Comparison of potency of human carcinogens: vinyl chloride, chloromethylmethyl ether and bis(chloromethyl)ether

The alpha-chloroether carcinogen chloromethylmethyl ether (CME) and its impurity bis(chloromethyl)ether (BCME) are direct-acting alkylating agents. Vinyl chloride (VC) is an indirect-acting carcinogen but its accepted carcinogenic intermediate, chloroethylene oxide, is also an alpha-chloroether. Both CME-BCME and VC have been in industrial use since about 1950. Hence, they were selected for comparison of potency as human carcinogens using numerous epidemiologic reports. There were 115 deaths due to angiosarcoma of the liver among several hundred thousand VC-exposed workers on the basis of reports from 10 countries during 1955 and 1984. Reports from five countries cited a total of 87 respiratory cancer deaths among only 3024 CME-BCME-exposed workers. If a recent court settlement in the United States is taken into account, the number of respiratory cancer deaths due to CME-BCME rises to 117. On the basis of these numbers of cancer deaths, and the levels and durations of exposure, it is concluded that VC is a weak human carcinogen compared to CME-BCME.     

Retained alloplastic temporomandibular joint disk implants: a retrospective study

The surgical treatment of intermediate- to late-stage temporomandibular joint disease often involves disk removal. In many instances, disks have not been replaced; long-term postsurgical findings of crepitation and osseous remodeling have been noted although subjective signs and symptoms have been few. Attempts to decrease the noises and bony changes, to enhance biologic resurfacing, and to prevent adhesions, recurrent pain, and dysfunction have prompted many surgeons to use various alloplastic materials to replace the disk, either in a planned permanent (retained) or a planned temporary (retrievable) manner. However, a certain degree of morbidity remains. This article reports clinical responses and radiographic findings in a series of patients who received retained alloplastic temporomandibular joint disk implants.     

Myoglobinuria from child abuse

A child with myoglobinuria following rhabdomyolysis from child abuse is described. The importance of early recognition and treatment of this condition is emphasized.     

Postnatal development of the chemosensitivity of rat cerebellar Purkinje cells to excitatory amino acids. An in vitro study

In vitro sagittal slices of immature rat cerebellum were used to study the development of the sensitivity of Purkinje cells (PCs) to L-aspartate (L-Asp), L-glutamate (L-Glu) and related derivatives. As early as postnatal day 0 all PCs already displayed clear excitatory responses to short iontophoretic applications of L-Asp, L-Glu and quisqualate while in the same conditions no effect of N-methyl-D,L-aspartate (NMDLA) was detected. By postnatal day 5, i.e. after the onset of the synaptogenesis, the sensitivity of PCs to L-Asp, L-Glu and quisqualate significantly increased up to values similar to those recorded in adult rat cerebellum and surprisingly nearly all (87%) the recorded cells now also displayed excitatory responses to NMDLA. Although this sensitivity of PCs to NMDLA was significantly lower than that observed with the other drugs, it persisted until the end of the first postnatal month when the adult type of connectivity is already well established but at this stage only 30 per cent of the tested cells were still sensitive to the agonist. During this period, excitatory responses elicited by NMDLA were selectively antagonized by 2-amino-5-phosphonovalerate (2-APV), suggesting that during postnatal development, NMDA receptor types are transiently expressed on PCs membranes since in the adult, NMDLA no longer had an excitatory effect. Instead, this drug now exerted a preferential antagonistic action on the excitatory response elicited by L-Asp. Also in the adult, no major changes occurred in the sensitivity of PCs to L-Asp, L-Glu and quisqualate when these drugs were ejected at a dendritic site whereas, when ejected at the somatic level, the sensitivity of the cell appeared 2-3 times lower.     

Mathematical modeling of nicotine and cotinine as biological markers of environmental tobacco smoke exposure

Computer software developed in our laboratory (CMATRIX) was used to design a physiological pharmacokinetic model of nicotine absorption, distribution, metabolism and excretion in man. The model accommodates inhalation of nicotine from various environmental settings and physiological conditions in man. It was also used to predict pharmacokinetic behavior of cotinine arising from nicotine metabolism. Model-predicted variations in body-fluid nicotine levels confirm that nicotine is not an acceptable quantitative marker of environmental tobacco smoke (ETS) exposure. Though cotinine provides a more stable pattern, predicted interindividual variation suggests the need for specific strict sampling and monitoring guidelines for cotinine to be a reliable quantitative marker.     

Predicting cerebral ischemia during carotid endarterectomy

We reviewed 86 consecutive patients undergoing elective carotid endarterectomy to determine whether preoperative clinical and angiographic data could be used to predict the risk of intraoperative cerebral ischemia during carotid occlusion. Electroencephalographic (EEG) monitoring with on-line Berg-Fourier transformation was carried out in all patients. A total of 32 patients (37.2%) underwent intraoperative shunting. Of these, 13 had no EEG changes but underwent shunting because of the surgeon's preference, while 19 patients underwent shunting because of EEG changes consistent with cerebral ischemia. There was one permanent (1.2%) and one transient (1.2%) neurologic deficit. Angiographic findings, clinical histories, and intraoperative EEGs were retrospectively reviewed to determine which risk factors best predicted the occurrence of intraoperative cerebral ischemia. Stroke within six weeks increased the risk of intraoperative cerebral ischemia 20-fold. Intracranial disease and contralateral carotid stenosis increased the risk of ischemia 17-fold and 16-fold, respectively. Statistical summation of all risk factors yielded a probability equation for EEG change that accurately quantitated pre-operative risk. Prospective application of this probability equation may simplify operative decision making if EEG monitoring is not available.     

Continuous venous oximetry in surgical patients.

A prospective study was performed to evaluate the efficacy of continuous venous oximetry to supplement traditional hemodynamic monitoring in 39 critically ill surgical patients. There was no statistically significant difference in SvO2 between the continuous in vivo values and in vitro values (0.694 +/- 0.095 vs. 0.698 +/- 0.108). There was no statistically significant correlation between continuously measured SvO2 and PaO2 (r = 0.09, p greater than 0.5), SaO2 (r = 0.08, p greater than 0.5), or oxygen consumption (r = 0.46, p greater than 0.5). There was a slight but statistically significant correlation between continuously measured SvO2 and cardiac output (r = 0.40, p less than 0.025) and oxygen delivery (r = 0.49, p less than 0.005). There was a highly significant correlation between continuously measured SvO2 and oxygen utilization coefficient (r = -0.96, p less than 0.001). Continuously measured SvO2 is a reliable predictor of SvO2 measured intermittently by in vitro methods. In critically ill surgical patients, SvO2 does not correlate highly with the individual determinants of oxygen transport but rather correlates with the oxygen utilization coefficient and therefore reflects the overall balance between oxygen consumption and delivery.