Comparing functional results one year and ten years after ileal pouch-anal anastomosis for chronic ulcerative colitis

Proctocolectomy with ileal pouch-anal anastomosis (IPAA) is the treatment of choice for most patients with chronic ulcerative colitis. Long-term results, however remain undefined; the major concern is that function may deteriorate. PURPOSE: The aim of this study was to assess functional outcome in a subgroup of patients who have an IPAA for chronic ulcerative colitis for > 10 years. METHODS: Among 1400 IPAA patients, 75 consecutive subjects (31 females and 44 males; median age 31 at operation) were identified who had the procedure prior to 1982. All patients had functional results recorded 1 year and 10 years following ileostomy closure. RESULTS: There were four deaths during the follow-up period; none were pouch related. Two patients refused ileostomy closure. Of the remaining 69 patients, there were 8 (11 percent) failures, leaving 61 subjects available for study. Stool frequency (7 +/- 3, mean +/- SD) remained unchanged. Of the 50 subjects with initially excellent daytime continence, 39 (78 percent) remained the same, 10 (20 percent) developed minor incontinence, and 1 developed poor control after 10 years. Four of 10 subjects (40 percent) with initial minor daytime incontinence remained unchanged, 4 (40 percent) improved, and 2 (20 percent) worsened. The one subject with poor control at one year was unchanged. Nocturnal fecal spotting increased over the 10-year period but not significantly (38 percent vs. 52 percent; P = 0.08). CONCLUSIONS: After IPAA, functional results in terms of stool frequency and rate of fecal incontinence did not deteriorate with time.     

CD4-mediated and CD8-mediated cytotoxic and proliferative immune responses to Toxoplasma gondii in seropositive humans

Both CD4+ and CD8+ cytotoxic T lymphocytes (CTL) are part of the human immune response to Toxoplasma gondii infection. To further our understanding of Toxoplasma immunity, we investigated factors influencing stimulation of CD4+ or CD8+ human T. gondii-specific immune cells. Both antigen-pulsed and Toxoplasma-infected antigen-presenting cells (APC) induced cell proliferation. Toxoplasma-infected APC elicited strong proliferation of CD4+ cells, but little or no proliferation of CD8+ cells, unless high antigen loads were used. Toxoplasma-infected APC stimulated specific cytotoxicity poorly or not at all, owing to death of stimulated cultures, whereas antigen-pulsed APC strongly elicited specific cytotoxicity. Cytotoxicity elicited by either type of APC resided exclusively in CD4+ T cells in polyclonal cultures. Thus, Toxoplasma-infected APC elicited stronger CD4-mediated than CD8-mediated cell proliferation and generated CD4+ CTL more readily than CD8+ CTL. Nonetheless, specific CD8+ memory cells were demonstrated, and rare CD8+ Toxoplasma-specific CTL were subcloned. Fixed Toxoplasma-infected APC (which induce CD8+ CTL) also elicited cell proliferation, but polyclonal cultures stimulated with these infected APC did not die. Unfixed Toxoplasma-infected APC strongly inhibited phytohemagglutinin-induced cell proliferation, whereas fixed APC did not. These data suggested that infected APC were inhibitory or lethal to some immune cells. Further investigations into interactions between immune cells and Toxoplasma-infected cells likely will help elucidate factors involved in the immunopathogenesis of Toxoplasma infection. As other intracellular parasites, including Plasmodium spp. and Leishmania spp., also elicit CD4+ CTL, such work may help establish paradigms governing immunity to intracellular parasites.     

The apparent diffusion coefficient of water in gray and white matter of the infant brain

PURPOSE: The purpose was to obtain normal values of the apparent diffusion coefficient (ADC) in the infant brain and to compare ADC maps with T1- and T2-weighted images. METHOD: Diffusion was measured in nine infants with an ECG-gated SE sequence compensated for first-order motion. One axial slice at the basal ganglia level was investigated with the diffusion-encoding gradients in the slice-selection direction. RESULTS: On ADC maps, the corpus callosum and the optic radiations appeared dark before the onset of myelination, and the crus posterior of the internal capsule could be visualized before it appeared on T1- or T2-weighted images. In gray and white matter, the mean ADC ranged from 0.95 x 10(-9) to 1.76 x 10(-9) m2/s. In the frontal and occipital white matter, in the genu corporis callosi, and in the lentiform nucleus, the ADC decreased with increasing age. The cortex/white matter ratio of the ADC increased with age and approached 1 at the age of 30 weeks. CONCLUSION: ADC maps add information to the T1 and T2 images about the size and course of unmyelinated as well as myelinated tracts in the immature brain.     

Brain monoamine output alterations after a single venlafaxine challenge in experimental hepatic encephalopathy

Venlafaxine (VEN) pharmacokinetics and effects on the brain monoamine output were investigated in the context of experimental hepatic encephalopathy (HE). Systemic VEN (10 mg/kg; subcutaneous) was administered to chronic portacaval shunted (PCS) and sham-operated rats. Their neocortical extracellular levels of 5-HT, 5-HIAA, NA, and DA were then assessed using microdialysis. Serum, brain extracellular, and brain tissue levels of racemic VEN and its main metabolites were also investigated. In a dose-equipotent manner, the VEN challenge increased the 5-HT levels in PCS rats compared with VEN-treated controls, whereas the 5-HIAA levels decreased similarly with time after the challenge in PCS and controls. Brain extracellular NA levels increased similarly in PCS and controls after VEN, but DA increased predominantly in controls. A similar single dose challenge resulted in clearly higher VEN levels in serum, brain extracellular fluid, and brain tissue in the PCS rats compared with controls. However, the VEN brain tissue/serum ratios were in the same order of magnitude for the two groups. Of the main VEN metabolites, only O-desmethylvenlafaxine (ODV) could be detected in pharmacologically significant amounts. The ODV concentration was also elevated in all three investigated biomatrices of the PCS rats versus control rats. The authors concluded that a typical novel brain monoamine-acting drug, such as VEN, exhibits both pharmacokinetic and pharmacodynamic alterations in experimental HE. Accordingly, the results of this study suggest that this frequently used type of drug should be further studied for its potential combined kinetic/dynamic actions in compromised patients with liver impairment.     

Pasteurella multocida toxin is a mitogen for bone cells in primary culture

The effect of recombinant Pasteurella multocida toxin (PMT) on primary cultures of embryonic chick bone-derived osteoblastic cells was investigated. It was found that PMT was a potent mitogen for primary derived chicken osteoblasts. The toxin stimulated DNA synthesis and cell proliferation in quiescent osteoblasts at the first passage and accelerated cell growth in subconfluent cultures. Cell viability was not affected by PMT, even at relatively high concentrations. Osteoblast numbers increased in a dose-dependent manner in response to PMT. Intracellular inositol phosphates were elevated in response to PMT, but no elevation in cyclic AMP (cAMP) levels was evident. Indeed, PMT inhibited cAMP elevation in osteoblasts in response to cholera toxin at a stage before other PMT-mediated events take place. In addition to increased cell turnover, PMT down-regulated the expression of several markers of osteoblast differentiation. Both alkaline phosphatase and type I collagen were reduced, but osteonectin was not affected. The in vitro deposition of mineral in cultures of primary osteoblasts and osteoblast-like osteosarcoma cells was also inhibited by the presence of PMT. This suggests that PMT interferes with differentiation at a preosteoblastic stage.