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Biomedical subjects

C M Martin

Publications and source records attributed to C M Martin.

At least 55 records · Page 3Linked to original sources

Decreased capillary density in vivo in bowel mucosa of rats with normotensive sepsis.

Translocation of bacteria and endotoxin leading to sepsis occurs in animals subjected to burns or intestinal ischemia. This may be mediated in part by bowel mucosal microcirculatory dysfunction. However, the direct effect of sepsis on the mucosal microcirculation is unknown. The objective of this study was to develop a technique for intravital microscopy of the mucosa of the small bowel in an animal model of normotensive sepsis. We tested the hypothesis that normotensive sepsis induced by cecal ligation and perforation leads to a decrease in perfused capillaries in the small bowel mucosa at 24 hr. Twelve male Sprague-Dawley rats were hemodynamically monitored and randomly assigned to cecal ligation and perforation (CLP) or control laparotomy (sham). Twenty-four hours after initial surgery each animal was reanesthetized and the mucosal surface of the distal small bowel prepared for intravital microscopy. Laser doppler measurements of bowel wall blood flow were made immediately and repeated after a 30-min stabilization period. Intravital microscopy of the mucosal microcirculation of six villi per animal was performed and the images recorded on videotape (2 min/villus). The areas surrounded by perfused capillaries (intercapillary area) were then measured using video analysis software. Laser doppler flowmetry revealed a decrease in bowel wall blood flow during the stabilization period in the shams that did not occur in the CLP rats. The intercapillary areas were significantly greater in the CLP rats compared to sham rats (1329 +/- 316 microns2 vs 979 +/- 217 microns2, P = 0.044). The intercapillary areas were also more highly variable in the CLP group (median coefficient of variation 102 vs 83% in the sham group, P = 0.025). Intravital microscopy may be used to examine microcirculatory function of the small bowel mucosa. Sepsis induced by CLP leads to a decrease in the number of perfused capillaries in the small bowel mucosa.

Animals↗

Intestinal mucosal permeability to 51Cr-ethylenediaminetetraacetic acid is increased after bilateral lower extremity ischemia-reperfusion in the rat.

BACKGROUND: Despite successful revascularization of ischemic extremities, multiorgan dysfunction syndrome develops in some patients. Mechanisms responsible for this are not known; however, the gastrointestinal tract has been implicated as a possible mediator. Our objective was to demonstrate increased intestinal mucosal permeability after bilateral hindlimb ischemia-reperfusion (I-R) in a rodent model. METHODS: Sixteen male Wistar rats were randomized either to 4 hours of bilateral hindlimb tourniquet ischemia and 24 hours of reperfusion (n = 8) or control groups (n = 8). The animals received 10 MuCi 51Cr-ethylenediaminetetraacetic acid (EDTA) by gavage, and excretion was measured in urine collected every 8 hours in 16 animals and every 4 hours in 8 animals. Arterial blood pressure was monitored continuously. Intravenous normal saline solution (3 ml/hr) with fentanyl (2 microgram/100 gm/hr) was continuously administered. Immediately before death complete blood count and levels of arterial lactate, creatinine, and urea were obtained. Mesenteric lymph nodes were harvested from the ileocecal region and cultured. Distal small bowel and proximal colon were preserved for histologic analysis. An additional 11 rats, six experimental and five control, were evaluated for mesenteric lymph node cultures only. RESULTS: Urinary excretion of 51Cr-EDTA was significantly greater in the I-R group between 0 and 8 hours (p < 0.02) and 8 to 16 hours (p < 0.0002) of reperfusion. This increase occurred as early as 4 to 8 hours of reperfusion (p < 0.0001). Urine volume in the I-R group was significantly reduced during 0 to 4 hours of reperfusion (p < 0.002). Hemoglobin and lactate level were significantly different in the I-R group. Leukocyte and platelet counts, levels of creatinine and urea, and colony counts from mesenteric lymph nodes were similar in I-R and control groups. Blinded histologic analysis of bowel segments did not reveal morphologic differences. CONCLUSIONS: Bilateral hindlimb I-R produces remote intestinal mucosal injury shown by significantly increased permeability to 51Cr-EDTA. Such increased mucosal permeability may be important in the development of multiorgan dysfunction syndrome in patients who sustain lower extremity I-R injury.

Animals↗

Local cholinergic mechanisms mediate nitric oxide-dependent flow-induced vasorelaxation in vitro.

To determine whether local cholinergic mechanisms evoke nitric oxide (NO)-mediated flow-induced vasorelaxation, canine coronary artery rings without endothelium were suspended beneath an organ chamber that contained a stainless steel tube and a femoral artery segment with endothelium. The rings were superfused at a basal rate of 1 ml/min with physiological salt solution that was bubbled with 95% O2-5% CO2 and maintained at 37 degrees C. They were stretched to optimal length and contracted with prostaglandin F 2 alpha (2 x 10(-6) M). When flow through the stainless steel tube (direct superfusion) was increased from the basal rate of 1 to 4 ml/min, coronary force did not change. Superfusion of the rings (n = 8) with effluent from the femoral segment (endothelial superfusion) at 4 ml/min to study flow-induced vasodilation caused a 67.3 +/- 10.8% relaxation. Treatment of the segment with the NO synthase blocker NG-monomethyl-L-arginine (10(-4) M) eliminated the relaxation seen during endothelial superfusion (P < 0.05 vs. control). Application of atropine (10(-6) M) to additional femoral segments (n = 8) abolished the coronary relaxation observed during endothelial superfusion at 1 ml/ min, and the flow-induced relaxation observed at 4 ml/min was reduced from 64 +/- 8.3 to 27 +/- 5.6% (P < 0.05 vs. control). In studies on additional segments and rings (n = 6), the flow-induced relaxations at 4 ml/min of endothelial superfusion were blunted from 86 +/- 10 to 28 +/- 13% after the segments were treated with acetylcholinesterase (0.00028 U/min for 20 min). These data indicate that basal- and flow-induced release of NO from the vascular endothelium can be mediated by local cholinergic mechanisms. It is possible that flow causes acetylcholine release from certain endothelial cells, which stimulates NO release from these cells or from neighboring endothelial cells.

Acetylcholine↗

Sepsis depresses the metabolic oxygen reserve of the coronary circulation in mature sheep.

This study was undertaken to describe the metabolic O2 reserve of the coronary circulation in an awake sheep model of hyperdynamic sepsis. Forty-eight hours after sheep were randomized to either a SHAM group (n = 8) or a cecal ligation and perforation (CLP) group (n = 8), we measured hemodynamics, organ blood flows, and systemic and myocardial O2 metabolism variables at baseline and through four stages of progressive hypoxia. A significant elevation in arterial lactate levels occurred at a higher O2 delivery in the CLP group (527 +/- 55 ml/min/m2) than in the SHAM group (357 +/- 29 ml/min/m2, p < 0.05). The heart's metabolic O2 reserve (difference in circulatory determinants of O2 availability between baseline and where O2 uptake could not be sustained) was exhausted at an O2 content of 56.9 +/- 4.2 ml O2/L in SHAM sheep and 79.6 +/- 7.2 ml O2/L (p < 0.05) in CLP sheep. An increase in coronary blood flow was three times greater in SHAM than in CLP animals. Myocardial O2 extraction increased in hypoxia in SHAM sheep (0.78 +/- 0.03 to 0.88 +/- 0.02, p < 0.05), but not in CLP sheep (0.79 +/- 0.02 to 0.80 +/- 0.04). We conclude that the metabolic O2 reserve of the coronary circulation is depressed in this model of hyperdynamic sepsis as the ability to increase both coronary blood flows and myocardial O2 extraction was significantly limited.

Animals↗

Pentoxifylline does not prevent microvascular injury in normotensive, septic rats.

OBJECTIVE: To determine if treatment with pentoxifylline would decrease the tissue injury that occurs in a normotensive model of sepsis. DESIGN: Random assignment to control, cecal ligation-perforation, or cecal ligation-perforation plus pentoxifylline groups for a 24-hr study. SETTING: Animal laboratory. SUBJECTS: Male Sprague-Dawley rats. INTERVENTIONS: Sepsis was induced by cecal ligation-perforation with aggressive fluid resuscitation (normal saline 10 mL/kg/hr). Pentoxifylline was administered as a 2-mg/kg bolus, followed by a continuous infusion of 6 mg/kg/hr. MEASUREMENTS AND MAIN RESULTS: Compared with controls, rats in the cecal ligation-perforation group had an increased heart rate (432 +/- 12 vs. 399 +/- 10 beats/min) and respiratory rate (129 +/- 6 vs. 94 +/- 7 breaths/min). Blood pressure was slightly decreased (104 +/- 4 vs. 125 +/- 5 mm Hg), while cardiac index was not significantly different (50.1 +/- 5.7 vs. 40.7 +/- 3.9 mL/min/100 g). Blood pressure (103 +/- 4 mm Hg) was the only parameter that was significantly different in the cecal ligation-perforation plus pentoxifylline group compared with controls. When compared with controls, tissue wet/dry weight ratios were increased in the diaphragm of the cecal ligation-perforation group and in the liver, pancreas, small bowel, and large bowel of the cecal ligation-perforation, and the cecal ligation-perforation plus pentoxifylline groups. Tissue/plasma albumin ratios were increased in the diaphragm of the cecal ligation-perforation group and in the liver, pancreas, and large bowel of the cecal ligation-perforation and the cecal ligation-perforation plus pentoxifylline groups. There were no significant differences between the cecal ligation-perforation and the cecal ligation-perforation plus pentoxifylline groups. CONCLUSIONS: Normotensive sepsis is accompanied by increased vascular permeability in the diaphragm and intra-abdominal organs. Pentoxifylline appears to attenuate some of the systemic manifestations of sepsis. However, pentoxifylline did not prevent the development of protein-rich tissue edema.

Animals↗

Modulation of hemodynamics and organ blood flow by nitric oxide synthase inhibition is not altered in normotensive, septic rats.

Hyperdynamic sepsis is associated with a redistribution of organ blood flow. We hypothesized that increased nitric oxide (NO) production could mediate this process. The objective of this study was to determine the effect of a NO synthesis inhibitor on systemic and organ blood flows in vivo in septic and in normal rats. Rats were instrumented for hemodynamic monitoring and randomized to undergo cecal ligation and perforation (CLP) or control laparotomy. Cardiac output and organ blood flow were measured by thermodilution and radioactive microspheres, respectively. Baseline values were obtained at 24 h after CLP or control laparotomy and after the administration of L-nitro-arginine methyl ester (L-NAME) at 2, 4, 8, and 16 mg/kg intravenously. All studies were performed in awake, unrestrained animals. Septic animals were normotensive and hyperdynamic. L-NAME decreased cardiac index and increased systemic vascular resistance and mean arterial blood pressure to an equivalent degree in control and in CLP animals. CLP was associated with significantly increased relative blood flow to the small bowel and portal circulation. Although cardiac output decreased with L-NAME, blood flow to the diaphragm, liver, and brain was relatively well preserved. Absolute blood flow to other organs, including small bowel, decreased in parallel to the cardiac output. The effect of L-NAME on organ blood flow was comparable in control and in CLP animals. We conclude that the influence of NO on organ blood flows appears to vary between organs, but that NO does not explain the redistribution of blood flow observed in hyperdynamic sepsis.

Amino Acid Oxidoreductases↗

Differential impairment of vascular reactivity of small pulmonary and systemic arteries in hyperdynamic sepsis.

We postulated that the redistribution of organ blood flow that occurs in hyperdynamic sepsis is secondary to organ-specific alterations in vascular reactivity. Chronically instrumented rats were randomized to cecal ligation and perforation (CLP) (n = 12) or to a control procedure (n = 11). Cardiac output increased from 107 +/- 23 ml/min at baseline to 152 +/- 32 ml/min at 24 h after CLP (p = 0.037 versus control values). Mean blood pressure did not change in either group. Small arterial ring segment (100- to 200-microns effective lumen radius) from the pulmonary, renal, celiac, and femora arteries were obtained for determination of in vitro responsiveness. Maximal contractile responses to three receptor-operated contractile agonists were significantly depressed in the pulmonary (p = 0.001) and the celiac (p = 0.001) arteries from CLP versus control rats. The renal artery showed a trend toward decreased responsiveness (p = 0.049), but not difference was seen in the femoral artery (p = 0.172). EC50 values were unchanged. A similar, but less marked, pattern was observed for KCI-induced contractions in that depressed responses were noted in the pulmonary (p = 0.045) and celiac (p = 0.064) arteries. Vasodilator responses to acetylcholine were normal in all vessels. Nitroprusside relaxant responses were enhanced in the pulmonary artery (p = 0.022), but they were normal in the other vessels. We conclude that hyperdynamic, normotensive sepsis is associated with an organ-specific alteration of vascular smooth muscle function that particularly affects receptor-operated contractile responses. The differential expression of this altered vascular responsiveness between organs may contribute to the observed variance in regional blood flows in sepsis.

Animals↗

Does implementing pulse oximetry in a critical care unit result in substantial arterial blood gas savings?

OBJECTIVES: To examine the impact of pulse oximetry on the use of arterial blood gas and other laboratory determinations and to examine predictors of the use of arterial blood gas measurements. DESIGN: Before (preoximetry)/after (postoximetry) study. SETTING: Thirty-bed multidisciplinary critical care unit. PATIENTS: Consecutive admissions of 300 patients (150 before and 150 after oximetry). MEASUREMENTS: For each patient examined, the number of arterial blood gas determinations, serum electrolyte levels, complete blood chemistries, arterial lactate levels, and creatinine samples were recorded for the initial 9 days of the stay in the critical care unit. These data were stratified by nursing shift (day vs night) and by the source of the admission (medical vs surgical). Other information collected included demographic variables, the severity of illness, the length of stay in the critical care unit, and various ventilatory parameters. RESULTS: Introducing pulse oximetry was associated with a marginal (10.3 percent; p < 0.025) reduction in the use of arterial blood gas determinations. This decrease was accounted for by changes occurring on the night shift and in the surgical patient. These findings were also observed for serum electrolyte determinations. No significant differences in the use of arterial blood gas measurements were found for medical patients. No significant differences were found in the use of arterial lactate levels, complete blood chemistries, or creatinine determinations. Significant predictors of arterial blood gas determinations included the number of days intubated, the number of ventilator orders, the number of days on an inspired oxygen content (FIO2) greater than 50 percent, and the acute physiology and chronic health evaluation II (APACHE II) score. CONCLUSIONS: The implementation of pulse oximetry in this manner gives an idea how effective the technology will be in reducing the use of arterial blood gas determinations without guidelines for the use of pulse oximetry. As only a marginal decrease was observed in the total population of medical and surgical patients, and only on the night shift, formal and standardized guidelines for the most efficient use of pulse oximetry should be considered. If these were considered, pulse oximetry may indeed make a significant contribution to improving the efficiency of care services.

Blood Chemical Analysis↗

Modeling mortality in the intensive care unit: comparing the performance of a back-propagation, associative-learning neural network with multivariate logistic regression.

The objective of this study was to compare and contrast two techniques of modeling mortality in a 30 bed multi-disciplinary ICU; neural networks and logistic regression. Fifteen physiological variables were recorded on day 3 for 422 consecutive patients whose duration of stay was over 72 hours. Two separate models were built using each technique. First, logistic and neural network models were constructed on the complete 422 patient dataset and discrimination was compared. Second, the database was randomly divided into a 284 patient developmental dataset and a 138 patient validation dataset. The developmental dataset was used to construct logistic and neural net models and the predictive power of these models was verified on the validation dataset. On the complete dataset, the neural network clearly outperformed the logistic model (sensitivity and specificity of 1 and .997 vs. .525 and .966, area under ROC curve .9993 vs. .9259), while both performed equally well on the validation dataset (area under ROC of .82). The excellent performance of the neural net on the complete dataset reveals that the problem is classifiable. Since our dataset only contained 40 mortality events, it is highly likely that the validation dataset was not representative of the developmental dataset, which led to a decreased predictive performance by both the neural net and the logistic regression models. Theoretically, given an extensive dataset, the neural network should be able to perform mortality prediction with a sensitivity and a specificity approaching 95%. Clinically, this would be an extremely important achievement.(ABSTRACT TRUNCATED AT 250 WORDS)

Hospital Mortality↗

Pregnancy in a woman with a uterine septum. A case report.

A term pregnancy occurred in the presence of a significant uterine septum. The changes in the anatomic appearance of the septum were documented sonographically throughout the gestation. A complete workup for other causes of pregnancy loss and attention to obstetric detail are central to the management of such patients.

Abortion, Spontaneous↗

Rh isoimmunization complicating a triplet gestation. A case report.

A case occurred of Rh isoimmunization complicating a triplet gestation. Management of that extremely rare situation required careful attention to the problems inherent in both multiple pregnancy and isoimmunization. Amniocentesis and frequent antepartum fetal monitoring were the cornerstones of therapy.

Adult↗

Transabdominal and transvaginal ultrasonography in the diagnosis of ectopic pregnancy: a comparative study.

Thirty-four patients believed to have ectopic pregnancies were examined by transabdominal and transvaginal ultrasonography. Twenty-five patients had tubal pregnancy confirmed operatively within 24 hours after ultrasonographic examination. In these cases adnexal findings highly suspicious for ectopic pregnancy were found in 68% of cases by transabdominal ultrasonography and in 84% by transvaginal ultrasonography. A distinct adnexal gestational sac was apparent in 32% of cases by transabdominal ultrasonography and in 64% of cases by transvaginal ultrasonography. Transvaginal ultrasonography was significantly more accurate (p less than 0.01) in identifying an adnexal gestational sac and allows more detailed adnexal imaging.

Abdomen↗

The importance of listening to medical students' experiences when teaching them medical ethics.

This paper describes the change of emphasis that occurred in the teaching of ethics to small groups of clinical students. Although the original focus of the course was on the analysis of ethical dilemmas associated with individual patients known to the students, it soon became evident that there were, for the students themselves, more fundamental ethical dilemmas in their new role as clinical students. These included worries about how to respond when patients asked questions which their consultants had previously deceived them about, worries about inflicting pain on patients, as with intravenous cannulation, and the role of the medical student in the clinical team. We emphasise the need to explore student experiences as part of the process of ethics teaching.

Ethics, Medical↗

Differential diagnosis of first trimester ventral wall defect.

Documentation of early fetal developmental events has become possible with the use of high-resolution sonography. We report two cases of first trimester physiologic bowel herniation and contrast them with a first trimester diagnosis of omphalocele. The normal development of the fetal abdominal wall and the mechanisms proposed for pathogenesis of omphalocele are reviewed. The sonographic differentiation between physiologic herniation and pathologic ventral wall defects may be very subtle, making definitive first trimester diagnosis difficult.

Abdominal Muscles↗

Mesenteric cysts in pregnancy. A case report.

Mesenteric cysts are rare. These large, often asymptomatic growths may be misinterpreted easily by the clinician as representing either benign or malignant ovarian tumors, renal masses, or hepatic tumors or cysts. We treated a women for a mesenteric cyst complicating her second pregnancy. Because of the increasing use of ultrasound in a wide variety of pregnancy complications, and because of the mesenteric cysts's unique sonographic appearance (resembling that of a benign ovarian tumor), such a cyst must be included in the differential diagnosis of large, cystic abdominal masses in pregnancy.

Adult↗

Hyperviscosity syndrome in a patient with acquired immunodeficiency syndrome.

The hyperviscosity syndrome is most commonly seen in association with monoclonal gammopathies and has only rarely been described in association with polyclonal hypergammaglobulinemia. We have recently seen a patient with known acquired immunodeficiency syndrome who presented with the hyperviscosity syndrome in the setting of polyclonal hypergammaglobulinemia. To our knowledge, this is the first reported case of a patient with the acquired immunodeficiency syndrome and the hyperviscosity syndrome. The case is presented and the pathogenesis and implications of this diagnosis are discussed.

Acquired Immunodeficiency Syndrome↗

Etiology of ammoniated hay toxicosis.

Some animals consuming hay treated with anhydrous ammonia have developed neurological signs including hyperexcitability, circling and convulsions. A series of experiments was conducted to identify tentatively the toxin and determine its mode of action. Three out of four sheep fed ammoniated orchardgrass hay (approximately 4% ammonia on a dry basis) developed convulsions. Two of the three sheep died within 18 h of the onset of signs. The concentrations of blood lactate and pyruvate were elevated in the symptomatic sheep (P less than .05). A proposed toxin, 4-methyl imidazole, did not induce the syndrome when 750 mg/d (approximately 10 times the dietary amount) were administered orally. Four out of five calves that received milk from cows fed ammoniated oat hay (approximately 5% ammonia on dry basis) displayed hyperexcitability and circling. Concentrations of blood lactate and pyruvate were also elevated in the calves. The crude alkaloid fraction of the toxic milk produced neurological signs similar to those of the calves when injected into mice. A fluorescent compound was found in the alkaloid fraction of toxic milk and ammoniated hay, but not in control milk or untreated hay. The fluorescent compound was quite labile; hence, characterization has been unsuccessful thus far.

Ammonia↗