Tolerability of 2.5% Lidocaine/Prilocaine Hydrogel in Children Undergoing Cryotherapy for Molluscum Contagiosum

The tolerability of a 2.5% lidocaine/prilocaine hydrogel (Nanorap, Biolab Indústria Farmacêutica Ltd., Sao Paulo, Brazil) was evaluated in 20 children ages 2 to 11 years undergoing cryotherapy for molluscum contagiosum (MC). The product was well tolerated, with only two children presenting with eczema at the application site. These adverse reactions were considered unlikely to be related to the test product, because a patch test was negative in one of the individuals and the other event occurred in only one of the two treated areas. Nanorap is an efficacious and well‐tolerated option for topical anesthesia in children undergoing cryotherapy for MC.     

Changes in thyroidal function and liver UDPglucuronosyltransferase activity in rats following administration of a novel imidazole (SC-37211)

SC-37211, an imidazole with antianaerobic activity, was administered po to male rats for 2 weeks at dosages of 20, 60, and 200 mg/kg/day. Histological changes in the thyroid included irregularly shaped follicles and slightly enlarged follicular cells. Serum triiodothyronine (T3) and/or thyroxine (T4) were significantly decreased in treated animals at all dosages; these decreases were not observed following a 2-week recovery period. The half-life of serum [125I]thyroxine was also significantly decreased in rats treated with SC-37211. Morphological changes in the thyroid are likely the result of thyroid-stimulating hormone (TSH) stimulation, a response to decreased serum T3 and T4 concentrations. The decreases in T3 and T4 were not due to decreases in iodide uptake or organification. There were dose-dependent increases in liver weights, liver-to-body weight ratios, and UDPglucuronosyltransferase activity toward p-nitrophenol and T4. Therefore, the decreases in serum T3 and T4 were probably due to an increase in hepatic metabolism rather than to a direct effect of SC-37211 on the thyroid.     

Development of a P-glycoprotein knockout model in rodents to define species differences in its functional effect at the blood-brain barrier

The objective of this study was to establish the optimal blood concentrations of the potent P-glycoprotein (P-gp) inhibitor GF120918 (Elacridar) required to achieve maximal knockout of this efflux transporter in the blood-brain barrier (BBB) of mice, rats, and guinea pigs. Genetic mdr1a/b(-/-) knockout mice and "chemical" P-gp knockout mice, rats, and guinea pigs, generated by 24 h continuous infusion of GF120918, were used to investigate the effects of P-gp modulation on the brain penetration of SB-487946. Genetic mdr1a/b(-/-) knockout mice demonstrated a >70-fold increase in brain:blood ratio of SB-487946 compared to mdr1a/b(+/+) wild-type mice. There was a similar increase in SB-487946 brain:blood ratio in GF120918-treated mice (ca. >67-fold) and rats (ca. 95-fold) but a significantly smaller increase (ca. 10-fold) in guinea pigs treated with GF120918. An appreciable difference was found in the BBB functional effect of P-gp efflux in rodents. GF120918 blood EC90 in mice and rats were similar however, the EC90 in guinea pigs was ca. 10-fold higher, suggesting a species difference in the activity of P-gp at the BBB in some rodents. This study establishes the optimal blood concentrations of GF120918 in relation to SB-487946, to achieve chemically induced P-gp knockout in rodents.     

Diagnostic reliability of FNAC for salivary gland swellings: A comparative study

A prospective study was conducted to see the sensitivity, specificity, and accuracy of fine needle aspiration cytology (FNAC) for 100 salivary gland swellings in comparison with biopsy. These randomized samples were submitted and reported at the department of pathology, Allama Iqbal Medical College, Lahore. The male to female ratio was 1:1.5. Ages of the patients ranged from 8.5 to 58 years with mean age 33.39 ± 12.37 years. Maximum number of lesions was found in age group between 21 and 40 years. Parotid gland was involved in 68%, submandibular gland in 30%, and minor salivary glands in 2% patients. Sublingual gland was not involved in any of our subjects. There were 14% cases of non‐neoplastic lesions and 86% cases of neoplastic lesions on biopsy. Non‐neoplastic lesions included 12 cases of inflammations (three cases of granulomatous inflammation and nine cases of nonspecific chronic inflammation) and two cases of inclusion cysts. Among neoplastic lesions, biopsy revealed 68 cases of benign neoplasia and 18 cases of malignant neoplasia. Non‐neoplastic lesions did not show any difference in diagnosis by both techniques. FNAC misdiagnosed four malignant and one benign lesion. Sensitivity, specificity, positive predictive value, and negative predictive value of FNAC for benign neoplastic lesions were 98.52, 87.05, 94.36, and 96.55%, respectively, whereas for malignant neoplastic lesions they were 77.77, 98.78, 93.33, and 95.29%, respectively. In conclusion, FNAC is found to be a highly sensitive and specific technique for diagnosis of most of salivary gland swellings, except for malignant neoplastic lesions where its sensitivity is intermediate. We strongly recommend that FNAC should be adopted as an initial investigation for all salivary gland swellings. Diagn. Cytopathol. 2010. © 2009 Wiley‐Liss, Inc.     

Eosinophilic Gastroenteritis with Eosinophilic Dermatitis

Eosinophilic gastroenteritis (EG) is characterized by eosinophilic infiltration of the bowel wall and variable gastrointestinal manifestations. Clinicians should have a high index of suspicion for EG when faced with gastrointestinal symptoms and peripheral eosinophilia to avoid incorrect diagnosis and inappropriate treatments. A 24-year-old woman was admitted to our hospital complaining of acute right lower quadrant abdominal pain and a laparoscopic appendectomy performed for a presumed diagnosis of an acute appendicitis. However, the procedure revealed bowel edema and a moderate amount of ascites without evidence of a suppurative appendicitis. Postoperatively, she showed persistent and progressive eosinophilia, exudative eosinophilic ascites, eosinophilic infiltration of the resected appendix wall, and eosinophilic infiltration of gastroduodenal mucosa. A punch biopsy of the abdominal skin also revealed inflammation with marked eosinophilic infiltration of the skin. She recovered after the treatment with a low dose of steroid for the EG with eosinophilic dermatitis. EG with eosinophilic dermatitis has not been reported yet and is considered fortuitous in this case.     

Expression of nitric oxide,peroxynitrite, and apoptosis in loose total hip replacements

Nitric oxide (NO) is an effector molecule associated with inflammation, immune function, bone metabolism, and the induction of apoptosis. This study examined the role of NO, peroxynitrite (ONOO(-)), and apoptosis in cases of revision total hip replacements (THRs). We hypothesized that apoptosis and excess production of NO contribute to the inflammatory reaction to orthopedic biomaterial wear debris that is associated with loosening and osteolysis. Periprosthetic membranous specimens were collected from revised cemented acetabular components with simple loosening and ballooning osteolysis. Synovial samples from patients undergoing primary THR were used as controls. The presence of macrophages (CD68(+)) and levels of inducible nitric oxide synthase (INOS), endothelial nitric oxide synthase (EcNOS), ONOO(-) (Nitro, assayed by the amount of nitrated tyrosine residues), and apoptosis (TUNEL staining) were examined using immunohistochemistry. Increased expression for INOS, EcNOS, and ONOO(-) in both the loose/osteolytic and the loose/non-osteolytic groups was observed when compared to the synovium group. There were no significant differences between the loose/osteolytic group and loose/non-osteolytic group for these biologic markers. TUNEL staining showed a significant increase in apoptosis in the loose/osteolytic group compared to the loose/non-osteolytic group and synovial tissues. These findings suggest that NO and NO-derived molecules, such as ONOO(-), may be involved in sustaining the foreign-body reaction to wear debris. NO and ONOO(-) may prove to be useful markers of prosthetic loosening whereas apoptosis may be a marker distinguishing ballooning from simple osteolysis.