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Biomedical subjects

B Kerzner

Publications and source records attributed to B Kerzner.

At least 19 recordsLinked to original sources

Efficacy and safety of ezetimibe coadministered with statins: randomised, placebo-controlled, blinded experience in 2382 patients with primary hypercholesterolemia.

We assessed pooled safety and lipid-regulating efficacy data from four similarly designed trials of ezetimibe coadministered with statins in 2382 patients with primary hypercholesterolemia. Patients were randomised to one of the following double-blind treatments for 12 weeks: placebo; ezetimibe 10 mg; statin; or statin + ezetimibe. Statin doses tested were 10, 20, 40 mg/day (atorvastatin, simvastatin, pravastatin or lovastatin) or 80 mg/day (atorvastatin, simvastatin). Treatment with ezetimibe + statin led to significantly greater reductions in low-density lipoprotein cholesterol (LDL-C), total cholesterol, triglycerides, non-high-density lipoprotein cholesterol (non-HDL-C), apolipoprotein B and increases in HDL-C, compared to statin alone. At each statin dose, treatment with ezetimibe + statin led to a greater LDL-C reduction compared to the next highest statin monotherapy dose. Ezetimibe + statin had a safety profile similar to statin monotherapy. Coadministration of ezetimibe + statin offers a well-tolerated, highly efficacious new treatment strategy for patients with hypercholesterolemia.

Adolescent↗

Inflammatory bowel disease in children and young adults: correlation of sonographic and clinical parameters during treatment.

OBJECTIVE: The objective of this study was to evaluate the sonographic findings of inflammatory bowel disease activity in children undergoing treatment. SUBJECTS AND METHODS: Eighty-eight sonograms were obtained of 23 bowel segments in 17 children and young adults (age range, 10-21 years; mean, 16 years) with new or recurrent inflammatory bowel disease. Sixteen segments were involved with Crohn's disease and seven with ulcerative colitis. Serial sonography (range, two to eight examinations; mean, four per segment) was performed while patients underwent treatment. Bowel wall thickness measurements and color and power Doppler sonography grading were recorded and compared with clinical data. RESULTS: All 17 patients had at least one abnormal bowel segment on initial sonography. The correlation was significant (p < 0.01). Agreement was 91% on direction of change over time between bowel wall thickness and Doppler grades, with 100% correlation between color and power Doppler sonography grades. In patients with Crohn's disease, the correlation was significant (p < 0.05) between bowel wall thickness and Doppler grades with two of seven and four of seven clinical parameters, respectively. In patients with ulcerative colitis, the correlation was significant (p < 0.05) between bowel wall thickness and Doppler sonography grades with four of seven and three of seven clinical parameters, respectively. The erythrocyte sedimentation rate correlated with all sonographic measurements in both patient groups. Combining bowel wall thickness and Doppler sonography, the percentage of agreement was significant in the direction of change, with five of seven clinical parameters in both patient groups. CONCLUSION: Gray-scale and color or power Doppler sonography can show changes in disease activity in children and young adults undergoing treatment for inflammatory bowel disease.

Adolescent↗

Ipecac toxicity in "Munchausen syndrome by proxy".

The authors report a case that offers insight into the diagnostic challenges of "Munchausen Syndrome by Proxy." Initial presentation with history of fever and later with intractable vomiting led to invasive and expensive diagnostic evaluation before confirming the diagnosis. Certain toxic effects of emetine were clinically noted. Biochemical and clinical improvement were clearly demonstrated after withdrawal of the toxic agent.

Child, Preschool↗

Preliminary assessment of glycine conjugation of para-aminobenzoic acid as a quantitative test of liver function.

OBJECTIVES: Our hypothesis is that because of its hepatic metabolism paraaminobenzoic acid (PABA) could be a test of liver function. DESIGN AND METHODS: PABA is well absorbed by the gastrointestinal tract and acetylated and conjugated in the liver to glycine before being excreted. Its three major metabolites include para-acetoamidobenzoic acid (PAABA), paraaminohippuric acid (PAHA), and paraacetamidohippuric acid (PAAHA). In this study, we measured the metabolism of lidocaine to monoethylglycinexylidide (MEGX) and PABA to PAHA+PAAHA/PABA+PAABA+PAHA+PAAHA (hippurate ratio) in 14 patients with liver disease and 12 control subjects. RESULTS: Comparison of the total bilirubin with the hippurate ratio (at 30 min) and the conventional MEGX test (at 15 min) was assessed. The 30 min hippurate ratio correlated well with the 15 min MEGX results (r = 0.69). CONCLUSIONS: While these results are preliminary the PABA test appears to be equally sensitive to MEGX and has the distinct advantage over the MEGX test of being administered orally versus the intravenous administration of lidocaine which is often associated with unwanted side-effects such as hypotension, drowsiness and paresthesias.

4-Aminobenzoic Acid↗

Biliary copper excretion in the neonatal rat: role of glutathione and metallothionein.

Metallothionein (MT) and glutathione (GSH) have been implicated as two major copper-binding agents involved in the hepatobiliary copper metabolism in the adult rat. This study was designed to explore their potential role in facilitating copper export from the copper-laden hepatocyte of the newborn rat. Biliary and hepatic copper, GSH, and immunoreactive MT-I concentrations were measured in Sprague-Dawley rats at 1, 2, 3, 4, and 8 weeks of age. Bile was collected by duct cannulation for 90 minutes before the rats were killed. Liver was removed, weighed, and freeze-dried. The bile flow rate (BFR) doubled and the liver weight increased 14-fold during maturation. Hepatic and biliary copper and MT-I concentrations were significantly higher in the suckling than in the weanling. The total biliary output of copper per 24 hours was low at 1 week and increased significantly by 8 weeks of age. MT-I-bound copper represented a maximum of only 3.4% of biliary copper at 1 week and 0.5% at 8 weeks. GSH was not detected in bile until 2 weeks and then increased 15-fold by 8 weeks, while hepatic GSH levels remained unchanged. Therefore, GSH levels did not correlate with the high biliary copper concentration at week 1, although there was a close correlation between the total daily biliary excretion of copper and GSH at 2 weeks and beyond. We conclude that the net biliary copper excretion per day is relatively low in the first week of life and is independent of MT and GSH secretion. It increases significantly once GSH is available in bile.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Early changes in the permeability of the blood-brain barrier produced by toxins associated with liver failure.

Our study was designed to determine whether substances that appear in the serum during the course of liver failure have a detrimental effect on the passive permeability of the blood-brain [blood-cerebrospinal fluid (CSF)] barrier. Lactic acid, octanoic acid, and ammonia were infused into rabbits for 4 h. The permeability changes of the blood-brain barrier were quantified by infusing polyethylene glycol 400 (PEG 400) and measuring the quantity and average mol wt of the PEG 400 that entered the CSF. The lipid solubility and effective diffusional radius of the PEG molecules were also quantified to provide greater precision for measurements using this probe. None of the animals receiving toxic infusions became seriously ill during the infusions. Low dose infusions of lactic acid, octanoic acid, and ammonia increased the effective pore diameter of the blood-brain barrier from 7.3 A to an average of 8.5 A. The amount of PEG entering the CSF increased from 1.7 to 4.0 (p less than 0.025), 4.7 (p less than 0.025), and 6.7 (p less than 0.001) mmol/L, respectively. Rabbits with galactosamine-induced liver failure had 10.1 mmol/L PEG 400 in the CSF (P less than 0.001) before any evidence of cerebral edema. These changes occur soon after these toxins accumulate in the plasma and may alone or together with other toxins account for the permeability changes that allow neurotoxic substances to enter the brain during hepatic disease and encephalopathies such as Reye's syndrome.

Animals↗

Feeding disorders and gastroesophageal reflux in infants with chronic renal failure.

Twenty-two infants (mean age 7.5 months) with chronic renal failure (CRF) were studied for their nutrition, growth, and upper gastrointestinal function. Most infants had a history of poor caloric intake and 7 had received supplemental feeding (SF) prior to the investigation. All infants were undergrown, underweight, and malnourished. The infants were characterized as having only a fair interest in food, refusing feedings, and vomiting excessively. Sixteen of 22 infants (73%) had significant gastroesophageal (GE) reflux demonstrated by 24-h esophageal pH monitoring. Gastroesophageal scintiscans were less sensitive and specific in detecting the reflux. Infants with GE reflux were significantly younger and more often required SF than those without GE reflux. There were no significant differences in the degree of renal failure, growth failure, caloric intake, protein intake, or nutritional status between the infants with and without GE reflux. From these studies we conclude that GE reflux should be considered as one of the factors contributing to the feeding problems of infants with CRF.

Energy Intake↗

Influence of saccharide length on polysaccharide appetite in the rat.

The appetite of female rats for saccharides of different chain lengths was assessed in brief (5-min) one-bottle acceptance and two-bottle preference tests. The saccharides (and their lengths in glucose units) included glucose (1), maltose (2), maltotriose (3), maltooligosaccharide (4-8), maltopolysaccharide (average length 43), and Polycose (1 to 30+); 0.0125 and 0.025 molar solutions of these saccharides were tested. The results revealed that the rats' order of preference for these saccharides was as follows: maltooligosaccharide greater than maltotriose = maltose greater than glucose; and maltooligosaccharide greater than Polycose = maltopolysaccharide greater than maltose. Thus, as saccharide chain length increased from 1 to 4-8 glucose units palatability increased, but with further increases in chain length palatability declined somewhat. Previous findings have suggested that rats have a "polysaccharide" taste receptor and the present results indicate that the receptor is maximally (or near-maximally) stimulated by saccharides of 4-8 glucose units in length.

Animals↗

Absorption of glucose polymers from canine jejunum deprived of pancreatic amylase.

We evaluated the absorption of glucose polymers in canine jejunal Thiry-Vella fistulas proven to be free of pancreatic amylase. Medium-length oligomers with degrees of polymerization of 6 through 10 glucose units (DP 6-10) and long-chain material (DPavg23) were isolated from a cornstarch hydrolysate. We perfused 90, 180, and 360 mg/dl solutions of glucose, DP 6-10, and DPavg23 at 0.4, 1.9, and 3.4 ml/min. At all perfusion rates carbohydrate absorption decreased as the chain length of the oligomers increased, and these differences persisted even at the slowest perfusion rate employed. In two additional animals the fistulas were perfused at 3.4 ml/min with the three test carbohydrates at concentrations of 90, 180, 225, 270, 315, 360, 405, and 450 mg/dl. At this flow rate, the assimilative process of DP 6-10 and the long-chain fraction appeared to be saturated at carbohydrate concentrations above 360 mg/dl, whereas the absorption of glucose was linearly related to concentration throughout the range studied. With both groups of polymers, the fluid emerging from the fistula was virtually free of glucose, a finding that suggests that polymer digestion, not glucose absorption, is the rate-limiting step for polymer assimilation.

Amylases↗

The contribution of salivary amylase to glucose polymer hydrolysis in premature infants.

To determine whether salivary amylase of premature infants can function as a surrogate for pancreatic amylase, we evaluated its production in the infant, acid resistance, and hydrolytic potency in a simulated oropharyngeal, gastric, and intestinal environment. The activity of salivary amylase in 11 prematures varied between 1 and 33 U/ml; the isozymic profile and acid resistance of the premature salivary amylase were identical to those of the enzyme of adults. A "modular" formula containing 7 g/dl of a 14C labeled long chain glucose polymer with degrees of polymerization ranging between 18 and 29 glucose units was prepared. Salivary amylase, 1.1 U/ml, was added to this formula. The progressive breakdown of the 14C polymers as the milk was subjected to oropharyngeal, gastric, and intestinal phase environments was evaluated by quantifying the liberation of short-chain oligomers from the 14C labeled substrates. The gastric pH was varied between 2 and 5 and the gastric incubation time was either 5 or 180 min. Substantial gastric phase breakdown only occurred after 3 h of exposure at the higher pHs of 4 (12%) and 5 (32%). During the intestinal phase, salivary amylase activity resumed. Prior gastric phase pH affected ultimate intestinal phase breakdown, p less than 0.001; after 5-min gastric phases at pHs ranging from 2 to 5, the intestinal phase breakdown ranged from 17 to 55%. We conclude that the limited salivary amylase in the saliva of premature infants can produce significant glucose polymer digestion in both the stomach and small intestine but the digestion falls substantially short of that accomplished by usual concentrations of pancreatic amylase.

Adult↗

Absorption and oxidation of glucose polymers of different lengths in young infants.

Because mucosal glucoamylase is most active against glucose polymers less than 10 glucose units in length, longer chain polymers may not be completely absorbed by young infants. In order to investigate this possibility, the absorption and oxidation of 13C-rich glucose, short-chain (3 to 8 glucose units in length) and long-chain (average length 43 units) glucose polymers (GP) were compared in 12 healthy, 1-month-old infants. Recovery of the GP and glucose in stool was measured by determining the 13C enrichment of stool. The oxidation of the GP was measured by tracing the increase in breath 13CO2 after GP were fed. Carbohydrate malabsorbed in the small bowel was assessed by measurement of breath H2, a gas formed from the fermentation of carbohydrate in the colon. Analysis of the infants' stools revealed that one infant excreted 9.7% of the dose of glucose, another 6.7% of the dose of short-chain GP, and five infants excreted 2.6 to 18.5% (mean 8.4%) of the dose of long-chain GP. The percent of the administered dose recovered in breath was similar among substrates (mean = 28.7% of the dose fed). A rise in breath H2 greater than 20 ppm was found in four of the 12 infants after the feeding of glucose, in five of 12 after the short-chain GP, and in six of 12 after the long-chain GP. None of the infants developed diarrhea. The results suggest that healthy young infants do not absorb long-chain GP as completely as they absorb short-chain GP.(ABSTRACT TRUNCATED AT 250 WORDS)

Glucans↗

Large scale production of glucose oligomers and polymers for physiological studies in humans.

Methods for isolating relatively large quantities of glucose oligomer and polymer subfractions from a partial corn starch hydrolysate (PCSH) are described. To ensure that the products are suitable for physiological studies in humans, potentially toxic substances were excluded from the preparative processes. For long chain glucose polymer fractions with degrees of polymerization (DP) averaging 43 glucose units, we employed molecular filtration through Amicon YM5 membranes. For fractions containing glucose oligomers with DP's 3 through 8, we employed yeast fermentation followed by ethanol fractionation.

Carbohydrates↗

Efficient storage system for breath hydrogen.

Recommended materials for breath hydrogen collection (plastic syringes with twist lock closure) are only adequate for relatively brief periods because of gradual hydrogen loss and considerable variability between duplicate samples. To document the most favorable storage conditions for breath hydrogen, we compared hydrogen retention in plastic syringes using a conventional twist-in-lock closure versus a simple, inexpensive syringe closure, a Critocap. Hydrogen retention was studied at 25, 5, and -20 degrees C in two different syringe brands over 72 h of storage. An analysis of variance confirms the superiority of Critocaps over twist-in-lock closures (p less than 0.001). Reliability was maximal when samples were placed in environments less than 5 degrees C. When storage time was extended to 7 days, mean hydrogen retention was 86 +/- 6% (means +/- SD).

Breath Tests↗