Influence of multi-lumen extensions on fluid flow through intravenous cannulae.

Multi-lumen extensions used to infuse multiple fluids via a single intravenous cannula might increase resistance and so limit the flow that can be achieved. We constructed low-pressure and high-pressure models and compared the effect of two different multi-lumen extensions on flow rate. Both multi-lumen extensions reduced flows by up to 76% (p < 0.001). The effect was greatest with large cannulae and in the high-pressure model, with the longer and narrower extension most impeding flow. Multi-lumen extensions can therefore significantly impede fluid flow, and should be avoided or removed when rapid infusion is required. These effects are less important in paediatric anaesthesia where smaller cannulae are used. Manufacturers should include internal diameter or flow effects on the packaging of these extensions to assist clinicians in making such decisions.

Linkage between cholesterol 7alpha-hydroxylase and high plasma low-density lipoprotein cholesterol concentrations.

Interindividual differences in plasma low-density lipoprotein cholesterol (LDL-C) levels reflect both environmental variation and genetic polymorphism, but the specific genes involved and their relative contributions to the variance in LDL-C are not known. In this study we investigated the relationship between plasma LDL-C concentrations and three genes with pivotal roles in LDL metabolism: the low-density lipoprotein receptor (LDLR), apolipoprotein B (APOB), and cholesterol 7alpha-hydroxylase (CYP7). Analysis of 150 nuclear families indicated statistically significant linkage between plasma LDL-C concentrations and CYP7, but not LDLR or APOB. Further sibling pair analyses using individuals with high plasma LDL-C concentrations as probands indicated that the CYP7 locus was linked to high plasma LDL-C, but not to low plasma LDL-C concentrations. This finding was replicated in an independent sample. DNA sequencing revealed two linked polymorphisms in the 5' flanking region of CYP7. The allele defined by these polymorphisms was associated with increased plasma LDL-C concentrations, both in sibling pairs and in unrelated individuals. Taken together, these findings indicate that polymorphism in CYP7 contributes to heritable variation in plasma LDL-C concentrations. Common polymorphisms in LDLR and APOB account for little of the heritable variation in plasma LDL-C concentrations in the general population.

Rapid infusion of a phospholipid emulsion attenuates the effects of endotoxaemia in horses.

REASONS FOR PERFORMING STUDY: Endotoxaemia currently is associated with a poor prognosis in horses. The results of recent trials in other species indicate that phospholipid emulsions reduce the deleterious effects of endotoxin (LPS). However, in a previous study in horses, a 2 h infusion of emulsion caused an unacceptable degree of haemolysis. HYPOTHESIS: Rapid administration of a lower total dose of emulsion would reduce the effects of LPS and induce less haemolysis; the emulsion would reduce inflammatory effects of LPS in vitro. METHODS: Twelve healthy horses received an i.v. infusion either of saline or a phospholipid emulsion (100 mg/kg), followed immediately by E. coli 055:B5 LPS (30 ng/kg). Clinical parameters, haematological profiles, serum tumour necrosis factor (TNF) activity, serum lipid profiles, urine analyses and severity of haemolysis were monitored before and at selected times after LPS. Monocytes were also incubated in vitro with LPS in the presence or absence of emulsion, after which TNF and tissue factor activities were determined. RESULTS: Clinical signs of endotoxaemia were reduced in horses receiving the emulsion, including clinical score, heart rate, rectal temperature, serum TNF activity, and the characteristic leucopenic response to LPS, when compared to horses not receiving the emulsion. Three horses receiving the emulsion had none, 2 had mild and one had moderate haemolysis. There were no differences in urinalysis results and creatinine concentrations, either within the groups over time or between the groups. Serum concentrations of phosphatidylcholine, bile acids and triglycerides peaked immediately after the infusion; there were no significant changes in concentrations of nonesterified fatty acids or cholesterol. Incubation of equine monocytes with emulsion prevented LPS-induced TNF and tissue factor activities. CONCLUSIONS: Rapid administration of emulsion significantly reduced inflammatory effects of LPS in vivo and caused a clinically insignificant degree of haemolysis. The results of the in vitro studies indicate that emulsion prevents not only LPS-induced synthesis of cytokines, but also expression of membrane-associated mediators (i.e. tissue factor). POTENTIAL RELEVANCE: Rapid i.v. administration of emulsions containing phospholipids that bind endotoxin may provide a clinically useful method of treating endotoxaemia in horses.

Risk factors in siblings of people with premature coronary heart disease.

Prior studies of the contribution of coronary disease risk factors to familial aggregation of premature coronary disease may have underestimated risk factors by relying on self-reported risk factor prevalence levels or, when risk factors have been measured, by using cut points in excess of the 90th percentile. To determine the actual prevalence of hyperlipidemia, hypertension and diabetes, and the awareness of these coronary risk factors in unaffected family members, 150 apparently coronary disease-free siblings of 86 people who had documented coronary disease before 60 years of age were studied. All subjects participated in a 1 day screening preceded by a self-administered risk factor questionnaire and a personal interview. Participation of both the index patients and siblings exceeded 86%. With the use of nationally established recommendations for blood pressure and lipids, which are based on coronary disease risk curves, screening revealed that 48% of brothers and 41% of sisters were hypertensive, 45% of brothers and 22% of sisters had a lipid abnormality, 38% of siblings were current cigarette smokers and 4.7% were diabetic. Two or more risk factors were present in 42% of brothers and 26% of sisters. More than 75% of siblings had one or more risk factors that would require intervention. When compared with a race-, gender- and age-matched reference population from the Lipid Research Clinics Prevalence Study, distributions for blood pressure and for total and low density lipoprotein cholesterol were higher for the siblings in every gender and age group.(ABSTRACT TRUNCATED AT 250 WORDS)

Medical house officers' knowledge, attitudes, and confidence regarding medical ethics.

As part of a trial of ethics education in a university-based, categorical, internal medicine training program, we surveyed all medical house officers at our institution regarding their knowledge of medical ethics, their attitudes and beliefs about selected issues in medical ethics, and their confidence in dealing with ethical problems. In a multivariate linear regression model, house officer knowledge scores were negatively correlated with postgraduate year, and positively correlated with age and with reporting a Jewish religious identity. A multivariate linear regression model predicting house officer confidence in dealing with ethical issues revealed a positive correlation with self-reported quality of ethics training in medical school and with being in the experimental group of house officers receiving ethics education. Attitudes and beliefs were largely uncorrelated with training or demographic characteristics. These results have implications for ethics education of both medical students and residents.

The preoperative consultation. Response to internists' recommendations.

Preoperative consultations are frequently performed; however, little is known about the way requesters respond to the recommendations offered. For this reason, 90 consecutive preoperative consultations, performed by a general medical unit, were reviewed and compared with 66 consecutive nonpreoperative consultations, performed by the same unit during the same period. Analysis disclosed that recommendations made during preoperative consultation were often not followed and were less likely to be followed than were those made during nonpreoperative consultation (53.9% v 68.9%). Controlling for the type of consultative advice offered and for the type of surgical service requesting the consultation did not alter this relationship. These results highlight the particular importance of consultant follow-up for recommendations made during preoperative consultations.

Medication problems among outpatients. A study with emphasis on the elderly.

When patients ascribe adverse symptoms to their medications, the medical care process can be affected. To investigate how often medical outpatients link various adverse symptoms with their medications and to learn what actions they take in response, 299 randomly selected medical outpatients were interviewed. Thirty percent of the subjects identified at least one medication as causing an undesirable symptom. Subjects 65 years or older attributed a lower mean number of adverse symptoms to their medications than did younger subjects. Subjects rarely reported modifying their medication regimens due to adverse symptoms, a finding supported by multiple regression analysis. Approximately one in four subjects did not discuss their symptoms with their providers. These results have important implications for medical care in general, and for the elderly in particular.

Health education program effects on the management of hypertension in the elderly.

Because the elderly are viewed as having more difficulty in complying with therapy, this analysis was directed at the effects of a health education program on their control of primary hypertension when compared with a younger population. The program consisted of three sequential interventions introduced in a randomized factorial design. Depsite the fact that elderly patients had more chronic disease, more complications from hypertension, and were receiving more complex drug therapies than younger patients exposed to the same experimental interventions, they demonstrated significantly higher levels of compliance with drug therapy, significantly higher levels of appointment keeping, and no difference in the proportion having their BP under control at two-year-follow-up. Longitudinal data collected at five-year follow-up indicate no decay effect. These results indicate such programs can be successfully implemented and equally effective for an elderly population.

Hemin stimulation of cAMP production in human lymphocytes.

Hemin stimulates cAMP production in human peripheral blood mononuclear cells (PBMC). The kinetics are similar to that of hormone-induced cAMP generation, namely a rapid effect followed by a desensitization phase. Several experimental findings suggest that prostaglandins do not mediate this effect. First, macrophage depleted T and B cells purified by erythrocyte-rosetting were as responsive as unfractionated PBMC to hemin. Second, indomethacin, an inhibitor of prostaglandin synthesis, and meclofenamate, a prostaglandin E2 receptor antagonist, had no effect on hemin stimulated cAMP production. In addition, propranolol, a beta-adrenergic receptor antagonist, had no effect on hemin-stimulated cAMP production. We also examined structural analogues of hemin. Among the metalloporphyrins (Fe, Ni, Co, Zn and Sn) and protoporphyrin IX tested only hemin (Fe-protoporphyrin) was active in stimulating cAMP production. No correlation was found between the ability of metalloporphyrins to stimulate cAMP production and their ability to generate H2O2. The data indicate that hemin stimulates cAMP production by directly affecting lymphocytes and that prostaglandins do not mediate this effect.

Polymerized liposomes as stable oxygen-carriers.

We have produced a surrogate erythrocyte ('hemosomes') by encapsulating human hemoglobin in polymerized vesicles composed of diacetylenic phospholipids plus or minus cholesterol. Hemoglobin (in the presence or absence of allosteric effectors) was encapsulated by a freeze-thaw method in large, unilamellar vesicles composed of monomeric lipids. Entrapment was demonstrated by molecular-sieve chromatography. Brief irradiation with ultraviolet light produced polymeric hemosomes with polymerization kinetics and conversions similar to liposomes in the absence of protein. Photo-induced oxidation of the heme was eliminated or severely limited by a combination of prior ligation with CO and the maintenance of high intravesicular hemoglobin concentrations (5-10 mM internal hemoglobin). The inclusion of allosteric effectors within polymerized hemosomes facilitated near-quantitative conversion to the oxy-HbA form. Gas permeability of monomeric and polymeric hemosomes was demonstrated by spectroscopic methods. Reversible spectral shifts, corresponding to oxygenation-deoxygenation, were obtained after brief evacuation and exposure to oxygen or nitrogen. The gas permeability of polymerized hemosomes appears sufficient for the vesicles to act as oxygen carriers in vivo, a notion that is strengthened by their apparent hemocompatibility.

Extracorporeal LDL cholesterol removal: role of LDL-pheresis in combination with other hypolipidemic therapy to regress vascular disease.

The direct relationship between hypercholesterolemia and atherosclerosis has resulted in formal cholesterol-lowering recommendations for patients at increased risk. The incomplete response to therapy of some forms of hypercholesterolemia as well as not uncommon drug intolerance prompted the development of extracorporeal techniques to reduce serum cholesterol levels. Nonhuman primate data and an analysis of human cholesterol epidemiology and reduction trials were used to establish guidelines that would maximize the likelihood of stabilizing or regressing established coronary artery atherosclerosis. These goals are a total cholesterol (TC) level of less than or equal to 150 mg/dL (3.9 mmol/L) and a ratio of TC to high-density lipoprotein cholesterol (HDL) of less than 2.8. Selective, extracorporeal removal of LDL cholesterol (LDL-pheresis) was combined with diet and hypolipidemic drugs in a pilot study at The Rogosin Institute to achieve these lipid end-points. Technical aspects of LDL-pheresis, the background rationale for its use as part of a combined hypolipidemic therapy, the initial experience at The Rogosin Institute, and plans for future studies and applications are presented.

Interleukin-6 predicts hypoalbuminemia, hypocholesterolemia, and mortality in hemodialysis patients.

Low serum albumin and low serum cholesterol levels are among the most consistent predictors of mortality in patients with end-stage renal disease (ESRD) undergoing hemodialysis. Hypoalbuminemia is often interpreted as a marker of poor nutrition, but serum albumin and cholesterol levels can also be low as part of a cytokine-mediated acute-phase reaction to acute or chronic inflammation. Here we report the results from a 900-day prospective study designed to determine whether tumor necrosis factor-alfa (TNF-alpha) and interleukin-6 (IL-6) predict serum albumin and cholesterol levels and mortality in a group of 90 ambulatory, adult hemodialysis patients with no acute infection, hospitalization or surgery, and no known acquired immunodeficiency syndrome (AIDS), malignancy, or liver disease. Measurable levels of TNF-alpha and/or IL-6 were found in 89 of 90 patients. Significant relationships were found between TNF-alpha and IL-6 and the degree of hypoalbuminemia and dyslipoproteinemia. IL-6 was the strongest predictor of mortality in univariate and multivariate analysis, followed by age, albumin level, and body mass index (BMI). Although the cause of hypercytokinemia was not addressed in this study, the data support the view that hypoalbuminemia and hypocholesterolemia are negative acute-phase responses to inflammatory stimuli. These results suggest that efforts to identify the nature of the stimuli for cytokine production and to lower cytokine levels in hemodialysis patients might be effective in improving the survival of patients undergoing hemodialysis.

Validity of physicians' self-reports of cardiovascular disease risk factors.

To determine the accuracy of self-reported risk factors in 78 physicians, self-reported information was compared to findings on a standardized examination. Measured weight (r = 0.98), height (r = 0.95), body mass index (r = 0.96), systolic blood pressure (SBP) (r = 0.72), and diastolic blood pressure (DBP) (r = 0.60) were highly correlated with self-reported values (all P < 0.0001). Mean self-reported SBP and DBP did not differ from measured values; measured weight was 1.5 kg greater and measured height 1.4 cm less than self-reported values (both p < 0.0001). Regression of measured on self-reported values indicated excellent agreement except for DBP and heart rate. Differences between measured and self-reported values were not associated with a variety of variables except for a greater difference in SBP at higher levels of SBP. None of the 60 self-reported nonsmokers had expired carbon monoxide levels greater than 10 ppm. These results indicate that physicians' self-reports of height, body mass index, SBP, and smoking are extremely accurate and suitable for research purposes.

Coffee intake and coronary heart disease.

We examined the risk of coronary heart disease (CHD) associated with coffee intake in 1040 male medical students followed for 28 to 44 years. During the follow-up, CHD developed in 111 men. The relative risks (95% confidence interval) associated with drinking 5 cups of coffee/d were 2.94 (1.27, 6.81) for baseline, 5.52 (1.31, 23.18) for average, and 1.95 (0.86, 4.40) for most recent intake after adjustment for baseline age, serum cholesterol levels, calendar time, and the time-dependent covariates number of cigarettes, body mass index, and incident hypertension and diabetes. Risks were elevated in both smokers and nonsmokers and were stronger for myocardial infarction. Most of the excess risk was associated with coffee drinking prior to 1975. The diagnosis of hypertension was associated with a subsequent reduction in coffee intake. Negative results in some studies may be due to the assessment of coffee intake later in life or to differences in methods of coffee preparation between study populations or over calendar time.

Symptoms of Raynaud's phenomenon in an inner-city African-American community: prevalence and self-reported cardiovascular comorbidity.

The objective of this study was to determine the prevalence of symptoms and the morbidity associated with Raynaud's phenomenon (RP) among African Americans. A total of 2196 randomly selected residents of an inner-city community, in Baltimore, completed a health-assessment survey. Symptoms of RP consisted of cold sensitivity plus cold-induced white or blue digital color change. One third (n = 703) reported cold sensitivity and 14% (n = 308) reported digital color change; 84 residents with symptoms of RP were identified, yielding an overall prevalence rate of 3.8% (95% confidence interval [CI] 3.0-4.6). RP was associated with poor or fair health status (odds ratio [OR] = 1.82, CI 1.18-2.81), heart disease (OR = 2.32, CI 1.39-3.87), and stroke (OR = 2.20, CI 1.17-4.15), after adjustment for age, gender, and physician-diagnosed arthritis. The prevalence of symptoms of RP in this African-American community is comparable to published reports from other populations. These community-based data suggest that identification of RP among African Americans should raise consideration of possible comorbidity, particularly cardiovascular disease.

Adverse drug reactions among the elderly: a reassessment.

The elderly are widely believed to be predisposed to adverse drug reactions, chiefly because of the large quantities of drugs they consume, combined with the effects of aging on distribution, metabolism, and the patterns of drug usage. These beliefs affect the physician's prescribing behavior. To study the validity of these concepts, the supporting medical literature was reviewed. Existing studies of the rates of adverse drug reactions have several methodologic limitations, including inadequate control for disease severity, the use of calculation denominators which overestimate incidence, and dependence upon definitions of medication error rates which do not adequately reflect the potential for adverse outcome. Further studies are needed for clarification of drug-use patterns and problems among the elderly.

Characteristics, diagnosis, and treatment of alcoholism in elderly patients.

The purpose of this study is to examine the ability of physicians to diagnose alcoholism in the elderly patient and to define characteristics specific to the elderly patient with alcoholism. During a 3-month period, all new admissions to the medical service of The Johns Hopkins Hospital were screened for alcoholism with two screening tests (the CAGE questionnaire and Short Michigan Alcohol Screening Test). The prevalence of screen-positive alcoholism was 27% in patients under 60 years of age and 21% in patients 60 years and older. Elderly patients with alcoholism were more likely to be black (P less than .01), but did not differ significantly in any other way from elderly patients who did not have alcoholism. Although 60% of screen-positive young patients with alcoholism were identified by their houseofficers, only 37% of elderly patients with screen-positive alcoholism were so identified (P less than .05). The elderly patients with alcoholism were significantly less likely to be diagnosed by their houseofficer if they were white, female, or had completed high school (P less than .01). Even when diagnosed, elderly patients with alcoholism were less likely than younger patients with alcoholism to have treatment recommended by their houseofficers (P less than .05) and, if treatment were recommended, it was less likely to be initiated (P less than .05). These data suggest that current medical education is deficient in providing physicians with the skills to detect and treat elderly patients with alcoholism.

Alcohol consumption and blood pressure in the 1982 Maryland Hypertension Survey.

This study examines the relationship between alcohol consumption and blood pressure in the 1982 Maryland Hypertension Survey, a crossectional population-based household survey of blood pressure control in adults residing in Maryland. In individuals less than 50 years old, a J shaped dose-response association was found with abstainers and heavy alcohol consumers having significantly higher blood pressures than moderate alcohol consumers (1 to 2 beverages per day). In individuals 50 years and older, alcohol was associated with higher blood pressures only at the highest levels of intake (greater than 2 beverages per day). The prevalence of hypertension was similarly affected in each age group. This association between alcohol consumption and blood pressure was independent of several variables that are associated with increased blood pressure such as age, sex, race, smoking, education, Quetelet index, social participation, and physical activity. The population attributable risk for hypertension due to heavy alcohol consumption is 5 to 7% in those greater than 50 years old and 6 to 8% in those less than 50 years old. These data suggest that alcohol consumption is a potentially important risk factor for elevations in blood pressure and hypertension.

A clinical trial to improve high blood pressure care in young urban black men: recruitment, follow-up, and outcomes.

This randomized trial recruited and followed underserved, inner-city, hypertensive (HTN), young black men and investigated whether a nurse-community health worker team in combination with usual medical care (SI) increased entry into care and reduced high blood pressure (HBP), in comparison to usual medical care (UC) alone. Emergency department records, advertising, and BP screenings identified potential participants with HBP. Telephone calls and personal contacts tracked enrollees. Of 1391 potential participants, 803 (58%) responded to an invitation to be screened and scheduled a visit. Of these, 528 (66%) kept an appointment, 207 (35%) were BP eligible, and 204 (99%) consented to enroll. At 12 months 91% of men were accounted for and 85.8% (adjusted for death, in jail, or moved away) were seen. Mean BP changed from 153(16)/98(10) to 152(19)/94(11) mm Hg in the SI group and 151(18)/98(11) to 147(21)/92(14) mm Hg in the UC group (P = NS). High rates of participation are attainable in this population; however, culturally acceptable ways of delivering HBP care are needed.

Barriers to hypertension care and control in young urban black men.

Barriers to high blood pressure (HBP) care and control have been reported in the literature for > 30 years. Few reports on barriers, however, have focused on the young black man with HBP, the age/sex/race group with the highest rates of early severe and complicated HBP and the lowest rates of awareness, treatment, and control. In a randomized clinical trial of comprehensive care for hypertensive young urban black men, factors potentially associated with care and control were assessed at baseline for the 309 enrolled men. A majority of the men encountered a variety of barriers including economic, social, and lifestyle obstacles to adequate BP care and control, including no current HBP care (49%), risk of alcoholism (62%), use of illicit drugs (45%), social isolation (47%), unemployment (40%), and lack of health insurance (51%). Having health insurance (odds ratio = 7.20, P = .00) and a negative urine drug screen (odds ratio = .56, P = .04) were significant predictors of being in HBP care. Low alcoholism risk and employment were identified as significant predictors of compliance with HBP medication-taking behavior. Men currently using illicit drugs were 2.64 times less likely to have controlled BP compared with their counterparts who did not use illicit drugs, and men currently taking HBP medication were 63 times more likely have controlled BP compared with men not taking HBP medication. Comprehensive interventions are needed to address socioeconomic and lifestyle issues as well as other barriers to care and treatment, if HBP care is to be salient and effective in this high risk group.