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F D Moore

Publications and source records attributed to F D Moore.

At least 19 recordsLinked to original sources

Soluble complement receptor type 1 ameliorates the local and remote organ injury after intestinal ischemia-reperfusion in the rat.

We examined the role of C activation in ischemia reperfusion injury by inhibiting C activation in a rat model of mesenteric arterial occlusion. In anesthetized rats, 60 min of mesenteric arterial occlusion was followed by 3 h of reperfusion. PBS alone or containing soluble C receptor 1 (3 or 6 mg) was administered i.v. Controls underwent laparotomy without ischemia. Relative serum C activities were assessed by hemolytic assay, neutrophil (polymorphonuclear leukocyte) sequestration by tissue content of myeloperoxidase (MPO) activity, intestinal mucosal injury by histologic grading, lung vascular permeability by the ratio of bronchoalveolar lavage to blood concentration of radiolabeled BSA, and endothelial cell injury was quantified by measurement of plasma factor VIII-related Ag. After reperfusion, PBS-treated animals had increased intestinal MPO (0.048 +/- 0.007 U/g) compared to sham (0.022 +/- 0.005 U/g (p less than 0.05)) and intestinal mucosal injury score (2.490 +/- 0.221) compared to sham (0.331 +/- 0.045 (p less than 0.05)). Treatment with 6 mg soluble C receptor 1 15 min before reperfusion reduced intestinal MPO (0.017 +/- 0.003 U/g (p less than 0.05)) and mucosal injury (1.733 +/- 0.168 (p less than 0.05)) compared to PBS control. PBS-treated animals also demonstrated increased lung MPO (0.314 +/- 0.025 U/g vs 0.085 +/- 0.018 in sham (p less than 0.05)) and increased lung permeability (bronchoalveolar lavage/blood cpm 11.32 +/- 1.35 x 10(-3) vs sham 2.22 +/- 0.19 x 10(-3) (p less than 0.05)). Treatment with 6 mg soluble C receptor 1 15 min before reperfusion or at reperfusion reduced the lung permeability (bronchoalveolar lavage/blood cpm 3.90 +/- 0.79 x 10(-3) and 5.08 +/- 0.75, respectively (both p less than 0.05)) compared to PBS control, but did not reduce lung MPO (0.342 +/- 0.031 U/g and 0.246 +/- 0.025), respectively. Treatment with sCR1 also reduced the release of factor VIII-related Ag, 5-day mortality, and C hemolytic activity. In this model, C is a major mediator of intestinal injury and extraintestinal injury.

Animals

Blockade of complement activation prevents local and pulmonary albumin leak after lower torso ischemia-reperfusion.

Lower torso ischemia and reperfusion leads to both local and remote tissue injuries. The purpose of this study was to assess the role of complement in mediating the local and remote microvascular permeability after bilateral hind limb tourniquet ischemia. Four hours of ischemia and 4 hours of reperfusion produced an increased skeletal muscle permeability index (muscle/blood 125I albumin ratio) of 2.90 +/- 0.35 compared with the index in nonischemic muscle of 0.25 +/- 0.02 (p < 0.01). Muscle wet-to-dry-weight ratio increased from 3.93 +/- 0.04 in sham to 5.55 +/- 0.09 in ischemic muscle (p < 0.0001). Lung permeability rose at 4 hours as indicated by the increased bronchoalveolar lavage (BAL)/blood 125I albumin ratio 4.36 +/- 0.41 x 10(-3) versus sham 2.64 +/- 0.28 x 10(-3) (p < 0.05) and neutrophil sequestration 0.28 +/- 0.02 U/g myeloperoxidase (MPO) versus sham 0.14 +/- 0.02 U/g (p < 0.001). Serum lytic activity of the classical but not the alternate complement pathway was reduced. The soluble complement receptor (sCR1) was used to inhibit complement activity and attenuated the increase in the permeability index after reperfusion in ischemic muscle 1.11 +/- 0.08 (p < 0.01) and reduced the lung BAL/blood 125I albumin ratio to sham levels 2.46 +/- 0.39 x 10(-3) (p < 0.05) at 6 mg/animal, without reducing the lung neutrophil sequestration, 0.24 +/- 0.02 U/g. The authors conclude that complement activation occurred during tourniquet ischemia and mediated permeability changes in the ischemic muscle and the lungs during reperfusion.

Albumins

Glucose promotes whole-body protein synthesis from infused aminoacids in fasting man. Isotopic demonstration.

15N-glycine constant infusion, with plateau urea enrichment as the endpoint, demonstrated a clear increase in whole-body protein synthesis when glucose was added to aminoacid infusion in fasting men. Whole-body protein-breakdown rates remained unchanged. There was an unexpected fall in whole-body nitrogen turnover when the subjects were changed from an oral intake to either of the intravenous programmes: this finding, not previously reported, may be due to the decrease in gastrointestinal enzyme synthesis and intestinal-lining cell-turnover when oral intake is replaced by total parenteral nutrition.

Administration, Oral

The effects of glucagon on protein metabolism in normal man.

Plasma glucagon rises after major injury and could act to increase gluconeogenesis and ureagenesis in the post-traumatic state. This study documents the effect of prolonged glucagon infusion on ureagenesis and nitrogen excretion, as well as possible sources of the increased ureagenesis, in normal man. Four healthy men fasted for 6 days during intravenous infusion of glucose (750 gmday), establishing a steady state of minimal ureagenesis. Glucagon (1 mg/day) then was added to the infusion for 5 days. Glucose alone was given for the final 2 days. Forearm muscle flux of metabolites was determined by standard arterial-deep venous sampling and capacitance plethysmography. Glucagon concentration was suppressed during glucose infusion (11 +/- 13 pg/ml) and rose to levels seen in subjects with major trauma during glucagon infusion (669 +/- 138 pg/ml). Glucose infusion stabilized urine nitrogen excretion at 1.54 +/- 0.42 gm of N/sq m/day. Nitrogen excretion increased to 2.40 +/- 0.53 gm of N/sq m/day with glucagon infusion, with urea accounting for the increased excretion. Excretion of 3-methylhistidine was unchanged. Plasma amino acid concentration was strikingly reduced on the first day of glucagon infusion, where it stabilized. Forearm flux showed a slight net release of amino acid nitrogen during glucose infusion. Addition of glucagon to the glucose infusion resulted in a net uptake of nitrogen by forearm skeletal muscle. These evidences strong suggest that glucagon infusion in normal man increases ureagenesis, not only at the expense of the free amino acid pool, but by the hydrolysis of visceral protein as well, with muscle protein being maintained.

Amino Acids

CAGS lecture. Scientific salients in surgery.

Surgery, as a field of clinical skill and scientific knowledge, advances by Discovery, Development and Delivery. While the basic biosciences have been more productive in Discovery than have the clinical fields, surgery has participated in several important areas of Discovery. Developmental science is often called biomedical engineering. In this activity, surgery has been pre-eminent, while it is the study and perfection of Delivery that holds such promise for the future of surgery. Distribution and regionalization of operations, bidirectional referral flow, manpower norms and analysis of adverse outcomes are important horizons for study in surgical care delivery.

Canada

The cost of misadventures in colonic surgery. A model for the analysis of adverse outcomes in standard procedures.

Analysis revealed an impressive number of patients transferred to intensive care at the Peter Bent Brigham Hospital after misadventures in standard medical and surgical procedures. The model explored here is that of colon surgery, a therapy standardized for decades. The courses of sixteen patients were studied, wherein adverse outcomes appeared to have been preventable. Failure to diagnose colonic leakage and failure to provide colostomy (or to do so safely) were the major underlying causes. Nephrotoxic antibiotics and immunosuppression were sometimes in the background. Nine patients died, all with severe sepsis. Multiple organ failure occurred in the majority of cases. The mortality was tenfold, the cost sevenfold, and the length of hospitalization fourfold that expected after uneventful operation. Current interest in cost-benefit analysis should be broadened standard medical and surgical procedures. Litigious potential should not be allowed to impede such analyses.

Adolescent

Endocarditis with the indwelling balloon-tipped pulmonary artery catheter in burn patients.

The postmortem finding of acute right-sided bacterial endocarditis in a burn patient monitored with an indwelling pulmonary artery (Swan-Ganz) catheter for 14 days prompted a review of burn autopsies in which the catheter had been used. Autopsies of six consecutive burn patients monitored with a pulmonary artery catheter and who then died showed septic or aseptic endocarditis. In two of the six patients, right-sided staphylococcal endocarditis was the anatomic cause of death. In the remaining four, the lesions were aseptic thrombotic vegetations involving primarily the right atrium, tricuspid valve, right ventricle, and pulmonic valve. Several factors in the severely burned patient would favor endocarditis where a foreign object impacts on the heart valves. These include intermittent bacteremia, hypercoagulability, hyperdynamic cardiovascular function, and the use of antibiotics resulting in resistant strains. While an indwelling pulmonary artery catheter can provide useful monitoring information, it is sometimes responsible for serious complications in burned or septic patients.

Adult

An aggressive multimodality approach to locally advanced carcinoma of the breast.

In a series of patients who were not candidates for mastectomy because of locally advanced disease or distant metastases, or both, excellent local control was obtained by radiation therapy and systemic therapy in the form of oophorectomy-adrenalectomy and chemotherapy. Local control was obtained in 12 of 15 patients with metastatic disease by systemic therapy without radiation. The median disease-free survival time for patients with advanced Stage III carcinoma of the breast was significantly prolonged from 9.5 to 15 months by oophorectomy-adrenalectomy with chemotherapy, although there was no definable difference in the over-all survival period for the two groups.

Adrenalectomy