Biomedical subjects

J J Murray

Publications and source records attributed to J J Murray.

At least 19 recordsLinked to original sources

PubMed1997

Naturally occurring mutations in the human 5-lipoxygenase gene promoter that modify transcription factor binding and reporter gene transcription.

Five lipoxygenase (5-LO) is the first committed enzyme in the metabolic pathway leading to the synthesis of the leukotrienes. We examined genomic DNA isolated from 25 normal subjects and 31 patients with asthma (6 of whom had aspirin-sensitive asthma) for mutations in the known transcription factor binding regions and the protein encoding region of the 5-LO gene. A family of mutations in the G + C-rich transcription factor binding region was identified consisting of the deletion of one, deletion of two, or addition of one zinc finger (Sp1/Egr-1) binding sites in the region 176 to 147 bp upstream from the ATG translation start site where there are normally 5 Sp1 binding motifs in tandem. Reporter gene activity directed by any of the mutant forms of the transcription factor binding region was significantly (P < 0.05) less effective than the activity driven by the wild type transcription factor binding region. Electrophoretic mobility shift assays (EMSAs) demonstrated the capacity of wild type and mutant transcription factor binding regions to bind nuclear extracts from human umbilical vein endothelial cells (HUVECs). These data are consistent with a family of mutations in the 5-LO gene that can modify reporter gene transcription possibly through differences in Sp1 and Egr-1 transactivation.

Alleles↗

PubMed1997

Cyclosporine reduces development of obliterative bronchiolitis in a murine heterotopic airway model.

Obliterative bronchiolitis (OB), an important threat to the long-term survival of lung transplant recipients, is characterized histologically by fibroproliferation within small airways. The pathogenesis of OB is thought to involve chronic allograft rejection, and therapy frequently includes augmentation of immunosuppression. We have developed a model that reproduces the pathologic lesion of OB and allows study of interventions designed to limit airway fibrosis. In this model, heterotopic transplantation of murine airways into immune-mismatched recipients results in epithelial abnormalities and fibroproliferation in the airway lumen, changes not seen in heterotopic isografts. Cyclosporine (CsA) inhibits activation and proliferation of T lymphocytes and is commonly administered after lung transplantation. We hypothesized that use of CsA in our model system would reduce fibroproliferation in tracheal allografts. To test this hypothesis, murine tracheas were transplanted heterotopically into allo matched and allomismatched recipients, and then treated with varying doses (5, 10, 15, or 25 mg/kg i.p. q.d.) of CsA. Controls included allografts and isografts not treated with CsA. After 30 days, tracheas were harvested and examined histologically. CsA markedly reduced the development of fibroproliferation in allografts (19% in treated allografts versus 90% in untreated allografts, P<0.0001), but did not reduce inflammation or airway epithelial cell injury. High-dose (25 mg/kg/day) CsA was more effective than lower doses in reducing fibroproliferation (0% in high dose versus 29% in low dose, P=0.04). These findings demonstrate that CsA significantly reduces development of the pathologic lesion of OB, and supports the role of alloimmunity in the pathogenesis of this disease.

Animals↗

PubMed1997

Reduction of myocardial infarct size in rabbits and inhibition of activation of rabbit and human neutrophils by lidocaine.

Myocardial reperfusion is associated with increased influx of activated neutrophils and intracellular accumulation of sodium in the ischemic zone. Lidocaine is a sodium channel blocker that also inhibits several neutrophil functions. We investigated the effect of lidocaine on infarct size in rabbits undergoing 30 minutes of ischemia and 48 hours of reperfusion. Animals randomly received lidocaine (10 mg/kg, n = 11) or saline (n = 11) during occlusion. The area of necrosis (AN) was measured histologically and expressed as a percentage of the area at risk (AR). Myocardial oxygen consumption and the perfusion bed at risk were similar in the two groups. Lidocaine reduced infarct size compared with control (AN/AR = 30% +/- 4% vs 61% +/- 5%, respectively; p = 0.0001). This reduction was associated with a significant decrease in neutrophil infiltration and in the degree of hemorrhage in the reperfused myocardium. Lidocaine also significantly inhibited superoxide anion production by rabbit and human neutrophils in whole blood. Therefore, lidocaine treatment results in a significant reduction in infarct size in the rabbit model, partly through reduction of neutrophil-mediated injury to viable cells, suggesting that lidocaine may be useful to enhance myocardial salvage in patients undergoing pharmacologic or mechanical reperfusion.

Animals↗

PubMed1996

Attendance patterns and oral health.

A recent general public survey on dental health identified "the missing 50 per cent'. In the light of this, Professor Murray considers the relationship between dental attendance and oral disease, the consequences of irregular attendance, and what advice on oral health practitioners should be giving their patients for the 21st century.

Adolescent↗

PubMed1996

Dental attitudes and behaviour among a sample of dentate older adults from three English communities.

Improvements in oral health have resulted in impressive reductions in edentulousness in the middle aged and elderly. As part of a large, three-centred survey of adults aged 60 or over, 1211 dentate subjects were interviewed about their dental attendance pattern, their reasons for non-attendance, attitudes to edentulousness, treatment preferences and oral hygiene practices. The three areas sampled allowed north-south and urban-rural comparisons to be assessed. 19-28% of all subjects were dental non-attenders, but the prevalence was highest in the north. A perception that there was no need to seek dental care was the commonest reason given for non-attendance. Subjects from the northern samples were less likely to be upset at the prospect of edentulousness and less likely to opt for restorative treatment than their southern counterparts. Gender differences were pronounced in the north, with men being less concerned about edentulousness, less likely to opt for restoration and less likely to visit the dentist than women. In the south this difference was less evident. Generally, expectations were high and attitudes were based on the preservation of natural teeth. This is a positive development, but caution must be exercised to ensure that expectations are realistic.

Aged↗

PubMed1996

The continuum of dental education--one year on.

Continuing professional development should embrace all aspects of our professional life. Changes in the pattern of oral disease, developing concepts of specialisation and delivery of dental care require a flexible approach to the interface between the end of the undergraduate dental course and the early years of general professional training. This report lists a number of proposals agreed by an ad hoc working group, meeting under the auspices of the General Dental Council.

Clinical Competence↗

PubMed1996

Major clinical findings from a dental survey of elderly people in three different English communities.

A random sample of 2280 subjects aged 60 years or over from three areas of England were examined clinically in order to assess their dental health and needs. Between 33% (south of England) and 57% (north of England) were edentulous. Twenty per cent of all dentate subjects were edentulous in one arch and thus still required a complete denture. Amongst the dentate subjects geographical differences were small, but social class and behavioural differences were large. Dental non-attenders were the group who stood out as having much poorer oral health, averaging six fewer natural teeth than attenders. Nearly 50% of all teeth either had coronal fillings or needed them. Root caries was common, 20-22% of vulnerable teeth were affected and there was an age related increase in disease risk. The mean number of teeth with decayed roots per subject (0.8) was similar to the mean number with decayed coronal surfaces (0.9). Moderate tooth wear and moderate periodontal disease were both widespread. A minority of subjects had a functional dentition of 21 or more teeth. Major changes in the dental status of older adults have taken place in the last 30 years and these will continue, resulting in lower levels of edentulousness but a large need for maintenance of existing restorations.

Age Factors↗

PubMed1996

Gastroduodenal polyps in familial adenomatous polyposis.

BACKGROUND: Malignant degeneration of gastroduodenal polyps has been noted in patients with familial adenomatous polyposis. To evaluate this problem further, patients with familial adenomatous polyposis were contacted and offered upper gastrointestinal tract endoscopy. METHODS: A prospective endoscopic examination was performed in 42 patients. RESULTS: The median age of patients at endoscopy was 35 years. The duration of known familial adenomatous polyposis at the time of endoscopy was 8 years. Polyps were visualized in 21 patients (50%). Gastric polyps were seen in 14 patients (33%), duodenal polyps were seen in 11 patients (26%), and ampullary polyps were seen in 7 patients (17%). Nine patients (43%) had polyps in more than one site. Adenomatous change was noted in 73% of duodenal lesions and in only 14% of gastric polyps. Surgical intervention was required in four patients; one patient had an early ampullary carcinoma, and three patients had severe dysplasia involving the duodenum or ampulla. All four patients had undergone a previous screening examination, results of which were normal in three patients. Compared with other patients, these four patients were older (median age, 58 years; p = 0.02) and had a longer duration of disease (median duration, 25 years; p = 0.002). CONCLUSIONS: All patients with familial adenomatous polyposis require lifelong endoscopic surveillance to detect malignant degeneration, which may appear later in life.

Adenomatous Polyposis Coli↗

PubMed1996

Spectrum of abnormal rectoanal reflex patterns in patients with fecal incontinence.

PURPOSE: Abnormalities of rectoanal inhibitory or excitatory reflex in patients with fecal incontinence are well described. A spectrum of abnormal responses, other than those already described in the literature, has been observed in some patients with fecal incontinence and forms the subject of this report. METHOD: Forty-three patients with idiopathic or traumatic fecal incontinence were studied to evaluate their reflex responses to balloon distention of the rectum, and results were compared with reflex responses of 29 control subjects with no anorectal complaints. RESULTS: Control subjects revealed normal reflex responses consisting of initial excitation followed by inhibition in the proximal anal canal and an excitatory response in the distal anal canal. Patients who were incontinent revealed five different types of reflex patterns. Eleven patients (25.5 percent) with segmental sphincter defects from obstetric injuries exhibited no distal excitation but had normal response in the proximal anal canal (Group 1). Eleven patients (25.5 percent) with idiopathic incontinence exhibited normal proximal response but an inhibitory as opposed to excitatory response in the distal anal canal (Group 2). Three patients (7 percent) with iatrogenic trauma failed to register an excitatory response in the proximal or distal anal canal but revealed a normal inhibitory reflex (Group 3). Nine patients (21 percent) with idiopathic incontinence revealed excitatory response in the entire anal canal but no inhibition (Group 4). Nine patients (21 percent) with idiopathic incontinence had a normal reflex pattern (Group 5). CONCLUSION: Excitatory and inhibitory components of rectoanal reflexes may selectively be abolished in neurogenic or traumatic insults to visceral and somatic anal sphincters, resulting in altered rectoanal reflex patterns.

Adult↗

PubMed1996

Unilateral pudendal neuropathy. Significance and implications.

PURPOSE: Obstetric trauma and excessive defecatory straining with perineal descent may lead to pudendal neuropathy with bilateral increase in pudendal nerve terminal motor latencies (PNTML). We have frequently observed unilateral prolongation of PNTML. Diagnostic and therapeutic implications of unilateral pudendal neuropathy are discussed. METHODS: Records of 174 patients referred to pelvic floor laboratory for anorectal manometry and PNTML testing were reviewed. Computerized and manometry was performed using dynamic pressure analysis, and PNTML was determined using a pudendal (St. Mark's) electrode. RESULTS: No response was elicited from pudendal nerves to electric stimulation from both sides in 14 patients (8 percent) and from one side in 24 patients (13.8 percent). Bilateral PNTML determination was possible in only 136 patients (78 percent), of whom 83 patients (61 percent) had no evidence of neuropathy, revealing normal PNTML on both sides. Of 53 patients (39 percent) with delayed conduction in pudendal nerves, in 15 patients (28 percent), PNTML was abnormally prolonged on both sides, with an abnormal mean value for PNTML. In the remaining 38 patients (72 percent), PNTML was abnormal on one side; in 27 patients with an abnormal mean PNTML and in 11 patients with a normal mean PNTML. CONCLUSIONS: A significant number of patients with pelvic floor disorders have only unilateral pudendal neuropathy. Patients with unilaterally prolonged PNTML should be considered to have pudendal neuropathy, despite normal value for mean PNTML. This fact may be relevant in planning surgical treatment and in predicting prognosis of patients with sphincter injuries.

Constipation↗

PubMed1996

Laparoscopic resection for diverticular disease.

PURPOSE: The role of laparoscopic surgery in treatment of patients with diverticulitis is unclear. A retrospective comparison of laparoscopic with conventional surgery for patients with chronic diverticulitis was performed to assess morbidity, recovery from surgery, and cost. METHODS: Records of patients undergoing elective resection for uncomplicated diverticulitis from 1992 to 1994 at a single institution were reviewed. Laparoscopic resection involved complete intracorporeal dissection, bowel division, and anastomosis with extracorporeal placement of an anvil. RESULTS: Sigmoid and left colon resections were performed laparoscopically in 25 patients and by open technique in 17 patients by two independent operating teams. No significant differences existed in age, gender, weight, comorbidities, or operations performed. In the laparoscopic group, three operations were converted to open laparotomy (12 percent) because of unclear anatomy. Major complications occurred in two patients who underwent laparoscopic resection, both requiring laparotomy, and in one patient in the conventional surgery group who underwent computed tomographic-guided drainage of an abscess. Patients who underwent laparoscopic resection tolerated a regular diet sooner than patients who underwent conventional surgery (3.2 +/- 0.9 vs. 5.7 +/- 1.1 days; P < 0.001) and were discharged from the hospital earlier (4.2 +/- 1.1 vs. 6.8 +/- 1.1 days; P < 0.001). Overall costs were higher in the laparoscopic group than the open surgery group ($10,230 +/- 49.1 vs. $7,068 +/- 37.1; P < 0.001) because of a significantly longer total operating room time (397 +/- 9.1 vs. 115 +/- 5.1 min; P < 0.001). Follow-up studies with a mean of one year revealed two port site infections in the laparoscopic group and one wound infection in the open group. Of patients undergoing conventional resection, one patient experienced a postoperative bowel obstruction that was managed nonoperatively, and, in one patient, an incarcerated incisional hernia developed that required urgent laparotomy. CONCLUSIONS: Laparoscopic resection in patients with chronic diverticulitis is safe, with faster recovery and shorter hospital stay compared with conventional open surgery. Higher cost of operating room usage time makes the laparoscopic technique difficult to justify economically. Simplification of operating room use and better case selection may improve cost-effectiveness of the laparoscopic approach.

Chronic Disease↗

PubMed1996

Ileocolic resection for acute presentation of Crohn's disease of the ileum.

PURPOSE: Traditional therapy for patients with terminal ileitis found at laparotomy for appendicitis has been to perform appendectomy when the cecum is normal and to leave the diseased ileum in place. METHODS: To determine the role of ileocolic resection in the setting of acute ileitis, records of 1,421 patients with Crohn's disease seen from 1986 to 1994 were retrospectively reviewed. RESULTS: Crohn's disease was found at laparotomy for presumed appendicitis in 36 patients (2.5 percent). Ten patients underwent ileocolic resection, 23 had appendectomy, and 3 had exploratory laparotomy alone. One patient whose appendix was removed also had ileocecal bypass. Of the 36 patients, 20 were women and 16 were men. Mean age at operation was 24 (range, 11-61) years, and mean follow-up time was 14 (range, 0.1-49) years. After initial ileocolic resection, five patients (50 percent) required no further resection, with a mean follow-up time of 12.4 (range, 4-19) years. None required more than three ileocolic resections, with a mean follow-up time of 18.1 (range, 4-49) years. Of 26 patients treated traditionally, 24 (92 percent) required ileocolic resection for intractability or complications of Crohn's disease. Thirty-eight percent required resection within one year and 65 percent within three years (intractability, 8; obstruction, 3; fistula, 4; and perforation, 2). Of 24 patients who subsequently underwent resection, only 6 (25 percent) required further small-bowel resection for Crohn's disease, with a mean follow-up time of 13 (range, 0.1-34) years. CONCLUSION: The majority of patients found to have Crohn's disease at laparotomy for appendicitis required early ileocolic resection. Therefore, the traditional dictum of nonoperative therapy for these patients may not be in their best long-term interest and merits re-evaluation.

Acute Disease↗

PubMed1996

Inpatient vs. outpatient bowel preparation for elective colorectal surgery.

BACKGROUND: Recent pressures to decrease the cost of medical care have mandated preoperative outpatient bowel preparation (OBP) for elective colorectal surgery without any data documenting equivalent quality of care. This study examined the safety and efficacy of OBP compared with inpatient bowel preparation (IBP). METHODS: Records of all patients who underwent OBP for elective colorectal resection since the inception of the OBP program from July 1993 to June 1994 were compared with records of all patients who received IBP for elective procedures from January to June 1993. RESULTS: The two groups, 90 patients who underwent OBP and 98 patients who had IBP, were well matched for age, sex, diagnosis, and operations performed. The OBP group had a shorter length of hospital stay (median, 7 vs. 9 days; P < 0.0001; chi-squared analysis), whereas the complication rate was similar (19 percent in the OBP group vs. 18 percent in the IBP group), including infectious complications (10 percent in the OBP group vs. 7 percent in the IBP group). Although operating time was similar (mean, 199 vs. 213 minutes) and estimated blood loss (mean, 528 vs. 536 ml), the OBP group had significantly higher perioperative fluid requirements: intraoperative fluids (median, 4300 vs. 3700 ml; P < 0.05; Student's t-test), intraoperative colloid administration (48 vs. 29 percent; P < 0.0002; chi-squared), 24-hour postoperative fluids (3224 vs. 2700 ml; P < 0.0001; Student's t-test), and postoperative fluid challenges (50 vs. 20 percent; P < 0.0001; chi-squared analysis). CONCLUSION: Outpatient bowel preparation for elective colorectal surgery is safe and effective. It offers shorter hospital stay, and, therefore, potentially reduces medical care cost. Patients with multiple medical problems may not tolerate extensive fluid shifts; therefore, other preoperative arrangements, such as inpatient or outpatient intravenous fluid therapy, need to be considered to minimize complications that may outweigh potential cost savings.

Ambulatory Care↗

PubMed1996

Prospective comparative study of abnormal distal rectoanal excitatory reflex, pudendal nerve terminal motor latency, and single fiber density as markers of pudendal neuropathy.

PURPOSE: This study was undertaken to determine the role of abnormal distal rectoanal excitatory reflex (RAER) as a marker of pudendal neuropathy and to compare results with pudendal nerve terminal motor latency (PNTML) and single fiber density (SFD) estimation. METHODS: Fifteen female patients (mean age, 47.1 (range, 20-70) years) referred to the pelvic floor laboratory with pelvic floor disorders (fecal incontinence, 13 patients; constipation, 2 patients) were evaluated prospectively with neurophysiologic tests and balloon reflex manometry for evidence of pudendal neuropathy. RESULTS: Pudendal nerve terminal motor latency provided evidence of pudendal neuropathy in ten patients (67 percent) and was normal in five patients (33 percent). Increased SFD confirmed denervation of the external anal sphincter in 12 patients (80 percent), being normal in 3 patients (20 percent). Distal RAER was abnormal in 13 patients (87 percent) and was normal in 2 patients (13 percent). In ten patients (67 percent), the three diagnostic modalities were in complete agreement, correctly identifying neuropathy in nine patients (60 percent) and excluding nerve damage in one patient (7 percent). Distal RAER was normal despite prolonged PNTML and increased SFD in one patient (7 percent). In two patients (13 percent), distal RAER was abnormal or absent despite normal PNTML and SFD. Pudendal nerve terminal motor latency was normal in the presence of abnormal distal RAER and increased SFD on electromyography in two patients (13 percent). CONCLUSIONS: Abnormal distal RAER compares favorably with current neurophysiologic tests used to diagnose pudendal neuropathy.

Adult↗

PubMed1996

Unilateral pudendal neuropathy. Impact on outcome of anal sphincter repair.

PURPOSE: Our purpose was to study the effect of unilateral pudendal neuropathy on the results of anal sphincter repair. METHOD: Fifteen female patients who underwent external sphincter repair for fecal incontinence were studied. In all instances, incontinence was the result of obstetric delivery injury. Anal manometry and neurophysiologic investigations to document sphincter defects and pudendal neuropathy were performed in all patients. Sphincter repair was performed using an overlapping suture technique. RESULTS: All patients had anterior sphincter defects. Seven patients (47 percent) had pudendal neuropathy: six (85 percent) had unilateral neuropathy, and one (15 percent) had bilateral neuropathy. Six patients (40 percent) had excellent results; three (20 percent) had good results; four (27 percent) were improved; two (13 percent) experienced no improvement after sphincter repair. All patients with excellent results had normal pudendal nerve terminal motor latency on both sides. Of the three patients with good results, one patient had unilateral pudendal neuropathy. The patients in the remaining two groups (improved and failed) had unilateral (six patients) or bilateral (one patient) pudendal neuropathy. CONCLUSION: We conclude that both pudendal nerves must be intact to achieve normal continence after sphincter repair. Patients with unilateral pudendal neuropathy are more likely to have poor than to have good postoperative function.

Adult↗

PubMed1996

Perianal Crohn's disease. Results of local surgical treatment.

PURPOSE: This study relates our experience with local surgical management of perianal Crohn's disease. METHOD: Of 1,735 patients with Crohn's disease seen between 1980 and 1990, records of 66 patients (3.8 percent) with symptomatic perianal Crohn's disease treated by local operations were retrospectively reviewed to study outcome of local surgical intervention. RESULTS: All patients had intestinal disease that was limited to the colon in 32 patients (48 percent), ileocolonic region in 22 patients (33 percent), and ileum in 12 patients (18 percent). Types of perianal disease encountered included perianal suppuration (57), anal fistula (47), anal fissure (21), anal stenosis (5), gluteal abscess (3), scrotal abscess (2), and anovaginal fistula (2). A total of 321 episodes of anal complications necessitated 256 local surgical interventions. Local anorectal operations performed included simple incision and drainage of abscess (57), fistulotomy (35), incision and drainage of complex anorectal abscesses and fistulas and insertion of seton (24), internal sphincterotomy (6), fissurectomy (1), and anal dilation (3). Of 24 patients with horseshoe abscesses and fistulas managed with insertion of a seton and 35 patients who underwent fistulotomy as a primary procedure or in conjunction with drainage of an abscess, none experienced fecal incontinence as a direct result of the operation. Thirteen patients required proctectomy to control perianal disease, and a similar number underwent total proctocolectomy for extensive intestinal disease. Forty patients (61 percent) continue to retain a functional anus. CONCLUSION: Patients with symptomatic low anal fistula involving minimum sphincter musculature can be treated safely with fistulotomy. In treatment of patients with horseshoe abscesses and high fistulas, aggressive local surgical intervention using a seton permits preservation of the sphincter and good postoperative function.

Abscess↗

PubMed1996

A clinical comparison of a light cured glass ionomer sealant restoration with a composite sealant restoration.

OBJECTIVE: To compare the durability of a minimal composite sealant restoration (MCR) with that of a glass ionomer sealant restoration (GSR). METHODS: Under local anaesthesia, a MCR and a GSR were placed in the mouths of selected patients; allocation of restoration type was made randomly. All restorations were placed by one operator using standard procedures and were then assessed clinically at baseline and thereafter every 6 months. RESULTS: Fifty-eight patients, with a total of 66 pairs of restorations, were reviewed for up to 27 months. Assessment criteria were based upon the amount of sealant lost, the state of the pit restoration and the occurrence of caries. There were no cases of recurrent caries, and a total of only four pit restorations failed, three (4.5%) GSRs and one (1.5%) MCR. Three MCRs and seven GSRs required further additions of sealant. Survival analysis was carried out using the loss of more than a third of the sealant as the failed status. At this level, the MCRs had a significantly greater Median Survival Time (MST) (24.7 months) than the GSRs (20.7 months) (p < 0.05). Only seven (10.6%) of the MCRs lost more than a third of their sealant as compared with 17 (25.8%) of the GSRs. CONCLUSIONS: There was no significant difference in the durability of the MCR compared with the GSR in the treatment of occlusal caries. However, there was significantly better retention of the fissure sealant over the composite restoration than over the glass ionomer.

Adolescent↗

PubMed1996

A controlled trial of the effect of the 5-lipoxygenase inhibitor, zileuton, on lung inflammation produced by segmental antigen challenge in human beings.

BACKGROUND: Segmental antigen challenge (SAC) and bronchoalveolar lavage (BAL) have been proven useful for investigating IgE-mediated lung inflammation in volunteers with allergies. OBJECTIVE: This model was used to evaluate the pulmonary antiinflammatory effects of an experimental 5-lipoxygenase inhibitor (zileuton) in subjects allergic to ragweed. We hypothesized that decreased generation of leukotrienes by inhibition of the 5-lipoxygenase pathway of arachidonic acid metabolism would diminish the subsequent inflammatory response resulting from antigen challenge. METHODS: Ten subjects with allergies received zileuton or placebo, 600 mg administered orally four times a day for 8 days, and then underwent bronchoscopy, BAL of a control segment, and SAC in the contralateral lung followed by BAL of the challenged segment 24 hours later in a double-blind, placebo-controlled, crossover protocol. Urinary excretion of leukotriene E4 induced by antigen challenge plus total and differential cell counts and the amount of total protein, albumin, urea, and eosinophil cationic protein in BAL fluid were determined. RESULTS: A significant inhibition of leukotriene production (approximately 86%) was observed in subjects receiving zileuton. In addition, there was a statistically significant increase in eosinophils after antigen challenge (0.6 +/- 0.2 x 10(4) eosinophils/ml increasing to 49.0 +/- 25.0 x 10(4) in subjects receiving placebo, whereas the influx of eosinophils in subjects receiving zileuton was not statistically different from baseline (1.1 +/- 0.7 x 10(4) eosinophils/ml increasing to 16.5 +/- 4.1 x 10(4); analysis of variance for repeated measures with post hoc comparisons). CONCLUSIONS: Treatment with zileuton altered the inflammatory response after antigen challenge. Products of the 5-lipoxygenase pathway appear to be important in recruiting eosinophils to the lung after SAC.

Adult↗