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Background: Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease that has been associated with a history of repetitive head impacts. The neuropathological diagnosis is based on a specific pattern of tau deposition with minimal amyloid-beta deposition that differs from other disorders, including Alzheimer's disease. The feasibility of detecting tau and amyloid deposition in the brains of living persons at risk for CTE has not been well studied.Methods: We used flortaucipir positron-emission tomography (PET) and florbetapir PET to measure deposition of tau and amyloid-beta, respectively, in the brains of former National Football League (NFL) players with cognitive and neuropsychiatric symptoms and in asymptomatic men with no history of traumatic brain injury. Automated image-analysis algorithms were used to compare the regional tau standardized uptake value ratio (SUVR, the ratio of radioactivity in a cerebral region to that in the cerebellum as a reference) between the two groups and to explore the associations of SUVR with symptom severity and with years of football play in the former-player group.Results: A total of 26 former players and 31 controls were included in the analysis. The mean flortaucipir SUVR was higher among former players than among controls in three regions of the brain: bilateral superior frontal (1.09 vs. 0.98; adjusted mean difference, 0.13; 95% confidence interval [CI], 0.06 to 0.20; P<0.001), bilateral medial temporal (1.23 vs. 1.12; adjusted mean difference, 0.13; 95% CI, 0.05 to 0.21; P<0.001), and left parietal (1.12 vs. 1.01; adjusted mean difference, 0.12; 95% CI, 0.05 to 0.20; P = 0.002). In exploratory analyses, the correlation coefficients in these three regions between the SUVRs and years of play were 0.58 (95% CI, 0.25 to 0.79), 0.45 (95% CI, 0.07 to 0.71), and 0.50 (95% CI, 0.14 to 0.74), respectively. There was no association between tau deposition and scores on cognitive and neuropsychiatric tests. Only one former player had levels of amyloid-beta deposition similar to those in persons with Alzheimer's disease.Conclusions: A group of living former NFL players with cognitive and neuropsychiatric symptoms had higher tau levels measured by PET than controls in brain regions that are affected by CTE and did not have elevated amyloid-beta levels. Further studies are needed to determine whether elevated CTE-associated tau can be detected in individual persons. (Funded by Avid Radiopharmaceuticals and others.). [ABSTRACT FROM AUTHOR]

A 24-year-old man presented to a university health center in January with a persistent headache that began abruptly 6 days earlier. He noted nonpulsating discomfort in the right retro-orbital area that was not relieved by ibuprofen (400 mg four times daily). He reported no prodromal symptoms, sensitivity to light or sound, neurologic symptoms, nausea, or vomiting and had no history of headaches. A day before presentation, he noted subjective fevers. The patient was evaluated, and amoxicillin was prescribed for presumed acute rhinosinusitis. [ABSTRACT FROM AUTHOR]

The article offers information on exanthematous drug eruptions, the most common drug-induced eruptions. Risk factors include changes in a patient's immune status and genetic factors associated with the immune system. Exanthematous drug eruption is characterized by a widespread, symmetrically distributed rash composed of pink-to-red macules and papules. The foundation for the management of drug-induced eruptions consists of identification and prompt withdrawal of the suspected drug.

This article presents a case vignette that includes a therapeutic recommendation. A 52-year-old man who had psoriasis for 30 years seeks further treatment. His psoriasis is not responsive to topical therapy, is worse in the winter and improves in sunlight. His psoriasis covers 20 percent of his body and is only partially responsive to narrow-band ultraviolet B (UVB) therapy. His dermatologist recommends oral psoralen and ultraviolet A (PUVA) therapy. The pathology and mechanisms of psoriasis are discussed. Clinical trials on the use of PUVA therapy are presented. Therapy choices are listed with the notation that optimal therapy for a patient will vary over the years of the disease. Different phototherapies are presented along with potential adverse reactions.

Reviews the epidemiology, recognition, treatment and prevention of basal-cell and squamous-cell carcinomas. Emphasis on risk factors for the development of these tumors; Relative costs, risks and benefits of alternative therapies; Importance of considering the patients' preferences in choosing treatment; Fraction of all cancers in the United States that are nonmelanoma skin cancers; Natural history and prognostic features; More.

Examines the efficacy of phenytoin in the treatment of recessive dystrophic epidermolysis bullosa. Epidermis bullosa as a group of rare, heritable disorders characterized by abnormal fragility of the skin; Formation of slow-healing blister s; Collagenase activity of the skin fibroblasts of patients with recessive dystrophic epidermolysis bullosa; More.

A letter to the editor is presented in response to the article "Lithium in the Treatment of Mood Disorders," by L.H. Price and G.R. Heninger in the September 1, 1995 issue.

Presents a case study of a 45-year-old fair-skinned woman who was noting increasing sallowness, roughness and mottled hyperpigmentation on her face. Her question to the doctor was what treatments may minimize skin aging and lower the risk of skin cancer; Photoaging by exposure to the sun which causes a number of physical signs; Causes of wrinkles and telangiectasia; Risk factors for photoaging and skin cancer; Role of ultraviolet B radiation in the development of skin cancer; Prevention and therapy which includes protection from the sun; Sunblocks which can stabilize the histologic changes to the skin; Limitations of hydroxy acids; Topical retinoids which reduce the severity of photoaging; Fluorouracil creams for the treatment of actinic keratoses and the cautions surrounding its use; Procedures for facial rejuvenation which include blepharoplasty and face-lifts; Use of botulinim toxin to decrease wrinkles which is a short term solution; Skin fillers which are injectable bovine collagen preparations which last 3 to 6 months; Simple office procedures which include the use of laser, cryosurgery, electrosurgery and microdermabrasion; Areas of uncertainty; Guidelines from the American Academy of Dermatology.

A response by Robert S. Stern to a letter to the editor about an article on mortality rates among patients with bullous pemphigoid in the January 31, 2002 issue is presented.

The article presents the author's comments on the economies of clinical research and medical care related to bullous pemphigoid therapy in the U.S. and in France, with reference to a study by researcher P. Joly and colleagues, published in the current issue. Joly's study was conducted in France. The author says that it is difficult to obtain funding for such studies as they are unlikely to provide an economic benefit to the health care industry.

A letter to the editor is presented concerning Merkel-cell carcinomas.

Background: Photochemotherapy with oral methoxsalen (psoralen) and ultraviolet A radiation (PUVA) is an effective treatment for psoriasis. However, PUVA is mutagenic, increases the risk of squamous-cell skin cancer, and can cause irregular, pigmented skin lesions. We studied the occurrence of melanoma among patients treated with PUVA. Methods: We prospectively identified cases of melanoma and documented the extent of exposure to PUVA among 1380 patients with psoriasis who were first treated with PUVA in 1975 or 1976. Using incidence data, we calculated the expected incidence of melanoma in this cohort and compared it with the observed incidence. Using regression models, we assessed the risks of melanoma associated with a long time (>15 years) since the first treatment and with a large number of PUVA treatments (>250). Results: From 1975 through 1990, we detected four malignant melanomas, about the number expected in the overall population (relative risk, 1.1). From 1991 through 1996, we detected seven malignant melanomas (relative risk, 5.4; 95 percent confidence interval, 2.2 to 11.1). The risk of melanoma was higher in the later period than in the earlier one (incidence-rate ratio, 3.8) and higher among patients who received at least 250 PUVA treatments than among those who received fewer treatments (incidence-rate ratio, 3.1). Conclusions: About 15 years after the first treatment with PUVA, the risk of malignant melanoma increases, especially among patients who receive 250 treatments or more. (N Engl J Med 1997;336:1041-5.) [ABSTRACT FROM AUTHOR]

Looks at new tests for cystic fibrosis and their influence on a reconsideration of the spectrum of the disease. Types of laboratory tests; Correlation of genotype and phenotype; Rational use of clinical signs and laboratory tests to diagnose or rule out cystic fibrosis; Relation of cystic fibrosis to congenital absence of the vas deferens; Conclusions; References.

A letter to the editor is presented in response to the article "Cardiac myxomas,' by K. Reynen in the December 14, 1995 issue.

A response by Robert S. Stern and Jean Claude Roujeau to various letters to the editor regarding their article "Severe adverse cutaneous reactions to drugs" that was published in the November 10, 1994 issue is presented.

The article focuses on the use of topical tretinoin for the treatment of acne in the U.S. Topical tretinoin became the therapy most often requested by patients after the highly publicized study on its use for photoaging in the year 1988. After 1988, the prescription rates for topical tretinoin more than doubled as compared with the average for earlier years. The rate of prescribing increased most for visits by women over the age of 30 years, visits to nondermatologists and visits that were not for acne. The National Ambulatory Medical Care Survey first collected data on prescriptions in 1980.

Focuses on aspects of acute severe cutaneous reactions to medications. Emphasis on the clinical recognition, epidemiology, pathophysiology and treatment of these reactions; Clinical features of selected severe cutaneous reactions often induced by drugs; Stevens-Johnson syndrome; Toxic epidermal necrolysis; Drugs associated with Stevens-Johnson syndrome and toxic epidermal necrolysis.

A letter to the editor is presented in response to the article "Shock and Multiple-Organ Dysfunction After Self-Administration of Salmonella Endotoxin," in the April 20, 1993 issue.

A response by Robert S. Stern and colleagues to letters to the editor about their article on nonmelanoma skin cancer published in the December 3, 1992 issue of the journal is presented.

A letter to the editor is presented in response to the article "Management of acquired bullous skin diseases," by J-D. Fine in the November 30, 1995 issue.

Background: Toxic epidermal necrolysis and Stevens–Johnson syndrome are rare, life-threatening, drug-induced cutaneous reactions. We conducted a case–control study to quantify the risks associated with the use of specific drugs. Methods: Data were obtained through surveillance networks in France, Germany, Italy, and Portugal. Drug use before the onset of disease was compared in 245 people who were hospitalized because of toxic epidermal necrolysis or Stevens–Johnson syndrome and 1147 patients hospitalized for other reasons (controls). Crude relative risks were calculated and adjusted for confounding by multivariate methods when numbers were large enough. Results: Among drugs usually used for short periods, the risks were increased for trimethoprim–sulfamethoxazole and other sulfonamide antibiotics (crude relative risk, 172; 95 percent confidence interval, 75 to 396), chlormezanone (crude relative risk, 62; 21 to 188), aminopenicillins (multivariate relative risk, 6.7; 2.5 to 18), quinolones (multivariate relative risk, 10; 2.6 to 38), and cephalosporins (multivariate relative risk, 14; 3.2 to 59). For acetaminophen, the multivariate relative risk was 0.6 (95 percent confidence interval, 0.2 to 1.3) in France but 9.3 (3.9 to 22) in the other countries. Among drugs usually used for months or years, the increased risk was confined largely to the first two months of treatment, when crude relative risks were as follows: carbamazepine, 90 (95 percent confidence interval, 19 to ∞); phenobarbital, 45 (19 to 108); phenytoin, 53 (11 to ∞); valproic acid, 25 (4.3 to ∞); oxicam nonsteroidal antiinflammatory drugs (NSAIDs), 72 (25 to 209); allopurinol, 52 (16 to 167); and corticosteroids, 54 (23 to 124). For many drugs, including thiazide diuretics and oral hypoglycemic agents, there was no significant increase in risk. Conclusions: The use of antibacterial sulfonamides, anticonvulsant agents, oxicam NSAIDs, allopurinol, chlormezanone, and corticosteroids is associated with large increases in the risk of Stevens–Johnson syndrome or toxic epidermal necrolysis. But for none of the drugs does the excess risk exceed five cases per million users per week. (N Engl J Med 1995;333:1600-7.) [ABSTRACT FROM AUTHOR]

Background: Skin diseases, including adverse reactions to drugs, are thought to be more common among patients with human immunodeficiency virus (HIV) infection and the acquired immunodeficiency syndrome (AIDS) than among other persons. These skin conditions can be disabling or disfiguring and may require discontinuation of essential drugs. Methods: We identified 684 HIV-infected members of a 265,000-member health maintenance organization and reviewed their medical records to determine the frequency of dermatologic diagnoses from April 1, 1988, through January 15, 1991. We compared the rates of visits per year for skin conditions by HIV-infected men, 20 to 49 years of age, with those by non-HIV-infected men. We used an automated prescription data base to quantify exposures to drugs. Results: Of the 684 HIV-infected patients, 540 (79 percent) were given one or more dermatologic diagnoses, for a total of 2281 diagnoses, including 188 cutaneous reactions to drugs. There were 43 hospitalizations for cellulitis (n = 15), cutaneous drug reactions (n = 13), or other skin problems. As compared with non-HIV-infected men, the men with AIDS had visit rates that were at least 5 times higher for 18 of the 20 most common infectious and inflammatory skin conditions and at least 15 times higher for 9 conditions. Drugs with the highest rate of cutaneous reactions (per 1000 courses) included trimethoprim-sulfamethoxazole (149), sulfadiazine (200), trimethoprim-dapsone (156), and aminopenicillins (93). The number of diagnoses of skin conditions increased according to the stage of disease: it was lowest in patients immediately before the documentation of HIV infection and highest in patients with a diagnosis of AIDS. Conclusions: Cutaneous diseases, including drug reactions, are extremely common in patients with HIV infection, and their incidence increases as immune function deteriorates. (N Engl J Med 1993;328:1670-4.) [ABSTRACT FROM AUTHOR]