Effect of nasal high-flow oxygen therapy on the swallowing reflex: an in vivo volunteer study

Clinical Oral Investigations - The advantages of nasal high-flow oxygen therapy (NHF) include not only allowing talking, but also eating and drinking, during the therapy. However, the effect of NHF...     

Development of apical hypertrophic cardiomyopathy with age in a transgenic mouse model carrying the cardiac actin E99K mutation

In both humans and mice, the Glu-99-Lys (E99K) mutation in the cardiac actin gene (ACTC) results in little understood apical hypertrophic cardiomyopathy (AHCM). To determine how cross-bridge kinetics change with AHCM development, we applied sinusoidal length perturbations to skinned papillary muscle fibres from 2- and 5-month old E99K transgenic (Tg) and non-transgenic (NTg) mice, and studied tension and its transients. These age groups were chosen because our preliminary studies indicated that AHCM develops with age. Fibres from 5-month old E99K mice showed significant decreases in tension, stiffness, the rate of the medium-speed exponential process and its magnitude compared to non-transgenic control. The nucleotide association constants increased with age, and they were significantly larger in E99K compared to NTg. However, there were no large differences in the rates of the cross-bridge detachment step, the rates of the force generation step, or the phosphate association constant. Our result on force/cross-bridge demonstrates that the decreased active tension of E99K fibres was caused by a decreased amount of force generated per each cross-bridge. The effects were generally less or insignificant at 2 months. A pCa-tension study showed increased Ca²⁺-sensitivity (pCa₅₀) with age in both the E99K and NTg sample groups, and pCa₅₀ was significantly larger (but only for 0.05–0.06 pCa units) in E99K than in NTg groups. A significant decrease in cooperativity (n_H) was observed only in 5-month old E99K mice. We conclude that the AHCM-causing ACTC E99K mutation is associated with progressive alterations in biomechanical parameters, with changes smaller at 2 months but larger at 5 months, correlating with the development of AHCM.     

Beneficial effects of exogenous tetrahydrobiopterin on left ventricular remodeling after myocardial infarction in rats

Background Reactive oxygen species (ROS) is deeply involved in the process of ventricular remodeling after myocardial infarction (MI). Under oxidative stress, endothelial nitric oxide synthase (eNOS) can be converted to a ROS generator, because a relative lack of tetrahydrobiopterin (BH4), an essential cofactor for NO synthesis, leads to eNOS uncoupling. The uncoupled eNOS generates superoxide rather than NO. The possible role of ROS generated by eNOS in ventricular remodeling after MI was investigated. Methods and Results Rats were treated with oral BH4 supplementation starting at 3 days before coronary artery ligation. At 4 weeks after MI, there was augmented superoxide production in association with reduced BH4/dihydrobiopterin (BH2) ratio and eNOS dimer/monomer protein ratio in the heart. Treatment with BH4 increased BH4/BH2 ratio and eNOS dimer/monomer ratio, and decreased superoxide production. In BH4-treated MI rats, left ventricular size was smaller, thickness of the non-infarcted posterior wall was thinner, and cardiac function was preserved compared with the control MI rats. Conclusions The present study suggested that ventricular remodeling process after MI leads to BH4 oxidation and resulted in uncoupled eNOS-derived superoxide generation, which further augmented the remodeling process and deteriorated cardiac function. (Circ J 2008; 72: 1512 - 1519).     

Human IgA1 half-molecules: clinical and immunologic features in a patient with multiple myeloma.

Abnormal IgA1 half-molecules consisting of one heavy and one light chain were found in a patient (N.N.) with typical multiple myeloma. The serum and the urine of this patient contained both 7.0S and 3.9S IgA myeloma proteins. The IgA half-molecules (3.9S) were found to have a molecular weight of 59,000 daltons and were composed of one alpha1 chain of about 40,000 daltons and one light chain of 22,000 daltons. Furthermore, enzymatic degradation suggested that the alpha chain of the N.N. half-molecules had a large deletion in its Fc portion. We suggest that its heavy and light chains were probably bound noncovalently, since the interchains connecting the heavy and light chains of these IgA half-molecules were easily dissociated with 1% SDS and 8 M urea. Cytologic studies identified at least two types of myeloma cells, and it is possible that half-molecule IgA production might result from mutation among the myeloma cells producing whole-molecule IgA.     

The short-term outcomes of robotic sphincter-preserving surgery for rectal cancer: comparison with open and laparoscopic surgery using a propensity score analysis

Purpose

The aim of this study is to clarify the short-term outcomes of robotic sphincter-preserving surgery for rectal cancer in a retrospective study.

Methods

The short-term outcomes of robotic sphincter-preserving surgery (n?=?130) were retrospectively compared to open (n?=?234) and laparoscopic surgery (n?=?318) by a propensity score analysis.

Results

Robotic surgery was performed more frequently for patients with lower rectal cancer (55%) than open (30%, p?<?0.0001) or laparoscopic surgery (36%, p?<?0.0001). None of the robotic surgery cases were converted to open surgery. After propensity score matching, robotic surgery was found to be associated with a longer operation time (342 vs. 230 min, p?<?0.0001) and less blood loss (7 vs. 420 mL, p?<?0.0001) than open surgery. The overall complication rate of robotic surgery was lower than that of open surgery (13 vs. 28%, p?=?0.032). Robotic surgery was associated with a lower incidence of surgical site infections (SSIs) than laparoscopic surgery (0 vs. 7%, p?=?0.028). There were no cases of anastomotic leakage after robotic surgery. The circumferential resection margin was involved in 0.8% of the patients who underwent robotic surgery; the incidence did not differ among the treatment groups.

Conclusions

Although robotic surgery for rectal cancer was associated with a longer operation time, it was associated with a very low incidence of SSIs. The degree of safety was comparable to both open and laparoscopic surgery.

     

Critical roles of VEGF-C-VEGF receptor 3 in reconnection of the collecting lymph vessels in mice

Molecular mechanisms of reconnection of collecting lymph vessels were analyzed by using murine popliteal prenodal lymph vessels. At 1 and 2 weeks after being divided by cutting the lymph vessel, lymphatic reconnection was frequently observed accompanied by mesh-like lymphatic channels. Electron microscopic study also showed a monolayer of endothelial cells in the newly developed lymph vessels. Smooth muscle markers were immunofluorescently demonstrated in the wall of the new vessels. At 1 week after the procedure of cutting, augmented expressions of VEGF receptors 1, 2 and 3 were found immunohistochemically at the site of the reconnected lymph vessels. The expression of mRNA for VEGF receptor 3 was enhanced at 5 days and 1 week in small pieces of the tissues containing the reconnected lymph vessels, compared with that in the corresponding tissues obtained with sham operated ones. The administration of VEGF-C at the cutting site of the collecting lymph vessel significantly increased the rate of the reconnected lymph vessels, whereas additional treatment with Flt4/Fc chimera protein significantly reduced the rate of the reconnected ones. These results suggest that activation of VEGF-C-VEGF receptor 3 has critical roles in reconnection of the collecting lymph vessels in adult mice.     

Left ventricular free wall rupture in transient left ventricular apical ballooning.

A 79-year-old woman presented with chest pain. Her symptoms, combined with the results of an electrocardiogram, echocardiogram and laboratory investigations were compatible with an extensive acute anterior myocardial infarction. However, emergency coronary angiography showed no stenotic lesion in any coronary artery, but left ventriculography revealed apical ballooning akinesis and basal hyperkinesis and she was diagnosed as having transient left ventricular apical ballooning. After 7 days, she suddenly went into cardiopulmonary arrest because of cardiac tamponade. The autopsy revealed a free wall rupture. Generally, the prognosis in transient left ventricular apical ballooning is good; left ventricular free wall rupture is very rare.