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Biomedical subjects

M Baum

Publications and source records attributed to M Baum.

At least 325 records · Page 18Linked to original sources
PubMed1990

Psychological outcomes of different treatment policies in women with early breast cancer outside a clinical trial.

OBJECTIVES: To assess outside a clinical trial the psychological outcome of different treatment policies in women with early breast cancer who underwent either mastectomy or breast conservation surgery depending on the surgeon's opinion or the patient's choice. To determine whether the extent of psychiatric morbidity reported in women who underwent breast conservation surgery was associated with their participation in a randomised clinical trial. DESIGN: Prospective, multicentre study capitalising on individual and motivational differences among patients and the different management policies among surgeons for treating patients with early breast cancer. SETTING: 12 District general hospitals, three London teaching hospitals, and four private hospitals. PATIENTS: 269 Women under 75 with a probable diagnosis of stage I or II breast cancer who were referred to 22 different surgeons. INTERVENTIONS: Surgery and radiotherapy or adjuvant chemotherapy, or both, depending on the individual surgeon's stated preferences for managing early breast cancer. MAIN OUTCOME MEASURES: Anxiety and depression as assessed by standard methods two weeks, three months, and 12 months after surgery. RESULTS: Of the 269 women, 31 were treated by surgeons who favoured mastectomy, 120 by surgeons who favoured breast conservation, and 118 by surgeons who offered a choice of treatment. Sixty two of the women treated by surgeons who offered a choice were eligible to choose their surgery, and 43 of these chose breast conserving surgery. The incidences of anxiety, depression, and sexual dysfunction were high in all treatment groups. There were no significant differences in the incidences of anxiety and depression between women who underwent mastectomy and those who underwent lumpectomy. A significant effect of surgeon type on the incidence of depression was observed, with patients treated by surgeons who offered a choice showing less depression than those treated by other surgeons (p = 0.06). There was no significant difference in psychiatric morbidity between women treated by surgeons who offered a choice who were eligible to choose their treatment and those in the same group who were not able to choose. Most of the women (159/244) gave fear of cancer as their primary fear rather than fear of losing a breast. The overall incidences of psychiatric morbidity in women who underwent mastectomy and those who underwent lumpectomy were similar to those found in the Cancer Research Campaign breast conservation study. At 12 months 28% of women who underwent mastectomy in the present study were anxious compared with 26% in the earlier study, and 27% of women in the present study who underwent lumpectomy were anxious compared with 31% in the earlier study. In both the present and earlier study 21% of women who underwent mastectomy were depressed, and 19% of women who underwent lumpectomy in the present study were depressed compared with 27% in the earlier study.) CONCLUSIONS: There is still no evidence that women with early breast cancer who undergo breast conservation surgery have less psychiatric morbidity after treatment than those who undergo mastectomy. Women who surrender autonomy for decision making by agreeing to participate in randomised clinical trials do not experience any different psychological, sexual, or social problems from those women who are treated for breast cancer outside a clinical trial.

Adult↗
PubMed1990

The role of endocrine therapy in primary breast cancer.

A recent overview of the results of all trials of adjuvant chemotherapy suggests a clinically and statistically significant advantage for premenopausal women with positive axillary nodes. The results of the same approach for all other women with early breast cancer are very disappointing. These data suggest that contrary to the original hypothetical model, adjuvant chemotherapy is exerting its effect indirectly via chemical castration. In contrast, the results of trials of adjuvant tamoxifen have been more promising and, again, in contrast to the original premises, it would appear that a modest improvement in survival and delay in recurrence can be achieved amongst all groups of women independent of age, nodal status and oestrogen receptor content of the primary tumour. In order to explain these counter-intuitive observations, it is necessary to elaborate an alternative biological model. This paper describes the current thinking on the mode of action of the "anti-oestrogens" and the possible role of inhibitory growth factors activated indirectly by anti-oestrogens. Future trials of adjuvant systemic therapy for early breast cancer should include studies on the duration of tamoxifen, comparing 2 yr with longer, and a comparison of tamoxifen alone with polychemotherapy for premenopausal node positive patients.

Breast Neoplasms↗
PubMed1990

Response to toremifene (Fc-1157a) therapy in tamoxifen failed patients with breast cancer. Preliminary communication.

Nine patients with measurable lesions of locally advanced or recurrent breast cancer have been treated with toremifene 200 mg daily. A response rate of 33% [complete remission (CR) + partial remission (PR)] or 78% [CR + PR + no change (NC)] has been achieved so far. As all our patients had previously relapsed on anti-oestrogen therapy (tamoxifen), we postulate that our response rate was achieved by a direct oncolytic effect.

Aged↗
PubMed1990

Extinction of a conditioned emotional response: massed and distributed exposures.

Using the lick-suppression methodology of Jacobs, Buttrick & Kennedy (Pavlovian Journal of Biological Science, 23, 29-34, 1988), a conditioned emotional response (CER) was established in 24 rats using off-the-baseline pairings of a light (the conditional stimulus) and brief footshock (the unconditioned stimulus). Following conditioning, the rats were assigned to one of three extinction groups differing in whether they received massed or distributed off-the-baseline exposure to the conditional stimulus. The effects of differential treatment were assessed on-the-baseline on test days, when the extinction of the CER was monitored. Rats receiving a single, long exposure to the conditional stimulus showed greater resistance to extinction than the rats in the distributed groups. They also showed a difference pattern of CER extinction. The results were discussed and compared to similar studies that have explored the massed vs distributed dimension, both in CER and avoidance-extinction (using response prevention or flooding). The relation of animal studies to parallel human studies using exposure therapy was also discussed.

Animals↗
PubMed1990

Trends in primary breast cancer management. Where are we going?

The treatment of cancer during any period has been based not on the whim of a clinician but on the therapeutic consequences of the dominant biologic model of the disease. Until the 1960s, the dominant model of breast cancer was of a disease that spread centrifugally along anatomic pathways, with time being the only determinant of prognosis. An alternative model, that of biologic determinism, posits that the outcomes of treatment are determined by the extent of microscopic dissemination that occurred before the tumor became detectable. This model, too, has flaws, and the author suggests that it is time for a Kuhnian paradigm shift. Breast cancer exhibits a heterogeneity of phenotypes resulting from one or perhaps two mutations. The multiple prognostic variables may be epiphenomena, expressing different degrees of amplification of a limited domain of the genome.

Breast Neoplasms↗
PubMed1990

Anti-oestrogens induce the secretion of active transforming growth factor beta from human fetal fibroblasts.

The clinical use of anti-oestrogens in breast cancer therapy has traditionally been restricted to tumours that contain measurable oestrogen receptor protein. However, it is now widely recognised that the clinical response to adjuvant anti-oestrogen therapy appears to be independent of the oestrogen receptor content of the primary tumour. The study reported here was designed to investigate the possibility that human stromal cells can respond to anti-oestrogens by an increased synthesis of the inhibitory growth factor, transforming growth factor beta (TGF-beta). Two established human fetal fibroblast strains were used as models for the breast cancer stromal fibroblasts. These cells were found to respond to the addition of anti-oestrogens by a large increase in their synthesis of biologically active TGF-beta. Despite the application of ligand binding, immunoassay and Northern analysis, no oestrogen receptor or oestrogen receptor mRNA was detected in either of the human fetal fibroblasts strains. These observations may provide a mechanism of action of anti-oestrogens that is independent of the presence of oestrogen receptor in the tumour epithelial cells, and thus provide an explantation for the counter-intuitive results of adjuvant anti-oestrogen action.

Blotting, Northern↗
PubMed1990

Acidification mechanisms on the basolateral membrane of renal vesicles from the developing nephron.

The present study examined acidification mechanisms on the basolateral membrane of the early renal vesicle, an undifferentiated ball of cells that will develop into parts of the glomerulus, proximal tubule, loop of Henle, and a portion of the distal convoluted tubule. Renal vesicles were dissected from newborn rabbit kidneys and bathed in vitro. To examine the basolateral membrane acidification mechanisms, intracellular pH (pHi) was measured by use of the pH-sensitive dye (2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein. Evidence for Cl(-)-base exchange included the fact that removal of bath Cl-resulted in cell alkalinization (7.35 +/- 0.03 to 7.48 +/- 0.05; P less than 0.01). Cell alkalinization induced by Cl- removal was also observed in presence of a voltage clamp without bath Na+ (7.18 +/- 0.02 to 7.39 +/- 0.04; P less than 0.01) and was inhibited by 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS). pHi recovery after acute alkalinization resulting from CO2 removal was 0.20 +/- 0.03 pH units/min in the presence of Cl-, 0.07 +/- 0.01 in experiments with 0.2 mM DIDS, and 0.07 +/- 0.01 in absence of bath Cl-. The early renal vesicle also has a basolateral Na(+)-H+ antiporter. Removal of bath Na+ resulted in cell acidification (7.36 +/- 0.09 to 7.18 +/- 0.06; P less than 0.01), which was inhibited by 2 mM amiloride. Cell pH recovery after acute acidification (NH4Cl prepulse technique) was entirely dependent on bath Na+ and inhibited by amiloride. Thus the renal vesicle has basolateral membrane Na(+)-H+ and Cl(-)-base exchangers that can defend against cell acidification and alkalinization, respectively.

Acids↗
PubMed1990

Intracellular cystine loading inhibits transport in the rabbit proximal convoluted tubule.

Cystinosis is an autosomal recessive disorder characterized by a high intracellular cystine concentration. To establish an in vitro model of this disorder and examine the mechanism of the proximal tubule transport defect seen with elevated intracellular cystine concentrations, rabbit proximal convoluted tubules (PCT) were perfused in vitro. PCTs were loaded with cystine using cystine dimethyl ester, a permeative methyl ester derivative. Bath cystine dimethyl ester (0.5 mM) reduced volume absorption (Jv) (0.67 +/- 0.07 to 0.15 +/- 0.09 nl/mm.min, P less than 0.01), bicarbonate transport (JTCO2) (47.2 +/- 4.9 to 11.1 +/- 2.8 pmol/mm.min, P less than 0.001) and glucose transport (JGLU) (34.1 +/- 1.5 to 19.7 +/- 1.5 pmol/mm.min, P less than 0.001). The methyl esters of leucine (0.5 mM), and tryptophan (0.5 and 2.0 mM) had no effect on these parameters. To examine if intracellular reduction of cystine to cysteine could contribute to the inhibition in transport, the effect of bath cysteine methyl ester on proximal tubular transport was examined. Bath cysteine methyl ester (2 but not 0.5 mM) resulted in an inhibition in Jv, JGLU, and JTCO2. Cystine dimethyl ester had no effect on mannitol or bicarbonate permeability. These data are consistent with intracellular proximal tubular cystine accumulation resulting in an inhibition of active transport.

Animals↗
PubMed1990

Neonatal rabbit juxtamedullary proximal convoluted tubule acidification.

The present in vitro microperfusion study examined apical membrane Na+/H+ antiporter and basolateral membrane Na(HCO3)3 symporter activity in newborn and adult juxtamedullary proximal convoluted tubules. Proton fluxes were determined from the initial rate of change of intracellular pH after a change in the luminal or bathing solution, buffer capacity, and tubular volume of newborn and adult tubules. Intracellular pH (pHi) was measured fluorometrically using the pH-sensitive dye (2',7')-bis (carboxyethyl)-(5,6)-carboxyfluorescein (BCECF). Apical Na+/H+ antiporter proton flux, assayed by the effect of sodium removal (147----0 meq/liter) on pHi, was one-third the adult level for the first 2 wk and doubled in the 3rd wk of life. Adult levels were achieved by 6 wk of age. Na+/H+ antiporter activity was not detected on the basolateral membrane of 1-wk-old newborns, indicating that polarity of this transporter was already present. Basolateral membrane Na(HCO3)3 proton flux, assayed by the effect of a bath bicarbonate change (25----5 meq/liter) and by a bath sodium change (147----0 meq/liter) on pHi, was 50-60% of adult values in 1-wk-old newborns. Basolateral membrane Na(HCO3)3 proton flux assayed by a bath bicarbonate change (25----5 meq/liter) remained at 50-60% of adult values for the 1st mo of life and increased to adult levels by 6 wk of age. This transporter not only plays a role in net acidification, but is an important determinant of cell pH in newborn juxtamedullary proximal convoluted tubules.

4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfo↗
PubMed1990

What are the psychological factors influencing attendance, non-attendance and re-attendance at a breast screening centre?

We describe some preliminary findings from a pilot study using three recently developed questionnaires which assessed items such as the health beliefs, knowledge about cancer and attitudes to breast cancer screening in 242 women invited to attend for mammographic screening in South East London. We suggest that these questionnaires should be used in all regional centres both to monitor psychological variables and to identify local problems within the service which may be influencing the up-take of invitations to come for screening.

Attitude to Health↗
PubMed1990

Developmental changes in rabbit juxtamedullary proximal convoluted tubule bicarbonate permeability.

The bicarbonate transport rate in neonatal rabbit juxtamedullary proximal convoluted tubules (JMPCT) is lower than that in adults. The reduced rate of transport could be due to a decrease in active bicarbonate transport or an increase in the passive permeability of the tubule to bicarbonate. The present in vitro microperfusion study directly measured the bicarbonate permeability of neonatal and adult JMPCT. Bicarbonate permeability was measured at both slow and fast perfusion rates to simulate the neonatal and adult proximal tubule flow rates, respectively. At 38 degrees C in tubules perfused at 3 nL/min, bicarbonate permeability was 0.29 +/- 0.11 x 10(-5) cm/s in neonates and 1.70 +/- 0.49 x 10(-5) cm/s in adult PCT (p less than 0.05). At a perfusion rate of 10 nL/min, bicarbonate permeability was 0.11 +/- 0.27 x 10(-5) cm/s in neonatal PCT and 2.31 +/- 0.15 x 10(-5) cm/s in adult PCT (p less than 0.05). These results demonstrate that bicarbonate permeability in neonatal JMPCT is significantly lower than that in adult JMPCT. Thus, the lower rate of bicarbonate transport in neonatal PCT is entirely due to a lower rate of active bicarbonate transport.

Animals↗
PubMed1990

[Initial experience with a new blood pump].

A new type of blood pump was tested in calves for 6 hours. The pump consists of a rigid housing with a trochoidal internal surface, an inlet and outlet, and two lateral walls. A two-corner piston rotating on an eccentric shaft, describes a trochoidal path, thus creating a gap seal, the gap measuring a constant 10-35 microns. The pump is driven by a watercooled DC motor. For right ventricular assist, a cannula is inserted into the right ventricle through the right atrium, and into the left ventricle for left ventricular assists. From a total of 10 experiments, two left ventricular assists, two right ventricular assists, and three biventricular assists were evaluated. The pump produced a pulsatile flow of 31 at 70 rpm. Energy requirements were 2.19 watts for left, 2.06 for right, and 7.26 for biventricular assists. Plasma hemoglobin remained as low as 10 mg/dl during monoventricular, and increased during biventricular assists to 20 mg/dl after 3 hours, and returned to 16 mg/dl after 6 hours. From these preliminary results it is concluded that this new rotary blood pump may be suitable as a circulatory assist device.

Animals↗