Tissue distribution and macromolecular interactions of 14[C-ring] melphalan in the rat

Summary The kinetics of uptake and elimination, covalent binding, and macromolecular interactions of ¹⁴[C-ring] melphalan was studied after a single oral dose (20 mg/kg, 0.1 mCi/kg) in normal rats. Peak radioactivity level in tissues was observed at 2–4 h after administration. Uptake of label in most tissues was rapid, with a t_1/2 of less than 1 h. Elimination was biphasic. Tissues of the gastrointestinal tract showed the most rapid rates of elimination, with t_1/2 of 13, 24, 18, and 19 h for stomach, duodenum, and small and large intestines, respectively. Bone marrow also showed a fast rate of elimination of radioactivity, with a t_1/2 of 30 h. Tissues with the slowest rates of elimination were skin, eye, spleen, pancreas, and lung, with t_1/2 of 333, 241, 149, 122, and 109 h, respectively. Covalent binding studies showed that melphalan, or its metabolites, bound irreversibly to all tissue macromolecular fractions. The percentage of covalently bound radioactivity increased with time in all tissues except kidney and eye, reaching up to 70%–80% of the total radioactivity remaining at 72 h. Elimination of covalently bound radioactivity was slower in the DNA fractions of the tissues of the gastrointestinal tract and heart compared with the elimination rate from lipid, protein, or RNA fractions. Slow elimination rates of ¹⁴[C-ring] melphalan equivalents from the protein fraction were observed in the skin, eye, and brain. Accumulation, rather than elimination, of radioactivity in this fraction was most prominent in the pancreas. In the bone marrow accumulation of radioactivity was observed in the lipid fraction.Abbreviations used in this paper are L-Pam Melphalan, l-phenylalanine mustard 4-bis (2-chloroethyl) amino-1-phenylalanine - l-DOH 4-bis (2-hydroxyethyl) amino-1-phenylalanine - l-MOH 4-2 hydroxyethyl 2 chloroethyl amino-1-phenylalanine - HPLC high-pressure liquid chromatography - TCA trichloroacetic acid - AUC area under the curve - GIT gastrointestinal tract     

Amyopathic dermatomyositis: retrospective review of 37 cases

Criteria for diagnosis of amyopathic dermatomyositis vary, and the prognosis is not clear. Our purpose was to investigate prognosis regarding progression to myositis and associated malignancy. We reviewed the medical records of patients with dermatomyositis evaluated at our institution from 1976 to 1994. Of 746 patients with dermatomyositis, 37 (5%) with the amyopathic subtype were divided into 3 groups: group 1 (73%), no subjective or objective evidence of myopathy; group 2 (13%), no subjective muscle weakness but abnormalities detected by objective tests; group 3 (13%), subjective muscle weakness but no objective evidence of myopathy. Follow-up was conducted by means of a mailed questionnaire. For 25 patients, follow-up of 1 to 17 years after diagnosis showed muscle weakness in 2 patients in group 1 within 5 years after diagnosis. Five patients (13%) had associated malignancies. Of 7 (19%) patients with disease onset before the age of 18 years, none had progression to myopathy. Although it presents with cutaneous lesions indistinguishable from those of classic dermatomyositis, amyopathic dermatomyositis is a distinct entity. In most patients, amyopathic dermatomyositis does not progress to myopathy. Prognosis appears favorable, but malignancy may develop.     

Destructive facial T-cell lymphoma: the difficulty in diagnosis of pyoderma-like processes

A 48-year-old woman presented with extensive facial ulceration of 1 year in duration. Based on the combination of the clinical appearance and a “nondiagnostic” biopsy taken elsewhere, the patient was started on oral prednisone at a dose of 40 mg/day, with a working diagnosis of pyoderma gangrenosum. According to the patient, the ulceration worsened over the 2 months whilst on prednisone and pain control was a major issue, controlled for the most part with oral oxycodone. One month prior to our evaluation of the patient, she was started on dapsone at 50 mg/day with no added benefit. Approximately 2 years prior to our evaluation, she developed raised, reddish, skin lesions on the abdomen and legs which recurred, but healed spontaneously each time after a few weeks. Her past medical history was remarkable for the remote use of intravenous drugs (which she had stopped for the past 20 years) and the past and continued use of alcohol on a daily basis. She had recently been tested elsewhere and was found to be positive for hepatitis C, but not human immunodeficiency virus (HIV). Examination revealed several ulcerations of the face and forehead, with an “apple jelly” coloration to the periphery and necrotic center. There was complete erosion of the nasal sidewall with apparent involvement of the septum ( Fig. 1 ). There were also scattered, smaller, nonulcerated, reddish to purplish lesions on the abdomen. Otolaryngologic examination revealed ulceration of the right ala and erosion of the nasal septum, but was otherwise unremarkable. No cervical or submental lymphadenopathy was noted.

Figure 1 Open in figure viewer PowerPoint Facial ulceration at the time of initial evaluation     

Topical tacrolimus in the treatment of symptomatic oral lichen planus: a series of 13 patients.

BACKGROUND: Oral lichen planus (OLP) is a relatively common, chronic inflammatory condition, which frequently presents with symptoms of pain and irritation. OLP is often difficult to manage. Therefore there is a need for more effective and safer therapies for symptomatic OLP. OBJECTIVE: Our purpose was to determine the effectiveness of topical tacrolimus as therapy for symptomatic OLP. METHODS: A retrospective review was performed of 13 patients with symptomatic OLP treated with topical tacrolimus between September 1999 and September 2000. RESULTS: Eleven of the 13 patients reported definite symptomatic response to treatment and 2 had no response. Eight patients had a partial response, whereas 3 patients had a complete response with respect to lesion clearance. Seven of the responding patients had no flares with continued treatment. The other 4 patients noted flares soon after stopping the treatment. Side effects were rare and minor. CONCLUSIONS: In this retrospective case series of 13 patients, topical tacrolimus was well tolerated and appeared to be an effective therapy to control symptoms and clear lesions of OLP.