Primary cutaneous mucoepidermoid carcinoma: report of a case

Primary mucoepidermoid carcinomas of the skin are extremely rare tumors. We describe a primary cutaneous mucoepidermoid carcinoma arising in the right ear (posterior mid helix) of a 66-year-old white man. The tumor was 0.6 cm in diameter, ulcerated and nonencapsulated. No other tumors were found in the patient. Histologically the tumor showed the characteristics of a "low grade" mucoepidermoid carcinoma, consisting of lobules of polygonal cells with vesicular nuclei. In the center of the lobules were large vacuolated cells (goblet cells). Transitions between the two cell populations were present throughout the tumor. An epidermal attachment of the tumor, as well as epidermal dysplasia, predominantly at the acrosyringium was present, consistent with the theory of sweat duct histogenesis of these tumors. Immunoperoxidase staining showed positivity for epithelial membrane antigen, keratin and carcinoembryonic antigen. The latter was predominantly positive in the goblet cells. Cutaneous metastasis of mucoepidermoid carcinomas with epidermal attachment has been reported. Our case showed only ear involvement and follow-up at 8 months has revealed no evidence of recurrence. These findings are consistent with the diagnosis of primary cutaneous mucoepidermoid carcinoma.     

The ultrastructure of the extracellular phase of bone as observed in frozen thin sections

Summary The fine structure of the extracellular phase of avian medullary bone and embryonic chick femur was examined in thin sections prepared by ultracryotomy and ultramicroincineration. Since contact with solutions was completely avoided, little or no loss or dislocation of mineral constituents could occur. Amorphous bone mineral (ABM) was present in two forms: as 15–30 nm spheres and as a structure-free haze. Removal of all organic material by low temperature ashing left the ABM intact. Crystals were usually associated with the ABM. In newly ossifying regions clusters or nodules of randomly oriented crystals and ABM appeared to coalesce when they reached approximately 1 m in diameter. In highly calcified regions crystals appeared to be oriented along collagen fibers. ABM did not appear to be associated with collagen. Unmineralized collagen was visible in osteoid after staining with dry OsO₄ vapor and it appeared to be diverted around nodules. Structures which resembled matrix vesicles were present. Selected area electron diffraction patterns indicated the presence of hydroxyapatite.     

Scorpion alpha and alpha-like toxins differentially interact with sodium channels in mammalian CNS and periphery

Scorpion alpha-toxins from Leiurus quinquestriatus hebraeus, LqhII and LqhIII, are similarly toxic to mice when administered by a subcutaneous route, but in mouse brain LqhII is 25-fold more toxic. Examination of the two toxins effects in central nervous system (CNS), peripheral preparations and expressed sodium channels revealed the basis for their differential toxicity. In rat brain synaptosomes, LqhII binds with high affinity, whereas LqhIII competes only at high concentration for LqhII-binding sites in a voltage-dependent manner. LqhII strongly inhibits sodium current inactivation of brain rBII subtype expressed in HEK293 cells, whereas LqhIII is weakly active at 2 microM, suggesting that LqhIII affects sodium channel subtypes other than rBII in the brain. In the periphery, both toxins inhibit tetrodotoxin-sensitive sodium current inactivation in dorsal root ganglion neurons, and are strongly active directly on the muscle and on expressed muI channels. Only LqhII, however, induced repetitive end-plate potentials in mouse phrenic nerve-hemidiaphragm muscle preparation by direct effect on the motor nerve. Thus, rBII and sodium channel subtypes expressed in peripheral nervous system (PNS) serve as the main targets for LqhII but are mostly not sensitive to LqhIII. Toxicity of both toxins in periphery may be attributed to the direct effect on muscle. Our data elucidate, for the first time, how different toxins affect mammalian central and peripheral excitable cells, and reveal unexpected subtype specificity of toxins that interact with receptor site 3.     

Spray-dried redispersible oil-in-water emulsion to improve oral bioavailability of poorly soluble drugs.

A physically stabilized dry emulsion dosage form reforming the original emulsion after rehydration was developed by spray-drying a liquid oil-in-water emulsion containing maltodextrin as carrier and sodium caseinate as emulsifying agent. Several oil:water as well as maltodextrin:water ratios were tested, the homogenization and spray-drying processes and the reconstitution properties were investigated and an optimum formulation was selected for poorly soluble drug incorporation, having an identical oil:water and carrier:water ratio of 10% (w/w) and a load of solid material of 20% (w/w). Lipophilic 5-phenyl-1,2-dithiole-3-thione (5-PDTT) was selected as a model drug. 5-PDTT release from the solid state emulsion was studied using an in vitro two-phase stirred model and the relative bioavailability of 5-PDTT in the dry emulsion was obtained in the rabbit after oral administration of the reconstituted emulsion, compared to a 5-PDTT-sulfobutyl ether 7 beta-cyclodextrin complex in solution. Incorporation of 5-PDTT in the oil phase neither affects the surface morphology of the powder nor the reconstitution, the droplet size or the drug releasing properties and, furthermore, allows a 3-fold improvement of 5-PDTT relative bioavailability in rabbit after oral administration. These results indicate that dry emulsions may be considered as relevant dosage forms to improve bioavailability of poorly absorbable lipophilic drugs.     

Loss of RhoB expression in human lung cancer progression.

PURPOSE: RhoB is a low molecular weight GTPase belonging to the Ras protein superfamily. Whereas most Rho proteins have been shown to have a positive role in proliferation and malignant transformation, the specific role of RhoB appears more divergent. We reported previously that RhoB inhibits cell proliferation in various human cancer cells. Here, we studied the specific role played by RhoB in human lung cancer. EXPERIMENTAL DESIGN: We analyzed the expression of RhoB protein by immunostaining in human lung tissues ranging from normal to invasive carcinoma from different histological types in two large independent studies of, respectively, 94 and 45 samples. We then studied the cellular effect of RhoB overexpression in a model of lung cancer (A549, adenocarcinoma) and tumorigenicity in nude mice. RESULTS: We showed in both studies that RhoB protein was expressed in normal lung and decreased dramatically through lung cancer progression (P < 0.01). Interestingly, RhoB expression was lost in 96% of invasive tumors and reduced by 86% in poorly differentiated tumors compared with the nonneoplastic epithelium. Moreover, the loss of expression of RhoB correlated significantly with tumor stage and proliferative index, whereas no correlation was found between RhoB and p53 or Bcl-2 expression. We then showed that ectopic expression of RhoB in lung cancer cell line A549 suppressed cell proliferation, anchorage-independent growth, and xenograft tumor growth in nude mice. CONCLUSIONS: RhoB loss of expression occurs very frequently in lung carcinogenesis, reinforcing its putative tumor suppressive activity, and raising the value of its potential use in cancer therapy.     

Randomized parallel study of doxorubicin plus paclitaxel and doxorubicin plus cyclophosphamide as neoadjuvant treatment of patients with breast cancer.

PURPOSE: This randomized, noncomparative, parallel-group study was designed to evaluate the pathologic complete response (pCR) rate of combined doxorubicin plus paclitaxel (AP) and doxorubicin plus cyclophosphamide (AC) as neoadjuvant chemotherapy in patients with previously untreated breast cancer who were unsuitable for conservative surgery. PATIENTS AND METHODS: A total of 200 patients with T2-3, N0-1, M0 disease were randomly assigned in a 2:1 ratio to receive preoperative chemotherapy with either doxorubicin 60 mg/m(2) plus paclitaxel 200 mg/m(2) as a 3-hour infusion (AP) or doxorubicin 60 mg/m(2) plus cyclophosphamide 600 mg/m(2) (AC) every 3 weeks for 4 courses followed by surgery. RESULTS: A pCR (eradication of invasive carcinoma in tumor and in axillary lymph nodes) was found in 16% and 10% of patients in the AP and AC arms, respectively, by study center pathologists, and in 8% and 6% of patients, respectively, by independent pathologists. Patients with pCRs tended to have unifocal disease, tumors with negative hormonal receptor status, and less differentiation (Scarff, Bloom, and Richardson scale grade 3). Breast-conserving surgery was performed in 58% and 45% of patients in the AP and AC arms, respectively. An objective clinical response was achieved in 89% of patients in the AP arm and 70% in the AC arm. At a median follow-up of 31 months, disease-free survival (DFS) was higher in patients who reached pCR versus those without pCR (91% v 70%). CONCLUSION: The encouraging pathologic and clinical responses of patients with breast cancer after neoadjuvant chemotherapy with doxorubicin plus paclitaxel warrant additional investigation of paclitaxel in the neoadjuvant setting of breast cancer management.     

Epidemiology of transmissible diseases after elimination

Elimination of an infectious disease is often understood to mean the total absence of cases in a population. This situation can occur only if the entire population is immune as a result of either natural disease or vaccination. However, this costly and unrealistic scenario is not necessary to ensure elimination, more appropriately defined as a situation in which sustained transmission cannot occur and secondary spread from importations of disease will end naturally, without intervention. The authors describe the size and duration of outbreaks caused by imported infections after indigenous transmission has been eliminated. They show that the status of the elimination process can be monitored by assessing the proportion of cases imported and the distribution of outbreak sizes. Measles in Canada, the United States, and the United Kingdom provides a good example of the relevance of these criteria. Surveillance of the size and duration of these outbreaks enables maintenance of elimination to be monitored.     

Domestic violence in Australia: definition, prevalence and nature of presentation in clinical practice

Domestic violence is a complex pattern of behaviours that may include, in addition to physical acts of violence, sexual abuse and emotional abuse. Women experience domestic violence at far greater rates than men do, and women and children often live in fear as a result of the abuse that is used by men to maintain control over their partners. Domestic violence is a major public health problem and is very common in women attending clinical practice. Women present most commonly with a range of chronic symptoms to unsuspecting general practitioners, emergency department doctors or medical specialists. Women who have experienced partner abuse want to be asked about it and are more likely to disclose if asked in an empathic, non-judgemental way. Doctors can make a difference.     

Posterior Laryngeal Clefts: Preliminary Report of a New Surgical Procedure Using Tibial Periosteum As an Interposition Graft

Objective: To present the preliminary results of a new surgical procedure for posterior laryngeal cleft repair. Design: Retrospective study in an academic tertiary care center. Method: The study included three male patients (age at surgery, 2, 13, and 14 mo). One presented with severe aspiration and cyanotic attacks, the two others with aspiration and recurrent chest infections. The types of laryngeal clefts included complete cleft of the cricoid with varying degrees of tracheal involvement but not further than the first six tracheal rings. Associated malformations included one VATER syndrome, one esophageal atresia, and one tracheoesophageal fistula. Surgery was performed under general anesthesia with nasotracheaI intubation. A vertical anterior laryngofissure was performed. The mucosal margins of the clefts were incised and then repaired in two layers with polyglactin sutures. The original feature of this procedure was the interposition of a small piece of tibial periosteum between the two layers. This fascia graft is known to be strong and resistant in cleft palate surgery. Main Outcome Measure: Clinical and endoscopic follow-up was used for evaluation of results. Results: The three patients had successful laryngeal repair at a mean follow-up of 6 months (range, 4-14 mo). Conclusion: The anterior laryngofissure provides a good surgical access to the cleft. The interposition of tibial periosteum allows durability of the cleft repair. A longer follow-up is needed to confirm these preliminary results. A computed tomography scan study and a study on the rabbit are planned in order to evaluate the outcome of these periosteal grafts.