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.     

Androgen receptors in colorectal adenomas

Summary To evaluate the potential effect of androgens on the development and growth of human colorectal adenomas, the prevalence and concentration of cytosolic androgen receptors (AR) were analysed in 26 adenomas and 19 samples of normal colonic mucosa by a hybrid ligand receptor-binding assay. AR were detected in 7 of the adenomas (26.9%), and in 6 of the normal mucosa samples (31.6%). In the adenomas, AR levels demonstrated were low, ranging from 6 to 31 fmol/mg cytosol protein, and dissociation constants (Kds) ranged from 0.17–2.7x10^-9 M. Of 13 adenomas excised from men, 6 (46%) had positive receptor activity, whereas only 1 of 13 (7.7%) from women was positive (P=0.03, Fisher's exact test). There was no correlation between AR titre and patient age, or between adenoma size and histological type or degree of dysplasia. In normal mucosa, AR levels ranged from 7 to 33 fmol/mg and Kds ranges from 0.24–3.1x10^-9 M. There was no significant difference between either AR prevalence or levels in the adenomas and normal mucosa. The sex difference was exclusive to the adenoma. Endogenous androgen may play a role in adenoma development early in the promotional process.     

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.     

Pulmonary valve insertion during reoperation for tetralogy of Fallot

Our experience with pulmonary valve insertion during reoperation for residual lesions after initial open repair of tetralogy of Fallot in 15 patients is reported. Preoperatively, 14 patients were in moderate to severe congestive heart failure, and all 15 had decreased right ventricular (RV) function at cardiac catheterization. All 15 patients had pulmonary insufficiency but not as an isolated finding. The most common residual lesions encountered were ventricular septal defect in 9, tricuspid insufficiency in 11, and peripheral pulmonary arterial stenosis in 6. Tissue valves were inserted in all patients. Mean peak RV-left ventricular pressure ratio measured in the operating room decreased from 0.61 +/- 0.10 (+/- the standard deviation) to 0.47 +/- 0.17 (p less than 0.05). There were no operative deaths. At follow-up (mean, 33 months), all but 1 patient were in New York Heart Association Class I or II. Pulmonary valve insertion should be considered during reoperation for tetralogy of Fallot when pulmonary insufficiency and RV failure are present.     

Adjuvant systemic treatment of resectable breast cancer: eleven years results of a monoinstitutional chemo-hormone-immunotherapy trial

131 patients with resectable, node-positive breast cancer were treated at the National Institute for Cancer Research of Genoa, Italy with a systemic adjuvant regimen based on 14 cycles of chemotherapy, immunostimulation with levamisole, and--for postmenopausal patients--hormone therapy with tamoxifen. The present evaluation is performed eleven years after the admission of the first patient: so far, 75 patients (57.3%) have relapsed and 52 (39.7%) have died. An analysis of prognostic factors for relapse and death shows that the number of positive axillary lymph nodes and the dimension of the primary tumor are significantly associated with survival and relapse-free survival, while age and menopausal status are not.     

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.     

Functional MR of the primary auditory cortex: an analysis of pure tone activation and tone discrimination.

PURPOSETo use functional MR imaging to measure the effect of frequency (pitch), intensity (loudness), and complexity of auditory stimuli on activation in the primary and secondary auditory cortexes.METHODSMultiplanar echo-planar images were acquired in healthy subjects with normal hearing to whom auditory stimuli were presented intermittently. Functional images were processed from the echo-planar images with conventional postprocessing methods. The stimuli included pure tones with a single frequency and intensity, pure tones with the frequency stepped between 1,000, 2,000, 3,000, or 4,000 Hz, and spoken text. The pixels activated by each task in the transverse temporal gyrus (TTG) and the auditory association areas were tabulated.RESULTSThe pure tone task activated the TTG. The 1,000-Hz tone activated significantly more pixels in the TTG than did the 4,000-Hz tone. The 4,000-Hz tone activated pixels primarily in the medial TTG, whereas the 1,000-Hz tone activated more pixels in the lateral TTG. Higher intensity tones activated significantly more pixels than did lower intensity tones at the same frequency. The stepped tones activated more pixels than the pure tones, but the difference was not significant. The text task produced significantly more activation than did the pure tones in the TTG and in the auditory association areas. The more complex tasks (stepped tones and listening to text) tended to activate more pixels in the left hemisphere than in the right, whereas the simpler tasks activated similar numbers of pixels in each hemisphere.CONCLUSIONAuditory stimuli activate the TTG and the association areas. Activation in the primary auditory cortex depends on frequency, intensity, and complexity of the auditory stimulus. Activation of the auditory association areas requires more complex auditory stimuli, such as the stepped tone task or text reading.