Long non-coding RNAs TUG1 and MEG3 in patients with type 2 diabetes and their association with endoplasmic reticulum stress markers.

BACKGROUND: Long non-coding RNAs (lncRNAs), including taurine upregulated gene 1 (TUG1), metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), and maternally expressed 3 (MEG3) play a regulatory role in endoplasmic reticulum (ER) stress. The present study aimed to investigate the expression of these lncRNAs in patients with type 2 diabetes and their association with biochemical and ER stress parameters. MATERIALS AND METHODS: Participants included 57 patients with diabetes and 32 healthy individuals. Real-time PCR was performed to assess MALAT1, TUG1, MEG3, ATF4, and CHOP gene expression in peripheral blood mononuclear cells. Plasma GRP78, advanced glycation end products (AGEs), and insulin were measured using enzyme-linked immunosorbent assay (ELISA), and insulin resistance (IR) was calculated by the homeostasis model assessment of insulin resistance (HOMA-IR). RESULTS: The expression of TUG1, MEG3, ATF4, and CHOP genes was significantly increased in the patients with diabetes compared to healthy individuals. MALAT1 gene expression was also higher in patients group; although it did not reach significant levels. TUG1 and MEG3 expression revealed significant positive correlations with the indices of glycemic control, including FBS, HbA1c, HOMA-IR, and AGEs, as well as markers of ER stress. MALAT1 expression was also positively correlated with ATF4 and AGEs. CONCLUSION: The expression levels of TUG1 and MEG3 lncRNAs were increased in patients with diabetes and were associated with glycemic control and components of ER stress. Thus, these lncRNAs might be considered appropriate markers to identify ER stress due to hyperglycemia.

Circulating TRB3 and GRP78 levels in type 2 diabetes patients: crosstalk between glucose homeostasis and endoplasmic reticulum stress.

PURPOSE: Endoplasmic reticulum (ER) stress is implicated in the development of type 2 diabetes mellitus (T2DM) and insulin resistance. Tribbles homolog 3 (TRB3) is a pseudokinase upregulated by ER stress and hyperglycemia. Glucose-regulated protein 78 (GRP78) is an ER stress protein that is overexpressed under ER stress conditions. The current study aimed to investigate serum levels of TRB3 and GRP78, as an ER stress marker, in T2DM patients and their correlations with the metabolic profile. METHODS: Fifty-seven patients with type 2 diabetes and 23 healthy control subjects were evaluated for serum concentrations of TRB3, GRP78, and AGEs by enzyme-linked immunosorbent assay (ELISA). Fasting plasma glucose (FPG), HbA1c, lipid profile, TNF-α and insulin were also measured, and insulin resistance was calculated using a homeostasis model assessment of insulin resistance (HOMA-IR). RESULTS: Serum concentrations of TRB3, GRP78, AGEs, and TNF-α were significantly higher in T2DM patients compared to the healthy controls. Moreover, a statistically significant positive correlation was observed between plasma concentrations of TRB3 and FPG, HbA1c, HOMA-IR, and AGE. GRP78 levels were positively correlated with HbA1c and AGEs. There was also a positive correlation between GRP78 and TRB3. AGEs levels were positively correlated with the levels of FPG, HbA1c, HOMA-IR, and TNF-α. CONCLUSION: The current findings suggest that TRB3 and GRP78 may contribute to the pathogenesis of T2DM and might be considered as a therapeutic targets for the treatment of this disease.

Effect of photobiomodulation on recovery from neurosensory disturbances after sagittal split ramus osteotomy: a triple-blind randomised controlled trial.

We have investigated the effect of photobiomodulation on the recovery of neurosensory function of the lip and chin after bilateral sagittal split osteotomy (BSSO). Laser irradiation was applied with a GaAs diode laser (continuous wave 980nm wavelength, power 100mW, and energy density 12J/cm2). It was maintained within a 0.5cm2 area in a total of 12 points for 60seconds at each visit on each point. Unilateral extraoral contact photobiomodulation treatment was applied the day before operation and then on days 1, 3, 7, 14, 21, and 28 postoperatively. One side of the mandible was the intervention side and the other the control side. On the control side, the laser probe was turned off and placed on the chosen area. Neurosensory evaluations were made before and immediately after operation, and 30 days and 60 days postoperatively. Twenty-five patients were screened, and 18 who met the inclusion criteria were included in the study; 14 were women and the mean (SD) age was 23 (5) years. Analysis of the visual analogue scales for general sensibility, pain discrimination, directional discrimination, and 2-point discrimination showed a significant difference between the intervention and control sides after 30 days (p=0.0011, 0.0034, 0.0023, and 0.0160, respectively). The difference was also significant after 60 days (p=0.0001, 0.0002, 0.0003, and 0.0010, respectively). The thermal discrimination rate was significantly higher in the laser group than the control group 30 days after surgery (p=0.002), but after 60 days the difference was not significant (p=1.000). We found no side effects from the laser radiation during the two-month follow up. The results suggest that photobiomodulation accelerated the patients' improvement from neurosensory disturbance after BSSO.

Finding an Optimal Corneal Xenograft Using Comparative Analysis of Corneal Matrix Proteins Across Species.

Numerous animal species have been proposed as sources of corneal tissue for obtaining decellularized xenografts. The selection of an appropriate animal model must take into consideration the differences in the composition and structure of corneal proteins between humans and other animal species in order to minimize immune response and improve outcome of the xenotransplant. Here, we compared the amino-acid sequences of 16 proteins present in the corneal stromal matrix of 14 different animal species using Basic Local Alignment Search Tool, and calculated a similarity score compared to the respective human sequence. Primary amino acid structures, isoelectric point and grand average of hydropathy (GRAVY) values of the 7 most abundant proteins (i.e. collagen α-1 (I), α-1 (VI), α-2 (I) and α-3 (VI), as well as decorin, lumican, and keratocan) were also extracted and compared to those of human. The pig had the highest similarity score (91.8%). All species showed a lower proline content compared to human. Isoelectric point of pig (7.1) was the closest to the human. Most species have higher GRAVY values compared to human except horse. Our results suggest that porcine cornea has a higher relative suitability for corneal transplantation into humans compared to other studied species.

Endocannabinoids as endometrial inflammatory markers in lactating Holstein cows.

The objective of this study was to consider endocannabinoid system as inflammatory markers in bovine endometrium to better understand the role of this system in regulating many of the functions that are related to inflammatory condition. At day 26 post-partum, fourteen cows were divided into two groups depending on the inflammatory condition: 1- subclinical endometritis (n = 7, with purulent or mucopurulent uterine discharge detectable in the vagina) and 2- healthy (n = 7, No (muco)) purulent discharge. Blood samples were collected at 26 and 30 days relative to calving to determine plasma tumour necrosis factor (TNF) and lipopolysaccharide-binding protein (LBP) concentrations; moreover, uterine biopsy was carried out on day 26 post-partum to measure mRNA abundance of TNF, interleukin-1B (IL1B), interleukin-6 (IL-6), C-X-C motif chemokine ligand 8 (CXCL8), endocannabinoid receptor (CNR2), N-acyl phosphatidylethanolamine phospholipase D (NAPEPLD), fatty acid amide hydrolase (FAAH), N-acylethanolamine acid amidase (NAAA) and monoglyceride lipase (MGLL) by real-time PCR. Results showed mean plasma concentrations of TNF and LBP were lower in healthy cows compared to subclinical endometritis cows (p < .05). Relative mRNA expression for NAAA and FAAH was decreased (p < .05), and relative mRNA expression for CNR2 and NAPEPLD increased in cows with subclinical endometritis compared to healthy cows. In conclusion, relative mRNA expression of TNF, IL1B and CXCL8 and plasma concentration of LBP increased during inflammatory condition along with decreased endocannabinoids hydrolyzing enzyme (NAAA and FAAH), increased enzymes that synthesize endocannabinoids (NAPEPLD) and relative gene expression of the endocannabinoid receptor; together, these contribute to increased endocannabinoids levels during inflammation. Overall, we provide evidence that endocannabinoid system is altered in endometrium tissue during inflammation through increased mRNA expression of CNR2 and synthesis enzyme and decreased mRNA expression of hydrolyzing enzymes interfere with pro-cytokine production and signalling, which may interfere with the onset and progression of inflammation.

Empirical comparison between different methods for genomic prediction of number of piglets born alive in moderate sized breeding populations.

Currently used multi-step methods to incorporate genomic information in the prediction of breeding values (BV) implicitly involve many assumptions which, if violated, may result in loss of information, inaccuracies and bias. To overcome this, single-step genomic best linear unbiased prediction (ssGBLUP) was proposed combining pedigree, phenotype and genotype of all individuals for genetic evaluation. Our objective was to implement ssGBLUP for genomic predictions in pigs and to compare the accuracy of ssGBLUP with that of multi-step methods with empirical data of moderately sized pig breeding populations. Different predictions were performed: conventional parent average (PA), direct genomic value (DGV) calculated with genomic BLUP (GBLUP), a GEBV obtained by blending the DGV with PA, and ssGBLUP. Data comprised individuals from a German Landrace (LR) and Large White (LW) population. The trait 'number of piglets born alive' (NBA) was available for 182,054 litters of 41,090 LR sows and 15,750 litters from 4534 LW sows. The pedigree contained 174,021 animals, of which 147,461 (26,560) animals were LR (LW) animals. In total, 526 LR and 455 LW animals were genotyped with the Illumina PorcineSNP60 BeadChip. After quality control and imputation, 495 LR (424 LW) animals with 44,368 (43,678) SNP on 18 autosomes remained for the analysis. Predictive abilities, i.e., correlations between de-regressed proofs and genomic BV, were calculated with a five-fold cross validation and with a forward prediction for young genotyped validation animals born after 2011. Generally, predictive abilities for LR were rather small (0.08 for GBLUP, 0.19 for GEBV and 0.18 for ssGBLUP). For LW, ssGBLUP had the greatest predictive ability (0.45). For both breeds, assessment of reliabilities for young genotyped animals indicated that genomic prediction outperforms PA with ssGBLUP providing greater reliabilities (0.40 for LR and 0.32 for LW) than GEBV (0.35 for LR and 0.29 for LW). Grouping of animals according to information sources revealed that genomic prediction had the highest potential benefit for genotyped animals without their own phenotype. Although, ssGBLUP did not generally outperform GBLUP or GEBV, the results suggest that ssGBLUP can be a useful and conceptually convincing approach for practical genomic prediction of NBA in moderately sized LR and LW populations.

Effect of temperature on the setting time of Mineral Trioxide Aggregate (MTA).

Introduction: Mineral trioxide aggregate (MTA) has numerous applications in dentistry due to various advantages. However, its long setting time has still remained a problem. The current study was conducted to investigate the effect of temperature (ambient and distilled water temperature) on the setting time of mineral trioxide aggregate (MTA). Materials and methods: This experimental study comprised of two parts. In the first part, MTA and distilled water samples were kept at ambient temperature for 24 hours (before mixing: effect of distilled water temperature on the setting time of MTA and after mixing: effect of distilled water and ambient temperature on the setting time of MTA), and analyzed and divided into three groups: group 1 (4°C), group 2 (37°C) and group 3 (90°C). The mixed samples were placed in the glass cylinders with an internal diameter of 8 mm and a height of 10 mm, and kept at 37°C temperature and 100% humidity. In the second part, the samples were prepared the same as those of the first part and divided into three groups according to the terms of maintenance: group 1 (4°C), group 2 (37°C) and group 3 (75°C). The mixed samples were then put in glass cylinders with an internal diameter of 8 mm and a height of 10 mm and the samples of groups 1, 2 and 3 were kept at 4, 37 and 75 °C, respectively. At the end of each part, the primary and final setting times were measured by Gilmore needle. Data were analyzed by SPSS using Kruskal-Wallis test (p<0.05). Results: The findings of this study showed a significant reduction of the primary and final setting time of MTA for the samples of both parts of the study with an increase in ambient temperature (p<0.05). Conclusion: This study indicated that increased ambient temperature caused a reduction in the setting time of MTA.

Isotopically induced variation in the stability of FMN-wrapped carbon nanotubes.

Isotopic, hydrogen-to-deuterium substitution has been an invaluable tool in the characterization of small molecules and biological nanostructures. The natural variability of most inorganic nanomaterials has hindered the use of isotopic substitution in gaining meaningful insights into their structure. The ideal helical wrapping of a flavin mononucleotide (FMN) around (8,6)-SWNTs (single-walled carbon nanotubes) is presently utilized to probe isotopically dependent intermolecular interactions. The facile proton-to-deuterium exchange of the imide group of FMN enabled us to alter the intermolecular stability of the helix depending on the surrounding solvent (i.e., H2O vs D2O). Our studies show that FMN-dispersed (8,6)-SWNTs exhibit greater stability in D2O than in H2O. The higher complex stability in D2O was verified on the basis of (i) FMN helix replacement with SDBS (sodium dodecylbenzenesulfate) and (ii) thermal- and (iii) pH-induced helix dissociation. This is in agreement with the previously observed stronger amide H-bonding of proteins in D2O, and to the best of our knowledge, it demonstrates the architectural fidelity of FMN-wrapped SWNTs, which is expected to enhance the assembly repertoire of carbon nanotubes further.

Combined use of Ovsynch and progesterone supplementation after artificial insemination in dairy cattle.

The objective of this study was to evaluate the effects of different Ovsynch protocols combined with progesterone (P4) supplementation after artificial insemination (AI) of Holstein-Friesian cows. Cows were randomly synchronized at 52 to 63 d after parturition with either the classical Ovsynch protocol (GnRH on d 0, PGF(2α) on d 7, GnRH 48 h after PGF(2α)) or with a modified Ovsynch protocol (second GnRH 60 h after PGF(2α)). On d 4 after timed AI (TAI), the cows were blocked by parity and randomly divided into 2 groups. Half of the cows were supplemented with P4 (P4+) by applying a P4-releasing intravaginal device intravaginally for 14 d, whereas the other half remained untreated (P4-). In 50% of randomly chosen cows, plasma P4 was measured on d 4, 5, and 18 after TAI. Sonographic pregnancy diagnosis was performed on d 33 after TAI in a total of 398 cows. Health status and body condition score (BCS) of all cows were examined at several stages of the study. Cows in the modified Ovsynch protocol tended to have higher P4 values on d 4 after TAI than cows in the classical Ovsynch protocol (2.1 ± 0.2 vs. 1.6 ± 0.2 ng/mL), but no difference in pregnancy per AI (P/AI) was observed between the 2 Ovsynch protocols (38.4% vs. 44.1%). Independent of the Ovsynch protocols, P4+ cows tended to have higher P/AI compared with P4- cows (44.4% vs. 38.1%). The retention of fetal membranes and BCS at the time of insemination affected P/AI. Moreover, an interaction between BCS at the time of insemination and P4 supplementation was apparent; that is, the difference in P/AI between P4+ and P4- cows was significant in cows with BCS ≥3.25. Progesterone-supplemented cows showed higher P4 values on d 5 (4.9 ± 0.2 vs. 2.6 ± 0.2) and d 18 (7.8 ± 0.2 vs. 6.3 ± 0.2) after TAI, respectively. In conclusion, the elongation of the time interval between the injections of PGF(2α) and the second GnRH from 48 to 60 h had no effect on P/AI. Progesterone supplementation after insemination improved the P/AI of the Ovsynch protocols, but this effect was more apparent in cows with BCS ≥3.25.

Effects of maxillary advancement and impaction on nasal airway function.

The effects of Le Fort I osteotomy on the nasal airway are controversial. This study aimed to evaluate nasal airway changes after Le Fort I. 25 patients underwent conventional Le Fort I osteotomy and were separated into three groups depending on the type of surgery they underwent. 11 patients needed maxillary impaction, 9 underwent maxillary advancement, and 5 had both maxillary impaction and advancement. Rhinological examinations, anterior rhinomanometry and acoustic rhinometry were carried out 1 week before surgery and 3 months after that. Wilcoxon and χ(2) tests were used for data analysis. The samples included 19 females and 6 males with a mean age of 22.4 ± 3.32 years. Rhinomanometric assessment showed that total nasal airflow was increased from 406 ± 202 ml/s to 543 ± 268 ml/s in all three groups. Significant decrease in nasal airway resistance was seen in all three groups. Acoustic rhinometry revealed a significant decrease in total nasal volume but an increase in the cross-sectional areas of isthmus nasi (IN) and inferior concha. The rhinomanometric measurements showed improvements in the total nasal airflow after Le Fort I osteotomy with alar base cinch suture in cases where the impaction was not higher than 5.5mm.

Frequency of ABO blood group in peptic ulcer disease in Iranian subjects.

The relationship between ABO blood group distribution and Peptic Ulcer Disease (PUD) has been widely evaluated in the past. But data concerning the same evaluation are very limited in Iran. This study sought to determine the distribution of ABO blood group in patients with PUD in Iranian subjects. Eighty-one patients with PUD (51 male and 30 female; mean age: 49 +/- 18 years) who attended our endoscopy section were enrolled. Blood samples were used for ABO/Rhesus (Rh) blood group antigen typing. The ABO blood group phenotype distribution in subjects was as follows: 37.1% (30/81) for group A, 23.4% (19/81) for group B, 35.6% (28/81) for group O and 4.9% (4/81) for group AB. Rh positivity was found in 63% (51/81) of patients. In local healthy population, ABO/Rh blood group distribution was 33.8, 20.7, 34.7, 8.4 and 89.6% for A, B, O, AB and Rh, respectively. AB blood group distribution in healthy population was higher than PUD (8.4 vs 4.9%). In contrast, Rh positivity of PUD in Iran is lower than healthy subjects (63 vs 89.6%). Variation in the results of studies is related to different study communities. According to these results, probably ABO/Rh blood group has an important role in patients with peptic ulceration. The functional significance of ABO blood group distribution might be associated with biological behavior of PUD. The impact of blood group on PUD may be a focus for further studies.

Practical methods for increasing light interception efficiency and root growth in soybean.

Determining the effect of different sources of nitrogen and weeds on two varieties of soybean, an experiment was conducted out at research station of Tabriz University, Iran. Treatments were two varieties (Williams and Harcor), four nitrogen levels (two levels of symbiotic bacteria and two levels of urea) and weeds (with and without control). Results showed that three various factors can significantly change the Photosynthetically Active Radiation (PAR) amount at different layers of canopy. Solar radiation decreased in a vertical profile of canopy because of increasing Leaf Area Index (LAI). At the bottom level of canopy only 6% of total arrived PAR was recorded. Increasing LAI caused a sharp decrease in Light Interception Efficiency (LIE) in the canopy. Weeds significantly affected root nodules in dry and fresh weights. So, in weedy condition of soybean canopy, accumulation of dry matter decreases due to decline in LIE. On the other hand, weeds can strongly affect on nodules activity and decrease potential of nitrogen fixation by symbiosis bacteria.

Relationship between genetic polymorphism of glutathione S-transferase-p1 and p53 protein accumulation in Iranian esophageal squamous cell carcinoma patients.

BACKGROUND: It has been reported that the activity of glutathione S-transferase (GST) is over-expressed in plasma and esophagus biopsies in Iranian patients suffering from esophageal squamous cell carcinoma (SCC). The aim of this study was to find out the frequency of GST-P genotypes in these patients. Moreover, the association of GST-P genotypes with p53 protein accumulation in esophageal epithelium was investigated. MATERIALS AND METHODS: DNA isolated from paraffin-embedded tissue biopsies from patients suffering from esophageal SCC (n = 56) were collected. polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) using Alw261 enzyme was applied to determine GST-P genotypes (Ile 105 Val). All the samples were also subjected to immunohistochemistry (IHC) for p53. RESULTS: The frequency of GST-P genotypes in Iranian esophagus SCC patients for Ile/Ile, Ile/Val and Val/Val was 73.2, 21.5 and 5.3%. There was no association between GST-P polymorphism and p53 accumulation in esophageal epithelial cells. CONCLUSIONS: The frequency of GST-P polymorphism was not associated with p53 protein accumulation in esophagus epithelium. The frequency of polymorphic variants of GST-P, Ile/Ile, Ile/Val and Val/Val in SCC patients may suggest that Ile to Val substitution in GST-P gene dose not represent susceptibility to SCC in high-risk Iranian population.

Oxidative DNA damage in prostate cancer patients consuming tomato sauce-based entrees as a whole-food intervention.

BACKGROUND: Human prostate tissues are vulnerable to oxidative DNA damage. The risk of prostate cancer is lower in men reporting higher consumption of tomato products, which contain high levels of the antioxidant lycopene. We examined the effects of consumption of tomato sauce-based pasta dishes on lycopene uptake, oxidative DNA damage, and prostate-specific antigen (PSA) levels in patients already diagnosed with prostate cancer. METHODS: Thirty-two patients with localized prostate adenocarcinoma consumed tomato sauce-based pasta dishes for the 3 weeks (30 mg of lycopene per day) preceding their scheduled radical prostatectomy. Serum and prostate lycopene concentrations, serum PSA levels, and leukocyte DNA oxidative damage (ratio of 8-hydroxy-2'-deoxyguanosine [8-OHdG] to 2'-deoxyguanosine [dG]) were assessed before and after the dietary intervention. DNA oxidative damage was assessed in resected prostate tissue from study participants and from seven randomly selected prostate cancer patients. All statistical tests were two-sided. RESULTS: After the dietary intervention, serum and prostate lycopene concentrations were statistically significantly increased, from 638 nM (95% confidence interval [CI] = 512 to 764 nM) to 1258 nM (95% CI = 1061 to 1455 nM) (P<.001) and from 0.28 nmol/g (95% CI = 0.18 to 0.37 nmol/g) to 0.82 nmol/g (95% CI = 0.57 to 1.11 nmol/g) (P <.001), respectively. Compared with preintervention levels, leukocyte oxidative DNA damage was statistically significantly reduced after the intervention, from 0.61 8-OHdG/10(5) dG (95% CI = 0.45 to 0.77 8-OHdG/10(5) dG) to 0.48 8-OHdG/ 10(5) dG (95% CI = 0.41 to 0.56 8-OHdG/10(5) dG) (P =.005). Furthermore, prostate tissue oxidative DNA damage was also statistically significantly lower in men who had the intervention (0.76 8-OHdG/10(5) dG [95% CI = 0.55 to 0.96 8-OHdG/10(5) dG]) than in the randomly selected patients (1.06 8-OHdG/10(5) dG [95% CI = 0.62 to 1.51 8-OHdG/10(5) dG]; P =.03). Serum PSA levels decreased after the intervention, from 10.9 ng/mL (95% CI = 8.7 to 13.2 ng/mL) to 8.7 ng/mL (95% CI = 6.8 to 10.6 ng/mL) (P<.001). CONCLUSION: These data indicate a possible role for a tomato sauce constituent, possibly lycopene, in the treatment of prostate cancer and warrant further testing with a larger sample of patients, including a control group.

Spouse ratings of quality of life in patients with metastatic prostate cancer of lower socioeconomic status: an assessment of feasibility, reliability, and validity.

OBJECTIVES: To examine the reliability and validity of spousal assessments by evaluating the collateral quality-of-life (QOL) ratings of patients of lower socioeconomic status with metastatic prostate cancer because collateral ratings provide supplemental information when advanced cancer limits patient self-report. METHODS: Patients with Stage D2 prostate cancer (n = 36) of lower socioeconomic status completed validated QOL instruments (Functional Assessment of Cancer Therapy-General [FACT-G], European Organization for Research and Treatment of Cancer-Quality of Life-30, and Quality of Life Index). Spouses completed a modified FACT-G, and physicians rated performance status using Karnofsky's scale. RESULTS: The internal consistency reliability was moderate to high for patient ratings on all FACT-G subscales and for spousal ratings on the modified FACT-G physical, functional, and emotional subscales. The spouses' ratings of the patients on the social and doctor relationship subscales were below the accepted criterion for a measure's use in group comparisons. The comparisons of the mean values of the FACT-G revealed agreement between patients and spouses, except that the spouses rated the patients as having poorer emotional function than did the patients. The intraclass correlations were moderate to high for the functional and emotional subscales and were low, but significant, for the physical and social subscales. The patient and spouse FACT-G ratings correlated with the patient ratings and physician ratings across the instruments for the functional and physical domains (r = 0.48 to 0.77, for patients; r = 0.31 to 0.70, for spouses), with less consistent relationships for the social and emotional domains. CONCLUSIONS: The collateral QOL assessments from spouses are potentially useful in assessing the functional status in patients of lower socioeconomic status with metastatic prostate cancer. For subjective domains, such as the social domain, direct patient assessments are needed.

Evaluation of an implant that delivers leuprolide for 1 year for the palliative treatment of prostate cancer.

OBJECTIVES: To evaluate the Viadur implant, which delivers leuprolide acetate for the palliative treatment of advanced prostate cancer. METHODS: Inserted subcutaneously, the 4 x 45-mm implant uses osmotic pressure to deliver leuprolide continuously at a controlled rate for 1 year. This 19-center open-label study enrolled patients with prostate cancer who had had no prior therapy or showed biochemical evidence of treatment failure after prostatectomy or radiotherapy. Each patient received one implant. After 1 year, that implant was removed, another was inserted, and patients were followed up for 2 additional months. The primary efficacy measure was suppression of testosterone to less than the castrate threshold (50 ng/dL). RESULTS: Eighty patients were enrolled. The implant effectively suppressed testosterone in 79 patients (99%) within 2 to 4 weeks and maintained that suppression through the study period. In 1 patient, the testosterone was suppressed to less than 100 ng/dL within 4 weeks but was not less than 50 ng/dL until week 24. Prostate-specific antigen levels normalized (4 ng/mL or less) or a clinically significant decrease occurred in all patients. Leuprolide was rapidly absorbed, resulting in mean serum concentrations of 16.8 ng/mL 4 hours after implant insertion and 2.4 ng/mL at 24 hours; steady mean serum leuprolide concentrations were then maintained throughout the year, at approximately 0.9 ng/mL. Investigators were satisfied with the insertion and removal procedures. All patients reported satisfaction after 1 year of treatment. The safety profile of the implant was consistent with androgen ablation therapy. Most adverse events were mild, and the most common event was hot flashes. CONCLUSIONS: The leuprolide implant effectively suppressed testosterone concentrations to less than the castrate threshold and maintained that suppression throughout the study period.

Quality of life in low-income patients with metastatic prostate cancer: divergent and convergent validity of three instruments.

Few studies have evaluated Quality Of Life (QOL) among low-income patients with cancer. Information is needed about the feasibility and psychometric characteristics of QOL instruments in these populations. The purpose of this study was to examine the convergent and discriminant relationships between scales of three QOL instruments: European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC), Functional Assessment of Cancer Therapy--General (FACT), and Quality of Life Index (QLI). Participants included 110 men with metastatic prostate cancer of whom 94% were low income and 62% were African-American. Interviewers administered the questionnaires. Cronbach alpha internal consistency reliabilities were 0.57 to 0.90 for the EORTC, 0.65 to 0.86 for the FACT, and 0.63 for the QLI. Convergent validity was supported for the EORTC and FACT scales measuring emotional, physical, and role/functional dimensions (r = 0.54 to 0.72), but not on scales measuring social function (r = 0.12). Divergent validity was supported between dissimilar scales (r = 0.14 to 0.38). Analysis with receiver operating characteristics curves provided empirical support for the EORTC and FACT as multidimensional measures. These findings suggest that, even in busy clinical settings with low literacy patients, interviewer-administered EORTC and FACT QOL instruments can provide valid and reliable information.

A multi-attribute model of prostate cancer patient's preferences for health states.

Multi-attribute utility theory (MAUT) provides a way to model decisions involving trade-offs among different aspects or goals of a problem. We used MAUT to model prostate cancer patients' preferences for their own health state and we compared this model to patients' global judgments of health state utility. 57 patients with prostate cancer (mean age = 70) at two Chicago Veterans Administration health clinics were asked to evaluate health states described in terms of five health attributes affected by prostate cancer: pain, mood, sexual function, bladder and bowel function, and fatigue and energy. Each attribute had three levels that were used to form three clinically realistic health state descriptions (A = high, B = moderate, C = low). A fourth personalized health description (P) matched the patient's current health. We first measured patients' preferences using time trade-off (TTO) judgments for the three health states (A, B, and C) and for their own current health state (P). The TTO for the patient's own health state (P) was standardized by comparing it to TTO judgments for states A and C. We next constructed a multi-attribute model using the relative importance of the five attributes. The MAU scores were moderately correlated with the TTO preference judgments for the personalized state (Pearson r = 0.38, N = 57, p < 0.01). Thus, patients' preference judgments are moderately consistent and systematic. MAUT appears to be a potentially feasible method for evaluating preferences of prostate cancer patients and may prove helpful in assisting with patient decision making.

Exploratory analysis on the effect of race on clinical outcome in patients with advanced prostate cancer receiving bicalutamide or flutamide, each in combination with LHRH analogues. The Casodex Combination Study Group.

BACKGROUND: Black race has been associated with a significantly increased risk of prostate cancer mortality. This exploratory analysis investigated the effect of race on the clinical outcome of combined androgen blockade (CAB). METHODS: Data for analysis were obtained from a double-blind, randomized, multicenter trial comparing CAB in the form of bicalutamide (50 mg once daily) or flutamide (250 mg three times daily) plus luteinizing hormone-releasing hormone analogs (LHRHa; goserelin acetate 3.6 mg, or leuprolide acetate 7.5 mg) in 813 patients with stage D(2) prostate cancer (median follow-up, 160 weeks). Patients were analyzed according to race (African American [AA], white, or other). The primary clinical events were disease progression and survival. RESULTS: Four hundred and four patients received bicalutamide/LHRHa and 409 received flutamide/LHRHa. Although treatment with bicalutamide/LHRHa resulted in slightly longer time to progression and survival time in white and AA males than treatment with flutamide/LHRHa, the differences between the treatment groups were not statistically significant. CONCLUSIONS: No marked effect of race on clinical outcome was observed regardless of antiandrogen, suggesting that similar treatment benefits are to be expected in either race.