FRA3B extends over a broad region and contains a spontaneous HPV16 integration site: direct evidence for the coincidence of viral integration sites and fragile sites

The common fragile site at 3p14.2 (FRA3B) is the most sensitive site on normal human chromosomes for the formation of gaps and breaks when DNA replication is perturbed by aphidicolin or folate stress. Although rare fragile sites are known to arise through the expansion of CCG repeats, the mechanism responsible for common fragile sites is unknown. Beyond being a basic component of chromosome structure, no biological effects of common fragile sites have been convincingly shown, although suggestions have been made that breakage and recombination at these sites may sometimes be mechanistically involved in deletions observed in many tumors and in constitutional deletions. In an observation related to the high rate of recombination at fragile sites, a number of studies have shown a statistical association between the integration of transforming DNA viruses and chromosomal fragile sites. Using FISH analysis we recently identified a 1.3 Mb YAC spanning both FRA3B and the t(3;8) translocation associated with hereditary RCC. Here we report the further localization of FRA3B within this YAC. Using lambda subclones of the YAC as FISH probes, gaps and breaks were found to occur over a broad region of at least 50 kb. Neither CCG nor CAG repeats were found in this region suggesting a different mechanism for fragility than seen with rare fragile sites. We further show that an area of frequent gaps and breaks within FRA3B, defined by a lambda contig, coincides with a previously characterized site of HPV16 integration in a primary cervical carcinoma. The HPV16 integration event gave rise to a short chromosomal deletion limited to the local FRA3B region within 3p14.2. Interestingly, 3p14.2 lies within the smallest commonly deleted region of 3p in cervical cancers, which are often HPV16 associated. To our knowledge this is the first molecular characterization of an in vivo viral integration event within a confirmed fragile site region, supporting previous cytogenetic observations linking viral integration sites and fragile sites.      

Circadian preference and cognitive functioning among rehabilitation inpatients

The influence of circadian preference was examined among 56 morning-oriented rehabilitation inpatients with cognitive (n=28) and noncognitive (n=28) impairments. Each individual was tested twice: morning (preferred time) and evening (nonpreferred time); sessions and test batteries were counterbalanced to control for practice effects. Standard measures assessed attention, language, memory, visuospatial, and executive functions. Persons with cognitive impairment showed disproportionate vulnerability to the effects of circadian preference and time of testing, performing more poorly at nonpreferred than preferred times. Substantial effects (eta2 .12 to .48) were found on tests of executive functioning and tasks incorporating similar higher-order demands (e/g/. complex figure copy). Results are supported by tympanic temperature changes during a vigilance task, and index of cerebral blood flow in response to cognitive challenge. Cognitive reserve theory is suggested as an explanation for the differential effects. These findings may have implications for inpatient therapeutic interventions and discharge planning.     

Blindness and low vision in a tertiary ophthalmologic center in Thailand: the importance of cytomegalovirus retinitis

PURPOSE: To determine the causes of blindness and low vision in patients consulting a tertiary ophthalmologic center in northern Thailand. METHODS: The study population included 2,951 new consecutive patients from the Department of Ophthalmology at University Hospital in Chiang-Mai, Thailand. Main outcome measures were blindness and low vision, which were defined according to World Health Organization criteria. RESULTS: Of 2,951 patients, 369 (12.5%) had blindness and/or low vision (bilateral blindness in 73, unilateral blindness in 129, bilateral low vision in 77, and unilateral low vision in 90). Of the etiological causes of visual loss, age-related ocular disease was the most frequent (128 patients [35%]) followed by infections (66 patients [18%]) and trauma (43 patients [12%]). Although infections and trauma were the predominant causes of blindness, age-related disorders were frequently found in patients with low vision. Of anatomical sites, the lens (134 patients [36%]) was the main location of visual loss, closely followed by disorders of the retina and/or uvea (126 patients [34%]). Blindness and low vision were considered avoidable in 70% of cases. Of 73 patients with bilateral blindness, 14 had active cytomegalovirus retinitis, accounting for 19% of all patients with bilateral blindness. CONCLUSION: The most common causes of blindness and low vision in a tertiary center in northern Thailand were age-related ocular disorders and infections, which were predominantly cases of cytomegalovirus retinitis in human immunodeficiency virus-infected patients.     

Self discipline and obesity in Bangkok school children

Background  

Childhood obesity has become an important public health problem in Thailand. This study aimed to determine the relationship between self discipline and obesity in Bangkok school children.     

Infectious causes of posterior uveitis and panuveitis in Thailand

Purpose  

To determine the infectious causes of posterior uveitis (PU) and panuveitis (panU) in Thailand.     

Self discipline and obesity in Bangkok school children

Background

In 2004, the Ministry of Health issued the policy of decentralising microscopy services (MCs) to one third of all township hospitals in China. The study was conducted in Gansu Province, a poor western one in China. Ganzhou was one county in Gansu Province. Ganzhou County was identified as a unique case of further decentralisation of tuberculosis (TB) treatment services in township hospitals. The study evaluated the impact of the MC policy on providers and patients in Gansu Province. The second objective was to assess the unique case of Ganzhou County compared with other counties in the province.

Methods

Both quantitative and qualitative methods were used. All 523 MCs in the province completed an institutional survey regarding their performance. Four counties were selected for in-depth investigation, where 169 TB suspects were randomly selected from the MC and county TB dispensary registers for questionnaire surveys. Informant interviews were conducted with 38 health staff at the township and county levels in the four counties.

Results

Gansu established MCs in 39% of its township hospitals. From January 2006 to June 2007, 8% of MCs identified more than 10 TB sputum smear positive patients while 54% did not find any. MCs identified 1546 TB sputum smear positive patients, accounting for 9% of the total in the province. The throughputs of MCs in Ganzhou County were eight times of those in other counties. Interviews identified several barriers to implement the MC policy, such as inadequate health financing, low laboratory capacity, lack of human resources, poor treatment and management capacities, and lack of supervisions from county TB dispensaries.

Conclusion

Microscopy centre throughputs were generally low in Gansu Province, and the contribution of MCs to TB case detection was insignificant taking account the number of MCs established. As a unique case of full decentralisation of TB service, Ganzhou County presented better results. However, standards and quality of TB care needed to be improved. The MC policy needs to be reviewed in light of evidence from this study.     

Association between HLA‐B*1502 and carbamazepine‐induced severe cutaneous adverse drug reactions in a Thai population

Carbamazepine (CBZ) has been reported as the most common culprit drug for Stevens‐Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) in several Asian countries including Thailand. A strong association between HLA‐B*1502 and CBZ‐induced SJS/TEN has been reported in Han Chinese but not in Caucasian and Japanese populations. A case–control study was conducted to determine whether HLA‐B*1502 is a valid pharmacogenetic test for SJS/TEN caused by CBZ in a Thai population. Among 42 CBZ‐induced patients with SJS/TEN, 37 (88.10%) patients carried the HLA‐B*1502 while only 5 (11.90%) of the CBZ‐tolerant controls had this allele. The risk of CBZ‐induced SJS/TEN was significantly higher in the patients with HLA‐B*1502, with an odds ratio (OR) of 54.76 [95% confidence interval (CI) 14.62–205.13, p = 2.89 × 10^?12]. The sensitivity and specificity of HLA‐B*1502 for prediction of CBZ‐induced SJS/TEN were 88.10%. By assuming a 0.27% as a prevalence rate of CBZ‐induced SJS/TEN in a Thai population, the positive predictive value (PPV) and negative predictive value (NPV) of the HLA‐B*1502 were 1.92% and 99.96%. Results from this study suggest that HLA‐B*1502 may be a useful pharmacogenetic test for screening Thai individuals who may be at risk for CBZ‐induced SJS and TEN.     

Purtscher-like Retinopathy Associated with Systemic Lupus Erythematosus

Purpose: To report on clinical manifestations of Purtscher-like retinopathy (PLR) associated with systemic lupus erythematosus (SLE) and visual outcomes.

Methods: We performed a retrospective cohort study of 11 patients (21 affected eyes) with PLR in SLE.

Results: All patients were treated with systemic corticosteroids?±?immunosuppressive agents. Ocular therapy included intravitreal injections with bevacizumab in 18/21 eyes and posterior sub-Tenon injections with triamcinolone acetonide 13/21 eyes. Panretinal photocoagulation (PRP) was performed in 19/21 eyes and pars plana vitrectomy was required in 5/21 eyes. Visual improvement was found at follow-up of 3 and 6 months (p?=?0.05). Poor visual outcome was associated with presence of neovascularizations at onset (p?=?0.009), development of vitreous hemorrhage during PRP (p?=?0.015), and active status of SLE after onset of PLR (p?=?0.029).

Conclusions: PLR might manifest as a devastating complication of SLE. We recommend treating any systemic activity of SLE and starting an early ocular treatment.