PubMed Health⌕ Search

Biomedical subjects

A J Botha

Publications and source records attributed to A J Botha.

8 recordsLinked to original sources
PubMed1995

Postinjury neutrophil priming and activation: an early vulnerable window.

BACKGROUND: Generation of extracellular, cytotoxic superoxide anion (O2-) by polymorphonuclear neutrophils (PMNs) contributes to an unbridled inflammatory response that can precipitate multiple organ failure (MOF). Release of O2- is markedly enhanced when activated PMNs have been previously "primed" by inflammatory mediators, such as those expressed after trauma. We therefore hypothesized that PMN priming occurs as an integral part of the early inflammatory response to trauma. METHODS: PMNs were obtained from 17 high-risk patients with torso trauma at 3, 6, 12, 24, 48, and 72 hours after injury, as well as from 10 healthy donors, and the in vitro release of O2- was quantitated with a kinetic, superoxide dismutase (SOD)-inhibitable cytochrome c reduction assay. PMN O2- release was measured in the presence and absence of 1 mumol/L N-formyl-methionyl-leucyl-phenylalanine (fMLP) and after priming and activation with 20 nmol/L platelet-activating factor (PAF) and 1 mumol/L fMLP, respectively. RESULTS: In vitro PMN O2- release was used to determine whether postinjury PMNs were (1) activated in vivo, (2) primed in vivo, or (3) primable in vitro. Unstimulated PMNs from trauma patients spontaneously expressed modest amounts of O2- in vitro from 6 to 48 hours after injury, suggesting endogenous activation. Also, fMLP-activated PMNs collected between 3 and 24 hours after injury expressed more O2- than controls (p < or = 0.02), indicating in vivo, trauma-related priming. Furthermore, postinjury PMNs were maximally primed in vivo (i.e., in vitro exposure to PAF before fMLP activation failed to significantly enhance O2- release) as compared to PMNs treated with fMLP. CONCLUSIONS: These data indicate that major torso trauma (first hit) primes and activates PMNs within 3 to 6 hours after injury. Consequently, we postulate that postinjury priming of PMNs may create an early vulnerable window during which a second hit (e.g., a secondary operation or delayed hemorrhage) activates exuberant PMN O2- release, rendering the injured patient at high risk for MOF.

Adolescent↗
PubMed1995

Early neutrophil sequestration after injury: a pathogenic mechanism for multiple organ failure.

Polymorphonuclear neutrophils (PMNs) play a pivotal role in the inflammation that precedes multiple organ failure (MOF). In a rat model of MOF, PMNs become primed for enhanced superoxide anion (O2-) release and CD11b expression, sequester in end organs, and produce organ failure. Therefore, we hypothesized that circulating PMNs harvested in the first 24 hours after injury from trauma patients at risk for MOF would (1) exhibit a primed O2- release, (2) upregulate CD11b expression, and (3) show evidence of sequestration in tissues. Extracellular PMN O2- release and CD11b receptor expression were measured at 3, 6, 12, and 24 hours after injury in 33 torso trauma patients with Injury Severity Scores > 15; eight patients (24%) developed MOF. Healthy adults served as controls. PMNs after injury were primed for enhanced in vitro O2- release at 3, 6, 12, and 24 hours after injury, indicating prior in vivo priming. CD11b expression was also increased at 6, 12, and 24 hours after injury. Circulating PMN numbers increased sharply at 3 hours after injury, before decreasing dramatically at 6 and 12 hours, suggesting end organ sequestration. At 12 hours after injury, declines in circulating PMNs were significantly greater in MOF than in non-MOF patients (p < 0.05). These data indicate that PMNs are quickly mobilized into the circulation after injury and then primed for enhanced O2- release and CD11b expression. PMN priming appears to be a necessary preamble to PMN sequestration in patients with major torso trauma. Upregulation of PMN function, accompanied by subsequent end organ sequestration, may represent an important early event in the pathogenesis of MOF after injury.

Adult↗
PubMed1995

Postinjury neutrophil priming and activation states: therapeutic challenges.

Both hyperactivity and hypoactivity of neutrophils (PMNs) have been implicated in the pathogenesis of postinjury multiple organ failure. In this paper, the cellular and molecular mechanisms involved in the regulation of PMN O2- production are reviewed. In addition, relevant research laboratory techniques for measuring both intracellular and extracellular O2- release are outlined. In a pilot study PMN O2- release in response to a battery of PMN agonists was determined, and four functional states of the NADPH were defined: resting, primed, activated, and unresponsive. PMNs from normal adult volunteers are in the resting state. In contrast, PMNs from patients with severe torso trauma are primed and activated in the first 24 h postinjury, but, after 48 h, become unresponsive to both receptor-dependent (platelet activating factor and N-formyl-methyl-leucyl-phenylalanine) and receptor-independent (phorbol 12-myristate 13-acetate) activation. The ability to identify at-risk patients and provide a rationale for ameliorating PMN-mediated tissue injury in patients with hyperinflammation syndromes are discussed. In addition, the importance of identifying patients with PMNs that are unresponsive, and the necessity for increasing PMN function in these patients in order to reduce the risk of sepsis, are also discussed.

Humans↗
PubMed1995

Laparoscopic appendicectomy: a trainee's perspective.

Minimally invasive surgery is rapidly becoming an integral part of general surgery. Many general surgeons have been trained to undertake laparoscopic cholecystectomy. It has been recommended that laparoscopic appendicectomy should be the training operation for junior surgeons. The aim of our study was to assess whether laparoscopic appendicectomy training can safely be introduced to junior surgeons in a district general hospital. During the 11 month study period, 27 laparoscopic and 38 open appendicectomies were performed. The median anaesthetic time was 80 min for laparoscopic and 52.5 min for open appendicectomies. Laparoscopic appendicectomies cost, on average, 618 pounds and open appendicectomies 770 pounds per case. The complication rate between the two procedures was equal. We therefore showed that laparoscopic appendicectomy by junior surgeons is both safe and cost-effective. Although the registrar did most of the laparoscopic appendicectomies, with resultant less operating for the SHO, laparoscopic appendicectomy provided the SHO with training in diagnostic laparoscopy and laparoscopic dissection. We conclude that basic laparoscopic training should be introduced early in surgical training, after which laparoscopic appendicectomy is a safe procedure for surgical trainees.

Adolescent↗
PubMed1992

The Royal London Hospital Helicopter Emergency Medical Service: first phase 1990.

A Helicopter Emergency Medical Service (HEMS) has been introduced to improve trauma care in the Southeast of England. The majority of the workload comes from the area bounded by the M25 ring road. In 1989 a Dauphin 365N helicopter equipped for pre-hospital primary rescue and emergency inter-hospital secondary transfer was certified by the Civil Aviation Authority. The helicopter commenced carrying patients with a paramedic and a doctor on board early in 1990. In September 1990 this service was further improved by the opening of a helipad at the Royal London Hospital and a designated HEMS desk at London Ambulance Service central control. Eighty-four patients were transported in primary rescue missions and 107 as emergency transfers in 1990.

Aircraft↗
PubMed1991

Endometriosis in gluteus muscle with surgical implantation. A case report.

Intrapelvic endometriosis is a fairly common condition affecting women during their reproductive years. Extrapelvic disease is, however, very rare. We report a case where an endometrioma was found in the body of the gluteus minimus muscle, and endometrial tissue was implanted in the wound at the time of excision.

Adult↗