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P D Klein

Publications and source records attributed to P D Klein.

At least 55 records · Page 3Linked to original sources
PubMed1993

Thiamin-responsive maple syrup urine disease in a patient antigenically missing dihydrolipoamide acyltransferase.

Maple syrup urine disease results from inherited defects in human nuclear genes for branched chain alpha-ketoacid dehydrogenase, a mitochondrial multienzyme complex. Thiamin pyrophosphate is necessary for complex activity and a thiamin-responsive form of maple syrup urine disease is known. Here we demonstrate the use of [1-13C]leucine oxidation to [13C]O2 quantified in breath samples as a means of assessing whole body leucine oxidation. Analysis of cultured cells from this patient shows the antigenic lack of the E2 subunit, yet she gained branched chain alpha-ketoacid dehydrogenase activity in response to diet supplementation with pharmacologic doses of thiamin. These cultured cells were used to seek a molecular basis for the observed thiamin response. Despite normal thiamin transport in these cells, medium supplementation of up to 1000 thiamin/liter failed to increase complex activity or cause the antigenic appearance of the missing protein. This lack of response in cultured cells suggests that the observed whole body response to thiamin must be a tissue-specific effect in liver, muscle, or kidney. In addition, allele-specific detection of paternal and maternal mutations was used to genotype family members in this pedigree.

Acyltransferases↗
PubMed1993

The use of cotton balls to collect infant urine samples for 2H/1H and 18O/16O isotope ratio measurements.

To test the validity of cotton balls as a urine collection medium for hydrogen and oxygen isotope ratio measurements, we moistened cotton balls with 1-, 5-, and 10-mL aliquots of urine that contained either natural abundances or one of two enriched levels of 2H and 18O. The liquids were then expressed from the cotton balls, either at once, or after 30 or 60 min of atmospheric exposure, and analyzed for their 2H/1H and 18O/16O isotope ratios. The 2H abundances of the fluids expressed from the cotton balls were significantly lower than the original values. This dilution of 2H, however, diminished in the samples that had a greater volume of urine. We observed no effects of volume or time on 18O. Our results indicate that at low urine volumes, ambient moisture dilutes 2H in the cotton balls, but isotope exchanges and evaporation have little or no effect on the hydrogen and oxygen isotopic abundances of the urine samples. Total body water and energy expenditure values calculated from the 2H and 18O enrichments of 5- and 10-mL urine samples were within 1% of the theoretical values. Therefore, cotton balls are suitable for collection of infant urine samples for hydrogen and oxygen isotope ratio measurements, if the volume of urine that can be expressed from a cotton ball is > or = 5 mL.

Adult↗
PubMed1993

Clarithromycin for the eradication of Helicobacter pylori.

Helicobacter pylori infection has proven to be extraordinarily difficult to eradicate. Antimicrobial monotherapies have been particularly disappointing, with most eradication rates in the range of 0-15%. Clarithromycin has potential advantages over other macrolides to which H. pylori is susceptible because of its acid stability and solubility at low pH. We evaluated clarithromycin therapy (250 mg four times daily for 14 days) in 12 H. pylori-infected patients. The 13C-urea breath test was used to evaluate the effectiveness of therapy. Eradication was defined as a negative urea breath test 4-6 weeks after the end of treatment. Suppression of H. pylori was demonstrated in 11 of 12 patients (92%) by a negative urea breath test 2 days after start of treatment. H. pylori was eradicated in five (42%) of 12 patients. Adverse events were intermittent and mild. Clarithromycin is the first antimicrobial agent that appears to offer promise as monotherapy for the eradication of H. pylori.

Adolescent↗
PubMed1993

Short report: a non-metronidazole triple therapy for eradication of Helicobacter pylori infection--tetracycline, amoxicillin, bismuth.

Triple therapies using bismuth, metronidazole and tetracycline or amoxicillin were the first truly successful anti-H. pylori therapies. Metronidazole resistance has become an increasing problem that has severely limited the usefulness of the original triple therapy. Resistance to tetracycline or amoxicillin has not been reported and both are effective against H. pylori. We therefore tested a new triple therapy consisting of 500 mg tetracycline, 500 mg amoxicillin, and 2 tablets of bismuth subsalicylate each administered four times daily (with meals and at bedtime) for 14 days during treatment with ranitidine 300 mg daily. H. pylori eradication was defined as no evidence of H. pylori one or more months after stopping therapy. H. pylori status was evaluated by a combination of urea breath test and histology. Sixteen patients with H. pylori infection and active peptic ulcers were enrolled. The new triple therapy was successful in only 7 individuals (43%). Metronidazole appears to be critical for the effectiveness of the original triple therapy. An alternative to metronidazole will be required for a new successful triple therapy.

Adult↗
PubMed1993

Practical methods to estimate whole body leucine oxidation in maple syrup urine disease.

We report the comparison of noninvasive methods to estimate whole body leucine oxidation in patients who have maple syrup urine disease. We used both an i.v. and an oral bolus of L-[1-13C]leucine and quantitated 13CO2 in expired air. Both methods differentiated patients with maple syrup urine disease from heterozygous and control subjects. Eight patients, whose disease differed in clinical severity, were selected for study and had a range of impaired values for whole body leucine oxidation. Six h after an i.v. bolus dose of L-[1-13C]-L-leucine, 13CO2 recoveries ranged from 0.8 to 19.7%. Three of the eight patients had significant increases in 13CO2 production after supraphysiologic thiamine therapy. After the oral dose of L-[1-13C]leucine, homozygous affected children produced less 13CO2 than normal, age-matched, childhood controls. In addition, the oxidation of orally administered L-[1-13C]leucine was reduced significantly in adult heterozygotes compared with adult controls. The proportion of whole body leucine oxidation by affected children was comparatively greater than that by their cultured cells, but cellular oxidation correlated significantly with whole body oxidation of leucine among affected patients. We conclude that these simplified analyses of whole body leucine oxidation define the degree of impaired branched-chain alpha-ketoacid dehydrogenase activity in patients with differing types of maple syrup urine disease and distinguish the subpopulation who might benefit from thiamine supplementation.

3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)↗
PubMed1993

Body weight gain is correlated with serum cholesterol at 8 weeks of age in pigs selected for four generations for low or high serum cholesterol.

We determined the relationship of BW at birth, weaning (4 wk of age), and 8 wk of age to serum total cholesterol (C), high-density lipoprotein-cholesterol (HDL-C), and triglycerides (TG) at 8 wk of age in pigs, from the fourth generation that had been selected for low (10 litters, 75 pigs, LC) or high (10 litters, 63 pigs, HC) C at 8 wk of age. Mean C concentration at 8 wk of age was 81 +/- 30 mg/dL for LC groups and 136 +/- 19 mg/dL for HC groups. Serum C, HDL-C, and TG concentrations were not correlated with birth weight, suggesting that the physiological factors that may cause reduced weight gain in older animals are not operative in newborn pigs. All three constituents were correlated (P < .05) with BW at weaning and at 8 wk. However, only 4% of the variation in weight at weaning and 7% at 8 wk could be explained by a relationship with serum TG. There was a positive correlation between C and BW at 8 wk (r = .46, P < .05), which was apparent within the subgroups of LC and HC females and LC males (r = .46, .48, .68, respectively); the correlation was low (r = .26) in HC males.

Animals↗
PubMed1993

Clarithromycin as monotherapy for eradication of Helicobacter pylori: a randomized, double-blind trial.

UNLABELLED: Current regimens to eradicate Helicobacter pylori usually consist of metronidazole plus a bismuth compound, as well as a third agent such as tetracycline. Such regimens are not ideal because organisms may be metronidazole-resistant, side-effects occur, and compliance is often poor. This randomized, double-blind study was designed to assess the ability of clarithromycin, a new macrolide antimicrobial, as monotherapy to eradicate H. pylori. Thirty-seven healthy volunteers who were H. pylori positive by 13C-urea breath test plus histology and/or culture completed 14 days of oral therapy with clarithromycin in one of three dosages. Eradication, defined as all three tests negative at 4-6 wk after the end of therapy, was achieved in 2/13 (15%) with clarithromycin 500 mg bid, 4/11 (36%) with 1000 mg bid, and 7/13 (54%) with 500 mg qid. Isolates of H. pylori were resistant to clarithromycin prior to therapy in 12% of subjects, and became resistant during therapy in 21% of subjects. Taste perversion, the most common side effect, resulted in one subject terminating therapy. CONCLUSIONS: Whereas clarithromycin is a promising antimicrobial in the eradication of H. pylori, it is not sufficient to be used as monotherapy.

Adult↗
PubMed1993

Minimum analysis requirements for the detection of Helicobacter pylori infection by the 13C-urea breath test.

BACKGROUND: In an attempt to identify the minimum criteria for scoring the 13C-urea breath test, we examined test results from 96 healthy subjects, 270 duodenal ulcer patients undergoing treatment to eradicate Helicobacter pylori, and 1000 consecutive breath tests analyzed in our laboratory. METHODS: The 13CO2/12CO2 isotope ratio in a baseline sample was compared with that of samples collected at 20, 30, 40, and 50 min post-dosing. A positive test was defined as an average increase in the ratio of 6/1000 over baseline. Values for a two-sample analysis (baseline and one other) and for a single-sample analysis were extracted from the data and compared with the original analysis outcome. RESULTS: Test results were negative for 186 patients and positive for 84. The two-sample method had high specificity (94-99/1000), sensitivity (95-99/1000), and positive predictive value (88-97/1000). False-positive results occurred most often with samples collected at 20 min and least often with the sample at 40 min (11 and 1, respectively). Analyses based on a single sample collected beyond 20 min, in which samples with an isotope ratio > or = -15/1000 versus the standard were defined as positive, gave comparable specificity (98-99/1000), slightly reduced sensitivity (92-94%), and positive predictive value (96-99%). The analyses of 1000 consecutive breath tests yielded approximately 1% false-positive and false-negative results by the two-sample method; the single-sample method yielded a 2% false-positive and false-negative result. CONCLUSION: The 13C-urea breath test can determine H. pylori infective status from a single breath sample collected at least 30 min post-dose in which the absolute 13C abundance is > or = -15/1000 versus the standard.

Breath Tests↗
PubMed1993

Effect of dietary cholesterol on cholesterol synthesis in breast-fed and formula-fed infants.

The fractional synthesis rate (FSR) of cholesterol was measured in 6 breast-fed and 12 formula-fed infants (ages 4 to 5 months) using the 2H2O method. The breast-fed infants had higher cholesterol intakes (18.2 +/- 4.0 vs. 3.4 +/- 1.8 mg/kg per day, P = 0.001), plasma total cholesterol (183 +/- 47 vs. 112 +/- 22 mg/dl, P = 0.013), and plasma low density lipoprotein (LDL)-cholesterol (83 +/- 26 vs. 48 +/- 16 mg/day, P = 0.023) than the formula-fed infants (6.9 +/- 2.6 vs. 2.1 +/- 0.6%/day, P < 0.001). Among all infants, there was a significant inverse relationship (P = 0.002, r = 0.66) between the FSR of cholesterol and dietary cholesterol intake. Our findings indicate that the greater cholesterol intake of the breast-fed infants was associated with elevated plasma LDL-cholesterol concentrations and that cholesterol synthesis in human infants may be efficiently regulated via HMG-CoA reductase when infants are challenged with high intakes of dietary cholesterol.

Breast Feeding↗
PubMed1992

Effect of treatment of Helicobacter pylori infection on the long-term recurrence of gastric or duodenal ulcer. A randomized, controlled study.

OBJECTIVE: To determine the effect of treating Helicobacter pylori infection on the recurrence of gastric and duodenal ulcer disease. DESIGN: Follow-up of up to 2 years in patients with healed ulcers who had participated in randomized, controlled trials. SETTING: A Veterans Affairs hospital. PARTICIPANTS: A total of 109 patients infected with H. pylori who had a recently healed duodenal (83 patients) or gastric ulcer (26 patients) as confirmed by endoscopy. INTERVENTION: Patients received ranitidine, 300 mg, or ranitidine plus triple therapy. Triple therapy consisted of tetracycline, 2 g; metronidazole, 750 mg; and bismuth subsalicylate, 5 or 8 tablets (151 mg bismuth per tablet) and was administered for the first 2 weeks of treatment; ranitidine therapy was continued until the ulcer had healed or 16 weeks had elapsed. After ulcer healing, no maintenance antiulcer therapy was given. MEASUREMENTS: Endoscopy to assess ulcer recurrence was done at 3-month intervals or when a patient developed symptoms, for a maximum of 2 years. RESULTS: The probability of recurrence for patients who received triple therapy plus ranitidine was significantly lower than that for patients who received ranitidine alone: for patients with duodenal ulcer, 12% (95% CI, 1% to 24%) compared with 95% (CI, 84% to 100%); for patients with gastric ulcer, 13% (CI, 4% to 31%) compared with 74% (44% to 100%). Fifty percent of patients who received ranitidine alone for healing of duodenal or gastric ulcer had a relapse within 12 weeks of healing. Ulcer recurrence in the triple therapy group was related to the failure to eradicate H. pylori and to the use of nonsteroidal anti-inflammatory drugs. CONCLUSIONS: Eradication of H. pylori infection markedly changes the natural history of peptic ulcer in patients with duodenal or gastric ulcer. Most peptic ulcers associated with H. pylori infection are curable.

Adult↗
PubMed1992

Factors influencing the eradication of Helicobacter pylori with triple therapy.

Helicobacter pylori infection has been associated with gastritis, duodenal ulcer, gastric ulcer, and the epidemic form of gastric carcinoma. Eradication of H. pylori infection has proven to be difficult. Recently, combinations of antimicrobial drugs have been shown to eradicate greater than 50% of infections; however, the results have proven variable, and the factors influencing effectiveness of therapy are unclear. In the present study, the effectiveness of a triple therapy for eradication of H. pylori infection was evaluated. Triple therapy consisted of 2 g tetracycline, 750 mg metronidazole, and five or eight tablets of bismuth subsalicylate daily in 93 patients (70 with duodenal ulcer, 17 with gastric ulcer, and 6 with simple H. pylori gastritis). Combinations of a sensitive urea breath test, serology, culture, and histology were used to confirm the presence of infection, eradication, or relapse. Eradication was defined as inability to show H. pylori greater than or equal to 1 month after ending therapy. The overall eradication rate was 87%. The factors evaluated for their effect on predicting eradication included age, gender, type of disease, duration of therapy, amount of bismuth subsalicylate [five or eight Pepto-Bismol tablets daily (Procter & Gamble, Cincinnati, OH)], and compliance with the prescribed medications. Stepwise regression showed that compliance was the most important factor predicting success; the success rate was 96% for patients who took greater than 60% of the prescribed medications and 69% for patients who took less. For those taking greater than 60% of the prescribed therapy, the eradication rates were similar (a) for patients receiving therapy for 14 days or when tetracycline and bismuth subsalicylate were taken for an additional 14 days; (b) for patients with duodenal ulcer, gastric ulcer, and simple H. pylori gastritis; and (c) whether five or eight bismuth subsalicylate tablets were taken. It is concluded that triple therapy is effective for eradication of H. pylori and that future studies need to take compliance into account for comparisons between regimens.

Adult↗
PubMed1992

VLDL apolipoprotein B-100, a potential indicator of the isotopic labeling of the hepatic protein synthetic precursor pool in humans: studies with multiple stable isotopically labeled amino acids.

Four adult men received a 48-h constant intravenous infusion of [2H4]lysine, [2H3]leucine, L-[ring-13C6]phenylalanine, and L-[1,2,3,-13C3]alanine. Subjects ingested hourly meals for two 12-h periods, separated to two 12-h fasting periods. The isotopic enrichments of free amino acids in venous plasma and in VLDL apolipoprotein B-100 (apoB)-bound amino acids, plasma alpha-keto isocaproic acid (alpha-KIC) and plasma pyruvic acid (PYR) were measured by negative chemical ionization gas chromatography-mass spectrometry. By 7 h of infusion, all four amino acids achieved an equilibrium isotopic enrichment (EIE) in plasma and in apoB. In the fed state, the EIE of the amino acids in apoB was lower than that in plasma free amino acids. The ratio EIE-apoB:EIE-plasma differed significantly among amino acids in the fed state (alanine 0.30; lysine 0.64; leucine 0.70; phenylalanine 0.81). In the postabsorptive state, the EIE-apoB:EIE-plasma ratio rose significantly compared with the fed state (alanine 0.38; lysine 0.73; leucine 0.94; phenylalanine 1.05). Plasma PYR and apoB-alanine were in isotopic equilibrium irrespective of nutritional state. The EIE-apoB-leucine:EIE-plasma-alpha-KIC ratio rose from 0.75 in the fed state to near 1 in the postabsorptive state. We conclude that the contribution of systemic amino acids to apoB-100 synthesis is sensitive to nutritional state, and that systemic essential amino acids seem to be preferentially incorporated into apoB.

Adult↗
PubMed1992

Neonatal genetically lean and obese pigs respond differently to dietary cholesterol.

The impact of cholesterol exposure in early life on later cholesterol metabolism is not clearly understood. Sixteen newborn genetically lean and obese pigs were fed 0 or 5.0 g cholesterol/kg diet (0 or 0.5%) (liquid diets for 12 d, dry diets thereafter) for 33 d, after which they were all fed 10.0 g cholesterol/kg diet (1.0%) for 23 d. All animals were killed on d 56 and whole-body protein, fat and water were determined on the ground carcass. Dietary cholesterol had no consistent effect on growth rates or body composition. Mean fat content of lean pigs was 15.1% compared with 22.7% for obese pigs; corresponding values were 14.8 and 14.4% for protein and 65.5 and 58.3% for water. Concentrations of plasma total cholesterol, HDL cholesterol and apolipoproteins B and A-1 were increased by 0.5% dietary cholesterol in obese but not in lean piglets, although dietary cholesterol caused HDL and LDL size distribution profiles to shift toward larger-sized components in both strains. Plasma total cholesterol and apolipoprotein B concentrations rose two- to eightfold in all groups after the 1% cholesterol diet was consumed; these changes were accompanied by shifts in LDL and HDL size distribution profiles towards larger-sized components. With 1.0% cholesterol in the diet of all groups, HDL cholesterol concentration increased by approximately 50% in both groups of lean pigs and in obese pigs previously fed cholesterol, but did not increase further in obese pigs previously fed 0.5% cholesterol. The magnitude of the hypercholesterolemic response in lean pigs was blunted by previous exposure to 0.5% dietary cholesterol, but the response was accentuated in obese animals that had been previously exposed to 0.5% dietary cholesterol. These data provide evidence that genetic differences between obese and lean pigs affect their serum lipoprotein responses to high cholesterol intake.

Animals↗
PubMed1992

Short report: cefprozil for the eradication of Helicobacter pylori infection.

Helicobacter pylori infection has proven to be extraordinarily difficult to eradicate. Antimicrobial monotherapies have been particularly disappointing, with most eradication rates in the range of 0 to 15%. We evaluated cefprozil (250 mg q.d.s. for 14 days) in 12 H. pylori-infected subjects. The 13C-urea breath test was used to evaluate effectiveness of therapy. Eradication was defined as a negative urea breath test 4 to 6 weeks after the end of treatment. Suppression of H. pylori was demonstrated in 4 of 12 (33%) by a negative urea breath test two days after start of treatment. H. pylori infection was not eradicated in any subject (0%). Adverse events were intermittent and mild. Cefprozil does not appear to offer promise as monotherapy for the eradication of H. pylori.

Adult↗
PubMed1992

The role of Helicobacter pylori in recurrent, functional abdominal pain in children.

Recurrent abdominal pain in children usually is considered to be functional in nature. We hypothesized that Helicobacter pylori infection might be the etiology of abdominal pain symptoms in some children with presumed functional abdominal pain. Therefore, we studied 20 children with a previous diagnosis of functional abdominal pain, using a 13C-urea breath test and an enzyme-linked immunosorbent assay for antibody to the H. pylori high molecular weight, cell-associated antigens. Two children had evidence of H. pylori infection, and both had clinical histories that suggested an acute H. pylori infection, at the onset of their abdominal pain. Seven children who had abrupt onset of their chronic abdominal symptoms were then identified prospectively. None of these patients had evidence of active H. pylori infection. We conclude that H. pylori infections are not common among children with recurrent abdominal pain, and are not predictable in such children, based on symptom patterns.

Abdominal Pain↗
PubMed1992

Lactate kinetics in severe COPD. Implications of an abnormal aminopyrine breath test.

The ability of the 13C aminopyrine breath test (APBT) to reflect hepatocellular metabolic capacity and therefore to predict lactate removal following incremental exercise in male COPD patients was evaluated. Two previous patients with COPD who had histories of heavy alcohol intake but no overt liver disease showed prolonged lactate elevation following exercise. The possibility of subclinical hepatic disease affecting lactate removal was considered. No patient in the present study had clinical evidence of liver disease. Four of 9 patients had an abnormal APBT (mean 5.0% cumulative dose 13CO2 excreted over 2 h). Patients with a normal APBT (group 1) and with an abnormal APBT (group 2) were compared. The groups did not differ in age or severity of lung disease. An incremental exercise test was performed and lactate samples were collected before, during, and for 90 min following exercise. Exercise parameters (work rate, duration, VO2max, VEmax, and peak lactate) did not differ between groups. Comparing group 1 with group 2 mean values, the time to recover to resting lactate values (Trecov 45 vs 76 min, respectively, p less than 0.005) and the time required for lactate level to return to the normal range (Tnorm 35 vs 65 min, respectively, p less than 0.005) were statistically different. Furthermore, the 2-h excretion of 13CO2 was inversely correlated with both Trecov (r = -0.76, p less than 0.05) and Tnorm (r = -0.79, p less than 0.05). We conclude that subclinical derangement of hepatocellular capacity, as determined by APBT, may adversely affect lactate removal following exercise.

Aminopyrine↗