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Biomedical subjects

G Klee

Publications and source records attributed to G Klee.

18 recordsLinked to original sources
PubMed2004

Investigating four 'myths' surrounding dysphagia in patients with metastatic esophageal cancer. A multi-institutional study from the North Central Cancer Treatment Group.

Eighty-five to 95% of esophageal cancer patients suffer dysphagia. Yet, few studies have focused on this symptom, and four 'myths' persist: (i) dysphagia cannot be measured; (ii) chemotherapy cannot palliate it; (iii) dysphagia predicts a poor prognosis; (iv) dysphagia is associated with a frustratingly insatiable appetite. Forty-four patients with metastatic esophageal cancer participated in this quality of life/translational component of a previously reported clinical trial. All were monitored for chemotherapy efficacy and toxicity and completed questionnaires on dysphagia and appetite at baseline and every 6 weeks. The appetite hormones, leptin and neuropeptide y, were also assessed. Forty-five per cent of patients could easily swallow solid foods; all others had varying dysphagia, thus enabling exploration of these four 'myths.' First, a single-item visual analog scale (Swallowing Scale), demonstrated excellent agreement with a previously validated questionnaire (81% at baseline), thus reminding us that dysphagia is measurable. Second, chemotherapy was associated with a trend towards improved dysphagia (P = 0.059). Third, dysphagia did not predict tumor response or survival. Fourth, dysphagia was not associated with appetite, leptin or neuropeptide y. This study helps to dispel these four 'myths' and underscores the need for further quality of life research on dysphagia.

Adenocarcinoma↗
PubMed2003

International Council for Standardization in Haematology (ICSH) recommendations for "surrogate reference" method for the packed cell volume.

The spun packed cell volume (PCV, hematocrit) is a key measurement on which are based hematology instrument calibration, reference range determination, and assignment of values to calibrators/controls. In 2001, the International Council for Standardization in Haematology (ICSH) recommended a Reference PCV method, which is fully traceable to the ICSH reference hemoglobin method. Because of its complexity, however, this method is impractical for occasional use in routine laboratories and is therefore intended primarily for use by manufacturers of capillary microhematocrit tubes, liquid calibrators, and multichannel analyzers. In response to the need for a simpler method--accessible to all routine laboratories--the ICSH offers this "Surrogate Reference" PCV procedure. It is traceable to the original ICSH Reference PCV method and is based on spun PCVs obtained using borosilicate capillary tubes with an already-known relationship to this reference procedure. This ICSH "Surrogate Reference" PCV method is substantially simpler, thus putting it within the reach of most routine hematology laboratories.

Blood Specimen Collection↗
PubMed2000

Clinical use of biochemical markers of bone remodeling: current status and future directions.

Biochemical markers of bone turnover provide a means of evaluating skeletal dynamics that complements static measurements of bone mineral density (BMD). This review evaluates the use of commercially available bone turnover markers as aids in diagnosis and monitoring response to treatment in patients with osteoporosis. High within-person variability complicates but does not preclude their use. Elevated bone resorption markers appear to be associated with increased fracture risk in elderly women, but there is less evidence of a relationship between bone formation markers and fracture risk. The critical question of predicting fracture efficacy with treatment has not been answered. Changes in bone markers as currently determined do not predict BMD response to either bisphosphonates or hormone replacement therapy. Single measurements of markers do not predict BMD cross-sectionally (except possibly in the very elderly), or change in BMD in individual patients, either treated or untreated. On the other hand, research applications of bone turnover markers are of value in investigating the pathogenesis and treatment of bone diseases. Markers have potential in the clinical management of osteoporosis, but their use in this regard is not established. Additional studies with fracture endpoints and information on negative and positive predictive value are needed to evaluate fully the utility of bone turnover markers in individual patients.

Biomarkers↗
PubMed1998

Guidelines for organisation and management of external quality assessment using proficiency testing. Expert Panel on Cytometry of the International Council for Standardization in Haematology.

This document is intended to assist towards the WHO objective that external quality assessment (EQA) schemes be established at national and/or regional levels world-wide. Quality assurance is defined as all steps taken by the director of a laboratory to ensure reliability of laboratory results and to increase accuracy, reproducibility and between-laboratory comparability. This includes the use of internal quality control procedures and participation in external quality assessment. Internal quality control provides the means for evaluation of analytic test results at the time of testing in order to decide whether they are reliable enough to be released to the requesting clinicians. EQA, on the other hand, refers to a system of retrospective and objective comparison of results from different laboratories by means of proficiency testing (PT) organised by an external agency. The main purpose is to establish between-laboratory and between-method (including between-instrument) comparability, and agreement with a reference standard where one exists. Internal quality control and EQA complement each other and must never be considered as alternatives.

Animals↗
PubMed1997

A conceptual model for establishing tolerance limits for analytic bias and imprecision based on variations in population test distributions.

A conceptual model is proposed for defining analytic bias limits utilizing the variations found in cumulative test value distributions. The model is based on the propositions that changes in analytic bias are more important than analytic imprecision in medical diagnoses and that analytic bias alters clinical specificity more than clinical sensitivity. The rationale for these propositions are presented along with a step-by-step procedure for estimating bias tolerance limits. These concepts are illustrated with an example using prostate-specific antigen. A second protocol is provided to define analytic imprecision tolerance limits, based on the quality control performance characteristics required to maintain the bias tolerance limits. This model can be applied to most chemistry, immunoassay, and hematologic quantitative assays. The relationship of this procedure to the published procedures using biologic variation for defining analytic tolerance limits is discussed.

Bias↗
PubMed1997

Regulation of migrating motor complexes by motilin and pancreatic polypeptide in human infants.

In adults, migrating motor complexes (MMCs) appear to be partially under hormonal modulation by motilin and pancreatic polypeptide. Preterm infants do not exhibit MMCs until 32 wk of gestation. Although plasma concentrations of motilin are similar in infants and adults, it is not known if actual hormonal modulation of MMCs is present in infants. In the first study we assessed whether plasma concentrations of motilin and pancreatic polypeptide surge with the occurrence of MMCs in term infants. In the second study we assessed whether erythromycin, a motilin receptor agonist, could induce migrating motor activity in preterm and term infants. In the first study we recorded motor activity in nine term infants who had never been fed. We determined plasma concentrations of motilin and pancreatic polypeptide in the presence and absence of MMCs. In the second study we gave the motilin agonist erythromycin intragastrically to 21 infants at a range of 24-42 wk of gestation to assess whether migrating activity could be induced via the motilin receptor. In the first study, plasma concentrations of motilin were similar during the presence and absence of MMCs, as were plasma concentrations of pancreatic polypeptide. In the second study, the administration of erythromycin induced the appearance of migrating activity in 7 of 14 infants who were older than 32 wk but in none of the infants who was younger than 32 wk. Although the motilin receptor appears to be functionally present beyond 32 wk of gestation, as assessed by in indirect pharmacologic challenge, hormonal modulation of migrating activity in the neonate by plasma motilin and pancreatic polypeptide is absent.

Anti-Bacterial Agents↗
PubMed1996

The impact of gender on alpha-methyl-para-tyrosine mediated changes in prolactin secretion and 6-hydroxymelatonin sulfate excretion.

Prolactin (PRL) and melatonin (ML) secretion are mediated by dopamine (DA) and norepinephrine (NE), respectively. Alpha-methyl-para-tyrosine (AMPT) inhibits the production of CNS catecholamines (CA). The purpose of the study is to determine: (1) if AMPT inhibition of ML has the same gender-dependent effect as on PRL secretion; (2) if there is a post AMPT-induced NE depletion mood change in men and/or women. In a randomized, double-blind cross-over fashion, five healthy young males and five females were either given five doses of AMPT 1 g (active) or promethazine 50 mg (placebo) over a 28 h period, separated by 4-6 weeks. The PRL and ML concentrations were collected at regular intervals via an indwelling venous catheter and concurrently, two 12 h urinary 6-hydroxymelatonin sulfate (6-MS) measurements were made. Mood and anxiety states of subjects at baseline and post drug were assessed with appropriate rating scales at regular intervals. Light exposure beginning at dusk and lasting until dawn was controlled to no more than 200 lux during all phases of the study. The PRL secretion showed a significant interaction of drug x time (p = .0001) in women and a non-significant trend (p = .056) in men. No difference in PRL secretion was found between the two genders in the placebo condition, whereas the PRL secretion was significantly higher in the AMPT condition in women when compared to men (df 17,119, F = 1.9, p = .021). Total 24 h urinary 6-MS secretion highly correlated with ML secretion expressed as area under the curve (AUC) during both active and placebo experiments (r = 0.8, p < .01) and (r = 0.86, p < or = .01), respectively. The ANOVA reveals a significant interaction of drug x time for 6-SM excretion. There was no gender difference in AMPT suppression of 6-MS excretion. No mood changes were detected in men or women. We conclude that urinary 6-MS is a reliable indirect measure of the degree of AMPT-induced decrease in CNS NE activity as part of overall AMPT-induced reduction of central catecholamine activities. The pre and post AMPT-induced changes in 6-MS are not gender dependent, dissimilar to the AMPT-induced changes in PRL secretion. Therefore, 6-MS, in addition to PRL, should be measured when applying the AMPT paradigm in future research.

Adult↗
PubMed1996

Examining serotonin function: a modified technique for rapid tryptophan depletion.

Tryptophan (TRP) depletion was used to study serotonin because the ratio of TRP to large neutral amino acids (TRP/LNAA) determines the quantity of TRP that enters the brain. Because TRP is not universally available, a modified technique of TRP depletion was developed where a 1/4 strength preparation of an amino acid mixture (AAM) replaces TRP as the placebo. Seven healthy subjects could not differentiate between the preparations in this double-blind, placebo-controlled study. Urinary 6-hydroxymelatonin sulfate (6-MS) was monitored as a biochemical marker of serotonin. The TRP/LNAA ratio (GG = 0.001) and 6-MS secretion (GG = 0.024) were decreased, but placebo TRP levels (GG = 0.062) were not altered significantly. This modified technique facilitates the use of TRP depletion in clinical research.

Adult↗
PubMed1996

Comparison of four digoxin immunoassays with respect to interference from digoxin-like immunoreactive factors.

OBJECTIVES: Comparison of a new monoclonal digoxin assay with three polyclonal digoxin assays for their cross-reactivity to digoxin-like immunoreactive factors (DLIF) and digoxin metabolites. DESIGN AND METHODS: Sixty-six nondigitalized patient samples from 5 different groups: neonates, women in 3rd trimester pregnancy, and patients with liver or renal diseases, or undergoing organ transplants, and 139 samples from digoxin-treated patients of 4 categories (hospital sick, liver, renal, and outpatients) were compared in 4 different digoxin assays: (a) ACS Digoxin (ACS) developed for the automated chemiluminescent Ciba Corning ACS 180 system, (b) Baxter Stratus (Stratus, a fluoroimmunoassay), (c) Ciba-Corning Magic (Magic, a radioimmunoassay), and (d) an in-house radioimmunoassay (RIA). The ACS and RIA were also compared for their cross-reactivity to four principal digoxin metabolites. RESULTS AND CONCLUSION: Among the nondigitalized specimens, no significant DLIF interference was found for all 4 assays among the pregnant women or liver and transplant patients. However, the neonates registered high DLIF interference with Magic and RIA, but none for ACS or Stratus. DLIF interference in renal samples was highest in the Magic assay and lowest in RIA. Among the specimens with digoxin, a higher number of discrepant samples were found from the sick patients than from outpatients. In 75% of such discrepant samples, the ACS result was less than other assay results, suggesting DLIF as the probable cause. The two assays differed most in their cross-reactivity to the deglycated metabolites, digoxigenin and its mono-digitoxoside.

Adult↗
PubMed1994

Screening for hemochromatosis: a cost-effectiveness study based on 12,258 patients.

BACKGROUND/AIMS: Current emphasis in hemochromatosis has focused on early detection and treatment to prevent permanent liver damage and hepatocellular carcinoma. Thus far, only normal population and high-risk groups have been screened but not patients seeking medical care. METHODS: Serum iron levels were determined in consecutive fasting blood samples collected in the morning from 12,258 Mayo Clinic patients. RESULTS: One hundred twenty-seven patients had an initial serum iron concentration > or = 180 micrograms/dL. Eight patients (age, 38-71 years; 7 men and 1 woman) had transferrin saturation > or = 62% (range, 84-99) and serum ferritin value > or = 400 micrograms/L (range, 457-4004) with no other explanation for the abnormal iron test results. Three patients (2 male and 1 female) had markedly elevated hepatic iron concentration (range, 11,080-29,719 micrograms/g dry wt) and hepatic iron index (range, 2.9-8.4) indicative of homozygous hemochromatosis. One patient who refused liver biopsy had 7 g of iron removed by phlebotomy and is likely homozygous. Two patients had hepatic iron indices < 1.5 and are probably heterozygous. The genetic status of 1 patient is indeterminate, and 1 patient with normal hepatic iron concentration and hepatic iron index had chronic active hepatitis. None had cirrhosis, diabetes, or cardiomyopathy. No patients with hemochromatosis would have been detected without this study. CONCLUSIONS: The yield in this study, 0.33 cases of 1000 screened, is approximately one tenth of the predicted homozygote frequency by recent estimates. Even at this yield, screening appears cost-effective.

Adolescent↗
PubMed1994

Inhibition of presynaptic catecholamine synthesis with alpha-methyl-para-tyrosine attenuates nocturnal melatonin secretion in humans.

The catecholamine dopamine (D) is involved in the regulation of LH and PRL secretion, whereas a dysregulated noradrenergic system may contribute significantly to symptoms encountered in affective disorders. This explains the attraction of using alpha-methyl-para-tyrosine (AMPT) in neuroendocrine and psychiatric research, as it inhibits both neurotransmitters. PRL has been used as a marker of the effectiveness of AMPT in blocking D function, but no good marker for the effectiveness of AMPT in blocking norepinephrine (NE) is available. The purpose of this study was to determine whether melatonin (M) might serve as such a marker, as its production and secretion are regulated by NE. Seven subjects were given either AMPT or promethazine, which does not alter M secretion, in a randomized, double blind fashion, and 24-h M secretion was studied. Two-way analysis of variance revealed a significant difference in M secretion (F = 13.2; df = 17,102; P = 0.0013), with the following time points being different: 22, 23, 24, 1, 2, 3, 4, 5, and 6 h. Also, 24-h urinary 6-sulfatoxymelatonin excretion correlated highly with 24-h M secretion, expressed as the area under the curve in the AMPT experiment (r = 0.93; P = 0.002), which indicates that AMPT does not alter the metabolism of M. These results demonstrate for the first time that AMPT significantly attenuates nocturnal M secretion. It is concluded that M is a good marker for characterizing the effectiveness of AMPT in inhibiting sympathetic NE activity.

Adult↗
PubMed1988

Cardiorenal endocrine dynamics during volume expansion in hypothyroid dogs.

To address the role of atrial natriuretic factor (ANF) in hypothyroidism in the control of cardiorenal-endocrine function during volume loading, the relationships between atrial pressure, ANF, the renin-angiotensin-aldosterone system, and renal hemodynamic and excretory function were examined during and after acute 10% body wt saline volume infusion in pentobarbital-anesthetized hypothyroid dogs (n = 8). Hormonal changes before and after thyroidectomy were also evaluated. Four to 6 wk after thyroidectomy, ANF decreased and arginine vasopressin (AVP) and plasma renin activity (PRA) increased. Acute saline volume expansion caused an increase in ANF and decreases in AVP and PRA. Atrial pressure increased throughout volume expansion. Despite the absence of an increase in glomerular filtration rate (GFR) during volume expansion, urinary sodium excretion increased due to a marked rise in fractional excretion of sodium. These studies demonstrate that in hypothyroidism 1) ANF is decreased; 2) despite the decrease in basal ANF, increases in atrial pressure can stimulate relase of ANF; 3) despite the absence of an increase in GFR during volume expansion, fractional excretion of sodium increases associated with an increase in ANF; and 4) a lack of an increase in GFR during volume expansion is not related to an inability to increase ANF.

Aldosterone↗
PubMed1987

Alpha-fetoprotein associated with islet cell tumors.

Elevated serum levels of alpha-fetoprotein (AFP) (100-1,000 ng/ml) were found in three patients with islet cell tumors. Serial levels correlated with progression of disease, suggesting that AFP could be a useful tumor marker substance for islet cell tumors. Survey sera from an expanded pool of 23 patients with islet cell tumors and nine with carcinoid tumors did not identify additional cases, however, suggesting that elevated AFP levels in these classes of Apudomas are uncommon. Nonetheless, the distinction from other AFP-producing tumors such as hepatocellular carcinoma is clinically important and warrants an awareness of the rare association of AFP with these tumors.

Adenoma, Islet Cell↗
PubMed1977

[The behavior of calves under various housing conditions].

Investigations were performed regarding the length of rest, sucking and feeding and the daily rhythm of these activities in calves kept with their mothers on pasture or in stables and the motility of the calves. Length of rest and feeding in breeding calves kept in groups and length of rest and sucking in breeding and fattening calves (automatic feeding and bucket feeding) were examined too. The examinations were performed starting from the morning feeding to the end of the day over a period of appr. 10.5 to 12 hours. During this time, calves 2--4 weeks of age ran about 550,7 m, 6--8 weeks of age 423.7 and 10--12 weeks of age 388.1 m. The length of sucking under automatic feeding conditions was comparable to the datas obtained from calves kept with their mothers. Bucket feeding took 2--4 minutes regardless whether rubber teats were used or not. Fattening calves in groups or single showed feint sucking or licking activities of 70.0 and 114.0 minutes/day respectively, breeding calves 39.8 and 20.8 minutes/day resp. Feint sucking in connection with a deficit of real sucking was observed regularly under bucket feeding conditions but only in those cases of automatic feeding, where the calves pushed each other aside from the feeding facilities. Feint rumination was observed in all fattening calves when kept strawlessly and lasted for about 31 minutes/day. Neither the feint rumination nor the feint sucking ever reached physiological lengths. Both behavioural patterns may be important in regard to animal welfare considerations of special maintenance conditions.

Animals↗