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Biomedical subjects

M J Murray

Publications and source records attributed to M J Murray.

At least 91 records · Page 5Linked to original sources
PubMed1995

Infections during severe primary undernutrition and subsequent refeeding: paradoxical findings.

BACKGROUND: Our earlier uncontrolled observations during primary famine and subsequent refeeding did not suggest that severe undernutrition inevitably increases vulnerability to infection. Some infections appeared suppressed by famine but reactivated by refeeding. AIMS: To examine prospectively the occurrence of infections in a large cohort of primary famine victims before and during refeeding. METHODS: From 1973 to 1993, 4382 famine victims aged 14 or more with an estimated weight loss greater than 25% were weighed and examined for infection before and after one, two, three and four weeks of refeeding. In 137, serum C-reactive protein was measured in an effort to detect latent asymptomatic infections before and after two weeks of refeeding. Refeeding diets included wheat, sorghum, millet, ghee and milk powder. RESULTS: Mean weight loss +/- SD was 28.7 +/- 2.3%. Before refeeding overt infections were found in 4.9%, an incidence rising to 29.1% at two weeks of refeeding and declining after four. Those developing infections gained more weight at two weeks, 4.6 3 +/- 0.81 kg, than those never infected, 3.94 +/- 0.76 (p = < 0.001 t test). C-reactive protein levels confirmed the presence of latent infections before refeeding. CONCLUSIONS: Severe undernutrition can suppress certain infections, mostly those due to intracellular pathogens and especially P. falciparum. Refeeding reactivates suppressed infection and can increase vulnerability to certain new infections especially of viral origin. Those gaining weight the most rapidly may be at greatest risk. Refeeding with foods alien to local culture could play a role in reactivating latent infections. Our findings may be limited to severe undernutrition and not apply to lesser forms or secondary undernutrition in hospital patients. These studies were done during charitable provision of medical care to famine victims.

Adolescent↗
PubMed1995

Thermogenesis after a mixed meal: role of leg and splanchnic tissues in men and women.

To determine the relative contribution of splanchnic and leg tissues to postprandial thermogenesis, systemic and regional oxygen consumption rates were measured in nine women and eight men before and for 6 h after the consumption of a mixed meal that provided one-third of the daily energy needs. In women, the increase in splanchnic oxygen uptake accounted for 63 +/- 12% of the postprandial increase in oxygen consumption, whereas in men it accounted for 35 +/- 14% (P = not significant between women and men). Leg oxygen uptake accounted for 11 +/- 4 and 10 +/- 3% of the increase in postprandial oxygen consumption in women and men, respectively. The combined data suggest that approximately 48% of postprandial thermogenesis over 6 h occurs in splanchnic tissues, whereas 30-35% occurs in skeletal muscle. Thus the increase in oxygen consumption after a mixed meal is primarily localized to splanchnic tissues, and major reductions in postprandial thermogenesis are unlikely to be attributable solely to abnormalities of skeletal muscle metabolism.

Adult↗
PubMed1995

Select dietary fatty acids attenuate cardiopulmonary dysfunction during acute lung injury in pigs.

We examined the effect of substituting linoleic acid (LA) with eicosapentaenoic acid (EPA) and gamma-linolenic acid (gamma-LA), precursors of trienoic and monoenoic eicosanoids, respectively, on acute lung injury (ALI). Three groups (n = 8/group) of pigs were fed enteral diets containing LA (diet A), EPA (diet B), or EPA+gamma-LA (diet C) for 8 days. ALI was then induced with a 0.1 mg/kg bolus of Escherichia coli endotoxin followed by a continuous infusion for 4 h (0.075 mg.kg-1.h-1). Pulmonary arterial and capillary wedge pressures, cardiac index (CI), arterial blood gases, arterial O2 content, and plasma thromboxane B2 (TxB2) were measured. Arterial PO2 decreased at 20 min in animals fed diet A. This change was attenuated with diets B and C. The EPA- and EPA + gamma-LA-enriched diets attenuated the fall in O2 delivery at 20 min, an improvement that was sustained throughout the 4-h study period with the EPA+gamma-LA-enriched diet only. This improvement in O2 delivery was due not only to the improved arterial PO2, but also to the maintenance of CI at 20 min in animals fed diets B and C and throughout the 4-h study period in animals fed diet C. At 4 h, TxB2 increased 10-fold over baseline in animals fed diet A, whereas in animals fed diets B and C the increase was only 3-fold. These decreased TxB2 levels in animals fed diets B and C correlate with an attenuation in the increase in pulmonary vascular resistance that was observed at 20 min after endotoxin infusion in animals fed diet A. These data suggest that specialized enteral diets enriched in EPA+gamma-LA improve gas exchange and O2 delivery, presumably in part through a modification of TxB2 production with a decrease in pulmonary vascular resistance and an increase in CI, during ALI.

6-Ketoprostaglandin F1 alpha↗
PubMed1995

Opioids and benzodiazepines.

Most patients in the intensive care unit experience pain and anxiety, which are treated most commonly with an opioid or a benzodiazepine. These compounds are effective and have a well-established safety record. With the exception of associated respiratory depression, they have a relatively wide therapeutic window. New approaches and formulations for opioids and benzodiazepines are being used with continued success in the clinical setting.

Analgesia, Patient-Controlled↗
PubMed1995

Complications associated with sedative and neuromuscular blocking drugs in critically ill patients.

Pharmacologic administration of sedatives is used routinely in the care of the critically ill to enhance patient comfort and optimize care. Long-term administration of NMB drugs is far less frequent but often occurs in patients with greater organ dysfunction. The experience of several authors using NMB drugs in the ICU is summarized in Table 5. Both classes of drugs have potential untoward effects. Some are readily predictable; others are not. NMB drugs enjoy a long record of safe, effective use during the perioperative period, but certain issues linger in defining appropriate administration to critically ill patients. Major concerns focus on the appropriate drug selection and delivery, monitoring, and neuromuscular recovery of patients who receive NMB drugs for longer than 24 hours. The development of myopathy and paresis has been increasingly recognized after prolonged use of NMB drugs in the ICU. Further investigation needs to fully characterize this process, identify those at risk, and outline a mechanism to prevent or limit the injury. Prolonged weakness may occur secondary to changes in the basic pharmacology and elimination of NMB drugs in ICU patients. Pathophysiologic changes in the nerve, muscle, or neuromuscular junction may also play a role in the development of some cases of prolonged weakness or myopathy after discontinuation of NMB drugs. Concerns about the potential for direct or indirect toxicity of NMB drugs to skeletal muscle and in the CNS remain. Resolution of these issues will improve the selection and optimal administration of sedative and NMB drugs in the ICU setting.

Central Nervous System Diseases↗
PubMed1994

Equine model of inducing ulceration in alimentary squamous epithelial mucosa.

Ulceration of the gastric squamous epithelial mucosa was induced in 10 horses using a feeding protocol previously shown to expose the gastric mucosa to repeated periods of high acidity. The feeding protocol consisted of alternating feed deprivation with free access to hay. Over a period of seven days, each horse was provided hay for 84 hr and deprived of hay for 84 hr. Hay was never withheld for longer than 24 hr at a time. Gastroscopy was performed on each horse at the beginning of the protocol after 12 hr of feed deprivation, and after a total of 36 hr, 60 hr, and 84 hr of feed deprivation. All horses had normal esophageal and gastric mucosa at the beginning of the protocol. Alternating periods of feeding and feed deprivation resulted in progressive ulceration of the gastric squamous epithelial mucosa in all but one of the horses. Lesions progressed from erosions to ulceration within 36-72 hr of feed deprivation, and by 84 hr of feed deprivation ulcers had developed thickened, raised margins. Esophageal mucosa appeared normal in all horses throughout the study. The protocol of alternating feeding with feed deprivation in horses consistently produced gastric squamous epithelial ulceration and provided a useful model for characterizing temporal transitions in peptic-injured alimentary squamous epithelia.

Animal Feed↗
PubMed1994

Serum D(-)-lactate levels as an aid to diagnosing acute intestinal ischemia.

No serum marker has consistently proved helpful in diagnosing early acute mesenteric ischemia. D(-)-lactate is a product of bacterial metabolism and was found to be elevated in peripheral blood in a rat model of intestinal ischemia. We conducted a prospective study to evaluate preoperative D(-)-lactate levels in 31 patients undergoing laparotomy for acute abdominal emergencies, including suspected acute mesenteric ischemia. The serum was deproteinated and D(-)-lactate concentration was determined by a spectrophotometric assay. A control group was composed of patients with a benign abdominal examination who were operated on for central venous line placement. We found significant elevations in D(-)-lactate levels in patients with mesenteric ischemia compared with controls (P < 0.00005), as well as in patients with other forms of abdominal catastrophes (P < 0.00005) and with bowel obstruction (P < 0.0005). Sensitivity and specificity were 90% and 87%, respectively. The negative predictive value was 96%, and the positive predictive value was 70%. We have found that D(-)-lactate serum levels can aid in diagnosing acute mesenteric ischemia.

Acute Disease↗
PubMed1994

Monitoring intrathecal temperature: does core temperature reflect intrathecal temperature during aortic surgery?

Paraplegia secondary to spinal cord ischemia is a common occurrence following proximal aortic surgery. Recent research has suggested that modest reductions in neuronal temperature (ie, a 2 to 5 degrees C reduction) may protect the central nervous system from ischemic injury, and several medical centers are now using modest whole body hypothermia in an attempt to protect the spinal cord during aortic surgery. However, to date, there are no reports to validate that reductions in core temperature will reduce intrathecal temperature during aortic surgery. In the present study, the correlation between core temperature, assessed with a pulmonary artery thermistor, and intrathecal temperature, assessed with a lumbar intrathecal thermocouple, were evaluated. Both devices were corrected for bias using a mercury thermometer standard. It was found that there was excellent correlation between pulmonary artery temperature and intrathecal temperature during all portions of the surgery (r = 0.948; P < 0.001). The regression line for the relationship was defined by the formula: intrathecal temperature = 0.98 x pulmonary artery temperature + 0.65. Furthermore, there was excellent correlation between bias-corrected intrathecal temperature and the temperature measured by commercially available, bias-uncorrected thermistors placed in the esophagus (r = 0.869; P < or = 0.001), urinary bladder (r = 0.873; P < 0.001), and pulmonary artery (r = 0.929; P < 0.001). Based on these data, it is concluded that there is a close correlation between intrathecal temperature and core temperatures during proximal aortic surgery, and commercially available thermistors provide sufficient accuracy to assess spinal cord cooling during attempts to protect the spinal cord from ischemic injury.

Aortic Aneurysm, Abdominal↗
PubMed1994

A computer-controlled, closed-loop infusion system for infusing muscle relaxants: its use during motor-evoked potential monitoring.

A microcomputer-controlled closed-loop infusion system (MCCLIS) has been developed that provides stable intraoperative levels of partial neuromuscular blockade. Complete neuromuscular blockade interferes with intraoperative motor-evoked potential (MEP) monitoring used for patients undergoing surgical procedures that place them at risk for spinal cord ischemia. Nine patients were studied during which the MCCLIS maintained stable levels of partial neuromuscular blockade and allowed transcranial magnetic motor-evoked potential (TcM-MEP) monitoring during thoracoabdominal aortic aneurysmectomy. The use of TcM-MEP for monitoring intraoperative spinal cord function was balanced against surgical considerations for muscle relaxation with 80% to 90% neuromuscular blockade fulfilling each requirement. Intraoperative adjustment of partial neuromuscular blockade to facilitate TcM-MEP monitoring was also possible with the MCCLIS. The MCCLIS should allow for further investigation into the sensitivity, specificity, and predictability of TcM-MEP monitoring for any patient at risk for intraoperative spinal cord ischemia including those undergoing thoracoabdominal aortic aneurysmectomy.

Action Potentials↗
PubMed1994

Analgesia in the critically ill patient.

Pain is a major problem and primary concern of patients in the ICU. While nonintubated patients can verbalize their discomfort to healthcare providers, intubated patients cannot effectively communicate and are more at risk for inadequate analgesia. Mechanically ventilated, paralyzed patients are at even greater risk for inadequate control of pain. Compassionate care of ICU patients requires clinicians to treat a patient's pain, which, in addition to improving patient satisfaction, may improve patient outcome by attenuating the stress response. Pain arises in the periphery, when tissue destruction causes the release of biochemical agents that activate peripheral pain receptors. These receptors, in turn, initiate an impulse in A-delta and C fibers, an impulse that is carried through neurons in the spinal cord to the brainstem and cerebral cortex. Effective treatment of pain is achieved using several modalities that modify the pain impulse, either in the periphery or within the central nervous system. A number of techniques are available, ranging from nonsteroidal anti-inflammatory drugs to other techniques and medications. However, analgesia usually requires the use of exogenous opioids. The most critically ill, mechanically ventilated patient receiving controlled alveolar minute ventilation is a candidate for continuous infusion of intravenous narcotics.(ABSTRACT TRUNCATED AT 250 WORDS)

Analgesia↗
PubMed1994

Glucose content of tracheal aspirates: implications for the detection of tube feeding aspiration.

OBJECTIVE: To determine, using a sensitive glucose assay, whether monitoring of tracheal aspirate glucose concentration could serve as a marker of aspiration of enteral feedings. DESIGN: Prospective, controlled trial. SETTING: Intensive care units of a tertiary care hospital. PATIENTS: Fifteen enterally fed and 15 nonenterally fed, tracheally intubated patients who had normal lung fields on a routine chest radiograph. INTERVENTIONS: Patients with endotracheal tubes undergoing routine tracheal suctioning had tracheal secretions collected three times per day with a minimum of 4 hrs between samples for up to 5 days. Daily chest radiographs were reviewed for evidence of the development of pneumonitis using defined criteria. MEASUREMENTS AND MAIN RESULTS: Glucose concentrations in five commonly used commercial feeding formulas, as well as in the medications patients were receiving enterally or as an oral wash, were measured. Tracheal secretion glucose concentrations were 66 +/- 54 (SD) mg/dL (3.7 +/- 3.0 mmol/L) and 105 +/- 70 mg/dL (5.8 +/- 3.9 mmol/L) in the enterally fed and nonenterally fed patients, respectively (p = NS). Of the medications administered, the majority contained negligible glucose, but ten had > 3 mg/dose of glucose. However, there was no correlation between administration of these medications and the tracheal glucose concentrations. Tracheal glucose concentrations were similar in patients who received medications containing glucose and patients who received either no medications or medications with negligible glucose content. A small but significant correlation between blood glucose and tracheal secretion glucose concentrations (r2 = .15, p < .05) was observed. None of the patients developed aspiration pneumonitis. Glucose concentrations in widely used commercial formulas (44 to 202 mg/dL; 2.4 to 11.2 mmol/L) overlapped considerably with glucose concentrations in tracheal secretions in the absence of aspiration and were for the most part within 2 SD of mean values in tracheal secretions. CONCLUSIONS: Tracheal secretions contain high glucose concentrations, both in enterally fed patients without evidence of aspiration pneumonitis and in nonenterally fed patients. The concentration of glucose in tracheal secretions appears to be determined, in part, by ambient extracellular glucose concentrations. We conclude that measurement of glucose in tracheal secretions is unlikely to be useful in monitoring for tube feeding aspiration in tracheally intubated, enterally fed patients.

Aged↗
PubMed1994

Reproductive function in the aging male.

Although the association between advanced paternal age and serious birth defects has received less attention than the effect of maternal age on such defects, this association has been demonstrated. This, as well as the potential decline in fertility among older men, should be borne in mind by men electing to defer establishing a family.

Adult↗
PubMed1993

Serum D(-)-lactate levels as a predictor of acute intestinal ischemia in a rat model.

Currently there exists no reliable serum marker for the early diagnosis of acute mesenteric ischemia. We investigated D(-)-lactate as a marker of acute mesenteric ischemia in a rat model. D(-)-Lactate is a byproduct of bacterial metabolism; it is neither produced nor metabolized by mammalian cells. In an ischemic segment of bowel the resident microflora rapidly proliferate and soon overgrow the affected intestinal segment. Additionally, the mucosal barrier of the gut begins to break down. Under these conditions we hypothesize that D(-)-lactate should cross the mucosal barrier in large quantities. To determine if this rapid bacterial proliferation and mucosal leakage produces D(-)-lactate concentrations in quantities sufficient to elevate peripheral blood levels, two models of acute intestinal ischemia and one model of simple obstruction were developed in rats. The three models included: strangulation obstruction of terminal ileum, superior mesenteric artery ligation, and simple intestinal obstruction of the ileum. Controls were divided into two groups: sham-operated controls and unoperated controls. Serum samples were collected via an internal jugular catheter at 5 min, 2 hr, and 4 hr after surgery. These samples were then assayed for D(-)-lactate using an enzymatic-spectrophotometric assay. Data was analyzed by repeated measures analysis of variance and where applicable the Student t test was used to determine statistical significance. We found statistically significant elevations in D(-)-lactate concentrations as early as t = 5 min in the strangulation obstruction model and SMA ligation model compared to unoperated controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1993

The effect of age on male reproductive function.

When couples elect to defer child bearing, the effects of age on reproductive potential must be considered. The impact of advancing age on female reproductive potential has been well documented. Relatively less attention, however, has been directed toward the effect of age on male reproductive function. Although less pronounced than its effect on female fertility, advancing age does have an impact on male reproduction. Among men, increasing age is associated with a decrease in sexual function as well as changes in testicular histology and a decline in basic fertility parameters. Additionally, there is an identifiable association between advanced paternal age and subsequent birth defects. These issues should be borne in mind when men are counseled regarding the age at which they elect to establish families.

Adult↗
PubMed1993

The fidelity and dynamic response of fluid-filled catheter systems for direct measurement of lumbar cerebrospinal fluid pressure.

OBJECTIVE: The purpose of this study was to determine the fidelity of pressure signals transmitted through long, narrow (epidural) catheters inserted into the lumbar intrathecal space. METHODS: Using a model of the spinal canal we tested three epidural catheters: 20-gauge Arrow, 20-gauge Abbott, 21-gauge Portex. We (1) determined the damping coefficient and natural frequency of the three catheters, (2) correlated the static pressures measured using the three catheters compared to the true pressure in the intrathecal space, and (3) compared the response time of the three catheters connected to transducers vs U-tube manometers. RESULTS: The three catheters had high damping coefficients (alpha) (Arrow, 0.75; Abbott, 0.85; Portex, 1.10) and low natural frequencies (Arrow, 15.23 Hz; Abbott, 12.83 Hz; Portex, 9.09 Hz). The dynamic response characteristics of the catheter with the largest internal diameter (20-gauge Arrow) were adequate to reproduce pulsatile cerebrospinal fluid pressure reliably. Smaller catheters tracked the mean pressure, although oscillations were damped. Static pressure measurements from all three catheters showed good correlation with test pressures (r = 0.99; p < 0.001). Using the U-tube manometer, it required 170, 140, and 130 minutes for the Portex, Abbott, and Arrow catheters, respectively, to equilibrate with a test pressure of 30 cm H2O. The rate of rise in the U-tube manometer pressure was limited by the rate of fluid flow through the catheters. CONCLUSIONS: We found that a catheter of at least 20 gauge connected to a transducer could record pressures in the cerebrospinal fluid compartment with a high degree of fidelity. The prolonged time to reach equilibrium made U-tube manometry unsuitable for clinical use.

Catheterization↗
PubMed1993

The use of neuromuscular blocking drugs in the intensive care unit: a US perspective.

Surprisingly little is known about the use of neuromuscular blockers (NMBs) in intensive care units (ICUs) in the USA. Recently, Klessig et al. surveyed anesthesiologists/intensivists in the USA and found that the 55% who responded used NMBs in the ICU in an average of 10 patients per ICU per month. Anxiolytics and analgesics were administered concomitantly with NMBs, but a majority of respondents did not use electrophysiologic measures of the degree of blockade. Another survey of predominantly medical ICUs also demonstrated widespread use of NMBs, but internists did not use sedation/analgesia as frequently as anesthesiologists for patients receiving NMBs, and infrequently monitored the degree of neuromuscular blockade. Because these were retrospective surveys, we decided to monitor prospectively the use of NMBs in our ICUs. The use of NMBs was ascertained by daily review of pharmacy records and, when use was documented, the patients' hospital records were reviewed. Where information was missing or not found, attending physicians were interviewed. On average, one patient per month per ICU received NMBs. Approximately 5% of neonatal and pediatric, and 1% of adult, ICU patients received NMBs. Eighty-three percent of patients received NMBs to facilitate mechanical ventilation, and mortality was high (51%) in those critically ill patients. More than half the patients were treated for < or = 24 h, the remainder for 2 days to > 3 weeks. Twitch monitors were used for monitoring the degree of neuromuscular blockade in adult patients, and all patients received sedatives/analgesics. We estimated that the risk of clinically significant, prolonged neuromuscular blockade following the discontinuation of NMBs was 5% per year.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Preliminary results with neoadjuvant therapy and resection for esophageal carcinoma.

Between December 1988 and August 1992, 68 patients with adenocarcinoma (n = 39) and squamous carcinoma (n = 29) of the esophagus were entered prospectively in a treatment protocol to receive two cycles of cisplatin, 5-fluorouracil, etoposide, leucovorin, and 3,000 cGy of radiation to the involved esophagus and adjacent mediastinum, followed by resection. There were four deaths during chemotherapy, and 7 patients had a decline in condition or were denied operation. Fifty-six patients have come to operation, and 1 awaits resection. Twenty-two patients had transhiatal esophagectomy and 29 patients had esophagogastrostomy with a combined abdominal and right thoracic approach. Five patients did not undergo resection at operation. There was one hospital death (2%). A complete response to preoperative therapy was seen in 12 patients (21%): 5 of 20 with squamous cancer (25%) and 7 of 36 with adenocarcinoma (19%). Average follow-up is 19 months. Median survival in these patients after entrance in the protocol is 24 months. Actuarial survival at 12, 18, and 24 months is 72% (confidence limits, 66% and 78%), 53% (confidence limits, 46% and 60%), and 51% (confidence limits, 44% and 58%). Significantly better survival was associated with adenocarcinoma (p = 0.041). There is no survival advantage based on complete response to preoperative therapy. This neoadjuvant regimen is effective in patients with squamous carcinoma and adenocarcinoma. These preliminary results demonstrate an improved median and actuarial survival compared with historical controls in 137 patients operated on between 1966 and 1985 at our institution.

Adenocarcinoma↗