Assessment of abnormal left atrial relaxation by transesophageal pulsed doppler echocardiography of pulmonary venous flow velocity

Background: Several studies on left ventricular relaxation have been undertaken in the past: however, left atrial (LA) relaxation has not been fully evaluated. Hypothesis: The purpose of this study was to assess abnormalities in LA relaxation by evaluating pulmonary venous flow velocity and interatrial septal motion using transesophageal echocardiography. Methods: The subjects were 56 untreated patients in sinus rhythm, including 25 with previous myocardial infarction, 9 with hypertrophic cardiomyopathy, 11 with dilated cardiomyopathy, as well as 11 with chest pain syndrome as controls. Peak first systolic velocity (PVS₁), peak atrial systolic velocity (PVA), and their time-velocity integrals (PVS₁-I and PVA-I, respectively) were calculated from the pulmonary venous flow velocity. Results: The PVS₁ and PVS₁-I correlated negatively with the maximum LA dimension and mean pulmonary capillary wedge pressure, and correlated positively with the amplitude of the interatrial septal motion during LA relaxation and percent fractional LA relaxation. The PVA and PVA-I did not correlate with the mean pulmonary capillary wedge pressure. There was a weak positive correlation between PVA and PVS₁, and a close positive correlation between the ratio of PVA to PVS₁ and mean pulmonary capillary wedge pressure. Multiple regression analysis indicated that the PVS₁ was most closely related to percent fractional LA relaxation, followed by mean pulmonary capillary wedge pressure. Conclusion: The PVS₁ determined from the pulmonary venous flow velocity is closely related to parameters of LA relaxation which may be determined by transesophageal M-mode echocardiography, and the ratio of PVA to PVS₁ is useful for noninvasive evaluation of LA pressure..     

Quinolone resistance mutations in the DNA gyrase gyrA and gyrB genes of Staphylococcus aureus.

A 6.4-kb DNA fragment containing the DNA gyrase gyrA and gyrB genes was cloned and sequenced from the quinolone-susceptible Staphylococcus aureus type strain ATCC 12600. An expression plasmid was constructed by inserting the cloned genes into the Escherichia coli-S. aureus shuttle vector pAT19, and deletion plasmids carrying only functional gyrA and gyrB genes were derived from this plasmid. An efficient transformation system for S. aureus RN4220 was established by using these plasmids. Quinolone-resistant mutants of S. aureus RN4220 were isolated by three-step selection with quinolones. The first- and second-step mutants were considered to be transport mutants, and the third-step mutants were divided into five groups with respect to their resistance patterns and transformation results with gyrA and gyrB genes. Sequencing analysis of the resulting mutant gyrase genes showed that they had the following point mutations: group 1, Ser-84 (TCA) to Leu (TTA) in GyrA; group 2, Ser-84 (TCA) to Ala (GCA), Ser-85 (TCT) to Pro (CCT), or Glu-88 (GAA) to Lys (AAA) in GyrA; group 3, Asp-437 (GAC) to Asn (AAC) in GyrB; group 4, Arg-458 (CGA) to Gln (CAA) in GyrB; and group 5, Ser-85 (TCT) to Pro (CCT) in GyrA and Asp-437 (GAC) to Asn (AAC) in GyrB. When the gyrA and/or gyrB mutants were transformed with the wild-type gyrA and/or gyrB plasmids, they became quinolone susceptible, but transformants with the plasmids having the same mutations on the gyrA and/or gyrB genes did not confer susceptibility. These results indicate that mutations in both gyrA and gyrB can be responsible for quinolone resistance in S. aureus.     

Neuronal cell death by Alzheimer's disease-relevant insults and its rescue

Neuronal cell death accounts for the clinical manifestations in Alzheimer's disease (AD). To establish the curative therapy of AD, neuroprotection is one of the primary therapeutic targets, and the elucidation of the mechanism of neuronal cell death is mandatory. Detailed characterization of neuronal cell death caused by familial AD (FAD)-linked mutant genes revealed that different cell death pathways are evoked by different types of mutants. Humanin (HN), a newly identified neuroprotective peptide, suppresses neuronal cell death caused by all known FAD mutants and A beta, while it has no effect on neuronal cell death caused by AD-irrelevant insults. The functional target of HN is the antagonism to neuronal death, not the modulation of A beta production, suggesting that HN-based medication can be combined with other remedies targeting A beta. HN is a promising seed for a novel therapy aiming at complete cure of AD through the suppression of neuronal loss.     

GATA3 abnormalities and the phenotypic spectrum of HDR syndrome

We report on GATA3 analysis and the phenotypic spectrum in nine Japanese families with the HDR syndrome (hypoparathyroidism, sensorineural deafness, and renal dysplasia) (MIM 146255). Fluorescence in situ hybridisation and microsatellite analyses showed heterozygous gross deletions including GATA3 in four families. Sequence analysis showed heterozygous novel mutations in three families: a missense mutation within the first zinc finger domain at exon 4 (T823A, W275R), an unusual mutation at exon 4 (900insAA plus 901insCCT or C901AACCCT) resulting in a premature stop at codon 357 with loss of the second zinc finger domain, and a nonsense mutation at exon 6 (C1099T, R367X). No GATA3 abnormalities were identified in the remaining two families. The triad of HDR syndrome was variably manifested by patients with GATA3 abnormalities. The results suggest that HDR syndrome is primarily caused by GATA3 haploinsufficiency and is associated with a wide phenotypic spectrum.


Keywords: GATA3; HDR syndrome; phenotypic spectrum; mutation analysis     

A standing posture support device that reduces laparoscopic surgeons’ occupational lower limb stress

Background: We developed a surgical knee rest (SKR) that can be used to decrease the stress placed on the lower half of the body when surgeons work in the standing position. We tested the effectiveness of this device in the context of laparoscopic surgery.

Material and methods: Five healthy, right-handed male surgeons participated, and we recorded surface electromyography (sEMG) signals from the two heads of the left and right gastrocnemius (Gc) muscles during laparoscopic resections of colorectal cancer. The outcome variable was the percentage of maximum Gc muscle effort generated, reported as percent maximal isometric voluntary contraction (%MVC), and this variable was compared between surgeries performed with and without use of the SKR. Assessment covered the first 100?min of surgery, subdivided into two 50-min periods.

Results: Mean %MVC of the left Gc muscle for the full 100-min test period was significantly decreased when the SKR was used (p?=?.027, vs. SKR not used). Notably, mean %MVC of both Gc muscles was significantly decreased during the first 50?min of surgery (p?=?.008 and p?=?.0046).

Conclusion: The SKR is useful for decreasing physical stress incurred by laparoscopic surgeons when working in the standing position.     

Phenolic constituents of Gnetum klossii

Four new phenolic derivatives, gnetofurans A-C (1-3) and dihydropinosylvindiol (4), were isolated from a methanol-soluble extract of the stems of Gnetum klossii, together with nine known compounds [gnetifolin F (5), isorhapontigenin, gnetulin, gnetins E and C, latifolol, gnetol, (-)-epsilon-viniferin, and trans-resveratrol]. The structures of the new compounds were determined by spectral data analysis.     

Thyroxine to triiodothyronine hyperconversion thyrotoxicosis in patients with large metastases of follicular thyroid carcinoma.

OBJECTIVE: We experienced two cases of follicular thyroid carcinoma with distant metastases, which showed high levels of free triiodothyronine (T(3)) while free thyroxine (T(4)) levels remained in the low or normal range. In this report, we described the detail of these cases and examined the cause of T(3) thyrotoxicosis. DESIGN: In one of the cases, quantitative measurement of types I and II iodothyronine deiodinase mRNAs was performed using a surgically dissected tissue from the primary tumor and a distant metastasis. MAIN OUTCOME: In the both tissues, types I and II iodothyronine deiodinase mRNAs were expressed in the same level as in the normal thyroid tissues. CONCLUSION: These results suggest that T(3) thyrotoxicosis in our patients was caused by hyperconversion of administered levothyroxine to T(3). In the follow-up of patients with distant metastases of follicular carcinoma, not only free T(4), but also free T(3) should be tested to avoid the excessive administration of levothyroxine.     

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.