Initial experiences in management of blunt aortic injury taking associated brain injury into consideration.

BACKGROUND: Although endovascular stent-grafting (SG) has become acceptable for blunt aortic injury (BAI), open surgical repair (OR) does provide reliable, good long-term results. A current surgical strategy for BAI, taking account of associated brain injury, is presented and preferable initial management for BAI is proposed. METHODS AND RESULTS: The surgical strategy for BAI was established in 2001: SG is performed for patients with obvious brain injuries, but OR is performed for patients without brain injury, and conservative treatment should be used initially for patients with critical non-aortic injuries. Between 2001 and 2004 20 patients with BAI were admitted to hospital: 16 blunt aortic ruptures and 4 blunt aortic dissections. Of them 15 patients underwent surgery (SG, 9; OR, 6) and 5 patients were treated conservatively. One patient died from associated lung injury after SG, all patients treated conservatively died because of associated brain injuries or another rupture of BAI, and 2 elderly patients treated by OR died within 1 year from postoperative respiratory failure. CONCLUSION: This brain-injury conscious surgical strategy for BAI provided acceptable early results. OR should be chosen for young patients without brain injury, but endovascular SG seems to be a better initial treatment for elderly patients or patients with other comorbidities.     

Conditioning regimen of melphalan, fludarabine and total body irradiation in unmanipulated HLA haploidentical stem cell transplantation based on feto-maternal tolerance

Unmanipulated hematopoietic stem cell transplantation from haploidentical family donors is frequently associated with graft failure and severe graft-versus-host disease (GVHD). We employed a myeloablative conditioning regimen consisting of 125 mg/m2 of fludarabine, 140 mg/m2 of melphalan and TBI of 10 to 12 Gy for three patients. The donor in each case was a haploidentical two-loci HLA mismatch mother or son. Engraftment failure was observed in one patient. In the other two patients, engraftment was confirmed within 15 days after transplantation. Acute and chronic GVHD was observed, but was controllable in both cases. HLA mismatched transplantation based on feto-maternal tolerance may provide an alternative option for patients who do not have HLA-matched donors.     

Outcome from severe accidental hypothermia with cardiac arrest resuscitated with extracorporeal cardiopulmonary resuscitation

Purpose

This study aimed to identify factors of neurologic prognosis in severe accidental hypothermic patients with cardiac arrest.

Basic procedures

This retrospective observational study was performed in a tertiary care university hospital in Sapporo, Japan (January 1994 to December 2012). We investigated 26 patients with accidental hypothermic cardiac arrest resuscitated with extracorporeal cardiopulmonary resuscitation (ECPR). We evaluated the neurologic outcome in patients who were resuscitated with ECPR at discharge from hospital.

Main findings

In those 26 patients, their median age was 50.5 years; and 69.2% were male. The cause of hypothermia was exposure to cold air in 46.1%, submersion in 46.1%, and avalanche in 7.8%. Ten (38.5%) of these patients survived to favorable neurological outcome at discharge. Factors associated with favorable neurological outcome were a cardiac rhythm other than asystole (P = .009), nonasphyxial hypothermia (P = .006), higher pH (P = .01), and lower serum lactate (P = .01). In subgroup analyses, the patients with hypothermic cardiac arrest due to submersion or avalanche (asphyxia group) showed no factors associated with good neurological outcome, whereas the nonasphyxia group showed a significantly lower core temperature (P = .02) and a trend towards a lower serum lactate (P = .09).

Principal conclusions

Patients with hypothermic cardiac arrest due to nonasphyxial hypothermia have improved neurologic outcomes when treated with ECPR compared to patients with asphyxial hypothermic cardiac arrest. Further investigation is needed to develop a prediction rule for patients with nonasphyxial hypothermic cardiac arrest to determine which patients would benefit from treatment with ECPR.     

The dose of radiotherapy in esophageal cancer combined with external beams and intracavitary radium brachytherapy

Between 1974 and 1982, 78 primary esophageal squamous cell carcinomas were treated by external irradiation combined with additional intracavitary radium therapy. 50 to 60 Gy were given by external irradiation, and 5 to 20 Gy were delivered on the surface of the esophageal mucosa. The combined dose ranged from TDF 110 to 140 on the esophageal mucosa and TDF 95 to 120 at a depth of 5 mm from the esophageal mucosa. The 5-year survival rate was 19.3% by this combined radiotherapy alone. We conclude that the optimal dose of the combined therapy for esophageal cancer ranges from TDF 95 to 120 at a depth of 5 mm from the esophageal mucosa.     

The affinity of betaxolol, a beta 1-adrenoceptor-selective blocking agent, for beta-adrenoceptors in the bovine trachea and heart.

1. The specificity of betaxolol, a beta-adrenoceptor antagonist, for beta 1- and beta 2-adrenoceptors was compared with that of other beta-antagonists, atenolol, ICI-118551, butoxamine and (+/-)-propranolol, in the bovine trachea and heart by competitive interaction with [3H]-CGP12177 as a radioligand. 2. The radioligand Kd values were 0.75 +/- 0.12 and 1.60 +/- 0.11 nM in the trachea and heart, respectively, and the Bmax values were 34.00 +/- 4.41 and 21.54 +/- 2.94 fmol mg-1 protein, respectively. 3. Using ICI-118551, we determined the ratio of beta 1:beta 2-adrenoceptors in the trachea and heart to be approximately 29:71 and 56:44, respectively. 4. In the trachea, a beta 2-predominant tissue, betaxolol and atenolol were more selective for beta 1-adrenoceptor binding sites than beta 2-adrenoceptor binding sites, whereas ICI-118551 and butoxamine were more selective for beta 2-adrenoceptor binding sites. 5. The beta 1-selectivity of betaxolol was 2.2 and 2.7 fold higher than that of atenolol in the bovine trachea and heart. These findings suggest that betaxolol may be useful in the treatment of hypertension, cardiac arrhythmia and angina pectoris.     

Enzymatic oxidation of 7-hydroxylated delta 8-tetrahydrocannabinol to 7-oxo-delta 8-tetrahydrocannabinol by hepatic microsomes of the guinea pig

Hepatic microsomes of the guinea pig converted delta 8-tetrahydrocannabinol (delta 8-THC) to various oxidized metabolites, including 7 alpha-hydroxy-delta 8-THC (7 alpha-OH-delta 8-THC), 7 beta-OH-delta 8-THC, and 7-oxo-delta 8-THC. The enzyme which mediates biotransformation of 7-OH-delta 8-THCs to 7-oxo-delta 8-THC was characterized in the present study. The oxidative activity was mainly located in microsomes. The microsomal reaction required NADPH and oxygen and showed an optimal pH around 7.5. The reaction was inhibited by beta-diethylaminoethyl diphenylpropylacetate (SKF 525-A), an inhibitor of cytochrome P-450, but not by pyrazole, a specific inhibitor of alcohol dehydrogenase. However, 7-oxo-delta 8-THC formation was not affected by carbon monoxide or by pretreatment of animals with cobaltous chloride (40 mg/kg, ip, once a day for 3 days). Atmospheric oxygen was incorporated into 7-oxo-delta 8-THC formed from 7 alpha-OH-delta 8-THC, but not into that from 7 beta-OH-delta 8-THC. Further, 7-oxo-delta 8-THC formed from 7 alpha-18OH-delta 8-THC released about half of 18O at the 7-position, whereas the 7-oxo metabolite from 7 beta-18OH-delta 8-THC lost little of the isotope at the 7 beta-position during the oxidative reaction. From these results, it is likely that hepatic microsomal monooxygenase (probably cytochrome P-450) plays a main role in the oxidation. In addition, mechanisms for 7-oxo-delta 8-THC formation from 7 alpha-OH-delta 8-THC or 7 beta-OH-delta 8-THC are different.     

Effects of betaxolol, a cardioselective beta-adrenoceptor antagonist, on ischemic myocardial energy and carbohydrate metabolism in dogs

The effect of betaxolol, a beta 1-adrenoceptor antagonist, on ischemic myocardial metabolism was studied in dog hearts subjected to an occlusion of the left anterior descending coronary artery for 10 or 30 min. Betaxolol (0.1 or 0.3 mg/kg) was injected i.v. 5 min before ischemia. Betaxolol decreased heart rate, (+)dp/dt, coronary flow and blood pressure. Coronary occlusion decreased the levels of creatine phosphate, adenosine triphosphate, total adenine nucleotides and energy charge potential in the ischemic myocardium. Ten minutes after ischemia, betaxolol significantly diminished these impairments of energy metabolism. Even 30 min after ischemia, a higher dose of betaxolol significantly inhibited the depletion of total adenine nucleotides. Myocardial ischemia produced a breakdown of glycogen, an accumulation of lactate and an inhibition of glycolytic flux through the phosphofructokinase reaction. Betaxolol also reduced these alterations of carbohydrate metabolism 10 min after ischemia. These results indicate that betaxolol delays the onset of myocardial metabolic change from aerobic to anaerobic during ischemia and hence reduces the severity of myocardial ischemic injury.     

Effects of terazosin on the blood pressure responses to tilting in conscious animals: comparison with prazosin

Inhibitory effects of terazosin on the compensatory blood pressure responses to tilting were studied in conscious rabbits and spontaneously hypertensive rats (SHR). In rabbits, doses which reduced the mean blood pressure by 15 mmHg were 330 micrograms/kg, i.v., for terazosin and 42 micrograms/kg, i.v., for prazosin, while those which depressed the blood pressure responses to tilting by 30 mmHg were 180 micrograms/kg, i.v., for terazosin and 54 micrograms/kg, i.v., for prazosin. In SHR, almost equal decreases in the mean blood pressure (about 30%) were observed by 1 mg/kg prazosin, p.o., 20 mg/kg hexamethonium, i.p., 3 mg/kg hydralazine, p.o., or 3 mg/kg nicardipine, p.o. In these conditions, prazosin and hexamethonium markedly depressed the blood pressure responses to tilting, whereas hydralazine and nicardipine showed little effect. The results with these antihypertensive drugs closely paralleled the established orthostatic profiles seen clinically. In this SHR tilting model, when the mean blood pressure was reduced by 15%, prazosin significantly depressed the tilting reflexes; however, terazosin produced no depression. Considering the dose ratio of terazosin to prazosin for antihypertensive effects and inhibitory effects on the tilting reflexes, the orthostatic liability of terazosin was about 3 times as low as that of prazosin. On the basis of these results, it is expected that terazosin causes less orthostatic hypotension than prazosin in clinical use.