The Japan Morning Surge-1 (JMS-1) study: protocol description.

Morning blood pressure is reported to be more closely related to hypertensive organ damages such as left ventricular mass index, microalbuminuria and silent cerebral infarcts, than blood pressure at other times of the day. Morning blood pressure may play an important role in the pathogenesis of hypertensive target organ damage. Increased sympathetic nerve activity is reported to be one of the mechanisms of morning hypertension; however, there are no available data that show whether strict home blood pressure control, especially in the morning period, can reduce target organ damage. The Japan Morning Surge-1 (JMS-1) study includes hypertensive outpatients with elevated morning systolic blood pressure (>or=135 mmHg) as assessed by self-measured blood pressure monitoring at home. All enrolled patients are under stable antihypertensive medication status. Exclusion criteria are arrhythmia, chronic inflammatory disease, and taking alpha-blockers or beta-blockers. The target number of patients to be enrolled in the JMS-1 study is 600, and the aim is to evaluate differences in the markers of hypertensive target organ damage, such as brain natriuretic peptide and the urinary albumin excretion/creatinine ratio. All of the patients are randomized to an experimental group or a control group, with randomization to be carried out by telephone interviews with the patients' physicians. In the experimental group, patients begin taking additional antihypertensive medication just before going to bed. This consists of doxazosin 1 mg/day, which then is increased to 2 mg/day and 4 mg/day, with a beta-blocker added after a 1-month interval until the morning systolic blood pressure is controlled to less than 135 mmHg. Patients in the control group continue the treatment they are receiving at the enrollment for 6 months. Blood pressure levels, adverse effects, and hypertensive target organ damage before and after the study are evaluated. In the JMS-1 study, we will evaluate whether strict morning blood pressure control by sympathetic nervous system blockade using an alpha-blocker, doxazosin, and with the addition of a beta-blocker if needed, can reduce hypertensive target organ damage.     

Skull metastasis of thyroid papillary carcinoma.

Skull metastasis of thyroid carcinoma is rare. The majority of skull metastases of thyroid carcinoma are of the follicular subtype, rather than thyroid papillary carcinoma. In this report, a 55-year-old woman with skull metastasis from thyroid papillary carcinoma is presented. The metastatic lesion of the skull was hypervascular and osteolytic, and the bleeding was profuse during resection. There have been only four reports of skull metastasis from thyroid papillary carcinoma. The mean period from the initial diagnosis of thyroid carcinoma until the detection of skull metastasis is 23.3 years, whereas in this patient, it was about 2 years. Therefore, in the clinical course of thyroid papillary carcinoma, skull metastasis should be considered, and the patient should be meticulously followed up.     

Cerebral vasculitis secondary to Wegener's granulomatosis: computed tomography and angiographic findings

The central nervous system is rarely involved by Wegener's granulomatosis. A case of Wegener's granulomatosis with involvement of the cerebral arteries was reported. Computed tomography showed extensive brain edema with angiographic demonstration of cerebral vasculitis.     

Safety and usefulness of a novel eMotion electric mesh nebulizer in children with asthma.

BACKGROUND: A new electronic mesh nebulizer, eMotion is known to have higher performance compared to conventional nebulizers. However, there are some concerns about whether too much delivered dose might cause side effects with higher frequency. METHODS: To evaluate the safety and usefulness of the nebulizer, we measured changes in heart rates and lung functions of 73 asthmatic children when they inhaled 1 microg/kg of procaterol with eMotion or a conventional nebulizer, Junior BOY. RESULTS: In 34 children with mild asthma exacerbation, physical findings, lung function and transcutaneous oxygen saturation levels were improved after inhalation using both nebulizers. No adverse effects including significant increase of heart rate were found. Improvements in the rates of the parameters were comparable. When response to beta2-agonist inhalation was checked in 39 children in stable condition, similar degrees of improvement in lung function were observed, and heart rates did not change after inhalation with either nebulizers. CONCLUSIONS: Safety and efficacy was comparable between eMotion and a conventional nebulizer when it was used to administer beta2-agonists in asthmatic children. However, from the fact that eMotion needs only 3-4 minutes to inhale 2 mL solution, eMotion could be more useful for most children who usually do not prefer longer inhalation time with conventional compressor nebulizers.     

Operational lumped constant for FDG in normal adult male rats.

We determined an operational value for the lumped constant to be used in measurements of the local rate of cerebral glucose use (lCMR(glc)) with FDG in normal adult male rats. METHODS: The standard quantitative autoradiographic method was used with 2-deoxy-d-(14)C-glucose ((14)C-DG) and with (14)C-FDG in awake normal adult male rats. Timed arterial blood samples were drawn for 45 min after the bolus and assayed for plasma glucose and (14)C concentrations. At the end of the 45-min experimental period, the rats were killed, and their brains were removed and divided in half sagittally. One hemisphere was immediately frozen and assayed for local (14)C concentrations by quantitative autoradiography; the other was weighed, homogenized in t-octylphenoxypolyethoxyethanol solution, and assayed for (14)C concentrations in the whole brain by liquid scintillation counting. Paired rats (3 pairs), one in each pair receiving (14)C-DG and the other receiving (14)C-FDG, were studied in parallel on the same day. Additional unpaired animals (n = 8) were studied with either (14)C-DG or (14)C-FDG but not in parallel on the same day. To calculate the lCMR(glc) in rats studied with (14)C-FDG, the rate constants for (14)C-FDG were estimated from the (14)C-DG values determined for rats and the (14)C-FDG/(14)C-DG ratios determined for humans. In all of the rats studied with either (14)C-DG or (14)C-FDG, the lCMR(glc) was first calculated in 12 representative brain structures with the lumped constant of 0.48 previously determined for (14)C-DG in rats. The ratio of the lCMR(glc) thus determined with (14)C-FDG to that determined with (14)C-DG for each structure was then multiplied by the lumped constant for (14)C-DG to estimate the lumped constant for (14)C-FDG. The lCMR(glc) and the lumped constant for FDG in the brain as a whole were similarly estimated from the tracer concentrations in the brain homogenates. RESULTS: The mean values for the lumped constant for FDG were found to be 0.71 and 0.70 in the autoradiographic assays and the assays with brain homogenates, respectively. CONCLUSION: The appropriate value for the lumped constant to be used in determinations of the lCMR(glc) in normal adult male rat studies with (18)F-FDG and small-animal PET scanners is 0.71.     

Movement of the lateral and medial poles of the working condyle during mastication in patients with unilateral posterior crossbite.

Patients with unilateral posterior crossbite often show reverse sequential jaw movement patterns on the frontal view during mastication on the crossbite side. Recent studies show that such patients are prone to suffer from temporomandibular joint (TMJ) disc displacement, particularly the lateral portion. The purpose of this study was to examine the movement of the lateral and medial poles of the working condyle during mastication in such patients. Subjects were 12 consecutive patients with unilateral posterior crossbites and without TMJ disc displacements and 12 normal subjects. An optoelectronic jaw-tracking system with 6 degrees of freedom was used to record the motion of the lateral and medial poles of the working condyle during mastication of standardized hard, gummy jelly. The data from the first 10 cycles were analyzed. The lateral and medial poles of the condyle on the crossbite side moved more in the medial direction and less in the lateral direction during mastication in the crossbite patients than the condyle in the normal subjects. The lateral pole of the working condyle moved more in the posterior and inferior directions and less in the anterior direction than the medial pole in all subjects. These results suggest that these condylar movements in patients with unilateral posterior crossbites might be related to the susceptibility to TMJ disc displacement, particularly the lateral portion.     

Dental management of a patient with takotsubo cardiomyopathy: a case report.

Takotsubo cardiomyopathy (TCM) is a relatively new concept in cardiovascular disease. The clinical symptoms of TCM are similar to those of a myocardial infarction, but both the mechanism and the management of TCM are different from those of myocardial infarction. The cause of TCM is unclear, but it is suggested to occur in conjunction with excessive circulating catecholamines due to stress. Thus, control of the stress reaction and restriction of catecholamine levels are considered important for prevent of TCM onset. We report the dental management of a patient with intellectual disability who had anamnesis of TCM and cardiopulmonary arrest under restraint during a previous dental appointment in another dental clinic. We used intravenous sedation with both midazolam and propofol, by which the excessive hormonal reaction that caused TCM onset and cardiopulmonary arrest was controlled, for dental treatment in our facility. All planned dental treatment was then performed without any problems.     

Whole genome association study of rheumatoid arthritis using 27 039 microsatellites

A major goal of current human genome-wide studies is to identify the genetic basis of complex disorders. However, the availability of an unbiased, reliable, cost efficient and comprehensive methodology to analyze the entire genome for complex disease association is still largely lacking or problematic. Therefore, we have developed a practical and efficient strategy for whole genome association studies of complex diseases by charting the human genome at 100 kb intervals using a collection of 27,039 microsatellites and the DNA pooling method in three successive genomic screens of independent case-control populations. The final step in our methodology consists of fine mapping of the candidate susceptible DNA regions by single nucleotide polymorphisms (SNPs) analysis. This approach was validated upon application to rheumatoid arthritis, a destructive joint disease affecting up to 1% of the population. A total of 47 candidate regions were identified. The top seven loci, withstanding the most stringent statistical tests, were dissected down to individual genes and/or SNPs on four chromosomes, including the previously known 6p21.3-encoded Major Histocompatibility Complex gene, HLA-DRB1. Hence, microsatellite-based genome-wide association analysis complemented by end stage SNP typing provides a new tool for genetic dissection of multifactorial pathologies including common diseases.     

Simple,rapid, and accurate determination of deletion mutations by automated dna sequencing of heteroduplex fragments of the adenomatous polyposis coli (APC) gene generated by PCR amplification

Germline mutations in patients with familial adenomatous polyposis were analyzed by polymerase chain reaction (PCR) amplification of the adenomatous polyposis coli gene. PCR products from heterozygous patients for deletions of this gene formed four distinct bands on polyacrylamide gel electrophoresis. The four fragments were subsequently purified and both strands of each fragment were directly sequenced, using an automated DNA sequencer and the same primers as those for PCR amplification. It was found that the two slower migrating fragments were “bulge” heteroduplexes, while the other two were homoduplexes made up of two wild-type strands and two deletion-mutant strands, respectively. The sites of deletions in the adenomatous polyposis coli gene could be exactly determined in four of the five patients. In an attempt to identify deletion-carriers of familial adenomatous polyposis at the presymptomatic stage, a family study was also carried out, and two children were found to have the same mutations as those of their affected parents. The direct sequencing of heteroduplex fragments generated during PCR amplification is a potentially useful method for detecting mutations of not only the adenomatous polyposis coli gene but also many other genes of genetic diseases. © 1993 Wiley-Liss, Inc.