucasians, both these groups had higher baseline testosterone concentrations (67 +/- 6.5 ng/dl in the Pimas, 55 +/- 5.9 ng/dl in the obese Caucasians) as compared with the nonobese Caucasians (28 +/- 2 ng/dl; p < 0.001). Baseline DHEA-S concentrations were not significantly different in the three groups. Given the hyperinsulinemic status of both the Pimas and the obese Caucasians, the finding of higher testosterone concentrations in these subjects as compared with nonobese Caucasians supports a role for insulin in ovarian androgen production and demonstrates that hormonal interactions that may be operating in obese hyperinsulinemic Caucasian subjects also operate in obese, hyperinsulinemic Pima Indians.

Fetal alcohol exposure and adult tumorigenesis.

Adult rats exposed to prenatal alcohol were evaluated for their susceptibility to either hormone- or chemical-inducing tumors. In the first study, rats exposed to prenatal alcohol displayed an increased propensity to beta-estradiol (E2)-induced adenohypophyseal prolactinoma. The susceptibility was manifest as a potentiated increase in anterior pituitary weight as well as in serum prolactin levels after 1 and 3 weeks but not 5 weeks of hormone treatment. Two weeks after withdrawing the E2-implant, the prolactinoma underwent involution and serum prolactin reversed to baseline levels. The high concentrations of serum corticosterone were also reduced but did not return to baseline levels after E2 removal. In the second study, nitrosomethylbenzylamine (NMBA) was utilized to induce esophageal cancer in adult rats. There were no significant differences in tumor incidence or size between the prenatal alcohol-exposed and the pair-fed cohorts. However, the NMBA-treated prenatal alcohol-exposed rats displayed a marked decrease in thymus: body wt ratio as well as adrenal gland hyperplasia. The results suggest that no single mechanism can account for the variable susceptibility displayed by the prenatal alcohol-exposed rats to chemical carcinogens. Some of the observed changes, however, may be attributable to the long-lasting adverse effects of prenatal alcohol exposure on the well-being of the adult host.

Endogenous luteinizing hormone surges following administration of human chorionic gonadotropin: further evidence for lack of loop feedback in humans.

The existence of inhibitory short- and ultrashort-loop feedback mechanisms for luteinizing hormone (LH), while documented in animals, has been questioned in humans. Since human chorionic gonadotropin (hCG) binds to LH receptors but can be distinguished from LH in immunoassays, it is possible to identify LH surges in the face of exogenously administered hCG. The present study demonstrates LH surges at midcycle in normal volunteers and in women undergoing controlled ovarian hyperstimulation, given hCG. This provides further evidence for lack of loop feedback control of LH secretion in humans.

Use of the hormonal response to clomiphene citrate as an endocrinological indicator of ovarian ageing.

We compared the gonadotrophin and oestradiol responses to clomiphene citrate (CC) in women aged 18-25 versus 35-40 years. Despite similar baseline hormone concentrations and the attainment of similar concentrations of the E and Z isomers of clomiphene, higher follicle stimulating hormone (FSH) concentrations were observed in the older women, possibly indicative of their ageing ovaries. Furthermore, diminished oestradiol responses occurred in a subgroup of women showing FSH hyper-responsiveness to CC. These preliminary results support the concept that the hormonal response to CC may be an indicator of approaching perimenopause.

Study of the pharmacokinetics of human chorionic gonadotropin and its relation to ovulation.

The pharmacokinetics of human chorionic gonadotropin (hCG) was studied in 15 normal volunteers and 15 patients undergoing in vitro fertilization (IVF). Each subject received 6000 IU hCG, intramuscularly (im), at midcycle, and serum was assayed for hCG frequently for 16 hr. All 30 subjects achieved hCG concentrations greater than or equal to 10 IU/liter within 2 hr and 19 (63%) did so within 1 hr of injection. The time taken to attain concentrations of greater than or equal to 20 and greater than or equal to 40 IU/liter correlated positively with the subjects' weight and/or surface area, but the correlation was not strong. Eleven of the 15 IVF patients had oocytes retrieved 34-35 + hr post hCG. Three of the 11 showed evidence of prior "undetected ovulation" at the time of surgery (definite in one, presumed in two). Taking into consideration the pharmacokinetics of hCG and other factors that could lead to undetected ovulation, the authors conclude that (1) hCG is rapidly absorbed in the majority of subjects following im injection, (2) ovulation may occur earlier than 36 hr following hCG in some individuals, and (3) implementation of a shorter (than 35 hr) hCG-to-oocyte retrieval interval would be advised if undetected ovulation is to be avoided.

Assessment in rats of the gonadotoxic and hepatorenal toxic potential of dibromochloropropane (DBCP) in drinking water.

This investigation was undertaken to assess the potential of ingested 1,2-dibromo-3-chloropropane (DBCP) to cause testicular and hepatorenal injury, in light of the paucity of data applicable to risk assessment of DBCP in drinking water. Adult male Sprague-Dawley rats were supplied ad libitum with water containing 0, 5, 50, 100, and 200 ppm DBCP for 64 days. A dose-related decrease in water consumption occurred during the study. The 200-ppm animals drank less than half as much water as controls, consumed less food, and subsequently exhibited significantly lower body weight gain. DBCP ingestion thus was not directly proportional to the level of chemical in the water, although daily and cumulative intake of DCP were concentration dependent. Average daily intake of DBCP for the 64-day exposure period was as follows: 5 ppm = 0.4 mg/kg/day; 50 ppm = 3.3 mg/kg/day; 100 ppm = 5.4 mg/kg/day; 200 ppm = 9.7 mg/kg/day. Blood samples were taken after 2, 4, and 6 weeks of exposure and at the terminal sacrifice and assayed for serum glutamic-oxaloacetic transaminase, glutamic-pyruvic transaminase, sorbitol dehydrogenase, and ornithine-carbamyl transferase activities and BUN levels. No evidence of liver damage at any exposure level was indicated by either the clinical chemistry indices or histopathology. Histologic examination revealed an apparent increase in the number of nuclei per renal proximal tubule cross-section in the 200-ppm group, possibly indicative of an increased turnover of proximal tubular cells. A slight, but statistically significant, decrease in absolute testicular weight was manifest in the 200-ppm animals, although the decrease was not significant when testicular weight was calculated as g/100 g body wt. Epididymal sperm counts and serum luteinizing hormone, follicle stimulating hormone, and intratesticular testosterone levels were not altered by any dose of DBCP. A qualitative histopathological examination of the testicular seminiferous epithelium failed to reveal any abnormalities in the spermatogenic process.

Pituitary and testicular function in the restricted (Hre) rat.

A systematic morphological and biochemical examination of the pituitary-testicular axis in the male restricted (Hre) rat was undertaken in order to understand the possible site(s) and mechanism(s) responsible for their infertility. The adult Hre rat had increased plasma levels of LH and FSH but normal levels of prolactin and testosterone, and normal weights of the sex accessory glands. The increased plasma levels of LH and FSH correlated with hypertrophy and vacuolation of the gonadotrophs in Hre rats. Leydig cells from adult Hre rats exhibited an enhanced testosterone response to LH and hCG in vitro but not in vivo. There was a shift in the normal age-related decline in the response of cultured Sertoli cells to FSH in Hre rats, which was evident as early as 25 days of age, and which corresponded to a delay of 10-14 days in the pubertal increase in testicular weight. The search for the mechanism of the suppression of spermatogenesis in the Hre rat should take into account two events, which may or may not be related: (i) the delay in the onset of spermatogenesis during puberty and (ii) inhibition of spermatogenesis in the adult, which may result from abnormal function of both the Sertoli and Leydig cells.

Inhibition of Dunning tumor growth by melatonin.

Injections of the pineal hormone melatonin reduced growth and increased doubling time of the R3327H Dunning prostatic adenocarcinoma in the Copenhagen X Fisher rat. This occurred even though testosterone levels (50% of normal) were ostensibly high enough to maintain normal tumor growth. Melatonin may act directly upon the conversion of testosterone to dihydrotestosterone to inhibit tumor growth. Alternatively, a more complicated mechanism may be involved since studies on MCF breast cancer tissue indicate an estrogen requirement for inhibition of growth by melatonin.

Luteal-phase support in stimulated cycles in an in vitro fertilization/embryo transfer program: progesterone versus human chorionic gonadotropin.

A study was undertaken to compare the hormonal parameters [serum concentrations of estradiol (E2), and progesterone (P) and P/E2 ratios] of patients undergoing in vitro fertilization/embryo transfer to whom either progesterone in oil or human chorionic gonadotropin (hCG) was administered as luteal support. Seventeen patients were studied in 20 cycles. In 10 randomly assigned cycles 25 mg of intramuscular progesterone in oil was administered daily from the day of embryo transfer (day +4) until day +18. In the other 10 cycles, 1500 IU of hCG was given intramuscularly on days +4, +7, +10, and +13. Even when accounting for the differences in recruitment in the two groups, the hCG-treated group had significantly higher concentrations of serum P (P less than 0.01) and E2 (P less than 0.05) during the luteal phase. The luteal P/E2 ratios were higher in the progesterone-treated group because of the lower E2 levels in that group, although the difference was not statistically significant. The ratio of the mean luteal P to the preovulatory serum E2 was significantly higher in the hCG-treated group (P less than 0.01). There were three clinical pregnancies in the hCG-treated group. We conclude that (1) higher P concentrations are achieved with hCG treatment than with progesterone treatment during the luteal phase; (2) high luteal P/E2 ratios per se may not be an important determinant of implantation; (3) progesterone production by the corpus luteum is not maximal in progesterone-treated cycles; and (4) the usefulness of hCG as a luteal support agent should be further evaluated.

Differences in the cyclic nucleotide mediation of luteinizing hormone-releasing hormone action on the rat and hamster anterior pituitary gland.

A continuous flow superfusion system which was previously developed in our laboratory was utilized to study the modulation of LH and FSH release by cyclic nucleotides and LHRH from anterior pituitary glands (APG) obtained from rats or hamsters. There was a transient increase in LH and FSH secretion from superfused rat APG in response to superfusion with 1 X 10(-3) M 1-methyl-3-isobutyl-xanthine (MIX), while 1 X 10(-4) MIX M had no effect. Furthermore, a dose of 5 X 10(-5) M MIX did not potentiate the gonadotrophin-releasing effect of 1 X 10(-10) M LHRH. Neither 1 X 10(-3) M 8-Br-cAMP nor 1 X 10(-3) M 8-Br-cGMP mimicked the gonadotrophin-releasing effects of 1 X 10(-9) M LHRH. In the experiments utilizing hamster APG, FSH release gradually increased during superfusion with 1 X 10(-3) M MIX or 1 X 10(-4) M MIX, while LH release was transient but significantly increased in response to superfusion with both doses of MIX. A dose of 5 X 10(-5) M MIX potentiated the effect of a low dose of LHRH (1 X 10(-10) M) upon both LH and FSH secretion. 1 X 10(-3) M 8-Br-cAMP mimicked the effect of LHRH upon LH and FSH released from superfused hamster APG, while 1 X 10(-3) M 8-Br-cGMP was inhibitory. These results suggest that cyclic nucleotides are involved in the mediation of the LHRH-induced release of gonadotropins from the anterior pituitary gland of the hamster, but do not mediate the LHRH-induced release of gonadotropins from the rat anterior pituitary gland.

Ovarian response to human menopausal gonadotropin after therapy with the gonadotropin-releasing hormone agonist leuprolide.

Two of three patients receiving leuprolide, a gonadotropin-releasing hormone agonist, demonstrated a decreased ovarian response to gonadotropin stimulation that was consistent with that of an earlier report involving two cases. It would appear that this agonist has direct antigonadal actions.

Patterns of increase in serum estradiol in response to ovarian stimulation and their relationship to oocyte fertilization and cleavage in vitro.

The in vitro fertilization and cleavage rates of oocytes obtained from patients exhibiting two different patterns of increase in serial serum concentrations of estradiol (E2) in response to ovarian stimulation were compared. Forty-two cycles (from 38 stimulated patients) were evaluated because they fulfilled requirements from two pre-defined patterns of E2 response to ovarian stimulation. In 16 cycles, serial serum E2 concentrations followed a "plateau" pattern (group A), viz., the rate of increase in the serum concentration of E2 decreased prior to the administration of human chorionic gonadotropin (hCG). In 26 cycles, serial serum E2 concentrations followed a "leap" pattern (group B), in which the rate of increase in serum concentrations of E2 increased progressively up to and including the day of hCG administration. There was no significant difference in the fertilization rate of oocytes obtained from patients exhibiting either pattern A or pattern B (78 versus 74%) but the cleavage rate was significantly higher in ova obtained from patients who exhibited pattern A rather than pattern B (72 vs 50%; P less than or equal to 0.01). In addition, embryos resulting from fertilized ova obtained from women in group A were of better quality morphologically than those obtained from women in group B (mean embryo grades, 3.9 vs 3.2; P less than or equal to 0.005). We conclude that cycles in which serial serum concentrations of E2 follow pattern A in response to stimulation give rise to oocytes that, when fertilized, yield higher cleavage rates and better-quality embryos than oocytes obtained from women in whom serial serum E2 concentrations follow pattern B.(ABSTRACT TRUNCATED AT 250 WORDS)

Inhibin production by Sertoli cells during testicular regression in the golden hamster.

The objective of this study was to determine if testicular regression in the hamster results in changes in Sertoli cell function that reflect altered pituitary function. Inhibin-like activity was measured in spent media from Sertoli cells cultured from adult control and optically enucleated hamsters with regressed testes using a homologous hamster Sertoli cell/hamster pituitary cell bioassay. The inhibin activity resulted in a dose-related decrease in FSH release from both normal and "regressed" pituitary cultures but maximal inhibition occurred at a 3- to 4-fold lower dose with media from Sertoli cells obtained from regressed hamsters. When pituitary cells from control adult or adult hamsters with regressed testes were incubated with Sertoli cell spent media, pituitary cells from regressed hamsters were more sensitive than normal pituitary cells to both normal and "regressed" inhibin. This greater production of inhibin-like activity and/or an enhanced sensitivity to inhibin in the regressed hamster may contribute to the decline in FSH levels during testicular regression. This data lends further support to a physiologic role for inhibin.

Undetected ovulation in in vitro fertilization-embryo transfer patients.

A retrospective evaluation was done of 102 consecutive in in vitro fertilization-embryo transfer (IVF-ET) treatment cycles that culminated in surgical intervention for oocyte pickup. In 35% of these patients, a disparity was noted in the number of mature follicles present on the day of human chorionic gonadotropin administration, compared with the day of surgery. This suggests the occurrence of undetected ovulation. An endogenous luteinizing hormone (LH) surge was detected in 14 of these patients. Another cohort showed evidence of early luteinization without a detected endogenous LH surge. Finally, a group without early luteinization was defined. Possible explanations for these outcomes and the implications for success of IVF-ET are discussed.

Patterns of estradiol response in patients with endogenous gonadotropin surges during follicular recruitment in an in vitro fertilization and embryo transfer program.

This report is an analysis of 16 cycles in 15 patients stimulated with human menopausal gonadotropin and clomiphene citrate for the purpose of follicular recruitment in an in vitro fertilization program, all of which resulted in endogenous luteinizing hormone (LH) surges. A study of the pattern of estradiol (E2) response to stimulation revealed two groups of cycles, designated "leap" pattern (9 cycles) and "plateau" pattern (7 cycles), the rate of rise of E2 increasing or decreasing, respectively, as the time of the LH surge was approached. There were no significant differences between these groups of cycles in the peak E2 level attained or the number of follicles greater than or equal to 12 mm on the day of peak E2. In the plateau, but not in the leap pattern cycles, a significant correlation (r = 0.958) was found between the number of follicles greater than or equal to 12 mm and the peak E2. We tentatively conclude that "plateau" pattern cycles reflect relatively synchronous follicular recruitment; the greater the number of follicles recruited, the higher the E2 level attained, increased amounts of inhibin-like substances being available to restrain the LH surge; "leap" pattern cycles reflect asynchronous follicular recruitment.

Melatonin's differential inhibition of FSH and LH release from hamster pituitary glands.

Melatonin initially inhibited FSH secretion from superfused adult male hamster anterior pituitary glands obtained at 8:30 a.m. However, there was a gradual rebound during melatonin superfusion followed by an overshoot above baseline when melatonin was discontinued (morning response). Melatonin continuously inhibited FSH secretion during superfusion of hamster anterior pituitary glands obtained at 3:30 p.m., with a rebound evident only when melatonin was withdrawn (afternoon response). Melatonin continuously inhibited LH secretion from these superfused pituitaries, with a return to baseline levels only upon melatonin withdrawal. Prior pinealectomy or constant light could reverse the FSH morning response to an afternoon response, and late-morning melatonin injections could reverse the FSH afternoon response to a morning response. Neither prior pinealectomy, constant light nor melatonin injections affected melatonin inhibition of LH secretion from superfused pituitary glands. These results suggest that melatonin differentially inhibits FSH and LH secretion from isolated superfused hamster anterior pituitary glands.