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Biomedical subjects

H V Gaskill

Publications and source records attributed to H V Gaskill.

At least 37 records · Page 2Linked to original sources

Pharmacologic analysis of the ip administration of fludarabine phosphate in the swine.

Fludarabine phosphate, an investigational water-soluble adenosine analog, was administered ip to five miniature swine at doses of 10, 16, and 25 mg/m2. Blood and peritoneal fluid samples were collected for 4 hours following drug administration and were submitted to high-performance liquid chromatographic analysis for the concentrations of the dephosphorylated derivative, 2-fluoro-ara-A. Peak peritoneal fluid concentrations of 2-fluoro-ara-A ranged from 7.72 to 18.01 micrograms/ml at the doses tested; peritoneal fluid areas-under-the-curve (AUCs) ranged from 19.23 to 47.33 micrograms X hour/ml. The peak serum concentrations of 2-fluoro-ara-A ranged from 0.15 to 0.46 micrograms/ml; serum AUCs ranged from 0.51 to 1.2 micrograms X hour/ml. The ip administration of fludarabine phosphate results in a 28-62-fold peak peritoneal concentration advantage over peak serum concentrations and a 20-53-fold advantage for peritoneal over serum AUCs. Comparison of data generated in this swine study to data from pilot studies of the ip administration of fludarabine phosphate in humans will be of interest.

Animals↗

Portasystemic shunting remains the procedure of choice for control of variceal hemorrhage.

We reviewed 108 patients (50% Child's C) who had been admitted with acutely bleeding esophageal varices to compare the efficacy of operative (portasystemic shunt) therapy with the reported efficacy of sclerotherapy. In the patients with shunts the early mortality (preoperative plus operative) was 13% and late mortality was 23%. Survival at five years was 50%. Recurrent variceal bleeding was seen in 4% of the patients. Procedure-related mortality and variceal rebleeding rates for the shunt group were respectively 50% and 8% of that reported for sclerotherapy. Variceal rebleeding in the sclerotherapy group required approximately 7 units of blood per episode. We concluded that immediate attempts at control of hemorrhage followed by portasystemic shunting remains the therapy of choice for these patients.

Adult↗

Iatrogenic vascular injury. A reducible problem.

During a six-year period 46 patients were treated for iatrogenic vascular injuries at the University of Texas Health Science Center, San Antonio. Diagnostic procedures led to 24 injuries, while therapeutic procedures were responsible for 22 vascular injuries. Trauma to the brachial and femoral arteries and the subclavian vein accounted for the majority of injuries. The most frequently encountered injuries were intimal tear, thrombosis, and laceration. Lateral suture, thrombectomy, and intimal repair were the most commonly employed forms of vascular repair. Postoperative complications were not related to the vascular injuries. Conclusions drawn from this review were as follows: (1) most injuries occur in nonsurgical areas of the hospital; (2) most injuries are related to improper placement, use, or manipulation of catheters; (3) mortality in these cases is caused by the underlying disease process; and (4) long-term sequelae secondary to the vascular injuries are rare.

Angiography↗

Topical prostaglandin E2 in the treatment of acute upper gastrointestinal tract hemorrhage. A prospective, randomized, double-blind study.

We performed a prospective, randomized, double-blind study to assess the efficacy of topical prostaglandin E2 (PGE2) in altering the course of patients with severe upper gastrointestinal tract hemorrhage. Forty-four patients with life-threatening, endoscopically proven hemorrhage were randomly allocated to receive either PGE2 or placebo for seven days. Severity of mucosal injury, determined by endoscopy, was scored both before and after completion of treatment. There were no significant differences between groups in either transfusion requirements or successful outcomes. However, the PGE2 group had significantly improved endoscopic injury scores while the placebo group did not. Therefore, topical PGE2 does not control acute hemorrhage from established upper gastrointestinal tract lesions, but it does result in an accelerated healing of established lesions.

Acute Disease↗

Upper gastrointestinal bleeding following renal transplantation.

Upper gastrointestinal bleeding has been shown to be a common complication of renal transplantation and one which carries a significant risk of mortality. In a retrospective review of 200 consecutive renal transplants in 194 patients, we found an incidence of only 6 per cent and a mortality rate of 8.3 per cent. Allograft survival in this group of patients was 58 per cent. These results are the product of careful preoperative evaluation, close attention to the patients for early signs of bleeding, and aggressive diagnostic and therapeutic intervention at the first evidence of bleeding. We also report an association of hypercalcemia with post-transplant upper gastrointestinal bleeding, with cessation of bleeding after parathyroidectomy.

Antacids↗

Traditional treatment of colon injuries. An effective method.

Several recent reports have described management of penetrating colon wounds with primary closure, exteriorization, and early return to the abdominal cavity. Since this procedure was not the technique practiced at our institution, we reviewed our five-year experience with 207 patients with such wounds to determine whether a change in methods was warranted. The patients, predominantly young and male, were often victims of gunshots or stabbings. Associated injuries (intra-abdominal, 64%; extra-abdominal, 35%) were frequent. Overall mortality was 4% and included three patients who died within 24 hours of admission. Morbidity was 43%, including 17% related to colon injury. All documented colostomy closures were without mortality. We concluded that management of penetrating colon injuries by traditional methods yields low morbidity and mortality. A comparison of our results with those obtained using alternative techniques convinced us that the continued use of traditional methods in treating colon trauma is warranted.

Adolescent↗

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.

Adult↗

Diagnosing appendicitis during pregnancy.

In a 10 year period, 29 of 36 pregnant patients (81 percent) thought preoperatively to have appendicitis had the diagnosis confirmed at operation. Postoperative fetal complications included one intrauterine death and five premature births. There were no maternal deaths and morbidity was limited to atelectasis in five patients. Prompt surgical intervention in 90 percent of our patients did not prevent fetal complications.

Appendicitis↗

Operative management of thyroid disease. Technical considerations in a residency training program.

Experience with 294 thyroid operations at Medical Center Hospital as performed by resident housestaff in general surgery has been reported. Operative results were consistent with the morbidity and mortality figures from large reviews. The importance of an active role for surgical housestaff in the operative management of thyroid disease is emphasized. With close supervision and attention to intraoperative identification of the recurrent laryngeal nerves and parathyroid glands, satisfactory results can be achieved.

Adult↗

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-PGE2's ability to reverse focal ischemia suggests a mechanism for prostaglandin-mediated cytoprotection.

16,16-Dimethylprostaglandin E2↗

The radiolabeled microsphere technique in gut blood flow measurement--current practice.

Measurement of blood flow to the gut has become an integral part of the physiologic study of the gastrointestinal tract. While many methods have been utilized in measuring tissue blood flow, the one most often practiced today is dependent on injection of radioactively labeled microspheres. The theoretical basis of the microsphere technique is analogous to that of the indicator-dilution method. A bolus of microspheres suspended in a suitable vehicle is injected into the left atrium or left ventricle where they mix uniformly with the oxygenated blood. They are then distributed via aortic blood flow to the capillary beds within each organ in proportion to the volume of microsphere-containing blood. Technical aspects of tissue processing, gamma energy detection, and gamma spectrum analysis are reviewed. Sources of experimental error and techniques for their reduction are also discussed.

Animals↗

Prostacyclin selectively enhances blood flow in areas of the GI tract prone to stress ulceration.

This study assessed the effect of continuous infusion of prostacyclin on tissue blood flow throughout the GI tract to see whether small and large bowel flow was also affected. Twelve miniature swine were anesthetized, ventilated, and hemodynamically monitored. After stabilization each animal received either prostacyclin in buffer at 0.1 mcg/kg/minute for 3 hours or buffer alone (controls). Tissue blood flow was documented at baseline and at 1, 2, and 3 hours of prostacyclin infusion by injection of radiolabeled spheres. Prostacyclin infusion did not significantly affect mean arterial pressure, heart rate, or cardiac index compared to controls. At 3 hours tissue blood flow was significantly increased in the gastric mucosa (225%), small bowel (110%), cecum (260%), and transverse colon (160%) compared to controls. Prostacyclin may be an effective agent for prevention of ischemia in all areas of the GI tract prone to stress ulceration.

Animals↗

PGF2 alpha mediated cytoprotection: a reassessment.

UNLABELLED: The demonstration of gastrointestinal ctyoprotection by PGF2 alpha (a supposed vasoconstrictor) has been cited as evidence against alteration of mucosal blood flow as a mechanism for the cytoprotection phenomenon. However, cytoprotection by PGF2 alpha has never been demonstrated in a model having concomitant documentation of gastrointestinal blood flow. This experiment was designed to accomplish two objectives. First, the effect of intravenous PGF2 alpha (0.1, 1.0, 10.0 mcg/kg/minute) on blood flow throughout the gastrointestinal tract was documented in a chloralose anesthetized miniature swine model (n = 7). Second, the effect of intravenous PGF2 alpha (1.0 mcg/kg/minute) on both gastric mucosal blood flow and stress ulceration was assessed during a 3-hour period of hemorrhagic shock in the same model (six controls, six PGF2 alpha). The radiolabeled microsphere technique of blood flow determination was employed. RESULTS: Intravenous PGF2 alpha significantly decreased myocardial blood flow at all doses employed. Although blood flow in the gastrointestinal tract tended to decrease with the largest dose of PGF2 alpha, this did not reach statistical significance. During shock PGF2 alpha had no effect on gastrointestinal blood flow. Furthermore, there was no evidence of gastric mucosal cytoprotection compared to controls. These results suggest that PGF2 alpha is neither vasoconstrictive nor cytoprotective when sub maximal doses are used. Dismissal of mucosal blood flow as a possible mechanism of prostaglandin-mediated cytoprotection is premature.

Animals↗

Hemodynamic effects of vasopressin. Can large doses be safely given?

We evaluated the effects of intravenous (IV) vasopressin on central hemodynamics, as well as myocardial and gastrointestinal (GI) blood flow, to delineate an optimal dosage balanced to yield maximum reduction of GI blood flow with minimal adverse cardiac effects. Eight miniature swine were anesthetized, ventilated, catheterized, and infused with vasopressin for three consecutive 30-minute periods at logarithmically increasing doses (0.001, 0.01, and 0.1 units/kg/min). We determined cardiac output, systemic arterial pressure, and microsphere tissue blood flow after each infusion. We found that IV vasopressin (0.001 units/kg/min) produced substantial reductions in blood flow to the GI tract and heart, and reduced the cardiac index (3.0 +/- 0.4 to 2.1 +/- 0.3 L/sq m/min). Increased doses of vasopressin (X 10 and X 100) decreased gastric mucosal blood flow even more, with minimal adverse effects on cardiac output and myocardial blood flow.

Animals↗

Gastric mucosal cytoprotection by splanchnicectomy is based on protection of gastric mucosal blood flow.

Prior reports have shown the protective effect of splanchnicectomy against stress-related gastric mucosal injury. The present study evaluated the possible relation of such cytoprotection with an effect on gastric acid secretion and gastric mucosal blood flow (GMBF). Miniature swine were divided into sham-operated and celiac ganglionectomy groups. Three weeks postoperatively all animals underwent hemorrhagic shock stress. Neither basal nor peak gastric acids was affected by splanchnicectomy or sham operations. Significant GMBF reductions occurred in early shock in both treatment groups. In the sham pigs these GMBF reductions persisted, while in the splanchnicectomy pigs, GMBF in late shock returned to normotensive levels. These results demonstrate that splanchnicectomy: 1) has no effect on basal or maximally stimulated gastric acid secretion, and 2) is associated with reestablishment of GMBF to preshock levels during sustained hypotension. These results indicate a beneficial effect on GMBF as a factor in gastric cytoprotection afforded by splanchnicectomy.

Animals↗

Exclusion angiography for patients with possible vascular injuries of the extremities--a better use of trauma center resources.

In this study we evaluated the capacity of selective angiography to reduce the number of exploratory procedures with negative results for suspected peripheral vascular injury. During the 4-year period ending December 1982, 316 trauma patients were evaluated for possible vascular injuries of the extremities. Exploration alone was performed for 124 patients, and 61 had vascular injuries; 192 patients were considered to be in stable condition and underwent selective angiography. Of these, 50 had vascular injuries and required operation. There were two false positive angiograms and one false negative angiogram (missed arteriovenous fistula). The overall diagnostic accuracy for angiography was 98%. The overall positive yield rate for operation was 64%. Selective angiography for the stable trauma patient to exclude vascular injury is safe, sensitive, and specific. Exclusion angiography has increased the overall positive yield rate for exploration of suspected vascular injury at our institution by 49%. Thus the selective use of exclusion angiography for patients who are stable and who do not have other indications for wound exploration is a reasonable and necessary mode of diagnosis for more effective use of operating room facilities.

Adolescent↗

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.

Abdomen↗