Immediate-Type allergy against human insulin associated with marked eosinophilia in type 2 diabetic patient. (41/527)

We describe a type 2 diabetic patient who showed immediate-type allergy against human insulin associated with marked eosinophilia at initial insulin therapy. Three months after initiation of insulin therapy, he noticed itchy skin wheals at the site of the insulin injection. Laboratory data at that time showed marked eosinophilia (2,512 /mm3) and progression of renal dysfunction. Skin test with semisynthetic human insulin and protamine sulfate resulted in local immediate skin reactions such as itchy erythema and wheals. Histopathology of the biopsy specimen from skin showed perivascular infiltration of lymphocytes and numerous eosinophils in the dermis and subcutaneous fat. Although the titer of total IgE antibody was within normal range, that of insulin-specific IgE antibody was high. Insulin administration was discontinued to preserve his insulin secretion, and stable control of his hyperglycemia was obtained by initiating nateglinide treatment (360 mg/day). His itchy skin lesions disappeared within two weeks after cessation of the insulin therapy and both eosinophilia and renal dysfunction gradually improved. Although the widespread use of human insulin in diabetic patients has greatly reduced the incidence of insulin allergy, the possibility of human insulin allergy should be kept in mind when initiating such therapy.  (+info)

Practical guidelines for the management of biochemotherapy-related toxicity in melanoma. (42/527)

The combination of cisplatin-based chemotherapy with interleukin 2 (IL-2) and IFN-alpha, referred to as biochemotherapy or chemoimmunotherapy, has shown promising antitumor activity in patients with metastatic melanoma. Phase II studies have reported overall response rates ranging from 40 to 60%, with durable complete remissions in approximately 10% of the patients. Toxicity, however, is often severe and can be life-threatening if the healthcare team is not familiar with toxicity management. In this report, we briefly describe the clinical results of the most effective biochemotherapy regimens and provide a detailed description and management of the most common toxic effects, with emphasis on the concurrent biochemotherapy program initially developed at M. D. Anderson Cancer Center and currently being tested in a slightly modified version in two large-scale Intergroup Phase III trials.  (+info)

Genotypic and phenotypic characterisation of Borrelia burgdorferi sensu lato strains isolated from human blood. (43/527)

Lyme borreliosis often presents initially with erythema migrans. Borreliae may disseminate from the primary skin lesion, and different organs and systems could be affected. Borrelia strains were isolated from blood of 70 patients with Lyme borreliosis, including 10 patients from whom borreliae were also isolated from skin. The aim of the present study was to characterise the isolates with regard to their phenotypic and genotypic characteristics. Borreliae were cultivated in MKP medium. Species identification and plasmid profiles were determined by pulsed-field gel electrophoresis (PFGE) and protein profiles by SDS-PAGE. Digestion of Borrelia burgdorferi sensu lato DNA showed 63 (90%) B. afzelii Mla1 and 7 (10%) B. garinii Mlg2. No B. burgdorferi sensu stricto were isolated. Borreliae were isolated from both skin and blood of 10 patients, nine pairs of isolates were identical: seven B. afzelii and two B. garinii. B. afzelii was isolated from the skin and B. garinii from blood of the tenth patient. All but one isolate possessed at least one large plasmid and varying numbers of smaller plasmids. Eight (11.4%) of 70 isolates possessed an unusual plasmid profile (2 of 63 B. afzelii and 6 of 7 B. garinii). Borreliae differed in their protein profiles. OspA and OspB proteins were expressed by all B. afzelii isolates; 85.7% of B. garinii isolates expressed OspA and 71.4% expressed OspB. OspC was expressed by 65% of B. afzelii isolates and all B. garinii isolates. The ratios of B. afzelii and B. garinii isolated from blood and skin were similar. These results do not support the hypothesis that B. garinii has a higher propensity for haematogenous dissemination than B. afzelii. Antigen diversity as well as species and plasmid heterogeneity could play a role in the pathogenesis of the infection, suggesting distinctive strain organotropism.  (+info)

Ultraviolet-B-induced erythema is mediated by nitric oxide and prostaglandin E2 in combination. (44/527)

Ultraviolet-B-induced erythema (one, two, or four times the minimal erythema dose) was reduced but not abolished by application of 1% indomethacin gel immediately after irradiation of human skin. Continuous synthesis of prostaglandins is reflected by similar levels of indomethacin-mediated inhibition of erythema at any time within 48 h after irradiation. Repeated applications of indomethacin did not increase the inhibition. Twenty-four hours after irradiation with four minimal erythema doses, mean prostaglandin E2 levels in suction blisters were 27.2 ng per ml (SEM 11) compared with 8.6 ng per ml in unirradiated skin (n = 25; p < 0.01). Prosta glandin E2 levels in dermal tissues, sampled by microdialysis (depth 0.6 +/- 0.1 mm), were 310 pg per ml (SEM 123) and 237 pg per ml (SEM 88) in irradiated and unirradiated skin, respectively (n = 7, n.s.). Nitric oxide also made a significant contribution to ultraviolet-B-induced erythema. Ultraviolet erythema was inhibited by L-NAME in a dose-related fashion with 2 mM L-NAME causing total abolition of the response. L-NAME was effective at all time points up to 48 h suggesting that NO was produced continuously. NO was undetectable in suction blister fluid but in dermal microdialysate NO was present at 44.3 ng per ml (SEM 6.2) following ultraviolet B compared with 26.0 ng per ml (SEM 8.0) in unirradiated skin (p < 0.05), approximately 1000 times the molar concentration of prostaglandin E2. These findings confirm prostaglandin E2 and NO to be mediators of ultraviolet-induced erythema. They also show that there is prolonged synthesis of both mediators within the erythemal response and that synthesis of NO is induced by lower doses of ultraviolet B compared with that of prostaglandin E2.  (+info)

The DNA damage signal for Mdm2 regulation, Trp53 induction, and sunburn cell formation in vivo originates from actively transcribed genes. (45/527)

The stratum corneum and DNA repair do not completely protect keratinocytes from ultraviolet B. A third defense prevents cells with DNA photoproducts from becoming precancerous mutant cells: apoptosis of ultraviolet-damaged keratinocytes ("sunburn cells"). As signals for ultraviolet-induced apoptosis, some studies implicate DNA photoproducts in actively transcribed genes; other studies implicate non-nuclear signals. We traced and quantitated the in vivo DNA signal through several steps in the apoptosis-signaling pathway in haired mice. Homozygous inactivation of Xpa, Csb, or Xpc nucleotide excision repair genes directed the accumulation of DNA photoproducts to specific genome regions. Repair-defective Xpa-/- mice were 7-10-fold more sensitive to sunburn cell induction than wild-type mice, indicating that 86-90% of the ultraviolet B signal for keratinocyte apoptosis involved repairable photoproducts in DNA; the remainder involves unrepaired DNA lesions or nongenomic targets. Csb-/- mice, defective only in excising photoproducts from actively transcribed genes, were as sensitive as Xpa-/-, indicating that virtually all of the DNA signal originates from photoproducts in active genes. Conversely, Xpc-/- mice, defective in repairing the untranscribed majority of the genome, were as resistant to apoptosis as wild type. Sunburn cell formation requires the Trp53 tumor suppressor protein; 90-96% of the signal for its induction in vivo involved transcribed genes. Mdm2, which regulates the stability of Trp53 through degradation, was induced in vivo by low ultraviolet B doses but was suppressed at erythemal doses. DNA photoproducts in actively transcribed genes were involved in approximately 89% of the Mdm2 response.  (+info)

The relation between melanocortin 1 receptor genotype and experimentally assessed ultraviolet radiation sensitivity. (46/527)

Pigmentary phenotype is a key determinant of an individual's response to ultraviolet radiation with the presence of phaeomelanin thought to be of particular importance. Reports of minimal erythema testing, however, have failed to show a consistent difference between skin type I and other skin types. The melanocortin 1 receptor is a key genetic determinant of the cutaneous response to ultraviolet radiation. In this study we investigate the relation between experimentally induced erythemal response to ultraviolet radiation and the melanocortin 1 receptor genotype. Phototesting was performed in 20 redheads and 20 nonredheaded subjects, the majority of whom were also screened for the presence of melanocortin 1 receptor variants. The majority of redheads sequenced (89%) had two melanocortin 1 receptor variants previously found to be associated with red hair compared to none of the controls. There was no significant difference between the groups in minimal erythema dose: the median minimal erythema dose in redheads was 44 mJ per cm2 (interquartile range 34-56) and in the nonredheaded group was 40 mJ per cm2 (interquartile range 40-56). Objective measurements of ultraviolet-B-induced erythema were performed using reflectance instrument measurements of erythema intensity and dose-response curves constructed for each subject. The slope of the dose-response curve in the redheaded group was statistically greater than in the nonredheaded group (median in redheads 4.08 vs 3.56 for controls, 95% confidence interval for the difference between the medians being 0.01-1.23, p = 0.043). In addition the ratio D0.05:D0.025 was significantly lower for the redheaded group (median in redheads 1.22, interquartile range 1.18-1.26; median in nonreds 1.28, interquartile range 1.23-1.32; p < 0.05). Thus, although the minimal erythema dose values were not different, subjects with red hair develop greater intensity of erythema than nonredheaded individuals when doses greater than the minimal erythema dose are given. Importantly, when analyzed by genotype alone rather than phenotype, the slope of the erythema dose-response differed between those persons who were homozygous or heterozygous mutants and wildtype/pseudo-wildtype (p = 0.026).  (+info)

Similar dose-response and persistence of erythema with broad-band and narrow-band ultraviolet B lamps. (47/527)

Psoriasis may be treated with ultraviolet B from lamps that have a broad emission spectrum or, more effectively, with lamps that have a narrow emission spectrum at 311 +/- 2 nm. There are conflicting reports of either greater or lesser burning episodes with narrow-band compared to broad-band ultraviolet B, even when treatments are based on predetermined minimal erythema dose measurements. This suggests that either the characteristics of the dose-response curve for erythema or the time course for erythema may be different for the two lamps. We examined the erythemal response to narrow-band and broad-band ultraviolet B in 12 patients with psoriasis. A geometric series of 10 doses from each lamp type were used on nonlesional skin on the back. Dose-response curves were constructed from reflectance measurements of erythema at 24 h and 72 h after irradiation. No significant difference was found in steepness of the erythema dose-response curve for the two lamps at 24 or 72 h. Persistence of erythema was assessed as the percentage of erythema remaining at 72 h. The mean persistence was 63% for narrow-band and 64% for broad-band lamps (p = 0.94). Therefore, in terms of erythemal response, no evidence has been found for a difference in burning potential for the two lamps.  (+info)

Metabolic studies on metiazinic acid I. Absorption, distribution, excretion and metabolism in rats and rabbits. (48/527)

Absorption, distribution, excretion and metabolism after oral administration of 3-H-labelled metiazinic acid were studied. The administered radioactivity was excreted through both the urinary and fecal routes. The maximum levels of concentration in blood and most tissues were shown with 3 hr after dosing. The highest radioactivity was found in the kidney throughout all experiments. Relatively high radioactivity was observed in inflammatory-treated parts in rats. Unchanged compound, metiazinic acid S-oxide and these conjugates were found in urine and feces. Approximately 60% of the unchanged form was observed in plasma after 6 hr.  (+info)