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Biomedical subjects

R J Andrassy

Publications and source records attributed to R J Andrassy.

At least 19 recordsLinked to original sources

Clinical comparison of tolerance to elemental or polymeric enteral feedings in the postoperative patient.

Thirty consecutive patients (19-71 years of age) undergoing abdominal operations and having feeding catheter jejunostomy tubes placed, were prospectively randomized and studied for tolerance to elemental (amino acid) or polymeric (intact protein isolates) dietary formulas. The groups were matched for sex, age, height, weight, operations, and caloric goal. Nutritional profiles of the patients were similar preoperatively. The number of stools/day and stool consistency were direct indicators of tolerance; nutrient intake was an indirect indicator. Diarrhea is defined as greater than or equal to five stools/day. We found no significant difference between the groups. There were no patients with diarrhea on days 1 or 2. Formula intake as an indirect measure of tolerance was not significantly different for the two groups from days 1-4. On day 5, intake of the elemental group exceeded that of the polymeric group (p less than 0.02). Enteral caloric intake as percent of caloric goal did not differ. Nitrogen intake, urinary nitrogen, serum prealbumin, body weight, serum sodium, and serum potassium did not differ significantly between the two groups throughout the study. Serum chloride decreased significantly (105 to 99.8 mEq/L) in the elemental group (p less than 0.03). Our study shows that patients undergoing routine gastrointestinal operations will tolerate early enteral feedings (day 1) and that there is no significant difference in tolerance to elemental or polymeric dietary formulas.

Adult

Early enteral feeding, compared with parenteral, reduces postoperative septic complications. The results of a meta-analysis.

This two-part meta-analysis combined data from eight prospective randomized trials designed to compare the nutritional efficacy of early enteral (TEN) and parenteral (TPN) nutrition in high-risk surgical patients. The combined data gave sufficient patient numbers (TEN, n = 118; TPN, n = 112) to adequately address whether route of substrate delivery affected septic complication incidence. Phase I (dropouts excluded) meta-analysis confirmed data homogeneity across study sites, that TEN and TPN groups were comparable, and that significantly fewer TEN patients experienced septic complications (TEN, 18%; TPN, 35%; p = 0.01). Phase II meta-analysis, an intent-to-treat analysis (dropouts included), confirmed that fewer TEN patients developed septic complications. Further breakdown by patient type showed that all trauma and blunt trauma subgroups had the most significant reduction in septic complications when fed enterally. In conclusion, this meta-analysis attests to the feasibility of early postoperative TEN in high-risk surgical patients and that these patients have reduced septic morbidity rates compared with those administered TPN.

Adult

Marked response to preoperative high-dose cis-platinum in children with unresectable hepatoblastoma.

Chemotherapy is the only effective method of treating unresectable hepatoblastoma. Most protocols require the administration of multiple highly toxic agents. We evaluated the ability of single-agent high-dose cis-platinum (HD-CDDP) to shrink unresectable primary hepatoblastoma to allow resection. Seven children aged 11 to 72 months had unresectable hepatoblastoma based on size and location. Initial alpha-fetoprotein (AFP) levels were between 4,900 and 1,840,000 ng/mL (mean, 555,900 ng/mL). Chest computed tomography (CT) scans obtained before beginning HD-CDDP therapy showed multiple or bilateral lung masses in 3 patients. Chemotherapy for each of the 7 children consisted of only HD-CDDP, 150 mg/m2, at 3-week intervals. HD-CDDP was stopped and prompt resection performed when AFP levels ceased to decline significantly (n = 4; mean nadir, 18,600); the corrected creatinine clearance decreased below 60 mL/min (n = 2); or, in one case, significant hemorrhage occurred within the tumor. Therefore, the number of HD-CDDP doses given preoperatively varied between 1 and 7 (mean, 3). No children required dialysis. Tumor cells in the bone marrow of one child disappeared completely after one dose of HD-CDDP. Follow-up CT scans showed complete resolution of the pulmonary metastases in 2 children, a partial response in the third, and a marked reduction of primary tumors to resectable sizes. Six children underwent tumor excision with adequate margins; parents of the seventh child refused permission for surgery. There were 2 operative deaths, 3 deaths due to local or distant disease, and 2 patients survived (postoperative follow-up, 22 and 14 months).(ABSTRACT TRUNCATED AT 250 WORDS)

Carcinoma, Hepatocellular

Aggressive excision of pulmonary metastases is warranted in the management of childhood hepatic tumors.

Although most children who die of liver malignancies do so as the result of complications of pulmonary metastases, little has been published regarding the efficacy of surgically excising such lesions. To the 12 previously reported cases of children who have undergone excision of pulmonary metastases of hepatic tumors, are added 5, 4 with hepatoblastoma and 1 with hepatocellular carcinoma. Total excision of a primary hepatic tumor leads to survival much more frequently than does incomplete excision. No patient had metastases at diagnosis. The length of time between resection of the primary tumor and the development of pulmonary disease resistant to chemotherapy is available for 9 of the 17 children; it was under 6 months for the 2 who died but over 6 months for the 7 who survived. Postoperative alpha-fetoprotein (AFP) levels accurately predicted the development of metastases in our 5 patients. Resection of metastases benefitted the 4 whose AFP levels had declined to less than 25 ng/mL following initial chemotherapy and who underwent operation before their levels increased above 1,000 ng/mL. They are alive and free of disease 4 to 83 months following excision of their lesions. Resection did not benefit the 1 nonsurvivor whose AFP level fell only to 5,000 ng/mL before beginning to increase, eventually reaching 58,000 ng/mL at the time of operation. Incomplete resection of metastases unresponsive to chemotherapy predictably leads to death. Multiple thoracotomies were successful in achieving the long-term survival of 4 children in this series.(ABSTRACT TRUNCATED AT 250 WORDS)

Carcinoma, Hepatocellular

Low-fat, high-carbohydrate diets improve wound healing and increase protein levels in surgically stressed rats.

The specific effects of omega 3 and omega 6 polyunsaturated fatty acids on wound healing, nutrition status, or immune function are controversial. Therefore, we investigated the effects of fatty acid supplementation on wound healing and nitrogen retention in a surgically stressed rat model. Male Sprague-Dawley rats (weighing 250 g) were placed into three isocaloric, isonitrogenous feeding groups (controls [standard Vivonex]; 30% safflower oil [omega 6]; or 30% fish oil [omega 3]) for 8 days prior to receiving subcutaneous vascular graft wound cylinders in their dorsal midline. Nitrogen balance was monitored daily. Wounds healed for 10 days, animals were then euthanized, serum was drawn, and wound cylinders were harvested for analyses. The low-fat, high-carbohydrate control group had higher serum albumin levels at 10 days than either fatty acid-supplemented group (3.5 +/- 0.4 g/dL v 2.9 +/- 0.3 g/dL and 2.7 +/- 0.2 g/dL, omega 3 and omega 6, respectively; both P less than .05) and had better nitrogen balance (8.6 +/- 0.8 mg N/d v -2.6 +/- 0.9 mg N/d and 0.8 +/- 1.2 mg N/d, omega 3 and omega 6, respectively; both P less than .05). They also had better healed wounds at 10 days (450 +/- 290 micrograms 5-hydroxyproline [OHP]/cm of wound cylinder v 150 +/- 40 micrograms OHP/cm and 145 +/- 90 micrograms OHP/cm, omega 3 and omega 6, respectively). Surgically stressed rats had higher protein levels, better nitrogen balance, and improved wound healing when fed a diet high in carbohydrates and low in fat.

Animals

The effects of an arginine-free enteral diet on wound healing and immune function in the postsurgical rat.

Critically ill patients have increased rates of sepsis partly due to a down-regulated immune system. Nutrients may modulate the immune system. The following studies were performed to determine whether arginine is one of these "essential" nutrients for the immune system. Thirty-two male Sprague-Dawley rats (weighing 175 g) were divided into two groups that were pair-fed with either an elemental, arginine-supplemented enteral diet, or the same diet with arginine removed and replaced with glycine. Both diets were isocaloric, isoosmolar, and isonitrogenous. After 6 days on the diet, animals underwent testing. There were no significant differences between the arginine-supplemented and the arginine-free diet groups in blood glucose or hematocrit. The arginine-supplemented animals had higher serum albumin (4.1 +/- 0.1 mg/dL v 3.6 +/- 0.1 mg/dL; P = .035) and serum protein levels (5.2 +/- 0.1 mg/dL v 4.3 +/- 0.1 mg/dL; P = .041); and had higher thymus gland (0.53 +/- 0.03 g v 0.44 +/- 0.02 g; P less than .0001) and spleen weights (0.66 +/- 0.01 g v 0.57 +/- 0.01 g; P less than .01). Daily total urinary nitrogen excretion, nitrogen balance, and weight gain showed a tendency for the arginine-supplemented animals to retain more of their nitrogen calories. There was no difference in the amount of hydroxyproline (OHP) found in the wound cylinders of either group (both 25.6 micrograms OHP/cm polytetrafluoroethylene) but the arginine-supplemented group's wounds had greater wound bursting strengths (429 +/- 3 g/cm v 350 +/- 7 g/cm; P = .044).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Continuous EGF application impairs long-term collagen accumulation during wound healing in rats.

Continuous topical application of epidermal growth factor (EGF) to granulation tissue has been demonstrated to increase the rate of collagen accumulation in wounds. Studies from this laboratory have indicated that a single topical application of EGF leads to a short period of elevated wound collagen content, followed by a rapid breakdown of this newly acquired collagen. In light of recent clinical trials of EGF as an aid to wound healing, we studied the long-term effects of continuous EGF injection. Standard polytetrafluoroethylene (PTFE) wound cylinders were surgically placed in the dorsal midline of 40 male Sprague-Dawley rats. Rats received EGF daily for 14 days, at which time all injections ceased. Wound cylinders were removed for analysis from five test animals and five controls on study days 14, 21, 28, and 35. Wound collagen content in EGF-treated animals was significantly higher than in controls on the 14th day of the study (330% higher, P less than .002), but dropped to lower levels on each succeeding day (day 21: 97% of control, NS; day 28: 63% of control, NS; day 35: 72% of control, P less than .03). There was a significant increase in wound collagenase activity only on days 14 and 21, but not on days 28 and 35. We demonstrated that continuous application of EGF may artificially elevate wound collagen content, thereby leading to increased wound catabolism on cessation of treatment.

Analysis of Variance

The effects of age and various fat/carbohydrate caloric ratios on nitrogen retention and wound healing in rats.

Recent reports have indicated a possible age-related component to the ability of various species to utilize either fat or carbohydrate as their preferential energy source. These studies have demonstrated that infant rats given a high-fat diet (50% fat, 35% carbohydrate, 15% protein) retain a significantly higher amount of nitrogen than do infant rats on a high-carbohydrate diet (82% carbohydrate, 3% fat, 15% protein). Conversely, adult rats maintain a higher positive nitrogen balance when given the high-carbohydrate diet. In light of these studies, and our interest in factors that contribute to wound healing in the surgical patient, we investigated the effects of low-, medium-, and high-fat enteral diets on wound healing and nitrogen balance in surgically stressed rats of various ages. Weanling (45 g) and young adult (175 g) male Sprague-Dawley rats (n = 16 per age group) were housed individually in metabolic cages. All animals had Impra vascular-graft wound cylinders placed subcutaneously in the dorsal midline and were placed in four dietary groups: high fat (50% kcal), medium fat (30% kcal), low fat (2.5% kcal), and chow (Purina Standard Laboratory Rodent Chow, 17% kcal as fat). All test diets were isonitrogenous (3.1 g nitrogen/1,000 kcal) and isocaloric for each age group. Animals in each age group were pair-fed (35 kcal/d, weanlings; 60 kcal/d, young adults) for 10 days and then euthanized. Wound cylinders were removed and analyzed for collagen content.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging

Epidermal growth factor and insulin act synergistically during diabetic healing.

Increased wound collagen catabolism is among the defects of diabetic wound repair. We studied the interactions of topically applied insulin and epidermal growth factor (EGF) in diabetic rats. Polytetrafluoroethylene cylinders were implanted in 80 diabetic rats and removed on postoperative days 1, 5, 10, and 15. Cylinders were analyzed for collagen concentration and collagenase activity. The EGF and insulin promoted a 202% increase over controls in collagen synthesis by day 15, while diabetic rats that received EGF or insulin alone had significantly less collagen than controls. All groups that received insulin had lower collagenase activity than both controls and diabetic rats that received EGF. The individual effects of insulin and EGF added synergistically for a net gain in wound collagen content after 15 days. This gain was not observed with either EGF or insulin alone.

Animals

EGF increases short-term type I collagen accumulation during wound healing in diabetic rats.

Continuous topical application of epidermal growth factor (EGF) to granulation tissue increases the rate of collagen accumulation. It is believed that the clinical use of growth factors, such as EGF, may become common in the treatment of impaired wound healing in the near future. Impairments in the production and degradation of wound collagens have been demonstrated in diabetes mellitus. We studied the effects of a single, local application of EGF on collagen content, collagenase activity, and the ratio of type III and type I collagens within granulation tissue using polytetrafluoroethylene (PTFE) wound cylinders in 48 streptozotocin-induced diabetic rats in order to determine potential benefits of EGF to wound healing in diabetics. Wound collagen content in EGF-treated diabetic animals was significantly higher than in diabetic controls during the first 10 days of wound healing (236% on day 5, P less than .001; 140% on day 10, P less than .01), but decreased to significantly lower levels by day 15 of healing (71% of diabetic controls, P less than .01; 47% of nondiabetic controls, P less than .01). An 18% increase in diabetic wound protease activity was observed following application of EGF (P less than .001). The ratio of type III collagen to total wound collagen within the granulation tissue was significantly reduced (P less than .001) following EGF application. We demonstrate that a single, topical application of EGF promotes early synthesis of type I collagen, thereby deranging the usual type III/total collagen ratio, and is associated with increased wound protease activity.

Administration, Topical

A potential basis for suppressed inflammatory cell function in pediatric cholestatic hosts.

Infective mortality is common in children who have hepatic failure. We have demonstrated that experimental hepatic failure (EHF) profoundly suppresses T cell function in vivo. To determine the basis for immune suppression in EHF we postulated that this phenomenon is attributable to alterations in accessory macrophage (Ma) function, T cell subsets, interleukin-2 (IL-2) production, or serum inhibition. Wistar Furth rats (200 g) were randomized to EHF (n = 23), Sham (n = 23), and normal control (NC) (n = 23) groups. On day 21, splenocytes and sera were harvested and immune assays performed in vitro. Following are the results (mean +/- SEM; Student's t test). Serum bilirubin was elevated in EHF versus Sham and NC groups (P less than .01). EHF splenic macrophages suppressed PHA when added to microcultures at 10(5) concentration (-140 +/- 550 v 12,263 +/- 2,492 [Sham] and 21,413 +/- 1,702 [NC] P less than .01). This effect was not evident when macrophages were added back to microcultures at 10(3) and 10(4) concentrations, suggesting a dose-dependent inhibitory effect. T helper: suppressor ratios did not differ in EHF (1.3 +/- 0.2) compared with Sham (1.4 +/- 0.2) and NC groups (1.2 +/- 0.1). IL-2 production was similar in EHF, Sham, and NC animals (112,141 +/- 5,232 versus 106,691 +/- 1,419 and 120,759 +/- 3,249 counts per minute). T cell inhibitory activity was not demonstrable in EHF sera. These data show that splenic macrophages can inhibit T cell function in vitro. This phenomenon may be paramount in predisposing children with liver disease to infection.

Animals

Wound collagenase activity correlates directly with collagen glycosylation in diabetic rats.

Extracellular glycosylation of proteins in diabetics may contribute to observed impairments in wound healing. We investigated the interactions of blood glucose concentration and wound collagen glycosylation, collagen content, and proteolytic activity during wound healing in diabetic animals. Rats were made differentially hyperglycemic with intraperitoneal injection of streptozotocin (0-65 mg/kg body weight). Animals with blood glucose concentrations greater than 240 mg glucose/dL were classified as diabetic, those with blood glucose concentrations less than 160 were grouped as nondiabetic. Polytetrafluoroethelene (PTFE) wound cylinders were surgically implanted in 32 rats and removed on postoperative day 5. Harvested cylinders were analyzed for hydroxyproline content, collagen glycosylation, and collagenase and protease activity. Collagenase activity was 14% higher in diabetics than nondiabetics (P less than .001). Glycosylation of wound collagen averaged 48.0% higher in diabetics (P less than .001). Wound hydroxyproline content was 39% lower in diabetics (P less than .05). Studies show a high degree of correlation (Pearson) of wound collagen nonenzymatic extracellular glycosylation (NEG) with mean blood glucose concentration (r = .98, P less than .001). Wound collagen glycosylation correlates strongly with both protease activity (r = .86, P less than .001) and collagenase activity (r = .83, P less than .001). This study demonstrates a significant blood glucose concentration dependent increase of glycosylation in newly synthesized collagen in hyperglycemic animals that is associated with increased collagenase activity and decreased wound collagen content.

Animals

Short-term hyperglycemia depresses immunity through nonenzymatic glycosylation of circulating immunoglobulin.

Hyperglycemia accompanies a myriad of clinical conditions and causes an acceleration in the nonenzymatic glycosylation (NEG) of proteins. Since many proteins lose function when glycosylated, we assessed the effect of hyperglycemia on the function of immunoglobulin G. Twenty newborn Sprague-Dawley rats underwent splenectomy and 20, splenic mobilization alone. After 3 weeks, all animals received an intraperitoneal injection of Streptococcus pneumoniae. Twelve hours later, ten animals from each group received either control (CIG) or glycosylated (GIG) human immunoglobulin (0.3 gm/kg) intraperitoneally. Asplenic animals receiving GIG lived 28.5 hours vs. 49.6 hours for those receiving CIG (p less than 0.0001). Animals with spleens receiving GIG lived 48.2 hours vs. 51.7 hours for those receiving CIG (p = 0.03). Short-term glycosylation of immunoglobulin causes its inactivation. This may contribute to the increased risk of infection noted in hyperglycemic animals.

Animals

Pheochromocytoma and acute myocardial infarction.

When a pheochromocytoma is manifested as an acute myocardial illness, diagnosis may be difficult to make. If the tumor is suspected early enough, a workup can be done while the complications of the myocardial illness are being controlled (as in our case). The tumor can then be expeditiously removed before any further problems develop. The case presented here underscores the importance of maintaining a high index of suspicion for a pheochromocytoma in any patient who has an unexpected myocardial event.

Adolescent

Protein glycosylation and collagen metabolism in normal and diabetic rats.

The high concentration of glycosylated extracellular proteins found in diabetics may contribute adversely to wound healing. The degree of collagen glycosylation was correlated with collagenase activity and 5-hydroxyproline (5-OHP) levels in surgical wounds of normal and diabetic animals. Expanded polytetrafluoroethylene (PTFE) wound cylinders were implanted subcutaneously in 10 normal and 10 streptozotocin-induced diabetic rats. Nonenzymatic glycosylation (NEG) of protein was inhibited in half the subjects in each group by daily enteral acetylsalicylic acid (ASA). Wound cylinders were removed on the fifth day and assayed for collagenase activity and 5-OHP levels, and the degree of collagen glycosylation was measured with an assay for 5-hydroxymethylfurfural (5-HMF). Results were compared using Student's two-tailed t test. When compared with controls, diabetic animals had less wound 5-OHP (1.87 +/- 0.01 vs 3.11 +/- 0.03 micrograms/cm PTFE) (P less than 0.0001), higher levels of glycosylated collagen (215 +/- 11 vs 150 +/- 9 micrograms 5-HMF/mg protein) (P less than 0.001), and increased collagenase activity (13.5 +/- 0.6 vs 11.7 +/- 0.5 microgram collagen/mg protein/hr) (P less than 0.001). When ASA was added to the diet of diabetic animals, results in each case were statistically indistinguishable from controls. The collagenase activity of nondiabetic animals receiving ASA was decreased from nondiabetic controls (7.6 +/- 0.5 vs 11.7 +/- 0.5 microgram collagen/mg protein/hr) (P less than 0.001). These data show that ASA inhibits NEG of wound collagen in vivo, and ASA may normalize some abnormalities of wound healing found in diabetic animals.

Animals

Gamma-globulin enhances survival in pneumococcal-challenged asplenic infant rats.

Early augmentation of a patient's immune system can be a valuable adjunct to standard supportive and antibiotic treatment of overwhelming postsplenectomy sepsis (OPSS). Normal humoral immune factors against pneumococcal sepsis are replenished by the parenteral administration of human gamma-globulin (HGG). Monthly prophylactic administration of HGG to asplenic individuals to prevent OPSS has been suggested. The cost of such measures is prohibitive, and the risk of serum-transmitted disease is significant. We administered HGG to splenectomized infant rats with pneumococcal sepsis to determine if mortality rates could be reduced and survival time prolonged. Fifty-six three-day-old rats underwent splenectomy and another 56, laparotomy without splenectomy. Twenty-eight animals from each operative group were administered HGG and the other 28, human serum albumin (HSA), 12 and 24 hours after inoculation with varying dosages of log-phase Streptococcus pneumoniae. The LD50 for asplenic animals was less than 50 colony forming units (cfu) per animal, while for the group with spleens, the LD50 was 250 to 500 cfu. There were no significant intragroup variations in LD50 between HGG and HSA subgroups. Survival times were compared using the BMDP1L-Life Tables and Survival Functions, and the generalized Wilcoxon t-test. These data show that host immunity to pneumococcal challenge in asplenic infant animals might be fully restored by the administration of HGG, even after the onset of symptoms. Survival of an asplenic child with evidence of OPSS might be enhanced by immediate administration of HGG.

Animals

Inflammatory cell function in young rodents with experimental cholestasis: investigations of functional deficits, their etiology, and their reversibility.

Children with cholestasis are susceptible to infective complications. This may be attributable to impaired host defense. We postulated that cholestasis affects systemic polymorphonuclear leukocyte (PMN) function by impeding chemotaxis, phagocytosis, and superoxide release, which are all critical in eliciting an adequate immune response. Sprague Dawley rats (225 g) were assigned to three groups: bile duct ligated (BDL), sham (SH), and normal control (NC). On day 21 after operation, PMN and sera were isolated. Chemotactic response to C5a and FMLP (formyl-methionyl-leucyl-phenylalanine), superoxide release, and phagocytic uptake of 14C-labeled Staphylococcus aureus were performed on pooled PMN samples. Results were expressed as mean +/- SD. Serum bilirubin at day 21 was 6.3 +/- 2.9 v 0.1 +/- 0.1 and 0.1 +/- 0 mg/dL (P less than .01) in BDL, SH, and NC groups, respectively. Kinetic studies of PMN phagocytosis demonstrated impaired 14C S aureus uptake by BDL neutrophils at 60 (P less than .05), 90 (P less than .05), and 120 minutes (P less than .05) compared with SH and NC groups. No differences in PMN chemotactic response to C5a and FMLP was observed in BDL, SH and NC groups (43 +/- 14 v 40 +/- 12 and 33 +/- 1, and 43 +/- 20 v 43 +/- 14 and 28 +/- 1 cell per field, respectively). Zymosan stimulated superoxide release did not differ between groups (14.3 +/- 3.6 (BDL) v 15.1 +/- 8.7 (SH) and 12 +/- 2.0 (NC) nmol/30 min/mg cell protein, respectively. Thus, cholestasis impairs neutrophil phagocytosis in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals