Successful treatment of aphthous ulcerations in AIDS patients using topical granulocyte-macrophage colony-stimulating factor.

Oral recurrent aphthous ulceration (RAU) is a well-recognized complication in patients infected with human immunodeficiency virus. RAU can be progressive and destructive, causing dysphagia and secondary malnutrition. The aetiology of RAU remains unknown, and its response to available treatments is often unsatisfactory. We describe three patients with advanced AIDS who suffered from extensive RAU which failed to respond to several treatments, including topical viscous lidocaine and topical and systemic glucocorticoids. Owing to difficulties in using thalidomide (two patients had neurological conditions which precluded thalidomide use), all three patients were treated with an oral solution containing recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF, 400 microg in 5% glucose 200 mL). From the first application, all three patients showed significant improvement of their lesions and amelioration of pain, and they were completely cured in a few days. No adverse effects were recorded. The patients did not show relapses of RAU over a prolonged follow-up. Controlled trials are warranted in order to establish the role of GM-CSF as a valid, alternative option for aphthous ulcerations of the mouth in AIDS patients in whom corticosteroids or thalidomide are not suitable.

Mondor's disease.

BACKGROUND: Mondor's disease is a rare entity characterized by thrombophlebitis of the subcutaneous veins of the anterolateral thoraco-abdominal wall. The most common clinical manifestations are a painful subcutaneous cord, sensation of tension, and skin retraction. This condition is usually a benign and self-limited process, although it has been associated with breast cancer. METHODS: We describe four new cases, two men and two women, and comment on the clinical signs and possible etiopathogenic features. General physical examination, radiologic and ecographic studies, laboratory analysis including tumor markers, and exhaustive coagulation study were carried out on all patients. RESULTS: No cases were associated with malignant disease and/or hypercoagulability stage. With conservative treatment, the evolution proved favorable in all patients. CONCLUSIONS: Mondor's disease is usually a benign and self-limited process, but we recommend laboratory studies and physical examination, including mammography in women, in order to rule out the presence of systemic disorders, especially breast cancer.

High incidence of porokeratosis in renal transplant recipients.

Immunosuppression is a well-documented precipitant of porokeratosis (PK). However, PK is not considered among the most common cutaneous disorders in immunosuppressed patients. We studied prospectively a series of 103 renal transplant patients and found 11 cases (10.68%) of PK. Our series represents the highest incidence of PK in transplant patients reported so far. Our findings suggest that PK in transplant recipients may be more frequent than previously thought.

Destructive herpetic whitlow in AIDS: report of three cases.

Herpes simplex virus infection in immunocompromised individuals, including AIDS patients, is characterized by its tendency for atypical presentations and unusual locations, often resulting in delayed diagnosis and treatment. Three HIV-infected patients who developed prolonged cutaneous lesions of the fingers are presented. These lesions were unmodified by previous antibiotic treatment, and rapidly progressed to the complete destruction of nail structures in two patients. Viral culture confirmed the diagnosis of herpetic whitlow in all cases, and treatment with oral acyclovir resulted in complete recovery. Surgical treatment was not necessary.

A pilot study of the bioavailability and pharmacokinetics of 2',3'-dideoxycytidine in patients with AIDS or AIDS-related complex.

Eight patients with AIDS or ARC received four single doses of 2',3'-dideoxycytidine (ddC). The treatments included 0.5 and 5 mg oral tablets, a 0.5 mg oral solution, and a 0.5 mg intravenous infusion. Blood samples were collected for 4 to 6 h after each dose. Plasma concentrations of ddC were determined by a specific gas chromatographic-mass spectrometric (GC-MS) assay. A combination of the low dose and the assay sensitivity of 2 ng/ml limited data treatment and comparison. Mean Cmax of 8.5, 7.6, and 79.0 ng/ml occurred at mean tmax of 1.1, 1.3, and 0.9 h for the 0.5 mg oral solution, the 0.5 mg tablet, and the 5 mg tablet, respectively. A mean clearance of 5.57 ml/min/kg and volume of distribution of 0.64 L/kg were determined from the 0.5 mg intravenous infusion. Half-life values ranged between 0.95 and 2.0 h and appeared to be independent of the dose and route of administration. The bioavailability values calculated for the oral tablets were variable, ranging from 54 to 127%. Single doses of ddC were well tolerated in this population. The results of this pilot study indicate that ddC is rapidly and extensively absorbed when administered as an oral tablet or solution to fasting AIDS or ARC patients. It is also rapidly eliminated with a half-life of 1-2 h. There are no apparent differences in the absorption or elimination of ddC between 0.5 and 5 mg oral doses.

Determination of rimantadine and its hydroxylated metabolites in human plasma and urine.

A gas chromatographic-mass spectrometric procedure has been developed for the quantitation of the antiviral agent rimantadine and its meta- and para-hydroxylated metabolites in human plasma and urine. The assay utilizes an extractive pentafluorobenzoylation at alkaline pH with cyclohexane saturated with triethanolamine-chloroform (2:1) containing pentafluorobenzoyl chloride, selective ion monitoring, methane negative ion chemical ionization mass spectrometry and stable isotope dilution. The method has been used to measure plasma concentrations of rimantadine, m-hydroxyrimantadine and the two epimers of p-hydroxyrimantadine between 5-250, 5-100 and 2.5-50 ng/ml, respectively. Similarly, the urine concentrations of these analytes measured were between 25-1250, 25-500 and 12.5-250 ng/ml, respectively.

Stereospecific assay and stereospecific disposition of racemic carprofen in rats.

A procedure was developed for the separation and selective quantitative determination of the (S)(+)- and (R)(-)-enantiomers of the racemic anti-inflammatory drug carprofen as their diastereomeric l-(-)-alpha-methylbenzylamides. These derivatives are obtained in equivalent yields by reacint purified 14C-carprofen from biological specimens with l-(-)-alpha-methylbenzylamine via the 1,1'-carbonyldiimidazole intermediate, followed by extraction and differential radiometric quantitation of the TLC-separated diastereomers. In the rat, the (R)(-)-carprofen enantiomer was eliminated from blood and secreted in the bile as the ester glucuronide at a rate approximately twice that of the (S)-(+)-enantiomer, resulting in the accumulation of the pharmacologically more active (S)(+)-enantiomer in the rat blood. Evidence for an additional process favoring the elimination of the (R)(-)-enantiomer in the rat was derived from pharmacokinetic data evaluation.