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Biomedical subjects

R L Reed

Publications and source records attributed to R L Reed.

At least 73 records · Page 4Linked to original sources

Decreased serum triiodothyronine is associated with increased concentrations of tumor necrosis factor.

Previous studies in laboratory animals have shown that tumor necrosis factor-alpha (TNF) may alter thyroid function tests. To determine whether elevated serum TNF levels are associated with altered serum concentrations of T4, T3, free T4, rT3, and TSH, we measured these parameters in 29 nursing home residents with detectable serum TNF levels and compared the levels to those found in 36 patients with undetectable serum TNF levels. The 2 groups were matched for age, sex, clinical problems, use of medications, and nutritional status. Patients with detectable serum TNF levels had significantly lower serum T3 concentrations compared to those with undetectable levels [1.072 +/- 0.588 vs. 1.621 +/- 0.594 nmol/L (mean +/- SD); P less than 0.01]. Differences in other tests did not achieve statistical significance. Thyroid function tests were not significantly different when patients with detectable interleukin-1 alpha levels, another cytokine secreted during endotoxemia, were compared to those with undetectable levels. These observations taken together with the previous findings in laboratory animals suggest that some of the alterations in thyroid hormone levels seen in nonthyroidal illness are associated with elevated serum concentrations of TNF.

Aged↗

Comprehensive geriatric assessment recommendations: adherence of family practice residents.

A study was performed to determine whether family practice residents followed recommendations made by a comprehensive geriatric assessment clinic. Of 109 consecutive consultations, 27 patients had follow-up visits with family practice residents who participated in the assessment and who subsequently served as their primary care physicians. Adherence of residents to 437 clinic recommendations was monitored for 90 days by medical record review. Although recommendations to begin or increase a medication were followed 85.4% of the time, residents followed recommendations to stop or decrease medications less than 65% of the time. Recommendations to order a specific laboratory test or x-ray examination were acted on 70.3% of the time. Preventive recommendations were followed only 54.3% of the time. Residents' adherence to team-based care plans varied widely by type of recommendation. Special efforts are needed to increase compliance with comprehensive geriatric assessment clinic recommendations, particularly those for preventive services.

Aged↗

Nutritional status and dietary management of elderly diabetic patients.

Dietary treatment of diabetes has long been the cornerstone of management of this common disease. Recent recommendations to increase the proportion of carbohydrate with concomitant reduction of dietary fat appear to be prudent, but scant data are available to support this supposition in the elderly. Modification of the source of carbohydrate as a means of providing better blood glucose control is based on limited data in controlled settings and needs to be tested in community settings before widespread alterations in the dietary composition can be widely recommended. Current recommendations for protein composition of the diet are probably adequate for the elderly diabetic patient who does not have obvious protein depletion. General guidelines for the dietary management of elderly diabetic patients are summarized in Table 5. Management of the elderly diabetic patient presents a strong challenge to the physician. Dietary recommendations for such patients should be highly individualized; patients' food preferences, ethnic background, financial resources, and support system should be taken into consideration. Simple recommendations drafted with the help of the patient are more likely to be successful. The elderly are often at risk for nutritional deficiency, and the presence of chronic disease such as diabetes profoundly affects metabolism, putting these individuals at still higher risk. Unfortunately, our current understanding of this problem is limited and additional research in this area is essential.

Aged↗

Hypothermia and blood coagulation: dissociation between enzyme activity and clotting factor levels.

Previous studies of hypothermia and blood coagulation have focused on alterations in the levels of blood clotting elements using coagulation tests performed under normothermic conditions. However, because of the enzymatic nature of activated clotting factors, hypothermia should also be expected to affect clotting factor activities. Multiple determinations of activated partial thromboplastin times (APTT), prothrombin times (PT), and thrombin times (TT) were performed on commercially available normal human plasma at assay temperatures similar to those encountered clinically (25-37 degrees C). Both the APTT and the PT were significantly prolonged at temperatures below 35 degrees C (P less than 0.05). Clotting time correlated significantly with assay temperature in a negative exponential fashion for all three tests (r = -0.97 for APTT, -0.93 for PT, -0.71 for TT, P less than 0.001 for all regressions). Clotting time prolongation appears proportional to the number of enzymatic steps involved. These data indicate that the coagulopathy observed during hypothermia is, in part, independent of clotting factor levels.

Blood Coagulation↗

Early fasciotomy for acute clinically evident posttraumatic compartment syndrome.

Our understanding of the effectiveness of early decompressive fasciotomy for acute posttraumatic compartment syndrome is incomplete. Thirty-two patients who developed acute clinically evident compartment syndrome (23 in the leg, 9 in the forearm) were treated with decompressive fasciotomy an average of 16 hours after injury. Thirty patients (94 percent) underwent fasciotomy in conjunction with other urgent operative procedures mandated by concomitant injuries. Three patients required early amputation for a failed arterial repair. Only 2 of 29 patients with limb salvage (7 percent) had postoperative myoneural deficits after decompressive fasciotomy. Both of these patients had preoperative myoneural deficits. Decompressive fasciotomy before the development of ischemic myoneural deficits prevents the ischemic sequelae of acute clinically evident compartment syndrome.

Acute Disease↗

Prostaglandin-induced gastric mucosal protection against stress injury. Absence of a relationship to tissue glutathione levels.

The effects of 16,16 dimethyl prostaglandin E2 (dmPGE2) on the gastric mucosa of rats subjected to 1, 2, and 24 hours of water immersion stress were examined histologically. Results indicated a time-related increase in the total percentage length of glandular mucosa injured in normal saline (NS) pretreated rats that was significantly attenuated by subcutaneous dmPGE2 pretreatment (5 micrograms/kg) after 1 hour (46.0 +/- 12.9 vs. 16.8 +/- 2.3; p less than 0.005), 2 hours (45.4 +/- 1.0 vs. 13.8 +/- 2.2; p less than 0.001), and 24 hours (93.1 +/- 2.6 vs. 65.1 +/- 7.0; p less than 0.005) of water immersion stress. Moreover, dmPGE2 essentially prevented the occurrence of deep, glandular injury that, in NS controls, involved approximately 13% and 26% of the mucosal surface after 2 and 24 hours of immersion stress, respectively. Additionally, tissue levels of glutathione (mumole/g weight of wet tissue) were measured to determine its role under such conditions. After 1 hour of stress, there were no differences in glutathione levels between NS or dmPGE2 pretreated animals and fasted controls. After 2 and 24 hours of stress, there were likewise no differences in glutathione levels between NS and dmPGE2 pretreated groups, although levels in both groups were significantly decreased from fasted controls by approximately 30% at 2 hours and 37-47% after 24 hours. These histologic and biochemical data indicate that dmPGE2 attenuates both the extent and depth of glandular mucosal injury and does so in a manner unrelated to alterations in glutathione levels in gastric epithelium.

16,16-Dimethylprostaglandin E2↗

Pharmacokinetic monitoring of nephrotoxic antibiotics in surgical intensive care patients.

An assessment of the dosage regimens prescribed for potentially nephrotoxic antibiotics (amikacin, gentamicin, tobramycin, and vancomycin) was undertaken on surgical intensive care unit patients. In 166 patients, 224 series of blood antibiotic level determinations were obtained. Using individualized pharmacokinetic determinations, the regimens were revised as necessary to provide optimal blood levels. Because of variable volumes of distribution and elimination rates, dosing according to standard clinical guidelines produced significantly lower peaks than did pharmacokinetically determined regimens for gentamicin (p less than 0.005), tobramycin (p less than 0.0001), and vancomycin (p less than 0.05). Importantly, fewer patients achieved therapeutic levels with the original regimens than with the revised regimens for gentamicin (9% vs. 91%, p less than 0.0005), tobramycin (27% vs. 92%, p less than 0.0001), and vancomycin (30% vs. 69%, p less than 0.0001). Individualized pharmacokinetic analysis of potentially nephrotoxic antibiotics in critically ill patients is essential if therapeutic, non-toxic levels are to be maintained.

Amikacin↗

Major injury as a unique opportunity to initiate treatment in the alcoholic.

A prospective study was performed on the use of a standard outpatient intervention technique to induce inpatient alcoholic trauma patients into accepting alcoholism treatment. Interventions were performed on 17 trauma patients. All patients who underwent intervention accepted treatment and were immediately transferred to a 28-day inpatient treatment facility. Alcoholic trauma patients are highly susceptible to intervention for their disease. We found that intervention performed upon discharge from the trauma service successfully initiates alcoholism treatment.

Alcoholism↗

The investigational use of tPA for stroke.

Stroke therapy trials have historically allowed for late patient entry (ie, within 24 to 48 hours from stroke onset) despite evidence suggesting the importance of early intervention. Experimental studies of cerebral infarction suggest treatment may be most effective when begun within three hours and may be only marginally effective when begun after 12 hours. Lysis of an acute intra-arterial thrombus in the setting of thrombolytic therapy is also time dependent. We describe an ongoing dose-escalation study of tissue plasminogen activator (tPA) as ultra-early therapy for cerebral infarction. The protocol requires that hemorrhage be ruled out by computed tomography scan of the brain prior to tPA infusion, and the infusion must begin within 90 minutes of symptom onset. The two primary goals of the study are to assess safety and potential efficacy. Preliminary results from the study and the future of ultra-early stroke intervention are discussed.

Cerebral Hemorrhage↗

Crosslinking of DNA by dehydroretronecine, a metabolite of pyrrolizidine alkaloids.

Dehydroretronecine (DHR), a major metabolite of the pyrrolizidine alkaloids, has been shown to bind and crosslink pBR322 plasmid DNA and M13 viral DNA, as monitored by electron microscopy and agarose gel electrophoresis. The crosslinking was alkali-stable and varied with time, temperature, pH and reactant ratios. Although the binding of DHR to single-stranded M13 DNA was 3-fold higher than to double-stranded M13 DNA, only the double-stranded DNA was crosslinked. Intra- and inter-molecular crosslinking occurred with both linear and circular forms of double-stranded DNA. Electron microscopy showed that incubations with low DHR/DNA ratios yielded mostly DNA monomers and dimers while higher ratios produced larger aggregations, some of which were equivalent in size to dozens of individual DNA molecules. The average number of intermolecular crosslinks per molecule estimated by Poisson statistics was essentially the same using data from electron microscopy or DHR-binding. DHR generated single strand scissions equally well in both single- and double-stranded molecules.

Alkylation↗

Gastrointestinal disruption: the hazard of nonoperative management in adults with blunt abdominal injury.

The danger inherent to nonoperative management of patients with blunt abdominal injury is that gastrointestinal disruptions will escape timely diagnosis and repair. However, children with blunt abdominal injury have been successfully treated nonoperatively for more than a decade. It has been recently proposed, based upon small series, that adults can be managed nonoperatively in a manner similar to that for children. To assess the likely safety for nonoperative management of adults with blunt abdominal injury, we determined the frequency of blunt gastrointestinal disruption in adults, and reviewed the sensitivity of the diagnosis of gastrointestinal disruption by computed tomography. The salient statistically significant findings, based upon an analysis of 6,301 adults and 1,275 children admitted following blunt trauma, were that blunt abdominal injury, blunt gastrointestinal injury, and blunt gastrointestinal disruption are much more frequent in adults. Based upon these findings and the low sensitivity reported for the diagnosis of gastrointestinal disruption by computed tomography, we conclude that the nonoperative management of adults with blunt abdominal injury is as a matter of routine not justified.

Abdominal Injuries↗

Pulmonary microembolism: a cause of lung injury.

Microthrombi found in the pulmonary capillaries in patients dying with post-traumatic pulmonary insufficiency suggests that pulmonary microembolism (PME) may be etiologically important, but a temporal relationship has not been demonstrated. We used a modified Lim-Blaisdell model of PME to cause a severe ischemic soft tissue injury in dogs. The appearance of microaggregates (MA) in the venous circulation was measured using a laser optical scanning technique. The effect of MA on pulmonary physiologic and histologic parameters was measured and compared to control animals. In the ischemic soft tissue injury group, following restoration of local circulation, the platelet count dropped by 72% (P less than 0.00002), the number of MA increased by 800% (P less than 0.00002), the mean pulmonary artery pressure (PA) increased from 15.6 to 32 mm Hg (P less than 0.00002), and electron micrographs of lung obtained at 4 hr after ischemic insult revealed PM with severe lung injury that was consistent with a capillary membrane leak. The control group never demonstrated a significant change in platelets, MA, PA, or histologic lung injury. These findings imply that MA found in the pulmonary microcirculation are temporally related to the development of physiologic and anatomic lung abnormalities.

Animals↗

Clotting factor levels and the risk of diffuse microvascular bleeding in the massively transfused patient.

Clotting factor activities and coagulation screening tests in 36 massively transfused patients were measured after every 12 units of blood and whenever diffuse microvascular bleeding (MVB) developed. Moderate deficiencies in clotting factors were common, but they were not associated with MVB. MVB was associated with severe abnormalities of coagulation, i.e. a fibrinogen level less than 0.5 g/l or clotting factor levels less than 20%. The quantitative relationship between the prothrombin (PT) and partial thromboplastin (PTT) times and underlying clotting factor levels was explored by multiple linear regression. Clotting factor levels accounted for only 65-85% of the variability in these tests. However, clotting factor activities less than 20% were reliably reflected by marked prolongations of the PT and PTT (values greater than 1.8 times control). Our data suggest that commonly used replacement formulas are not likely to prevent MVB, since consumption of platelets and/or clotting factors, rather than simple dilution, is a major cause of the deficiencies leading to MVB. Modified whole blood alone was sufficient replacement therapy for most patients. Guidelines for transfusion of supplemental components during massive transfusion are given.

Blood Coagulation Factors↗

Prophylactic platelet administration during massive transfusion. A prospective, randomized, double-blind clinical study.

Prior studies at Harborview Medical Center have suggested that dilutional thrombocytopenia is a major etiology of microvascular, nonmechanical bleeding (MVB). We undertook a prospective randomized double-blind clinical study to compare the prophylactic effects of 6 units of platelet concentrates (PLT) versus 2 units of fresh frozen plasma (FFP) administered with every 12 units of modified whole blood in patients undergoing massive transfusion (12 or more units in 12 hours). After exclusions, three of 17 patients who received PLT and three of 16 patients who received FFP developed MVB, an incidence no different from our previous findings. Regression lines of platelet counts during transfusion were no different between groups, and both groups had higher platelet counts than predicted from a standard washout equation. Only one patient had evidence of dilutional thrombocytopenia as a cause for MVB. Prophylactic platelet administration is not warranted as a routine measure to prevent MVB.

Adult↗