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Biomedical subjects

F B Keane

Publications and source records attributed to F B Keane.

At least 19 recordsLinked to original sources

An immunohistochemical study of p21 and p53 expression in primary node-positive breast carcinoma.

AIMS: p21, an inhibitor of cyclin-dependent kinase, is involved in the p53 pathway of growth control. Its expression has been linked to cellular differentiation. It has been implicated in p53-mediated growth arrest following DNA damage and in terminally differentiated cells. This study analysed p21 and p53 expression, in a series of node-positive patients with breast carcinoma and examined histopathological parameters of the tumour and the prognostic implications of p21 and p53 expression. METHODS: One hundred and five consecutive patients with node-positive disease and at least 3 years follow-up were identified. Sections were stained for p53 and p21 using monoclonal antibodies. Results were expressed as percentage positive cells, and over 20% considered positive for p53 and over 10% considered for p21. RESULTS: p21 was overexpressed (>10% of cells positive) in 65% of patients and p53 was overexpressed (>20% of cells positive in 68%. The mean (SEM) level of p21 staining was 5.7(0.8)% and was 54.9(4.0)% for p53. There was no correlation between p21 and p53 expression (r=0.071 P=0.5). There were no significant differences in demographic criteria between patients that were p21 positive or negative and p53 positive or negative. There were no significant differences in tumour type, grade or stage between the groups. p21 expression did not have prognostic significance; however, p53 positivity was associated with a worse prognosis, which remained when controlled for stage. CONCLUSIONS: This study demonstrated p21 overexpression in 65% of patients with node-positive breast carcinoma. Levels did not correlate with p53 status and unlike p53 failed to have prognostic significance.

Adenocarcinoma↗

Should an appendix that looks 'normal' be removed at diagnostic laparoscopy for acute right iliac fossa pain?

OBJECTIVE: To find out whether the removal of the appendix from patients in whom laparoscopy for acute right iliac fossa pain shows no abnormality is justified to avoid the risk of missing acute appendicitis. PATIENTS: The records of patients who, between 1990 and 1997 had emergency laparoscopy for acute right iliac fossa pain were reviewed. Only those in whom laparoscopy had shown no abnormality and had not had the appendix removed were included in the study. METHODS: Outcome was assessed by telephone questionnaire to the patient, the general practitioner, or both. RESULTS: Emergency laparoscopy had been done for 254 patients. No abnormality was detected in 41. Full follow up was available on 34 patients (83%). 21 patients have remained entirely free of symptoms. Of the 13 patients who had recurrent symptoms, 2 subsequently had a histologically normal appendix removed, yet still had symptoms; 2 had a second laparoscopy that showed no abnormality; 5 had ultrasound; and 4 had colonoscopy or a barium enema examination. CONCLUSION: Removal of an appendix that looks 'normal' at emergency laparoscopy for right iliac fossa pain is unjustified.

Abdominal Pain↗

Laparoscopic extraperitoneal inguinal hernia repair in the day-care setting.

BACKGROUND: Totally extraperitoneal (TEP) laparoscopic inguinal hernia repair is gaining popularity, and our preference is to perform this procedure as a day case. This study evaluates the suitability of TEP repair in the day-care setting. METHODS: A policy of day-care TEP repair, unless contraindicated, was adopted for inguinal hernia repair, and the outcome was prospectively evaluated. Of 87 consecutive inguinal hernia repairs, day-care TEP was possible in 54 (62%); 17 (20%) were in-patient TEP, 14 (16%) were open repairs, and 2 (2%) were converted from TEP to open repairs. RESULTS: Among day-care TEP repairs, median visual analog pain score at discharge was 2.3/10, and 43% of patients had no pain. Complications included cord hematoma 2 (4%) and seroma 3 (6%). Median times for stopping analgesia, resumption of full activity, and return to work were 3, 3, and 6 days respectively. Complete satisfaction with day-care TEP was expressed by 91% of patients; 9% were moderately satisfied, and none expressed dissatisfaction. CONCLUSIONS: Day-care TEP repair is feasible in the majority of patients with inguinal hernias, and it is associated with minimal complications, excellent recovery, and a high degree of patient satisfaction.

Adolescent↗

A randomized controlled trial of extraperitoneal bupivacaine analgesia in laparoscopic hernia repair.

BACKGROUND: The limited space developed in totally extraperitoneal laparoscopic inguinal hernia repair (TEP) provides the ideal setting for direct instillation of local anesthetic. This study evaluates the efficacy of extraperitoneal bupivacaine analgesia in patients undergoing day-care TEP. METHODS: Fifty-six consecutive patients were randomized to intraoperative extraperitoneal instillation of bupivacaine (n = 29) or normal saline control (n = 27). Patients were blindly assessed on discharge from hospital, at 24 hours, 1 week, and 1 month postoperatively. RESULTS: Compared with controls, patients treated with bupivacaine had lower median (range) visual analogue pain scores on discharge (1.5 [0 to 5.9] versus 3.7 [0.2 to 6.9], P = 0.03), and were more frequently pain free (54% versus 31%, P = 0.078). Although this difference had gone by 24 hours, the bupivacaine group continued to recover faster; stopping analgesia earlier (2 [0 to 7] days versus 3 [0 to 21] days, P = 0.01) and returning to full activity earlier (2.5 [1 to 14] days versus 5 [1 to 21] days, P = 0.013). Of bupivacaine patients 100% were completely satisfied with the procedure compared with 81% of controls (P = 0.02). CONCLUSION: Extraperitoneal bupivacaine minimizes pain following day-care TEP repair, facilitates recovery, and increases patient satisfaction. Benefits persist beyond the pharmacological action of bupivacaine.

Adolescent↗

Evolving management of common bile duct stones in the laparoscopic era.

The role of laparoscopic duct exploration in the management of common bile duct (CBD) stones is unclear. The aim of this study is to audit the current management of choledocholithiasis in our unit and to report on the introduction of laparoscopic management, comparing it with established techniques. Over a 5-year period, 173 patients presented with CBD stones. In 105 (61%) patients, primary management of choledocholithiasis was by endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic sphincterotomy (ES) which was successful in 85 (81%) cases. Of the 20 patients with retained stones following ES, 18 underwent subsequent surgical exploration. Fifty (29%) patients underwent open CBD exploration as a primary treatment, resulting in complete clearance in 43 (86%) cases. Retained CBD calculi following open surgery occurred in seven cases and were ultimately treated by post-operative ES (n = 5), and observation (n = 2). Eighteen (10%) patients underwent primary laparoscopic CBD exploration. Four cases were converted to open surgery. Of the 14 completed laparoscopic duct explorations, 12 (86%) were successful. Two patients had retained stones, requiring secondary treatment with ERCP and ES. There was no mortality in the entire series. The complication rate was 12.4% with ERCP, 14% with open surgery, and zero with laparoscopic CBD exploration. There was no significant difference in hospital stay between groups. We conclude that the management of choledocholithiasis is in evolution, and early results suggest that laparoscopic CBD exploration compares favourably with established open surgical and endoscopic methods.

Cholangiopancreatography, Endoscopic Retrograde↗

Gut barrier failure in experimental obstructive jaundice.

Bacterial translocation from the gastrointestinal tract is central to current concepts of endogenous sepsis. Studies were designed to evaluate the potential relevance of translocation to the high incidence of infection in obstructive jaundice. Sprague-Dawley rats underwent laparotomy and division of the bile duct or sham ligation. In Study 1, rats were sacrificed after 24 hr, 1 week, and 3 weeks and the mesenteric lymph node complex, cecum, and blood were cultured and plasma endotoxin was measured. In Studies 2 and 3, sham-and bile duct-ligated rats were challenged after 1 week with operative trauma and intravenous endotoxin, respectively. Animals were sacrificed after a further 24 hr. No translocation was observed in sham-operated rats. Although colonization of the mesenteric lymph nodes was not seen in bile duct-ligated rats after 24 hr, this was evident in 75% of rats after 1 and 3 weeks. Surgical trauma and endotoxin produced bacterial translocation in 33 and 40%, respectively, of sham-operated animals; this was enhanced in bile duct-ligated rats to 75% (P < 0.01 vs shams) and 93% (P < 0.001 vs shams), respectively. Endotoxin resulted in positive blood cultures in 71% of jaundiced rats compared with none of the sham group injected with endotoxin (P < 0.001). Biliary obstruction produces bacterial translocation and this process is enhanced by surgical trauma and endotoxin. The data support the thesis of gut barrier failure in jaundice and suggest that therapies targeted toward decreasing bacterial translocation may merit evaluation in the prophylaxis and treatment of infection in the jaundiced patient.

Animals↗

Morphology, mucin histochemistry and crypt cell kinetics of ileal mucosa in an experimental model.

An animal model was used to investigate the morphology, mucin hisotchemistry and crypt cell kinetics of ileal pouch mucosa. Forty-eight Sprague Dawley rats underwent control laparotomy with ileal transection and reanastomosis, leocolic transposition of a 3 cm segment of ileum or colectomy and ileal pouch rectal anastomosis. Animals were sacrificed 20 weeks later. Partial villous atrophy and chronic inflammation were found in both transposed and pouch ileum. Although mucin histochemistry showed patchy colonic type changes, overall there was preservation of a small bowel pattern in both transposed and pouch ileum. Crypt cell mitosis, measured by bromodeoxyuridine labelling index, was reduced in ileal pouch mucosa. These data indicate that predominantly villous atrophy, rather than colonic metaplasia occurs in ileal pouch mucosa and suggest that there is a low propensity for dysplastic change in such mucosa.

Animals↗

Reversible colostomy--what is the outcome?

PURPOSE: The trend toward avoidance of a colostomy at both elective and emergency large-bowel surgery is partly driven by the perceived morbidity and low closure rates of temporary stomas. The aim of this study was to examine whether significant colostomy-related morbidity remains persistently high. METHODS: To examine this, we reviewed 120 patients with a potentially reversible colostomy performed during either elective or emergency large-bowel surgery during a seven-year period. RESULTS: Forty-seven patients underwent elective and 73 patients underwent emergency colonic or colorectal resection. Fifty-eight patients had colorectal carcinoma (48.3 percent), diverticular disease accounted for 39 patients (32.5 percent), and a miscellaneous group of 23 patients (19.2 percent) made-up the remainder. Seven patients died, all in the emergency group (9.6 percent). Colostomy-related morbidity, which included stenosis, retraction, prolapse, and hernia formation, occurred in 19.2 percent of patients, with no difference between the elective (14.9 percent) and emergency (21.9 percent) groups or underlying pathologic condition. Colostomy closure was performed initially in 71 patients (59.2 percent). Highest closure rates occurred in the diverticular group (84.6 percent), followed by the colorectal carcinoma group (48.3 percent), and then the miscellaneous group (43.5 percent). One patient died undergoing colostomy closure, and complications occurred in 25 patients (35.2 percent), requiring fashioning of a second colostomy in eight patients, two of whom were closed. Final colostomy closure rate was 54.2 percent. CONCLUSIONS: This study confirms the contention that both formation and closure of defunctioning colostomies are associated with significant complications; furthermore, approximately one-half of patients will not have their colostomy closed.

Colonic Diseases↗

Propranolol reduces the anxiety associated with day case surgery.

OBJECTIVE: To find out if propranolol, a non-cardioselective beta-blocker, can reduce the anxiety associated with day case surgery. DESIGN: Prospective randomized double blind trial. SETTING: University hospital, Ireland. SUBJECTS: An unselected group of 53 patients undergoing day case surgery. INTERVENTION: Subjects randomised to receive either propranolol (10 mg) or placebo on the morning of operation. MAIN OUTCOME MEASURES: Blood pressure; pulse, anxiety, pain score and patient satisfaction. RESULTS: Mean (SD) Hospital Anxiety and Depression score was significantly lower in the propranolol group than in the control group (2.5 (0.7) compared with 4.6 (0.7), p < 0.0001) before discharge. CONCLUSION: A low dose of propranolol given on the morning of day case surgery significantly reduced patients' anxiety.

Adrenergic beta-Antagonists↗

Impaired gut barrier function in malnourished patients.

The gastrointestinal tract is essential to host defence, acting as a barrier to absorption and translocation of gut antigens, including bacteria. In experimental models, protein malnutrition is permissive to gut barrier failure and endogenous infection. A clinical correlate has not been described. Intestinal morphology and barrier function to food protein antigens was studied in malnourished patients. Thirty-five individuals were evaluated, 20 malnourished patients and 15 well nourished hospital controls. Morphology was assessed from endoscopic biopsies of the second part of the duodenum, and serum immunoglobulin (Ig) G antibodies to gliadin and beta-lactoglobulin were measured. No antibody to food proteins was evident in the control group. In contrast, serum IgG antibodies to at least one antigen were present in 15 malnourished patients and to both antigens in ten (P < 0.0001 versus controls). Severely malnourished patients were more likely to have both antibodies present than those with mild or moderate malnutrition (P < 0.05). Antibody-positive malnourished patients had significantly better nutritional status than antibody-negative patients with malnutrition (P < 0.05). In no group of patients was there morphological evidence of abnormal mucosa or an immunological infiltrate. Gut barrier function is compromised in malnourished patients which suggests a mechanism that may facilitate gut-derived infection and sepsis.

Adult↗

Failure of macrophage activation in experimental obstructive jaundice: association with bacterial translocation.

Bacterial translocation from the gastrointestinal tract and macrophage activation are central to current theories of sepsis. The relevance of both in obstructive jaundice is unclear. The effect of bile duct ligation for 7 days on bacterial translocation to mesenteric lymph nodes and on macrophage activation in a rat model was examined. Compared with an incidence of zero in sham-ligated controls, bile-duct ligated rats had a 67 per cent incidence of Gram-negative colonization of mesenteric lymph nodes. This was associated with a significant (P < 0.001) decrease in macrophage tumour necrosis factor, superoxide anion and nitric oxide production compared with that in sham controls. Spontaneous bacterial translocation occurs in experimental obstructive jaundice and is associated with marked suppression of macrophage activation. This suggests a mechanism whereby jaundiced patients may be more susceptible to persistent infection but relatively protected against uncontrolled sepsis.

Animals↗

Results of a prospective randomized trial using DTIC and interferon as adjuvant therapy for stage I malignant melanoma.

This prospective randomized trial evaluated the effect of DTIC and interferon as adjuvant therapy for high risk stage 1 malignant melanoma in 26 patients. Both groups were well matched for depth of disease, site of melanoma and other prognostic criteria. Like other studies the findings of 2.6 times increased relative risk of mortality in the treatment arm do not support a rationale for adjuvant immuno-chemotherapy even in patients at high risk of recurrence.

Adult↗

High-dose interleukin 2 promotes bacterial translocation from the gut.

Toxicity associated with high-dose recombinant interleukin 2 (rIL-2) therapy simulates a sepsis syndrome, but the mechanism remains unclear. We hypothesised that translocated gut-origin bacteria may be important. Fifty-one male rats were randomised to receive rIL-2 by intraperitoneal injection at doses (IU) of 10(5) (n = 15), 10(4) (n = 8), 10(3) (n = 8) or 10(2) (n = 8) twice daily, or a saline bolus (n = 12). After 5 days, ileal histomorphology was assessed and the mesenteric lymph node complex cultured. Results showed that colonisation of mesenteric lymph nodes with Escherichia coli occurred in all rats treated with 10(5) IU of rIL-2, and in 62%, 37% and 12% of rats treated with decreasing doses of rIL-2. No translocation was observed in control animals. An increase in submucosal lymphatics and occasional mucosal disruption was seen only in the group receiving 10(5) IU. These data show that rIL-2 promotes bacterial translocation and suggests a mechanism that may fuel high-dose rIL-2 toxicity in man.

Animals↗

Management of bile duct stones in the era of laparoscopic cholecystectomy.

The introduction of laparoscopic cholecystectomy has resulted in increased options for the management of bile duct stones and has stimulated a fundamental reappraisal of the situation before the laparoscopic era. This article reviews the natural history of bile duct stones and details the different ways in which they may now be treated. New areas of controversy are highlighted and the need for further studies is emphasized.

Aged↗

Wedge resection alone or combined with segmental phenolization for the treatment of ingrowing toenail.

A retrospective analysis was undertaken of 387 patients treated surgically for ingrowing toenail between 1987 and 1989. In all, 203 patients were assessed and had 309 procedures performed on the median and/or lateral margins of one or both halluces. The procedures were performed by all grades of surgeon. A total of 126 wedge resections and 183 wedge resection-segmental phenolization combination treatments were performed. There were significantly fewer recurrences in the group receiving combination treatment (eight; 4.4 per cent) than in that having wedge resection alone (22; 17.5 per cent) (P < 0.001). Patients having procedures performed by senior house officers had a significantly greater chance of recurrence if a wedge resection alone was performed. It is concluded that the combination procedure gives better long-term results than wedge resection alone and can be used successfully by all grades of surgeon.

Adolescent↗

Beneficial effects of taurolidine in experimental pancreatitis.

Taurolidine has potent antiendotoxin and antimicrobial effects in vitro. This study assessed the effect of taurolidine in a well-described model of acute pancreatitis. Ninety-five male Wistar rats (250 g) were studied. Pancreatitis was induced by intraductal injection of 50 microliters of a 4% sodium taurocholate solution at a pressure of 25 cm water. Animals were randomly allocated to 1 of 10 groups: 4 groups were used to characterize the model and there were 6 treatment groups. Taurolidine (100 mg/kg) or saline was administered intravenously at Time 1, 4 hr, or 4 and 24 hr following induction of pancreatitis. Serum amylase, endotoxin levels, and blood cultures were assessed at 4 and 24 hr. Survival was documented at 1 week. Serum amylase levels were elevated in animals in whom acute pancreatitis was induced; however, there was no difference in serum amylase between animals treated with taurolidine and those treated with saline. Positive blood cultures were more numerous in saline-treated groups. Treatment with taurolidine was associated with significantly (P < 0.01) lower endotoxin levels (14 +/- 8 pg/ml) compared with saline-treated animals (350 +/- 87 pg/ml). Taurolidine administration significantly improved survival compared with controls, when given at 4, 24, and 4/24 hr postinduction of pancreatitis (P < 0.05). Taurolidine was beneficial in this model of acute pancreatitis.

Acute Disease↗

The pros and cons of laparoscopic cholecystectomy and extracorporeal shock wave lithotripsy in the management of gallstone disease.

The recent introduction of laparoscopic cholecystectomy (LAPC) has revolutionised the surgical treatment of gallstone disease. However, it has also raised doubts about the future role of extracorporeal shock wave lithotripsy (ESWL) in the treatment of gallstones. In this study, we compared patients treated successfully with ESWL and dissolution therapy with patients treated by LAPC. Out of 67 patients, 50 had successful clearance with ESWL while 50 out of 54 had successful LAPC. We evaluate treatment duration, recurrence rate (ESWL) and cost of treatment in both groups. All patients had uncomplicated symptomatic gallstones. The inclusion criteria were similar in both groups with the exception of patients with non-functioning gallbladders who were excluded from ESWL. The results of the study show that although ESWL is noninvasive and associated with minimal morbidity, it is also costly and has a high failure and recurrence rate. In contrast, laparoscopic cholecystectomy, while requiring short-term hospital stay and debility, seems to be a safe and effective alternative with an advantage in terms of cost and duration of treatment.

Adult↗