Antibody Response Against the Glomerular Basement Membrane Protein Agrin in Patients with Transplant Glomerulopathy

Chronic allograft nephropathy (CAN) of renal allografts is still the most important cause of graft loss. A subset of these patients have transplant glomerulopathy (TGP), characterized by glomerular basement membrane (GBM) duplications, but of unknown etiology. Recently, a role for the immune system in the pathogenesis of TGP has been suggested. In 11 of 16 patients with TGP and in 3 of 16 controls with CAN in the absence of TGP we demonstrate circulating antibodies reactive with GBM isolates. The presence of anti-GBM antibodies was associated with the number of rejection episodes prior to diagnosis of TGP. Sera from the TGP patients also reacted with highly purified GBM heparan sulphate proteoglycans (HSPG). Indirect immunofluorescence with patient IgG showed a GBM-like staining pattern and colocalization with the HSPGs perlecan and especially agrin. Using patient IgG, we affinity purified the antigen and identified it as agrin. Reactivity with agrin was found in 7 of 16 (44%) of patients with TGP and in 7 of 11 (64%) patients with anti-GBM reactivity. In conclusion, we have identified a humoral response against the GBM-HSPG agrin in patients with TGP, which may play a role in the pathogenesis of TGP.     

Severe methemoglobinemia due to topical dapsone misuse in a teenage girl

Dapsone gel is a topical treatment for facial acne in adolescents and adults, and while systemic dapsone therapy is known to be associated with methemoglobinemia, once-daily topical dapsone has been well tolerated with few side effects in large randomized controlled trials. We describe the first reported case of severe methemoglobinemia in a healthy adolescent using daily topical dapsone. Although the medication was prescribed for facial use only, the patient reported topical use over her back and chest as well. This case illustrates the potential for significant systemic dapsone absorption even with daily topical dosing and demonstrates the need for clear anticipatory guidance to prevent the potential morbidity and mortality associated with methemoglobinemia from improper topical dapsone use.     

An evaluation of the treatment of parapsoriasis with phototherapy

Whether parapsoriasis represents an early stage of T-cell cutaneous lymphoma is stillthe subject of controversy. We evaluated the efficacy of phototherapy in thetreatment of parapsoriasis and its relation with TCCL. Patients diagnosed withparapsoriasis and treated with phototherapy PUVA or UVB-NB were selected. Between 1to 8 years following treatment the evolution of their disease was evaluated. In 62patients the cure rate was 79.3% and 17.2% showed improvement of the lesions. Onlytwo patients developed full blown T-cell cutaneous lymphoma. Phototherapy is anexcellent treatment for parapsoriasis, with high cure rates, regardless of the typeof phototherapy employed. Of the 62 patients under study, parapsoriasis showed nogeneral tendency to progress to T-cell cutaneous lymphoma.     

Dermoscopic features of thin melanomas: a comparative study of melanoma in situ and invasive melanomas smaller than or equal to 1mm

BACKGROUND

Dermoscopy allows the early detection of melanomas. The preoperative determination of Breslow index by dermoscopy could be useful in planning the surgical approach and in selecting patients for sentinel lymph node biopsy.

OBJECTIVES

This study aims at describing the dermoscopic features of thin melanomas and comparing melanomas in situ with invasive melanomas less than or equal to 1 mm thick.

METHODS

This was an observational retrospective study in which the dermoscopy photographs of 41 thin melanomas were evaluated. Three observers evaluated together 14 dermoscopic criteria.

RESULTS

Among thin melanomas, the most frequent criteria were presence of asymmetry in two axes in 95% of cases (39 cases), 3 or more colors in 80.4% of cases (33 cases), atypical dots or globules in 58.5% of cases (24 cases) and atypical network or streaks in 53.6% of cases (22 cases). The group of invasive melanomas presented with a higher frequency and statistical significance (p <0.05) 3 or more colors (OR: 16.1), milky red areas (OR: 4.8) and blue-white veil (OR: 20.4), and a greater tendency to have streaks or atypical network (OR: 3.66).

CONCLUSIONS

Thin melanomas tend to have asymmetry in the two axes, 3 or more colors, atypical dots or globules and atypical network or streaks. Melanomas in situ tend to have up to 2 colors, no blue-white veil and no milky red area. Invasive melanomas tend to have 3 or more colors, a milky red area, blue-white veil, and atypical network or streaks. Further studies are needed to confirm these findings.     

Peel bond strength of resilient liner modified by the addition of antimicrobial agents to denture base acrylic resin

In order to prolong the clinical longevity of resilient denture relining materials and reduce plaque accumulation, incorporation of antimicrobial agents into these materials has been proposed. However, this addition may affect their properties.

Objective

This study evaluated the effect of the addition of antimicrobial agents into one soft liner (Soft Confort, Dencril) on its peel bond strength to one denture base (QC 20, Dentsply).

Material and Methods

Acrylic specimens (n=9) were made (75x10x3 mm) and stored in distilled water at 37ºC for 48 h. The drug powder concentrations (nystatin 500,000U - G2; nystatin 1,000,000U - G3; miconazole 125 mg - G4; miconazole 250 mg - G5; ketoconazole 100 mg - G6; ketoconazole 200 mg - G7; chlorhexidine diacetate 5% - G8; and 10% chlorhexidine diacetate - G9) were blended with the soft liner powder before the addition of the soft liner liquid. A group (G1) without any drug incorporation was used as control. Specimens (n=9) (75x10x6 mm) were plasticized according to the manufacturers'' instructions and stored in distilled water at 37ºC for 24 h. Relined specimens were then submitted to a 180-degree peel test at a crosshead speed of 10 mm/min. Data (MPa) were analyzed by analysis of variance (α=0.05) and the failure modes were visually classified.

Results

No significant difference was found among experimental groups (p=0.148). Cohesive failure located within the resilient material was predominantly observed in all tested groups.

Conclusions

Peel bond strength between the denture base and the modified soft liner was not affected by the addition of antimicrobial agents.     

A retrospective study on 69 cases of maxillary tooth transposition

The published literature on tooth transposition includes only a few studies that have involved more than 50 subjects. The aim of the present study was to investigate the prevalence of true maxillary tooth transposition and possible associated dental anomalies in a larger sample of children. The dental records and radiographs of children who had been diagnosed as having true maxillary tooth transposition at a School Dental Clinic in Hong Kong were studied retrospectively. Data were analyzed for sex and side distribution, as well as for associated dental anomalies. Trends of differences were analyzed statistically using the Fisher exact or chi-squared test. A total of 69 cases of true maxillary tooth transposition were identified and studied; its prevalence in Hong Kong Chinese children was 0.81%. More females than males were affected, and the difference between the sexes was statistically significant (P < 0.05). The prevalence of congenitally missing teeth, microdontia of the maxillary lateral incisors or dental impaction was higher in patients with maxillary tooth transposition than in the general population (P < 0.05, P < 0.0005, and P < 0.0001, respectively). The fact that patients with maxillary tooth transposition were more likely to have congenital absence or microdontia of the maxillary lateral incisors lent further support to the contention that a developmental field defect plays a role in the pathogenesis of maxillary tooth transposition.     

Novel Linker Variants of Antileishmanial/Antitubercular 7-Substituted 2-Nitroimidazooxazines Offer Enhanced Solubility

Antitubercular 7-substituted 2-nitroimidazo[2,1-b][1,3]oxazines were previously shown to exhibit potent antileishmanial and antitrypanosomal activities, culminating in a new clinical investigational drug for visceral leishmaniasis (DNDI-0690). To offset development risks, we continued to seek further leads with divergent candidate profiles, especially analogues possessing greater aqueous solubility. Starting from an efficacious monoaryl derivative, replacement of the side chain ether linkage by novel amine, amide, and urea functionality was first explored; the former substitution was well-tolerated in vitro and in vivo but elicited marginal alterations to solubility (except through a less stable benzylamine), whereas the latter groups resulted in significant solubility improvements (up to 53-fold) but an antileishmanial potency reduction of at least 10-fold. Ultimately, we discovered that O-carbamate 66 offered a more optimal balance of increased solubility, suitable metabolic stability, excellent oral bioavailability (100%), and strong in vivo efficacy in a visceral leishmaniasis mouse model (97% parasite load reduction at 25 mg/kg).