[A Case of General Fatigue Caused by Enzalutamide that was Evaluated Using the Cancer Fatigue Scale and Overcome by Switching to Nighttime Treatment].

An 81-year-old man with castration-resistant prostate cancer experienced general fatigue while receiving enzalutamide treatment. In some patients we encountered the enzalutamide treatment had to be interrupted or the dose decreased because of this adverse effect. We evaluated the patient's general fatigue using the Cancer Fatigue Scale (CFS) score and clarified the quantitative information about his general fatigue. In order to maintain the optimal dose, we advised the patient to take enzalutamide at night. This alleviated the adverse effect, and he could maintain the optimal dose of this medicine. We compared the CFS score before and after switching to nighttime treatment and found improvement. This is the first report of a CFS-based evaluation of the improvement in general fatigue caused by enzalutamide by switching to nighttime treatment.

Silodosin versus naftopidil in the treatment of premature ejaculation: A prospective multicenter trial.

OBJECTIVES: To determine the efficacy of two α1-adrenoceptor antagonists with different affinities for α1-adrenoceptor subtypes, silodosin and naftopidil, in the treatment of premature ejaculation. METHODS: This was a prospective, open-label, multicenter trial. A total of 26 patients with untreated acquired premature ejaculation were enrolled. Premature ejaculation was defined based on the International Society for Sexual Medicine recommendation. Patients self-administered on demand silodosin 4 mg or naftopidil 25 mg 1 h before intercourse, alternating drugs at least three times each. Clinical global impression change for premature ejaculation, premature ejaculation profile, and intravaginal ejaculation latency time were evaluated at baseline and during treatment. RESULTS: Due to clinical global impression change, 24 patients (92%) and 12 patients (46%) reported improvement in their own premature ejaculation problems under silodosin and nafitopidil administration, respectively. Silodosin treatment produced a significantly higher improvement rate compared with naftopidil (P = 0.0002). Objectively, silodosin significantly prolonged intravaginal ejaculation latency time compared with baseline and naftopidil (P < 0.01). Mean intravaginal ejaculation latency times were 1.9, 4.1, and 7.6 min at baseline, control and with silodosin, respectively. The rate of reduced semen volume during silodosin treatment was higher than during naftopidil treatment. There were no adverse systemic effects in either group. CONCLUSIONS: Silodosin, a highly selective α1A-adrenoceptor antagonist, produces greater improvements in premature ejaculation profiles and related symptoms along with intravaginal ejaculation latency time in acquired premature ejaculation patients with or without erectile dysfunction. This result supports the clinical use of silodosin as an alternative treatment for premature ejaculation.

In vitro assessment of six aspiration catheters using a distal protection filter.

BACKGROUND: We assessed performance of 6 aspiration catheters for distal embolization using a distal protection filter in an in vitro experiment. In acute myocardial infarction, a distal protection filter is used for lesions likely to induce a distal embolism. Which aspiration cathether is most effective when used with a distal protection filter remains still unclear. METHODS: A 0.5-cm3 bolus of gelatin as a model of stagnant pools of coronary plaque debris was captured in the distal protection filter and aspirated by 6 aspiration catheters. We measured and compared the length of the suspended embolus matter. RESULTS: Among the 6 catheters evaluated, the use of the Export Advance catheter (Medtronic) resulted in significantly shorter lengths of the suspended embolus matter compared to the use of the TVAC II (Nipro), Thrombuster III SL (Kaneka), and Rebirth Pro (Goodman) catheters (p < 0.01). The residual embolus matter in all cases had drained distally to the distal protection filter when the filter was retrieved. CONCLUSIONS: The use of the Export Advance catheter showed better performance using a distal protection filter in this in vitro experiment, and its use might be more effective in preventing distal embolisms in combination with a distal protection filter.

[Protein-losing enteropathy with systemic lupus erythematosus effectively treated with octreotide and medium chain triglyceride diet: A case report].

In January 2009, a 62-year-old man presented with diarrhea, leg edema, and thrombopenia and was admitted to our hospital. The past medical history revealed Sjögren's syndrome and autoimmune hepatitis for which he had been administered prednisolone. On admission, a laboratory examination revealed massive hypoalbuminemia and high levels of C-reactive protein and platelet-associated IgG. Anti-double stranded DNA and anti-Sm antibodies were negative. Analysis of the bone marrow aspirate and Tc-99m albumin scintigraphy findings suggested autoimmune thrombocytopenic purpura (AITP) and protein-losing enteropathy (PLE), respectively. We diagnosed him as SLE, because past immunoserological testing had showed positivity for anti-double stranded DNA antibody and LE cells. Methylprednisolone pulse therapy and intravenous immunoglobulin therapy were ineffective. Rituximab was ineffective against PLE but was effective against AITP. Cyclosporine and Cyclophosphamide were ineffective against PLE. Subcutaneous injection of 200-µg octreotide daily and a medium chain triglyceride (MCT) diet was effective against PLE, and the patient's condition dramatically improved. The effectiveness of octreotide treatment and an MCT diet in the treatment of PLE with SLE is discussed.

Marked cortisol production by intracrine ACTH in GIP-treated cultured adrenal cells in which the GIP receptor was exogenously introduced.

The ectopic expression of the glucose-dependent insulinotropic polypeptide receptor (GIPR) in the human adrenal gland causes significant hypercortisolemia after ingestion of each meal and leads to Cushing's syndrome, implying that human GIPR activation is capable of robustly activating adrenal glucocorticoid secretion. In this study, we transiently transfected the human GIPR expression vector into cultured human adrenocortical carcinoma cells (H295R) and treated them with GIP to examine the direct link between GIPR activation and steroidogenesis. Using quantitative RT-PCR assay, we examined gene expression of steroidogenic related proteins, and carried out immunofluorescence analysis to prove that forced GIPR overexpression directly promotes production of steroidogenic enzymes CYP17A1 and CYP21A2 at the single cell level. Immunofluorescence showed that the transfection efficiency of the GIPR gene in H295R cells was approximately 5%, and GIP stimulation enhanced CYP21A2 and CYP17A1 expression in GIPR-introduced H295R cells (H295R-GIPR). Interestingly, these steroidogenic enzymes were also expressed in the GIPR (-) cells adjacent to the GIPR (+) cells. The mRNA levels of a cholesterol transport protein required for all steroidogenesis, StAR, and steroidogenic enzymes, HSD3ß2, CYP11A1, CYP21A2, and CYP17A1 increased 1.2-2.1-fold in GIP-stimulated H295R-GIPR cells. These changes were reflected in the culture medium in which 1.5-fold increase in the cortisol concentration was confirmed. Furthermore, the levels of adenocorticotropic hormone (ACTH) receptor and ACTH precursor proopiomelanocortin (POMC) mRNA were upregulated 2- and 1.5-fold, respectively. Immunofluorescence showed that ACTH expression was detected in GIP-stimulated H295R-GIPR cells. An ACTH-receptor antagonist significantly inhibited steroidogenic gene expression and cortisol production. Immunostaining for both CYP17A1 and CYP21A2 was attenuated in cells treated with ACTH receptor antagonists as well as with POMC siRNA. These results demonstrated that GIPR activation promoted production and release of ACTH, and that steroidogenesis is activated by endogenously secreted ACTH following GIP administration, at least in part, in H295R cells.

Isolated ACTH deficiency in self referred patients for LOH syndrome: two case reports.

We experienced two cases of isolated ACTH deficiency (IAD) in patients self referred for late-onset hypogonadism (LOH) syndrome. IAD is secondary adrenal insufficiency due to lack of secretion of ACTH and delayed diagnosis of this rare condition may be life-threatening. The predominant symptoms of IAD, such as general malaise and weakness, resemble those of LOH syndrome creating the possibility that IAD may be referred as LOH syndrome. Two middle aged men with severe general malaise visited our clinic requesting evaluation for LOH syndrome. Previous treatments had been ineffective and based on varying incorrect diagnoses by previous doctors. The patients self referred themselves for LOH syndrome. Some of their symptoms were consistent with LOH syndrome but others were atypical, in particular, the severity of malaise and appetite loss. Hormonal assays were compatible with adrenal insufficiency secondary to ACTH deficiency. Steroid replacement dramatically improved their symptoms. The clinical course of our two patients and points of differential diagnosis between IAD and LOH syndrome are reported here.

Testing a single monthly dose of darbepoetin alpha to maintain hemoglobin levels in continuous ambulatory peritoneal dialysis patients.

The newly developed erythropoiesis agent darbepoetin alpha (DA) allows for once-monthly dosing in the treatment of anemia in patients on dialysis. This dosing schedule has prompted some studies to examine the efficacy of DA in patients on continuous ambulatory peritoneal dialysis (CAPD). In the present study, we assessed whether intravenous (IV) administration of DA once monthly is effective for maintaining hemoglobin levels near 10.5 g/dL in patients on CAPD. This single-center prospective cohort study included 52 clinically stable patients (25 men, 27 women; mean age: 59 +/- 10 years). All patients had been on a stable weekly or twice monthly regimen of recombinant human erythropoietin (rHuEPO) before initiation of the study. To determine the monthly dose of DA, the previously used mean weekly dose of rHuEPO was divided by 200 to determine the equivalent weekly dose of DA in micrograms; that number was then multiplied by 4 to generate the monthly dose requirement. For example, if 3000 IUrHuEPO was being administered weekly, then the monthly dose of DA was calculated to be 60 microg (3000/200 x 4). All patients received a monthly dose of DA the first month, and hemoglobin and other routine laboratory tests were performed monthly for 24 consecutive weeks. In 26 patients, the calculated monthly DA dose remained stable. The monthly dose was increased by 25% in 22 patients and by 50% in 4 patients. With regard to iron stores and iron availability for erythropoiesis, no significant differences were observed in the patients on various doses of DA. Nonsignificant differences in weekly creatinine clearance as determined using the PD Adequest software (Baxter Healthcare, Tokyo, Japan) were observed between the groups. No clinically meaningful differences in other laboratory values between the groups were observed. Once-monthly administration of DA is not always sufficient to maintain hemoglobin levels in patients on CAPD when adequate dialysis therapy is not achieved.

Does cinacalcet HCl, an oral calcimimetic agent for the treatment of secondary hyperparathyroidism, improve arterial stiffness in patients on continuous ambulatory peritoneal dialysis?

Vascular calcification (VC) and arterial stiffness (AS) are major contributors to cardiovascular disease, and in chronic kidney disease, VC and AS are correlated. Disorders of calcium and phosphate metabolism contribute to the progression of VC and to increases in AS. The efficacy of cinacalcet (CIN) in reducing AS in patients on continuous ambulatory peritoneal dialysis (CAPD) has not been determined. The present study enrolled 19 CAPD patients (12 women, 7 men; mean age: 62.2 +/- 3.6 years) with serum intact parathyroid hormone (iPTH) greater than 500 ng/dL (mean value: 675 +/- 106 ng/dL) in whom daily oral treatment with CIN 25 mg was started. If administration of CIN for 3 months failed to reduce the level of iPTH to less than 300 ng/dL, the dose of CIN was increased to 50 mg daily. Before the start of CIN and at 3 years after the start of CIN, pulse wave velocity (PWV) was determined. In 11 patients, levels of iPTH were reduced to less than 300 ng/dL; levels in the rest of the patients remained high. We observed no significant differences in PWV before CIN and at 3 years after CIN start (1856 +/- 198 cm/s vs. 1726 +/- 187 cm/s). Multivariate regression analysis of PWV demonstrated that both systolic blood pressure and changes in serum levels of phosphate contributed to decreases in PWV In patients receiving CAPD, VC and AS might be the result of higher systolic blood pressure and increased serum levels of phosphate.

[Association between long-term smoking and hypertension and early-onset nodular glomerulosclerosis].

Diabetic nodular glomerulosclerosis, also known as Kimmelstiel-Wilson syndrome, is a specific pathological variant of diabetic nephropathy ; however, histological findings similar to diabetic nephropathy are observed occasionally without glucose intolerance. Therefore, such nodular glomerulosclerosis is called idiopathic nodular glomerulosclerosis. Several case reports that have been published recently indicate that smoking and hypertension, which are classical renal risk factors, may be attributed to this form of glomerular degeneration. Accordingly smoking- and hypertension-associated nodular glomerulosclerosis has been considered to be different from the idiopathic form. This novel form of nodular glomerulosclerosis is associated with a history of long-term smoking and hypertension, and the age of onset of this disease is more than 60 years. We present the case of a 27-year-old Japanese male who was admitted to our hospital with nephrotic syndrome, hypertension, and renal impairment. He had a smoking history of at least 13 years, and had been exposed to passive smoking for several years because his parents were smokers. Renal biopsy revealed diffuse and global nodular glomerulosclerosis, although the patient did not have any primary diseases such as diabetes mellitus or paraproteinemia, that can cause this condition. We diagnosed smoking- and hypertension-associated nodular glomerulosclerosis. Cessation of smoking and the administration of an angiotensin II receptor blocker decreased his proteinuria and showed recovery of kidney function. This case report suggests that long-term smoking is closely associated with nodular glomerulosclerosis. Further, in our case, the age of the patient was lower than that of patients with the same disease among cases that have been reported previously.

Comparison and survival of patients receiving hemodialysis and peritoneal dialysis in a single center.

The influence of the type of dialysis on survival of patients with end-stage renal disease (ESRD) is controversial. To compare survival among patients with ESRD receiving peritoneal dialysis (PD) or hemodialysis (HD), we conducted a prospective cohort study in a single center from April 1995 to March 2005. During that period, 454 patients (161 women, 293 men; mean age: 61.7 +/- 14.4 years; 46.6% with diabetic nephropathy) were started on HD therapy, and 120 patients (40 women, 80 men; mean age: 54.5 +/- 11.3 years; 16.7% with diabetic nephropathy) were started on PD therapy; all patients were followed for at least 3 years. The 3-year survival rates were 65% for the HD patients and 81% for the PD patients (p < 0.05). The causes of death in patients undergoing HD were 52% cardiovascular 25% infectious diseases, and 12% cancer; in patients undergoing PD, the causes were 36% infectious diseases, 24% cardiovascular, and 6% cancer Median time from initiation of dialysis to study enrollment was 90 days for HD patients and 180 days for PD patients. Although patients in this study were not randomly assigned to their initial type of dialysis therapy, survival rate was found to be dependent on dialysis type. Moreover, this study suggests the importance of early referral and evaluation of risk factors in individual patients before they are started on dialysis therapy.