Regional cerebrovascular reactivity to carbon dioxide during cardiopulmonary bypass in patients with cerebrovascular disease

In patients with cerebrovascular disease, hypercarbia may cause redistribution of regional cerebral blood flow from marginally perfused to well-perfused regions (intracerebral steal), as evidenced by regional cerebral blood flow studies during carotid endarterectomy. During hypothermic cardiopulmonary bypass, the pH-stat method of acid-base management produces relative hypercarbia. To determine whether pH-stat management produces relative hypercarbia. To determine whether pH-stat management induces intracerebral steals, we investigated nine patients with cerebrovascular disease undergoing coronary artery bypass grafting. During hypothermic cardiopulmonary bypass, arterial carbon dioxide tension was varied in random order between 40 mm Hg and 60 mm Hg (uncorrected for body temperature). Regional cerebral blood flow was measured by clearance of 133 xenon injected into the arterial inflow cannula. Nasopharyngeal temperature (26.8 degrees-28.0 degrees +/- 2.2 degrees-3.0 degrees C), perfusion flow rate (2.14-2.18 +/- 0.70-0.73 L/min/m2), mean arterial pressure (67-68 +/- 6-9 mm Hg), arterial carbon dioxide tension (302-308 +/- 109-113 mm Hg), and hematocrit (23% +/- 4%) were maintained within narrow limits in each patient during arterial carbon dioxide tension manipulation. Global mean cerebral blood flow values were similar to previously reported values in patients free of cerebrovascular disease; patients in this study averaged 15.2 +/- 2.5 ml/100 gm/min at an arterial carbon dioxide tension of 46.1 +/- 8.4 mm Hg and 25.3 +/- 6.1 ml/100 gm/min at an arterial carbon dioxide tension of 71.1 +/- 11.8 mm Hg. Carbon dioxide reactivity, defined as mean global cerebral blood flow (in ml/100 gm/min) divided by arterial carbon dioxide tension (in mm Hg), was similar in the region having the lowest regional cerebral blood flow and in the brain as a whole. No patient developed evidence of an intracerebral steal at the higher arterial carbon dioxide tension. During hypothermic cardiopulmonary bypass, higher levels of arterial carbon dioxide tension, such as those associated with the pH-stat management technique, are apparently not associated with potentially harmful redistribution of cerebral blood flow in patients with cerebrovascular disease.     

Genetics: Changing Health Care in the 21st Century

Advances in human genetics are rapidly changing the scope of information and care that can be provided to health care consumers. By the year 2005 it is expected that the entire human genome will be mapped and all 70,000–100,000 genes will be identified. Currently, there are more than 5,000 known single-gene disorders. With the movement of specialized health services into the primary care setting, nurses increasingly will need to be knowledgeable about genetic disorders, screening/diagnostic tests, and implications for health care. In addition, the management of genetic information raises issues of informed consent, privacy and confidentiality, truth telling and disclosure, and nondiscrimination.     

Nutritional determinants of haemostatic factors in the Caerphilly Study

A study of possible nutritional determinants of certain haemostatic factors (heparin-neutralizing activity, fibrinogen and antithrombin III) was conducted in the Caerphilly cohort of 2512 men. Data on diet were obtained in a sub-sample of 665 men by a 7-d weighed dietary inventory and in the complete cohort by questionnaire. All the associations between major nutrients and haemostatic factors were weak and few achieved statistical significance. There were significant associations between two of the blood tests and total energy intake which suggests that, in general, relationships between nutritional variables and thrombosis-related factors should be standardized for total energy intake. Negative associations between alcohol, fibrinogen and antithrombin III and positive associations between fibre, polyunsaturated fat and antithrombin III are of possible clinical or public health importance. However, nutritional factors appear to explain only about 3 per cent of the variance in the distributions of the haemostatic factors examined. The extent to which uncertainties in the measurement of dietary intake will have led to the underestimate of the true association is, of course, unknown. At the same time it is of relevance that in similar studies of dietary determinants of plasma cholesterol only about 3 per cent of the variance of cholesterol levels can be explained.     

Regional activity of galactose-1-phosphate uridyltransferase in rat brain.

The sp act of galactose-1-phosphate uridyltransferase has been measured in individual regions of adult rat brain to see if site-specific differences in enzyme activity can aid in the understanding of brain abnormalities observed in well-treated galactosemic patients. The sp act in the cerebellum, brain stem, and midbrain were higher than in the cortex, hippocampus, and striatum. Activity in the cerebellum was 2-fold greater than that found in the cortex. Steady state levels of mRNA of the enzyme in the cerebellum were twice that of the cortex corresponding to the ratio of enzyme sp act in the two regions. Measurement of the kinetic parameters in tissue from the cerebellum and cortex revealed that the regional specificity in enzyme activity observed in the brain represents differences in the Vmax. Inhibition of the enzyme by uridine and uridine triphosphate was essentially the same for all regions and was not influenced by the 2-fold differences observed in the levels of enzyme. Inhibition by uridine was significantly greater than that for uridine triphosphate.     

The bioavailability and nonlinear pharmacokinetics of MK-679 in humans

MK-679 (R(?)-3-((3-(2-(7-chloro-2-quinolinyl)ethenyl)phenyl)(3-(dimethylamino)-3-oxopropyl)thio)methyl)thio(propanoic acid) is a potent and specific LTD₄-receptor antagonist. The disposition of MK-679 was investigated in a three-way crossover study in 12 healthy males receiving single intravenous doses of 75, 250, and 500 mg of MK-679. A greater than proportional increase in the area under the plasma concentration—time curve of MK-679 was observed with increase in dose. The plasma concentration data for each subject fitted well to the differential equations for a two-compartment model with linear tissue distribution and Michaelis-Menten elimination from the central compartment, indicating that the elimination of MK-679 in humans is saturable. In a previous study, the disposition of MK-679 in humans was also dose-dependent when given together with its S(+)-isomer, L-668,018. Thus, the disposition of MK-679 in humans is dose-dependent regardless of the presence of its stereoisomer. Also, the bioavailability of MK-679 was determined in six healthy males receiving simultaneously an oral dose of 250 mg of MK-679 and intravenous infusion of 1 mg ¹⁴C-MK-679. Results of this study indicate that the oral bioavailability of MK-679 is nearly quantitative.     

Are Continuity Clinic Patients Less Satisfied When the Resident Is Postcall?

Due to recent public debate and newly imposed resident work hour restrictions, we decided to investigate the relationship of resident call status to their ambulatory patients' satisfaction. Resident continuity clinic patients were asked to rate their level of satisfaction on a 10-point Likert-type scale. Using multiple regression approaches, these data were then assessed as a function of resident call status. We found that in 646 patient encounters, patient satisfaction scores were significantly less when the resident was postcall, 8.99 ± 1.8, than when not postcall, 9.31 ± 1.3. We herein discuss etiologies and implications of these findings for both patient care and medical education.