Biomedical subjects
C D George
Publications and source records attributed to C D George.
Subcutaneous sarcoidosis mimicking carcinoma of the breast.
A 65 year old woman presented with bilateral breast lumps. Clinical examination suggested a diagnosis of mammary carcinoma, but a histological diagnosis of sarcoidosis was made. Subsequent investigations revealed evidence of pulmonary sarcoidosis.
An experimental assessment of the effect of blood transfusion on susceptibility to bacterial infection.
Clinical investigations in patients who have undergone transplantation and patients with cancer and infection suggest that blood transfusions have an immunosuppressive effect. To investigate the impact on responses to infection, an experimental transfusion model was developed in the rat with allogeneic or syngeneic transfusions. Animals were given either a moderate or severe bacterial challenge, both simulating a clinical surgical infection, immediately after transfusion or 1 week later; hypotension and hemodilution were especially avoided. Blood transfusion adversely affected the animals' capacity to resist immediate moderate challenge, but not a later one. The effect was maximized by allogeneic transfusion but was not demonstrable after severe bacterial challenge, whether immediate or late.
Comparison of antibody response with delayed hypersensitivity in severely injured patients.
Twenty-seven severely injured patients had antibody response to gram-negative organisms measured of whom 25 also had skin testing. Twenty-three patients (92%) were anergic at admission. Injury Severity Scores were greater in patients who remained anergic for three weeks compared with patients whose skin tests became positive. Patients with major infection had longer anergy duration than uninfected patients. Twenty-two (81%) of 27 anergic patients mounted antibody responses. Initial bacterial contamination determined the clinical outcome and antibody response. Six of eight patients with moderate contamination mounted IgM responses to all organisms and/or an IgG response to Escherichia coli, and they remained uninfected. Of the other two patients, one died, and the other developed chronic infection. Seven of eight patients with heavy contamination developed major sepsis despite mounting several antibody responses. Six patients without contamination mounted no antibody responses and remained uninfected.
The use of a new assay for detecting antibody to Staphylococcus aureus in severely injured patients.
Investigation of the antibody response to Staphylococcus aureus infection has been hindered by lack of a simple and specific assay. We report an enzyme-linked immunosorbent assay (ELISA) using a strain of S. aureus devoid of Protein A, a frequent cause of false positive results in ELISAs, and have used this assay to study antibody responses of 23 severely injured patients. This IgM ELISA had a diagnostic sensitivity for major Staphylococcal infection of 70% (seven of ten patients with major infection) and a specificity of 92% (12 of 13 patients without major infection). Of three patients with major Staphylococcal infections who mounted no IgM response, two died and the other developed severe chronic Staphylococcal infection, and hence prompt initiation of appropriate therapy was necessary. Furthermore, the ability to mount IgM response to Staphylococcal infections appears to contribute to an orchestrated host defense response against this organism.
An outcome predictive score for sepsis and death following injury.
Injury is an important cause of both morbidity and mortality, particularly in the young. Scoring systems have been developed to establish guidelines of transfer and compare patient outcome, but no scoring system as yet has been constructed that focuses upon immune capability of these patients. We report an outcome predictive score (OPS) which appears to distinguish good outcome from sepsis in patients who survive, and between patients with sepsis who survive from patients with sepsis who die. The score is based on (1) Injury severity score (ISS) expressed as percentage of the 50 per cent lethal dose of injury for age (%LD50), (2) Degree of bacterial contamination at initial injury, (3) The patient's monocyte DR antigen expression. Fifty-one severely injured patients were divided into three groups: (1) A group without infection (N = 15), (2) A major sepsis group which survived (N = 24), (3) A group who died (N = 12). There was no difference between the ISS of these groups. The mean OPS of the good outcome group was significantly less than the mean OPS of both the septic (P less than 0.0002) and dead (P less than 0.00001) groups. The mean OPS of the septic group was also significantly less than the mean of the group that died (P less than 0.002). Identification of high risk patients may be important to determine priority of patient care and to institute additional therapeutic measures.
The capacity of serum to support neutrophil phagocytosis is a vital host defense mechanism in severely injured patients.
The opsonic capacity of patient serum was studied in 43 trauma patients of whom 13 recovered uneventfully, 21 developed major infection, and nine died, mostly of infection. Blood samples were taken within 24 hours of injury. Fifteen patients were studied serially of whom 14 developed severe infection and/or died. Opsonic capacity was determined by flow cytometry and measured as the ability of normal neutrophils to phagocytose killed bacteria previously incubated with patient serum. The most dilute sera reflected changes for better and worse most clearly. On initial assessment, those who died of sepsis showed a 61% mean fluorescent intensity (MFI), which was significantly lower than the 99% MFI for those who survived infection (p less than 0.01) and the 78% MFI of those who developed no infection (p less than 0.05). Serial samples demonstrated a super serum response in four of seven patients surviving major sepsis but in none of the seven who died of infection.
The response of immunoglobulins to infection after thermal and nonthermal injury.
Traumatic and thermal injuries are leading causes of mortality and morbidity due to their high incidence of infection. Host defense is vital to recovery in these patients yet incompletely understood. On days 1, 7, and 14, serum immunoglobulins of the IgA, IgG, and IgM classes were measured in 46 consecutive patients who sustained severe trauma with an injury severity score of at least 20. The patients were divided into four groups: 1) an uneventful recovery group (n = 11) of nonthermal trauma patients who did not become infected; 2) an infected nonthermal group without splenectomy; 3) an infected group of burn patients; and 4) 12 patients who underwent splenectomy of which nine became infected following nonthermal trauma. In each patient group, IgA, IgG, and IgM were all reduced, and group 1 had a steady return to normal range. Group 2 patients exhibited supranormal responses in all 3 classes at one week and supranormal IgA and IgG responses at two weeks. In contrast, both infected burn and splenectomized patients had markedly reduced IgG and IgM levels compared with the group 2 patients (P less than 0.05). Splenectomy sharply reduced IgM response to infection at 7 and 14 days compared with nonsplenectomized infected posttraumatic patients. Immunoglobulin response after trauma depended on the type of injury, presence of infection, splenic function, and type of immunoglobulin. Recognition of immunoglobulin deficiencies in both the burn and splenectomized patient may permit focused therapy, such as specific replacement of these proteins.
A randomized, double-blind trial of single dose piperacillin versus multidose cefoxitin in alimentary tract operations.
For elective alimentary tract operations in which contamination is moderate, single dose prophylaxis with piperacillin is equivalent to triple dose cefoxitin, a well established and effective regimen. Both methods failed to control infection arising in the perineal wound after abdominoperineal resection. Just as is the case with drain site infection, such infection often evolves from postoperative contamination and, indeed, is in theory and in fact unlikely to be controlled by perioperative prophylaxis. This study is among the first of several examining the issue of single dose prophylaxis and will be the harbinger of other studies from other groups examining whether or not the course of therapeutic antibiotics can be safely shortened in patients with peritoneal contamination.
Immunologic effects of blood transfusion upon renal transplantation, tumor operations, and bacterial infections.
Blood transfusions appear to exert a suppressive effect on many aspects of the immune system. In transplantation, this has been used to advantage; in other areas, the consequences can be deleterious. It is likely that various components of the immune system are affected by different mechanisms and possibly by different components of transfused blood. Before rational strategies can be evolved for minimizing the deleterious effects of blood transfusions, it is essential that these mechanisms be clearly defined. Studies must take into account any influence the underlying disease state might have on the immune system. In the absence of any satisfactory substitute, blood transfusion remains an essential therapeutic modality in the management of surgical patients. With current evidence, however, it seems reasonable to avoid the administration of small-volume transfusions whenever possible and encourage the use of autodonated blood for elective surgery.
A systematic study of host defense processes in badly injured patients.
A prospective study of factors predisposing to infection in badly injured patients has disclosed: the dominant roles of two specific parameters: monocyte antigen presenting capacity, and opsonic capacity of diluted serum; the potential value of further assessment of: the predictive value of plots of activated T-cells/total T-cells versus monocyte antigen presenting capacity, the apparent protective effect of the ability to sharply increase specific IgM in response to infection, and the apparent protective effect of cytomegalovirus (CMV) infection in the first 28 days after injury against major bacterial infection; the lack of value of analysis of other T- and B-cell subsets in such patients; and the need to clarify CMV and transfusion status with respect to interpretation of such data. The specific role of variable transfusion and of specific serum immunoglobulins will require further and more discriminating study.
The results of incisional hernia repair: a twelve year review.
A series of 81 incisional hernia repairs is presented. Two main types of repair were performed, the 'keel' repair and a mass closure repair. In both repairs monofilament nylon was used. The recurrence rate was 46% (37 patients), the major predisposing factor being postoperative wound infection or haematoma formation. Subsequent repairs were no more successful. These poor results are compared with other published series.
Excision of pharyngoesophageal diverticula using a surgical stapling device.
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Incisional hernias: when do they occur?
Incisional herniation remains a major problem for the general surgeon. Most published studies have followed up patients for 6-12 months after operation. In this study, 363 patients, known not to have an incisional hernia at 1 year, were reviewed between 2.5 and 5.5 years after operation. Twenty-one patients (5.8 per cent) were found to have developed incisional hernias. None of the causal factors previously implicated in the aetiology of incisional herniation (wound infection, male sex, obesity, age, postoperative chest infection or abdominal distension), was found to be associated with the development of these 'late hernias'.
Effect of cachexia on lipid saturation of erythrocyte membranes.
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