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Biomedical subjects

K Isaacson

Publications and source records attributed to K Isaacson.

At least 19 recordsLinked to original sources

Outcome and resource use associated with myomectomy.

OBJECTIVE: To evaluate the outcomes and cost of myomectomy through retrospective claims data analysis. METHODS: The study was performed using a retrospective database of private insurance claims from 1995 to 1997. Records were selected for analysis based on the presence of ICD-9-CM procedure and/or CPT-4 codes associated with myomectomy. In addition, diagnosis of uterine leiomyoma and related symptoms for these patients were confirmed through ICD-9-CM diagnosis codes. Inpatient, outpatient, and physician costs were estimated. All cost data were converted into 1997 dollars. RESULTS: A total of 4394 women, between the ages of 14 and 70, were available for analysis. Of these, 3305 were classified by type of myomectomy procedure, and complete data were available on 820 at 1 year and 236 at 2 years. Abdominal myomectomies were the most common procedures, followed by hysteroscopic and laparoscopic myomectomies. Conversion to a more invasive procedure occurred in 5.4% of the patients. The rate of additional surgeries was 8.3% in 6 months, 10.6% in 1 year, and 16.5% in 2 years. Overall cost increased from an initial 6,737 dollars per patient to 7,575 dollars in 1 year and to 8,001 dollars in 2 years. CONCLUSION: The repeat procedures required after the initial myomectomy add significantly to total cost and highlight the importance of assessing post-procedure health care use. This comprehensive analysis facilitates the systematic evaluation of myomectomy with current and emerging alternative treatments for uterine leiomyomas.

Adolescent↗

Antral follicle assessment as a tool for predicting outcome in IVF--is it a better predictor than age and FSH?

PURPOSE: The purpose of this study is to determine if baseline antral follicle assessment may serve as additional information in predicting in vitro fertilization outcome. METHODS: Prospective, descriptive preliminary study of in vitro fertilization outcome. From July 1998 to July 1999, 224 patients underwent antral follicle assessment (follicle 2-6 mm in diameter) on baseline of the planned, stimulated in vitro fertilization cycle. The outcomes were analyzed with respect to antral follicle assessment (< or = 6 or > 6), basal cycle day 3 follicle stimulated hormone (< or = 10 or > 10 IU/L) and maternal age (< or = 35 or > 35 years). RESULTS: The clinical pregnancy rate was significantly higher in the group with baseline antral follicle > 6 compared to that in the group with antral follicle < or = 6 (51% vs. 19%, respectively). Controlling for patient age, and basal follicle stimulated hormone, the pregnancy rate was significantly higher in the group with antral follicle > 6 compared to that in the group with antral follicle < or = 6. The cancellation rate was significantly increased with advancing maternal age, elevated basal follicle stimulated hormone levels, and baseline antral follicle < or = 6. The cancellation rate was significantly higher in the group with antral follicle < or = 6 compared to that in the group with antral follicle > or = 6 (33% vs. 1%, respectively). CONCLUSIONS: In vitro fertilization outcome is strongly correlated with both maternal ages, basal cycle, day 3 follicle, stimulated hormone, and antral follicle assessment. Antral follicle assessment was a better predictor of in vitro fertilization outcome than were age or follicle stimulated hormone. Antral follicle assessment may provide a marker for ovarian age that is distinct from chronological age or hormonal markers.

Adult↗

Analysis of follicular fluid hormone concentrations and granulosa cell mRNA levels for the inhibin-activin-follistatin system: relation to oocyte and embryo characteristics.

OBJECTIVE: To explore the potential roles of inhibin, activin, and follistatin in human oocyte development by quantifying their intrafollicular biosynthesis. DESIGN: Prospective, nonrandomized study. SETTING: An IVF unit and academic research laboratory. PATIENT(S): Thirty one patients undergoing IVF. INTERVENTION(S): Human menopausal gonadotropins or human FSH (or both) were administered. Single-follicle aspirates (n = 110) were collected for analysis. MAIN OUTCOME MEASURE(S): Concentrations of dimeric, total and pro-alphaC inhibin forms; activin A; follistatin; estradiol; and progesterone were measured in follicular fluids. Granulosa-cell mRNA was analyzed for alpha, beta A, and beta B inhibin and activin subunits; follistatin; activin receptors; and beta-actin. Hormone concentrations and mRNA levels were correlated with oocytes or embryos from the same follicles. RESULT(S): Levels of progesterone and follistatin were significantly greater in follicles containing MI or MII oocytes than in those containing GV oocytes. Inhibin alpha-subunit mRNA levels were significantly higher in follicles containing maturing oocytes, the highest-quality oocytes, and oocytes that were subsequently fertilized. In contrast, inhibin alpha-subunit mRNA levels were significantly lower in follicles from which higher-quality embryos were obtained. CONCLUSION(S): Inhibin alpha-subunit biosynthesis is associated with normal oocyte and follicle maturation, but excessive alpha-inhibin is associated with poor embryo quality. None of the hormones analyzed were associated with oocyte or embryo quality.

Actins↗

New developments in operative hysteroscopy.

Although there is a plethora of new devices currently being investigated that can ablate the endometrial cavity successfully, it is most certain that a strong place remains for operative hysteroscopy for the therapy of benign uterine conditions. New instruments that continue to make operative hysteroscopy a safer and easier procedure to perform should continue in their development.

Female↗

The SCID mouse: an experimental model for endometriosis.

The purpose of this study was to validate the suitability of the severe combined immunodeficient (SCID) mouse as an experimental model for endometriosis, by defining the morphological and histological features of induced endometrial implants, and characterizing specific biochemical properties of these implants. Human secretory endometrial tissues were injected into the peritoneal cavity of SCID/SCID CB17 mature female mice. Successful peritoneal implantation was observed in 55 of 57 (96.5%) SCID mice and consisted of circumscribed elevated nodules. Haematoxylin-eosin staining of implanting lesions demonstrated the presence of endometrial glandular tissue in a mixed background of stromal and inflammatory cells. When progesterone was administered to mice, epithelial glands underwent well-defined secretory changes. Immunohistochemical analysis using polyclonal human pan-cytokeratin antibodies demonstrated selective positive staining in the glandular epithelium of the human implants with none in the surrounding stroma. In-situ hybridization analysis using complement component 3 cDNA radiolabelled riboprobes yielded significantly more intense signals in glands compared to stroma. As human endometrial implants in SCID mice were shown to retain specific histological, functional and biochemical properties, we conclude that the SCID mouse is an attractive animal model for the study of endometriosis.

Animals↗

Preparation by differential gradient centrifugation is better than swim-up in selecting sperm with normal morphology (strict criteria).

OBJECTIVE: To evaluate two commonly used methods of sperm preparation with respect to their effects on sperm morphology (strict criteria). DESIGN: Auto-controlled, split sample study performed on the semen of 74 male partners of couples enrolled for IVF. SETTING: In vitro fertilization and andrology laboratories at a tertiary care, major teaching hospital. PATIENT(S): Seventy-four male partners of couples who were scheduled to undergo IVF. INTERVENTION(S): Equal halves of the same semen sample were evaluated for strict criteria sperm morphology before and after preparation by differential gradient centrifugation using Percoll (Pacific Andrology, Montrose, CA) and by the standard swim-up method. MAIN OUTCOME MEASURE(S): The percentage of morphologically normal sperm was assessed using strict criteria before and after the two methods of sperm preparation. Specific parameters studied were individual abnormalities of the head, midpiece, and tail. RESULT(S): Sperm preparation using differential gradient centrifugation with Percoll produced a significantly greater number of specimens with normal sperm morphology and also showed higher absolute quantitative improvement over the swim-up method. The two methods were comparable in regard to their effects on specific sperm abnormalities (i.e., head, midpiece, and tail defects). CONCLUSION(S): The differential gradient sperm separation method using Percoll is superior to the swim-up method for selecting sperm with normal morphology as assessed by strict criteria. Because sperm morphology as assessed by strict criteria is a good predictor of oocyte fertilization, this method can be recommended as the method of choice for assisted reproductive technology laboratories. Use of this method may help improve outcome by increasing fertilization rates.

Centrifugation, Density Gradient↗

Characterization of inhibin/activin subunit, activin receptor, and follistatin messenger ribonucleic acid in human and mouse oocytes: evidence for activin's paracrine signaling from granulosa cells to oocytes.

Inhibin, activin, and follistatin (FS) are gonadal proteins that appear to have a role in regulating folliculogenesis through possible paracrine and/or autocrine interactions. To further examine the potential role of activin in oocyte-granulosa cell communication, we developed a sensitive reverse transcription-polymerase chain reaction protocol to analyze mRNA for the alpha, betaA, and betaB inhibin/activin subunits, FS, and the four activin receptor subtypes in individual human and mouse oocytes. The resulting expression pattern was further compared to that in human cumulus granulosa cells. Our results indicate that neither ssA nor betaB mRNA was detectable in any human or mouse oocyte, that alpha subunit was marginally present in some of the human oocytes, and that FS mRNA was detectable in human but not mouse oocytes. On the other hand, inhibin/activin subunit and FS mRNAs were abundantly expressed in cumulus cells. In addition, mRNAs for all four activin receptor subtypes (ActRIA, ActRIB, ActRIIA, and ActRIIB) were easily detectable in both oocytes and granulosa cells and appeared to be differentially expressed in oocytes during nuclear maturation. Finally, RNAs for both zona pellucida 3 and growth-differentiation factor-9, which were originally used as oocyte-specific markers, were detected in human but not mouse cumulus cells, although at lower levels than observed in oocytes. Taken together with previous studies, these results indicate that oocytes may be capable of responding to, but not synthesizing, activin.

Activin Receptors↗

Development and use of a bipolar resectoscope in endometrial electrosurgery.

We conducted a prospective, blinded study to compare the tissue response and mechanical properties of a bipolar resectoscope with standard monopolar cutting and coagulation instruments. At the animal care facility of Tufts Medical School (Medford, MA), four surgeons blinded to instrumentation and distention media cut segments out of a rabbit uterine horn and desiccated the abdominal wall using either the bipolar device in 0.9% saline or the monopolar system in 1.5% glycine. Both systems used a Force 2 Valleylab radiofrequency generator at identical power settings. Cut and desiccated sections were fixed and stained with hematoxylin and eosin as well as Masson's trichrome to evaluate thermal damage. The pathologist was blinded to the system used to make the cut or desiccation. Both systems cut and coagulated tissue with similar properties. Most surgeons noted a longer delay from radiofrequency activation to actual cutting with the bipolar system. The depth of thermal damage when cutting or desiccating tissue was similar for the two systems. This disposable, inexpensive device allows for standard resectoscopic hardware to be transformed into a bipolar device. All current techniques of intrauterine cutting and coagulation may soon be performed in the presence of physiologic uterine distention media. Human clinical data remain to be gathered.

Abdominal Muscles↗

Characterization of intrafollicular steroid hormones, inhibin, and follistatin in women with and without polycystic ovarian syndrome following gonadotropin hyperstimulation.

The etiology of polycystic ovary syndrome (PCOS) is unexplained. Since no major deficiencies are reported in serum FSH or inhibin, we hypothesized that abnormal levels of a paracrine modulator of FSH action within the ovary may be associated with the arrest of follicular growth seen in the PCOS ovary. Follicular fluid aspirates were collected from women with (n = 7) or without (n = 17) PCOS during oocyte retrieval for in vitro fertilization. Aspirates were assayed for total inhibin, inhibin A (InhA), inhibin B (InhB), and follistatin (FS), as well as for estradiol, progesterone (P4), androstenedione, and total protein. Hormone levels were compared between women with and without PCOS using all aspirates (some of which were collected from multiple follicles at once) and also between aspirates containing fluid from a single follicle only (PCOS, n = 30; non-PCOS, n = 107). P4 levels were significantly (p < 0.01) reduced in PCOS versus non-PCOS women as evidenced by analysis of all follicles as well as in single-follicle aspirates only. In addition, InhA, P4, and FS increased with follicle volume, and InhB decreased significantly in non-PCOS, but not in PCOS, follicles. Therefore, although follicular development can be induced in PCOS patients with gonadotropins, hormonal responses within the ovary appear inappropriate in terms of concentrations or patterns of secretion. These data support the concept that PCOS is associated with a deficit in the paracrine control of folliculogenesis.

Adult↗

The harmonic scalpel: an intraoperative complication.

BACKGROUND: The harmonic scalpel is an ultrasonically activated surgical instrument for tissue dissection. Despite its expanding surgical applications, there are no reports about associated complications. CASE: A 35-year-old woman sustained injury to the sigmoid colon from the use of the harmonic scalpel during laparoscopic lysis of pelvic adhesions. The injury was identified and repaired laparoscopically in a primary fashion with no subsequent sequelae. CONCLUSION: Acoustic energy coupling and overheating of the laparosonic blade extender sheath occur with bending of the instrument. This can happen with steering of the blade extender during laparoscopic surgery and may increase the exposure risk of adjacent tissues to injury.

Adult↗

Observations on the nutrient intakes of eating-dependent nursing home residents: underutilization of micronutrient supplements.

OBJECTIVE: To estimate the intakes of essential nutrients by eating-dependent nursing home residents (EDR). METHODS: This study was done in a 190 bed VA nursing home. Thirty-four EDR were selected for the study. Clinical data base which included age, sex, primary diagnosis, body mass index, albumin, hematocrit, activities of daily living status, decubitus ulcer medications and use of multivitamin/trace mineral supplement were recorded from the medical records. Caloric and essential nutrient intakes were determined over a 3-day period by a registered dietitian. RESULTS: Seventy percent (24/34) residents in the study group were underweight (body mass index < 23 kg/m2), 26% were hypoalbuminemic (serum level < 3.5 g/dl), 50% were anemic (hematocrit < 37%); and 38% had pressure ulcers. In 88% EDR, the dietary intakes of three or more essential nutrients were below 50% of the RDA. Most frequent and severely deficient were zinc, copper, and vitamin B6. Despite the inadequate essential micronutrient intakes in the majority of EDR, only 35% received a multivitamin supplement and only 3% received a trace mineral supplement. A survey of 30 other VA nursing homes indicated generally similar findings to those in the Milwaukee facility with regard to the high frequency for eating-dependence, and the low frequency for administration of multivitamin and trace mineral supplements. CONCLUSIONS: Despite eating supervision and assistance, the majority of EDR have inadequate intakes of numerous essential macro- and micronutrients. The deficient micronutrient intakes could be normalized by administration of a multivitamin/trace mineral supplement daily. Nevertheless, only a minority of EDR in VA nursing homes currently receive such a supplement.

Aged↗

Prediction of dangerous behaviour in male erotomania.

BACKGROUND: New cases of erotomania in men, plus cases from the literature, were analysed to explore any association between erotomania and dangerousness, and to identify possible predictors. METHOD: Files at two in-patient facilities were examined to determine the presence of DSM-III-R delusional disorder, erotomanic type. The sample (13 cases) was divided into dangerous and benign groups on the basis of serious antisocial behaviour directly related to erotomanic delusions. These cases were combined with all reports of erotomania in men (16 cases), found in the English language psychiatric literature, to allow for statistical analysis. RESULTS: Two factors, multiple delusional objects (P < 0.0005) and serious antisocial behaviour unrelated to the delusions (P < 0.05), were found to be significantly associated with dangerousness. Using a combination of these two variables it was possible to predict dangerousness with an accuracy of 88.9% (weighted prediction accuracy or 'hit rate'). We identified no false negatives but three false positives. CONCLUSIONS: The presence of multiple objects, and a history of serious antisocial behaviour unrelated to the erotomanic delusions, are useful predictors of dangerous behaviour in men with erotomania.

Adult↗

Alpha 2-macroglobulin production by the human endometrium.

alpha 2-Macroglobulin (A2M) is a broad spectrum plasma protease inhibitor previously described in uterine effluents and recently demonstrated to bind and possibly modulate the functions of cytokines. As cytokines, proteases, and protease inhibitors are important in implantation and endometrial physiology, we sought to investigate and characterize the pattern of production of A2M in the endometrium. Endometrial tissues from different phases of the menstrual cycle were analyzed for A2M production. Tissues were incubated in methionine-free Minimum Essential Medium with [35S]methionine for 12 h at 37 C in 5% CO2. Conditioned media were immunoprecipitated with a polyclonal antibody to human A2M. Recovered proteins were resolved under reducing and nonreducing conditions by 5% sodium dodecyl sulfate-polyacrylamide gel electrophoresis and analyzed by autoradiography. Immunohistochemistry was performed on both cryostat sections of OCT-embedded tissue and formalin-fixed paraffin-embedded tissue. The intensity of staining was evaluated, and a histochemical score was assigned. Comparisons between histochemical scores were performed using the nonparametric Wilcoxon rank sum test. Immunoprecipitation with A2M antibody yielded a single 320-kilodalton protein band under nonreducing conditions and a single 182-kilodalton band under reducing conditions. Both physical and immunological properties of the recovered protein were consistent with A2M. A2M was identified in all endometrial samples and represented approximately 2% of the total radiolabeled proteins produced. Immunohistochemical analysis revealed prominent stromal, but no glandular, staining for A2M throughout the menstrual cycle. The stromal staining in secretory endometrial samples was significantly more intense than that in proliferative samples. In the proliferative phase, staining was more intense in the spongiosum and basalis layers, and less intense in the superficial compactum layer. In the secretory phase, it remained very intense in the spongiosum, but less so in the basalis layer. These findings indicate that A2M is predominantly produced by the stromal component of endometrial tissue. This production is menstrual cycle dependent, with zonal differences in A2M expression within the endometrium, which may indicate a functional significance relevant to the process of implantation that merits further investigation.

Endometrium↗

Comparative study of different laser systems.

OBJECTIVE: To review lasers, laser physics, laser-tissue interaction, delivery systems, and their clinical applications relevant to gynecology. SETTINGS: Gynecological Service at Massachusetts General Hospital (MGH) and MGH Laser Center. INTERVENTIONS: None. DESIGN: Laser literature review and personal experiences of the authors were used to prepare this manuscript. CONCLUSIONS: Lasers have been used in gynecologic practice for cutting and coagulating purposes. Photodynamic therapy has been used clinically for malignant conditions and is being investigated for dysplastic lesions of the lower genital tract and for endometrial ablation. Laser welding has potential, but further work is required in this field before it finds a clinical application. The main lasers used in gynecology are CO2, neodymium-yttrium aluminum garnet (Nd:YAG), and potassium tatanyl-phosphate-doubled Nd:YAG. Pulsed Ho:YAG laser looks promising, as does diode lasers. Holmium-yttrium aluminum garnet and diode lasers will be soon available commercially. Improvements in delivery systems have increased user friendliness, and more developments in this area are anticipated, for example, a fiber-optic delivery system for CO2 lasers. We believe that enhanced understanding of laser technology will provide unique applications for development in gynecology.

Female↗

Human follicular fluid contains pro- and C-terminal immunoreactive alpha-inhibin precursor proteins.

The majority of immunoactive inhibin in human follicular fluid (hFF) is devoid of pituitary cell bioactivity and is hypothesized to contain alpha-inhibin monomeric proteins known to cross-react with an inhibin antiserum (Monash 1989). The aim of this study was to define more precisely the nature of these inhibin-immunoreactive proteins using alpha-inhibin sequence-specific antisera. First, a polyclonal antiserum was raised to precursor amino acids 21-35 (PIN-1) and was used in a RIA to measure pro-alpha-inhibin-immunoreactive proteins. Western blotting was used to confirm these findings. Secondly, the binding epitope of the Monash antiserum was defined by peptide analysis to be located within the C-terminus (precursor amino acids 326-341) of alpha-inhibin, and this assay was then used to monitor the presence of C-terminal sequences. Similar levels of pro-alpha-inhibin immunoreactivity (PIN-1 RIA; N-terminus alpha-inhibin precursor) were detected in hFF collected from women with normal menstrual cycles during the follicular phase and from multiple follicles from a woman undergoing ovarian hyperstimulation during an in vitro fertilization (IVF) protocol. Western blotting with the PIN-1 antibody confirmed the presence of immunoreactive proteins of 57,000 and 29,000 mol wt in the follicular fluids of both normal cycle and IVF follicles. However, ovarian hyperstimulation elevated intrafollicular C-terminal immunoreactivity (Monash RIA) compared to that in normal cycle hFF. Furthermore, intrafollicular estradiol and progesterone were significantly correlated to C-terminal activity in follicles from IVF, but not in normal cycles. These data show that 1) both pro- and C-terminal alpha-inhibin proteins are secreted into follicular fluids from normal and IVF cycles, suggesting that alpha-inhibin precursor proteins may be physiologically relevant in the process of folliculogenesis; and 2) IVF and normal cycle follicular fluids differ in their production and processing of inhibin.

Amino Acids↗

Injury and adhesion formation following ovarian wedge resection with different thermal surgical modalities.

The purpose of this study is to determine the role of bleeding, acute thermal damage, and charring in adhesion formation. Postoperative adhesions were compared following ovarian wedge resection in 48 rabbits using different lasers, electrosurgery, and scalpel. Twelve ovaries were sectioned per modality, in randomized pairs. Acute thermal injury as assessed by histology, bleeding, and charring differed among the modalities used. Adhesions were assessed 4 weeks later, by an investigator completely blinded of the treatment protocol. The adhesion scores were 11.6 +/- 8.0 with pulsed Er:YAG laser; 11.9 +/- 7.5 with scalpel; 8.3 +/- 9.3 with electrocautery; 6.7 +/- 8.8 with a continuous (c.w.) Nd:YAG laser; 5.3 +/- 4.8 with c.w. CO2 laser; 3.1 +/- 2.7 with pulsed CO2 laser; 1.7 +/- 1.8 with pulsed Ho:YAG laser; and 0.8 +/- 1.5 in the control (no resection) group. Ho:YAG, Nd:YAG, and electrocautery were completely hemostatic. Bleeding was minimal with the CO2 lasers. Er:YAG and scalpel caused maximum bleeding, requiring hemostatic measures to prevent exsanguination. Charring occurred with electrocautery, CO2 laser, and Nd:YAG laser. Bleeding and charring correlated with adhesion formation, but the histological depth of thermal damage did not. The Ho:YAG laser is a hemostatic, fiber-optic compatible laser causing significantly fewer adhesions (P < 0.04) than scalpel, electrocautery, Nd:YAG, Er:YAG, and c.w. CO2 lasers. Clinical use of the Ho:YAG laser, and the role of carbonization in promoting adhesions, deserve further study.

Adnexal Diseases↗

Hormonal regulation of 3 alpha-hydroxysteroid/dihydrodiol dehydrogenase in rat liver cytosol.

In rat liver, dihydrodiol dehydrogenase and 3 alpha-hydroxysteroid dehydrogenase activities are catalyzed by the same protein. This study shows that estrogen and growth hormone can induce the enzyme in hypophysectomized rats. This implies that estrogen can exert an effect on hepatic steroid and carcinogen metabolism in the absence of the anterior pituitary.

3-Hydroxysteroid Dehydrogenases↗