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Biomedical subjects

R L Reed

Publications and source records attributed to R L Reed.

At least 55 records · Page 3Linked to original sources
PubMed1992

The pharmacokinetics of prophylactic antibiotics in trauma.

Despite prophylactic antibiotic use in abdominal trauma patients, infection rates remain high. A previous study from our institution indicated that higher doses of prophylactic antibiotics in trauma patients could significantly reduce subsequent infection rates. To determine if this resulted from altered pharmacokinetic profiles, we performed individualized pharmacokinetic analysis of the prophylactic amikacin regimens given to 28 trauma patients undergoing laparotomy. Patients were prospectively randomized to receive a standard regimen of 11 mg/kg of amikacin every 12 hours or to have their regimens adjusted based upon pharmacokinetic analysis. Repeated pharmacokinetic analyses were performed daily for the three-day prophylactic regimen. There was a significant expansion in the apparent volume of distribution for amikacin that correlated with fluid resuscitation. This, along with increased elimination rates, helps to explain the failure to achieve adequate amikacin levels using standard regimens in trauma patients. Such underdosing may contribute to relatively high infection rates following major abdominal injury.

Abdominal Injuries↗
PubMed1992

The disparity between hypothermic coagulopathy and clotting studies.

Hypothermic patients commonly develop coagulopathy, but the effects of hypothermia on coagulation remain unclear because clinical laboratories routinely perform clotting tests only at 37 degrees C. Measurements of activated partial thromboplastin times (APTT), prothrombin times (PT), and thrombin times (TT) were performed on plasma from normothermic and hypothermic rats at a range of temperatures (25 degrees-37 degrees C) to assess the effects of hypothermia on apparent clotting factor levels and clotting factor activities. In general, clotting times were more severely prolonged when test temperatures were hypothermic than when body temperatures were hypothermic. Indeed, little to no prolongation resulted from body hypothermia alone. These findings reveal the observed disparity between clinically evident hypothermic coagulopathy and near-normal clotting studies. Clotting studies performed at 37 degrees C will not confirm hypothermic coagulopathy. These results indicate that the appropriate treatment for hypothermia-induced coagulopathy is rewarming rather than administration of clotting factors.

Animals↗
PubMed1992

Microsomal formation of a pyrrolic alcohol glutathione conjugate of the pyrrolizidine alkaloid senecionine.

1. Pyrrolizidine alkaloids (PAs) are metabolized primarily to putative dehydroalkaloid (PA pyrrole) metabolites and to PA N-oxide by rat liver microsomal monooxygenases. 2. The dehydroalkaloids are highly reactive and either bind covalentely to tissue nucleophiles or are hydrolysed to the more stable pyrrole, (R,S)-6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (DHP), and the corresponding necic acid. 3. Addition of glutathione (GSH 1 mM) to incubation mixtures containing rat liver microsomes and the PA senecionine (SN), resulted in the formation of a conjugate of DHP with GSH. 5. The mass spectrum of this DHP-GSH conjugate was identical to that of the chemically-synthesized dehydroretronecine (the R enantiomer of the racemic DHP) and GSH. 6. Only negligible amounts of DHP-GSH conjugate were formed when DHP itself was incubated with GSH at physiological pH. 7. These findings provide strong evidence for the microsomal conversion of SN to a highly reactive metabolite, presumably dehydrosenecionine, which then reacts with GSH to form the DHP-GSH conjugate. 8. It is likely that a similar mechanism is responsible in vivo for the formation of GSH conjugates of DHP from SN and other PAs.

Alcohols↗
PubMed1992

Readers' responses ... medical noncompliance.

The Second Opinion staff invited a number of its readers who are physicians to respond to our recent Case Stories section on medical noncompliance, which included a case story by Kevin Coleman and commentary and overview by Arthur W. Frank (Second Opinion 17, no. 3 [January 1992]). Our thanks to those who shared their reflections, a number of which have been excerpted here.

Attitude of Health Personnel↗
PubMed1991

Antibiotic choices in surgical intensive care unit patients.

Antibiotics have dramatically changed the care of the critically ill patient over the last 60 years. Patients with complex physiological conditions present with infectious processes requiring the effective use of antimicrobial drugs. In many situations, the inability to eradicate the infectious process is complicated by the progressive development of resistance among the causative organisms. Systemic antibiotic prophylaxis is warranted only for the prevention of wound infections. Regimens in these cases should use large doses of nontoxic antibiotics covering the spectrum of organisms likely to contaminate the wound. The duration of wound prophylaxis should be short, essentially covering only the period of active wound closure; this is usually less than 24 hours. Prevention of most other infections in the ICU depends on the recognition and correction of the various disturbances of host defenses. Topical antibiotic therapy may reduce the level of colonization for a few specific types of infection. Initial empiric antibiotic therapy should be started for clear indications. The antibiotics chosen should be those most likely to be effective against the probable organisms, those which have the lowest toxicity, and those with the smallest likelihood of inducing multiresistance. They must be adjusted promptly based on the microbiologic sensitivities observed. The realization that the physiology of critical illness may alter the normal relations between drug dosages and the tissue antibiotic levels obtained mandates a different approach to the treatment of these patients. The drug volumes of distribution are generally markedly expanded in these patients. Furthermore, these patients require high tissue antibiotic concentrations to improve the chances for successful therapy. Thus, the antibiotics selected must be capable of providing these levels without significant toxicity to the host. Therapy should be continued based on the clinical response observed. Premature cessation of effective therapy often results in relapse.

Aminoglycosides↗
PubMed1991

Role of cytochrome P450IIIA4 in the metabolism of the pyrrolizidine alkaloid senecionine in human liver.

Studies were carried out to investigate the metabolism of senecionine by human liver microsomes and the role of human cytochrome P450IIIA4 in this process. Human liver microsomes metabolized senecionine to two major products, (+/-)-6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (DHP) and senecionine N-oxide. The rates of product formation (DHP and senecionine N-oxide) varied widely with the microsomal samples tested. There was a 30-fold difference in DHP formation and a 25-fold difference in N-oxidation between the poorest metabolizer and the highest metabolizer of senecionine. The conversion of senecionine to DHP and senecionine N-oxide in human liver microsomes was markedly inhibited by the mechanism-based inactivators of P450IIIA4, gestodene and triacetyloleandomycin. Anti-P450IIIA4 IgG, at a concentration of 1 mg/nmol of P450, was found to inhibit completely the formation of DHP and senecionine N-oxide in human liver microsomes (HL101) having low activity toward senecionine. At 5 mg IgG/nmol P450, anti-P450IIIA4 inhibited 90 and 84% respectively of the formation of DHP and senecionine N-oxide in liver microsomes (HL110) with the highest activity toward senecionine. The formation of DHP or senecionine N-oxide was highly correlated with the amount of P450IIIA4 measured in the microsomes using polyclonal anti-P450IIIA4 IgG. The rate of DHP production also had a strong correlation with the rate of senecionine N-oxide formation (r = 0.999) and with the rate of nifedipine oxidation (r = 0.998). Our present studies provide evidence that P450IIIA4 is the major enzyme catalyzing the bioactivation (DHP formation) and detoxication (senecionine N-oxide formation) of senecionine in human liver.

Antineoplastic Agents, Phytogenic↗
PubMed1991

Hypertonic saline alters plasma clotting times and platelet aggregation.

Hypertonic (7.5%) saline (HS) is advocated for resuscitation of injured and burned patients. Recent animal studies indicate that HS increases bleeding during uncontrolled hemorrhage, although the mechanisms for this are unclear. To investigate potential anticoagulant effects of HS (without dextran), normal human plasma was serially diluted with either HS or normal (0.9%) saline (NS). Prothrombin times (PT), activated partial thromboplastin times (APTT), and platelet aggregation studies were performed. Significant (p less than 0.05) deteriorations in clotting tests and platelet aggregation developed when 10% or more of normal plasma was replaced by HS, whereas there was no effect from similar NS dilutions. Strong correlations were observed between clotting test changes and sodium concentrations (R2 greater than 0.80, p less than 0.0001). Thus, HS exhibits anticoagulant activity, but not at the usual small volumes necessary to produce hemodynamic improvement. Nevertheless, the anticoagulant effect may be more pronounced with ongoing clotting factor losses or with the addition of dextran.

Blood Coagulation↗
PubMed1991

The interrelationship between physical exercise, muscle strength and body adiposity in a healthy elderly population.

OBJECTIVE: To determine the relationship between habitual physical exercise and body adiposity in a healthy elderly population. RESEARCH DESIGN AND METHODS: Physical exercise was measured by a questionnaire previously adapted for use with the healthy elderly. The level of exercise was converted into calories expended over the previous 14 days and was divided into tertiles. Body adiposity was measured at six sites by anthropometry, and overall percent body fat was measured by bioelectric impedence. PARTICIPANTS AND SETTING: Two hundred and thirteen healthy ambulatory subjects over the age of 60 (116 females and 97 males) were recruited from a large retirement community in Southern Arizona. The mean age of the subjects was 70.0 years. RESULTS: Percent body fat was similar in men with different levels of physical activity (27.9% for lowest tertile of activity, 28.1% for middle tertile of activity, and 28.5% for highest tertile of activity). The corresponding values of percent fat in women was 38.0%, 36.0%, and 37%, respectively. There was a statistically significant increase in muscle strength measured in five muscle groups with a hand-held dynamometer with increasing levels of activity. CONCLUSIONS: These data indicate that level of physical exercise, over the range of 0 to 1,528 Kcal/day, does not predict body adiposity in the healthy elderly population. To decrease body fat without a change in dietary habits would require a more intensive exercise regimen than currently being undertaken by most healthy elderly people.

Aged↗
PubMed1991

The relationship between muscle mass and muscle strength in the elderly.

To determine the extent that muscle mass is predictive of muscle strength in the elderly, anthropomorphic estimates of muscle area and impedance measurements of muscle mass and peak isometric muscle strength were obtained in a relatively healthy older population over 65 years of age (mean age = 71.7; n = 218). Midarm muscle area correlated strongly with upper arm strength (r = 0.68, P less than 0.0001) while midthigh muscle area had a much lower correlation with thigh muscle strength (r = 0.29, P less than 0.0001). These muscle area calculations also include bone area. Lean body mass calculated by bioelectric impedance correlated highly with cumulative muscle strength measured by summing all muscle groups (r = 0.79, P less than 0.0001). To determine whether aging alters muscle strength per unit of muscle mass, additional middle-aged subjects were included, and three groups, middle-aged (55-64) (n = 78), young-old (65-74) (n = 161), and old-old (75+) (n = 57), were compared. A significant age-related trend of decreasing muscle strength per unit of lean body mass was noted. It is concluded that although muscle mass correlates with muscle strength in a healthy older population, use of simple age-independent clinical measurements of body mass should not be used to predict muscle strength.

Aged↗
PubMed1991

Detectable serum levels of tumor necrosis factor alpha may predict early mortality in elderly institutionalized patients.

OBJECTIVE: To determine if detectable serum tumor necrosis factor alpha (TNF) levels are associated with higher mortality in nursing home residents. SUBJECTS AND METHODS: The basal serum concentrations of TNF and interleukin-1 alpha (IL-1) were measured in 129 elderly nursing home patients (mean age of 89 years), and survival in the cohort was monitored over a 13-month period. RESULTS: At 4 months follow-up, seven out of 33 patients with detectable serum TNF levels had died (21.2%), and only three out of 96 patients with undetectable serum TNF levels had died (3.1%) (P less than 0.001). The difference in mortality remained significant up to 13 months of follow-up (P less than 0.05). Those with detectable serum TNF levels and those with undetectable levels were comparable in age, body mass index, hematocrit, lymphocyte counts, and serum level of albumin, prealbumin, and retinol-binding protein. When patients with detectable serum IL-1 levels were compared to those with undetectable levels, there were no significant differences in mortality over a 13-month period. CONCLUSION: Detectable serum TNF levels in elderly nursing home patients may be a predictor of early mortality.

Aged↗
PubMed1991

Serum levels of tumor necrosis factor and IL-1 alpha and IL-1 beta in diabetic patients.

OBJECTIVE: To determine whether chronic hyperglycemia causes increased levels of serum tumor necrosis factor (TNF) and interleukin 1 alpha (IL-1 alpha) and IL-1 beta. RESEARCH DESIGN AND METHODS: Sera were obtained from 59 diabetic patients, 44 chronically ill nondiabetic patients, and 34 age-matched healthy control subjects. Mononuclear cells were isolated from a subgroup of diabetic patients and healthy control subjects. RESULTS: Except for a modest increase in the prevalence of detectable serum TNF levels in diabetic patients, the serum cytokines measured in this study did not appear to be altered in diabetes. In vitro TNF production by mononuclear cells was not altered in diabetic patients. However, in vitro IL-1 beta secretion, in response to lipopolysaccharides, was reduced. CONCLUSIONS: Diabetes mellitus is not associated with significant changes in serum levels of TNF, IL-1 alpha, or IL-1 beta. In vitro secretion of IL-1 beta in response to lipopolysaccharides may be reduced in diabetes.

Aged↗
PubMed1991

Treatment of diabetes in the elderly.

Diabetes mellitus is one of the most common medical problems in elderly patients. There is a strong rationale for therapy in most patients with diabetes, even those who are asymptomatic. Family physicians should be aware of several age-associated differences in the management and treatment of diabetes in older patients. For elderly patients, dietary modifications may include an increase in the percentage of carbohydrates and a decrease in the percentage of fat. For obese patients, dietary therapy should also emphasize a decrease in overall calories. Oral hypoglycemic agents are generally used as the initial drug therapy. Insulin therapy should be instituted when oral agents fail to reduce the blood glucose level, when the blood glucose level is very high and in other special circumstances. A careful choice of medications for other common problems associated with diabetes, such as hypertension, hyperlipidemia and peripheral neuropathy, is also essential.

Aged↗
PubMed1990

Determination of Senecio alkaloids by thermospray liquid chromatography/mass spectrometry.

A series of Senecio alkaloid and alkaloid N-oxide standards has been analyzed using positive and negative ion thermospray liquid chromatography/mass spectrometry (LC/MS) with an ammonium acetate-containing mobile phase. On-line separations of pyrrolizidine alkaloids from extracts of Senecio jacobaea (tansy ragwort) and Senecio vulgaris (common groundsel) were done using an ammonium hydroxide-containing mobile phase. All of the alkaloids known to be present in the extracts were detected by ammonium hydroxide thermospray LC/MS, as well as many other components which may be as-yet-unidentified alkaloids.

Acetates↗
PubMed1990

Academic consequences of a trauma system failure.

Houston is served by only two trauma centers: Hermann Hospital (University of Texas Medical School at Houston [UTMSH]), and Ben Taub General Hospital (Baylor College of Medicine). In mid-1988, Hermann Hospital, prompted by a shortage of ICU nurses and +8.0 million/yr of uncollectible trauma charges, began to divert critically ill and injured patients to the already overburdened Ben Taub General Hospital. The academic consequences to UTMSH included a severe loss of clinical experience by the surgical residents and medical students and a severe reduction in faculty-generated billing. The lost billing from the trauma service and the other clinical services approximated +8.0 million/yr. This equated to an +13.5 million decrease in the anticipated billings for the year. Alternative revenue sources were not apparent. Other centers with a heavy trauma system commitment are at risk to suffer similar unsettling academic sequelae as our trauma systems fail.

Academic Medical Centers↗
PubMed1990

Lack of an association between the presence of tumor necrosis factor or interleukin-1 alpha in the blood and weight loss among elderly patients.

To determine the association between blood cytokine levels and body weight loss in elderly patients, serum levels of cachectin/tumor necrosis factor alpha (TNF) and interleukin-1 alpha (IL-1) were measured with specific and sensitive ELISA systems. Of the 19 healthy young subjects, two (10.5%) had detectable levels of serum TNF and one (5.3%) was positive for IL-1. In the healthy elderly group, two of the 12 subjects (16.7%) had measurable TNF levels and four (33.3%) had elevated IL-1 levels. Of the 61 ambulatory elderly patients, 31.1% had serum that contained TNF and 22.9% had IL-1. Similar proportions were found in 127 nursing home patients. None of the common diseases examined in this study nor any commonly used medications were associated with increased serum cytokine levels. Patients with weight loss of more than 5 lbs were less likely to have elevated serum TNF and IL-1 levels compared to the rest of the group. It is concluded that although elevated levels of TNF or IL-1 may occur more frequently in older groups, there is no evidence for a causal relationship between these circulating cytokines and clinically significant weight loss in the elderly.

Adult↗