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8794406 | Evaluation and prognostic value of DNA content and of morphometric parameters in malignant mesothelioma using digital image analysis. | Fifty-seven cases of malignant mesothelioma were analyzed for nuclear diameter, DNA content and ploidy-related parameters, using Feulgen stained paraffin sections with a digital imaging analysis system. Thirty cases had a mean nuclear diameter > 7 microns and 31 cases were classified as near-diploid. A statistically significant correlation between survival and the mean nuclear diameter (P = 0.0006) and between survival and DNA index (P = 0.007) was obtained. For other DNA content parameters (proliferation index, 5c exceeding rate), only one of the two statistical tests showed a significant correlation with survival while the other test was of borderline significance. In this malignant mesothelioma population, the prognosis for patients with the epithelial type was better than for those with atous tumours (P = 0.01). In this population of patients, about half of the malignant mesotheliomas were aneuploid. The mean nuclear diameter, DNA index analysis and proliferation index analysis of the tumour cells on Feulgen stained paraffin sections can be used as independent prognostic parameters. |
8794407 | Peptide amidating activity in human bronchoalveolar lavage fluid. | Monitoring respiratory epithelial biology may reveal individuals with incipient lung cancer. The expression of neuroendocrine (NE) markers in pulmonary epithelium is thought to be central to lung development, repair of injury and may contribute to carcinogenesis. In this study, we evaluate several candidate NE markers to determine the feasibility of prospective analysis of clinical specimens. The potential NE markers include the enzyme L-DOPA decarboxylase (DDC), the neuropeptide gastrin releasing peptide (GRP), and peptidyl-glycine alpha-amidating monooxygenase (PAM), the bifunctional enzyme responsible for the final bioactivation step of many neuropeptides. parison of PAM activity and DDC levels in 30 lung cancer cell lines indicated that peptide amidating activity may be an indicator of NE status. Bronchoalveolar lavage (BAL) fluid from subjects at risk of developing second primary lung cancer and from volunteers was obtained. The activity of the first PAM enzyme, peptidylglycine alpha-hydroxylating monooxygenase (PHM), ranged from not detectable to 507 pmol/h/mg protein in 57 specimens. The second PAM enzyme, peptidylamidoglycolate lyase (PAL), ranged from not detectable to 414 pmol/h/mg protein in 56 specimens. Using cluster analysis by the average linkage method, a group of enzyme values with PHM greater than 230 pmol/h/mg protein was determined. Long-term follow-up of these patients for new second primary lung cancers may help to determine the potential predictive value of PAM detected in the BAL fluid. |
8794408 | Lung cancer-induced blindness. | Early investigations into the pathogenesis of vision loss in cancer patients noted the higher incidence with small cell carcinoma of the lung (SCCL), a neoplasia with suspected neuroendocrine origins [2-5,12,20,25,56,63,64]. The cause and effect relationship between the cancer and retinal deterioration was recognized, but the processes involved were not understood. Research eventually identified a sub-group of paraneoplastic retinopathy patients who exhibited indications of retinal hypersensitivity through their production of autoantibodies reactive with a single photoreceptor protein. The discovery of a small cell lung cancer culture actively expressing this same retinal autoantigen, provided tangible evidence to define a molecular basis for at least one type of paraneoplastic retinopathy. The identification of this immunologic anomaly illustrates how blindness can occur in some cancer patients, through the serendipitous initiation of ocular hypersensitivity, with vision loss developing as a cancer-induced autoimmune retinopathy. |
8794409 | Cancer-associated retinopathy syndrome: a case of small cell lung cancer expressing recoverin immunoreactivity. | Cancer-associated retinopathy (CAR) syndrome is a rare paraneoplastic neuropathy syndrome often found in patients with small cell lung cancer (SCLC). Serological studies have indicated that the process could include autoimmune reactions directing retinal antigens. Recently, the CAR antigen was identified as a photoreceptor protein, recoverin, by screening retinal proteins using the CAR patient's serum. The present case of SCLC showed rapidly deteriorated bilateral visual acuity lacking the inflammatory findings at the retina which patible with CAR. The immunohistochemical study revealed that the cancer cells expressed recoverin or recoverin-like immunoreactivity. This is the first observation in CAR syndrome. The presence of recoverin or recoverin-like immunoreactivity in SCLC with CAR syndrome supports the hypothesis that the cancer-retina immunologic cross-reaction contributes to visual loss in this syndrome. |
8794410 | Primary lung cancer of the middle lobe. Is its prognosis poor? | The right middle lobe is unique because it is surrounded by two other lobes and the pericardium, and it is the smallest lobe. The proper surgical treatment and prognosis for cancer of the right middle lobe has not been definitively established. In order to clarify its prognosis and the best operative technique, 31 surgically treated patients with lung cancer of the right middle lobe were studied clinically and pathologically. The e of surgical treatment of the right middle lobe cancer pared with other locations in the lung. The 5-year survival rate of this group was 51.5%, with a median survival time of 82.3 months. For resectable cases, the e for carcinomas of the middle lobe was no worse than for other locations. However the rate of exploratory thoracotomy was highest for the right middle lobe. All five patients with lobectomies are alive and disease free at 26.4-151.4 months. The 5-year survival rate of 23 bilobectomies was 40.0%, with a median survival time of 48.4 months. The difference between lobectomy and bilobectomy cases was statistically significant (P < 0.025). When the tumor was limited to pletely separated middle lobe without dissemination, pulmonary or mediastinal lymph node metastasis, lobectomy was sufficient for curative treatment. |
8794411 | Therapeutic options for regionally advanced non-small cell lung cancer. | The optimal treatment for regionally advanced non-small cell lung cancer (NSCLC, Stage IIIa/IIIb) remains unknown. Proposed approaches include surgery, radiotherapy, chemotherapy, binations of these. No treatment modality, however, has ever shown other than modest or minimal beneficial effects. When differences between new and old treatments appear trivial, as in the management of the locally advanced NSCLC, controlled studies are necessary to select the best approach. This review is based on a systematic overview of data from randomized paring different treatment modalities. The following six points emerged from the cited literature. (1) It is sufficiently proved that chemotherapy alone prolongs survival in patients with both locally advanced and metastatic disease. (2) Although it is probably true that radiation therapy is better than no active treatment, this idea is supported by very limited evidence. (3) Although it is probably also true that radiotherapy alone is not worse than chemotherapy alone, this is another insufficiently proved issue. (4) The possible superiority of chemo-radiotherapy to chemotherapy alone or to supportive care is also poorly documented. (5) There is abundant evidence that chemo-radiotherapy is better than radiotherapy alone (however, this information may be unhelpful if point 2, or 3 remains unclarified). (6) Although neoadjuvant treatments have improved resectability and may ensure overall better results, the surgical cure, either alone or bination with chemotherapy or chemo-radiotherapy, is another unproved option. Based on the above six points, it was concluded that new randomized studies are urgently needed to confirm the possible superiority of chemo-radiotherapy to chemotherapy. Only after such a validation, will the many ongoing trials, designed to prove the possible superiority of local surgical control to the more traditional approaches based on thoracic irradiation, have a practical sense. |
8794412 | Adjuvant chemo-immunotherapy after curative resection of Stage II and IIIA primary lung cancer. | Out of 642 primary lung cancer patients who underwent surgery between 1986 and 1992, 82 cases who underwent curative resection were enrolled for a randomized prospective controlled study of postsurgical adjuvant immunotherapy using Interleukin 2 (IL-2) and lymphokine activated killer (LAK) cells. From 1986 to 1989 (the initial period), Stage IIIA patients were divided into three groups: group A (chemo-immunotherapy) received IL-2, LAK cell adoptive immunotherapy after two courses of anticancer (CDDP, VDS, MMC) chemotherapy, group B (control) received no adjuvant therapy, and group C (chemotherapy) received the same anticancer chemotherapy as group A. In the latter (1990-1992) period, group C was discontinued because of poor results and Stage II and IIIA cases were randomly assigned to group A or B. The 5- and 7-year survival rates of group A (33 cases) and B (36 cases) were 58.2% and 31.5%, respectively in Stage II and IIIA cases. The prognosis of group A was significantly better than that of group B (P = 0.0038 by the Cox-Mantel (C-M) test and 0.0033 by the generalized Wilcoxon (G-W) test). The 5- and 8-year survival rates of each group for Stage IIIA cases were 53.4% (group A, 25 cases), 33.4% (group B, 26 cases), and 30.8%, 15.3% (group C, 13 cases). The prognosis of group A was significantly better than that of group B (P = 0.045 by the C-M and 0.036 by the G-W test). The difference between group A and B was also significant in N0, N1 (P < 0.01), in T1, T2 (P < 0.01), and T3 (P < 0.05) cases. These results indicate that adjuvant immunotherapy using IL-2 and LAK cells bination with chemotherapy is significantly effective in improving the postsurgical prognosis of lung cancer patients. |
8794414 | The limits of chemotherapy dose intensification using granulocyte colony stimulating factor alone in extensive small cell lung cancer. | Human binant Granulocyte Colony Stimulating Factor (G-CSF) allows rapid neutrophil recovery after chemotherapy-induced leukopenia. In a prospective series of 54 patients with extensive small cell lung cancer, we evaluated the feasibility and efficacy of accelerated delivery of the AVI chemotherapy regimen. Treatment consisted of Doxorubicin 50 mg/m2 day 1, Etoposide 120 mg/m2 day 1-3 and Ifosfamide 2 g/m2 (+ Mesna 4 g) day 1 and 2 given every 2 weeks and followed by G-CSF (Neupogen, Amgen Roche 5 micrograms/kg/day s.c. day 4-14). Twenty-seven (50%) patients could not receive the total of six courses, seven because of severe plication, 10 because of Grade 4 thrombopenia, seven because of non-response and three because of patient refusal. Chemotherapy had to be delayed in 58 out of the 244 administered courses and this was due to thrombopenia in 48% of cases. The probability of optimal dose-on-time administration was 64% at three courses. The mean actually received dose intensity was 93% at six courses (27 patients treated). It was increased by pared to our previously published conventional 3-week interval chemotherapy. The median neutrophil nadirs were stable during the successive treatment courses while haemoglobin and platelet values significantly worsened from cycle 1 to cycle 6. The overall response rate after three courses was 77% in the 48 evaluable patients. The median survival is 8 months overall and 5 months disease free. The actuarial survival is 22% at 2 years. We conclude that substantial dose intensification with accelerated chemotherapy and G-CSF support is feasible. However, the rate of severe infectious episodes is too high and thrombopenia is the main limiting factor. Either growth factors active on the megacaryocytic lineage or haematological rescue with peripheral blood stem cells might be useful in this setting. |
8794415 | r-metHuG-CSF support to ifosfamide, cisplatin, etoposide chemotherapy in non-small cell lung cancer. | Twenty patients with locally advanced or metastatic non-small cell lung cancer entered a study of binant human methionyl G-CSF (r-metHuG-CSF) as an adjunct to ifosfamide, cisplatin and etoposide (IPE) regimen. Chemotherapy consisted of three courses of cisplatin 25 mg/m2, ifosfamide 1.5 g/m2 (with uroprotection) and etoposide 100 mg/m2 given on days 1-4 of a 21-day cycle. r-metHuG-CSF, 5 micrograms/kg, was administered subcutaneously from day 5 to day 14. Eighteen out of 20 pleted the three courses (57 evaluable cycles). Grade 3-4 neutropenia affected 50, 42 and 22% of the patients during cycles 1, 2 and 3, respectively, whereas thrombocytopenia was observed in 25% of the patients throughout the chemotherapy protocol. Haematological toxic events requiring transfusions and/or antibiotics were responsible for 11 unplanned hospitalizations. Among these only three were exclusively devoted to febrile neutropenia care, the remaining eight being mainly required for blood transfusions. There were no deaths during the study duration. Dose reductions were needed in 65% of the patients and chemotherapy was delayed by thrombocytopenia in five patients. The total relative dose intensity was 84%. Eleven (55%) patients responded plete and 10 partial responses). Median survival was 9.5 months. We concluded that bination chemotherapy can be administered safely with the support of r-metHuG-CSF inasmuch as neutropenia appears as mild to moderate and manageable. Optimal delivery of chemotherapy is still limited by other toxicities, mainly thrombocytopenia, but the successful relative dose intensity observed herein deserves further studies designed to analyze a dose intensity-survival relationship in non-small cell lung cancer. |
8794413 | A randomized phase II study of ifosfamide/mesna/cisplatin plus G-CSF or etoposide/cisplatin plus G-CSF in advanced non-small cell lung cancer: a Cancer and Leukemia Group B study. | This Phase II study was designed to determine the efficacy of two chemotherapy regimens with G-CSF support for patients with advanced non-small cell lung cancer (NSCLC). One-hundred and one patients with Stage IIIB or IV NSCLC and performance status 0-1 were randomized to receive ifosfamide 2.0 g/m2 days 1-3, mesna 400 mg/m2 at 0, 4, 6 h days 1-3, cisplatin 33 mg/m2 days 1-3 or etoposide 200 mg/m2 days 1-3, cisplatin 35 mg/m2 days 1-3. Both groups received G-CSF 5 micrograms/kg SQ day 4 to the post day 11 absolute neutrophil count > 10 000. For the 47 eligible patients receiving ifosfamide/mesna/cisplatin, the response rate was 26% (95% confidence interval: 14-40%) and the median survival 7.5 months (95% confidence interval: 5.8-11.0 months). Grade 3 or worse toxicities were: neutropenia 75%, thrombocytopenia 70%, infection 21%. There were two treatment-related deaths due to infection. For course 1, the median absolute neutrophil count nadir was 1.3, platelet nadir 96 000 and incidence of febrile neutropenia 16%. For the 48 eligible patients receiving etoposide/cisplatin, the response rate was 21% (95% confidence interval: 11-35%) and median survival 5.8 months (95% confidence interval: 4.5-9.7 months). Grade 3 or worse toxicities were: neutropenia 90%, thrombocytopenia 58%, infection 29%. There were three treatment-related deaths due to infection. For course 1, the median absolute neutrophil count was 0.2, platelet nadir 80 000 and incidence of febrile neutropenia 33%. For both ifosfamide/mesna/cisplatin and etoposide/cisplatin, median duration of Grade IV neutropenia was short (< or = 4 days), time to subsequent courses 21 days and dose delivered > 95% of planned dose. Although G-CSF allowed full doses of drugs to be delivered on schedule, both ifosfamide/mesna/cisplatin and etoposide/cisplatin produced response rates and survival similar to other cisplatin-based regimens. In view of the significant cost of G-CSF and no obvious improvement in response rate, survival or toxicity profile, G-CSF cannot be mended with these chemotherapy regimens for patients with advanced NSCLC. |
8794418 | Replens versus dienoestrol cream in the symptomatic treatment of vaginal atrophy in postmenopausal women. | This study was designed to evaluate the efficacy of Replens, a non-hormonal moisturizing vaginal gel, on symptoms of vaginal atrophy in postmenopausal women, parison with Dienoestrol (Cilag), an oestrogenic vaginal cream. |
8794419 | Association between urinary incontinence and urinary tract infections, and fractures in postmenopausal women. | The association between urinary disorders, such as ongoing urinary incontinence (UI), history of urinary incontinence (HIST-UI) and urinary tract infections (UTI), and fractures in peri- and postmenopausal women was assessed in an epidemiological study. |
8794416 | Multicenter Phase II trial of intermediate dose cisplatin and vinorelbine in inoperable non-small cell lung cancer patients. | Vinorelbine (VNB) and cisplatin bination regimen was found active in the treatment of advanced non-small cell lung cancer (NSCLC) patients, but significant toxicity was observed. We evaluated the activity and toxicity of bination administered at lower doses than previously reported. From March 1992 to March 1994, 99 patients (pts) were enrolled in a multicentric Phase II study and received intravenous CDDP at 80 mg/m2 on day 1, associated with intravenous VNB at 25 mg/m2 on days 1 and 8. Cycles were repeated every 3 weeks. The reduced doses led to a consistently lower myelotoxicity (8% Grade III-IV leukopenia) parison to two related Phase III studies, recently published. Conversely, the incidence of neurological toxicity was superimposable. Considering all eligible patients, the overall response rate was 28.3%, and this is similar to the monly observed employing the most active CDDP containing regimens. In conclusion, CDDP and bination chemotherapy at the schedule performed in the present study led to a reduction of hematologic toxicity, while an appreciable activity was maintained. |
8794420 | Comparative effect of short-term topical tretinoin and glycolic acid on mechanical properties of photodamaged facial skin in HRT-treated menopausal women. | Cutaneous intrinsic ageing has been shown to be improved by hormone replacement therapy (HRT). Photoageing is, however, unresponsive to such treatment. The present double-blind study was undertaken pare the beneficial effect of a 1-month topical treatment with 0.05% all-trans-retinoic acid or 6% glycolic acid. |
8794421 | Conservative management of postmenopausal pelvic echo-free findings--preliminary results. | To develop a conservative protocol for the treatment of echo-free findings in the pelvis, diagnosed by sonography in post-menopausal women, in order to avoid unnecessary surgical intervention. |
8794423 | Vasomotor symptoms and well-being in the climacteric years. | To determine more closely the relationship between vasomotor symptoms, well-being and climacteric status according to the last menstrual bleeding and according to the women themselves. |
8794422 | Comparative bioavailability study of an once-a-week matrix versus a twice-a-week reservoir transdermal estradiol delivery systems in postmenopausal women. | An open-label, randomised, crossover study was conducted with in healthy postmenopausal women pare the relative bioavailability of a matrix transdermal estradiol delivery system worn for 7 consecutive days, versus a reservoir transdermal patch worn for 4 days followed by its immediate replacement by another patch worn for further 3 consecutive days. There was a minimum 7-day washout period between the two study periods. Both systems were labelled to release approximately 50 micrograms/day of estradiol. Twenty-six subjects were evaluated with regard to estradiol serum levels. Blood samples were taken immediately before and at regular intervals until 192 h after the initiation of each study treatment (patch application) and assayed for estradiol. There was no difference between the patches with regard to Cmax. Based on the relative bioavailability, one matrix patch proved to be bioequivalent to two reservoir patches worn consecutively for 7 days. These results demonstrate the ability of one matrix patch to deliver consistent therapeutic levels of estradiol over a 7-day period. |
8794424 | Obesity and fat distribution in relation to hot flashes in Dutch women from the DOM-project. | The authors studied obesity and fat distribution in relation to the occurrence of hot flashes in a population-based prising 2904 women aged 40-44 and 569 women aged 54-69 presenting for mammographic screening (the DOM-project). Women aged 40-44 in the upper tertiles of Quetelet's index and waist/hip ratio reported hot flashes significantly more often than women in the respective lower tertiles. These associations were independent of each other and independent of age. After adjustment for age, waist/hip ratio and menopausal status, the odds paring the upper tertile of Quetelet's index to the lower tertile was 1.70 (95% confidence interval, 1.30-2.21). After adjustment for age, Quetelet's index and menopausal status, the odds paring the upper tertile of waist/hip ratio to the lower tertile was 1.37 (95% CI, 1.05-1.78). In women aged 54-69 no significant associations between Quetelet's index plaints of hot flashes were observed. Women in the upper tertile of waist/hip ratio reported hot flashes more often than women in the lower tertile, but this result was not significant (OR 1.38; 95% CI, 0.87-2.22). |
8794425 | The effect of hormone replacement therapy on bone mass in patients with ovarian failure due to bone marrow transplantation. | Long permanent remissions in malignant hematopoietic disorders can often be achieved by autologous bone marrow transplantation (ABMT) or by allogenic bone marrow transplantation (BMT). Previous studies have shown that such therapies may induce osteoporosis due to iatrogenic ovarian failure. The administration of hormone replacement therapy (HRT) in these women could prevent the adverse effects of long-term ovarian failure without remarkable side effects. The aim of this study was to evaluate how the bone mass is affected by HRT in patients undergoing ABMT or BMT adjusting the results for age, weight, and height. |
8794426 | Uterine findings by transvaginal sonography during percutaneous estrogen treatment in postmenopausal women. | To evaluate the effect of hormone replacement treatment (HRT) with percutaneous estradiol and cyclical peroral medroxyprogesterone acetate (MPA) every month or every third month on the uterus and endometrium of postmenopausal women. |
8794427 | Predicting age at menopause. | This article reviews methodologic and clinical aspects of predicting age at menopause. Lifetable methods or logistic models applied to a perimenopausal population represent the most feasible and the least biased methods for estimating the probability of menopause by age. Information is emerging about risk factors besides age which influence risk for an earlier menopause and include a variety of medical, demographic, environmental, and genetic factors. The concept of menopause as a consequence of depleted oocytes suggests that the estimated number of ovulatory cycles might also be a useful predictor. Using these variables in a logistic model yields estimated probabilities of menopause for various risk profiles. Smokers who have accumulated more than 10 pack-years, women estimated to have had more than 300 ovulatory cycles, women with a history of depression, women who have lost one ovary at an early age, and women who have a family history of early menopause have earlier menopause and the greatest shift in the cumulative probability of menopause occurs in women with multiple risk factors. |
8794429 | Effects of progestogens on haemostasis. | Epidemiological data suggested an involvement of the ponent in the pathomechanism of venous and arterial diseases during intake of oral contraceptives. The influence of progestogens on haemostasis parameters depend on type and dose of the progestogen, the presence of an estrogen, the route of application, and the duration of use. Treatment of women with progestogen-only preparations caused only minor effects on coagulation and fibrinolysis. Similarly, during hormone replacement therapy with natural estrogens, the additional application of progestogens induced no unfavourable changes on haemostasis. In contrast, the use of ovulation inhibitors resulted in an acceleration of coagulation and fibrinolysis. This is primarily induced by the marked action of ethinylestradiol on hepatic and vascular function. Progestogens with androgenic properties may counteract the estrogen-induced changes in the hepatic synthesis of platelet aggregation and readiness for coagulation. Estrogen and progesterone receptors are localized in endothelial and smooth muscle cells of the vessel wall, but there are differences in the response of veins and arteries to sex steroids. Estrogens and progestogens may influence collagen and elastin synthesis, and the release of pounds and of factors controlling fibrinolysis from endothelium. In veins, progestogens may increase distensibility and capacitance resulting in a decreased blood flow. In predisposed women, this may lead to venous stasis and thrombosis. In arteries, progestogens may act as vasoconstrictors, and may enhance vasospasms at sites of injured endothelium which finally may lead to ischemic diseases. |
8794428 | Prophylaxis of osteoporosis with calcium, estrogens and/or eelcatonin: comparative longitudinal study of bone mass. | To evaluate three different therapeutic regimens for the prevention of osteoporosis in natural and surgical postmenopausal women who had been found to have rapid bone loss in analytical studies. |
8794430 | Endometrial thickness assessed by transvaginal ultrasound insufficiently predicts occurrence of hyperplasia during unopposed oestrogen use. | In the present study, unopposed oestrogens were given to 184 non-hysterectomized women, for a duration varying from four weeks to 24 months, while the endometrial responses were monitored by transvaginal sonography (TVS) and backed up by endometrial sampling (conducted when the endometrial thickness reached 8 mm (double layer) or more, vaginal bleeding occurred during oestrogen administration, or after one year of unopposed oestrogen use). In cases where the endometrial thickness reached 8 mm or more, progestogens were administered for 12 days. In 64% of the women, administration of progestogen could be postponed until at least the fourth month of treatment under the pre-defined decision criteria. Eleven percent of the patients used oestrogens continuously during the two year study period, without any need of additional progestogen. In total, 338 endometrial biopsies were performed; 16 cases of hyperplasia were detected. In three cases, the corresponding endometrial thickness was below 8 mm (in one case, 5 mm). Endometrial thickness could not consistently predict occurrence of hyperplasia. In eight cases, hyperplasia occurred within 4 months of treatment, and in four cases, within only 2 months (of which only one case could possibly be attributed to previous hormone use and none to endogenous oestrogen production). The rapid occurrence of hyperplasia should be taken into account in studies of quarterly progestogen administration with hormone replacement therapy. It is concluded that postponement of progestogen administration with hormone replacement therapy under guidance of TVS only (without biopsies) would not be adequately safe to be mended for clinical practice. |
8794432 | Serotonin metabolite excretion after postmenopausal estradiol therapy. | Serotonin, known for its beneficial action on mood and well-being, is also involved in cardiovascular functions. Thus the current work was undertaken to study the effect of hormone replacement therapy on serotonin turnover in postmenopausal women. Eighteen women received estradiol transdermally and 17 women estradiol valerate orally for 4 weeks. The serotonin metabolite 5-hydroxyindole acetic acid (5-HIAA) was determined in the urine before, and after 2 and 4 weeks' estradiol treatment. With both administration routes estradiol produced a significant increase in urinary 5-HIAA excretion, greatest with transdermal estradiol after 28 days of treatment. The enhancement of serotonin turnover may contribute not only to an improvement of mood and well-being but also to a cardioprotective effect of estradiol observed after hormone substitution in postmenopausal women. |
8794431 | Prevalence of genitourinary and other climacteric symptoms in 61-year-old women. | In a population-based cohort study, 1280 women, aged 61, were interviewed regarding their genitourinary and other postmenopausal symptoms by means of an anonymous questionnaire. The group selected was to constitute all women of 61 years of age living in Uppsala county, Sweden. The response rate was 84%. All were postmenopausal women. Seventy-three percent of the women answering admitted some degree of urinary incontinence and 33% more severe degree. Forty-nine percent reported some degree of stress incontinence, 25% a more severe degree. Thirty-one percent experienced urge incontinence, 14% severely. A minority (4%), had had more than two urinary infections during the last year. The majority (67%) had changed urinating habits, going to the toilet at night and a plained of increased frequency of micturation (8%). Of the participating women, 59% were still sexually active, 43% had trouble with vaginal dryness and 10% with vaginal burning. Vasomotor problems such as hot flushes (30%), daily (33%) and nightly sweating (36%) were mon troubles. Forty-seven percent of the women had asked for medical help for estrogen deficiency problems, 82% were satisfied with the help they had received. Thirty-four percent were on estrogen therapy, 16% had systemic therapy 18% low dose estrogen treatment. |
8794433 | Transdermal estrogen replacement therapy: beneficial effects on hemostatic risk factors for cardiovascular disease. | To assess the effect of estrogen replacement therapy on hemostatic risk factors for cardiovascular disease (CVD) in postmenopausal women during 2 years of treatment. |
8794434 | The effect of medroxyprogesterone acetate and clomiphene citrate on platelet function in menopausal women. | We sought to determine if antiestrogens such as clomiphene citrate (CC) and medroxyprogesterone acetate (MPA) affect platelet activity in postmenopausal patients before and after treatment with estrogens. |
8794435 | Effect of bone density evaluation on hormone replacement therapy prescription. | This study evaluates whether Bone Mineral Density (BMD) results influence HRT prescription. |
8794436 | Endometrial response in estrogen replacement therapy quarterly combined with a progestogen. | The aim of the study was to investigate the endometrial histology and the bleeding pattern under a hormone replacement therapy regimen with continuous estrogen quarterly bined with a progestogen. |
8794437 | Nocturnal micturition, sleep and well-being in women of ages 40-64 years. | To study the relationship between sleep and nocturnal micturition in women 40-64 years old. |
8794439 | Genotypes of the vitamin-D-receptor gene and bone mineral density in Caucasoid postmenopausal females. | To evaluate the relation of bone mineral density (BMD) to inherited polymorphisms within the gene coding for the vitamin D receptor (VDR) in postmenopausal women. |
8794438 | Salmon calcitonin plus intravaginal estriol: an effective treatment for the menopause. | Intravaginal estriol (E3) effectively improves postmenopausal genito-urinary disturbances, without stimulating endometrial proliferation. The aim of the present study was to evaluate the effect of intravaginal estriol (E3) plus nasal spray salmon calcitonin (sCT), to improve neurovegetative symptoms and to prevent the decline of bone mineral density (BMD) of postmenopausal women. |
8794442 | A randomized, double-blind, multicentre study comparing the clinical effects of two sequential estradiol-progestin combinations containing either desogestrel or norethisterone acetate in climacteric women with estrogen deficiency symptoms. | The aim of this study was pare a new estradiol-desogestrel (E2-DG) regimen with an E2-norethisterone acetate bination (Trisekvens) regarding the treatment of plaints, bleeding pattern, histology of the endometrium and the occurrence of adverse experiences. |
8794443 | Interferon-beta, an autocrine cytokine, suppresses human fetal skin fibroblast migration into a denuded area in a cell monolayer but is not involved in the age-related decline of cell migration. | The migration of human skin fibroblasts into a denuded area in a cell monolayer declined during in vitro and in vivo aging. We carried out a study to determine whether this age-related decline in cell migration was mediated by the autocrine cytokine interferon-beta (IFN-beta), which has been reported to suppress the proliferation, chemotaxis and collagen synthesis of human fibroblasts. Actually, IFN-beta specifically suppressed the migration of TIG-3S human fetal skin fibroblasts into a denuded area in a cell monolayer, as shown by the dose response experiments of IFN-beta and neutralizing anti-IFN-beta antibody. IFN-beta also inhibited their collagen synthesis but the addition of type I collagen could not reverse IFN-beta-induced inhibition of cell migration. Double strand RNA, which has been generally known to induce IFN-beta in human skin fibroblasts, suppressed the migration of TIG-3S cells. Next, a study was done to determine whether IFN-beta and double strand RNA suppressed the migration of TIG-3S cells in late passages as well as early passages, or whether neutralizing anti-IFN-beta antibody stimulated the migration of TIG-3S cells in late and middle passages. IFN-beta and double strand RNA suppressed the migration of TIG-3S cells in middle (PD45) and late (PD55) passages as well as in early passages (PD23-28). Neutralizing anti-IFN-beta antibodies could not reverse the low migratory activity of middle and late passage cells to the high migratory activity of early passage cells. These results indicated that the autocrine cytokine IFN-beta did not seem to be involved in the age-dependent decline of fibroblast migration. |
8794440 | An earlier fracture as a risk factor for new fracture and its association with smoking and menopausal age in women. | The purpose of this study was to investigate whether a previous fracture is a risk factor for fracture later in life and its association with tobacco smoking, menopausal age and the use of oral contraceptives. This is an epidemiological population study based on a questionnaire. A sample of 10000 women from seven birth cohorts between 1900-1940 was obtained at random from the population register. The overall response rate was 74.6%. The responders (n = 7459) represented 53% of the total population. |
8794444 | Age-related morphological changes in the hippocampus in two mouse strains. | The granule cell number (nGR) in the dentate gyrus (DG) has been reported to vary considerably among inbred strains of mice, thus providing proof of some genetically ponents to this variation. Furthermore, several authors have described age-related morphological changes in the DG in both humans and animals, but there is no general agreement in the literature about the occurrence of such changes. The purpose of this study was to investigate for strain differences in hippocampal structure changes in old C57BL/6J (B) and DBA/2J (D) mice pared with younger ones. The nGR in the DG, as well as other structural parameters of the hippocampus, were determined in female B and D mice of 4 and 24 months. The two-way analysis of variance indicated a significant interaction between 'strain' and 'age' for the nGR, suggesting that this parameter changes differently with age in B and D mice. This finding indicates that these strains could present a differential susceptibility in granule cell aging raising the possibility that age effects on the granule cell population in the DG could be influenced by some hereditary factors. |
8794441 | Cause of vaginal bleeding in postmenopausal women taking tibolone. | To determine the cause of vaginal bleeding in postmenopausal women treated with tibolone. |
8794445 | Epigenetic selection as a possible component of transdifferentiation. Further study of the commitment of hypertrophic chondrocytes to become osteocytes. | Transdifferentiation of hypertrophic chondrocytes into osteogenic cells was induced in 14 day chick embryo femurs by cutting through the region of hypertrophic cartilage. The process was studied in organ culture, using electron microscopy, staining for alkaline phosphatase, immunocytochemistry of collagen type I and proliferative cell nuclear antigen, and in situ localization of DNA strand-breaks. In addition, DNA and RNA synthesis were studied by 3[H]-T and 3[H]-U radioautography. Loss of ponents from the cut edge occurred in culture. During the 12 day period necessary for transdifferentiation we observed phenotypic instability and bi-potentiality, the death of some cells and the gradual promotion of the osteoblastic phenotype in the survivors. Transition from chondrocytic to osteoblastic phenotype progressed stepwise, through variable mosaic intermediates, and involved a few cell cycles including asymmetric (differential) divisions. Proliferating and apoptotic cells were found in close proximity. As judged by the relative proportion of apoptotic cells position of the surrounding intralacunar matrix, negative selection of intermediate cell types displaying chondrocytic and altered mosaic phenotypes occurred. When the osteoblastic lineage was finally established, apoptotic cells were no longer present. Our hypothesis is that after disruption of cell-cell or cell-matrix interactions and lack of growth factors certain cells are selected and channelled through proliferation into the new stable phenotype. This process is targeted by the environment through a set of pre-determined steps. |
8794446 | Heterogeneous aging of macrophage-lineage cells in the capacity for TNF production and self renewal in C57BL/6 mice. | We examined age-related changes in both tumor necrosis factor-alpha (TNF) producing ability and the replicative capacity of macrophage-lineage cells from different anatomical tissues itantly in mice. We have previously demonstrated that alveolar macrophages of aged mice secreted decreased amounts of TNF pared with that of younger counterpart. In this study, it is demonstrated that peritoneal macrophages exhibited increased TNF activity with aging, while the bone marrow-derived adherent cells secreted less TNF activity. In addition, we showed that the numbers of their progenitor cells (GM-CFUs) in the bone marrow increased with age, whereas those in the spleen did not change with aging. We conclude that age associated changes in functions and proliferative capacities of macrophage-lineage cells are tissue dependent. |
8794447 | Dysregulation between TH1 and TH2 T cell subpopulations in the elderly. | We investigated the influence of zinc and its binding proteins on the immune system in 21 elderly and 20 young subjects. We detected a deficiency of zinc in the serum of the elderly. Albumin levels were within physiological range, but alpha 2-macroglobulin was significantly increased in the serum of elderly subjects. Using a whole blood assay, we found decreased production of interferon-gamma (IFN-gamma) and soluble interleukin-2 receptors (SIL-2R) in the elderly, whereas interleukin-10 (IL-10) production was greater than in the young controls. To exclude cellular defects, we measured lymphocyte subpopulations. In elderly subjects, we detected lower quantities of CD8+, CD8+/CD45RA+ and CD4+/CD45RO+ cells, but not CD4+ cells, than in young subjects. Other lymphocyte subpopulations parable for both groups. These findings suggest a dysregulation between TH1 cells and TH2 cells in the elderly, which may be a result of long-term zinc deficiency. Zinc reconstitution showed no beneficial effects as measured by T cell activity. |
8794448 | The limit to human longevity: an approach through a stress theory of ageing. | Survival to old age is enhanced by high vitality and resilience associated with substantial physiological and morphological homeostasis. This is underlain by genes for stress resistance, which confer high metabolic efficiency and hence adaptation to the energy costs of the stresses to which free-living populations are exposed. Under the stress theory of ageing, selection for genes for stress resistance is primary, and achieved life-span is secondary. In some human populations of the modern era, selection for stress resistance is less intense than in earlier times, because of adequate nutrition and reduced exposure to environmental stresses. Such relaxed selection should permit the accumulation of deleterious mutants that are likely to be stress sensitive. Accordingly, increased maximum life-span in future human populations would appear difficult to achieve. |
8794449 | Gene regulation of senescence marker protein-30 (SMP30): coordinated up-regulation with tissue maturation and gradual down-regulation with aging. | Senescence marker protein-30 (SMP30) is a calcium binding protein also called regucalcin. The amounts of SMP30 decrease androgen-independently with aging in the livers of rats. We have studied the expression of SMP30 in livers and kidneys of rats from the embryonic to the senescent stages of life. No transcript was detected in livers or kidneys in day 18 embryos. However, Northern blot analysis showed a marked increase of SMP30 mRNA in livers of neonatal and young rats. The first peak of SMP30 transcript was found in a 5-day-old neonate, in which the amount of mRNA was threefold higher parison with 3- to 6.5-month-old adults. The expression of SMP30 protein started to increase from day 7 and rapidly reached a plateau at day 10. The substantial amounts of protein and transcript were maintained in adults up to 3-6.5 months of age. In the kidney, SMP30 mRNA and protein started to increase at day 21 and reached near-maximal levels at day 35. The levels of transcript and protein remained high in adults up to 3 months of age. As the aging process progressed to senescent stages, the levels of transcript and protein decreased significantly in the liver and kidney of aged rats. Therefore, the age-associated decrease of SMP30 in the liver and kidney may be, in a large part, controlled at transcriptional levels. Furthermore, immunohistochemical analysis showed a similar pattern of changes in SMP30 protein expression during neonate, adult and senescent stages in hepatocytes and renal proximal tubular epithelia. The high expression of SMP30 in the tissue-maturing process and adulthood suggests that SMP30 may be required for the maintenance of highly differentiated hepatic and renal functions. |
8794450 | Abnormal theta response to nociceptive stimuli during sleep EEG in children with febrile convulsions and control children. | Nociceptive stimuli were tested in 373 sleep EEG from 349 children with febrile convulsions and 50 control children (mean age: 2.54 and 2.05 years, respectively). Stimuli consisted of light pecks on each limb with a beveled cut plastic straw or a toothpick. Responses were deemed abnormal if frontal theta episodes would repeat three times without awakening. These abnormal responses appeared in 232 (62%) out of the 373 children of the febrile convulsive group, and in only 4 (8%) out of the 50 children in the normal control group: confidence interval significant at 95%. During sleep recording without stimulation, this sign is directly related to spontaneous theta bursts and inversely related to focal activity, but bears no relationship with sleep induction agents, generalized spike and waves, or delta discharges. In 24 repeat recordings, it begins to disappear at 3.7 years of age. Such responses to nociceptive stimuli should be considered characteristic of febrile convulsions. |
8794452 | Incorporating political socialization theory into baccalaureate nursing education. | Political socialization theory explains how an individual develops a political belief system. As the health care system undergoes dramatic changes, nursing faculty should use political socialization theory to enhance the education of student nurses. A political thread can be woven through the nursing curricula, and students can be socialized to the political role. The new generation of nurses must incorporate a ponent into their professional role identity. Political socialization theory can guide nursing faculty as knowledge of the political system and political skills are incorporated into nursing curricula. |
8794453 | Guiding dialogue in the transformation of teacher-student relationships. | The National League for Nursing at its 1989 biennial convention resolved that nursing curricula be revised to reflect enriched caring practices through egalitarian teacher-student and teacher-to-teacher relationships that reflect cooperation and a sense munity. The distribution of power relationships between student and teacher, teacher and teacher, and teacher and administrator must be reconceptualized and realized before any significant change in nursing education's curriculum can occur. Revising curricula to incorporate such a change in teacher-student relationships begins with dialogue with teachers that is authentic. Authentic dialogue will cause examination and reexamination of assumptions and ideologies about teacher-student relationships. |
8794456 | Women for women's health: Uganda. | The primary health care model targets social, political, and economic environments as key determinants of health for populations, as well as for individuals. If nursing in Uganda is to make a difference in health care es and in the health of all Ugandans, nurses must look broadly at situations and be educated to practice primary health care nursing. After 14 years of civil war, Uganda is finally experiencing a period of reconstruction and rehabilitation: the whole infrastructure is undergoing a face-lift. Ugandan nurses recognize that their educational preparation has stagnated for many years and that it was not only the political unrest in their country that put them behind professionally. They realize that, given the new directions set by the government, they must e prepared to implement primary health care. They are demanding a university education so they may take their place alongside other health care providers prepared at the university level. Some of the most convincing arguments for a university program for nurses came from doctors at the university who spoke about the need to raise the standards of nursing practice, the quality of teachers, and the morale of practitioners. One nurse said: "If we lose hope for a BScN program, I think all the nurses will quit and we won't have any new students going into the profession." This program is designed to improve the health and well-being of all Ugandans, especially the most vulnerable groups of women and children in rural areas, through strengthening and expanding health services by targeting the educational preparation of nurses. Health planners in Uganda envision the professional nurse as key to the implementation of the national health policy of primary health care. University-educated nurses should be able to assess problems, make clinically sound decisions, and act appropriately within the scope of nursing practice. They should be able to interact and consult collegially with other health care professionals. Placed in munity sites, nurses should function independently munity leaders, health education facilitators, primary health care practitioners, and educators for nursing students. Such intervention munity health care by BScN nurses should improve health care utilization and decrease mortality and morbidity from preventable causes. BScN nurses should make an impact on health care policy, nursing education, and primary health care. The evaluation of this project needs to be prehensive as its development and implementation. It will focus on health es, particularly for women and children in rural areas of Uganda. Measurement of the effects of the process of nursing education (the BScN curriculum) in terms of output (nurses educated and placed in rural practice, nursing education, or government policy posts), es (change in health status of munities), and broader impacts (changes in the status of women and in government policy toward women, nurses, or health at the local, regional, and national levels) is planned. An element of sustainability is present, as an operations research structure will be left in place at munity level. Timing, as the saying goes, is everything, and this project has had good timing. Our belief in the efforts and the goals of the project also gave us the strength to get support from various funding agencies for "small" things. For example, we got support from churches in the United States for building schools in Uganda; we persisted with the women's e-generating project when other support was pulled; we got books for the library in Uganda and got clothes, books, and furnishings for the students who came to this country. The motivation for project personnel has been altruism. The services that the two consultants provided to their Ugandan colleagues have extended far beyond the scope of the project. |
8794464 | Synthesis and antihypertensive activity of novel 1-(4-benzyl-1-phthalazinyl)-pyrazolo[3,4-d]pyrimidines. | Convenient Syntheses of derivatives of the pyrazolo[3,4-d]pyrimidines from 1-(4-benzyl-1-phthalazinyl)-3-amino-4-cyano-5-methylpyrazole (1) and carbon disulphide, aryl isothiocyanates, nitriles or guanidine are described. Derivatives pound 1 undergo cyclization to the titled ring system by action of dimethylformamide dimethylacetal or hydrogen sulphide followed by treatment with triethylamine. Some of the pounds were studied as antihypertensive agents. |
8794465 | New 2-pyrazolines of anticipated molluscicidal activity. | A facile one-pot synthesis of 1-substituted carbamoyl or thiocarbamoyl-2-pyrazolines 6 is described. Also, the synthesis as well as the molluscicidal activity of 1,3,5-triaryl- (2), 1-acetyl-3,5-diaryl- (4) 2-pyrazolines are outlined. |
8794466 | Targeting of multiple emulsions to the lungs. | The conventional W/O/W emulsions are readily taken up by the reticuloendothelial system (RES) so that it is necessary to develop either stealth type or tissue specific multiple emulsion for effective targeting. A multiple emulsion system W/O/W containing rifampicin as encapsulant (W/O/W) was prepared. The droplet size was kept small to study targeting independent of passive embolism of larger droplets in the lung capillaries. It was characterised in vitro for drug release through a treated cellophane membrane. A prolonged first order drug release was observed. The W/O/W multiple emulsion system was coated with an o-palmitoyl derivative of mannan (mol.wt. 20,000) to assess its toxicity in vitro and its distribution behaviour in vivo. The multiple emulsion was found to be non toxic at 0.2 ml formulation/10(6) cells level in presence or absence of serum. An intravenous injection of the polysaccharide coated multiple emulsion was given and the tissue distribution of the drug after 1 h and 24 h was investigated. A significant enhancement in lung uptake and a decreased internalisation by spleen was noticed. |
8794467 | Improvement of some pharmaceutical properties of drugs by cyclodextrin complexation. Part 6: Ampicillin. | The potentiality of interaction of ampicillin with beta-cyclodextrin (beta-CD) was investigated by spectrophotometric and vapour pressure osmometric methods. The results revealed formation of a two-to-one plex of the drug in beta-CD. Complexation of the drug with beta-CD was found to increase both the solubility as well as the dissolution rate of the drug. On the other hand, assessment of bioavailability in human subjects depicted highly significant increase in both the rate and extent of absorption of the drug. |
8794468 | Interspecies comparison of in vitro plasma degradation of dynorphin A 1-13. | Enzymatic cleavage of peptides might release metabolites with distinct pharmacological profile. Interspecies differences in the metabolism of peptides might represent a potential source of error when animal data are intended to predict the human situation. Therefore, the metabolism of dynorphin (Dyn) A1-13 was investigated in the plasma of various species used in experimental practice (monkey, rabbit, rat, guinea pig) pared to previously reported human data. The metabolic pathways were evaluated by enzyme inhibition and kinetic analysis, both yielding almost identical results. Rapid metabolism was observed with all dynorphin fragments across all species (half-lives from 0.3 min for Dyn A1-12 in guinea pig plasma to 2.6 min for Dyn A2-12 in monkey plasma). The metabolism of Dyn A1-13 differed mainly with respect to the half-life (from 0.5 min in guinea pig plasma) to 1.1 min in monkey plasma), while the metabolic routes were similar across the species (Dyn A1-12 major metabolite of Dyn A1-13: from 88% in guinea pig plasma to 71% in rabbit plasma). The metabolic fate of Dyn A1-12, the most important metabolite of Dyn A1-13 is much more heterogeneous across the species then the one observed for Dyn A1-13. For a first assessment, the metabolic routes and rates of Dyn A1-13 in plasma of all investigated species, except from guinea pigs, resemble those in human plasma sufficiently. |
8794470 | Influence of sanguinarine on the GABA synthesizing enzyme glutamate decarboxylase in vitro. | The inhibitory activity of the quaternary benzophenanthridine alkaloid sanguinarine on rat brain glutamate decarboxylase (GAD; EC 4.1.1.15) was studied in vitro. A value of Ki 7.10(-4) mol.1(-1) for sanguinarine was found. The inhibition was irreversible and increased during the preincubation time of sanguinarine with the GAD preparation. The results suggest that reaction of the iminium bond in the benzophenanthridine molecule with thiol groups of the enzyme participates in GAD inhibition. As GAD catalyzes the rate-limiting step of GABA synthesis, its inhibition by sanguinarine may contribute to its physiological action in vivo. |
8794469 | Metabolism of dextromethorphan in human liver microsomes: a rapid HPCL assay to monitor cytochrome P450 2D6 activity. | A new HPLC assay was developed to study dextromethorphan O-demethylation to dextrorphan in vitro using human liver microsomes to investigate the activity of the polymorphic monooxygenase cytochrome P450 2D6 (CYP 2D6). The separation of dextromethorphan and its main metabolite dextrorphan was performed on a polymeric C18 reversed-phase column with UV-detection using levallorphan as an internal standard. Liver samples from ten subjects were screened for dextrorphan formation whereby three groups with different abilities to metabolize dextromethorphan could be found. Seven microsomal preparations from extensive metabolizers showed an average dextrorphan formation rate of 298 +/- 68 pmol/mg protein.min, one sample was classified to belong to an intermediate dextromethorphan metabolizer (79 pmol/mg protein.min), whereas two samples of poor metabolizers exhibited significantly lower rates of dextromethorphan metabolism with values of 11 and 27 pmol/mg protein.min, respectively. This assay permits not only a fast in vitro screening for cytochrome P450 2D6 monooxygenase activity but is also an excellent tool to determine potential drug-drug interactions with this important metabolizing enzyme. |
8794471 | Hepato-protective effect of daturaolone isolated from Solanum arundo. | The triterpene daturaolone was isolated for the first time from Solanum arundo Mattei. The structure has been elucidated parison of MS and 1H NMR spectra with the reported literature data, and was confirmed by 13C NMR. pound proved its potency in reducing the harmful effects or in maintaining the normal hepatic physiological mechanisms in both acute and chronic hepato-toxic induced liver damage in rats. |
8794477 | Light distribution by linear diffusing sources for photodynamic therapy. | The distribution of the light emitted by linear light monly employed in photodynamic therapy (PDT) has been investigated. A device is presented which measures the angular distribution of the exiting light at each point of the diffuser. With these data the fluence rate in air or in a cavity at some distance from the diffuser can be predicted. The results show that the light is scattered from the diffuser predominantly in the forward direction. Experiments and calculations show that the fluence rate in air and in a cavity of scattering tissue at some distance from the diffuser has a maximum near the tip of the diffuser, instead of near the middle. However, the fluence rate resulting from an interstitial diffuser in a purely scattering tissue phantom shows a maximum in the bisecting plane of the diffuser as would be predicted when the diffuser emitted light isotropically. The scattering nature of the tissue is expected to cancel the anisotropy of the diffuser. |
8794478 | Quantification of dopamine metabolism in man: a mathematically justifiable approach. | Model derivation, the proposal of the best model to fit the measured data, is a crucial and often neglected step partmental analysis. Since the model which best fits the data in a statistical sense may be simpler than the known physiology of the system, the order plexity) of the model that can be accepted must be determined independently of physiological considerations. Although [18F]6-fluoro-L-dopa (F-dopa) has been used as a tracer for the investigation of presynaptic dopamine metabolism for a number of years, a definitive method of quantitative analysis has not yet emerged. Simple graphical analyses have been used predominantly in clinical studies, partmental analyses have been used to gain a better understanding of F-dopa kinetics. Over the years quantitative approaches to F-dopa metabolism have grown plicated, plex models that rely on the use of parameter constraints, or simplifying assumptions in order to collapse the model to solvable dimensions, have been developed. We propose a partmental model to quantify the metabolism of F-dopa in the striatum. partmental and graphical analyses were performed using this model, and the mathematical expression which relates the results of the two analyses was derived. The ability of our approach to reveal and quantify differences in the dopaminergic metabolism of individuals has been demonstrated in a small number of studies. |
8794479 | The energy correction factor of LiF thermoluminescent dosemeters in megavoltage electron beams: Monte Carlo simulations and experiments. | The energy correction factor of LiF thermoluminescent dosemeters (TLDs) calibrated in Co-60 gamma-rays and used for measurements in megavoltage electron beams has been determined experimentally and theoretically using Monte Carlo simulations. The experiments show that the energy correction factor of 1 mm thick TLD-100 has an average for both rods and chips which varies from 1.036 +/- 1.3% (1 SD) for 4 MeV electron beams to 1.021 +/- 1.3% (1 SD) for 20 MeV electron beams for measurement performed at dmax in PMMA (Perspex). The results of the Monte Carlo simulations were within 0.6% of the experimental results and ranged from 1.041 +/- 0.9% (1 SD) for 2 MeV electrons to 1.028 +/- 0.8% (1 SD) for 20 MeV electron beams. There was no significant difference in the energy correction factors of LiF TLDs irradiated in PMMA or water by Monte Carlo simulation and experiments. Differences in the energy correction factors between rods and chips of the same thickness were negligible both in the experiments and in Monte Carlo calculation. When the diameter of the LiF TLD micro-rod was increased from 1 to 5 mm, the simulated energy correction factors increased by as much as 5% over this energy range. The energy correction factors changed by up to 4% for irradiation of TLD at depths other than at dmax for a 5 MeV mono-energetic electron beam. |
8794480 | Accuracy of Monte Carlo photon transport simulation in characterizing brachytherapy dosimeter energy-response artefacts. | Practical dosimeters in brachytherapy, such as thermoluminescent dosimeters (TLD) and diodes, are usually calibrated against low-energy megavoltage beams. To measure absolute dose rate near a brachytherapy source, it is necessary to establish the energy response of the detector relative to that of the calibration energy. The purpose of this paper is to assess the accuracy of Monte Carlo photon transport (MCPT) simulation in modelling the absolute detector response as a function of detector geometry and photon energy. We have exposed two different sizes of TLD-100 (LiF chips) and p-type silicon diode detectors to calibrated 60Co, HDR source (192Ir) and superficial x-ray beams. For the Scanditronix electron-field diode, the relative detector response, defined as the measured detector readings per measured unit of air kerma, varied from 38.46 V cGy-1 (40 kVp beam) to 6.22 V cGy-1 (60Co beam). Similarly for the large and small chips the same quantity varied from 2.08-3.02 nC cGy-1 and 0.171-0.244 nC cGy-1, respectively. Monte Carlo simulation was used to calculate the absorbed dose to the active volume of the detector per unit air kerma. If the Monte Carlo simulation is accurate, then the absolute detector response, which is defined as the measured detector reading per unit dose absorbed by the active detector volume, and is calculated by Monte Carlo simulation, should be a constant. For the diode, the absolute response is 5.86 +/- 0.15 (V cGy-1). For TLDs of size 3 x 3 x 1 mm3 the absolute response is 2.47 +/- 0.07 (nC cGy-1) and for TLDs of 1 x 1 x 1 mm3 it is 0.201 +/- 0.008 (nC cGy-1). From the above results we can conclude that the absolute response function of detectors (TLDs and diodes) is directly proportional to absorbed dose by the active volume of the detector and is independent of beam quality. |
8794481 | Dose calculation in brachytherapy for a 192Ir source using a primary and scatter dose separation technique. | A dose calculation algorithm for brachytherapy is presented that reduces errors in absolute dose calculation and facilitates new techniques for modelling heterogeneity effects from tissues, internal shields and superficially positioned sources. The algorithm is based on Monte Carlo simulations for specific source and binations. The dose is scored separately, in absolute units, for the primary and different categories of scatter according to the photon scatter generation. Radial dose distributions for the primary dose and the total scatter dose are parametrized using functions based on simple one-dimensional transport theory. The fitted radial parameters are functions of the angle to the long axis of the source to account for the anisotropy of the dose distribution. The kerma in air at the reference point 1 m from the source is also simulated using Monte Carlo techniques and both the dose and kerma are normalized per source emitted radiant energy. The calculated kerma per radiant energy is used together with the measured reference air kerma rate and the ratio of the dose to the kerma to calibrate the calculated absolute dose rate. Data are presented for an 192Ir cylindrical source, bination with water, nylon and stainless steel applicators. Values of the radial dose profiles, specific dose rate constants and corrections to the air kerma for attenuation and scatter in air are calculated. Anisotropy functions for the 192Ir source and a water-equivalent applicator pared to published values. The effects of the applicator wall material on the radial dose distribution are also discussed. |
8794482 | Ion-recombination correction factor ksat for spherical ion chambers irradiated by continuous photon beams. | The large range of reference air kerma rates of brachytherapy sources involves the use of large-volume ionization chambers. When such ionization chambers are used the bination correction factor ksat has to be determined. In this paper three spherical ion chambers with volumes ranging from 30 to 10(4) cm3 have been irradiated by photons of a 192Ir source to determine the ksat factors. The ionization currents of the ion chambers as a function of the applied voltage and the air kerma rate have been analysed to determine the contribution of the initial and general ion bination. The ksat values for large-volume ionization chambers obtained by considering the general ion bination as predominant (Almond's approach) are in disagreement with the results obtained using methods that consider both initial and general bination contributions (Niatel's approach). Such disagreement can reach 0.7% when high currents are measured for a high-activity source calibration in terms of reference air kerma rate. In this study a new 'two-voltage' method, independent of the voltage ratio given by a dosimetry system, is proposed for practical dosimetry of continuous x- and gamma-radiation beams. In the case where the Almond approach is utilized, the voltage ratio V1/V2 should be less than 2 instead of Almond's limit of V1/V2 < 5. |
8794483 | Determination of the relative neutron sensitivity of a C-CO2 ionization chamber. | The neutron sensitivity of a C-CO2 ionization chamber has been experimentally determined in the neutron energy range of 0.1-1.2 MeV. Eleven kU data were obtained which ranged from 0.04 to 0.1 as a function of neutron energy. There were two peaks in the spectrum of the kU factor, and their positions corresponded to the resonance energies of the kerma factors of carbon dioxide, of which the energies are about 0.4 and 1 MeV. The present data agree with the data obtained at the National Institute for Radiological Sciences in Chiba, Japan (NIRS). The energy dependences of the sensitivity were calculated by using the kerma and the W-value ratios of gas to soft tissue parison. The experimental data were reproduced well by the calculations. |
8794484 | Investigation of a phase-only correlation technique for anatomical alignment of portal images in radiation therapy. | A new image registration algorithm based on phase-only correlation is applied to portal images in radiation therapy to detect translational shift. The phase-only correlation shows a sharp peak in the correlation distribution pared to the broad puted from conventional correlation using fast Fourier transform. In this paper, the algorithm of phase-only correlation is described and its applicability and robustness are tested when applied to portal images used in clinical radiation oncology. The results achieved give evidence that the phase-only correlation will deliver an alternative approach for image registration and parison, that may be applicable in routine clinical practice. |
8794485 | A Monte Carlo evaluation of the channel ratio scatter correction method. | Several methods exist to eliminate the contribution of scattered photons during imaging. One of these, the channel ratio (CR) scatter correction technique, uses the change in the ratio of counts from two symmetrical adjacent energy windows straddling the energy photopeak. The accuracy of the results depends upon the assumption that the ratio of the ponents in the two windows (H value) is constant and is independent of the relative size of the scatter contribution. In this study a Monte Carlo simulation was used to investigate the behaviour of the ponent for different source sizes at different depths. Four disc sources containing a 99Tcm solution were simulated at different depths as imaged with a scintillation camera. Two 10% energy windows with 5% offsets to either side of the 140 keV photopeak of 99Tcm were used. The ratio of the scattered counts in the lower energy window to the scattered counts in the upper window (true H value) was determined from the simulation for each source at every depth. Since it is impossible to measure the true H value at different organ depths during a clinical study, the use of an average H value was considered. Scatter correction was applied to the images simulated at the various depths in water. The geometric mean was calculated and attenuation correction performed assuming mono-exponential attenuation. For quantitation purposes the corrected counts were expressed in terms of a references source. The choice of the reference source yielding the best quantitative results was also investigated. Results of this Monte Carlo simulation study show that although the true H value depends on both source size and depth of the source in the scattering medium, the CR scatter correction technique can be applied successfully when an average H value is used. |
8794486 | Optical properties of multicellular tumour spheroids. | Multicellular tumour spheroids grown in vitro have been widely used in cancer research as an experimental preparation with many of the characteristics of tumours. They provide a model system for understanding the optical behaviour of tumour tissue, which is of interest in novel diagnostic and therapeutic procedures. Optical measurements on fresh spheroids in the wavelength range of 600-1000 nm yielded scattering coefficients, absorption coefficients and g values (mean cosine of scatter) of 160-90 mm-1, 0.1-0.4 mm-1 and 0.99, respectively. Following fixation, considerably higher values of scattering and absorption coefficients were seen. The values pared with those reported elsewhere for excised tumour tissue and interpretations of the optical behaviour are suggested. |
8794487 | Radiochromic film as a radiotherapy surface-dose detector. | Radiochromic film is shown to be a useful surface-dose detector for radiotherapy x-ray beams. Central-axis percentage surface-dose results as measured by Gafchromic film for a 6 MVp x-ray beam produced by a Varian 2100C Linac at 100 cm SSD are 16%, 25%, 35%, 41% for 10, 20, 30 and 40 cm square field sizes, respectively. Using a simple, uniform light source and a CCD camera connected to an image analysis system, quantitative 3D surface doses are accurately attainable in real time as either numerical data, a black-and-white image or a colour-enhanced image. |
8794489 | Neurological frontal signs and neuropsychological deficits in schizophrenic patients. | A higher prevalence of neurological signs (NS) has been described in schizophrenic patients pared with controls or patients with other mental illnesses. This study, which includes a sample of 66 DSM-IIIR schizophrenics, was designed to assess the relationship between 7 frontal neurologic signs described by Luria and cognitive disturbances measured by an exhaustive neuropsychological battery. There was a statistically significant relationships between the frontal signs and the cognitive deficits (mean shared variance was 22%) which persisted after correcting for the influence of age, education, and duration of illness. |
8794488 | Working memory capacity predicts language comprehension in schizophrenic patients. | The association between prehension and working memory capacity was evaluated in 25 male DSM-III-R schizophrenic patients (14 inpatients; 11 outpatients), and in 11 male normal controls (no lifetime DSM-III-R disorder). Patients and controls did not differ significantly on age and education. prehension was examined as a function of two types of processing demand: plexity (complex versus simple sentences) and presentation rate (accelerated versus conversational). Schizophrenic patients showed significantly reduced prehension and decreased working memory capacity for pared with controls. Patients showed general difficulty prehending accurately, rather than exhibiting problems with specific grammatical structures. Subject groups were highly accurate and did not differ in their ability to perceive the individual words in sentences presented at the accelerated rate (intelligibility). Presentation rate and plexity prehension accuracy in all groups, however, with increases in rate plexity producing decreases in understanding. Of most importance, theoretically, is the finding that working memory capacity predicted prehension accuracy in both schizophrenic patients and normal controls. Results suggest that prehension deficits in schizophrenic patients may involve a general dysfunction that is associated with working memory capacity for language. |
8794490 | A neuropsychological study of early onset schizophrenia. | Characterizing a pattern of cognitive dysfunction in early onset schizophrenic patients may illuminate neurodevelopmental contributions to the illness. A cohort of chronically institutionalized schizophrenic patients with a variable range of age of onset (range 7-29 years) was administered prehensive battery of neuropsychological tests that included the Luria-Nebraska Neuropsychological Test Battery. After statistical control of age, parental socioeconomic class (SES) effects, and thorazine equivalents, age of illness onset was positively correlated with performance on measures of motor ability, perceptual motor and pure motor speed, receptive and expressive speech, and overall cognition function, and inversely related to severity of negative symptoms; that is, earlier age of onset was associated with worse cognitive performance and an increase in negative symptoms. This study demonstrates that an early age of onset in schizophrenic illness is associated with impairment on tasks which involve motor and language abilities, functions linked to the frontal, temporal, and subcortical regions of the brain. This association is not due to the effects of medication, negative symptoms, or duration of illness. |
8794491 | D-amphetamine challenge effects on Wisconsin Card Sort Test. Performance in schizotypal personality disorder. | The authors assessed the effects on Wisconsin Card Sort (WCST) performance and psychiatric symptoms of 30 mg d-amphetamine, a dopamine and norepinephrine agonist, vs placebo in nine patients with schizotypal personality disorder (SPD). Patients, particularly those who made more perseverative errors, demonstrated amphetamine-associated improvement on WCST performance. The data in this preliminary study suggest that some of the cognitive dysfunction present in SPD may improve with amphetamine challenge. |
8794493 | Span of apprehension deficits in older outpatients with schizophrenia. | Performance on the span of apprehension task, a well-studied information processing task in schizophrenia research, was examined in 11 schizophrenia patients and 11 parison participants, all over the age of 45 years. Subjects detected "T' and "F' targets in briefly-flashed arrays of 1, 6, and 12 letters on the span task. Consistent with previously reported findings in younger schizophrenia patients, the older patients detected significantly fewer targets in the larger (12-letter), but not smaller (1-, or 6-letter), arrays. The older schizophrenia patients also showed significantly slower reaction times in all array-size conditions. Neither age of onset nor duration of illness was significantly correlated with span task performance. The characteristic span of apprehension task deficit found in the older schizophrenia patients suggests that late-life schizophrenia shares mon cognitive impairment with childhood and young adulthood schizophrenia, and provides supportive evidence for a possible stable vulnerability trait deficit in schizophrenia that is independent of age of onset and duration of illness. |
8794492 | Spatial selective attention in schizophrenic, affective disorder, and normal subjects. | Schizophrenic, affective disorder, and normal subjects performed tasks involving exogenous (automatic) and endogenous (voluntary) attention. In the exogenous attention task, schizophrenic subjects demonstrated a greater benefit in response time than did normal subjects. In the endogenous attention task, however, schizophrenic subjects showed a smaller benefit in response time than did normal subjects. These results are consistent with a model of schizophrenia that predicts a deficit in voluntary (endogenous) control, and a disinhibition and therefore enhancement of the automatic (exogenous) processes of spatial selective attention. Affective disorder subjects did not demonstrate a greater benefit in response time than normal subjects in the exogenous attention task, but did show a smaller benefit in response time than normal subjects in the endogenous attention task. The somewhat similar pattern of behavior of schizophrenic and affective disorder subjects suggests that abnormal spatial selective attentional processes may not be specific to schizophrenia. |
8794494 | Stroop interference and facilitation in the cerebral hemispheres in schizophrenia. | A divided visual field presentation of the Stroop colour-word test was used to study interhemispheric (transcallosal) function in schizophrenic and normal subjects. The modified test used a colour strip paired with either an incongruent, neutral or congruent colour word. Interference and facilitation were defined as the difference between the mean reaction times for incongruent stimuli and neutral stimuli and that between neutral stimuli and congruent stimuli, respectively. The stimuli were presented tachistoscopically with the ponents either separated across the midline centrally, up or down from the midpoint (bilateral presentation), or presented to a single visual half-field (unilateral presentation). The inclusion of the 'up' and 'down' bilateral conditions controlled for the reaction time advantage for pared with unilateral stimulus presentations noted in an earlier study (David, 1993a). The difference in reaction time to an pared with a congruent colour-word pairing, the Combined Stroop Effect (CSE), was not affected significantly by stimulus presentation position (bilateral vs. unilateral) in either the control or schizophrenic group, unlike in the earlier study of David. For controls, interference was significantly greater than facilitation for both bilaterally- and unilaterally-presented stimuli. Schizophrenics had a significantly smaller interference effect for bilaterally-presented stimuli, indicating reduced interhemispheric interference in this group. For the control group, there was no significant difference between right and left CSEs, interference being significantly greater than facilitation on both visual half-field presentations. For schizophrenics, the CSE for left-presented stimuli was significantly greater than that for right-presented stimuli. In addition, left-field facilitation was significantly greater than right-field. Reduced Stroop facilitation with right-field presentations in schizophrenic subjects may reflect increased vulnerability of colour-naming by word-reading in the left hemisphere-evidence for the non-unitary nature of attentional processes and disintegration of these in schizophrenia. |
8794496 | The deficit syndrome in the DSM-IV Field Trial. Part II. Depressive episodes and persecutory beliefs. | Patients with the deficit syndrome are remarkable for their decrease in interest in social relationships, suggesting they have an abnormality in those brain regions controlling social behavior and social cognition. To further assess social behavior and social cognition in this group of patients, we examined the relationships among three aspects of the psychopathology: suspiciousness; major depressive episodes; and the deficit syndrome. These features of psychopathology were examined in two clinical samples: stable outpatients from a research clinic (the MPRC sample), and patients in the DSM-IV Field Trial. In both samples, patients with history of a depressive episode had more severe suspiciousness than those without such a history; other psychotic symptoms were not associated with depressive episodes. In the MPRC sample, patients with the deficit syndrome exhibited less severe suspiciousness than nondeficit patients; in the Field Trial sample, this parison had a nonsignificant trend in the same direction. In the Field Trial sample, patients with the deficit syndrome also had less severe delusions with a predominantly social content than did nondeficit patients. These findings suggest suspiciousness is a risk factor for major depression in schizophrenia, and that the decreased interests in social relationships exhibited by deficit syndrome patients is reflected in the content of their delusions. |
8794495 | The deficit syndrome in the DSM-IV Field Trial: I. Alcohol and other drug abuse. | Drug abuse mon in schizophrenia. Previous studies suggested patients with the deficit syndrome have a lower risk of drug abuse than do patients without deficit features. We distinguished deficit and nondeficit groups in the DSM-IV Field Trial dataset, pared the two groups relative to current and lifetime (worst ever) severity of alcohol, cannabis, and other drugs of abuse. Deficit syndrome patients had a lower severity of current use of alcohol and other drugs, but the two groups did not differ significantly relative to cannabis use. Deficit patients also had less severe lifetime use of all three classes of drugs. These findings could not be attributed to differences between the deficit and nondeficit groups in demographics, severity of psychotic symptoms, chronicity of illness, or the quality of information available for the two groups. Deficit categorization and drug abuse were independently associated with poor level of function. Negative symptoms broadly defined were weaker predictors of drug abuse than was the deficit/nondeficit categorization. These findings further support the validity of the deficit syndrome of schizophrenia. Within schizophrenia, groups with relatively high or low risk for substance abuse can be identified. |
8794497 | Latent inhibition in schizophrenia. | Latent inhibition (LI) refers to the retarded acquisition of a conditioned response that occurs if the subject being tested is first preexposed to the to-be-conditioned stimulus (CS) without the paired unconditioned stimulus (UCS). Because the 'irrelevance' of the to-be-conditioned stimulus is established during non-contingent preexposure, the slowed acquisition of the CS-UCS association is thought to reflect the process of ing this learned irrelevance. Latent inhibition has been reported to be diminished in acutely hospitalized schizophrenia patients. If acutely hospitalized schizophrenia patients are preexposed to the CS, they learn the association as fast as, and perhaps faster than, patients who are not preexposed to the CS. This finding has been interpreted as reflecting the inability of acute schizophrenia patients to ignore irrelevant stimuli. In this study, the LI paradigm was identical to the one used in previous reports of LI deficits in schizophrenia patients (Baruch et al., 1988). Latent inhibition was observed in normal control subjects (n = 73), including individuals identified as 'psychosis-prone' based on established screening criteria, and in anxiety (n = 19) and mood disorder (n = 13) patients. Learning scores (trials to criterion) in "acutely' hospitalized as well as "chronic' hospitalized schizophrenia patients (n = 45) were significantly elevated in both preexposed and non-preexposed pared to controls. Acute schizophrenia patients exhibited intact LI. Separate cohorts of acute and chronic schizophrenia patients (n = 23) and normal controls (n = 34) exhibited intact LI when tested in a new, puterized LI paradigm. These results fail to identify specific LI deficits in schizophrenia patients, and raise the possibility that previously observed LI deficits in schizophrenia patients may reflect, at least in part, performance deficits related to learning acquisition. |
8794498 | Further exploration of a latent class typology of schizophrenia. | We previously derived a typology of schizophrenia from a latent class analysis of 447 first-contact non-affective functional psychotic patients from a defined catchment area. Here, using the same sample, we show that the three subtypes, 'neurodevelopmental' (Type A), 'paranoid' (Type B) and 'schizoaffective' (Type C) have different premorbid, phenomenological and treatment response characteristics. A canonical variate analysis of the three subtypes achieved partial separation between the first two subtypes, but the 'schizoaffective' type was less distinct. |
8794499 | Do obstetric complications cause the earlier age at onset in male than female schizophrenics? | pared the age at onset of 184 patients with functional psychoses with and without a history of plications (OCs) as defined by the scale of Lewis et al. (1989). OCs had no significant influence on the age at onset in those patients who had affective psychoses or were non-white. There were 73 white patients with a DSM-III-R diagnosis of schizophrenia. The mean age at onset of those 25 who had a history of at least one definite OC was 2.6 years earlier than that of the 48 patients with no history of OCs. This effect was entirely due to the male patients with histories of OCs who had, on average, a 3.5 years earlier age at onset. There were no gender differences in age at onset among schizophrenics without a history of OCs. We suggest that a subgroup of male patients with a history of OCs is responsible for the earlier age at onset in pared to female schizophrenics. |
8794500 | Incorporating lag effects in register-based age-of-onset distributions in schizophrenia. | Epidemiological studies often use age-of-first-admission from psychiatric case registers to estimate age-of-onset in schizophrenia. Retrospective, interview-based methods have shown that there is a delay between onset of symptoms and eventual contact with psychiatric services, and that this delay can vary both among individuals and at different ages. This delay or lag can confound the interpretation of first admission data such as age-of-onset. To evaluate the potential impact of this factor, we constructed a flexible mathematical model which integrates age-at-first-admission with estimates of this lag, which were derived from interview-based studies and clinical judgement. We applied this model to age-of-first-admission data for 4218 patients with ICD8/9 schizophrenia drawn from a state-wide psychiatric register. Both the raw age-of-first-admission distribution curve and the transformed data ('estimated age-of-onset') reinforce previous findings that (a) there is a wide range of age-of-onset and (b) the shapes of the curves differ between the sexes. Inspection of the mathematically derived distribution supports the proposition that (a) transformation for a lag effect produces a lower onset age and (b) including a variable length of lag produces a change in shape of the distribution. We propose that the mathematical transformation of age-of-first-admission data may have heuristic value, but requires further empirical data on which to base the assumptions of the model. |
8794501 | Month of birth and schizophrenia in Taiwan: effect of gender, family history and age at onset. | Schizophrenic patients have been shown to have a moderate excess of winter births in the areas where seasonal variations in weather are large. In this report, we examined the seasonality of schizophrenic births in Taiwan, which has a subtropical climate. Using nationwide hospitalization data (2429 male and 1320 female schizophrenic patients), we applied the life table method pare the risk of schizophrenia among 12 cohorts of month-of-birth for males and females, respectively. Differences among the risks of the 12 cohorts were tested using the logrank test. The samples were further stratified by family history and age at onset. There was a significant association between the risk of being admitted as a schizophrenic and month of birth for both males and females. The cohorts born in November and January had the highest risks. After stratification, the association was significant only for non-familial, male, and early onset schizophrenic patients. The results indicate that seasonally varying factors might increase the risk of schizophrenia, especially in those without a family history of the disease. Men are more vulnerable to such factors than women, and the schizophrenics resulting from such insults tend to be early onset. |
8794502 | Substance use: a powerful predictor of relapse in schizophrenia. | This study examined substance use among a group of 37 schizophrenia patients participating in a year-long fluphenazine decanoate (FD; Prolixin) dosage reduction study (Inderbitzin et al. (1994) Am. J. Psychiatry 151, 1753-1759). Ten (50%) of the 20 FD dose-reduced patients, and 6 (35%) of the 17 control group patients were identified as substance users. The dose-reduced and control groups did not differ significantly in substance use. We examine here the 37 patients regrouped by substance users (n = 16) versus non-users (n = 21) to determine the effects of substance use. In addition to identifying substance users and types of substances used, we hypothesize that substance users differ demographically from non-users, have worse symptomatology, pliance, higher rates of relapse, and therefore, can confound studies. Clinical and demographic data were obtained. At least half of the substance users were using alcohol or cocaine. The substance use group had a significantly higher severity of illness score on the BPRS at study onset. We found no significant differences between the two groups on other rating scales. The non-use group lived more independently, and the substance use group was younger. The substance use group had nearly twice as many hospitalizations in the 2 years prior to the study, a greater rate of missed appointments in the year before and during the study, and 4 times as many relapses during the year of the study than the non-use group. The key finding was that among 9 of the 37 patients who relapsed in the year of the study, 7 of the 9 had a history of substance use. Substance use was found to be a better predictor of relapse and hospitalization than gradual 50% dosage reduction of FD in the related study. Substance use among schizophrenia patients is a plicating factor. |
8794503 | Relapse in schizophrenia: is there a relationship to substance abuse? | This retrospective study evaluated relapse in 22 patients with paring substance abusers with nonabusers. pliance was ensured as all subjects were treated with decanoate neuroleptics. Substance abuse was documented by multiple urine drug screens. Substance abusers had a significantly higher readmission rate to the pared to nonabusers. These data suggest that in the presence of documented pliance substance abuse remains a major factor contributing towards relapse. |
8794504 | Cortical gray matter volume deficits in schizophrenia: a replication. | We sought to replicate an earlier finding of widespread deficit in cortical gray matter in schizophrenia by testing new samples of 22 schizophrenic patients and 27 controls between the ages of 21-46 years. Brain values for both patients and controls were standardized against age and head size norms derived from a larger control group (n = 73) spanning a wider age range (21-70). Compared to the new age-matched controls, the new schizophrenic sample showed a deficit in gray matter volume affecting the cortex as a whole and enlargement of the lateral and third ventricles. Thus, widespread cortical gray matter deficit is a replicable feature of the brain dysmorphology of schizophrenia in young to middle-aged men. |
8794506 | The relative abundance of dopamine D4 receptor mRNA in post mortem brains of schizophrenics and controls. | An increase in dopamine D4 receptors has recently been reported in post mortem brain samples from schizophrenics. We have attempted plement this finding by assessing the levels of the specific messenger RNA (mRNA) for the D4 receptor, using the technique of quantitative RNA-PCR. No significant differences in the levels of expression of mRNA for the D4 receptor were found in the brains from pared to controls. The relationship between D4 receptors and schizophrenia, therefore, remains unclear. |
8794505 | Small head circumference at birth in schizophrenia. | The growing evidence for neurodevelopmental basis to schizophrenia has focused attention on the prenatal development of individuals who later develop the illness. Several previous studies have shown reduced birth weight (BW) in schizophrenics and one recently reported smaller birth head circumference (BHC). The current pared 67 DSM-III-R schizophrenics and a general population group of 1640, using information obtained from contemporaneous birth records. When gestational age and gender were controlled for, no significant difference was found in BW between the schizophrenics and parison population. However, the preschizophrenics showed significantly smaller BHC for gestational age, suggestive of slower fetal brain growth. |
8794507 | Genetic relationship between dopamine transporter gene and schizophrenia: linkage and association. | This study explores the genetic relationship between schizophrenia and the dopamine transporter gene (DAT) by a variety of methods. In a sample of 48 families--each family containing at least one nuclear family with a pair of affected siblings--we performed linkage analysis using the maximum likelihood (LOD score) method as well as sibpair analysis (identity by descent). In addition, we investigated a sample of 108 nuclear families--index case affected with schizophrenia/chronic schizoaffective disorder--for association using the haplotype relative risk method. Linkage between schizophrenia and DAT using two- and three-point linkage analysis was excluded with all disease models employed. No evidence for association between haplotypes of the VNTR-probe of the DAT and schizophrenia has been detected. Thus, a contribution of the DAT gene to the genetic diathesis of schizophrenia is unlikely in the families studied. |
8794508 | Dopamine D3 receptor Gly9/Ser9 polymorphism and schizophrenia: no increased frequency of homozygosity in German familial cases. | Disturbances in the dopaminergic transmission have been implicated in the etiology of schizophrenia. Recently, an association of schizophrenia with increased homozygosity of a Gly9/Ser9 polymorphism in the dopamine D3 receptor gene (DRD3) has been reported (Crocq et al., 1992; Mant et al., 1994). This finding reflected a departure from the Hardy-Weinberg equilibrium in the genotype distribution observed in schizophrenic patients. The effect was found to be at its strongest in patients with a high familial loading. In the present study, we tried to replicate this finding in a sample of 146 German patients with a DSM-III-R diagnosis of schizophrenia. All patients had a positive family history of major psychiatric disorder including 70 patients with a family history of schizophrenia. Given our sample size, we have a power of 99.8% to detect 2. deviation from the Hardy-Weinberg equilibrium of the reported magnitude. However, we found no evidence of an excess of homozygosity in our schizophrenic patients. This seems to indicate that homozygosity for the Gly9/Ser9 polymorphism at the DRD3 locus is unlikely to confer susceptibility to schizophrenia in the German population. This held true whether the psychiatric diagnoses in the affected relatives of the patient samples was established by the family history or family interview method. |
8794509 | Effect of clozapine on motor function in schizophrenic patients. | It is well established that clozapine is less likely than typical antipsychotic drugs to cause clinically discernible extrapyramidal side-effects. There is a paucity of data, however, on clozapine's motor effects. In this report pare normal controls to groups of chronic schizophrenic patients treated with either typical antipsychotic drugs or with clozapine. Motor function was measured with a target-matching task, a test relying on submaximal sustained force control. Results indicated that patients on clozapine performed with significantly lower accuracy (greater variability) of force control. Even though the clozapine patients were treatment resistant to typical antipsychotic drugs, and many had a history of tardive dyskinesia, we postulate that the observed deficit is likely due to clozapine treatment rather than to earlier treatments or other factors. The observed force control deficit may be the result of an increase in myoclonus and a generally lower level of overall motor activity. |
8794510 | Serum cytokine concentrations in patients with schizophrenia. | Interleukin-1 beta, interleukin-6, tumor necrosis factor-alpha and the soluble interleukin-2 receptor were measured in the serum of 34 healthy controls and 48 patients with chronic schizophrenia using ELISA sandwich assays. No differences were found between the controls and patients. |
8794511 | Depression in schizophrenia: a comparison of three measures. | Depression, as a feature of schizophrenia, is well established. However, clarifying the exact nature of this relationship has been problematic. The clinical measures routinely utilized to evaluate depression have not been specifically designed for use in schizophrenia, and it is well recognized that a variety of depressive symptoms overlap with other mon to this illness, e.g. negative symptoms, neuroleptic induced side effects. The present pared monly used measures of depression (Hamilton Depression Rating Scale (Ham-D), Calgary Depression Scale (CDS) and the depression subscale of the Positive and Negative Syndrome scale (PANSS-D) in a group of outpatients with schizophrenia, evaluating the degree of association between the scales. Additionally, the relationship between each of the depression measures, negative symptoms and extrapyramidal symptoms (EPS) was calculated. Results revealed that all three measures of depression were significantly correlated, although the CDS was unique in its ability to distinguish between depression, negative symptoms and EPS. It is concluded that the CDS, pared with the HAM-D and the PANSS-D, is the most suitable measure of depression in schizophrenia. |
8794512 | The social dysfunction index (SDI) for patients with schizophrenia and related disorders. | The social dysfunction index (SDI) is a new measure designed to assess social dysfunction in schizophrenia and other severe mental illnesses. It is intended to serve clinical and research purposes. Raters can be readily trained and there is low respondent burden with its use. Good psychometric properties were identified in three studies (sample sizes 33, 67 and 113). The SDI assesses a wide prehensive range of social functioning. It includes objective assessment of dysfunction and subjective client assessment of satisfaction with functioning. It produces a summary score, a satisfaction score and a score for each of the ponents of social functioning assessed. Internal consistency is good (alpha = 0.80). Inter-rater reliability is high (r = 0.96). Use of ponent scores was confirmed by factor analysis. There is modest correlation with other measures of social functioning. Evidence of construct validity is demonstrated by findings of differences in social dysfunction between subjects who lived independently vs. those who lived in boarding homes; differences between subjects who were unemployed vs. subjects who were employed; and independence of social functioning from both age and education. |
8794513 | Repetitive behaviors in schizophrenia: a single disturbance or discrete symptoms? | Schizophrenia patients often display multiple repetitive behaviors. We investigated relations among nine repetitive behaviors and evaluated the hypothesis that these behaviors are varied manifestations of a single underlying biobehavioral disturbance. Nine repetitive behaviors from the Elgin Behavioral Rating Scale were assessed in 400 schizophrenia patients residing at a state hospital. A majority of patients were smokers (76.3%) and very few had pica (3%). Several other repetitive behaviors showed substantial frequency. A ponents analysis revealed eight of nine behaviors shared at least 10% of their variance with a ponent. However, a principal factor analysis suggested a five-factor model best represented the data. The five factors and items identifying them were: (1) 'oral consumption' behaviors-polydipsia and smoking; (2) 'Kluver-Bucy' behaviors-bulimia and hypersexuality; (3) 'movement' behaviors-mannerisms/postures and pacing; (4) 'bizarre use of objects'-bizarre grooming and hoarding; (5) 'Pica'. Associations among repetitive behaviors varied. Symptoms such as smoking and polydipsia appeared reliably related, and others such as pica appeared discrete and independent. Overall, the data did not support the 'single disturbance' hypothesis and suggested a multifactorial model is needed to characterize repetitive behavior disturbances in schizophrenia. |
8794514 | Left cerebral hemiatrophy and schizophrenia-like psychosis in an adolescent. | A previous report of cerebral hemiatrophy and schizophrenia added to the list of neurodevelopmental abnormalities associated with schizophrenia. In a new case, the birth history indicated perinatal hemorrhage and prematurity (30-31 weeks of gestation). CT and MR imaging showed reduction in left hemisphere size with ventricular enlargement and mild skull thickening. Loss of periventricular white matter was detected. Changes in skull thickness, size of air cells and volume of the cranial vault may be measurable correlates of putative developmental abnormalities in schizophrenia. |
8794518 | Activation of coagulation and fibrinolysis despite heparinization during successful elective coronary angioplasty. | Our aim was to assess whether the vessel wall trauma induced by balloon inflation during successful elective PTCA results in activation of coagulation and fibrinolysis detectable in circulating blood. In the pilot group (10 patients), when blood was collected under heparinization with adequate anti-Factor Xa activity, catheter-induced thrombin generation was not detected and results obtained from local coronary arterial versus systemic samples did not differ. Locally, von Willebrand factor antigen increased from 73.5 +/- 8.8% to 77.8 +/- 13.1% (p < 0.05) at 5 min after PTCA. In the study group with its 21 patients having adequate heparinization fibrinogen decreased when blood was collected from aorta 15 min after PTCA. In 30% of the patients having the largest calculated area of vessel damage, thrombin-antithrombin III plex and prothrombin fragments (F1+2) spiked by at least 25% during PTCA. In all patients the mean TAT values did not increase, but F1+2 (from 0.56 +/- 0.36 to 0.63 +/- 0.39 nmol/l, mean +/- SD, p < 0.05) and D-dimer (from 268 +/- 37 to 325 +/- 45 ng/ml, p < 0.05) rose between 15 to 30 min after PTCA. In conclusion, in every third patient thrombin generation occurs after successful elective PTCA, implying a need for a tighter control than heparin provides. |
8794519 | Antithrombotic effects of aspirin and LMWH in a laser-induced model of arterials and venous thrombosis. | Antiplatelet drug aspirin and anticoagulant low molecular weight heparin (LMWH) pared as arterial and venous antithrombotic preparations in the rat experimental model of the laser induced thrombus formation. A method to induce microthrombi in small mesenteric vessel (15-25 microns) has been developed to investigate antithrombotic drugs and to study platelet reactions. Mesenteric injuries are induced in the vascular system of Wistar rats with an argon laser. The laser beam induced formation of the vessel wall injury with damage of endothelial cells. Thrombus was formed within seconds after laser injury and grew rapidly. The aggregate can be swept away by the flow and a new thrombus was formed again. This embolization began within the minute following the laser flash. Thrombus formation and embolization were repetitive phenoma. Aspirin (100 mg/kg) and LMWH (1 mg/kg) are approximately the same as to decrease the number of emboli detached from the thrombus and the duration of embolization; both in venules and in arterioles. This results suggest reflexion about the role of platelets in venous thrombosis induced by laser beam. |
8794521 | The Dami cell possesses the platelet collagen receptor VLA-2, but does not mobilize calcium. | Flow cytometric and Western blot analysis showed that Dami cells possess the major platelet collagen adhesion receptor, the integrin VLA-2, and that VLA-2 was expressed in higher levels in a time-dependent manner in DMSO-induced Dami cells. Both control and DMSO-induced Dami cells were able to adhere to collagen as measured in a microtiter-based adhesion assay. It appeared that collagen adhesion was solely mediated by VLA-2, since inclusion of a monoclonal antibody directed against the alpha-2 subunit of VLA-2 in the adhesion assay was able to totally inhibit adhesion. Although Dami cells possess a variety of platelet markers, and are able to mobilize intracellular calcium in response to ADP, U-46619, and thrombin, they were unable to respond to collagen challenge. We concluded that Dami cells may lack some key transducing element present in platelets that prevents them from being activated by collagen. |
8794520 | Effect of aspirin-dipyridamole and heparin and their combination on venous thrombosis in hypercoagulable or thrombotic animals. | Epsilon-amino-caproic acid (EACA) induces a clinically-useful anti-haemorrhagic, mildly thrombotic state while ellagic acid (EA) induces a severe hypercoagulable one. Reversal of these states may on occasion be necessary. The effectiveness of the antiplatelet drugs, aspirin and dipyridamole (ASA/D), in reducing thrombus weight was studied in normocoagulable animals and animals made hypercoagulable with EACA (333mg/kg) or EA (1.2mg/kg). Heparin (114iu/kg) was tested in the EACA group, both alone and bination with ASA/D. Thrombogenicity was measured by weight formed on intravenous platinum wire in one hour. In normocoagulable animals, ASA/D reduced thrombus by 32%. Ellagic acid trebled mean thrombus weight and ASA/D reduced this by 49%, but did not restore normality. EACA increased mean thrombosis by one sixth. Treatment with heparin reduced this by 48% to a level well below that of untreated animals. Addition of a single dose of aspirin/dipyridamole to the heparin regime, reduced thrombosis by a further 31%, reaching to 21% of control thrombus. The results were statistically significant. Kaolin-activated blood clotting time was shortened by EA, but EACA had little effect on it, while ASA/D slightly and heparin markedly lengthened it. |
8794522 | Anti-thrombotic activity of RG13965, a novel platelet fibrinogen receptor antagonist. | RG13965, a pseudotetrapeptide analogue of Arg-Gly-Asp (RGD), inhibited collagen-induced dog, monkey, human, hamster, mouse, and pig platelet aggregation in vitro with IC50 values of 3.7, 4.6, 6.3, 126, 136 and 1600 microM, respectively. RG13965 (3, 10, and 30 mg/kg, i.v.) decreased the incidence of collagen/epinephrine-induced thrombosis in mice from 90% in untreated animals to 63, 37, and 0%, respectively. In hamsters, RG13965 (10 and 30 mg/kg, i.v.) prolonged the time required for formation of a hemostatic plug in severed mesenteric arteries by 1.6- and 3.6-fold, respectively. In a canine model of repetitive platelet thrombus formation in the coronary artery, RG13965 (0.1, 0.3, and 1 mg/kg, i.v.) reversibly inhibited cyclic flow reductions (CFRs) and inhibited ADP-induced ex vivo platelet aggregation by 29, 57, and 77%, respectively. RG13965 (1 pletely inhibited CFRs for at least 40 min. Platelet count was not altered at any dose and template bleeding time was prolonged modestly (1.8-fold) at only the highest dose. RG13965 dose-dependently and reversibly inhibited thrombus formation at doses which did pletely inhibit ex vivo platelet aggregation and only modestly prolonged template bleeding time. |
8794523 | Procoagulant activity and active calpain in platelet-derived microparticles. | Microparticles are released during in vitro platelet activation and have been detected in vivo in several pathologies. Their characterization is of interest as they may play a potential role in hemostasis. Here, we report the formation of microparticles as the result of increases in intracellular Ca2+ brought about by inhibition of Ca(2+)-ATPases. They were isolated following centrifugation of the activated platelet suspension over a sucrose layer. Flow cytometric studies using annexin V-FITC as a probe for aminophospholipids, prothrombinase activity measurements and annexin V inhibition experiments enabled us to evaluate the procoagulant activity of microparticles prepared in this way. The efficiency of the annexin V inhibition (IC50 = 10-20 nM) of this activity confirmed significant anticoagulant properties for this protein. Microparticles also contained the glycoprotein plex, detected in flow cytometry at a density higher than on the remnant platelets. The activation of calpain, a Ca(2+)-dependent protease, in platelets was shown to be more efficient under conditions of a sudden Ca2+ influx. The microparticles contained only the active form of calpain detected by Western blotting using a monoclonal antibody able to recognize both the unactivated and the activated catalytic subunit of the enzyme. However, flow cytometry failed to find significant amounts of active calpain on the microparticle or on the platelet surface. Our results, while confirming the procoagulant activity of microparticles, also document for the first time the exclusive presence of the activated form of calpain, inferring a possible role for this protease in microparticle-mediated functions. |
8794524 | Increased platelet and coagulatory activity indicate ongoing thrombogenesis in peripheral arterial disease. | In peripheral arterial disease (PAD) risk of thrombosis is high and systemic haemostatic derangement thought contributory. We investigated platelet and coagulatory activity in patients with PAD and sought to find the best disease indicator. Stagnation point flow adhesion-aggregometry (SPAA) enables real-time quantitative assessment of platelet adhesion and aggregation under well-defined flow conditions. SPAA and agonist-induced aggregometry (Born method) were performed and concentrations of fibrinogen, fibrin monomer (FM), D-dimer, and plex (TAT) measured in 92 PAD patients and 70 healthy volunteers. Agonist-induced aggregometry detected no differences between patients and controls. SPAA-measured platelet adhesion and spontaneous aggregation (p < 0.001), and concentrations of fibrinogen (p < 0.001), FM (p < 0.001), TAT (p < 0.02) and D-dimer (p < 0.001) were all significantly increased in patients. Neither platelet function nor coagulatory activity was altered in patients receiving aspirin. Sensitivity and specificity in detecting PAD were as follows: SPAA (95%, 93%), fibrinogen (36%, 91%), FM (48%, 84%), TAT (36%, 78%), D-dimer (73%, 80%). Our findings support the concept of ongoing thrombogenesis as being contributory to the progression and possibly to the initiation of PAD. Aspirin alone did not prevent haemostatic hyperreactivity in these patients and flow-mediated platelet function was the most sensitive and specific indicator of advanced disease. This technique thus appears to be valuable, not only for evaluating therapeutic strategies to prevent platelet activation, but also in elaborating platelet-related mechanisms involved in thrombogenesis and atheroma formation. |