Clinical efficacy and safety of monthly oral ibandronate 100 mg versus monthly intravenous ibandronate 1 mg in Japanese patients with primary osteoporosis.

UNLABELLED: The MOVEST study evaluated the efficacy and safety of monthly oral ibandronate versus licensed monthly IV ibandronate in Japanese osteoporotic patients. Relative BMD gains after 12 months were 5.22 % oral and 5.34 % IV, showing non-inferiority of oral to IV ibandronate (primary endpoint). No new safety concerns were identified. INTRODUCTION: The randomized, phase 3, double-blind MOVEST (Monthly Oral VErsus intravenouS ibandronaTe) study evaluated the efficacy and safety of monthly oral ibandronate versus the licensed monthly intravenous (IV) ibandronate regimen in Japanese patients with osteoporosis. METHODS: Ambulatory patients aged ≥ 55 years with primary osteoporosis were randomized to receive oral ibandronate 100 mg/month plus monthly IV placebo, or IV ibandronate 1 mg/month plus monthly oral placebo. The primary endpoint was non-inferiority of oral versus IV ibandronate with respect to bone mineral density (BMD) gains at the lumbar spine after 12 months of treatment. RESULTS: Four hundred twenty-two patients were enrolled with 372 patients in the per-protocol set (183 and 189 in the oral and IV ibandronate groups, respectively). The relative change from baseline in lumbar spine BMD values for the oral and IV ibandronate groups, respectively, was 5.22 % (95 % confidence interval [CI] 4.65, 5.80) and 5.34 % (95 % CI 4.78, 5.90). The least squares mean difference between the two groups was -0.23 % (95 % CI -0.97, 0.51), showing non-inferiority of oral ibandronate to IV ibandronate (non-inferiority limit = -1.60). Changes in BMD values at other sites, and bone turnover marker levels in the oral ibandronate group, were comparable with those of the IV group. The safety profile was similar to that previously demonstrated; no new safety concerns were identified. CONCLUSIONS: This study demonstrated the non-inferiority of oral ibandronate 100 mg/month to IV ibandronate 1 mg/month (licensed dose in Japan) in increasing lumbar spine BMD in Japanese patients with primary osteoporosis.

The effect of improving oral health literacy among teachers on the oral health condition of primary schoolchildren in Cambodia.

AIM: In Cambodia, civil unrest has led to insufficient and inaccessible dental health services. Oral health education and awareness are lacking, thus childhood dental caries is highly prevalent. This study aimed to examine the effects of an oral health education programme for public primary school teachers on the pupils' oral health. METHODS: Between 2011 and 2015, an oral health education workshop was presented annually to primary school educators employed at a public school in Siem Reap, Cambodia. Oral screenings of 2,637 pupils (grades 1-6; subdivided between the lower 1-3 and upper 4-6 grades) were undertaken and the prevalence of dental caries, mean number of DFT, and mean percentage of DFT rate were calculated. CONCLUSION: Despite the persistently high prevalence of dental caries, the oral health status of the schoolchildren improved every year. Participation in the workshops may have improved the teachers' ability to provide oral healthcare instructions, leading to the reduced dental caries prevalence among pupils.

Label-free photoacoustic imaging of human palmar vessels: a structural morphological analysis.

We analysed the vascular morphology of the palm using a photoacoustic tomography (PAT) instrument with a hemispherical detector array. The three-dimensional (3D) morphology of blood vessels was determined noninvasively. Overall, 12 females and 11 males were recruited as healthy volunteers. Their ages were distributed almost evenly from 22 to 59 years. In all cases, many vascular networks were observed just beneath the skin and were determined to be veins anatomically. To analyse the major arteries, the layer containing the subcutaneous venous network was removed from the image. The analysis focused on the common and proper palmar digital arteries. We used the curvature of these arteries as a parameter to analyse their morphologies. There was no significant difference in the curvature between genders when comparing the subjects as a whole. The blood vessel curvature increased with age. Good agreement was found between the 3D numerical analysis results and the subjective evaluation of the two-dimensional (2D) projection image. The PAT system enabled visualization of the 3D features of blood vessels in the palm and noninvasive analysis of arterial tortuousness.

Visualization of tumor-related blood vessels in human breast by photoacoustic imaging system with a hemispherical detector array.

Noninvasive measurement of the distribution and oxygenation state of hemoglobin (Hb) inside the tissue is strongly required to analyze the tumor-associated vasculatures. We developed a photoacoustic imaging (PAI) system with a hemispherical-shaped detector array (HDA). Here, we show that PAI system with HDA revealed finer vasculature, more detailed blood-vessel branching structures, and more detailed morphological vessel characteristics compared with MRI by the use of breast shape deformation of MRI to PAI and their fused image. Morphologically abnormal peritumoral blood vessel features, including centripetal photoacoustic signals and disruption or narrowing of vessel signals, were observed and intratumoral signals were detected by PAI in breast cancer tissues as a result of the clinical study of 22 malignant cases. Interestingly, it was also possible to analyze anticancer treatment-driven changes in vascular morphological features and function, such as improvement of intratumoral blood perfusion and relevant changes in intravascular hemoglobin saturation of oxygen. This clinical study indicated that PAI appears to be a promising tool for noninvasive analysis of human blood vessels and may contribute to improve cancer diagnosis.

Fulminant pneumonia and sepsis due to Aeromonas hydrophila in an alcohol abuser.

A 69-year-old alcoholic man with pneumonia and sepsis due to Aeromonas hydrophila is presented. He died of suffocation by a copious amount of hemoptysis six hours after his first symptoms of abdominal pain, diarrhea and dyspnea. Aeromonas hydrophila was isolated from blood and bronchial secretion. A fulminant form of pneumonia could develop in patients with predisposing underlying conditions such as alcoholism with chronic hepatitis and diabetes mellitus. Aeromonas hydrophila pneumonia may be characterized by hemoptysis and rapid clinical deterioration with a high mortality rate.

[The effect of endotoxin on the neutrophil chemiluminescence in the rabbit].

To examine the effects of endotoxin on the neutrophil function, neutrophil-dependent microbicidal activities were evaluated by the chemiluminescence (CL) method in rabbits injected with endotoxin. Six rabbits in the first group were administered saline intravenously as control. Ten rabbits each in the second and third group received endotoxin 0.7 microgram.kg-1 and 70 micrograms.kg-1 respectively. Luminol-dependent CL in whole blood (whole blood CL) and in isolated neutrophils (neutrophil CL) were examined before administration and 30, 60, 180 and 360 min after administration. Peak values of whole blood CL in the second group were significantly depressed at 30 and 60 min, and elevated at 360 min. Those in the third group were depressed more than in the second group at all times after endotoxin administration. Peak values of neutrophil CL in the second group at 180 and 360 min were significantly elevated, but those in the third group at 30, 60, 180 min were markedly depressed. Experiments combining neutrophils and pooled plasma revealed that these CL responses were associated with the neutrophils themselves. It is speculated that the neutrophil suppression observed in the third group was caused by the overactivation of neutrophils induced by the activated complements and some other stimulating factors, and/or may be due to the abundant appearance of immature granulocytes with lesser activities.

[Awake pronation of surgical patients with cervical spinal lesions].

Positioning of patients with cervical spinal lesions under general anesthesia may lead to serious neurological complications. The authors attempted awake pronation in eighteen patients to minimize the risks. In all patients, cervical instability or cervical spinal cord compression was diagnosed, and posterior fusion or laminoplasty under general anesthesia was planned. Naso-tracheal intubation was performed by broncho-fiberoptic scope under topical anesthesia and light sedation. After tracheal intubation, pronation was completed while patients were still awake. Twelve patients could change their position almost by themselves, and needed only a little assistance of the medical staff. After the patients settled in appropriate position, general anesthesia was induced. Neurological status was assessed before and after the intubation, and just before the induction of general anesthesia, to prove the absence of complications. Operations were accomplished without major troubles in all patients. During post anesthetic interviews, eight patients had memory of the positioning, but none of them had any complaints about the procedure. Awake pronation may be useful to minimize the risk of neurological complications related to positioning of surgical patients, and also need less assistance by medical staff.

[A patient who recovered successfully from severe anemia which continued for one hour].

A 79-year-old woman had her cervical spinal cord injured and laminoplasty of the neck was performed. Uncontrollable venous bleeding was encountered during the operation and about 5000 ml of blood was lost in one hour. Massive infusion of 5% albumin and hydroxyethylstarch (HES) was done to maintain the intravascular volume. Therefore, her hematocrit value (Ht) decreased to 4.5%. Her rectal temperature went down to 34.5 degrees C. The operation was finished in haste. We studied leg pain experienced under spinal anesthesia in leprosy patients. Seven of twenty patients complained of the leg pain a few minutes after spinal block. The pain was localized in the parts of deafferentation or phantom limb, and was relatively mild and controllable. We consider that the inhibitory system is inactivated when the somatic impulse is blocked by spinal anesthesia, and as a result the abnormal burst activity of dorsal horn produced by peripheral nerve damage of leprosy causes phantom pain.

[Transient complete left bundle branch block during epidural anesthesia with mepivacaine].

A 65-year-old woman with ovarian tumor was scheduled for abdominal total hysterectomy and bilateral adnexectomy under epidural anesthesia. Preoperative examinations revealed no abnormalities including ECG. Twenty minites after the epidural injection of mepivacaine, widened QRS complexes, which were diagnosed as complete left bundle branch block (CLBBB) later, appeared on ECG. At that time, heart rate (HR) was 150.min-1. CLBBB disappeared when HR decreased to 110.min-1 following the administration of pindolol and verapamil. The operation was postponed. Exercise-treated ECG showed neither CLBBB nor ischemic change even when HR increased to 160.min-1. Two weeks later the operation was attempted again. CLBBB appeared again twenty minites after the epidural injection of mepivacaine. The CLBBB disappeared 5 minites after the induction of general anesthesia when HR decreased to 100.min-1. The operation was performed uneventfully. The effective refractory period (ERP) is shortened with the increase in HR, but the shortning of ERP varies in different part of the cardiac conduction system. In tachycardia, ERP of left bundle branch is longer than that of right one. Because the cardiac conduction system is depressed by local anesthetics, it is speculated that ERP of left bundle branch is elongated further by mepivacaine and CLBBB appeared in this case.

[A case of coronary spasm during the operation for lung cancer].

We reported a case of coronary spasm during the operation for lung cancer. A 72-year-old man underwent left upper lobectomy for lung cancer under general anesthesia with the aid of thoracic epidural anesthesia. Preoperative examinations did not reveal any clinical problems in the past. Hypotension and premature ventricular beats were observed for several times during operation due to the compression of the heart and left pulmonary artery by the surgeon's hands in stopping brisk bleeding. After this event, ST-segment of ECG was elevated abruptly. Intravenous administration of nitroglycerin was effective to relieve the coronary spasm in this case. Possible triggering factors were mechanical injury of the coronary artery due to compression of the heart, vagal stimuli under thoracic epidural anesthesia and alpha-stimulating drugs to treat hypotension. The importance of preoperative evaluation of coronary lesions, perioperative treatments with nitrates and calcium-channel blockers, and avoidance of intraoperative triggering factors are emphasized to prevent the coronary spasm.

[Myasthenia gravis is improved temporarily at postburn period].

A 62-year-old woman with a 25-year history of myasthenia gravis (MG) was admitted to our hospital due to burn injury over 20-25% of the total body surface area. Five months before admission, the serum concentration of acetylcholine receptor (AchR) antibodies was 80.9 nmol.l-1 (normal range < 0.3 nmol.l-1). Anticholinesterase agents had been administered for MG, but were discontinued six days after admission due to muscarinic side effects, but no symptoms of MG appeared. Thirteen days after admission, the AchR antibody titer was 21.2 nmol.l-1. Free skin grafting was performed under general anesthesia without any event. About 80 days after admission, weakness of extraocular muscles appeared. Positive tensilon test and the characteristic electromyographic findings revealed deterioration of MG, and anticholinesterase agents were resumed. Ten months after admission, the AchR antibody titer was 50.4 nmol.l-1. The mechanism of the temporary improvement of MG symptoms does not appear to be explained by the diffuse immunosuppression after burn. At a postburn period, nicotinic AchRs at the neuromuscular junction are known to be temporarily induced. This up-regulation may have caused the temporary improvement in this patient.

[Extracorporeal circulation for removal of carcinoma of the lung invading the left atrium].

A 42-year-old man with one year history of cough and chest pain due to right upper lung cancer was scheduled for radical surgery. An echocardiogram and a lung scan showed a tumor mass in the left atrium, which was originating from carcinoma of the right upper lobe. Right pneumonectomy and atrial tumor extirpation were done successfully under the state of cardiac arrest using extracorporeal circulation with topical cooling by crushed ice in order not to spread the tumor cells into systemic circulation. He was extubated on the 1st postoperative day. But, thereafter he developed moderate dyspnea. On 7, 10 and 13th postoperative days he fell into the state of CO2 narcosis. Decreased capacity of the lung after the pneumonectomy and left phrenic nerve injury during the operation were considered factors causing the respiratory insufficiency. Patient was discharged 6 weeks later and continued to have consultations at the outpatient clinic.

[A case of coronary spasm during general anesthesia successfully treated with nitroglycerin and verapamil].

We had a patient without history of angina, who repetitively showed transient elevation of ST-segment during general anesthesia. Coronary spasm was suspected, but no triggering factors could be detected; the spasm being observed under deep and stable anesthesia and at this point no surgical stimulations were interposed. It was treated successfully with intravenous administrations of nitroglycerin and verapamil and no further elevations of ST-segment could be observed.

[Usefulness of rapid detection of plasma insulin levels during resection of insulinoma].

Insulinoma is one of the causes of hypoglycemia and can be cured by surgery. Using the enzyme immunoassay kit (ERUMOTEC INSULIN, Mochida Pharmacy Co.), immunoreactive insulin (IRI) can be measured within one hour. Curative operation was confirmed by normalized IRI level. A 58-year-old man had an episode of loss of consciousness. His blood glucose was below, and his IRI was above, normal. These and other examinations revealed that he was suffering from insulinoma. Tumor resection under general anesthesia was scheduled. Glucose was continuously administered intravenously to prevent hypoglycemia until the end of tumor resection. Frequent blood glucose measurement showed that he had no hypoglycemic episodes. Using the enzyme immunoassay kit, IRI was found to be 704 microU.ml-1 during manipulation of the tumor. At 30 minutes after the tumor resection, it decreased to 9.8 microU.ml-1 (within normal ranges). These data suggested that the operation was curative and that no further hypoglycemic attacks by remnant insulinomas would be anticipated.

[A severe case of reexpansion pulmonary edema in an asthmatic patient].

A 60-year-old man with poorly controlled bronchial asthma was proposed for an emergency appendectomy. His preoperative chest X-P revealed that his left lung was completely collapsed with pneumothorax, but its onset was unclear. Following the left thoracocentesis, appendectomy was performed under general anesthesia (oxygen-halothane). About one hour after the thoracocentesis, pinkish foamy tracheal secretion was massively drained and its protein concentration was 3.8 g.dl-1.PaCO2 was 95 mmHg and PaO2 was 69 mmHg (FIO2 1.0). His chest X-P showed signs of pulmonary edema in his left lung and infiltrating shadow was observed in his right lung. IMV with PEEP, aminophylline and prednisolone improved his respiratory status and on the 11 th day he was weaned from the respirator. In a case of pneumothorax with unclear duration like ours, it is necessary to consider the possibility of the reexpansion pulmonary edema.

A possible mechanism for elevation of glucose-6-phosphatase activity in kidney and liver of fluoride-treated rats.

Glucose-6-phosphatase (EC 3.1.3.9) activity in kidney and liver was found to be markedly elevated 3 hr after a single large dose of fluoride (NaF, 35 mg/kg, i.p.). The increases in renal and hepatic glucose-6-phosphatase activity were completely suppressed by adrenalectomy. Moreover, the increments were markedly suppressed by injection of dibenamine as an alpha-adrenergic blocker or by injection of propranolol as a beta-adrenergic blocker.

Changes in adrenal function as a possible mechanism for elevation of serum glucose by a single large dose of fluoride.

Serum glucose was elevated immediately after ip administration of a single large dose of fluoride (NaF 35 mg/kg) to rats. Moreover, elevation of serum glucose following ip administration of 35 mg/kg of fluoride to rats was suppressed by adrenalectomy, dibenamine, or propranolol, but not by thyroid-parathyroidectomy. The elevation of serum glucose was associated with enhancement of glucose-6-phosphatase activities in liver and kidney in fluoride-treated rats.

Epitopes associated with major histocompatibility complex (MHC) restriction site of T cells. IV. I-J epitopes on MHC-restricted cloned T cells.

We studied the expression of an I-Jk epitope on class II-restricted cloned L3T4+ T cells established from H-2k, H-2b, F1 and semiallogeneic radiation bone marrow chimeras by the inhibition of antigen-induced T cell proliferation and in vitro secondary antibody response, and by the direct immunofluorescence with a monoclonal anti-I-Jk. Both I-Ak- and I-Ek-restricted T cells were shown to carry the identical I-Jk epitope regardless of their genotypic origins, antigen specificity, and helper or suppressor function. None of the I-Ab-restricted clones derived from similar animals showed the I-Jk epitope. This isomorphism, regardless of the restriction specificity for I-Ak or I-Ek, contradicts the idea that I-J is an idiotypic determinant on class II-restricted T cell antigen receptor (TcR). In fact, the I-Jk epitope was not comodulated with TcR/T3 complex when incubated with an anti-T3 antibody, indicating that I-J is a new isomorphic receptor for self different from TcR alpha/beta heterodimers.