Commissioning 6 MV photon beams of a stereotactic radiosurgery system for Monte Carlo treatment planning

The goal of this work is to implement a beam commissioning procedure to generate a multiple source model using a set of standard measurement data for possible Monte Carlo treatment planning in the clinic for a Cyberknife stereotactic radiosurgery system. The required measurement data include the central axis depth dose curve (PDD), the dose profile at dmax(= 1.5 cm) of 60 mm cone at 80 cm source-to-surface distance (SSD), and the cone output factors for cones of 5 mm to 60 mm at 80 cm source-to-axis distance (SAD). The employed dual source model has the same structure as the one that has been studied in our previous work while most of the parameters of each source are extracted from the measurement data rather than the beam phase space. The energy spectra will be extracted from the central axis PDD, the fluence distributions will be deconvoluted from the dose profile at dmax, and the source distributions will be determined from the measured cone output factors. Monte Carlo dose calculations in various water phantoms have been performed to verify the beam commissioning procedure. The agreement between the measurements and the commissioning results was within 2%/1 mm for the central axis PDDs and the dose profiles at various depths when an IC-3 chamber was used and within 2% for the cone output factors for various collimator sizes of 5 to 60 mm. Largest difference (9.5%) was observed for the 7.5 mm cone when an IC-10 chamber was used. The large differences can be attributed to the volumetric averaging effect of the IC-10 chamber, whose dimension is comparable to the field of the small cones. The overall agreement between the measurements and the commissioning results is clinically acceptable, which implies that our commissioning tool is adequate for clinical applications of Monte Carlo dose calculations for the Cyberknife stereotactic radiosurgery system.     

ORIGINAL ARTICLE: Can Sulfasalazine Prevent Infection‐Mediated Pre‐Term Birth in a Murine Model?

Citation Nath CA, Ananth CV, Smulian JC, Peltier MR. Can sulfasalazine prevent infection‐mediated pre‐term birth in a murine model? Am J Reprod Immunol 2010; 63: 144–149 Problem Sulfasalazine (SASP) blocks activation of nuclear factor‐kappa B (NF‐κB) in gestational tissues in vitro– one of the earliest signals in the inflammatory response. We hypothesized that the administration of SASP would reduce the rate of infection‐mediated pre‐term birth in a murine model. Method of study CD‐1 mice (n = 40) were assigned on gestational day (gd) 14.5 to 1 of 3 treatments: (1) Sham infection and vehicle; (2) 10⁴ CFU Escherichia coli and vehicle; or (3) 10⁴ CFU E. coli and SASP (150 mg/Kg daily). Mice were observed twice daily and deliveries prior to gd 18.5 were considered pre‐term. Results Significantly more mice delivered prior to gd 18.5 when infected with 10⁴ CFU E. coli than sham‐infected mice (P < 0.001) and this effect was significantly reduced in mice also treated with SASP (P = 0.002). SASP also tended to increase litter size (P = 0.060) and significantly increased weight of pups born to dams with intrauterine infections (P = 0.001). Conclusion SASP reduced rates of pre‐term delivery and improved pregnancy outcomes for mice infected with 10⁴ CFU E. coli. This suggests that SASP has the potential to play a role in strategies to prevent pre‐term birth in women.     

Increased venous proinflammatory gene expression and intimal hyperplasia in an aorto-caval fistula model in the rat

We hypothesized that the venous limb of an arteriovenous (AV) fistula would evince up-regulation of genes relevant to vascular remodeling along with neointimal hyperplasia and relevant histological changes. Using the aorto-caval model of an AV fistula model in the rat, we demonstrate marked up-regulation in such proinflammatory genes as monocyte chemoattractant protein-1, plasminogen activator inhibitor-1, and endothelin-1, 2 weeks after the creation of the fistula. Neointimal hyperplasia occurred in variable degrees by 5 weeks after establishing the fistula, and by 16 weeks, such neointimal hyperplasia was progressive and pronounced; at this time point, abundant extracellular matrix was also observed. Smooth muscle cells were present in the hyperplastic neointima as evidenced by staining for alpha-smooth muscle actin; ultrastructurally, smooth muscle cells with a synthetic as well as a contractile phenotype were readily observed. Accumulation of extracellular matrix in the model at 16 weeks was accompanied by increased expression of transforming growth factor-beta1 mRNA, the latter finding contrasting with the suppression of transforming growth factor-beta1 mRNA observed in this model at 2 weeks. In summary, we describe marked up-regulation in proinflammatory genes and progressive neointimal formation in the venous vasculature in an AV fistula model in the rat. We suggest that such alteration in gene expression and histological injury, in conjunction with the relative simplicity of this model, offer a new approach in the study of such timely biological and clinically relevant phenomena as differential gene expression in response to hemodynamic forces, processes involved in vascular remodeling, mechanisms of injury in venous bypass grafts, and mechanisms of dysfunction of AV fistulae used in hemodialysis.     

Prevalence of methicillin resistant Staphylococcus aureus in a tertiary referral hospital in eastern Uttar Pradesh

We report the prevalence of methicillin resistant Staphylococcus aureus (MRSA) infections and their antibiotic susceptibility pattern in our hospital located in eastern Uttar Pradesh. Out of total 549 strains of Staphylococcus aureus isolated from different clinical specimens 301 (54.85%) were found to be methicillin resistant. More than 80% of MRSA were found to be resistant to penicillin, cotrimoxazole, ciprofloxacin, gentamicin, erythromycin, tetracycline, 60.5% to amikacin and 47.5% to netilmicin. However, no strains were resistant to vancomycin. Many MRSA strains (32.0%) were multi-drug resistant. To reduce the prevalence of MRSA, the regular surveillance of hospital associated infection, monitoring of antibiotic sensitivity pattern and formulation of definite antibiotic policy may be helpful.     

Meta-analysis of TNF-alpha promoter -308 A/G polymorphism and SLE susceptibility

Alleles of tumor necrosis factor-alpha (TNF-alpha) gene have been inconsistently associated with systemic lupus erythematosus (SLE), particularly the 308-A/G functional promoter polymorphism. To generate large-scale evidence on whether 308-A/G promoter polymorphism is associated with SLE susceptibility we have conducted a meta-analysis. We have identified 21 studies of this polymorphism and SLE using MEDLINE search. Meta-analysis was performed for genotypes A/A (recessive effect), A/A+A/G (dominant effect), and A allele in fixed or random effects models. All control samples were in Hardy-Weinberg proportion. The overall odds ratio (OR) of the A/A genotype was 3.2 (95% CI=2.0-5.3, P<0.001). Stratification by ethnicity indicated that the A/A genotype was associated with SLE in European-derived population (OR=4.0, CI=2.5-6.4, P<0.001). No association was detected in Asian-derived population (OR, 1.3, CI=0.3-6.3, P=0.76). The overall OR for the risk genotypes (A/A and A/G) was 2.0 (CI=1.3-3.1, P<0.001). Similar results were found between the risk allele A and SLE where a significant association was found in European population (OR=2.1, CI=1.6-2.7, P<0.001), but not in Asian (OR=1.4, CI=0.8-2.3, P=0.2) or African (OR=1.2, CI=0.6-2.5, P=0.59) populations. In summary, this meta-analysis demonstrates that the TNF-alpha promoter -308 A/G polymorphism may confer susceptibility to SLE, especially in European-derived population.     

Interleukin-17 in transverse myelitis and multiple sclerosis

CSF IL-6 is elevated in transverse myelitis (TM) and predicts disability. Since IL-17 regulates cytokines (TNFalpha, IL-1beta and IL-6) known to stimulate IL-6 production by astrocytes, we sought to determine whether IL-17 was increased in TM and MS compared to healthy controls (HC) and other neurologic diseases (OND). IL-17 and IL-6 levels were measured in stimulated peripheral blood mononuclear cell (PBMC) supernatants from HC, MS, TM and OND. IL-17 was increased in TM compared to HC, MS, and OND (mean pg/ml+/-standard error; HC: 36.1+/-11.7, MS: 89.4+/-23.3, TM: 302.6+/-152.5, OND: 41.2+/-13.0, p=0.01). IL-6 was increased in TM relative to MS and HC (HC: 2624 pg/ml+/-641, MS: 6129+/-982, TM: 12,536+/-2657, OND: 6920+/-1801, p<0.002). MS patients with early disease (<2 years) also had increased levels of IL-17 (p<0.04) and IL-6 (p<0.05). Cytokine neutralization experiments demonstrated that IL-6 was the main inducer of astrocyte IL-6 production. We conclude that IL-17 and IL-6 production from PBMC in TM and early MS are increased and induce astrocyte IL-6 production through IL-6.     

Robot assisted “en bloc” radical nephrectomy,splenectomy and distal pancreatectomy for renal cell carcinoma: case report and illustration of technique

A 57-year-old female presented with recurrent gross hematuria and a large left renal mass with solitary pancreatic metastasis. After thorough evaluation, an en bloc robot assisted radical nephrectomy, distal pancreatectomy and splenectomy was performed using a team-based approach between urologists and the transplant/hepatobiliary teams. A standard robotic nephrectomy approach was used with intraoperative ultrasound to determine the extent of pancreatic involvement. Left kidney, left adrenal gland, spleen and pancreatic tail were resected en bloc. Total operative time was 194 min. Perioperative Hemoglobin change was 2.3 g/dL. The final pathology demonstrated a 12.5 cm, Fuhrman grade 3, clear cell RCC along with a 2.5 cm pancreatic metastasis consistent with pT3a, N0, M1 with negative surgical margins. The patient was discharged on post-operative day three and experienced no postoperative complications. This case report highlights the feasibility of this procedure and calls for evaluation of surgical outcomes in this disease category.     

Multiple keratotic papules on palm

Porokeratotic eccrine ostial and dermal duct nevus (PEODDN) is a rare nonhereditary malformation of the eccrine duct. A relationship with linear porokeratosis is not yet established; some consider it as a rare variant of porokeratosis involving the acrosyringium, whereas others consider it a separate entity based on distinctive clinical features and histologic accentuation within ostial structures. A 7-year-old girl presented with multiple asymptomatic keratotic papules over her right palm, present since the age of 6 months. These papules were arranged in a linear distribution over the palm and middle finger of the right hand. Most of the papules were discrete. However, lesions on the middle finger coalesced to form a plaque. Histology revealed a keratin filled deep invagination of the epidermis, notable for a column of parakeratosis ("cornoid lamella"). The dermis was notable for dilated eccrine ducts and absent inflammation. Considering the clinical and histological evidence, a diagnosis of PEODDN was made. Its clinical resemblance to linear lichen planus and linear porokeratosis is discussed. Also, we provide a brief review of this rare condition.     

Hemodynamic and neurohumoral factors in the response of hypertensives to hydrochlorothiazide therapy

We investigated the roles of the renin-angiotensin-aldosterone axis, the sympathetic nervous system, and the responses of the forearm vascular bed in the antihypertensive action of hydrochlorothiazide. Plasma renin activity, aldosterone, catecholamines, blood pressure, and forearm blood flow were measured before and after 8 weeks of hydrochlorothiazide therapy in 21 hypertensive patients whose blood pressures responded to the diuretic, and were then compared to a similar group of 19 hypertensives who did not respond to the thiazide therapy. Dietary salt intake was stable and comparable for the two groups. In the responsive patients, administration of the diuretic caused a significant fall in supine systolic and diastolic blood pressure and forearm vascular resistance, with constant forearm blood flow. No significant changes were noted in these parameters in the non-responsive group. Plasma renin activity and aldosterone concentration was increased in both groups to a comparable extent but plasma norepinephrine and epinephrine concentrations were increased to a greater extent (p less than 0.01) in the responsive group. Heart rate did not change significantly in either group in spite of significant increases in circulating epinephrine. The results are consistent with minimal thiazide-induced volume and salt depletion in either study group. The reduction in blood pressure and forearm vascular resistance observed in the responsive group appears to be the result of diminished target-organ sensitivity towards catecholamines and possibly angiotensin II.