Longitudinal variation in O(6)-alkylguanine DNA-alkyltransferase activity in the human colon and rectum

In a systematic study of O(6)-alkylguanine DNA-alkyltransferase activity in the human colon and rectum, tumours were found to occur in regions of low activity. These results are consistent with the hypothesis that O(6)-alkylguanine DNA-alkyltransferase levels and alkylating agent exposure may be important determinants of large bowel tumorigenesis.     

Initial treatment for prostate carcinoma in relation to comorbidity and symptoms

BACKGROUND: Evidence suggests the type of treatment received for prostate carcinoma is associated with comorbidity, but little information is available on associations with specific comorbid disease or symptoms. The authors examined the relations between treatment and comorbidity, specific comorbid disease, and symptoms. METHODS: Medical records were abstracted for 1054 male members of the Kaiser Permanente medical care program diagnosed with prostate carcinoma from 1975 to 1987. Information was obtained on demographic characteristics, comorbid conditions, symptoms, tumor stage and grade, and treatment. Logistic regression was used to determine the significant predictors of treatment (radiation vs. nonaggressive treatment and surgery vs. nonaggressive treatment). RESULTS: Compared to nonaggressive treatment, radiation treatment was less likely among men who had prior cancer (adjusted odds ratio [OR] 0.29, 95% confidence interval [CI] 0.09-0.90) or cerebrovascular disease (OR 0.33, 95% CI 0.13-0.83). There was a significant interaction between race and myocardial infarction (P = 0.02). Surgery, compared to nonaggressive treatment, was less common among men with a prior cancer (OR 0.21, 95% CI 0.07-0.63) or congestive heart failure (OR 0.29, 95% CI 0.09-0.90). Significant interactions were observed between race and myocardial infarction (P = 0.01), diabetes and dysuria or hematuria (P = 0.02), and para- or hemiplegia and urinary frequency or nocturia (P = 0.01). CONCLUSIONS: Specific symptoms and comorbidity appear to influence treatment for prostate carcinoma. More research is needed on treatment differences by race.     

Vascular Thoracic Outlet Syndrome

Vascular thoracic outlet syndrome generally affects young, active, otherwise healthy patients. The diagnosis is suspected by clinical presentation, and can be confirmed with angiography or venography. Conservative management has been associated with significant morbidity and long-term residual disability. We have used a multimodal treatment protocol that includes thrombolysis, anticoagulation, surgical decompression, and interventional procedures. Catheter-directed recombinant tissue-type plasminogen activator and intravenous heparin infusion are instituted at the time of diagnosis to promote recanalization and prevent propagation of thrombus. Surgical decompression of the thoracic outlet can be readily achieved by first rib resection during the same hospitalization. Postoperative venograms are obtained in all patients. Residual stenoses can be managed with angioplasty alone in some patients but more commonly require stent placement. We believe thrombolysis, anticoagulation, surgical decompression, and percutaneous interventions act synergistically to improve results of therapy in patients with vascular thoracic outlet syndrome.     

Long-term follow-up of 246 adults with juvenile idiopathic arthritis: predictive factors for mood and pain

OBJECTIVE: To examine the predictive factors for anxiety, depression and pain in adults with juvenile idiopathic arthritis (JIA). PATIENTS AND METHODS: Two hundred and forty-six adults identified with long-standing JIA had an average disease duration of 28.3 yr. Candidate factors potentially predictive for pain, anxiety and depression were assessed by multiple regression analysis. RESULTS: Of the patients, 31.6% were anxious, 5.2% were depressed, and 21.1% had previously suffered from depression. The percentage of the variance accounted for by other variables was 78.8 for anxiety variance and 54.5 for depression, but there was little influence from physical disease-related factors. Severe pain, measured on a visual analogue scale, occurred in 32.9% of patients, and 22.8% had poor perceived control over their pain. Function, coping strategies, pain self-efficacy, inflammation and previous depression could predict 39.6% of the variance in pain. CONCLUSIONS: Comparing adults with children, disease activity and control over pain remain predictors of pain but become less important than disability and coping strategies.     

U.K. guidelines for the management of cutaneous melanoma

These guidelines for management of cutaneous melanoma present evidence-based guidance for treatment, with identification of the strength of evidence available at the time of preparation of the guidelines, and a brief overview of epidemiological aspects, diagnosis and investigation. To reflect the collaborative process for the U.K., they are subject to dual publication in the British Journal of Dermatology and the British Journal of Plastic Surgery.     

Neutrophil CD11b,L-selectin and Fc IgA receptors in patients with dermatitis herpetiformis

BACKGROUND: The skin lesions found in patients with dermatitis herpetiformis (DH) are characterized by the presence of neutrophils at the dermal papillary tips in areas where the diagnostic cutaneous IgA deposits are found. Although the presence of the skin lesions of DH is known to be associated with gluten-sensitive enteropathy, the mechanisms that control the development of skin lesions are not known. OBJECTIVES: To determine if circulating neutrophils from patients with DH have evidence of priming as shown by increased expression of CD11b, decreased expression of L-selectin and increased function of neutrophil Fc IgA receptor. METHODS: Neutrophils from 12 normal subjects and 10 DH patients with active, ongoing disease and 14 DH patients with quiescent disease activity were examined by fluorescence-activated cell sorter for expression of cell surface CD11b, L-selectin expression, Fc IgA expression (CD89) and for the function of the Fc IgA receptor by determining the binding capacity of neutrophils for monoclonal human IgA. RESULTS: Neutrophils from patients with active, ongoing DH had increased expression of CD11b when compared with patients with inactive DH or normal subjects [mean net geometric mean channel fluorescence (GMCF): active DH, 403.3; inactive DH, 237.8; normal subjects, 290.5; P < 0.05]. L-selectin expression in both groups of DH patients was significantly lower than that seen in normal subjects (mean net GMCF: active DH, 363.2; inactive DH, 375.2; normal subjects, 432.7; P < 0.05). No difference in CD89 expression was seen in any of the groups; however, the function of Fc IgA receptor was increased in patients with active DH when compared with patients with inactive DH and normal subjects. CONCLUSIONS: Neutrophils from patients with active, ongoing DH show an increased expression of CD11b, decreased expression of L-selectin and increased ability to bind IgA, consistent with a pattern of priming of the neutrophils. This priming may occur in the gut as a result of the ongoing mucosal immune response that is present in patients with DH on a gluten-containing diet and may predispose neutrophils to localize in the skin of patients with DH.     

Structure and function of human stratum corneum under deformation

BACKGROUND: The stratum corneum (SC) has an important barrier function. The effect of a mechanical stress applied to the SC is controversial on this important physiological parameter. OBJECTIVES AND METHODS: To assess both in vitro and in vivo the structure and function of human SC submitted to controlled strains, we measured the transepidermal water loss (TEWL), in vivo, on human skin submitted to controlled strains ranging from 0 to 20% extension imposed by a Densi-score device. We also looked at the structure of the SC by means of X-ray diffraction and transmission electron microscopy. RESULTS: Transmission electron microscopy and X-ray diffraction analysis were performed on harvested and stretched human SC. TEWL was not significantly influenced by the relative deformation applied to the skin. At high strain (60%) imposed in vitro to the SC, lipid bilayers and corneosomes were detached from corneocytes. Only rare corneosomes showed internal disruption. X-ray analysis did not reveal modifications in the supramolecular organization of intercellular lipids while stretching the SC. CONCLUSION: Submitting human SC to an extension force up to 20% elongation does not significantly alter the barrier function.     

Contact sensitivity to hair dyes can be detected by the consumer open test

To avoid allergic reactions to hair dyes, an open test ("skin sensitivity test" or "dab test") is recommended 48 hours before the hair colouring procedure. We have investigated in a multicenter study, under standardized conditions and medical supervision, the validity of this test as a practical method to detect allergy to paraphenylenediamine (PPD)-containing hair dyes in 30 PPD patch test-positive and 30 PPD patch test-negative subjects. A defined volume of a marketed hair colouring product containing 1.8% PPD was applied in an open patch test to the retroauricular area. The grading method comprised the dermatologist's clinical evaluation and objective numerical scores. Allergic reactions were elicited in all PPD-positive subjects with a maximal intensity on Day 2; no allergic reactions were elicited in PPD-negative subjects. Increased severity of reactions by the dermatologist's clinical evaluation was correlated strongly with increasing numerical scores. The "skin sensitivity test" can be considered as an effective method to detect type IV hair dye allergy and as such, as an important factor in its secondary prevention.