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Biomedical subjects

M Bessler

Publications and source records attributed to M Bessler.

At least 55 records · Page 3Linked to original sources
PubMed1997

Postoperative immune function varies inversely with the degree of surgical trauma in a murine model.

BACKGROUND: Major surgery through a laparotomy incision is associated with a postoperative reduction in immune function. Studies in rats involving sham procedures suggest that immune function may be preserved after laparoscopy. This study investigates the effects of incision length and exposure method for bowel resection with respect to postoperative immune function as assessed by delayed-type hypersensitivity (DTH) reactions. METHODS: Male Sprague Dawley rats (n = 175) were challenged preoperatively, immediately postoperatively, and on postoperative day 2 with an intradermal injection of 0.2 mg phytohemagglutinin (PHA), a nonspecific T-cell mitogen. The averages of two measures of perpendicular diameters were used to calculate the area of induration. Anesthesia control rats underwent no procedure. Minilaparotomy rats underwent a 3.5-cm midline incision. Sham full laparotomy rats underwent a 7-cm midline incision. The open bowel-resection group underwent a cecal ligation and resection through a 7-cm midline incision. In the laparoscopic-assisted resection group a CO2 pneumoperitoneum and four-port technique was utilized to deliver the cecum through a 4-mm port where the cecum was extracorporeally ligated and resected. RESULTS: Preoperative responses were similar in all five groups. Incision length: Full laparotomy group responses were 20% smaller than anesthesia control responses on postoperative day (POD)1 through POD4 (p < 0.02). At no time point were the responses in the minilaparotomy group significantly different from either anesthesia control or full laparotomy group responses. Exposure method: The laparoscopic-assisted resection group responses were 20% larger than open group responses at the time of two of the four postoperative measurements (p < 0.05, both comparisons). At all postoperative time points, open resection group responses were significantly smaller than control responses (p < 0.05, all comparisons), whereas at no time point were laparoscopic group responses significantly different from control responses. CONCLUSION: We conclude that postoperative cell-mediated immune function varies inversely with the degree of surgical trauma. Results from the minilaparotomy and laparoscopy groups suggest that procedures done through small incisions may result in preservation of postoperative immune function.

Analysis of Variance↗
PubMed1997

A murine model of laparoscopic-assisted intervention.

BACKGROUND: In order to better investigate the effects of laparoscopic surgery, it is necessary to establish reliable, reproducible, and economical animal models of laparoscopic intervention. Here we describe a mouse model of laparoscopic-assisted colon resection. METHODS: After successful induction of anesthesia the mouse is placed in Trendelenburg position and the peritoneal cavity is insufflated with carbon dioxide gas through an angiocatheter placed in the right upper quadrant. A 4-mm rigid scope with camera attachment is then inserted through a midline port created just caudal to the xiphoid. A second port is then created in the right lower quadrant to allow introduction of laparoscopic forceps into the peritoneal cavity. The cecum, which extends 1.5 cm beyond the ileocecal valve, is grasped with forceps and exteriorized through the operative port. Extracorporeally, the cecum is ligated and resected before the cecal stump is returned to the peritoneal cavity. The abdominal wall defects are then stapled closed. RESULTS: This simple model can be mastered by individuals with very limited surgical experience. This laparoscopic model has been used successfully in our laboratory in a number of experiments with an intraoperative complication rate of 3. 2% (3/94), which was similar to the open surgery group rate of 2.1% (2/95, p = 0.99 by chi square). We observed no postoperative leaks in either group. The only postoperative death occurred in the open resection group due to dehiscence of the laparotomy wound. CONCLUSIONS: We propose that this model may be useful for comparing the effects of open to laparoscopic surgery.

Animals↗
PubMed1997

A prospective comparison of laparoscopic exposure techniques for rectal mobilization and sigmoid resection.

BACKGROUND: We determined the efficacy of a pneumoperitoneum and a gasless abdominal wall lifting device in providing exposure for low rectal mobilization and sigmoid resection in a swine model. The results of these laparoscopic techniques were compared with those obtained using standard open surgical methods. STUDY DESIGN: We conducted a prospective randomized nonblinded trial. Twenty-four adult female pigs were randomized into three groups depending on exposure technique: group 1, open (n = 6); group 2, carbon dioxide (n = 6) or helium (n = 6) pneumoperitoneum; and group 3, a mechanical abdominal wall lifting device (n = 6). A low rectal mobilization and sigmoid resection with a double-stapled, circular, end-to-end anastomosis was performed in all pigs. In group 2, a laparoscopic-assisted approach was used. Parameters assessed included length of operation, length of the colonic specimen, number of lymph nodes per specimen, and extent of anterior and posterior rectal mobilization (centimeters from the anal verge). RESULTS: Operative times were significantly shorter for group 1 than for group 2; no significant differences were found between the two laparoscopic subgroups. No significant difference was found in length of the colonic specimen or in number of lymph nodes harvested for each group. Extent of anterior and posterior rectal mobilization was also not significantly different for the three groups. Although mean mobilization lengths for each group were not significantly different, the range of values was broader in the laparoscopic groups. CONCLUSIONS: A comparable mobilization and bowel resection can be performed laparoscopically, regardless of the exposure technique used. Gasless laparoscopy may prove useful in patients in whom pneumoperitoneum is contraindicated; it will not replace pneumoperitoneum as the only method for obtaining laparoscopic exposure because of the ease of use and frank superiority of the pneumoperitoneum in most circumstances. Abdominal wall lifting devices seem to be a reasonable alternative to pneumoperitoneum for sigmoid resection and rectal mobilization.

Animals↗
PubMed1996

Paroxysmal nocturnal hemoglobinuria: the price for a chance.

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired hemolytic blood disease. The dramatic symptoms that gave the disease its name and the unique nature of the underlying cellular abnormality made the disease for many years a curiosity amongst human blood disorders. Clinical manifestations of PNH are chronic hemolytic anemia with acute exacerbations, bone marrow failure, an increased tendency to thrombosis, and episodes of severe abdominal pain. PNH has a close although not yet fully understood relationship to aplastic anemia (AA), and probably also to acute myeloid leukemia (AML). Blood cells in patients with PNH have a defect in the biosynthesis of a complex glycolipid structure which is a glycosyl phosphatidylinositol (GPI) molecule and serves as an anchor for many surface proteins. Red cells, granulocytes, monocytes, lymphocytes and platelets are therefore deficient in all proteins which are anchored to the cell membrane by such a molecule. Biochemical analysis pinpointed the metabolic block in PNH cells to an early step in the anchor biosynthesis. The block in the biosynthetic pathway is due to the deficiency of a protein called PIG-A. The PIG-A gene maps to the X-chromosome. Cloning of the gene and analysis of the gene in PNH patients lead to the identification of a number of somatic mutations which occur on the active X-chromosome in an early hematopoietic stem cell. All mutations identified thus far inactivate or impair the function of the PIG-A protein and therefore fully explain the deficiency of the missing surface proteins, which in turn explain some of the clinical features of the disease. However, the characterization of the molecular lesion does not explain how the PNH clone can expand to the extent of contributing a substantial proportion of the patient's hematopoiesis. Thus a second factor is needed to explain the pathogenesis of PNH. We hypothesize that this is most likely the coexistence of bone marrow failure that produces paradoxically a growth or survival advantage for the PNH clone. The coexistence of more than one PNH clone in many patients supports this hypothesis and suggests that bone marrow failure is the primary event. The occurrence of the PIG-A mutation causing the absence of GPI-linked proteins on blood cells allows the PNH clone to flourish and to maintain hematopoiesis; thus it seems that the PIG-A mutation is nature's own gene therapy and the price that these patients have to pay is PNH.

Adult↗
PubMed1996

Controlled trial of laparoscopic-assisted vs open colon resection in a porcine model.

BACKGROUND: Several series of laparoscopic colon resection have been reported in the literature with varied results; however, no controlled series of laparoscopic vs open colon resection has been reported. The purpose of this study was to determine the relative safety and adequacy of laparoscopic colon resection in a controlled trial using a porcine model. METHODS: Domestic pigs (n = 23) were randomly divided into two groups. Animals underwent either an open or laparoscopic-assisted segmental resection of the sigmoid colon. The open resections were performed through a 20-cm midline incision and the laparoscopic technique utilized five 12-mm ports. Laparoscopic resection took twice as long to complete as open resection (P < 0.001). Return of gastric function was significantly faster in the laparoscopic group than in the open group (P < 0.032). RESULTS: No significant differences were found in total length of resection, proximal or distal margins, number of lymph nodes recovered, length of mesenteric vessel resected, or time to return of bowel function. At vivisection, more adhesions to the abdominal wall were noted in the open group (P < 0.002). One death occurred in the laparoscopic group 2 h postoperatively (8.3% mortality) while all open group pigs survived. However, there was no statistically significant difference in mortality rates by chi-square analysis (P > 0.5). CONCLUSIONS: Despite longer operative time, laparoscopic intervention is technically feasible, safe, and may offer significant postoperative benefits due to fewer abdominal adhesions.

Anastomosis, Surgical↗
PubMed1996

Better preservation of immune function after laparoscopic-assisted vs. open bowel resection in a murine model.

UNLABELLED: We evaluated cell-mediated immune function after laparoscopic-assisted and open bowel resection in rats by measuring delayed-type hypersensitivity responses to keyhole limpet hemocyanin (KLH) and phytohemagglutinin (PHA). METHODS: Male Sprague-Dawley rats (n = 120) were sensitized to 1 mg of KLH ten days before investigations. Rats were challenged preoperatively, immediately postoperatively, and on postoperative day (POD) 2 with an intradermal injection of 0.3 mg of KLH and 0.2 mg of PHA (at different sites). Averages of two measures of perpendicular diameters (taken 24 and 48 hours postchallenge) were used to calculate the area of induration using the formula for the area of an ellipse, A = (D1/2 x D2/2) x pi. Anesthesia control animals underwent no procedure (n = 40). Open resection group underwent ligation and resection of the cecum (length = 2 cm) through a 7 cm midline incision (n = 40). In the laparoscopic-assisted resection group, under CO2 pneumoperitoneum (4-6 mmHg), the cecum was identified, dissected free, and exteriorized through a 4 mm port. The cecum was then ligated and resected extracorporeally (n = 40). RESULTS: Preoperative responses to both KLH and PHA were the same in all three groups. Furthermore, within each group, postoperative responses were similar. When groups were compared, the anesthesia group responses were significantly greater than the open resection group responses at all time points (P < 0.05 for all comparisons). Laparoscopic assisted resection group responses differed from control at only two of eight postoperative measures. Laparoscopic resection group responses were significantly greater than open resection group responses to challenge with both KLH and PHA on POD1 (P < 0.02, for both comparisons) and POD 4 (P < 0.05, for both comparisons). CONCLUSIONS: Postoperative cell-mediated immune function is better preserved after laparoscopic-assisted bowel resection than after open resection as assessed by skin antigen testing.

Animals↗
PubMed1996

The dual pathogenesis of paroxysmal nocturnal hemoglobinuria.

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired blood disease with distinct and rather peculiar characteristics that have puzzled hematologists for more than a century. PNH cells are deficient in a set of membrane proteins that have in common a glycolipid anchor. We refer to this combination of deficiencies as the PNH abnormality or the PNH phenotype. Biochemical analysis has recently made it possible to pinpoint the metabolic block in PNH cells to an early step in the biosynthesis of the glycolipid anchor. This block is due in turn to the deficiency of a protein, called PIG-A, which is encoded by an X-linked gene. Expression cloning of the PIG-A gene has been followed by the identification in patients with PNH of somatic mutations in this gene that inactivate or impair the function of the PIG-A protein. These findings explain in full the molecular basis of the PNH abnormality, but they do not explain how the PNH clone, which is biochemically defective, can expand to the extent of contributing a substantial proportion of the patient's hematopoiesis. Thus a second factor is required to explain the pathogenesis of PNH. This is most likely the coexistence of an element of bone marrow failure that produces, paradoxically, a survival or growth advantage for the PNH clone. The notion that the injury causing failure of normal stem cells spares selectively cells with the PNH phenotype is supported by a number of observations, including the finding of multiple independently arisen PNH clones in patients with PNH.

Bone Marrow↗
PubMed1995

Mutations in the PIG-A gene causing paroxysmal nocturnal hemoglobinuria are mainly of the frameshift type.

Paroxysmal nocturnal hemoglobinuria is an acquired hemolytic anemia associated with somatic mutations in the X-linked gene PIG-A, which encodes a protein involved in the biosynthesis of glycosyl phosphatidylinositol anchors. To further elucidate the molecular basis of paroxysmal nocturnal hemoglobinuria, we have worked out a systematic and relatively rapid methodology to scan for mutations in the entire coding region of the PIG-A gene. By this methodology, we have identified 15 different somatic mutations in 12 patients. The mutations were spread throughout the entire PIG-A-coding region. Of the mutations, 10 caused frameshifts, 6 caused small deletions, 3 caused small insertions, and 1 caused deletion-insertion. Five single base pair substitutions caused three missense mutations, one nonsense mutation, and one defect in the donor splice site of intron 4. In each of 3 patients, two independent mutations were identified. The predominance of frameshift mutations may reflect selection for somatic mutations giving rise to clones with a completely nonfunctional PIG-A protein.

Amino Acid Sequence↗
PubMed1995

Natural history of paroxysmal nocturnal hemoglobinuria.

BACKGROUND: Paroxysmal nocturnal hemoglobinuria (PNH), which is characterized by intravascular hemolysis and venous thrombosis, is an acquired clonal disorder associated with a somatic mutation in a totipotent hematopoietic stem cell. An understanding of the natural history of PNH is essential to improve therapy. METHODS: We have followed a group of 80 consecutive patients with PNH who were referred to Hammersmith Hospital, London, between 1940 and 1970. They were treated with supportive measures, such as oral anticoagulant therapy after established thromboses, and transfusions. RESULTS: The median age of the patients at the time of diagnosis was 42 years (range, 16 to 75), and the median survival after diagnosis was 10 years, with 22 patients (28 percent) surviving for 25 years. Sixty patients have died; 28 of the 48 patients for whom the cause of death is known died from either venous thrombosis or hemorrhage. Thirty-one patients (39 percent) had one or more episodes of venous thrombosis during their illness. Of the 35 patients who survived for 10 years or more, 12 had a spontaneous clinical recovery. No PNH-affected cells were found among the erythrocytes or neutrophils of the patients in prolonged remission, but a few PNH-affected lymphocytes were detectable in three of the four patients tested. Leukemia did not develop in any of the patients. CONCLUSIONS: PNH is a chronic disorder that curtails life. A spontaneous long-term remission can occur, which must be taken into account when considering potentially dangerous treatments, such as bone marrow transplantation. Platelet transfusions should be given, as appropriate, and long-term anticoagulation therapy should be considered for all patients.

Adolescent↗
PubMed1995

Increased tumor establishment and growth after laparotomy vs laparoscopy in a murine model.

OBJECTIVE: To test our hypothesis that tumors would be more easily established and grow more aggressively after laparotomy than after laparoscopy. This hypothesis was based on studies that have demonstrated that surgery can suppress immune function and facilitate tumor growth and that have shown preservation of immune function after laparoscopic procedures. DESIGN: Double-blinded, randomized, control trial. SETTING: Research laboratory and animal care facility. ANIMALS: One hundred forty 5- to 6-week-old C3H/He female mice. INTERVENTIONS: Three experiments with three groups each: laparotomy, insufflation, and anesthesia controls. All animals received an intradermal inoculation of tumor cells in the dorsal skin. The anesthesia control cohort underwent no procedure. The laparotomy cohort underwent a midline laparotomy from the xiphoid process to the pubis, which was closed after 30 minutes. The insufflation cohort underwent peritoneal insufflation with carbon dioxide for 30 minutes. MAIN OUTCOME MEASURES: Tumor volume, tumor mass, and incidence of tumor establishment. RESULTS: In the first experiment, the tumor volumes of the anesthesia control and insufflation groups followed a similar pattern of plateau and regression. The tumor volumes of the laparotomy group followed a different pattern and were significantly larger than those of the control and insufflation groups on postoperative days 6 and 12 (P < .05 for all comparisons). In the second experiment, tumors in the laparotomy group were approximately three times larger than those of the control group (P < .01) and almost twice as large as insufflation group tumors (P < .01) by mass. In the third experiment, there was a significantly higher incidence of tumor establishment in the laparotomy group than in the insufflation (P < .04) or control (P < .01) groups. The incidence was not different between the control and insufflation groups. CONCLUSIONS: Tumors were more easily established and grew more aggressively after laparotomy than after insufflation. These results, coupled with those that demonstrate an immune advantage to laparoscopy over laparotomy, suggest that the difference in observed tumor growth may be related to immune function. While much work remains to be done, we believe these data provide evidence of a previously undemonstrated benefit of laparoscopic intervention.

Animals↗
PubMed1995

Tumor growth after laparotomy or laparoscopy. A preliminary study.

We investigated the effects of laparotomy and insufflation on tumor establishment and growth in a murine model. Twenty female mice received intradermal inoculation of a low dose of tumor cells (2 x 10(3)) derived from the MC2 mouse mammary carcinoma cell line. Ten of these mice underwent laparotomy and ten received intraperitoneal insufflation with carbon dioxide gas at a pressure of 5 mmHg for 30 min. Tumor growth was followed postoperatively. By postoperative day 14, tumors had grown in zero of the ten insufflated mice and in seven of the ten laparotomy-group mice (P < 0.005). By postoperative day 30, tumors had grown in one of the ten insufflated mice and in eight of the ten laparotomy-group mice (P < 0.007). Ten additional mice received a high-dose inoculum of cells (1 x 10(6)) followed by either laparotomy or intraperitoneal insufflation. Upon sacrifice 12 days later, all mice had developed tumors, but the laparotomy group's tumors were almost three times as large, by mass, as tumors in the insufflated group (70.5 +/- 23.5 mg vs 25.8 +/- 9.5 mg; P < 0.02). These results suggest that laparotomy confers a permissive effect on tumor establishment and growth in a murine model not seen after peritoneal insufflation. We hypothesize that this may be a function of relative immunosuppression following laparotomy which is not present following peritoneal insufflation. These data may be important when choosing a route of access to the peritoneal cavity for cancer resection.

Animals↗
PubMed1995

Mechanisms to Reduce Incidence of Tumor Implantaton During Minimal Access Procedures for Colon Cancer.

Implantation of tumor during minimal access procedures such as laparoscopic colectomy is a disturbing phenomenon. Although the actual incidence of this problem is unknown, its existence is a threat to the further clinical development of minimally invasive oncological procedures. We have adopted the hypothesis that these recurrences are the result of suboptimal technique or instrumentation and therefore that the problem can be avoided by identifying and correcting these technical factors. Our purpose is to analyze the possible mechanisms by which tumor cells become implanted in the trocar sites and to propose rational solutions to the problem.

Journal Article↗
PubMed1995

Laparoscopic harvesting of jejunal free flaps.

We studied the safety and efficacy of laparoscopic jejunal free flap harvesting with total intracorporeal small-bowel anastomosis in an animal model. Eight dogs underwent laparoscopic resection of 8 to 15 cm of jejunum with endoscopic GIA anastomoses and jejunal segment harvesting through the periumbilical laparoscopic port. In six animals, the harvested jejunum was implanted subcutaneously and revascularized by anastomosis of the mesenteric artery and vein to the femoral vessels. Both the microvascular and intracorporeal jejunal anastomoses were studied at 10 days. Mean laparoscopic operative time was 2.9 hours, with the last five procedures all completed in fewer than 2 hours. Mean ischemic time was 1.9 hours. The laparoscopically performed small-bowel anastomoses were all successful. All dogs took regular diets within 1 day, with normal bowel function returning by the second day. Both clinically and histologically, the bowel wall and mesenteric vessels of all the segments harvested demonstrated no injury despite their laparoscopic harvest. Five of the free flaps remained fully viable at 10 days. One flap failed after prolapse of the flap resulting from inadequate fixation. Laparoscopic harvesting of the jejunal free flap is safe and efficacious and offers all of the potential advantages of laparoscopic abdominal surgery.

Anastomosis, Surgical↗
PubMed1994

Expression of recombinant transmembrane CD59 in paroxysmal nocturnal hemoglobinuria B cells confers resistance to human complement.

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired hematopoietic disorder characterized by complement-mediated hemolytic anemia, pancytopenia, and venous thrombosis. These clinical manifestations arise from an underlying molecular defect of bone marrow stem cells. Specifically, somatic mutations in the phosphatidylinositol glycan class A gene result in the ability of blood cells to anchor complement-regulatory proteins (CD59 and DAF) to the cell surface via glycosyl phosphatidylinositol (GPI). In an attempt to circumvent the functional defect in PNH cells, a recombinant transmembrane form of CD59 (CD59-TM) was analyzed for the ability to regulate complement activity. Balb/3T3 stable transfectants expressing similar levels of either CD59-TM or native CD59 (CD59-GPI) were equally protected against human complement-mediated membrane damage. Treatment of these cells with phosphatidylinositol-specific phospholipase C failed to release CD59-TM from the cell surface. Retroviral transduction of GPI-anchoring deficient mouse L cells with CD59-TM resulted in surface expression of the protein and rendered these cells resistant to human complement-mediated membrane damage. Conversely, L cells transduced with CD59-GPI failed to express this protein on the cell surface. A GPI-anchoring deficient complement-sensitive B-cell line derived from a PNH patient was successfully transduced with CD59-TM, resulting in surface expression of the protein. The PNH B cells expressing CD59-TM were protected against classical complement-mediated membrane damage by human serum. Taken together, these data establish that a functional recombinant transmembrane form of CD59 can be expressed on the surface of GPI-anchoring deficient PNH cells and suggest that retroviral gene therapy with this molecule could provide a treatment for PNH patients.

3T3 Cells↗
PubMed1994

Somatic mutations and cellular selection in paroxysmal nocturnal haemoglobinuria.

Patients with paroxysmal nocturnal haemoglobinuria (PNH) have in their blood two red-cell populations, one normal and one deficient in proteins anchored to the membrane through a glycan phosphatidylinositol (GPI) structure. The PNH abnormality is due to a somatic mutation in the PIG-A gene, whose product is required for an early step in GPI anchor biosynthesis. We show that in two patients, two PNH clones with different mutations co-exist, and must therefore have arisen independently. This finding supports the concept that PNH develops under the pressures of a positive selection mechanism whereby GPI-anchor-deficient haemopoietic cells have a survival advantage.

Cell Line↗
PubMed1994

Paroxysmal nocturnal haemoglobinuria (PNH) is caused by somatic mutations in the PIG-A gene.

Paroxysmal nocturnal haemoglobinuria (PNH), an acquired clonal blood disorder, is caused by the absence of glycosyl phosphatidylinositol (GPI)-anchored surface proteins due to a defect in a specific step of GPI-anchor synthesis. The cDNA of the X-linked gene, PIG-A, which encodes a protein required for this step has recently been isolated. We have carried out a molecular and functional analysis of the PIG-A gene in four cell lines deficient in GPI-linked proteins, obtained by Epstein-Barr virus (EBV) transformation of affected B-lymphocytes from PNH patients. In all four cell lines transfection with PIG-A cDNA restored normal expression of GPI-linked proteins. In three of the four cell lines the primary lesion is a frameshift mutation. In two of these there is a reduction in the amount of full-length mRNA. The fourth cell line contains a missense mutation in PIG-A. In each case the mutation was present in the affected granulocytes from peripheral blood of the patients, but not in normal sister cell lines from the same patient. These data prove that PNH is caused in most patients by a single mutation in the PIG-A gene. The nature of the mutation can vary and most likely occurs on the active X-chromosome in an early haematopoietic stem cell.

Amino Acid Sequence↗
PubMed1994

Preservation of immune response after laparoscopy.

We evaluated the immunologic responses following laparoscopic and open surgery by comparing delayed type hypersensitivity induration size before and after each method of accessing the abdominal cavity. One hundred and thirty-two male Sprague-Dawley rats were sensitized with keyhole limpet hemocyanine (KLH). Animals were challenged with KLH and phytohemaglutanin (PHA) 10 days after sensitization. On day 14 after initial sensitization animals were randomly divided into three groups. Group one served as controls and had no procedure performed, group two underwent peritoneal insufflation with carbon dioxide gas to a pressure of 6-8 mm Hg for one half hour, and rats in group three had a midline laparotomy which was closed after one half hour. Each rat was challenged with KLH immediately and at three days postoperatively. The area of induration in response to each of the challenges was measured with calipers 24 and 48 hours after the challenge. Results of this skin testing showed that the group of animals that underwent laparotomy, despite having normal responses preoperatively, had significantly diminished responses to both KLH and PHA when challenged postoperatively. The insufflated group showed no differences from control animals at any time point examined. We conclude that DTH response in this model is better preserved after laparoscopy than laparotomy. We further conclude that the defect in DTH response is in the effector arm. The question of the clinical significance of these findings is addressed.

Adjuvants, Immunologic↗