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Biomedical subjects

J A Myburgh

Publications and source records attributed to J A Myburgh.

At least 19 recordsLinked to original sources

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.

Adult

Enhanced spontaneous and induced LAK function in baboons receiving total lymphoid irradiation (TLI).

TLI has potent immunosuppressive effects, but there is concern over its possible carcinogenic properties. The aim of the study was to assess to what degree TLI may compromise natural killer (NK) and lymphokine activated killer (LAK) cell function. There was a significant increase (P less than 0.0001) in both NK-cell function (measured against K562 targets) and spontaneous LAK-cell function (measured against DAUDI targets) in fresh blood lymphocytes throughout a course of 8 x 100 cGy fractionated TLI. This may be related to a three- and sevenfold increase, respectively, in CD16+ CD8- and CD56+ CD2- cell frequencies over the same period. Mitogen-induced interleukin 2 (IL-2) synthesis from blood lymphocytes was inhibited by up to 75% with as little as 100 cGy of TLI. Expression of IL-2 receptors on fresh lymphocytes did not vary and remained low. Therefore spontaneous LAK occurrence appeared to be triggered through an IL-2-independent pathway. The in vitro addition of IL-2 verified that cells retained their ability to respond to this lymphokine resulting in greatly enhanced induced LAK function. This was most probably mediated by CD56+ cells which were found to readily express IL-2 receptors upon mitogen stimulation. In conclusion, fractionated low-dose TLI appears to enhance MHC unrestricted immune surveillance in a manner independent of IL-2 production.

Animals

Derived oxygen saturations are not clinically useful for the calculation of oxygen consumption.

In critically ill patients, oxygen consumption (VO2) and delivery (DO2) are used to determine optimal haemodynamic management and to grade severity of illness. VO2 may be measured by indirect calorimetry with metabolic gas monitoring systems or derived using the reverse Fick principle. Oxygen saturation (SaO2) may be measured directly by co-oximetry or derived by equations for incorporation into reverse Fick equations. A prospective study comparing VO2 measured by these methods was performed in 20 critically ill patients. The mean VO2 measured by the metabolic gas monitoring system (308 +/- 63.9 ml/min) was significantly greater than that measured by reverse Fick using measured SaO2 (284 +/- 72.0 ml/min) (P < 0.01). This difference may be due to intrapulmonary VO2. When SaO2 was calculated from three logarithmic equations and incorporated into the reverse Fick equations, calculated VO2's were significantly greater (P < 0.001) than those measured by indirect calorimetry. Correlation was poor and wide limits of agreement (-118 to +350 ml/min) were demonstrated. VO2 should ideally be measured by indirect calorimetry in the critically ill, or if reverse Fick is used, SaO2 should be measured by co-oximetry as the use of equations for clinical measurement of SaO2 is clinically suspect.

Adult

The relevance of more sensitive ancillary crossmatch techniques in predicting early cadaver renal graft outcome.

The predictive value of varying levels of antibody activity, its class and antigen specificity in sera of 81 recipients of cadaver renal allografts was evaluated. Recipients for transplantation were selected on the basis of a negative dye uptake T-cell crossmatch, after which the more sensitive 51Cr release technique was employed in a blind study using unseparated donor target cells. Recipient sera with peak panel reactivity and current samples were evaluated before and after reduction with dithiothreitol to destroy the IgM subclass. Double absorption with pooled platelets allowed antibodies against HLA class I antigens to be distinguished from those against HLA class II/non-HLA antigens. Optimal levels of cytotoxicity were established, giving a sensitivity of 73%. Data were assessed in terms of positive predictive value, and showed that conventional T-cell crossmatching is adequate for the primary transplant group, but more sensitive ancillary tests are indicated for regrafts. In this category of patients, IgG antibodies, whether against HLA class I antigens or HLA class II/non-HLA antigens, were highly predictive of early graft loss (positive predictive value 50%-100%). Using this protocol for patient selection, 1-month graft survival would have improved from 73% to 96%.

Adolescent

A prospective comparison of a percutaneous tracheostomy technique with standard surgical tracheostomy.

A prospective non-randomized study was undertaken to compare, in intensive care patients, the safety and utility of a percutaneous tracheostomy technique performed at the bedside with a surgical tracheostomy technique performed in the operating room. During a 21 month period, 153 percutaneous tracheostomies were performed. Complications occurred in 6 patients (3.9%). Secondary wound haemorrhage occurred in 4 patients and primary wound haemorrhage occurred in 2 patients. During the same period, 74 surgical tracheostomies were performed. Complications occurred in 14 patients (18.9%) which included tracheal obstruction, haemorrhage, pneumothorax, wound infection, wound breakdown and one death. In comparison to surgical tracheostomies, percutaneous tracheostomies were rapidly and easily performed at the bedside and were associated with significantly fewer complications.

Adolescent

The P50 is reduced in critically ill patients.

A prospective study was designed to measure the P50 in 20 critically ill patients, and compare it with the P50 measured in 20 normal individuals. Arterial blood gases, lactate, haemoglobin (Hb) and phosphate (PO4) levels were also measured and compared with the P50 in the critically ill patients. The mean P50 of the critically ill patients was 24.5 mmHg (SD +/- 2.9) and was significantly lower than the mean P50 of 26.2 (SD +/- 2.2) in the normal individuals (p less than 0.05). In the critically ill patients, strong correlations were observed between the P50 and the arterial pH and base excess (BE) levels, with coefficients of 0.79 and 0.69 respectively whereas correlations between the P50 and arterial oxygen tension (PO2), carbon dioxide tension (PCO2), lactate, Hb and PO4 levels were poor, with correlations of 0.001, 0.008, 0.07, 0.13 respectively. It is concluded that the P50 is commonly reduced in critically ill patients, and has a strong correlation with arterial pH and BE.

Adult

Properties of the isoenzyme forms A-1, A-2 and B of N-acetyl-beta-D-glucosaminidase purified from baboon kidneys.

Three forms of N-acetyl-beta-D-glucosaminidase (NAG: A, B and I) were separated from baboon kidney using Con A-Sepharose and DEAE-Trisacryl chromatography. 2. The A form was further purified into two forms A-1 and A-2 using hydroxylapatite chromatography and anodic PAGE. Both were homogeneous on SDS-PAGE and anodic PAGE but microheterogeneous on PAG-IEF, which could be eliminated by prior treatment with endoglycosidase H or glycopeptidase F. 3. The carbohydrate content accounted for some of this microheterogeneity since it varied from 31 for A-1 to 17% for A-2 and the sialic acid was 6 and 1%. Deamidation may also contribute since the acidic amino acids (29 mol%) and ammonia were high following acid hydrolysis. 4. The mol. wt for A-1, determined by SDS-PAGE, was 52.1 K. 5. The pH optimum was 4.55 and the pI4.97. 6. The optimum temperature for NAG A and B was 50 degrees and 42 degrees C, but B retained more activity above 55 degrees C. 7. The Km for N-acetyl-beta-D-glucosamine and -galactosamine for both isoforms was 0.497 and 0.627 mM respectively. 8. Several ions were found to be uncompetitive inhibitors. Ag+ and Pb2+ were the most potent having Ki values of 3.6 and 8.5 mM respectively. Acetate acted as a competitive inhibitor.

Acetylglucosaminidase

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.

Animals

Selective shunts: the Johannesburg experience.

My personal 15-year experience with 141 selective shunts (127 elective, 14 emergency) for portal hypertension is reported. Alcoholic cirrhosis comprised 54% of elective operations, and of the nonalcoholic patients, 22% were cirrhotic and 24% were noncirrhotic. Adequate and, if necessary, prolonged (mean 6 weeks) in-hospital preparation resulted in Hospital mortality and long-term actuarial survival were better in nonalcoholics compared with alcoholics, but there was no significant difference between cirrhotic nonalcoholics and alcoholics. Variceal rebleeding was rare (4% of Warren procedures) and, when present, was usually related to shunt failure. Gastric fundal variceal rebleeding did not occur in 44 patients undergoing splenopancreatic disconnection. Postoperative encephalopathy occurred in 13% of patients; however, it did not occur at all in noncirrhotic patients. Prograde portal venous perfusion was preserved in 77% of patients. Fifteen alternate selective operations to the Warren shunt were performed, usually because of antecedent splenectomy. Shunt failure and variceal rebleeding occurred more frequently with these more vulnerable shunts, but 66% had a satisfactory outcome. Selective shunts have produced highly satisfactory results in appropriately selected patients.

Emergencies

An explanation of the noncorrespondence between assessment methods of cyclosporin.

Various methods of determining cyclosporin (CyA) levels in patients after kidney transplantation were compared. These included polyclonal antibody (pcAb-), specific and nonspecific monoclonal antibody (S- and NmcAb-) radioimmunoassays (RIA), and high performance liquid chromatography (HPLC). The results obtained by the various methods when compared showed some correlation but did not correspond. A probable explanation for part of this noncorrespondence is the presence of monoclonally crossreactive metabolites (CyA-M). Another reason was that the concentration of CyA in the standards supplied with the RIA kits was found to be higher than stated.

Antibodies, Monoclonal