Recognition of pathogenically relevant house dust mite hypersensitivity in adults with atopic dermatitis: a new approach?

BACKGROUND: The pathogenic importance of the ubiquitous house dust mite, Dermatophagoides pteronyssinus (Dp), in atopic dermatitis is unclear. OBJECTIVE: We aimed to explore the relevance of Dp hypersensitivity in adult patients with atopic dermatitis by using an in vivo topical challenge method and in vitro assays for T-cell reactivity. METHODS: Dp and control skin prick test solutions were applied to the cubital fossae of 20 patients twice daily for 4 days; the severity of dermatitis and pruritus in the challenge sites were determined before and after testing. The same solutions were used in PBMC proliferation assays that included 10% fresh, autologous serum, the latter aimed at maximizing IgE facilitated allergen presentation. RESULTS: Although most patients had markedly elevated Dp-specific serum IgE levels, only 6 of 20 patients developed increases in cubital fossa dermatitis severity and pruritus scores that were greater at sites of application of Dp solution than at control sites. In addition, PBMC proliferation in response to Dp solution in the presence of autologous serum was significantly greater in the in vivo challenge-positive patients than in those who did not respond to challenge. A subgroup of patients (7/20) also developed transient but pronounced contact urticaria at sites of Dp application. CONCLUSION: These findings suggest that hypersensitivity to Dp might be clinically relevant in approximately one third of the adult atopic dermatitis population studied. They also point to methods of identifying patients who might respond to house dust avoidance measures.     

Adult Facial Growth: Applications to Aesthetic Surgery

Background: Reshaping of the face with age is a result of volume change and loss of support. It is not well understood which tissues are involved in this process. Recent publications suggest that adult bone growth may have a significant role. Objective: We report a longitudinal cephalometric analysis of midfacial growth in adults to determine the role of bone in facial aging. Methods: The Behrents modification of the Bolton Cephalometric study in patients up to age 83 was reviewed. A trigonometric analysis targeted orbital and anterior maxillary growth. Results: Facial bone growth is shown to continue throughout adulthood. Anterior descent creates increased bone projection. Conclusions: The appearance of facial aging is caused by attrition of soft tissue volume and loss of support. The deficiency of maxillary bone projection seen in some patients, with tear trough depression and negative vector eyelid (polar bear), preexists adulthood and is unmasked with age.     

Infliximab in the treatment of refractory posterior uveitis

PURPOSE: To determine the efficacy and safety of infliximab in the treatment of refractory posterior uveitis. DESIGN: Noncomparative interventional case series. PARTICIPANTS: Five patients with posterior uveitis were treated: 3 had Beh?et's syndrome, and 2 had idiopathic posterior uveitis. INTERVENTIONS: Patients with sight-threatening uveitis refractory to other immunosuppressive agents were treated with infliximab. MAIN OUTCOME MEASURES: Intraocular inflammation, by using binocular indirect ophthalmoscopy score, retinal vasculitis, and visual acuity. Adverse effects of infliximab were documented. RESULTS: Within 2 weeks of the first infusion of infliximab, 4 of 5 patients showed marked improvement in vitreous haze and visual acuity. By the 6-month follow-up, the same four patients had achieved remission of posterior uveitis and had successfully withdrawn all other immunosuppressive therapy. Further infusions of infliximab were required in 3 patients. One patient developed ocular and systemic tuberculosis, which responded to antituberculous treatment. CONCLUSIONS: Infliximab is effective in the treatment of sight-threatening refractory posterior uveitis. However, patients should be thoroughly screened for tuberculosis before treatment and followed up closely during and after therapy with infliximab.     

Management of intracranial dural arteriovenous shunts in adults

Dural arteriovenous shunts are abnormal arteriovenous communications within the dura. They are thought to be an acquired condition in adults and can present with a variety of clinical features, ranging from benign bruits to intracranial hemorrhage and neurological deficits. The presentation and natural history of these shunts is largely determined by the pattern of venous drainage. Knowledge of natural history and careful study of the angioarchitexture by angiography is therefore mandatory for correct management of these lesions. In this review, principles of management in adults and the various factors that influence treatment decisions are discussed, with a focus on endovascular therapy. Retrograde leptomeningeal or cortical venous drainage has a strong correlation with adverse clinical events and the requirement for aggressive management in this situation is highlighted. Indications for endovascular treatment, therapeutic goals, approaches and techniques are reviewed. The role of surgical treatment is also briefly discussed.     

Relationship of family history of type 2 diabetes, hypoglycemia, and autoantibodies to weight gain and lipids with intensive and conventional therapy in the Diabetes Control and Complications Trial

Intensive therapy for type 1 diabetes results in greater weight gain than conventional therapy. Many factors may predispose to this greater weight gain, including improved glycemic control, genetic susceptibility to obesity, and hypoglycemia. To study this, relationships among family history of type 2 diabetes, frequency of severe hypoglycemia, beta-cell autoantibodies, and weight gain were examined in 1,168 subjects aged > or =18 years at baseline randomized to intensive and conventional therapy groups in the Diabetes Control and Complications Trial. With intensive therapy, subjects with a family history of type 2 diabetes had greater central weight gain and dyslipidemia characterized by higher triglyceride levels and greater cholesterol in VLDLs and intermediate-density lipoproteins compared with subjects with no family history. Neither the frequency of severe hypoglycemia nor positivity to GAD65 and insulinoma-associated protein 2 antibodies was associated with increased weight gain with either intensive or conventional therapy. These data support the hypothesis that increased weight gain with intensive therapy might be explained, in part, by genetic traits.     

Hypoglycaemic and hypolipidemic effect of ethanolic extract of seeds of Eugenia jambolana in alloxan-induced diabetic rabbits

The hypoglycaemic and hypolipidemic effect of ethanolic extract obtained from seeds of E. jambolana was investigated in alloxan-induced diabetic rabbits. Hypoglycaemic activity was assessed by reduction in fasting blood glucose (FBG) at 90min and also fall in peak blood glucose during glucose tolerance test (GTT) in sub-diabetic and mild diabetic (MD) rabbits, but in severe diabetic (SD) rabbits by reduction in FBG at 90min. Ethanolic extract (100mg/kg body weight) when given orally to sub-diabetic (AR) for 1 day, MD for 7 days and SD for 15 days showed significant fall in FBG at 90min (12% AR, 18.9% MD and 29% SD) and also produced 16.9% fall in peak blood glucose in AR and 21% in MD rabbits during GTT. When administered daily for 15 days to MD and SD rabbits, significant fall in FBG (41.3% MD, 31.6% SD) and glycosylated haemoglobin (GHb) levels (23.3% MD, 26.6% SD) were observed, while serum insulin level showed significant increase (32.8% MD, 26.9% SD). Liver and muscle glycogen content also increased. The ethanolic extract of seeds also exhibited significant hypolipidemic effect as evident from fall in total serum cholesterol (TC)/high density lipoprotein cholesterol (HDL-c) ratio, serum low density lipoprotein cholesterol (LDL-c) levels and decreased activity of HMG-CoA reductase. The histopathological studies of liver, pancreas and aorta in alcoholic extract treated diabetic groups revealed almost normal appearance.     

Downregulation of hepatitis B surface antigen expression in human hepatocellular carcinoma cell lines by HD-03, a polyherbal formulation

Hepatitis B virus is associated with chronic or acute liver diseases and with hepatocellular carcinoma. In the present study, we examined the activity of HD-03, a polyherbal formulation, on two hepatitis B surface antigen (HBsAg) expressing human hepatocellular carcinoma cell lines, PLC/PRF/5 and HepG2/A2. We observed that HD-03 downregulates HBsAg expression from these cell lines. Our studies have also shown that this effect is neither due to cytotoxicity on the cell lines nor due to blockade of the release of the antigen from the cells nor due to binding of the substance with the antigen. The possible mode of its antiviral activity is explained.     

High incidence of head and neck squamous cell carcinoma in patients with Fanconi anemia

BACKGROUND: Fanconi anemia (FA) is a rare autosomal recessive disorder characterized by a high degree of genomic instability and predisposition to cancer development. Recent evidence suggests that the incidence of head and neck squamous cell carcinoma (HNSCC) may be increased in patients with FA. OBJECTIVE: To determine the cumulative incidence, tumor distribution, and outcome of HNSCC in patients with FA. DESIGN AND SETTING: We analyzed data from 754 subjects from the International Fanconi Anemia Registry, a prospectively collected database of patients with FA. MAIN OUTCOME MEASURES: Cumulative incidence of HNSCC and 2-year overall, relapse-free and disease-specific survival. RESULTS: Of the 754 patients in the International Fanconi Anemia Registry, 19 (3%) had HNSCC. This is a significantly higher incidence of HNSCC compared with that observed in the general population (standardized incidence ratio, 500; 95% confidence interval, 300-781) (P<.001). The patients' age ranged from 15 to 49 years (median, 31 years), and there was a 2:1 female predominance. Surgical treatment was well tolerated (n = 17); however, radiation therapy and chemotherapy were associated with significant morbidity and mortality. Of the 19 patients, 10 (53%) developed locoregional recurrences within a median of 16 months from diagnosis. The median follow-up was 29 months. The 2-year disease-specific, overall, and relapse-free survival rates were 49%, 49%, and 42%, respectively. The cumulative incidence of relapse by the age of 40 years was 50%. CONCLUSIONS: In patients with FA, there is a high incidence of aggressive HNSCC at a young age. Surgery remains the mainstay of treatment because patients with FA tolerate radiation therapy and chemotherapy poorly, with significant morbidity. An increased understanding of FA-associated malignancies is not only important in the clinical management of patients with FA but can also elucidate the role of chromosomal instability in the development of HNSCC in general.