Bone metabolism after cinacalcet administration in patients with secondary hyperparathyroidism.

Cinacalcet, an allosteric modulator of a calcium (Ca)-sensing receptor, significantly suppresses parathyroid hormone (PTH) secretion and bone turnover rate in chronic hemodialysis (HD) patients with secondary hyperparathyroidism (SHPT). In this study, bone metabolism after cinacalcet treatment was examined, because hungry bone syndrome is sometimes experienced after parathyroidectomy in severe SHPT. We conducted a prospective observational study in 17 HD patients with SHPT. Cinacalcet was started at 25 mg/day, and the dose was increased step by step based on serum calcium level. A significant decrease in serum Ca and intact PTH concentration was found within 2 weeks. Tartrate-resistant acid phosphatase 5b, a good bone resorption marker, was significantly decreased at week 2 of the study. Serum bone alkaline phosphatase, a marker of bone formation, was increased at week 2 compared with the basal level. It became, however, gradually decreased until week 14. Only one patient whose bone turnover was considerably high had a mild numbness feeling. These results suggest that cinacalcet treatment might transiently accelerate bone formation with rapid suppression of bone resorption. This uncoupling could be involved in a mechanism by which cinacalcet decreases serum Ca level.

A population-based study of gefitinib in patients with non-small cell lung cancer.

Survival data for non-small cell lung cancer is typically reported from clinical trials that include patients fit enough to meet treatment criteria. The denominator of all patients from which the gefitinib-treated population is derived has rarely been reported and the impact of gefitinib on population-based outcomes is difficult to measure. We have retrospectively reviewed data of 626 patients who received gefitinib in Ibaraki Prefecture (with a population of 3 million) in Japan from July 2002 until September 2007. Overall response rate was found to 30.8%, and the median survival time was 8.0 months (95% confidence interval: 7.0-9.0 months). Female gender, good PS, and adenocarcinoma were significantly associated with prolonged survival. Adverse events were generally mild and were mostly skin reactions and diarrhea. Our population-based study has generated similar results to those previously reported in published clinical trials, which had restrictive criteria for eligible patients.

Association between erythropoietin requirements and antihypertensive agents.

BACKGROUND: Angiotensin-converting enzyme inhibitors (ACI) and angiotensin II receptor blockers (ARB) have been reported to increase recombinant human erythropoietin (rHuEPO) requirements. We performed a cross-sectional study to investigate an association of antihypertensive agents including these two with the rHuEPO dose in chronic hemodialysis patients. METHODS: We studied 625 patients undergoing hemodialysis therapy in 11 dialysis units. The association between the rHuEPO dose and antihypertensive agents was statistically analyzed. RESULTS: The mean hemoglobin (Hb) level and rHuEPO dose corrected by body weight were 10.5 g/dl and 95.2 U/kg/week, respectively. When the patients were subdivided into four groups according to the number of prescribed antihypertensive agents (G-0, G-1, G-2, and G-3; patients prescribed with no medication, 1, 2, and >3 drugs, respectively), a significantly low dose of rHuEPO was observed in G-0 compared to the other groups. Unpaired t test showed a higher dose of rHuEPO in the presence of ARB, alpha-blockers, or calcium channel blockers (CCB). The rHuEPO dose was higher in the elderly, in females, and in patients with diabetes or hypertension. In multiple regression analysis, age, sex, rHuEPO dose, serum albumin level, and duration of dialysis therapy but not antihypertensive drugs were independent factors for the Hb level. In contrast, the rHuEPO dose was significantly associated with a low level of Hb, age, females, and CCB use. However, since CCB use was strongly associated not only with rHuEPO dose but also with systolic blood pressure and the use of alpha-blockers and ARB, these findings might be caused by erythropoietin (EPO)-induced hypertension. CONCLUSION: There was an association between the number of antihypertensive agents and rHuEPO dose in chronic hemodialysis patients. However, no significant relation was indicated between ARB/ACI use and EPO requirements.

Co-morbid illnesses in patients with respiratory disease.

With the rising age, more patients will be diagnosed with one or more other serious illnesses. This study was undertaken to evaluate the frequency of co-morbid illnesses in patients with respiratory diseases, and to compare the frequency between the elderly and the younger patients. We performed chart review of 2764 patients with respiratory disease who admitted in three hospitals in Japan between January 1990 and March 2005. Co-morbid illnesses were observed in 69.5% of 2764 patients with respiratory disease. In 1150 patients 70 years or older, 83.9% of them had co-morbid illnesses. The prevalence of co-morbid illnesses in patients with respiratory disease clearly rose with increasing age (p= 0.0001), the largest increase occurring after the age of 50. Charlson index in patients with respiratory disease clearly rose with increasing age (p= 0.0001). In both elderly (>or= 70 years) or younger (< 70 years) groups of patients, co-morbid illnesses did not influence on the choice of diagnostic procedure. Although the presence of co-morbid illnesses in our patients with non-malignant respiratory disease did not influence on the choice of treatment, however, the presence of co-morbid illnesses in elderly patients with malignant respiratory disease apparently discouraged the choice of standard therapy. Clinical research should address appropriate therapies not only for the elderly patients without co-morbid illness but also for those with co-morbid illnesses. Being aware of the co-morbid illnesses will allow improved management and the planning of appropriate support to a wide range of elderly patients with respiratory disease with important and peculiar needs for care.

Increased serum levels of endostatin in patients with idiopathic pulmonary fibrosis.

Endostatin is an angiogenesis inhibitor that is an endogenously produced proteolytic fragment of type XVIII collagen. Serum levels of endostatin have been studied extensively in patients with malignant diseases. Recently, elevated serum endostatin levels were observed in patients with systemic sclerosis accompanying pulmonary fibrosis. To determine whether elevated serum endostatin can be observed in patients with idiopathic pulmonary fibrosis (IPF), we measured serum levels of endostatin in 69 patients with benign respiratory disease using an ELISA kit. The median of the serum endostatin levels in these patients was 50.8 pg/mL. Seven of 11 patients (63.6%) with collagen disease-associated pulmonary fibrosis (CDPF), and 19 of 24 patients (79.2%) with IPF had higher serum endostatin levels than the median level of the 69 patients. There was no statistical difference in serum endostatin levels between the patients with IPF and those with CDPF (P=0.7898). Serum endostatin levels in 24 patients with IPF were significantly higher than those in 34 patients with respiratory diseases other than IPF and CDPF (P=0.0001). Elevated serum levels of endostatin were observed in patients with IPF. Although the mechanisms are unclear, elevated serum levels of endostatin may be related to the fibrosing process in the lung.

Pneumonia in elderly patients with preexisting respiratory disease.

To evaluate the optimal duration of appropriate antibiotic therapy for pneumonia in elderly patients with preexisting respiratory disease, we studied improvement of infectious parameters in these patients. The medical record database was used to identify patients admitted with the following characteristics: primary diagnosis of benign respiratory disease; aged 65 years or over; no active malignant diseases in any organs; and at least one admission for pneumonia during April 2001 to May 2003. We observed 47 pneumonia episodes in 30 patients. Elevated CRP levels more than 8.0 mg/ml and leukocytosis more than 10.0 x 10(3) mm(-3) was seen in 21 and 29 pneumonia episodes, respectively. With appropriate intravenous antimicrobial therapy, average of CRP levels on day 0 (9.16 +/- 6.81 mg/dl) decreased to 5.18 +/- 4.67 mg/dl on day 3 (P = 0.0073). In more than 70% of pneumonia episodes, serum levels of CRP normalized on day 10. Average of leukocyte counts on day 0 ((12.3 +/- 4.7) x 10(3) mm(-3)) decreased to (8.1 +/- 3.5) x 10(3) mm(-3) on day 3 (P = 0.0001). In more than 80% of pneumonia episodes, leukocyte count normalized on day 7. The clinical response to appropriate antimicrobial therapy for pneumonia occurs within the first 3 days of therapy. Duration of intravenous antimicrobial therapy for pneumonia in these patients of 10 days would be sufficient and could prevent recurrent infection with resistant bacteria.