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Biomedical subjects

G L Klein

Publications and source records attributed to G L Klein.

At least 55 records · Page 3Linked to original sources
PubMed1990

Serum markers of bone formation in parenteral nutrition patients.

Bone gamma-carboxyglutamic acid containing protein (BGP) has been utilized effectively as a serum marker of bone turnover in healthy normals and in individuals with a variety of metabolic bone disorders including postmenopausal osteoporosis and Paget's disease. The utility of this serum marker in other bone disorders, including that associated with the maintenance of patients on long-term parenteral nutrition, still requires definition. Because of our interest in this clinical syndrome and the availability of serum and of bone formation rates (BFR) measured directly from double tetracycline labeling in 11 long-term parenteral nutrition patients, we measured BGP levels in these patients and attempted to correlate this measure with BFR. Serum vitamin D metabolites, immunoreactive parathyroid hormone (PTH), and alkaline phosphatase (alk phos) were also measured. Serum BGP was only weakly and not significantly correlated (r = 0.24, p = NS) with bone formation rate for the group as a whole. However, in a subgroup of 10 patients without hyperparathyroidism, there was strong and significant correlation (r = 0.81, P less than 0.01) between BGP and BFR. There was also a strong correlation between bone formation rate and serum 1,25 dihydroxyvitamin D [1,25(OH)2D] levels (r = 0.89, P less than 0.01, n = 11). The mechanism of this association could not be established. A correlation of borderline significance was observed between bone formation rate and serum alk phos (r = 0.60, P = 0.05, n = 11). The current data suggest that additional studies may help to more fully define the utility of serum measurements in quantifying bone dynamics in parenteral nutrition patients, and that measures of vitamin D metabolites, BGP, and alk phos may prove useful.

1-Carboxyglutamic Acid↗
PubMed1990

Skeletal effects of sodium fluoride during hypokinesia.

This study tested the capacity of fluoride (F) to prevent the disuse-associated reduction in bone formation/growth. Suspending young male Wistar rats by the tail for 2-2.5 weeks reduced femoral cortical (P less than 0.05) and trabecular (P less than 0.01) bone areas. Tetracycline labelling showed that the decrement in cortical area was largely due to a reduction in the percent periosteal mineralizing surface (PsMS). Periosteal mineral apposition rate (PsMAR) was not affected. Endosteal mineralizing surface (EsMS) and mineral apposition rate (EsMAR) were significantly stimulated spontaneously during the second week of suspension. F treatment (5 mg/kg/day i.p.) prevented the loss in bone area, and established a trend toward increased PsMS without affecting EsMS and EsMAR. None of these changes are associated with alterations in serum Ca, P or osteocalcin. F treatment in hypokinetic animals caused a decrease in serum PTH (-21% compared to control; P = 0.001). We conclude that F prevents the development of hypokinetic osteopenia in rats.

Animals↗
PubMed1990

A simplified screening test for the diagnosis of allergy.

The Quidel allergy screen is a relatively rapid (less than 2 hours) multiallergen dipstick method for detecting specific immunoglobin E antibodies in serum. It was developed to answer the need of primary physician nonspecialists in allergy for a convenient in-office screening test for diagnosing allergy. The new test was evaluated against the benchmark diagnostic skin tests and the radioallergosorbent serologic tests for sensitivity, specificity, accuracy, and technical feasibility in an office setting. It was found that while the Quidel allergy screen lacks the specificity of the standard tests, its overall sensitivity, as defined by the percentage of patients with positive skin reactions who also tested positive with the Quidel screen (68%), its ease of use, and its rapidity warrant its consideration as a screening tool for confirming a possible case of allergy.

Humans↗
PubMed1989

Treatment of hay fever. Allergen avoidance and medication to control symptoms.

Therapy for hay fever should begin with environmental control, because sometimes avoidance of allergens is all that is needed to adequately control symptoms. If not, useful medications include antihistamines, decongestants, combinations of the two, prescription nasal sprays, and allergy immunotherapy. The best method and correct dosage are important, both to ensure patient comfort and to prevent the side effects of allergic disorders.

Environment↗
PubMed1989

Absence of hyperparathyroidism in severe liver disease.

Elevated serum levels of intact parathyroid hormone (PTH) have been reported in severe versus mild biliary cirrhosis. The aim of this study was to determine whether hyperparathyroidism was present in severe liver disease on the basis of the inability of the liver to catabolize the hormone. Because biologic activity resides in the amino terminal, and amino terminal PTH determinations have not been routinely made in liver disease, it is possible that hyperparathyroidism was previously missed in these patients. Accordingly, we obtained fasting blood from 11 patients with severe liver disease and 8 age-matched controls. We measured intact, amino terminal, and mid-region PTH, vitamin D metabolites, bone gamma carboxyglutamic acid protein (BGP), ionized calcium, phosphorus, magnesium, and liver function tests. Serum levels of PTH were normal with all assays and 1,25(OH)2D levels were not elevated. These findings argue against the possibility that hyperparathyroidism plays a role in the pathogenesis of hepatic osteodystrophy.

Adult↗
PubMed1989

Altered glycine and taurine conjugation of bile acids following aluminum administration to rats.

Aluminum contaminates components of intravenous nutrient solutions and accumulates in the liver with parenteral feeding. Abnormalities in hepatic function associated with aluminum accumulation include increased serum bile acid concentration and glucuronyl transferase activity and reduced mixed function oxidase levels and bile flow. Whether there are other biochemical responses of the liver to aluminum is unclear. We report the effects of aluminum administration on bile acid conjugation in rats given aluminum intravenously as follows: group I, 1 mg/kg/day for 14 days; group II, 5 mg/kg/day for 14 days; and group III, 5 mg/kg/day for 7 days. Taurine-conjugated bile acids were reduced and glycine/taurine elevated in all groups compared with pair-fed controls. Glycine/taurine was greater in group II versus III and varied directly with serum bile acid concentration. These findings suggest that aluminum administration is associated with decreased taurine conjugation of bile acids, a phenomenon that may be associated with cholestasis.

Aluminum↗
PubMed1989

Hypocalcemia complicating deferoxamine therapy in an infant with parenteral nutrition-associated aluminum overload: evidence for a role of aluminum in the bone disease of infants.

Aluminum (Al) contaminates total parenteral nutrition (TPN) solutions given to infants, and high levels of Al have been demonstrated in their bone, serum, and urine. However, it is uncertain whether Al at current levels of contamination of TPN solutions is harmful to bone. We report an 8-month-old infant who developed osteopenic bone disease while receiving TPN, which did not respond to large amounts of calcium, phosphate, and vitamin D2. Serum and urine Al levels were greatly elevated and fell after a short course of deferoxamine. However, shortly after treatment began, serum calcium levels fell in the absence of hypercalciuria. We postulate that chelation of Al from this patient's bone permitted increased bone calcium uptake. This would suggest that Al at current levels of contamination of TPN solutions may impair bone calcium uptake and thus contribute to the pathogenesis or exacerbation of TPN-related osteopenia.

Adult↗
PubMed1989

Effects of aluminum on the liver following high-dose enteral administration to rats.

Parenteral administration of aluminum (Al) to animals can result in hepatobiliary dysfunction, including elevated total serum bile acid concentration, reduced bile flow, and reduction of mixed function oxidase activities. Despite substantial hepatic Al accumulation, biliary Al excretion is negligible. We studied the effects of enteral administration of pharmacologic doses of Al to rats in order to see if by this route Al also produced hepatobiliary dysfunction or if biliary Al excretion was enhanced following enteral administration, protecting the liver from the effects of Al. Six rats were given 100 mg/kg/day of Al for 14 days as Al citrate by duodenal cannula. Pair-fed littermate controls were given sodium citrate. Serum Al and urinary Al/creatinine were significantly higher in Al-fed rats than in controls. Liver Al was significantly increased in the Al-fed group, but very low when compared to liver Al concentration with intravenous Al administration. Biliary Al was only 2 +/- 1% of urinary Al in the experimental group. Serum bile acid concentration and bile flow were not different between groups. We conclude that Al given in pharmacologic doses is absorbed but does not accumulate in the liver. We hypothesize that a slow rate of Al absorption may not overwhelm plasma transferrin carrying capacity or renal Al excretory capacity.

Aluminum↗
PubMed1988

Metabolic bone disease of total parenteral nutrition: course after changing from casein to amino acids in parenteral solutions with reduced aluminum content.

Bone disease with total parenteral nutrition (TPN) has been attributed to aluminum loading or vitamin D therapy. We studied 17 patients who first received TPN containing casein hydrolysate with high Al and ergocalciferol (25 micrograms/d) for 6-72 mo followed by TPN containing amino acids with reduced Al and ergocalciferol (5 micrograms/d) for 9-58 mo. We also did a cross-sectional study of 22 patients receiving casein and ergocalciferol (25 micrograms/d) compared with 46 patients receiving amino acids and ergocalciferol (5 micrograms/d) for 6-58 mo. Bone formation was higher and osteoid area, bone-surface stainable Al and total bone Al were lower with amino acid TPN than with casein TPN. Bone formation varied inversely with both plasma Al and bone-surface Al, suggesting that plasma or bone-surface Al, acquired during TPN, can reduce bone formation and lead to patchy osteomalacia. Serum levels of iPTH and 1,25-dihydroxyvitamin D were higher with amino acid TPN.

Aluminum↗
PubMed1988

Aluminum-associated hepatobiliary dysfunction in rats: relationships to dosage and duration of exposure.

Aluminum may contaminate parenteral nutrition solutions and accumulate in bone and liver of patients receiving this therapy. Although aluminum exposure is associated with low-turnover osteomalacia, there are few studies of hepatotoxicity. We therefore studied the effects of aluminum given to rats on total serum bile acid concentration and bile flow to determine if aluminum administration could produce abnormalities. Aluminum was given intravenously as follows: 5 mg/kg daily for 7 or 14 days and 1 mg/kg for 14 days. Hepatic aluminum was high in treated rats and undetectable in controls. Total serum bile acid concentrations were significantly higher in treated rats than in pair-fed controls with higher concentrations after 14 days than after 7 days. Bile flow was reduced by 33% in rats given 5 mg/kg but not in rats given 1 mg/kg. Hepatic aluminum correlated inversely with bile flow but not with serum bile acid concentration. Aluminum exposure in rats is associated with elevated serum bile acid concentration and diminished bile flow and may play a role in the pathogenesis of parenteral nutrition-induced hepatobiliary dysfunction.

Aluminum↗
PubMed1987

Heterogeneity of bone histology in parenteral nutrition patients.

The characteristics of bone disease associated with parenteral nutrition are controversial. To further elucidate the contribution of aluminum deposition to this syndrome and the spectrum of pathology in patients supported by current regimens utilizing crystalline amino acids, quantitative histomorphometry and staining for Al were performed on iliac crest bone biopsies from 26 long-term parenteral nutrition patients and 16 normal volunteers. Compared with normal subjects, median trabecular bone area (TBA) for a group with positive Al staining (n = 14) who were exposed to casein hydrolysate was significantly less (12.9% vs 20.7, p less than 0.05) as was the median rate of bone formation (RBF) (29 micron2 X mm-2 X d-1 vs 360, p less than 0.05). A variety of abnormal histological findings were present in patients without positive aluminum stains (n = 12) who were supported solely by regimens utilizing crystalline amino acids. However, neither decreased TBA (median TBA = 15.3%) nor decreased RBF (median RBF = 126 micron2 X mm-2 X d-1) was uniformly characteristic of the latter patient group.

Adult↗
PubMed1987

Persistent allergic rhinitis in older patients: therapies worth trying.

Allergic rhinitis (hayfever) is a common problem found in the geriatric population. This problem should be aggressively treated with environmental control, prescription nasal sprays and/or antihistamines (if tolerated). Allergy immunotherapy can be a very effective treatment for the elderly, without the side effects commonly found when hayfever medication is used.

Adrenal Cortex Hormones↗
PubMed1987

Effect of aluminum on the hepatic mixed function oxidase and drug metabolism.

The effect of aluminum injection on the hepatic mixed function oxidase was examined in male Wistar rats. A cannula was surgically implanted in both the control and aluminum treated animals to provide a common port for aluminum injection. In addition, the control animals were pair-fed to the aluminum treated animals. The treated animals accumulated aluminum at about 0.1 mg/gm dry weight of liver/day. At 14 days, the cytochrome P-450 was decreased 20%, but the other components, cytochrome b5 and cytochrome reductases, were unchanged. By day 21 both cytochrome P-450 and cytochrome b5 were reduced 25%. Although NADPH cytochrome c reductase was not affected, the other flavoprotein, NADH cytochrome c reductase, was reduced. Drug metabolism, O-demethylation of p-nitroanisole and p-hydroxylation of aniline, was not affected at 14 days. However, at 21 days O-demethylation was not affected, but aniline hydroxylation was decreased, indicating an affect of aluminum on a specific isoenzyme of cytochrome P-450. Uniquely, the nonactivated glucuronyl transferase activity was fourfold greater in the aluminum treated animals. The increase was greater than cation activation and was similar to the detergent activated activity. Thus, aluminum infusion does produce specific alterations in microsomal function, including drug metabolism and conjugation.

Aluminum↗
PubMed1987

Problems with generic theophylline and indiscriminate brand switching.

Theophylline is a very efficacious medication for the treatment of bronchospastic disorders: however, it has a narrow therapeutic range of 10 to 20 micrograms/mL. Pharmacokinetics of theophylline can be affected by diverse factors, such as viral infections, fever, circadian rhythms, food ingestion, and a large number of medications. Theophylline is monitored through a serum theophylline level, which is dependent both on the amount of medication taken, the specific preparation ingested, as well as the amount of time between medication ingestion and serum level. The physician must know specific pharmacokinetic data to ascertain the preparation to use and the proper time to draw levels. This paper also discusses the toxic effects that a patient could incur if one theophylline preparation is indiscriminately substituted for another.

Asthma↗
PubMed1986

The effects of aluminum loading on the renal response to parathyroid hormone in the vitamin D-replete rat.

Aluminum (Al) may cause vitamin D-resistant osteomalacia and depress the serum levels of immunoreactive parathyroid hormone (iPTH) in patients treated with maintenance dialysis and those on total parental nutrition (TPN). Both conditions have been associated with low serum levels of 1,25(OH)2-vitamin D (1,25(OH)2D). Al may inhibit PTH secretion in vitro; however, induction of hypocalcemia can enhance endogenous PTH secretion in Al-loaded dogs and TPN patients. Despite hypocalcemia and/or increased endogenous iPTH levels, Al-loaded TPN patients fail to show the expected rise in serum 1,25(OH)2D levels. Such observations suggest that Al may impair the renal response to PTH. We studied vitamin D-replete rats given Al or saline vehicle IP for 5 days. Al and control rats then received a saline infusion with an IV bolus of PTH 1-34. Urinary cyclic AMP and P excretion rose in Al and control rats by 1 hr post-PTH, without differences between the groups. Serum P and ionized Ca levels were not different between Al and control rats. In other Al and control rats, serum 1,25(OH)2D levels were measured after saline without PTH. Serum 1,25(OH)2D levels were higher in controls given PTH than in those without, but 1,25(OH)2D levels were not different between Al rats given PTH and those with none. Thus, aluminum does not affect cyclic AMP or P excretion but may impair 25(OH)D-1 alpha-hydroxylase activity in response to PTH.

Aluminum↗