Allergic Contact Dermatitis to Benzoyl Peroxide Resembling Impetigo

A 17‐year‐old boy presented with recurring severe dermatitis of the face of 5‐months duration that resembled impetigo. He had been treated with several courses of antibiotics without improvement. Biopsy showed changes consistent with allergic contact dermatitis and patch testing later revealed sensitization to benzoyl peroxide, which the patient had been using for the treatment of acne vulgaris.     

Analysis of epidermal growth factor receptor and activated epidermal growth factor receptor expression in pituitary adenomas and carcinomas.

Epidermal growth factor receptor plays an important role in the pathogenesis of many malignancies. Various growth factors, including epidermal growth factor receptor, have been shown to influence pituitary tumor growth and differentiation. To analyze the role of epidermal growth factor receptor in pituitary tumor development, we examined normal pituitaries (n=8), pituitary adenomas (n=158), and pituitary carcinomas (n=7) for expression of epidermal growth factor receptor protein and messenger RNA using tissue microarrays and RT-PCR. We also examined (a) the expression of phospho-epidermal growth factor receptor, the activated form of epidermal growth factor receptor, in pituitary tumors and normal pituitaries by immunohistochemistry and (b) the effects on epidermal growth factor receptor expression of treating pituitary cells (HP75 cell line) with epidermal growth factor. Epidermal growth factor receptor and the phosphorylated variant expression were present in normal pituitary cells. Epidermal growth factor receptor messenger RNA was also detected in normal pituitaries, pituitary adenomas, and carcinomas by in situ hybridization and RT-PCR. Most pituitary adenomas showed expression of epidermal growth factor receptor and the phosphorylated variant. Nonfunctional adenomas showed higher levels of expression of epidermal growth factor receptor (76 vs 34%) and of phospho-epidermal growth factor receptor (26 vs 8%) as compared to functional adenomas. Five of seven pituitary carcinomas showed strong expression of both epidermal growth factor receptor and phospho-epidermal growth factor receptor. When a human pituitary cell line (HP75) was cultured in the presence of epidermal growth factor receptor, there was an increase in the levels of both epidermal growth factor receptor and phospho-epidermal growth factor receptor after 5 h of treatment, thus confirming that epidermal growth factor receptor signaling was active in pituitary tumors. These results indicate that activated epidermal growth factor receptor is expressed in pituitary adenomas and carcinomas. Higher levels in pituitary carcinomas suggest a role in pituitary tumor progression.     

Flow-independent angiography for peripheral vascular disease: Initial in-vivo results

Flow-independent angiography (FIA), an approach that isolates arterial blood using MR relaxation characteristics rather than flow effects, was evaluated for application in peripheral vascular disease (PVD). First, pilot studies were conducted in which FIA coronal projection images were obtained from controls and symptomatic patients with PVD to assess clinical utility. All control images corresponded to the expected leg arterial anatomy with little interference from deep veins (one of five) and muscle (zero of five). Superficial venous signal was less well suppressed in comparison to deep veins (four of five). Images of symptomatic patients were less consistent with difficulty suppressing muscle and deep venous signal in some cases and edema when present. We then compared T2 values for muscle (T2_m, tibialis anterior), arterial blood (femoral and popliteal arteries), and venous blood (femoral, popliteal, and saphenous veins) in controls (n = 8) and symptomatic patients with intermittent claudication (n = 5) or ischemic rest pain (n = 7). Changes in T2 measurements of various tissues accounted for poorer contrast in symptomatic patients. Patients with ischemic rest pain had significantly higher T2_m compared with controls (T2_m = 39.3 ± 2.1 (1 standard error of the mean [SEM]) versus 30.9 ± .4, P < .01). For all measurements, other than saphenous vein, variances were greater in symptomatic patients. To realize the inherent advantages of FIA for this clinical application, additional work on suppression of signals from muscle, veins, and edema is required. One promising approach involves shifting from projection images to three-dimensional acquisitions for improved tissue suppression.     

Industrial hygiene, chemical and biological assessments of exposures to a chlorinated phenolic sapstain control agent

A two-year study of the occupational exposure of workers in a lumber mill to a wood preservative containing chlorophenol has been conducted. The methods were biological (urine) monitoring, industrial hygiene assessment and a questionnaire related to worker-perceived health effects. Approximately 40 workers exposed to the wood preservative and 40 unexposed controls working in other locations of the plant participated in the study. Evaluation of work conditions, assessment of urinary levels of tetra- and pentachlorophenol, and administration of a medical questionnaire were performed at a six-month intervals over a two-year period. Industrial hygiene ratings of exposures and adequacy of protection were evaluated in relation to the results of biological monitoring. Workers who came into contact with freshly treated and still wet wood had consistently higher urinary levels of tetrachlorophenol. Workers stationed adjacent to the spray applicator also had higher tetrachlorophenol levels. There was no statistically significant relationship between the subjective ratings by the industrial hygienist of exposure and adequacy of worker protection with the urinary levels of tetrachlorophenol. Nor was there a consistent pattern linking exposure ratings with adequacy of protection. The short half-life of tetrachlorophenol in the urine makes this a good indicator of only the most recent exposure. The differences in urinary levels between controls and exposed workers were large, with averages of 240.4 ppb for exposed workers and 14.6 for controls. Traditional industrial hygiene evaluation techniques, in conjunction with biological monitoring, proved to be the most effective method of assessing both exposure and work practices. Exposed workers reported a statistically significant increase of positive answers to known signs and symptoms of chlorophenol exposure compared with the controls. There was no statistically significant relationship between the number of these health problems reported and the mean urinary levels of tetra- or pentachlorophenol for the exposed group; however, for certain variables (heavy vs. light exposure, inadequate vs. adequate protection, greater than 100 ppb urinary tetrachlorophenol vs. less than 100 ppb), those with heavier exposure, inadequate protection or higher urinary tetrachlorophenol reported on the average more health problems over the two-year period. Firm statistical conclusions could not be drawn because of the small size of the study population.     

Highly water-soluble lipophilic prodrugs of the anti-HIV nucleoside analogue 2',3'-dideoxycytidine and its 3'-fluoro derivative.

The synthesis of a novel series of lipophilic prodrug derivatives of the anti-HIV drugs 2',3'-dideoxycytidine (ddC, 1) and 3'-fluoro-ddC (2), involving N4-substitution with (N,N-dialkylamino)methylene side chains, is described. The increase in the partition coefficients for the prodrug series, compared to those of the parent drugs 1 and 2, ranged from 1.5- to 122-fold and from 1.6- to 175-fold, respectively. At pH 7.4, 37 degrees C, the hydrolytic t1/2 values ranged from 2 to 52 h, the diisopropyl derivatives (3d and 4d) being most stable in the series. 3d and 4d were greater than or equal to 4-fold and 1.7-fold more soluble in water than 1 and 2, respectively. The in vitro antiretroviral activities of 3d, 4a, and 4d were evaluated; the results indicate efficient prodrug-to-drug conversion under the assay conditions. The results of this investigation demonstrate that it is indeed feasible to chemically modify certain nucleoside analogues with inferior solubility properties to simultaneously achieve significantly enhanced lipid and water solubility.     

Ribavirin disposition in high-risk patients for acquired immunodeficiency syndrome

Ribavirin is a broad-spectrum antiviral drug that has in vitro activity against human immunodeficiency virus. To determine the kinetics of ribavirin, 17 symptom-free homosexual men with lymphadenopathy were studied. Single doses of ribavirin, 600, 1200, or 2400 mg, were given orally or intravenously. The plasma ribavirin concentration-time profiles were well fitted by a three-compartment open model. Ribavirin followed linear kinetics over the dose range studied. The mean 1-hour postinfusion concentrations after intravenous ribavirin, 600, 1200, and 2400 mg, were 8.0, 19.7, and 37.1 mumol/L, respectively. The mean +/- SD plasma beta-phase half-life, terminal-phase (gamma) half-life, and volume of distribution at steady state were 2.0 +/- 1.1 hours, 35.5 +/- 14.0 hours, and 647 +/- 258 L, respectively. The mean ribavirin renal clearance and total body clearance were 99 +/- 30 and 283 +/- 37 ml/min, respectively. After an oral dose of 600, 1200, and 2400 mg, the mean peak plasma ribavirin concentrations (which occurred 1.5 hours after administration) were 5.1, 9.9, and 12.6 mumol/L, respectively. The mean absorption half-life and bioavailability of ribavirin were 0.5 hour and 45%. Ribavirin had no plasma protein binding and the drug accumulated within red blood cells. In conclusion, ribavirin is incompletely absorbed from the gastrointestinal tract, its renal excretion accounts for approximately one third of the drug's elimination, and drug accumulation (greater than threefold) will result with repetitive dosing at the 6- to 8-hour dosing interval currently used.     

Familial thyroglossal duct cyst

Thyroglossal duct cysts are common congenital abnormalities or developmental field defects, usually detected in early childhood. Despite their frequent occurrence, familial patterns are rare. We report on two new families with thyroglossal duct cysts. In the first family three siblings were involved, while in the second one, father and son were affected. This trait may be autosomal recessive or possibly multifactorial, as the first family would indicate, and also autosomal dominant, as the second family would suggest.     

Effects of somatostatin on somatotroph adenomas of the human pituitary: An in vitro functional and morphological study

The effects of somatostatin or the somatostatin analog SMS 201–995 were studied on 4 densely granulated somatotroph adenomas and 4 sparsely granulated somatotroph adenomas in vitro. Release of growth hormone (GH) into culture media during incubation with somatostatin or SMS 201 -995 were measured by radioimmunoassay, and light-microscopical and ultrastructural morphometric parameters were compared with those of cultured control somatotroph adenoma cells of the same tumor. In all tumors except for 1 densely granulated somatotroph adenoma, somatostatin or SMS 201–995 decreased GH release into culture media in 24- and 2-hour incubations. After 48-hour incubation with somatostatin or SMS 201–995, there was no change in cell size or secretory granule diameter. One densely granulated adenoma showed decreased cytoplasmic volume density (CVD) of Golgi apparatus and secretory granules, and a sparsely granulated adenoma had reduced CVD of endoplasmic reticulum. All the tumors that responded with decreased GH release exhibited increased CVD of lysosomes after incubation with somatostatin or SMS 201–995. These results indicate that both densely and sparsely granulated somatotroph adenomas respond to somatostatin inhibition and, furthermore, that inhibition of hormone release is associated with accumulation of lysosomes, suggesting lysosomal degradation of stored hormone. Hospital 20 Nov. (ISSSTE) Coyoacan y Felix Cuevas, Colonia del Valle and (Dept Patologia) y Hospital de Especialidades (C.M.N., IMSS) Cuauhtemoc y Dr. Marquez, Mexico City (IF).