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Biomedical subjects

W W Turner

Publications and source records attributed to W W Turner.

At least 19 recordsLinked to original sources

Semisynthetic chemical modification of the antifungal lipopeptide echinocandin B (ECB): structure-activity studies of the lipophilic and geometric parameters of polyarylated acyl analogs of ECB.

Echinocandin B (ECB) is a lipopeptide composed of a complex cyclic peptide acylated at the N-terminus by linoleic acid. Enzymatic deacylation of ECB provided the peptide "nucleus" as a biologically inactive substrate from which novel ECB analogs were generated by chemical reacylation at the N-terminus. Varying the acyl group revealed that the structure and physical properties of the side chain, particularly its geometry and lipophilicity, played a pivotal role in determining the antifungal potency properties of the analog. Using CLOGP values to describe and compare the lipophilicities of the side chain fragments, it was shown that values of > 3.5 were required for expression of antifungal activity. Secondly, a linearly rigid geometry of the side chain was the most effective shape in enhancing the antifungal potency. Using these parameters as a guide, a variety of novel ECB analogs were synthesized which included arylacyl groups that incorporated biphenyl, terphenyl, tetraphenyl, and arylethynyl groups. Generally the glucan synthase inhibition by these analogs correlated well with in vitro and in vivo activities and was likewise influenced by the structure of the side chain. These structural variations resulted in enhancement of antifungal activity in both in vitro and in vivo assays. Some of these analogs, including LY303366 (14a), were effective by the oral route of administration.

Acylation

Intravenous cholangiography and the management of choledocholithiasis prior to laparoscopic cholecystectomy.

The preoperative diagnosis of choledocholithiasis simplifies the laparoscopic management of biliary tract disease. Slow infusion intravenous cholangiography (SI-IVC) may be an accurate and cost-effective screening test for choledocholithiasis, and it is safer than traditional intravenous cholangiography. Forty-nine patients underwent SI-IVCs for suspected choledocholithiasis. These patients subsequently had endoscopic retrograde cholangiograms (ERC) or intraoperative cholangiograms (IOC) during laparoscopic cholecystectomies. Sixteen SI-IVCs demonstrated choledocholithiasis; 13 were confirmed by ERCs or by IOCs. The remaining 33 patients with negative SI-IVCs had negative ERCs or IOCs. The sensitivity, specificity, and accuracy of detecting choledocholithiasis by SI-IVC were 100%, 92%, and 94%. Only one patient had a mild reaction to the contrast agent. In our hospital the cost of an SI-IVC is $324, the cost of an IOC is $393 (including operating room and anesthesia costs), and the cost of an ERC is $1,085. SI-IVC is an accurate method of preoperative screening for choledocholithiasis. It is safe and cost-effective.

Adolescent

Intraarterial drug abuse: new treatment options.

Accidental, intraarterial injections of abused substances continue to be difficult management problems because of severe vascular complications. Vasospasm probably plays an important role in the pathophysiology of this injury, in addition to the more accepted roles of thrombosis and endarteritis. Three patients with severe, upper extremity ischemia after intraarterial injection of heroin, methamphetamine, and meperidine were treated with intraarterial tolazoline and streptokinase, along with intravenous heparin. All three patients had improved perfusion, assessed both clinically and by angiography. The responses to treatment in these patients demonstrated the roles of vasospasm and thrombosis in the origin of this injury and the therapeutic benefits of appropriately administered vasodilators and thrombolytic agents.

Adult

Actual or ideal body weight: which should be used to predict energy expenditure?

Assessing energy expenditure in obese people is problematic. Two questions arise: Can we predict energy expenditure accurately? Does actual or ideal body weight better predict energy expenditure? Two groups of obese subjects--65 hospitalized adults and 65 nonhospitalized adults--were studied. Both groups had actual body weights that were at least 30% above ideal body weights. For both groups, energy expenditure was measured by indirect calorimetry and calculated using the variables sex, actual and ideal body weight, age, and ventilatory status. All but three patients were receiving nutrition support by the enteral route (either orally or by tube) or by the parenteral route (with hypertonic dextrose, amino acid, and fat). The nonhospitalized subjects fasted during measurements of energy expenditure. Regression equations were derived to predict energy expenditure. Actual body weight better predicted energy expenditure than did ideal body weight. We conclude that actual weight should be used to predict energy expenditure in obese individuals.

Adult

Postoperative nutritional support of patients with abdominal trauma.

The response to major trauma is characterized by a significant erosion of the body cell mass. Intensive nutritional support can decrease morbidity and mortality. Preservation and restoration of the body cell mass involves amino acid synthesis into protein, and this process requires nutrient energy. Newer methods of assessing energy expenditure have revised traditional concepts about energy requirements following trauma. The use of fat to meet some of the caloric requirements may obviate problems with ventilatory distress, glucose intolerance, and hepatic steatosis that occur with glucose-based nutritional regimens. Selection of the delivery method for intensive nutritional support should consider gastrointestinal integrity, physiologic tolerance, and cost. Enteral nutrition is superior to parenteral nutrition in maintaining gastrointestinal mucosal integrity, hormonal balance, and nutrient utilization. Furthermore, it is safer, more convenient, and more economical than parenteral nutrition.

Abdominal Injuries

Perforated gastric ulcers. A plea for management by simple closures.

One hundred seven patients with perforated gastric ulcers were treated by either simple closures (omental patches, 81 patients; primary suture without patches, 13 patients; or ulcer excisions with closures, two patients) or primary gastric resections (11 patients). The latter were performed when ulcers were too large to be treated by simple closures. The mortality rate after omental patches or ulcer excisions with closures was 12%, while that following primary gastric resections was 45%. Patients who underwent closures with suturing only had a mortality rate of 62%, which was significantly higher than the mortality rate following patch closures. Gastric outlet obstructions developed following 15% of simple closures of prepyloric ulcers. Closures of perforated gastric ulcers with omental patches or ulcer excisions can be undertaken with low mortality and morbidity rates. Primary gastric resections are reserved for patients with ulcers that are large or located in the prepyloric area.

Adult

The effect of burn wound excision on measured energy expenditure and urinary nitrogen excretion.

The effect of wound closure on the metabolic response to burn injury is uncertain. Energy expenditures were measured in 20 patients by indirect calorimetry (MEE) and estimated initially by the Curreri formula (CEE) and subsequently by a modification of the Curreri formula (MCEE), adjusted for changes in open wound size and body weight. Urinary urea nitrogen (UUN) excretions were measured over 24 hours. Second- and third-degree burns, initially involving 31% to 74% of the body surface areas, were reduced in size to less than 15% by excisions and grafting procedures. The correlations among percentage open wounds, MEE's, CEE's, and MCEE's were low. UUN excretions were not correlated with percentage open wounds or with MEE's. Estimates of energy expenditures using the Curreri formula appear to be of limited usefulness in prescribing caloric intakes in burned patients. Serial UUN's are useful in determining protein requirements, but were not correlated with MEE's or with the extent of open wounds.

Adolescent

The use of respiratory quotient to determine the efficacy of nutrition support regimens.

Respiratory quotient (RQ) is an indicator of fuel utilization. This study examined the RQs of patients receiving intensive nutrition support to assess the frequency with which net fat synthesis occurred, as determined by RQs greater than 1.0. One hundred twelve RQs were calculated from data obtained using indirect calorimetry. Seventy-four measurements were made while patients were receiving parenteral nutrition--55 with glucose and amino acid (GAAPN) and 19 with glucose, fat, and amino acid (GFAAPN). Thirty-eight measurements were made while patients were receiving either oral or nasoenterally administered carbohydrate, fat, and protein in the form of standard hospital diets or liquid defined formula diets (CFPEN). The mean RQ of the GAAPN patients was significantly higher than those of both the GFAAPN and the CFPEN patients. RQs were greater than 1.0 in a significantly greater number of the GAAPN patients than the GFAAPN or CFPEN patients. The route of nutrient intake did not influence energy nutrient utilization, as determined by RQ. This study suggests that nutrition support regimens containing fat, in addition to carbohydrate and protein, are more efficiently utilized to meet the energy requirements of hospitalized patients than are regimens containing only glucose and amino acid.

Calorimetry, Indirect

Successful use of the Denver peritoneovenous shunt in patients with nephrogenic ascites.

Tense ascites in patients who require hemodialysis for renal failure (nephrogenic ascites) is a rare but ominous complication. Its appearance is often followed by a rapid physical deterioration. Nonsurgical attempts to control the ascites are often unsuccessful. Four patients with refractory ascites were treated with Denver peritoneovenous shunts (DPVS). These patients suffered from ventilatory failure, anorexia with malnutrition, and hypotension during hemodialysis. Patients were followed for as long as 18 months after DPVS, and all experienced clinical resolution of the ascites. Ventilatory failure, malnutrition, and hypotension either improved or resolved after shunting. Shunt-related morbidity occurred in all patients and consisted of mechanical complications in four patients and bacteremia in one patient. These problems were resolved by either revision or removal of the DPVS. No deaths were directly related to shunting. Peritoneovenous shunting successfully treats nephrogenic ascites and reverses the morbid sequelae usually associated with this syndrome.

Adult

Does nasoenteral feeding afford adequate gastroduodenal stress prophylaxis?

Serial pH measurements were performed on 366 gastric aspirates from 20 critically ill patients receiving nasoenteral feeding with Osmolite or Isocal HCN, with no other means of gastric acid buffering. Ten patients (group A) received continuous intraduodenal feeding, and ten patients (group B) received continuous intragastric feeding. Gastric pH was at least 5.0 in 33 (23%) aspirates from group A, compared to 120 (54%) from group B (p less than .001). Only two (20%) group A patients had gastric pH values of 5.0 or greater for at least half of the measurements, compared to six (60%) group B patients. These data indicate that continuous intragastric feeding with Osmolite or Isocal HCN controlled gastric pH better than did intraduodenal feeding. However, neither technique adequately neutralized gastric acidity in these critically ill patients.

Adolescent

Evaluation of energy expenditures in burn patients.

Energy expenditures were estimated using the Curreri equation (CEE), the Harris-Benedict equations (HBEE), and a modification of the Harris-Benedict equations (MHBEE) and then were measured by indirect calorimetry (MEE) in 17 adult patients with burns covering 26% to 79% of their body surface areas. The mean CEE (3,831 kcal/day) was significantly greater, and the mean HBEE (1,813 kcal/day) was significantly less than the mean MEE (2,500 kcal/day). The mean MHBEE (2,720 kcal/day) and the mean MEE were not significantly different.

Adult

Predicting energy expenditures in burned patients.

Daily caloric requirements in patients with major burns are frequently estimated using the Curreri formula (25 X body weight (kg) + 40 X % BSA burned). In nonburned patients modifications of the Harris-Benedict formulas have been used to estimate energy requirements. These equations have not been validated against measured energy expenditures in burned patients. Thirty-five patients with second- and third-degree burns covering from 10 to 75% of the body surface area underwent assessments of energy expenditures by indirect calorimetry and by the Curreri and Harris-Benedict formulas. The mean energy expenditure calculated from the Harris-Benedict formulas (BEE) underestimated the mean measured energy expenditure (MEE) by 23% (p less than 0.001), while the mean energy expenditure calculated from the Curreri formula (CEE) overestimated the mean MEE by 58% (p less than 0.001). There were significant correlations between the MEE, BEE, and CEE. In patients with burns greater than 20% of the body surface area, the correlation between MEE and BEE was higher than that found with the Curreri formula.

Adolescent

Nutritional considerations in the patient with disabling brain disease.

Increased nutritional requirements are now recognized as the typical sequellae of head injury. Whether similar nutritional demands routinely accompany nontraumatic, disabling brain diseases is uncertain. Experience with patients suffering from head injury indicates that clinical criteria for differentiating the severity of neurological impairments categorize rather poorly the levels of nutritional need. Based on available data, "nutritional risk" can only be assigned to broad patient categories. Head-injured patients seem to be at nutritional risk and, by virtue of increased caloric and protein requirements, may benefit, in terms of reduced mortality, from early, intensive nutritional intervention. Because the nutritional risk cannot be established, the indications for aggressive nutritional support in the noninjured patient are even less clear than those for the trauma patient. Parenteral nutrition is often required to meet the goals of nutritional support because inadequacies in gastrointestinal function frequently mitigate successful enteral nutrition. Selective nutritional therapies involving the branched chain amino acids may reduce the attrition of the body cell mass seen in head injury patients. Furthermore, improvements in energy nutrient utilization in other than head-injured patients have been suggested when fat is provided in addition to glucose as a caloric source. When clinically feasible, enteral nutrition offers significant economic and physiological benefits over parenteral nutrition. In this regard, increasing attention has been focused on newer techniques of enteral access. These include percutaneous gastrostomies and nasally inserted small bore feeding tubes. The latter achieve duodenal intubation with a high success rate, and they offer the prospects of improved feeding tolerance and reduced tracheobronchial aspiration by allowing the administration of nutrients distal to the pylorus.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids

Mortality and renal salvage after renovascular trauma. A review of 94 patients treated in a 20 year period.

Ninety-four patients with 96 renovascular injuries underwent operations over a 20 year period. Forty-nine patients had renal artery injury, 45 had isolated venous injury, and 33 had both vessels injured. Arterial revascularization succeeded in four patients, failed in five, and the results were not documented in three. Revascularization of acute renal artery thromboses was unsuccessful. Isolated renal vein injuries were repaired in 28 patients. The mortality rate was 37 percent for renal artery injuries and 28 percent for isolated renal vein injuries, despite the frequent choice of nephrectomy instead of reconstruction in unstable patients. Renal salvage was accomplished in 10 percent of patients with renal artery injury and in 51 percent of patients with isolated renal vein injury. Renal salvage is not often feasible in patients with renal arterial injuries because of associated renal vein injuries. The success of revascularization of traumatically occluded renal arteries is low and should probably be attempted only in unusual circumstances, such as bilateral injuries. Most isolated renal vein injuries are repairable, and reconstruction should be attempted in stable patients.

Adolescent