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Biomedical subjects

C Weinkove

Publications and source records attributed to C Weinkove.

At least 19 recordsLinked to original sources
PubMed1999

Freedom from drug interference in new immunoassays for urinary catecholamines and metanephrines.

BACKGROUND: Determination of urinary free catecholamine and total (i. e., free plus conjugated) metanephrine excretion is considered the most clinically sensitive biochemical test for pheochromocytoma. In this study, we evaluated new immunoassay methods for the measurement of these analytes for potential drug-based interference. METHODS: Urine samples collected from patients on a variety of medications were grouped by specific drug type. The significance of any difference in the free catecholamine or total metanephrine concentrations in the different groups was assessed by one-way ANOVA. A group of patients receiving no medication was included as a control (no analytical interference). Additionally, analytical accuracy, detection limit, and precision were determined. RESULTS: No significant differences were found in the concentrations of free catecholamines or total metanephrines in urine from patients taking the medications investigated and the control group: P = 0.649 (fE), 0.221 (fNE), 0.149 (tM), and 0.170 (tNM). For free catecholamines, intraassay CVs were 4.6-18%; interassay CVs were 10-25%. For total metanephrines, intraassay CVs were 9.6-27%; interassay CVs were 5. 8-22%. Detection limits were 0.009 and 0.027 micromol/L for fE and fNE and 0.119 and 0.346 micromol/L for tM and tNM, respectively. CONCLUSIONS: None of the drugs examined in this study interfered in the measurement of free catecholamines or total metanephrines by these immunoassays. The technique is easier to use, requires less equipment, and is more accessible than HPLC. In combination, these assays are suitable as initial screening tests for pheochromocytoma.

Adrenergic beta-Antagonists↗
PubMed1996

A double-blind, placebo-controlled, crossover trial of oral vitamin C in erythropoietic protoporphyria.

There is evidence that reactive oxygen species and free radicals may be involved in the pathogenesis of photosensitivity in erythropoietic protoporphyria (EPP). Considering the well-known antioxidant properties of vitamin C, we investigated whether oral supplementation with this vitamin was photoprotective in patients with EPP. Twelve patients with EPP received either oral vitamin C 1 g daily or placebo, for 4 weeks, followed by a crossover period of another 4 weeks. Nine patients were already receiving beta carotene at entry and continued this at the same dose throughout the study. Patients compared their sunlight tolerance throughout each of the treatment periods with sunlight tolerance at entry on a 10 cm visual analogue scale; at the end of the study, they were asked to choose which treatment period they felt had been associated with least photosensitivity. Eight patients stated that they were able to tolerate sunshine better during the vitamin C period, 2 during the placebo period and 2 noticed no difference between the two periods. This distribution of preferences approached but did not reach statistical significance in favour of vitamin C. Visual analogue scores improved by a median of 1.2 cm in the vitamin C period. This change too approached but did not reach statistical significance. Although these results do not reach statistical significance, it appears possible that oral vitamin C may reduce photosensitivity in some patients with EPP. A larger study is necessary to confirm this impression.

Administration, Oral↗
PubMed1995

Hypertrichosis as the presenting feature of porphyria cutanea tarda.

We report a case of porphyria cutanea tarda in which the only cutaneous abnormality and initial presenting complaint was hypertrichosis. The patient had a history of excessive alcohol consumption. Alcohol avoidance and treatment with low-dose hydroxychloroquine resulted in resolution of the hypertrichosis and normalization of biochemical abnormalities.

Alcohol Drinking↗
PubMed1994

Fatty acids in erythrocytes measured by isocratic HPLC.

We developed an isocratic reversed-phase HPLC method to measure arachidonic, palmitoleic, linoleic, eicosatrienoic, oleic, palmitic, and stearic acids from hydrolyzed erythrocytes. Washed erythrocytes were heated in methanol:HCl and the fatty acids extracted into hexane:amyl alcohol. After derivatization with 4-bromomethyl-7-methoxycoumarin, samples diluted in mobile phase (acetonitrile:water, 85:15 by vol) were injected onto a 250 x 4.6 mm C18 column, and the eluted fatty acids were detected fluorometrically. For all analytes, the mean within-batch CV was 8.2% (5.5-10.8%), the mean limit of detection was 7.0 mumol/L, a linear response was maintained up to 400 mumol/L, and results agreed well with those by gas chromatography. The addition of antioxidant (butylated hydroxytoluene) was essential for sample stability. We discuss hydrolysis and extraction times, derivatization temperature, critical steps in chromatography, and concentration units.

Chromatography, High Pressure Liquid↗
PubMed1993

Biochemical diagnosis of phaeochromocytoma: two instructive case reports.

The biochemical features of two patients with phaeochromocytomas illustrate the inadvisability of depending on a single group of analytes for the diagnosis. The first case presented as a surgical emergency with retroperitoneal haemorrhage. Biochemical diagnosis was difficult since total 24 hour urinary free catecholamine excretion was within normal limits in two out of three samples, and only marginally raised in the third with an atypical preponderance of adrenaline. Plasma catecholamine concentrations were also normal. But urinary excretion of the catecholamine metabolites, metadrenaline and 4-hydroxy-3-methoxy mandelic acid (HMMA), was consistently raised. In contrast, the second patient presenting with headache and labile hypertension showed normal metabolite excretion in the face of grossly increased free noradrenaline excretion and raised plasma noradrenaline concentrations. It is therefore recommend that, as well as urinary free catecholamines, one group of their main metabolites, the 3-methoxy amines (normetadrenaline and metadrenaline) or HMMA, should routinely be measured whenever a phaeochromocytoma is suspected.

Adrenal Gland Neoplasms↗
PubMed1993

Plasma norepinephrine in sensory diabetic polyneuropathy.

OBJECTIVE: To examine whether changes in circulating norepinephrine are associated with the sensory disturbances of diabetic polyneuropathy. Experimental studies have indicated that NE can excite sprouts from injured nerves, producing pain. RESEARCH DESIGN AND METHODS: We measured supine and erect plasma NE in 13 normal, nondiabetic control subjects and three groups of diabetic patients: 20 without clinical neuropathy, 20 with chronic painful neuropathy, and 15 with painless neuropathy and foot ulceration. Neuropathy was characterized by symptom and deficit scores, sensory thresholds, electrophysiology, and cardiovascular autonomic function tests. Neuropathic pain was scored by the patients on a linear analogue scale. RESULTS: In painless neuropathy, NE levels were greatly reduced (supine, 1.3 nM; erect, 2.2 nM) compared with control subjects (supine, 2.4 nM; erect, 4.0 nM; P < 0.001) and were combined with grossly abnormal autonomic reflexes. NE also was reduced in the diabetic group without neuropathy (supine, 1.7 nM; erect, 2.7 nM; P < 0.01 vs. control subjects). By contrast, in painful neuropathy NE levels (supine, 2.2 nM; erect, 3.6 nM) were similar to control subjects and significantly higher than in painless neuropathy (P < 0.01). Furthermore, NE correlated with the severity of neuropathic pain (r = 0.46, P = 0.02). To assess whether pain, acting as a stressor, could account for the observed differences in NE, we also measured the stress hormones epinephrine and cortisol. They did not differ among the diabetic groups. CONCLUSIONS: Circulating NE is higher in painful than painless diabetic neuropathy. We suggest that painful neuropathy is associated with a relatively higher number of functioning sympathetic fibers that may contribute to pain.

Adult↗
PubMed1992

Acute intermittent porphyria treated by testosterone implant.

The hereditary disorder acute intermittent porphyria is potentially fatal. Many more females present with active disease than males and some have attacks related to their menstrual cycle and pregnancy. We present a female patient who was diagnosed while pregnant at 19 years. She subsequently developed life-threatening attacks pre-menstrually at 24 years; these were associated with weight loss. Initial treatment was with high calorie feeding via a naso-gastric tube, followed by a gastrostomy. Subsequent gonadotrophin suppression with intranasal luteinizing hormone-releasing hormone analogue (buserelin) thrice daily met with limited success. We implanted 100 mg of testosterone subcutaneously in November 1989. The buserelin was discontinued in January 1990 and menses returned 3 months later. There have been no serious attacks since then. Repeat implantation was performed at 6 monthly intervals until her present pregnancy. Baseline biochemical parameters have remained high and unaltered despite treatment although the testosterone has clearly had a marked clinical benefit, without side effects.

Acute Disease↗
PubMed1991

Bone-marrow transplantation for congenital erythropoietic porphyria.

Congenital erythropoietic porphyria, a disorder of haem synthesis, is caused by uroporphyrinogen III synthase deficiency in bone-marrow normoblasts. Uroporphyrins and coproporphyrins accumulate and cause oxidative damage to cells exposed to sunlight. Uroporphyrin overproduction was greatly reduced and skin changes reversed in a girl who received a bone-marrow graft from an HLA-identical sibling at 10 years of age. The patient died 11 months after transplantation because of severe progressive pneumonitis and encephalopathy associated with cytomegalovirus infection, but the encouraging response up to 8 months after engraftment indicates a possible benefit of bone-marrow transplantation in the treatment of this rare but usually fatal inherited disease.

Bone Marrow Transplantation↗
PubMed1990

Raised dopamine metabolites in a case of malignant paraganglioma.

This paper describes the case of a malignant retroperitoneal paraganglioma with extensive metastases. The patient presented with a supraclavicular mass and an absence of hypertension. Exclusively raised dopamine metabolites were detected which may be a marker of a malignant process and account for the lack of hypertension.

Adult↗
PubMed1990

Plasma porphyrins in chronic renal failure.

Using a quantitative sensitive HPLC fluorometric assay for the measurement of plasma and urine porphyrins, we have calculated the renal clearance of uro- and coproporphyrin in normal volunteers and in patients with congenital erythropoietic porphyria and hereditary coproporphyria (HCP). In patients with porphyria cutanea tarda (PCT), only uroporphyrin clearance was calculated. Plasma porphyrin concentrations were measured in patients with chronic renal failure (CRF). All our CRF patients on haemodialysis (10) had raised plasma uroporphyrin, 4 had raised plasma heptacarboxyporphyrins and 2 had raised plasma coproporphyrin, unchanged by haemodialysis. CRF patients with raised uroporphyrins and 7-carboxyporphyrins could be distinguished from PCT in patients with normal renal function, by their higher uro/7-carboxyporphyrin ratio (8.0 vs. 1.7). Renal clearance of coproporphyrin was much greater in HCP than in any of the other groups studied. Since coproporphyrin clearance was less than creatinine clearance in most normal subjects, and because 2 patients with CRF had raised plasma coproporphyrin concentrations, we argue that the kidney is probably not a major source of coproporphyrin, as previously reported. Furthermore, the variability and degree of abnormality in plasma porphyrins in CRF would suggest caution in diagnosing chronic porphyria in patients with renal impairment.

Adult↗
PubMed1990

Platelet and plasma vasoactive amines in type 1 (insulin-dependent) diabetes mellitus with and without vascular disease.

Platelet and plasma vasoactive amine concentrations were measured in healthy controls and in type 1 (insulin-dependent) diabetic patients with or without vascular disease. Platelet concentrations of serotonin and noradrenaline were similar in all groups and were unrelated to age or gender, or to duration of diabetes, blood pressure, glycaemia or renal function in the diabetic subjects. Plasma concentrations of serotonin in the diabetic groups were comparable (118 +/- 16 (mean +/- SEM) and 127 +/- 21 pmol/mL), and were significantly higher in comparison to the healthy controls (66 +/- 12 pmol/mL, P = 0.002).

Adolescent↗
PubMed1989

Platelet serotonin in systemic sclerosis.

Platelet serotonin concentrations were measured in 43 patients with systemic sclerosis, in 11 patients with primary Raynaud's phenomenon, and in 38 normal controls. Patients with the CREST variant (calcinosis, Raynaud's phenomenon, oesophageal dysmotility, sclerodactyly, telangiectasia) had significantly lower platelet serotonin concentrations than normal controls. Patients with diffuse systemic sclerosis had normal platelet serotonin concentrations. In patients with CREST treatment with ketanserin, a specific serotonin antagonist, normalised platelet serotonin concentrations. These data provide further evidence suggesting that in systemic sclerosis, particularly the CREST variant, there is widespread platelet activation.

Adult↗