Biomedical subjects
M J Girotti
Publications and source records attributed to M J Girotti.
Induced immunoglobulin secretion by T-cell-replacing products from blunt trauma patients.
The capacity to induce immunoglobulin (Ig) secretion by soluble T-cell-replacing (TCR) factors derived from alloantigen-stimulated T lymphocytes of blunt trauma patients (n = 15, mean ISS = 24) was examined in Staphylococcus aureus (SAC)-activated normal B-cell cultures. The majority of the patients studied demonstrated a profound suppression of the T-cell-dependent, pokeweed-mitogen-induced Ig production. However, the activity to induce Ig secretion associated with TCRs from the same patients was not reduced compared with that of TCRs from normal subjects. IgM synthesis was normal and IgG secretion induced by TCRs was within the control range (in 6 of 15 patients) or significantly higher (p less than 0.05) than that in the remaining patients. Both patient-derived and control TCRs failed to induce Ig synthesis in cultures of resting B cells and had comparable mitogenic effects on normal SAC-activated and phytohemagglutinin A-activated B and T lymphocytes, respectively. Thus, the intrinsic ability of T lymphocytes to produce B-cell helper factors appears to be unaffected following blunt trauma. Suppression of the T-cell-regulated Ig secretion in traumatized patients may therefore reflect an altered B lymphocyte response to such factors.
History of laparoscopic surgery.
Since the beginning of the 20th century physicians have promoted laparoscopy as a valuable adjunct to the diagnosis of diseases of the abdominal cavity. Laparoscopy, however, failed to become popular among abdominal surgeons until the advent of laparoscopic cholecystectomy. This single new operative approach to the treatment of gallbladder stones gave rise to such enthusiasm among general surgeons that other innovative laparoscopic procedures are now being promoted in ever-increasing numbers. The general surgeon has again become the leader in the introduction of a new surgical approach. This new technique must be developed with great care, and there must be rigorous criteria for its use, critical analysis of the technique and honest reporting of results.
Laparoscopic surgery--basic armamentarium.
The introduction of laparoscopic techniques into standard intracavitary surgery has received widespread acceptance in North American surgical practice in a very short time. To complete these procedures successfully a basic armamentarium is required by surgeons. The equipment should provide safe conduct of the procedure and maximum flexibility in the types of surgical procedures to be undertaken. The basic laparoscopic equipment needed to facilitate minimal-access-site surgery is reviewed, from the operating table and lighting in the operating room through optics, cameras and television monitors to the instruments and agents needed for the surgical techniques and for securing hemostasis.
Laparoscopic cholecystectomy: strategy and concerns.
After briefly describing the first laparoscopic cholecystectomy performed by Philippe Mouret, the authors review some of the differences in strategy, management and concerns between conventional and laparoscopic cholecystectomy. They address the problems relating to the required skills of triangulation and camera handling, the presence of common-duct stones and concomitant disease, the issues of drainage, hemostasis, access in difficult cases, iatrogenic trauma to the bile ducts and pertinent differences in cardiorespiratory function.
Laparoscopic cholecystectomy: trans-Canada experience with 2201 cases.
The authors carried out a prospective review of the initial and consecutive experience with laparoscopic cholecystectomy of 58 surgeons from 31 teaching and nonteaching institutions throughout Canada. The perioperative morbidity of 2201 cases is described, with special attention to iatrogenic complications. The data suggest that complications, including bile-duct injury, are not frequent. Pneumonia and wound infection rates appear lower than after open surgery. There were no deaths. Laparoscopic cholecystectomy is replacing open cholecystectomy for the management of symptomatic cholelithiasis.
Bacterial translocation induces procoagulant activity in tissue macrophages. A potential mechanism for end-organ dysfunction.
The ability of bacterial translocation to induce cell-associated procoagulant activity was examined in a rodent model. Intestinal decontamination with streptomycin sulfate and bacitracin followed by oral feeding with a streptomycin-resistant strain of Escherichia coli produced monoassociation of the gastrointestinal tract with this microorganism. Using this model, the rate of bacterial translocation at day 3 increased from 6% (1 of 17) to 90% (28 of 31). Cell-associated procoagulant activity was measured in the mononuclear cell population of mesenteric lymph nodes as well as portal and systemic blood and also in hepatic nonparenchymal cells. In monoassociated animals, the procoagulant activity of mesenteric lymph node mononuclear cells was significantly greater than in control animals at day 3 (210% +/- 28% vs 100% +/- 6%) but not at days 1 or 6. Procoagulant activity of hepatic nonparenchymal cells was elevated in monoassociated animals at days 3 and 6 compared with control animals. Both control and monoassociated animals remained well throughout the experiment. The histologic features of the gastrointestinal tract, mesenteric nodes, and liver did not differ between groups. These studies provide evidence that bacterial translocation, in the absence of external stimuli, is able to induce cell activation at sites remote from the gastrointestinal tract and may therefore contribute to the pathogenesis of multiple organ failure.
Early measurement of systemic lipid peroxidation products in the plasma of major blunt trauma patients.
We sought evidence of oxidant-induced biological membrane damage in 43 resuscitated blunt trauma patients (average ISS, 36.9) within 2-6 hours of injury and before anaesthesia and surgery. The plasma levels of the lipid peroxidation products (conjugated dienes, CDs A 233 nm) and malondialdehyde (MDA, nMol/ml) and the oxidant-inducing effect of the trauma plasma on normal FMLP-stimulated neutrophils were compared to those of control subjects. No differences were observed in the plasma levels of MDA (1.73 +/- 2.15 vs. 1.45 +/- 0.70 nMol/ml) and CDs (2.07 +/- 2.16 vs. 1.28 +/- 0.60 A 233nm), or on stimulated neutrophil superoxide production (26.4 +/- 6.9 vs. 29.0 +/- 6.2 nMol O2-/2 x 10(6) PMNs). These observations persisted when the patients were analyzed based on injury severity, the presence of long bone fractures, and the class of shock at presentation. We conclude that there is no evidence of oxidant-induced membrane damage manifested by increased plasma levels of CDs or MDA within 2 to 6 hours of blunt injury.
Is outcome worse in a small volume Canadian trauma centre?
The minimum number of seriously injured patients required to maintain clinical competence and achieve acceptable clinical competence in a single trauma centre is unknown. It has been suggested that the probability of survival is improved in hospitals treating greater than 200 trauma patients annually. We sought to determine if probability of survival was lower in our small volume centre. Between 1986 and 1989, 752 (522 male, 230 female; average age, 36 years) trauma patients were admitted to our institution. The major mechanism of injury was blunt (89%). All patients underwent trauma severity scoring. Trauma Score, Injury Severity Score, and a Revised Trauma Score were used to derived the probability of survival by the TRISS method. The mean Injury Severity Score was 23.3 and the mean Trauma Score was 13.2. The overall mortality rate was 15.8%. The Z statistic demonstrated no significant difference between actual and predicted deaths for the 4-year period or for any individual year (range, -1.05 to 1.26, p greater than 0.05). The M statistic was 0.753. We conclude that, despite fewer trauma patient admissions (less than 200 per year), comparable clinical results can be achieved by surgeons dedicated to trauma management.
Effect of systemic fibrinogen depletion on intraabdominal abscess formation.
Deposition of fibrin within the peritoneal cavity is an integral host response to local infection. To directly assess the role of fibrin deposition in the pathogenesis of intraabdominal abscess formation, the ability to induce abscesses in fibrinogen-depleted mice was examined. We hypothesized that systemic defibrinogenation with ancrod would limit the availability of fibrinogen for deposition within the peritoneal cavity and would therefore impair intraabdominal abscess formation. A gelatin capsule containing 50% sterile feces plus Bacteroides fragilis 1 x 10(9) CFU was inserted IP into control or defibrinogenated mice. System defibrinogenation resulted in alteration of the character of abscess formation, as manifested by reduced abscess size and degree of purulence. Abscesses were significantly smaller (0.18 +/- 0.02 gm [n = 29] vs. 0.09 +/- 0.02 gm [n = 11], p less than 0.01) and less purulent (p less than 0.001) in the ancrod-treated mice than in control animals, despite equal numbers of bacteria in the abscesses recovered from both groups. The effect of ancrod was specific for defibrinogenation, because IP repletion with fibrinogen reversed the ancrod effect on abscess size. In addition to its local effects, systemic fibrinogen depletion resulted in a significant elevation in mortality following IP infection (1 of 30 control animals vs. 10 of 23 ancrod-treated animals, p less than 0.01). However, this was not due to an increase in the magnitude of the B. fragilis bacteremia. These studies demonstrate that fibrin deposition contributes to the pathogenesis of purulent abscess formation and that systemic depletion of fibrinogen may alter host susceptibility to the consequences of infection.
Making hockey safer.
Explore the source record for details and available documents.
Impaired antibody production in blunt trauma. Possible role for T cell dysfunction.
This study investigates mechanisms of impaired humoral immune response in a well-defined population of blunt trauma patients (n = 18, Injury Severity Score greater than or equal to 20). Spontaneous and pokeweed mitogen-induced polyclonal immunoglobulin production were assessed in cultures of peripheral blood mononuclear cells. The proliferative response to alloantigen and mitogen was assessed in parallel by the mixed lymphocyte reaction and pokeweed mitogen-induced blastogenesis, respectively. Pokeweed mitogen-induced IgG and IgM production was significantly reduced in trauma patients compared with controls. This effect was not reversed by depletion of adherent cells or by the addition of indomethacin. Exogenous interleukin 2 was also ineffective. However, the addition of normal T cells or supernatants from isoantigen-stimulated cultures of these cells to patient B cell-enriched cultures significantly enhanced (by 1.4- to 5.1-fold) the antibody response to pokeweed mitogen. Thus, suppression of humoral antibody response in blunt trauma patients may be due to failure of T-cell mediated help, resulting in insufficient secretion or activity of cytokines required for adequate B cell activation, proliferation, or differentiation into immunoglobulin-secreting cells.
Expression and secretion of IL-2 receptor in trauma patients.
The high-affinity cell-surface receptor for interleukin-2 (IL-2R) consists of the 75-kilodalton (kd) chain and a 55-kd glycoprotein known as Tac. This report examines the cellular expression of IL-2R and secretion of the soluble form of Tac in immunosuppressed blunt trauma (n = 20, injury severity score -20) and thermally injured (n = 20, Total body surface area greater than 35%) patients. The percentage of IL-2R-expressing peripheral blood mononuclear cells (PBMC) in mitogen-stimulated cultures from patients and age-matched normal donors was determined by direct immunofluorescence with a monoclonal anti-Tac followed by flow cytometry analysis. Levels of soluble Tac in patient sera were measured by a monoclonal antibody-based enzyme-linked immunosorbent assay. Expression of Tac antigen by mitogen-activated PBMC cultures from blunt trauma patients was transiently reduced (by as much as 40%) in 4 of 14 patients examined. Levels of serum Tac were significantly elevated (p less than 0.05) in 15 of 20 blunt trauma patients ranging from 750 to 3000 U/mL compared with 180 to 420 U/mL in control subjects. All burn patients studied 10 to 50 days after the injury demonstrated a significant reduction (by 50% to more than 90%) in the percentage of IL-2 receptor-bearing cells. Similarly serum levels of IL-2R increased significantly (p less than 0.001 to 0.05) in all burn patients studied, reaching concentrations as high as 5500 U/mL. These results suggest that major trauma, whether mechanical or thermal, induces alterations in the T-lymphocyte activation process. However the degree and duration of such changes may vary based on the nature of the injury.
Antibiotic handbook and pre-printed perioperative order forms for surgical antibiotic prophylaxis: do they work?
The authors attempted to compare the value of two strategies--an educational (antibiotic handbook) and a control (perioperative pre-printed physician order form, which contained antibiotic orders)--in modifying physicians' patterns of antibiotic prophylaxis for preventing infection in patients who undergo elective surgery. They reviewed the charts of 240 such patients on five different surgical services in one teaching hospital. Use of the antibiotic handbook (educational strategy) increased overall compliance with the recommended regimens from 11% to 18% (p = 0.06). The control strategy (perioperative pre-printed physician order form) increased compliance from 17% to 78% (p less than 0.01).
Small intestinal villous adenoma and celiac disease.
We describe the first patient with presumed celiac disease to present with a jejunal villous adenoma. Small bowel adenocarcinoma complicating celiac disease probably arises from adenoma, although this has not been previously addressed. The literature concerning factors in celiac disease predisposing to small intestinal epithelial neoplasia is reviewed.
Aggregation by fragilis and non-fragilis Bacteroides strains in vitro.
Bacteroides fragilis is associated with the formation of intra-abdominal abscesses, whereas other Bacteroides species are rarely involved. Since bacterial clumping may contribute to the survival of bacteria in the face of host defence mechanisms, the hypothesis has been put forward that differences in aggregation between fragilis and non-fragilis strains of Bacteroides may account for their differences in survival in vivo. All seven B. fragilis strains tested formed aggregates within 4 h, but strains not associated with intra-abdominal sepsis--B. vulgatus, B. thetaiotaomicron and B. distasonis--did not form aggregates in vitro. Aggregation occurred at 37 degrees C, but not at 4 degrees C or 20 degrees C. Treatment with pronase partially inhibited aggregation. Periodate treatment killed the cells and caused them to form clumps which were distinguishable from the control aggregates. Heat-killed B. fragilis cells formed similar distinct clumps, but cells killed by glutaraldehyde and formaldehyde did so to a lesser degree. No inhibition was found upon addition of carbohydrates, ethylenediaminetetraacetic acid or after treatment with trypsin. These results demonstrate that aggregate formation occurs with B. fragilis strains alone, and that surface proteins probably mediate this interaction.
Physician-accompanied transport of surgical intensive care patients.
During a one-year period, 107 critically ill adult patients were transferred by a physician-accompanied transport system (PATS). Most patients required both tracheal intubation (82 per cent) and mechanical ventilation (71 per cent), while continuous vasopressor support was required in 27 per cent of transfers. Patients were classified as either potential organ donors (n = 21) or nondonor patients (n = 86). Nondonor patients had a mean time of patient transfer documented from the initial telephone contact to final arrival of the patient in the ICU of 345 +/- 221 min (range 65-1350 min); the mean time the patients were out-of-hospital was 73 +/- 58 min (range 5-330 min); the average distance travelled by the patient and PATS was 342 +/- 692 km (range 1-4000 km). Ultimate nonsurvivors of ICU admission (36 per cent) had shorter out-of-hospital times, shorter travel distances, and increased interventional support, as assessed by the Therapeutic Intervention Scoring System applied over the telephone and prior to departure at the referring hospital. Significant interventions were undertaken by PATS in 23 per cent of the nondonor patients prior to departure. During the transport process, there was at least a seven per cent morbidity (arrhythmia, hypotension, and vehicular difficulties) and a 0.9 mortality rate. We conclude that PATS offered significant advantages to this patient population through its ability to maintain acceptable morbidity and mortality rates while transferring patients over long distances and for prolonged periods of time.
Major disasters will not go away!
Explore the source record for details and available documents.