Ameloblastic carcinoma arising from anterior skull base.

Ameloblastic carcinoma (AC) is an aggressive malignant epithelial odontogenic tumor. It may appear de novo or originate from a pre-existing ameloblastoma or odontogenic cyst. To our knowledge, an AC that originates from the anterior skull base has not been reported before in the English literature. We report a case of an AC that originated from the anterior skull base and invaded the dura of the anterior fossa and discuss its clinical course and treatment.     

Capillary Gas Chromatography and Thermionic N-P-Specific Detection of 13-Bis(2-chloroethyl)-l-nitrosourea (BCNU) or l-(2-Chloroethyl)-3-cyclohexyl-l-nitrosourea (CCNU) in Stability and Pharmacokinetic Studies

An expedient, rapid, and sensitive capillary gas chromatographic method for the analysis of l,3-bis(2-chloroethyl)-l-nitrosourea (BCNU) or l-(2-chloroethyl)-3-cyclohexyl-l-nitrosourea (CCNU) in plasma is described. Separation of the underivatized nitrosourea compounds was performed on a 0.33-mm-i.d., 25-m fused-silica, SE-30 capillary column, and detection was carried out using a thermionic N–P-specific detector. The compounds were extracted from plasma with benzene with a yield of >87%. The assay was linear in the ranges of 0.001 to 0.5 and 0.5 to 25 µg/ml for CCNU or 0.003 to 0.50 and 0.5 to 25 µg/ml for BCNU, with correlation coefficients from 0.9914 to 0.9999 and coefficients of variation (CV) of <3.3%. Other antineoplastic agents did not interfere in the assay. The method was employed to study the pharmacokinetics of BCNU in rabbits. The plasma concentration-time curves were fit to a two-compartment model with a mean (SE) , , and total-body clearance of 2.898 (0.913) hr^–1, 0.1228 (0.0179) hr^–1, and 7.211 (2.862) liters/hr · kg, respectively. Further, the stability of BCNU and CCNU in solution was examined at different temperatures. Both compounds were stable in benzene or acetone (4 to 37°C) but labile in plasma even if refrigerated. The apparent rate constants for degradation of BCNU and CCNU were 0.09921 and 0.02853 hr^–1 at 4°C and 5.998 and 2.553 hr^–1 at 37°C, respectively.     

Antibody Responses to Group A Streptococcal Infections in the Hamster

The immune response after streptococcal infections of the skin and of the joints was studied in an experimental animal model. Hamsters were challenged intradermally or intra-articularly with different streptococcal serotypes, and antibodies for streptolysin O (ASO), deoxyribonuclease B (anti-deoxyribonuclease B), and group A carbohydrate (anti-group A CHO) were determined. After a single injection at either site, 7 of 48 animals (14%) developed group A-CHO antibodies; however, none of the animals developed detectable levels of ASO or anti-deoxyribonuclease B. After repeated infections of the skin or joint, anti-deoxyribonuclease B antibodies were detectable in 13% (4 of 30) and 30% (5 of 17) of the animals, respectively. Elevations of ASO occurred after repeated joint infections in 4 of 16 animals (25%), whereas none of 30 hamsters repeatedly infected intradermally developed antibodies against streptolysin O. For all three antibodies tested, elevated levels were more frequently noted after repeated joint infections than after repeated skin infections with the same streptococcal serotype. These data, similar to ones previously noted in human impetigo, indicate that ASO responses are feeble after streptococcal skin infections and that the site of infection per se, rather than the infecting strain, appears to be responsible for this poor response.     

Ellis‐van Creveld syndrome in a patient from Tanzania

We report an African infant with Ellis‐van Creveld (EVC) syndrome. EVC syndrome is a chondral and ectodermal dysplasia with autosomal recessive transmission. The baby presented with polydactyly, short limbs and atrioventricular septal defect, but was withdrawn from clinical follow up for the first year of life. Initial hematological abnormalities could not be explained and normalized later. EVC syndrome was confirmed by genetic analysis that showed two pathogenic mutations in the EVC2 gene, c.653_654del, p.Val218Glyfs*12 in exon 5, and c.2710C>T, p.Gln904* in exon 16. The variant c.653_654del; p.Val218Glyfs*12 in exon 5 has not been described before. Our review of medical literature suggested this is the first molecularly confirmed case of EVC syndrome in sub‐Saharan Africa.     

Relationship among pulmonary function, bronchial reactivity, and exhaled nitric oxide in a large group of asthmatic patients.

BACKGROUND: Bronchial reactivity and exhaled nitric oxide (eNO) are not often used to monitor control and severity of asthma in clinical practice. OBJECTIVE: To evaluate the relationship among different physiologic measures (pulmonary function, nonspecific bronchial reactivity, and eNO) in asthmatic patients. METHODS: Cross-sectional, hospital-based study conducted in patients with varied asthma severity. RESULTS: A total of 392 patients participated in the study. There was no difference in eNO levels between patients taking inhaled corticosteroids (ICS group) and patients not receiving inhaled corticosteroids (NICS group). However, the percentage of predicted forced expiratory volume in 1 second (FEV1) and the provocative dose of methacholine causing a 20% decrease in FEV1 were significantly lower in the ICS group compared with the NICS group (mean, 83.2%; 95% confidence interval [CI], 80.4%-86.0%; vs mean, 94.1%; 95% CI, 91.1%-97.1%; P = .001; and geometric mean, 0.32 mg; 95% CI, 0.23-0.45 mg; vs geometric mean, 0.58 mg; 95% CI, 0.42-0.81 mg; P = .01; respectively). Patients with more severe bronchial hyperresponsiveness had a lower percentage of predicted FEV1 values (P < .001) and levels of eNO were significantly increased with increasing bronchial hyperresponsiveness (P < .001). There was no relationship between the percentage of predicted FEV1 and eNO. Atopic patients had significantly higher eNO levels than nonatopic patients (geometric mean, 11.21 ppb; 95% CI, 10.07-12.49 ppb; vs geometric mean, 7.76 ppb; 95% CI, 6.11-9.85 ppb; P = .006; respectively). CONCLUSIONS: eNO values are not related to the degree of airway obstruction but are related to airway reactivity and atopic status independent of inhaled corticosteroid use. Higher values of eNO are seen with increased airway reactivity.     

Defining the role of myoepithelium in salivary gland neoplasia

Neoplastic myoepithelium is considered to be the key cellular participant in morphogenetic processes responsible for the variable histologic appearances of many salivary gland tumors. Nevertheless, controversy still exists concerning its participation in some types of salivary gland neoplasms. This has been largely due to the difficulty in fully characterizing the wide spectrum of morphologic and immunophenotypic expressions of neoplastic myoepithelium compared with the normal counterpart. However, in recent years, our understanding regarding the phenotypic, immunophenotypic, ultrastructural, and biochemical properties of myoepithelium has advanced. Here we discuss the role of neoplastic myoepithelium in the scope of salivary gland neoplasia and present this information from a practical diagnostic standpoint.     

Methimazole as a protectant against cisplatin-induced nephrotoxicity using the dog as a model

Dexniguldipine-HCl (DNIG) — a prospective clinical modulator of p170-glycoprotein (pgp170)-mediated multidrug resistance (MRD) — was evaluated in a drug-accumulation assay in MDR murine leukemia cell strain F4-6RADR expressing pgp170. The compound elevated low accumulation of either doxorubicin (DOX), daunorubicin (DNR), or mitoxantrone (MITO) in resistant F4-6RADR cells to the very levels observed in drug-sensitive F4-6 precursor cells. In parallel with the increase in DNR content (F4-6RADR, solvent: 303±27 pmol/mg protein; DNIG (3.3 mol/l): 1,067±174 pmol/mg protein; F4-6P, solvent: 948±110 pmol/mg protein;n=8–9, SEM), the amount of DNR tightly bound to the acid precipitate pellet obtained from F4-6RADR (i.e., protein, DNA, RNA) increased 3.9-times to the levels observed in sensitive F4-6 cells. The main pyridine metabolite of DNIG displayed similar activity. Concentration-response analysis revealed that DNIG and R,S-verapamil (VER) induced 100% reversal of the DNR accumulation shortage associated with the MDR phenotype but DNIG was 8 times more potent than VER (50% inhibitory concentration (IC₅₀), 0.73 vs 5.4 mol/l). In keeping with the accumulation assay, DNIG was about 10 times more potent than VER in sensitizing F4-6RADR cells to the cytostatic and cytotoxic effects of DNR in proliferation assays. In conclusion, DNIG is a potent in vitro modulator, improving (a) the accumulation of anthracycline-like cytostatics, (B) drug access to cellular binding sites, and (c) the cytostatic action of DNR in F4-6RADR leukemia cells of the MDR phenotype.Abbreviations DOX doxorubicin - CSA cyclosporin A - DMSO dimethylsulfoxide - DNIG dexniguldipine-HCl - DNR daunorubicin - MDR multidrug resistance - MITO mitoxantrone - pgp170 permease glycoprotein 170 - VER R.S.-verapamil Dexniguldipine-HCl is the proposed INN for compound B859-35, the R-enantiomer of niguldipine. Segments of this work have been reported in the abstract form