Intra-abdominal packing for uncontrollable haemorrhage during ruptured abdominal aortic aneurysm repair.

OBJECTIVE: Intra-abdominal packing is a valuable adjunct in patients with abdominal trauma and uncontrollable bleeding but few data exist regarding early and late outcome associated with this technique in patients with ruptured abdominal aortic aneurysm (AAA). METHODS: Interrogation of a prospective vascular surgical database identified 23 patients (22 men; median age 69, range 59-82, years) with ruptured AAA who required intra-abdominal packing for control of coagulopathic haemorrhage after insertion of an aortic graft between January 1982 and December 2003. Co-morbidity, operative and outcome data were retrieved. RESULTS: Haemostasis was achieved and packs were removed within 48 h in 20 patients. In those patients who had a graft inserted, the peri-operative mortality rate was 12 of 23 (52%) patients (vs. 172 of 455 (38%) patients who were not packed, NS). Three (13%) patients developed early intra-abdominal sepsis, which was universally fatal: graft-enteric fistula, intra-abdominal abscess with necrotizing fasciitis of the abdominal wound, and infected retroperitoneal haematoma. Two of 11 (18%) survivors developed late graft-related infective complications: major aortic graft infection at 6 months and symptomatic infected para-anastomotic aortic false aneurysm at 39 months. Early and late intra-abdominal infective complications were significantly more common in patients who were packed than in those who were not (packed: five of 23, 22% vs. non-packed: five of 455, 1%; p < 0.001). CONCLUSION: These data demonstrate that intra-abdominal packing in coagulopathic patients with ruptured AAA can achieve an acceptable survival rate. However, this technique may be associated with an increased incidence of early and late intra-abdominal infective complications.     

Anesthesia in 'stone man': myositis ossificans progressiva

Myositis ossificans progressiva is a rare disease leading to complete ossification of the muscular system. Very little information about this rare disease and its anesthetic implications has appeared in anesthetic literature. This disease is felt to have an autosomal dominant pattern of inheritance and is usually associated with anomalies of the hands and feet. Afflicted patients are frequently misdiagnosed in childhood as having a rheumatologic disorder. Later in life (as true bone is formed in striated muscle, ligaments, and fascia), the correct diagnosis becomes obvious. Although muscles of the heart, diaphragm, larynx, and sphincters are spared, those of the chest wall are not, and pulmonary function progressively deteriorates. Death frequently occurs as a result of a pulmonary infection. Specific anesthetic considerations include positioning to avoid injury, potential need for fiberoptic intubation or tracheostomy, decreased thoracic compliance with the need for increased ventilating pressures, and the ultimate in disuse atrophy contraindicating the use of succinylcholine. Myositis ossificans progressiva can present the anesthesiologist with interesting challenges. Anesthetic management will need to be individualized according to the severity of the disease.     

Transgenic mice that express different forms of the influenza virus hemagglutinin as a neo-self-antigen

We have generated transgenic mouse lineages that express the influenza virus hemagglutinin in different physical forms. One kind expresses the full-length hemagglutinin molecule as a cell surface glycoprotein and can be recognized by hemagglutinin-specific B and T cells. The other expresses a truncated polypeptide corresponding to the N-terminal third of the hemagglutinin molecule. This polypeptide encodes known hemagglutinin-specific T-cell determinants; however, it contains no native B-cell epitopes, since these depend on the conformation of the fully folded protein. In each case, the hemagglutinin transgenic mice display ubiquitous expression of transgenic messenger RNA and induce T-cell tolerance to the transgene-encoded T-cell determinant site 1. Thus, the hemagglutinin is a neo-self-antigen in both kinds of hemagglutinin transgenic mice and should provide a useful system for understanding the factors and mechanisms that govern tolerance and autoimmunity to self-antigens.     

New Potent Azomethine Prodrugs of the Histamine H3-Receptor Agonist (R)-α-Methylhistamine Containing a Heteroarylphenyl Partial Structure

The therapeutic value of histamine H₃-receptor ligands is under current investigation. On the basis of recently described diaryl imine prodrugs of the histamine H₃-receptor agonist (R)-α-methyl-histamine ( 1 ) a series of new azomethine prodrugs containing five- and six-membered heterocycles were synthesized and tested for their in vitro hydrolysis rates and in vitro activity after oral application. It was found that electron-deficient six-membered heterocycles drastically destabilized the imine double bond so that these prodrugs decomposed unsuitably fast. On the contrary, prodrugs containing five-membered heterocycles appeared to be highly effective for the CNS delivery of 1 , and a remarkable correlation between chemical structure and pharmacokinetic profile was observed. Particularly (R)-4-fluoro-2-[[N-[1-(1H-imidazol-4-yl)-2-propyl]imino](1H-pyrrol-2-yl)methyl]phenol ( 8c ), the 2-furanyl analogue 8d , and its 3-furanyl isomer 8e proved to be equipotent to the most potent of recently described halogenated diaryl imine prodrugs of 1. However, in contrast to any other azomethine prodrug, 8c exhibited an incomparably long lasting delivery of 1 in the CNS and can thus be regarded as a ‘retard’ prodrug. Assuming that a therapeutic indication of histamine H₃-receptor agonists will soon be established, these highly potent heteroarylphenyl azomethine prodrugs, which already serve as valuable pharmacological tools, may also become potential drugs in clinical use.