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Biomedical subjects

D S Camara

Publications and source records attributed to D S Camara.

At least 19 recordsLinked to original sources
PubMed1993

Pharmacokinetics of methylprednisolone hemisuccinate and methylprednisolone in chronic liver disease.

The disposition of methylprednisolone (MP) and its prodrug hemisuccinate (MPHS) was assessed in six middle-aged patients with chronic liver disease (CLD) and compared with six younger, healthy subjects after a single IV dose of 25.4 mg of MPHS. Blood and urine samples were collected over 12 hours. Plasma and urine concentrations of MPHS and MP and plasma cortisol were measured by HPLC. MPHS clearance (CL) was significantly reduced in the CLD group (495 vs. 1389 mL/hr/kg) whereas volume of distribution (Vss) of MPHS (about 0.35 1/kg) did not differ. The elimination half-life, t1/2 beta, was significantly longer in CLD (0.61 vs. 0.32 hr). The percent recovery of unchanged MPHS in urine was similar (about 9%) in both groups. The kinetic parameters of MP did not differ between the two groups for: clearance (about 370 L/hr/kg IBW), Vss (about 1.3 L/kg), and t1/2 beta (about 3.0 hr). The suppression t1/2 of cortisol after MPHS was longer (3.9 vs. 1.9 hr) indicating metabolic pathways for cortisol and MP are affected differently in CLD. Reduction in MPHS CL may reflect altered hepatic blood flow due to both cirrhosis and age effects. However, good availability of MP from MPHS and lack of perturbation of MP pharmacokinetics in CLD patients may provide therapeutic advantages in selection of this glucocorticoid. This is the first study that characterizes the disposition of the prodrug MPHS and the formation of MP simultaneously in CLD patients.

Adult↗
PubMed1991

Pharmacokinetics and pharmacodynamics of methylprednisolone in obesity.

Methylprednisolone pharmacokinetics and its directly suppressive effects on plasma cortisol, blood histamine (basophils), and circulating helper T cells were evaluated in six obese (at least 35% above ideal body weight) men and six nonobese male volunteers. Methylprednisolone doses of 0.6 mg/kg total body weight were administered as the 21-succinate sodium salt. Absolute clearance (in liters per hour) of methylprednisolone was 40% less in the obese subjects. Total volume of distribution (Vss) of methylprednisolone was unchanged (about 120 L), but when normalized for total body weight, Vss per kilogram was less in obesity. The patterns of cortisol, blood histamine, and helper T cell responses after methylprednisolone administration were similar in both groups, but more profound effects were observed in the obese subjects. Pharmacodynamic models were applied for these immediate effects of methylprednisolone based on the premise that receptor interactions of steroids are followed by rapid suppression of the circadian rhythm of cortisol and recirculation of basophils and helper T cells, which persist until inhibitory concentrations (IC50) of methylprednisolone disappear. Similar IC50 values for the three effects were obtained in both groups, indicating no intrinsic pharmacodynamic differences in sensitivity to these methylprednisolone effects in obesity. However, methylprednisolone should be administered on the basis of ideal body weight, and the dosing interval should be potentially lengthened because of decreased methylprednisolone clearance in obesity.

Adult↗
PubMed1989

Peritoneovenous shunting as compared with medical treatment in patients with alcoholic cirrhosis and massive ascites. Veterans Administration Cooperative Study on Treatment of Alcoholic Cirrhosis with Ascites.

The optimal management of severe ascites in patients with alcoholic cirrhosis has not been defined. in a 5 1/2-year study, we randomly assigned 299 men with alcoholic cirrhosis, who had persistent or recurrent severe ascites despite a standard medical regimen, to receive either intensive medical treatment or peritoneovenous (LeVeen) shunting. We identified three risk groups: Group 1 had normal or mildly abnormal results on liver-function tests, Group 2 had more severe liver dysfunction or previous complications, and Group 3 had severe prerenal azotemia without kidney disease. For the patients who received the medical treatment and those who received the surgical treatment combined, the median survival times were 1093 days in Group 1, 222 days in Group 2, and 37 days in Group 3 (P less than or equal to 0.01) for all comparisons). For all the groups combined, the median time to the resolution of ascites was 5.4 weeks for medical patients and 3.0 weeks for surgical patients (P less than 0.01). Within each risk group, mortality during the initial hospitalization and median long-term survival were similar among patients receiving either treatment. However, the median time to the recurrence of ascites in Group 1 was 4 months in medical patients, as compared with 18 months in surgical patients (P = 0.01); in Group 2 it was 3 months in medical patients as compared with 12 months in surgical patients (P = 0.04). The median duration of hospitalization was longer in medical patients than in surgical patients (6.1 vs. 2.4 weeks in Group 1 [P less than 0.001] and 5.0 vs. 3.1 weeks in Group 2 [P less than 0.01]). Group 3 was too small to permit a meaningful comparison. During the initial hospitalization, the incidence of infections, gastrointestinal bleeding, and encephalopathy was similar among the medical and surgical patients. We conclude that peritoneovenous shunting alleviated disabling ascites more rapidly than medical management. However, survival was closely related to the severity of the illness at the time of randomization and was not altered by shunting.

Ascites↗
PubMed1988

Complications of gastrostomy.

Despite its simplicity, gastrostomy has been associated with a relatively high incidence of complications. We have described two unusual complications: inadvertent duodenostomy, resulting in gastric outlet obstruction, and the migration of a gastrostomy feeding tube into the midportion of the jejunum, resulting in obstruction of the small bowel.

Aged↗
PubMed1986

IgA antibody to lipid A in alcoholic liver disease.

To find out whether the increased immunoglobulin A (IgA) levels commonly reported in patients with alcoholic liver disease (ALD) are part of the immune response to gut-derived endotoxin antigen, an enzyme-linked immunoabsorbent assay was used to measure serum levels of antibodies to lipid A (the shared core of various lipopolysaccharides and the biologically active component of endotoxins) in patients with various diseases and in controls. Of 41 patients with ALD, 35 had significantly raised titres of IgA anti-lipid A. Rises of antilipid A were found in the secretory fraction of IgA as well, and titres of IgG antibody were also consistently increased. IgM titres were high in only 7 of 35 ALD patients tested. Patients with other diseases did not show significantly high titres of IgA antibodies to lipid A even though many had rises in total concentration of their serum IgA.

Antibodies↗
PubMed1985

Safety and pharmacokinetics of ceftazidime in patients with chronic hepatic dysfunction.

Safety and pharmacokinetic parameters of ceftazidime were evaluated in twelve male volunteers mean age 54.6 +/- 9.2 years. All had chronically impaired hepatic function which remained stable or normalized during ceftazidime administration. There was neither nephrotoxicity nor haematological toxicity. Serum concentration time curves of ceftazidime exhibited a biexponential decline. Drug accumulation was not apparent. Following doses 4 and 13, mean serum half-lives were 2.8 and 2.9 h, volumes of distribution 0.15 +/- 0.04 l/kg and 0.17 +/- 0.041 l/kg and plasma clearance values 1.320 +/- 0.50 ml/min/kg and 1.096 +/- 0.48 ml/min/kg, respectively. Dose modification based on hepatic dysfunction is unnecessary.

Ceftazidime↗
PubMed1985

Heterotopic gastric mucosa: a case report.

A case of heterotopic gastric mucosa in discrete nodules of the duodenum is presented. Its radiographic and endoscopic appearance is described. The light and electron microscopic features are analyzed. Ultrastructural examination of its organization, cellular and subcellular components revealed similarities to normal fundic gastric mucosa. The histological and clinical differences between heterotopic gastric mucosa and duodenal metaplastic change are discussed.

Choristoma↗
PubMed1985

The importance of intestinal endotoxins in liver disease.

The development and wider use of the Limulus amoebocyte lysate assay (LAL) for the detection of endotoxin, has led to renewed interest in the link between gut-derived endotoxin, liver injury and the extra-hepatic manifestations of clinical liver disease. The concept that endotoxemia may occur and be harmful in clinical states without the concomitant presence of Gram-negative bacteria is a relatively recent one and has been most intensively studied in the context of liver injury. Since the liver stands between the gut and the systemic circulation, it has been postulated that failure to detoxify endotoxins absorbed into the portal circulation after hepatic injury might lead to further liver damage and escape of this toxic material into the general circulation. The present review will update the status of this hypothesis, discuss mechanisms proposed for the damage and present evidence for the association in animal models. Finally, studies both positive and negative, will be cited that have used the LAL to detect endotoxemia and its consequences in human liver disease.

Absorption↗
PubMed1985

The hemodynamic effects of the sclerosant sodium morrhuate in dogs.

The hemodynamic effects of systemic administration of 5 per cent sodium morrhuate was evaluated in normal dogs. Dogs in the control group were injected with 2 per cent benzyl alcohol with pH adjusted to 9.5. Animals injected with sodium morrhuate had a significant reduction in cardiac output, arterial blood pressure, portal vein and hepatic artery flows. These changes occurred primarily in the first 30 minutes of observation. In response to the reduction of the hepatic blood flow, there was an increase in portal vein pressure and resistance.

Animals↗
PubMed1984

Rapid alterations in substrate profiles after partial hepatectomy in the rat.

We compared alterations in circulating levels of insulin and glucagon and metabolic fuels in response to partial (70%) hepatectomy (HP) and sham hepatectomy (SHP) in fasting rats and in unanesthetized, fasting control rats. Within 15 minutes, animals in the HP group were hypoglycemic compared with the SHP and control groups. After 30 minutes, the insulin concentration and the insulin-glucagon molar ratio (IGR) rose in the HP group. After four hours, animals in the HP group were hyperglycemic compared with the SHP and control animals. Comparison of the lipid and amino acid profiles suggested use of these substrates by eight hours. The levels of branched-chain amino acids, although depressed early after HP, were markedly elevated later, when the IGR in the HP group had normalized. The acute loss of hepatic mass by limiting gluconeogenesis may be the cause of hypoglycemia and also could alter the plasma IGR because of the different hepatic clearance rates of these hormones. A switch to lipid and protein as metabolic fuels appears to follow these early changes.

Amino Acids↗
PubMed1984

Simplified portoazygous disconnection (Tanner's operation) combined with operative sclerotherapy for bleeding varices.

A simplified method of portoazygous disconnection employing the linear stapler and operative sclerotherapy was employed in six patients. Endoscopic maintenance sclerotherapy was instituted for five patients in the follow-up period. Combining the operative and endoscopic modalities is attractive, since the deficiencies of each tend to be offset by the other.

Combined Modality Therapy↗
PubMed1984

The clearance capacity of the canine liver for a portal vein endotoxin infusion.

The capacity of the livers of anesthetized dogs to clear a portal vein infusion of Escherichia coli 026 endotoxin was evaluated. Appearance of the endotoxin in arterial blood was quantitated by immunoradiometric assay. Various hemodynamic and metabolic parameters were monitored throughout the infusion to corroborate the development of systemic endotoxemia. Significant amounts of E. coli 026 endotoxin were detected in arterial blood after infusion of 240 micrograms endotoxin. As expected, systemic endotoxemia was associated with decreased cardiac index, mean arterial blood pressure, heart rate, and splanchnic (portal vein) blood flow. Changes in plasma levels of glucose, insulin, and glucagon and in the pancreatic outputs of insulin and glucagon did not occur before the development of severe hypotension and the termination of the study. It was concluded that the liver clearance capacity for endotoxin in the dog is 0.72 microgram/gm liver/hour and that severe hemodynamic alterations develop in this animal model before changes in carbohydrate balance.

Animals↗