Traumatic rupture of the aorta. A five-year experience

In the five-year period ending in October, 1975, 31 consecutive patients with traumatic rupture of the thoracic aorta underwent surgery at the University of Maryland Hospital or the Maryland Institute for Emergency Medicine. All cases were confirmed by preoperative aortogram. Rupture was confined to one or more sites in the descending thoracic aorta at or distal to the origin of the left subclavian artery. The age was a mean of 26 years. Operation was done within an average of 18 hours after injury. Significant nonthoracic injuries were present in every case. Six patients with positive findings on peritoneal lavage underwent exploratory laparotomy prior to thoracotomy because of shock. Surgical repair was done by use of left heart bypass in 2 cases (one death), a passive aorta-aorta shunt in 23 cases (5 deaths), and without shunt or bypass in 6 cases (no deaths). An end-to-end tubular Dacron graft was used to reconstruct the aorta in all but one patient. Over-all survival rate was 25 of 31 patients (81 per cent). Paraplegia developed in one patient and renal failure in 3 patients (2 deaths) in the aorta-aorta shunt group. Hypertension was present in 18 (72 per cent) of the survivors. Palsy of the left recurrent laryngeal nerve persisted in 8 (32 per cent) of the survivors. Two of the deaths were related to technical problems of the shunting procedure and 2 to intrapleural exsanguination before proximal aortic control could be achieved. Complications and blood loss were reduced in the group with no shunt. The series lends support to the rigorous aortographic search for ruptured thoracic aortas in trauma patients with widened mediastinum. Once experience has been gained with shunting techniques, tears of the descending thoracic aorta may be safely repaired without shunt if done expeditiously.     

Defendants are clueless--the 30-day psychiatric observation

OBJECTIVE: To investigate the understanding and expectations of defendants referred to Valkenberg Hospital for 30-day observation. DESIGN: Defendants referred for 30 days of psychiatric assessment were surveyed by means of a semi-structured interview within 3 days of admission. PARTICIPANTS: One hundred consecutive referrals from the Western, Northern and Eastern Cape were considered; 88 were eventually entered into the study. RESULTS: All defendants were generally ignorant of the reasons for referral, but had a good understanding of court procedure and wrongfulness. Mentally ill subjects differed only in their not being able to distinguish between a guilty/not guilty plea. Most did not have legal representation, did not personally request the assessment and denied guilt of the alleged offence. CONCLUSIONS: Mental illness affects triability but not necessarily criminal responsibility. Disturbingly, most defendants were without legal representation and were unaware of the purpose, implications and possible outcomes of psychiatric observation. It is imperative that the legislation governing these aspects be reviewed.     

Helicobacter pylori induces interleukin-8 expression in endothelial cells and the signal pathway is protein tyrosine kinase dependent

Helicobacter pylori (HP) infection has been shown to increase gastric mucosal interleukin 8 (IL-8) expression, and whether HP or its toxin induces endothelial cell IL-8 expression is unknown. We aimed to compare the IL-8 expression in endothelial cells after stimulation with HP toxin, tumor necrosis factor alpha (TNF-alpha), and lipopolysaccharide (LPS) and to study their signal pathways. HP or its toxin induced significant IL-8 expression in endothelial cells. HP toxin, TNF-alpha, and LPS also showed a time- and dose-dependent increase in IL-8 expression over the control. Both protein kinase C (PKC) and protein kinase A (PKA) inhibitors had no effect on IL-8 response to these stimuli. Protein tyrosine kinase (PTK) inhibitor genistein at concentrations of 150, 300, and 450 microM dose-dependently reduced LPS- and TNF-alpha-induced IL-8 expression by 29.43, 43.8, and 47.3% and 20.5, 49.9, and 61.8% respectively, whereas HP toxin-induced IL-8 secretion could only be reduced at 450 microM by 35.7%. Geldanamycin, a more potent PTK inhibitor, at doses of 0.5, 1, and 2 microM dose-dependently reduced HP toxin induced endothelial cell IL-8 expression by 24.8, 26, and 44.3% respectively. It is concluded that HP and its toxin can increase IL-8 expression in endothelial cells, and the expression of IL-8 elicited by HP toxin, TNF-alpha, and LPS is partially dependent on PTK but not PKA or PKC activation.     

Role of glutathione modulation in acrylonitrile-induced gastric DNA damage in rats

Acrylonitrile (VCN) or its reactive metabolites irreversibly interact with gastric DNA in vivo and cause DNA damage. The effect of glutathione (GSH) modulation on VCN-induced genotoxicity and unscheduled DNA repair synthesis (UDRS) in DNA of gastric mucosal tissues was investigated. VCN-induced UDRS was determined: in control rats, rats with depleted gastric GSH contents, and rats treated with sulfhydryl compounds. A single oral dose (23 mg/kg) of VCN induced a time- and dose-dependent increase in gastric UDRS and decrease in GSH levels. While maximal UDRS in gastric mucosa was observed 2 h following oral administration of 23 mg/kg VCN, maximal GSH depletion (50% of control) was detected 4 h following treatment. Increasing the VCN dose to 46 mg/kg caused a further decrease in gastric GSH level (27% of control), while UDRS was elevated. Inhibition of VCN oxidation by treatment of the animals with the cytochrome P450 inhibitor, SKF 525-A, prior to VCN administration caused 65% reduction in VCN-induced UDRS. Treatment of rats with the GSH depletor diethylmaleate (DEM) prior to VCN administration caused 167% increase in UDRS in gastric mucosal tissues. Treatment of the animals with the sulfhydryl compounds, cysteine and penicillamine, prior to VCN administration protected against VCN-induced UDRS. The results demonstrated an inverse and highly significant correlation between gastric GSH levels and VCN-induced UDRS (r = -0.873, P < 0.0001). In conclusion, our study indicates that VCN bioactivation and the homeostasis of gastric GSH may play a major, role in the initial processes underlying VCN-induced gastric carcinogenesis.     

Lidocaine block of LQT-3 mutant human Na+ channels

In transiently transfected mammalian cells we have identified pharmacological consequences of a naturally occurring deletion mutation, delta KPQ, of the human heart Na+ channel alpha subunit that previously has been linked to one form of the long QT syndrome, an inherited heart disease. Our results show that the Class IB antiarrhythmic agent lidocaine blocks maintained inward current through and slows recovery from inactivation of delta KPQ-encoded Na+ channels. Block is greater for maintained than for peak current. Because incomplete inactivation of mutant Na+ channels is now thought to underlie the prolonged ventricular action potential, which is the phenotype of this disease, and we find that the delta KPQ mutation speeds the recovery from inactivation of drug-free mutant channels, our results provide evidence, for the first time, that clinically relevant dysfunctional properties of an ion channel can be selectively targeted on the basis of the molecular properties conferred on the channel by an inherited genetic disorder.     

Adeno-associated virus 2-mediated transduction and erythroid cell-specific expression of a human beta-globin gene

Two strategies for crossbreeding of indigenous and exotic cattle for milk production in the tropics, viz. rotational crossing and formation of a composite breed, have been compared. Genetic considerations suggest that rotational crossing would lead to somewhat better dairy performance, mainly because of more heterozygosity. Predictions based on the performance of adjacent genetic groups as obtained from a comprehensive literature review point in the same direction. Rotational crossbreeding depends on a continuous introduction of bulls of both parental breeds. The herd will consist of 2 (or more) genetic groups, which might be inconvenient for breeding arrangements, but provides more flexibility. The system requires good organisation and is most suitable in large farms. In small scale dairying the composite breed strategy is the most practical approach to dairy cattle breeding in the tropics.