Harold V. Gaskill

Civilian Vascular Trauma of the Upper Extremity

One hundred forty-three patients with 163 upper extremity vascular injuries were reviewed. Penetrating trauma accounted for 94% of the injuries and blunt trauma for 6%. Absent pulses are not a completely reliable sign of upper extremity arterial injury. The most frequently injured upper extremity vessel is the brachial artery, followed in decreasing frequency by ulnar, radial, and axillary arterial injuries and axillary venous injuries. The most common technique of vascular repair was end-to-end anastomosis, followed by vein graft interposition. No amputations were required. Despite excellent results of vascular reconstruction, functional impairment due to associated nerve injuries was a distressingly predominant finding.

Chronic renal failure: Effect of hemodialysis on gastrointestinal hormones

Fifteen patients with chronic renal failure (serum creatinine level greater than 5 mg/dl) of long duration (more than 2 years) requiring hemodialysis were studied. Blood samples before and after 4 hours of hemodialysis were assayed for creatinine, blood urea nitrogen, potassium, calcium, glucose, insulin, gastrin, gastric inhibitory polypeptide, vasoactive intestinal polypeptide, pancreatic polypeptide, somatostatin, motilin, and neurotensin levels. Before dialysis, serum gastrin was minimally increased whereas gastric inhibitory polypeptide and pancreatic polypeptide were grossly increased compared with normal fasting values. Hemodialysis produced no changes in serum gastric inhibitory polypeptide, vasoactive intestinal polypeptide, pancreatic polypeptide, somatostatin, motilin, and neurotensin. Slight increases in serum insulin and gastrin levels may have occurred secondary to a dialysis-induced increase in the serum calcium level. The kidneys appear to be a major site of inactivation of insulin, gastrin, gastric inhibitory polypeptide, and pancreatic polypeptide. The gastrin level, although elevated in renal failure patients, may be suppressed by very high circulating levels of gastric inhibitory polypeptide.

Operations for peptic ulcer disease: paradigm lost

Over the past several decades, the pharmacologic and endoscopic treatment of peptic ulcer disease (PUD) has dramatically improved. To determine the effects of these and other changes on the operative management of PUD, we reviewed our surgical experience with gastroduodenal ulcers over the past 20 years. A computerized surgical database was used to analyze the frequencies of all operations for PUD performed in two training hospitals during four consecutive 5-year intervals beginning in 1980. Operative rates for both intractable and complicated PUD were compared with those for other general surgical procedures and operations for gastric malignancy. In the first 5-year period (1980 to 1984), a yearly average of 70 upper gastrointestinal operations were performed. This experience included 36 operations for intractability, 15 for hemorrhage, 12 for perforation, and seven for obstruction. During the same time span, 13 resections were performed annually for gastric malignancy, By the most recent 5-year interval (1994 to 1999), the total number of upper gastrointestinal operations had declined by 80% (14 cases), although the number of operations for gastric cancer had changed only slightly. Operations decreased most markedly for patients with intractability, but the prevalence of operations for bleeding, obstruction, and perforation was also decreased. We conclude that improved pharmacologic and endoscopic approaches have progressively curtailed the use of operative therapy for PUD. Elective surgery is now rarely indicated, and emergency operations are much less common. This changed paradigm poses new challenges for training and suggests different approaches for practice.

Truncal Vascular Injury—factors Influencing Survival

During the 10-year period ending June 1982, 219 patients were treated for 269 injuries to the major vessels of the abdominal and thoracic cavities, with 28% morbidity and 32% mortality. One hundred eighty patients (82%) had 377 associated injuries consisting primarily of damage to the small intestine (79), liver (45), and large intestine (34). Factors associated with an increased mortality included: more than three associated injuries; two or more nonvascular complications; more than two vessels injured; admission to ER in shock; injury to abdominal aorta or inferior vena cava; and injury to the porta hepatis. The majority of deaths (73%) were due to acute blood loss and irreversible shock. Factors unrelated to acute blood loss and shock had minimal effects on survival.

Portal infusion of tumor necrosis factor increases mortality in rats

Tumor necrosis factor (TNF) is a protein found in the serum of mice presensitized with BCG following injection of endotoxin. Although TNF has been shown to cause hemorrhagic necrosis of certain tumors, the marked toxicity of recombinant human TNF has limited the clinical usefulness of this compound. This experiment was designed to determine whether hepatic metabolism would reduce the systemic toxicity of TNF delivered by the portal circulation. Twenty male Fischer rats received a continuous infusion of recombinant human TNF (100 micrograms/kg/day), 10 through a portal venous branch, and 10 through a branch of the inferior vena cava. Control animals received an infusion of carrier solution by the same route. After 7 days the animals were sacrificed and their organs weighed and sectioned. Mortality in the portal TNF group was 100%. The animals followed the clinical pattern seen with lethal TNF injection. Histologic sections revealed significant gastric and small intestinal mucosal injury, pulmonary edema, and acute tubular necrosis. Animals receiving TNF systemically lost more weight per day of infusion than controls, but followed a relatively benign course. Systemically infused animals had evidence of mild pulmonary edema, and a periportal mononuclear infiltrate in the liver, but no obvious renal or gastrointestinal injury. In a second experiment the effect of escalating doses of portal TNF infusion on liver enzymes was assessed. TNF was infused intraportally at 10, 50, or 100 micrograms/kg/day for 3 days. Control animals received a carrier solution. Mortality was dose-related with 100% mortality in animals receiving 100 micrograms/kg/day, and 40% mortality in the 50 micrograms/kg/day group.(ABSTRACT TRUNCATED AT 250 WORDS)

Enhanced drug retention in VX2 tumors by use of degradable starch microspheres.

Twenty-nine rabbits with 12- to 14-day-old VX2 tumors in the hind leg were injected intraarterially with technetium-99m (99mTc) DTPA and various combinations of biodegradable starch microspheres, Spherex (Pharmacia, Sweden), to evaluate the efficacy of the microspheres in enhancing tumor retention of 99mTc DTPA. A gamma camera and nuclear medicine computer were used to generate time activity curves of 99mTc DTPA concentration in the tumors. Blood flow to the tumor and various muscles was also measured at intervals by left ventricular injection of 15 micron radiolabeled plastic microspheres. Ninety minutes following the administration of 99mTc DTPA, specimens from the tumor, plasma and different muscles were counted in a NaI well counter connected to a multichannel analyzer. When biodegradable microspheres mixed with 99mTc DTPA were injected and followed by a slow infusion of plain starch microspheres, the 99mTc DTPA was retained in the tumor at concentrations up to 11 times that seen when 99mTc DTPA alone was injected; the corresponding biological half-time was 13 times longer than control values. Additionally, the degree of drug retention was inversely related to blood flow, with retention increasing as blood flow decreased. The results have possible applications to the use of biodegradable microspheres in the intraarterial delivery of chemotherapeutic agents to solid tumors.

Evaluation of nonpalpable breast lesions: Experience in a training institution

Biopsy directed by needle localization is a safe and relatively simple method of obtaining abnormal tissue for histologic examination without sacrificing surrounding normal breast tissue. In the setting of a training institution, accurate results can be expected as technical skills are obtained by a variety of housestaff. In this series of 70 biopsies, the lesion targeted on mammography was removed on the initial attempt in all but 1 instance, for an overall accuracy of 99 percent.

Continuous infusion of tumor necrosis factor: Mechanisms of toxicity in the rat

UNLABELLED This study was designed to assess the toxicity of continuous infusion of tumor necrosis factor (TNF) in the rat model. The effect of TNF on cell membranes was assessed by diffusion of radiolabeled inulin (RI). The effect of concomitant administration of the cytoprotectant prostaglandin E1 (PGE1) was also assessed. Eighty rats were anesthetized and two osmotic pumps were implanted in the peritoneal cavity of each rat. One pump contained either TNF (0.1 mg/kg/day) or vehicle and the other either PGE1 (0.1 mcg/kg/min) or vehicle. Four groups resulted: vehicle alone, PGE1 alone, TNF alone, and TNF + PGE1. After 5 days, half of each group received intravenous RI and organ/blood radioactivity ratios were compared at sacrifice 7 min later. Remaining animals had serum drawn for CBC and electrolyte determination. Organ weights were determined in all animals. The effects of TNF and PGE1 were assessed by two-way ANOVA. Mortality in animals infused with TNF was 20%. One animal in the control group died. TNF infusion increased lung weight by 38% (697 +/- 49 vs 937 +/- 77 mg; P less than 0.05). Liver weight was also increased in animals infused with TNF (6.7 +/- 0.2 vs 7.0 +/- 0.3 g; P less than 0.05). TNF infusion increased blood urea nitrogen and decreased serum bicarbonate compared to controls. TNF had no effect on RI diffusion. PGE1 did not alter the response to TNF. CONCLUSIONS Continuous infusion of TNF does not affect membrane permeability as assessed by inulin diffusion. PGE1 does not cytoprotect against the toxicity of TNF. Evidence of direct hepatic toxicity suggests that regional therapy via the hepatic artery or portal vein is contraindicated.

Bidirectional endoscopy in patients with fecal occult blood

Background: Current screening protocols for colorectal cancer depend primarily on fecal occult blood testing (FOBT). However, positive test results do not always indicate the presence of a colonic neoplasm. Methods: We reviewed the results of 100 consecutive bidirectional (upper and lower) endoscopic procedures performed to evaluate positive FOBT results. Patients were excluded if they presented with gross bleeding, a history of bowel lesions, or previous intestinal operations. There were 31 women and 69 men whose mean age was 51 years. Results: Major abnormalities were found on esophagogastroduodenoscopy (n = 24), colonoscopy (n = 13), or both studies (n = 2). Active bleeding was manifested in two patients, (Barretts ulcer, duodenal arteriovenous malformation). Two other patients had malignancy: One had a cecal adenocarcinoma and the other a gastric adenocarcinoma. Various benign lesions also were identified in the stomach including esophagitis (n = 8), ulcers/erosions (n = 8) varices (n = 5), and arteriovenous malformations (n = 2). Colonic pathology included polyps (n = 8), arteriovenous malformations (n = 3), and rectal varices (n = 1). Diverticulosis and hemorrhoidal disease were present in 29 and 16 patients, respectively, but were not considered to be likely sources of a positive FOBT. Conclusion: Positive FOBT results may indicate the presence of either upper or lower intestinal pathology, and bidirectional endoscopy is an efficient and accurate technique for the comprehensive evaluation of occult bleeding.

16,16-Dimethyl prostaglandin E2 reverses focal mucosal ischemia associated with stress ulcers☆

UNLABELLED Focal ischemia is postulated to contribute to gastric mucosal stress ulceration. This study evaluated directly whether or not mucosal ulceration during hemorrhagic shock is preceded by focal gastric mucosal blood flow changes, and whether or not topical Dm-PGE2 (16,16-dimethyl prostaglandin E2) affects focal gastric mucosal blood flow during hemorrhagic shock. Twelve anesthetized miniature swine had pyloric ligation and intragastric infusion of 5 ml/kg autogenous bile in 140 mM HCl. Gastric mucosal blood flow was documented by radiolabeled microspheres during normotension, initial hemorrhagic shock (50 mm Hg), and hemorrhagic shock + 50 micrograms topical Dm-PGE2. Stable shock was then maintained for 3 hr. During this time ulceration developed, shedding radiolabeled microsphere-bearing mucosa into the lumen. Intact gastric mucosa and luminal contents were collected, weighed, and gamma counted. Blood flow to intact mucosa was calculated by standard techniques. The weight of shed tissue, as well as the blood flow to shed tissue, was calculated from luminal microspheres. RESULTS gastric mucosal blood flow was decreased 35% with hemorrhagic shock (28.8 +/- 4.0 vs 18.7 +/- 2.7 ml/100 g/min, P less than 0.05). Blood flow to tissue which was subsequently shed averaged 6.4 +/- 3.1 ml/100 g/min at the same time period (P less than 0.05 vs surrounding tissue). Addition of Dm-PGE2 increased blood flow to shed tissue from 29 +/- 8% to 48 +/- 10% of blood flow to intact tissue (P less than 0.05). CONCLUSIONS (1) gastric mucosal ulceration is preceded by focal decreases in gastric mucosal blood flow, and (2) topical Dm-PGE2 reverses focal mucosal ischemia during hemorrhagic shock. Dm-PGE2s ability to reverse focal ischemia suggests a mechanism for prostaglandin-mediated cytoprotection.