Immunohistochemical evaluation of toxic epidermal necrolysis treated with human intravenous immunoglobulin.

AIM: Toxic epidermal necrolysis (TEN) is a severe drug reaction characterized by massive epidermal cell death. The authors of the current study and others have noted improved outcomes in TEN patients treated with human intravenous immunoglobulin (IVIG), purportedly due to its ability to inhibit the fas/fas-ligand (Fas-L) apoptotic pathway, but published case series evaluating TEN through the use of immunohistochemical antibody stains for Fas and Fas-L before and after IVIG treatment are lacking. The authors hypothesized that due to IVIG's ability to arrest the evolution of TEN, expression of Fas/Fas-L on keratinocytes would be decreased or absent following IVIG treatment. METHODS: Ten patients diagnosed with TEN underwent biopsies of their lesions prior to and five days after treatment with IVIG. Seven post-treatment biopsies were of sufficient quality to undergo evaluation. RESULTS: All ten pretreatment biopsies had Fas and Fas-L expression by immunohistochemistry, while six out of seven (85.7%) post-treatment biopsies failed to demonstrate Fas or Fas-L expression. One of seven post-treatment biopsies stained positive for Fas and Fas-L. CONCLUSION: This reduced immunohistochemical expression of apoptotic markers may represent IVIG inhibition of the pathogenic mechanism of TEN. Alternatively reduced Fas and Fas-L may be a feature of reepithelialization in TEN, or characteristic of rapidly proliferating epidermis.

Ligand binding and hexacoordination in synechocystis hemoglobin.

A large and phylogenetically diverse group of organisms contain truncated hemoglobins, including the unicellular cyanobacterium Synechocystis (Pesce, A., Couture, M., Dewilde, S., Guertin, M., Yamauchi, K., Ascenzi, P., Moens, L., and Bolognesi, M. (2000) EMBO J. 19, 2424-2434). Synechocystis hemoglobin is also hexacoordinate, with a heme pocket histidine that reversibly coordinates the ligand binding site. Hexacoordinate hemoglobins are ubiquitous in plants and are now being identified in a diverse array of organisms including humans (Arredondo-Peter, R., Hargrove, M. S., Moran, J. F., Sarath, G., and Klucas, R. V. (1998) Plant Physiol. 118, 1121-1125; Trent, J. T., III, Watts, R. A., and Hargrove, M. S. (2001) J. Biol. Chem. 276, 30106-30110). Rate constants for association and dissociation of the hexacoordinating amino acid side chain in Synechocystis hemoglobin have been measured along with bimolecular rate constants for association of oxygen and carbon monoxide following laser flash photolysis. These values were compared with ligand binding initiated by rapid mixing. Site-directed mutagenesis was used to determine the roles of several heme pocket amino acids in facilitating hexacoordination and stabilizing bound oxygen. It is demonstrated that Synechocystis hemoglobin contains a very reactive binding site and that ligand migration through the protein is rapid. Rate constants for hexacoordination by His(46) are also large and facilitated by other heme pocket amino acids including Gln(43).

Human neuroglobin, a hexacoordinate hemoglobin that reversibly binds oxygen.

Neuroglobin is a newly discovered mammalian hemoglobin that is expressed predominately in the brain (Burmester, T., Welch, B., Reinhardt, S., and Hankeln, T. (2000) Nature 407, 520-523). Neuroglobin has less than 25% identity with other vertebrate globins and shares less than 30% identity with the annelid nerve myoglobin it most closely resembles among known hemoglobins. Spectroscopic and kinetic experiments with the recombinant protein indicate that human neuroglobin is the first example of a hexacoordinate hemoglobin in vertebrates and is similar to plant and bacterial hexacoordinate hemoglobins in several respects. The ramifications of hexacoordination and potential physiological roles are explored in light of the determination of an O(2) affinity that precludes neuroglobin from functioning in traditional O(2) storage and transport.

A model for ligand binding to hexacoordinate hemoglobins.

Hexacoordinate hemoglobins are heme proteins capable of reversible intramolecular coordination of the ligand binding site by an amino acid side chain from within the heme pocket. Examples of these proteins are found in many living organisms ranging from prokaryotes to humans. The nonsymbiotic hemoglobins (nsHbs) are a class of hexacoordinate heme proteins present in all plants. The nsHb from rice (rHb1) has been used as a model system to develop methods for determining rate constants characterizing binding and dissociation of the His residue responsible for hexacoordination. Measurement of these reactions exploits laser flash photolysis to initiate the reaction from the unligated, pentacoordinate form of the heme protein. A model for ligand binding is presented that incorporates the reaction following rapid mixing with the reaction starting from the pentacoordinate hemoglobin (Hb). This model is based on results indicating that ligand binding to hexacoordinate Hbs is not a simple combination of competing first order (hexacoordination) and second order (exogenous ligand binding) reactions. Ligand binding following rapid mixing is a multiphasic reaction displaying time courses ranging from milliseconds to minutes. The new model incorporates a "closed", slow reacting form of the protein that is not at rapid equilibrium with the reactive conformation. It is also demonstrated that formation of the closed protein species is not dependent on hexacoordination.

Toxic epidermal necrolysis of the scalp following anticonvulsant use and cranial irradiation.

BACKGROUND: Toxic epidermal necrolysis (TEN) of the scalp is rare but it has been shown to occur in patients who had been given a combination of cranial radiation and anticonvulsant therapies. OBJECTIVE: We present a 62-year-old man who received cranial irradiation following craniotomy for glioblastoma multiforme. After he was prescribed the anticonvulsant phenytoin for postsurgical seizure prophylaxis, the patient developed TEN which began on the scalp before spreading to involve other parts of his body. Our second case was a 55-year-old woman who had been diagnosed with lung carcinoma with metastasis to the brain. She was treated with cranial irradiation and the anticonvulsant carbamazepine. TEN developed first on the scalp and then became generalized. CONCLUSIONS: While the combination of radiation and anticonvulsants leads to an increased risk of developing TEN, cranial irradiation appears to be the localizing factor in the development of TEN of the scalp.

Common bacterial skin infections.

Skin infections account for a significant portion of dermatologic disease, often resulting in or as a consequence of a disruption in the skin's integrity. This article covers the presentation, diagnosis, and treatment of the more common bacterial infections. The infections presented herein include impetigo, ecthyma, folliculitis, carbuncles/furuncles, cellulitis, toxic shock syndrome, and ecthyma gangrenosum. Once a diagnosis is made, treatment is based on the culture and antibiotic sensitivities of the offending organisms.

Common viral and fungal skin infections.

Skin infections account for a significant portion of dermatologic diseases, often resulting in, or as a consequence of a disruption in the skin's integrity. This paper covers the presentation, diagnosis, and treatment of the more common viral and fungal skin infections. The viral infections presented in this paper include herpes simplex virus, herpes zoster, condyloma acuminata, and molluscum contagiosum. The fungal infections presented include tinea pedis, tinea cruris, tinea capitis, tinea unguium, tinea versicolor, and candidiasis. Once a diagnosis is made, treatment with appropriate antifungal, antiviral, destructive, or immune modifying therapies can be instituted.

Epidemiology of peripheral vascular disease: a predictor of systemic vascular disease.

It is estimated that peripheral vascular disease (PVD) affects 30 percent of the adult population, and two-thirds of all cases are asymptomatic. Detecting PVD can be relatively easy and inexpensive, and based either on subjectively supplied historical information (claudication) or upon physical examination findings [ankle-brachial index (ABI)]. The ABI may serve as a marker for increased risk for systemic vascular disease as an abnormally low ABI has been shown to be associated with systemic vascular disease. Epidemiology of and risk factors for PVD are in similar to coronary heart disease. PVD is uncommon until middle age and then increases dramatically. Prevalence of PVD is slightly higher in men than women, yet this tends to diminish with age. Cigarette smoking is probably the most important risk factor for PVD. Hypertension, hypercholesterolemia, and diabetes are also risk factors for the development of symptomatic PVD. Conversely, the presence of a high degree of physical activity and higher levels of HDL-cholesterol as well as a lower body mass index (BMI) are protective. Patients who have vascular disease in one organ system often exhibit evidence of vascular disease elsewhere. Presence of coronary artery disease among patients with symptomatic PVD is between two and four times higher than those without PVD, and PVD is also associated with cerebrovascular disease.

Telecommuting: stress and social support.

Occupational stress and social support were measured in adults, 15 working as telecommuters, 9 working at home, and 14 working in a company office. Analysis showed telecommuters and office workers perceived more support than those working at home. Telecommuters also reported less stress and a stronger preference for this new work option.

Issues and concerns in master's-level training and employment.

The controversy that surrounds Master's-level training in psychology prompted a study of the training and professional activities of those with subdoctoral training. Individuals with a Master's degree in psychology and agencies that employ them were surveyed independently to ascertain the duties performed by and assigned to them. Response rates of 21% and 24% for individuals and agencies, respectively, resulted from the mailing. The results suggested a discrepancy between the projections of agencies and individuals about the need for services in the future. Both agencies and individuals reported a substantial amount of time spent in direct services, therapy, or psychological testing. While individuals generally were satisfied with their career decision, they were less so with the decision to seek licensure as a psychological examiner.