Efficacy of combined treatment with alendronate (ALN) and eldecalcitol, a new active vitamin D analog, compared to that of concomitant ALN, vitamin D plus calcium treatment in Japanese patients with primary osteoporosis.

UNLABELLED: Combined treatment with alendronate and eldecalcitol was found to be more effective in reducing the bone turnover markers and increasing bone mineral density than alendronate treatment with vitamin D3 and calcium supplementation in the osteoporotic patients. INTRODUCTION: We compared the clinical efficacy and safety of combined treatment with alendronate plus eldecalcitol (ALN + ELD) with those of treatment with ALN plus vitamin D and calcium (ALN + VitD). METHODS: Osteoporotic 219 patients were randomly assigned to the ALN + ELD, or the ALN + VitD group. Primary endpoint was the inter-group differences in lumbar spine BMD (L-BMD) at patient's last visit. Secondary endpoints included the differences in BMD at other sites and the bone turnover marker (BTM) levels. RESULTS: L-BMD, total hip BMD and femoral neck (FN-BMD) increased from baseline by 7.30, 2.41, and 2.70 % in the ALN + ELD group, and by 6.52, 2.27, and 1.18% in the ALN + VitD group, respectively. Inter-group differences of the L-BMD and total hip BMD values were not significant. The increase of the FN-BMD was larger in the ALN + ELD group than the ALN + VitD group. Reductions of the BTMs were greater in the ALN + ELD group than the ALN + VitD group. Interaction of the percent increase of the L-BMD with the baseline values of the BTMs was observed in the ALN + VitD group only. The increases of the FN-BMD in patients with lower baseline values of type-I-collagen C-telopeptide (sCTX) and serum 25(OH) D levels <20 ng/mL were significantly larger in the ALN + ELD group than the other group. CONCLUSION: Combination treatment of ALN plus ELD was more effective in reducing the BTMs and increasing the FN-BMD than ALN treatment with vitamin D3 and calcium.

Clinical efficacy and treatment persistence of monthly minodronate for osteoporotic patients unsatisfied with, and shifted from, daily or weekly bisphosphonates: the BP-MUSASHI study.

UNLABELLED: This multi-center, prospective, open-label, observational study evaluated the effects of once-monthly minodronate (50 mg) on treatment persistence, bone turnover markers, bone mineral density, low back pain, and upper gastrointestinal symptoms in outpatients with osteoporosis previously treated with daily or weekly bisphosphonate products. INTRODUCTION: The purposes of this study were to investigate the effects of once-monthly oral minodronate (MIN 50 mg) on bone turnover markers and bone mineral density, low back pain, and upper gastrointestinal symptoms, as well as preference for and treatment persistence of MIN 50 mg among Japanese osteoporosis patients currently treated with daily or weekly bisphosphonates. METHODS: Study patients were allocated based on their preference to either the Switch group (patients willing to switch over to MIN 50 mg) or the Continue group (patients wanting to continue their current therapies). Patients' treatment persistence and satisfaction levels with the therapies were assessed using a self-administered questionnaire. The study endpoints were serum TRACP-5b, serum P1NP, bone mineral density, upper gastrointestinal symptoms, and low back pain. RESULTS: In total, 264 and 133 patients were allocated into the Switch and Continue groups, respectively. Approximately, 65 % of patients were willing to switch to MIN 50 mg, with the predominant reason being "less frequent dosing more convenient." Treatment persistence was significantly higher in the Switch group (MIN 50 mg) than the Continue group. Almost all patients with abnormal bone metabolism markers demonstrated normalization after switchover. MIN 50 mg alleviated low back pain and upper gastrointestinal symptoms induced by prior bisphosphonate use. CONCLUSIONS: MIN 50 mg alleviates low back pain, reduces bone turnover markers and increases bone density, and induces fewer upper gastrointestinal symptoms after switchover from prior bisphosphonate products, and therefore, it may provide patients with a more convenient treatment option and enhance long-term treatment persistence.

Immunohistochemical detection of cytokeratin 18 and its neo-epitope in Warthin's tumor (adenolymphoma) of the parotid glands.

An immunohistochemical method using a monoclonal antibody M30 (MAb M30), which reacts with the product released by cleavage of cytokeratin 18 (CK18) by activated caspase, was used to investigate the presence and extent of apoptosis in 36 cases of Warthin's tumor (WT) of the parotid glands. The distribution of CK18 in WT was also determined and compared with that of the product detected by MAb M30. In WT, CK18 was observed mainly in the tumor cells of duct-like structures, but not in the cells of lymphatic tissues. Positive MAb M30 reaction products were found in luminal contents, duct-like structures and the cytoplasm of some macrophages in lymphatic areas near the duct-like structures in WT. These findings indicated that apoptotic cells are phagocytosed and eliminated as waste by macrophages. It is suggested that a mechanism which regulates the balance of proliferative activity and apoptosis may be closely linked to the growth of WT.

Therapeutic effect of basic fibroblast growth factor on experimental pancreatitis in rat.

Basic fibroblast growth factor (bFGF) is one of the mitogens that facilitate endothelial proliferation and angiogenesis. This study was designed to examine the therapeutic effect of bFGF on experimental pancreatitis in rat. Edematous pancreatitis was induced by intraperitoneal injections of cerulein (50 microg/kg) at hourly intervals. BFGF (70 nmol/kg) was administered intraperitoneally after induction of pancreatitis. DNA synthesis of isolated pancreatic acinar cells of normal rats was determined as the uptake of 5-bromo-2'-deoxyuridine (BrdU) into the cells. Immunohistochemical staining of DNA synthesis in acinar cells during cerulein-induced pancreatitis was also examined with BrdU labeling in vivo technique. Cerulein administration increased serum amylase, lipase level, and wet weight of pancreatic tissue. Treatment with bFGF markedly ameliorated all these parameters. In primary culture system of isolated pancreatic acinar cells of normal rats, bFGF caused a dose-dependent increase in BrdU incorporation into DNA, showing an EC50 value of 0.8 nmol/L and a maximum response of 2.5-fold increase at a concentration of 400 nmol/L. bFGF treatment (70 nmol/kg) markedly increased BrdU labeling in the nucleus of acinar cells of the pancreatitis rats group in immunohistochemical examination when compared with control without bFGF treatment. Treatment with bFGF may represent a promising therapeutic concept for patients with acute pancreatitis.

Thyroid hormone-free albumin: charcoal treatment or resin treatment.

Free thyroid hormone measurement by means of immunoassay kits is greatly influenced by the altered serum albumin and free fatty acid (FFA) levels. In the evaluation of these kits, it is therefore essential to study the interferences due to these factors by adding FFA or thyroid hormone-free human serum albumin (HSA) to the assay mixture, but little attention has been paid to the selection of albumin. In the present study, FFA content in various preparations of thyroid hormone-free HSA was compared. Charcoal-treated HSA was free from both thyroid hormone and FFA, whereas anion exchange resin-treated HSA was only free from thyroid hormone. Commercially available "FFA-free HSA" was also free from thyroid hormone. Our results suggest that attention must be paid to the nature of albumin when studying the interference by albumin in free thyroid hormone measurement and that commercially available "FFA-free HSA" is a ready-to-use thyroid hormone-free HSA when HSA free from both FFA and thyroid hormone is desired.

Fluorescent substances and high molecular weight protein aggregates formed in rat heart mitochondria upon doxorubicin-induced lipid peroxidation.

A rat heart mitochondrial suspension was incubated with doxorubicin, FeCl3 and NADH. Fluorescent substances and high molecular weight protein aggregates were observed in the mitochondrial membranes upon the formation of thiobarbituric acid-reactive substances. Since both fluorescent substances and high molecular weight protein aggregates are retained in mitochondrial membranes, they can be of use in the clarification of the site of doxorubicin-induced lipid peroxidation.

Evaluation of adriamycin-induced lipid peroxidation.

Lipid peroxidation is known to be a mechanism for Adriamycin-induced toxicity. In the present study, two methods which detect fluorescent substances and high molecular weight protein aggregates in peroxidized membranes were applied to Adriamycin-induced lipid peroxidation in liver microsomes. A rat liver microsomal suspension containing an NADPH-generating system was incubated with Adriamycin. Thiobarbituric acid reactive substances (TBA-RS), formed during this incubation, were transferred from the microsomes to the medium. Fluorescent substances determined by the fluorescence emitted from both the microsomes themselves and the chloroform/methanol extracts of the microsomes, were found to be formed during this incubation. High molecular weight protein aggregates determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, were also formed. Fluorescent substances and high molecular weight protein aggregates were found in microsomal membranes themselves and increased time dependently. These substances retained in membranes can be of great use to delineate the site of Adriamycin-induced lipid peroxidation in vitro and in vivo and to determine how this lipid peroxidation affects the membrane.

[Fundamental and clinical studies on ceftazidime in the field of paediatrics].

Ceftazidime (CAZ), a new cephem antibiotic for injection, was used in the field of paediatrics, and the following results were obtained. Antibacterial activity of CAZ was high against Gram-negative rods including P. aeruginosa, but slightly low against Gram-positive cocci. Absorption and excretion of CAZ were rapid, and 90% or more was excreted at 6 hours after administration. The clinical efficacy was excellent or good in all the 4 cases treated with CAZ, and no side effects were observed.

Video integrated measurement system.

A Video Integrated Measurement (VIM) System is described which incorporates the use of various noninvasive diagnostic procedures (moire contourography, electromyography, posturometry, infrared thermography, etc.), used individually or in combination, for the evaluation of neuromusculoskeletal and other disorders and their management with biofeedback and other therapeutic procedures. The system provides for measuring individual diagnostic and therapeutic modes, or multiple modes by split screen superimposition, of real time (actual) images of the patient and idealized (ideal-normal) models on a video monitor, along with analog and digital data, graphics, color, and other transduced symbolic information. It is concluded that this system provides an innovative and efficient method by which the therapist and patient can interact in biofeedback training/learning processes and holds considerable promise for more effective measurement and treatment of a wide variety of physical and behavioral disorders.

[A case of primary reticulum cell sarcoma of the brain with uveitis (author's transl)].

In 1972, Neault and his co-workers reported seven cases of uveitis associated with intracranial reticulum cell sarcoma. Recently we have experienced a similar case for the first time in Japan. A 32-year-old woman registered on March 10, 1971, complaining of blurred vision in the left eye for about two weeks. By ophthalmic examination, left posterior uveitis was diagnosed but the etiology was unknown. Treatment with corticosteroids was begun, but her left eye continued to fail in spite of the treatment. In August, 1971, she complained of weakness of left arm and leg, and in October, she suffered from severe headache and vomiting. At that time, uveitis appeared in the right eye too. Neurological findings and carotid angiogram indicated a right cerebral lesion. On November 5, 1971, a right frontoparietal craniotomy was performed but no tumor was found. Since then her neurological and eye symptoms had been progressively worse. The patient died on July 12, 1972. Postmortem examination revealed the tumor infiltrating in the bilateral diencephalon, left internal capsule, left lenticular nucleus, left temporal lobe, midbrain, pons, left dentate nucleus, optic chiasma and intracranial portion of the optic nerves. But no tumor was found at any other parts of the body. Histologically the tumor was a reticulum cell sarcoma. The eyeballs were not examined histologically, but the uveitis in this case was thought to be closely related to the intracranial reticulum cell sarcoma. If the uveitis is resistant to the treatment, we must consider a possibility of reticulum cell sarcoma of the brain.