Association between neoadjuvant chemoradiation and survival for patients with locally advanced rectal cancer.

AIM: To examine the overall survival differences for the following neoadjuvant therapy modalities - no therapy, chemotherapy alone, radiation alone and chemoradiation - in a large cohort of patients with locally advanced rectal cancer. METHOD: Adults with clinical Stage II and III rectal adenocarcinoma were selected from the National Cancer Database and grouped by type of neoadjuvant therapy received: no therapy, chemotherapy only, radiotherapy only or chemoradiation. Multivariable regression methods were used to compare adjusted differences in perioperative outcomes and overall survival. RESULTS: Among 32 978 patients included, 9714 (29.5%) received no neoadjuvant therapy, 890 (2.7%) chemotherapy only, 1170 (3.5%) radiotherapy only and 21 204 (64.3%) chemoradiation. Compared with no therapy, chemotherapy or radiotherapy alone were not associated with any adjusted differences in surgical margin positivity, permanent colostomy rate or overall survival (all P > 0.05). With adjustment, neoadjuvant chemoradiation vs no therapy was associated with a lower likelihood of surgical margin positivity (OR 0.74, P < 0.001), decreased rate of permanent colostomy (OR 0.77, P < 0.001) and overall survival [hazard ratio (HR) 0.79, P < 0.001]. When compared with chemotherapy or radiotherapy alone, chemoradiation remained associated with improved overall survival (vs chemotherapy alone HR 0.83, P = 0.04; vs radiotherapy alone HR 0.83, P < 0.019). CONCLUSION: Neoadjuvant chemoradiation, not chemotherapy or radiotherapy alone, is important for sphincter preservation, R0 resection and survival for patients with locally advanced rectal cancer. Despite this finding, one-third of patients in the United States with locally advanced rectal cancer fail to receive stage-appropriate chemoradiation.

Effectiveness of skin cancer screening programmes.

Skin cancer, nonmelanoma skin cancer (NMSC) and cutaneous malignant melanoma (CMM), is the most frequent cancer worldwide. It is amenable to early detection, and screening for skin cancer has the potential to reduce mortality and morbidity. However, there are no recommendations for population-based skin cancer screening programmes due to the lack of evidence for the effectiveness from epidemiological studies. In 2008 the first nationwide screening programme for NMSC and CMM in the world was established in Germany. The decision for implementing such a programme was based on the results and evidence of a pilot study that was conducted from 2003 to 2004. The pilot study revealed that a population-based screening programme for skin cancer is feasible and effective. Careful evaluation of the nationwide programme is crucial to generate strong evidence for long-term public health benefits.

A threonine to isoleucine missense mutation in the pericentriolar material 1 gene is strongly associated with schizophrenia.

Markers at the pericentriolar material 1 gene (PCM1) have shown genetic association with schizophrenia in both a University College London (UCL) and a USA-based case-control sample. In this paper we report a statistically significant replication of the PCM1 association in a large Scottish case-control sample from Aberdeen. Resequencing of the genomic DNA from research volunteers who had inherited haplotypes associated with schizophrenia showed a threonine to isoleucine missense mutation in exon 24 which was likely to change the structure and function of PCM1 (rs370429). This mutation was found only as a heterozygote in 98 schizophrenic research subjects and controls out of 2246 case and control research subjects. Among the 98 carriers of rs370429, 67 were affected with schizophrenia. The same alleles and haplotypes were associated with schizophrenia in both the London and Aberdeen samples. Another potential aetiological base pair change in PCM1 was rs445422, which altered a splice site signal. A further mutation, rs208747, was shown by electrophoretic mobility shift assays to create or destroy a promoter transcription factor site. Five further non-synonymous changes in exons were also found. Genotyping of the new variants discovered in the UCL case-control sample strengthened the evidence for allelic and haplotypic association (P=0.02-0.0002). Given the number and identity of the haplotypes associated with schizophrenia, further aetiological base pair changes must exist within and around the PCM1 gene. PCM1 protein has been shown to interact directly with the disrupted-in-schizophrenia 1 (DISC1) protein, Bardet-Biedl syndrome 4, and Huntingtin-associated protein 1, and is important in neuronal cell growth. In a separate study we found that clozapine but not haloperidol downregulated PCM1 expression in the mouse brain. We hypothesize that mutant PCM1 may be responsible for causing a subtype of schizophrenia through abnormal cell division and abnormal regeneration in dividing cells in the central nervous system. This is supported by our previous finding of orbitofrontal volumetric deficits in PCM1-associated schizophrenia patients as opposed to temporal pole deficits in non-PCM1-associated schizophrenia patients. Caution needs to be exercised in interpreting the actual biological effects of the mutations we have found without further cell biology. However, the DNA changes we have found deserve widespread genotyping in multiple case-control populations.

Case-control studies show that a non-conservative amino-acid change from a glutamine to arginine in the P2RX7 purinergic receptor protein is associated with both bipolar- and unipolar-affective disorders.

Three linkage studies of bipolar disorder have implicated chromosome 12q24.3 with lod scores of over 3.0 and several other linkage studies have found lods between 2 and 3. Fine mapping within the original chromosomal linkage regions has identified several loci that show association with bipolar disorder. One of these is the P2RX7 gene encoding a central nervous system-expressed purinergic receptor. A non-synonymous single nucleotide polymorphism, rs2230912 (P2RX7-E13A, G allele) and a microsatellite marker NBG6 were both previously found to be associated with bipolar disorder (P=0.00071 and 0.008, respectively). rs2230912 has also been found to show association with unipolar depression. The effect of the polymorphism is non-conservative and results in a glutamine to arginine change (Gln460Arg), which is likely to affect P2RX7 dimerization and protein-protein interactions. We have confirmed the allelic associations between bipolar disorder and the markers rs2230912 (P2RX7-E13A, G allele, P=0.043) and NBG6 (P=0.010) in a London-based sample of 604 bipolar cases and 560 controls. When we combined these data with the published case-control studies of P2RX7 and mood disorder (3586 individuals) the association between rs2230912 (Gln460Arg) and affective disorders became more robust (P=0.002). The increase in Gln460Arg was confined to heterozygotes rather than homozygotes suggesting a dominant effect (odds ratio 1.302, CI=1.129-1.503). Although further research is needed to prove that the Gln460Arg change has an aetiological role, it is so far the most convincing mutation to have been found with a role for increasing susceptibility to bipolar and genetically related unipolar disorders.

Effect of probiotic Pediococcus acidilactici FT28 on growth performance, nutrient digestibility, health status, meat quality, and intestinal morphology in growing pigs.

AIM: The experiment was conducted to evaluate the effect of swine-origin probiotic Pediococcus acidilactici FT28 on growth, nutrient utilization, health status, meat quality and intestinal morphology in growing female pigs. MATERIALS AND METHODS: Pigs (n=27) were distributed into three groups (3 replicates of 3 each) and supplemented with basal diet either without probiotics (C) or with a probiotic of dairy-based (Lactobacillus acidophilus NCDC-15; TLact) or swine based (P. acidilactici FT28; TPedic). The probiotics were fed as fermented feed at 200 g/pig/day. At the end of the trial, six pigs from each group were selected for metabolism trial and then sacrificed to determine meat quality and intestinal morphology. RESULTS: Supplementation of both probiotics improved growth performance, whereas feed intake, digestibility of CP and N retention were better (p<0.05) in P. acidilactici FT28-fed group. However , the digestibility of dry matter (DM), organic matter (OM), ether extracts (EE), crude fiber and nitrogen free extract did not show any significant effect on probiotic supplementation. The serum A: G ratio, triglyceride, and cholesterol level were also improved (p<0.05) in TPedic group compared to other treatment groups. Both probiotic supplementations showed lower (p<0.05) serum glucose level with similar protein and albumin value, which indicated good utilization of feed as well as health status of growing pigs. Dressing percentage, vital organ weight, and EE of loin meat were higher (p<0.05) in probiotic-supplemented groups compared to control. However, P. acidilactici FT28-fed animals showed higher (p<0.05) CP and total ash percentage of meat without affecting pH, water holding capacity, and extract release volume of loin muscle. The villi height and crypt depth were better in both supplemented groups compared to control. CONCLUSION: Results of the present study revealed that P. acidilactici FT28 could serve as better probiotic source in swine production for the better utilization of CP and N-retention in meat with improved health status and intestinal morphology.

White Matter Changes Related to Subconcussive Impact Frequency during a Single Season of High School Football.

BACKGROUND AND PURPOSE: The effect of exposing the developing brain of a high school football player to subconcussive impacts during a single season is unknown. The purpose of this pilot study was to use diffusion tensor imaging to assess white matter changes during a single high school football season, and to correlate these changes with impacts measured by helmet accelerometer data and neurocognitive test scores collected during the same period. MATERIALS AND METHODS: Seventeen male athletes (mean age, 16 ± 0.73 years) underwent MR imaging before and after the season. Changes in fractional anisotropy across the white matter skeleton were assessed with Tract-Based Spatial Statistics and ROI analysis. RESULTS: The mean number of impacts over a 10-g threshold sustained was 414 ± 291. Voxelwise analysis failed to show significant changes in fractional anisotropy across the season or a correlation with impact frequency, after correcting for multiple comparisons. ROI analysis showed significant (P < .05, corrected) decreases in fractional anisotropy in the fornix-stria terminalis and cingulum hippocampus, which were related to impact frequency. The effects were strongest in the fornix-stria terminalis, where decreases in fractional anisotropy correlated with worsening visual memory. CONCLUSIONS: Our findings suggest that subclinical neurotrauma related to participation in American football may result in white matter injury and that alterations in white matter tracts within the limbic system may be detectable after only 1 season of play at the high school level.

Morbidity profile of paediatric inpatents at a community health centre and a nearby [correction of near by] district hospital in northern India.

The study was conducted to ascertain the morbidity profile among children by retrospective review of inpatient data of children admitted to Comprehensive Rural Health Services Project (CRHSP), Ballabgarh, a model CHC and Badshah Khan (B.K.) hospital, Faridabad, a district hospital over a period of one year. Diarrhea and pneumonia comprised 64% of all admissions at the model CHC and 30% at the district hospital. Thalassemics requiring blood transfusion formed 21% of inpatients at the district hospital. Common paediatric ailments can be managed appropriately at CHC level, provided the infrastructure as recommended by Indian Public Health sandards for CHC under National Rural Health Mission (NRHM) is available. The blood bank or blood storage facility at a CHC is desirable.

Clinical profile of nonsmall cell lung carcinoma patients treated in a single unit at a tertiary cancer care center.

BACKGROUND: Recent advances and understanding in the field of lung cancer and advent of newer treatments have shown a significant improvement in survival in the patients. The present study was conducted to analyze the clinical profile of nonsmall cell lung cancer (NSCLC) patients treated in a single unit at a tertiary cancer care center. MATERIALS AND METHODS: In this retrospective analysis, 322 consecutive NSCLC patients from the year 2011 to 2012 treated in a single unit were included in the study. Patients with proven NSCLC were included in the study. The details of the patients included the demographic profile, pathological diagnosis as well as imaging data, tumor profile, details of treatment, and follow-up information. RESULTS: The majority of the patients (95.6%) were in the age group >40 years. A large group of the patients (57.1%) were present/reformed smokers. The major histological type was adenocarcinoma (60.9%), of which 22.8% patients were found to be epidermal growth factor receptor positive. Anaplastic lymphoma kinase rearrangement positivity rate was 4.8%. Furthermore, 68% patients had Stage 4 disease. Upfront palliative chemotherapy (CT) was offered in 61.8% patients and pemetrexed with platinum compounds was the main CT regimen (46.6%). Partial response was achieved in 45.7% patients, whereas stable disease was observed in 10.9% cases. Median progression-free survival was 5 months and overall survival was 55% at 36 months. CONCLUSION: NSCLC forms the largest subgroup of lung cancer with the patients presenting with advanced stages of disease. This area needs to be explored for the early detection and subsequently the radical treatment of the patients. Personalized approach may be considered for the management of lung cancer by identifying new predictive and prognostic biomarkers of this disease.

Inadvertent Intrafacet Injection during Lumbar Interlaminar Epidural Steroid Injection: A Comparison of CT Fluoroscopic and Conventional Fluoroscopic Guidance.

BACKGROUND AND PURPOSE: Inadvertent intrafacet injection can occur during interlaminar epidural steroid injection, resulting in a false-positive loss of resistance and nontarget injection of medication. The purpose of this investigation was to compare the observed rates of this phenomenon during lumbar interlaminar epidural steroid injection performed by using conventional fluoroscopic and CT fluoroscopic guidance. MATERIALS AND METHODS: We retrospectively reviewed 349 lumbar interlaminar epidural steroid injections performed by using conventional fluoroscopy or CT fluoroscopic guidance to determine the observed rates of inadvertent intrafacet injection with each technique. Cases of inadvertent intrafacet injection were classified as either recognized or unrecognized by the proceduralist at the time of the procedure. Multivariate logistic regression was used to determine the independent effect of imaging guidance technique, age, and sex. RESULTS: The rate of inadvertent intrafacet injection was observed to be 7.5% in the CT fluoroscopic group and 0.75% in the conventional fluoroscopy group. All 16 cases identified from CT fluoroscopic procedures were recognized during the procedure; the single case identified from conventional fluoroscopy procedures was not recognized prospectively. The type of imaging guidance showed a statistically significant effect on the detection of the phenomenon (OR for conventional fluoroscopy versus CT fluoroscopy = 0.10, P = .03) that was independent of differences in age or sex. CONCLUSIONS: Inadvertent intrafacet injection is identified during CT fluoroscopic-guided interlaminar epidural steroid injection at a rate that is 10-fold greater than the same procedure performed under conventional fluoroscopy guidance.

Rapid assessment of avoidable blindness and needs assessment of cataract surgical services in Satkhira District, Bangladesh.

AIMS: To estimate the magnitude and causes of blindness in people aged > or =50 years in Satkhira district, Bangladesh, and to assess the availability of cataract surgical services. METHODS: 106 clusters of 50 people aged > or =50 years were selected by probability-proportionate to size sampling. Households were selected by compact segment sampling. Eligible participants had their visual acuity measured. Those with visual acuity <6/18 were examined by an ophthalmologist. A needs assessment of surgical services was conducted by interviewing service providers. RESULTS: 4868 people were examined (response rate 91.9%). The prevalence of bilateral blindness was 2.9% (95% confidence interval (CI) 2.4% to 3.5%), that of severe visual impairment was 1.6% (95% CI 1.2% to 2.0%) and that of visual impairment was 8.4% (95% CI 7.5% to 9.3%). 79% of bilateral blindness was due to cataract. The cataract surgical coverage was moderate; 61% of people with bilateral cataract blindness (visual acuity <3/60) had undergone surgery. 20% of the 213 eyes that had undergone cataract surgery had a best-corrected poor outcome (visual acuity <6/60). The cataract surgical rate (CSR) in Satkhira was 547 cataract surgeries per million people per year. CONCLUSIONS: Although the prevalence of blindness and visual impairment was lower than expected, the CSR is inadequate to meet the existing need, and the quality of surgery needs to be improved.

Imaging Signs in Spontaneous Intracranial Hypotension: Prevalence and Relationship to CSF Pressure.

BACKGROUND AND PURPOSE: Patients with spontaneous intracranial hypotension often exhibit low CSF pressure and changes on brain MR imaging and/or evidence of CSF leak on myelography. We investigated whether individual imaging signs of spontaneous intracranial hypotension correlate with measured CSF pressure and how frequently these 2 markers of spontaneous intracranial hypotension were concordant. MATERIALS AND METHODS: We performed a retrospective, cross-sectional study of 99 subjects with spontaneous intracranial hypotension. Prevalence of brain and myelographic imaging signs of spontaneous intracranial hypotension was recorded. CSF pressure among subjects with or without individual imaging signs was compared by using a 2-tailed t test and ANOVA. Concordance between low CSF pressure (≤6 cm H2O) and imaging was defined as the presence of the sign in a subject with low CSF pressure or absence of the sign when pressure was not low. RESULTS: Dural enhancement, brain sagging, and venous distension sign were present in 83%, 61%, and 75% of subjects, respectively, and myelographic evidence of CSF leak was seen in 55%. Marginal correlations between CSF pressure and brain sagging (P = .046) and the venous distension sign (P = .047) were found. Dural enhancement and myelographic evidence of leak were not significantly correlated with CSF pressure. Rates of concordance between imaging signs and low CSF pressure were generally low, ranging from 39% to 55%. CONCLUSIONS: Brain and myelographic signs of spontaneous intracranial hypotension correlate poorly with CSF pressure. These findings reinforce the need to base the diagnosis of spontaneous intracranial hypotension on multiple diagnostic criteria and suggest the presence of patient-specific variables that influence CSF pressure in these individuals.

Radiology reports for incidental thyroid nodules on CT and MRI: high variability across subspecialties.

BACKGROUND AND PURPOSE: Variability in radiologists' reporting styles and recommendations for incidental thyroid nodules can lead to confusion among clinicians and may contribute to inconsistent patient care. Our aim was to describe reporting practices of radiologists for incidental thyroid nodules seen on CT and MR imaging and to determine factors that influence reporting styles. MATERIALS AND METHODS: This is a retrospective study of patients with incidental thyroid nodules reported on CT and MR imaging between January and December 2011, identified by text search for "thyroid nodule" in all CT and MR imaging reports. The studies included CT and MR imaging scans of the neck, spine, and chest. Radiology reports were divided into those that mentioned the incidental thyroid nodules only in the "Findings" section versus those that reported the incidental thyroid nodules in the "Impression" section as well, because this latter reporting style gives more emphasis to the finding. Univariate and multivariate analyses were performed to identify radiologist, patient, and nodule characteristics that influenced reporting styles. RESULTS: Three hundred seventy-five patients met the criterion of having incidental thyroid nodules. One hundred thirty-eight (37%) patients had incidental thyroid nodules reported in the "Impression" section. On multivariate analysis, only radiologists' divisions and nodule size were associated with reporting in "Impression." Chest radiologists and neuroradiologists were more likely to report incidental thyroid nodules in the "Impression" section than their abdominal imaging colleagues, and larger incidental thyroid nodules were more likely to be reported in "Impression" (P ≤ .03). Seventy-three percent of patients with incidental thyroid nodules of ≥20 mm were reported in the "Impression" section, but higher variability in reporting was seen for incidental thyroid nodules measuring 10-14 mm and 15-19 mm, which were reported in "Impression" for 61% and 50% of patients, respectively. CONCLUSIONS: Reporting practices for incidental thyroid nodules detected on CT and MR imaging are predominantly influenced by nodule size and the radiologist's subspecialty. Reporting was highly variable for nodules measuring 10-19 mm; this finding can be partially attributed to different reporting styles among radiology subspecialty divisions. The variability demonstrated in this study further underscores the need to develop CT and MR imaging practice guidelines with the goal of standardizing reporting of incidental thyroid nodules and thereby potentially improving the consistency and quality of patient care.

Regulation of the glial glutamate transporter GLT-1 by glutamate and delta-opioid receptor stimulation.

The excitatory effect of presynaptically released glutamate is tightly regulated and terminated by high affinity sodium-dependent glutamate transporters. The regulation of the glial glutamate transporter GLT-1 is potentially important in synaptic modulation. Using astroglial cultures prepared from the rat cerebral cortex, we found that the delta-opioid receptor agonist [D-pen2,D-pen5]-enkephalin decreases and glutamate increases the expression of the GLT-1 transporter mRNA. Corresponding changes in the uptake kinetics were found after incubation for 48 h with the respective agonists when glial glutamate uptake was measured in primary astroglial cultures. The data suggest that long-term receptor activation induces alterations in glial glutamate uptake properties.

Congenital inclusion cyst of the subgaleal space.

An unusual type of congenital subgaleal cyst, either dermoid or epidermoid, was found in 21 Nigerian infants. This entity was located in the midline of the scalp, anywhere from above the nasion to the inion, and occupied the subgaleal space. These cysts were noted soon after birth and gradually enlarged. They had no intracranial extension and were easily excised intact. Clinically, radiologically, and histologically they were similar to congenital inclusion dermoid cysts of the anterior fontanel. The histology and some of the peculiarities of these cysts are described. Although most of these cysts occur at the anterior fontanel, they can occur anywhere in the midline, and the subgaleal space of the anterior fontanel is not the exclusive site, as has been claimed by previous authors.

Preferential binding of adriamycin and nogalamycin to DNase-I hypersensitive sites of Sarcoma-180 chromatin.

Binding of nogalamycin and adriamycin with Sarcoma-180 ascites tumor cell chromatin was studied by a spectrofluorometric method. There was significant reduction in the number of available drug binding sites per nucleotide when the chromatin was digested with DNase I for a period which releases only 7% of the chromosomal DNA. Results indicate preferential binding of these drugs with DNase I hypersensitive sites of chromatin. The DNase-I hypersensitive sites of chromatin were shown to correlate to the sequences required for gene expression. Further digestion with DNase I increases availability of drug binding sites, probably due to relaxation of the compact chromatin.

Gender inequality and severe malnutrition among children in a remote rural area of Bangladesh.

Bangladesh typifies many south-eastern countries where female children experience inferior health and uncertain survival, especially after the neonatal period. This paper attempts to study the gender inequality in nutritional status and the effects of various socioeconomic, demographic, and health-programme factors on gender inequality in a remote rural area of Bangladesh. Measurements of mid-upper arm circumference (MUAC) were taken from 2,016 children aged less than 5 years (50.8% male, 49.2% female) in 1994. Children were characterized as severely malnourished if MUAC was < 125 mm. Independent variables included various characteristics of children, households, and mothers. Average MUAC for all children was 130 mm; 33% were severely malnourished. Of the severely-malnourished children, 54.2% were female, and 45.8% were male. The gender gap persisted in the multivariate situation, with female 1.44 times more likely to be severely malnourished. Other variables with a statistically significant relationship included the age of children, acceptance of DPT1, and education of household heads. The persistence of such a gender discrimination now when the country has achieved a lot in terms of child survival is striking. The issue is important and demands appropriate corrective actions.

Isolation and characterization of nonhistone proteins associated with DNase-II hypersensitive sites of Sarcoma-180 chromatin.

Limited digestion (2 min) of Sarcoma-180 nuclei by DNase-II released two nonhistone proteins from the hypersensitive sites of chromatin. The apparent molecular weights of these two proteins were 34 and 21 kDa. These proteins showed a moderate but specific inhibition in in vitro cell free transcription assay with native chromatin as template as opposed to no effect on native DNA transcription.

Experience with intrathecal cold saline injection in the treatment of cancer pain in the Lagos University Teaching Hospital.

Effective control of terminal cancer pain is usually associated with a higher incidence of toxicities or complications. Intrathecal injection of cold normal saline offers a good option. It is easy to perform, provides good pain-relief, is cost effective, and is well accepted by patients. It can be repeated if necessary and is free from complications associated with the Intrathecal use of neurolytic agents. It is recommended for greater use in patients with terminal cancer even in smaller hospitals.

Effect of anthracycline antibiotics on in vitro transcription of chromatin in a Sarcoma-180 whole cell extract.

A soluble extract capable of transcribing Sarcoma-180 chromatin and DNA in a cell-free transcription system was prepared from Sarcoma-180 mouse ascites tumour cells. Incorporation of [3H]UTP into trichloroacetic acid-precipitable fraction is (i) reduced by 50% on removing DNase I hypersensitive sites of chromatin and (ii) inhibited by DNA binding antitumour anthracyclines, suggesting that this cell-free assay represents true transcription of active genes of Sarcoma-180 chromatin. Preparation of this soluble extract from mouse ascites tumour cells thus presents a very convenient way of studying cell-free transcription of active genes of chromatin and effect of antitumour agents on chromatin transcription.

Effect of suxamethonium, pancuronium, neostigmine and halothane on serum cholinesterase activity.

Serum cholinesterase (Ch E) estimations were done in 30 healthy Nigerians scheduled for elective surgical procedures and were studied in two groups. Half of the patients were given general anesthesia using a muscle relaxant technique and the other half had halothane as the main anesthetic. Suxamethonium reduced Ch E by 9%, pancuronium by 25% and neostigmine by 58% compared to preinduction levels. Halothane reduced Ch E by 7% and 15% at 10 minutes and 24 hours postanesthetic respectively, compared to preinduction levels. The normal control value of Ch E in 30 healthy Nigerians was on the lower side of the normal range, observed mostly in Caucasians.