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C McClain

Publications and source records attributed to C McClain.

At least 37 records · Page 2Linked to original sources
PubMed1993

Long-term ethanol consumption alters the hepatic response to the regenerative effects of tumor necrosis factor-alpha.

The pathogenesis of chronic alcoholic liver disease is uncertain, but it may reflect an impaired wound healing response to ethanol-induced liver injury. Cell-to-cell communication such as that mediated by the cytokine tumor necrosis factor is necessary for successful liver regeneration and complete recovery from liver injury. Hence disruption of intercellular regenerative signaling may contribute to the pathogenesis of chronic alcoholic liver disease. To test this hypothesis, the cytokine and regenerative responses triggered by partial hepatectomy were compared in ethanol-fed rats and isocalorically maintained, pair-fed controls. To further clarify the effect of ethanol on tumor necrosis factor-modulated regenerative effects, we evaluated some of the rats in each feeding group after pretreatment with antibodies to tumor necrosis factor. As expected, ethanol inhibited DNA synthesis and liver cell proliferation after partial hepatectomy. Ethanol-associated inhibition of liver regeneration occurred despite apparently similar serum concentrations of the tumor necrosis factor-inducible cytokine interleukin-6. Treatment with antibodies to tumor necrosis factor 1 hr before partial hepatectomy inhibited post-partial hepatectomy induction of interleukin-6 and liver regeneration in ethanol-fed and pair-fed rats. However, serum interleukin-6 was reduced more in ethanol-fed rats than in control rats (93% vs. 66%; p < 0.05). Antibodies to tumor necrosis factor also inhibited hepatic DNA synthesis more in ethanol-fed rats than in controls (85% vs. 50%; p < 0.05). In ethanol-fed rats, the increased effect of tumor necrosis factor antibody on post-partial hepatectomy DNA synthesis suggests heightened sensitivity of hepatocytes to tumor necrosis factor.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

The protective effect of FK506 pretreatment against renal ischemia/reperfusion injury in rats.

The effect of pretreatment with FK506 on renal ischemia and reperfusion (I/R) injury was investigated using a rat model. Animals were assigned to one of two groups (20 rats each). Group 1 animals (controls) received 0.5 ml saline while group 2 animals received FK506 (0.3 mg/kg), administered intravenously 24 hr prior to the induction of renal ischemia. A 60-min period of ischemia of the right kidney was induced, and upon reperfusion a left nephrectomy was performed. Blood samples for estimation of BUN, creatinine, and tumor necrosis factor were collected on days 0 (preischemia), 1, 2, 3, 5, 7, and 10 (postischemia). Rats were sacrificed after day 10 and renal tissue was examined histologically. All animals survived the ischemic episode. FK506 pretreatment significantly reduced the serum levels of BUN (P less than 0.02), creatinine (P less than 0.02), and TNF (P less than 0.05) as compared with that seen in controls. Histologically, at day 10, the kidneys showed the expected sequelae of prior renal I/R with various degrees of tubular damage. However, no objective differences were evident between the two groups. Based upon these data, it can be concluded that (1) FK506 pretreatment ameliorates the functional renal injury associated with I/R, (2) renal ischemia induces the release of TNF, and (3) FK506 pretreatment results in a significant inhibition of TNF production. These data suggest that the release of TNF may be responsible for the increasing of BUN and creatinine levels seen after renal I/R and that pretreatment of renal donors with FK506 may improve renal function in the immediate post-transplant period.

Animals↗
PubMed1992

Antibodies to tumor necrosis factor-alpha inhibit liver regeneration after partial hepatectomy.

Certain cytokines that are produced in liver may act as growth factors to facilitate wound healing and, hence, may influence liver regeneration. However, this hypothesis has not been directly tested. To determine whether the cytokine response evoked by partial hepatectomy (PH) modulates the process of liver regeneration, adult male rats were injected intraperitoneally with either goat polyclonal antibodies to rat tumor necrosis factor (TNF; 15 micrograms/g body wt) or an equal amount of goat anti-rat immunoglobulin G 1 h before PH. Animals were killed at 12, 24, 48, or 72 h post-PH, 1 h after injection with [3H]thymidine. Serum TNF levels were measured with the L929 cytotoxicity assay, titers of antibody to TNF were determined by enzyme-linked immunoabsorbent assay, and interleukin-6 (IL-6) concentrations were measured by B9 cell bioassay. Liver regeneration was assessed by [3H]thymidine incorporation into hepatic DNA and by immunohistochemical evidence of proliferating cell nuclear antigen (PCNA) expression. Antibodies to TNF were detected in treated rats but not in controls. Titers were highest at 12 h and progressively fell. Although TNF was never detected in serum, treatment with anti-TNF pre-PH significantly inhibited increases in serum IL-6 concentration post-PH. Anti-TNF pretreatment also inhibited [3H]thymidine incorporation into DNA, as well as expression of PCNA by both hepatocytes and liver nonparenchymal cells. These data indicate that TNF positively modulates liver regeneration after PH.

Animals↗
PubMed1992

FK 506 reduces the injury experienced following renal ischemia and reperfusion.

The effect of FK 506 pretreatment on renal ischemia and reperfusion (I/R) injury was investigated. Adult male rats were assigned to one of two groups (20 animals each). Group 1 (controls) received 0.5 mL saline while group 2 received FK 506 (0.3 mg/kg) intravenously 24 h prior to the induction of renal ischemia. After a 60-min period of ischemia of the right kidney, a left nephrectomy was performed. Blood for BUN, creatinine, and tumor necrosis factor (TNF) was obtained prior to ischemia and on days 1, 2, 3, 5, 7, and 10. All surviving animals were sacrificed at day 10. FK 506 pretreatment reduced the serum levels of BUN (p less than .02), creatinine (p less than .02) and TNF (p less than .05) as compared to that seen in controls. Based upon these data, it appears that: (a) renal ischemia induces the release of TNF; (b) FK 506 pretreatment inhibits TNF production; and (c) FK 506 reduces renal injury association with I/R.

Animals↗
PubMed1992

Nutrition and brain injury.

The patient with head injury must overcome central and systemic insults. In addition to the head injury itself, the patient suffers a systemic metabolic response to injury. Both of these insults can affect the patient's ability to survive and recover. During the past decade, investigators have described the systemic metabolic result identified by hypermetabolism, hypercatabolism, the acute-phase response, decreased immunocompetence, hyperglycemia, increased counterregulatory hormone levels, increased ventricular fluid and serum cytokine levels, and altered gastric function. During the next decade, investigators will attempt to modulate this response by manipulating the types of nutrients administered, use of pharmacologic and physiological agents, and administration of growth factors.

Brain Injuries↗
PubMed1991

Altered gastric emptying in the head-injured patient: relationship to feeding intolerance.

Most patients with moderate to severe head injury initially do not tolerate enteral feedings postinjury. This intolerance is more prolonged than that found in patients suffering other types of trauma. The authors prospectively evaluated 12 patients with moderate to severe head injury (Glasgow Coma Scale score between 4 and 10) throughout their hospitalization for liquid gastric emptying as a possible mechanism for intolerance to enteral feeding. During Week 1, the majority of patients displayed a delay in gastric emptying. Patients also displayed an abnormal biphasic response (gastric emptying faster than normal during the early stage but prolonged later). By Week 2, many patients still had delayed and abnormal biphasic responses to gastric emptying. By Week 3, an improvement was observed with the majority of patients exhibiting rapid gastric emptying, but delays and abnormal biphasic responses were still seen. Patients who initially had rapid or normal gastric emptying tolerated full-strength full-rate feedings significantly earlier compared with those who experienced delayed gastric emptying (8.5 +/- 0.5 days vs. 13.7 +/- 3.2 days, p less than 0.001). All patients tolerated full-strength full-rate feedings by Day 16 postinjury (range 7 to 16 days) except the two patients who displayed delayed gastric emptying for prolonged periods of time (mean 25 days). This is the first study to longitudinally evaluate gastric emptying following head injury. The authors suggest that patients with moderate to severe head injury often experience alterations in gastric emptying which may affect their ability to tolerate enteral feedings.

Adolescent↗
PubMed1991

Metabolic management of the patient with head injury.

Patients with severe head injury have a disruption in metabolic homeostasis that includes increased energy expenditure and increased protein catabolism. These changes have been suggested to occur secondary to steroid administration, immobility, and other factors. A review of investigations indicates that the head injury itself causes these metabolic changes, although steroid administration can further alter plasma amino acid changes. Altered plasma amino acid profiles after head injury may have an effect on substrate availability to the brain, bacterial translocation, and overall nitrogen balance. Patients with severe head injury have increased skeletal muscle efflux of amino acids. Lack of nutrient supplementation in these patients is associated with increased morbidity and mortality. Enteral nutrition is the preferred mode of feeding but often is not tolerated in the patient with head injury. Parenteral nutritional support can be given to these patients without worsening cerebral edema.

Amino Acids↗
PubMed1991

Increased plasma and ventricular fluid interleukin-6 levels in patients with head injury.

The cytokine interleukin-6 (IL-6) plays a major role in initiating the acute phase response, especially in the production of acute phase reactants such as C-reactive protein. The objectives of this study were to determine whether plasma or ventricular fluid IL-6 levels were elevated at time of admission after head injury and whether plasma IL-6 levels related temporally to clinical improvement of levels of acute phase reactants. Thirty patients with Glasgow Coma Scale (GCS) scores of 3 through 10 were observed for 15 days after head injury. Peak elevation of plasma IL-6 occurred on admission (85 +/- 12 U/ml; normal level is less than 2 U/ml) and then decreased during the hospital course to a level of 29 +/- 4 U/ml on day 15. Plasma IL-6 levels decreased significantly faster in patients with admission peak 24-hour GCS scores of 8 through 10 compared with patients with GCS score less than 8 (p less than 0.01). Patients had markedly elevated and variable ventricular fluid IL-6 levels on admission (mean 3880 +/- 2022 U/ml; normal, less than 2 U/ml). A temporal relationship was found between plasma IL-6 levels and multiple acute phase reactants thought to be mediated by IL-6. We conclude that plasma and ventricular fluid levels of IL-6 are elevated after head injury and that plasma IL-6 level is temporally related to acute phase reactants and clinical improvement. We suggest that IL-6 may play an etiologic role in many of the metabolic or nutritional sequelae of head injury.

Adolescent↗
PubMed1990

Gastrointestinal behavior of orally administered radiolabeled erythromycin pellets in man as determined by gamma scintigraphy.

The behavior of single 250-mg doses of a multiparticulate form of erythromycin base (ERYC(R)), each including five pellets radiolabeled with neutron-activated samarium-153, was observed by gamma scintigraphy in seven male subjects under fasting and nonfasting conditions. The residence time and locus of radiolabeled pellets within regions of the gastrointestinal tract were determined and were correlated with plasma concentrations of erythromycin at coincident time points. Administration of food 30 minutes postdosing reduced fasting plasma erythromycin Cmax and area under the plasma erythromycin versus time curve (AUC) values by 43% and 54%, respectively. Mean peak plasma concentration of erythromycin (Cmax) in the fasting state was 1.64 micrograms/mL versus 0.94 micrograms/mL in the nonfasting state. Total oral bioavailability, as determined by mean AUC (0-infinity) of the plasma erythromycin concentration versus time curve, was 7.6 hr/micrograms/mL in the fasted state, versus 3.5 hr/micrograms/mL in the nonfasting state. Mean time to peak plasma erythromycin concentration (tmax) in the fasting state was 3.3 hours, versus 2.3 hours in the nonfasting state. Plasma concentrations of erythromycin in both fasting and nonfasting states were within acceptable therapeutic ranges. Evidence provided by this study: 1) indicates that pellet erosion and absorption of active erythromycin base begins when the enteric-coated pellets reach the highly vascular mucosa of the jejunum and proximal ileum, and is essentially completed within the ileum, with a significant portion absorbed in the medial-to-distal ileum; 2) confirms that acceptable therapeutic plasma levels of erythromycin are attained in nonfasting subjects (Cmax = 0.94 microgram/mL) and that superior plasma erythromycin concentrations (Cmax = 1.64 micrograms/mL) are achieved by administration of the dose on an empty stomach 1 to 2 hours before or after meals; 3) corroborates other comparative studies reporting greater fasting bioavailability with this multiparticulate dosage form of erythromycin base than with reference single tablet or particle-in-tablet formulations; and 4) indicates that neutron activation of stable isotopes incorporated as a normal excipient in industrially-produced formulations provides an effective means for in vivo evaluation of dosage forms through gamma scintigraphy.

Administration, Oral↗
PubMed1990

Brain injury and nutrition.

This review has discussed the current status of metabolic alterations and demands, nutrient administration, and nutritional assessment of the head-injured patient. More work is necessary in all areas to further describe and ascertain the nutritional requirements of these patients. Future research in this area should involve specific nutrient requirement, modification of the acute-phase response, and possibly administration of growth factors.

Brain Injuries↗
PubMed1988

Intolerance to enteral feeding in the brain-injured patient.

Calorie and protein supplementation improves nutritional status. This support may improve outcome and decrease morbidity and mortality in acutely brain-injured patients. Investigators have observed a poor tolerance to enteral feedings after brain injury and have noted that this persists for approximately 14 days postinjury. This delay has been attributed to increased gastric residuals, prolonged paralytic ileus, abdominal distention, aspiration pneumonitis, and diarrhea. In the present investigation, 23 brain-injured patients with an admission 24-hour peak Glasgow Coma Scale (GCS) score between 4 and 10 were studied for 18 days from hospital admission. The mean duration from injury to initiation of full-strength, full-rate enteral feeding was 11.5 days. Seven of the 23 patients tolerated enteral feedings within the first 7 days following hospital admission (mean 4.3 days), four patients tolerated feedings between 7 and 10 days postadmission (mean 9 days), and 12 patients did not tolerate feedings until after 10 days postinjury (mean 15.9 days). There was a marginally significant relationship between low GCS scores on admission and length of days to enteral feeding tolerance (p = 0.07). A significant inverse relationship was observed between daily peak intracranial pressure (ICP) and time to tolerance of feedings (p = 0.02). There was no significant relationship between feeding tolerance and days to return of bowel sounds (p = 0.12). Serum albumin levels decreased during the investigation (mean +/- standard error to the mean: 3.2 +/- 0.12 gm/dl on Day 1; 2.7 +/- 0.23 gm/dl on Day 16; normal = 3.5 to 5.0 gm/dl), whereas the percentage of patients tolerating feedings increased over the course of the study. The authors conclude that patients with acute severe brain injury do not adequately tolerate feedings via the enteral route in the early postinjury period. Tolerance of enteral feeding is inversely related to increased ICP and severity of brain injury. It is suggested that parenteral nutritional support is required following brain injury until enteral nutrition can be tolerated.

Adult↗
PubMed1987

Phenobarbital induction and acetaminophen hepatotoxicity: resistance in the obese Zucker rodent.

The obese Zucker rodent appears to lack a significant induction response after phenobarbital pretreatment. Induction of the hepatic cytochrome P-450 system with phenobarbital is known to enhance acetaminophen hepatotoxicity. The purpose of this study was to evaluate the influence of phenobarbital enzyme induction on acetaminophen hepatotoxicity in the obese and lean Zucker rodent. A preliminary study was performed evaluating the pharmacokinetics of acetaminophen in both the obese and lean Zucker rats. Data were utilized to calculate appropriate loading doses of acetaminophen during the subsequent hepatotoxicity study. Phenobarbital enzyme-inducing regimens were administered p.o. to achieve similar steady-state phenobarbital plasma concentrations. Control rats received appropriate placebo solutions. Serum hepatic transaminase enzymes and histologic evidence of hepatocellular necrosis were utilized to evaluate hepatic damage after p.o. administration of 1300 mg of acetaminophen to both obese and lean Zucker rats. Obese Zucker control animals had approximately 2.5 times the total hepatic glutathione content compared to their lean control (164.9 +/- 43.2 vs. 65.3 +/- 18.4 mumol/whole liver). Obese Zucker animals receiving only acetaminophen showed a trend toward a reduced incidence of hepatocellular necrosis compared to similarly treated lean littermates. Obese Zucker rodents pretreated with phenobarbital had an even more pronounced resistance to acetaminophen-induced hepatocellular necrosis (P less than .01) when compared to similarly treated lean littermates. Thus, acetaminophen hepatotoxicity is reduced in the obese Zucker rat and pretreatment with phenobarbital offers further protection against hepatocellular damage. We suggest that the previously unrecognized increase in hepatic glutathione plays a major role in the resistance of the obese Zucker rat to acetaminophen hepatotoxicity.

Acetaminophen↗
PubMed1985

Abnormal polyunsaturated fatty acid patterns of serum lipids in alcoholism and cirrhosis: arachidonic acid deficiency in cirrhosis.

Patterns of polyunsaturated fatty acids of serum phospholipids were measured for groups of alcoholics without cirrhosis, alcoholics with cirrhosis, cirrhotics without alcoholism, and a control population. Alcoholics without cirrhosis showed increased polyunsaturated fatty acids derived from linoleic and linolenic acids, but in cirrhotics these products were decreased. Alcoholism accentuated the abnormal polyunsaturated fatty acid pattern of cirrhosis. In alcohol abuse without cirrhosis, the level of 20:3 omega 9 (20 acyl carbon atoms:3 double bonds, omega, 9 carbon atoms beyond last double bond) was significantly increased, despite adequate levels of linoleic and arachidonic acids. Liver involvement appears necessary for development of deficiencies of polyunsaturated fatty acids in serum phospholipids, of which arachidonic acid deficiency is of the largest magnitude.

Adolescent↗
PubMed1985

Metabolic and nutritional sequelae in the non-steroid treated head injury patient.

Energy production, substrate oxidation, serum protein levels, and weight change were studied in 16 non-steroid treated patients with severe head injury. Patients were evaluated during an average of 31.3 days from hospital admission to discharge. The mean measured energy expenditure (MEE) was 1.40 +/- 0.5 times predicted energy expenditure. Caloric balance [calories received = calories expended] was achieved by the 2nd week. Despite caloric balance and the administration of at least 1.5 g of protein per kg of body weight per day, the mean nitrogen balance was negative. There was a positive nitrogen balance in only 2 patients. These patients received a mean of 1.43 times the MEE in total kilocalories and 2.3 g of protein per kg of body weight. Fat and protein oxidation exceeded protein and fat administration for 3 weeks postinjury. Albumin levels dropped from a mean of 3.09 +/- 0.2 on admission to 1.98 +/- 0.4 within 2 weeks. The initial retinol binding protein levels were within the normal range, and the levels increased over time. There was marked weight loss (mean, 15.6 +/- 5.9 lb). Head injury induces a profound traumatic response identified by increased energy expenditure, a negative nitrogen balance, weight loss, hypoalbuminemia, and altered substrate oxidation. This response seems to be caused by the head injury alone and is not due to the administration of corticosteroids.

Adolescent↗
PubMed1981

Women's choice of home or hospital birth.

In the current professional debate over the relative advantages and disadvantages of birth in hospitals vs birth at home, chief concern has been given to issues of medical risk. However, little is known about how lay women as consumers of maternity care assess the risks of birth location. This paper briefly reviews the social literature examining the factors that influence women's obstetric plans in a variety of social and cultural contexts. Two important considerations emerge. First, women's perceptions of medical risk frequently do not conform to mainstream obstetrics doctrine, and second, women's birth plans are based on evaluations of social as well as medical risks and benefits connected with place of birth.

Decision Making↗
PubMed1980

Zinc deficiency: a complication of Crohn's disease.

Twenty-one of 52 patients with regional enteritis had low serum zinc concentrations on initial testing. Fourteen of 31 patients followed longitudinally had low serum zinc concentrations. Two patients are presented as case reports who developed acrodermatitis skin lesions that responded to zinc therapy. Hypogonadism, growth retardation, and abnormalities in taste were frequent complications in Crohn's patients with low serum zinc levels. Certain complications of regional enteritis may be due, in part, to zinc deficiency.

Adult↗