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S R Goldstein

Publications and source records attributed to S R Goldstein.

At least 19 recordsLinked to original sources
PubMed2000

A 12-month comparative study of raloxifene, estrogen, and placebo on the postmenopausal endometrium.

OBJECTIVE: To determine the effects of a selective estrogen receptor modulator, raloxifene, on postmenopausal endometrium. METHODS: Healthy postmenopausal women (n = 415) were randomly assigned to one of the following four groups: 60 or 150 mg/day raloxifene hydrochloride, 0.625 mg/day conjugated equine estrogens, or placebo, and treated for 1 year. Endometrial biopsies were obtained in a blinded fashion at baseline and every 6 months after the ultrasound studies. Transvaginal ultrasound, with uterine size measurements, was done at baseline and at 3-month intervals. Saline-infusion sonohysterography was done at baseline and every 6 months. RESULTS: There were no statistically significant differences in baseline characteristics. Mean endometrial thickness, measured by transvaginal ultrasound, was unchanged from baseline to end point in the placebo and raloxifene groups, whereas in the estrogen group it was significantly thicker by 5.5 mm (P < .001). Mean uterine volume, calculated from transvaginal ultrasound measurements, was higher in the estrogen group only (22 cm3, P < .001). Of the 358 women with paired biopsies, endometrial hyperplasia was present in 2.1%, 0%, and 26.1% of the end-point biopsies in the placebo, raloxifene, and estrogen groups, respectively (P < .001). Proliferative endometrium was present in 2.1% of the end-point biopsies in the placebo group, 1.7% in the combined raloxifene groups, and 39.8% in the estrogen group (P < .001). CONCLUSION: Raloxifene, at 60 or 150 mg/day for 1 year, did not stimulate the postmenopausal endometrium. End-point endometrial thickness, morphology, and uterine volume in the raloxifene groups were similar to those observed at baseline and in the placebo group.

Adult↗
PubMed1999

Effect of muscle activity immediately after botulinum toxin injection for writer's cramp.

Animal and human studies have shown that nerve stimulation enhances some effects of botulinum toxin (btx A) injection. Voluntary muscle activity might work similarly and would focus the effect of an injection into the active muscles. We studied the effects of exercise immediately after btx A injection in eight patients with writer's cramp with established response to btx A over two injection cycles with a single-blinded, randomized, crossover design. Immediately after the first study injection, they were randomly assigned to write continuously for 30 min or have their hand and forearm immobilized for 30 min. Following the second injection, they were assigned the alternate condition. Patients were assessed just before each injection, and at 2 weeks, 6 weeks, and 3 months post-injection. Assessment included objective strength testing, self-reported rating of benefit and weakness, and blinded evaluation of videotapes and writing samples of the patients writing a standard passage. Strength testing showed that the maximum weakness occurred at 2 weeks post-injection, but the benefit was maximum at 6 weeks post-injection. The "write" condition resulted in greater reduction in strength than the "rest" condition. Btx A treatment led to improvement in self-reported ratings, writer's cramp rating scale scores by blinded raters, and reduction in writing time, but the differences between the "write" and "rest" conditions were not significant. We conclude that voluntary muscle activity immediately after btx A injection leads to greater reduction in muscle strength. Our findings raise the possibility that voluntary muscle activation may allow reduction of btx A doses and favorably alter the balance of benefit and side effects of btx A injections.

Adult↗
PubMed1999

An open trial of clozapine for dystonia.

Pharmacologic treatment of severe dystonia is often unsatisfactory. The atypical antipsychotic medication clozapine appears to improve tardive dystonia associated with conventional neuroleptic use. We studied the efficacy of clozapine for severe dystonia in five patients in an open trial. The patient cohort included four with generalized dystonia and one with Meige syndrome. All patients were evaluated at baseline and at least weekly while on medication with subjective assessment of response by the patient and physician rating using the Burke-Fahn-Marsden Evaluation Scale for Dystonia. All five subjects had significant improvement detected by the Burke-Fahn-Marsden Evaluation Scale as well as subjective improvement while on clozapine. Side effects, such as sedation and orthostatic hypotension, developed in all patients but was only treatment-limiting in one subject who developed persistent symptomatic orthostatic hypotension and tachycardia. Two of the four remaining patients continued clozapine after completion of the study; an additional patient was uncertain if the benefit outweighed the side effects. One patient discontinued treatment because of difficulty obtaining the FDA-required weekly white blood cell counts for patients on clozapine. We conclude that clozapine appears to be effective for generalized and refractory focal dystonia although its use may be limited by the side effects and need for hematologic monitoring.

Adult↗
PubMed1999

Laser capture microdissection of single cells from complex tissues.

Laser capture microdissection (LCM) is a new method used to select and procure cell clusters from tissue sections. Once captured, the DNA, RNA or protein can be easily extracted from the isolated cells and analyzed by conventional PCR, reverse transcription (RT)-PCR or polyacrylamide gel electrophoresis, including protein zymography for specific macromolecular changes. In LCM, a thermoplastic polymer coating [ethylene vinyl acetate (EVA)] attached to a rigid support is placed in contact with a tissue section. The EVA polymer over microscopically selected cell clusters is precisely activated by a near-infrared laser pulse and then bonds to the targeted area. Removal of the EVA and its support from the tissue section procures the selected cell aggregates for molecular analysis. This initial NIH LCM approach using a flat transfer EVA film has been recently commercialized and has proven to be an effective routine microdissection technique for subsequent macromolecular analysis in many laboratories around the world. However, reliable and precise capture of individual cells from tissue sections has been difficult to perform with the current LCM instruments. In this report, we describe the capture of individual cells with a new NIH LCM microscope, which epi-irradiates the EVA polymer overlying individual cells with 1-ms laser pulses focused to 6 microns. A computer-controlled arm precisely positions a 40-micron-wide strip of a cylindrical EVA surface onto a sample with a light contact force (ca. 0.1 g). The small contact force and contact area on the film on the sample diminishes nonspecific transfer to negligible levels. By slightly rotating the cylinder to provide a renewable transfer surface, concentration of a distinct cell type on a single cylinder is possible. Using this novel adaptation, we demonstrate the rapid and practical capture of single cells from different types of tissue sections, including immunostained cells.

Animals↗
PubMed1998

Selective estrogen receptor modulators: a new category of therapeutic agents for extending the health of postmenopausal women.

Selective estrogen receptor modulators are a new category of therapeutic agents that bind with high affinity to estrogen receptors and mimic the effect of estrogens in some tissues but act as estrogen antagonists in others. Tamoxifen, a triphenylethylene derivative, was the first clinically available selective estrogen receptor modulator. It is a potent antiestrogen in the breast, and its use in breast cancer patients has made it the most prescribed antineoplastic drug worldwide. It has estrogen-like activity on bone metabolism, and it also reduces cholesterol. However, its ability to produce proliferation, polyp formation, and even carcinomas in the endometrium is well known. A new selective estrogen receptor modulator, raloxifene, a benzothiopene derivative, has a clinical profile similar to that of tamoxifen. However, both preclinical and clinical studies reveal that, unlike tamoxifen, it is a pure antiestrogen in the uterus. It has recently been approved by the Food and Drug Administration for prevention of osteoporosis in postmenopausal women. This report reviews pertinent preclinical and currently available clinical studies about this new selective estrogen receptor modulator and discusses clinical applicability.

Female↗
PubMed1998

The use of transvaginal ultrasound and saline infusion sonohysterography for the evaluation of asymptomatic postmenopausal breast cancer patients on tamoxifen.

Tamoxifen has been shown to decrease the recurrence rate of breast cancer. Evidence that tamoxifen use may be associated with an increased risk of endometrial cancer has caused investigators to recommend routine invasive sampling. We have assessed a minimally invasive alternative for endometrial surveillance of tamoxifen-treated patients utilizing transvaginal ultrasound and saline infusion sonohysterography. Asymptomatic women (n = 44) with breast cancer on postoperative tamoxifen treatment were referred to our gynecological ultrasound unit. Initially, the endometrial echo was measured with unenhanced transvaginal ultrasound. If a distinct echo measured < or = 5 mm, no further procedure was performed. For thickened or inadequately visualized echoes, sonohysterography was performed. If a thin echo was noted on sonohysterography, no further procedure was performed. If focal changes were detected, hysteroscopy/dilatation and curettage (D&C) was performed. For generalized symmetrically thickened echoes, a blind biopsy was done. If sonohysterography was unsuccessful, hysteroscopy/D&C was performed. Eleven (25%) patients had thin unenhanced echoes of < or = 5 mm. Twenty-five (57%) patients had thickened endometrial echoes. Three (7%) had naturally occurring endometrial fluid outlining a polyp. An endometrial echo could not be visualized in five (11%) patients. Sonohysterography was successfully performed in 21 out of 30 (70%) patients with either thickened or non-visualized unenhanced echoes. Of these, two patients had thin endometria with coexisting myomas; seven had thin endometria with typical tamoxifen-induced subendometrial changes: and seven had focal polypoid thickening confirmed by hysteroscopy/D&C. Histology revealed carcinoma associated with two, proliferation in one and four polyps. Five patients had thickened unenhanced echoes with symmetrically thickened single-layer measurements on sonohysterography. Histology revealed that three were proliferative, one was inactive and one was hyperplastic. In the nine patients with unsuccessful sonohysterography, hysteroscopy/D&C revealed inactive endometria in six, and three polyps. Our paradigm of evaluating the endometrial response to tamoxifen is concluded to overcome the shortcomings of either unenhanced transvaginal ultrasound or blind biopsy alone while it kept the number of invasive sampling procedures to 55% (24 out of 44).

Aged↗
PubMed1998

Studies of iron deposits, inducible nitric oxide synthase and nitrotyrosine in a rat model for esophageal adenocarcinoma.

A rat model was developed recently in our laboratory to study the pathogenesis of Barrett's esophagus (BE) and its progression to esophageal adenocarcinoma (EAC). Eight-week-old male Sprague-Dawley rats underwent esophagoduodenal anastomosis (EDA) to produce gastric and duodenal reflux in their distal esophagi. The rats were given iron dextran (50 mg of Fe/kg, i.p.) starting 2 weeks after surgery and this was continued once a month. BE was observed as early as week 3 and the incidence of BE and EAC increased with time: 58 and 17% at week 23; 91 and 73% at week 31. There was a progression in epithelial cell proliferation and inflammation from mild to severe in the distal one-third of the esophagus. Iron deposition in the esophagus also increased with time. Iron deposits in the stromal tissue adjacent to the epithelium in the distal one-third of the esophagus were associated with areas of severe inflammation. Immunohistochemical analysis showed positive inducible nitric oxide synthase (iNOS) expression in the stromal macrophages directly beneath the epithelium in the distal one-third of the esophagus in 36, 83 and 100% of the rats at weeks 17, 23 and 31, respectively. A significant increasing linear trend (P=0.001) was seen in nitrotyrosine immunostaining (number of positive cells/high power field) in the distal esophagus. Strong positive nitrotyrosine staining was seen in the macrophages and weaker positive staining was seen in the adjacent epithelium starting at week 17. Furthermore, iron supplemented rats killed at week 31 had significantly higher (P < 0.05) levels of inflammation, cell proliferation, iNOS and nitrotyrosine as well as more tumors in their distal esophagi than did rats that received no iron supplement. These results suggest that iron supplementation enhanced inflammation and the production of reactive oxygen and nitrogen species in the esophageal epithelium. These processes could contribute to the formation of BE and its progression to EAC.

Adenocarcinoma↗
PubMed1998

Use of transvaginal ultrasonography to monitor the effects of tamoxifen on uterine leiomyoma size and ovarian cyst formation.

To evaluate the effects of tamoxifen on leiomyomas and ovarian cysts in postmenopausal breast cancer patients, uterine and leiomyoma volumes were monitored sonographically in 17 postmenopausal women receiving postoperative tamoxifen for breast cancer; patients were examined twice with a mean of 1.18 +/- 0.17 years between examinations. The mean increase in leiomyoma volume was 1.26 +/- 0.73 cm3. The mean myoma volume was significantly larger at follow-up evaluation than at initial ultrasonography (5.75 +/- 1.09 cm3 versus 4.36 +/- 0.817 cm3, respectively; Wilcoxon signed rank test, P = 0.0218). Six women developed new leiomyomas. Of the 21 leiomyomas initially detected, 13 increased, six decreased, and two were unchanged in volume. The mean increase in uterine volume was 17.45 +/- 8.49 cm3. Three patients had simple ovarian cysts at initial ultrasonographic examination, two of which remained unchanged in size, and the third resolved. Two patients had newly developed simple ovarian cysts. The increase in uterine and leiomyoma volumes with the development of new leiomyomas and the persistence or development of ovarian cysts in some patients support the existence of agonistic tamoxifen effects. Serial measurements of uterine and leiomyoma volumes and surveillance for ovarian cysts is recommended for tamoxifen users.

Aged↗
PubMed1997

Evaluation of abnormal vaginal bleeding in perimenopausal women with endovaginal ultrasound and saline infusion sonohysterography.

Saline infusion sonohysterography enhances endovaginal ultrasound examination of the uterine cavity in perimenopausal patients with abnormal uterine bleeding. It is easily and rapidly performed at minimal cost, is extremely well tolerated by patients, and is virtually devoid of complications. Its use can prevent invasive diagnostic procedures in some patients as well as optimize the preoperative triage process for those patients who will require therapeutic intervention.

Female↗
PubMed1997

Ultrasonography-based triage for perimenopausal patients with abnormal uterine bleeding.

OBJECTIVE: Abnormal perimenopausal bleeding is common and accounts for much medical and surgical intervention. This study was undertaken to evaluate an ultrasonography-based triage paradigm for perimenopausal patients with abnormal uterine bleeding. STUDY DESIGN: Four hundred thirty-three perimenopausal patients with abnormal uterine bleeding (either metrorrhagia, menorrhagia, or both) were evaluated. In lieu of undergoing a sampling procedure they were brought back on days 4 to 6 of the subsequent bleeding cycle, when the endometrium was expected to be its thinnest. If a distinct endometrial echo < or = 5 mm (double layer) was imaged by endovaginal ultrasonography, dysfunctional uterine bleeding was diagnosed. If a thickened endometrial echo > 5 mm or no endometrial echo was reliably visualized, a saline infusion sonohysterography was performed. If saline infusion sonohysterography revealed a symmetric single-layer endometrial thickness < 3 mm, dysfunctional uterine bleeding was diagnosed. If focal lesions were noted (polyps, submucous myomas, focal thickening), the patient was scheduled for curettage with hysteroscopy. If the endometrium was globally thickened, nondirected office biopsy was performed. RESULTS: A total of 341 patients (79%) had ultrasonographic evidence of no anatomic abnormality, and dysfunctional uterine bleeding requiring no further studies was diagnosed. Fifty-eight patients (13%) had focal polypold masses, all of which were removed hysteroscopically and confirmed pathologically. Twenty-two patients (5%) had submucous myomas; 10 patients (23%) had globally thickened endometrium on saline infusion sonohysterography, and then nondirected office sampling revealed hyperplasia in 5 and proliferation in 5. Two patients had technically inadequate saline infusion sonohysterography, and thus we proceeded to hysteroscopy with curettage. CONCLUSION: Nondirected office biopsy alone without imaging would have potentially missed the diagnosis of focal lesions such as polyps, submucous myomas, and focal hyperplasia in up to 80 patients (18%). Our clinical algorithm for perimenopausal patients with abnormal uterine bleeding used unenhanced endovaginal ultrasonography followed by saline infusion sonohysterography for selected patients. This approach allowed for no endometrial sampling, nondirected sampling, or directed sampling depending on whether the ultrasonography-based triage revealed no anatomic abnormalities, globally thickened endometrial tissue, or focal abnormalities, respectively.

Adolescent↗
PubMed1997

Alterations in steroid hormone receptors in the tamoxifen-treated endometrium.

OBJECTIVE: Our purpose was to evaluate whether tamoxifen has estrogenic endometrial effects as defined by histologic study or alterations in steroid hormone receptor expression. STUDY DESIGN: Nineteen postmenopausal tamoxifen-treated breast cancer patients who also had endometrial sampling were identified from files in the Department of Obstetrics and Gynecology. To examine the subgroup of 15 polyps, age-matched, non-hormonally treated patients with polyps (n = 8) or atrophic endometria (n = 5) served as comparison groups. Proliferative (n = 3) and secretory (n = 5) endometria served as procedural controls. Immunohistochemical studies for steroid receptors (estrogen, progesterone) were performed. RESULTS: Glandular cell progesterone receptor was significantly increased and stromal cell estrogen receptor was significantly decreased in tamoxifen-treated versus atrophic endometria. Progesterone receptor staining was not significantly different in tamoxifen-treated versus control polyps, although staining was high in both groups. Stromal cell estrogen receptor staining was significantly reduced in tamoxifen-treated versus control polyps, although there were no histologic differences. Reduced stromal cell estrogen receptor and increased glandular cell progesterone receptor staining was found in all tamoxifen-treated endometria regardless of the diagnosis. CONCLUSION: The tamoxifen-associated changes in endometrial steroid receptors support an estrogenic effect that is independent of histologic diagnosis and duration of use. This may contribute to the pathogenesis of tamoxifen-associated polyps and carcinomas.

Aged↗
PubMed1997

Development of esophageal metaplasia and adenocarcinoma in a rat surgical model without the use of a carcinogen.

In order to establish an animal model for studying the cause and prevention of esophageal adenocarcinoma (EAC) and its frequent precursor, Barrett's esophagus (BE), factors affecting the pathogenic processes were investigated in an esophagoduodenal anastomosis model with rats. Experiments by us and others have shown that surgical treatment produced reflux esophagitis with cell hyperproliferation, but not EAC. Additional treatment with a carcinogen has been shown to be necessary for the development of EAC, squamous cell carcinomas (SCC) or EAC/SCC mixtures. We found that the surgically treated animals developed anemia due possibly to reduced iron absorption. When the operated animals were supplemented with iron, EAC occurred at a high rate (73%) after 30 weeks, and treatment with N'-nitrosonornicotine did not enhance the rate of tumorigenesis. Treatment with carcinogen, however, induced SCC in the group of rats killed after 22 weeks. The results suggest that iron overload, which is known to cause oxidative damage, is an enhancing factor for adenocarcinogenesis. The pathogenesis of EAC in the iron-supplemented, non-carcinogen treated group resembles human esophageal adenocarcinogenesis in many features. All the BE was the specialized type with goblet cells (containing sialomucin or sulfomucin) and columnar cells (containing acid or neutral mucin) as well as an incompletely developed brush border. Almost all of the BE was located at the bottom of the esophagus and was continuous with the duodenal mucosa; dysplasia became more frequent at later time points. All of the cancers were well-differentiated mucinous EAC, and most of the EAC had an adjacent area of BE with dysplasia. The results are consistent with the proposed human sequence for pathogenic events of BE progression to 'BE with dysplasia' and then to EAC. Esophagoduodenal anastomosis and iron treatment in rats produces a high rate of BE and EAC which are morphologically similar to human BE and EAC; this may be a useful animal model to study the development and prevention of EAC in humans.

Adenocarcinoma↗
PubMed1997

A head motion measurement system suitable for emission computed tomography.

Subject motion during brain imaging studies can adversely affect the images through loss of resolution and other artifacts related to movement. We have developed and tested a device to measure head motion externally in real-time during emission computed tomographic (ECT) brain imaging studies, to be used eventually to correct ECT data for that motion. The system is based on optical triangulation of three miniature lights affixed to the patient's head and viewed by two position-sensitive detectors. The computer-controlled device converts the three sets of lamp positions into rotational and translational coordinates every 0.7 seconds. When compared against a mechanical test fixture, the optical system was found to be linear and accurate with minimal crosstalk between the coordinates. In a study of two subjects, comparing the angular motions measured by the optical device and a commercially available electromagnetic motion detector, the two systems agreed well, with an root mean square (rms) difference of less than 0.6 degree for all rotations.

Algorithms↗