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Biomedical subjects

M Baum

Publications and source records attributed to M Baum.

At least 253 records · Page 14Linked to original sources

Cause-specific mortality in long-term survivors of breast cancer who participated in trials of radiotherapy.

PURPOSE: To examine long-term cause-specific mortality in patients irradiated for breast cancer as part of a randomized clinical trial. PATIENTS AND METHODS: We studied all available information from randomized trials initiated before 1975 in which radiotherapy was the randomized option and surgery was the same for both treatment arms. Eight such trials were identified. RESULTS: The increased all-cause mortality rate in 10-year survivors previously reported is no longer significant, although a numerical difference in favor of non-irradiated patients remains. This result was strongly influenced by the earliest trials, and more recent trials have found a nonsignificant net benefit in overall mortality associated with radiation therapy. An excess of cardiac deaths was apparent in both early and more recent trials (P < .001), but this was offset by a reduced number of deaths due to breast cancer, especially in more recent trials. CONCLUSION: The reduction of breast cancer deaths suggests that radiation therapy may have a value beyond the clearly established improvements obtainable for local control. Use of techniques that minimize cardiac dose is important in reducing the risks of adjuvant radiotherapy, especially in good-prognosis patients.

Breast Neoplasms↗

The effect of phosphate supplementation on linear growth in children with X-linked hypophosphatemia.

BACKGROUND: X-linked hypophosphatemia is the most common inherited cause of rickets. Current therapy for this disorder includes vitamin D and phosphate supplementation; however, phosphate therapy has been associated with nephrocalcinosis. The purpose of this study is to evaluate the effect of oral phosphate therapy on growth in patients with X-linked hypophosphatemia treated with either calcitriol or dihydrotachysterol (vitamin D). METHODS: We retrospectively evaluated the prepubertal growth of 36 children with X-linked hypophosphatemia. The height standard deviation score (Z-score) of patients initially treated with vitamin D alone and the Z-scores of patients treated with vitamin D and phosphate therapy were compared. In addition, the growth of therapy were compared. In addition, the growth of patients treated with vitamin D was compared with that of patients treated with vitamin D and phosphate from the outset of therapy. RESULTS: Patients treated with vitamin D alone for 5.36 +/- 2.18 years had an improvement in Z-score from -3.1 +/- 1.10 to -2.49 +/- 0.66 SDS, P < .05. Adding phosphate therapy for patients initially treated with vitamin D alone for 4.83 +/- 2.99 years did not further improve Z-score (-2.49 +/- 0.66 vs -2.35 +/- 0.83). Initial therapy with vitamin D and phosphate for 4.33 +/- 2.19 years also improved Z-score, (-2.84 +/- 1.02 vs -1.98 +/- 0.82, P < .05). The change in Z-score was similar to the group treated with vitamin D alone compared with the group treated initially with vitamin D and phosphate (0.65 +/- 0.54 vs 0.85 +/- 0.65, respectively). CONCLUSION: These data demonstrate that both vitamin D alone and in combination with phosphate improved linear growth. Adding oral phosphate for children initially treated with vitamin D alone did not improve Z-score. Initial therapy with vitamin D and vitamin D plus phosphate produced similar changes in linear growth.

Administration, Oral↗

Intracellular distribution of cystine in cystine-loaded proximal tubules.

Cellular cystine loading with cystine dimethyl ester has been shown to inhibit transport in proximal convoluted tubules perfused in vitro and decrease the rate of oxygen consumption in suspensions of proximal tubules. The present study was designed to examine the intracellular distribution of cystine in this model of the Fanconi syndrome of cystinosis and to determine whether cystine or its degradation product, cysteine, is the cytotoxic agent in cystine-loaded rabbit proximal tubules. Tubules were incubated with 2 mmol/L cystine dimethyl ester for 10 min at 37 degrees C and subjected to cellular fractionation. The intralysosomal cystine content (272 +/- 125 nmol/mg protein) was significantly higher than that measured in the nucleus (8.7 +/- 2.0 nmol/mg protein) and cytosol (9.8 +/- 4.0 nmol/mg protein (p < 0.05). Electron micrographs of tubules loaded with cystine depicted large swollen lysosomes. To determine whether cystine or its breakdown product, cysteine, was the cytotoxic agent in tubules incubated with cystine dimethyl ester, the intracellular cystine and cysteine contents were measured and found to be 86.5 +/- 14.8 and 5.7 +/- 1.7 nmol/mg protein, respectively. These tubules had a 50% decrease in the rate of O2 consumption. To examine whether the increased level of intracellular cysteine played a role in this decrease in O2 consumption, we loaded tubules with 2 mmol/L cysteine methyl ester for 10 min. Despite an intracellular cysteine concentration of 59.6 +/- 5.8 nmol/mg protein, cysteine-loaded tubules had a rate of O2 consumption equal to that measured in control tubules. Thus, intracellular cystine loading significantly increases intralysosomal cystine content.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Maturational effects of glucocorticoids on neonatal brush-border membrane phosphate transport.

Previous studies have implicated glucocorticoids as an important factor in the postnatal maturational increase in proximal tubule volume absorption, Na+/H+ antiporter, Na(HCO3)3 symporter, and Na(+)-K(+)-ATPase activity. The present study examined whether glucocorticoids are also a potentially important factor in the maturational decrease in proximal tubule phosphate transport. Renal BBMs were prepared from neonatal rabbits who received dexamethasone (10 micrograms/100 g body weight) or vehicle. Brush-border membrane vesicles from dexamethasone-treated neonates had a lower rate of Na-phosphate cotransport than controls (50.8 +/- 3.6 versus 29.2 +/- 2.6 pmol 32P(i)/10 s/mg protein, p < 0.001). This decrease was due to a decrease in the Vmax with no change in the affinity of the transporter for phosphate. The dexamethasone-induced decrease in BBM Na-phosphate transport was not due to a reduction in transporters as assayed by phosphate-protectable Na-dependent equilibrium binding of phosphonoformic acid. Dexamethasone treatment caused an increase in the fluorescence anisotropy of 1,6-diphenyl-1,3,5-hexatriene and trimethylammonium-1,6-diphenyl-1,3,5-hexatriene (i.e. a decrease in membrane fluidity). Brush-border membranes from dexamethasone-treated neonates had a decrease in sphingomyelin and an increase in phosphatidylcholine and phosphatidylinositol content but no change in cholesterol or total phospholipid content. These data are consistent with glucocorticoids playing a role in the postnatal maturational decrease in proximal tubule phosphate transport by altering membrane characteristics.

Animals↗

Biphasic positive airway pressure (BIPAP)--a new mode of ventilatory support.

Biphasic Positive Airway Pressure (BIPAP) can be described as pressure controlled ventilation in a system allowing unrestricted spontaneous breathing at any moment of the ventilatory cycle. It can also be described as a Continuous Positive Airway Pressure (CPAP) system with a time-cycled change of the applied CPAP level. As with a pressure controlled, time-cycled mode, the duration of each phase (T(high), T(low)) as well as the corresponding pressure levels (P(high), P(low)) can be adjusted independently. Depending on the spontaneous breathing activity, BIPAP can be subdivided into: no spontaneous breathing: CMV-BIPAP; spontaneous breathing at the lower pressure level: IMV-BIPAP; spontaneous breathing at the upper pressure level: APRV-BIPAP; spontaneous breathing at both CPAP levels: genuine BIPAP. Since it enables progressive transition from controlled to all levels of augmented mechanical ventilation, BIPAP appears to be a suitable mode for the entire period of mechanical ventilation of the patient. There are difficulties neither in choosing the correct moment for switching nor the further respiratory management of the ventilated patient under BIPAP. The necessary adaptation (ventilation, oxygenation) can be individualized on the basis of blood gas analyses. An increase or reduction of the invasivity of ventilation can be attained without any problems with BIPAP. Furthermore, spontaneous breathing of the patient does not necessitate any switching of the mode of ventilation. The transition from controlled to augmented ventilation is smooth. BIPAP enables the therapist to let the patient breathe freely even under the most invasive ventilation conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗

American and European recommendations for screening mammography in younger women: a cultural divide?

The American Cancer Society advocates mammography screening for all women from age 40, whereas in Europe it is not recommended for women below the age of 50. Randomised prospective studies have failed to show a significant benefit from screening women aged under 50 and five potentially harmful effects of screening should be considered: lead time, overdiagnosis, radiation exposure, false positive results, and cost. Younger women must be properly informed about the potential for harm as well as for benefit before screening.

Adult↗

The cellular basis of Fanconi syndrome.

In this syndrome, all solutes are prevented from crossing the apical membrane of the proximal renal tubule cell; hence, investigations have focused on generalized transport dysfunction, namely intracellular ATP activity. Experiments suggest that intracellular adenine nucleotide degradation secondary to phosphate depletion causes a decline in ATP.

Adenosine Triphosphate↗

Breast cancer, desmoid tumours, and familial adenomatous polyposis--a unifying hypothesis.

There is widespread agreement that epithelial tumours develop as a consequence of primary events within epithelial cells. According to the monoclonal theory, a tumour is caused by genetic change within a single cell, which imparts a selective growth advantage. This simple theory fails to take into account two important concepts. First, tumour generation is likely to involve multiple genetic events, some of which initiate a tumour, and others promote its growth. Second, tumours are usually composed of several tissue components, although they are known by the dominant proliferative cell type. This convention has tended to obscure the importance of "secondary" tissue components in carcinogenesis, despite evidence for the involvement of mesenchymal elements both in the induction and maintenance of transformation. To shift emphasis from the monoclonal theory, we propose a unifying hypothesis accounting for the effect of adjuvant tamoxifen in early breast cancer and the association between gastrointestinal polyps and desmoid tumours.

Adenomatous Polyposis Coli↗