Expression of cell surface receptors and oxidative metabolism modulation in the clinical continuum of sepsis

Background  

Infection control depends on adequate microbe recognition and cell activation, yet inflammatory response may lead to organ dysfunction in sepsis. The aims of this study were to evaluate cell activation in the context of sepsis and its correlation with organ dysfunction.     

Orthotopic liver transplantation in a patient with carbamyl phosphate synthetase deficiency and cystic fibrosis

A 15-year-old female with carbamyl phosphate synthetase deficiency, cystic fibrosis, and cystic fibrosis-related diabetes underwent orthotopic cadaveric liver transplantation. Metabolic control was maintained during the procedure with nutritional support and the use of intravenous sodium phenylacetate and benzoate. Her postoperative course was complicated by seizures and a transient decline in her pulmonary function tests, which returned to preoperative levels within one year of the transplant. Now, four years post-transplant, her quality of life has dramatically improved. There are only four Canadian centres with paediatric liver transplantation programs. However, expert medical care for adults with inborn error of metabolism is even more limited, suggesting that access to adult medical care is one of the many factors to be considered when liver transplantation is contemplated for patients with metabolically unstable conditions.     

Prognostic significance of HIV-associated oral lesions and their relation to therapy

The oral manifestations of HIV infection have been considered to be of value in assessing disease progression in the developed world. However, the potential use of oral lesions as prognostic markers in resource-poor countries has yet to be fully investigated. There is reasonably compelling evidence in the developed world for an association between oral lesions and viral load. However, the true nature of this association is less clear and there are few data available from the developing world. With the introduction of HAART, a change in prevalence of the oral manifestations of HIV infection has been observed, including regression of oral candidiasis, Kaposi's sarcoma and oral hairy leukoplakia. However, oral condylomata and herpes simplex virus infection appear to persist with HMRT therapy. Further research in partnership with resource-poor countries is required to document disease progression and the associated oral lesions in both adults and children.     

Thrombolytic Therapy Within One Hour of the Onset of Acute Myocardial Infarction

Between 1986 and 1988, 239 consecutive patients with acute myocardialinfarction received thrombolytic therapy up to 285 minutes afteronset of symptoms; in 39 (17 with anterior infarction, 21 inferior,one lateral infarction) recombinant tissue plasminogen activatoror anistreplase was administered a mean of 51 minutes (range20–60 minutes) after the onset of symptoms. The patencyrates (26 of 30; 87 per cent), rapid ST segment resolution (36of 38; 95 per cent) and QRS score of 3 (28 of 38; 74 per cent)were statistically significantly higher for those seen and treatedin the first hour in comparison with those seen and treatedlater. For those treated within the first hour mean peak creatine kinasewas 1264 U/I for those with TIMI grade 2 or 3 (partial or completeperfusion) compared with 3005 U/I for those with TIMI grade0 or 1 (no perfusion or penetration without perfusion) (p=0.02):mean peak creatine kinase-MB for those with TIMI grade 2 or3 perfusion was 115 U/I compared with 312 U/I for those withTIMI grade 0 or 1 (p=0.01). Four of the 39 patients developedventricular fibrillation following thrombolytic therapy, threewithin 24 hours of infarction and one following reinfarctionon day 15. There were no significant bleeding complications.One patient died. Thrombolytic therapy within 1 hour of the onset of symptomsled to a very high angiographic patency rate, rapid ST segmentresolution with preservation of left ventricular function. Thistherapy is without significant complications.     

Characterization of normal peripheral blood lymphocyte colony-forming cells: cell cycle status, surface markers, and cellular growth requirements

We performed a series of studies to further clarify the nature of lymphocyte colony-forming cells (CFC) from normal peripheral blood. Mononuclear cells were separated into E-rosette-enriched (E+) and E- rosette-depleted (E-) populations and cultured in methylcellulose with conditioned media and irradiated mononuclear cells. Linear plating relationships were obtained with plating efficiencies of 0.26% +/- .02% (mean +/- SE) for E+ CFC and 0.18% +/- .02% for E- CFC. Cells in E+ colonies were T lymphocytes and in E- colonies were B lymphocytes as determined by cell surface marker analysis. Using the thymidine suicide technique, approximately one-half of CFC were found to be in cycle at any moment, and plating efficiencies and cell cycle status of E+ CFC were not changed by preincubation with PHA in liquid culture for 48 hr. Using antibody complement-mediated cytotoxicity, E+ CFC were found to be T101+, OKT3+, and Ia-, while E- CFC were OKT3- and Ia+. Using monocyte-depleted populations obtained by sedimentation at unit gravity, lymphocyte colony growth was absent in monocyte-depleted fractions, and optimal growth occurred with 40% monocytes in culture. In contrast to some previous studies, we find that lymphocyte CFC originate from a small, cycling population of cells bearing mature T or B lymphocyte markers. Entry into cell division, however, does not confer colony-forming capacity on lymphocytes. Monocytes are critical to growth of E+ CFC, and cultures severely depleted of monocytes would not be expected to form colonies.     

Intussusception of the small bowel discovered incidentally by computed tomography

Three cases of asymptomatic intussusception in adults are reported, discovered incidentally during a CT scan of the abdomen. It is being increasingly observed in adults, possibly aided by the reformatting capabilities of the new multislice CT scanners. It has been documented in children where it is considered to be transient and of no clinical significance.     

Biologic and immunohistochemical analysis of macrophage interleukin- 1 alpha, - 1 beta, and tumor necrosis factor production during the peritoneal exudative response

The present study examined changes in lipopolysaccharide (LPS)-induced interleukin 1 (IL-1) and tumor necrosis factor (TNF) production by murine peritoneal macrophages during the chronic exudative response to Freund's complete adjuvant (CFA). Macrophages were isolated by peritoneal lavage and adherence at intervals over a 32 day period following i.p. injection of CFA. Optimal culture conditions for IL-1 and TNF production were predetermined, and it was found that IL-1 production was profoundly impaired at densities of above 150 cells/mm2, whereas TNF synthesis was more resistant to density effects. Using optimal conditions, we observed a sequential appearance of monokines. On day 0 there was minimal IL-1 production and no detectable TNF production. By days 4-7, IL-1 production reached maximum levels with a steady decline to baseline by day 32. TNF production steadily increased after day 2, reached maximal levels by days 16-20, and then partly declined by day 32. These findings were supported by kinetic analyses at specified days. When related to exudative events, it appeared that maximal IL-1 was associated with the recruitment stage of the reaction, whereas TNF production was associated with the established exudate. Immunohistochemical analysis revealed that TNF production could be related to the proportion of macrophages with cytoplasmic TNF expression. In contrast, IL-1 alpha and -1 beta expression was comparable among populations with 85-100% of cells showing cytoplasmic expression 6 hr after LPS stimulus. Whereas cytoplasmic IL-1 alpha persisted for the 18 hr study period, IL-1 beta disappeared from many adjuvant recruited cells. Our findings suggest that monokine production is orchestrated during macrophage recruitment and activation at sites of chronic inflammation.