Dosimetric analysis and clinical outcomes of brachial plexus as an organ-at-risk in head-and-neck cancer patients treated with intensity-modulated radiotherapy.

OBJECTIVES: To document the dose received by brachial plexus (BP) in patients treated with intensity-modulated radiotherapy (IMRT) for head-and-neck squamous cell carcinoma (HNSCC) and report the incidence of brachial plexopathy. METHODS: Newly diagnosed patients of HNSCC treated with radical or adjuvant IMRT were included in this retrospective study. No dosimetric constraints were applied for BP maximum dose equivalent dose (EQD2 α/ß = 3). Patients with minimum 6-month follow-up were included and patients with suspicion of plexopathy were evaluated further. RESULTS: Sixty-seven patients were eligible and 127 BP were analyzed. The mean BP maximum dose (BPmax) was 62.4 Gy (+6.9), while mean BP volume was 28.1 cc (+4.1). Proportion of patients receiving BPmax >66 and >70 Gy were 34.7% and 14.2%. The mean BPmax for T4 tumors was significantly higher than T1 tumors (65 vs. 57.5 Gy, P = 0.005) but when adjusted for N-category, T-category was not independently significant in accounting for BPmax >66 or >70 Gy. Mean BPmax for N0 versus N2+ was 59.8 versus 65.6 Gy (P = 0.0001) and N1 versus N2+ was 61.6 versus 65.6 Gy (P = 0.018). After adjusting for T-category, patients with N2+ had a mean 4.2 Gy higher BPmax than N0-N1 (P = 0.0001). Stage III-IV patients had a mean six Gy higher BPmax doses than Stage I-II disease (P = 0.0001). With a median follow-up of 28 months (interquartile range 16-42), no patient had brachial plexopathy. CONCLUSION: Clinically significant plexopathy was not seen in spite of majority having over 2-years follow-up and a third of patients having dose above the recommended tolerance. Only nodal category independently influenced dose to the brachial plexii.

Patterns of Recurrence, Long-term Survival and Toxicity Analysis of Endometrial Adenocarcinoma Patients Reclassified Under the Recent ESMO-ESGO-ESTRO Stratification: Seven-Year Results From a Single Institution.

AIM: The aim of this study was to report the patterns of recurrence, locoregional control, and survival of patients diagnosed with endometrial adenocarcinomas over a 7-year period after reclassifying them under the recent ESMO-ESGO-ESTRO (European Society of Medical Oncology/European Society of Gynaecological Oncology/European Society for Radiotherapy and Oncology) consensus classification. METHODS: Archives of a single institution from 2008 to 2014 were studied and patients with stages I-II endometrial adenocarcinoma were reclassified as per the new classification for uniformity. On magnetic resonance imaging, if found to be stage I, total abdominal hysterectomy with bilateral salpingo-oophorectomy alone was performed. The indications for adjuvant external beam radiotherapy (EBRT) and vaginal brachytherapy (VBT) were based on standard recommendations. Survival was calculated from Kaplan-Meier curves, and toxicity was recorded using Common Terminology Criteria for Adverse Events version 3. RESULTS: Of the 132 patients registered, 101 patients were included for analysis. A total of 18 patients have died, and information on outcome is available for 84% of patients. Five patients were metastatic at presentation. Five patients received definitive EBRT + intracavitary brachytherapy because of surgical inoperability, four of whom are disease-free locoregionally with median overall survival of 33.8 months. Of the 91 patients operated on, the incidence of low, intermediate, high-intermediate, and high risk was 34%, 29%, 2%, and 19%, whereas 16% were stage III. The overall recurrence rates were 10%, 15%, and 23% for low, intermediate, and high risk, respectively. With median follow-up of 32 months (range, 2-93 months), the disease-free survival for low, intermediate, and high risk and stage III were 92%, 81%, and 64% and 55%, whereas the mean survival for the same groups were 53, 44, and 34 and 22 months, respectively (P = 0.047). External beam radiotherapy resulted in significantly higher proctitis than VBT alone (P = 0.02). The median time to cystitis, proctitis, and enteritis were 27, 19, and 28 months, respectively. CONCLUSIONS: Recurrence rates, survival rates, and the patterns of recurrence are comparable with published literature and partly validates the ESMO-ESGO-ESTRO consensus statement. Addition of EBRT significantly increases risk of late proctitis as compared with VBT alone.

Inpatient treatment of diabetic patients in Asia: evidence from India, China, Thailand and Malaysia.

AIMS: The prevalence of Type 2 diabetes mellitus (DM) has grown rapidly, but little is known about the drivers of inpatient spending in low- and middle-income countries. This study aims to compare the clinical presentation and expenditure on hospital admission for inpatients with a primary diagnosis of Type 2 DM in India, China, Thailand and Malaysia. METHODS: We analysed data on adult, Type 2 DM patients admitted between 2005 and 2008 to five tertiary hospitals in the four countries, reporting expenditures relative to income per capita in 2007. RESULTS: Hospital admission spending for diabetic inpatients with no complications ranged from 11 to 75% of per-capita income. Spending for patients with complications ranged from 6% to over 300% more than spending for patients without complications treated at the same hospital. Glycated haemoglobin was significantly higher for the uninsured patients, compared with insured patients, in India (8.6 vs. 8.1%), Hangzhou, China (9.0 vs. 8.1%), and Shandong, China (10.9 vs. 9.9%). When the hospital admission expenditures of the insured and uninsured patients were statistically different in India and China, the uninsured always spent less than the insured patients. CONCLUSIONS: With the rising prevalence of DM, households and health systems in these countries will face greater economic burdens. The returns to investment in preventing diabetic complications appear substantial. Countries with large out-of-pocket financing burdens such as India and China are associated with the widest gaps in resource use between insured and uninsured patients. This probably reflects both overuse by the insured and underuse by the uninsured.

A distinct physiological role of MutY in mutation prevention in mycobacteria.

Oxidative damage to DNA results in the occurrence of 7,8-dihydro-8-oxoguanine (8-oxoG) in the genome. In eubacteria, repair of such damage is initiated by two major base-excision repair enzymes, MutM and MutY. We generated a MutY-deficient strain of Mycobacterium smegmatis to investigate the role of this enzyme in DNA repair. The MutY deficiency in M. smegmatis did not result in either a noteworthy susceptibility to oxidative stress or an increase in the mutation rate. However, rifampicin-resistant isolates of the MutY-deficient strain showed distinct mutations in the rifampicin-resistance-determining region of rpoB. Besides the expected C to A (or G to T) mutations, an increase in A to C (or T to G) mutations was also observed. Biochemical characterization of mycobacterial MutY (M. smegmatis and M. tuberculosis) revealed an expected excision of A opposite 8-oxoG in DNA. Additionally, excision of G and T opposite 8-oxoG was detected. MutY formed complexes with DNA containing 8-oxoG : A, 8-oxoG : G or 8-oxoG : T but not 8-oxoG : C pairs. Primer extension reactions in cell-free extracts of M. smegmatis suggested error-prone incorporation of nucleotides into the DNA. Based on these observations, we discuss the physiological role of MutY in specific mutation prevention in mycobacteria.

Synergistic effects of UdgB and Ung in mutation prevention and protection against commonly encountered DNA damaging agents in Mycobacterium smegmatis.

The incorporation of dUMP during replication or the deamination of cytosine in DNA results in the occurrence of uracils in genomes. To maintain genomic integrity, uracil DNA glycosylases (UDGs) excise uracil from DNA and initiate the base-excision repair pathway. Here, we cloned, purified and biochemically characterized a family 5 UDG, UdgB, from Mycobacterium smegmatis to allow us to use it as a model organism to investigate the physiological significance of the novel enzyme. Studies with knockout strains showed that compared with the wild-type parent, the mutation rate of the udgB( -) strain was approximately twofold higher, whereas the mutation rate of a strain deficient in the family 1 UDG (ung(- )) was found to be approximately 8.4-fold higher. Interestingly, the mutation rate of the double-knockout (ung(-)/ udgB(-)) strain was remarkably high, at approximately 19.6-fold. While CG to TA mutations predominated in the ung(-) and ung(-)/udgB(-) strains, AT to GC mutations were enhanced in the udgB(-) strain. The ung(-)/udgB(-) strain was notably more sensitive to acidified nitrite and hydrogen peroxide stresses compared with the single knockouts (ung(-) or udgB(-)). These observations reveal a synergistic effect of UdgB and Ung in DNA repair, and could have implications for the generation of attenuated strains of Mycobacterium tuberculosis.

Effects of butyrate on active sodium and chloride transport in rat and rabbit distal colon.

Short chain fatty acids, particularly butyrate, stimulate electroneutral NaCl absorption from the colon. Their effect in colonic epithelia lacking basal electroneutral NaCl absorption is unknown. Butyrate is also reported to inhibit active Cl- secretion in the colon. The present studies were undertaken to investigate the inter-relationships between the effects of butyrate on active Na+ and Cl- transport in the colon. Studies were carried out in rabbit distal colon (known to have predominant electrogenic Na+ absorption), rat distal colon (characterised by electroneutral Na+ absorption), and hyperaldosteronaemic rat distal colon (characterised by electrogenic Na+ absorption). The effect of cholera toxin (CT) was also noted. Potential difference, short-circuit current (I(SC)) and fluxes of Na+ and Cl- were measured in stripped mucosa under voltage-clamp conditions. Butyrate stimulated electroneutral Na+ and Cl- absorption in distal colon of normal and salt-depleted rats, and stimulated Na+ absorption in rabbit distal colon. Amiloride (10(-4) M) or CT did not inhibit this process. In rabbit distal colon, stimulation of Na+ absorption by butyrate was not dependent on the presence of Cl- in the medium. Butyrate significantly decreased conductance, decreased flux of sodium from serosa to mucosa (particularly in rabbit distal colon), and decreased I(SC). Net Cl- secretion, induced by CT, was completely inhibited by butyrate. Stimulation of Na+ absorption was independent of exposure to CT. Bumetanide reversed net Cl- secretion to net absorption, but did not alter Na+ or Cl- fluxes in tissues exposed to butyrate. Thus butyrate stimulates active Na+ absorption in colonic epithelia, with or without expression of basal Na+-H+ exchange. Independently, butyrate inhibits active Cl- secretion induced by cAMP in these epithelia.

Nitric oxide protects the intestine from the damage induced by laparotomy and gut manipulation.

BACKGROUND: The intestine is highly susceptible to free radical-induced damage, and our earlier work has shown that surgical stress induces the generation of oxygen free radicals in enterocytes, resulting in intestinal damage along with ultrastructural changes. Since nitric oxide (NO) is an important mediator of gastrointestinal function, this study looked at the effect of NO on surgical stress-induced intestinal alterations. MATERIALS AND METHODS: Control rats and rats pretreated with the NO donor l-arginine were subjected to surgical stress by opening the abdominal wall and handling the intestine as done during laparotomy. Enterocytes were isolated and homogenate prepared, and the protection offered by l-arginine against damage due to surgical stress was determined and compared with normal controls. Protection to structural as well as functional aspects of the intestine was also examined. RESULTS: Intestinal manipulation affected intestinal structure as assessed by electron microscopy. Functional impairment of the enterocyte was also evident, with increased xanthine oxidase activity resulting in production of superoxide anion. This impairment is more dramatic in the crypt cells. Increased protease activity was also seen following laparotomy and handling. Pretreatment with the NO synthase substrate l-arginine prevented these damaging effects. Arginine protection was abolished in the presence of the NO synthase inhibitor NG-nitro-l-arginine methyl ester, indicating the role of NO. CONCLUSION: Stress in the small intestine due to any surgery can affect enterocyte structure and function. These damaging effects can be prevented by NO, an important modulator of cellular function.

Vincristine (Vinca-alkaloid) as a sclerosing agent for malignant pleural effusions.

Vincristine, extracted from Vinca rosea Linn., is an effective antineoplastic chemotherapeutic drug used in oncology practice. This drug has never been used as a sclerosing agent for the treatment of malignant pleural effusion for reasons unknown. A study was conducted to examine the use of Vinca-Alkaloid as a sclerosing agent (pleurodesis) for the palliative treatment of malignant pleural effusions. The study included 15 patients, all diagnosed to have cytology-proven malignant pleural effusions. Intercostal tube drainage followed by chemical sclerotherapy with 2 mg vincristine was performed on all patients and a high success rate was noted. Twelve procedures out of 15 (12/15) achieved complete resolution of pleural fluid with a success rate of 80%. In two procedures the pleural effusion was reduced and then recurred but did not require re-aspiration. One procedure failed and repeated pleural aspiration was required. In this study, with adequate pleural drainage and the proper technique, vincristine was found to be an effective sclerosing agent for malignant pleural effusion. Further randomized trials are necessary in order to establish the role of this drug.

Pseudohypertension with calcific aortic stenosis and angina pectoris.

A case of pseudohypertension as demonstrated by a very high systolic blood pressure (more than 280 mm of Hg) by sphygmomanometry and low blood pressure (148/30 mm of Hg) as evidenced by intra-arterial recording who also had severe calcific aortic stenosis, calcified right brachial artery and angina pectoris is described. This case is reported because of the unusual combination of lesions and the therapeutic challenge it poses.

Infancy and early childhood follow-up of neonates with periventricular or intraventricular hemorrhage or isolated ventricular dilation: a case controlled study.

Survivors of periventricular or intraventricular hemorrhage and isolated ventricular dilation showed a higher incidence of major developmental problems in the motor areas than matched control subjects in infancy. This effect is still seen, but less evident in early childhood. Problems were mainly related to grades III and IV periventricular or intraventricular hemorrhage and isolated ventricular dilation. The outcome of newborns with grades I and II hemorrhage was benign.