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Biomedical subjects

J A Myburgh

Publications and source records attributed to J A Myburgh.

At least 37 records · Page 2Linked to original sources
PubMed2000

Mannitol for resuscitation in acute head injury: effects on cerebral perfusion and osmolality.

OBJECTIVE: To review the use of mannitol during initial resuscitation following traumatic brain injury and to determine the effects of mannitol on subsequent management following resuscitation and commencement of neuromonitoring. METHODS: A retrospective audit of patients presenting to a tertiary hospital with severe head injury (Glasgow coma score < or = 8). Patients were divided into two groups according to whether they received mannitol during initial resuscitation. Measurements included initial plasma osmolality, cerebral perfusion pressure (CPP), intracranial pressure (ICP) and jugular venous saturation (SjO2). RESULTS: Forty patients were identified: 19 received mannitol prior to admission to the intensive care unit. Of these, only 2 patients fulfilled acceptable neurological indications for mannitol. The mannitol patients received a mean dose of 237 mL of 20% mannitol (47.4 g) and had significantly higher initial osmolalities than the patients who did not receive mannitol (293 vs 279 mosmol/L, p < 0.05). No significant difference in initial CPP, ICP, or SjO2 was identified. The mannitol patients were further subdivided into two 12-month periods (1994 and 1995). A dose related, significant difference in initial osmolalities was identified (140 vs 344 mL and 284 vs 304 mosmol/L respectively, p < 0.05). The latter group (n = 9) had significantly lower initial CPPs (72 vs 59 mmHg) and higher ICPs (14 vs 18 mmHg). No difference in 6 month Glasgow outcome scores between groups was demonstrated. CONCLUSIONS: The empirical overuse of mannitol is common. Mannitol did not exert any beneficial effect on CPP, ICP or SjO2 in the initial phases of management. Larger doses (i.e. > 20 g) are associated with increased osmolality which may reduce CPP.

Journal Article↗
PubMed1999

Definition and characterization of chicken Gal alpha(1,3)Gal antibodies.

BACKGROUND: The Gal alpha(1,3)Gal epitope is of interest as, in pig-to-primate xenotransplantation, it is the major target of naturally occurring human IgM and IgG antibodies, leading to hyperacute rejection. Human and Old World monkeys make anti-Gal alpha(1,3)Gal antibodies as they lack a functional gene and do not express Gal alpha(1,3)Gal. Interestingly, the cultured fibroblasts of some other species, such as chickens, have been reported also not to express Gal alpha(1,3)Gal--if this is true for other tissues, and chickens do not express Gal alpha(1,3)Gal antigen, then they would have anti-Gal antibodies--which could have diagnostic and therapeutic value, particularly as chicken antibodies do not fix mammalian complement. METHODS: Standard serological methods were used to characterize the antibodies. Several baboons received pig kidney xenografts that had been perfused with hyperimmune chicken anti-Gal antibodies. RESULTS AND CONCLUSIONS: We now demonstrate that chickens do not express Gal alpha(1,3)Gal on their red cells, leukocytes, or tissues, and that their serum contains large amounts of anti-Gal alpha(1,3)Gal antibodies. In addition, chickens could be immunized to produce high-titer, high-avidity antibodies (9.5x10(9) M(-1))--an avidity considerably greater than that of the Gal alpha(1,3)Gal binding lectin IB4 (2.9x10(8) M(-1)) or Gal antibodies in human serum (2.2x10(5) M(-1)). Chicken antibodies, obtained from both normal and immunized chickens, could block the in vitro cytolysis of pig endothelial cells or lymphocytes by human or baboon antibodies. However, such antibodies tested in vivo in pig-to-baboon xenotransplantation failed to block hyperacute rejection and, indeed, may have accelerated this.

Animals↗
PubMed1999

An appraisal of the impact of management guidelines in traumatic brain injury.

OBJECTIVE: To consider the evidence for the beneficial effects of the current management guidelines in traumatic brain injury, and to highlight the important issues. DATA SOURCES: Articles and published peer-review abstracts about the mechanisms and management of traumatic brain injury. SUMMARY OF REVIEW: Guidelines for the management of traumatic brain injury focus on the recognition, detection and prevention of secondary brain insults. Defence of cerebral perfusion pressure with optimisation of cerebral blood flow and substrate delivery, form the vanguard of these guidelines. The impact of guidelines per se on outcome is difficult to determine due to rapid changes in practice and a dearth of controlled evidence predating these guidelines. Technological developments in multimodal monitoring may identify trends in changing practice. However, there are still significant limitations in the accuracy of assessment of the underlying neuropathological processes. The impact of management strategies using current or novel therapies on these neuropathological processes is difficult to assess in randomised controlled trials due to small sample sizes and heterogeneous practice. Preliminary studies using continuous multimodal monitoring in accordance with current management guidelines have identified that episodes of sustained jugular venous desaturation were significantly reduced, indicating that potentially harmful episodes of cerebral oligaemia were prevented. Although the impact of these strategies on outcome was favourable, limitations in these studies do not allow firm outcome based assessments. However, these studies suggest that by defending cerebral perfusion pressure, potentially ischaemic or hypoxic cerebral insults may be prevented and may result in a reassessment of the indications and clinical utility of neuromonitoring. CONCLUSIONS: The impact of management guidelines in traumatic brain injury on patient outcome has been difficult to determine. However, there is a large body of uncontrolled evidence that suggests secondary global cerebral ischaemia-hypoxic insults are the major determinants in influencing outcome and that therapeutic interventions that maintain and defend cerebral perfusion pressures may improve outcome.

Journal Article↗
PubMed1998

A comparison of the effects of norepinephrine, epinephrine, and dopamine on cerebral blood flow and oxygen utilisation.

The concomitant effects of infusions of catecholamines on cerebral blood flow (CBF), intracranial pressure (ICP), arterio-venous oxygen content difference (AVDO2), and cerebral oxygen utilization (COU) were prospectively studied in an intact cerebral autoregulatory model. Epinephrine, norepinephrine and dopamine were infused at doses used in clinical practice in awake, chronically catheterized sheep (n = 5). Mean arterial pressure (MAP), CBF and ICP were measured continuously, COU was expressed as delta CBF x AVDO2. All 3 drugs significantly increased MAP in a dose dependent manner. Norepinephrine and epinephrine had no significant effects on ICP, CBF, AVDO2 or COU at infusions of 0-60 micrograms/min. Infusions of dopamine from 0-60 micrograms/kg/min resulted in statistically significant increases in ICP (+34.5 +/- 3.7 to +97.2 +/- 6.8) and CBF (+13.3 +/- 3.2 to +52.6 +/- 24.3) (% change baseline +/- SEM, 95% CI, ANOVA), reduction in AVDO2 (3.54 +/- 0.2. to 2.69 +/- 0.2 mg%) and a biphasic response in COU. In the intact physiological model, induced hypertension by epinephrine and norepinephrine is not associated with global changes in CBF, ICP or COU which remain constant. At equivalent doses, dopamine causes cerebral hyperaemia, increased ICP and increased global cerebral oxygen utilization.

Animals↗
PubMed1996

Cerebral oxygenation monitoring by near-infrared spectroscopy is not clinically useful in patients with severe closed-head injury: a comparison with jugular venous bulb oximetry.

OBJECTIVE: To compare continuous jugular venous bulb oximetry and cerebral near-infrared spectroscopy in patients with severe closed head injury. DESIGN: A prospective observational study. SETTING: Intensive care unit of a major teaching hospital. PATIENTS: Adults (n = 10) with severe closed-head injury (Glasgow Coma Scale score of < or = 8). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Jugular venous bulb oximetry, cerebral near-infrared spectroscopy, and cerebral perfusion pressure were measured continuously. A total of 3,691 paired measurements of near-infrared spectroscopy and jugular venous bulb oximetry were analyzed. Poor correlation (r2 = .04) between paired measurements and wide limits of agreement (-13% to +21%) were demonstrated. The mean difference between measurements was +/- 4% and the standard deviation of the mean difference was +/- 8.69%. The data were subsequently grouped according to three clinically significant subgroups of jugular venous bulb oxygen saturation reflecting low ( < 55%), normal (55% to 75%) and high ( > 75%) saturation values. Poor correlation and wide limits of agreement between the two methods of measurement were observed in all groups. Values recorded by near-infrared spectroscopy did not significantly change between the groups, and 14 clinically significant episodes of jugular venous bulb desaturation were not detected by near-infrared spectroscopy. CONCLUSIONS: Tissue oxygen saturation determined by near-infrared spectroscopy does not reflect significant changes in cerebral oxygenation detected by the global measurement of jugular venous bulb oximetry. This finding may be explained by inadequate signal detection and inaccuracies in the algorithm used to filter out extracranial components. Until these technical difficulties are addressed, near-infrared spectroscopy, as measured by the machine assessed in this study, cannot be routinely recommended for assessment of cerebral oxygenation in patients with acute head injury.

Adolescent↗
PubMed1995

Detection of cerebral venous desaturation by continuous jugular bulb oximetry following acute neurotrauma.

A prospective observational study was performed to assess the reliability of fibreoptic oximetric catheters and to identify the incidence and causes of jugular bulb oxygen desaturation in patients with acute closed head injury. There were twenty-five patients (30 +/- 16 years) with GCS < or = 8 in this study. Jugular bulb oximetry, mean arterial pressure, intracranial pressure, end-tidal CO2 and pulse oximetry were monitored continuously. Catheter calibration against a laboratory oximeter was performed post insertion and thereafter eight-hourly. Cerebral venous desaturation was defined as a jugular bulb oxygen saturation < 55% of > 10 minutes duration. There was a poor correlation for the first in vivo calibration (r2 = 0.602, P < 0.001, n = 25). Thereafter a close correlation between jugular bulb catheter and oximetry values was demonstrated (r2 = 0.868, P < 0.001, n = 205). Forty-two episodes of jugular bulb oxygen desaturation of 88 minutes mean duration (range 10 to 555) were observed. 83% occurred within 48 hours following injury. Hypocapnia was associated in 45% of episodes; hypoperfusion in 22%; raised ICP in 9% and a combination of the above in 24%. Validation with a laboratory oximeter is essential prior to continuous jugular bulb oximetry. Sustained episodes of cerebral venous desaturation are frequent within the first 48 hours following acute head injury. Factors such as hypocapnia and cerebral hypoperfusion that primarily reduce cerebral blood flow are predominant.

Acute Disease↗
PubMed1994

Nonspecific mixed lymphocyte culture inhibitory antibodies in sera of tolerant transplanted baboons conditioned with total lymphoid irradiation.

Pretransplant conditioning of baboons with total lymphoid irradiation allows long-term renal allograft acceptance in one third of the recipients. Brief additional immunosuppression was given to some animals, but always for less than 14 days after transplant. This enabled us to study mechanisms of graft tolerance in the absence of long-term, nonspecific drug immunosuppression. While 3 patterns of unresponsiveness were noted, this study concentrated on serum-mediated suppression. Eleven of 16 (69%) baboons destined to become tolerant to their grafts developed a nonspecific MLC inhibitory factor in their sera. In most animals it appeared within 3-5 weeks after transplantation and persisted over the period of study (91-793 days after Tx). The suppressor factor was absent in sera from 38 control animals and 8/9 rejectors. It was shown to be a low affinity IgG antibody that inhibited MLC by binding to stimulator cells, an effect that could be overcome by addition of rIL-2 to cultures. NK cell lysis, cell-mediated lympholysis, and polyclonal mitogenesis were unaffected. Antibody binding to purified baboon T cells could not be demonstrated, though binding to EBV-transformed B cells was readily shown. Our study shows that total lymphoid irradiation permits the generation of blocking antibodies directed against APCs as one mechanism of maintaining T cell unresponsiveness. These observations are consistent with the masking of ligands involved in antigen presentation or costimulation leading to a sustained state of autoenhancement.

Animals↗
PubMed1994

Surgical biliary drainage in primary sclerosing cholangitis. The role of the Hepp-Couinaud approach.

OBJECTIVE: To assess the value of bilioenteric bypass, particularly by the Hepp-Couinaud technique, in patients with primary sclerosing cholangitis and dominant strictures in the extrahepatic biliary tract. DESIGN: Prospective study and analysis of a personal series. SETTING: Academic hospital. PATIENTS: Twenty-four of 69 patients with primary sclerosing cholangitis were selected for operative intervention. In all patients both intrahepatic and extrahepatic ducts had multiple strictures. In 22 patients the major proximal extrahepatic site of stricturing was at the confluence of the right, left, and common hepatic ducts. All patients were jaundiced at some stage before operation and 19 had persistent jaundice. Five patients were cirrhotic at presentation. INTERVENTIONS: Twenty Hepp procedures were performed in 19 patients, involving a side-to-side anastomosis 2.5 to 3.5 cm wide between a Roux-en-Y loop and the right and left hepatic ducts at their confluence. No transanastomotic stents were used. MAIN OUTCOME MEASURES: Survival and relief of jaundice. RESULTS: Follow-up ranged from 20 months to 11 years; median, 6.5 years. At the time of this report, three of the five cirrhotic patients had died, and the two surviving patients had progressive liver disease. In the 16 noncirrhotic patients who underwent bypass, actuarial survival was 100% up to 8 years. Four of these patients were mildly icteric but stable 2.3 and 7 years after bypass. Eleven patients remained free of jaundice for 2.3 to 9 years after bypass. One patient died of hepatic failure 8.5 years after bypass. CONCLUSIONS: In noncirrhotic patients with primary sclerosing cholangitis and dominant extrahepatic biliary strictures, bilioenteric bypass with the Hepp technique and without transanastomotic stenting relieves jaundice durably, safely, and effectively and is associated with freedom from recurrent bouts of cholangitis. This may attenuate or halt the development of secondary biliary cirrhosis. Patients with cirrhosis derive minimal benefit from biliary bypass and should undergo liver transplantation.

Actuarial Analysis↗
PubMed1994

Distal splenorenal shunt for non-cirrhotic variceal bleeding in black South Africans.

Distal splenorenal shunt (DSRS) is a once-only form of treatment. It is suitable for many black South Africans with non-cirrhotic variceal bleeding who cannot attend repeated follow-up sclerotherapy sessions. However, persistent hyperbilirubinaemia and encephalopathy may occur following DSRS in schistosomiasis. Forty-one consecutive patients with DSRS have been treated over a 7-year period. The causes of portal hypertension were schistosomiasis (32), portal vein thrombosis (8) and diffuse nodular hyperplasia (1). Operative mortality was 6%. Encephalopathy was observed in 1 patient. Galactose elimination capacity (GEC) and technetium-diethylenetriamine penta-acetic acid hepatic perfusion index (HPI) were used to assess liver function and hepatic perfusion pre- and postoperatively, respectively, in schistosomiasis. GEC was 348 +/- 37 (M +/- SD) before, compared with 343 +/- 67 postoperatively (P = 0.78). HPI showed long-term preservation of hepatopetal portal venous flow following DSRS. Morbidity and mortality were observed only in patients with schistosomiasis associated with hepatitis B chronic active hepatitis. DSRS is ideal treatment in selected patients with non-cirrhotic variceal bleeding.

Adult↗