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Biomedical subjects

B M Wolfe

Publications and source records attributed to B M Wolfe.

At least 145 records · Page 8Linked to original sources
PubMed1971

Quantitative studies of the metabolism of chylomicron triglycerides and cholesterol by liver and extrahepatic tissues of sheep and dogs.

Unanesthetized sheep and dogs, previously fitted with indwelling catheters in the aorta, lower vena cava, mesenteric, portal, left hepatic and jugular veins, were given constant intravenous infusions of lymph in which the chylomicron lipids were variously labeled with (3)H or (14)C. Para-aminohippuric acid was infused into the mesenteric venous catheter for measurement of portal and hepatic venous blood flow. In some animals, alternately labeled free fatty acids bound to albumin were mixed with the lymph to be infused. In both species, chylomicron triglyceride fatty acids were taken up in the region drained by the lower vena cava and portal vein and free fatty acids derived from hydrolysis of these triglycerides were extensively recycled in the blood. Direct uptake of triglyceride fatty acids also occurred in liver and accounted for about 10% of the total triglyceride fatty acids removed from the blood in sheep and 22% in dogs. In sheep, 10% and, in dogs, about 40% of these triglyceride-fatty acids were released into the blood as free fatty acids. The free fatty acids recycled from various regions accounted for a substantial fraction of the chylomicron fat eventually deposited in each tissue. Uptake of chylomicron cholesterol from the blood of sheep occurred primarily in liver and to a small extent in certain tissues drained by the portal vein. The results obtained, together with other available data, demonstrate that chylomicron triglycerides are removed primarily in extrahepatic tissues of both species, while the liver removes cholesterol contained in chylomicron "skeletons" from which most of the triglycerides have been removed. The quantitative differences between transport of chylomicron lipid in sheep and dogs may be related to known differences in the structure of their hepatic sinusoids.

Animals↗
PubMedDate not supplied

Training for minimally invasive surgery. Need for surgical skills.

Controversy exists regarding the training of surgeons for the performance of minimally invasive surgical procedures. The use of live animals is essential, especially in teaching dissection techniques. Seventeen percent of animals experienced excessive operative hemorrhage, which contributed to premature mortality during training exercises, demonstrating the need for live animals in this component of the training. A number of abdominal procedures can be performed with minimally invasive techniques without suturing by utilizing a rapidly expanding array of devices. However, other procedures cannot be successfully accomplished without suturing skills. Laparoscopic suturing skills are particularly demanding; thus specific training and practice prior to hands-on exercises in animal models is recommended. Emphasis on acquisition of advanced laparoscopic surgical skills is a necessity.

Animals↗
PubMedDate not supplied

Preparation of the intensive care patient for major surgery.

Improved methods for monitoring and treating critically ill patients have increased the number of surgical candidates with multiorgan system impairment. Whereas such patients may have been considered "too sick to undergo surgery" in the past, many such patients linger in the intensive care unit unless definitive therapy is accomplished. Specific attention to review of the patient's preoperative preparation for surgery on a system-by-system basis may improve outcome substantially. The need for possible mechanical ventilation prior to transport to the operating room must receive particular attention. Pneumothorax, if present, must be treated prior to institution of positive-pressure ventilation so progression to tension pneumothorax can be avoided. Deficits in the circulating blood volume must be identified and corrected preoperatively if possible. A need for enhancement of cardiac output or alteration of vascular tone requires pulmonary arterial catheterization and indicates an increased operative risk. Metabolic abnormalities such as disturbances of acid-base balance, sodium or potassium concentration, and endocrinopathies are identified and corrected as much as possible prior to operation. Antibiotics are instituted as appropriate. Replacement of the red blood cell mass is dictated primarily by anticipated or actual blood loss. Factors of coagulation are infused on a replacement basis as necessary. Great care must be taken during transport to the operating room, as maintenance of intravascular monitoring devices, therapeutic infusions, and mechanical ventilation must continue during transport. Precautions must be taken to avoid hypothermia during transport and institution of anesthesia. Critical illness mandates specific considerations of the anesthetic agents to be utilized.

Critical Care↗
PubMedDate not supplied

Cholesterol accumulation in J774 macrophages induced by triglyceride-rich lipoproteins. Comparison of very low density lipoprotein from subjects with type III, IV, and V hyperlipoproteinemias.

The capacity of human triglyceride-rich lipoproteins to induce cholesterol accumulation in the murine J774 macrophage cell line was investigated with large very low density lipoprotein (VLDL, Sf 60-400) obtained from subjects with type III, IV, and V hyperlipoproteinemias. After incubation for 24 hours, VLDLs from type IV and type V subjects were similar in their ability to raise cellular cholesterol deposition threefold to fourfold and cellular triglyceride 16-fold. The increase in cholesterol was entirely due to the dramatic increase in cholesterol ester, from less than 1 to greater than 50 micrograms/mg cell protein. Total cholesterol accumulation was fourfold to fivefold greater than the cholesterol accumulation observed for VLDL or low density lipoprotein (LDL) from normal subjects. Cholesterol esterification (acyl coenzyme A: cholesterol acyltransferase [ACAT] activity) paralleled the rate of cholesterol accumulation in these cells. Treating the macrophages with the ACAT inhibitor 58035, which is known to downregulate the LDL receptor in these cells, diminished cholesterol accumulation by 40% for type IV VLDL and by 23% for normal LDL. Since hypertriglyceridemic VLDL carries excess apoprotein (apo) E molecules, we investigated the role of normal and abnormal apo E. An anti-apo E monoclonal antibody, known to block the binding of apo E to the LDL receptor, blocked type IV VLDL-induced cholesterol ester accumulation by approximately 70%. In contrast to type IV subjects, VLDL from type III subjects (homozygous for apo E2) when incubated with J774 macrophages (which do not secrete apo E) caused only a modest 1.5-2-fold increase in cellular cholesterol. Pre-beta- and beta-migrating VLDL subfractions from type III subjects were equally ineffective in causing cholesterol accumulation. By contrast, beta-VLDL from cholesterol-fed rabbits caused a sevenfold to eightfold increase in cellular cholesterol content. These results indicate that triglyceride-rich lipoproteins from type IV and type V subjects can cause substantial cholesterol ester accumulation and enhanced cholesterol esterification in J774 cells. The lower cholesterol accumulation with type IV VLDL in the presence of apo E antibodies and VLDL from type III subjects demonstrates the importance of functional apo E in this process.

Animals↗
PubMedDate not supplied

Metabolism of apolipoproteins C-II, C-III, and B in hypertriglyceridemic men. Changes after heparin-induced lipolysis.

The C apolipoproteins are normally transferred to high density lipoproteins (HDL) after lipolysis of very low density lipoprotein (VLDL) triglyceride. In previous studies, a loss of plasma C apolipoproteins was documented after heparin-induced lipolysis in hypertriglyceridemic subjects. The present studies were designed to determine if this decline in plasma C apolipoproteins was due to their clearance with VLDL remnants. Five Type IV hypertriglyceridemic and two normal subjects were injected with 125I-VLDL and 131I-low density lipoproteins (LDL) to document kinetically an excess of VLDL apolipoprotein (apo) B flux relative to LDL apo B flux in the Type IV subjects. A mean of 46% VLDL apo B was cleared from the circulation, without conversion to intermediate density lipoprotein (IDL) or LDL. Heparin was then infused (9000 IU over 4 hours) to generate an excess of VLDL remnants that were not converted to IDL or LDL. VLDL triglyceride, apo B, and apo C concentrations fell at a similar rate. VLDL apo B declined by 42% (p less than 0.01). However, no increases were observed in IDL or LDL apo B in the Type IV subjects. This resulted in a 14% (p less than 0.01) decline in plasma apo B concentrations, indicating a clearance of VLDL remnants. VLDL apo C-II and C-III concentrations fell by 42% (p less than 0.025) and 52% (p less than 0.01), respectively. During the first 2.5 hours of infusion, they were almost quantitatively recovered in HDL. Thereafter, the C apolipoproteins declined in HDL during which time VLDL apo C concentrations continued to decline.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMedDate not supplied

Muscle protein metabolism of rats in surgical trauma.

The effects of decreased food intake and degree of surgical trauma on total, myofibrillar and sarcoplasmic muscle protein synthesis and degradation were assessed in two experiments (A and B). Trauma consisted of an abdominal incision with or without hysterectomy. The degree of trauma in experiment B was increased relative to that in experiment A by extending the length of the incision, operative manipulation and time required to perform the surgery. To account for postoperative diminutions in food intake on protein turnover, a group of nonoperated rats were pair-fed to the level of food consumed by hysterectomized rats. Traumatized rats in experiment B lost more weight, ate less, and had a lower muscle total protein concentration than corresponding rats in experiment A, confirming a more severe trauma in experiment B. In both experiments, trauma depressed total protein content of muscle. Synthesis was measured by the incorporation of L-[U-14C] tyrosine from a single meal into total, sarcoplasmic and myofibrillar proteins of gastrocnemius muscle. Degradation was calculated as the difference between the growth rate and the synthetic rate. Synthetic rate (ks) of total protein was depressed by surgical trauma; the more severe the trauma, the greater the depression. In mild trauma, the depression in ks was due only to a decrease in sarcoplasmic protein synthesis (ke), whereas with more severe trauma, synthetic rates of both sarcoplasmic (kes) and myofibrillar (kem) proteins were decreased. Protein degradation (kd,) was increased on day 2 in experiments A and B, had returned to control values on day 4 in experiment A and had decreased below control values in experiment B.(ABSTRACT TRUNCATED AT 250 WORDS)

Abdomen↗
PubMedDate not supplied

Postsurgical muscle protein turnover in perfused hindquarters of the rat.

Skeletal muscle protein synthesis and degradation were measured simultaneously in perfused hindquarters of adult female rats 0, 2, and 4 days after surgical trauma. In order to explore the role of decreased postoperative nutrient intake on muscle protein turnover, a group of rats were pair-fed to the level of food consumed by surgical traumatized animals. Protein synthesis was measured by the incorporation of 3H-L-phenylalanine into the myofibrillar (contractile) and sarcoplasmic (soluble) proteins of gastrocnemius muscle. Protein degradation rates were calculated from the release of myofibrillar 3-methyl histidine (3MH) during the perfusion. Surgical trauma significantly depressed myofibrillar and sarcoplasmic protein synthetic rates by 33 and 29%, respectively. Protein degradation, as assessed by 3MH release into perfusate, increased 25% on the second postoperative day but returned to control levels by the 4th day after surgery. Food restriction of the pair-fed control rats did not alter protein synthesis, however, protein degradation decreased significantly. In conclusion, the effect of trauma on protein turnover appears not to be due to decreased nutrient consumption.

Animals↗
PubMedDate not supplied

Microbial contamination of continuous drip feedings.

We evaluated the extent and effects of bacterial contamination of an open continuous enteral feeding system. Eighty-two quantitative enteral feeding cultures and clinical data were obtained during 8 days of observation on each of 33 patients. Cultures of appropriate sites were obtained on febrile patients and compared to the enteral feeding culture. Gram negative bacilli (GNB) in the enteral feeding correlated with abdominal distension in the patients (10 of 12 patients with GNB compared to 5 of 21 without GNB; p less than 0.01). Nine of the 10 patients with GNB and distension were receiving systemic antimicrobics to which the organism was resistant. Contamination of feeding with Serratia marcescens correlated with cultures for the same organism in patients' other body sites (p less than 0.01). The feeding contaminant may have been the source of sepsis in one patient who expired from septic shock. No relationship was demonstrated between contamination and liquid stools or fever. Undiluted, canned feedings were significantly less contaminated at 24 hr (15%) than those requiring mixing of powder (94%) (p less than 0.0001). The canned feedings grew primarily enteric organisms, whereas the powder feedings grew flora typically resident on the skin. Mixing or diluting feedings appears to represent an increased risk of contamination. Growth of GNB may produce adverse effects. Further investigation into methods to limit contamination and growth is warranted.

Adolescent↗
PubMedDate not supplied

Comparative effects of thermal and surgical trauma on rat muscle protein metabolism.

A modified intraperitoneal pool flooding technique, employing L-3H-tyrosine, was developed for measuring muscle protein synthetic rates following traumatic injury. Sufficient radiolabeled tyrosine was injected intraperitoneally to effect a six-fold increase in plasma tyrosine concentration (124-800 microM) resulting in constant, sustained specific radioactivities in plasma- and intracellular-free tyrosine pools. Localized vs systemic effects of thermal and surgical trauma on gastrocnemius muscle protein turnover were assessed 2 and 4 days postinjury. Thermal trauma increased total, myofibrillar, and sarcoplasmic muscle protein synthesis (44%) and protein degradation (300%). Conversely, surgical trauma decreased synthesis of total (24%), myofibrillar (14%), and sarcoplasmic (43%) muscle proteins without altering protein degradation. Short-term restriction of pair-fed controls did not affect either aspect of protein turnover.

Animals↗
PubMedDate not supplied

Spinal osteomyelitis after TPN catheter-induced septicemia.

Osteomyelitis of the spine is a well-recognized delayed manifestation of septicemia but has not been recognized as a complication of total parenteral nutrition. We report five cases of spinal osteomyelitis that were clinically recognized 1 to 13 months after total parenteral nutrition catheter-induced septicemia. Radiographic evidence of osteomyelitis was seen in all five patients. In three patients, culture of bony aspirates was positive for the same organism as from the blood. In one case, the diagnosis was established by histology, and in one the diagnosis was based on radiographic and radionuclide evidence of osteomyelitis. The organism responsible was Staphylococcus aureus in two cases, Candida albicans in another two cases and C tropicalis in one case. The septic episode that preceded osteomyelitis was treated with systemic antibiotics and catheter removal in four patients, and antibiotics without catheter removal in one patient. Nevertheless, osteomyelitis occurred, requiring bracing or operative debridement as well as prolonged antibiotic therapy. Spinal osteomyelitis may occur as a delayed manifestation of total parenteral nutrition catheter-induced septicemia. Prompt and effective treatment of septicemia is indicated but may not always be sufficient. Clinical suspicion is the key to the correct and early diagnosis of osteomyelitis and therefore to adequate treatment.

Adult↗
PubMedDate not supplied

Clinical practice guidelines in nutrition support: can they be based on randomized clinical trials?

As rationing of health care services becomes an increasing reality, the pressure to justify interventions such as nutrition support will intensify. The establishment of clinical practice guidelines is one means of providing practitioners with such justification, but clinical practice guidelines for nutrition support cannot be based primarily on prospective randomized trials. This situation arises as the result of limitations specific to nutrition support whereby the most malnourished patients-those who appear most likely to show a benefit from the treatment-cannot be randomized to a no feeding group and are therefore excluded from participation in the study. As the result of this limitation, marginal candidates for nutrition support have been included in some trials, potentially masking the benefits of this treatment. An additional problem limiting present interpretation of published reports of randomized trials in nutrition support is the fact that ongoing research continues to yield improvements in the clinical practice of nutrition support. Thus the nutrition support group in such trials may not have received this treatment according to current practice. The A.S.P.E.N. Guidelines, based on both randomized prospective trials and other types of evidence, represent an important contribution to the practice of nutrition support. Testing of the performance of these and other guidelines in clinical practice and further outcomes research will be important steps toward revision and improvement of nutrition support, but may be difficult to achieve in the near future.

Humans↗