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Biomedical subjects

W Browder

Publications and source records attributed to W Browder.

At least 37 records · Page 2Linked to original sources
PubMed1995

Third place winner of the Conrad Jobst Award in the gold medal paper competition. Prevention of spinal cord dysfunction in a new model of spinal cord ischemia.

Paraplegia or paraparesis caused by temporary cross-clamping of the aorta is a devastating sequela in patients after surgery of the thoracoabdominal aorta. No effective clinical method is available to protect the spinal cord from ischemic reperfusion injury. A small animal (rat) model of spinal cord ischemia is established to better understand the pathophysiological events and to evaluate potential treatments. Eighty-one male Sprague-Dawley rats weighing 300 g to 350 g were used for model development (45) and treatment evaluation (36). The heparinized and anesthetized rat was supported by a respirator following tracheostomy. The thoracic aorta was cannulated via the left carotid artery for post-clamping intra-aortic treatment solution administration. After thoracotomy, the aorta was freed and temporarily clamped just distal to the left subclavian artery and just proximal to the diaphragm for different time intervals: 0, 5, 10, 15, 20, 25, 30, 35, and 40 minutes (five animals per group). The motor function of the lower extremities postoperatively showed consistent impairment after 30 minutes clamping (5/5 rats were paralyzed), and this time interval was used for treatment evaluation. For each treatment, six animals per group were used, and direct local intra-aortic infusion of physiologic solution (2 mL) at different temperatures with or without buffer substances was given immediately after double cross-clamp to protect the ischemic spinal cord. Arterial blood (2 mL) was infused in the control group. The data indicate that the addition of HCO3-(20 mM) to the hypothermic (15 degrees C) solution offered complete protection of the spinal cord from ischemic injury.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetates↗
PubMed1994

Lipid content of microparticulate (1-->3)-beta-D-glucan isolated from Saccharomyces cerevisiae.

The preparation of pharmaceutical grade (1-->3)-beta-D-glucans from Saccharomyces cerevisiae requires that the microparticulate glucans which are employed as the starting material for drug production be of the highest purity. Potential contaminants of the (1-->3)-beta-D-glucan isolation process are yeast cell wall lipids, which are frequently found in association with glucans. The lipid content of yeast-derived (1-->3)-beta-D-glucan during various stages of the isolation process by methyl esterification and total ion gas chromatography and mass spectrometry (GC-MS) was examined. Following sequential alkaline and acid hydrolyses, the total lipid content of (1-->3)-beta-D-glucan was 100.4 nmol/mg with 9-cis-C 18:1 fatty acid accounting for 45.3 nmol/mg glucan (45%). Following ethanol extraction of the (1-->3)-beta-D-glucan, lipid was not detected. Indeed, fatty acid methyl esters were not detectable by total ion GC-MS in all twelve samples investigated. These data demonstrate that the isolation process for yeast-derived (1-->3)-beta-D-glucan effectively reduces contamination by yeast cell wall lipids.

Cell Wall↗
PubMed1993

Acute pancreatitis of unknown etiology in the elderly.

OBJECTIVE: The incidence of acute pancreatitis in the elderly patient is increasing, and a significant number of such patients have no clearly defined etiology of their pancreatitis. To delineate the role of early organ failure versus progressive pancreatic disease in the morbidity and mortality, the authors' experience with patients older than 60 years with acute pancreatitis was reviewed. SUMMARY BACKGROUND DATA: As many as 30%-40% of elderly patients with acute pancreatitis have an unclear etiology and such patients have high rates of early organ failure and death. While some authorities have shown that pre-existing disease in these elderly patients did not contribute to subsequent morbidity, others have demonstrated that poor outcome was related to co-existing medical illness. METHODS: Their review of acute pancreatitis in the elderly was grouped into known and unknown etiology patients. Various parameters such as morbidity, mortality and length of stay were then compared between the two groups. Severity of organ failure and acute pancreatitis on admission were both graded and attempts made to correlate this severity with subsequent outcome. RESULTS: Unknown etiology patients had a greater number of Ranson's criteria (3.5 +/- .44 vs. 2.4 +/- .18) (p < 0.02), higher morbidity (48% vs. 22%) (p < 0.05), higher mortality (24% vs. 8.3%), and more SICU days (4.4 +/- 1.3 vs. 1.6 +/- .44) (p < 0.05) when compared with the known etiology group. Duration of symptoms, admission hypotension, and Ranson's criteria were unsuccessful in predicting mortality. Functional status of the various organ systems on admission did predict subsequent mortality. CONCLUSIONS: Elderly patients with acute pancreatitis of unknown etiology present with a more severe disease, have higher morbidity and longer SICU stays, and appear to have greater compromise of organ function. Organ function compromise correlates with mortality and appears more significant than severity of pancreatic disease. Aggressive support of such organ systems may be beneficial in the management of these patients.

Acute Disease↗
PubMed1993

Postoperative bowel obstruction following laparoscopic surgery.

The rapid expansion of laparoscopic surgery has not been achieved without attendant complications, some of them unique. Visceral herniation into abdominal trocar entry sites is occasionally mentioned but seldom reported. We present three cases of postoperative bowel obstruction resulting from visceral herniation into trocar entry sites in different surgical settings, suggesting that this complication may be more common than is appreciated. Awareness of this clinical problem confirms the need for meticulous closure of larger abdominal trocar sites and should be considered when dealing with abdominal disorders following laparoscopic surgery.

Aged↗
PubMed1990

Beneficial effect of enhanced macrophage function in the trauma patient.

Host immunosuppression after trauma contributes to septic morbidity. The macrophage is a key element in the host immune response. This study evaluated glucan, a macrophage stimulant, in a prospective, randomized, double-blind study of 38 trauma patients undergoing surgery. Glucan (21 patients), 50 mg/m2, or placebo (17 patients) was given intravenously daily for 7 days. Delayed hypersensitivity skin testing was performed on days 1 and 7 after trauma. Serum interleukin-1 (IL-1) and tumor necrosis factor (TNF) were assayed after trauma. While the total mortality rate was significantly less in the glucan group (0% versus 29%) (p less than 0.05), the mortality rate from sepsis was not statistically different (0% versus 17.6%). Glucan therapy significantly decreased septic morbidity (9.5% versus 49%; p less than 0.05). Serum IL-1 had a greater increase in glucan patients on day 3 after trauma (143.4 +/- 19.3% versus 78.6 +/- 11.7%; p less than 0.05), but there was no difference thereafter. Serum TNF did not vary between groups. Early increase in IL-1 correlated with subsequent skin test conversion to positive. Neither serum IL-1 nor TNF was a reliable indicator of future sepsis. Further clinical trials are indicated to evaluate biologic response modifiers that activate macrophages in the trauma patient.

Adult↗
PubMed1989

Nonperforative appendicitis: a continuing surgical dilemma.

Acute appendicitis continues as a medical challenge with newer approaches failing to improve diagnostic accuracy. The role of antibiotics in acute nonperforative appendicitis (NPA) remains unclear. In 175 patients studied at two hospitals, preoperative guidelines were used to exclude perforative appendicitis. Nevertheless, 14% of patients were found to have this condition. Surgeon's reports significantly underestimated the diagnosis when compared with the pathologists' reports. Antibiotic prophylaxis in 122 patients with NPA was studied prospectively comparing ceftizoxime (CTZ), cefamandole (CFM), and placebo (PLA). Ceftizoxime decreased the infection rate compared with PLA (0 vs. 8; P less than .01). Use of antibiotics (CTZ or CFM) resulted in decreased infections when compared with PLA (3 vs. 8; P less than .01) and fewer days of hospitalization (3.8 vs. 5.4 d, P less than .005). Analysis of infection risk factors showed no correlations except for failure to administer antibiotics and the finding of a gangrenous appendix. Operative culture results had no predictive value for either infection or pathogen identification. It is recommended that all patients undergoing surgery for NPA be given 1 d of antibiotic prophylaxis.

Acute Disease↗
PubMed1989

Villous tumors of the ampulla of Vater: local resection versus pancreatoduodenectomy.

Villous adenomas involving the ampulla of Vater are uncommon. In particular, malignant potential of villous tumors may be difficult to determine preoperatively. In such cases, the decision to perform a conservative local excision or the more radical pancreatoduodenectomy should be based on accurate histologic assessment and the possibility of obtaining adequate margins of resection.

Adenoma↗
PubMed1988

Adrenal myelolipoma: rationale for nonoperative management.

With increasing use of computerized tomography and ultrasonography, asymptomatic lesions of the adrenal gland are frequently detected. One such tumor is the adrenal myelolipoma, composed of adipose and hemic elements histologically resembling bone marrow. This tumor can be diagnosed by its characteristic appearance on CT scan, and fine-needle biopsy guided by CT can be used to obtain a tissue diagnosis. Because patients with adrenal myelolipoma typically have recurrence of symptoms after resection, surgical intervention is not indicated unless an enlarging tumor impinges on surrounding structures.

Adrenal Gland Neoplasms↗
PubMed1988

Immunosuppression in the surgical patient.

A review of both the healthy and altered immune response as it relates to the surgical patient is presented. An increasing number of immunosuppressive states have been defined in the surgical patient including trauma, burns, sepsis, malnutrition, cancer, and, more recently, acquired immunodeficiency syndrome (AIDS).Investigations of the healthy and altered immune response have led to the development of immunopharmacology, which involves the study of pharmacologic agents that modify host immune response to achieve desired therapeutic goals. Endogenous and exogenous immunomodulators are described that affect uniquely the host immune response as well as their therapeutic implications.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Acalculous hypersensitivity cholecystitis: hypothesis of a new clinicopathologic entity.

Acute acalculous cholecystitis is common, accounting for 5% to 10% of cases of acute cholecystitis. Although originally attributed to stasis and inspissated bile with subsequent obstruction of the cystic duct, acalculous cholecystitis has more recently been attributed to gallbladder ischemia from such conditions as hypotension or vasculitis. However, a significant number of cases of acute acalculous cholecystitis occur with no obvious cause. This report notes acute acalculous cholecystitis, diagnosed in 12 patients from 1982 to 1987, that was apparently precipitated by initiation of antibiotic therapy. Histologic sections of these gallbladders each disclosed a massive eosinophilic infiltrate. Two of the patients had identical signs, symptoms, and abnormal laboratory values during a previous course of erythromycin. These findings subsided when the antibiotic therapy was discontinued. We hypothesize that a significant cause of acute acalculous cholecystitis may be a hypersensitivity reaction to concurrent antibiotic therapy. Such patients should have antibiotic therapy halted or altered, which, it is hoped, will result in resolution of symptoms and avoidance of unnecessary laparotomy.

Acute Disease↗
PubMed1988

Effect of enhanced macrophage function on early wound healing.

Although the macrophage is important to wound healing, research has focused on its relationship to fibroblast and collagen synthesis. This study was designed to assess effects of enhanced macrophage function on early wound healing, before established collagen synthesis. Sprague-Dawley rats had dorsal incisions after one of three treatment regimens: (1) saline solution, 0.5 ml administered intravenously, (2) intravenous glucan, a macrophage stimulant, 20 mg; (3) topical glucan, 20 mg. Intravenous therapy was administered 24 hours before and after incision. Breaking strength was significantly increased (p less than 0.01) by both intravenous glucan (49.8 +/- 5.5 gm) and topical glucan (59.7 +/- 5.6 gm) on the fourth day after incision, compared with controls (22.0 +/- 2.6 gm). Similar results occurred on the seventh day after incision. Although formalin fixation significantly enhanced breaking strength in fresh control wounds (22.0 +/- 2.6 vs 39.5 +/- 2.2 gm), no increase occurred in wounds treated with intravenous glucan (49.8 +/- 5.0 vs 55.3 +/- 6.4 gm), indicating maximal cross-linking of collagen. Collagen synthesis, reflected by tritiated proline uptake, was no different in control versus glucan groups. Supernatants from control or glucan-activated macrophages were injected intraperitoneally or applied topically in the rat model. Activated supernatant, both intraperitoneal and topical, resulted in increased breaking strength on the fourth day after incision. Formalin fixation did not increase breaking strength in the activated supernatant groups. We conclude that enhanced macrophage function increases early wound breaking strength. This effect appears unrelated to collagen synthesis but may be related to increased cross-linking of collagen. Similar effects are seen with activated macrophage secretory products administered intraperitoneally or topically.

Administration, Topical↗
PubMed1987

Previously undescribed treatment for persistent peritoneal-perineal fistula following proctectomy.

Persistent perineal sinus is a common complication following proctectomy for inflammatory bowel disease. Complete excision of the sinus tract and obliteration of dead space have been stressed as important aspects of treatment. A patient is described in whom the perineal sinus persisted despite three surgical attempts at cure. Combined perineal exploration and laparotomy revealed a communicating peritoneal-perineal fistula. A combined perineal and peritoneal approach may be indicated in treating the perineal sinus that persists despite perineal excision.

Abscess↗
PubMed1987

Synergistic effect of nonspecific immunostimulation and antibiotics in experimental peritonitis.

To assess the role of combined immunomodulator and antibiotic therapy in sepsis, glucan--a beta 1,3 polyglucose--and gentamicin were administered in a model of murine peritonitis. ICR/HSD mice received one of four treatment regimens: 5% dextrose; gentamicin 0.02 mg intramuscularly (sub-MIC) 2 hours before peritonitis; glucan 0.1 mg intraperitoneally 24 hours before peritonitis; combined glucan-gentamicin treatment. All animals were challenged with 1 X 10(8) Escherichia coli intraperitoneally. Long-term survival was significantly enhanced in the combined therapy group (56%, p less than 0.05) when compared with D5W (0%), gentamicin alone (0%), or glucan alone (9%). Macrophage secretory activity, as assayed by interleukin-1 (IL-1) production, was significantly enhanced by combined therapy when compared with the other three treatment groups. Combined therapy significantly reduced E. coli bacteremia at 8 hours after inoculation, when compared with the other three groups. Availability of host neutrophils was assessed by peripheral counts and bone marrow proliferation assay. Combined glucan-gentamicin significantly enhanced bone marrow proliferation when compared with the other three groups and this enhancement correlated with increased circulating neutrophils. Combined immunomodulator and antibiotic therapy had synergistic effects on survival in E. coli peritonitis. This combined therapy enhanced macrophage secretory activity and bone marrow proliferation. Clinical use of immunomodulators may alter conventional use and dosage of antibiotics.

Animals↗
PubMed1987

Obstructing pseudocyst of the duct of Santorini in pancreas divisum.

Pancreas divisum is a pancreatic duct anomaly that occurs due to failure of fusion of the dorsal and ventral ducts. While recognition of this anomaly is increasing due to more aggressive endoscopic retrograde cholangiopancreatography, its significance remains unclear. A patient with chronic pancreatitis and a history of alcohol abuse was noted to have pancreas divisum. At surgical exploration, intraoperative pancreatography revealed an obstructing pseudocyst of the duct of Santorini. Extended sphincteroplasty and cystduodenostomy as well as Roux-en-Y pancreatojejunostomy were necessary to insure adequate accessory duct drainage. Surgical therapy of pancreas divisum in chronic pancreatitis should be designed to correct existing pancreatic duct obstruction.

Adult↗
PubMed1986

Impact of emergency angiography in massive lower gastrointestinal bleeding.

Fifty patients with massive lower gastrointestinal bleeding were initially managed with emergency angiography. The average age was 67.2; mean hematocrit, 23.7; and average transfusion, 7.6 units. Thirty-six patients (72%) had bleeding site located; bleeding sites were distributed throughout the colon. Etiologies of bleeding included diverticular disease (19 patients) and arteriovenous malformations (15 patients). Twenty of 22 (91%) patients receiving selective intra-arterial vasopressin stopped bleeding; however, 50% rebled on cessation of vasopressin. Thirty-five of 50 (70%) patients underwent surgery, with 57% operated on electively after vasopressin therapy. Seventeen patients had segmental colectomy, with no rebleeding. Nine of the 17 patients had diverticular disease in the remaining colon. Operative morbidity in these 35 patients was significantly improved when compared to previously reported patients undergoing emergency subtotal colectomy without angiography (8.6% vs. 37%) (p less than 0.02). Emergency angiography successfully locates the bleeding site, allowing for segmental colectomy. Vasopressin infusion transiently halts bleeding, permitting elective surgery in many instances.

Adult↗
PubMed1985

Adverse effect of splenectomy in experimental peritonitis.

Patients undergoing splenectomy have increased operative morbidity and mortality, especially when associated with gastrointestinal surgery or injury. This present study was designed to assess the effect of splenectomy on mortality in a polymicrobial fecal peritonitis model and evaluate therapy with antibiotic (cefoxitin) or immunomodulation (glucan). Human stool-barium (0.15 cc) was placed in the peritoneum of Sprague-Dawley rats at the time of splenectomy or sham surgery. Splenectomy animals were then treated with 5% dextrose, cefoxitin (60 mg im q 6 hr), glucan (7.5 mg ip prior to surgery), or cefoxitin plus glucan. Splenectomy resulted in decreased survival (5% vs 30%, P less than 0.05). Treatment with cefoxitin (90%) or glucan (47%) significantly improved survival. Combined glucan-cefoxitin therapy had no improvement over cefoxitin alone. Peritoneal and blood cultures were performed 12 hr postoperatively. There were no significant differences in growth of bacteria between sham and splenectomy animals. Cefoxitin treatment resulted in lower growth of bacteria from both blood and peritoneum (P less than 0.05). Glucan treatment caused a significant decrease in the number of bloodborne bacteria (P less than 0.05). Intravascular colloidal carbon clearance and leucocyte counts were performed at 12 hr postoperatively. Presence of peritonitis significantly enhanced intravascular clearance, while splenectomy had no effect. Addition of glucan or cefoxitin therapy to splenectomy animals did not enhance intravascular clearance. Leucocyte counts were significantly lower (P less than 0.05) when splenectomy was added to peritonitis animals. Glucan and cefoxitin therapy did not increase leucocyte counts. Based on these studies we conclude that (1) splenectomy increases mortality in fecal peritonitis, (2) antibiotic and immunomodulator afford some protection, and (3) exact mechanism of protection remains unclear.

Adjuvants, Immunologic↗
PubMed1983

Primary hyperparathyroidism in the seventies. A decade of change?

In an effort to identify new trends in the presentation and treatment of primary hyperparathyroidism, 66 patients treated since 1975 were compared with 100 patients diagnosed and treated from 1948 to 1970. Despite widespread use of multichannel analyzers, the late patients had an insignificant increase in diagnosis while asymptomatic (18 percent versus 9 percent in the early group). Hypertension was the most common presenting complaint in patients seen since 1975, compared with renal disease in patients seen before 1970. Findings of diffuse hyperplasia were more common in the late patients (17 percent versus 3 percent in the early patients). There were no differences in rates of operative complications or persistent postoperative hypercalcemia. In the late series of patients persistent hypercalcemia after surgery for hyperplasia was due to inadequate resection of parathyroid tissue. In the adenoma patients, failure to locate the abnormal parathyroid gland was the cause of operative failure.

Adult↗