Coronary operations in patients with spinal cord injury.

BACKGROUND: The risk of heart disease in patients with spinal cord injury is similar to that in the general population. The physiologic derangements raise special problems in patients with SCI having coronary operations. METHODS: From January 1980 to May 1995, we performed coronary artery bypass procedures on 20 patients with SCI; 4 were tetraplegic and the remainder were paraplegic. The indication for operation was angina: unstable (13), exertional (4), or postinfarctional (3). Bowel and bladder care was given immediately before operation; operating room tables were double padded and a pelvic wrap was used to protect the back. Electric wheelchairs were used for early mobilization. RESULTS: Vasomotor instability from cardiopulmonary bypass was not present in patients with SCI. Pharmacologic support was required in the operating room by 4 patients for low vascular resistance, but in only one case in the intensive care unit. One patient required ventilation support for more than 24 hours. All patients were able to cough effectively. No thoracic wound complications occurred. There were three operative deaths, all in patients with multiple risk factors. The acute hospital stay averaged 9.3 days; patients were then transferred to an SCI unit for rehabilitation, were upper-extremity weight bearing was restricted for 2 to 4 weeks. CONCLUSIONS: Patients should not be denied coronary artery bypass procedures because of an SCI, but their special needs must be managed properly.

An effect of cell-cycle position on ultraviolet-light-induced mutagenesis in Chinese hamster ovary cells.

Using synchronous populations obtained by selectively detaching mitotic cells from cultures grown in monolayer, we demonstrate here that Chinese hamster ovary (CHO) cells exhibit a differential sensitivity to mutation induction by UV as a function of position in the cell cycle. When mutation induction to 6-thioguanine (TG) resistance is monitored, several maxima and minima are displayed during cell-cycle traverse, with a major maximum occurring in early S phase. Although cells in S phase are more sensitive to UV-mediated cell lethality than those in G1 or G2/M phases, there is not a strict correlation with induced mutation frequency. Fluence-response curves obtained at several times during the cell cycle yield Dq values approximating 6 J/m2. The primary survival characteristic which varies with cell cycle position is D0, ranging from 2.5 J/m2 at 6 h after mitotic selection to 5.5 J/m2 at 11 h afterward. Based on studies with asynchronous, logarithmically growing populations, as well as those mitotically selected to be synchronous, the optimum phenotypic expression time for induced TG resistance is 7--9 days and is essentially independent of both UV fluence and position in the cell cycle. All isolated mutants have altered hypozanthine-guanine phosphoribosyl transferase (HGPRT) activity, and no difference in the residual level of activity was detected among isolated clones receiving UV radiation during G1, S, or late S/G2 phases of the cell cycle. Changes in cellular morphology during cell-cycle traverse do not contribute to the differential susceptibility to UV-induced mutagenesis.

Evidence for altered vascular reactivity in sodium-sensitive young subjects with borderline hypertension.

To assess mechanisms associated with the pressor effects of a high sodium diet in susceptible individuals, the hemodynamic and hormonal effects of sodium depletion and repletion were studied in 33 normal subjects and 30 subjects with borderline hypertension. The hypertensive group had significantly higher mean arterial pressure, weight, hematocrit, and upright plasma renin activity. Forearm hemodynamics were measured during periods of ad lib diet, 10 mEq, and 200 mEq sodium diet. The fall in forearm resistance during reactive hyperemia was inversely related to mean arterial pressure at rest (R = .400, p less than .005) and rose significantly in hypertensive subjects during salt depletion, 39 +/- 3.6 to 61 +/- 6.1 mmHg/ml/min/100 g (p less than .05). Sodium sensitivity in either normotensive or borderline hypertensive subjects was defined as an increase in mean blood pressure of more than 5% when sodium repleted. The individuals who were sodium sensitive had a higher forearm vascular resistance during sodium depletion than those who were sodium resistant, 67 +/- 10.5 versus 45 +/- 4.1 mm/ml/min/100 g (p less than .03). We conclude that young individuals with borderline hypertension already have alterations in vascular reactivity. This trait is shared by normotensive individuals whose blood pressure rises in response to sodium.

An evaluation of the roles of mammalian cell mutation assays in the testing of chemical genotoxicity.

The present status of the applicability of mammalian cell gene mutation assays in the safety evaluation of industrial chemicals is evaluated from the industrial and regulatory point of view, with emphasis being placed on the CHO/HGPRT and mouse lymphoma tk +/- assays. The CHO/HGPRT assay was concluded to be a highly specific assay, but it might be less sensitive to mutagens that mainly induced large deletions. The mouse lymphoma assay was concluded to be sensitive, but it might have a lower specificity due to experimental artifacts such as pH and osmolality changes. Mammalian gene mutation assays, when conducted within their limitations, are concluded to be valuable in safety evaluation, providing results complementary to the Ames test and cytogenetic assays.

Mutagenic evaluations of four rubber accelerators in a battery of in vitro mutagenic assays.

The mutagenic/carcinogenic potential of four commercial accelerators were evaluated using a battery of in vitro assays. All of these compounds were mutagenic in one or more assays. Positive responses were noted in the Escherichia coli pol A+/pol A- DNA repair, mouse lymphoma L5178Y TK+/- forward mutation, BALB/3T3 cell transformation, and CHO cell chromosome aberration assays. In contrast to previous studies of accelerators, no mutagenic response was observed in the E coli WP2 uvrA- assay or in any of the Salmonella typhimurium strains tested. These studies have indicated that rubber accelerators should be regarded as potential human health hazards and that further in vitro and in vivo studies are needed to assess the potential genetic hazards of this large class of chemicals.