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Biomedical subjects

G S Moss

Publications and source records attributed to G S Moss.

At least 37 records · Page 2Linked to original sources

Total parenteral nutrition promotes bacterial translocation from the gut.

Bacterial translocation from the gut may be the primary event in many disease processes. The purpose of this study was to examine the route of nutrient administration on bacterial translocation from the gut. Each of 90 female Fischer rats underwent placement of a central venous catheter and was randomized to one of three groups. Group I (control) received food and water ad libitum. Group II received standard TPN solution orally from a bottle sipper and drank the solution ad libitum. Group III underwent TPN via the central catheter by pair feeding of the animals with group II. Animals were fed for 2 weeks, and liver, spleen, mesenteric lymph nodes, blood, and cecum were aseptically obtained for culture. A statistically significant difference (p less than 0.014) was found between translocation rates of parenterally fed animals compared with enterally fed animals. Two thirds of the animals (18/27) fed parenterally had culture-positive mesenteric lymph nodes compared with one third (9/27) of the enterally fed group and none (0/30) of the control group. A statistically significant increase in the cecal bacterial count was demonstrated in the animals fed the TPN solution, independent of route. Parenteral nutrition promotes bacterial translocation from the gut by increasing the cecal bacterial count and impairing intestinal defense.

Animals↗

Limits of cardiac compensation in anemic baboons.

The risk of homologous blood may cause physicians to withhold red cell treatment after acute blood loss. We believe that in the euvolemic patient with acute anemia, the heart is the principal organ at risk. The cardiac compensation to extreme anemia is unknown and is the purpose of this report. Fourteen adult baboons were anesthetized, paralyzed, and ventilated with room air. Left atrial and coronary sinus catheters were inserted surgically. Experimental animals (n = 7) were hemodiluted at constant left atrial pressure with 5% human serum albumin. Control animals (n = 7) underwent similar volume exchanges with fresh, cross-matched, homologous red blood cells resuspended in human serum albumin, also at constant left atrial pressure. Six of seven experimental animals survived until hematocrit levels were 4%. Adequate cardiac compensation was observed until hematocrit levels were less than 10%. Increased flow, without increases in the O2 extraction ratio, was the mechanism of compensation used by the healthy heart with patent coronary vessels.

Adaptation, Physiological↗

Diagnostic peritoneal lavage in intra-abdominal sepsis.

Despite the advent of sophisticated diagnostic technology the diagnosis of the surgical abdomen in the Intensive Care Unit continues to pose a problem for the surgeon. A retrospective analysis was carried out to evaluate the utility of diagnostic peritoneal lavage to diagnose intra-abdominal surgical disease. Diagnostic peritoneal lavage was carried out in patients in whom the physical exam was deemed unreliable, such as in patients with cardiopulmonary instability or mental obtundation. Patients were included in the study if autopsy or laparotomy confirmation of the lavage data was available. Forty four patients met the inclusion criteria and formed the basis of this study. Of the twenty three patients with a positive lavage, three false-positive diagnostic peritoneal lavages were discovered, either at laparotomy or postmortem exam. Of the twenty one patients where diagnostic peritoneal lavage was negative, no false-negatives were discovered at autopsy or laparatomy. Therefore, this test is 100 per cent sensitive and 88 per cent specific. It is concluded that a negative diagnostic peritoneal lavage makes intra-abdominal surgical disease highly unlikely. However, a positive lavage may require further diagnostic work-up.

Abdomen↗

Recombinant human erythropoietin and autologous blood donation.

Risks of transfusion are minimized with autologous blood. However, autologous donation programs require 2 to 5 weeks to yield only 2.2 units per patient. Recombinant human erythropoietin (r-HuEPO) has been shown to increase erythropoiesis. This study evaluated the effects of r-HuEPO on an aggressive autologous donation program. Twelve adult male baboons were randomized into two groups of six. All animals were studied three times per week for 5 weeks. A unit of blood was donated when on any study day the hematocrit was greater than 30%. Animals received intravenously either 750 units/kg of r-HuEPO (n = 6) or placebo (n = 6) on each study day. Iron dextran was given intravenously to replace 150% of shed iron. The r-HuEPO group had an earlier onset of reticulocytosis (2.7 vs 5.5 days, p less than 0.01) and donated 35% more blood (13.5 vs 10.0 units, p = 0.01) than the control group. No adverse reactions to r-HuEPO were observed. The data show that an aggressive autologous donation program can yield 10 units of blood over a 5-week period. Further, r-HuEPO increases that yield by an additional 35%. This aggressive autologous donation program with r-HuEPO may significantly reduce the need for homologous transfusion and its attendant risks.

Animals↗

Oxygen extraction ratio: a valid indicator of myocardial metabolism in anemia.

We have shown that primates adequately compensate for acute normovolemic anemia to hematocrits (HCT) of 10%. We have described a whole-body extraction ratio (O2 consumption/O2 delivery; ER) of 50% as a reliable physiologic indicator of transfusion need. There is concern that whole-body ER may not accurately reflect impaired myocardial metabolism. The onset of significant lactate production by the left ventricle is an indicator of anaerobic metabolism. Our purpose is to compare left ventricular lactate metabolism (arterial-coronary sinus lactate; delta [L]) to ER in acute normovolemic anemia. Fourteen adult baboons were anesthetized, paralyzed, and ventilated on room air. Left atrial, coronary sinus, aortic, and Swan-Ganz catheters were inserted. Experimental animals (N = 7) were hemodiluted, at constant left atrial pressure (LAP), with 5% human serum albumin (HSA) to a HCT below 4%. Control animals (N = 7) underwent similar volume exchanges, also at constant LAP, with homologous RBCs resuspended in HSA. Whole-body extraction ratio and left ventricular lactate production were measured at baseline and at hematocrits of 20, 10, 6, and 4% in the experimental group. Data were obtained at similar volume exchange points in the control group. Significant lactate production occurred only in the experimental animals (P less than 0.05) when extraction ratio exceeded 50%. Significant lactate production does not occur before the whole-body ER exceeds 50%. ER appears to be a valid indicator of myocardial metabolism in anemia, in this setting.

Anemia↗

Fluosol-DA as a red-cell substitute in acute anemia.

We assessed the safety and efficacy of Fluosol-DA as a red-cell substitute in acute anemia. Twenty-three surgical patients with blood loss and religious objections to receiving blood transfusions were evaluated. Fifteen moderately anemic patients with a mean hemoglobin level (+/- SE) of 7.2 +/- 0.5 g per deciliter had no evidence of a physiologic need for increased arterial oxygen content and did not receive Fluosol-DA. Eight severely anemic patients with a mean hemoglobin level of 3.0 +/- 0.4 g per deciliter met the criteria of need and received the drug until the physiologic need disappeared or a maximal dose of 40 ml per kilogram of body weight was reached. We observed no adverse reactions to Fluosol-DA. The average peak increment in arterial oxygen content with the drug was only 0.7 +/- 0.1 ml per deciliter. There were no appreciable beneficial effects of Fluosol-DA, perhaps because of the small increase in arterial oxygen content, the brief half-life of the drug (24.3 +/- 4.3 hours), and the limited total dose. Six of the eight patients receiving Fluosol-DA died. One of the survivors received red-cell transfusions against his wishes, under a court order, after his total Fluosol-DA dose. Fourteen of the 15 moderately anemic patients survived. The data in this select group of patients refusing blood products suggest that, after blood loss, Fluosol-DA is unnecessary in moderate anemia and ineffective in severe anemia.

Acute Disease↗

The development of polymerized pyridoxylated hemoglobin solution as a red cell substitute.

Development continues for a safe and effective hemoglobin solution to be used as a temporary red cell substitute. Our own efforts have progressed from the unmodified tetramer, to the pyridoxylated tetramer, to our current product--polymerized, pyridoxylated hemoglobin (Poly SFH-P). We recently completed two studies to evaluate the efficacy of Poly SFH-P. The results document that Poly SFH-P supports life in the absence of red cells while maintaining baseline hemodynamics and O2 consumption. In addition, Poly SFH-P achieves a near-normal plasma [Hb], and has a longer intravascular persistence than any unpolymerized product. Poly SFH-P thus is an improved red cell substitute for use in the clinical setting.

Anemia↗

Methodology to assess the oxygen concentration of red cells and stroma-free hemoglobin solutions.

Stroma-free hemoglobin (SFH) solution is an acellular oxygen carrier under development as a temporary red blood cell (rbc) substitute. SFH will be of value if it contributes to oxygen loading (delivery) and unloading (consumption). If there is no interaction between red cell hemoglobin and SFH, then the composite oxygen dissociation curve for whole blood (WB) can be written as: SWB = rSSFH + (1 - r) Srbc, where S is the fractional saturation, and r is the SFH/WB hemoglobin ratio. This composite whole-blood curve was compared with the calculated curve, and the root mean square difference was 0.9%. Direct and indirect methods of measuring oxygen concentration ([O2]) of whole blood or plasma were compared. The regression line was [O2]indirect = 0.995 [O2]direct + 0.07 (r = 0.995, N = 16, p less than .01). The adequacy of anaerobic separation of plasma was evaluated by measuring the changes in PO2 and PCO2. The PO2 increased by less than 2 torr and the PCO2 decreased by less than 1 torr during in vitro tests. Both the direct and indirect methodology yielded consistent [O2] values for each carrier.

Blood Substitutes↗

Polymerized pyridoxylated hemoglobin: efficacy as an O2 carrier.

We have prepared a polymerized pyridoxylated hemoglobin solution (Poly SFH-P) with a normal [Hb] of 14 gm/dl and a normal COP of 20 torr. Although this normal [Hb] is a significant improvement over prior products, the P50 of 16-20 torr raises a concern about the ability of Poly SFH-P to effectively transport O2 in the presence of red cells with their normal P50 of 26 torr. This study quantitatively assessed the contribution of Poly SFH-P to total O2 delivery and consumption in the clinically relevant range of hematocrits. The results document that Poly SFH-P supports life at zero hematocrit, and makes significant contributions to total O2 delivery and consumption in the presence of red cells. Poly SFH-P permits a higher plasma [Hb], and has a longer intravascular persistence than any unpolymerized hemoglobin solution. Poly SFH-P is thus an effective O2 carrier, and offers greater potential than prior products as a clinically useful red cell substitute.

Animals↗

Effect of positive-end expiratory pressure on accuracy of thermal-dye measurements of lung water.

The thermal-dye indicator dilution technique of measuring extravascular lung water (EVLW-TD) correlates well with gravimetric measurement of lung water (EVLW-GR) when no positive-end expiratory pressure (PEEP) is used in both normal and edematous lungs. PEEP is often used to raise arterial oxygen tension in acute respiratory failure. This study was designed to answer the question: Does PEEP have an effect on the accuracy of the EVLW measurement by thermal dye? Sixteen mongrel dogs were anesthetized and intubated. Arterial and PA catheters were placed. They were divided into three groups and ventilated at PEEP levels of 5, 10, or 15 cm H2O. Fluids were given to minimize decrease in cardiac output with institution of PEEP. They were maintained for 5 hr with measurement of vital signs made hourly and measurement of blood gases and EVLW-TD made at baseline, 1, 3, and 5 hr. After final measurements, gravimetric determination of EVLW was done. Correlation between EVLWTD and EVLWGR remained good when low levels of PEEP were used. At 5 cm H2O PEEP, EVLWTD was 7.5 +/- 0.9 and EVLWGR was 5.4 +/- .3. At 10 cm H2O PEEP, they were 10.0 +/- 0.9 and 6.5 +/- 0.3. The correlations were 0.87 and 0.97, respectively. However, at 15 cm H2O PEEP, EVLWTD was 11.4 +/- 1.3 and EVLWGR was 7.5 +/- 0.6, with a correlation of only 0.59. The correlation between the two techniques seems to break down with higher levels of PEEP in dogs with normal lungs.

Animals↗

Red cell substitutes: an update.

The two acellular oxygen carriers currently being evaluated as red cell substitutes are hemoglobin solutions and fluorocarbon emulsions. We have shown that both products can maintain normal levels of oxygen consumption, CO2 production, and circulatory dynamics in primates in the virtual absence of the red blood cell. Although each solution thus satisfies the most important criteria for a red cell substitute, development continues with both products. The clinical trials with the fluorocarbons have been discontinued due to the lack of efficacy of Fluosol-DA--20% in the setting of acute blood loss. Our current hemoglobin preparation is a polymerized, pyridoxylated product that has a normal oxygen-carrying capacity. Clinical testing must await further evaluation of the safety and efficacy of this product. Alternative uses for both of these oxygen carriers continue to be explored, and may eventually be the area of their greatest utility in the clinical setting.

Animals↗

The role of C5 in septic lung injury.

One proposed mechanism for the pathogenesis of lung injury in septic animals is the stimulation by C5a of granulocytes to produce and release toxic oxygen radicals that damage cellular membranes in pulmonary capillaries. The authors have investigated the possible role of C5 in septic lung injury, utilizing C5-sufficient and C5-deficient twin mice strains. In this lethal sepsis model, mean survival time is increased in C5-deficient mice in comparison to the survival of their C5-sufficient twins. Morphometric results demonstrate a significant increase in intracapillary granulocrit and air-blood barrier thickness 24 hours after cecal ligation and puncture in C5-sufficient septic mice. Similarly, mean arterial pO2 is significantly decreased in the C5-sufficient animals. Intracapillary granulocrit, air-blood barrier thickness, and arterial pO2 are normal in the septic C5-deficient twins of these animals. These data support the hypothesis that C5 is involved in the pathogenesis of septic lung injury.

Animals↗

Effect of Intralipid on measurements of total hemoglobin and oxyhemoglobin in whole blood.

A co-oximeter study of whole blood samples containing Intralipid concentrations of 100 to 2000 mg/dl found that the light-scattering effect was greater at lower hematocrits. The methemoglobin reading was affected the most, and led to erroneous displays of total hemoglobin and percent oxyhemoglobin. The O2-content value, however, was accurate over the entire hematocrit and Intralipid concentration range tested. We suggest that an unexplained high methemoglobin value in whole blood samples from patients receiving Intralipid may reflect a light-scattering problem in the instrument.

Blood↗

Penetrating duodenal trauma.

Ten cases of penetrating injuries to the duodenum are presented. Six injuries were treated with primary repair, retrograde decompressing jejunostomy, and feeding jejunostomy. There was no postoperative duodenal leak in any patient treated with primary repair and retrograde decompressing jejunostomy. In a review of 563 cases of penetrating duodenal trauma, the superiority of primary repair of duodenal injuries with decompression of the suture line by a tube inserted in a remote site of the bowel (stomach or jejunum) was demonstrated. This technique afforded the lowest mortality and incidence of postoperative duodenal fistulae. When applicable, primary repair with retrograde decompressing jejunostomy and feeding jejunostomy is a rapid, simple, and safe method for the treatment of penetrating duodenal injuries.

Adolescent↗