Cohort study of mesenteric panniculitis and its relationship to malignancy.

BACKGROUND: Mesenteric panniculitis (MP) is a rare condition that historically has been associated with the presence of malignancy. Paraneoplastic phenomena in general regress with cure and in most cases with treatment of the cancer. This study was undertaken to determine whether MP regressed with cancer treatment and cure. METHODS: This was a retrospective review of a database of all patients with MP confirmed on CT between 2003 and August 2015 at Christchurch Hospital. Patients were categorized as having malignant or non-malignant disease, and follow-up scans were assessed for remission of MP. Patients with malignancy were further categorized as having malignancy cured or not cured. RESULTS: A total of 308 patients were identified with possible MP; 135 were excluded as radiological appearances were not typical of MP (43 patients) or there was no follow-up CT (92). Of 173 patients (131 men) included, 75 (43·4 per cent) were diagnosed with malignancy. Follow-up imaging showed that 33 patients (19·1 per cent) had remission of MP, whereas 140 (80·9 per cent) had no remission. There was no difference in the rates of MP remission in the malignancy versus no malignancy groups (P = 1·000), or between groups in which malignancy was cured or not cured (P = 0·572). Nor was there any difference in the rates of MP remission in malignancy cured versus no malignancy groups (P = 0·524). CONCLUSION: MP does not behave like a paraneoplastic phenomenon. The association with malignancy is most likely an epiphenomenon of the many CT images acquired for staging of cancer.

Salvage surgery in patients with recurrent or residual squamous cell carcinoma of the anus.

INTRODUCTION: Anal squamous cell cancers are uncommon, and primary treatment is radical chemoradiotherapy. The role of radical surgery is in salvage of patients with residual and recurrent disease. The primary aim of the study is to determine how often such salvage surgery is required, while the secondary aim is to determine which features indicate salvage surgery may be required and to determine the outcome of salvage surgery. METHODS: A prospective database was analysed of all patients with anal cancer over an 18 year period (Dec 1996-Jan 2015). The records of patients requiring salvage surgery were reviewed. RESULTS: 203 Patients were identified with anal cancers, of which 180 had squamous cell anal carcinoma. 112 Female (median age 59.4, range 33-92) 68 male (median age 63.8 range 36-87). Of these 27 patients (15%) required salvage surgery. 23 Patients had a R0 resection. 18 Patients had an extended resection (16 R0) while 9 had a routine APR (7 R0). The 30-day post-operative mortality rate was 0%. The overall 5 year survival was 78%, not significantly different from those not requiring salvage surgery (p = 0.23). Age, gender, AJCC stage, T stage, radiation therapy alone, were not predicators of the need for salvage surgery. CONCLUSIONS: Salvage surgery is uncommonly required. Extended surgery beyond routine APR is often required to obtain an R0 resection. Excellent patient survival can be achieved in highly selected cases. There were no identifiable clinical predictors of those needing salvage surgery, and consideration should be given to explore molecular and genetic factors.

Progress in the management of retrorectal tumours.

AIM: Tumours in the retrorectal space are rare and pathologically heterogeneous. The roles of imaging and preoperative biopsy, nonoperative management and the indications for surgical resection are controversial. This study investigated a series of retrorectal tumours treated in a single institution with the aim of producing a modern improved management algorithm. METHOD: A retrospective analysis was conducted of the management of all retrorectal lesions identified between 1998 and 2013 from a radiology database search. Patient demographics, presenting symptoms, imaging, biopsy, management and the results were recorded. Descriptive statistics were used and Kaplan-Meier survival analysis was performed. RESULTS: Sixty-nine patients with a confirmed retrorectal tumour were identified. The median age was 50 (36-67 interquartile range) and 42 (56%) were female. Twenty (29%) of the tumours were malignant: 4 of 41 cystic lesions were malignant (12.9%) vs. 16 of 28 solid (or heterogeneous) lesions (57.1%) (P < 0.0001). Imaging demonstrated a 95% sensitivity and 64% specificity for differentiating benign from malignant tumours. Magnetic resonance imaging (MRI) was significantly better at distinguishing between benign and malignant tumours than computed tomography (94% vs. 64%, P = 0.03). Percutaneous biopsy was performed in 16 patients and only 27 underwent resection. There was no evidence of local recurrence associated with biopsy. Solid lesions were associated with a nonsignificant decreased overall survival (P = 0.348). CONCLUSION: This study demonstrated that MRI should be the investigation of choice for retrorectal lesions. Biopsy of solid lesions is safe and useful for guiding neoadjuvant and surgical therapy. Cystic lesions without suspicious radiological features can be followed by serial imaging without resection.

Malignancy and mesenteric panniculitis.

AIM: Mesenteric panniculitis (MP) is a chronic inflammatory process of the small bowel mesentery that has been reported in conjunction with malignancy. The objectives of the present study were to identify the frequency and type of cancers that may coexist with MP and whether these can be seen on the initial diagnostic computerised tomography (CT). METHOD: A prospective database was kept of patients diagnosed with MP in the Canterbury region of New Zealand between 1 January 2003 and 31 December 2014. CT scans were independently reviewed. Clinical records were reviewed and family doctors were contacted for additional information. RESULTS: There were 302 patients with possible MP identified and 259 in whom it was confirmed on review. Seventy-eight patients had a diagnosis of malignancy, with 54 having a current cancer (59 total cancers), 33 a past cancer and nine both. Of the 59 current cancers the most common primary sites were colorectum (19), lymph nodes (17), kidney (six) and prostate (four). Fifty-four were at sites included on an abdominal CT scan. At all sites [except prostate (0/4)] there were high rates of detection on CT with 44/54 cancers visible including 20/23 gastrointestinal tract, 14/17 lymphomas and 9/9 non-prostate urogenital tract malignancies. Six people were subsequently diagnosed with cancer after the index CT. CONCLUSION: When MP occurs in association with malignancy, the commonest primary sites are large bowel, the lymph nodes and the urogenital tract. In those with MP on imaging, any cancer except prostate can usually be seen on the index CT. Further extensive investigation in asymptomatic patients is therefore likely to be of low yield.

Does Bowel Preparation for Colonoscopy Affect Cognitive Function?

Colonoscopy is a common procedure used in the diagnosis and treatment of a range of bowel disorders. Prior preparation involving potent laxatives is a necessary stage to ensure adequate visualization of the bowel wall. It is known that the sedatives given to most patients during the colonoscopy cause a temporary impairment in cognitive function; however, the potential for bowel preparation to affect cognitive function has not previously been investigated. To assess the effect of bowel preparation for colonoscopy on cognitive function. This was a prospective, nonrandomized controlled study of cognitive function in patients who had bowel preparation for colonoscopy compared with those having gastroscopy and therefore no bowel preparation. Cognitive function was assessed using the Modified Mini Mental State Examination (MMMSE) and selected tests from the Cambridge Neuropsychological Test Automated Battery. Individual test scores and changes between initial and subsequent tests were compared between the groups. Age, gender, and weight were also compared. Forty-three colonoscopy and 25 gastroscopy patients were recruited. The 2 groups were similar for age and gender; however, patients having gastroscopy were heavier. MMMSE scores for colonoscopy and gastroscopy groups, respectively, were 28.6 and 29.5 (P = 0.24) at baseline, 28.7 and 29.8 (P = 0.32) at test 2, 28.1 and 28.5 (P = 0.76) at test 3. Motor screening scores for colonoscopy and gastroscopy groups, respectively, were 349.3 and 354.1 (P = 0.97) at baseline, 307.5 and 199.7 (P = 0.06) at test 2, 212.0 and 183.2 (P = 0.33) at test 3. Spatial working memory scores for colonoscopy and gastroscopy groups, respectively, were 14.4 and 6.7 (P = 0.29) at baseline, 9.7 and 4.3 (P = 0.27) at test 2, 10 and 4.5 (P = 0.33) at test 3. Digit Symbol Substitution Test scores for colonoscopy and gastroscopy groups, respectively, were 36.3 and 37.8 (P = 0.84) at baseline, 36.4 and 40.0 (P = 0.59) at test 2, 38.6 and 40.8 (P = 0.76) at test 3.This study did not find evidence of cognitive impairment resulting from administration of bowel preparation before colonoscopy.

Prevalence and Types of Anemia and Associations with Functional Decline in Geriatric Inpatients.

BACKGROUND: The prevalence of anemia in hospitalized seniors has been linked to poor functional outcomes, increased mortality, and longer hospital stays, and has been associated with advancing age, male sex, and cognitive impairment. Despite the potential for complications, anemia often is undiagnosed and/or untreated in seniors. OBJECTIVES: Examine (a) the distribution of anemia diagnosis and treatment in patients in a rehabilitation hospital, and (b) patients' cognitive and functional outcomes. DESIGN: Retrospective chart review of medical records of 132 patients. MEASUREMENTS: The presence and type of anemia were determined based on the World Health Organization criteria for adults and Smith's algorithm, respectively. The Mini-Mental State Exam (MMSE) was used to measure cognitive status. Functional impairment was assessed using the Functional Independence Measure (FIM). RESULTS: The mean age of the sample was 82.20 years, with 68% being female, the mean MMSE and FIM scores were 23.95 (SD = 4.3) and 82.82 (SD = 15.63), respectively. In total, 67% of males and 46% of females were anemic (P < 0.05). The majority of anemias were caused by nutritional deficiencies. The percent of anemic females receiving treatment for anemia was higher (71%) than the percent of anemic males (46%) (P < 0.05). The majority of the patients improved functionally regardless of anemia status. CONCLUSIONS: Results indicated that a substantial number of patients in a geriatric hospital were anemic, with significant percentage going untreated. The overall improvement in patients' functional abilities suggests that remedial rehabilitation of frail seniors has an impact on recovery during their hospital stay.

The low FODMAP diet improves gastrointestinal symptoms in patients with irritable bowel syndrome: a prospective study.

BACKGROUND AND AIM: Current treatment for irritable bowel syndrome (IBS) is suboptimal. Fermentable oligo-, di-, mono-saccharides and polyols (FODMAPs) may trigger gastrointestinal symptoms in IBS patients. Our aim was to determine whether a low FODMAP diet improves symptoms in IBS patients. METHODS: Irritable bowel syndrome patients, who had performed hydrogen/methane breath testing for fructose and lactose malabsorption and had received dietary advice regarding the low FODMAP diet, were included. The effect of low FODMAP diet was prospectively evaluated using a symptom questionnaire. Furthermore, questions about adherence and satisfaction with symptom improvement, dietary advice and diet were assessed. RESULTS: Ninety patients with a mean follow up of 15.7 months were studied. Most symptoms including abdominal pain, bloating, flatulence and diarrhoea significantly improved (p < 0.001 for all). 75.6%, 37.8% and 13.3% of patients had fructose, lactose malabsorption or small intestinal bacterial overgrowth respectively. Fructose malabsorption was significantly associated with symptom improvement (abdominal pain odds ratio (OR) 7.09 [95% confidence interval (CI) 2.01-25.0], bloating OR 8.71 (95% CI 2.76-27.5), flatulence OR 7.64 (95% CI 2.53-23.0) and diarrhoea OR 3.39 (95% CI 1.17-9.78), p < 0.029 for all). Most patients (75.6%) were adherent to the diet, which was associated with symptom improvement (abdominal pain, bloating, flatulence and diarrhoea all significantly associated with adherence, r > 0.27, p < 0.011). Most patients (72.1%) were satisfied with their symptoms. CONCLUSIONS: The low FODMAP diet shows efficacy for IBS patients. The current strategy of breath testing and dietary advice provides a good basis to understand and adhere to the diet.

Patterns of recurrence in patients with acute diverticulitis.

BACKGROUND: The natural history of acute diverticulitis remains unclear, with the role of prophylactic surgery following conservatively managed diverticulitis increasingly controversial. This study investigated recurrence rates, patterns and complications after conservatively managed diverticulitis. METHODS: This was a retrospective chart review of all patients admitted with diverticulitis between June 1997 and June 2002. Demographic data, management, recurrence rates, complications and subsequent surgery were recorded. RESULTS: Some 502 patients were identified, 337 with uncomplicated and 165 with complicated diverticulitis. Median follow-up was 101 (range 60-124) months. Of 320 patients with uncomplicated diverticulitis managed conservatively, 60 (18.8 per cent) had one episode of recurrence, whereas 15 (4.7 per cent) had two or more episodes. After an initial attack of uncomplicated diverticulitis, only 5.0 per cent developed complicated disease. Complicated disease recurred in 24 per cent, compared with a recurrence rate of 23.4 per cent in those with uncomplicated diverticulitis (P = 0.622). When recurrence occurred, it usually did so within 12 months of the initial episode. CONCLUSION: Acute diverticulitis has a low recurrence rate and rarely progresses to complications. Any recurrence is usually early, in a pattern more consistent with failure of the index episode to settle. Subsequent elective surgery to prevent recurrence and the development of complications should be used sparingly.

Immunomodulation does not alter histology in resected Crohn's disease.

BACKGROUND: The use of immunomodulators (Azathioprine, 6-Mercaptopurine and Methotrexate) and biological agents (Infliximab and adalimumab) for the treatment of Crohn's disease (CD) has increased in the recent years with the aim of treating the inflammatory component of the disease and hoping to change the natural history of the disease. The aim of this study was to determine if the use of immunomodulators or biological agents in the 2 years prior to resection affects the histopathological characteristics of the patient's disease. METHODS: A retrospective review was conducted over a 10-year period (1996-2005) of patients who underwent resection for CD. Clinical case notes and histology specimens were reviewed. Patients treated with Azathioprine, 6-Mercaptopurine, Methotrexate or Infliximab for more than 3 months within the 2 years preceding surgery were deemed to have been immunomodulated. The results were also analysed by Montreal phenotype. RESULTS: A total of 165 patients were identified. 52 patients had been treated with either immunomodulator or biological agent. Of 20 histological features examined, only muscular hypertrophy approached significance (P = 0.05), Montreal A and Montreal L phenotypes were the same regardless on immunomodulators, however, there was a significant difference (P = 0.03) with regard to Montreal B in patients with stricturing disease being more likely to have received an immunomodulator. CONCLUSIONS: In this cohort of patients requiring resection for CD, those with stricturing disease were more likely to receive immunomodulators or biologics than those without stricturing disease. However, there were no significant histological differences in the resected specimens between those who did and those who did not receive these drugs.

The impact of splenectomy on outcome after resection for colorectal cancer: a multicenter, nested, paired cohort study.

PURPOSE: This study was designed to determine whether incidental splenectomy for iatrogenic injury affects long-term cancer-specific survival in patients having resection of an adenocarcinoma of the sigmoid or rectum. METHODS: A retrospective case-matched review of patients undergoing surgery for colorectal cancer with incidental splenectomy between January 1, 1990 and December 31, 1999 was undertaken. Data were analysed for age, American Society of Anesthesiologists physical status, gender, disease stage, operation type, and outcome. These cases were matched with patients from the same center, of the same age and gender, with the same stage of disease and operation, who did not require a splenectomy at the time of their surgery. RESULTS: Fifty-five patients were identified who had an iatrogenic splenectomy. Matched gender, stage, and American Society of Anesthesiologists-matched controls were identified. Follow-up from time of surgery to death or last follow-up ranged from 2 to 205 (median, 43) months. A Kaplan-Meier survival analysis using the Cox proportional hazards model to define the statistical significance found a significant difference between the groups favoring those without splenectomy (hazard ratio, 1.8; 95 percent confidence interval (CI), 1-3.3; P=0.0399). Cancer-specific survival at five years was 70 vs. 47 percent and at ten years was 55 vs. 38 percent. DISCUSSION: Patients with colorectal cancer who had splenectomy as a result of iatrogenic damage of the spleen while undergoing resection of the sigmoid or rectum for adenocarcinoma had a significantly worse prognosis.

Reasons for failure to diagnose colorectal carcinoma at colonoscopy.

BACKGROUND AND STUDY AIMS: Colonoscopy can produce false-negative results, and the reasons for this remain obscure. The aim of this study was to examine why cancers are missed at colonoscopy. PATIENTS AND METHODS: All colonoscopies carried out at Christchurch Hospital, New Zealand, over a 43-month period (1 October 1997 - 30 April 2001) were retrospectively analyzed (the data having been prospectively collected). All cases of colorectal carcinoma during the period 1 October 1997 - 30 July 2001 (3 months longer, to capture delayed diagnoses) were also identified. The two databases were then compared, and all cases in which a colonoscopy had been performed more than 6 weeks before a colorectal carcinoma specimen being received by the pathology department were identified and analyzed. RESULTS: A total of 5055 colonoscopies were undertaken in 4598 patients. Over this period, 630 colorectal carcinomas were identified in the pathology database; 286 of the patients affected were in the colonoscopy and pathology database. Sixty-six patients had had a colonoscopy performed more than 6 weeks before the diagnosis of colorectal carcinoma. Carcinoma was identified in 48 of these 66 patients, and management was being provided. Seventeen cancers (5.9 %) were missed at colonoscopy, and the patients had had an incomplete colonoscopy in nine of these cases. In seven of the 17, an alternative benign cause was recorded. In four patients, a lesion was seen and thought to be benign, although subsequently proven not to be. In another four cases, the cancer was not diagnosed despite adequate bowel preparation and what was thought by the colonoscopist to be an adequate colonoscopy. CONCLUSIONS: Colonoscopy missed 17 of 286 cancers (5.9 %). The reasons why cancers were missed relate to incomplete colonoscopy, poor bowel preparation, misinterpretation of what was seen, failure to carry out adequate biopsy (and follow-up) of lesions seen, and systems failures related to follow-up investigations in patients who had an incomplete colonoscopy. The fact that colonoscopy and barium enema investigations may fail to diagnose cancers has important medicolegal implications. The recognition that colonoscopy may miss a cancer should encourage doctors to reinvestigate patients when there is a lack of correlation between the clinical and investigative findings.

Penile and clitoral stimulation for faecal incontinence: external application of a bipolar electrode for patients with faecal incontinence.

OBJECTIVE: The aim of this study was to assess the effect of a novel pudendal nerve stimulator on clinical and anorectal manometric parameters in patients with faecal incontinence. METHOD: Retrospective cohort analysis of consecutive patients presenting with faecal incontinence who had failed initial conservative treatment and were not suitable for surgical intervention in a university hospital incontinence clinic. Biofeedback using a pudendal nerve stimulator comprising a bipolar electrode applied to the base of the clitoris or penis. Electrical pulse voltage was self-titrated and defined periods of treatment were prescribed. Anorectal manometry and Cleveland incontinence scores were assessed. RESULTS: There was a significant reduction in incontinence symptom score after pudendal nerve stimulator treatment in the 42 patients treated and who had a complete set of data (median age 57 years (range 37-81); 39 female, 3 male). This was accompanied by significant improvements (P < 0.05) in anal sphincter tone, maximal tolerated rectal volume and the sustained rectoanal inhibitory reflex. CONCLUSIONS: An externally applied pudendal nerve stimulator improves symptoms and physiological evidence of faecal incontinence but long-term follow up is not available for these patients.

A retrospective audit of long-term lower limb complications following leg vein harvesting for coronary artery bypass grafting.

OBJECTIVE: To evaluate the prevalence of leg complications following leg-vein harvest for coronary artery bypass grafting. METHOD: A questionnaire was sent to patients who had coronary artery bypass surgery between January 1993 and December 1998. Questions addressed pain, numbness, infection, swelling and general healing. The relationship between the risk factors of diabetes, peripheral vascular disease, previous fractures/injuries to legs, previous deep vein clots and arthritis affecting the legs with post operative symptoms of pain, numbness, swelling and general healing was explored with multivariate analysis. RESULTS: Of 700 questionnaires sent out 497 were returned, of which 422 (60%) were suitable for analysis. Numbness or tingling related to the wound was reported by 256 (61%), of whom 94 (37%) improved within 3 months. However, 105 (41%) had persistent numbness beyond 2 years. Pain in the wound was reported by 193 (46%), of whom 149 (77%) reported that this had improved by 3 months and only 19 (10%) had pain persisting beyond 2 years. A leg wound infection was reported by 126 (32%) patients, with 82 (65%) of these receiving antibiotics. A total of 336 (87% of 387 responses) described their wound as completely healed at 3 months. Unilateral leg swelling was reported by 175 (41%) with 98 of these (56% of those with swelling) improving by 3 months and 41 (23%) with swelling persisting beyond 2 years. There was no relation of wound problems to examined risk factors diabetes (P-values for numbness 0.31, wound healing 0.15, swelling 0.21, pain 0.22) and peripheral vascular disease (P-values for numbness 0.8, wound healing 0.21, swelling 0.18, pain 0.09). There was insufficient data to comment on the influence of fractures/injuries to legs, previous deep vein clots and arthritis affecting the legs. CONCLUSIONS: Wound complications are common following leg vein harvest. Prevalence of infection was higher than has previously been reported. Few people suffer long-term pain from saphenous nerve damage although paraesthesia and swelling were common long-term complications. We did not identify either diabetes or peripheral vascular disease as a risk factor for pain, numbness, swelling or problems with general healing. There is a need for a large multicentre prospective study.

The utility of laparoscopy in the diagnosis of acute appendicitis in women of reproductive age.

AIM: To see whether laparoscopy improves the accuracy of a clinical diagnosis of acute appendicitis in women of reproductive age, and to determine what the long-term sequelae are of not removing an appendix deemed at laparoscopy to be normal. METHOD: The initial part of the study was undertaken during 1991-1992. Female patients between 16 and 45 years were eligible for inclusion once a clinical decision had been made to perform an appendicectomy for suspected acute appendicitis. Following consent, patients were randomized into two groups. One group had open appendicectomy, as planned. The other group had laparoscopy, followed by open appendicectomy only if the appendix was seen to be inflamed or was not visualized. The end points for the study were the clinical outcomes of all patients, and the results of histology, where appropriate. An attempt was made to contact all patients at 10 years to determine whether they had had a subsequent appendicectomy, or had been diagnosed with another abdominal condition that might be relevant to the initial presentation in 1991-1992. RESULTS: Laparoscopic assessment was correct in all cases in which the appendix was visualized. Diagnostic accuracy was improved from 75% to 97%. Laparoscopy was associated with no added complications, no increase in hospital stay in patients who went on to appendicectomy, and a reduction in hospital stay for those who underwent laparoscopy alone. No patients developed a problem over the 10-year follow-up period from having a normal-looking appendix not removed at laparoscopy. CONCLUSION: Laparoscopic assessment of the appendix is reliable, and to leave a normal-looking appendix at laparoscopy does not appear to cause any long-term problems.

A multicentre retrospective audit of outcome of patients undergoing curative resection for rectal cancer.

AIM: This study describes the outcome of patients with rectal cancer treated in four New Zealand public hospitals before the advent of specialised colorectal units in order to provide a baseline against which any changes in management can be measured. METHODS: A retrospective review of case notes of patients who underwent resection of rectal cancer with curative intent over a period of 7-10 years up to 1995 in Christchurch, Wellington, Nelson, and Masterton Public Hospital's, was undertaken. Patients were identified from hospital records using a combination of methods (pathology data bases, clinical case mix data, operating logs and audit data). Metastatic disease was considered to be present if confirmed on histology or the clinical course of the patient was consistent with metastatic disease. Patients were excluded if there was perioperative evidence of metastatic disease or if they had transanal excision. Previously published results from Auckland and Dunedin Hospitals are compared. RESULTS: 524 patients with rectal cancer were identified who had undergone surgery with curative intent in the four hospitals. The overall permanent stoma rate was 37%. The overall 30-day mortality was 2.9%, five-year survival was 63% and local recurrence at five years was 26%. CONCLUSION: While low perioperative mortality and good long-term survival were achieved, there were high rates of local recurrence. These data are a baseline against which the impact of new approaches to curative resection for rectal cancer can be measured.

Postoperative epidural analgesia following elective major abdominal surgery in high risk patients: a retrospective cohort study.

AIM: To describe the effect of post-operative epidural analgesia on morbidity and mortality rates in a group of high-risk patients undergoing elective major abdominal surgery. METHODS: Retrospective chart review of patients in American Society of Anaesthetists Physical Status (ASA) category III or IV, who underwent elective major I or II general surgical procedures between 01/01/1996 and 01/09/1998. Patients were identified from a prospective audit database. Patients who had epidural analgesia or conventional parenteral opioids were compared for outcome measures. RESULTS: There were 167 patients identified (72 epidural, 95 non-epidural group). There was no significant difference in demographic data, inpatient stay, intensive care unit stay, or mortality rates (11% epidural v 17% non-epidural, p>0.05). There was no significant difference in morbidity rates, however there was a non-significant trend towards a lower morbidity in the epidural group. CONCLUSIONS: This study does not show any benefit from post-operative epidural analgesia on morbidity and mortality rates in high risk patients undergoing major abdominal surgery. It does illustrate that ASA 3 and 4 patients undergoing major abdominal surgery have a high morbidity and mortality.

The use of 3-[2-(N,N-diethyl-N-methylammonium)ethyl]-7-methoxy-4-methylcoumarin (AMMC) as a specific CYP2D6 probe in human liver microsomes.

Recently, a novel nonfluorescent probe 3-[2-(N,N-diethyl-N-methylammonium)-ethyl]-7-methoxy-4-methylcoumarin (AMMC), which produces a fluorescent metabolite AMHC (3-[2-(N,N-diethyl-N-methylammonium)ethyl]-7-hydroxy-4-methylcoumarin) was used with microsomes containing recombinant enzymes (rCYP) to monitor CYP2D6 inhibition in a microtiter plate assay. This article describes the studies that were performed in human liver microsomes (HLM) to establish the selectivity of AMMC toward CYP2D6. Metabolism studies in HLM showed that AMMC was converted to one metabolite identified by mass spectrometry as AMHC. Kinetic studies indicated an apparent K(m) of 3 microM with a V(max) of 20 pmol/min. mg of protein for the O-demethylation reaction. The O-demethylation of AMMC in HLM was inhibited significantly in the presence of a CYP2D6 inhibitory antibody. Using a panel of various HLM preparations (n = 12), a good correlation (r(2) = 0.95) was obtained between AMMC O-demethylation and bufuralol metabolism, a known CYP2D6 substrate, but not with probes for the other major xenobiotic metabolizing CYPs. Finally, only rCYP2D6 showed detectable metabolism in experiments conducted with rCYPs using AMMC at a concentration of 1.5 microM (near K(m)). However, at a concentration of 25 microM AMMC, rCYP1A also contributed significantly to the formation of AMHC. Knowing the experimental conditions under which AMMC was selective for CYP2D6, a microtiter assay was developed to study the inhibition of various compounds in HLM using the fluorescence of AMHC as an indication of CYP2D6 activity. The inhibition potential of various chemicals was found to be comparable to those determined using the standard CYP2D6 probe, bufuralol, which requires high-performance liquid chromatography separation for the analysis of its CYP2D6-mediated 1'-hydoxylated metabolite.

Does a colostomy alter quality of life in patients with spinal cord injury? A controlled study.

STUDY DESIGN: Prospective controlled comparative analysis. OBJECTIVE: To determine whether a colostomy changes quality of life in patients with a spinal cord injury. METHOD: A previously validated questionnaire designed to assess quality of life in spinal injured patients (Burwood Questionnaire) was sent to 26 spinal cord injured patients with colostomies and 26 spinal cord injured patients without colostomy. The two groups were matched for level of injury, completeness of injury, length of time since injury, age (+/- 5 years) and gender. RESULTS: There was 100% completion of the questionnaire. There was no significant difference (P > 0.05) in the two groups of patients in regard to their general well being, emotional, social, or work functioning. CONCLUSIONS: Patients with colostomy following spinal injury are no worse off in regard to quality of life, than those without. The inference is that perhaps a colostomy should be considered earlier in patients with major bowel dysfunction following spinal cord injury. SPONSORSHIP: Financial support for Dr AC Lynch was provided by Royal Australian College of Surgeons with a Foundation Scholarship and Grant in aid by the Burwood International Spinal Trust. Mr N Randell was supported by the Canterbury Medical Research Foundation with a summer studentship.

Bowel dysfunction following spinal cord injury.

STUDY DESIGN: Review. OBJECTIVES: To outline the present knowledge of bowel dysfunction following spinal injury, and look at future directions of management and research. SETTING: Spinal Unit and Colorectal Unit, Christchurch, New Zealand. METHODOLOGY: Review. RESULTS: The underlying physiology of colorectal motility and defecation is reviewed, and consequences of spinal cord injury on defecation are reported. A discussion of present management techniques is undertaken and new directions in management and research are suggested. CONCLUSION: There is need for more intervention in regard to bowel function that could improve quality of life, but there is also a need for more research in this area.

Working memory deficits associated with chronic fatigue syndrome.

Cognitive impairments are among the most frequently reported and least investigated components of the chronic fatigue syndrome (CFS). As part of a multifaceted study of the CFS, the present study investigated the cognitive functioning of chronic fatigue patients. The performance of 20 CFS patients was compared to that of controls (N = 20) on 4 tests of working memory (WM). Digit Span Forward was used to assess the storage capacity of WM. Multiple aspects of central executive functioning were assessed using several standard measures: Digit Span Backward, and Trails A and Trails B. More recently developed measures of WM were used to assess control of processing under temporal demands (working memory task) and resistance to interference (a sustained attention task). Deficits were restricted to more demanding tasks, requiring resistance to interference and efficient switching between processing routines. The overall results clearly implicate deficits in the control aspects of central executive function in CFS.