A Cross-Sectional Evaluation of the Usefulness of the Minor Features of Hanifin and Rajka Diagnostic Criteria for the Diagnosis of Atopic Dermatitis in the Pediatric Population.

Background: Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disease. Hanifin and Rajka's criteria is the most common diagnostic criteria used for the clinical diagnosis of this condition. However, many find that it is too exhaustive to be used in routine practice, and the specificity of many of the minor criteria poses challenges, particularly from Asian countries with type III, IV, and V skin. Aims and Objectives: The aim of the study is to evaluate the effectiveness of the minor features of the Hanifin and Rajka criteria for AD in comparison to the UK working party's diagnostic criteria in pediatric populations of India. Methodology: A hospital-based cross-sectional study of 100 patients in the pediatric age group (3 months-12 years) with AD was conducted based on history, clinical, and laboratory evaluation. An age-matched control group of 100 pediatric patients who did not have a personal or family history of atopic dermatitis was included after obtaining informed consent to find out the prevalence of minor criteria among the control group. Results: Mean of the number of minor clinical criteria found positive in our study population in the infantile and toddler (below 2 years) and childhood groups (2-12 years) was (4.72 ± 1.75) and (5.67 ± 1.78), respectively. Early-onset of disease was the most consistent feature among the minor criteria found in 83% of patients, followed by xerosis (71%), hyperlinearity of palm (56%), pityriasis alba (54%), Denny Morgan fold (52%), elevated serum IgE (47%), perifollicular accentuation (37%), and tendency toward cutaneous infections (37%). Conclusion: We found that though some of the minor criteria are highly sensitive and specific to the diagnosis of AD (xerosis, ichthyosis, palmar hyperlinearity, tendency of cutaneous infections, Dennie-Morgan infraorbital fold, pityriasis alba, and perifollicular accentuation), some other criteria were either very rare or nonspecific for AD. We suggest that many of the minor criteria of Hanifin and Rajka may not have much significance for Indian patients and a multicentric nationwide study with a larger patient pool is required to create a trimmed and improved version of Hanifin and Rajka criteria.

Klebsiella pneumoniae brain abscess in two neonates.

We report two premature infants who developed multiple brain abscesses following Klebsiella pneumoniae infection. Both the cases were diagnosed by ultrasonogram (USG) and cranial tomography. Abscess had intraventricular communication in one case. One infant was managed conservatively while the other required surgical drainage.

Discovery of potent, nonsystemic apical sodium-codependent bile acid transporter inhibitors (Part 1).

Elevated plasma levels of low-density lipoprotein (LDL) cholesterol are a major risk factor for atherosclerosis leading to coronary artery disease (CAD), which remains the main cause of mortality in Western society. We believe that by preventing the reabsorption of bile acids, a minimally absorbed apical sodium-codependent bile acid transporter (ASBT) inhibitor would lower the serum cholesterol without the potential systemic side effects of an absorbed drug. A series of novel benzothiepines (3R,3R'-2,3,4,5-tetrahydro-5-aryl-1-benzothiepin-4-ol 1,1-dioxides) were synthesized and tested for their ability to inhibit the apical sodium dependent bile acid transport (ASBT)-mediated uptake of [(14)C]taurocholate (TC) in H14 cells. A 3R,4R,5R/3S,4S,5S racemate was found to have greater potency than the other three possible racemates. Addition of electron-donating groups such as a dimethylamino substituent at the 7 position greatly enhanced potency, and incorporation of a long-chain quaternary ammonium substituent on the 5-phenyl ring was useful in minimizing systemic exposure of this locally active ASBT inhibitor while also increasing water solubility and maintaining potency. The reported results describe the synthesis and SAR development of this benzothiepine class of ASBT inhibitors resulting in an 6000-fold improvement in ASBT inhibition with desired minimal systemic exposure of this locally acting drug candidate.

Discovery of potent, nonsystemic apical sodium-codependent bile acid transporter inhibitors (Part 2).

In the preceding paper several compounds were reported as potent apical sodium-codependent bile acid transporter (ASBT) inhibitors. Since the primary site for active bile acid reabsorption is via ASBT, which is localized on the luminal surface of the distal ileum, we reasoned that a nonsystemic inhibitor would be desirable to minimize or eliminate potential systemic side effects of an absorbed drug. To ensure bioequivalency and product stability, it was also essential that we identify a nonhygroscopic inhibitor in its most stable crystalline form. A series of benzothiepines were prepared to refine the structure-activity relationship of the substituted phenyl ring at the 5-position of benzothiepine ring and to identify potent, crystalline, nonhygroscopic, and efficacious ASBT inhibitors with low systemic exposure.