Determination of 3,4-dihydroxyphenylalanine (DOPA) in plasma and cerebrospinal fluid by high performance liquid chromatography with electrochemical detection

We report a reliable method for determining DOPA levels in plasma and cerebrospinal fluid. The method is based on complete conversion of DOPA to dopamine and quantification by HPLC-ECD of the dopamine formed. Lower limit of detection was 0.5 nmol/l. No differences in plasma DOPA levels were found between normal children (0-15 yr, n = 60), normal adults (n = 39) and patients with essential hypertension (n = 40) or Parkinson's disease (no DOPA therapy, n = 30). In normal individuals and in patients with essential hypertension venous plasma levels were higher than arterial levels (10.2 vs 9.3 nmol/l, p less than 0.001, V/A ratio 1.11 (SD 0.08), n = 15). Sympathetic stimuli (standing, tilting, bicycle exercise, tyramine) did not influence DOPA levels. In untreated depressed patients (n = 10) and in non-parkinsonian neurological patients (n = 12) cerebrospinal fluid levels of DOPA were 4.5 (SD 2.4) and 5.2 (SD 1.3) nmol/l respectively. A direct method for the measurement of DOPA by HPLC-ECD after deproteinization of plasma is also described and compared with the conversion method. Good agreement was found when plasma DOPA levels exceeded 0.25 mumol/l (y(conversion method) = 0.943x (direct method) + 0.118; n = 60; r = 0.985). The direct method, because of greater simplicity and the possibility of simultaneous measurement of the DOPA metabolite 3-O-methyldopa, is the method of choice with plasma samples from DOPA-treated patients. In non-DOPA treated individuals the conversion method is superior and has proved to be an accurate and sensitive method for the determination of DOPA levels in plasma and cerebrospinal fluid.     

Angiotensin Converting Enzyme Inhibitors: Animal Experiments Suggest a New Pharmacological Treatment for Alcohol Abuse in Humans

The prevalence of heavy alcohol consumption is a major problem of increasing proportions throughout the world. Although alcohol sensitizing drugs and more recently serotonin uptake inhibitors are drug interventions with some following, their long term beneficial consequences have yet to be demonstrated. In recent years, we have demonstrated that manipulating activity in the renin-angiotensin system will dramatically alter voluntary alcohol consumption in rats. Based on these findings, the present study evaluated the ability of a class of drugs known as the angiotensin converting enzyme inhibitors to reduce voluntary alcohol drinking in laboratory animals. These drugs prevent the conversion of angiotensin I to angiotensin II. They have been licensed for use in Europe and North America and are indicated in the treatment of hypertension. Our experiments showed that both captopril (Capoten, Squibb) and enalapril (Vasotec, Merck Sharpe & Dohme) can reduce alcohol drinking in both normotensive and hypertensive animals regardless of whether the pattern of intake is in a bout or of a less exaggerated nature. Furthermore, this change in alcohol intake can occur without concomitant changes in blood pressure, plasma renin activity, overall fluid balance, or the distribution and metabolism of alcohol. Taken together these findings suggest that the angiotensin converting enzyme inhibitors should be evaluated in a clinical setting for they may prove to be a useful new treatment or treatment adjunct for alcohol abuse in humans.     

Memory clinic attenders: A review of 150 consecutive patients

The Dundee Memory Clinic was established in 1991. This paper reviews the diagnosis of the first 150 attenders and compares the findings with those of other memory clinics.     

Regulation of fibroblast-induced collagen gel contraction by interleukin-1β

Fibroblasts incorporated within collagen gels induce a cell-mediated contraction of the gel to form a three-dimensional, tissue-like structure by a mechanism thought to mimic wound contraction in vivo . In this study a gel contraction model was used to investigate the ability of fibroblasts derived from adult gingiva, adult skin and fetal skin to organise a collagen matrix. In addition the effects of interleukin-1β (IL-1β) on the contraction process was also investigated. Over the concentration range 5-50 U/ml, IL-1β induced a statistically significant inhibition of gel contraction in all fibroblast cell types ( P <0.05), although fetal fibroblasts appeared least responsive and gingival fibroblasts most responsive to the inhibitory effects of this cytokine. Comparison of gel contraction by the different fibroblast strains indicated that fetal and gingival fibroblasts shared similar contraction kinetics. For the adult skin fibroblasts, three of five strains studied showed significantly diminished levels of gel contraction compared to fetal and gingival cells. This apparent difference in fibroblast phenotype may, at least in part, explain the fetal-like wound healing pattern seen in the oral mucosa.     

Diagnostic Value of the Preoperative Sestamibi Scan in Intraoperative Localization of Parathyroid Adenomas: A Case Study

A retrospective chart review of 43 patients who underwent technetium 99m (Tc-99m) sestamibi scans from June 1995 to January 1997 was performed. Only those who underwent subsequent parathyroid exploration with excision were included in the study. Twenty subjects (13 women and seven men) were included in the study. Ages ranged from 21 to 84 years (mean, 58 years). All patients had laboratory values and clinical findings consistent with primary hyperparathyroidism. Two patients had preoperative magnetic resonance imaging (MRI) scans (one patient with recurrent disease), and one had a preoperative computed tomography (CT) scan. The remaining patients had the sestamibi scan as the only preoperative localization study. There were 18 pathologic diagnoses of parathyroid adenoma and two of parathyroid hyperplasia. Sestamibi failed to correctly identify the location of the parathyroid lesion in two cases. In 18 cases the preoperative sestamibi scan correctly localized the lesion, a predictive value of 90%. We conclude that the Tc-99m sestamibi scan is an accurate preoperative tool that can be used as a single modality to localize parathyroid adenomas.     

Acute disseminated encephalomyelitis: the importance of early magnetic resonance imaging

The diagnosis of acute disseminated encephalomyelitis (ADEM) is frequently missed or delayed with consequent delay in instituting therapy in the crucial phase of the illness. The role of MRI in the diagnosis of ADEM is well established, however, the value of its early utilization of treatment on the outcome of patients has not been adequately stressed. Three patients with ADEM are described. Delay in the diagnosis of the first was associated with severe sequelae, while in the other two early diagnosis and institution of corticosteroid therapy which was facilitated by MRI, was associated with a better outcome. MRI should be carried out early once the diagosis of ADEM is entertained.