Effects of cinacalcet on bone mineral density and bone markers in hemodialysis patients with secondary hyperparathyroidism

Background

Cinacalcet markedly reduces the serum intact parathyroid hormone (PTH) level of hemodialysis (HD) patients with secondary hyperparathyroidism. Parathyroidectomy also reduces the serum intact PTH level of HD patients and it increases their bone mineral density (BMD). However, there is little information about the effect of cinacalcet on BMD or on the associations between bone markers and BMD in HD patients.

Methods

We performed a 1-year cohort study of 25 HD patients who had a serum intact PTH level above 300 pg/ml during treatment by conventional therapies, such as with active vitamin D, and cinacalcet was prescribed for 14 of them. BMD of the femoral neck and the serum levels of two circulating bone markers, alkaline phosphatase (ALP) and bone-specific alkaline phosphatase (BSAP), were measured before and after treatment. The other 11 HD patients without cinacalcet treatment were defined as control group.

Results

BMD significantly increased by 7.3 % during the 1 year of treatment in the cinacalcet group and decreased by 6.2 % during the same period in the control group, and cinacalcet therapy was independently associated with the changes in BMD after multiple regression analysis that included intact PTH (β = 7.57, P < 0.01). In the cinacalcet group, the serum ALP levels (R ² = 0.315, P < 0.05) and BSAP levels (R ² = 0.682, P < 0.01) levels were significantly negatively correlated with the changes in BMD, but the serum intact PTH levels were not significantly associated with the changes in BMD (R ² = 0.011, P = 0.72).

Conclusions

One year of treatment with cinacalcet increased the BMD of the femoral neck in the HD cohort, especially in the patients who had higher serum ALP and BSAP levels at baseline.     

Thyroidectomy Using Pure Natural Orifice Transluminal Endoscopic Surgery in a Porcine Model

Surgical procedures for thyroid disease that provide cosmetically acceptable results are in demand. Natural orifice transluminal endoscopic surgery (NOTES) is performed through natural orifices and thus avoids incision of the body wall. This study aimed to develop an incision‐free surgical procedure for thyroid lobectomy using pure NOTES with an oral approach. In six pig carcasses, an incision was made between the mandible and subcutaneous tissue under direct vision. After subcutaneous dissection and identification of the hyoid bone, the operative field was developed under endoscopic view. After the thyrohyoid membrane was identified, dissection was continued along the thyroid cartilage until the cricoid cartilage was identified and the thyroid isthmus was reached. An original retractor was inserted between dissected tissues to lift and fix the carcass. The thyroid gland was successfully removed through the incision. Similar macroscopic and histological findings were observed on the normal and treated sides, with no damage to the recurrent laryngeal nerves. The times required for securing the operative field and thyroidectomy improved with each operation. This study suggests the feasibility and safety of using pure NOTES for thyroidectomy through a subcutaneous route with an original retractor.     

Assessment of coronary artery calcification in hemodialysis patients using multi-detector spiral CT scan.

Cardiovascular disease in association with coronary artery calcification (CAC) is the leading cause of death in patients with end-stage renal disease (ESRD). The evaluation of CAC has been performed by electron beam CT scan. The purpose of the present study was to assess CAC using multi-detector spiral CT (MDCT) and to evaluate contributors to CAC in these patients. Fifty-three patients on chronic hemodialysis participated in this study. Their mean age was 61.0+/-9.6 years, and the mean duration of dialysis therapy was 6.7+/-5.4 years. We used an automatic device to measure arterial pulse wave velocity (PWV) as an index of arterial wall stiffness. The aortic calcification index (ACI) was quantified morphometrically by CT scan. The CAC score correlated positively with ACI score (r =0.863, p <0.0001). Linear regression analysis indicated that the CAC scores correlated positively with age (r =0.406, p =0.0023), C-reactive protein (r =0.38, p =0.0047) and PWV (r =0.303, p =0.0271). Stepwise regression analysis indicated that ACI (beta-coefficient=0.862, p <0.0001) and arterial PWV (beta-coefficient=0.303, p <0.0001) were independently associated with CAC score. The mean CAC score of patients with cardiac events (2,568.5+/-2,575.1 mm3) was significantly higher than that (258.0+/-409.2 mm3) of patients without cardiac events. In conclusion, our results showed clearly that assessment of CAC score using MDCT may be predictive for detecting the presence of coronary artery disease. CAC is indirectly associated with increased arterial stiffness and the extent of aortic calcification in hemodialysis patients. We did not find a significant correlation between CAC score and parameters of mineral metabolism, including serum levels of calcium, phosphorus and parathyroid hormone. A longitudinal prospective study is required to assess the predictive value of this technique in determining cardiac events in large numbers of hemodialysis patients.     

Effect of hourly concentration of particulate matter on peak expiratory flow in hospitalized children: A panel study

Background  

Little information is available on the possible association between hourly short-term air pollution and peak expiratory flow (PEF) in asthmatic children.     

Significance of Serum Neuron-specific Enolase as a Predictor of Relapse of Small Cell Lung Cancer

We conducted a prospective study to evaluate the significanceof serum neuron-specific enolase (NSE) as a predictor of relapseof small cell lung cancer (SCLC). Patients entered into thestudy were drawn from those who had shown a complete or partialresponse to first-line chemotherapy with a concurrent declinein the NSE level to less than 10 ng/ml. When the serum NSE levelincreased to more than 15 ng/ml, the patient was restaged onthe basis of clinical, radiological, and bronchoscopic examinations.During the period from August 1988 to December 1990, 57 patientswith SCLC were enrolled and followed up until May 1992; Of thesepatients, 45 had clinical relapses, and 14 (31%) of them showeda clear elevation of the serum NSE level prior to the clinicalrecognition of relapse. Although one false-positive case wasnoted, this involved only a transient elevation of the NSE level.In patients who showed increased NSE levels, the relapses occurredin more difficult to detect silent sites such as the adrenalgland, liver, and deep lymph nodes. In addition, the percentageof patients demonstrating high NSE levels who were able to benefitfrom salvage chemotherapy was higher than for those who didnot (P<0.05). Our results indicate that serial NSE measurementsare useful for the early prediction of SCLC relapse and shouldhelp to facilitate early administration of salvage chemotherapyfor affected patients.(P<0.05)     

Superior efficacy of MMCP regimen compared with VMCP and MMPP regimens in the treatment of multiple myeloma

OBJECTIVE: A newly designed combination chemotherapy for multiple myeloma, MMCP [ranimustine (MCNU), melphalan (MPH), cyclophosphamide (CPM) and prednisolone (PSL)], was analyzed and compared with the results of our previous randomized trial of VMCP [vincristine, MPH, CPM and PSL] and MMPP [MCNU, MPH, procarbazine and PSL]. METHODS: MCNU (33.3 mg/m2, div) on day 1 and MPH (4 mg/m2, po), CPM (66.7 mg/m2, po) and PSL (30 mg/m2, po) from day 1 to 4, were administered. Each cycle was repeated every 3 weeks. PATIENTS OR MATERIALS: From January 1991 until August 1995, 104 patients with multiple myeloma diagnosed at 10 hospitals of Nagoya Cooperative Study Group were enrolled. RESULTS: Of the 87 evaluable patients, partial response rate for MMCP was 65.5% and was significantly higher than that of VMCP (13/47=27.7%, p<0.0001) and that of MMPP (21/47=44.7%, p=0.0196). A plateau attainment was observed in 49.4%. The percentage of the patients who attained plateau was significantly increased in the MMCP arm than in the VMCP arm (19.1 %, p=0.0017) but was not in comparison with that of MMPP arm (42.6%, p=0.6790). Patients treated with MMCP survived significantly longer than those treated with VMCP or MMPP (p=0.0009 by generalized Wilcoxon test, p=0.0023 by log-rank test) with median survival for MMCP being 31.6 months, for VMCP 22.5 months, and for MMPP 22.9 months. No significant differences were observed with respect to adverse effects among the three regimens. CONCLUSION: The newly designed MMCP is a candidate as an induction chemotherapy for multiple myeloma.     

Aneurysm originating from the fenestration of the posterior cerebral artery: case report

OBJECTIVE AND IMPORTANCE: A rare case of an aneurysm arising at the fenestration of the P2 segment of the posterior cerebral artery is reported. CLINICAL PRESENTATION: A 37-year-old man presented with severe headache and disturbance of consciousness. Computed tomographic scanning showed diffuse subarachnoid hemorrhage. Cerebral angiography revealed an aneurysm at the fenestration of the P2 segment of the right posterior cerebral artery. The aneurysm was located at the middle portion of the lower trunk of the fenestration. An unruptured arteriovenous malformation was incidentally found in the right thalamus. INTERVENTION: A right frontotemporal craniotomy with orbitozygomatic osteotomy was made, and the aneurysm was successfully clipped. One year after the operation, gamma knife surgery was performed for the right thalamic arteriovenous malformation. CONCLUSION: This is the first reported case of an aneurysm originating from the middle portion of a fenestrated posterior cerebral artery.     

A novel protein with alkaline phosphatase and protease inhibitor activities in Streptomyces hiroshimensis

A novel alkaline phosphatase (S-ALP) was found in the culture filtrate of Streptomyces hiroshimensis IFO 12785. Purification was achieved on Sephadex G-75 column, palmitoylated gauze column, and Superdex 75 HR column chromatographies. The molecular weight of S-ALP was estimated to be 14200 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The isoelectric point is 9.2. S-ALP had maximum enzyme activity at pH 9.5. S-ALP efficiently catalyzed both p-nitrophenyl phosphate and p-nitrophenyl phosphorylcholine substrates, particularly the latter. The N-terminal amino acid sequence (25 residues) of S-ALP was 60 to 72% identical to that of Streptomyces subtilisin inhibitor-like proteins. S-ALP exhibited trypsin inhibition in addition to a strong inhibition of subtilisin.     

Therapeutic approaches to the treatment of Alzheimer's disease

Alzheimer's disease is the most common cause of progressive decline of cognitive function in aged humans and is characterized by the presence of numerous senile plaques and neurofibrillary tangles accompanied by neuronal loss. The only treatment currently available for the disease is pharmacotherapy with acetylcholinesterase inhibitors, a palliative strategy aimed at the temporary improvement of cognitive function. Other strategies with disease-modifying potential may include the use of antiinflammatory drugs, estrogen replacement therapy and antioxidants. Recent progress in understanding the molecular and cellular pathophysiology of Alzheimer's disease has suggested possible pharmacological interventions that could modify the development and progress of the disease (disease-modifying therapy), such as treatment with secretase inhibitors, transition metal chelators, HMG-CoA reductase inhibitors and amyloid-b immunization. Inhibitors of tau hyperphosphorylation may also modulate the development and progress of the disease.