Antioxidant effects in the development of Ehrlich ascites carcinoma.

The effect of Ehrlich ascites tumor growth on selenium-turnover rates and selenium-75 distribution in liver, kidney, and immunological tissues (spleen, thymus, and lymph nodes) was investigated in Swiss Webster mice that had been prelabeled with selenium-75. Ehrlich ascites tumor caused a decrease in the selenium-75 content of liver, kidney, and thymus; it also decreased the rate of the total-body selenium-turnover. In liver, depletion of selenium-75 was almost as great as that produced by a selenium and vitamin E-deficient diet. When mice had been fed an antioxidant-deficient diet, considerable quantities of selenium-75 were accumulated by the tumor; the specific activity of the tumor increased 9-fold over that in antioxidant-supplemented mice. The same diet produced a premature, and in some cases drastic, contraction in tumor volume. The possible significance of tumor-induced antioxidant deficiencies to the etiology of certain paraneoplastic syndromes is discussed.

Anomalous vitamin E effects in mitochondrial oxidative metabolism.

Three different vitamin E effects, suggestive of specific antioxidant effects, were discovered in the protective action of vitamin E against respiratory decline (a decrease in mitochondrial respiration attributed to a "leakage" of electron transport radicals). No correlation was found between respiraotry decline and random lipid peroxidation. The mechanisms behind two of the three atypical vitamin E effects were defined. Both involve an artifact in the TBA assay for lipid peroxidation. This artifact occurs when TBA assays are carried out in the presence of sucrose and acetaldehyde; the latter is produced from ethanol, the solvent used to add vitamin E to preparations. The artifact in the TBA assay for peroxidations appears also to be responsible for differing interpretations of the hepatotoxic effect of ethanol.

Serum thyroglobulin, a monitor of differentiated thyroid carcinoma in patients receiving thyroid hormone suppression therapy: concise communication.

Serum thyroglobulin levels were obtained in 86 patients who had undergone thyroidectomy and I-131 ablation for differentiated thyroid cancer, and who were receiving or had recently discontinued thyroid hormone suppression therapy. Excellent correlation was observed between serum thyroglobulin levels in patients receiving thyroid hormone suppression therapy and I-131 imaging studies. Serum thyroglobulin levels equal to or below 20 ng/ml indicate the absence of thyroid carcinoma, and values exceeding 60 ng/ml were indicative of active thyroid cancer but may include some patients without clinical evidence of disease. Intermediate serum thyroglobulin levels were observed in a small number of patients with postsurgical thyroid remnants or active disease. Serum thyroglobulin levels are of considerable value in monitoring the activity of thyroid cancer in patients who are receiving thyroid hormone suppression therapy.

Novel interference in thiobarbituric acid assay for lipid peroxidation.

The thiobarbituric acid test for lipid peroxidation, when applied to a mixture of acetaldehyde and sucrose, produces a 532 nm aborbing chromogen which is indistinguishable from that formed by malonaldehyde and thiobarbituric acid. Unless special procedures are adopted to correct for this effect, the combined action of acetaldehyde and sucrose interferes seriously with the assay of lipid peroxidation reactions, notably those implicated in alcohol-induced liver injuries. However, this unusual thiobarbituric acid effect also can be used as a sensitive method for the detection of acetaldehyde.

Sample preparation techniques.

Evidentiary false positives are caused by passive exposure to drugs in the environment rather than by active use of drugs. The avoidance of such positives is essential for both hair and urine analysis. Hair analysis enjoys the advantage over urinalysis in having a number of approaches for making this distinction. These include: methylene blue staining of the hair specimen for selecting the appropriate wash solvent; application of hair digestion techniques for the complete release of chemically unaltered analytes; the determination of three diagnostic ratios from wash and digestion data; the measurement of metabolite:drug ratios; the use of cut-off levels setting the limits for passive endogenous drug exposure; reproducibility of results (including segmental analysis) with a newly collected hair specimen; and the reporting of results as either negative, positive, or contaminated. Our sample preparation procedures have been effectively applied to the analyses of nearly 200,000 specimens, i.e. to approximately one million drug analyses for cocaine, opiates, methamphetamine, phencyclidine or marijuana. On the basis of this experience we conclude that hair analysis is a safe and effective method for workplace drug testing.

Hair analysis for drugs of abuse. XVII. Simultaneous detection of PCP, PCHP, and PCPdiol in human hair for confirmation of PCP use.

The paper reports the simultaneous detection hair of phencyclidine (PCP) and its two major metabolites, 1-(1-phenylcyclohexyl)-4-hydroxypiperidine (PCHP) and trans-1-(1-phenyl-4-hydroxycyclohexyl)-4'-hydroxypiperidine (t-PCPdiol) in human hair. The detection of these metabolites provides definitive evidence that a positive hair analysis result is due to active PCP use and not due to external contamination of the hair specimen. Hair (5 mg) from known PCP users was washed three times with 0.1% sodium dodecyl sulfate for 1 min before analysis. Three extraction methods were compared: methanol-5N HCl (20:1) (Method A), 10% HCl (Method B), and 2N sodium hydroxide digestion (Method C). PCP-d5 and PCHP-d5 were used as internal standards. Extracts were purified by Bond Elut Certify solid-phase extraction procedures. Samples were derivatized with N,O-bis-trimethylsilyl acetamide and analyzed by gas chromatography-mass spectrometry. Compared with Method A, the extraction efficiencies of Methods B and C for PCP were 83-89%; however, the extraction efficiencies of Methods B and C for the two metabolites were only half or less than that of Method A. Method A was therefore selected for the analysis of clinical hair specimens from eight PCP users. The coefficients of variation of this method (n = 5) for PCP at 4 ng/mg and for PCHP and t-PCPdiol at 0.2 ng/mg were 2.13, 6.09, and 9.38%, respectively. In the eight hair specimens, PCP values ranged between 0.33 and 14 ng/mg. PCHP between 0.02 and 0.12 ng/mg, and trans-PCPdiol between 0.09 and 0.45 ng/mg. It was found that t-PCPdiol was the major metabolite in the PCP users' hair specimens, although t-PCPdiol was a minor metabolite in the hair specimens of rats intoxicated with PCP.

Anomalous antioxidant effects in selenium- and vitamin E-deficient liver mitochondria.

In this study, we investigate the mechanisms of two anomalous protective effects of exogenous vitamin E that had previously been postulated to involve either a specific antioxidant effect or a non-antioxidant function of the vitamin. These atypical vitamin E effects were observed during the prevention of NAD-induced respiratory decline occurring in homogenates and mitochondria prepared from vitamin E- and selenium-deficient rat liver. The study showed neither hypothesis to be true; rather, the two effects, one in homogenates and the other in isolated mitochondria, were explained by other mechanisms. The protective effect against respiratory decline in homogenates was found to result from interference in the thiobarbituric acid assay for lipid peroxidation by ethanol (the conventional solvent for vitamin E addition). With other non-interfering solvents, inhibition of lipid peroxidation by vitamin E, in contrast to previous studies, correlated perfectly with prevention of respiratory decline. The atypical vitamin E effect occurring in isolated mitochondria-and consisting of a requirement for cytosol proteins for the prevention of respiratory decline by exogenous vitamin E-was found to be caused by the prevention of adverse glass effects and not by the action of vitamin E-specific binding proteins. Frequent failures in the combined protective effect of vitamin E and cytosol, which had been a major complication of respiratory decline studies, were found to be caused by phospholipase activity generated during isolation procedures. Irreversible deactivation of respiratory enzymes by lipid peroxidation was found not to be involved in the respiratory decline mechanism.

Skin surveillance of a U.K. paediatric transplant population.

BACKGROUND: Solid organ transplant recipients are at increased risk of skin cancer. Melanoma is less common than nonmelanoma skin cancer (NMSC) although the relative proportion of melanoma among skin cancers has been shown to be higher in paediatric than adult recipients. Multiple melanocytic naevi and/or atypical naevi may be a risk factor for the development of melanoma. The relationship between naevus counts and phenotypic characteristics, disease-related variables and sun exposure has not been explored in paediatric transplant patients. OBJECTIVES: To determine the prevalence of premalignant and malignant skin lesions and to identify known risk factors associated with benign and atypical melanocytic naevi in a U.K. paediatric transplant population. METHODS: Paediatric (< or = 19 years) renal and liver transplant patients, who were 5 or more years post-transplantation, were reviewed over 12 months. Lifetime history of sun exposure, episodes of sunburn, sunny holidays, sunscreen use, sun bed use, demographic and transplantation details were collected using interview, questionnaire and case note review. A skin examination was performed for regional counts of malignant lesions, benign and atypical naevi. RESULTS: Ninety-eight patients (82 liver, 13 renal, three multiorgan) with a median follow up of 9 years (range 5-16) were reviewed. Neither skin cancer nor premalignant lesions for NMSC were detected in this group. Eighty-five patients had benign naevi (median 6, range 1-57). Clinical risk factors for increased counts of benign naevi included increasing age (P = 0.03), more episodes of sunburn (P = 0.003) and prolonged treatment with cyclosporin (P = 0.009). The presence of atypical naevi in six patients was significantly associated with more episodes of sunburn (P = 0.006) and more transplants (P = 0.04). Other variables including phenotype, skin type, sun exposure, holidays abroad, residence abroad and total duration of immunosuppression did not correlate with benign or atypical naevus counts. CONCLUSIONS: Skin cancer was not observed in paediatric solid organ transplant recipients who were 5-16 years post-transplantation. Both benign and atypical naevus counts were higher in children with frequent episodes of sunburn. As both naevi and sunburn are risk factors for melanoma, we should target fair-skinned transplant recipients with naevi for intensive sun avoidance education. A prospective, longitudinal follow-up study should determine the onset of skin cancer post-transplantation and the significance of benign and atypical naevus counts in this cohort.

Three cases of severe Rhus dermatitis in an English primary school.

We report three paediatric cases of severe allergic contact dermatitis caused by a Japanese lacquer tree (Rhus verniciflua), which is a rare specimen plant in the UK. The diagnosis of allergic contact dermatitis produced by plants that are not indigenous to a particular country is more likely to be delayed, as well as mistaken for cellulitis.

An unusual ectodermal dysplasia with unique eye defects.

We report a 12-year-old boy with dental, auricular, nasolacrimal duct and unique eyelid anomalies as well as cribriform scrotal atrophy. We believe this is the first description of such a case, although many of the features fit within the spectrum of the ankyloblepharon/ectodermal dysplasia/clefting (AEC) syndrome.

General practitioner referral guidelines for dermatology: do they improve the quality of referrals?

Guidelines have proliferated in recent years in all areas of medicine, sometimes with little evaluation of their effect. Referral guidelines for dermatology were compiled by the dermatologist at the Royal Surrey County Hospital in consultation with local general practitioners. An audit was undertaken to assess how appropriate referrals were just before and after distribution of the guidelines and was repeated 2 years later to determine whether they had made any significant impact. The results revealed a 40% increase in the number of appropriate referrals immediately after introduction of the guidelines, but this was not sustained 2 years later. Five common conditions accounted for two-thirds of inappropriate referrals before and after the guidelines were sent. The need for continued general practitioner education in dermatology to reinforce referral guidelines is demonstrated.

Cutaneous T-cell lymphoma presenting with atypical perianal lesions.

A patient with an atypical presentation of cutaneous T-cell lymphoma is reported. For many years, there were perianal lesions only, which were initially diagnosed as a non-specific severe perianal dermatitis, possibly due to psoriasis. There was little response, however, to potent topical steroids. Further patch and plaque lesions then developed elsewhere and plaque stage mycosis fungoides was diagnosed, allowing effective treatment with superficial radiotherapy and PUVA to be given. The difficulties that may be encountered in the diagnosis of cutaneous T-cell lymphoma are discussed.

Cutaneous necrosis associated with the antiphospholipid syndrome and mycosis fungoides.

The development of extensive cutaneous necrosis in a patient with tumour-stage mycosis fungoides is described. Skin biopsies showed a lymphomatous infiltrate, and thrombosis of dermal blood vessels. Investigation revealed the presence of anticardiolipin antibodies, a lupus anticoagulant, and low free protein S, which contributed to a prothrombotic state. Antiphospholipid antibodies have been detected in non-Hodgkin's lymphoma, but clinical manifestations are uncommon. Such autoantibodies may be produced by neoplastic lymphoid cells. The frequency with which antiphospholipid antibodies occur in mycosis fungoides is currently unknown.

Detection of benzodiazepines in human hair by radioimmunoassay.

OBJECTIVE: In this preliminary investigation, we sought to determine whether a standard benzodiazepine radioimmunoassay (RIA) could detect three benzodiazepines in human hair. DESIGN: Hair samples of 20-50 strands (minimum 10 mg) were cut from eight patients receiving diazepam, two patients receiving alprazolam, three patients receiving lorazepam, and two negative controls. Samples were treated with ethanol and phosphate buffer washes at 37 degrees C to remove external contamination. The protein hair matrix was destroyed using proprietary procedures, then analyzed with Abuscreen RIA designed to detect various benzodiazepines and their metabolites, using oxazepam as a reference standard. SETTING: Patients were hospitalized in a locked psychiatric facility. PATIENTS: Twelve patients with chronic psychiatric conditions who had received therapeutic dosages of benzodiazepines for 1-11 months were included in the sample. One outpatient who reported heavy prior diazepam use was also included. MAIN OUTCOME MEASURE: Detection of benzodiazepines was well above a 1.5 ng/10 mg cutoff level with the Abuscreen assay. RESULTS: Diazepam was readily detected, but alprazolam and lorazepam were not detected. CONCLUSIONS: There is no test that can currently determine duration and extent of prior benzodiazepine use. Hair analysis for diazepam offers a potential, new clinical and research tool for characterizing prior level and extent of usage.