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Biomedical subjects

K Waxman

Publications and source records attributed to K Waxman.

At least 73 records · Page 4Linked to original sources

Superoxide dismutase polyethylene glycol improves survival in hemorrhagic shock.

Oxygen free radicals are known to form after reperfusion of ischemic tissue. To test the role and importance of oxygen free radicals in hemorrhagic shock, an animal model of hemorrhagic shock and resuscitation was utilized. Sprague-Dawley rats were anesthetized with halothane and then subjected to approximately 50 per cent blood volume hemorrhage (30 cc/kg), followed by a 60 min shock period. Resuscitation was performed over 1 hour with lactated ringers (LR) at a volume of two times blood loss (60 cc/kg). This model results in a survival rate of 25 per cent over 72 hrs. Using this model, animals were randomized to receive either LR, Superoxide Dismutase-Polyethylene Glycol (SOD-PEG) (15,000 units/kg) with LR or Catalase-Polyethylene Glycol (CAT-PEG) (175,000 units/kg) with LR. The group treated with SOD-PEG demonstrated significantly increased survival rates vs the group treated with LR (67% vs 25%, P = 0.02). The group treated with CAT-PEG demonstrated no significant improvement in survival when compared to the LR-treated group (20% vs 24%). These data suggest that treatment directed toward oxygen free radicals and reperfusion injury may play an important role in hemorrhagic shock resuscitation.

Animals↗

Helmet use improves outcomes after motorcycle accidents.

To determine the effects of motorcycle helmet use on the outcome of patients admitted to a Level I trauma center, we studied patient outcomes and demographic and epidemiologic variables of 474 patients injured in motorcycle collisions and treated at such a center over a 45-month period. Of those involved in a motorcycle collision, 50% were not wearing a helmet, 23% were wearing a helmet, and in 27% helmet use was unknown. Those who were wearing a helmet had fewer and less severe head and facial injuries, required fewer days on a ventilator, and sustained no serious neck injuries; fewer patients who wore helmets were discharged with disability, and hospital charges were lower. These data support the need for both increased public education regarding helmet use and mandatory helmet use legislation.

Accidents, Traffic↗

Advances in the management of hemorrhagic shock.

The Scientific Board of the California Medical Association presents the following inventory of items of progress in general surgery. Each item, in the judgment of a panel of knowledgeable physicians, has recently become reasonably firmly established, both as to scientific fact and important clinical significance. The items are presented in simple epitome, and an authoritative reference, both to the item itself and to the subject as a whole, is generally given for those who may be unfamiliar with a particular item. The purpose is to assist busy practitioners, students, researchers, or scholars to stay abreast of these items of progress in general surgery that have recently achieved a substantial degree of authoritative acceptance, whether in their own field of special interest or another. The items of progress listed below were selected by the Advisory Panel to the Section on General Surgery of the California Medical Association, and the summaries were prepared under its direction.

Humans↗

Diagnosis of traumatic cardiac contusion utilizing single photon-emission computed tomography.

One hundred twenty-five consecutive patients with a diagnosis of blunt chest trauma underwent T1-201 thallous chloride single photon-emission computed tomography (SPECT) scan, as well as physical examination, serial ECG and cardiac enzymes. A subset of patients had 24-h Holter monitoring. SPECT scan was performed within 24 h of injury. Seventy-five patients had positive scans and 48 had negative. Two studies could not be completed. Eleven patients with positive studies developed serious arrhythmias (multiple premature ventricular beats or atrial fibrillation). None of these patients had a prior history of cardiac disease. While three patients with negative SPECT scans had arrhythmias, each had a prior history of cardiac disease and two were on chronic antiarrhythmia therapy. Neither ECG findings, creatinine phosphokinase (CPK), nor CPK-isoenzymes distinguished between those patients who did and did not develop arrhythmias. We conclude that SPECT scan is useful in screening patients at risk of developing arrhythmias from cardiac contusion. Utilization of SPECT scan allows early discharge of a significant number of patients with blunt chest trauma who would otherwise require hospitalization for arrhythmia monitoring.

Adolescent↗

Survival after hypertonic saline resuscitation from hemorrhage.

There has been recent increased interest in hypertonic saline resuscitation from shock and hemorrhage. This study was performed to evaluate the survival effects of hypertonic saline resuscitation. Fifty male Sprague-Dawley rats of average weight of 325 grams were anesthetized with halothane. Animals were subjected to blood loss of 21 ml/kg over 5 minutes. Intravenous infusion was started 10 minutes after hemorrhage with either lactated Ringer's injection (42 ml/kg) or three per cent NaCl (10.64 ml/kg) chosen randomly. These doses provided equal amounts of sodium. At the end of fluid infusion, blood samples were obtained for electrolyte determination. Rats were observed 3 days for survival. Survival was significantly lower in the three per cent NaCl group compared with the lactated Ringer's group. It is probable that worsened outcome with three per cent NaCl was associated with intracellular dehydration.

Animals↗

Computerized tomography as an indicator of isolated mesenteric injury. A comparison with peritoneal lavage.

This study evaluated 18 patients with blunt abdominal trauma who suffered isolated mesenteric injuries, diagnosed at exploratory laparotomy. Thirteen had diagnostic peritoneal lavage (PL) as their initial diagnostic study, and five had computed tomography (CT). All patients who had positive PL were explored emergently, undergoing repair of mesenteric injuries. Three of the five patients with CT as initial studies had delayed recognition of their injuries due to incorrect initial interpretation of the scan in two, and a false negative scan in one. Two of these patients developed intestinal infarction and required bowel resection. There were no complications in the PL group related to surgery; morbidity was greater in those undergoing CT. We conclude that early laparotomy and repair of significant mesenteric injuries is necessary to reduce morbidity, and that PL is a more sensitive indicator of this injury than CT.

Abdominal Injuries↗

A preliminary trial of the programmable implantable medication system for insulin delivery.

We undertook a trial to determine whether an implanted insulin-delivery system, the programmable implantable medication system (PIMS), could be used to treat patients with insulin-dependent diabetes. PIMS is a pulsatile, programmable pump with a battery life expectancy of five years. The reservoir is refilled transcutaneously every two months with a surfactant-stabilized human insulin preparation containing 400 U of insulin per milliliter. Eighteen patients received PIMS-delivered insulin for 4 to 25 months (mean, 18). The total PIMS-implantation experience comprised 28 patient-years. Good glycemic control was established and sustained during treatment (mean plasma glucose level, 7.3 mmol per liter; mean glycohemoglobin level, 8 percent [upper limit of normal, 7.5 percent]), with significantly reduced glycemic fluctuations. The total mean daily insulin dose did not change. Insulin solutions withdrawn from the pump reservoirs contained 92 percent native insulin and preserved biologic activity. There were no surgical or skin complications, severe hypoglycemic episodes, or instances of diabetic ketoacidosis. One pump was replaced because of a manufacturing defect, and four patients had catheter blockages due to omental-tissue encapsulation; two withdrew from the study and two had devices that were repaired successfully. The actuarial rate of survival of catheter function was 78 percent at 1.5 years. We conclude from this pilot study that insulin treatment with an implanted, variable-rate, programmable pump is feasible for periods up to two years.

Adult↗

Impaired oxygenation of gastric mucosa in portal hypertension. The basis for increased susceptibility to injury.

Increased susceptibility to mucosal damage is a prominent feature of portal hypertensive gastropathy. Since the portal hypertensive gastric mucosa has extensive microvascular changes, we postulated that the increased sensitivity to mucosal damage could have an ischemic basis. We measured distribution of gastric serosal and mucosal oxygenation in a group of portal hypertensive and sham-operated rats, and then studied the effects of intragastric aspirin. In the basal state, gastric mucosa of portal hypertensive rats had significantly reduced oxygenation compared to controls (24 +/- 5 vs 45 +/- 7 mm Hg PO2, P less than 0.02), while serosal oxygenation was similar between the two groups. Intragastric aspirin produced significantly greater mucosal damage to portal hypertensive rats and mucosal oxygenation was almost one third that of sham-operated controls. Systemic arterial pressures and oxygenation were similar between the two groups. We conclude that there is impairment of gastric mucosal oxygenation and increased mucosal damage by aspirin in portal hypertensive rats compared with sham-operated controls. These results support our hypothesis that the increased sensitivity of the portal hypertensive mucosa to damage is a consequence of impaired mucosal oxygenation.

Animals↗

Heated laser Doppler flow measurements to determine depth of burn injury.

The ability to predict whether burn wounds will heal spontaneously or will require skin grafting is important because of increasing utilization of primary excision and grafting. This study prospectively evaluated the ability of heated laser Doppler flow measurements obtained in the first 48 hours after burn injury to predict whether burn wounds would heal within 3 weeks. Further, the severity of scarring at 3 months was compared with the initial measurements. The measurements predicted healing with 100 percent accuracy and failure to heal with 93 percent accuracy. There was also a significant correlation between initial flow measurements and severity of scarring at 3 months. We conclude that heated laser Doppler flow measurements performed early after burn injury are useful in predicting whether healing is likely to occur, as well as the quality of late scar formation; therefore, the method is useful in selecting patients for primary excision and grafting of burn wounds.

Blood Flow Velocity↗

Hemodynamic and oxygen transport effects of pentastarch in burn resuscitation.

If nonprotein colloid plasma expanders could be demonstrated to be safe and efficacious in burn resuscitation, a significant cost benefit would result. This study was a randomized cross-over comparison of 500 ml of 5% albumin and 500 ml of 10% pentastarch, a new hydroxyethyl starch, in acute burn resuscitation. Pentastarch was an effective plasma expander, resulting in increases of preload, cardiac output, oxygen delivery, and oxygen consumption; the hemodynamic effects of pentastarch infusion were equal or superior to those of albumin. Both albumin and pentastarch infusions resulted in increased bleeding and clotting times; these effects were most likely dilutional. Pentastarch is a promising plasma substitute for burn resuscitation; the effects of a 500 ml infusion are equal or superior to those of albumin. Further study is necessary to assess the safety of larger infusion volumes.

Adult↗

Pentoxifylline improves survival following hemorrhagic shock.

Pentoxifylline is an agent which improves microcirculatory blood flow, but its use as therapy for shock has not been reported. We performed this study to determine if pentoxifylline improves survival following experimental hemorrhagic shock. Anesthetized Sprague-Dawley rats were studied; the animals were subjected to hemorrhage and then resuscitated using lactated Ringer's solution, with either placebo or pentoxifylline added by random selecting. Animals were then observed for 3 days. There was significantly increased survival in pentoxifylline-treated animals (p less than .05). In additional experiments, animals received more aggressive fluid resuscitation; improved survival in the pentoxifylline group was noted almost immediately and persisted through the 72-h period. This was significant at the p less than .01 level. We conclude that pentoxifylline improves survival from hemorrhagic shock in this experimental model, and has additive survival value to fluid resuscitation.

Animals↗

Multicenter open trial of cefotetan and cefoxitin in elective biliary surgery.

The present study was performed in two phases. In phase I, 112 patients were randomized to either 2 g cefotetan as a single prophylactic dose or 2 g cefoxitin every 6 hours for a maximum of 4 doses; phase II included 148 patients who were randomized to either 1 g cefotetan as a single dose or cefoxitin dosed as in phase I. The randomization was 2:1 cefotetan to cefoxitin in both phases. Nonevaluability rates were 10 percent for the cefotetan patients and 22 percent for the cefoxitin patients, the majority being due to dosing errors. Demographic characteristics demonstrated 88 percent to be female, 81 percent to be less than 65 years of age, and the average weight to be 165 lb. There were no differences in these characteristics among the groups. Common duct exploration was performed in 6 percent of the 2 g cefotetan patients, 9 percent in the 1 g cefotetan patients, and 13 percent in the 2 g cefoxitin patients. There were five clinical failures of prophylaxis: one wound infection in the 2 g cefotetan patients, one wound infection and one drain tract infection in the 1 g cefotetan patients, and one wound infection and one case of cholangitis in the 2 g cefoxitin patients. The clinical success rates were 98 percent in the 2 g cefotetan patients, 98 percent in the 1 g cefotetan patients, and 97 percent in the 2 g cefoxitin patients.

Aged↗

Nitrogen balance in adult hospitalized patients with the use of a pediatric amino acid model.

Normalization of plasma amino acid patterns and that relationship to improved nitrogen balance was studied using a pediatric-specific amino acid solution in 21 adults requiring total parenteral nutrition therapy. There was a significantly positive correlation between improved nitrogen balance and the amino acids cystine, tyrosine, total cysteine/cystine, and ornithine. When additional cysteine was added to the solution of 11 subjects, taurine also correlated with nitrogen balance. Despite higher amounts of histidine in solution, plasma amino acid levels were not normalized. These amino acids, heretofore considered nonessential, may be required in specific molar ratios in stress. The use of a 30% branched-chain pediatric-balanced amino acid solution resulted in near normalization of plasma amino acid levels and group mean positive nitrogen balance.

Adult↗

Protective effect of pentoxifylline on gastric mucosa.

Pentoxifylline (PF) has been shown to increase tissue oxygen tension. This study was performed to determine if PF has a protective effect on the gastric mucosa against alcohol (EtOH)-induced injury. Fasted Sprague-Dawley rats were pretreated with randomized test solution (control, normal saline, or PF, 75 mg/kg) intraperitoneally (ip). At 30 min, 100% EtOH (pH 8.5) was given intragastric. At 90 min, laparotomy was performed and gastric serosal stomach surface oxygen tensions (pO2) were measured. Stomachs were excised and opened and pH was measured. Photographs were taken and sections were obtained for histologic analysis to determine mucosal injury. The PF-pretreated rats had significantly higher serosal pO2 and significantly lower intragastric pH than control animals. There was significantly less gross and histologic mucosal injury in PF-treated animals. We conclude that PF is protective against EtOH gastric mucosal injury. This effect correlates with increased gastric serosal pO2 and is likely due to improved microcirculatory blood flow following PF administration.

Animals↗