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Biomedical subjects

J Shapira

Publications and source records attributed to J Shapira.

At least 73 records · Page 4Linked to original sources

Doppler flow evaluation of pathologic endometrial conditions in postmenopausal breast cancer patients treated with tamoxifen.

A prospective pilot study was conducted to evaluate the usefulness of uterine artery blood flow in the detection of various pathologic endometrial conditions in 39 asymptomatic postmenopausal breast cancer patients who were treated with tamoxifen. No specific pattern was seen for the uterine artery pulsatility index values in the tamoxifen-treated patients that could be related to any specific endometrial lesions, nor were any specific changes observed in the pulsatility index value with increasing severity of the pathologic endometrial conditions. Similarly, no correlation was found between ultrasonographically measured endometrial widths and uterine artery pulsatility index values. Thus, although pulsed Doppler flow ultrasonography has been shown previously to be effective in the detection of uterine cancer in non-tamoxifen-treated post-menopausal patients, it probably does not contribute to the assessment of endometrial lesions in post-menopausal breast cancer patients treated with tamoxifen.

Arteries↗

The expression of HLA class I antigen in prostate cancer in relation to tumor differentiation and patient survival.

The expression of HLA class I antigens was studied using the immunoperoxidase technique on 30 patients with prostate cancer and 29 patients with benign prostatic hypertrophy (BPH). Forty-three percent of the tumors stained positive, in contrast to 21% of the BPH. An inverse relationship was noted between class I expression and degree of tumor differentiation: 88% of the well-differentiated tumors (8/9) expressed class I antigen, compared with 33% (3/9) of the moderately differentiated and 16% (2/12) of the poorly differentiated tumors. No significant survival difference was found between those with class I-positive and -negative tumors. However, when both class I expression and degree of differentiation were considered, those with positive tumors at each level of differentiation had better survival than those with negative tumors. These data suggest that HLA class I expression may serve as a finite prognostic factor and may have relevance in future immunotherapy.

Adenocarcinoma↗

Physostigmine ameliorates the delusions of Alzheimer's disease.

Alzheimer's disease (AD) patients frequently manifest delusions, and the cholinergic deficiency of AD may contribute to this aspect of the psychopathology of the disorder. In a double-blind, crossover study involving two patients, we compared the antidelusional efficacy of physostigmine, an acetylcholinesterase inhibitor, with haloperidol, a widely used neuroleptic agent. Physostigmine ameliorated the delusions and produced fewer side effects. These preliminary observations suggest that the cholinergic deficiency contributes to the occurrence of delusions in AD and cholinergic therapy may have a role in the treatment of the delusional symptoms.

Aged↗

Endometrial changes in postmenopausal women treated with tamoxifen for breast cancer.

OBJECTIVE: To evaluate whether risk factors, other than tamoxifen, can be identified for the development of endometrial pathologies in postmenopausal breast cancer patients treated with tamoxifen. DESIGN: A cross-sectional study. SETTING: Department of Obstetrics and Gynaecology and Oncology Clinic, Sapir Medical Center, Kfar Saba, Israel. SUBJECTS: 77 asymptomatic postmenopausal women, treated with tamoxifen for breast cancer. Of these, 55 had no endometrial tissue and 22 had endometrial tissue obtained by biopsy. MAIN OUTCOME MEASURES: Demographic characteristics, health habits, risk factors, vaginal ultrasonographic evaluations of endometrial thickness and texture, and histologic evaluations of endometrial biopsies. RESULTS: Overall, there was a high rate (29%) of endometrial pathological change among the 77 asymptomatic postmenopausal women. There were no significant statistical differences in the features tested between the two groups. CONCLUSION: It is impossible to predict which postmenopausal women will develop pathological endometrial changes after treatment with tamoxifen and thus a routine periodic endometrial sampling-follow up is suggested for all postmenopausal women being treated with this agent.

Aged↗

Adriamycin nephropathy: a model to study effects of pregnancy on renal disease in rats.

The influence of pregnancy on the evolution of primary renal disease is still a matter of controversy. Hypertension and derangement of renal function may occur. The pathophysiology of these complications is poorly understood. In the present study, we assessed the influence of pregnancy on the evolution of adriamycin (Adr) nephropathy. Four groups of animals were studied: 1) control virgin rats (C), 2) normal pregnant rats (NP), 3) virgin rats with nephropathy (Adr), and 4) pregnant rats with nephropathy (Adr-P). Inulin clearance measured at the end of pregnancy in awake rats was similar in NP (1.68 +/- 0.20 ml/min) and C (1.39 +/- 0.03 ml/min). In Adr-P rats, it tended to decrease (1.22 +/- 0.7 vs. 1.93 +/- 0.44 ml/min in Adr rats). Mean arterial pressure was increased in Adr-P rats (137 +/- 2.5 vs. 95 +/- 3.2 mmHg in NP; P < 0.001). Urinary protein excretion was 216 +/- 61 mg/day in Adr-P compared with 28.7 +/- 18 mg/day in Adr (P < 0.001). A significant increase in the glomerular thromboxane B2-to-prostaglandin E2 ratio was found in Adr-P rats (1.15 +/- 0.26 vs. 0.52 +/- 0.12 in Adr rats; P < 0.03). In NP rats, no change was observed. Kidneys and placentas were normal on light and electron microscopy. Thus pregnant rats with adriamycin nephropathy developed a clinical picture with several features of preeclampsia. Changes in glomerular prostanoid synthesis might play a role in the development of this complication.

Anesthesia↗

Soluble histocompatibility antigen class I in breast cancer patients in relation to tumor burden.

Serum beta-2 microglobulin (B-2M) levels were studied in 365 breast cancer patients and 210 age-matched controls. The patients were divided into three groups: Group A, new patients at diagnosis; Group B, patients at follow-up; and Group C, metastatic patients. The mean B-2M of all breast cancer patients plus or minus one standard deviation (3.5 +/- 1.2; range, 1.1 to 5.9) was significantly higher than normal controls (1.29 +/- 0.49; range, 0.3 to 2.3; P less than 0.005). When the three patient groups were compared with each other, the mean B-2M level of Group A (3.0 +/- 1.5; range, 0.9 to 6.9) was similar to that of Group C (4.22 +/- 1.1; range, 2.0 to 6.4). The mean B-2M of both Groups A and C was significantly higher than that of Group B (2.38 +/- 1.02, range, 0.4 to 5.4; P less than 0.001). In Group A the mean B-2M decreased significantly after a 12-month period and reached the mean level of Group B but not that of normal controls. When patients in Group B were analyzed by their stage of disease at diagnosis, there was no significant difference between Stages I and II. There was a significant difference in the mean B-2M levels between Stages I and III. In relapsing patients, mean B-2M levels increased. These findings suggest that serum B-2M levels may reflect tumor burden, and even in patients at follow-up, occult tumor cells may activate the immune system.

Adult↗

Expression of HLA class I and class II in gastric carcinoma in relation to pathologic stage.

The expression of HLA class I and II antigens was studied in 41 patients with gastric cancer and in 2 normal stomachs. The normal gastric epithelia were diffusely stained for class I antigens. No staining was observed for class II. In gastric cancer an overall reduction in staining was observed, which was related to the degree of tumor penetration through the gastric wall. In tumors which penetrated the mucosa and submucosa only, 80-90% of tumor cells were stained for class I, as well as the normal areas surrounding the tumor. On the other hand, in tumors which penetrated through the organ to the fat, only 10-20% of cells were stained. Staining for class II was observed in only 12 cases, all of them advanced, with penetration to muscle or fat. No staining was observed in the normal areas surrounding the tumor. The importance of HLA antigens in immune surveillance is discussed.

Gastric Mucosa↗

Agitation in the demented patient. A framework for management.

The inability to manage agitation has led to institutionalization of the patient by the family, overuse of physical restraints, and inappropriate use of psychotropic medication, all of which confound the behavior of the demented individual. It is not only the behavior of the patient but also the interpretation of that behavior that is critically important in the successful management of agitation. Caregivers must be careful to assess their own reactions and responses to patient behaviors before actions are taken that may not lessen agitation but increase the frequency and intensity of patient action.

Aged↗

Stable bimodal response to cholinomimetic drugs in Alzheimer's disease. Brain mapping correlates.

We investigated quantitative EEG brain mapping as a physiologic marker of drug response while studying the stability of intersubject variability in patients with Alzheimer's disease (AD) who were receiving bethanechol through intracerebroventricular (ICV) shunts. Two of the patients had previously demonstrated cognitive and behavioral improvements on medication; the third had cognitive deterioration complicated by agitated depression. All three patients were reexamined in a dose-response paradigm. Serial brain mapping examinations were performed along with brief cognitive testing. All patients showed drug responses that were comparable with responses during their initial dose-response phase. There were strong linear correlations between global decreases in 2 to 6 Hz slow-wave activity and cognitive improvement. Brain mapping demonstrated that slowing decreased in magnitude and field with increasing dose until optimal dose was reached; with supra-optimal doses, the magnitude and field of the slowing increased dramatically. These results suggest that the quality of cholinomimetic drug responses are stable over time in individual patients, and that magnitude and pattern of slow-wave activity as measured by brain mapping may be useful in monitoring treatment with cholinomimetic agents.

Alzheimer Disease↗

Reduced cardiotoxicity of doxorubicin by a 6-hour infusion regimen. A prospective randomized evaluation.

In order to evaluate the possible cardiosparing effect of a prolonged infusion of doxorubicin as compared with the standard mode of administration 62 consecutive patients with metastatic carcinoma of the breast or carcinoma of the ovary Stage III or IV were prospectively randomized to receive doxorubicin either as a rapid infusion over 15 to 20 minutes at 8 AM or as a continuous infusion over 6 hours, 8 AM to 2 PM. The remaining protocol was identical for the two groups. The cardiotoxic effect of doxorubicin was evaluated by history and physical examination and by the decline in resting ventricular ejection fraction (LVEF) as determined by gated pool radionuclide angiography with technetium 99m (99mTc) and by the decline in the height of the QRS complexes in the standard leads of the echocardiogram (ECG). Initially there were 31 patients in each group. The cumulative dose of doxorubicin, was 410 mg/m2 +/- 42 SD in the standard infusion group and 428 mg/m2 +/- 48 SD in the 6-hour infusion group. The mean decline in LVEF after a cumulative doxorubicin dose of 300 mg/m2 was 17% in the first group and only 4.1% in the second. After 400 mg/m2 the mean fall in LVEF was 21% in the first group and 6% in the second. The mean decline in QRS voltage after 300 mg/m2 was 29% and 1.5%, respectively. Four patients, all in the standard infusion group, developed congestive heart failure. These data suggest that slow infusion of doxorubicin is associated with reduced cardiotoxicity.

Breast Neoplasms↗

Intracerebroventricular bethanechol for Alzheimer's disease. Variable dose-related responses.

Five male patients participated in a pilot open-label study of dose-related aspects of response to intracerebroventricular bethanechol in Alzheimer's disease. No patient had remission of symptoms, but three patients improved symptomatically and on tests of memory. Improvement was evident over a restricted range of doses for each subject, and symptoms were worse at doses below and above the optimal range. There was little overlap in the range of doses producing improvement among these three. Two patients had no consistent improvement in memory, and agitation, depression, paranoia, and seizures developed during treatment. Qualitative differences and variability in dosages producing responses complicate the identification of true drug response in the treatment of Alzheimer's disease.

Alzheimer Disease↗

Captopril, but not diltiazem, favorably affects the course of early chronic renal disease in rats.

The concepts that increased intracellular Ca2+ content and increased glomerular capillary pressure play an important role in the progression of chronic renal diseases has led to the suggestion that treatment with calcium-blocking agents (diltiazem; CBB) or converting enzyme inhibitors (captopril; CEI) may be indicated to prevent renal failure. We studied the effects of CCB and CEI on the early course of adriamycin (ADR) nephropathy, where glomerular pressure has been shown to be unchanged, blood pressure was only mildly elevated and renal failure incipient. Animals were studied 2, 7, 12, 16 and 20 weeks after the second injection of ADR, 2 mg/kg. In treated rats, blood pressure remained normal. At the end of the study, proteinuria and serum creatine were lower in ADR-CEI than in ADR rats (149 +/- 42 vs. 616 +/- 90 mg/day, p less than 0.01 and 0.36 +/- 0.04 vs. 0.58 +/- 0.02 mg%, p less than 0.01, respectively). ADR-CCB had values similar to those of untreated ADR rats. Mesangial expansion and focal glomerulosclerosis were present only in ADR and ADR-CCB rats, whereas in ADR-CEI rats the glomeruli were virtually normal. Glomerular 45Ca uptake was increased in ADR, decreased in ADR-CCB rats, and normal in ADR-CEI. Glomerular 6-keto PGF1 alpha and TxB2 were significantly increased in ADR rats, and both treatments decreased TxB2. The results suggest that endogenous angiotensin II is important for the early progression of glomerular injury toward renal insufficiency, while tissue Ca2+ accumulation may play an important role in more advanced phases.

Animals↗

Organic personality disorder in dementia syndromes: an inventory approach.

Personality alterations were investigated in patients with dementia of the Alzheimer type (DAT), multi-infarct dementia (MID), and normal control subjects, using a standardized informant-rated personality inventory. Personality alterations were observed in all patients, and the two diagnostic groups exhibited many similar behavioral alterations. DAT patients had significantly greater alterations in maturity and exhibited less personal control compared with the MID patients; the latter manifested more apathy and remained more affectionate and easy-going. Few correlations were found between the severity of dementia and the magnitude of behavioral changes. Personality alterations are an important and consistent aspect of the phenomenology of dementing disorders.

Aged↗

Effects of changes in sodium balance on prostaglandin synthesis and prostaglandin E2 9-ketoreductase activity in the rat kidney.

The in vitro synthesis of prostaglandins E2 and F2 alpha by renal cortex, medulla and papilla was measured in normal rats and in rats receiving either a low or a high sodium intake for 14 days. The production of both prostaglandins was unchanged in the cortex. In the medulla, both low and high sodium intakes led to a similar decrease in prostaglandin E2 synthesis in vitro, but prostaglandin F2 alpha synthesis was unchanged. In the papilla, a low sodium intake increased prostaglandin E2 synthesis. The activity of prostaglandin E2 9-ketoreductase, a cytosolic enzyme catalysing the conversion of prostaglandin E2 to prostaglandin F2 alpha, was unchanged in cortical preparations. In medullary slices, prostaglandin E2 9-ketoreductase activity was decreased by both sodium depletion and loading. In the papilla, prostaglandin E2 9-ketoreductase activity was slightly decreased by sodium loading and increased with sodium depletion. These results obtained in the rat are at variance with findings in the rabbit. The role played by prostaglandin E2 9-ketoreductase in the regulation of prostaglandin biosynthesis during changes of sodium balance remains controversial.

Animals↗

Tissue regeneration principles applied to separation of fused teeth.

A two-step surgical procedure for separating a central incisor fused to a supernumerary tooth with a 4-year follow-up is described. The fusion was between the crowns and 3/4 of the root length. The roots were connected by web-like radio-opaque tissue. The periodontal ligament could be followed along the lateral aspect of the roots and was continuous along the base of the web. In the first surgical phase, a full-thickness semilunar flap was raised; a fissure bar was cut along and through the web up to the approximate location of the junctional epithelium and the flap was sutured. It was assumed that cells from the bone surrounding the web and/or connective tissue cells from the flap had migrated into contact with the web hard tissue. This resulted in replacement resorption of the web. The connective tissue replacing the web acted as a septum separating the 2 parts of the root. The distal root was extracted. Resorption continued until most of the web disappeared from the wound. At this point, the remaining layer of web tissue was thin enough to allow repopulation of the resorbed surface with periodontal cells from the buccal and palatal sides of the web. The successful clinical outcome supports the assumption that new attachment consisting of periodontal ligament and cementum was formed following the 2-step surgical procedure. Application of the technique is limited by the width of the fusion rather than by its length.

Child↗