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Biomedical subjects

J Shapira

Publications and source records attributed to J Shapira.

At least 55 records · Page 3Linked to original sources
PubMed1996

The protective role of the immunomodulator AS101 against chemotherapy-induced alopecia studies on human and animal models.

The immunomodulator AS101 has been demonstrated to exhibit radioprotective and chemoprotective effects in mice. Following phase-I studies, preliminary results from phase-II clinical trials on non-small-cell-lung-cancer patients showed a reduction in the severity of alopecia in patients treated with AS101 in combination with chemotherapy. To further substantiate these findings, the present study was extended to include 58 patients treated either with the optimal dose of 3 mg/m2 AS101 combined with carboplatin and VP-16, or with chemotherapy alone. As compared with patients treated with chemotherapy alone, there was a significant decrease in the level of alopecia in patients receiving the combined therapy. The newly developed rat model was used to elucidate the protective mechanism involved in this effect. We show that significant prevention of chemotherapy-induced alopecia is obtained in rats treated with Ara-C combined with AS101, administered i.p. or s.c. or applied topically to the dorsal skin. We show that this protection by AS101 is mediated by macrophage-derived factors induced by AS101. Protection by AS101 can be ascribed, at least in part, to IL-1, since treatment of rats with IL-1 RA largely abrogated the protective effect of AS101. Moreover, we demonstrate that in humans there is an inverse correlation between the grade of alopecia and the increase in IL-1 alpha. In addition, protection by AS101 could be related to PGE2 secretion, since injection of indomethacin before treatment with AS101 and Ara-C partly abrogated the protective effect of AS101. To assess the ability of AS101 to protect against chemotherapy-induced alopecia, phase-II clinical trials have been initiated with cancer patients suffering from various malignancies.

Alopecia↗
PubMed1996

Ovarian tumors in postmenopausal breast cancer patients treated with tamoxifen.

From September 1, 1989, to November 30, 1994, 175 menopausal breast cancer patients treated with tamoxifen were followed at the authors' institutions. During this period. 16 (9.1%) underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy, for various indications. Of these, 10 (62.5%) had either uni- or bilateral ovarian tumors. The analysis of surgical findings showed an incidence of 5.7% (10/175) ovarian tumors among all the patients. In 2 (20%), the ovarian masses displayed enlargement over a relatively short period while on treatment. In 5 (50%) patients, the findings were bilateral. All tumors were detectable by ultrasonography, except four serous cystadenomas found in 3 women. The mean duration of tamoxifen treatment was 36.6 +/- 24.9 (range 9-86) months. The rate of 5.7% for ovarian tumors, in this selected group of patients, is four to five times higher than that reported for similar pathologic conditions detected by general screening with ultrasonographic scans among nonselected, asymptomatic, and untreated postmenopausal women. Two possibilities should be considered in the development of ovarian tumors coinciding with tamoxifen treatment; (1) women with breast malignancy are prone to develop benign or malignant ovarian tumors in relation to genetic factors, regardless of tamoxifen treatment; and (2) tamoxifen may stimulate enlargement of such tumors and may even cause them.

Aged↗
PubMed1996

Orthodontics for the handicapped child.

The broad spectrum of difficulties that exist in providing orthodontic treatment for handicapped children is well known and few practitioners offer such a service. The present article offers an analysis of the problems involved and provides some practical answers designed to overcome them. It describes some of the newer modalities that have become available to the dental profession over the last few years and shows how advantage may be gained by their exploitation, in orthodontic treatment. Additionally, some of the older and largely-forgotten methods, appropriately modified and updated, are represented in this context, where they find particular relevance. Guidelines are given to enable the orthodontic profession to gain therapeutic access to a section of the population that urgently requires treatment.

Behavior Therapy↗
PubMed1996

Common endometrial decidual reaction in postmenopausal breast cancer patients treated with tamoxifen and progestogens.

In order to assess endometrial reaction to the combined treatment of tamoxifen and progestogens in asymptomatic postmenopausal breast cancer patients, we evaluated all such patients by vaginal ultrasonography and by histological examination of endometrial samplings. All patients were initially treated with tamoxifen, and progestogens were then added when metastases became evident. Of 12 patients included in the study, eight (66.66%) showed evidence of strong endometrial stromal decidualization, while three (25%) had decidual reactions in endometrial polyps. Overall, 11 (91.66%) of the patients had decidual reactions, and all were treated with progestogens for > or = 3 consecutive months. One patient, treated with progestogens for 1 months, had an inactive endometrium. All but three had thickened endometria (> 10 mm) on ultrasonographic evaluation. These data show that postmenopausal breast cancer patients who received progestogens for < or = 3 months, and who concomitantly took tamoxifen, had a uniform decidual reaction in all uteri.

Adult↗
PubMed1996

Time-dependent effect of tamoxifen therapy on endometrial pathology in asymptomatic postmenopausal breast cancer patients.

Various endometrial lesions were more frequent among asymptomatic postmenopausal breast cancer patients who were treated with tamoxifen for > 48 consecutive months (30.8%) when compared with similar patients who were treated for 6-24 months or for 25-48 months (20.8% and 12.5%, respectively). However, this difference was not statistically significant. There were also no significant differences in the frequency of the various endometrial lesions between these three groups, although endometrial polyps were more frequently found among those treated for > 48 months. Overall, 20.7% of the 164 tamoxifen-treated patients in the study had an endometrial pathology. It can be concluded that there is a slight tendency among those postmenopausal patients who have been treated for > 48 consecutive months to have a higher frequency of endometrial lesions.

Analysis of Variance↗
PubMed1996

Teething and acute graft vs. host disease: a clinical observation.

A 5-month-old girl, treated with bone marrow transplantation for severe combined immunodeficiency, developed two episodes of severe acute graft vs. host disease (GVHD) while teething. A dramatic improvement in GVHD was noted after the completion of tooth eruption. It is suggested that the release of interleukin-1, associated with the traumatized gingival tissue, is the triggering mediator for the GVHD.

Acute Disease↗
PubMed1996

Modification of tooth size and shape in Down's syndrome.

Individuals with Down's syndrome (DS) tend to display a reduction in size of permanent teeth, and reduced intercuspal distances in molars. A total of 51 permanent maxillary 1st molars of 26 DS children were examined from dental casts, 65 permanent maxillary 1st molars of normal children were examined from dental casts of 33 individuals. The following measurements were performed on both right and left molars (teeth 16 and 26 respectively): (1) all intercusp distance (distobuccal, db; distolingual, dl; mesiobuccal, mb; mesiolingual, ml); (2) the db-mb-ml, mb-db-ml, db-ml-mb, dl-mb-db, mb-dl-db, and dl-db-mb angles; (3) the area of the quadrangle shaped by connecting the cusp tips. All the intercusp distances were significantly smaller in the DS group. Stepwise logistic regression, applied to all the intercusp distances, was used to build a multivariate probability model for DS and normals. The mb-dl and mb-ml distances of the upper right molar (tooth 16) were sufficient to discriminate between DS and normal teeth: [table: see text] The probability for DS is higher when mb-ml is relatively higher in the mb-ml/mb-dl ratio. Another logistic analysis based on groups of angles revealed a combination of 3 angles which gave highly statistically significant discrimination between both groups: the mb-db-dl angle was higher in DS, the mb-dl-db angle was slightly smaller in DS, and the mb-ml-db angle was slightly smaller in DS. The dl cusp was located closer to the centre of the tooth. The change in size occurs at an early stage, while the change in shape occurs in a later stage of tooth formation in DS population. Our probability model for DS teeth is simple and practical because it requires only 2 intercusp distances to be put into the formula.

Adolescent↗
PubMed1995

Adenomyosis in postmenopausal breast cancer patients treated with tamoxifen: a new entity?

Between September 1, 1989 and October 31, 1994, 173 postmenopausal breast cancer women on tamoxifen treatment were followed up in the authors' institutions. During this period, 14 (8.1%) underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy for various indications. Eight (57.1%) were found to have adenomyosis, of whom one had a large fundal adenomyotic lump and the other seven patients had two to four small microscopic foci of adenomyosis. In this study, the rate of adenomyosis described among those postmenopausal breast cancer patients treated with tamoxifen is nearly three to four times higher than the rate reported in the literature for pre- and postmenopausal women. There is no previous reported increased incidence of adenomyosis in postmenopausal breast cancer patients treated with tamoxifen. Thus, it is suggested that the prolonged and unopposed estrogen-like stimulation by tamoxifen may play a causal role rather than be a casual factor in the development of this pathologic entity.

Adult↗
PubMed1995

Retrospective epidemiological study of Burkitt's lymphoma in Israel and diagnosis by a conservative incisional biopsy.

The clinical features of 74 patients with Burkitt's lymphoma diagnosed at the Hadassah Medical Center in Jerusalem, Israel, are described. The prompt diagnosis of a child with high grade malignant jaw involvement of non-Hodgkin's Burkitt's lymphoma is reported. The use of the open biopsy with special emphasis on the incisional biopsy is discussed in light of the incidental exfoliation of the two primary molar teeth and one permanent successor in this case.

Adolescent↗
PubMed1995

Bone marrow-sparing and prevention of alopecia by AS101 in non-small-cell lung cancer patients treated with carboplatin and etoposide.

PURPOSE: The aim of this study was to evaluate the ability of the immunomodulator AS101 to prevent chemotherapy-induced neutropenia and thrombocytopenia and thus allow patients to receive full-dose antineoplastic agents according to protocol design. We also aimed to determine the production level of various hematopoietic growth factors in treated patients. PATIENTS AND METHODS: This study of 44 unresectable or metastatic non-small-cell lung cancer (NSCLC) patients was an open-label prospective randomized study of standard chemotherapy alone versus chemotherapy plus AS101. Each patient received carboplatin (300 mg/m2 intravenously [IV] on day 1 of a 28-day cycle, and etoposide (VP-16) (200 mg/m2 orally) on days 3, 5, and 7 of each cycle. AS101 was administered at 3 mg/m2 three times per week starting 2 weeks before chemotherapy. RESULTS: AS101, which manifested no major toxicity, significantly reduced neutropenia and thrombocytopenia and thus allowed all treated patients to receive full-dose antineoplastic agents, in contrast to only 28.5% of the control group. Continuous treatment with AS101 significantly reduced the number of days per patient of thrombocytopenia and neutropenia and did not provide protection to tumor cells as reflected by the higher overall response rate compared with the chemotherapy-alone arm. Interestingly, AS101 treatment also significantly prevented chemotherapy-induced alopecia. These effects correlate with the ability of AS101-treated patients to increase significantly the production of colony-stimulating factors (CSFs) interleukin-1 alpha (IL-1 alpha) and IL-6. CONCLUSION: AS101 has significant bone marrow (BM)-sparing effects and prevents hair loss in chemotherapy-treated patients, with minimal overall toxicity. These effects are probably due to increased production of IL-1 alpha, IL-6, and granulocyte-macrophage (GM)-CSF.

Adjuvants, Immunologic↗
PubMed1995

The significance of soluble interleukin-2, soluble interleukin-2 receptors, soluble ICAM-1 and beta 2-microglobulin in breast cancer patients.

The serum levels of soluble interleukin-2 (sIL-2), sIL-2 receptors (sIL-2R), beta 2-microglobulin (beta 2M) and soluble intercellular adhesion molecule-1 (sICAM-1) were measured by the ELISA technique in 129 breast cancer patients and 40 controls. The median serum levels of sIL2-R, beta 2M and sICAM-1 were significantly higher and sIL-2 significantly lower than controls. sIL-2R, sICAM-1 and beta 2M levels were significantly higher in patients with metastatic disease compared to patients on long-term follow-up with no active disease. Initial study measurements of these markers could not identify patients at high risk for relapse. These findings suggest that the sIL-2R level is indicative of metastatic disease and together with other parameters of immune activation may be of help in monitoring disease activity in breast cancer patients.

Adult↗
PubMed1994

Delta-T-lymphocytosis in a patient with thymoma.

BACKGROUND: Malignant thymoma is composed of neoplastic epithelial cells and small lymphocytes. Rarely, patients also may have peripheral T-lymphocytosis. These lymphocytes have been considered nonneoplastic because of their microscopic appearance and immunophenotype, as well as gene rearrangement studies. METHODS: A 42-year-old man developed lymphocytosis 3 years after the completion of intensive combined chemoradiotherapy protocol for lymphocytic thymoma. These peripheral blood lymphocytes were evaluated phenotypically and genotypically. RESULTS: Immunophenotyping established that the cells were CD3 positive, CD4 negative, CD8 negative, T-cell receptor (TCR)-alpha/beta negative, and TCR-gamma/delta positive. Gene rearrangement studies with TCR-delta probe confirmed the monoclonality of these cells. Chromosome analysis showed deletion of chromosome Y. The clinical course was progressive and had the features of malignant lymphoma. CONCLUSIONS: To the authors' knowledge, this is the first report of a patient with thymoma in whom monoclonal proliferation of T-gamma/delta peripheral blood lymphocytes was confirmed immunophenotypically and genotypically. These monoclonal TCR-gamma/delta lymphocytes may belong to the malignant clone of the thymoma; however, the possibility that they represent an evolution of a second lymphatic malignancy cannot be excluded.

Adult↗
PubMed1994

Endometrial changes with tamoxifen: comparison between tamoxifen-treated and nontreated asymptomatic, postmenopausal breast cancer patients.

Endometrial thickness, as evaluated by vaginal ultrasonography, and endometrial histologic findings, as well as demographic characteristics, health habits, and risk factors for endometrial cancer, were compared between 93 asymptomatic postmenopausal breast cancer patients who had been on tamoxifen treatment and 20 patients who had not. The mean ultrasonographic endometrial thickness in the women on tamoxifen treatment was 13.1 +/- 10.4 mm, which was significantly thicker than the 4.0 +/- 3.2 mm found in the nontreated women (P = 0.001). The frequency of endometrial pathological findings was remarkably high (35.5%) among the tamoxifen-treated patients, compared with nontreated patients (20.0%), with a P value of 0.058 and an odd ratio of 4.6. Thus, it is suggested that the remarkably high prevalence of pathological endometrial changes was due to the continuous and unopposed exposure of the endometrium to tamoxifen.

Aged↗
PubMed1994

Continuous tamoxifen treatment in asymptomatic, postmenopausal breast cancer patients does not cause aggravation of endometrial pathologies.

Adjuvant tamoxifen therapy for breast cancer patients has been found to be associated with various endometrial pathologic conditions, including endometrial cancer. This preliminary case control study evaluated whether prolonged and continuous exposure to tamoxifen in the menopause may aggravate existing endometrial pathologies. Two vaginal ultrasound evaluations of endometrial thickness and histologic findings of two endometrial biopsies, performed 18 months apart, were evaluated for 25 asymptomatic, postmenopausal breast cancer patients who were continuously treated with tamoxifen. In the first endometrial biopsy, 4 patients (16.0%) were found to have endometrial pathologies: 2 patients had proliferative endometrium, 1 had hyperplastic endometrium, and 1 had an endometrial polyp. In the second endometrial biopsy, none of these patients showed any endometrial pathologies. Another patient (4.0%) with no endometrial pathology in the first visit had endometrial hyperplasia in the second visit. None of the patients developed endometrial cancer, and generally there was no increase in ultrasonographically-measured endometrial widths. The results of this preliminary study may suggest that there is no increased risk of development of endometrial pathologies during an additional 18 months of continuous tamoxifen therapy nor is there aggravation of already existing endometrial pathologies.

Aged↗
PubMed1994

Postmenopausal tamoxifen treatment and endometrial pathology.

Tamoxifen is widely used as adjuvant therapy for postmenopausal breast cancer patients with positive estrogen receptors. Data on a possible association of endometrial pathologies with tamoxifen treatment have been accumulating. In this review, we examine the current literature and include our own experience with this occurrence. We recommend close supervision of these patients.

Breast↗
PubMed1994

Research trends in Alzheimer's disease.

Alzheimer's disease (AD) is a tragic condition. The individual experiencing the loss of memory, difficulty with language, change in personality, and disturbance in behavior associated with AD is not alone; the number of people with AD is estimated at 4 million; by the year 2050, as many as 14 million Americans may be afflicted (National Institute of Aging, 1992). AD is the fourth leading cause of death for adults, taking more than 100,000 lives annually. The families of these patients also are victims, as they watch their loved ones slowly forget them and all that was once meaningful in their lives.

Adult↗