Variations in serum thyroxine concentrations with time after an oral replacement dose

Serum thyroxine concentrations were measured sequentially in eight healthy male volunteers after the oral administration of one of two brand name, commercially available thyroxine tablets. In all cases, levels peaked at 2 hours and did not return to baseline values until 24 hours after dosing. From 2 through 10 hours, statistically significant elevations in serum thyroxine concentrations were observed. Such fluctuations may be important in evaluating laboratory results in patients receiving replacement doses of thyroxine.     

Pneumonia: a deadly disease despite intensive care treatment

In a retrospective study of 30 patients with pneumonia treated in the intensive care unit, it was found that cultures from sputum and bronchial secretions did poorly correspond with blood cultures or serological tests. In only 15 of the patients a reliable etiological diagnosis was ever established. Mechanical ventilation was used in 22 patients, usually with a high oxygen need. At the start of this ventilation a significant blood pressure fall and a further pulmonary deterioration was observed. In fatal cases this pulmonary dysfunction was progressive. The overall mortality was 47%. When an FI02 above 0.6 was needed in the ventilator the mortality was 13/14 (93%).     

The relation between sodium chloride concentration in drinking water and egg-shell damage

1. A significant linear increase in egg-shell defects from 60-week-old laying hens, and corresponding significant linear decreases in various egg-shell-quality measurements, were observed in response to increasing concentrations of sodium chloride in the drinking water, to the maximum concentration of 600 mg/l used in the present study. 2. The incidence of damaged egg shells was increased 3-fold by including NaCl in the drinking water at a concentration of 600 mg/l. 3. Shell defects declined when birds were placed on normal water for 5 weeks but were still 1.4- to 2.1-fold greater than control values. 4. After an induced rest from lay on normal water, shell defects were still 1.3- to 3.2-fold greater in birds which had previously received the NaCl in the drinking water. 5. The increased incidence of shell damage was not related to decreased food intake or increased egg weight or production.     

Resistive breathing training in patients with chronic obstructive pulmonary disease

In order to investigate the effect of resistive breathing training on ventilatory muscular endurance, we examined the maximal sustained ventilatory capacity in ten patients with chronic obstructive pulmonary disease (COPD) before and after a six-week program of resistive breathing training. In addition, we investigated the effect of altered breathing strategy on resistive breathing performance. The patients performed two 15-minute sessions of resistive breathing daily for six weeks using an inspiratory resistive device (Pflex). Before and after the training, we found no significant change in spirometric data, pulmonary volumes, maximal inspiratory pressure, and maximal expiratory pressure. Of the ten patients, seven failed to show an improvement in their performance of resistive breathing. Furthermore, the maximal sustained ventilatory capacity was unchanged after the resistive breathing training. After the completion of the training program, seven of the patients participated in an additional experiment in which they were instructed to take long slow inspirations while breathing through the resistive device. With this change in breathing pattern, five of the seven were able to improve their performance of resistive breathing. Analysis of the breathing strategy showed that a reduction in the peak mouth pressure, breathing frequency, and external resistive work with a longer inspiratory time was beneficial. We conclude that neither resistive breathing performance nor ventilatory muscular endurance, as measured by sustained hyperpnea, is improved by resistive breathing training performed according to the current instructions with the resistive device, and alterations in breathing strategy have a profound effect on the performance of resistive breathing. The lack of details of breathing strategy in previous studies of resistive breathing makes it difficult to determine if previously demonstrated improvements were due to a real enhancement of ventilatory muscular performance or merely secondary to a different strategy.     

New potent verapamil derivatives that reverse multidrug resistance in human renal carcinoma cells and in transgenic mice expressing the human MDR1 gene.

Multidrug resistance in human renal cell carcinoma is mainly caused by expression of the MDR1 gene and is characterized by a broad spectrum cross resistance to many natural product chemotherapeutic agents. This resistance can be overcome by applying chemosensitizers which inhibit the function of the MDR1 gene product P-glycoprotein. The development of new reversing agents with fewer side effects and a higher potency in modifying resistance is a high priority of research on drug resistance. We have evaluated four new verapamil derivatives on 21 primary human renal cell carcinomas in vitro, and also tested them in an MDR-transgenic mice model. These mice express the human MDR1 gene in their bone marrow cells and measurement of their white blood counts provides a simple, rapid and reliable system to screen for the potency of MDR-reversing agents in vivo. We demonstrate here that all four drugs are effective in reversing multidrug resistance in primary cultures of human renal cell carcinomas when used in combination with vinblastine chemotherapy, and to a lesser extent with doxorubicin or daunomycin chemotherapy. Our in vivo data indicate that two of these reversing agents display low toxicity at high concentrations and are more effective at low, clinically achievable concentrations, than the other two drugs and R-verapamil. These results make the two new drugs attractive candidates to be taken into clinical trials.