An investigation of the effects of music on anxiety and pain perception in patients undergoing haemodialysis treatment.

This study aimed to investigate the effects of preferred music listening on anxiety and pain perception in patients undergoing haemodialysis. A two group experimental design was used. Sixty people diagnosed with end stage renal failure undergoing haemodialysis treatment participated in this study. Preferred music listening was applied as an intervention. Anxiety and pain were measured pre-test and post-test. The control group scored significantly higher in state anxiety than the experimental group and experienced significantly higher pain intensity in post-test phase. Findings provide experimental evidence to support the effectiveness of preferred music listening in medical settings.

Plasma adiponectin concentrations in patients with chronic renal failure: relationship with metabolic risk factors and ischemic heart disease.

AIMS: To compare plasma adiponectin levels between healthy controls and patients with chronic renal failure and to examine for a relationship between plasma adiponectin levels and ischemic heart disease as well as aortic distensibility which is an early marker of atherosclerosis. METHODS: We included 89 patients with CRF (45 on and 44 not on hemodialysis) and 70 controls in a cross-sectional study. Plasma adiponectin levels were measured by radioimmunoassay. Aortic distensibility was assessed by high-resolution ultrasonography. RESULTS: Plasma adiponectin levels were significantly almost twice as high in patients with renal failure compared to controls (9.7 +/- 1.1 vs. 5.4 +/- 0.6 microg/ml, p < 0.0001). No significant differences were found between renal patients on hemodialysis and not on hemodialysis (p = 0.71). Multivariate linear regression analysis in the renal patient group demonstrated a significant negative relationship between plasma adiponectin levels and ischemic heart disease (p = 0.02). The same analysis in the control subjects group showed a significant, negative relationship between plasma adiponectin levels and body mass index (p = 0.02) and a highly significant positive relationship with the high density lipoprotein cholesterol (p < 0.0001). In the total study population, glomerular filtration rate was the only independent predictor of plasma adiponectin concentrations. Aortic distensibility was lower in renal patients than in controls at a high level of significance (p < 0.0001). However, no significant relationship could be found between plasma adiponectin and aortic distensibility in either the controls or the renal patients. CONCLUSIONS: Plasma adiponectin levels are almost twice as high in patients with chronic renal failure in comparison with healthy controls, but not different between renal patients on and those not on hemodialysis. In addition, low plasma adiponectin levels are strongly associated with ischemic heart disease, but not with aortic distensibility in chronic renal failure.

Hemodialysis for patients bleeding or at risk for bleeding, can be simple, safe and efficient.

AIM: Hemodialysis for patients bleeding or at risk for bleeding requires special modalities of treatment that are difficult to perform without potential side effects. A simple, safe and adequate method may be applied. METHODS: A modified way of extracorporeal circuit preparation, which focuses on minimizing the blood-air interface and negligible saline flushing of 50 ml/h, is applied for a maximum of 3-hour session with routine (not one-to-one) nursing attendance. Data from 16,954 sessions performed with patients bleeding or at risk for bleeding (15,730 retrospectively and 1,224 prospectively collected) were analyzed. RESULTS: Cumulative failure of treatment, as defined by clotting of the extracorporeal circuit requiring termination of the procedure or replacement of the clotted part, was not more than 5% as expected for anticoagulation-free hemodialysis. For the prospectively recorded sessions, blood flow was 234 +/- 30 ml/min with less than 250 ml/min in 42.4% of the sessions. Native blood access was used in 426 (34.8%), double-lumen catheter in 798 (65.2%), 42 were isolated ultrafiltration sessions and 64 blood, 21 plasma, 9 platelet units were transfused. Post/pre urea ratio was 0.50 +/- 0.12. Logistic regression showed that among the following: duration of the session, type of dialysis, ultrafiltration rate, hematocrit, number of platelets, serum total protein, transfusions, blood flow and type of access, only blood flow significantly affected failure incidence (coefficient B = -0.041, exp(B) = 0.96, p = 0.04). No complications due to treatment were noted. CONCLUSION: In patients with active, or at risk for, bleeding, hemodialysis without systemic anticoagulation can be adequately and safely performed almost as a routine session.

Full dose paclitaxel plus vinorelbine as salvage chemotherapy in anthracycline-resistant advanced breast cancer: a phase II study.

This phase II trial studied the efficacy and toxicity of full dose paclitaxel plus vinorelbine, as salvage chemotherapy in patients with metastatic breast cancer resistant to anthracyclines. Patients received vinorelbine (30 mg/m2) followed 1 hour later by full dose paclitaxel (175 mg/m2) every 3 weeks for a maximum of 8 cycles or until disease progression. Because of the heavy pretreatment of the patients, prophylactic granulocyte-colony stimulating factor (5 microg/kg) was administered daily for 5-10 days. To minimize potentially cumulative neurotoxicity due to both agents, amifostine was given prior to chemotherapy. Thirty-four patients: 8 with tumors primary resistant and 26 with tumors recurring within 3-6 months after anthracycline treatment, were evaluable for efficacy and toxicity. Objective responses occurred in 11 patients [32%; 95% confidence interval (CI): 16.3-47.7%), all partial responses. Responses were observed in lung and liver. The median response duration was 4 months (range 3-7), median time to progression was 5 months (range 3-9) and median overall survival was 8 months (range 4-24). Neutropenia was dose limiting (35% grade 3-4 toxicity). The left ventricular ejection fraction, measured and followed in 18 patients, fell less than 20% below baseline level in 9 patients (50%), but only one patient developed congestive cardiac failure. The paclitaxel-vinorelbine regimen was moderately tolerated and moderately effective in poor prognosis breast cancer patients with visceral metastases and tumors resistant to anthracyclines. The combination at these doses and schedules should be considered in the design of regimens for advanced breast cancer.

Intradialytic and interdialytic effects of treatment with 1.25 and 1. 75 Mmol/L of calcium dialysate on arterial compliance in patients on hemodialysis.

Arterial compliance (AC) is an important determinant of vascular structure, and abnormalities of AC can greatly affect the cardiovascular system. Given the vasoconstrictive properties of increased levels of serum ionized calcium (iCa), we investigated the way that dialysate calcium level can influence AC in the hemodialysis (HD) population. In a crossover randomized design, 19 dialysis patients undergoing regular bicarbonate HD (three times weekly) underwent two cycles of four successive HD sessions each with a low (LdCa; 1.25 mmol/L) and high dialysate calcium concentration (HdCa; 1.75 mmol/L). At the fourth session of each cycle, iCa level and hemodynamic parameters (systolic blood pressure [SBP], diastolic blood pressure, mean arterial pressure [MAP], pulse pressure [PP], heart rate, and AC) were measured pre-HD and post-HD. AC was measured noninvasively at the brachial artery by arterial pulse waveform analysis. The dialysate calcium level was a significant determinant of both pre-HD (r = 0.335; P < 0.05) and post-HD iCa level (r = 0.767; P < 0.001). Pre-HD AC increased significantly (P < 0.05) by 0.01+/- 0.02 mL/mm Hg (7% +/- 19%) on switching from HdCa to LdCa treatment. Multiple regression analysis showed that both pre-HD PP and iCa level were major inverse determinants of pre-HD AC in both the LdCa (R(2) = 0.65; P < 0.001) and HdCa (R(2) = 0.51; P < 0.01) treatment groups. AC increased by 32% (P < 0.01) and 37% (P < 0.05) during LdCa and HdCa dialysis, respectively. Intradialytic changes in AC were inversely correlated with changes in SBP and PP. In the HdCa group, changes in iCa level related significantly to MAP (r = 0.464; P < 0.05). The results show that changes in AC during HD are mainly mediated through concurrent changes of systemic hemodynamics, which are largely affected by dialysate calcium level through parallel changes in iCa level. Interdialytically, a significant, blood pressure-independent, inverse relationship between AC and iCa level exists. Therefore, HD with LdCa, by reducing the incidence of HD-induced hypercalcemia, may have a beneficial role in preventing the ongoing reduction of AC in HD patients and thus improving cardiovascular prognosis.

A comparative study of intraperitoneal carboplatin versus intravenous carboplatin with intravenous cyclophosphamide in both arms as initial chemotherapy for stage III ovarian cancer.

Cisplatin (C) or carboplatin (CBP) plus cyclophosphamide (CTX) was until recently considered standard chemotherapy for advanced ovarian cancer (OC). Attempts to maximize platinum and its analog activity against OC include its administration directly into the peritoneal cavity. In the past we have shown that intraperitoneal (IP) CBP administration is a safe and effective treatment for OC [Polyzos et al: Proc Am Assoc Cancer Res 1990;31: 1120]. In the present study we aimed to compare the effectiveness and toxicity of CBP administration either intravenously (IV) or IP plus CTX IV. Since 1990, 90 evaluable patients with stage III OC were prospectively randomized to receive CBP 350 mg/m2 IV or IP plus CTX 600 mg/m2 IV (in both groups) every 3-4 weeks for six courses. The randomization incorporated stratification according to performance status and the amount of residual tumor (maximum diameter 2 cm). Clinical assessment was performed with abdominal CT and serum CA-125. Responses were observed in 33/46 = 72% (95/CI 56.5-84.0) of the IV group and in 33/44 = 75% (95/CI 59.7-86.8) of the IP group with 48 and 45% clinical complete responses, respectively. Times to progression were 19 months (8-62+) for the IV group and 18 (6-72+) for the IP group. Median survivals were: 25 months (6-80+) and 26 months (6-72+), respectively. Significantly more patients in the IV group than in the IP group had grade 3 or higher leukopenia (p < 0. 01) and grade 3 thrombocytopenia (p < 0.09). Morbidity due to infectious complications in the IP group was minimal. It seems that IP CBP is equally effective to IV administration in terms of response and survival with less myelotoxicity. The favorable results on survival demonstrated in studies with IP C administration in patients with small volume disease [Alberts et al: N Engl J Med 1996;335:1950-1965] could not be repeated in the present study applying CBP in patients with variable tumor size and a relatively small number of patients. The likelihood that patients with large volume disease would benefit from a regional approach compared to systemic administration is small and this explains the inability to detect a difference between the two arms.

Optimal duration of chemotherapy in small cell lung cancer: a randomized study of 4 versus 6 cycles of cisplatin-etoposide.

With the purpose of investigating whether the 6-course standard dose treatment of etoposide-platinum (EP) in small cell lung cancer could be reduced to 4 courses without compromising patient's survival, 70 patients were randomized to receive either 4 or 6 cycles of etoposide 120 mg/m2 i.v. days 1-3 and cisplatin 80 mg/m2 day 1. With the intention of comparing these two durations as primary treatment policies, patients were randomized on admission and not after the fourth course. From the 69 evaluable patients 34 received EPx4 cycles and 35 EPx6 cycles. Objective response for EPx4 was achieved by 21 patients (62%, 95% CI 44%-78%) compared to 24 patients (69%, 95% CI 51%-83%) of the EPx6 group. Median times to progression were 6 mo (4-19) and 7 mo (4-40) respectively (P=0.06) in the two groups. Median survivals were 8.5 mo (4-28.5) and 9.5 mo (4-51) (p=0.04) respectively. No differences in the survival of limited-disease patients were shown with 10.5 mo (6-28.5) and 12 mo (8-51) respectively, in the two groups. Patients with extensive disease had a trend favoring prolonged chemotherapy with a median survival of 9 mo (5-16) versus 6.5 mo (4-16.5) for those in the EPx4 group (p=0.09). Toxicity was not significantly more severe in the EPx6 group. In conclusion, patients achieving complete response within 4 cycles may not need continued chemotherapy, but patients with extensive disease may benefit from 2 more cycles.

The smoking-cessation promotion practices of physician smokers in Greece.

In order to investigate Greek physicians' smoking habits and how these affect their role in promoting smoking cessation, a survey of 148 hospital physicians was undertaken. According to their answers, 44% of the internists and 54% of the surgeons admitted to smoking more than 20 cigarettes per day for at least five years. Major obstacles for quitting were their personalities (70-80%) and stress in hospitals (40%). For those willing to quit, an antismoking policy in their homes (32%) and hospitals (26-29%) could have been of a great help. With respect to smoking cessation, all (100%) of the non-smoking physicians were involved in smoking-cessation counseling or stressing the health hazards of smoking, compared with only 50% of the smoking group (p < 0.001). Moreover, the smokers tended to underestimate the risks of several smoking-related health hazards and did not emphasize them when counseling patients. Major obstacles to advising smoking cessation were lack of counseling time (53-70%) and pessimism regarding the outcomes of their efforts (60%), while 8% of the internists and 14% of the surgeons believed that counseling was not part of their role. The authors conclude that physician smokers need to be encouraged in their efforts to quit by their colleagues and by members of their families. Quitting smoking might help them to develop an optimistic view of success in their cancer-prevention practices.

Isoelectric focusing and 2D electrophoresis of the human androgen receptor.

Nuclear androgen receptors from cultured genital skin fibroblasts were analyzed by non-denaturing isoelectric focusing (IEF) in ultrathin polyacrylamide gels before and after photoaffinity labeling with [3H]methyltrienolone. Both reversibly and covalently labeled receptors focused at pH 5.28 +/- 0.20 when extracted from nuclei with high salt. Lowering of the salt concentration yielded, in both cases, a second species which focused at pH 7.16. This species became predominant when nuclei were sonicated in IEF sample buffer containing no salt, even after extensive nucleic acid digestion. Low salt cytosols from both prostate and foreskin focused as a single peak of pI: 4.93 +/- 0.31 which remained unchanged when KCl was added to the cytosol up to a concentration of 0.6 M. SDS-polyacrylamide gel electrophoresis of photoaffinity labeled receptors revealed labeled proteins with Mw 90-95 kDa. Two-dimensional electrophoresis of photoaffinity labeled nuclear receptors, extracted in low or high salt, showed that the two isoforms (pI 5.28 and 7.16) contain the same steroid-binding subunit with Mw 90-95 kDa. Nuclear receptors from 4 patients with the receptor positive form of the Complete Androgen Insensitivity Syndrome (CAIS, Rc+) were analyzed by non-denaturing IEF: a single species was observed, focusing at pH 6.0 whether in high or low salt conditions. These results indicate that the nuclear androgen receptor is an acidic protein with pI 5.28 and Mw 90-95 kDa under maximum protein dissociation conditions. When extracted under low salt conditions, it can be isolated in a neutral form (pI 7.16) suggesting its association with a nuclear protein. Receptors of (CAIS, Rc+) patients have an abnormal charge and show no pI shift upon lowering of the salt concentration suggesting that this shift could be a significant step in the mechanism of action of androgens.

Androgen receptor in sexual differentiation.

Androgens play an essential role in sexual differentiation and their action is mediated by the androgen receptor (AR). The normal AR is a soluble protein, highly thermolabile, with a mol. wt of 90 kDa and a pI of 5.2 as determined by 2 dimensional (2D) gel electrophoresis. It is regulated by androgens in culture conditions but the physiological relevance of this regulation remains controversial. The presence of a functional AR is an absolute requirement for male sexual differentiation and its absence results in complete insensitivity. However, androgen insensitivity (complete or partial) can develop in the presence of a normal androgen binding capacity and there is no correlation between the clinical and the biochemical findings. A number of qualitative abnormalities have been described to explain the failure of androgen action in these cases: they all emphasize the extreme instability of the abnormal AR. It is difficult at the present time to determine whether these abnormalities result from structural mutations of the AR gene, transcriptional or post-transcriptional abnormalities. Further elucidation of these defects awaits for an antibody and/or a cDNA probe for the AR.

Inhibition of 5 alpha-reductase activity in human skin by zinc and azelaic acid.

The effects of zinc sulphate and azelaic acid on 5 alpha-reductase activity in human skin were studied using an in vitro assay with 1,2[3H]-testosterone as substrate. When added at concentrations of 3 or 9 mmol/l, zinc was a potent inhibitor of 5 alpha-reductase activity. At high concentrations, zinc could completely inhibit the enzyme activity. Azelaic acid was also a potent inhibitor of 5 alpha-reductase; inhibition was detectable at concentrations as low as 0.2 mmol/l and was complete at 3 mmol/l. An additive effect of the two inhibitors was observed. Vitamin B6 potentiated the inhibitory effect of zinc, but not of azelaic acid, suggesting that two different mechanisms are involved. When the three substances were added together at very low concentrations which had been shown to be ineffective alone, 90% inhibition of 5 alpha-reductase activity was obtained. If this inhibition is confirmed in vivo, zinc sulphate combined with azelaic acid could be an effective agent in the treatment of androgen related pathology of human skin.

Photoaffinity labeling of the androgen receptor from human skin fibroblasts.

The reproducible photolabeling of the androgen receptor from human skin fibroblasts, using [3H]methyltrienolone (R-1881) as ligand is described. Crude nuclei were irradiated for 2 min using a UV lamp with an emission line at 352 nm and a CuSO4 filter. After KCl extraction, proteins were precipitated with trichloroacetic acid, washed with ether and assayed for radioactivity. Specific binding was determined as the difference in bound radioactivity between cells incubated with [3H]R-1881 +/- a 200-fold excess of unlabeled dihydrotestosterone (DHT). The photolabeled proteins were analyzed on SDS-polyacrylamide gel electrophoresis yielding one peak of 90 kDa and in several cases, one of 43 kDa. These peaks comprised 60 +/- 20% of the saturable binding recovered on the gels. The overall efficiency of photolabeling was between 1 and 5%. The amount of covalently bound radioactivity was proportional to the number of cells used. The labeling was inhibited by R-1881, DHT, the anti-androgens hydroxyflutamide and cyproterone acetate and to a lesser extent by estradiol and progesterone. No covalent attachment of R-1881 to any protein was observed when nuclei from patients with androgen insensitivity were irradiated, whether or not the cells were receptor positive or negative. In conclusion the androgen receptor from human skin fibroblast can be efficiently photolabeled and could be used as a marker to follow receptor purification. The absence of photolabeling of nuclear extracts from receptor-positive androgen-insensitive patients may reflect some abnormality of the receptor.