High frequency percussive ventilation and low FiO(2)

Background

High-frequency percussive ventilation (HFPV) is an effective rescue therapy in ventilated patients with acute lung injury. High levels of inspired oxygen (FiO₂) are toxic to the lungs. The objective of this study was to review a low FiO₂ (0.25)/HFPV protocol as a protective strategy in burn patients receiving mechanical ventilation greater than 10 days.

Methods

A single-center, retrospective study in burn patients between December 2002 and May 2005 at the LAC + USC Burn Center. Demographic and physiologic data were recorded from time of admission to extubation, 4 weeks, or death.

Results

32 subjects were included in this study, 1 patient failed the protocol. 23 of 32 (72%) patients were men and mean age was 46 ± 15 years. Average TBSA burn was 30 ± 20 with 9 of 32 (28%) having >40% TBSA involved. Average burn index was 76 ± 21. 22 of 32 (69%) had inhalation injury and 23 of 32 (72%) had significant comorbidities. Average ventilator parameters included ventilator days 24 ± 12, FiO₂ 0.28 ± 0.03, PaO₂ 107 ± 15 Torr, PaCO₂ 42 ± 4 Torr, and PaO₂/FiO₂ ratio 395 ± 69. 16 of 32 (50%) patients developed pneumonia and 9 of 32 (28%) died. No patient developed ARDS, barotrauma, or died from respiratory failure. There was no association between inhalation injury and mortality in this group of patients.

Conclusion

A low FiO₂/HFPV protocol is a safe and effective way to ventilate critically ill burn patients. Reducing the oxidative stress of high inspired oxygen levels may improve outcome.     

Intimal hyperplasia and coronary flow reserve after heart transplantation: association with big endothelin-1

BACKGROUND: Endothelin, a peptide with strong vasoconstrictive and mitogenic properties, has been found to increase after cardiac transplantation. We therefore assessed the association between its precursor peptide, big endothelin-1, and intimal hyperplasia and coronary flow reserve after heart transplantation. METHODS: Thirty-five patients without hemodynamically significant coronary artery disease after heart transplantation were investigated: Average peak flow velocity in the left anterior descending artery (LAD) was assessed by intracoronary Doppler at baseline as well as after injection of adenosine; coronary flow reserve was calculated as a ratio of both and was corrected for patient age and baseline average peak flow velocity. Lumen, intima + media and total vessel area were measured by intracoronary ultrasound. The plasma concentration of big endothelin-1 in venous blood was determined by radioimmunoassay. RESULTS: Patients with elevated big endothelin-1 levels (>2 fmol/ml) tended to have a decreased corrected coronary flow reserve (2.60 +/- 0.9 vs 3.21 +/- 1.0, p = 0.078). They also had a significantly larger intima + media area (5.82 +/- 2.9 vs 2.37 +/- 2.9 mm(2), p = 0.004) and total vessel area (18.36 +/- 5.8 vs 12.81 +/- 4.8 mm(2), p = 0.012) than those with normal plasma concentrations. CONCLUSIONS: Our study suggests an association between elevated big endothelin-1 plasma levels and the development of intimal hyperplasia and reduction of coronary flow reserve after cardiac transplantation.     

Bone marrow mesenchymal stem cells undergo nemosis and induce keratinocyte wound healing utilizing the HGF/c-Met/PI3K pathway

We previously showed cell–cell contacts of human dermal fibroblasts to induce expression of the hepatocyte growth factor/scatter factor (HGF) in a process designated as nemosis. Now we report on nemosis initiation in bone marrow mesenchymal stem cells (BMSCs). Because BMSCs are being used increasingly in cell transplantation therapy we aimed to demonstrate a functional effect and benefit of BMSC nemosis for wound healing. Nemotic and monolayer cells were used to stimulate HaCaT keratinocyte migration in a scratch-wound healing assay. Both indicators of nemosis, HGF production and cyclooxygenase-2 expression, were induced in BMSC spheroids. When compared with a similar amount of cells as monolayer, nemotic cells induced keratinocyte in vitro scratch-wound healing in a concentration-dependent manner. The HGF receptor, c-Met, was rapidly phosphorylated in the nemosis-stimulated keratinocytes. Nemosis-induced in vitro scratch-wound healing was inhibited by an HGF-neutralizing antibody as well as the small molecule c-Met inhibitor, SU11274. HGF-induced in vitro scratch-wound healing was inhibited by PI3K inhibitors, wortmannin and LY294002, while LY303511, an inactive structural analogue of LY294002, had no effect. Inhibitors of the mitogen-activated protein kinases MEK/ERK1/2 (PD98059 and U0126), and p38 (SB203580) attenuated HGF-induced keratinocyte in vitro scratch-wound healing. We conclude that nemosis of BMSCs can induce keratinocyte in vitro scratch-wound healing, and that in this effect signaling via HGF/c-Met is involved.     

急性重度毒蕈中毒性肝炎抢救成功1例

1　病例报告　男 ,16岁 .误食毒蕈后出现恶心 ,呕吐伴有腹痛、腹泻 4d,每日大便 4～ 12次 ,为稀水便 ,有心慌、气短、发热 ,在当地医院以“毒蕈中毒”救治 ,症状无缓解 ,为进一步治疗于 2 0 0 0 - 0 8- 31转入我院 .查体 :T37.8℃ ,P110次·min-1 ,R18次·min-1 ,BP14/ 9k Pa.全身皮肤黄染 ,巩膜重度黄染 ,心肺无阳性体征 .腹平坦 ,上腹部有压痛 ,肌紧张及反跳痛 ,肝脾未触及 ,肝区有叩击痛 ,移动性浊音阳性 .入院后患者出现烦躁 ,意识不清 ,心率时快时慢 ,血压不稳定 .肝功 :T- BIL 2 5 4.1μmol· L-1 ,D- BIL 16 9.5 μmol· L-1 …     

An antibody that facilitates hematopoietic engraftment recognizes CD44

Pretreatment of recipients with the monoclonal antibody (MoAb) S5 facilitates engraftment of bone marrow from mismatched, unrelated donors in the canine transplantation model. In the direct comparisons reported here, the S5 glycoprotein (gp) was found to have structural homology to CD44 that in humans has been implicated in adhesive interactions of one type of effector cell, the lymphocyte. The S5 antigen and gp90Hermes-1 exhibited codistribution on canine peripheral blood cells. Both S5 and Hermes-1 (anti-CD44) MoAbs recognized 90-Kd species in radioimmune precipitations of 125I surface-labeled canine peripheral blood lymphocytes and bone marrow cells. Competitive antibody binding experiments showed that the epitope detected by S5 was distinct from that bound by Hermes-1 but overlapped with those defined by two other known anti-CD44 reagents, IM7 and Hutch-1. Sequential immunoprecipitation with S5 and Hermes-1 indicated that the two antibodies recognize the same or overlapping subsets of membrane gps. Tryptic digestion of S5 and anti-CD44 immunoprecipitates generated two major iodinated peptides of 27 and 35 Kd in both cases, a further indication of structural homology. Similarly, after N-glycanase digestion, S5 and CD44 immunoprecipitates were resolved to a single 68- Kd species. These findings suggest that CD44-mediated adhesive events may affect the fate of transplanted hematopoietic cells. The previous implications of this gp in T-lymphocyte activation and lymphocyte adhesion to endothelium thus provide useful paradigms to analyze its function in the bone marrow transplant setting.     

Tricuspid annulus motion and mitral annulus motion: Anatomical intimacy causing a good correlation?

BACKGROUND:

Echocardiographic evaluation of the heart and its function, especially left ventricular systolic function, has great clinical importance. Systolic function can be measured using several methods, such as the amplitude of motion of the left atrioventricular plane (mitral annulus motion [MAM]) toward the apex during systole. Similarly, right ventricular systolic function can be measured using the motion of the right atrioventricular plane (tricuspid annulus motion [TAM]) toward the apex during systole.

OBJECTIVES:

Because the mitral and tricuspid annuli are situated close to each other in the fibrous skeleton between both ventricles and atria, one might think that a decrease in the amplitude of MAM would be followed by a decrease in the amplitude of TAM. The present study was developed to determinine if this anatomical intimacy causes a good correlation between the amplitudes of TAM and MAM.

METHODS:

Nineteen healthy subjects and 103 consecutive patients were included in the study and examined using echocardiography. The amplitudes of TAM and MAM were measured and the correlation between the amplitudes was calculated.

RESULTS:

In the 103 consecutive patients, a significant but relatively weak positive correlation was found between TAM and MAM amplitudes (Pearson’s correlation coefficient [r]=0.58; P<0.001). In the 19 healthy subjects, no significant correlation was found.

CONCLUSIONS:

Despite the anatomical intimacy of the annuli, the correlation between the amplitudes of TAM and MAM in consecutive patients was rather weak, and there was no correlation in healthy subjects. These findings could be due to anatomical and physiological differences between the right and left ventricles.