The relationships between cerebral blood volume (CBV), cerebral blood flow (CBF), and the cerebral vascular mean transit time (t v ) during acute changes in the PaCO 2 over a range of 15 to 76 torr were investigated in vivo in rhesus monkeys by serially determining the mean transit time of a vascular tracer, 15 O-labeled carboxyhemoglobin, and the mean transit time of a diffusible tracer, 15 O-labeled water. Over this range of PaCO 2 , a significant linear relationship of CBV = 0.041 PaCO 2 + 2.0 was found. For each one torr change in PaCO 2 , there is a change in CBV of 0.041 ml/100 gm of perfused tissue. At a normocarbic value of PaCO 2 (37 torr), an average value of 3.5 ml/100 gm was found. A nonlinear relationship of CBV and CBF was found. This relationship is expressed in the equation, CBV = 0.80 CBF 0.38 . A significant linear relationship was found between CBF and PaCO 2 . This was described by the equation, CBF = 1.8 PaCO 2 - 16.75. For each one torr change in the PaCO 2 , there is a 1.8 ml/100 gm per minute change in the CBF. At a normocarbic value of PaCO 2 (37 torr), an average value of CBF of 50 ml/100 gm per minute was found. The relationship of CBV and t v was nonlinear and was expressed in the equation, t C15O = 41 CBF -0.62 .

The Effects of Changes in PaCO2 Cerebral Blood Volume, Blood Flow, and Vascular Mean Transit Time

Lipoprotein lipase and lipolysis: central roles in lipoprotein metabolism and atherogenesis.

Background The role of antithrombotic therapy in secondary prevention after myocardial infarction is well established. Although the available literature suggests that warfarin is superior to aspirin, aspirin is currently the more widely used drug. We studied the efficacy and safety of warfarin, aspirin, or both after myocardial infarction. Methods In a randomized, multicenter trial in 3630 patients, 1216 received warfarin (in a dose intended to achieve an international normalized ratio [INR] of 2.8 to 4.2), 1206 received aspirin (160 mg daily), and 1208 received aspirin (75 mg daily) combined with warfarin (in a dose intended to achieve an INR of 2.0 to 2.5). The mean duration of observation was four years. Results The primary outcome, a composite of death, nonfatal reinfarction, or thromboembolic cerebral stroke, occurred in 241 of 1206 patients receiving aspirin (20.0 percent), 203 of 1216 receiving warfarin (16.7 percent; rate ratio as compared with aspirin, 0.81; 95 percent confidence interval, 0.69 t...

Warfarin, aspirin, or both after myocardial infarction

Randomized versus historical controls for clinical trials

Objective. —To quantify the type and frequency of identifiable factors associated with medication prescribing errors. Design and Setting. —Systematic evaluation of every third prescribing error detected and averted by pharmacists in a 631-bed tertiary care teaching hospital between July 1,1994, and June 30, 1995. Each error was concurrently evaluated for the potential to result in adverse patient consequences. Each error was retrospectively evaluated by a physician and 2 pharmacists and a factor likely related to the error was identified. Participants. —All physicians prescribing medications during the study period and all staff pharmacists involved in the routine review of medication orders. Main Outcome Measures. —Frequency of association of factors likely related to medication errors in general and specific to medication classes and prescribing services (needed for medical, pediatric, obstetric-gynecologic, surgical, or emergency department patients); and potential consequences of errors for negative patient outcomes. Results. —A total of 2103 errors thought to have potential clinical importance were detected during the 1-year study period. The overall rate of errors was 3.99 errors per 1000 medication orders, and the error rate varied among medication classes and prescribing services. A total of 696 errors met study criteria (ie, errors with the potential for adverse patient effects) and were evaluated for a likely related factor. The most common specific factors associated with errors were decline in renal or hepatic function requiring alteration of drug therapy (97 errors, 13.9%), patient history of allergy to the same medication class (84 errors, 12.1%), using the wrong drug name, dosage form, or abbreviation (total of 79 errors, 11.4%, for both brand name and generic name orders), incorrect dosage calculations (77 errors, 11.1%), and atypical or unusual and critical dosage frequency considerations (75 errors, 10.8%). The most common groups of factors associated with errors were those related to knowledge and the application of knowledge regarding drug therapy (209 errors, 30%); knowledge and use of knowledge regarding patient factors that affect drug therapy (203 errors, 29.2%); use of calculations, decimal points, or unit and rate expression factors (122 errors, 17.5%); and nomenclature factors (incorrect drug name, dosage form, or abbreviation) (93 errors, 13.4%). Conclusions. —Several easily identified factors are associated with a large proportion of medication prescribing errors. By improving the focus of organizational, technological, and risk management educational and training efforts using the factors commonly associated with prescribing errors, risk to patients from adverse drug events should be reduced.

https://jamanetwork.com/journals/jama/articlepdf/413555/jama_277_4_033.pdf

Factors related to errors in medication prescribing.

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The cerebral vascular response to reduction in arterial carbon dioxide tension

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General and regional circulatory responses to change in blood pH and carbon dioxide tension.

Resting human muscle blood flow (MBF) was determined simultaneously in the usual intramuscular injection sites to resolve whether variance in MBF could account for differences in drug absorption. Three pairs of muscles (gluteus maximus, vastus lateralis, and deltoid) were studied in each of 20 adult subjects. Use of dual, matched linear rate meters allowed two muscles to be studied simultaneously, with the order of injection random within an incomplete block design. MBF was calculated from the 133xenon washout rate using a single exponential that the computer found to best fit the data. Deltoid MBF (11.6 ml/100 gm/min plus or minus 0.5) was significantly (p smaller than 0.05) greater than gluteus MBF (9.6 plus or minus 0.5), with vastus or between right and left sides for each muscle. These data indicate that there are consistent differencies in resting MBF among specific muscle groups of sufficient magnitude (19%) to affect the rate of absorption and peak serum levels following intramuscular administration of drugs.

Blood flow in muscle groups and drug absorption.

Lipoprotein lipase activity (LLA) was measured in the adipose tissue of six healthy subjects and five members of a family in whom the trait for familial exogenous hypertriglyceridemia was segregating. The lipase activity measured was characteristic of lipoprotein lipase: increased by feeding, dependent on the presence of serum, and inhibited by sodium chloride and protamine sulfate. When compared with lipase activity in healthy individuals, LLA was grossly deficient in two siblings with postabsorptive chylomicronemia and was intermediate in both parents and one sibling, who had normal postabsorptive triglycerides. These findings are compatible with autosomal recessive inheritance. The hormone-sensitive lipolytic enzyme responsible for mobilization of free fatty acids from adipose storage was normal in the hyperlipemic subjects.

After a 104-g fat meal, the serum triglyceride increased more in subjects heterozygotic for LLA deficiency than in the healthy subjects, and there was a relatively greater increase in chylomicrons and very low density lipoproteins in the affected individuals. These observations demonstrate the physiologic importance of lipoprotein lipase in removal of these lipoprotein groups and further clarify the differences between endogenous and exogenous hypertriglyceridemia.

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Tissue Lipoprotein Lipase in Normal Individuals and in Individuals with Exogenous Hypertriglyceridemia and the Relationship of this Enzyme to Assimilation of Fat

The responses of the blood vessels of the hand to intra-arterial infusion of tyramine and to application of ice to the forehead were examined in patients with Raynaud's phenomenon and in normal subjects. The vasoconstrictor responses to tyramine and to ice were not significantly different in the patients and control subjects. Following intra-arterial administration of reserpine the vasoconstrictor response to tyramine was unaffected, while that in response to ice was significantly reduced to a comparable extent in both the patients and the control subjects. Catecholamine concentrations in brachial arterial and hand venous plasma were not significantly different in the patients and in the control subjects. Following oral administration of reserpine (1 mg/day) the vasoconstrictor responses to intra-arterial tyramine and to the application of ice were markedly reduced in patients with Raynaud's phenomenon. In response to this form of treatment eight of the nine patients followed for 1 to 3 years showed improvement characterized by decreased frequency and severity of vasospastic attacks and by healing of ulcerations. In two patients the improvement was temporary despite continued reserpine therapy.

Albert J. Wasserman

Papers

The cerebral vascular response to reduction in arterial carbon dioxide tension

General and regional circulatory responses to change in blood pH and carbon dioxide tension.

Blood flow in muscle groups and drug absorption.

Tissue Lipoprotein Lipase in Normal Individuals and in Individuals with Exogenous Hypertriglyceridemia and the Relationship of this Enzyme to Assimilation of Fat

Effect of Reserpine in Raynaud's Phenomenon