Ventilation/perfusion indices do not correlate with the difference between oxygen consumption measured by the Fick principle and metabolic monitoring systems in critically ill patients.

OBJECTIVE: To determine whether the difference between oxygen consumption (VO2) measured by metabolic gas monitoring systems and by the Fick principle is related to venous admixture, deadspace/tidal volume ratio, or alveolar-arterial oxygen tension gradient in critically ill patients. DESIGN: A prospective study. SETTING: An 11-bed general ICU in a 900-bed teaching hospital. PATIENTS: Twenty critically ill patients admitted to the ICU who required mechanical ventilation, right heart catheterization, and arterial and mixed venous gas measurements for normal clinical management. RESULTS: Thirty-three recordings were analyzed. The mean VO2 measured by the metabolic gas monitoring system was 308 +/- 63.9 (SD) mL/min and was significantly greater than the mean VO2 measured by the Fick principle of 284 +/- 72.0 mL/min. The difference between the two measurements of 24.3 +/- 47.6 mL/min correlated poorly with venous admixture (r2 = .0009), dead-space/tidal volume ratio (r2 = .0064) and alveolar-arterial oxygen tension gradient (r2 = .017). CONCLUSIONS: If the difference in VO2 measured by metabolic gas monitoring systems and the Fick principle is due to intrapulmonary VO2 then in critically ill patients the ventilation/perfusion indices of venous admixture, deadspace/tidal volume ratio and alveolar-arterial oxygen tension gradient correlate poorly with intrapulmonary VO2.     

Immunological compatibility between the chacma baboon and man.

Predictions of an increasing shortage of donor organs for the future has led to a resurgence of interest in xenotransplantation. We have methodically assessed the immunological compatibility of humans against the chacma baboon with a view to narrowing the gap of concordance by careful immunological screening. The necessity of major blood group compatibility in xenotransplantation is now established. While no group O universal donor exists in the baboon, groups A (45%), B (15%), and AB (40%) are well represented. Baboon histocompatibility antigens could not be precisely defined using human antisera. This does not necessarily imply lack of homology between the species, as we have shown specific crossreactivity of numerous antihuman monoclonal antibodies with baboon leukocytes. Normal humans do not exhibit preformed agglutinins to erythrocytes of the chacma baboon (Papio ursinus orientalis)) but cytotoxic antibodies are occasionally found. Sera from allosensitized patients may contain crossreacting hemagglutinins, leukoagglutinins and complement-dependent cytotoxic antibodies. Binding of human immunoglobulin-G and -M to baboon targets was demonstrated by flow cytometry. Negative crossmatch combinations for antibodies of the IgG subclass were easily found, but IgM antibodies from allosensitized patients were polyspecific in their action. In vitro assessment of lymphocyte mediated cytotoxicity showed that preformed cellular immunity between the species was rare. The response of human lymphocytes to xenoantigen stimulation in mixed lymphocyte cultures showed a normal distribution, permitting the selection of low-responding combinations. Screening for viruses, especially HTLV-1 and Coxsackie-BL34, is important. These findings demonstrate a closer degree of concordance than has previously been suspected.     

Suppressor mechanisms in neonatally acquired tolerance to a Gross virus-induced lymphoma in rats.

Tolerance to a highly immunogenic Gross virus-induced tumour in Wistar/Furth rats (C58NT)D was produced by neonatal infection of the rats with the virus. These rats failed to reject the tumours when challenged 8 weeks after virus inoculation and to mount the appropriate cell-mediated immune response to the tumour. The mechanisms involved were studied in vivo by adoptive transfers into sub-lethally irradiated rats of tumour cells mixed with spleen cells and/or sera from normal, tolerant, or tumour immune rats, and in vitro by a 51Cr release assay involving similar mixtures. The results indicate the presence of a suppression mechanism which is sensitive to irradiation and abolished by trypsinisation. Weak blocking factors can also be detected in serum. An interpretation in terms of the release of virion proteins from infected cells is proposed, although participation of suppressor lymphocytes has not been excluded.     

Prophylactic antimicrobials in elective colorectal and biliary surgery

In 97 patients undergoing elective biliary (44) or colorectal (53) surgery, cases were randomly allocated to receive peri-operative prophylaxis with either cefoxitin (Mefoxin; MSD) or metronidazole, penicillin and tobramycin (MPT). Sepsis occurred in 3 of the biliary cases (6,8%) and in 16 of the colorectal cases (30,2%). In the colorectal group sepsis occurred equally in patients receiving cefoxitin (22,2%) or MPT (38,5%) (P = 0,20). Patients who developed sepsis did not have a prolonged hospital stay; strict criteria were used to define sepsis in this study and this explains the apparently high sepsis rate. A positive wound culture at the end of the operation was more common after colorectal surgery (30,2%) than after biliary surgery (4,6%) and was associated with a higher subsequent infection rate (P = 0,02).     

Bezafibrate and simvastatin (MK-733) in the treatment of primary hypercholesterolaemia

Simvastatin, a new 3-hydroxy-3-methylglutaryl co-enzyme A reductase inhibitor, was compared to bezafibrate, a fibric acid derivative, in an open cross-over placebo-controlled study. Bezafibrate was administered as a 200 mg dose 3 times daily, while simvastatin dosage ranged from 10 mg to 40 mg once daily at night. Bezafibrate produced a non-significant 13.1% (P = 0.113) decrease in total cholesterol (TC), a 20.7% (P less than 0.05) decrease in low-density lipoprotein cholesterol (LDL-C), an increase of 26.5% (P less than 0.01) in high-density lipoprotein cholesterol (HDL-C) and an improvement in the HDL:LDL ratio of 77.3% (P less than 0.01). Simvastatin 10 mg and 20 mg daily reduced TC by 18.6% and 22.6%, respectively, and LDL-C by 23.9% and 28.6% respectively (P less than 0.01), while no significant increase was noted in HDL-C. Simvastatin 40 mg daily reduced TC and LDL-C by 27.1% and 37.6%, respectively (P less than 0.01), increased HDL-C by 32.0% (P less than 0.05) and improved on the HDL:LDL ratio by 130.8% (P less than 0.01). This showed improvements over bezafibrate of 13.5% for TC, 18.9% for LDL-C, 6.0% for HDL-C and 55.8% for HDL:LDL ratio. It was concluded that simvastatin was well tolerated and had significant hypocholesterolaemic effects when taken once daily.