The interaction of the diltiazem with oral and intravenous cyclosporine in rats.

This study investigated the effect of diltiazem on the bioavailability of oral and intravenous cyclosporine (CsA) in rats. While control rats received normal saline, experimental groups received 60 or 90 mg/kg diltiazem orally for 3 days. Each group divided into 2 equal groups that received a single oral dose or i.v. injection of CsA. Pharmacokinetic parameters were analyzed by nonparametric analysis of variance. Pretreatment with 60 or 90 mg/kg diltiazem decreased the area under the blood CsA concentration-time curve (AUC) of oral CsA compared to control group (54.5% and 65.5% for AUC(0-24), 57.6% and 62.2% for AUC(0-infinity), respectively, p<0.05). Mean CsA maximum concentration (Cmax) decreased from 0.4 +/- 0.1 microg/ml to 0.1 +/- 0.0 microg/mL in rats pretreated with 90 mg/kg diltiazem (p<0.05). The absolute bioavailability after oral administration (F(p.o.)) in the 60 or 90 mg/kg diltiazem groups were lower than the control group (9.6% and 8.5% versus 22.6%). Pretreatment with 90 mg/kg but not 60 mg/kg of diltiazem increased the AUC(0-infinity), elimination half-life (t1/2) of intravenous CsA (116.0%, 219.2%, respectively, p<0.05) and decreased the intravenous CsA clearence (CL(i.v.)) (62.9%, p<0.05). Diltiazem decreased the bioavailability of oral CsA, while it increased the bioavailability of intravenous CsA. One must consider this interaction when administering oral or intravenous CsA concomitantly with diltiazem.     

Left ventricular remodeling and aortic distensibility in elite power athletes

The aim of this study was to determine left ventricular (LV) morphology and aortic function in power athletes and to compare them with normal subjects. Thirty-two elite male wrestlers and 15 age-matched healthy male controls were included. All subjects underwent echocardiographic examination. Measurements included LV cavity dimension at systole and diastole, wall thickness, diastolic parameters, and aortic diameter, 3cm above aortic valve, at systole and diastole. Left ventricular mass and mass index were found to be higher in the athletes than in control subjects. The aortic distensibility index was found to be reduced in the athletes compared with controls (2.53 ± 0.91 vs 3.94 ± 1.77cm²dyne^–1 10^–6, P = 0.003), while the aortic stiffness index was significantly higher in the athletes than in controls (9.12 ± 3.23 vs 6.65 ± 2.35, P = 0.02). However, LV end-systolic wall stress was lower in the athletes than in controls. Furthermore, transmitral early (E) and late (A) peak velocity, peak velocity of the myocardial systolic wave (S _m), and early (E _m) and atrial (A _m) diastolic waves at the inferior wall were higher in the athletes than in controls. Reduced aortic distensibility in elite power athletes may be one of the cardiovascular adaptation factors which affect LV hypertrophy.     

Pentraxin 3 concentrations of the mothers with preterm premature rupture of membranes and their neonates,and early neonatal outcome

Background: Pentraxin 3 (PTX3) is an acute phase reactant which has been used to detect intra-amniotic infections (IAI) in pregnancy, but the prognostic value of PTX3 concentrations on neonates has not been studied. We aimed to investigate the relationship between maternal PTX3–neonatal PTX3 concentrations and early neonatal outcome.

Methods: The mothers diagnosed with preterm prelabor rupture of membranes (PPROM) (n?=?28) and their preterm infants (n?=?28) were included in the study. PTX3 concentrations were studied in plasma in the maternal peripheral blood and umbilical/peripheral vein in the neonates. The relationship between the mPTX3–nPTX3 concentrations and neonatal outcome were investigated using non-parametric tests and binary logistic regression analysis.

Results: The mean mPTX3 concentration was 10.35?±?7.82?μg/L. Ten (35.7%) of all mothers were within the normal range and 18 (64.3%) in high percentile (≥97.5 percentile). There was no relation between mPTX3 concentrations and clinical or histologic chorioamnionitis, latency of PPROM, and early neonatal outcome. Mean nPTX3 concentrations was 9.18?±?7.83?μg/L and high nPTX3 concentrations were detected in five (17.8%) neonates. nPTX3 concentrations were inversely correlated with gestational age and correlated with rate of intraventricular hemorrhage (IVH) and mortality. Neonates with high nPTX3 concentrations also have lowered APGAR scores, increased rate of respiratory distress syndrome, clinical sepsis, IVH, necrotizing enterocolitis and prolonged NICU stay.

Conclusion: High PTX3 concentrations of the newborns are associated with some worsened early neonatal outcome including lower gestational age at delivery, increased rate of IVH and mortality. Maternal PTX3 concentrations are not an adequate marker in defining clinical or histologic chorioamnionitis and early neonatal outcome.     

Cone-beam computed tomography evaluation of impacted and transmigrated mandibular canines: a retrospective study

Oral Radiology - The purpose of this study is to evaluate CBCT images of impacted mandibular canines in detail and to discuss implications for diagnosis and treatment. CBCT images of dental...     

Factors affecting symptoms and functionality of patients with carpal tunnel syndrome: a retrospective study

[Purpose] The aim of this retrospective study was to determine the associations between clinical, physical, and neurophysiological outcomes and self-reported symptoms and functions of patients after surgical carpal tunnel release. [Subjects and Methods] Among 261 patients who had undergone open surgical carpal tunnel release within the last three years, 83 (mean age 50.27 ± 11.13 years) participated in this study. Their socio-demographics and comorbidities were recorded. The intensity of pain, paresthesia, and fatigue symptoms in the hand were assessed by means of a Visual Analogue Scale, the Semmes-Weinstein Monofilaments test of light touch pressure sensation, and Jamar dynamometry for measurement of grip and pinch strengths. The Boston Carpal Tunnel Questionnaire evaluated the severity of symptoms and hand functional status, and the variables were analyzed by multivariate linear regression. [Results] The severity of the symptoms and functional status of release surgery patients was associated with diabetes mellitus, migraine, night pain, paresthesia and fatigue symptoms, impaired light touch pressure, and lack of medical treatment. [Conclusion] Appropriate post-surgery treatment programs for these factors should be taken into consideration to help patients obtain optimal functionality and health in their daily lives.Key words: Carpal tunnel syndrome, Patient outcome assessment, Surgical therapy     

Effects of glutamine on wound healing

Studies reporting the need for replacing amino acids such as glutamine (Gln), hydroxymethyl butyrate (HMB) and arginine (Arg) to accelerate wound healing are available in the literature. The primary objective of this study was to present the effects of Gln on tissue hydroxyproline (OHP) levels in wound healing. This study was conducted on 30 female Sprague Dawley rats with a mean weight of 230 ± 20 g. Secondary wounds were formed by excising 2 × 1 cm skin subcutaneous tissue on the back of the rats. The rats were divided into three equal groups. Group C (Control): the group received 1 ml/day isotonic solution by gastric gavage after secondary wound was formed. Group A (Abound): the group received 0·3 g/kg/day/ml Gln, 0·052 g/kg/day/ml HMB and 0·3 g/kg/day/ml Arg by gastric gavage after secondary wound was formed. Group R (Resource): the group received 0·3 g/kg/day/ml Gln by gastric gavage after secondary wound was formed. The OHP levels of the tissues obtained from the upper half region on the 8th day and the lower half region on the 21st day from the same rats in the groups were examined. Statistical analysis was performed using the statistics program SPSS version 17.0. No statistically significant differences were reported with regard to the OHP measurements on the 8th and 21st days (8th day: F = 0·068, P = 0·935 > 0·05; 21st day: F = 0·018, P = 0·983 > 0·05). The increase in mean OHP levels on the 8th and 21st days within each group was found to be statistically significant (F = 1146·34, P = 0·000 < 0·001). We conclude that in adults who eat healthy food, who do not have any factor that can affect wound healing negatively and who do not have large tissue loss at critical level, Gln, Arg and HMB support would not be required to accelerate secondary wound healing.     

Effects of occupational therapy on quality of life of patients with metastatic prostate cancer: A randomized controlled study

Objectives:

To evaluate the efficiency of occupational therapy relative to a home program in improving quality of life (QoL) among men who were treated for metastatic prostate cancer (MPC).

Methods:

Fifty-five men were assigned randomly to either the 12-week cognitive behavioral therapy based occupational therapy (OT-CBSM) intervention (treatment group) or a home program (control group) between March 2012 and August 2014 in the Department of Occupational Therapy, Faculty of Health Sciences, Hacettepe University, Ankara, Turkey. The Canadian Occupational Performance Measure (COPM) was used to measure the occupational performance and identify difficulties in daily living activities. The QoL and symptom status were measured by The European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire C30 and its Prostate Cancer Module. A 12-week OT-CBSM intervention including client-centered training of daily living activities, recreational group activities, and cognitive behavioral stress management intervention were applied.

Results:

The COPM performance and satisfaction scores, which indicate occupational participation and QoL increased statistically in the treatment group in relation to men who were included in the home-program (p≤0.05).

Conclusion:

A 12-week OT-CBSM intervention was effective in improving QoL in men treated for MPC, and these changes were associated significantly with occupational performance.Prostate cancer is one of the most frequent male malignancies in the world.1 The development of serum prostate-specific antigen (PSA) and advanced prostate cancer treatment modalities increased 10-year survival rates from ~60% to >70%.2 Prostate cancer can be occurred as a local disease or advanced metastatic disease. The standard of care for metastatic prostate cancer (MPC) is hormone (androgen blockade) therapy, which delays progression and relieves pain for an average of 18 months to 24 months.3,4 Nearly all patients who have hormone therapy eventually develop significant disease and treatment related morbidity including fatigue, decrease in bone density, bone pain, weight loss, gynecomastia, and hot flushes.3 Increased survival and subsequent functional, physical, and psychological needs produced a growing acceptance of understanding the rehabilitation needs to increase the occupational performance and quality of life (QoL) of the patients with MPC.5 Occupational therapy (OT), one of the core elements of oncologic rehabilitation, is in a unique position to contribute to the development and fulfillment of occupational performance and participation with the motto of ‘live life to its fullest’.6 The role of the occupational therapist in oncology is to facilitate and enable an individual to achieve maximum functional performance, both physically and psychologically, in everyday living skills regardless of his or her life expectancy.6 Occupational performance or participation in everyday occupations is vital for all humans as defined by the International Classification of Functioning, Disability and Health7 (ICF). Occupational performance has a positive influence on health, well-being, and the presence of cancer has been found to lead to participation in meaningful activities /occupations that are effected by the cancer and its treatments.8 Previous studies9-14 have ably identified OT interventions mostly in general oncology and palliative care. The literature on OT, specifically on patients with breast cancer, investigates management of pain, fatigue, nausea, metastatic patients intervention, stress reducing and management program, the value of engagement in meaningful activities, lymphedema, vocational rehabilitation, creative and therapeutic use of activity, cognitive therapy, and, changing life style with cognitive behavioral therapy.9-14 According to the literature, a survey on women with breast cancer provides a picture of the interventions employed by the occupational therapists and can help to create an OT service to regain the patients level of control and independence by maintaining or resuming engagement in purposeful occupations and meaningful activities; however, the effect of OT in patients’ QoL was not completely specified.15,16 Another interdisciplinary study recommended examination of the effectiveness of OT in patients’ functional needs and to promote evidence-based practice of OT in oncology.8,17Prostate cancer oriented rehabilitation interventions may be valuable in functioning, and activity participation in daily living activities and also in helping men to acknowledge, express, accept, and use a problem solving approach on the changes that occur as a result of treatment and to seek out adaptive solutions for enduring fatigue, bone pain, weight loss, gynecomastia, and hot flushes.18 Such interventions may lead to significant improvements in functional, cognitive, and emotional coping skills, use of social support, utilization of health care, and management of symptoms.5,18-21 Rehabilitation interventions were adapted to meet the needs of cancer patients including functional individualized support and group therapy interventions22 and stress management intervention23 approaches. The research shows that effective stress management components include relaxation training to lower arousal, disease information and management, an emotionally supportive environment in which participants can address fears and anxieties, behavioral and cognitive coping strategies, and social support.19,20 Participation in rehabilitation intervention provides a clear and robust benefit to cancer patients by relieving treatment-related symptoms, reducing the physiologic concomitants of stress, and improving mood. Previous study19 found that the benefits in coping with cancer may be quite significant in male participants.19 This is supported by the positive experiences that men report from their participation in rehabilitation programs. Although, collectively, these findings indicated that men treated for prostate cancer derive benefit from a rehabilitation experience, most studies did not include a randomized intervention design and did not study the occupational performance of the participants.15,23 Only a few studies20,21 have investigated the efficacy of structured stress-management interventions in improving QoL and the mechanisms associated with such improvements despite stressful and negative side effects associated with treatment with limited activity participation.The limited reports in the literature indicates that there is a lack of study on the effect of OT combined cognitive behavioral stress management skills in patients with MPC. In the current study, it was hypothesized that participants treated for MPC enrolled in the cognitive behavioral stress management based OT (OT-CBSM) would demonstrate greater improvements in occupational performance and QoL compared with a control group (CG) enrolled in the home-program. The objectives of this study were to identify the effect of OT-CBSM on occupational participation and QoL, and to explore the areas/activities of daily life that were the most commonly affected, and needed support in patients with MPC.     

Serum-free liquid marrow culture in patients with acute lymphoblastic leukaemia: a potential application to purge marrow for autologous transplantation

We have previously established a serum-free (SF) culture medium, which supports normal haemopoietic progenitor cell growth for at least 4 weeks as does conventional serum dependent (SD) medium. In the present study, we investigated the efficacy of such a defined SF liquid medium which sustained in vitro residual normal haemopoietic proliferation of marrow derived from ALL patients and which was detrimental for the leukaemic population. Evidence for a potential selective effect of SF culture was obtained by a leukaemic progenitor cell assay (ALL-CFU) and the detection of the bcr/abl translocation by polymerase chain reaction (PCR). In 13 experiments including 12 patients, morphological blast cells and ALL-CFU were dramatically reduced within 3 weeks of incubation in both SF and SD cultures. Likewise, in 5/5 experiments in SD and 2/5 experiments in SF conditions, leukaemic cells expressing the bcr/abl fusion gene disappeared within 3-4 weeks. In contrast, the absolute numbers of supernatant cells harvested weekly from SF and SD cultures were similar. No difference in CFU-GM production was detected for the two culture systems. Erythropoiesis in SF medium exhibited a slower decline than that found in SD. These results indicate that liquid marrow culture may selectively deplete leukaemic lymphoblastic cells and enable repopulation by residual normal haemopoietic cells. This technique may be useful to purge leukaemic cells for clinical autologous bone marrow transplantation in patients with ALL.     

A new silent germline mutation of the TSH receptor: coexpression in a hyperthyroid family member with a second activating somatic mutation.

BACKGROUND: Up to date, three thyroid-stimulating hormone receptor (TSHR) germline variants have been reported for which no functional consequences have been detected by in vitro characterizations. However, familial nonautoimmune hyperthyroidism and hot nodules are clearly associated with constitutively activating TSHR germline mutations. We describe a family with a new TSHR germline mutation that is associated with euthyroidism in 13 family members and hyperthyroidism in 1 family member. METHODS: Mutation analysis of the TSHR gene was performed by denaturing gradient gel electrophoresis. TSHR constructs were characterized by determination of cell surface expression, 3'-5'-cyclic adenosine monophosphate (cAMP) accumulation, and constitutive cAMP activity. RESULTS: A novel TSHR germline mutation (N372T) was found in a man who presented with thyrotoxicosis. The mutation was also detected in 13 family members, all of whom were euthyroid. Interestingly, an additional constitutively active somatic mutation (S281N) was identified on the second parental TSHR allele of the hyperthyroid index patient. Linear regression analysis showed a lack of constitutive activity for N372T. Moreover, coexpression studies of N372T with S281N did not reveal any evidence for a functional influence of N372T on the constitutively active mutation (CAM). CONCLUSIONS: N372T is unlikely to cause altered thyroid function. This is consistent with the finding that only the index patient with the additional somatic mutation S281N was hyperthyroid.