Urinary excretion of 5-S-cysteinyldopa in patients with primary melanoma or melanoma metastasis.

Urinary excretion of 5-S-cysteinyldopa was studied in 9 patients with primary melanoma. All had 5-S-cysteinyldopa excretion in the normal range. In 8 of the patients excretion values decreased after removal of the tumour. Twenty-four patients with clinical signs of melanoma metastasis were examined for 5-S-cysteinyldopa and dopa+dopamine in the urine. 16 of the 24 had pathologically increased excretion of 5-S-cysteinyldopa and 7 of the 24 had pathological excretion of dopa+dopamine. Six of the latter belonged to the group with increased 5-S-cysteinyldopa excretion and one patient had a borderline value of 5-S-cysteinyldopa. Determination of 5-S-cysteinyldopa seems to be of value in the follow-up of patients operated on for primary melanoma.     

Outliers,a way to detect abnormality in quantitative EMG

In visual analysis of motor unit potentials it is common to decide abnormality by a few motor unit potentials with definitely abnormal amplitude, duration, and shape. The aim of the present investigation was to define limits of normal values and to compare the diagnostic yield of assessing definitely abnormal values outliers, with conventional mean values of MUP parameters. MUPs were extracted and measured with a new decomposition method. Reference values were obtained for three commonly studied muscles. Patients with various types of neuropathies and myopathies were studied in the same way with measurement of outliers and mean values. It was found that outliers were as sensitive as mean values in neuropathies and better in myopathies. Often an increased number of outliers could already be detected after only a few MUPs had been obtained. It would not have been necessary to obtain all 20 MUPs in these patients. The conclusion is that the outlier method is as sensitive as mean values. Because the number of MUPs required may be reduced, the investigation takes a shorter time and is less painful for the patient. If the degree of abnormality is to be quantified, calculation of mean values is still necessary. The combination of outliers and mean values may be the optimal way to detect and express abnormality. © 1994 John Wiley & Sons, Inc.     

Promoting the health of aging adults in the community

Journal of Community Health -     

Multi-sample standardization and decomposition analysis: an application to comparisons of methamphetamine use among rural drug users in three American states

This study demonstrates how to use standardization and decomposition analysis (SDA) techniques to compare outcome measures simultaneously among multiple populations. Methamphetamine use among rural stimulant drug users in three geographically distinct areas of the US (Arkansas, Kentucky, and Ohio) is presented as an example of applying SDA. Findings show that the observed crude rate of 'ever used' methamphetamine in the past 30 days and the frequency of methamphetamine use in the past 30 days were much higher in Kentucky than in the other two states. However, after the compositions of socio-demographic confounding factors were standardized across the samples, the two measures of methamphetamine use ranked highest in Arkansas, followed by Kentucky, and then Ohio. Confounding factors contributed in various dimensions to the differences in the observed outcome measures among the distinct samples. The study shows that SDA is a useful technique for multi-population comparisons, providing an opportunity to look at data from a different perspective in medical studies.     

The rabbit pulmonary cytochrome P450 arachidonic acid metabolic pathway: characterization and significance.

Cytochrome P450 metabolizes arachidonic acid to several unique and biologically active compounds in rabbit liver and kidney. Microsomal fractions prepared from rabbit lung homogenates metabolized arachidonic acid through cytochrome P450 pathways, yielding cis-epoxyeicosatrienoic acids (EETs) and their hydration products, vic-dihydroxyeicosatrienoic acids, mid-chain cis-trans conjugated dienols, and 19- and 20-hydroxyeicosatetraenoic acids. Inhibition studies using polyclonal antibodies prepared against purified CYP2B4 demonstrated 100% inhibition of arachidonic acid epoxide formation. Purified CYP2B4, reconstituted in the presence of NADPH-cytochrome P450 reductase and cytochrome b5, metabolized arachidonic acid, producing primarily EETs. EETs were detected in lung homogenate using gas chromatography/mass spectroscopy, providing evidence for the in vivo pulmonary cytochrome P450 epoxidation of arachidonic acid. Chiral analysis of these lung EETs demonstrated a preference for the 14(R),15(S)-, 11(S),12(R)-, and 8(S),9(R)-EET enantiomers. Both EETs and vic-dihydroxyeicosatrienoic acids were detected in bronchoalveolar lavage fluid. At micromolar concentrations, methylated 5,6-EET and 8,9-EET significantly relaxed histamine-contracted guinea pig hilar bronchi in vitro. In contrast, 20-hydroxyeicosatetraenoic acid caused contraction to near maximal tension. We conclude that CYP2B4, an abundant rabbit lung cytochrome P450 enzyme, is the primary constitutive pulmonary arachidonic acid epoxygenase and that these locally produced, biologically active eicosanoids may be involved in maintaining homeostasis within the lung.     

Alterations in the regulation of androgen-sensitive Cyp 4a monooxygenases cause hypertension

Hypertension is a leading cause of cardiovascular, cerebral, and renal disease morbidity and mortality. Here we show that disruption of the Cyp 4a14 gene causes hypertension, which is, like most human hypertension, more severe in males. Male Cyp 4a14 (-/-) mice show increases in plasma androgens, kidney Cyp 4a12 expression, and the formation of prohypertensive 20-hydroxyarachidonate. Castration normalizes the blood pressure of Cyp 4a14 (-/-) mice and minimizes Cyp 4a12 expression and arachidonate omega-hydroxylation. Androgen replacement restores hypertensive phenotype, Cyp 4a12 expression, and 20-hydroxy-arachidonate formation. We conclude that the androgen-mediated regulation of Cyp 4a arachidonate monooxygenases is an important component of the renal mechanisms that control systemic blood pressures. These results provide direct evidence for a role of Cyp 4a isoforms in cardiovascular physiology, establish Cyp 4a14 (-/-) mice as a monogenic model for the study of cause/effect relationships between blood pressure, sex hormones, and P450 omega-hydroxylases, and suggest the human CYP 4A homologues as candidate genes for the analysis of the genetic and molecular basis of human hypertension.