Long-term follow-up of patients with Crohn's disease. Relationship between the clinical pattern and prognosis

In a study of 615 new patients with Crohn's disease consecutively diagnosed at the Cleveland Clinic between 1966 and 1969, 592 patients were observed (mean greater than 13 yr, minimum 7 yr), giving a follow-up rate of 96.3%. The original hypothesis was that initial anatomic involvement (the clinical pattern) bears directly on clinical course and prognosis. Disease sites were as follows: 246 ileocolic, 165 small intestine, and 181 colon/anorectal. Among patients with ileocolic disease, 225 (91.5%) had surgery. For the small intestine pattern, the operative incidence was 65.5%; for the colon/anorectal pattern, it was 58%. Operations were for specific reasons: internal fistula with abscess or intestinal obstruction for ileocolic pattern; intestinal obstruction for small intestine pattern; and severe perianal disease or toxic megacolon for colon/anorectal pattern. Complications among nonoperated patients included perianal fistulas and extraintestinal manifestations. No statistical correlation existed between type and duration of medical treatment and prognosis. Seventy-five deaths occurred (12.8%), 36 of which related directly to Crohn's disease. Even after many years, symptoms continued and quality of life tended to be suboptimal among operated patients. For nonoperated patients, the most favorable quality of life was experienced by those with segmental involvement of the colon or ileum. Poor prognosis correlated with ileocolic disease and presence of sepsis because of an internal fistula.     

Rapid method for isolation of normal human peripheral blood eosinophils on discontinuous Percoll gradients and comparison with neutrophils

Previous studies on human eosinophils often have used cells from patients with hypereosinophilia syndrome or parasitosis owing to the difficulty in isolating pure populations of eosinophils from normal individuals. In the present study, human eosinophils were isolated with a purity of 97%, with 70% recovery from normal individuals with blood eosinophil counts of less than 3%. Human eosinophils are denser than neutrophils, but the range of densities of the two cell types overlap, making purification of eosinophils by density-gradient centrifugation difficult. However, if neutrophils were exposed to the chemotactic peptide (f-Met-Leu-Phe), which did not stimulate eosinophils, the neutrophils' density decreased, shifting them away from the density of eosinophils. Whole normal blood anticoagulated with EDTA was incubated at 37 degrees C for 15 minutes with 10(-6) mol/L f-Met-Leu-Phe and then layered over a discontinuous Percoll gradient (65% and 75% in diluted phosphate-buffered saline) and centrifuged at 400 g for 25 minutes at 22 degrees C. The cell layer between the 65% and 75% Percoll was collected and washed, and hypotonic lysis was used to remove erythrocytes. This cell layer contained 97.3 +/- 0.7% eosinophils (N = 8) with a yield of 4.9 X 10(4) eosinophils per milliliter of whole blood, or 70% of the total eosinophil count. The isolated eosinophils were in a quiescent state but responded to Escherichia coli endotoxin- activated serum with shape change and chemotaxis, membrane depolarization, and reduced nitroblue tetrazolium (96.0 +/- 1.0%), when stimulated with phorbol myristate acetate. In phagocytic assays, 89.3 +/- 1.3% of the eosinophils ingested Candida albicans v 96.0% +/- 1.0% of neutrophils. In contrast, the eosinophils did not respond chemotactically, alter membrane potential, or reduce nitroblue tetrazolium when treated with f-Met-Leu-Phe, and studies with f-Met-Leu- [3H]Phe showed that normal eosinophils lacked expression of receptors for f-Met-Leu-Phe. In control studies, normal eosinophils that were not exposed to f-Met-Leu-Phe during purification also failed to respond to f-Met-Leu-Phe, indicating intrinsic differences between normal eosinophils and neutrophils. Thus, exposure of whole blood to f-Met-Leu- Phe, followed by separation on Percoll is a simple method for rapid isolation of normal human eosinophils.     

Effects on the buoyant density of rabbit platelets of ADP and agents that increase the concentration of cyclic AMP

Rabbit platelets were aggregated by adenosine diphosphate (ADP), allowed to deaggregate and then separated into density subpopulations by centrifugation through discontinuous Stractan density gradients. Although ADP causes little or no release of the contents of the amine storage granules of rabbit platelets, ADP caused a decrease in platelet density as compared with control platelets subjected to the same procedures except for exposure to ADP. The density change persisted for at least four hours. The apparent size of platelets stimulated with ADP increased initially, but returned to control values during a one-hour period. A similar decrease in platelet density was observed with an albumin density gradient. Under conditions in which aggregation did not occur in response to ADP with ethylenediaminetetraacetic acid (EDTA) in the medium, little or no decrease in platelet density was observed. Agglutination with polylysine did not change platelet density. Thus, not only agents such as thrombin and plasmin that cause the release of the contents of the platelet granules decrease platelet density, but ADP also has this effect. Platelets would be exposed to all of these stimuli during thromboembolic processes, and their effect on platelets may account for the decrease in platelet density observed previously in experiments with rabbits with indwelling aortic catheters. Agents that increase the concentration of cyclic AMP (cAMP) in platelets (PGE1, adenosine, dibutyryl cAMP, forskolin, and papaverine) also decreased platelet density. This effect persisted when the platelets were washed and resuspended in fresh medium and was also demonstrable in plasma. Platelet size was gradually increased by prostaglandin E1 (PGE1) which maintains platelets in a disc shape and does not cause the release of granule contents, indicating that the decrease in platelet density caused by PGE1 may be attributable to platelet swelling.     

Percutaneous suprapubic cystolithotripsy for treatment of large bladder calculi

BACKGROUND AND PURPOSE: The treatment options available for managing bladder calculi include transurethral cystolithotripsy, open cystolithotomy, and shockwave lithotripsy. For larger calculi, transurethral treatment can be time consuming, and the manipulation has the potential to cause urethral injury. Percutaneous suprapubic cystolithotripsy represents another treatment option for bladder calculi which is effective and minimally invasive. PATIENTS AND METHODS: Fifteen patients had bladder calculi treated with percutaneous cystolithotripsy over a 3-year period. The mean stone size was 39 mm (range 10-64 mm). Stones were single in seven patients and multiple in eight patients. The indications for cystolithotripsy were stone size >3 cm, multiple stones >1 cm, and inability to perform transurethral cystolithotripsy because of patient anatomy. Percutaneous suprapubic cystolithotripsy was done through either a 30F or a 36F cystotomy tract. Fragmentation and removal was performed with a 26F rigid nephroscope and the pneumatic Swiss Lithoclast. Suprapubic and urethral catheters were placed postoperatively in all patients. RESULTS: Each patient was cleared of the stone burden with a single procedure, and there were no major complications. The mean duration of suprapubic catheterization was 2.6 (range 1-5) days. CONCLUSION: Percutaneous suprapubic cystolithotripsy is an effective and safe technique for treating large bladder calculi. It is minimally invasive, avoids urethral injury, and, in combination with the pneumatic Swiss Lithoclast, can be used to fragment and remove large and hard bladder calculi.     

B cell response to tumor antigens is associated with depletion of B progenitors in murine colocarcinoma

BACKGROUND: B cells that produce antibodies to autologous tumor antigens have been found in patients with colon cancer; the significance of this phenomenon remains unknown. Normally, the elimination of autoreactive B cells occurs in the bone marrow during their maturation. We studied the production of antibodies to syngeneic tumor antigens and the maturation of bone marrow B cells in experimental colocarcinoma model. METHODS: BALB/c mice and syngeneic CT26 colon cancer cell line were used. Reactivity of serum antibodies was tested in Western blot analysis and flow cytometry against CT26 antigens. The number of bone marrow B lineage cells was evaluated with specific antibodies and flow cytometry analysis. RESULTS: A significant decrease in the number of B cell precursors occurred in tumor-bearing mice; it normalized 3 weeks after the removal of CT26 tumors. The number of mature B cells was normal. Serum antibodies from tumor-bearing mice recognized intracellular and not surface antigens of CT26 cells. CONCLUSION: Experimental colon cancer induces B cell response to intracellular, but not surface, tumor cell antigens and restricts the B cell repertoire by depleting their precursors.     

Is Minimal Access Surgery for Cancer Associated with Immunologic Benefits?

Minimal-access surgical techniques have been shown to be beneficial to patients in terms of shorter convalescence, reduced pain, and improved cosmesis. Although systemic immune function is better preserved following laparoscopic procedures when compared with their respective open approaches, CO₂ pneumoperitoneum may significantly affect local (i.e., infra-abdominal) cellular immunity by reducing regional macrophage function. Results to date are conflicting with regard to the impact of closed and open methods on intraabdominal immunity. Impaired cellular immunity after CO₂ pneumoperitoneum may have significant undesirable intra-abdominal effects on tumor surveillance after oncological surgery; however, at present, there is no clinical evidence to support this position. The VATS techniques avoid the use of CO₂ insufflation, which may offer some advantages from the immune function perspective over laparoscopic procedures accomplished with CO₂ pneumoperitoneum. Better preservation of early postoperative cellular immune function and attenuated disturbance in the inflammatory mediators are likely contributing factors to the clinical benefits that follow laparoscopic surgery and VATS. Larger multi-center randomized trials are needed to confirm the potential benefits of minimal-access surgery on patient survival after cancer surgery. Future research should focus on the effects of minimal-access surgery on other mediators (such as MMP-9, IGFBP-3, IL-12, IL-17, and IL-23) that may be important in tumor cell dissemination, deposition, and propagation in the early postoperative period. Furthermore, additional searches for other factors or mediators, heretofore unrecognized, should be carried out. Such studies will, we hope, increase our knowledge and understanding of the impact of surgery on immune and other physiologic functions.     

Increased tumor establishment and growth after open vs laparoscopic bowel resection in mice

Background: Surgery can suppress immune function and facilitate tumor growth. Several studies have demonstrated better preservation of immune function following laparoscopic procedures. Our laboratory has also shown that tumors are more easily established and grow larger after sham laparotomy than after pneumoperitoneum in mice. The purpose of this study was to determine if the previously reported differences in tumor establishment and growth would persist in the setting of an intraabdominal manipulation. Methods: Syngeneic mice received intradermal injections of tumor cells and underwent either an open or laparoscopic cecal resection. In study 1, the incidence of tumor development was observed after a low dose inoculum; whereas in study 2, tumor mass was compared on postoperative day 12 after a high-dose inoculum. Results: In study 1, tumors were established in 5% of control mice, 30% of laparoscopy mice, and 83% of open surgery mice (p < 0.01 for all comparisons). In study 2, open surgery group tumors were 1.5 times as large as laparoscopy group tumors (p < 0.01), which were 1.5 times as large as control group tumors (p < 0.02). Conclusion: We conclude that tumors are more easily established and grow larger after open laparoscopic bowel resection in mice. Received: 27 October 1997/Accepted: 19 January 1998     

Prognosis of patients with acute renal failure requiring dialysis: results of a multicenter study

Despite several decades of clinical experience, the mortality rate for patients with acute renal failure (ARF) requiring dialysis remains high, and the evaluation of the patients prognosis has been difficult. To date, the Acute Physiology and Chronic Health Evaluation II (APACHE II) scoring system has been used more frequently for prediction in studies of ARF than any other scoring system, but has not been prospectively validated in controlled multicenter studies of this entity. In a multicenter, prospective, controlled trial evaluating the use of biocompatible hemodialysis membranes (BCMs) in patients with ARF, we evaluated the extent to which the APACHE II scoring system, based on the physiological variables in the 24 hours before the onset of dialysis and the presence or absence of oliguria, is predictive of outcome. Analysis of survival and recovery of renal function for the 153 patients treated in this study show that APACHE II scores are predictive both of survival and recovery of renal function, whether analyzed separately by type of dialysis membrane used (BCM or bioincompatible [BICM]) or for both groups combined (all P < 0.01). There was no evidence of a significant center effect or interaction of APACHE II score with dialysis membrane in our study. After adjusting for the APACHE II score, there was a positive effect of the BCM on both probability of survival (P < 0.05) and recovery of renal function (P < 0.01). In patients dialyzed with BCMs, oliguria at onset of dialysis had an adverse effect on both survival and recovery of renal function (both P < 0.01). Receiver operator curves (ROCs) using APACHE II score and the use of BCMs in nonoliguric patients yielded a statistically significant improvement versus the use of APACHE II score alone in the area under the curve (AUC) for survival (0.747 to 0.801; P < 0.05) and recovery of renal function (0.712 to 0.775; P < 0.05). We conclude that the use of the APACHE II score determined at the time of initiation of dialysis for patients with ARF is a statistically significant predictor of patient survival and recovery of renal function. The use of the APACHE II score measured at the time of dialysis initiation, especially when modified by the presence or absence of oliguria, should help in predicting outcome when evaluating interventions for patients with ARF.