Cervical cancer screening in Tamilnadu, India: a feasibility study of training the village health nurse

Uterine cervical cancer is the most common malignancy among females in developing countries, including India. The success of cervical cancer screening programs in North America and Western Europe has been the result of centralized cervical-cytology screening. This is not possible in the villages (n=17,000) of Tamilnadu where 58 percent of females in rural areas are illiterate, health infrastructure is mediocre, and cervical cytology is unknow. The present study was undertaken to examine if the village health nurse (VHN) could be trained quickly to identify a cervical abnormality by visual inspection so that we could down stage the cancer to earlier stages, more amenable to treatment. VHNs also would be trained to take an adequate Pap smear. A total of 101 VHNs were trained in batches and returned to their villages. Within two years, 6,459 engible women in the study area were screened. The agreement between the gynecologists and the VHNs in identifying cancer among those with abnormal cervix was 95 percent, and 80 percent of the Pap smears taken by VHNs were adequate by WHO criteria, making the feasibility study highly successful.Authors are with The Cancer Institute (WIA), Adyar, Madras, Tamil Nadu,India. Address correspondence to Dr Gajalakshmi, Epidemiology Division and Cancer Registry, 18, Sardar Patel Road, Cancer Institute (WIA), Madras-600 036, Tamilnadu, India. This project was funded by the Indian Council of Medical Research, Government of India, New Delhi, India.520 Cancer Causes and Control. Vol 7. 1996     

N-terminal tripeptide of IGF-1 (GPE) prevents the loss of TH positive neurons after 6-OHDA induced nigral lesion in rats

The effect of the N-terminal tripeptide of insulin-like growth factor (IGF)-1, glycine-proline-glutamate (GPE), as a neuroprotective agent for nigro-striatal dopaminergic neurons was examined in the present study using a rat model of Parkinson's disease. A unilateral nigro-striatal lesion was induced in rats by injecting 6-hydroxydopamine (6-OHDA) into the right medial forebrain bundle (MFB). GPE (3 microgram) or its vehicle was administered intracerebroventricularly (i.c.v.) 2 h after the 6-OHDA lesion. Tyrosine-hydroxylase (TH) immunohistochemistry in the substantia nigra compacta (SNc) and the striatum were examined 2 weeks after the lesion. Following 6-OHDA injection, the number of TH immunopositive neurons in the ipsilateral SNc was reduced. The density of TH immunostaining was also reduced in the ipsilateral SNc and the striatum. Treatment with a single dose of GPE (n=9) significantly prevented the loss of TH immunopositive neurons (p<0. 001) and restored the TH immunoreactivity in both the SNc and the striatum compared with the vehicle control group (n=9, p<0.001). The results suggest that GPE showed promise as a potential treatment for Parkinson's disease.     

Molecular composition of the alveolar lining fluid in the aging lung

As we age, there is an increased risk for the development of pulmonary diseases, including infections, but few studies have considered changes in lung surfactant and components of the innate immune system as contributing factors to the increased susceptibility of the elderly to succumb to infections. We and others have demonstrated that human alveolar lining fluid (ALF) components, such as surfactant protein (SP)-A, SP-D, complement protein C3, and alveolar hydrolases, play a significant innate immune role in controlling microbial infections. However, there is a lack of information regarding the effect of increasing age on the level and function of ALF components in the lung. Here we addressed this gap in knowledge by determining the levels of ALF components in the aging lung that are important in controlling infection. Our findings demonstrate that pro-inflammatory cytokines, surfactant proteins and lipids, and complement components are significantly altered in the aged lung in both mice and humans. Further, we show that the aging lung is a relatively oxidized environment. Our study provides new information on how the pulmonary environment in old age can potentially modify mucosal immune responses, thereby impacting pulmonary infections and other pulmonary diseases in the elderly population.     

Relative percentage signal intensity recovery of perfusion metrics—an efficient tool for differentiating grades of glioma

Objective:

Glioma classification and characterization may be facilitated by a multiparametric approach of perfusion metrics, which could not be achieved by conventional MRI alone. Our aim is to explore the potential of relative percentage signal intensity recovery (rPSR) values, in addition to relative cerebral blood volume (rCBV) and relative cerebral blood flow (rCBF) of first-pass T₂* dynamic susceptibility contrast (DSC) perfusion MRI, in differentiating high- and low-grade glioma.

Methods:

This prospective study included 39 patients with low-grade and 25 patients with high-grade glioma. rPSR, rCBV and rCBF were calculated from the first-pass T₂* DSC perfusion MRI. rPSR was calculated using standard software and validated with dedicated perfusion metrics analysis software. The statistical analysis was performed using analysis of variance and receiver operating characteristic (ROC) curves.

Results:

Variation in rPSR, rCBV and rCBF values between low- and high-grade gliomas were statistically significant (p < 0.005). The ROC curve analysis for each of them yielded 96% sensitivity and 71.8% specificity; 88% sensitivity and 69.2% specificity; and 72% sensitivity and 66.7% specificity. The area under the curve (AUC) from the ROC curve analysis yielded 0.893, 0.852 and 0.702 for rPSR, rCBV and rCBF, respectively. The rPSR calculation with the validation software yielded 92.3% sensitivity and 72% specificity with an AUC of 0.864.

Conclusion:

rPSR inversely correlates while rCBV and rCBF values directly correlate with the tumour grade. Furthermore, the overall diagnostic performance of rPSR is better than rCBV and rCBF values.

Advances in knowledge:

rPSR of T₂* DSC perfusion is an indicator of blood–brain barrier status and lesion leakiness, which has not been explored yet compared with the usual haemodynamic parameters, rCBV and rCBF.Gliomas, the most common primary brain tumour of the brain, are heterogeneous, showing highly varied histopathological features during malignant transformation of the tumour reflecting alterations in the tumour vasculature.¹ The broad category of glioma represents approximately 30% of all the tumours. Low-grade astrocytomas (60–70%) and oligodendrogliomas (10–30%) are two common subtypes of low-grade gliomas. Among them, glioblastoma and astrocytoma account for 75% of gliomas.² With the advent of advanced imaging technologies, heterogeneity in gliomas such as neovascularization, angiogenesis, loss of blood–brain barrier (BBB) integrity, tortuousness, disorganized and highly permeable vessels may be non-invasively measured with the help of perfusion imaging.^3–5 Dynamic susceptibility contrast (DSC) perfusion MRI is a widely accepted tool for evaluating the haemodynamic characteristics of the brain, which are of great interest since it helps in assessing the malignancy of the tumour. The common haemodynamic parameters assessed using perfusion MRI are relative cerebral blood volume (rCBV) and relative cerebral blood flow (rCBF).^6–8 In this study, we use a comparatively newer parameter, relative percentage signal intensity recovery (rPSR), whose potential has not been exploited to its best for haemodynamic calculations, even though this parameter has shown promise in the differentiation of brain tumours.^9–11 PSR is the percentage of the signal intensity recovered at the end of the first pass of the contrast agent with respect to the pre-contrast baseline signal intensity. After the administration of the contrast agent, there is a sudden decrease in the signal intensity owing to the variation in the local magnetic field leading to T₂* decay, which is seen as a dip in the mean signal intensity–time curve, and then the signal returns towards the baseline.^9–11The tumour rCBV provides information about the tumour blood levels and degree of angiogenesis but fails to provide information regarding capillary permeability. This drawback of DSC-MR perfusion imaging can be addressed by evaluating the rPSR obtained from the signal intensity–time curve formed at the end of the first pass of contrast agent in DSC-MR perfusion imaging.^9,10 Previous studies have observed that the contrast agent leakage, size of the extravascular space and the rate of blood flow that reflects the alterations in capillary permeability are related to rPSR.^10,11 There are reports which state that information regarding capillary permeability and lesion leakiness can be gathered from the signal intensity–time curve obtained from the first-pass T₂* DSC perfusion. Usually, this is performed using dynamic contrast-enhanced perfusion MRI, which involves additional scan time and also post-processing assumptions and extrapolations.^9–11Lupo et al⁴ was the first to report the characterization of high-grade gliomas using the PSR and peak height. rPSR is the only parameter among the different perfusion metrics which takes into account the leakage factor for the characterization of heterogeneity of brain tissues, compared with the other two parameters rCBV and rCBF where the leakage is neglected during the evaluation. The rPSR values of lower grade gliomas have not been explored, and hence an effort to differentiate between high- and low-grade gliomas using this new parameter will be advantageous. Hence, in the present study, we have evaluated all the parameters rPSR, rCBV and rCBF of low- and high-grade gliomas to find the potential of rPSR to differentiate different grades of glioma over the other two conventionally used parameters rCBV and rCBF. rPSR values were evaluated using two different standard software programs. Furthermore, we have performed a test for correlation between these parameters.     

Childhood cancer incidence in India: A review of population-based cancer registries

Objectives

To summarize and provide an overview of the childhood cancer incidence reported in 25 population-based cancer registries of India.

Methods

Secondary data on age-adjusted rates of cancer incidence for children (0–14 years) were collected from the report of the National Cancer Registry Programme in the year 2013. range of age-adjusted-rates per million children were tabulated for six regions of the country.

Results

Age-adjusted cancer incidence rates ranged from 18.6 per million to 159.6 per million for boys and 11.3 to 112.4 for girls. The highest incidence was observed for males (159.6) in Southern region of the country and the lowest in North-east in both boys (18.6) and girls (11.3). Leukemia and lymphoma were the commonest malignancies in boys whereas leukemia and brain tumors were commonest in girls.

Conclusion

Childhood cancer indicidence appears to be increasing in India.     

Health-related quality of life in children with cerebral palsy and their families

Objective

To determine the health-related quality of life in children with cerebral palsy and their families.

Methods

One hundred children (3–10 years of age) receiving regular rehabilitation therapy for cerebral palsy for last 1 year at a Child Development Centrer were enrolled and the Lifestyle assessment questionnaire — cerebral palsy was administered to the parents.

Results

9% had good, 24% had mildly-affected, 37% had moderately-affected and 30% had severely-affected healthrelated quality of life. The physical independence, mobility and social integration dimensions were much more severely affected than the clinical burden, economic burden and schooling dimensions.

Conclusion

Health-related quality of child is affected in most children with cerebral palsy.     

Addition of Algenpantucel-L Immunotherapy to Standard Adjuvant Therapy for Pancreatic Cancer: a Phase 2 Study

Background

Despite continued investigation, limited progress has been made in the adjuvant treatment of resected pancreatic cancer. Novel or targeted therapies are needed.

Methods

Multi-institutional, open-label, dose-finding, phase 2 trial evaluating the use of algenpantucel-L (NewLink Genetics Corporation, Ames, IA) immunotherapy in addition to chemotherapy and chemoradiotherapy in the adjuvant setting for resected pancreatic cancer (ClinicalTrials.gov identifier, NCT00569387). The primary outcome was 12-month disease-free survival. Secondary outcomes included overall survival and toxicity.

Results

Seventy patients were treated with gemcitabine and 5-fluorouracil-based chemoradiotherapy as well as algenpantucel-L (mean 12 doses, range 1–14). After a median follow-up of 21 months, the 12-month disease-free survival was 62 %, and the 12-month overall survival was 86 %. The most common adverse events were injection site pain and induration.

Conclusions

The addition of algenpantucel-L to standard adjuvant therapy for resected pancreatic cancer may improve survival. A multi-institutional, phase 3 study is ongoing (ClinicalTrials.gov identifier, NCT01072981).     

Bax phosphorylation association with nucleus and oligomerization after neonatal Hypoxia–ischemia

Neonatal hypoxia–ischemia (HI) is a common occurrence in preterm and low‐birth‐weight infants, and the incidence of low‐birth‐weight and preterm births is increasing. Characterization of brain injury after HI is of critical importance in developing new treatments that more accurately target the injury. After severe HI, neuronal cells undergo necrosis and secondary apoptosis of the surrounding cells as a result of neuroinflammation. We sought to characterize the biochemical pathways associated with cell death after HI. Bax, a cell death signaling protein, is activated after HI and translocates to the nucleus, endoplasmic reticulum, and mitochondria. The translocation patterns of Bax affect the resultant cell death phenotype (necrotic or apoptotic) observed. Although Bax is known to oligomerize once it is activated, less is known about the factors that control its translocation and oligomerization. We hypothesize that Bax kinase‐specific phosphorylation determines its oligomerization and intracellular localization. Using well‐established in vivo and in vitro models of neonatal HI, we characterized Bax oligomerization and multiorganelle translocation. We found that HI‐dependent phosphorylation of Bax determines its oligomerization status and multiorganelle localization, and, ultimately, the cell death phenotype observed. Understanding the mechanisms of Bax translocation will aid in the rational design of therapeutic strategies that decrease the trauma resulting from HI‐associated inflammation. © 2013 Wiley Periodicals, Inc.