Medicine's Expectations and Responsibilities in an Industrial Health Program

Clinical trials have proved citrated calcium carbimide (CCC) to be a valuable agent in treating chronic alcoholism. Fewer side effects occur with use of this drug than with disulfiram. Reaction to alcohol intake begins within five minutes after administration of CCC. Maximal effect is observed within 30 minutes to an hour.

The authors report the results of a study in which CCC was administered to 24 adults, including five normal subjects and 19 alcoholics. Improvement was noted in four subjects, and alcoholism was alleviated in eight.     

Relationship of ventricular ectopy to nocturnal oxygen desaturation in patients with chronic obstructive pulmonary disease

Sudden death and oxyhemoglobin desaturation are known to occur during sleep in patients with chronic obstructive pulmonary disease. The present study was undertaken to determine the frequency with which nocturnal oxygen desaturation promotes an increase in ventricular ectopic activity, since such a relationship could represent a potential pathophysiologic mechanism for sudden death during sleep. Forty-two clinically stable subjects with moderately severe obstructive airways disease, mean ratio of one-second forced expiratory volume to forced vital capacity = 51 +/- 12 percent, underwent overnight polygraphic sleep study. Oxyhemoglobin saturation was monitored by ear oximetry, and electrocardiographic leads CC5 and CM5 were employed for arrhythmia detection. Premature ventricular complexes were detected in 27 (64 percent) of the subjects and were complex (multifocal, repetitive, or both) in 17. No significant relationship between premature ventricular complex frequency and arterial oxygen saturation was detected for the group as a whole. In part, this result can be attributed to the relatively mild hypoxemic stress experienced by the 22 subjects in whom arterial oxygen saturation remained greater than 80 percent. In contrast, six (30 percent) of the 20 patients who had desaturation to less than 80 percent showed a greater than 150 percent increase in premature ventricular complex frequency with oxygen desaturation. These results suggest that nocturnal hypoxemia, if of sufficient magnitude, is capable of increasing ventricular ectopy during sleep in a substantial number of patients with chronic obstructive pulmonary disease.     

Reversible oxidant-induced increases in albumin transfer across cultured endothelium: alterations in cell shape and calcium homeostasis

To determine whether reactive oxygen molecules could directly and reversibly increase the transfer of albumin across an endothelial barrier, we measured albumin transfer across monolayers of endothelium cultured on micropore filters before and after exposure to xanthine and xanthine oxidase. Xanthine and xanthine oxidase increased endothelial albumin transfer in a dose-dependent fashion. Parallel phase contrast and fluorescence microscopy demonstrated retraction of adjacent cells from one another and disruption of the actin filaments. The oxidant- induced increases in albumin transfer and changes in cell shape were reversed by removing xanthine oxidase and then incubating the monolayers for 3 1/2 hours in tissue culture media enriched with fetal bovine serum. However, incubation in tissue culture media without serum resulted in progressive injury and cell death. Hence, the brief exposure to oxidants initiated a progressive injury process that was reversed by incubation in serum. Because intracellular and extracellular calcium are important determinants of cell shape, and because some oxidized membrane lipids act as calcium ionophores, we asked whether oxidants altered endothelial calcium homeostasis. Xanthine-xanthine oxidase increased release of 45Ca++ from preloaded cells. The calcium antagonist lanthanum chloride prevented xanthine- xanthine oxidase increases in endothelial albumin transfer and prevented the changes in cell shape; chelation of extracellular calcium inhibited lysis of endothelium by xanthine-xanthine oxidase; and the calcium ionophore A23187 increased endothelial albumin transfer and mimicked the oxidant-induced changes in cell shape. Lanthanum chloride inhibited these effects of A23187. These data suggest that oxygen radicals can reversibly increase endothelial permeability to macromolecules, that this is associated with reversible changes in endothelial cell shape and actin filaments, and that the changes in cell shape are related to oxidant-induced changes in endothelial calcium homeostasis.     

Relationship of ventricular ectopy to oxyhemoglobin desaturation in patients with obstructive sleep apnea

Patients with obstructive sleep apnea are considered to be at increased risk of sudden, presumably arrhythmia-related death during sleep. The present study was undertaken to determine the relationship between ventricular ectopy and the severity of oxyhemoglobin desaturation in these patients. Thirty-one male patients with obstructive sleep apnea (mean age, 55 +/- 11 years) underwent overnight polysomnography. Arterial oxyhemoglobin saturation (SaO2) was monitored by ear oximetry, and premature ventricular complexes (PVC) were detected using electrocardiographic leads CC5 and CM5. The data were recorded on electromagnetic tape for subsequent computer-assisted analysis to obtain PVC frequency as a function of decile levels of SaO2. Total sleep time averaged 333 +/- 75 minutes, the apnea index was 44 +/- 26 per hour, and the hypopnea index was 18 +/- 24 per hour. Premature ventricular complexes were observed in 23 (74 percent) of the subjects. By analysis of variance, no significant relationship was found between PVC frequency and decile levels of SaO2 for saturations greater than 60 percent; however, in the 16 subjects with SaO2 below 60 percent, a significant increase in PVC frequency was detected with decreasing SaO2 (p less than 0.01). Ventricular bigeminy was observed with SaO2 below 60 percent in three of these 16 subjects. From these results, we conclude that patients with obstructive sleep apnea are at relatively low risk of developing ventricular arrhythmias provided SaO2 remains greater than 60 percent, while those with SaO2 below 60 percent are at increased risk and should be managed accordingly.     

Treatment of metastatic colorectal carcinoma with cisplatin and 5-FU

Twenty patients with measurable metastatic colorectal carcinoma were treated every 3 weeks with cisplatin (100 mg/m2 iv) on Day 1 and 5-FU (1000 mg/m2/day by iv infusion over 24 hours) on Days 1-5. Seven patients were previously treated with chemotherapy. The mean performance status for all of the patients was 1.5 (Eastern Cooperative Oncology Group). None of the patients had an objective response to the chemotherapy; 11 patients had stable disease and nine had no response. This study demonstrates that the combination of cisplatin and 5-FU, administered at this dose and schedule, has minimal activity in patients with metastatic colorectal cancer.