Expression analysis and clinical utility of L-Dopa decarboxylase (DDC) in prostate cancer

BackgroundL-Dopa decarboxylase (DDC) is a pyridoxal 5′-phosphate-dependent enzyme that was found to be involved in many malignancies. The aim of this study was to investigate the mRNA expression levels of DDC in prostate tissues and to evaluate its clinical utility in prostate cancer (CaP).MethodsTotal RNA was isolated from 118 tissue specimens from benign prostate hyperplasia (BPH) and CaP patients and a highly sensitive quantitative real-time RT-PCR (qRT-PCR) method for DDC mRNA quantification has been developed using the SYBR Green^® chemistry. LNCaP prostate cancer cell line was used as a calibrator and GAPDH as a housekeeping gene.ResultsDDC was found to be overexpressed, at the mRNA level, in the specimens from prostate cancer patients, in comparison to those from benign prostate hyperplasia patients (p < 0.001). Logistic regression and ROC analysis have demonstrated that the DDC expression has significant discriminatory value between CaP and BPH (p < 0.001). DDC expression status was compared with other established prognostic factors, in prostate cancer. High expression levels of DDC were found more frequently in high Gleason's score tumors (p = 0.022) as well as in advanced stage patients (p = 0.032).ConclusionsOur data reveal the potential of DDC expression, at the mRNA level, as a novel biomarker in prostate cancer.     

Diode laser treatment of human prostates – Clinical 6-month experience

ObjectivesLaser-assisted vaporization of prostate tissue by means of the KTP laser is in clinical use. Alternative laser sources are available but are lacking clinical experience. In this study, the capability, feasibility, and post-operative outcome of vaporization of prostate by means of a diode laser were investigated.MethodsThe light (λ=1470 nm, 50 W) of a diode laser (Biolitec AG, Jena, Germany) was fed into a side-fire fiber introduced through a 24F continuous-flow cystoscope and thus transmitted to prostate tissue. Normal saline was used for irrigation with additive of 1% ethanol for observation of TUR syndrome. The study includes 10 men suffering from bladder outlet obstruction due to benign prostatic hyperplasia (BPH) (prostate volume range: 35–78 ml). The prostatic lobes were vaporized within the prostatic capsule. Depending on the vaporized tissue the exposure time was in the range of 1220–4000 s (mean: 2397±757 s) during which a mean of 121±38 kJ (range: 61–200 kJ) of energy was delivered. Post-operative outcome and voiding were evaluated during a follow-up of 6 months.ResultsDuring surgery no significant blood loss or any fluid absorption occurred. Catheters were removed in the mean after 50 h (range: 18–168 h). All patients excepted two, were satisfied with their voiding outcome. After removing the catheter the mean peak urine flow rate significantly (p=0.05) increased from 8.9±2.9 ml/s pre-operatively to 15.7±5 ml/s post-operatively. No evidence of urgency, dysuria, hematuria, or incontinence was observed. Two patients required re-catheterization and consecutive TURP. After 1 month as well as after 6-month follow-up, 8/10 patients are still satisfied with the outcome.ConclusionThis first and limited experience showed that 50 W-1470 nm-diode-laser vaporization prostatectomy is feasible and appears to be safe and effective for quickly relieving bladder outlet obstruction due to BPH. Long-term efficacy and durability should be evaluated in a randomized clinical trial with long-term follow-up.     

Backboards are important when chest compressions are provided on a soft mattress

AimDetermine the impact of backboard placement, torso weight and bed compression on chest compression (CC) depth feedback in simulated cardiac arrest patients.MethodsEpochs of 50 high quality CCs with real-time feedback of sternum-to-spine compression depth were provided by a blinded BLS/ACLS/PALS certified provider on manikins of two torso weights (25 vs. 50 kg), using three bed surfaces (stretcher, Stryker hospital bed with Impression mattress, soft Total Care ICU bed), with/without a backboard (BB). Two BB sizes were tested (small: 60 cm × 50 cm; large: 89 cm × 50 cm) in vertical vs. horizontal orientation. Mattress displacement was measured using an accelerometer placed internally on the spine plate of the manikin. Mattress displacement of ≥5 mm was prospectively defined as the minimal clinically important difference.ResultsDuring CPR (CC depth: 51.8 ± 2.8 mm), BB use significantly reduced mattress displacement only for soft ICU beds. Mattress displacement was reduced (vs. no BB) for 25 kg torso weight: small BB12.3 mm (95%CI 11.9–12.6), horizontally oriented large BB 11.2 mm (95%CI 10.8–11.7), and vertically oriented large BB 12.2 mm (95%CI 11.8–12.6), and for 50 kg torso weight: small BB 7.4 mm (95%CI 7.1–7.8), horizontally oriented large BB 7.9 mm (95%CI 7.6–8.3), and vertically oriented large BB 6.2 mm (95%CI 5.8–6.5; all p < 0.001). BB size and orientation did not significantly affect mattress displacement. Lighter torso weight was associated with larger displacement in soft ICU beds without BB (difference: 6.9 mm, p < 0.001).ConclusionBB is important for CPR when performed on soft surfaces, such as ICU beds, especially when torso weight is light. BB may not be needed on stretchers, relatively firm hospital beds, or for patients with heavy torso weights.     

Association of beta 1-adrenergic receptor gene polymorphisms with left ventricular hypertrophy in human essential hypertension

ObjectivesExperimental evidence support a key role for beta (1)-adrenergic receptor (ADRB1) in the modulation of cardiac mass. This relationship has not yet been described in Chinese population. The goal of our study was to investigate the relationships between ADRB1 gene polymorphisms and left ventricular structure in human essential hypertension.Design and methodsA total of 2417 hypertensive patients were successfully investigated. The polymorphisms of ADRB1 gene (Arg389Gly and Gly49Ser) were genotyped by using PCR-RFLP and confirmed by sequencing.ResultsPatients carrying the Arg389Arg genotype had an increase in the left ventricular septal thickness (10.4 ± 1.5 mm vs. 9.6 ± 1.5 mm, P < 0.01 or 9.4 ± 1.4 mm, P < 0.01); left ventricular posterior wall thickness (10.4 ± 2.4 mm vs. 9.6 ± 2.4 mm or 9.7 ± 2.9 mm, P < 0.01); left ventricular mass index (51.6 ± 13.3 g/m^2.7 vs. 44.6 ± 12.9 g/m^2.7, P < 0.01 or 43.2 ± 14.4 g/m^2.7, P < 0.01) and relative wall thickness (45.0 ± 9.0% vs. 42.6 ± 8.1%, P < 0.01 or 43.2 ± 8.8%, P < 0.01) as compared with those carrying genotypes Arg389Gly and Gly389Gly. These associations were independent of anthropometric factors and major clinical features and were replicated in another independent hypertensive population (n = 327).ConclusionsOur findings show that the Arg389Gly polymorphism of the ADRB1 gene confers higher risk of left ventricular hypertrophy in human essential hypertension.     

Quantitative analysis of chest compression interruptions during in-hospital resuscitation of older children and adolescents

AimTo quantitatively describe pauses in chest compression (CC) delivery during resuscitation from in-hospital pediatric and adolescent cardiac arrest. We hypothesized that CPR error will be more likely after a chest compression provider change compared to other causes for pauses.MethodsCPR recording/feedback defibrillators were used to evaluate CPR quality for victims ≥8 years who received CPR in the PICU/ED. Audiovisual feedback was supplied in accordance with AHA targets. Etiology of CC pauses identified by post-event debriefing/reviews of stored CPR quality data.ResultsAnalysis yielded 205 pauses during 304.8 min of CPR from 20 consecutive cardiac arrests. Etiologies were: 57.1% for provider switch; 23.9% for pulse/rhythm analysis; 4.4% for defibrillation; and 14.6% “other.” Provider switch accounted for 41.2% of no-flow duration. Compared to other causes, CPR epochs following pauses due to provider switch were more likely to have measurable residual leaning (OR: 5.52; CI⁹⁵: 2.94, 10.32; p < 0.001) and were shallower (43 ± 8 vs. 46 ± 7 mm; mean difference: ?2.42 mm; CI⁹⁵: ?4.71, ?0.13; p = 0.04). Individuals performing continuous CPR ≥ 120 s as compared to those switching earlier performed deeper chest compressions (42 ± 6 vs. 38 ± 7 mm; mean difference: 4.44 mm; CI⁹⁵: 2.39, 6.49; p < 0.001) and were more compliant with guideline depth recommendations (OR: 5.11; CI⁹⁵: 1.67, 15.66; p = 0.004).ConclusionsProvider switches account for a significant portion of no-flow time. Measurable residual leaning is more likely after provider switch. Feedback systems may allow some providers to continue high quality CPR past the recommended switch time of 2 min during in-hospital resuscitation attempts.     

Lipid transfers to HDL are predictors of precocious clinical coronary heart disease

BackgroundHigh-density-lipoprotein (HDL) has several antiatherogenic properties and, although the concentration of HDL-cholesterol negatively correlates with incidence of coronary artery disease (CAD), this is not sufficient to evaluate the overall HDL protective role. The aim was to investigate whether precocious CAD patients show abnormalities in lipid transfers to HDL, a fundamental step in HDL metabolism and function.MethodsThirty normocholesterolemic CAD patients aged < 50 y and 30 controls paired for sex, age and B.M.I. were studied. Fasting blood samples were collected for the in vitro lipid transfer assay and plasma lipid determination. A donor nanoemulsion labeled with radioactive free-cholesterol, cholesteryl esters, phospholipids and triglycerides was incubated with whole plasma and after chemical precipitation of non-HDL fractions, supernatant was counted for radioactivity in HDL.ResultsLDL and HDL-cholesterol and triglycerides were equal in both groups. Transfers of free-cholesterol (3.8 ± 1.2%vs 7.0 ± 3.3%,p < 0.0001) and triglycerides (3.7 ± 1.7%vs 4.9 ± 1.9%, p = 0.0125) were diminished in CAD patients whereas cholesteryl ester transfer increased (6.5 ± 1.9%vs 4.8 ± 1.8%, p = 0.0008); phospholipid transfer was equal (17.8 ± 3.5% vs19.5 ± 3.9%).ConclusionAlterations in the transfer of lipids to HDL may constitute a new marker for precocious CAD and relation of this metabolic alteration with HDL antiatherogenic function should be investigated in future studies.     

UPLC MS/MS method for quantification of mycophenolic acid and metabolites in human plasma: Application to pharmacokinetic study

BackgroundWe described the development and full validation of a rapid, high throughput sensible and accurate UPLC method using tandem mass spectrometry detection for mycophenolate acid (MPA) and its metabolites, MPA glucuronide (MPAG) and acyl MPA glucuronide (AcMPAG) concentration determination with MPA-D3 as internal standard in human plasma.MethodsPlasma pretreatment involved a one-step protein precipitation with acetonitrile. The separation was performed by reverse-phase chromatography on a Waters BEH HSST3 100 mm*2.1 mm*1.8 μm column. The multiple reaction monitoring transitions used for quantification were m/z 321.04 → 303.02 for MPA, 524.09 → 303.02 for AcMPAG and MPAG and 324.03 → 306.04 for MPA-D3 in the electrospray positive ionization mode.ResultsThe method was linear over the concentration range of 0.1–20 mg/L for MPA and AcMPAG and 1–200 mg/L for MPAG respectively. The intra- and inter-day precision values were below 14% and accuracy was from 94.0 to 103.3% at all quality control levels. The lower LOQ was 0.1 mg/L for MPA and AcMPAG, 1 mg/L for MPAG.ConclusionSample analysis time was reduced to 7 min including sample preparation. The present method was successfully applied to a pharmacokinetic study following oral administration of enterocoated sodium mycophenolate in de novo renal transplantation.     

Effect of lidocaine phonophoresis on sensory blockade: pulsed or continuous mode of therapeutic ultrasound?

ObjectiveThe optimisation of drug absorption through skin is of great value in modern therapy. Phonophoresis is the use of therapeutic ultrasound to increase percutaneous drug absorption. However, few studies have compared pulsed and continuous modes of therapeutic ultrasound. This study compared these two modes by investigating the effect of lidocaine phonophoresis on sensory blockade. Lidocaine is a common local anaesthetic drug that is used topically to relieve pain and also for minor surgery.DesignPre–post intervention study.ParticipantsNinety-three healthy volunteers, assigned at random to one of three ultrasound groups: pulsed (ultrasound + lidocaine), continuous (ultrasound + lidocaine) and control (sham ultrasound + lidocaine).InterventionLidocaine (approximately 2 cm³) was administered transdermally using a transducer.Outcome measuresTwo-point discrimination, touch and maximum pain thresholds were assessed before and after the intervention in each group.ResultsThere were significant increases in two-point discrimination, touch and maximum pain thresholds after the intervention in all groups (P < 0.05). The mean differences in the threshold changes between the pulsed and continuous groups were significant [two-point discrimination: mean difference 0.66 (standard deviation, SD 0.41) mm, 95% confidence interval (CI) 0.18 to 1.21, P < 0.001; touch: mean difference 1.31 (SD 0.23) mA, 95% CI 0.98 to 1.96, P < 0.001; maximum pain: mean difference 5.59 (SD 4.01) mA, 95% CI 1.01 to 10.11, P < 0.001]. Statistical analysis also revealed significant differences for all senses between the pulsed and control groups [two-point discrimination: mean difference 0.61 (SD 0.29) mm, 95% CI 0.26 to 1.3, P < 0.001; touch: mean difference 1.45 (SD 0.38) mA, 95% CI 0.96 to 2.1, P < 0.001; maximum pain difference 9.17 (SD 4.13) mA, 95% CI 4.32 to 14.1, P < 0.001]. The mean difference in the change in maximum pain threshold between the continuous and control groups was significant [mean difference 3.58 (SD 3.44) mA, 95% CI 0.09 to 8.3, P = 0.001], but two-point discrimination and touch threshold changes revealed no significant difference between the continuous and control groups [two-point discrimination: mean difference 0.05 (SD 0.28) mm, 95% CI ?0.31 to 0.48, P = 0.968; touch: mean difference 0.14 (SD 0.19) mA, 95% CI ?0.21 to 0.43, P = 0.339].ConclusionPulsed ultrasound with topical lidocaine gel induced greater anaesthetic effect compared with continuous ultrasound with topical lidocaine gel and lidocaine application alone. The mechanical properties of pulsed ultrasound appear to be responsible for greater drug penetration.     

Sensitivity of Erythrocyte Sedimentation Rate and C-reactive Protein for the Exclusion of Septic Arthritis in Emergency Department Patients

BackgroundPrevious studies in post-operative orthopedic and pediatric patients suggest that erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) testing may be helpful in ruling out septic arthritis. However, these tests have not been evaluated in a population of adult Emergency Department (ED) patients.Study ObjectiveDetermine the sensitivity of ESR and CRP in patients with septic arthritis.MethodsRetrospective analysis of ED patients with septic arthritis from 2003 to 2008. Eligible patients had an International Classification of Diseases - Ninth Revision diagnosis of pyogenic arthritis (711.0x) plus: positive synovial fluid culture, positive synovial Gram stain, or operative irrigation. Patients were excluded if no ESR or CRP was performed within 24 h. Sensitivity of ESR and CRP at various cutoffs was calculated with 95% confidence intervals (CI).ResultsWe identified 167 patients with septic arthritis. We included 143 (86%) who had ESR (n = 140, 84%) or CRP (n = 96, 57%) performed. Mean age was 49 (± 22) years, and 85 (59%) were male. Race was: 125 (87%) white, 4 (3%) black, and 12 (8%) Hispanic. Thirty-five (24%) had infection of prosthetic joints. Synovial cultures were positive in 102 (71%). Sensitivity of ESR was: 98% (95% CI 94–100%) using a cutoff of ≥ 10 mm/h (n = 134) and 94% (95% CI 88–97%) using a cutoff of ≥ 15 mm/h (n = 131). The sensitivity of CRP was 92% (95% CI 84–96%) using a cutoff of ≥ 20 mg/L (n = 88).ConclusionESR and CRP have sensitivities of > 90% for septic arthritis, but only when low thresholds are used. Further study is required to determine the clinical usefulness of ESR and CRP testing.     

Association of high sensitivity C-reactive protein (hsCRP) and tumour necrosis factor-alpha (TNF-alpha) with carotid intimal medial thickness in subjects with different grades of glucose intolerance--the Chennai Urban Rural Epidemiology Study (CURES-31)

ObjectiveTo assess the association of high sensitivity C-Reactive Protein [hsCRP] and Tumour Necrosis Factor-α [TNF-α] with IMT in Asian Indians with different grades of glucose intolerance.Design and methodsSubjects with normal glucose tolerance [NGT](n = 150), impaired glucose tolerance [IGT] (n = 150) and type 2 diabetes (DM) (n = 150) were recruited from the Chennai Urban Rural Epidemiology Study [CURES], in south India. hsCRP was estimated by nephelometry and TNF-α by enzyme linked immunosorbent assay. Carotid IMT was assessed by high resolution B-mode ultrasonography.ResultshsCRP and TNF-α levels were higher in those with DM [p < 0.001] and IGT [p < 0.001] compared to NGT. In linear regression analysis, both hsCRP [p = 0.003] and TNF-α [p =0.001] showed an association with IMT among NGT subjects even after adjusting for age and gender. Among IGT subjects, TNF-α was associated with IMT [p < 0.001], while no association was observed either with hsCRP or TNF-α in diabetic subjects. In NGT subjects, mean IMT was highest in those with high values [III tertile] of both TNF-α and hsCRP [0.83 ± 0.1 mm; p < 0.001] followed by those with high TNF-α + low hsCRP [0.74 ± 0.09 mm; p < 0.001], high hsCRP  low TNF-α [0.67 ± 0.09 mm; p < 0.001], and lowest in those with both low TNF-α and hsCRP [I tertile] [0.63 ± 0.05 mm.ConclusionWe conclude that in Asian Indians 1. Levels of hsCRP and TNF-α increase with increasing severity of glucose intolerance 2. Both hsCRP and TNF-α are associated with IMT in NGT subjects while TNF-α alone is associated with IMT in IGT subjects 3. hsCRP and TNF-α have a cumulative effect on mean IMT values in NGT subjects.     

CLSI EP17-A protocol: a useful tool for better understanding the low end performance of total prostate-specific antigen assays

BackgroundClinical Laboratory and Standards Institute (CLSI) published EP17-A guideline, recommending new definitions for low end performances: Limit of Blank (LoB), Limit of Detection (LoD) and Limit of Quantitation (LoQ). The aim of this study was to determine LoB, LoD and LoQ by applying EP17-A to Hybritech and World Health Organization (WHO) calibrated Access Total PSA assays, and verify the correlation between results generated by the same reagent with both calibrations, particularly at low end concentrations.MethodsAccording to EP17-A, serum pools of anonymous routine patient samples residuals were analyzed on a UniCelDxI800 with the chemiluminescent Access®Hybritech®TotalPSA assay.ResultsLoB: 0.0046 μg/L Hybritech, 0.005 μg/L WHO calibration; LoD: 0.014 μg/L Hybritech, 0.015 μg/L WHO; LoQ at 20% coefficient of variation (CV%) 0.0414 μg/L Hybritech, 0.034 μg/L WHO. Regression Hybritech y = 0.2398× + 4.2017 (R² = 0.9515); WHO y = 0.2248× + 3.4335 (R² = 0.9596) with no statistical difference. Comparison between Hybritech and WHO at low PSA levels indicated an excellent Pearson's and intraclass correlation (r = 0.999, p < 0.001; ICC = 0.974, p < 0.001).ConclusionsOur results show that the Access Total PSA assay is suitable for prostate cancer recurrence and PSA velocity evaluation; Hybritech and WHO calibrated values can both be used for clinical purposes even at low levels.     

Effect of somatostatin analogue octreotide on pain relief after major abdominal surgery

BackgroundOctreotide acetate is an 8-amino-acids synthetic octapeptide analogue of somatostatin with much-enhanced duration of action and lower incidence of side effects. We assessed the utility of using intravenous octreotide as an adjuvant to opioid analgesia that might exert a post-operative opioid-sparing effect.MethodsForty-four patients were randomly allocated, to receive either a placebo or intraoperative octreotide 0.33 μg kg^?1 h^?1 intravenous infusion that was maintained in the post-operative period. Patients received for post-operative analgesia an intravenous piritramide patient controlled analgesia (PCA), set to deliver a piritramide 0.02 mg kg^?1 dose.ResultsTwo-way ANOVA revealed significantly fewer (P = 0.0003) mean ± SD weighted piritramide dose requirements in the octreotide group (19.5 ± 6.3 μg kg^?1 h^?1) than in the control group (35.7 ± 8.2 μg kg^?1 h^?1). Dunnett’s two-sided multiple-comparison post hoc test revealed a significant difference between the two groups during the first 22 post-operative hours, following which there were no differences between the two groups. There were no significant differences over time in the mean arterial pressure (P = 0.722), heart rate (P = 0.579) and respiratory rate (P = 0.823) between the octreotide group (80 ± 10 mm Hg, 74 ± 12, 14 ± 2) and the control group (82 ± 9 mm Hg, 76 ± 11, 15 ± 3), respectively.ConclusionWe demonstrated that perioperative octreotide intravenous infusion could be an adjuvant to opioid analgesia as it exerted a piritramide opioid-sparing effect. We encountered more systemic side effects such as nausea, abdominal discomfort, and diarrhea in the octreotide group than in the control group. Our findings could be beneficial to patients who cannot tolerate the adverse effects of opioids.     

Advantages of prostate-specific antigen (PSA) clearance model over simple PSA half-life computation to describe PSA decrease after prostate adenomectomy

ObjectivesA population kinetic approach based on PSA clearance (CL_PSA) may be a more rational strategy to characterize prostate-specific antigen (PSA) decrease profile after prostate surgery than the commonly used method (half-life from mono/bi-exponential models).MethodsWe used 182 post-adenomectomy PSA concentrations from 56 benign prostatic hyperplasia patients to build, with NONMEM software, a multi-exponential and a CL_PSA model for comparison.ResultsThe best multi-exponential model was PSA(t) = 4.96e^? 0.269t + 3.10e^? 0.16t + 0.746e^+ 0.0002t with a stable median residual PSA at 0.64 ng/mL. The best model parametrized with clearance was CL_PSA = 0.0229 ^? (AGE/69)^3.78. Akaike information criteria and standard errors favored the CL_PSA model. Median peripheral zone and transitional zone productions were 0.034 ng/mL/cm³ and 0.136 ng/mL/g. A threshold at 2 ng/mL on day 90 allowed for a diagnostic of biochemical relapse diagnostic.ConclusionsThe population CL_PSA model was superior to the multi-exponential approach for investigating individual post-adenomectomy PSA decreases.     

HPLC-FLD determination of serum aromatic amino acids: application in chronic kidney disease patients

BackgroundThe aromatic amino acids (AAA) are very important amino acids in the body and have been suggested to be involved in many diseases. We describe the development and full validation of a high performance liquid chromatography with fluorescence detection (HPLC–FLD) method for simultaneously quantitative determination of serum AAA. Furthermore, we aimed to explore the clinical significances of AAA for chronic kidney disease (CKD).MethodsSerum samples were deproteinized by perchloric acid. Separation was carried out on a Megres C18 column (4.6 mm × 250 mm i.d., 5 μm). The mobile phase consisted of 10% acetonitrile (v/v) in water and was run at a flow rate of 1.0 ml/min. The eluted AAA was monitored by measuring the fluorescence intensity using the programmed wavelength detection setting.ResultsAAA determination in a serum sample was achieved in < 10 min. The linear ranges of the method were 0.55–275 μmol/l, 3.05–1220.0 μmol/l and 0.049–49 μmol/l for Tyr, Phe and Trp, respectively. The limit of detection (LOD) was 0.014 μmol/l for Tyr, 0.5 μmol/l for Phe, and 0.0049 μmol/l for Trp. Recovery and reproducibility were satisfactory. Compared with healthy control subjects, the CKD patients showed lower serum levels of AAA. It should probably available to apply for screening and monitoring of CKD.ConclusionsThe method is simple, fast, accurate, and suitable for routine analysis.     

Quality of life and brace-treated idiopathic scoliosis: a cross-sectional study performed at the Centre des Massues on a population of 120 children and adolescents

ObjectivesTo determine the influence of orthopedic treatment on quality of life (QoL) in children and adolescents with idiopathic scoliosis and treated with either the carbon brace (CMCR, corset monocoque carbone respectant la respiration) or the Lyon brace. To compare these braces.Patients and methodsA cross-sectional study on a population of 120 patients with idiopathic scoliosis, visiting for routine evaluation following the onset of an orthopedic treatment at the Centre des Massues in Lyon. Eighty-two patients used the carbon brace and 38 patients used the Lyon brace. The patients completed the SRS-22 questionnaire (where a low score means a bad QoL), an evaluation scale of QoL specific to spinal deformities, and visual analogue scales (VAS) for pain, motivation and QoL ranging from 0 to 100 mm.ResultsThe QoL of Lyon brace-treated patients is significantly worse than that of patients treated with a carbon brace for the overall score (mean ± SD, 4.05 ± 0.37 vs 3.77 ± 0.46, P = 0.002) as well as for function (P = 0.01), pain (P = 0.001), and appearance (P = 0.004). These results are confirmed by the VAS for QoL (P = 0.001).ConclusionThe use of the carbon brace and of the Lyon brace induces a reduction in QoL whatever the evaluation tool, either SRS-22 or VAS. However, the use of the Lyon brace impairs QoL more than the use of the carbon brace.     

Emesis and gastrointestinal problems during radiotherapy: A comparison of performance of daily activities between patients experiencing nausea and patients free from nausea

Purpose of the researchTo describe the experiences of nausea, vomiting and gastrointestinal problems during radiotherapy, and to compare patients experiencing nausea with patients not experiencing nausea regarding performance in daily activities, sleeping and eating capacity.Methods and sampleA cross-sectional sample of 131 Swedish radiotherapy patients answered a questionnaire regarding the preceding week of radiotherapy. Mean age was 63 years (standard deviation 12.1) and 56% were women. The radiotherapy fields were breast (35%), abdomen/pelvis (15%), prostate/bladder (21%), head/neck (10%) and other (8%).Key resultsThe patients experiencing nausea within the observed week (n = 31) had, compared to the patients not experiencing nausea (n = 100), lower ability in daily activities in general (p = 0.001), in shopping (p = 0.014), walking (p = 0.007) and social interaction (p = 0.007). Of the patients with nausea 48% had seldom woken up rested and 34% were not able to eat as much as they used to. Corresponding figures for nausea free patients were 27% (not significant; ns) and 16% (ns). Six (5%) experienced vomiting, 15 (12%) diarrhoea, 23 (18%) constipation and 52 (40%) any gastrointestinal symptoms. Forty seven (90%) were negatively bothered by the experienced gastrointestinal symptoms.ConclusionsThe fourth of patients experiencing nausea during radiotherapy had lower ability to perform daily activities than the three quarters of patients who were free from nausea. Few patients vomited while 40% experienced gastrointestinal symptoms during the observed week of radiotherapy. This implies that health care professionals could consider identifying nauseous patients that possibly need support in nausea-reduction and in daily activities during radiotherapy.     

Intraoperative segmentation of iodine and palladium radioactive sources in C-arm images

Purpose

   Dynamic dosimetry is becoming the standard to evaluate the quality of radioactive implants during brachytherapy. For this, it is essential to obtain a 3D visualization of the implanted seeds and their relative position to the prostate. A method was developed to obtain a robust and precise segmentation of seeds in C-arm images, and this approach was tested using clinical datasets.

Method

   A region-based implicit active contour approach was used to delineate implanted seeds. Then, a template-based matching was employed to segment iodine implants whereas a K-means algorithm is implemented to resolve palladium seed clusters. To validate the method, 55 C-arm images from 10 patients were used for the segmentation of iodine sources, whereas 225 C-arm images from 16 patients were used for the palladium case.

Results

   Compared to manual ground truth segmentation of 6,002 iodine seeds and 15,354 palladium seeds, 98.7 % of iodine sources were automatically detected and declustered showing a false-positive rate of only 1.7 %. A total of 98.7 % of palladium sources were automatically detected and declustered with a false-positive rate of only 2.0 %.

Conclusion

   An automated segmentation method was developed that is able to perform the identification and annotation processes of seeds on par with a human expert. This method was shown to be robust and suitable for integration in the dynamic dosimetry workflow of prostate brachytherapy interventions.     

Analysis of glucocerebrosidase activity in dry blood spots using tandem mass spectrometry

BackgroundGaucher disease (GD) is due to deficiency of acid-β-glucosidase (ABG) and comprises a clinical spectrum with variable age of onset and severity. We evaluated a tandem mass spectrometry (MS/MS) method to measure ABG activity for high through-put screening.MethodsABG activity was measured in 3.2 mm punches from dry blood spots (DBS). Each punch was incubated for 21 h with the substrate D-Glucosyl-β1-1′-N-dodecanoyl-D-erythro-sphingosine [C12-glucocerebroside (C₃₆H₆₉NO₈)] and internal standard N-myristoyl-D-erythro-sphingosine [C14-ceramide (C₃₂H₆₃NO₃)]. The product and internal standard were quantified using MS/MS.ResultsABG activities in anonymized newborn screening samples from NY State were (mean) 22.0 μmol/h/L ± (SD) 13.8 μmol/h/L (n = 2088, median 19.9 μmol/h/L, 95%CI 22.59–21.41 μmol/h/L). The enzymatic activity in DBS from 10 treatment naïve adult Gaucher patients was less than 4.2 μmol/h/L. ABG activity was stable for 3 months at room temperature a 20% activity reduction was observed. Inter- and intra-run imprecisions were 8% and 13.7%, respectively. The limit of detection was 0.75 μmol/h/L and limit of quantification was 1.25 μmol/h/L.ConclusionsThe measurement of ABG activities in DBS using MS/MS is suitable for high-throughput analysis of at-risk individuals and potentially for newborn screening for GD.     

Relationship between circulating cytokine levels and physical or psychological functioning in patients with advanced cancer

ObjectiveTo investigate the relation between functional impairments of cancer patients and circulating cytokines using a multiplex technique.Design and methods50 patients with cancer were assessed using the quality of life (QOL) questionnaire. 27 plasma cytokine levels were determined by using the Bio-Plex array system. The relation to QOL scores was assessed using Chi-square test for categorical variables and univariate linear regression analysis for cytokine levels.ResultsMultivariate analysis showed that interleukin-6 (IL-6) level is a significant independent determinant of physical (β = ? 0.238, P = 0.0126) and cognitive functioning (β = ? 0.462, P = 0.0006) and that vascular endothelial growth factor (VEGF) level is a significant independent determinant of emotional functioning (β = ? 0.414, P = 0.039).ConclusionThis study, in which 27 cytokines are simultaneously tested with cutting edge technology, demonstrates that plasma IL-6 and VEGF are significant independent determinants of functional impairments in patients with cancer.     

Serum MMPs and TIMPs: May be predictors of breast carcinogenesis?

BackgroundThe involvement of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in breast cancer has been documented on palpable lesions. This study aims to assess serum MMP1, MMP-2, TIMP-1, and TIMP-2 in atypical ductal hyperplasia (ADH), lobular neoplasia (LN), ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) specifically in non-palpable mammographic breast lesions.MethodsOn women with benign (n = 65), precursor [ADH (n = 18) and LN (n = 15)], preinvasive [DCIS (n = 32)] and invasive [IDC (n = 28)] lesions the serum concentrations of MMP-1, MMP-2, TIMP-1, TIMP-2, TPS, and TPA were determined with immunoenzymatic assays. All women had non-palpable mammographic breast lesions of less than 10 mm in diameter, as estimated on the mammographic views. Statistical analysis followed.ResultsTIMP-2 serum concentrations were positively associated with the severity of the lesion. On the contrary, MMP-2 levels were marginally negatively associated with severity; as evident, the MMP-2/TIMP-2 ratio significantly decreased along with severity. Regarding TIMP-1, TPS, TPA, and TIMP-1/TIMP-2, no significant associations were demonstrated. MMP-2 and the MMP-2/TIMP-2 ratio were significantly higher in the LN subgroup versus the ADH subgroup.ConclusionTIMP-2 and MMP-2/TIMP-2 ratio may exhibit meaningful changes along with progression of lesions. Extracellular cell matrix remodeling in ductal and lobular lesions may follow distinct patterns.