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Biomedical subjects

H R Freund

Publications and source records attributed to H R Freund.

At least 19 recordsLinked to original sources

Brain edema and neurologic status following head trauma in the rat. No effect from large volumes of isotonic or hypertonic intravenous fluids, with or without glucose.

Disagreement exists regarding the need to restrict the administration of fluid and glucose following head injury to prevent cerebral edema and neurologic deterioration. We examined whether blood osmolality and glucose, neurologic outcome, and the development of brain edema following head trauma were altered by intravenous infusion of large volumes of isotonic or hypertonic fluids that contained or did not contain glucose. Fifty-five rats that survived ether anesthesia and closed head trauma (delivered using a weight drop device) were assigned to one of five groups. In the first group no fluid was infused. In the second group minimal volumes of saline were infused during placement of a jugular vein catheter. In the three remaining groups 10 ml.kg-1.h-1 of either total parenteral nutrition (TPN) (glucose 25%, amino acids 4.25%, 40 mEq/l sodium and 40 mEq/l potassium, 1935 mOsm/kg), dextrose 5% in 0.45% saline (495 mOsm/kg), or Haemaccel (isotonic plasma expander, 298 mOsm/kg) was infused via the jugular vein. Following head trauma and cannula placement, ether was discontinued. Neurologic severity score at 1 and 18 h after head trauma was used to assess neurologic outcome. A score between 0 and 6 was assigned by an observer who was blinded as to the experimental groups, with 0 representing no neurologic damage and 6 representing severe damage. Specific gravity of brain tissue samples containing gray matter and subcortical white matter from the traumatized and contralateral hemispheres was measured at 18 h after head trauma to determine the development of brain edema. There were no statistically significant differences in neurologic outcome and brain edema between the groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

[Sutureless bowel anastomosis with a biofragmentable ring in Crohn's disease].

A biofragmentable anastomosis ring has recently been developed and is used in end-to-end intestinal anastomosis. It is composed of 2 circular polyglycolic acid (Dexon) components which are interdigitated to form a sutureless anastomosis. We used it in an ileo-ileal and 2 ileo-colic end-to-end anastomoses in 3 patients with Crohn's disease in the past 6 months. Postoperative recovery of bowel function and oral feeding were comparable to that in patients after conventional anastomoses with sutures or staplers. Experience accumulated in 2 large multicentric comparative studies proved that the ring is a safe, fast and effective method for bowel anastomosis. We found it to be safe even in Crohn's disease.

Anastomosis, Surgical

[A decade of experience with home total parenteral nutrition].

Between August 1980 and October 1990 we treated 36 patients with home total parenteral nutrition (HTPN) with a cumulative treatment duration of 92 years. They included 14 females and 22 males ranging in age from newborn to 75 years, with a mean of 38 +/- 21. The 4 commonest indications for HTPN were short bowel syndrome (mainly due to mesenteric occlusion (50%), inflammatory bowel disease 14%), motility disorders (14%) and malabsorption (11%). All-in-one nutritional mixtures utilizing the big-bag technique were used for all patients. Broviac or Hickman catheters were implanted in 35 patients and an infusion port in 2. Infusions were administered during the night for 8-12 hours with a volumetric pump. 14 patients are still receiving HTPN (39%) while in 8 it was discontinued as they can maintain their nutritional status by the gastrointestinal route (22%). 14 patients have died (39%), 3 from HTPN-related causes (2 of sepsis and 1 of liver failure). Catheter-related sepsis was 0.42/year of HTPN. Other common complications were metabolic bone disease, deranged liver function and cholecystolithiasis. 80% were able to return to work, school, or housekeeping activities, or at least to take care of themselves and cope with HTPN unaided. Social rehabilitation was full or partial in 72% and only 29% were house-bound and needed major assistance. Patients with a poor life quality tended to be older and suffer from intestinal diseases as a manifestation of a systemic disorder, such as atherosclerosis or malignancy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Polymyxin B reduces cecal flora, TNF production and hepatic steatosis during total parenteral nutrition in the rat.

Hepatic complications are common in patients receiving total parental nutrition (TPN) and who have no underlying liver disease. In the present study we examined the hypothesis that endotoxin (LPS) or possibly TNF derived from the overgrowth of intestinal gram-negative bacteria is responsible for TPN-associated hepatic steatosis, and that bowel decontamination and specific anti-LPS activity of polymyxin B will reduce fatty infiltration of the liver during TPN. Forty-five male Sabra rats underwent jugular vein cannulation, were placed in metabolic cages, and were randomized into five groups. Group I was continuously infused with normal saline and allowed food ad lib, while group II-V were continuously infused with a TPN formula containing 4.25% amino acids and 25% dextrose for a total of 36 calories and 3.0 g protein per 100 g body weight/day. In addition, groups III-IV were also treated by oral polymyxin B while Groups IV and V received a combination of neomycin, metronidazole, and vancomycin (NMV). Thus, Group III received polymyxin B, Group IV received both polymyxin B and NMV, while Group V received NMV only. On Days 7-8 of the study, all animals were sacrificed and spontaneous production of TNF by peritoneal macrophages, bacterial translocation to mesenteric lymph nodes, culture of the cecum, and fat, triglyceride, and cholesterol contents of the liver were determined. All groups infused with TPN exhibited higher levels of total fat, triglycerides, and cholesterol compared to the free feeding control group (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue

Amino acid alterations and encephalopathy in the sepsis syndrome.

OBJECTIVE: To evaluate the role of amino acid profiles in septic encephalopathy. DESIGN: Retrospective analysis. SETTING: Medical wards and medical ICU of a university hospital. PATIENTS: Patients with infections and normal mental status were compared with patients with septic shock and altered sensorium. INTERVENTIONS: Plasma amino acid levels and Acute Physiology and Chronic Health Evaluation (APACHE II) scores were determined. MEASUREMENTS AND MAIN RESULTS: Patients with septic shock and altered sensorium had higher circulating concentrations of ammonia (425 +/- 55 vs. 127 +/- 7 mmol/L) and the aromatic amino acids phenylalanine (122 +/- 19 vs. 74 +/- 3 mmol/L) and tryptophan (97 +/- 7 vs. 32 +/- 13 mmol/L), and lower levels of the branch-chain amino acid isoleucine (48 +/- 7 vs. 68 +/- 5 mmol/L) than patients with infections and normal sensorium (p less than .05). Aromatic amino acid levels correlated with APACHE II scores (R2 = .4, p less than .001) and mortality. APACHE II scores were higher in the septic shock patients (30 +/- 2 vs. 8 +/- 1, p less than .001), and these patients had a higher mortality rate (71% vs. 12%, p less than .01). Patients with septic shock who died had higher levels of ammonia (524 +/- 58 vs. 227 +/- 40 mmol/L, p less than .05) and sulfur-containing amino acids (172 +/- 31 vs. 61 +/- 7 mmol/L, p less than .05) than patients who survived. CONCLUSIONS: Plasma amino acid profiles appear to be important in septic encephalopathy and the severity of septic disease.

Amino Acids

Primary choledochoduodenostomy for benign obstructive biliary tract disease.

Repeated surgical interventions on the biliary ductal system increase morbidity and mortality, particularly in the geriatric patient. In an attempt to prevent these complications, side-to-side choledochoduodenostomy was performed as the primary operative procedure in 54 patients, age 72 +/- 13 years. This was the patients' first surgical intervention for benign obstructive lesions of the biliary tract system. Indications for choledochoduodenostomy were: multiple or irremovable common or hepatic duct stones, doubtfulness of complete clearing of the duct, primary common bile duct stones or mud and sludge, a grossly dilated biliary duct system, and ampullary stenosis. We encountered no operative or hospital mortality among this group of 54 patients. The mean postoperative hospital stay for this aged and relatively sick group of patients was 12.3 +/- 6.2 days. Twenty-three minor postoperative complications occurred in 18 patients, none of them requiring reoperation. The patients were followed for 2-16 years. Thirteen patients (24%) were lost to follow-up. Of the 41 patients available for follow-up, 14 died, none from biliary tract associated causes--mostly from cerebrocardiovascular disease. Twenty-seven patients still alive were found to be free of biliary tract associated abdominal complaints or recurrent cholangitis for a mean period of 7.8 +/- 3.7 years. The data indicate a zero reoperation rate during long-term follow-up, zero mortality rate, and low morbidity in a group of elderly, mostly poor risk patients. This leads us to conclude that a side-to-side choledochoduodenostomy is both the best therapy as well as prophylaxis against common duct stones. This, even in this era of endoscopic papillotomy and biliary lithotripsy.

Adolescent

Role of total parenteral nutrition in the treatment of Crohn's disease.

We studied 49 patients with severe nonresponsive Crohn's disease receiving 73 courses of total parenteral nutrition (TPN) for a total of 2,153 days (30 +/- 18 days/admission). Forty-five percent of all courses of TPN resulted in patients not being operated on, whereas 55 percent resulted in surgical intervention. Fifty percent of patients who did not undergo operation initially as a result of a successful course of bowel rest and TPN had surgery within 15.4 +/- 13.9 months, whereas 75 percent of patients operated on immediately after a course of TPN did not need additional surgery during a follow-up of 36.1 +/- 31.2 months. Thus, a total of 80 percent of patients underwent gastrointestinal surgery sometime during the study and follow-up periods. TPN has an important role in replenishment of nutritional deficits and perioperative nutritional support; however, from the results of the present study, it is difficult to advocate it as the sole primary therapy for Crohn's disease.

Adolescent

[Extracorporeal shock-wave lithotripsy of gallstones].

We performed 16 extracorporeal shock-wave lithotripsies (ESWL) to fragment gallstones in 11 women and 2 men, aged 19 to 57 (mean 41 +/- 10) years, during the past 10 months. Criteria for selection included a history of biliary colic, not more than 3 stones with a total diameter of not more than 30 mm, and a functioning gallbladder. 210 patients were examined, of whom 98 were referred for additional screening by combined ultrasonography and oral cholecystography. This resulted in rejection of another 71 patients due to multiple stones (38%), nonfunctioning gallbladder (22%), calcified stones (12%), stones not visualized in the prone position (9%), excessively large stones (3%) and other reasons (16%). Only 27 patients fulfilled all the criteria. Under epidural or general anesthesia (11 and 2 patients, respectively), we administered 1200-3500 (mean 2250 +/- 750) shock waves at 20-24 KV with the Tripter X1 (Direx, Israel-USA). This is an ultrasound-guided, modular portable, shock-wave generator utilizing underwater high energy spark discharge. Chenodeoxycholic or ursodeoxycholic acid, 10 mg/kg/day, was started 1 week prior to ESWL and continued for 3 months after disappearance of fragments and debris. We encountered skin petechiae in all patients, transient hematuria in 8, mild biliary colic in 1 and a small liver hematoma in 1. To date, 3 patients are free of stones, while in 7 only sludge and tiny fragments are present which we expect to disappear as a result of the litholytic therapy. 3 patients had fragments larger than 5 mm and required a second ESWL. Thus ESWL, which was indicated in only 13% of screened patients, proved to be safe and can be expected to be successful in 75% of selected candidates.

Adult

Protective effect of branched chain-enriched amino acid formulation in myocardial ischemia.

The protective effect of a branched chain amino acid (BCAA) formulation on the ischemic myocardium was determined in four groups of passively perfused normothermic (37 C) isolated rat hearts perfused with Krebs-Henseleit (KH) or KH + BCAA. Time to ischemic contracture was significantly increased by the infusion of BCAA compared with KH (19.4 +/- 2.3 vs. 15.9 +/- 1.7 min). In a second set of experiments, rat hearts were perfused with KH or KH + BCAA solution followed by 2 min of glucose-free KH buffer. After 17 min of ischemia, both groups were reperfused for another 15 min. Percent of pressure recovery was significantly better with KH + BCAA (90.1 +/- 8.4) than with KH (56.4 +/- 40.0). Percent +dP/dt (time derivative of pressure at contraction) recovery was also significantly improved with KH + BCAA (96.5 +/- 26.9 vs. 58.1 +/- 44.0). Furthermore, arrhythmias were minimized by BCAA. There was no difference in change of coronary flow between these two groups. Thus, BCAAs appear to protect the heart against myocardial ischemic injury and to delay the time to ischemic contracture, particularly in the depleted ischemic heart. BCAAs enhance postischemic pressure recovery and improve postischemic systolic and diastolic myocardial function.

Amino Acids, Branched-Chain

Renal prostaglandin production is increased during abdominal sepsis in the rat and unaffected by the infusion of different amino acid formulations.

Renal prostaglandin (PG) production was studied in 32 laparotomized (control) and 33 septic rats (cecal ligation and puncture). Control and septic rats were infused for 18 hr with 5% glucose or 5% glucose and one of three amino acid formulations containing 22, 35, or 45% branched chain amino acids. When comparing renal PG production from endogenous precursors in septic versus control rats, significant increases (P less than 0.01) could be detected for PGE2, 6-keto-PGF1 alpha, and TxB2. The infusion of either 5% glucose alone or 5% glucose with 4.25% of any of the three amino acid formulations tested did not change renal PG production in either control or septic rats.

6-Ketoprostaglandin F1 alpha

Resting energy expenditure of host and tumor is similar in rats with methylcholanthrene-induced sarcoma.

In the present study we assessed the resting energy expenditure of 30 free-feeding control and methylcholanthrene-induced sarcoma-bearing rats prior to and following surgical removal of the tumor. Tumor-bearing rats demonstrated carcass wasting and massive tumor growth. The resting energy expenditure data in our model suggest that neither the presence and growth of a tumor nor its removal significantly change resting energy expenditure beyond the normal range for non-tumor-bearing rats. We suggest that in the partition of energy costs between host and tumor, both carry a similar input, proportional to their relative weight, into the total combined resting energy expenditure of host and tumor.

Animals

Regional brain amino acid and neurotransmitter derangements during abdominal sepsis and septic encephalopathy in the rat. The effect of amino acid infusions.

Regional amino acids and brain neurotransmitters were studied in 33 normal and 32 rats with sepsis (induced by cecal ligation and puncture) infused with different amino acid formulations. The brain amino acid pattern during sepsis showed increased concentrations of most essential and six of the nonessential amino acids. The most consistent finding was the accumulation of indoleamines in all six brain regions studied during sepsis; increased brain tryptophan levels presumably resulted in enhanced metabolism of serotonin (5HT), increased production of 5-hydroxyindoleacetic acid (5HIAA), and a high 5HT/5HIAA ratio. Infusion of branched-chain amino acid-enriched formulas restored brain amino acid and neurotransmitter profiles, decreasing levels of tryptophan, tyrosine, 5HIAA, and 5HT/5HIAA ratios while increasing norepinephrine levels in some regions. These alterations in brain neurotransmitter metabolism may be at least partially responsible for the development of septic encephalopathy.

Amino Acids

The effect of indomethacin on muscle and liver protein synthesis and on whole-body protein degradation during abdominal sepsis in the rat.

It has been recently suggested that increased muscle protein degradation during injury or infection is at least partially mediated by the increased production of prostaglandin E2 in muscle, and some have suggested that cyclooxygenase inhibitors might decrease protein loss in injured or septic patients. In these experiments, fractional synthesis rates of mixed muscle and liver protein and whole-body tyrosine flux were measured by constant intravenous infusion of tyrosine labeled with carbon 14 in 17 rats with sham operations and 15 severely septic rats with or without indomethacin treatment (20 mg/kg/d). Fractional synthesis rates in muscle and liver were decreased in late sepsis and were lowest in the septic group receiving indomethacin. Unlike the fractional synthesis rate, which was affected by indomethacin in septic rats only, tyrosine flux was significantly lower in indomethacin-treated rats with sham operations and those with sepsis. Although indomethacin reduced total-body protein breakdown during sepsis, it was also associated with lower plasma albumin levels and with decreased protein synthesis in muscle and liver at a time when the survival of the septic host may be dependent on its ability to produce new protein for a variety of vital functions. These results do not support the use of indomethacin in sepsis.

Abdomen

Paracecal hernia: a cause of intestinal obstruction.

During a two-year period, five patients were treated by us for acute intestinal obstruction caused by an incarcerated paracecal hernia. All patients underwent surgery early, so none required bowel resection. The possibility of an internal hernia as a cause of intestinal obstruction and a profound knowledge of the pericecal anatomy, however, are necessary for successful diagnosis and treatment of paracecal hernias.

Adult