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Biomedical subjects

D E Fry

Publications and source records attributed to D E Fry.

At least 19 recordsLinked to original sources

Effects of oligosaccharide binding on glycogen debranching enzyme activity and conformation.

Glycogen debranching enzyme contains two catalytic activities (4-alpha-glucanotransferase and amylo-1,6-glucosidase) on its single polypeptide chain, and they are affected differently by the binding of oligosaccharides. Glucose, maltose, and maltotriose are competitive inhibitors of the amylo-1,6-glucosidase activity measured by the hydrolysis of alpha-glucosyl fluoride, whereas saccharides with four or more glucose units are activators of the same activity, showing apparent "uncompetitive" kinetics. This suggests that they do not bind until the alpha-glucosyl fluoride is bound. In either case the potency of the effect increases with the length of the oligosaccharide chain. On the other hand, all oligosaccharides tested (maltose to maltohexaose, alpha-cyclodextrin, and beta-cyclodextrin) are competitive inhibitors of the transferase activity and also cause a decrease in the intrinsic fluorescence, both functions again increased by chain length, thus indicating that these saccharides do bind to the free enzyme. These interesting results can be reconciled if the extended main chain resulting from the transferase reaction has to be reoriented into a different binding mode in order to position the alpha-1,6-linked side-chain glucose into the correct position for the glucosidase reaction. Therefore, activating oligosaccharides behave kinetically as if they had not been previously bound. It is concluded that the main chain of the natural limit dextrin substrate has a different mode of binding for the two catalytic reactions in order to position properly first the maltotetraosyl side chain in the transferase catalytic site and then the glucosyl side chain in the glucosidase catalytic site.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Occupational risk of infection with human immunodeficiency virus.

The risk of HIV infection in surgical settings is a composite of overlapping risks related to the local prevalence of HIV, the route of exposure to HIV-infected blood, and the susceptibility of the worker. Studies continue to suggest that the risk of blood contact, including percutaneous injuries, remains appreciable. Prevention of such exposures in the operating and delivery room by adoption of safer instruments, work practices, and techniques and by the consistent use of appropriate personnel protective equipment must be viewed as a priority.

Acquired Immunodeficiency Syndrome

Prevention of blood exposure. Body and facial protection.

Regardless of the specific clinical setting in the operating room, it is clear that better protection of all personnel is an appropriate objective in the current environment. Better protection through improved PPE and modification of operational practices is essential. A prompt response to blood contact when it does occur is likewise appropriate. With conscientious applications of methods to reduce blood exposure, it is hoped that the operating room can become a safer place with respect to occupational infections from bloodborne pathogens.

Blood-Borne Pathogens

Human glucocerebrosidase catalyses transglucosylation between glucocerebroside and retinol.

The basal activity of human placental glucocerebrosidase is elevated 16-fold by n-pentanol when assayed using p-nitrophenyl beta-D-glucopyranoside (pNPGlc) as the beta-glucosidase substrate. This enhancement of activity is the result of the formation of a transglucosylation product, n-pentyl beta-D-glucoside, in rate-determining competition with the hydrolytic reaction. The transglucosylation product accounts for approximately 80% of the reaction product generated in the presence of n-pentanol (0.18 M) when either glucocerebroside or pNPGlc was used as the substrate. This stimulatory effect can be increased an additional 3-fold by the inclusion of phosphatidylserine (20 micrograms/ml) or sodium taurodeoxycholate (0.3%, w/v) in the incubation medium. In the presence of retinol, glucocerebrosidase also catalyses the synthesis of a novel lipid glucoside, retinyl glucoside, when either glucocerebroside or pNPGlc serves as the substrate. The reaction product was identified as retinyl beta-D-glucoside, based on its susceptibility to hydrolysis by almond beta-D-glucosidase and the subsequent release of equimolar amounts of retinol and glucose. The rate of retinyl-beta-glucoside formation is dependent on the concentration of retinol in the incubation medium, reaching saturation at approximately 0.3 mM retinol. Retinyl beta-D-glucoside is a substrate for two broad-specificity mammalian beta-glucosidases, namely the cytosolic and membrane-associated beta-glucosidases of guinea pig liver. However, retinyl beta-D-glucoside is not hydrolysed by placental glucocerebrosidase. These data indicate that the glucocerebrosidase-catalysed transfer of glucose from glucocerebroside to natural endogenous lipid alcohols, followed by the action of a broad-specificity beta-glucosidase on the transglucosylation product, could provide mammals with an alternative pathway for the breakdown of glucocerebroside to glucose and ceramide.

Animals

Evaluation of pulmonary infections in patients with extremity fractures and blunt chest trauma.

The use of preventive antibiotics has become the standard of care in the management of patients with multiple trauma who have injuries at risk for infection. In many areas of surgical practice, preventive antibiotic utilization has been restricted to the perioperative period only. In this study we reviewed a series of trauma patients with combined blunt chest injuries and extremity fractures to determine whether the duration of postoperative antibiotic administration would have adverse effects upon nosocomial pneumonia rates and severity.

Adolescent

Protein and energy tolerance by stressed geriatric patients.

Nutritional support of stressed geriatric patients remains empiric and has classically been limited by tolerance. Although the hypermetabolic response is known to increase protein and calorie demands, tolerance to increased loads of delivered nutrients in older patients has been questioned. We compared tolerance to nutrient delivery and nitrogen metabolism in 38 stressed surgical patients over age 65 to 38 Injury Severity Score or disease matched younger controls. Twenty-seven of the 31 geriatric patients (87%) who maintained normal renal function (serum creatinine less than 2.0 mg/dl) became azotemic (BUN greater than 30) while receiving 1.5 to 2.0 g of protein per kilogram of ideal body weight compared to only 21% of controls. This phenomenon led to inaccuracies in 17% of geriatric nitrogen balance studies because of unaccounted for serum accumulation of urea nitrogen (compared to only 6% in the control group). When calculated protein requirements were administered to the geriatric group, the mean nitrogen balance was -1.6. Resting energy expenditure as measured by indirect calorimetry demonstrated a strong correlation between actual calorie expenditures and calculated needs based on the Harris-Benedict basal energy expenditure (BEE) multiplied by an activity factor of 1.2 and a stress factor of 1.75 for trauma (r = 0.86, P less than 0.05) or 1.5 for general surgery patients (r = 0.72, P less than 0.05). In summary, energy requirements by stressed geriatric patients can be closely defined by calculation of the Harris-Benedict BEE in conjunction with appropriate activity and stress factors. However, attempts to deliver traditional levels of protein lead to azotemia and are frequently unsuccessful in achieving positive nitrogen balance.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Colonic diverticular disease in patients 40 years old or younger.

Diverticular disease in patients 40 years of age or younger has been described as rare but virulent. Previous studies, based on age, on diverticular disease are often confusing because of inexact definitions of the disease status. With these criticisms in mind, the authors studied 322 clinical records on patients admitted with a diagnosis of colonic diverticulosis or diverticulitis to the University of New Mexico Hospital and the Lovelace Medical Center. Of these patients, 285 had documented evidence of colonic diverticula with only 6 per cent of these being 40 years of age or younger. The criteria for acute diverticulitis were met by 86 patients, 17 of whom were 40 years of age or younger. The younger group had disproportionately more men, particularly Hispanics. The authors conclude that acute diverticulitis is more common in the young than suggested by previous reports, but the behavior of the disease is not distinctive.

Acute Disease

Abdominal wall considerations and complications in reoperative surgery.

The abdominal wall is the source of significant problems for patients undergoing multiple abdominal operations. The orientation of sequential incisions must be carefully considered to avoid compromise of the abdominal wall blood supply, which may result in either acute (dehiscence) or delayed (ventral hernia) complications. Infections are the most serious problems of the multiply operated on abdominal wall. These complications may range from simple wound infection to necrotizing fasciitis. Management may require only simple drainage of the infection or may entail extensive debridement for the necrotizing processes. Regardless of the cause, the multiply operated on abdominal wall may require reconstruction because of lost fascia. Polypropylene mesh can be employed safely and effectively for this purpose.

Abdomen

Reoperation for intra-abdominal abscess.

Reoperative procedures for patients with abscess and other septic complications remain among the most difficult management problems in general surgery. The diagnosis of intra-abdominal septic complications has been greatly enhanced within the last 10 years but remains imperfect and requires clinical judgment that transcends objective methods. Surgical drainage remains the mainstay of care for patients with postoperative intraabdominal abscess.

Abdomen

Antibiotic treatment for surgical peritonitis.

The charts of 480 patients with secondary bacterial peritonitis were reviewed. The antibiotics used were compared with the culture and sensitivity data obtained at surgery, and the outcomes of patients were evaluated. Patients treated with a single broad-spectrum antibiotic had a better outcome than patients treated with multiple drug treatment. Inadequate empiric antibiotic treatment was associated with poorer outcome than any other type of treatment. The outcome of this inadequate treatment group could not be improved by any antibiotic response to culture and sensitivity information after operation. Those patients treated with antibiotic coverage for anticipated organisms and having no cultures taken did as well as patients having cultures taken. Surgeons typically ignore culture data after operation, and only 8.8% of patients in this study had an appropriate change in antibiotic treatment after operation. A benefit from obtaining operative cultures could not be identified.

Acute Disease

Blood contact and exposure in the operating room.

We prospectively studied 684 operations from all surgical specialties to describe the frequency and character of blood contact and exposure during the procedures. Blood contact was defined as percutaneous, mucous membrane, nonintact skin or intact skin contact of patient blood with any member of the operative team. Blood exposure was defined as contact in any of the preceding categories excluding intact skin. Over-all, 28 per cent of the patients had one or more blood contact events that involved 293 operating room personnel. Risk of blood contact was significantly greater for cardiothoracic (p less than 0.001), trauma (p less than 0.003) and obstetric cesarean section (p less than 0.021) procedures when compared with all other procedures. Three services (Ophthalmology, Transplant and Oral Surgery) had no contact events. The remaining nine had rates ranging from 17 to 33 per cent. Eight per cent of the procedures (n = 54) resulted in blood exposure to 63 individuals. Percutaneous exposure occurred in 3 per cent of all procedures. Blood contact events increased with increasing operative time. Blood contact most commonly occurred among circulating nurses (n = 79), anesthesia personnel (n = 65), surgeons (n = 59) and first assistants (n = 49). Despite increased concerns over the risk of occupationally acquired viral diseases, blood contact and exposure continue to be frequent events. Surgeons must assume that all patients are potentially infected and should adopt universally applied standards of behavior to minimize contact with blood.

Allied Health Personnel

Antibiotic pharmacokinetics in surgery.

Pharmacokinetics is the study of variables that affect drug concentrations at the effector site. The descriptive terms peak concentration, elimination half-life, volume of distribution, and bioavailability are commonly used to express pharmacokinetic variability among drugs used in patient care. The pharmacokinetic characteristics of drugs are important for surgeons to understand because they represent differences that may assume clinical significance when selecting antibiotics for preoperative preventive indications. In addition, the changing hemodynamic pattern of the stressed and septic patient may result in changing pharmacokinetic patterns for an antibiotic, which, in turn, may require changes in the dosing regimen during the course of treatment.

Anti-Bacterial Agents

Barotrauma associated with high-frequency jet ventilation for hypoxic salvage.

Most reports describe reduction in proximal airway pressures with high-frequency jet ventilation. This led us to speculate that high-frequency jet ventilation might reduce barotrauma by providing alveolar ventilation at lower airway pressures. We describe a group of patients in whom a high incidence of barotrauma was observed after institution of high-frequency jet ventilation despite reduction in measured airway pressures. Fifteen hypoxic patients who could not be treated with conventional ventilation and who had no roentgenographic evidence of barotrauma were entered into the study. Airway pressures were measured during conventional ventilation and at 2 and 24 hours after high-frequency jet ventilation. Despite significant reduction in peak inspiratory and mean airway pressures, pneumothorax developed in seven of the 15 patients, an average of 21 hours after initiation of high-frequency jet ventilation. Five patients had bilateral pneumothorax and three developed tension pneumothorax. Despite reductions in proximal airway pressures, barotrauma is a significant potential complication of high-frequency jet ventilation in patients with noncompliant lungs. We currently place bilateral prophylactic thoracostomy tubes in patients with adult respiratory distress syndrome prior to initiation of high-frequency jet ventilation.

Adult

A computerized approach to injury description.

The study of trauma has been handicapped from its inception by the absence of a single coherent method of cataloging injuries. The AIS and ICD-9 systems have failed to fill this void because they lack the precision necessary to describe surgically treated injuries. We conceived a simple system of injury description in which injuries are rapidly encoded using a microcomputer in sufficient detail to distinguish among millions of different injuries. This system is easily searched by a microcomputer and allows for the automatic assignment of AIS, ISS, and CPT codes. In this system a patient is described by a 'paragraph' consisting of any number of identically patterned 'sentences,' each describing one of the patient's injuries. Each 'sentence' is composed of a string of six 'words' from controlled vocabularies and has the following structure: "Body region, Organ, Anatomic region, Injury, Physiology, Treatment." Defining the vocabulary allowed for each 'word' in a 'sentence' is complex because the allowed vocabulary is dependent upon the preceding 'words' in a 'sentence,' but in practice a microcomputer simply provides short lists of acceptable choices at each step of injury description, and records the user's selections. Additionally, the microcomputer assigns AIS, ISS, and CPT codes appropriate to the injury description sentence. The ease of data entry, the fineness of detail captured, the automation of code assignment, and the accuracy of database searching for specific injuries, classes of injuries, or combinations of injuries, we believe will give this approach widespread application in academic trauma centers where an accurate and accessible trauma database is important.

Humans

Recombinant human tumor necrosis factor produces hemodynamic changes characteristic of sepsis and endotoxemia.

Tumor necrosis factor (TNF) is a macrophage-derived peptide mediator released during endotoxemia and sepsis. We examined the systemic and visceral hemodynamic response to low doses of human recombinant TNF in rats. Each animal received a 30-minute intravenous infusion of either saline solution (n = 8) or TNF (n = 8) in a dose of 0.25 mg/kg or 1.0 mg/kg. Thermodilution cardiac output, blood pressure, pulse, vascular resistance, effective hepatic blood flow (galactose clearance), and effective renal plasma flow (p-aminohippurate clearance) were determined at time = 2 hours. The 0.25-mg/kg dose had no apparent effect on systemic hemodynamics. The 1.0-mg/kg dose produced a hyperdynamic systemic circulatory response with an elevated cardiac output, tachycardia, and a diminished systemic vascular resistance. Effective hepatic blood flow was exquisitely sensitive to even the lowest dose of TNF, with a 29% reduction despite the normal cardiac output. Renal flow was unaffected by either dose. Tumor necrosis factor-induced systemic and visceral hemodynamic changes are remarkably similar to those seen in gram-negative sepsis, suggesting that TNF may occupy a proximal position in the pathogenesis of overwhelming infection.

Animals

Effective hepatic blood flow during cardiopulmonary bypass.

Hepatic dysfunction following cardiopulmonary bypass (CPB) is a relatively frequent finding, and jaundice occurring after CPB is associated with an increased mortality rate. Post-CPB jaundice may be a consequence of inadequate liver perfusion during CPB. To evaluate the potential impact of CPB on effective hepatic blood flow, 10 patients undergoing CPB for cardiac procedures were studied. Effective hepatic blood flow was measured in each patient during the operative procedure but before institution of CPB and during CPB as well. Effective hepatic blood flow was measured by the galactose clearance technique. Blood lactate and pyruvate levels were also measured before and during CPB. During CPB, effective hepatic blood flow was consistently reduced by an average of 19%. Although for most patients this reduction seems well tolerated, in a minority of patients it may contribute to postoperative hepatic dysfunction.

Cardiopulmonary Bypass

Complement-mediated hemodynamic depression in the early postburn period.

This study examines the influence of complement on systemic hemodynamics following severe thermal injury in rats. Animals were injected intraperitoneally at t = -36 and t = -24 hours with either cobra venom factor (20 units/kg/dose; n = 56) to delete circulating complement or with saline alone (n = 64). Rats within each subset were then subjected to either a 50% TBSA full-thickness scald burn or sham burn. Cardiac output (CO), mean arterial pressure (MAP), heart rate, systemic vascular resistance (SVR), stroke volume, and cardiac power as well as hematocrit and the change in per cent complement activity were determined at various time periods between 15 minutes and 25 hours after the burn. In normocomplementemic animals the burn produced a marked early (t = 3-6 hours) depression in CO and MAP with a rise in SVR. Over time the hemodynamics returned to normal (t = 12 hours) and eventually approached a hyperdynamic response (t = 24 hours). Serum hemolytic complement activity fell immediately and progressively after the burn, indicating significant complement activation. Complement depletion attenuated the early decline in CO and sharply lowered the rise in SVR in the early postburn period. In addition, complement depletion improved heart rate and stroke volume and appeared to preserve/enhance late (t = 24 hours) cardiac function. This study suggests that complement activation contributes to the depression in cardiac output in the early postburn period.

Animals