Helicobacter pylori products upregulate neutrophil superoxide anion production.

Helicobacter pylori-neutrophil interactions may play a pathogenic role in H. pylori-induced gastritis and peptic ulcer disease. To understand these interactions, we explored the effects of H. pylori-derived products on neutrophil chemotaxis and superoxide anion production. H. pylori bacteria were cultured and supernatants fractionated. Neutrophil chemotactic activity was confirmed in the crude supernatants and in one fractionated peak corresponding to a previously described neutrophil chemotactic factor. H. pylori-derived crude supernatant, sonicate and all chromatography-derived peaks failed to directly stimulate neutrophil superoxide anion production. However, after pretreatment with sonicate, neutrophils demonstrated increased superoxide anion production (priming) following subsequent exposure to the secretagogue fmet-leu-phe. These results suggest that H. pylori products may attract neutrophils to the gastric mucosa without initially stimulating superoxide anion production or tissue injury. Oxygen radical-mediated gastric mucosal injury may subsequently result when these primed neutrophils undergo additional stimulation by as yet unidentified factors.

Laparoscopic/endoscopic repair of rectal stricture.

Although uncommon, anastomotic stricture after low anterior resection may require additional repair beyond dilatation. Two alternate approaches are described wherein laparoscopic and endoscopic techniques were utilized to avoid repeat pelvic surgery in two cases. These can be used whether a stapled or hand-sewn approach was used for the initial anastomosis. Photo documentation demonstrates a widely patent anastomosis after repair. There is early return of bowel function by these methods, and long-term results (3 years) are excellent.

Prospective double-arm study of fibrinolysis in surgical patients.

BACKGROUND: During surgery, the balance between thrombosis and fibrinolysis is altered. Methods reported to increase fibrinolysis, such as compression devices, may reduce venous thrombosis. However, there are no prospective studies comparing methods and the effect on fibrinolysis. MATERIALS AND METHODS: In a prospective study, general surgical patients were randomized to either sequential compression devices (Group 1) or subcutaneous heparin (Group 2), and fibrinolysis factors were measured in order to determine the effect on the fibrinolysis system. Blood samples were drawn at a similar time of the day with the tourniquet off. Specifically, t-PA antigen, plasminogen activator inhibitor-1 (PAI-1), and D-dimer were measured preoperatively (preop) and on Postoperative Days (POD) 1 and 7 by the ELISA method. Fibrinolysis factors were reported as the mean +/- SD and as percentage change from preoperative values. Noninvasive vascular studies were performed preop, and on POD 1, 7, and 30, by an examination of the infrainguinal venous system and external iliac veins in bilateral lower extremities. Nonambulatory patients were excluded from the study and DVT prophylaxis methods were initiated at surgery and used through POD 2. RESULTS: For the 136 patients in the study, there were no differences in clinical characteristics such as age, surgical time (all > 60 min), anesthesia type (general or spinal), type of surgical procedure, or other risk factors for DVT. Two DVTs occurred at POD 1 and 30 (both Group 2), and one pulmonary embolism in each group (POD 7 for Group 1; POD 1 for Group 2). For subjects without thrombosis, D-dimer changes were parallel for both groups, increasing through POD 7. Similarly, t-PA antigen levels rose from baseline on POD 1 in both groups, with a return toward baseline by POD 7. The PAI-1 levels increased on POD 1 in both groups, but severalfold more in Group 1 (compression devices). The elevation in PAI-1 decreased by 50% in Group 1 by POD 7, while values returned to normal in Group 2. These changes were not significant using the Mann-Whitney test. Only three patients had thrombotic episodes so that data on changes in fibrinolysis factors are difficult to compare with the larger group. CONCLUSIONS: This is the first report of a prospective, randomized comparison of fibrinolysis factors using sequential compression devices in comparison to low dose unfractionated heparin in general surgical patients, and comparing postoperative values to preop. Both groups showed an enhanced fibrinolysis by elevation in t-PA antigen and D-dimer on POD 1, as expected when fibrinolysis occurs. While PAI-1 and t-PA work in parallel, the marked elevation of PAI-1 on POD 1 (although only slightly above reference values) and continuing into POD 7 for subjects using compression devices requires further inquiry. The elevation of PAI-1 in the face of elevated t-PA and D-dimer has been reported, but the comparison between patients using sequential compression devices and mini-dose heparin has not been reported. The reason for the elevation requires additional study into other influences on the synthesis, secretion, and/or function of PAI-1 that do not affect t-PA.

Is DVT prophylaxis overemphasized? A randomized prospective study.

This study was designed to prospectively evaluate a previously published prognostic index for predicting deep venous thrombosis (DVT) in general surgical patients with conventional prophylaxis. Patients undergoing procedures of at least 1 hr duration (abdominal, thoracic, head and neck, inguinal) requiring general or spinal anesthetic were prospectively randomized into the following groups: Group 1, sequential pneumatic compression devices during surgery and 2 days postoperatively; Group 2, subcutaneous heparin (5000 U q 12 hr) starting 1 hr before surgery and for 7 days postop; Group 3, control group. All patients underwent duplex evaluation of bilateral lower extremity deep venous systems preoperatively and on postoperative Days 1, 3, and 30. In addition, a previously developed predictive DVT incidence indicator, the prognostic index (PI), was calculated for each patient. A total of 137 patients were entered into the study with 29 removed for patient/staff reasons. There were no differences in PI among the three groups at the 0.05 level (ANOVA). The distribution of risk factors for DVT including increased age, body size, hemoglobin (Hb), and colorectal procedures were distributed evenly among the groups. Additional factors such as diabetes, COPD, PVD, immobilization, and cancer were also evenly distributed among the groups. The PI predicted a 20% incidence of DVT. For Groups 1 (n = 25), 2 (n = 38), and 3 (n = 45) no DVTs were detected over the 30 days of study. During the study period, 8 DVTs were detected by duplex evaluation in general surgical patients not in the study (1.5%). In conclusion, in a prospective randomized study using sequential pneumatic compression devices, subcutaneous heparin or no prophylaxis in matched general surgical patients at moderate to high risk for thromboembolism, no DVTs occurred for up to 30 days. Furthermore, neither a PI nor other factors associated with DVT accurately predicted the incidence of DVT in this patient population.

Interferon-gamma primes neutrophil-mediated gastric surface cell cytotoxicity.

The T lymphocyte product interferon-gamma (IFN-gamma) upregulates or primes polymorphonuclear leukocyte (PMN) oxidative responses to the receptor-initiated stimulant N-formyl-methionyl-leucyl-phenylalanine (FMLP) but not to the transduction-mediated stimulant phorbol myristate acetate (PMA). We sought a functional correlation between IFN-gamma-induced oxidative priming of PMNs and PMN-mediated cytotoxicity, using an in vitro assay of 51Cr release from rabbit gastric surface cells. Compared with control PMNs, IFN-gamma-primed PMNs exhibited a significant increase in cytotoxicity when stimulated with FMLP, but not when stimulated with PMA. IFN-gamma-induced, FMLP-stimulated, PMN-mediated cytotoxicity was reduced by adding superoxide dismutase to scavenge superoxide anion or by adding catalase or glutathione peroxidase to scavenge hydrogen peroxide. Cytotoxicity was also reduced by inhibiting myeloperoxidase activity with azide or scavenging HOCl with alanine or methionine. Cytotoxicity was blocked by a monoclonal antibody against the CD11/CD18 integrin of PMNs. The results indicate that the immunoregulatory lymphokine IFN-gamma primes the FMLP-stimulated cytotoxic activity of PMNs via the increased generation of reactive oxygen metabolites and indicate that cytotoxicity may require effector-target cell adherence. Therefore, T lymphocyte-derived IFN-gamma may have a role in the pathogenesis of PMN-mediated injury to gastric and gastrointestinal tract mucosa.

Helicobacter pylori and the pathogenesis of duodenal ulcer.

In summary, it appears that the role of H. pylori in duodenal ulcerogenesis is not directly associated with acid hypersecretion. Similarly, it seems unlikely that H. pylori-induced autoimmune injury is an important mechanism in duodenal ulcerogenesis. An essential question remaining is whether H. pylori infection of areas of gastric metaplasia in the duodenum is essential to ulcer pathogenesis. The low yield of H. pylori in duodenal biopsy studies argues against this mechanism. It is possible that H. pylori gastritis (present in greater than 90% of duodenal ulcer patients) results in the release of inflammatory mediators into the gastric lumen that wash down to the duodenum with gastric emptying. Such a mechanism would explain both the low recovery rate of H. pylori from duodenal biopsies in ulcer patients and the local IgA response seen in the first part of the duodenum in response to H. pylori antigens. This could also explain the high incidence of H. pylori gastritis in patients with duodenal ulcers. Obviously the four theories discussed in this review are not mutually exclusive. Significant interaction may occur between the mechanisms described. In addition, bacterial strain differences may be more important than variations in host response to H. pylori infection. Genetic studies focused on strain differences regarding mediator production and release will help clarify these issues. In the vast majority of patients with duodenal ulcer, H. pylori infection appears to be required but is not sufficient for pathogenesis of the disease. The mechanisms of ulcerogenesis related to H. pylori remain incompletely understood. Several recently identified animal models including the gnotobiotic piglet and the naturally occurring H. mustelae infection in ferrets hold substantial promise for solving the puzzle of H. pylori disease.

Gangrenous cholecystitis in an urban VA hospital.

Gangrenous cholecystitis is an advanced form of acute cholecystitis associated with increased morbidity and mortality. We sought to determine the incidence of gangrenous cholecystitis in an urban VA hospital patient population and identify any distinguishing characteristics that may aid in its preoperative diagnosis. We retrospectively reviewed all urgent admissions that underwent cholecystectomy (n = 65) over the past 7 years at the Allen Park VAMC. Using histologic criteria, 17 (26%) of these patients had gangrenous cholecystitis. As a group compared to patients with nongangrenous cholecystitis, patients with gangrenous cholecystitis were statistically older (64 vs 54) and had an elevated WBC (15.4 vs 11.5) and increased serum glucose levels (203 vs 141). Preoperative imaging studies (ultrasound and cholescintigraphy) correctly identified only 31% of the gangrenous cholecystitis patients. We conclude that in an urban VA hospital patient population, the diagnosis of gangrenous cholecystitis cannot be accurately made or ruled out among urgent admissions with acute biliary disease. Considering the high incidence (26%) and difficulty confirming the diagnosis of gangrenous cholecystitis in this setting, we recommend early surgical intervention for this and similar patient populations.

Management of ectopic thyroid nodules.

BACKGROUND: Surgical dictum states that the so-called lateral aberrant thyroid represents metastatic thyroid cancer. METHODS AND RESULTS: We present sixteen cases of patients with benign ectopic thyroid tissue. Seven cases were discovered during evaluation and treatment of hyperparathyroidism. The remaining nine cases were discovered during the evaluation and treatment of thyroid disorders or cervical nodules. In fifteen cases there is benign histology on the nodules. One case has been followed for 4 years with scans revealing a normal thyroid gland with an unchanging ectopic thyroid nodule in the superior mediastinum. In eight of our cases there have been thyroid resections searching for occult carcinomas. Histologic examination on these eight thyroid glands revealed either normal thyroid or benign nodules. CONCLUSIONS: Not all lateral aberrant thyroid tissue is malignant. The histologic condition of the nodule combined with intraoperative examination of the ipsilateral thyroid lobe can reliably guide therapy. The old dictum concerning lateral aberrant thyroid representing metastatic cancer should be removed from or modified in review texts and surgical examinations.

Neutrophil recruitment to the gastrointestinal tract.

The infiltration of an organ or tissue by neutrophils is the hallmark of acute inflammation. Recent work from many laboratories suggests that neutrophils may play a role in the development of tissue injury in a variety of disease states in the gastrointestinal tract. These diseases include gastritis, necrotizing enterocolitis, ileitis, ulcerative colitis, and ischemia reperfusion injuries. In view of this recent interest in the neutrophil and its relationship to GI diseases, it seems timely to review what is known about neutrophil recruitment to the gastrointestinal tract. This review will therefore focus on the sojourn of the neutrophil from the circulation to its destination in the GI tract.

Post-herniorrhaphy urinary retention: a randomized prospective study.

Urinary retention is a known complication of inguinal herniorrhaphy. Bladder distension due to vigorous fluid administration is believed to contribute to this problem. Our hypothesis is that fluid restriction will lower the incidence of urinary retention, post-herniorrhaphy. From January 1989 through March 1991, 113 male patients entered the study. Sixty patients (Group I) received unlimited iv fluids (1294 +/- 58 ml) and 9 patients (15%) developed urinary retention. Fifty-three patients (Group II) received 500 ml or less by protocol (485 +/- 2 ml) and 5 of these patients developed retention (9%). Thus, fluid restriction lowered the incidence of urinary retention post-herniorrhaphy but the difference did not reach statistical significance. In addition age over 60 years approached significance as a risk factor for postoperative urinary retention.

Neutrophil chemotactic activity in human gastric secretions.

To study levels of neutrophil chemotactic activity in human gastric secretions, these secretions were collected via the endoscope during elective esophagogastroduodenoscopy. Fresh samples were then prepared for the neutrophil chemotactic assay with the use of human peripheral neutrophils in modified Boyden chambers. Mean maximum chemotactic activity was 45.8% +/- 11.2% in patients with gastric inflammation compared with only 10.1% +/- 4.2% in patients with normal results of endoscopic examination. The chemotactic factors responsible for this chemotactic activity may play a role in the recruitment of neutrophils to areas of gastric mucosal injury.

Release of neutrophil chemotactic factors from gastric tissue. Initial biochemical characterization.

This study was designed to characterize neutrophil chemotactic factors released by gastric tissue. Full-thickness rabbit stomach (organ culture) was prepared and incubated in Ringer's solution at 37 degrees C. Culture supernatants were collected at 1, 2, 3, and 4 hr and assayed for neutrophil chemotactic activity in modified Boyden chambers. High levels of chemotactic activity were seen at 3 hr of incubation. Antral and fundic tissue were equally capable of producing neutrophil chemotactic activity. In addition, high levels of activity were seen from both the serosal and mucosal surfaces. Initial biochemical characterization of these gastric-derived factors revealed that: (1) a majority of the activity (80-90%) exhibited molecular weight values of greater than 300 kDa, (2) the chemotactic activity was heat stable but was partially reduced by treatment with a protease, subtilisin (37% inhibition), and (3) 70-80% of the activity in the supernatants was extracted into organic solvent (ethyl acetate). These factors may prove to be important in recruitment of neutrophils to areas of gastric injury.

Adrenocorticotropin-independent bilateral macronodular adrenal hyperplasia: an unusual cause of Cushing's syndrome.

Inappropriate ACTH secretion with bilateral diffuse or macronodular adrenal hyperplasia is the most common cause of Cushing's syndrome. This report describes a patient with Cushing's syndrome and feminization due to ACTH-independent bilateral macronodular adrenal hyperplasia. A 47-yr-old black man presented with Cushingoid features, diabetes mellitus, hypertension, impotence, and gynecomastia. Urinary cortisol and 17-hydroxycorticosteroid excretion were 94 nmol/mmol creatinine (normal, less than 32) and 5.8 mumol/mmol creatinine (normal, 0.6-3.6), respectively. Both decreased by less than 30% after administration of dexamethasone (8 and 16 mg/day), and urinary 17-hydroxycorticosteroid excretion did not increase after metyrapone (750 mg, orally, every 4 h for six doses). Plasma ACTH was undetectable (less than 1 pmol/L) and was not stimulated by administration of metyrapone or ovine CRH. Serum testosterone was 5.2 nmol/L (normal, 7-30), FSH was 5 U/L (normal, 3-18), LH was 2.8 U/L (normal, 1.5-9.2), and estrone was 767 pmol/L (normal, 55-240). Both adrenal glands were enlarged, with a total weight of 86 g (normal, 8-10), and contained multiple nodules (diameter, greater than 0.5 cm) composed of two active cell types, one of which was also observed between the nodules. Cushing's syndrome with feminization due to ACTH-independent bilateral macronodular adrenal hyperplasia is an unusual process of unknown etiology that should be included with the other known causes of Cushing's syndrome.

Early colonic anastomotic edema. Evaluation of stapled vs. hand-sewn anastomoses.

Early dysfunction of intestinal anastomoses is sometimes blamed on anastomotic edema. This study compares stapled and hand-sewn anastomoses for the development of early anastomotic edema. After segmental colon resections, one group of dogs was reconstructed with two-layered handsewn anastomoses, and the other group had stapled anastomoses. Controls were untouched small bowel in each operated animal and untouched colon in a separate group of dogs. At 24 hours postoperatively, all animals were given 125I albumin and at 28 hours the animals were killed, venous blood was obtained, and the anastomoses were harvested. Tissue levels of 125I albumin were measured at 1-mm and 1-cm distances from each anastomosis and compared with controls. This quantitative measure of edema was compared with the histologic appearance of the tissue specimens. The results show significant edema formation in both stapled and handsewn anastomoses compared with control tissues (P less than .05 for each animal). Although quantitative and histologic results demonstrate less edema in the stapled group, the difference is not significant by the Wilcoxin rank test. These and similar studies may allow improvement in surgical technique.

Effects of sodium hypochlorite (Dakin's solution) on cells of the wound module.

This study investigates the effects of sodium hypochlorite, or Dakin's solution (DS), on the function and viability of cells of the wound module (neutrophils, fibroblasts, and endothelial cells). For functional studies, the influence of DS on the in vitro migration of neutrophils was evaluated. Our data indicate that DS (2.5 x 10(-2)% to 2.5 x 10(-4)%) results in greater than 90% inhibition of the migration of both stimulated and nonstimulated neutrophils. Electron microscopy and trypan blue evaluation of neutrophils exposed to DS at these concentrations revealed normal structural features, which indicates that the observed reduction in neutrophil migration is not a result of cell death. In contrast to neutrophils, cultured fibroblasts and endothelial cells exposed to DS (2.5 x 10(-2)% or 2.5 x 10(-3)%) for 30 minutes show marked cell injury characterized by convoluted nuclei, cytoplasmic vacuolization, dilated endoplasmic reticulum, and swollen mitochondria on electron microscopy. These data suggest that DS, even at very dilute concentrations, is toxic to cells of the wound module. We therefore recommend abandonment of the use of DS in open wounds.

Frank Hastings Hamilton: medical educator and surgeon to President Garfield.

Frank Hastings Hamilton was a pioneer in academic surgery. His career involved the development of several medical schools. At the request of Mrs. Garfield, Hamilton was consulted after the shooting of President James Garfield. Surgical thinking at that time did not favor operation for gunshot wounds. Garfield's death reflected the lack of understanding in trauma care during that era. Hamilton's many contributions to medical education shall be remembered.