Cellular manifestations of human papillomavirus infection in laryngeal tissues

BACKGROUND AND OBJECTIVES: Although epidemiologic studies have suggested human papillomavirus (HPV) to be an etiological agent in laryngeal carcinogenesis, little is known on the cellular manifestations of HPV infection in these tumors. In this study, we investigated the frequency of HPV infection in various neoplastic and non-neoplastic laryngeal tissue and its association with expression of the proliferating cell nuclear antigen (PCNA) and the tumor suppressor protein p53. METHODS: Tissues were analyzed by polymerase chain reaction (PCR) for the presence of HPV and by immunocytochemistry for the expression of p53 and PCNA. RESULTS: None of the six normal laryngeal tissues showed the presence of HPV. Thirteen out of the 16 papillomas were positive for HPV, while 15 out of the 44 invasive cancers were HPV positive. PCNA expression increased as the lesion progressed through increasing histological abnormality (r = 0.64400, P = 0.00000). The correlation between the type of laryngeal neoplasm and p53 accumulation was significant (r = 0.54839, P = 0.00000). Significant correlation was also evident between presence of HPV and p53 accumulation (r = 0.34259, P = 0.00424) and PCNA expression (r = 0.036024, P = 0.00266) indicating that HPV positive tumors showed significant p53 accumulation and increased proliferation.There was also correlation between p53 and PCNA expression (r = 0.67475, P = 0.00000) indicating that in all tumors with p53 accumulation, there was a corresponding increase in PCNA expression. CONCLUSIONS: The results suggests that changes in p53 and PCNA expression may be associated with HPV infection, and could play a role in laryngeal carcinogenesis.     

Increased presence of white matter hyperintensities in adolescent patients with bipolar disorder

Several reports have noted an increase in white matter hyperintensities (WMH) on MRI scans of adult patients with bipolar disorder. We investigated whether this increase was also evident in a group of adolescent patients with bipolar disorder. The sample consisted of 15 bipolar patients, 19 patients with schizophrenia and 16 healthy comparison subjects. All subjects were adolescents. WMH were blindly rated on T2-weighted and PD-weighted MRI scans using our own scale with documented inter-rater reliability. WMH were present in 10 of 15 bipolar patients (67%), seven of 19 patients with schizophrenia (37%) and five of 16 comparison subjects (31%). The bipolar adolescent group had a statistically significant increased presence of WMH compared both with healthy comparison subjects and the schizophrenic group. The association between WMH and bipolar disorder appears to extend to the adolescent years.     

Preparation and evaluation of 90 Y skin patches for therapy of superficial tumours in mice

90Y, a beta emitting radionuclide, was immobilized in a bandage patch for possible application for the therapy of superficial maladies such as tumours and skin cancers. The aim was to prepare a radiation source that could deliver uniform dose within a short duration and avoid the inconveniences faced with the gamma sources used in teletherapy and brachytherapy. 90Y-ferric hydroxide macroaggregates were prepared, filtered and immobilized between two layers of gauze. When placed in saline, no radioactivity leached for 3 days, proving its safety for external application. Fibrosarcoma was induced in mice for checking the efficacy of 90Y patches. 90Y patches of various activities were prepared and applied on the tumours. The effect of time gap between inception and treatment of tumour, dose delivered and multiple application in fractionated doses was studied. In all the cases, tumour growth in the treated animals was considerably reduced in comparison with controls. It was concluded from the experiments that treatment should be started at the earliest stage possible, i.e. when the tumour is palpable. Delivery of dose from radioactive patches of approximately 90-100 MBq each, thrice at weekly intervals proved to be more effective for regression of tumour growth.     

Impact of a medically supervised safer injecting facility on drug dealing and other drug-related crime

North America's first medically supervised safer injecting facility (SIF) recently opened in Vancouver, Canada. One of the concerns prior to the SIF's opening was that the facility might lead to a migration of drug activity and an increase in drug-related crime. Therefore, we examined crime rates in the neighborhood where the SIF is located in the year before versus the year after the SIF opened. No increases were seen with respect to drug trafficking (124 vs. 116) or assaults/robbery (174 vs. 180), although a decline in vehicle break-ins/vehicle theft was observed (302 vs. 227). The SIF was not associated with increased drug trafficking or crimes commonly linked to drug use.     

HIV seroprevalence among participants at a Supervised Injection Facility in Vancouver, Canada: implications for prevention, care and treatment

North America's first government sanctioned medically supervised injection facility (SIF) was opened during September 2003 in Vancouver, Canada. This was in response to a large open public drug scene, high rates of HIV and hepatitis C transmission, fatal drug overdoses, and poor health outcomes among the city's injection drug users. Between December 2003 and April 2005, a representative sample of 1,035 SIF participants were enrolled in a prospective cohort that required completing an interviewer-administered questionnaire and providing a blood sample for HIV testing. HIV infection was detected in 170/1007 (17%) participants and was associated with Aboriginal ethnicity (adjusted Odds Ratio [aOR], 2.70, 95% Confidence Interval [95% CI], 1.84–3.97), a history of borrowing used needles/syringes (aOR, 2.0, 95% CI, 1.37–2.93), previous incarceration (aOR, 1.87, 95% CI, 1.11–3.14), and daily injection cocaine use (aOR, 1.42, 95% CI, 1.00–2.03). The SIF has attracted a large number of marginalized injection drug users and presents an excellent opportunity to enhance HIV prevention through education, the provision of sterile injecting equipment, and a supervised environment to self-inject. In addition, the SIF is an important point of contact for HIV positive individuals who may not be participating in HIV care and treatment.     

曲安奈德辅助玻璃体切割术的应用

目的研究曲安奈德（TA）辅助玻璃体切割手术在临床的应用价值。方法28例（29只眼）于2004年1月～2004年12月行玻璃体切割术，术中注入已过滤的TA悬浮液0．1ml（40mg／m1），以帮助辨认玻璃体后皮质、视网膜前增殖膜、黄斑前膜、内界膜，9例硅油填充，7例C3FR（15％）填充。手术后17例随访6个月以上，11例随访3至4个月。结果所有的病例，经TA注入后，可明显的改善玻璃体后皮质、视网膜前膜、内界膜的辨认情况。糖尿病视网膜病变术后视力提高占61．5％，伴PVR的视网膜脱离术后视力提高占61．3％，黄斑裂孔4例中3例术后视力提高，4例黄斑前膜术后视力均有提高。所有28例均没有出现高眼压。8例伴PVR的视网膜脱离中6例（占75％）视网膜复位，4例黄斑裂孔均关闭，2例糖尿病黄斑水肿手术后明显减轻。结论经过滤的TA可作为玻璃体切割手术中较好的辅助工具，TA悬浮液是呈白色胶样，可粘附于玻璃体皮质、视网膜前膜或内界膜，帮助分辨玻璃体后皮质、视网膜前膜、内界膜，提高手术效率。没有发现与TA有关的副作用。     

Plasmodium falciparum malaria in Laos: chloroquine treatment outcome and predictive value of molecular markers

A 28-day treatment trial was undertaken, to determine the efficacy of chloroquine in Laos and to assess the predictive value of molecular markers (cg2, pfmdr1, and pfcrt) that were previously linked to chloroquine resistance. In total, 522 febrile patients were screened for falciparum malaria by rapid diagnostic assays. Of 81 patients (15.5% prevalence) who were positive by the assays and microscopy, 48 were eligible to participate in the 28-day trial. Nine patients defaulted. Chloroquine cured 54% (95% confidence interval, 45.8-61.8) of falciparum-infected patients. Of 18 (46%) patients with treatment failure, 13 (72%) experienced high-grade resistance. Polymorphisms in cg2 and the N86Y mutation in PfMDR1 were not predictive of treatment outcome. A mutation in PfCRT (K76T) was perfectly associated with in vivo chloroquine resistance. However, K76T was also present in in vivo-sensitive isolates, which suggests that the presence of this mutation was necessary, but not sufficient, to predict in vivo outcome in this cohort.     

Tc-99m and Re-186 complexes of tetraphosphonate ligands and their biodistribution pattern in animal models

The syntheses of four alpha-aminomethyl phosphonates and their complexation studies with (99m)Tc and (186/188)Re are reported. Complexation conditions were standardized to give maximum yields, which ranged from 90-97%. The yields of complexation were estimated by paper chromatography. The (99m)Tc complexes were stable for more than 4 h, while the (186/188)Re complexes were stable for 3-8 days when stored at 4 degrees C. Biodistribution of these complexes in Wistar rats were carried out, and the uptake in bone and other soft tissue are detailed. Bone uptake of the (99m)Tc complexes varied from 40-60% at 30 min postinjection depending on the ligands. The uptake in soft tissue was minimum with all the complexes. A comparison of the biodistribution studies of the (99m)Tc complexes with that of the well-established radiopharmaceutical (99m)Tc-MDP was carried out for the purpose of evaluating the efficacy of the radiopharmaceutical preparation with the complexes of these ligands. The bone uptake of the (186/188)Re complexes varied from 19-28% corresponding to 1.6-3% per g at 3 h postinjection. The residual activity in both (99m)Tc and (186/188)Re complexes showed renal clearance.     

186Re-1,4,8,11-tetraaza cyclotetradecyl-1,4,8,11-tetramethylene phosphonic acid: a novel agent for possible use in metastatic bone-pain palliation

In connection with our work on the development of 186Re-tetra-phosphonates with optimum properties for use in bone pain palliation, a novel cyclic tetraphosphonate derivative, has been synthesized, complexed with 186Re and evaluated with promising results. The ligand, which consists of a cyclic array of tetra-aminomethylphosphonate groups, was synthesized using orthophosphorus acid, 1,4,8,11-tetraazacyclotetradecane and formaldehyde. The labeling conditions with 186Re have been standardized under varying reaction conditions to give maximum yield. In a reaction volume of 1 mL, maximum complexation yield of 98% was observed at pH 2 using 0.1 mg Re (37-370 MBq) for a ligand concentration at 9 x 10(-2) M/L, under heating at 100 degrees C for 30 min with 2 mg of stannous chloride. The complex was found to be stable for 6 days with RC purity remaining approximately 97%. The complex was characterized by paper chromatography in saline and acetone, wherein the R(f) exhibited were 0.9 and 0, respectively. Biodistribution studies of the complex were performed in male Wistar rats. Activity in femur which was observed to be 1.8%/g (equivalent to about 23% of the injected activity in skeleton) at 3 h post injection remained almost constant up to 48 h. Minimum activity was observed in blood and other soft tissues. The complex showed major renal clearance. Scintigraphic images in rabbits after injecting 70-100 MBq of 186Re-CTMP and using a dual head gamma camera were observed to be superior to 186Re-HEDP, prepared by a procedure standardized by us. Insignificant activity was observed in other vital organs. The results suggest the suitability of the complex for further evaluation in higher animals for bone pain palliation.