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Biomedical subjects

C M Ryan

Publications and source records attributed to C M Ryan.

At least 19 recordsLinked to original sources

Hypertension and neuropsychological performance in men: interactive effects of age.

Potentially interactive effects of hypertension and age on the performance of neuropsychological and information processing tests were examined in 123 untreated hypertensive and 50 normotensive men. After covarying education, average alcohol consumption, trait anxiety, and depression scores, results indicated an interaction of age and hypertension. Young hypertensive men (23-40 years) scored significantly worse than young normotensive men on tests of attention/executive function and working memory; middle-aged hypertensive (41-56 years) and normotensive participants were not distinguished by any measures. Hypertensive men performed significantly more poorly than normotensive men on tests of manual dexterity. Results suggest that neuropsychological sequelae of hypertension are more pronounced in young than in middle-aged hypertensive individuals and are independent of various demographic, psychosocial, and alcohol-related factors.

Adult

Regional cerebral blood flow during hypoglycaemia in children with IDDM.

Hypoglycaemia may cause transient cognitive impairment and neurological deficits that are frequently unilateral. The effect of mild hypoglycaemia (serum glucose level 3.4 +/- 0.1 mmol/l; mean +/- SEM) on regional cerebral blood flow and cerebrovascular resistance was studied in eight right-handed children with insulin-dependent diabetes mellitus (age 14.9 +/- 0.7 years; diabetes duration 7.4 +/- 1.1 years; six males) using the intravenous xenon-133 clearance method. Global mean cerebral grey and white matter blood flow, adjusted to mean pCO2 of cohort, showed a trend towards an increase from 54.7 +/- 3.5 ml.100 g-1.min-1 at baseline euglycaemia to 58.0 +/- 4.1 ml.100 g-1.min-1 during hypoglycaemia (p = 0.075). Statistically significant changes were seen in global mean cerebral grey matter blood flow, as indexed by initial slope, which increased from 88.0 +/- 6.5 min-1 before hypoglycaemia to 96.3 +/- 7.2 min-1 during hypoglycaemia (p < 0.05). Cerebral grey matter blood flow was significantly higher in the right hemisphere compared to the left during hypoglycaemia (p < 0.01) but not at baseline euglycaemia. Measurements of global cerebrovascular resistance showed a borderline decrease from 1.64 +/- 0.11 to 1.54 +/- 0.11 mm Hg.ml-1.100 g-1.min-1 (p < 0.09). In conclusion, mild hypoglycaemia is associated with increases in cerebral blood flow which are greater in grey matter flow indices and in the right hemisphere. We speculate that asymmetrical cerebral blood flow changes may explain the frequent laterality of neurological deficits during severe hypoglycaemia.

Adolescent

Plasma arginine and leucine kinetics and urea production rates in burn patients.

We measured plasma arginine and leucine kinetics and rates of urea production (appearance) in 12 severely burned patients (mean body surface burn area, 48%) during a basal state (low-dose intravenous glucose) and while receiving routine, total parenteral nutrition ([TPN] fed state) including an L-amino acid mixture, supplying a generous level of nitrogen (mean, 0.36 g N.kg-1.d-1). The two nutritional states were studied in random order using a primed 4-hour constant intravenous tracer infusion protocol. Stable-nuclide-labeled tracers were L-[guanidino-13C]arginine, L-[1-13C]leucine, [18O]urea, and NaH13CO3 (prime only), with blood and expired air samples drawn at intervals to determine isotopic abundance of arginine, citrulline, ornithine, alpha-ketoisocaproate ([KIC] for leucine), and urea in plasma and 13CO2 in breath. Results are compared with data obtained in these laboratories in healthy adults. Leucine kinetics (flux and disappearance into protein synthesis) indicated the expected higher turnover in burn patients than in healthy controls. Mean leucine oxidation rates are also higher and compared well with values predicted from urea production rates, provided that urea nitrogen recycling via intestinal hydrolysis is taken into account. The plasma urea flux was also higher than for normal subjects. Arginine fluxes as measured in the systemic whole body, via the plasma pool, were correspondingly higher in burned patients than in healthy controls and were in good agreement with values predicted from leucine-KIC kinetics. However, systemic whole-body arginine flux measured via the plasma pool was only 20% of the arginine flux estimated from the urea flux plus the rate of protein synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Emergency management of major hydrofluoric acid exposures.

Exposures of as little as 2.5 per cent of the body surface to concentrated hydrofluoric acid (HF) may be fatal. Survival after major HF exposures is facilitated by aggressive emergency management which, we feel, includes wound irrigation, subeschar injection of calcium gluconate, monitored supplementation of serum calcium, and prompt wound excision carried out as an emergency procedure. The following case reports and literature review illustrate the important differences between exposures to concentrated HF of as little as 2 per cent of the body surface and smaller exposures to concentrated HF or exposure to dilute HF.

Accidents, Occupational

Cognitive function in patients with insulin-dependent diabetes mellitus during hyperglycemia and hypoglycemia.

BACKGROUND: To determine the impact of glycemic control, gender, and other relevant parameters on cognitive function during exposure to different blood glucose levels in patients with insulin-dependent diabetes mellitus (IDDM), we examined neuropsychologic function during experimentally induced periods of hyperglycemia and hypoglycemia. METHODS: We studied 20 men and 22 women, aged 18 to 44 years, with IDDM duration of 3 to 14 years and HbA1 values ranging from 5.8% to 18.0% (nondiabetic range 5.4% to 7.4%). We used a controlled experimental setting involving tests of sensory perceptual processing, simple motor abilities, attention, learning and memory, language, and spatial and constructional abilities at plasma glucose levels of 2.2, 5.6, 8.9, 14.4, and 21.1 mmol/L. Patients were blind to the glucose level. Tests used at each glucose level included reaction time (simple and choice), digit vigilance, trail making part B, word recall, digit sequence learning, and verbal fluency. RESULTS: All aspects of neuropsychologic function were diminished at 2.2 mmol/L when compared with basal levels of performance at 8.9 mmol/L, whereas no alterations were observed at 14.4 or 21.1 mmol/L. Tests involving associative learning, attention, and mental flexibility were the most affected during hypoglycemia. Glycemic control was not correlated with neuropsychologic function at any glucose level. Women demonstrated less of an impairment in neuropsychologic function than men at 2.2 mmol/L. CONCLUSIONS: Cognitive function in IDDM patients was generally well-preserved even at substantially elevated blood glucose levels. Deficits in all relevant areas of cognitive function occurred during hypoglycemia (2.2 mmol/L), irrespective of prior glycemic control, and women with IDDM were less cognitively impaired than men with IDDM during hypoglycemia.

Adult

Relations among arginine, citrulline, ornithine, and leucine kinetics in adult burn patients.

Plasma fluxes of arginine, citrulline, and leucine, and the rate of conversion of labeled citrulline to arginine (Qcit-->arg) were determined in nine severely burned patients (mean: 56% body surface burn area, mean 10 d postinjury) while they received total parenteral nutrition (TPN) including an L-amino acid mixture that supplied a generous amount of nitrogen (mean: 0.39 +/- 0.02 g.kg-1.d-1). Plasma fluxes were also studied in these patients during a basal state (low-dose intravenous glucose) by using a primed, 4-h constant intravenous tracer-infusion protocol. Stable-nuclide labeled tracers were L-[15N-15N-guanidino,5,5,2H2]arginine; L-[13C-ureido]citrulline; L-[1-13C]leucine; and NaH13CO3 (prime only), with blood and expired air samples drawn at intervals to determine isotopic abundance of arginine, citrulline, ornithine, and alpha-ketoisocaproate (KIC; for leucine) in plasma and 13CO2 in breath. Leucine kinetics (flux and disappearance into protein synthesis) confirmed the anticipated higher protein turnover in these burn patients compared with healthy control subjects. The plasma arginine fluxes were correspondingly higher in burn patients than in healthy control subjects. However, the citrulline flux and rate of conversion of citrulline to arginine were not higher than values obtained in our laboratories in healthy adult subjects. We hypothesize that the higher rates of arginine loss from the body after burn injury would need to be balanced by an appropriate exogenous intake of preformed arginine to maintain protein homeostasis and promote recovery from this catabolic condition.

Adult

Postburn pancreatitis.

OBJECTIVE: The authors examined the prevalence and complications of pancreatitis in severely burned patients. Factors predictive for the development of pancreatitis after burns are considered. SUMMARY BACKGROUND DATA: Pancreatitis has been documented at necropsy after burns; however, it is not clinically recognized as a common complication of burn injury. Recent improvements in survival rates could yield previously unrecognized complications, such as pancreatitis, particularly in those patients who previously would have not survived. The hypothesis is that pancreatitis is a frequent complication after major burn injury and causes significant morbidity for patients with large burns. METHODS: This retrospective review of adult patients with large burns examines postburn pancreatitis using stepwise logistic regression analysis. RESULTS: Forty-nine of 121 (40%) patients developed hyperamylasemia or hyperlipasemia well after the admission period (23 +/- 3 days), and all enzyme abnormalities were temporally associated with emerging infections. Most of these patients (40/49, 82%) had symptoms of pancreatitis. Three patients (6%) had pancreatic pseudocysts or abscesses. Inhalation injury (p = 0.0001), associated trauma (p = 0.0311), and escharotomy (p = 0.0415) were risk factors for pancreatitis. Using Fischer's exact test, patients with pancreatitis had increased mortality and length of stay. Patients with high enzyme elevations and > or = 50% body surface area burned were at severe risk of pancreatic pseudocyst or abscess development (43%; 90% confidence interval of 23-77%). CONCLUSIONS: Pancreatitis is a frequent complication after large burn injuries. Patients at high risk for pancreatitis complications should receive surveillance examinations during their acute hospitalization.

Abscess

Effects of malignancy and interleukin-2 infusion on gut macromolecular permeability.

OBJECTIVE: Enhanced gut permeability has been shown in patients with advanced malignancy. The dramatic inflammatory shock syndrome produced by high-dose interleukin-2 immune therapy could further change gut barrier function. This study measured the effect of advanced renal cell carcinoma and malignant melanoma, and interleukin-2 treatment on gut permeability. DESIGN: Nonrandomized, controlled study. SETTING: University hospital. PATIENTS: Adults with metastatic, unresectable renal cell carcinoma or metastatic, malignant melanoma, and normal volunteers. INTERVENTIONS: Gut permeability was measured in patients with renal cell carcinoma or malignant melanoma before and during interleukin-2 infusions, using polyethylene glycol 3350 and polyethylene glycol 400. The polyethylene glycols were administered orally within 48 hrs of interleukin-2 therapy and the 24-hr urine excretions were measured. MEASUREMENTS AND MAIN RESULTS: Increased permeability was seen in the baseline state of these patients (ratio of polyethylene glycol 3350 to polyethylene glycol 400 = 1.1 +/- 0.7 x 10(-2)) when compared with normal volunteers (ratio = 0.48 +/- 0.2 x 10(-2); p < .05). However, after interleukin-2 treatment, no further increase in permeability was seen (ratio = 1.4 +/- 0.8 x 10(-2)). CONCLUSIONS: Gut permeability to polyethylene glycol 3350 is enhanced in advanced malignancy. High-dose interleukin-2 therapy does not further increase permeability of the gut.

Adult

Percutaneous cholecystostomy in the critically ill burn patient.

OBJECTIVE: We desired to demonstrate the utility of percutaneous cholecystostomy in the evaluation and management of critically ill burn patients with fever and rising cholestatic chemistries. DESIGN: Retrospective review. MATERIALS AND METHODS: Over a 2 1/2-year period there were 411 admissions to a regional adult burn until of whom six patients (1.5%) were strongly suspected of having developed acute cholecystitis. Five were managed with percutaneous cholecystostomy. MEASUREMENTS AND MAIN RESULTS: All patients had sonographic signs consistent with acute cholecystitis. One was managed with immediate laparotomy and the remaining five patients underwent ultrasound-guided percutaneous transhepatic cholecystostomy at the bedside (n = 4) or in the ultrasonography suite (n = 1) without complication. One patient died of multiple organ failure 3 days after catheter placement despite good catheter position and function. Two of the surviving patients responded promptly to drainage of the gallbladder with resolution of fever and normalization of liver function tests. Two patients did not respond despite catheters that were properly placed and functioning, reliably eliminating the diagnosis of acute cholecystitis. One patient underwent interval cholecystectomy after wound closure and the remaining patients were discharged after catheters were removed. CONCLUSIONS: Bedside percutaneous cholecystostomy is a minimally invasive procedure that can facilitate the evaluation and management of the critically ill burn patient with fever and rising cholestatic chemistries in whom a diagnosis of acute cholecystitis is suspected.

Acute Disease

The acutely burned hand: management and outcome based on a ten-year experience with 1047 acute hand burns.

Optimal hand function has a very positive impact on the quality of survival after burn injury. Over a 10-year period, 659 patients with 1047 acutely burned hands were managed at the Sumner Redstone Burn Center of the Massachusetts General Hospital. Our approach to acutely burned hands emphasizes ranging and splinting throughout hospitalization, prompt sheet autograft wound closure as soon as practical, and the selective use of axial pin fixation and flaps. This approach is associated with normal function in 97% of those with superficial injuries and 81% of those with deep dermal and full-thickness injuries requiring surgery. Although only 9% of those with injuries involving the extensor mechanism, joint capsule, or bone had normal functional outcomes, 90% were able to independently perform activities of daily living.

Acute Disease

Permissive hypercapnia as a ventilatory strategy in burned children: effect on barotrauma, pneumonia, and mortality.

OBJECTIVE: To document the incidence of barotrauma, pneumonia, and respiratory death associated with a mechanical ventilation protocol based on permissive hypercapnia in pediatric burn patients. DESIGN: Retrospective review. MATERIALS AND METHODS: Patients were managed using a mechanical ventilation protocol based on permissive hypercapnia, tolerating moderate (pH > 7.20) respiratory acidosis to keep inflating pressures below 40 cm H2O. MAIN RESULTS: Over a 2.5-year interval, 54 burned children (11% of 495 acute admissions) with an average age of 6.5 years (range 5 weeks to 17 years), average burn size of 44% (range 0 to 98%), and median burn size of 46% required mechanical ventilatory support for an average of 12.5 days (range 1 to 56 days). Inhalation injury was diagnosed in 34 (63%) of the children and 72% percent were admitted within 24 hours of injury. Overt barotrauma occurred in 5.6% of the patients, pneumonia in 32%, and respiratory death in 0%. CONCLUSIONS: A conventional ventilation protocol based on permissive hypercapnia is associated with acceptable rates of barotrauma and pneumonia. The low incidence of respiratory death associated with this strategy suggests that it also minimizes ventilator-induced lung injury.

Acidosis, Respiratory

Cognitive effects of ketogenic weight-reducing diets.

OBJECTIVE: To determine whether ketogenic weight reducing diets have adverse effects on cognitive performance. SUBJECTS: 21 overweight women (mean BMI = 41 kg/m2). DESIGN: Randomized double-blinded study. METHOD: Subjects were randomized to ketogenic or nonketogenic liquid formula very low energy diets, that were comparable in energy and in protein content. Subjects remained on the diet for 28 days and were reevaluated periodically with brief measures of cognitive performance assessing attention and mental flexibility. RESULTS: Weight losses were comparable on the two diets (Mean = 8.1 kg). Performance on attention tasks did not differ as a function of the diet. However, performance on the trail making task, a neuropsychological test that requires higher order mental processing and flexibility, was adversely affected by the ketogenic diet. The worsening in performance was observed primarily between baseline and week one of the ketogenic diet. CONCLUSIONS: Further research is needed to confirm this finding and to determine whether ketogenic diets negatively affect other complex mental tasks, such as problem solving.

Adult

Additive effects of thermal injury and infection on gut permeability.

OBJECTIVE: To determine the effects of burn size and burn wound infection on gut permeability to the macromolecule polyethylene glycol 3350 (PEG 3350; molecular weight, 3350 d). DESIGN: Randomized, controlled study using 36 male Sprague-Dawley rats. SETTING: Hospital research laboratory. INTERVENTIONS: Animals received scald burns to 0%, 20%, or 35% of their total body surface area. Half of the animals in each group were infected with Pseudomonas aeruginosa. MAIN OUTCOME MEASURES: Gut permeability was measured using the intestinal absorption and renal excretion of enterally administered PEG 3350 and mannitol (molecular weight, 182 d). RESULTS: There were dramatic increases in PEG 3350 excretion and in the PEG 3350/mannitol ratios (P = .0001 in both instances) that were seen in relation to burn size. Significant increases in PEG 3350 excretion and in the PEG 3350/mannitol ratios (P = .017 and P = .045, respectively) were also seen in animals in which infection was present. This was in addition to the effects of burn size already noted. CONCLUSIONS: A direct relationship between gut permeability and the extent of burn injury was found, which is consistent with the results from a previous study in humans. In addition, this study found that further separate increases in gut permeability occur in the presence of P aeruginosa in burn wound infections.

Animals

Individual differences in neurobehavioral disruption during mild and moderate hypoglycemia in adults with IDDM.

This study investigated the neurobehavioral effects of mild and moderate hypoglycemia in adults with insulin-dependent diabetes mellitus (IDDM). On 2 consecutive days, 26 subjects were tested in a counterbalanced, randomized, single-blind, crossover design. On the experimental day, subjects performed tests at 6.4, 3.6, and 2.6 mmol/l and again after glycemic recovery to 6.3 mmol/l. On the control day, subjects performed tests four times at euglycemia. Three months after testing, 15 subjects repeated the experimental day protocol. Results demonstrated that both mild and moderate hypoglycemia significantly disrupted performance. However, performance deterioration varied substantially across individual subjects. Men exhibited significantly more deterioration than women at mild hypoglycemia, and subjects with a history of unconsciousness due to hypoglycemia exhibited more deterioration than subjects with no such history. Individual deterioration scores during repeat testing significantly correlated with performance during original testing. Recovery from hypoglycemia-related impairment varied across individuals and was correlated with degree of impairment during hypoglycemia. These results suggest that the glycemic threshold for onset and recovery from neurobehavioral deterioration with hypoglycemia, as well as degree of impairment experienced, varies across individuals. Furthermore, these individual differences are stable across time.

Adult

Cognitive dysfunction in adults with type 1 (insulin-dependent) diabetes mellitus of long duration: effects of recurrent hypoglycaemia and other chronic complications.

To examine the long-term effects of recurrent severe hypoglycaemia and other biomedical complications on mental efficiency, a battery of cognitive tests was administered to 142 Type 1 (insulin-dependent) diabetic adult patients (age 33.5 +/- 5.6 years; mean +/- SD) and 100 demographically similar non-diabetic control subjects. All diabetic subjects had been diagnosed before the age of 17 years. Diabetic subjects with one or more complications (distal symmetrical polyneuropathy; advanced background or proliferative retinopathy; overt nephropathy; one or more episodes of severe hypoglycaemia) performed significantly (p < 0.001) more poorly than non-diabetic control subjects on tests requiring sustained attention, rapid analysis of visuospatial detail, and hand eye co-ordination. Regression analyses indicated that the best biomedical predictor of cognitive test performance was a diagnosis of polyneuropathy. Although severe recurrent hypoglycaemia was not associated with performance on any test, the neuropathy x recurrent hypoglycaemia interaction term was significant. These results suggest that in adults with Type 1 diabetes of long duration, recurrent hypoglycaemia does not appear to influence cognitive performance directly, but may interact with neuropathy to exaggerate or otherwise magnify the extent of neurobehavioural dysfunction.

Adult

Gut macromolecular permeability in pancreatitis correlates with severity of disease in rats.

BACKGROUND: Increased intestinal macromolecular permeability could allow absorption of substances from the bowel into the systemic circulation and contribute to multiple organ system failure. METHODS: Mild, intermediate, and severe grades of pancreatitis were induced in rats using intravenous caerulein and intraductal glycodeoxycholic acid. [14C]polyethylene glycol (molecular weight, 3350 daltons; 1.1 microCi/142 mg) was instilled into the distal duodenum. At 24 hours, the animals were killed, ascitic fluid was collected for trypsinogen activation peptide measurement, and pancreatic specimens were collected and scored for based on the degree of necrosis, inflammation, and hemorrhage. RESULTS: Gut permeability to polyethylene glycol 3350 (PEG 3350) was increased in animals with early experimental pancreatitis (5.4% +/- 1.2%, n = 20) when compared with control animals (1.8% +/- 0.2%; n = 6) (P = 0.0005). Furthermore, intestinal macromolecular permeability to PEG 3350 correlated with severity of disease as predicted by the method of induction of pancreatitis (P = 0.0003), the histological findings (P = 0.0002), and total ascitic trypsinogen activation peptides content (P = 0.029). CONCLUSIONS: Increased gut permeability in experimental pancreatitis can be correlated with pancreatitis severity.

Animals

Acute adrenal insufficiency in the burn intensive care unit.

Acute adrenal insufficiency may underlie a confusing, stormy, intensive care unit course after a burn. The aetiology is most likely to be adrenal haemorrhage despite the absence of a coagulopathy. This report describes two patients who were diagnosed antemortem and successfully treated with replacement therapy. The aetiology, presentation, diagnosis and treatment of acute adrenal insufficiency in the intensive care unit is reviewed.

Acute Disease

Effects of insulin-dependent diabetes on learning and memory efficiency in adults.

Previous work with elderly adults with maturity-onset non-insulin-dependent diabetes has demonstrated the presence of significant learning and memory deficits which are correlated with the degree of chronic hyperglycemia. This study was conducted to examine learning and memory processes in a group of 82 younger adults (mean age = 33.4 years) with a long history (mean duration = 26.2 years) of childhood-onset insulin-dependent diabetes. Contrary to expectation, diabetic subjects performed as well as a group of 82 age- and SES-matched nondiabetic control subjects on all measures of learning and memory. On the other hand, they performed significantly worse on measures of psychomotor efficiency, with degree of chronic hyperglycemia being the best predictor of psychomotor slowing. These findings, together with earlier studies of elderly diabetic patients, suggest that specific neural systems within the aging brain may be differentially sensitive to the "toxic" effects of chronic hyperglycemia.

Adult