Search PubMed⌕ Search

Biomedical subjects

K D Mullen

Publications and source records attributed to K D Mullen.

At least 55 records · Page 3Linked to original sources
PubMed1992

Large-cell carcinoma of the lung. With major bleeding and intussusception.

We describe an unusual case of major small-bowel bleeding and intussusception due to jejunal metastases from a large-cell type carcinoma of the lung. Review of the surprisingly frequent case reports of small bowel metastases from primary lung tumors indicates that there is only one prior case report of intussusception and that ours is the first description of major intestinal hemorrhage due to metastatic pulmonary carcinoma.

Carcinoma, Bronchogenic↗
PubMed1992

Body cell mass and leucine metabolism in cirrhosis.

To investigate the influence of body composition on leucine metabolism, leucine turnover and oxidation were measured in six patients with stable biopsy-proven cirrhosis and in six age- and gender-matched controls using [1-14C]leucine tracer. Fat-free body mass and body cell mass were estimated from quantified measurements of H2(18)O and bromide dilution. Although there were no differences in body weight, body surface area, body mass index, or fat-free body mass between study groups, body cell mass was decreased in cirrhotic patients (37.6 +/- 0.1 vs. 46.4 +/- 1.8 kg; P less than 0.05). Leucine turnover did not significantly differ between groups in absolute values or when corrected for body weight or fat free body mass. However, cirrhotic patients had accelerated leucine turnover based on body cell mass (171.3 +/- 8.2 vs. 143 +/- 7.6 mumol.kg-1.h-1; P less than 0.03). Plasma leucine levels were decreased in cirrhosis (76.9 +/- 9.7 vs. 117.9 +/- 8.1 mumol/L; P less than 0.001) and correlated with an expanded extracellular water compartment (r = -0.91; P less than 0.001) and leucine oxidation (r = 0.91; P less than 0.01) in the cirrhotic patients but not in the control subjects. These data indicate that body composition and fluid compartments are important factors influencing leucine metabolism in cirrhosis and should be considered in future studies.

Adult↗
PubMed1991

The influence of portacaval anastomosis on gonadal and anterior pituitary hormones in a rat model standardized for gender, food intake, and time after surgery.

Portacaval anastomosis causes delayed growth, decreased testes and liver weights, and elevated estradiol serum levels in male rats compared with sham-operated controls. Female rats treated with portacaval anastomosis grow at a normal rate despite changes in liver weight and estradiol levels similar to those observed in the male rats. This study examined the pituitary gonadal axis in both genders in this animal model. The rats receiving portacaval anastomosis were compared with both pair-fed and sham-operated control groups. Portacaval anastomosis decreased serum testosterone and increased estradiol in the male animals, while both testosterone and estradiol were increased in the females compared with gender-matched pair-fed and sham controls. Because pair feeding lowers male testosterone to a lesser extent, impaired nutrition may partially account for the decrease in the males treated with portacaval anastomosis. The ratio of estradiol to testosterone increased following anastomosis in male rats, but it was decreased in similarly treated females. Portacaval and anastomosis decreased luteinizing hormone without changing follicle-stimulating hormone in both male and female rats compared with sham-operated controls. Growth hormone was significantly decreased in male portacaval-treated rats compared with sham- and pair-fed animals. Increased insulin levels were found in both male and female pair-fed and portacaval anastomosis-treated animals. These data suggest that following portacaval anastomosis in rats, growth, serum testosterone, estradiol to testosterone ratios, and growth hormone are altered in a gender-specific manner with gender-independent changes in insulin and luteinizing hormone levels. These gender-specific effects may protect the portacaval anastomosis-treated female rat from growth retardation.

Animals↗
PubMed1991

Measurements of total body and extracellular water in cirrhotic patients with and without ascites.

Using H2[18O] tracer isotope dilution and corrected bromide space as standard reference techniques, we determined total body water and extracellular water in cirrhotic patients with (four men and four women) and without (seven men and six women) ascites and compared them with a normal control group (eight men and six women). These results were then compared with calculations of total body and extracellular water determined by the bioelectrical impedance analysis technique. According to H2[18(O)] dilution, total body water was similar in cirrhotic patients without ascites and in controls (60.8% +/- 2.1% vs. 60.3% +/- 1.4% body wt), but was increased in patients with ascites (69.7% +/- 1.2% body wt; p less than 0.002). Correlation was excellent between the H2[18(O)] dilution and bioelectrical impedance measurements of total body water in controls and cirrhotic patients without ascites (r = 0.98; p less than 0.0001). However, this correlation was poor in cirrhotic patients with ascites (r = 0.17; not significant). According to the bromide space, extracellular water (expressed as a percentage of total body water) was increased in cirrhotic patients with (57.8% +/- 1.8%; p less than 0.001) and without (44.0% +/- 1.2%; p less than 0.001) ascites compared with controls (36.6% +/- 1.0%). A poor correlation (r = 0.41; p less than 0.13) was seen for extracellular water measurements between the bromide space method and the bioelectrical impedance method, which failed to detect the differences among the three groups observed with the bromide space technique. Furthermore, bioelectrical impedance failed to detect any change in total body or extracellular water after paracentesis, with a degree of inaccuracy that increased linearly as the amount of ascitic fluid removed increased (r = 0.97; p less than 0.001). All these intergroup comparisons remained the same, whether the analysis was of both men and women combined or for each gender individually. However, we saw differences between men and women in the control group and cirrhotic group without ascites. These results demonstrate that abnormalities in water homeostasis and compartmentalization between intracellular (the difference between total body and extracellular water fluid) and extracellular water may exist in cirrhosis whether or not fluid accumulation is clinically evident. These data further indicate that alterations in the metabolically active body cell mass (as represented by intracellular water) in cirrhosis may occur independently of total body water and calculated fat-free body mass. In addition, gender is an important variable to control for in studies of this type.(ABSTRACT TRUNCATED AT 400 WORDS)

Abdomen↗
PubMed1991

Shock wave-induced pancreatic trauma.

A case is described of the appearance of a pancreatic or peripancreatic lesion after left renal calculus fragmentation by extracorporeal shock wave lithotripsy (ESWL). Its anatomical location and subsequent disappearance suggest it was related to trauma caused by the shock waves. The brief literature on pancreatic injury after ESWL is reviewed, and the role of the patient's underlying liver disease in the genesis of this complication is discussed.

Adult↗
PubMed1990

"Endogenous" benzodiazepine activity in body fluids of patients with hepatic encephalopathy.

Body fluids from patients with hepatic encephalopathy and from controls with no renal or hepatic disease were assayed for benzodiazepine immunoreactivity and benzodiazepine-receptor-binding activity. The subjects had taken no synthetic benzodiazepines for at least 3 months. Benzodiazepine receptor binding in cerebrospinal fluid was significantly higher in hepatic encephalopathy patients than in controls (210 [SE 50.2] vs 40.7 [7.3] oxazepam equivalents [ng/ml]). The severity of hepatic encephalopathy was directly and significantly correlated with the level of benzodiazepine activity by radioreceptor assay or radioimmunoassay in urine and in plasma. Benzodiazepine activity equivalent to levels of more than 900 ng/ml was found in patients with advanced encephalopathy. Although the chemical identity and source of this substance (or substances) are still unknown, its properties and the estimated levels of activity suggest it may have a role in the pathogenesis of the neural inhibition seen in hepatic encephalopathy.

Benzodiazepines↗
PubMed1990

Quinine hepatotoxicity. An underrecognized or rare phenomenon?

Quinine-induced hepatic injury has been reported very rarely. We report a case involving a patient with an apparent hypersensitivity to quinine, manifested by a clinical syndrome mimicking a viral illness and a mixed hepatocellular-cholestatic liver injury pattern. We briefly review the unusual literature on this topic, which features many cases of hypersensitivity to the optical isomer of quinine, quinidine; yet, to our knowledge, there has only been one prior report of quinine hepatotoxicity.

Adult↗
PubMed1990

Synaptic membrane complex carbohydrates in experimental hepatic encephalopathy.

To evaluate further the status of synaptic plasma membranes (SPMs) in the brain in the syndrome of hepatic encephalopathy (HE) lipid- and protein-bound sialic acid and ganglioside and protein composition were investigated in SPMs from the brains of six rabbits with galactosamine-induced fulminant hepatic failure and five normal rabbits. HE was associated with no appreciable changes in the chromatographic pattern of gangliosides or the concentration of protein-bound sialic acid, but the syndrome was associated with a 20% increase in lipid-bound sialic acid and, as assessed electrophoretically, an increase in the concentration of a protein with a molecular weight of about 70 kDa. Thus, changes in the composition of complex carbohydrates and protein in SPMs occur in a model of HE. The findings raise the possibility that nonhumoral factors, such as increased sialylation of glycolipids, contribute to the generation of abnormal neurotransmission in HE.

Animals↗
PubMed1990

Increased brain uptake of gamma-aminobutyric acid in a rabbit model of hepatic encephalopathy.

Transfer of the inhibitory neurotransmitter gamma-aminobutyric acid across the normal blood-brain barrier is minimal. One prerequisite for gamma-aminobutyric acid in plasma contributing to the neural inhibition of hepatic encephalopathy would be that increased transfer of gamma-aminobutyric acid across the blood-brain barrier occurs in liver failure. The aim of the present study was to determine if brain gamma-aminobutyric acid uptake is increased in rabbits with stage II-III (precoma) hepatic encephalopathy due to galactosamine-induced fulminant hepatic failure. A modification of the Oldendorf intracarotid artery-injection technique was applied. [3H] gamma-aminobutyric acid, [14C] butanol, and 113mIn-labeled serum protein (transferrin) were injected simultaneously 4 s before decapitation. The ipsilateral brain uptake index of gamma-aminobutyric acid was determined from measurements of the 3 isotopes in 5 brain regions. Uncorrected or simple brain uptake indices of [3H] gamma-aminobutyric acid and [113mIn] transferrin were calculated using [14C] butanol as the highly extracted reference compound. The [113mIn] transferrin data were also used to "correct" the brain uptake index of [3H] gamma-aminobutyric acid for intravascular retention of [3H] gamma-aminobutyric acid. The methodology adopted minimized problems attributable to rapid [3H] gamma-aminobutyric acid metabolism, and slow brain washout and recirculation of the radiolabeled tracers. Both the uncorrected and corrected brain uptake indices of gamma-aminobutyric acid as well as the simple brain uptake index of transferrin were significantly increased in both stage II and III hepatic encephalopathy in all brain regions studied. Moreover, these brain uptake indices were significantly greater in stage III hepatic encephalopathy than in stage II hepatic encephalopathy. These findings indicate that transfer of gamma-aminobutyric acid from plasma to brain extracellular fluid is increased in the model of hepatic encephalopathy studied; hence, they provide support for the hypothesis that plasma-derived gamma-aminobutyric acid may contribute to the neural inhibition of hepatic encephalopathy due to fulminant hepatic failure.

Animals↗
PubMed1990

[Autoradiography determination of the GABA(A) receptor density in the brain of rats with portacaval shunt].

Quantitative autoradiography was used to assess the densities of gamma-aminobutyric acid (GABAA) receptors in the brains of rats with a portacaval end-to-side shunt (PCA). The shunt alone induced only mild encephalopathy with ataxia and decreased locomotion. Aggravation of the encephalopathy was achieved by gavage feeding of packed erythrocytes or by induction of severe hyperammonemia by intraperitoneal injection of urease. Gavage feeding of erythrocytes led to severe encephalopathy in about 50% of the animals with PCA. The combination of PCA and urease treatment caused severe encephalopathy in every animal. The serum ammonia concentration increased 5 times normal by PCA alone, 20 times normal by gavage feeding of erythrocytes and more than 30 times normal by urease-treatment of the PCA-animals. For autoradiography, coronal slices were cut at the level of the hippocampal formation and through the cerebellum. Radioligand binding was measured using as a ligand 3H-muscimol, a specific GABAA receptor agonist. The specific binding of 3H-muscimol was assessed densitometrically in several microregions of cerebral cortex, hippocampus and cerebellar cortex. No significant differences were observed between the magnitude of ligand binding to specific microregions of brains from normal animals, animals with PCA without overt encephalopathy and animals with severe encephalopathy induced by a combination of PCA and gavage feeding of erythrocytes or urease treatment.

Ammonia↗
PubMed1989

NIH conference. The gamma-aminobutyric acid A (GABAA) receptor complex and hepatic encephalopathy. Some recent advances.

Increased neural inhibition appears to be an important component of the syndrome of hepatic encephalopathy. The pathways subserved by the gamma-aminobutyric acid (GABA)-benzodiazepine receptor complex are the principal inhibitory systems in the mammalian brain. Hyperpolarization of neural membranes is accomplished by an increase in transmembrane chloride flux through a GABA-gated chloride channel in the complex. The opening of the chloride channel is induced by the binding of GABA to its receptors, and it is potentiated by barbiturates or benzodiazepines that act at distinct recognition sites on the complex. Involvement of the GABA neurotransmitter system in hepatic encephalopathy is suggested by several findings in animal models of fulminant hepatic failure. For example, hepatic encephalopathy resembles encephalopathies induced by drugs (including benzodiazepines) that potentiate GABAergic neurotransmission. In addition, neurons from animals with hepatic encephalopathy show increased sensitivity to benzodiazepine and GABA receptor agonists. Moreover, these neurons are excited by benzodiazepine receptor antagonists at concentrations that do not affect control neurons. Also, elevated levels of a substance that inhibits radioligand binding to benzodiazepine receptors have been found in cerebrospinal fluid from animals with hepatic encephalopathy. Furthermore, manifestations of hepatic encephalopathy can be ameliorated by benzodiazepine receptor antagonists. The relevance of these findings to hepatic encephalopathy in human beings is supported by clinical observations showing that a benzodiazepine receptor antagonist can lessen the degree of hepatic encephalopathy. These findings suggest that an endogenous substance with benzodiazepine-like properties contributes to the neuropsychiatric manifestations of hepatic encephalopathy by augmenting GABAergic neurotransmission.

Action Potentials↗
PubMed1989

Evidence for the presence of a benzodiazepine receptor binding substance in cerebrospinal fluid of a rabbit model of hepatic encephalopathy.

Based on the reversal of hepatic encephalopathy in animal models with administration of specific benzodiazepine receptor antagonists, it has been postulated that this syndrome may be mediated by an endogenous benzodiazepine-like compound. In this study using a radio-receptor assay, evidence for the existence of this substance has been demonstrated in cerebrospinal fluid but not sera of rabbits with hepatic encephalopathy due to galactosamine-induced hepature failure. Cerebrospinal fluid from rabbits with hepatic encephalopathy caused 36.1 +/- 5.03% displacement of 3H-Ro 15-1788 specific binding to cortical benzodiazepine receptors, compared to 11.7 +/- 0.76% in control animals (P less than 0.01). The benzodiazepine receptor binding activity has been shown to behave as a competitive inhibitor of radiolabeled benzodiazepine receptor binding. The finding of endogenous benzodiazepine binding activity affords a potential explanation for the amelioration of hepatic encephalopathy in this model with the administration of benzodiazepine receptor antagonists.

Aminocaproates↗
PubMed1989

Cortical benzodiazepine receptor binding in a rabbit model of hepatic encephalopathy: the effect of Triton X-100 on receptor solubilization.

Increased benzodiazepine (BZ) receptor density has been reported in brains of rabbits with hepatic encephalopathy (HE) due to galactosamine (GalN)-induced fulminant hepatic failure (FHF). These data were generated using detergent-Triton X-100-treated neural membranes. While performing further studies it was noted that the increase in BZ receptor density was not demonstrable when Triton X-100 preparation was not employed. Accordingly the binding of [3H] flunitrazepam, a BZ ligand, to neural membranes from cortices of normal rabbits and rabbits with HE due to (GalN)-induced FHF was studied with and without detergent preparation. Scatchard plot analysis of the binding data indicated that when no detergent was employed, the apparent affinity and density of BZ receptors were similar for control membranes and membranes from animals in HE. BZ receptors from animals in HE were shown to be more resistant to solubilization by Triton than control membranes. These findings (a) afford a potential explanation for the apparent increase in density of BZ receptors in this model when Triton treatment of neural membranes is utilized and (b) suggest that recent evidence for increased GABAergic tone in the syndrome of HE is not dependent on an increased density of BZ receptors.

Animals↗