Integration of human papillomavirus type 16 into cellular DNA of cervical carcinoma: preferential deletion of the E2 gene and invariable retention of the long control region and the E6/E7 open reading frames

The integration patterns of human papillomavirus (HPV) type 16 in the cellular DNA of six cervical carcinoma samples were analyzed by the Southern blot procedure. None of the HPV integrants retained the entire viral genome. Double HPV integration was found in one case while all other cases were single integrants. In some samples, internal deletion and selective amplification of the viral sequences were observed. On integration, the E2 open reading frame (ORF) was invariably lost but the E6/E7 ORFs and the long control region of the HPV-16 genome were retained in all seven integrations analyzed and may play a role in cellular transformation and/or maintenance of the transformed phenotype.     

Dynamic assessment of the electrocardiographic QT interval during citrate infusion in healthy volunteers.

OBJECTIVE--To investigate changes in the electrocardiographic QT interval during rapidly induced, sustained hypocalcaemia in healthy volunteers. DESIGN--Serial rate corrected QT measurements were made during and after a variable rate trisodium citrate infusion designed to "clamp" the whole blood ionised calcium concentration 0.20 mmol/l below baseline for 120 min. SUBJECTS--12 healthy teetotallers aged 19- 36 years who were not receiving medication known to influence calcium homoeostasis. MAIN OUTCOME MEASURES--Whole blood ionised calcium concentration and QaTc intervals (onset of the Q wave to T wave apex divided by the square root of the RR interval). RESULTS--Mean (SD) ionised calcium concentration decreased from 1.18 (0.03) mmol/l preinfusion to values close to target (0.98 mmol/l) between 10 and 120 min. The QaTc interval lengthened from a baseline of 0.309 (0.021) to a maximum 0.343 (0.024) s0.5 at 10 min before returning to a stable level from 15 to 120 min (0.334 (0.023) and 0.330 (0.023) s0.5 respectively). The change from baseline of both variables expressed as a ratio (delta QaTc/ delta [Ca2+]) was greater during rapid induction of hypocalcaemia (at 5 and 10 min) than at other times during and after the infusion (P < 0.02). CONCLUSIONS--The disproportionate prolongation of QaTc interval during prompt induction of hypocalcaemia suggests rate dependency which can be represented by a hysteresis relation between (ionised calcium, QaTc) coordinates. This finding may have clinical implications.     

Burden of caregiving in mild to moderate dementia: an Asian experience

This survey sought to determine (a) the prevalence of carer stress in patients with mild to moderate dementia, (b) whether caregiver burden was already associated with plans to institutionalize patients, and (c) which patient-related and caregiver-related variables best predicted caregiver burden. The principal caregivers of 93 Asian patients with mild to moderate dementia attending an outpatient cognitive assessment clinic were interviewed via a structured questionnaire that focused upon (a) patient-related variables such as their behavioral and functional abnormalities; and (b) caregiver-related variables such as whether they were having problems looking after the patients, the duration of their caregiving, their associated feelings of anger and/or depression, and their financial status as well as intentions to institutionalize patients. Forty-nine percent of caregivers reported problems in looking after the patients, and their perception of difficulties was significantly associated with institutionalization plans for the patients. Logistic regression analysis using a forward variable selection procedure showed two of the patients' behavioral abnormalities (repetition, agitation) and one of their functional impairments (urinary incontinence) as well as the carers' depressed feelings to be predictive of the carers' problematic status, explaining 40% of the variance. It is important that even in the early stages of dementia, the medical assessment also evaluate behavioral, functional, and social dimensions of the illness, so that appropriate interventions can be implemented to reduce caregiving burden and delay institutionalization.     

Exposure of expanded polytetrafluoroethylene-wrapped hydroxyapatite orbital implant: a report of two patients

PURPOSE: Hydroxyapatite (HA) spheres used to replace volume after an enucleation are often wrapped with autologous tissue before orbital implantation. Man-made materials are less expensive and pose no risk for viral transmission. The use of expanded polytetrafluoroethylene (ePTFE) to wrap HA spheres was evaluated. METHODS: The medical records of 2 consecutive patients who underwent uncomplicated implantation of an HA sphere wrapped in ePTFE were reviewed. RESULTS: An unusual reaction to the ePTFE material that was nonresponsive to topical or systemic antibiotic therapy developed in these 2 patients. Eventual wound erosion and bacterial infection of the implant necessitated its removal. CONCLUSIONS: Although well tolerated in other surgeries, ePTFE, when used to wrap HA spheres and placed into the orbit, may cause persistent conjunctival discharge, pyogenic granuloma formation, and eventual wound erosion. Therefore, the use of this material to wrap HA spheres is not recommended.     

Semiinvasive pulmonary aspergillosis: CT and pathologic findings in six patients

OBJECTIVE: We describe the chest CT and pathologic findings of semiinvasive pulmonary aspergillosis in six patients. CONCLUSION: Semiinvasive pulmonary aspergillosis should be considered in the mildly immunocompromised patient with CT findings that reveal persistent parenchymal abnormalities. Patterns include consolidation and mass.     

HLA‐A SNPs and amino acid variants are associated with nasopharyngeal carcinoma in Malaysian Chinese

Nasopharyngeal carcinoma (NPC) arises from the mucosal epithelium of the nasopharynx and is constantly associated with Epstein–Barr virus type 1 (EBV‐1) infection. We carried out a genome‐wide association study (GWAS) of 575,247 autosomal SNPs in 184 NPC patients and 236 healthy controls of Malaysian Chinese ethnicity. Potential association signals were replicated in a separate cohort of 260 NPC patients and 245 healthy controls. We confirmed the association of HLA‐A to NPC with the strongest signal detected in rs3869062 (p = 1.73 × 10^?9). HLA‐A fine mapping revealed associations in the amino acid variants as well as its corresponding SNPs in the antigen peptide binding groove (p_{HLA‐A‐aa‐site‐99} = 3.79 × 10^?8, p_rs1136697 = 3.79 × 10^?8) and T‐cell receptor binding site (p_{HLA‐A‐aa‐site‐145} = 1.41 × 10^?4, p_rs1059520 = 1.41 × 10^?4) of the HLA‐A. We also detected strong association signals in the 5′‐UTR region with predicted active promoter states (p_rs41545520 = 7.91 × 10^?8). SNP rs41545520 is a potential binding site for repressor ATF3, with increased binding affinity for rs41545520‐G correlated with reduced HLA‐A expression. Multivariate logistic regression diminished the effects of HLA‐A amino acid variants and SNPs, indicating a correlation with the effects of HLA‐A*11:01, and to a lesser extent HLA‐A*02:07. We report the strong genetic influence of HLA‐A on NPC susceptibility in the Malaysian Chinese.     

A case study of pyelolymphatic backflow demonstrated on CT

Pyelolymphatic backflow is a rare type of pyelolymphatic fistula that occurs in cases of urinary obstruction. This phenomenon may help to decompress an acutely obstructed kidney, and therefore, alleviate renal function from deteriorating. Pyelolymphatic backflow has specific imaging characteristics best shown on CT urography. Our case study aims to improve the understanding and diagnosis of pyelolymphatic backflow by presenting a case of pyelolymphatic backflow seen on CT urography, including discussions on the pathophysiology, clinical relevance and management of this phenomenon. Our case study demonstrates the opacification of landmark lymphatic structures including the retroperitoneal para-aortic lymphatic chain, cisterna chyli and thoracic duct, which have not been demonstrated previously.