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Biomedical subjects

M Baum

Publications and source records attributed to M Baum.

At least 235 records · Page 13Linked to original sources
PubMed1994

Alternative mechanisms of action of anti-oestrogens.

The molecular mechanism of action of anti-oestrogens such as tamoxifen appears to be a complex mixture of antagonism of the mitogenic action of oestradiol at the level of the oestrogen receptor, plus a range of other activities from enzyme inhibition to growth factor modulation. This article will concentrate on two specific areas: 1) the inhibition of protein kinase C and calmodulin-dependent cAMP phosphodiesterase; and 2) the regulation by tamoxifen of peptide regulators of breast cancer epithelial cell growth such as insulin-like growth factor I (IGF I) and transforming growth factor beta (TGF-beta). The elucidation of these mechanisms is potentially important in the treatment and chemoprevention of breast cancer-the quantitative contribution of each individual mechanism of the overall antineoplastic action of anti-oestrogens is central to developing new and possibly more effective anti-oestrogens and optimizing strategies for their use.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1994

The Royal Marsden Hospital pilot tamoxifen chemoprevention trial.

A pilot randomised placebo controlled trial using tamoxifen in healthy women at increased risk of developing breast cancer, has been undertaken in order to evaluate the problems of accrual, acute symptomatic toxicity, compliance, and safety as a basis for subsequent large national multicentre trials designed to test whether tamoxifen can chemoprevent breast cancer. From October 1986 until June 1993, 2012 healthy women with an increased risk of developing breast cancer, usually because of a strong family history, were randomly allocated to receive tamoxifen 20 mgs/day or placebo for up to 8 years if possible. Accrual remained high in spite of extensive informed consent regarding potential risk. Acute symptomatic toxicity was low for participants on tamoxifen or placebo and compliance remained correspondingly high with a predicted 77% of women on tamoxifen and 82% of women on placebo continuing medication at 5 years. There was a significant increase in hot flushes (34% versus 20%) mostly in premenopausal women (p < 0.005), vaginal discharge (16% versus 4%, p < 0.005), and menstrual irregularities (14% versus 9%, p < 0.005). The requirements for hormone replacement therapy for women on tamoxifen or placebo were the same. Safety monitoring indicates no adverse anti oestrogenic effects of tamoxifen. There was no obvious effect of tamoxifen on bone mineral densities (single photon radial absorption). The fibrinogen and antithrombin III were both lowered, resulting in no observed detrimental effect on the ratio of these clotting factors. There was a significant reduction in the serum cholesterol maintained out to 5 years. Annual pelvic assessment using transvaginal ultrasound indicates an increased incidence of uterine fibromata and benign ovarian cysts.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

[The prone position in ARDS. A successful therapeutic strategy].

As early as 1974, Brian advocated the prone position for ventilated patients. He suggested that this position might enhance ventilation of the dorsal parts of the lungs, thereby improving oxygenation. These considerations have been confirmed by several experimental and clinical studies. Better secretion removal, decreased intrapulmonary shunting, and an increased FRC are thought to be responsible for the observed improvement of oxygenation. However, the prone position never became very popular in the clinical treatment of the adult respiratory distress syndrome (ARDS). Routine performance of thoracic CT scans in ARDS patients demonstrated preferential distribution of pathological densities in the dependent lung areas. The prone position therefore could possibly benefit these patients, as shown by two recent studies. The aim of our study was to evaluate the influence of repeatedly turning the patient to the prone position on gas exchange and thoracic CT findings in multiple-trauma patients. METHODS. Seven ventilated intensive care patients with severe ARDS (Murray Score > 2.5, Quotient > 0.7, mean airway pressure > 18 cm H2O, thoracic CT scan showing dorsal atelectases) were included in the study. Patients were turned from the supine to the prone position at 12-h intervals using an air-cushion bed (Mediscus, Austria). Redistribution of dystelectatic or atelectatic dependent lung areas was verified by means of repeated thoracic CT scans (Figs. 1, 8). RESULTS. The patients were intermittently turned for 6.5 +/- 1.1 days. The course of gas exchange is shown in Figs. 2 and 3. Initially, improvement of the respiratory quotient could only be achieved during prone positioning, from the 2nd day in the supine position as well. Intrapulmonary shunting showed a similar trend (Figs. 4 and 5). No significant changes in cardiovascular parameters could be observed. Control thoracic CT scans showed uniform reduction of atelectases in dependent lung areas (Figs. 1 and 8). The inspiratory fraction of oxygen could be reduced significantly as of the 2nd day (Fig. 7). Constant levels of positive end-expiratory pressure and tidal volume were associated with decreasing mean and plateau airway pressures (Fig. 6). DISCUSSION. Repeatedly turning the patient to the prone position produced long-lasting improvement of arterial oxygenation, which persists up to the end of the weaning process. This is in good accordance with other studies, however, this is the first study to report an observation period of more than 6 days of repeatedly turning the patient. These positive effects on gas exchange can be attributed to sudden improvement of the ventilation-perfusion ratio within the lung areas that become dependent after turning to the prone position. Due to reduced hydrostatic pressure and relative hyperventilation, previously collapsed alveoli are recruited in the lung areas that become non-dependent after turning to the prone position.

Adult↗
PubMed1994

Aminoglycoside-induced Fanconi's syndrome.

Nephrotoxicity manifested by renal insufficiency is a well-known consequence of aminoglycoside administration in hospitalized patients. We report two cases of aminoglycoside-induced nephrotoxicity as manifested by proximal tubular dysfunction (Fanconi's syndrome). In the two patients reported, the tubular dysfunction occurred at the extremes of renal function. In both patients, tubular function returned to normal when the antibiotic was discontinued. Because of the widespread use of these antibiotics in the critically ill patient, it may be prudent to recognize this disorder when managing fluids, electrolytes, and nutrition.

Adult↗
PubMed1994

Leucocytes, lymphocytes, activation parameters and cell adhesion molecules in middle-distance runners under different training conditions.

20 young male track and field runners (400 m-3000 m) with a 4 mmol/l lactic acid threshold of x = 4.97 +/- 0.35 m/s were tested after three different training periods: 1. at the end of a two month endurance training, practised nearly every day; 2. after a period of speed and strength training, which was specific with respect to their discipline, with anaerobic lactic energy production up to 15 mmol/l lactic acid; 3. during the competition period. The blood samples were taken at rest (4 p.m.) and 22 hrs after the last exercise. On the cell surface the antigens CD3+, CD20+CD23+, CD4+HLADR, CD4+CD25+, CD8+CD28+, CD4+CD45RO+, CD16+CD56+, CD54+ and in the blood serum the concentrations of s-IL-2-R, s-ICAM-1 were analysed. 13 students of physical education served as a control group. The main results were: Only at the end of the endurance training period (1) an increase of s-ICAM-1 was found, which may be interpreted as a protective mechanism against infections. Compared with the control group CD20+CD23+ antigen was constantly elevated and during the transition from the training to the competition period the CD4+CD45RO+ subset increased. These results may provide evidence for a connection to a susceptibility to allergic disease and to overtraining. Furthermore, an activation of the specific immune system was indicated by an elevation of the s-IL-2-R and an activation of the monocytic-phagocytic system was shown by increased levels of ICAM-1. The importance of these results for the training process and with regard to susceptibility to infections is discussed.

Adult↗
PubMed1994

The centromeric K-type repeat and the central core are together sufficient to establish a functional Schizosaccharomyces pombe centromere.

The DNA requirements for centromere function in fission yeast have been investigated using a minichromosome assay system. Critical elements of Schizosaccharomyces pombe centromeric DNA are portions of the centromeric central core and sequences within a 2.1-kilobase segment found on all three chromosomes as part of the K-type (K/K"/dg) centromeric repeat. The S. pombe centromeric central core contains DNA sequences that appear functionally redundant, and the inverted repeat motif that flanks the central core in all native fission yeast centromeres is not essential for centromere function in circular minichromosomes. Tandem copies of centromeric repeat K", in conjunction with the central core, exert an additive effect on centromere function, increasing minichromosome mitotic stability with each additional copy. Centromeric repeats B and L, however, and parts of the central core and its core-associated repeat are dispensable and cannot substitute for K-type sequences. Several specific protein binding sites have been identified within the centromeric K-type repeat, consistent with a recently proposed model for centromere/kinetochore function in S. pombe.

Autoantigens↗
PubMed1994

Subglottic positive end-expiratory pressure in extubated patients recovering from acute lung injury.

OBJECTIVE: To examine the glottic function in extubated patients recovering from acute lung injury by simultaneous measurement of airway opening and subglottic airway pressures while patients are breathing at ambient pressure and receiving continuous positive airway pressure by a face mask. DESIGN: Descriptive, prospective study. SETTING: Intensive care unit at a university hospital. PATIENTS: Ten patients who required continuous positive airway pressure of at least 7 cm H2O in order to restore gas exchange after mechanical ventilation for acute lung injury. INTERVENTIONS: Spontaneous breathing at ambient airway pressure and with continuous positive airway pressures of 5 and 10 cm H2O via face mask. MEASUREMENTS AND MAIN RESULTS: Intratracheal pressure, airway opening pressure, and airflow at the airway opening were measured. Breathing at ambient pressure resulted in significantly higher end-expiratory intratracheal pressure than end-expiratory airway opening pressure (p < .01). No significant differences between end-expiratory intratracheal pressure and end-expiratory airway opening pressure were observed during breathing with continuous positive airway pressures of 5 and 10 cm H2O. A significant end-expiratory airflow at the airway opening (p < .01), observed during ambient pressure breathing, was not detectable while the patient received mask continuous positive airway pressure. The partial pressure of oxygen in the arterial blood (Pao2) increased significantly while patients breathed with 10 cm H2O, but not while patients breathed 5 cm H2O continuous positive airway pressure compared with breathing at ambient pressure (p < .05). CONCLUSIONS: Our data imply that patients recovering from acute lung injury create an intratracheal positive end-expiratory pressure by braking the expiratory airflow, probably by glottic narrowing. Despite compensatory glottic narrowing, extubated patients with reduced lung function may benefit from higher levels of continuous positive airway pressure.

Adolescent↗
PubMed1994

Reconstruction of the nose utilizing a bilobed flap.

BACKGROUND: Defects of the distal nose are particularly challenging to reconstruct because of this area's unique texture, lack of elasticity, and possible distortion of the alar rim. The bilobed flap has been criticized for having a high incidence of "trapdooring," flap necrosis, dog ears, and prominent suture lines. METHODS: Patients who underwent bilobed flap repairs of the distal nose (n = 171) were reviewed for complications and cosmetic results. The modifications from the traditional design include minimizing the angle of transposition between lobes, thinning of the flap, basing the pedicle on the lateral aspect of the nose, and creating the lobes of the flap to be of equal diameter to the defect. RESULTS: There was a 3% incidence of infection, 7% incidence of partial flap necrosis, and 5% incidence of "trapdooring" and contour distortion. Color match and contour were excellent for all other patients. CONCLUSIONS: The modified bilobed flap is an excellent choice for reconstruction of defects of the lower nose because of the good skin match and low incidence of complications.

Humans↗
PubMed1994

Effects of epidermal growth factor and transforming growth factor-alpha on rabbit proximal tubule solute transport.

The present in vitro microperfusion study examined the direct effects of epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha) on rabbit proximal convoluted tubule (PCT) solute transport. Tubules were perfused with an ultrafiltrate-like solution and bathed in an ultrafiltrate-like solution containing albumin. Albumin binding studies showed that both growth factors were highly protein bound with a free fraction of EGF of 0.31 +/- 0.04% and TGF-alpha of 1.08 +/- 0.15%. EGF at concentrations from 3 x 10(-11) M to 3 x 10(-8) M stimulated phosphate transport (JPhos) in a dose-dependent fashion but did not affect volume absorption (Jv) or bicarbonate transport (JtCO2). At 3 x 10(-7) M, EGF stimulated PCT Jv and JtCO2 in addition to the stimulation in JPhos. TGF-alpha stimulated Jv, JtCO2, and JPhos, but its effects were seen at a concentration that was 100-fold lower than that where EGF affected PCT transport. At 3 x 10(-13) M, TGF-alpha stimulated JtCO2, and at 3 x 10(-12) M, TGF-alpha also stimulated Jv and JPhos. EGF receptor downregulation with 3 x 10(-8) M EGF was able to block the effect of 3 x 10(-10) M TGF-alpha on Jv and JtCO2. Neither luminal EGF nor TGF-alpha had an effect on PCT transport. PCT bicarbonate and mannitol permeabilities were also not affected by either growth factor. These results demonstrate that EGF and TGF-alpha have direct effects on PCT solute transport.

Animals↗
PubMed1994

Effect of glucocorticoids on renal cortical NHE-3 and NHE-1 mRNA.

Glucocorticoids play an important role in modulating proximal tubule acidification. Chronic systemic administration of dexamethasone increases the rate of bicarbonate absorption in isolated perfused proximal convoluted tubules and Na+/H+ antiporter activity in renal brush-border membrane vesicles. The proximal tubule expresses mRNA corresponding to two known Na+/H+ antiporter isoforms: NHE-3, an amiloride-resistant apical membrane Na+/H+ antiporter; and NHE-1, an amiloride-sensitive Na+/H+ antiporter found on most mammalian cells. Administration of dexamethasone for 1 and 2 days (600 micrograms/kg twice daily and 2 h before animals were killed) increased NHE-3 mRNA abundance 1.3- and 2.5-fold, respectively, but had no effect on NHE-1 mRNA abundance. Aminoglutethimide-induced glucocorticoid deficiency had no effect on NHE-1 or NHE-3 mRNA abundance. Incubation of proximal tubules for 3 h with 10(-5) M dexamethasone increased proximal tubule Na+/H+ antiporter activity from 0.69 +/- 0.04 to 0.92 +/- 0.03 pH units/min (P < 0.01); however, there was no increase in NHE-3 or NHE-1 mRNA abundance. Similarly, there was no effect on NHE-3 or NHE-1 mRNA abundance in rabbit renal cortex 4 h after intravenous administration of 600 micrograms/kg dexamethasone. Thus chronic dexamethasone increases NHE-3 but not NHE-1 mRNA abundance. The acute increase in Na+/H+ antiporter activity induced by dexamethasone occurs by mechanisms independent of changes in NHE-1 and NHE-3 mRNA abundance.

Aminoglutethimide↗