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Biomedical subjects

G L Carlson

Publications and source records attributed to G L Carlson.

At least 55 records · Page 3Linked to original sources

Thermogenic, hormonal, and metabolic effects of a TPN mixture. Influence of glucose and amino acids.

The thermogenic, hormonal, and metabolic effects of intravenous nutrition were examined by administering a complete total parenteral nutrition (TPN) mixture to 11 subjects, and the relative contributions of the glucose and amino acid components of the mixture were evaluated by administering these nutrients separately (n = 7 and n = 6, respectively). The complete TPN mixture caused a 22.9% rise in resting energy expenditure (REE), which significantly exceeded that associated with glucose (10.4% P < 0.02). The rise in REE produced by the amino acids (11.5%) did not differ significantly from that associated with administration of the TPN or glucose. The rise in REE associated with the TPN was almost exactly equal to the sum of the rises associated with the separate components of the mixture (22.9% and 22.0%, respectively), indicating that glucose and amino acids contributed equally to the thermogenic effect of the TPN mixture. In contrast, although the amino acid component of the TPN mixture was associated with small but significant reductions in plasma free fatty acid and glycerol concentration and with small increases in plasma insulin concentration, the effects of the complete TPN mixture were significantly greater and attributable to the glucose component.

Adult↗

Total parenteral nutrition modifies the acute phase response to Crohn's disease.

Measurements of the acute phase proteins, C-reactive protein (CRP) and orosomucoid are widely used to monitor the activity of Crohn's disease. The effect of TPN upon the levels of acute phase proteins is unknown. Serum levels of CRP and orosomucoid were measured simultaneously over a four year period in 13 patients receiving TPN for Crohn's disease, nine patients with noninflammatory causes of intestinal failure, and 16 patients with Crohn's disease treated without TPN. An acute phase response was found with a similar frequency in both groups of patients with Crohn's disease (73.6% and 83.9% for Crohn's with and without TPN respectively), but was less prevalent in patients receiving TPN for non-inflammatory causes of intestinal failure (56.1%, P < 0.01). In this latter group, the acute phase response consisted primarily of an isolated elevation of orosomucoid (78.4%), compared with patients with Crohn's disease alone (21.1%, P < 0.001) and with Crohn's disease and TPN (46.6%, P < 0.05). Liver function abnormalities were seen on 68.8% of occasions in patients with noninflammatory causes of intestinal failure who had elevated levels of orosomucoid, compared with 34.9% of occasions on which orosomucoid levels were normal (P < 0.001). TPN may lead to isolated elevation of serum levels of orosomucoid, reducing the value of this acute phase protein in monitoring the activity of Crohn's disease in patients receiving TPN.

Acute-Phase Proteins↗

Occlusion of silastic broviac catheters as a result of twisting between the catheter and hub assembly.

Occlusion is a common cause of catheter malfunction during home parenteral nutrition (HPN). We report 5 cases of central venous catheter occlusion, encountered over a 24 month period, which were associated with twisting of the catheter at the hub assembly. One catheter was replaced before the cause of the occlusion was identified. In 4 cases, twisting was noted prior to catheter removal, and this was corrected in three, allowing HPN to continue without catheter replacement. In 1 case the catheter was repaired. The current design of silastic Broviac catheters allows the catheter to twist around the hub assembly. Over-enthusiastic tightening of the cap of the catheter leads to twisting which causes catheter occlusion. A high index of suspicion should be maintained when dealing with catheter occlusion associated with silastic Broviac catheters. Recognition of the problem allows catheter salvage without recourse to catheter replacement.

Journal Article↗

Pseudomonas infection of the catheter exit site successfully managed with topical acetic acid.

A case of recurrent catheter exit site infection with Pseudomonas aeruginosa is presented in a patient receiving home parenteral nutrition. The past episodes were managed by elective catheter replacement following extrusion of the catheter cuff. We describe the successful use of acetic acid to the exit site which resulted in the eradication of the organism and complete resolution of all signs.

Journal Article↗

Polymicrobial catheter sepsis in long term central venous catheters.

We present 2 cases of polymicrobial catheter sepsis in patients with long term central venous catheters who were receiving home parenteral nutrition. Both patients were generally unwell with haemodynamic instability. Attempts at catheter salvage by combined antibiotic and fibrinolytic administration through the central line were unsuccessful and resulted in patient deterioration. Catheters were removed in both patients. We conclude that catheter salvage should be considered very carefully in patients with polymicrobial catheter sepsis and there should be a low threshold for catheter removal in these cases.

Journal Article↗

Treatment of common bile duct stones using mono-octanoin.

A retrospective analysis of 48 patients undergoing mono-octanoin infusion via nasobiliary catheter following failure of endoscopic extraction of common bile duct stones is reported. Among 35 patients who received a complete course of treatment, nine (26 per cent) had duct clearance by the completion of the infusion and a further eight on subsequent endoscopic retrograde cholangiopancreatography (ERCP) (total 49 per cent). Two patients had a successful stone extraction after enlargement of the sphincterotomy (total non-surgical clearance rate 54 per cent). None of five patients with stones greater than 2 cm in diameter had stone clearance at the completion of the infusion and only one at subsequent ERCP. Among 13 patients receiving an incomplete course of treatment seven had clear ducts on repeat ERCP (54 per cent). Mono-octanoin infusion via a nasobiliary catheter is of limited value in the management of this difficult group of patients, although it may be successful in some.

Aged↗

Role of endoscopic retrograde cholangiopancreatography in the investigation of pain after cholecystectomy.

Patients who continue to have or who develop abdominal pain after apparently successful cholecystectomy pose diagnostic difficulties. This study reports 384 such patients, investigated by endoscopic retrograde cholangiopancreatography (ERCP). There were 146 patients with abdominal pain alone with no previous history of common bile duct (CBD) exploration, of whom only 17 (11.6 per cent) had CBD stones on ERCP. Bile duct calculi were present in 76 of 140 patients (54.3 per cent) with abnormal biochemical findings (raised alkaline phosphatase and/or amylase level) and in 34 of 57 (60 per cent) with an abnormality detected on ultrasonography or intravenous cholangiography. A combination of biochemical and radiological abnormalities was present in 37 patients and was associated with CBD stones in 28 (76 per cent). Patients who had undergone CBD exploration represented a special group, of whom the majority (75 per cent) had common duct stones at ERCP even in the absence of biochemical and radiological abnormalities. ERCP is a useful investigation in patients with persistent postcholecystectomy symptoms. Other features in addition to pain or a history of CBD exploration may be relevant to the decision to perform ERCP in the investigation of these patients.

Abdominal Pain↗

Correspondence.

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Letter↗

Thallium isotope scintigraphy and ultrasonography: comparative studies of localization techniques in primary hyperparathyroidism.

Controversy exists about whether preoperative localization procedures are indicated in patients with primary hyperparathyroidism before first neck exploration. Currently, thallium subtraction scintigraphy and ultrasonography are the techniques used most frequently. This paper examines prospectively the accuracy and value of these techniques in a group of 71 patients with primary hyperparathyroidism. When considering all glands, thallium scanning produced a sensitivity of 46.6 per cent with a specificity of 91.5 per cent, compared with a sensitivity of only 21.4 per cent and specificity of 94.5 per cent for ultrasonography. Accuracy rates, for all glands, were 80 per cent and 75.7 per cent respectively. Both localization procedures were consistently ineffective in localizing adenomas weighing less than 500 mg, over 80 per cent of which went undetected by both scanning modalities. While both scans produced satisfactory results in localizing adenomas weighing more than 1 g, these adenomas should not represent a challenge to an experienced endocrine surgeon and, therefore, neither localization is recommended before first neck exploration.

Adenoma↗

Thallous chloride uptake and DNA profile in parathyroid adenomas.

Thallium isotope scintigraphy is used to localize parathyroid adenomas but the mechanism underlying the technique is poorly understood. While larger adenomas are reliably localized the results are less certain for small tumours. This study explores the relationship between cellular DNA profile and thallium uptake (localization accuracy) in 24 parathyroid adenomas. The DNA profile was assessed using flow cytometry and standard subtraction thallium scintigraphy was performed before surgery. Fifteen of the 24 adenomas demonstrated excessive mitotic activity and 13 of these glands were accurately localized. Of the remaining nine glands, only five were localized accurately (P less than 0.01, chi 2 test including Yates' correction). This difference in thallium uptake could not be accounted for on the basis of gland weight. Thallium localization of parathyroid adenomas is related to mitotic activity. This may explain some of the limitations of this technique.

Adenoma↗

Synthesis of prodan-phosphatidylcholine, a new fluorescent probe, and its interactions with pancreatic and snake venom phospholipases A2.

A new fluorescent probe, prodan-PC, was synthesized by incubating thio-PC, a thiol ester analogue of phosphatidylcholine [1,2-bis(decanoylthio)-1,2-dideoxy-sn-glycero-3-phosphocholine], with acrylodan, a fluorescent thiol-reactive reagent [6-acryloyl-2-(dimethylamino)naphthalene], in the presence of phospholipase A2, which served to generate lysothio-PC in situ. Prodan-PC (PPC) showed maximum absorption in ethanol at 370 nm. The fluorescence emission spectrum showed maximum emission at 530 nm in water and at 498 nm in ethanol. In the presence of a saturating amount of phospholipase A2, the emission maximum shifted to about 470 nm. PPC showed a critical micellar concentration around 5 microM, with evidence of premicellar aggregation above 1 microM. Binding of PPC to Crotalus adamanteus phospholipase A2 was evidenced by an increase in emission at 480 nm and an increase in fluorescence anisotropy. An apparent dissociation constant of 0.323 microM was calculated for this enzyme complex. Binding was dependent on the presence of calcium ion and was abolished by blocking the active site with p-bromophenacyl bromide. Binding was also followed by energy transfer from tryptophan in the enzyme to PPC. Apparent dissociation constants for PPC complexes with phospholipases A2 from Naja naja naja and porcine pancreas and the prophospholipase A2 from porcine pancreas were 0.509, 0.107, and 0.114 microM, respectively. PPC was shown to inhibit the activity of pancreatic phospholipase A2 in thio-PC-sodium cholate mixed micelles. Inhibition studies were complicated because PPC can also serve as an activator of the snake venom enzymes.(ABSTRACT TRUNCATED AT 250 WORDS)

2-Naphthylamine↗

Effect of a purified amylase inhibitor on carbohydrate tolerance in normal subjects and patients with diabetes mellitus.

Slowing starch digestion by inhibiting amylase activity in the intestinal lumen should improve postprandial carbohydrate tolerance in patients with diabetes mellitus. Crude bean-derived amylase inhibitor ("starch blocker") that contains only minimal antiamylase activity, however, does not modify carbohydrate assimilation. To test the validity of the "starch blockade" concept, we assessed the effect of a partially purified bean-derived amylase inhibitor with increased antiamylase activity on carbohydrate tolerance in normal subjects and in patients with non-insulin-dependent diabetes mellitus. In comparison with a placebo, ingestion of this inhibitor with 50 g of starch substantially reduced postprandial increases in plasma concentrations of glucose and insulin in both normal subjects and those with diabetes. We conclude that a purified amylase inhibitor is effective and potentially beneficial in the treatment of diabetes mellitus.

Adult↗

Partially purified white bean amylase inhibitor reduces starch digestion in vitro and inactivates intraduodenal amylase in humans.

Whether commercial, bean-derived alpha-amylase inhibitor preparations failed to decrease starch digestion in humans because of insufficient antiamylase activity, destruction by gastrointestinal secretions, or decreased activity in the presence of starch is unknown. We used a simple partial purification procedure to markedly concentrate the inhibitor (sixfold to eightfold by total protein content, and 30-40-fold by dry weight). Compared with a commercial preparation and crude bean extract, this partially purified inhibitor inactivated intraduodenal, intraileal, and salivary amylase in vitro faster and more completely (p less than 0.001); its specific activity was not affected by exposure to gastric juice and was only minimally reduced by duodenal juice. Whereas the rate of amylase inhibition by inhibitor was markedly slowed in the presence of nondietary liquid starch, dietary solid starch had only a minimal effect. Consequently, the partially purified inhibitor had no effect on liquid starch digestion, but decreased in vitro digestion of dietary starch in a dose-dependent manner (p less than 0.001). Perfusion of the partially purified inhibitor (2.0, 3.5, or 5.0 mg/ml at 5 ml/min) into the duodenum of humans rapidly inhibited greater than 94%, greater than 99%, or greater than 99.9% of intraluminal amylase activity. We conclude that commercial amylase inhibitors failed to decrease starch digestion in vivo mainly because they have insufficient antiamylase activity. However, a partially purified inhibitor with increased specific activity is stable in human gastrointestinal secretions, slows dietary starch digestion in vitro, rapidly inactivates amylase in the human intestinal lumen, and, at acceptable oral doses, may decrease intraluminal digestion of starch in humans. Such an inhibitor therefore deserves study.

Adult↗

Quantitation of flecainide acetate, a new antiarrhythmic agent, in biological fluids by gas chromatography with electron-capture detection.

A sensitive and selective gas chromatographic (GC) method for the quantitation of flecainide acetate, a new antiarrhythmic agent, was developed. The unchanged drug and internal standard were separated from biological fluids by a sequence of solvent extractions and then the drug was derivatized. The pentafluorobenzamide derivatives were chromatographed on a 3% SP-2250 glass column and detected with a nickel-63 electron-capture detector. By this method, greater than or equal to 12.5 ng of flecainide/mL can be quantitated in a 1-mL sample of plasma, saliva, or urine. The intraday precision, expressed as the RSD, at plasma levels of 12.5, 25, 50, 100, 200, 300, 400, and 600 ng/mL was 3.4, 6.2, 5.3, 6.4, 1.0, 1.6, 2.0, and 0.5%, respectively; the accuracy, expressed as relative error at these levels was -24.6, -6.9, -6.0, +0.6, +3.8, -0.3, +2.4, and -1.4%, respectively. The interday precision at these levels was 13.8, 13.0, 5.7, 7.6, 8.3, 6.1, 9.0, and 5.4%, respectively. Several other antiarrhythmic agents and one beta-blocker, which might be administered concurrently with flecainide acetate, do not interfere with the assay.

Anti-Arrhythmia Agents↗

Detection of a pheromone-binding protein in the aquatic fungus Achlya ambisexualis.

Sexual reproduction among the eukaryotic fungi of the genus, Achlya, is controlled by two steroid pheromones. Antheridiol is the pheromone constitutively produced by female cells that induces male sexual differentiation and development. A biologically active tritium-labeled derivative of antheridiol, [1,2-3H]7-deoxy-7-dihydro-antheridiol ( [3H]7dA), has been synthesized. Radioligand-binding studies have revealed the presence of a specific binding protein in the cytosol of male cells that may represent the endogenous receptor for antheridiol. Binding to this macromolecule was characterized by an apparent equilibrium dissociation constant and maximum binding capacity of approx. 7 X 10(-10) M and 1 100-2 000 fmoles/mg protein, respectively. Sedimentation analysis in sucrose gradients revealed that the binding protein distributes in the 8S region under low ionic strength and sodium molybdate-stabilized conditions. Under conditions of high ionic strength, in the presence or absence of 10 mM sodium molybdate, the binding site distributes in the 3.6S region of the gradient. Analysis of radioligand binding in the presence of other steroids and steroid hormones revealed that the binding is specific for antheridiol and its analog.

Centrifugation, Density Gradient↗

Plasma concentrations of flecainide acetate, a new antiarrhythmic agent, in humans.

Flecainide, a new antiarrhythmic agent, was given to eight healthy men to ascertain plasma drug levels and to assess tolerance for the drug. Each subject received a single intravenous (IV) dose (0.5, 1, 1.5, or 2 mg/kg) of flecainide, and plasma levels of unchanged flecainide were measured by gas-liquid chromatography. After an initial rapid distribution phase, the drug's plasma half-life (terminal elimination phase) ranged from seven to 15 hours (mean, 11 hours); half-life was apparently independent of dose level. Immediately after IV administration, the relatively high plasma drug levels seen during the short distribution phase were associated with minor and transient side effects in some subjects receiving the two higher doses; overall, the drug was well tolerated. Plasma flecainide levels 60 minutes after administration (after distribution) ranged from 52 to 300 ng/ml and were reasonably proportional to dose level. The drug's relatively long plasma half-life in humans indicates that plasma levels will be maintained for prolonged periods; thus flecainide should provide sustained therapeutic activity in patients with cardiac arrhythmias.

Adult↗