Pseudomonas aeruginosa elastase stimulates ERK signaling pathway and enhances IL-8 production by alveolar epithelial cells in culture.

OBJECTIVE AND DESIGN: Bacterial products as well as the host airway inflammatory responses contribute to the pathogenesis of Pseudomonas infections. We sought to determine if Pseudomonas elastase (PE) induces mitogen-activated protein (MAP) kinase activity in association with interleukin-8 (IL-8) production by alveolar epithelial cells. METHODS: We utilized Western blot analysis to detect phosphorylation of signaling intermediates and ELISA was used to measure IL-8 production. RESULTS: We found that PE induces phosphorylation of the extracellular signal-regulated (ERK1/2) proteins of the MAPK pathway in A549 epithelial cells. Similar results were obtained using primary cultures of rabbit alveolar type II epithelial cells. PE also enhanced IL-8 production, which was abolished in the presence of the ERK activation inhibitor U0126. CONCLUSIONS: We conclude that PE activates the ERK1/2 arm of the MAPK pathway and that activation of this pathway results in enhanced IL-8 production. The results demonstrate that PE may augment pulmonary inflammation via cellular signaling that regulates expression of IL-8.

Early diagnosis of colonic carcinoma: a haemorrhagic complication after the use of tissue plasminogen activator.

Haemorrhagic complications of thrombolytic therapy for myocardial infarction are common. A 68 year old man presented with a myocardial infarction and was started on tissue plasminogen activator. Soon after he experienced rectal bleeding and a barium enema showed a small carcinoma in the colon, which was treated surgically. It is important that gastrointestinal bleeding secondary to thrombolysis is always investigated for an underlying cause.

Comparison of premorbid and postinjury mmpi-2 profiles in late postconcussion claimants.

A comparison of premorbid and postinjury MMPI-2 profiles was performed in 23 patients with mild cranial/cervical injuries. All claimants attributed major personality change to their injuries during the course of compensation-related neuropsychological examinations. Their premorbid MMPI-2 profiles were all abnormal and the modal code-type indicated somatoform psychopathology. The post-accident MMPI profiles showed continuous somatization trends, but they unexpectedly showed (a) increased defensiveness and (b) a general decrease in global psychopathology. The findings did not support an 'eggshell plaintiff' theory of chronic postconcussive complaints. The view that chronic postconcussive complaints require a wider focus on non-neuropsychological factors is enhanced.

Effect of long-term salmeterol therapy compared with as-needed albuterol use on airway hyperresponsiveness.

STUDY OBJECTIVES: To determine the effect of long-term salmeterol aerosol therapy on airway hyperresponsiveness measured by methacholine challenge. DESIGN: Randomized, double-blind, placebo-controlled, multicenter study. SETTING: Thirty-one clinical centers in the United States. PATIENTS: Four hundred eight asthmatic patients > or = 12 years of age with baseline FEV1 of > or = 70% of predicted values. Patients were not using inhaled corticosteroids. INTERVENTIONS: Twice-daily salmeterol aerosol, 42 microg, or placebo via metered-dose inhaler for 24 weeks. Backup albuterol was available. MEASUREMENTS AND RESULTS: Pulmonary function tests were performed before, during, and after treatment. Subjects recorded asthma-related symptoms, morning and evening peak expiratory flow (PEF) levels, and use of supplemental albuterol daily on diary cards. Methacholine challenges were performed 10 to 14 h postdose at weeks 4, 12, and 24, and 3 and 7 days posttreatment. Over 24 weeks of treatment, salmeterol provided significant (p < 0.001) protection against methacholine-induced bronchoconstriction of approximately one doubling dose of methacholine when compared to placebo with no evidence for a progressive decrease in protection. A rebound increase in airway hyperresponsiveness was not observed 3 and 7 days after cessation of salmeterol therapy. Salmeterol treatment resulted in sustained improvements of 0.21 to 0.26 L in morning premedication FEV1 and an improvement of 26.2 L/min in morning PEF when compared to placebo (p < 0.001). The use of salmeterol significantly reduced combined daytime asthma symptoms by 20% when compared to placebo (p = 0.005). A total of 34 and 48 exacerbations, respectively, were reported in the Salmeterol and placebo groups, and no evidence was present for a difference in the severity of asthma exacerbations between groups. Adverse event profiles were similar for the salmeterol and placebo groups. CONCLUSIONS: Regular long-term use of salmeterol aerosol resulted in sustained improvements in pulmonary function and asthma symptom control over the 24-week treatment period. There was no increase in bronchial hyperresponsiveness or loss of bronchoprotection at 24 weeks from that seen following 4 weeks of therapy. There was no evidence of rebound airway hyperresponsiveness after cessation of salmeterol treatment. Regular treatment with the long-acting beta-agonist salmeterol does not lead to clinical instability or vulnerability to unpredictable asthma attacks.

A multiple-dosing, placebo-controlled study of budesonide inhalation suspension given once or twice daily for treatment of persistent asthma in young children and infants.

RATIONALE: Topical antiinflammatory medications such as inhaled corticosteroids are recommended for therapy of asthma, but no formulation suitable for administration to infants and young children is available in the United States. METHODS: This was a 12-week, multicenter, double-blind, randomized, parallel-group study comparing the efficacy and safety of four dosing regimens of bude-sonide inhalation suspension (BIS) or placebo in 480 asthmatic infants and children (64% boys), ages 6 months to 8 years, with moderate persistent asthma. Approximately 30% of children were previously on inhaled corticosteroids that were discontinued before the study. Active treatments were comprised of BIS 0.25 mg once daily (QD), 0.25 mg twice a day (BID), 0.5 mg BID, or 1.0 mg QD. Efficacy was assessed by twice daily recording at home of asthma symptom scores and use of rescue medication, and discontinuation from the study because of worsening asthma and/or a requirement for systemic steroids. Peak flow measurements were recorded twice daily on diary and spirometry was recorded at clinic visits for those children able to perform these tests. Safety was assessed by reported adverse events and by cortisol testing (adrenocorticotropic hormone stimulation) in a subset of patients. RESULTS: Patients enrolled had an average duration of asthma of 34 months; the mean asthma symptom score was approximately 1.3 (scale of 0-3). All dosing regimens with BIS produced statistically significant improvement in various clinical efficacy measures for asthma control compared with placebo. The lowest dose used, 0.25 mg QD, was efficacious but with fewer efficacy parameters than seen with the other doses administered. Separation between active treatment and placebo in daytime and nighttime symptom scores were observed by week 2 of treatment for all BIS treatment regimens. A significant increase in peak flow measurement was observed in most active treatment groups compared with placebo in the subset of children able to do pulmonary function testing. All treatment groups showed numerical improvement in forced expiratory volume in 1 second but only the 0.5-mg BID dose was significantly different from placebo. Adverse events for the entire group and response to adrenocorticotropic hormone in a subgroup of children who underwent cortisol testing before and at the end of the treatment period were no different in budesonide-treated patients in comparison to placebo. CONCLUSION: Results of this study demonstrate that BIS is effective and safe for infants and young children with moderate persistent asthma in a multiple dose range, and that QD dosing is an important option to be considered by the prescribing physician.

Providing public health services through an integrated delivery system.

This article examines a recently implemented strategy to transfer responsibility for local public health service delivery from a county health department to a hospital-based integrated delivery system. Innovative quality management efforts at both local and state levels offer opportunities for sustained improvement in the availability and adequacy of public health services under this arrangement.

Minimally invasive surgery for colorectal cancer. Initial follow-up.

OBJECTIVE: An analysis was performed to evaluate early patterns of recurrence and survival in patients undergoing laparoscopic-assisted colectomies for primary colorectal cancer. Thirty-nine patients are available with a minimum of 24 months postoperative follow-up. SUMMARY BACKGROUND DATA: The techniques and expected surgical outcomes for patients undergoing laparoscopically assisted colectomies are slowly being defined as these procedures become more common and more widely available. One of the areas of greatest concern is the use of laparoscopic-assisted colectomy for the surgical treatment of patients with primary colorectal cancer. There are anecdotal reports in the literature describing both port site recurrence and wound recurrence in patients undergoing laparoscopic-assisted colectomies for colorectal cancer. This raises concerns about whether these recurrences are more common in patients undergoing laparoscopic procedures and whether overall survival is compromised. Wound recurrences and laparoscopic port site recurrences have been described with numerous other intra-abdominal tumors, but the precise incidence remains unknown. The authors reviewed data from 39 patients to determine early patterns of recurrence and overall survival. METHODS: Two-hundred thirty-eight laparoscopic-assisted colectomies were performed by the Norfolk Surgical Group between June 1992 and September 1995. Thirty-nine of the patients who underwent resection for colorectal cancer between June 1992 and September 1993 currently are available for at least a 2-year follow-up. Preoperative evaluation included physical examination, liver function studies, carcinoembryonic antigen, chest x-ray, computed tomography scans, and endoscopies with biopsy. Postoperative follow-up data consisted of physical examination, liver function tests, CEA, chest X-ray, computed tomography scan of the abdomen, and endoscopy of the colon. No patients have been lost to follow-up. Survival rates and patterns of recurrence were compared between node-negative and node-positive patients and compared with conventional data after open surgery. RESULTS: There were 22 men and 17 women ranging in age from 33 to 89 years. Mean follow-up was 30 months, with a range of 24 to 40 months. There were three patients with recurrence and nine deaths. Recurrence and tumor-related death rates, respectively, for each Dukes' stage were 0/1 and 0/1 for stage A, 0/7 and 0/7 for stage B-1, 1/16 and 2/16 for stage B-2, 0/1 and 0/1 for stage C-1, and 2/8 and 1/8 for Stage C-2. All six patients with Dukes' stage D disease died of metastatic colorectal cancer within 4 to 14 months of surgery. There were two patients with anastomotic recurrence. No unusual patterns of recurrent disease were noted, and there were no wound or port site recurrences. CONCLUSIONS: In this group of patients undergoing laparoscopic-assisted colectomies for primary colorectal malignancy, no adverse patterns of recurrence or decreased survival has been noted at 2-year follow-up when compared with standard open colorectal cancer surgery statistics. Prospective randomized studies with long-term follow-up will be required to better define the potential benefits and adverse effects of laparoscopic surgery for colorectal malignancy.

Laparoscopic cholecystectomy in pregnancy. A report of 6 cases and review of the literature.

BACKGROUND: Although pregnancy was initially considered an absolute contraindication to laparoscopic cholecystectomy, there have been several case reports of successful laparoscopic cholecystectomy in pregnant patients in the literature over the past 4 years. We report our experience with six patients managed successfully with laparoscopic cholecystectomy during pregnancy. METHODS: More than 1,300 laparoscopic cholecystectomies were performed by the Norfolk Surgical Group between May 1991 and June 1994. Six of these patients (approximately 0.5%) were operated on during pregnancy. We reviewed the management and operative technique used in these patients compared to our standard approach. The available literature was reviewed to identify any other factors which might be helpful in the management of these patients. RESULTS: In this series we were able to perform laparoscopic cholecystectomy successfully in all six patients in whom it was attempted, with an overall course similar to that of nonpregnant patients. There were no significant complications to the patient or the fetus. All six patients have delivered healthy children and continue to do well. DISCUSSION: With the addition of our 6 patients, there have been 32 successful laparoscopic cholecystectomies during pregnancy reported in the English literature. We feel laparoscopic cholecystectomy can be performed safely in pregnant patients and should be considered in any patient who presents with symptomatic cholelithiasis during pregnancy.

Laparoscopic-assisted colectomy. The learning curve.

One hundred fifty consecutive laparoscopic-assisted colectomies performed by a surgical team were analyzed in an attempt to define a learning curve. These colectomies performed by the Norfolk Surgical Group over a 24-month period, were divided chronologically into six groups of 25 patients each. The groups were then compared to determine if any improvement in length of procedure, complication rate, conversion rate, or length of stay developed as experience increased. Colon cancer and diverticular disease were the most common indications for surgery in all groups. Right hemicolectomy, left colectomy, and low anterior resection accounted for the majority of procedures in all groups. A significant decrease in mean operative time, from 250 min to 156 min over the first 35-50 cases was observed before leveling off at approximately 140 min for the remaining group. Intraoperative complications were low in all groups (range zero to two) and did not show any trend. There was no statistically significant difference in the conversion rate (23.3% overall) among the six groups. Length of stay decreased from 6 days in the first two groups to 5 days in the last four groups, although the difference was not statistically significant. The learning curve for laparoscopic-assisted colectomies is longer than appreciated by many surgeons, requiring as many as 35-50 procedures to decrease operative time to baseline. Complications can be kept at an acceptably low level while on the curve if a cautious approach is taken and the surgeon realizes that a prolonged operative time is not only acceptable, but appropriate during this long learning process. A conversion rate of 20-25% at any phase of the learning process may in fact represent a limitation of current technology. When combined with a low complication rate it may be the sign of a careful surgeon.

Laparoscopic-assisted colectomy. Initial experience.

OBJECTIVE: The authors studied the results of laparoscopic colectomies performed by a surgical team on 80 consecutive patients and compared these results with standard open colectomies. METHODS: Eight consecutive laparoscopic-assisted colectomies were performed by Norfolk Surgical Group in a 14-month period and compared to 53 patients who had a conventional open colectomies. Analysis included indications for surgery, types of procedure, complications, incidence and causes for conversion, length of procedure, duration of postoperative ileus, hospital stay, operating room and total hospital charges, and examination of the pathologic specimens. RESULTS: Many different types of colectomies were performed successfully and safely for a variety of surgical indications. The conversion rate was 22.5%, which decreased to 15% in the second half of the series. Complications in patients who underwent laparoscopic operations were not severe in number of type. The length of the operative procedure, operating room charge, and the total hospital charge were greater for patients undergoing laparoscopic-assisted colectomies. Patients who underwent laparoscopic operations had a shorter period of postoperative ileus and less pain, resumed a regular diet sooner, and were discharged from the hospital sooner than patients who underwent open colectomies. There was no significant difference in the pathology specimens obtained by laparoscopic-assisted colectomies compared with conventional open colectomies for length of specimen, surgical margins, and number of lymph nodes retrieved. CONCLUSIONS: This study indicated that laparoscopic techniques can be applied safely and effectively to a broad range of colonic operations. Laparoscopic-assisted colectomies take longer to perform and are more costly, but are associated with less paralytic ileus, less pain, and reduced hospital stay. Laparoscopic colectomies for the treatment of malignancy are achievable technically, but will require careful long-term study.

Ogilvie's syndrome: colonoscopic decompression and analysis of predisposing factors.

Forty-eight cases of Ogilvie's syndrome, colonic pseudo-obstruction, presenting between 1983 and 1989 were retrospectively reviewed to assess the results of colonoscopic decompression and to identify potential etiologic factors. Three patients had spontaneous resolution with medical treatment. Forty-five patients required 60 colonoscopic decompressions: 38 (84 percent) were successfully treated using colonoscopy; five (11 percent) required an operation; and two died within 48 hours of colonoscopy from medical causes. No complications or deaths were the result of colonoscopy. Twenty-nine patients (64 percent) were successfully treated with a single colonoscopy. One-third of patients required serial decompressions. Average cecal diameter in patients with successful colonoscopic decompression was 12.4 cm but was larger for patients requiring more than one colonoscopy (13.3 cm) and for those who failed colonoscopic therapy (13.4 cm). The spine or retroperitoneum had been traumatized or manipulated in 52 percent of patients. Patients with Ogilvie's syndrome were being treated with narcotics (56 percent), H-2 blockers (52 percent), phenothiazines (42 percent), calcium-channel blockers (27 percent), steroids (23 percent), tricyclic antidepressants (15 percent), and epidural analgesics (6 percent) at diagnosis. Electrolyte abnormalities included hypocalcemia (63 percent), hyponatremia (38 percent), hypokalemia (29 percent), hypomagnesemia (21 percent), and hypophosphatemia (19 percent). Colonoscopic decompression in Ogilvie's syndrome is safe and effective management. Multiple pharmacologic and metabolic factors, as well as spinal and retroperitoneal trauma, appear to alter autonomic regulation of colonic function, resulting in colonic pseudo-obstruction.

Successful treatment of postoperative chylothorax using an external pleuroperitoneal shunt.

We report 3 patients with chylothorax who were successfully managed as outpatients using external pleuroperitoneal shunts. This external shunt has the advantage over subcutaneously placed shunts of pumping large volumes of fluid with each compression of the pumping chamber, of not causing the discomfort associated with pumping a subcutaneous chamber, of not becoming difficult to find in the subcutaneous space, and of being constructed of larger components which do not kink or become easily clogged with fibrinous debris.

Injury surveillance: a method for recording E codes for injured emergency department patients.

STUDY PURPOSE: Little information exists on the cause of injury for patients who are treated and discharged from emergency departments; these patients comprise approximately 90% of all injured patients requiring medical care. A method is described to assign external cause of injury codes (E codes) prospectively to all injured patients seen in a large-volume ED. METHODS: E code assignment was performed by the ED triage nurses on entrance to the ED. A checklist was used that contained frequently occurring codes as identified in a pilot study. E codes were entered into the patients' records on the hospital mainframe computer by a medical records technician. These were acquired for a nine-month period to determine feasibility, accuracy, and ease of use. Accuracy was verified retrospectively. RESULTS: During the nine-month period, 67,495 patients were treated. Acute injury accounted for 16,186 of the visits, and 2,085 were return visits for a previously treated injury. The majority of patients with any injury type were treated and discharged and would not have been included in traditional data sets of injured patients. Overall admission rate for injury was 13%. Accuracy of prospectively assigned E codes was 98%, and this method of assigning E codes resulted in no additional effort by the triage nurse. CONCLUSION: E coding is a valuable method for injury surveillance, easily performed in EDs with high volume. Its value is essential for injury prevention research on injuries from any cause.

Change in endothelial cell morphology at arterial branch sites caused by a reduction of intramural stress.

Arterial branch sites have very high intramural stresses at physiologic intraluminal pressures; the same sites have a predilection for atherosclerosis. The effect of intramural stress on endothelial cell morphology was investigated. Five rabbits had permanent casts placed around a segment of the abdominal aorta-left renal artery branch area during controlled hypotension, thus reducing intramural stress without narrowing the lumen. These five animals, and three normal rabbits, were sacrificed after 4-8 weeks, and the vessels were perfused with buffered 2.5% glutaraldehyde for 2 h at 100 mm Hg pressure. The aortas were examined by scanning electron microscopy. In normal aortas, the distal region of the ostia of the left renal and celiac arteries just beyond the flow divider displayed many morphologically altered endothelial cells ranging from spindle shape to cobble-stone shape. The same aortic area of casted rabbits, as well as the straight abdominal aorta in all rabbits, showed a smooth surface of endothelial cells with intact cell borders and no morphologically altered cells. At branch sites, the occurrence of morphologically altered endothelial cells may be due to increased intramural stress. When intramural stress is reduced, the morphology of branch endothelial cells changes to resemble that of the unbranched regions. In conclusion, endothelial cell morphology changes in response to changes in intramural stress.

The Flying Obstetric and Gynaecology Service in rural Queensland: its first two years.

OBJECTIVE: To present a report of the first two years of the Queensland Flying Obstetric and Gynaecology (FOG) Service which commenced operation in July 1988, and to assess the impact of the service on rural Queensland. DESIGN: Data were collected retrospectively for the surgical treatment and consultations provided by the FOG Service in its first two years, and for the obstetric and gynaecological surgery performed at Alpha Hospital, a typical rural hospital, before and after the inception of the service. SETTING: The service provides specialist routine and emergency care for the women of 24 western Queensland towns scattered over approximately three-quarters of the area of the State. RESULTS: In the first two years of operation of the service, the team performed 4985 consultations, 1127 colposcopies, 1793 operations, 1143 ultrasound scans, answered 100 emergency calls and flew 318,650 km, equivalent to eight times around the world. In the seven years before the FOG Service began, only 17 gynaecological operations were performed at Alpha Hospital; in the first two years of the service the team performed 47 operations in this town. CONCLUSIONS: The FOG Service has made a very significant impact on the delivery of specialist services to the women of outback Queensland, and has also provided continuing education opportunities and professional support for remotely placed rural medical and nursing staff. The service has proved its worth in Queensland, and provides a model for the development of similar services in other large States of Australia.

Pleural anesthetics given through an epidural catheter secured inside a chest tube.

Pain management after thoracic surgical procedures is a difficult clinical problem. A variety of pain management methods are used with variable efficacy. This paper presents an effective method of pleural anesthetic administration using a pleural catheter inserted through a chest tube.