Late functional adaptation after colectomy, mucosal proctectomy, and ileal pouch-anal anastomosis

Ileal pouch-anal anastomosis (IPAA) is currently an alternative to proctocolectomy and ileostomy for patients with ulcerative colitis or familial polyposis. Some studies have suggested significant anal sphincter damage after mucosal proctectomy. Our aim was to assess prospectively late sphincter function after IPAA. In 250 patients, anorectal pressures were assessed with a pneumohydraulic perfused catheter manometry system. Each patient underwent colectomy, mucosal proctectomy, ileoanal anastomosis of a 15 cm ileal J-pouch, and loop ileostomy. Eight weeks after IPAA, anal manometry was repeated, and the ileostomy was closed. Manometry was repeated at yearly intervals. A decline in resting tone of the anal sphincter occurred early after IPAA with a gradual recovery toward control. External sphincter squeeze after pressures were not affected by IPAA and steadily increased to 8 years after operation. During this time, a progressive increase in J-pouch capacity was noted, and 24-hour stool frequency declined from 7.9 +/- 0.3 stools to 6.5 +/- 0.3 stools (p less than 0.05). We conclude that mucosal proctectomy results in internal anal sphincter trauma but is associated with long-term sphincter recovery, coupled with a significant improvement in external sphincter capacity, ileal pouch volume, and stool frequency.     

Associative learning and memory for an antinociceptive response in the spinalized rat

Prior research suggests that associative and memorial processes can modulate the activation of the endogenous antinociceptive systems. It has been generally assumed that forebrain systems play an essential role in mediating the impact of these processes. The present experiments explored whether the behavioral effects indicative of associative and memorial processes can be obtained in spinalized rats. Experiment 1 demonstrated that a conditioned nonopioid antinociception can be established after rats have experienced a spinal transection at the level of the 2nd thoracic vertebrae. Experiment 2 showed that a postshock distractor can speed the decay of shock-induced antinociception in the spinalized rat. These findings suggest that the circuitry needed to obtain associative and memorylike effects is present within the spinal cord.     

Alcohol-induced generation of lipid peroxidation products in humans

To address the hypothesis that elevated blood alcohol increases systemic oxidant stress, we measured urinary excretion of isoprostanes (iPs), free radical-catalyzed products of arachidonic acid. Ten healthy volunteers received acute doses of alcohol (Everclear-R) or placebo under randomized, controlled, double-blind conditions. Urinary iPF2a-III increased in a time- and dosage-dependent manner after dosing with alcohol, with the peak urinary iPF2a-III excretion correlating with the rise in blood alcohol. To determine whether oxidant stress was associated with alcohol-induced liver disease (ALD), we then studied the excretion of iP in individuals with a documented history of alcohol-induced hepatitis or alcohol-induced chronic liver disease (AC). Both urinary iPF2a-III and urinary iPF2a-VI were markedly increased in patients with acute alcoholic hepatitis. In general, urinary iPF2a-III was significantly elevated in cirrhotic patients, relative to controls, but excretion was more pronounced when cirrhosis was induced by alcohol than by hepatitis C. Excretion of iPF2a-VI, as well as 4-hydroxynonenal and the iPF2a-III metabolite, 2,3-dinor-5, 6-dihydro-iPF2a-III, was also increased in AC. Vitamin C, but not aspirin, reduced urinary iPs in AC. Thus, vasoactive iPs, which serve as indices of oxidant stress, are elevated in the urine in both acute and chronic ALD. Increased generation of iPs by alcohol in healthy volunteers is consistent with the hypothesis that oxidant stress precedes and contributes to the evolution of ALD.     

Acute aortic occlusion presenting with lower limb paralysis

In a two year period eight patients have presented with acute aortic occlusion and a poor outcome in seven. Initial failure to diagnose aortic occlusion, with a mean delay from presentation to diagnosis of 24 hours, was mainly responsible. All patients had varying degrees of paralysis on presentation which misled clinicians although other findings of acute ischaemia (pain, absent pulses, colour change and anaesthesia) were always present. Two patients were initially referred to a neurologist, another to a neurosurgeon, and the fourth to an orthopaedic surgeon. Even after diagnosis had been established, the need for urgent revascularization was not always recognized, the mean time from diagnosis to revascularization being 13 hours. Unnecessary aortography contributed to this delay in four patients. In two patients operative treatment was not undertaken while six were treated operatively by: aortic bifurcation graft (3), aortic thromboendarterectomy and femoropopliteal bypass (1), open aortic embolectomy (1) and bilateral femoral embolectomy (1). The causes of aortic occlusion were thrombosis of an atherosclerotic aorta (5), thrombosis of an aneurysm (2) and embolism (1). In the latter patient, the heparin induced thrombocytopenia syndrome (HITS) was primarily responsible. The outcomes in the eight patients were death (5), paraplegia (1), amputation (1), and uncomplicated recovery (1). The single patient who made an uncomplicated recovery had the shortest delay from presentation to revascularization of only 2 1/4 hours. Acute aortic occlusion rivals aortic rupture as a vascular emergency and demands immediate operative intervention.     

The Xanthomonas Hrp type III system secretes proteins from plant and mammalian bacterial pathogens

Studies of essential pathogenicity determinants in Gram-negative bacteria have revealed the conservation of type III protein secretion systems that allow delivery of virulence factors into host cells from plant and animal pathogens. Ten of 21 Hrp proteins of the plant pathogen Xanthomonas campestris pv. vesicatoria have been suggested to be part of a type III machinery. Here, we report the hrp-dependent secretion of two avirulence proteins, AvrBs3 and AvrRxv, by X. campestris pv. vesicatoria strains that constitutively express hrp genes. Secretion occurred without leakage of a cytoplasmic marker in minimal medium containing BSA, at pH 5.4. Secretion was strictly hrp-dependent because a mutant carrying a deletion in hrcV, a conserved hrp gene, did not secrete AvrBs3 and AvrRxv. Moreover, the Hrp system of X. campestris pv. vesicatoria was able to secrete proteins from two other plant pathogens: PopA, a protein secreted via the Hrp system in Ralstonia solanacearum, and AvrB, an avirulence protein from Pseudomonas syringae pv. glycinea. Interestingly, X. campestris pv. vesicatoria also secreted YopE, a type III-secreted cytotoxin of the mammalian pathogen Yersinia pseudotuberculosis in a hrp-dependent manner. YerA, a YopE-specific chaperone, was required for YopE stability but not for secretion in X. campestris pv. vesicatoria. Our results demonstrate the functional conservation of the type III system of X. campestris for secretion of proteins from both plant and mammalian pathogens and imply recognition of their respective secretion signals.