Efficacy and safety of carfilzomib regimens in multiple myeloma patients relapsing after autologous stem cell transplant: ASPIRE and ENDEAVOR outcomes.

Autologous stem cell transplantation (ASCT) is a standard treatment for eligible multiple myeloma (MM) patients, but many patients will relapse after ASCT and require subsequent therapy. The proteasome inhibitor carfilzomib is approved for relapsed or refractory MM (RRMM). In phase 3 trials, carfilzomib-based regimens (ASPIRE, carfilzomib-lenalidomide-dexamethasone; ENDEAVOR, carfilzomib-dexamethasone) demonstrated superior progression-free survival (PFS) compared with standard therapies for RRMM (ASPIRE: lenalidomide-dexamethasone; ENDEAVOR, bortezomib-dexamethasone). This subgroup analysis of ASPIRE and ENDEAVOR evaluated outcomes according to prior ASCT status. In total, 446 patients in ASPIRE and 538 in ENDEAVOR had prior ASCT. Median PFS was longer for carfilzomib-based regimens vs non-carfilzomib-based regimens for patients with prior ASCT (ASPIRE: 26.3 vs 17.8 months (hazard ratio (HR)=0.68); ENDEAVOR: not estimable vs 10.2 months (HR=0.61)), those with one prior line of therapy that included ASCT (ASPIRE: 29.7 vs 17.8 months (HR=0.70); ENDEAVOR: not estimable vs 11.2 months (HR=0.46)), and those without prior ASCT (ASPIRE: 26.4 vs 16.6 months (HR=0.76); ENDEAVOR: 17.7 vs 8.5 months (HR=0.43)). Overall response rates also favored the carfilzomib-based regimens. No new safety signals were detected. This analysis suggests that carfilzomib-based treatment may lead to improvement in PFS and response rates regardless of prior transplant status. Further evaluation is warranted.

A clinico-epidemiological study of herpes zoster.

BACKGROUND: Herpes zoster is a common viral infection of skin caused by reactivation of varicella zoster virus infection from the spinal ganglia. The clinico-epidemiological patterns of this disease in an Indian setting required to be studied. METHODS: A cross sectional study was conducted on all consecutive cases of herpes zoster reporting to the Dermatology Outpatient Department at a Tertiary Care Hospital in Bangalore during a period of one year from 01 Jun 2013 to 31 May 2014. Detailed history, examination, HIV screening and Tzanck smear were carried out in all cases. RESULTS: 84 cases of herpes zoster were seen with a mean age of 30 years. Majority (39%) of cases were seen in the 21-30 year age group. Thoracic segments were involved in 65.4%, cervical in 11.9%, cranial in 11.5%, lumbar in 8.3% and sacral segments in 3.5%. 63% of cases had zoster associated pain. One case had motor involvement.3.57% of the patients were HIV positive. CONCLUSION: This study shows a lower age incidence of herpes zoster HIV positivity and zoster associated pain as compared to other studies. The pattern of segmental involvement in herpes zoster seen in this study was similar to other studies.

Chemically selective polymer substrate based direct isotope dilution alpha spectrometry of Pu.

Quantification of actinides in the complex environmental, biological, process and waste streams samples requires multiple steps like selective preconcentration and matrix elimination, solid source preparations generally by evaporation or electrodeposition, and finally alpha spectrometry. To minimize the sample manipulation steps, a membrane based isotope dilution alpha spectrometry method was developed for the determination of plutonium concentrations in the complex aqueous solutions. The advantages of this method are that it is Pu(IV) selective at 3M HNO3, high preconcentration factor can be achieved, and obviates the need of solid source preparation. For this, a thin phosphate-sulfate bifunctional polymer layer was anchored on the surface of microporous poly(ethersulfone) membrane by UV induced surface grafting. The thickness of the bifunctional layer on one surface of the poly(ethersulfone) membrane was optimized. The thickness, physical and chemical structures of the bifunctional layer were studied by secondary ionization mass spectrometry (SIMS), scanning electron microscopy (SEM) and SEM-EDS (energy-dispersive spectroscopy). The optimized membrane was used for preconcentration of Pu(IV) from aqueous solutions having 3-4M HNO3, followed by direct quantification of the preconcentrated Pu(IV) by isotope dilution alpha spectrometry using (238)Pu spike. The chemical recovery efficiency of Pu(IV) was found to be 86±3% below Pu(IV) loading capacity (1.08 µg in 2×1 cm(2)) of the membrane sample. The experiments with single representative actinides indicated that Am(III) did not sorb to significant extent (7%) but U(VI) sorbed with 78±3% efficiency from the solutions having 3M HNO3 concentration. However, Pu(IV) chemical recovery in the membrane remained unaffected from the solution containing 1:1000 wt. proportion of Pu(IV) to U(VI). Pu concentrations in the (U, Pu)C samples and in the irradiated fuel dissolver solutions were determined. The results thus obtained were found to be in good agreement with those obtained by conventional alpha spectrometry, biamperometry and thermal ionization mass spectrometry.

Isotopic correlation for 242Pu composition prediction: Multivariate regresssion approach.

Multivariate regression calibration using multiple linear regression (MLR), principle component regression (PCR) and partial least squares regression (PLSR) algorithm was performed on 238Pu, 239Pu, 240Pu and 241Pu atom% abundances to predict 242Pu isotopic abundance. The MLR algorithm was found to be the best among these three algorithms. The effect of 238Pu composition on the 242Pu abundance prediction was found to be small but significant especially for achieving high accuracy of <0.5%. PCR and PLSR generated nearly identical results and were inferior to the MLR results. A comparison of MLR results with those obtained by employing seven previously reported empirical methods revealed far superior prediction capability of MLR model. Among the seven empirical models, the best prediction capability was found for Bignan correlation containing 238Pu isotopic data. The study clearly demonstrates that the production of 238Pu and 242Pu has some small correlation and the use of 238Pu in isotopic correlation for 242Pu prediction is important to get accurate results.

Evaluation of the oxidative stress in chronic alcoholics.

AIM: The present study was conducted to assess the activity of Gamma Glutamyl Transferase (GGT) and its association with oxidative stress in alcoholics. METHOD: Sixty male alcoholics with a history of alcohol abuse for more than five years were the subjects of this study. Twenty healthy male volunteers who matched in age and the socio-economic status, served as the control subjects. RESULTS: GGT, reduced glutathione (GSH, a key intra-cellular antioxidant) and malondialdehyde (MDA, a marker of the oxidative stress) were assayed in the plasma of the two groups, and the results were statistically analyzed. The activity of the plasma GGT, known as a marker of Alcoholic Liver Disease (ALD); was significantly higher in the alcoholics as compared to that in the healthy controls. CONCLUSION: There was a significant positive correlation between the enzyme activity and the plasma levels of MDA and this indicated that there was an increased release of this enzyme with enhanced oxidative damage, due to the generation of oxygen free radicals in the study group. There was a significantly increased level of MDA and a decrease in the level of GSH in the alcoholics as compared to those in the controls. Significant negative correlations between GGT and GSH, and between MDA and GSH were observed. The present study demonstrates that alcoholics have a compromised antioxidant defense system.

Immature teratoma of the nose and paranasal sinuses masquerading as bilateral nasal polyposis: a unique presentation.

Teratomas are tumors of multipotent cells derived from all three germ cell layers and recapitulate normal organogenesis. Teratomas are hypothesized to arise by misplacement of multipotent germ cells. Teratoma is usually developmental and sometimes congenital neoplasm which displays both solid and cystic components with gross and microscopic differentiation into a wide variety of tissues representative of all three germ layers--ectoderm, mesoderm and endoderm. We are describing a case which was initially diagnosed as bilateral nasal polyposis clinically but histopathology report came out to be immature teratoma. This case is being reported to make aware all ENT surgeons of such unique presentation of sinonasal teratomas as such presentation of these tumors has not been reported in literature previously, and hence teratomas should be considered in the differential diagnosis of nasal polyposis in future.

Prospectively surveying health-related quality of life and symptom relief in a lot-based sample of medical cannabis-using patients in urban Washington State reveals managed chronic illness and debility.

OBJECTIVES: To characterize health-related quality of life (HRQoL) in medical cannabis patients. METHODS: Short Form 36 (SF-36) Physical Health Component Score and Mental Health Component Score (MCS) surveys as well has CDC (Centers for Disease Control) HRQoL-14 surveys were completed by 37 qualified patients. RESULTS: Mean SF-36 PCS and MCS, normalized at 50, were 37.4 and 44.2, respectively. Eighty percent of participants reported activity/functional limitations secondary to impairments or health problems. Patients reported using medical cannabis to treat a wide array of symptoms across multiple body systems with relief ratings consistently in the 7-10/10 range. CONCLUSION: The HRQoL results in this sample of medical cannabis-using patients are comparable with published norms in other chronically ill populations. Data presented provide insight into medical cannabis-using patients' self-rated health, HRQoL, disease incidences, and cannabis-related symptom relief.

Megacystis, microcolon, intestinal hypoperistalsis syndrome and bilateral streak gonads.

Megacystis, microcolon, intestinal hypoperistalsis is an uncommon condition presenting in neonatal age with features of intestinal obstruction and bladder evacuation abnormalities. We present here an infant girl with the diagnosis consistent with this entity.

Renal tuberculosis in infancy.

We report a case of congenital renal tuberculosis in a 34-day-old child presenting as severe hematuria. Adequate antitubercular treatment may provide protection to fetus in subsequent pregnancies.

Meconium peritonitis presenting as abdominal calcification: three cases with different pathology.

Intra-abdominal calcification is uncommon in newborns and has several causes of which meconium peritonitis is the most frequent. Three neonates with intra-abdominal calcification as a complication of meconium peritonitis are presented. The types of meconium peritonitis were cystic, meconium pseudocyst and meconium ascites. Two required surgical intervention. Meconium peritonitis should be considered in newborns with intra-abdominal calcification.

Use of fission track analysis technique for the determination of MicroBequerel level of 239Pu in urine samples from radiation workers handling MOX fuel.

Fission track analysis (FTA) technique for the determination of (239)Pu excreted through urine has been standardized using blank samples, tracer and (239)Pu spikes. Double stage anion exchange separation protocol has been applied and an average radiochemical recovery of (239)Pu of 18% was obtained. An average track registration efficiency of 11 tracks per µBq of (239)Pu, irradiated to 0.35×10(17) neutron fluence was established. Reagent blank urine samples from 11 controlled subjects were analyzed by FTA and an average of 149±14 tracks was obtained. Minimum detectable activity of 34µBqL(-1) of urine sample was obtained and will be useful for monitoring chronic exposure cases handling MOX fuel.

Outbreak of Meningococcal Infection amongst Soldiers Deployed in Operations.

BACKGROUND: Meningococcal infection may lead to life threatening meningitis and fulminant meningococcal sepsis. Sporadic cases of meningococcal infection have been reported in soldiers but no outbreak in soldiers has been reported earlier from India. This outbreak in soldiers serving in counter insurgency role under field setting was effectively controlled without compromising their operational commitment. METHODS: This is an epidemiological investigation and control of an outbreak of meningococcal infection, bringing out the predisposing factors and highlighting the role of early diagnosis and management of cases. Mass chemoprophylaxis in contacts was used as an effective control measure in the absence of vaccine in this institution based outbreak. RESULT: Out of a total of 17 cases reported, 14 presented as meningitis and three as meningococcemia. Two cases of meningococcemia ended fatally. Serogroup A of Neisseria meningitidis was responsible for this outbreak. Gross over- crowding was the predisposing factor. CONCLUSION: An outbreak of meningococcal infection in soldiers deployed in counter- insurgency role was effectively contained using mass chemoprophylaxis in the absence of meningococcal vaccine.

Determination of 235U/238U atom ratio in uranium samples using liquid scintillation counting (LSC).

A correlation has been developed for the determination of (235)U/(238)U atom ratio in uranium samples using liquid scintillation counting (LSC). The (235)U/(238)U atom ratio determined by thermal ionization mass spectrometry (TIMS) was correlated to the ratio of (i) alpha-count rate and (ii) Cerenkov count rate due to (234 m)Pa in the sample; both measured by LSC. This correlation is linear over the range of (235)U/(238)U atom ratio encountered in the nuclear fuel samples, i.e. the low enriched uranium (LEU) samples with (235)U<20 atom%. The methodology based on this correlation will be useful for the quick determination and verification of (235)U/(238)U atom ratios in fuel samples using cost effective technique of LSC.

Laser-induced breakdown spectroscopy for simultaneous determination of Sm, Eu and Gd in aqueous solution.

This paper reports studies on the determination of trace levels of samarium, europium and gadolinium in aqueous samples by laser-induced breakdown spectroscopy (LIBS). In this work, a membrane-based filter paper was used as a sample support for the liquid samples. The laser-induced plasma was produced in air at atmospheric pressure, using a pulsed Nd:YAG laser. Calibration standards and synthetic mixtures of these lanthanides were prepared using solutions prepared from respective high purity oxides. Linear calibration was obtained for Sm, Eu and Gd by normalizing the intensities of lanthanides emission lines with respective to C(I) 193.029 nm emission line. The concentrations of Sm, Eu and Gd were then determined in a solution containing a mixture of these lanthanides. The concentrations of individual lanthanides were obtained within 5% of the expected values. Limits of detection were found to be 1.3 ppmw (Sm), 1.9 ppmw (Eu) and 2.3 ppmw (Gd).

Use of faecal excretion function for quick estimation of initial and existing lung burden for occupational exposure control due to 239Pu for S-class of intake.

Two functions namely initial lung deposition and lung retention per unit faecal excretion rate are constructed primarily based on the excretion pattern of four subjects exposed to (239)Pu. In the absence of initial clear knowledge about the class of compound inhaled, faecal to urine excretion ratio was used to infer the type of inhaled class. Trends in the urine and faecal data had suggested that the intake was due to mixed class of plutonium compound for each case. With the assumption of 1:1 mixture of plutonium M&S class inhaled compound, faecal excretion rates for only S-class intake were worked out. Uptake inferred based on their urinary data had suggested it to be of similar level within 40% of uncertainty for 5 microm particle size distribution. Data, all the four cases, were pooled for analysis citing the similar level of intake, particle size distribution, nature and pattern of work. The function obtained was tested for S-class lung retention and faecal excretion rate value. These functions are handy tool for estimating initial lung burden and lung retention value for low level of S-class plutonium intake based on subject faecal analysis data.

Derivation and validation of a urinary excretion function for plutonium based on occupational exposure.

Formation of a three-component urinary excretion function using the data of occupational exposure cases is described. Measurement results of plutonium inhalation from two subjects over 6000 and 2500 d are used in the derivation of this function. The three-component excretion function obtained is U(t) = 0.0008e(-0.0566(t)) + 0.00009e(-0.0042(t)) + 0.00004e(-0.00008(t)). The function is therefore proposed as a reliable basis to make an uptake assessment for operational control for mixed class of plutonium dominated by M-class chronic exposure.

Blood glutathione levels in head and neck malignancies.

Blood glutathione was estimated in fifty patients of head and neck cancer in the age group of 18-76 years and the results were compared with a group of normal healthy controls. Mean blood glutathione level was found to be significantly lowered in patients than the controls. Irrespective of the site, TNM classification, histopathology, and character of lesion, fall in blood glutathione was nearly same in all the patients. The mean level was significantly increased after radiotherapy when compared with the levels before radiotherapy. The decreased levels of GSH in-patients with head and neck cancer, observed in the present study, may be due to its increased utilization by the cells. The results suggest that patients with head and neck cancer have increased oxidative stress.