Very Elevated IgE, Atopy, and Severe Infection: A Genomics-Based Diagnostic Approach to a Spectrum of Diseases.

Elevated IgE has been long recognized as an important clinical marker of atopy but can be seen in a myriad of conditions. The discovery of autosomal dominant STAT3 deficiency marked the first recognition of hyper-IgE syndrome (HIES) and the first primary immunodeficiency linked to elevated IgE. Since then, genomic testing has increased the number of defects with associated mutations causing hyper-IgE syndrome and atopic diseases with FLG, DOCK8, SPINK5, and CARD11, among others. A spectrum of recurrent infections and atopy are hallmarks of elevated IgE with significant phenotypic overlap between each underlying condition. As treatment is predicated on early diagnosis, genomic testing is becoming a more commonly used diagnostic tool. We present a 6-year-old male patient with markedly elevated IgE and severe atopic dermatitis presenting with staphylococcal bacteremia found to have a heterozygous variant in FLG (p.S3247X) and multiple variants of unknown significance in BCL11B, ZAP70, LYST, and PTPRC. We review the genetic defects underpinning elevated IgE and highlight the spectrum of atopy and immunodeficiency seen in patients with underlying mutations. Although no one mutation is completely causative of the constellation of symptoms in this patient, we suggest the synergism of these variants is an impetus of disease.

Acknowledgement of horizon of oral and maxillofacial surgery by health care professionals and general population.

BACKGROUND: Oral and maxillofacial surgery (OMFS) is a dental specialty evolving from the anatomical region of head and neck. Differing from the belief, its scope does not start and end with teeth. The aim of the study was to survey the perception of OMFS among dental, medical, and paramedical professionals. MATERIALS AND METHODS: A structured questionnaire cross-sectional survey made up of 17 clinical situations pertaining to various complaints of patients was distributed among 50 medical and dental undergraduates, 50 medical and dental practitioners, and 50 general populations with a total number of 250 samples who were selected randomly. The collected data was tabulated using Microsoft excel for any predictable patterns. The results were analyzed taking absolute percentages of the responses into consideration. RESULTS: The results were compiled and tabulated and the data analyzed. While wisdom tooth removal, trauma, and facial bone fractures were recognized to be mainly treated by maxillofacial surgeons, the other maxillofacial problems were poorly recognized to be treated by our specialty. In our study, 67.3% of general public and 62.4% of medical professionals approached other medical specialist for the clinical conditions. The Chi-square results of few clinical situations were statistically significant with a P value of less than 0.05, which suggest that there is indeed a statistically significant difference between the responses of medical profession and the public on whom to approach regarding certain clinical cases. CONCLUSION: The study revealed that the majority of the public are lacking in knowledge about the benefits that the specialty can offer. It has been found that even though the Medical professionals are better informed, lacunae existed about information as to where our major activity lies. If patients are to have access to the best treatment available, it is essential that we edify the public about the scope of our specialty.

A comparative evaluation of impact strength of conventionally heat cured and high impact heat cured polymethyl methacrylate denture base resins: an in vitro study.

UNLABELLED: The denture bases made by using polymethyl methacrylates of Acrylic resin family have excellent physical properties, simple to process and easy to reline, rebase and repair. One of the inherent disadvantages of this material is the liability to break during function. The strength assessment of acrylic resins have been made generally by transverse defection tests. AIM: To evaluate the impact strength valves of certain brands of commercially available denture base resins and suggest their suitability. MATERIALS AND METHODS: The denture bases we made using polymethyl methacrylates of acrylic resin family because they have excellent physical properties, simple to process and easy to reline and rebase. Six commercial brands of polymethyl meth- acrylate, namely Stellon (DPI-India), Acralyn-H (Asian Acrylate, India), Trevalon (Dentsply-England), Lucitone 199 (Dentsply/ York division), Acralyn-H (Super Unbreakable), Trevalon HI (Dentsply, Detray division, England) were tested by breaking them using Analog Pendulum (ASTM D 256). RESULTS: From the entire study the maximum impact strength was reported for Acralyn-H super unbreakable (Asian Acrylates, India) 62.19 joules. CONCLUSION: All the analysis led to conclusion that there is basic change in material composition within and among the different groups of denture base resins. CLINICAL IMPLICATIONS: The complete dentures made using denture base resins with high impact strength valves (e.g. Acralyn-H super unbreakable) will be more durable and can be used by the patient for considerable period of time, i.e. beyond 4 to 5 years.

Efficacy of single-dose chemotherapy (rifampicin, ofloxacin and minocycline-ROM) in PB leprosy patients with 2 to 5 skin lesions, India: randomised double-blind trial.

UNLABELLED: We conducted randomized double-blind trial for single-dose of Rifampicin, Ofloxacin and Minocycline (ROM) compared to WHO-PB-MDT among paucibacillary (PB) leprosy patients with 2-5 skin lesions. We enrolled 1526 patients from five centres (ROM=762; WHO-PB-MDT=764) and followed them for 36 months posttreatment during 1998-2003. We generated information on clearance of skin lesions and relapse rates per 100 person-years (PY) for all the five centres. At base-line, the patients in the two arms were comparable. Complete clearance of skin lesions was similar (72% vs. 72.1%; p=0.95) in both the arms. Clinical scores declined steadily and equally. Difference in relapse rates was statistically highly significant (ROM=1.13 and WHO-PB-MDT=0.35 per 100 PY; mid-p exact=0.001016). Twenty eight of 38 of these relapses occurred within 18 months. In all, 10 suspected adverse drug reactions were.observed (ROM=2; WHO-PB-MDT=8). We extended the follow-up to 48 months for 1082 of 1526 patients from two programme-based centres. No further relapses occurred. Decline in clinical score was not dependent on age, gender, number of lesions or affected body parts. Single dose ROM, though less effective than the standard WHO-PB-MDT regimen conceptually offers an alternative treatment regimen for PB leprosy patients with 2-5 lesions only when careful follow-up for relapse is possible. Registered at the Clinical Trials Registry of India; REGISTRATION NUMBER: CTRI/2012/05/002645

Studies on rapid assessment methods in leprosy.

A study was undertaken in Pudukottai district, Tamilnadu, India to test rapid assessment methods: viz (i) sample surveys with lower coverages for clinical examination in estimating the disease problem in the community, (ii) utility of registered case prevalence for estimating the actual prevalence in a given area, (iii) leprosy in school-going children and its utility in estimating leprosy prevalence in the community, and (iv) information on disability and smear positivity in estimating leprosy prevalence; and develop correction factors for estimating leprosy situation. A sample of 23 clusters from 582 clusters of contiguous villages and hamlets was further divided into two random sub-samples for two surveys with differing coverages. One team covered nine clusters comprising 34 villages with a population of 17,562 and examined 15,596 with a population of 26,927 and examined 16,622 (62%) persons for leprosy. The results showed that: (i) leprosy sample surveys with lowered coverages would tend to miss valuable information, in terms of quality and quantity; (ii) from 'known case' registers, to estimate the true burden of leprosy disease and to monitor its trend over time is inadequate; (iii) school surveys are of limited value for estimating the disease burden in the community or to monitor its trend over time; (iv) the number of smear-positive cases is to small to serve as an indicator for the total case load in the community; and (v) the prevalence of active disease and that of grade 2 disability in the community are poorly correlated. Reliable methods other than those used here need to be developed for evaluation and monitoring of the disease burden particularly in the post-MDT era.

Comparative leprosy vaccine trial in south India.

This report provides results from a controlled, double blind, randomized, prophylactic leprosy vaccine trial conducted in South India. Four vaccines, viz BCG, BCG+ killed M. leprae, M.w and ICRC were studied in this trial in comparison with normal saline placebo. From about 3,00,000 people, 2,16,000 were found eligible for vaccination and among them, 1,71,400 volunteered to participate in the study. Intake for the study was completed in two and a half years from January 1991. There was no instance of serious toxicity or side effects subsequent to vaccination for which premature decoding was required. All the vaccine candidates were safe for human use. Decoding was done after the completion of the second resurvey in December 1998. Results for vaccine efficacy are based on examination of more than 70% of the original "vaccinated" cohort population, in both the first and the second resurveys. It was possible to assess the overall protective efficacy of the candidate vaccines against leprosy as such. Observed incidence rates were not sufficiently high to ascertain the protective efficacy of the candidate vaccines against progressive and serious forms of leprosy. BCG+ killed M. leprae provided 64% protection (CI 50.4-73.9), ICRC provided 65.5% protection (CI 48.0-77.0), M.w gave 25.7% protection (CI 1.9-43.8) and BCG gave 34.1% protection (CI 13.5-49.8). Protection observed with the ICRC vaccine and the combination vaccine (BCG+ killed M. leprae) meets the requirement of public health utility and these vaccines deserve further consideration for their ultimate applicability in leprosy prevention.