Increased serum lysozyme in the presence of abscesses.
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Intra-abdominal abscess is seldom adequately treated by systemic antibiotics alone and often requires surgical or computed tomography-guided drainage for resolution. Abscess penetration of six currently used antibiotics was examined in a murine intra-abdominal abscess model. Ampicillin/sulbactam, cefmetazole, clindamycin, and trospectomycin penetrated intra-abdominal abscesses to a greater degree than cefoxitin and ceftriaxone. Abscess pus antibiotic levels were not significantly higher after multiple doses than after a single dose. Pus antibiotic levels below the MIC90 for Bacteroides and E. coli within intra-abdominal abscess were observed for most antibiotics with the doses used in this study. Selection of antibiotics with a greater ability to penetrate abscess may be important in optimally treating patients with abdominal infection.
OBJECTIVE: To measure the effectiveness of peer review as a screening process to evaluate medical manuscripts. DESIGN: Retrospective. SETTING: The editorial office of the American Journal of Surgery (AJS). METHOD: A MEDLINE search was conducted of publications from 1984 to 1992 for manuscripts that were identical or similar to those rejected by AJS between January and December 1989. Manuscripts that were submitted to AJS by foreign authors were excluded because of the presumed difficulty in tracking foreign-language publications. MAIN OUTCOME MEASURES: The percentage of manuscripts rejected by AJS that were subsequently published in journals indexed by MEDLINE, the time from rejection to ultimate publication, and the journal of publication. The reasons for rejection were also documented. We assumed that the majority of rejected manuscripts would be published within 3 years after rejection. RESULTS: One hundred twenty-five manuscripts submitted by North American authors were rejected by AJS in 1989, and 62% were not subsequently published in another core medical journal during the study period. The average duration between rejection and later publication was 17 months. Of those manuscripts subsequently published, 54% appeared in general surgical journals, including 12% that were revised, reevaluated, and later accepted by AJS. Twenty-nine percent of the rejected manuscripts were published in specialty medical journals, 10% in state and local journals, and the remainder in general medical journals. Twenty-eight percent of the authors of rejected manuscripts had previously and subsequently published manuscripts on very similar subjects. CONCLUSIONS: Our data indicate that the review process serves as a sieve and influences whether manuscripts are published in core medical journals. This was demonstrated by the fact that rejected manuscripts often were not published in other indexed medical journals.
PURPOSE: The role of immunoscintigraphy with 111In-satumomab pendetide in the medical and/or surgical management of colorectal cancer patients was evaluated in a multicenter trial. METHODS: This 103 patient study population included 46 individuals with rising serum carcinoembryonic antigen levels and otherwise negative diagnostic evaluation, 29 patients with known recurrence, presumed to be isolated and resectable, and 28 patients for whom standard diagnostic tests provided equivocal information. RESULTS: No adverse reactions were noted following intravenous administration of 1 mg of satumomab pendetide radiolabeled with approximately 5 mCi of 111In. Thirty percent of patients developed human anti-mouse antibodies postinfusion. In the 84 patients for whom correlation with histopathologic, diagnostic, and/or clinical findings was available, antibody imaging demonstrated a sensitivity of 73 percent in patients with confirmed tumor (36/49) and negative results for all 35 patients with no evidence of malignancy. Occult disease was detected in 18 patients. CONCLUSION: 111In-satumomab pendetide immunoscintigraphy was helpful in the medical and/or surgical management of 45 (44 percent) patients and provided information unavailable from other diagnostic modalities.
BACKGROUND: Chronic ulcerative colitis and familial adenomatous polyposis are associated with an increased risk of colorectal carcinoma. Currently, there are no reliable methods to assess carcinoma risk. METHODS: Several prognostic factors known to be useful in breast carcinoma were determined in 102 specimens of colonic mucosa from 38 patients: 22 specimens from "normal," non-neoplastic colon, 49 from chronic ulcerative colitis, 10 from Crohn's colitis, 14 from familial adenomatous polyposis, four from mucosa adjacent to carcinoma, and three from colon carcinoma. Expression of estrogen receptor, progestin receptor, epidermal growth factor receptor, HER-2/neu (c-erb B-2) oncoprotein, and cathepsin D were determined. RESULTS: Epidermal growth factor receptor expression was higher in chronic ulcerative colitis, Crohn's colitis, familial adenomatous polyposis, and colon carcinoma and varied with location within the colon for chronic ulcerative colitis, Crohn's colitis, and familial adenomatous polyposis. Epidermal growth factor receptor expression in mucosa adjacent to carcinoma was similar to that in "normal" colon. CONCLUSION: Further analyses are needed to determine which parameters are related to and possibly predictive of increased carcinoma risk.
OBJECTIVE: This study determines whether there are any differences in several immunologic parameters in circulating peripheral blood leukocytes, serum, and plasma compared with pus leukocytes, and supernatant of various types of abscess. SUMMARY BACKGROUND DATA: Although there have been reports of high lysozyme levels and low complement levels within pus, there has been no systemic comparison of concentrations of these substances and others within pus compared with those within peripheral blood. METHODS: Peripheral blood and abscess pus were collected from 31 patients with abscesses and percent and mean channel of monocytes expressing complement receptor and major histocompatibility antigen HLA-DR, the percent and mean channel of polymorphonuclear leukocytes (PMN) expressing complement receptor, lysozyme level, and levels of total hemolytic complement, iC3b, C5b-9, and immunoglobulins were measured within both pus and peripheral blood. RESULTS: Percent of monocytes expressing HLA-DR and percent of monocytes and PMN expressing complement receptor, total hemolytic complement, and IgM were reduced within pus compared with peripheral blood, whereas the mean channel of monocytes expressing HLA-DR and the mean channel of PMNs expressing CR3, C5b-9, and lysozyme were increased in pus. CONCLUSIONS: There are marked differences in immunologic parameters measured within pus of abscesses versus that seen in peripheral blood.
OBJECTIVE: In 1990, large-dose steroid administration was advocated in spine-injured patients to lessen neurologic deficits. The authors undertook both prospective and retrospective studies to evaluate the response of such profound pharmacologic intervention. SUMMARY BACKGROUND DATA: Of all sources of nonfatal injury, spinal cord trauma remains the most devastating in both cost and impact on the quality of the patient's life. One study found that routine large-dose steroid administration after injury lessened the extent of neurologic injury. After uncommonly prompt and broad lay press publicity, this practice was widely accepted. Biased by knowledge of the known immunosuppressive effects of steroids, the authors suspected that pneumonia was both more frequent and severe in steroid-treated patients. METHODS: Thirty-two patients with cervical or upper thoracic spinal injuries (C3-6, 20 patients; C6-7, 6 patients; and T1-6, 6 patients) were studied at an urban level I trauma center from January 1987 to February 1993. Complete spinal cord injury was present in 22 of 32 patients; 14 patients received steroids postinjury. There was no difference in mean age, cord level, age-adjusted injury severity score, or the percent of injury severity score caused by the spinal injury. RESULTS: The length of hospital stay was longer in steroid-treated patients (S) than in nonsteroid (NS) patients, that is, 44.4 days versus 27.7 days, respectively (p = 0.065). Seventy-nine per cent of S patients had pneumonia compared with 50% of NS patients (p = 0.614). There was no statistical difference in the episodes of pneumonia per patient between the two groups (p > 0.05). Prospectively, the authors evaluated sequentially several parameters known to be important in human immune responses to bacterial challenges in nine S and five NS patients. In S patients, both the per cent and density of monocyte class II antigen expression and T-helper/suppressor cell ratios were lower than in NS patients. However, S patients did have an initially higher, earlier boost in some host defense parameters that rapidly declined, and their subsequent response was both blunted and delayed. These differences became even clearer when stratified according to cord level and incomplete versus complete cord status. Not surprisingly, infected patients, whether S or NS, had lower levels of monocyte antigen expression, CR3, and helper/suppressor ratios. CONCLUSIONS: These data do not permit a judgment to be made whether neurologic status was improved by S administration. It is known that vital immune responses were adversely affected, that pneumonia was somewhat more prevalent, and that hospitalization was prolonged and costs therefore increased by an average of $51,504 per admission. Further clinical studies will be needed to determine to what extent these observations offset the putative benefits of large-dose steroids in the treatment of spinal trauma.
The role of immunoscintigraphy in patients with colorectal cancer is being defined in ongoing clinical trials. Currently, most follow-up examination after "curative" resection of colorectal carcinoma are performed by surgeons, oncologists and gastroenterologists. They are largely focused on detecting recurrent intraluminal disease and measuring serial serum carcinoembryonic antigen (CEA) levels. Although rising CEA is often indicative of nonresectable disease, some patients with elevated CEA levels have no evidence of recurrent disease using conventional diagnostic modalities. In these patients, immunoscintigraphy will probably have a major diagnostic role. In addition, immunoscintigraphy may become valuable in screening patients at high risk for recurrence postoperatively, such as those with Dukes' stage C lesions, aneuploidy, poor tumor differentiation or tumor adhesion to or invasion of adjacent organs. Immunoscintigraphy may allow earlier diagnosis of recurrent disease and permit more targeted follow-up studies. Intensive, timely follow-up of these patients should lead to early detection of recurrent disease at a time when these lesions are still resectable.
UNLABELLED: Among 914 patients undergoing ileal pouch-anal anastomosis (IPAA) between January 1981 and June 1989, 463 (51 percent) had a pouchogram (meglumine diatrizoate [Gastrografin; E.R. Squibb & Sons, Inc., Princeton, NJ] enema) to assess anastomosis and ileal pouch integrity before closure of the ileostomy. The aim was to determine whether a pouchogram was useful in predicting clinical outcome. RESULTS: Abnormal findings were present in 74 patients (16 percent). These included anastomotic and pouch leaks and anstomotic strictures. Pouchograms were normal in the remaining 389 patients (84 percent). The incidence of significant anastomotic stricturing requiring dilatation under anesthesia was much higher in the abnormal than in the normal pouchogram group (33 percent vs. 4 percent, respectively; P less than 0.001). More significantly, an abnormal pouchogram was associated with an overall long-term failure rate of 23 percent, compared with 6 percent for a normal pouchogram (P less than 0.001). CONCLUSION: Abnormal findings in a pouchogram prior to ileostomy closure indicated those patients at high risk of long-term complications following IPAA.
Leucocytes in different body compartments were examined in a murine intra-abdominal abscess model: (i) peripheral blood; (ii) peritoneal exudate; (iii) abscess wall; and (iv) abscess pus, with respect to their phagocytic ability, CR3 expression and Ia antigen expression (murine MHC antigen). The ability of serum or supernatant in each compartment to opsonize Staphylococcus aureus was also determined. Mice responded to caecal ligation and puncture (CLP) with systemic monocytosis, an increased amount of opsonins in peritoneal fluid and an increased phagocytosis in pus leucocytes. This increased phagocytic ability and CR3 expression both subsequently decreased. Monocyte/macrophage Ia expression was reduced in all measured compartments over time. In contrast, sham-operated animals, without an intra-abdominal abscess, responded to operation with an even greater increase in peritoneal exudate phagocytic ability and in monocyte/macrophage Ia expression in all compartments which was sustained beyond 1 week. Decreased peritoneal exudate cell and peripheral blood Ia was still present after 28 days in CLP animals, compared with both sham and normal animals (P less than 0.05, P less than 0.02, respectively). For all parameters, changes observed in peripheral blood did not reflect those present near the site of infection. Proper understanding of local or regional infection must take into account and ultimately alter these generally unappreciated changes in and about the actual site of infection.
Over the past 20 years, there have been major changes in the philosophy of treating inflammatory bowel disease. Significant advances include the development of continence preserving or sphincter saving procedures for ulcerative colitis patients and recognition of the need for bowel conservation in patients with Crohn's disease. Illustrative cases are presented followed by a brief description of state-of-the-art surgical management in these patients.
Data on 818 patients who had undergone curative resection for Dukes' B2 or Dukes' C carcinoma of the colon and rectum were analyzed to determine the timing and patterns of recurrence based on such tumor characteristics as location, Dukes' stage, grade, ploidy and the presence of obstruction, perforation or adherence to adjacent organs or tissues. Three hundred and fifty-three patients (43 per cent) had recurrent disease. There was recurrence in 52 per cent of patients with carcinoma of the rectum and in 40 per cent of patients with carcinoma of the colon. The median time to recurrence for all patients was 16.7 months, with a range from 1 month to 7.5 years. Dukes' C lesions and the presence of adhesion or invasion, or both, or perforation were associated with significantly earlier recurrence. Among patients with recurrence, the most frequent sites were hepatic in 33 per cent, pulmonary in 22 per cent, local or regional, or both, in 21 per cent, intra-abdominal in 18 per cent, retroperitoneal in 10 per cent and peripheral lymph nodes in 4 per cent. Rectal primary sites, when compared with colonic, had proportionally more local or regional, or both, recurrences (p = 0.00003) and fewer involving retroperitoneal nodes (p = 0.022). Both primaries of the rectum and colon at stage C, when compared with stage B, had fewer local or regional recurrences, or both (p = 0.01), but a greater tendency to involve retroperitoneal or peripheral nodes. Primaries of the colon with adhesion to, or invasion of, adjacent organs had a lesser tendency to pulmonary metastasis (p = 0.036). Whereas the grade of anaplasia and ploidy had a strong influence on the rate of recurrence, they did not influence timing or patterns of recurrence. Patterns of recurrence based on the characteristics of the tumor may facilitate selection of the most appropriate adjuvant procedures, particularly those directed toward local or regional recurrence, or both, and also may guide efforts at early recognition of recurrence.
Thirty-seven patients underwent construction of a J-ileal pouch-anal anastomosis (IPAA) without temporary diverting ileostomy for chronic ulcerative colitis (CUC) (20 patients), familial adenomatous polyposis (FAP) (15 patients), indeterminate colitis (1 patient) and nonhereditary polyposis coli (1 patient) between 1981 and 1990. Seven of 20 CUC patients (35 percent) were on steroids at the time of hospital admission. The postoperative course of these patients was compared with that of a group of patients undergoing IPAA with ileostomy during that same time period and matched for age, sex, diagnosis, date of surgery, and steroid use. Eight patients (22 percent) in the group without ileostomy and four patients (11 percent) with ileostomy experienced one or more postoperative pouch-related complications. Complications requiring reoperation in patients without ileostomy occurred more frequently in patients either taking steroids or having previous pelvic radiation therapy. Functional results in patients undergoing one-stage procedures after a mean of 28 postoperative months were comparable to those in patients having staged procedures. Surgeons' criteria for a one-stage procedure in these patients should include absolute lack of tension on the anastomosis, good blood supply to the terminal ileum, good general health, and absence of recent intake of steroids at the time of surgery. We conclude that J-pouch construction with IPAA can be safely performed without diverting ileostomy, provided that these selection factors are taken into account.
In patients with chronic ulcerative colitis (CUC), ileal pouch-anal anastomosis (IPAA) can be performed either at the time of colectomy or as a delayed procedure after total abdominal colectomy and ileostomy. There has been debate as to whether delayed IPAA results in superior functional results, since patients are frequently steroid-free and have little evidence of active disease. To assess this, we analyzed 95 patients who had undergone total abdominal colectomy, either with ileostomy and Hartmann's procedure or with ileorectostomy, 2-183 months prior to IPAA. Postoperative complications and functional results were compared with those of 776 CUC patients who underwent IPAA at the time of abdominal colectomy. Indications for prior colectomy included toxic megacolon (40 percent), failed medical therapy (36 percent), other reasons (e.g., iatrogenic perforation, cancer) (6 percent), and reasons unclear (18 percent). Nineteen percent of delayed-IPAA patients were taking steroids at the time of pouch construction. Follow-ups were similar in the two groups. The incidence of septic and obstructive complications after delayed IPAA vs. IPAA at the time of colectomy were 10.5 percent vs. 5.4 percent and 6.5 percent vs. 14.5 percent, respectively. There were no significant differences in postoperative functional results between the two groups. Delayed IPAA confers no advantage over IPAA performed at the time of colectomy in terms of functional outcome. Delayed IPAA was associated with a significantly higher rate of septic complications but a lower incidence of postoperative obstruction.
A 2-year randomized prospective clinical trial was undertaken to determine whether postoperative irrigation of the pelvis would result in a decreased incidence of local septic complications. Two hundred consecutive patients undergoing low pelvic procedures with rectal resection and entry of the presacral space by a single surgeon, were randomized. In the irrigation group, two of four presacral sump drains were placed to low intermittent suction and the remaining sumps infused continuously with saline until the effluent was clear. In the drainage alone group, all four presacral sump drains were placed to suction. Drains were removed when drainage was less than 50 ml/24 hours. Perioperative antibiotics and bowel preparation were identical. Postoperative complications included pelvic abscess (n = 7), anastomotic leak/cuff sinus (n = 11), abdominal wound infection (n = 19), and perineal wound infection (n = 5). Postoperative irrigation of the pelvis did not result in a reduction in the overall rate of local pelvic septic complications. Positive intraoperative presacral cultures, the presence of anaerobes in the presacral space, and duration of pelvic drainage had no effect on the development of pelvic sepsis.
During an 11-year period, 41 patients with Crohn's disease were placed on home parenteral nutrition (HPN) for a mean of 1,083 days (range: 33 to 3,258 days). Data were retrospectively analyzed to determine whether HPN had an effect on the course of their disease, i.e., on the number of operative procedures performed and the intensity of required medical therapy. Data represented information obtained during a total of 121 patient-years of HPN for Crohn's disease. The main indications for HPN were short bowel syndrome (66%) and high stoma output. Twenty-four of 41 patients (59%) underwent surgery for Crohn's disease during the course of HPN. There was no significant difference between the number of procedures performed per patient per year of Crohn's disease during pre-HPN and HPN periods (p greater than 0.25). Although there was no significant change in body weight, both serum albumin and transferrin levels increased during HPN (p less than 0.01 and p less than 0.01, respectively). Twenty-nine percent of patients were taking prednisone while on HPN, compared with 54% of patients during the pre-HPN period (p less than 0.01). HPN appeared to result in a significant improvement in the numerically assessed quality of life. During the HPN period, 24 patients had 1 or more HPN-related complications that required 1 to 13 hospital admissions (mean: 1.8). These complications included catheter sepsis in 19 patients, blocked or damaged catheters in 15 patients, and dehydration and/or electrolyte imbalance in 5 patients. Eight patients died, with 7% of deaths secondary to catheter-related sepsis. Although permanent HPN is associated with an identifiable morbidity and mortality and is not associated with a reduction in the frequency of surgery for Crohn's disease, benefits include a decrease in the intensity of medical therapy, an improvement in patients' nutritional state, and a significant perceived improvement in patients' quality of life. Without HPN, we believe all patients would have died secondary to malnutrition and/or dehydration.
The aim was to assess the value of reoperative surgery for pouch-related complications after ileal pouch-anal anastomosis (IPAA) for chronic ulcerative colitis and familial adenomatous polyposis. Between January 1981 and August 1989, 114 of 982 IPAA patients (12%) seen at the Mayo Clinic had complications directly related to IPAA that required reoperation. Among the 114 patients, the complications prevented initial ileostomy closure in 33 patients (25%), occurred after ileostomy closure in 68 patients (60%), and delayed ileostomy closure in the remaining patients. The salvage procedures performed included anal dilatation under anesthesia for anastomotic strictures, placement of setons and/or fistulotomy for perianal fistulae, unroofing of anastomotic sinuses, simple drainage and antibiotics for perianal abscesses, abdominal exploration with drainage of intra-abdominal abscesses with or without establishment of ileostomy, and complete or partial reconstruction of the reservoir for patients with inadequate emptying. None of the reoperated patients died. Reoperation led to restoration of pouch function in two thirds of patients and, of these, 70% had an excellent clinical outcome. However approximately 20% of the 114 pouches required excision. Excision was common, especially among patients who had pelvic sepsis. Salvage procedures for pouch-specific complications can be done safely and will restore pouch function in two thirds of patients. Complications after reoperation, however, may ultimately lead to loss of the reservoir in one in five patients.
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.