Histological aspects of lesions of the cervix uteri correlated with different types of human papillomavirus

Cervical biopsies from 66 women presenting an abnormal smear, with HPV related features were studied and histologic features were correlated to the HPV type, as determined by molecular hybridisation studies. HPV DNA sequences were evidenced in 13 of 19 lesions corresponding to exophytic or flat condyloma (HPV type 16 in seven cases, HPV type 11 in four cases, as yet uncharacterized HPV types, HPV X, in two cases). Fourty biopsies were histologically interpreted as CIN, on the basis of atypical mitotic figures (AMF) and/or basal-parabasal cell atypia. HPV type 16 was evidenced in 20 cases (3 cases of double infection: HPV types 16 and 18, HPV types 16 and 33, HPV types 16 and X). In 10 other cases, HPV DNA sequences corresponding to HPV type 11 (one case), HPV 18 (one case) and HPV X (8 cases) were evidenced. In this study, potentially oncogenic HPV types (HPV 16, HPV 18, HPV 33) have been found only in CIN lesions defined on the presence of AMFs and/or basal-parabasal cells atypia. These histologic criteria seem to allow a distinction between low and high risk cervical lesions.     

Pharmacokinetic and pharmacodynamic drug interactions between digoxin and macrogol 4000, a laxative polymer, in healthy volunteers

AIMS: The aim of this study was to examine the bioequivalence between a single oral dose of digoxin administered alone and with a coadministration of macrogol 4000 (a laxative polymer) in 18 healthy volunteers. METHODS: This was an open, randomised, two-way cross-over study, with a single dose oral administration of 0.5 mg digoxin administered alone or in combination with macrogol 4000, 20 g day-1 during 8 days. Pharmacokinetics of digoxin, heart rate and PR ECG interval at rest were assessed. RESULTS: Macrogol 4000 coadministration was associated with a 30% decrease of digoxin AUC and a 40% decrease in its Cmax (P<0.05). Digoxin tmax and t1/2,z were not significantly altered. Heart rate and PR interval did not differ during the two therapeutic sequences, digoxin alone and digoxin in combination. CONCLUSIONS: Macrogol 4000 coadministration interacts with single-dose digoxin pharmacokinetics. This is most likely due to a reduction of the intestinal absorption of digoxin. However, there was no consequence of this interaction on heart rate and AV conduction.     

Alternative catecholamine pathways after tyrosine hydroxylase inhibition in malignant pheochromocytoma

A suppression of norepinephrine, epinephrine, and its metabolites in malignant pheochromocytoma by metyrosine was associated with an increase in tyrosine, plasma DOPA, and sulfate esters of DOPA and dopamine, followed, with continuing metyrosine administration, by a further rise of both DOPA sulfate and dopamine sulfate. Urinary dopamine progressively increased in the course of metyrosine treatment, and this, along with the increase of the dopamine metabolite, dihydroxyphenylethanol, and plasma dopamine sulfate, occurred in the absence of any change in plasma dopamine. The octopamine metabolite para-hydroxyphenylglycol, which was initially elevated at least 10-fold, also increased after metyrosine treatment. The unexpected increase of DOPA (progressively more converted toward DOPA sulfate) in the presence of tyrosine hydroxylase inhibition and increase in tyrosine may result from channeling the excess tyrosine toward DOPA and melanin through tyrosinase. Increases in plasma dopamine sulfate and urinary dopamine suggest that dopamine sulfate may be generated via DOPA sulfate and urinary dopamine may originate from circulating DOPA. Tyrosine hydroxylase inhibition may thus result in DOPA generation in non-catecholamine-producing tissues by an alternative pathway. The resulting progressive increase in DOPA and its sulfate may lead to increased urinary dopamine. DOPA sulfate may be an alternative source of dopamine sulfate.     

Implementation of an image-guided radiation therapy program: Lessons learnt and future challenges

The aim of this paper is to detail the experience obtained in implementing an image-guided radiation therapy program at the Northern Sydney Cancer Centre. This required retrofitting a Varian Clinac 21EX with an on-board imager. The commissioning and quality assurance procedures, organisation of a multidisciplinary image guided radiation therapy group, and the development of clinical protocols for orthogonal kV and cone beam computed tomography implementation are described. Reassessment of the image-guided radiation therapy program has continued as new equipment and software versions were made available in the department.     

Tuberculosis Acquired Outside of Households, Rural Vietnam

Using population-based data from rural Vietnam, we assessed tuberculosis (TB) transmission within and outside of households. Eighty-three percent of persons with recent household TB were infected by different strains of Mycobacterium tuberculosis than were their household members. This result argues against the effectiveness of active TB case finding among household members.     

Metabolism and storage of catecholamines in rats with pheochromocytoma implants

New England Deaconess Hospital rats implanted with a pheochromocytoma P259 became hypertensive and showed high concentrations of plasma dopamine (42.0 +/- 14.6 ng/ml) and norepinephrine (45.7 +/- 8.4 ng/ml). However, the norepinephrine content of several peripheral tissues of these rats did not differ from those of the New England Deaconess Hospital control rats, and their dopamine content, although slightly higher, was much lower than would have been expected from the plasma dopamine levels. Methylation by catechol-O-methyltransferase did not appear to play a major role in the inactivation of tissue catecholamines since there were no noticeable increases of normetanephrine or 3-methoxytyramine in the tissues of the rats with pheochromocytoma. There was also no increase in conjugated dopamine, in either the sulfate or glucuronide form, in the plasma or tissue of the hypertensive rats, although injection of L-dopa induced a large increase in dopamine sulfate in the plasma and urine of these rats. This finding indicated that, although their sulfoconjugation mechanism was intact and not affected by the pheochromocytoma, it did not participate in the metabolism of dopamine released by the tumor into the blood. On the other hand, plasma and urine of tumor-bearing rats exhibited abnormally high concentrations of homovanillic acid, the main metabolite of dopamine resulting from monoamine oxidase action. In contrast to the control rats, intravenous infusion of free dopamine in rats with pheochromocytoma had no effect on plasma free dopamine levels but increased homovanillic acid levels considerably. The present data underline the important role of monoamine oxidase in the removal of excessive quantities of catecholamines released by the tumor in New England Deaconess Hospital rats with the pheochromocytoma implant.     

Survival after out-of-hospital cardiac arrest,Viet Nam: multicentre prospective cohort study

ObjectiveTo investigate factors associated with survival after out-of-hospital cardiac arrest in Viet Nam.MethodsWe did a multicentre prospective observational study of people (> 18 years) presenting with out-of-hospital cardiac arrest (not caused by trauma) to three tertiary hospitals in Viet Nam from February 2014 to December 2018. We collected data on characteristics, management and outcomes of patients with out-of-hospital cardiac arrest and compared these data by type of transportation to hospital and survival to hospital admission. We assessed factors associated with survival to admission to and discharge from hospital using logistic regression analysis.FindingsOf 590 eligible people with out-of-hospital cardiac arrest, 440 (74.6%) were male and the mean age was 56.1 years (standard deviation: 17.2). Only 24.2% (143/590) of these people survived to hospital admission and 14.1% (83/590) survived to hospital discharge. Most cardiac arrests (67.8%; 400/590) occurred at home, 79.4% (444/559) were witnessed by bystanders and 22.3% (124/555) were given cardiopulmonary resuscitation by a bystander. Only 8.6% (51/590) of the people were taken to hospital by the emergency medical services and 32.2% (49/152) received pre-hospital defibrillation. Pre-hospital defibrillation (odds ratio, OR: 3.90; 95% confidence interval, CI: 1.54–9.90) and return of spontaneous circulation in the emergency department (OR: 2.89; 95% CI: 1.03–8.12) were associated with survival to hospital admission. Hypothermia therapy during post-resuscitation care was associated with survival to discharge (OR: 5.44; 95% CI: 2.33–12.74).ConclusionImprovements are needed in the emergency medical services in Viet Nam such as increasing bystander cardiopulmonary resuscitation and public access defibrillation, and improving ambulance and post-resuscitation care.     

Statistical models for longitudinal zero‐inflated count data with applications to the substance abuse field

This study fills in the current knowledge gaps in statistical analysis of longitudinal zero‐inflated count data by providing a comprehensive review and comparison of the hurdle and zero‐inflated Poisson models in terms of the conceptual framework, computational advantage, and performance under different real data situations. The design of simulations represents the special features of a well‐known longitudinal study of alcoholism so that the results can be generalizable to the substance abuse field. When the hurdle model is more natural under the conceptual framework of the data, the zero‐inflated Poisson model tends to produce inaccurate estimates. Model performance improves with larger sample sizes, lower proportions of missing data, and lower correlations between covariates. The simulation also shows that the computational strength of the hurdle model disappears when random effects are included. Copyright © 2012 John Wiley & Sons, Ltd.     

The costs of traumatic brain injury due to motorcycle accidents in Hanoi, Vietnam

Background

Road traffic accidents are the leading cause of fatal and non-fatal injuries in Vietnam. The purpose of this study is to estimate the costs, in the first year post-injury, of non-fatal traumatic brain injury (TBI) in motorcycle users not wearing helmets in Hanoi, Vietnam. The costs are calculated from the perspective of the injured patients and their families, and include quantification of direct, indirect and intangible costs, using years lost due to disability as a proxy.

Methods

The study was a retrospective cross-sectional study. Data on treatment and rehabilitation costs, employment and support were obtained from patients and their families using a structured questionnaire and The European Quality of Life instrument (EQ6D).

Results

Thirty-five patients and their families were interviewed. On average, patients with severe, moderate and minor TBI incurred direct costs at USD 2,365, USD 1,390 and USD 849, with time lost for normal activities averaging 54 weeks, 26 weeks and 17 weeks and years lived with disability (YLD) of 0.46, 0.25 and 0.15 year, respectively.

Conclusion

All three component costs of TBI were high; the direct cost accounted for the largest proportion, with costs rising with the severity of TBI. The results suggest that the burden of TBI can be catastrophic for families because of high direct costs, significant time off work for patients and caregivers, and impact on health-related quality of life. Further research is warranted to explore the actual social and economic benefits of mandatory helmet use.