Steven F. Palter

DECREASED BONE MINERAL DENSITY IN MEDICATED PSYCHIATRIC PATIENTS

Osteoporosis is a common problem in postmenopausal women.It has been linked to estrogen deficiency, other neuroendocrine processes such as hypercortisolemia and male hypogonadism, nutritional deficiencies, and other mechanisms. Some of these changes have been also reported in male and female patients with mental disorders, especially those receiving psychotropic medications. Therefore, bone mineral density was measured by dual-photon absorptiometry in the lumbar spine and in the femoral neck of 33 female and 35 male consenting psychiatric inpatients admitted consecutively. Patients were diagnosed as having major depressive disorder (N = 21), schizophrenia (N = 33), schizoaffective disorder (N = 7), mania (N = 2), and adjustment disorder (N = 5). Plasma levels of prolactin, estrogen, cortisol, and testosterone were also measured in a subgroup of these patients. It is reported that female patients, but especially male patients, had a highly significant decrease in bone mineral density when compared with age- and sex-matched normal data. It is suggested that psychiatric patients treated with antidepressants or neuroleptics might have decreased bone mineral density than is normal for their age and sex, and may be at an increased risk for fractures. These results may be related to low levels of gonadal hormones, especially in male subjects. Data should be confirmed with a larger number of patients with and without medications to distinguish between diagnosis-related and treatment-related effects.

Possible acceleration of age effects on cognition following menopause

Many cognitive functions have been shown to deteriorate with age. Because of the importance of the menopause as a milestone in the life cycles of women, we examined whether the aging-over-time process in some cognitive functions differs between women of reproductive age and postmenopausal women. It is demonstrated here that in some cognitive tests, including driving simulation, reaction time and some visuospatial tests, there is a significant acceleration in deterioration of functioning following menopause. It is suggested that this acceleration might be associated with the lack of gonadal hormones or other reproduction-related factors which may play a protective role against age-related deterioration in some cognitive functions in women.

Cryomyolysis, a new procedure for the conservative treatment of uterine fibroids

Conservative surgical options for uterine myomata traditionally were abdominal myomectomy, laparoscopic myomectomy, and, more recently, myolysis. Each of these procedures has distinct advantages, but also apparent disadvantages. We attempted to introduce an additional option for conservative surgical treatment of fibroids by freezing the structures, a procedure termed cryomyolysis. In this pilot study, 14 women were pretreated with a gonadotropin-releasing hormone (GnRH) agonist for a minimum of 2 months preoperatively to minimize uterine and myoma size. Cryomyolysis was performed and the GnRH agonist was discontinued. Magnetic resonance imaging scans were performed in 10 of the 14 women after GnRH agonist treatment but before surgery, and 4 months postoperatively. Total uterine volume ranged from 41.3 to 1134.8 ml preoperatively, and 49.5 to 1320 ml postoperatively (mean increase 22% after discontinuation of GnRH agonist). Normal uterine volume ranged from 35.6 to 548.7 ml preoperatively and 45.1 to 729.6 ml postoperatively (mean increase 40%); however, myoma volume showed a mean decrease of 6% (range -87-28%). Analysis of only frozen myomata revealed a mean volume decrease of 10%. Cryomyolysis maintains at or slightly reduces these lesions to post-GnRH agonist size, and all other uterine tissue returns to pretreatment size. We believe cryomyolysis may be an effective conservative surgical approach to uterine fibroids.

OFFICE MICROLAPAROSCOPY UNDER LOCAL ANESTHESIA FOR CHRONIC PELVIC PAIN

STUDY OBJECTIVE To investigate the utility, tolerance, and costs associated with a program of office laparoscopy under local anesthesia using fiberoptic microlaparoscopes (<2 mm) and accessory instrumentation (<2 mm) for the evaluation of patients with chronic pelvic pain (CPP). DESIGN Prospective, nonselected cohort study. SETTING Office-based free-standing faculty practice at a tertiary care referral center. PATIENTS All women with a history of CPP from February to June 1995 who required diagnostic laparoscopy were compared with a cohort of patients undergoing in office diagnostic laparoscopy for the evaluation of infertility during the same period. INTERVENTIONS All patients underwent diagnostic office microlaparoscopy under local anesthesia (OLULA) with supplemental intravenous sedation, as well as conscious pain mapping. MEASUREMENTS AND MAIN RESULTS A specific questionnaire was developed to follow all aspects of patient acceptance and tolerance of the procedures, and all patients were queried preoperatively, and 30 minutes and 1 week postoperatively. Pain was evaluated with a modification of the McGill pain inventory. A subset of questions evaluated the length of time until usual activities were resumed, anxiety level, and general acceptance of the procedure including set-up, operative time, and recovery time until discharge. Overall, there was a high degree of patient acceptance and satisfaction with OLULA; however, women with CPP experienced greater intraoperative and postoperative pain than those with infertility. Some patients with CPP had a generalized visceral hypersensitivity to pain; all areas of the pelvis and bowel were sensitive, and pain was not completely blocked with local anesthesia. Average procedure length was similar for the two groups. Patients with CPP required greater postoperative analgesia and took longer to return to work. Conscious pain mapping identified a focal source of pain in three patients and generalized visceral hypersensitivity in a majority of patients with CPP. Neither of these were found in patients with infertility. Compared with traditional laparoscopy there was almost an 80% reduction in costs. CONCLUSION Office laparoscopy under local anesthesia is safe and effective for the evaluation of patients with CPP and is less expensive than traditional laparoscopy. Although the procedure is better tolerated by women undergoing infertility evaluation, it was well tolerated by both groups. Conscious pain mapping helps identify potential areas of pelvic pain and helps further characterize patients with CPP.

Elimination of ovulation and menstrual cyclicity (with danazol) improves dysphoric premenstrual syndromes

OBJECTIVE To assess whether the therapeutic effect of danazol on premenstrual syndromes (PMS) is associated with suppression of ovulation. DESIGN After 1 month on placebo, we administered 200 mg/d of danazol for 90 days to 24 women with dysphoric PMS. Symptoms during ovulatory cycles were compared with anovulatory periods. SETTING Outpatient PMS program in a general hospital. PATIENTS Twenty-four women who had dysphoric PMS and otherwise were physically and mentally healthy. INTERVENTIONS None (except the oral medication). MAIN OUTCOME MEASURE Prospective daily monitoring of symptoms with the Daily Rating Form, before, during, and after treatment. RESULTS Twenty of 23 anovulatory periods were symptom-free versus 6 of 32 ovulatory periods (chi 2 = 15.63, P = 0.0002). CONCLUSION The beneficial effect of danazol as treatment depends mostly on achieving an an-ovulatory state and elimination of hormonal cyclicity and not on the drug per se.

Chemokine Receptor Expression in Human Endometrium

Abstract Chemokines play a role in endometrial physiology and pathology and may affect endometrial receptivity and menstrual shedding. Chemokines exert their effect by binding to their relevant receptors, the expression levels of which may modulate their action. In the present study, we examined the expression of chemokine receptors CXCR1 and CXCR2 (receptors for interleukin-8) and CCR5 (receptor for RANTES [regulated-on-activation, normal-T-cell-expressed and -secreted], macrophage inflammatory protein [MIP]-1α, and MIP-1β) in human endometrium. Human endometria (n = 35) were grouped according to the menstrual cycle phase and examined by immunohistochemistry for CXCR1, CXCR2, and CCR5. In both epithelial and stromal cells, CXCR1 and CXCR2 immunoreactivity was detected. Staining was most prominent at the apical and basal aspects of epithelial cells. Intense CCR5 immunostaining was observed in epithelial and stromal compartments throughout the menstrual cycle. Epithelial and stromal staining for CXCR1 reached a peak at the midsecretory phase, during which it was significantly higher than the level of staining during the proliferative phase (P < 0.05). Immunostaining for CXCR2 and CCR5 showed no significant variation across the menstrual cycle. Expression of interleukin-8 and RANTES in endometrium, together with the presence of their receptors, suggests that autocrine and paracrine interactions involving these chemokines may participate in endometrial physiology.

Is tubal embryo transfer of any value? A meta-analysis and comparison with the Society for Assisted Reproductive Technology database

OBJECTIVE To analyze published randomized trials of ZIFT and ET via meta-analysis and compare the results with those of the Society for Assisted Reproductive Technology database. DESIGN Meta-analysis and comparison to SART data sets for 1991-1996. SETTING University medical center. PATIENT(S) Patients from the literature with infertility, randomized to either tubal or uterine embryo transfer. INTERVENTION(S) All published articles in English were identified using an electronic database spanning January 1966 to December 1998 by keyword and text word searches, supplemented with a hand search through the references of original studies, review articles, and conference abstracts to identify randomized trials comparing ZIFT and IVF-ET. Additional data was obtained through correspondence with authors. MAIN OUTCOME MEASURE(S) Implantation and clinical pregnancy rates were compared. Ectopic pregnancy rate was a secondary outcome measure. RESULT(S) Six randomized controlled trials including 548 cycles, 514 retrievals, and 388 transfers were reviewed. Demographic and stimulation and transfer details were comparable between the groups. Implantation and pregnancy rates did not differ significantly, and there was a trend toward increased risk of ectopic pregnancy with ZIFT. CONCLUSION(S) Published randomized trials suggest that there is no difference in implantation and pregnancy rates between women undergoing ZIFT and IVF-ET.

Endometrial cryoablation, a minimally invasive procedure for abnormal uterine bleeding

STUDY OBJECTIVE To evaluate the effectiveness of endometrial cyroablation for abnormal uterine bleeding. DESIGN Prospective study with 22 months follow-up (Canadian Task Force classification II-2). SETTING University Medical Center. PATIENTS Fifteen consecutive patients treated for metrorrhagia or menorrhagia refractory to medical or surgical therapy, and who were either not operative candidates or did not desire hysterectomy. INTERVENTION Cyroablation of the endometrium. MEASUREMENTS AND MAIN RESULTS Fifteen patients underwent 16 procedures for dysfunctional uterine bleeding. Uterine sounding depth was 6 to 15 cm. One patient had spinal anesthesia, seven had general anesthesia, and seven had intravenous conscious sedation with a cervical block. Eight patients underwent cryosurgery while fully anticoagulated. Posttreatment endometrial biopsies were performed on three patients and showed only granulation tissue. Life table calculations give amenorrhea rates of 75.5% at 6 months and 50.3% at 22 months. One woman underwent a repeat procedure, resulting in hypomenorrhea at 7-month follow-up. CONCLUSION This pilot study suggests that endometrial cryoablation may be performed simply and effectively. Future studies should be designed to optimize the technical aspects of the procedure, determine its relative efficacy, and investigate the indications.

Cryomyolysis in the conservative treatment of uterine fibroids

Conservative surgical options for uterine fibroids are abdominal myomectomy, laparoscopic myomectomy, and, more recently, myolysis. Another option for the conservative surgical treatment of fibroids is freezing the structures. This procedure, cryomyolysis, can be performed rapidly by laparoscopic or hysteroscopic access. We performed a pilot study of 14 women with uterine fibroids. All were pretreated with a gonadotropin-releasing hormone (GnRH) agonist for 3 months to reduce uterine and myoma size. Cryomyolysis was performed in each, and the GnRH agonist was discontinued. Magnetic resonance imaging scans were performed in 10 of the 14 women after GnRH agonist treatment before surgery and 4 months postoperatively. Total uterine volume ranged from 41.3 to 1134.8 ml preoperatively and 49.5 to 1320 ml postoperatively, for a mean increase of 22%. Normal uterine volume ranged from 35.6 to 548.7 ml preoperatively and 45.1 to 729.6 ml postoperatively, for a mean increase of 40%. Myoma volume showed a mean decrease of 6% (range 87-28%). Analysis of frozen fibroids revealed a mean volume decrease of 10%. We conclude that cryomyolysis is able to maintain (or slightly reduce) the uterine fibroid at its post-GnRH agonist size, whereas all other uterine tissues return to pretreatment size.

Decreased performance of skilled laparoscopic surgeons at microlaparoscopy versus traditional laparoscopy

The skill requirements for microlaparoscopy are significantly higher than those for the traditional technique. This program was designed to meet the demands of compensated two-dimensional depth perception, instrument accuracy, and ambidexterity. Three specialized drills were constructed and 60 experienced laparoscopists with advanced operative skills were evaluated. The three skill-assessment tasks were first performed using traditional laparoscopic instrumentation (10-mm laparoscopes, 5-mm accessory instruments). The performance of the study group was compared with an extensive database of over 1000 laparoscopic surgeons from around the world and did not reveal any significant deficits with traditional-size equipment. Next, the tasks were performed using miniature 2-mm laparoscopes and accessory instruments. Performance levels for all tasks were significantly lower than with traditional-size equipment. These results demonstrate the increased difficulty of performing laparoscopy with 2-mm instruments and underscore the importance of formal training and objective skill assessment. The relationship of skill to credentialing must be considered.