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Biomedical subjects

M Baum

Publications and source records attributed to M Baum.

At least 19 recordsLinked to original sources
PubMed1992

Induction of transforming growth factor beta 1 in human breast cancer in vivo following tamoxifen treatment.

We have investigated the ability of tamoxifen to regulate members of the transforming growth factor beta (TGF-beta) family in human breast cancers in vivo. Using immunohistochemical techniques, we find that 3 months of tamoxifen treatment causes a consistent induction of extracellular TGF-beta 1 in breast cancer biopsies, compared with matched pretreatment samples from the same patient. The induced TGF-beta is localized between and around stromal fibroblasts and appears to be derived from these cells. Lower levels of TGF-beta 1,-beta 2, and -beta 3 seen in epithelial cells were not altered by tamoxifen treatment. The increased stromal staining of TGF-beta 1 occurred in estrogen receptor-negative as well as estrogen receptor-positive tumors. These results provide in vivo evidence for a novel, estrogen receptor-independent mechanism of action for tamoxifen, involving the stromal induction of a potent growth inhibitor for epithelial cells.

Biomarkers, Tumor↗
PubMed1992

Tidal volume, breathing frequency, and oxygen consumption at different pressure support levels in the early stage of weaning in patients without chronic obstructive pulmonary disease.

The objective of this study was to evaluate the influence of different PSV levels on VT, F, VO2 in the early weaning phase of patients without chronic obstructive pulmonary disease. These parameters were tested for the predictive power for the success of the weaning. Patients on SIMV were studied during the first weaning attempt with PSV. Depending on their ventilatory support demands after 24 h they were divided into responders (patients breathing on CPAP) and nonresponders (patients being on a more invasive ventilatory mode). 14 ICU patients without pre-existing pulmonary disease being ventilated for at least 3 days entered the study. 2 of them could be studied a second time after failing the first weaning attempt. Beside the level of ventilatory support no other changes (drugs, nutrition) were allowed. VO2, VT, F were measured by a computer controlled, metabolic unit connected to the expiratory port of a Siemens Servo Ventilator. In addition, airway pressures, arterial pressure and heart rate were recorded. The measurements were performed at PSV of 5, 10 and 20 cmH2O. Arterial blood-gases were drawn at the end of each 60 min lasting PS period. Responders and nonresponders could be separated by the response of VO2, VT and F to a change in PS 10 to PS 20 cmH2O. Patients who significantly increased VT and significantly decreased F did not fulfil our weaning criteria. Our responders did not show a significant change in these two parameters, but a significant increase in VO2 at PS 20 cmH2O could be observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Desmoid tumours treated with triphenylethylenes.

Desmoids are uncommon mesenchymal tumours that occur at single or multiple anatomical sites, occasionally in association with polyposis coli. This paper describes the use of the triphenylethylene tamoxifen, and a new chlorinated analogue, toremifene, in 20 patients with progressive desmoid disease. Clinical responses ranging from stabilisation of disease to complete resolution were observed in 65% of cases. The antitumour activity of this group of drugs has been attributed to their anti-oestrogenic behaviour. However, desmoids provide a clinical model of a purely mesenchymal tumour which appears to respond despite having generally low levels of hormone receptor. This emphasises the significance of stroma within breast (and other) tumours, in particular how the stroma may regulate the response to these drugs regardless of receptor status.

Adult↗
PubMed1992

Long term effects of tamoxifen. Biological effects of Tamoxifen Working Party.

A total of 153 breast cancer patients who participated in two trials of adjuvant tamoxifen and who had not recurred were recruited into a study of the long term effects of tamoxifen. There were 60 controls (no tamoxifen), 73 ex-users (mostly for 2 years) and 20 current users (median treatment duration 72 months) and the median follow-up time was 7 years. A wide ranging study of lipids, hormones, bone density and haemostasis was undertaken. When compared with controls, current users had lower cholesterol levels (especially low density cholesterol), and increased triglyceride levels. Thyroid hormones were higher and sex hormone binding globulin was almost doubled. Bone density was non-significantly higher, clotting times were slightly shorter and fibrinogen and antithrombin III levels were reduced. However few of these changes persisted in ex-users, suggesting that most of the biological effects of treatment are reversible on cessation of treatment. This is reassuring for potentially negative side-effects, but also indicates that potentially positive 'side-effects' such as cholesterol lowering only occur while on active treatment.

Bone Density↗
PubMed1992

Contralateral renal abnormalities in multicystic-dysplastic kidney disease.

Multicystic-dysplastic kidney (MCDK) disease has been associated with contralateral genitourinary tract abnormalities; however, neither the nature nor the prevalence of the contralateral renal lesion has been delineated. We retrospectively studied patients with MCDK disease to determine the prevalence of contralateral renal abnormalities and of other urologic anomalies. Forty-nine patients, ranging in age from neonates to 6 years, were examined by renal ultrasonography, excretory urography or nuclear medicine scanning, and voiding cystourethrography; 51% of the patients had an associated urologic abnormality. The abnormality was contralateral to the MCDK in 19 patients (39%), ipsilateral in 3 patients (6%), and involved the bladder wall in 3 patients (6%). The most common contralateral genitourinary tract abnormality was vesicoureteral reflux (18%) followed by ureteropelvic junction obstruction (12%). We conclude that urologic anomalies are common in patients with MCDK disease; contralateral vesicoureteral reflux is the most common abnormality identified.

Child↗
PubMed1992

Cognition and immune function in HIV-1 infection.

OBJECTIVES: To determine (1) whether there were differences in cognition between HIV-1-seropositive and HIV-1-seronegative homosexual men and (2), if so, whether these differences could be explained by the degree of immunosuppression [i.e., CD4 cell count and immunoglobulin A (IgA) levels]. DESIGN: A cross-sectional design was used to compare 66 HIV-1-seropositives (Centers for Disease Control stages II and III, n = 56; stages IVA and IVC-2, n = 10) and 37 HIV-1-seronegatives. The HIV-1-seropositives were classified into three immune groups based on their CD4 cell count (x 10(6)/l) and serum IgA level (mg/dl): (1) moderate [(n = 35) CD4 greater than 400, IgA less than 300]; (2) mixed [(n = 22) either CD4 greater than 400 and IgA greater than 300 or CD4 less than 400 and IgA less than 300] and (3) poor [(n = 9) CD4 less than 400, IgA greater than 300]. HIV-1-seronegatives formed the 'good' immune group (CD4 greater than 400 and IgA less than 300). METHODS: The four groups were compared on tests of verbal and visual memory, information-processing speeds, visuospatial skills, language processes, attention, psychomotor reaction time, and mental status. Factors other than HIV-1 sero-status that can influence cognitive performance were tested as covariates. RESULTS: HIV-1-seropositives had slower information-processing speeds and decreased verbal and visual memory, compared with HIV-1-seronegatives. These differences in cognition were not due to differential immunosuppression or to clinical status among the HIV-1-seropositives. CONCLUSIONS: Cognitive alterations occur in HIV-1-infected individuals before AIDS and appear to be independent of clinical status and degree of immunosuppression as measured by CD4 cell count and IgA levels.

Adult↗
PubMed1992

Developmental changes in rabbit juxtamedullary proximal convoluted tubule acidification.

The transporters responsible for apical proton secretion were examined in neonatal and adult proximal convoluted tubules (PCT). Transporter activity was assayed from the rate of recovery of cell pH after cell acidification following exposure to NH4Cl. Cell pH was monitored in in vitro perfused tubules using the pH sensitive dye 2',7'-bis(carboxyethyl)-5,6-carboxyfluorescein. Recovery from an acid load in adult PCT occurred at 0.52 +/- 0.09 pH units/min in the presence of sodium and 0.25 +/- 0.05 in the absence of sodium (p less than 0.05). One mmol/L N-ethylmaleimide, an inhibitor of the H(+)-ATPase, inhibited the sodium-independent pH recovery from an acid load consistent with a H(+)-ATPase on the apical membrane. In neonatal PCT, recovery from an acid load was 0.39 +/- 0.08 pH units/min in the presence of sodium and only 0.08 pH units/min in the absence of sodium (p less than 0.05). Studies using 4 mmol/L luminal amiloride, an inhibitor of the Na+/H+ antiporter, were consistent with a larger fraction of pH recovery from an acid load in neonatal PCT being due to the Na+/H+ antiporter compared with adult PCT. Thus, maturation of the PCT involves an increase in activity of a sodium-independent proton secretory mechanism, presumably the H(+)-ATPase.

Animals↗
PubMed1992

Intracellular cystine loading causes proximal tubule respiratory dysfunction: effect of glycine.

The present study examined proximal tubular respiration in control proximal tubules and proximal tubules loaded with cystine using 2 mmol/L cystine dimethyl ester. Basal oxygen consumption was significantly less in cystine-loaded tubules (20.6 +/- 0.5 versus 12.1 +/- 0.6 nmol O2.min-1.mg protein-1, p < 0.001). In the presence of 10(-4) mol/L ouabain, an inhibitor of the NaK ATPase, oxygen consumption was 10.2 +/- 0.7 nmol O2.min-1.mg protein-1 in control tubules and 11.4 +/- 1.0 nmol O2.min-1.mg protein-1 in cystine-loaded tubules. Thus, proximal tubular intracellular cystine loading specifically inhibits oxygen metabolism directed toward transport. Compared with control proximal tubules, cystine-loaded proximal tubules also had a lower rate of O2 consumption when the cells were permeabilized to sodium with nystatin and when mitochondrial respiration was uncoupled. Glycine, an amino acid that is cytoprotective to hypoxic proximal tubule injury, ameliorated the respiratory dysfunction observed in cystine-loaded tubules.

Animals↗
PubMed1992

Chest radiography in the management of breast cancer.

This study was undertaken to assess the utility of chest radiography (CXR) in the management of patients with breast cancer and to devise a suitable imaging policy for such patients. A retrospective analysis was performed of the case notes and the CXRs of a series of 141 patients presenting to this hospital in 1980 with a diagnosis of early breast cancer. Data retrieved covered the entire clinical course to date and included the number of CXRs performed for a clinical reason and the number performed as "routine". Correlation of the result of every CXR requested to subsequent therapeutic decision-making throughout the complete clinical course of each patient was undertaken and the proportion of CXRs initiating a management change, or performed for a clinical reason, out of the total requested was assessed. A total of 1161 CXRs were performed on the 141 patients studied. Of these, only 174 (15%) were undertaken for a direct clinical reason and 987 (85%) were undertaken as part of "routine" follow-up procedures and had no impact on patient management. Four "routine" CXRs (< 0.4%) demonstrated previously undiagnosed pulmonary metastases, in patients with no other history of metastatic disease. Thus, routine chest radiography is not a cost-effective method of monitoring asymptomatic patients with breast cancer for metastasis. It is recommended that outside staging procedures for clinical trials, the CXR is used only to address a clinical problem relating specifically to the thorax. It is anticipated that the cessation of all other chest radiography in patients being followed up for breast cancer at this institution will have significant budgetary implications.

Bone Neoplasms↗
PubMed1992

Results of the Cancer Research Campaign Adjuvant Trial for Perioperative Cyclophosphamide and Long-Term Tamoxifen in Early Breast Cancer reported at the tenth year of follow-up. Cancer Research Campaign Breast Cancer Trials Group.

Over 2,000 patients with early breast cancer were recruited into a trial between 1980 and 1985. This trial was of a factorial 2 x 2 design to investigate the benefits of a short course of perioperative cyclophosphamide or tamoxifen 20 mg daily for 2 years. At the tenth year of follow-up no significant benefit is noted for perioperative cyclophosphamide, however the main effect analysis for adjuvant tamoxifen demonstrates a significant improvement in disease-free survival which increases with time during the follow-up period. These results are in keeping with the World Overview of Trials of Adjuvant Tamoxifen. However, this study is unique, having a large number of node negative patients and over 500 premenopausal women in a comparison of tamoxifen and control. The relative risk reductions for the node negative patients for disease-free survival are greater than for the node positive patients. This might suggest that the absolute benefit for adjuvant tamoxifen is similar in both groups of patients, bearing in mind the increased risk of relapse with the node positive patients. No trend for interaction emerges according to age or menopausal status suggesting an identical benefit for premenopausal women. Of particular interest is the development of contralateral breast cancer. The initial overall effect which emerged at the third year of follow-up ceases to be apparent. However, subgroup analysis according to menopausal status suggests a trend for interaction with a reduction in the risk of contralateral breast cancer in the postmenopausal women and an increase in the risk of contralateral breast cancer in premenopausal women. Plausible mechanisms exist to explain this difference in outcome and these data need to be checked against other large trials of adjuvant tamoxifen at a time when we are considering the chemoprophylaxis of breast cancer in high risk premenopausal women.

Breast Neoplasms↗
PubMed1991

Breast cancer in elderly women: a Cancer Research Campaign trial comparing treatment with tamoxifen and optimal surgery with tamoxifen alone. The Elderly Breast Cancer Working Party.

Three hundred and eighty-one women with operable breast cancer aged over 70 years were randomly allocated to 40 mg tamoxifen daily and optimal surgery or to tamoxifen alone. At a median follow-up of 34 months there was no demonstrable difference in survival rate or in quality of life between the two treatment groups. More patients treated with tamoxifen alone had a subsequent change of management and this was usually an operation for local treatment failure. This progression to surgery has not been shown to be disadvantageous and the study will continue. Informed consent for randomization was difficult to obtain, leading to the exclusion of eligible patients, and it is therefore proposed to include non-randomized patients in a total cohort study.

Aged↗