Expression of mitotic checkpoint proteins BUB1B and MAD2L1 in salivary duct carcinomas

J Oral Pathol Med (2010) 39 : 349–355 Objective: Defects in the mitotic checkpoint lead to aneuploidy and might facilitate tumorigenesis. However, the ploidy status in salivary duct carcinoma (SDC) has been reported to play limited role in prediction of prognosis. Thus, we need more reliable markers to reflect the rapid tumor progression in SDCs. We aimed here to investigate the expression of mitotic checkpoint proteins benzimidazole 1 homolog beta (BUB1B) and mitosis arrest‐deficient 2 like 1 (MAD2L1) in SDCs and to determine their possible role as surrogate prognostic markers. Methods: We analyzed the clinical courses, pathologic findings and immunohistochemical profiles of mitotic checkpoint proteins (BUB1B and MAD2L1) in 27 pathologically confirmed SDCs. The expression status of BUB1B and MAD2L1 was compared with clinicopathologic factors and other molecular markers, such as TGF‐beta, c‐erb‐B2, androgen receptor, vascular endothelial growth factor, and epidermal growth factor receptor, for prognostic significance. Results: High BUB1B expression was detected in 25.9% of subjects, and high MAD2L1 expression was in 55.6% of subjects. However, survival analysis revealed that mitotic checkpoint expression did not have prognostic significance in SDCs, nor did the other studied markers. Rather, the clinical variable of N classification at diagnosis (in N+ status, hazard ratio 5.19, 95% CI 1.26–21.32 for disease‐free survival and hazard ratio 7.18, 95% CI 1.09–46.99 for overall survival) was strongly associated with survival and prognosis based on the Cox proportional hazard model. Conclusions: Mitotic checkpoint proteins appeared to play a limited role in predicting prognosis in SDCs. Further study is required to elucidate the exact role of mitotic checkpoint proteins in SDCs.     

A comparative study of biweekly disposable contact lenses: silicone hydrogel versus hydrogel

Background: Our aim was to compare the clinical performance of a biweekly (second generation) silicone hydrogel lens and a biweekly hydrogel lens worn for daily wear modality. Methods: We used a double‐masked study, in which non‐presbyopic, asymptomatic and adapted soft lens wearers were recruited. Subjects wore a silicone hydrogel lens in one eye and a hydrogel lens in the other (lens types and eyes were randomly assigned) for one month. Lenses were replaced every two weeks. Contact lens fitting, pre‐lens tear film thinning time, vision, corneal integrity and lens deposits were assessed before and every fortnight after delivery of new lenses. A questionnaire was used to compare the subjective performance of the two lens types. Results: Thirty of the 33 subjects completed the study. There were no significant differences in lens fitting (centration and movement), pre‐lens tear film thinning time, vision or corneal integrity between the two lens types. Statistically, there was no significant difference in lens deposits between the two lens types but silicone hydrogel lenses tended to have more Grade 3 to 4 lipid deposits than hydrogel lenses. Subjects found no significant differences between the two lens types in terms of vision and comfort. Preference for silicone hydrogel lenses increased from 33 at the first after‐care visit to 50 per cent at the second after‐care visit. Conclusion: This short‐term study demonstrates that the performance of silicone hydrogel and hydrogel lenses is comparable but the former tends to build up more lipid deposits than the latter. We did not find better performance in terms of ocular integrity of silicone hydrogel lenses compared to the hydrogel lenses, probably because the subjects were adapted asymptomatic contact lens wearers before commencing the study. Contact lens wearers having hypoxia‐related problems are likely to benefit from using silicone hydrogel lenses, as these lenses provide at least three times more oxygen than conventional hydrogel lenses.     

Incidence,mortality and survival patterns of prostate cancer among residents in Singapore from 1968 to 2002

Background  

From 1968 to 2002, Singapore experienced an almost four-fold increase in prostate cancer incidence. This paper examines the incidence, mortality and survival patterns for prostate cancer among all residents in Singapore from 1968 to 2002.     

Improving DNA vaccines targeting viral infection

DNA vaccination techniques have been recently under intensive investigation both preclinically and in human studies aimed at impacting viral infection. Collectively, DNA vaccines expressing viral antigens induce both antigen-specific humoral and cellular immune responses which in model systems are capable of impacting viral infection. However, in clinical settings the potency of this approach is still under investigation. Efficacy is improved in specific circumstances through the addition of immunomodulatory molecules including cytokines as plasmid cassettes or through modification of the numbers of specific CpG sequences present in the backbone. Furthermore, combined vaccination schemes have been an important research focus for generating enhanced immunogenicity against viral infections. The ultimate utility of these approaches to prevent viral infection will require more work. However, improvements in the potency and focus of DNA vaccines present us with new opportunities for both basic research into protective immunity as well as novel strategies for immune therapy and prophylaxis.     

Ten years' experience of antenatal mean corpuscular volume screening and prenatal diagnosis for thalassaemias in Hong Kong

OBJECTIVE: To determine the prevalence of thalassaemia carriers in Hong Kong. SUBJECTS AND METHODS: From 1988 to 1997, 25,834 (53.7%) of 48,089 mothers were screened for thalassaemias by mean corpuscular volume (MCV) at the first antenatal visit. RESULTS: In the screened population of 25,834, 2229 (8.6%) had MCV < or = 75 fl. Of these, 1121 (4.3%) were alpha-thal, 715 (2.8%) were beta-thal, 23 (0.1%) were alpha beta-thal, 57 (0.2%) were other haemoglobin variants, and 281 (1.1%) had either iron deficiency or uncertain causes. Out of 200 pregnancies at risk for homozygous alpha-thal-1 and 32 at risk for beta-thal major, 27 homozygous alpha-thal-1 and 7 beta-thal major were identified, compared favourably with the expected figures of 23 and 9. CONCLUSION: Antenatal screening for thalassaemias by MCV is simple, effective and reliable. Universal screening has a different impact as bone marrow or cord blood stem cell transplant provides cure for beta-thal major. At risk couples have, as an alternative to termination of pregnancy, the option of early detection and treatment for their affected newborns or fetuses.     

Survey of raw egg use by home caterers

Outbreaks of egg related salmonella infection continue to occur despite over ten years of national guidance on this subject. Fifty-four out of 70 registered home caterers in Cheshire responded to a telephone questionnaire, which revealed that a sixth prepared raw egg dishes containing shell eggs, none used pasteurised egg, and advice about storage of eggs and handwashing was not always followed. A postal questionnaire sent to 13 wholesalers and major supermarket chains showed that pasteurised egg was available in large packs from wholesalers but not from supermarkets. It is time to consider new approaches to reinforce advice about pasteurised egg use for raw egg dishes, storage, and measures to prevent cross contamination. These findings have implications for the training of home caterers and the general public.     

Relapsed and late-onset Nipah encephalitis

An outbreak of infection with the Nipah virus, a novel paramyxovirus, occurred among pig farmers between September 1998 and June 1999 in Malaysia, involving 265 patients with 105 fatalities. This is a follow-up study 24 months after the outbreak. Twelve survivors (7.5%) of acute encephalitis had recurrent neurological disease (relapsed encephalitis). Of those who initially had acute nonencephalitic or asymptomatic infection, 10 patients (3.4%) had late-onset encephalitis. The mean interval between the first neurological episode and the time of initial infection was 8.4 months. Three patients had a second neurological episode. The onset of the relapsed or late-onset encephalitis was usually acute. Common clinical features were fever, headache, seizures, and focal neurological signs. Four of the 22 relapsed and late-onset encephalitis patients (18%) died. Magnetic resonance imaging typically showed patchy areas of confluent cortical lesions. Serial single-photon emission computed tomography showed the evolution of focal hyperperfusion to hypoperfusion in the corresponding areas. Necropsy of 2 patients showed changes of focal encephalitis with positive immunolocalization for Nipah virus antigens but no evidence of perivenous demyelination. We concluded that a unique relapsing and remitting encephalitis or late-onset encephalitis may result as a complication of persistent Nipah virus infection in the central nervous system.     

Etoposide, ifosfamide and cisplatin (VIP) plus concurrent radiation therapy for previously untreated limited small cell lung cancer (SCLC): a Hoosier Oncology Group (HOG) phase II study

Results of a previous Hoosier Oncology Group (HOG) study revealed a small survival advantage for VIP versus etoposide and cisplatin (EP) for patients with extensive stage small cell lung cancer (SCLC). This phase II study evaluated VIP with concurrent thoracic radiotherapy in patients with limited stage SCLC. Eligible patients had a Karnofsky Performance Score > or = 50, no prior chemotherapy or radiotherapy, and adequate end organ function. Fifty-three patients were entered. Radiotherapy was given as a daily fraction of 1.8 Gy, five fractions per week for 5 weeks for a total dose of 45 Gy, beginning on day 1 of VIP. The first 13 patients received etoposide 75 mg/m(2), cisplatin 20 mg/m(2), and ifosfamide 1.2 g/m(2) on days 1-4 with Mesna every 3 weeks for four cycles unless the patient demonstrated disease progression or undue toxicity. Excessive toxicity was seen in the first 13 patients; therefore, VIP was modified by deleting the 4th day for all subsequent patients. The major toxicity in this trial was myelosuppression. Grade 3/4 anemia, granulocytopenia, and thrombocytopenia occurred in 38, 75, and 34% of patients, respectively. There were four treatment-related deaths [three patients (23%) on the 4-day regimen and one patient (2.5%) on the 3-day regimen]. Twenty-five patients (47.2%) achieved a CR and 11 patients (20.8%) had a PR for an overall response rate of 68%. Minimum follow up for all patients is 5 years. Overall, 46 of 53 patients have died. Median, 1, 2 and 5 year overall survival for the entire group is 15.1 months, 69.8, 35.9, and 13.2, respectively. The results of this phase II trial of VIP with concurrent early thoracic radiotherapy failed to demonstrate a superior response rate over other series utilizing EP. In addition, treatment-related morbidity and mortality appears to be unacceptably high with the VIP regimen.