Assessment of peripouch inflammation after ileoanal anastomosis using endoluminal ultrasonography

PURPOSE: This study was designed to assess the impact of endoluminal transpouch ultrasonography in the investigation and management of inflammatory complications of pelvic pouches and to compare endoluminal transpouch ultrasonography to pouchography and computerized axial tomograph scanning. METHODS: A prospective evaluation was made of the presentation, investigation, treatment, and clinical outcome of 16 patients referred for endoluminal transpouch ultrasonography with dysfunctional pelvic pouches and no evidence of pouchitis on endoscopy. RESULTS: There were 5 normal and 11 abnormal examinations. Six patients had peripouch inflammatory phlegmons, four patients had peripouch abscesses, and one patient had a rectovaginal fistula. A total of nine patients had anastomotic leaks detected. Two patients had abscesses drained under ultrasound guidance and a pigtail catheter left in situ.Pouchography detected only 3 of 8 (38 percent) anastomotic leaks detected by endoluminal transpouch ultrasonography. Computerized axial tomograph scan detected 2 of 5 (40 percent) peripouch abscesses or phlegmon detected by endoluminal transpouch ultrasonography. Patients with peripouch sepsis had significantly thicker anal wall thickness (23.8 vs. 16.8 mm; P<0.02) and external sphincter thickness (9.1 vs. 7.3 mm;P<0.05) than pouches with no sepsis. CONCLUSIONS: Endoluminal transpouch ultrasonography appears to detect anastomotic leaks and peripouch sepsis and may guide the initial management of patients with dysfunctional pelvic pouches and an inconclusive clinical and endoscopic examination.M. J. Solomon was supported in part by The Wigston Foundation, Toronto, Canada, Ethicon Canada Ltd., Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Canada, and the Jenour Foundation, Australia.Presented at the Royal College of Physicians and Surgeons meeting, Vancouver, Canada, September 1993.     

Patterns of cell proliferation and cell migration in the Sezary syndrome

The patterns of cell proliferation and cell migration were studied in three patients with the Sezary syndrome using autoradiographic techniques. Cell labeling patterns following pulse labeling with tritiated thymidine in vivo indicated that Sezary cells proliferate actively in skin and in lymph nodes but that few if any Sezary cells proliferate in the peripheral blood. In two of the patients serial samples were obtained. Label dilution patterns in skin and blood over time suggested that circulating Sezary cells originated in extracutaneous sites where cells were proliferating more rapidly than in the skin. Cells labeled in extracutaneous sites of proliferation appear rapidly in the blood, and their transit time through the peripheral blood compartment is short. Circulating Sezary cells may then be deposited in the skin where they resume proliferation at a low rate. Thus, while Sezary cells proliferate in both cutaneous and extracutaneous sites, proliferation appears to be more rapid in extracutaneous sites such as lymph nodes. This suggests that trials of systemic therapeutic approaches should be undertaken.     

Monoclonal immunoglobulin deposition disease: light chain and light and heavy chain deposition diseases and their relation to light chain amyloidosis. Clinical features, immunopathology, and molecular analysis

Monoclonal immunoglobulin deposition occurs in tissues as Congo Red binding fibrils in light chain amyloidosis, as less structured deposits in light chain deposition disease, and as similar but distinct deposits in light and heavy chain deposition disease. The nonamyloid forms were found in 13 patients who had evidence of plasmacytic dyscrasia by the immunohistochemical detection of immunoglobulin light chains of kappa or lambda class (with or without staining for a single heavy chain isotype) and by the absence of amyloid P component in tissue sections that did not show the birefringence characteristic of amyloid after Congo Red staining. All but two of the patients presented with proteinuria with or without azotemia. Clinical syndromes involving other organ systems were less common but occasionally severe. Four patients had overt multiple myeloma. Three others had hypercalcemia and mild bone marrow plasmacytosis but no lytic lesions. Analyses of immunoglobulin synthesis in bone marrow cells from seven patients showed excess light chains in all and incomplete light chains or heavy chain fragments in six, regardless of whether an intact monoclonal protein or related subunit was in the serum or urine. The fibrillar (amyloidotic) and nonfibrillar forms of monoclonal immunoglobulin deposition occur either in overt multiple myeloma or in the course of less neoplastically aggressive plasmacytic dyscrasias. Bone marrow cells from patients with either type produce immunoglobulin fragments that are related to those deposited in the affected tissues.     

Taking the next step in 2005, the year of the diabetic foot

OBJECTIVES: To determine the age-standardized rate of lower limb amputations among Type 2 diabetics admitted to the Port of Spain General Hospital (POSGH), San Fernando General Hospital (SFGH) and Sangre Grande County Hospital (SGCH) for the period 2000-2004. To determine in-hospital mortality following amputation, for the same period. To determine the risk factors that contributed to diabetic foot complications. DESIGN AND METHODS: All patients who had a lower limb amputation at the three major public health institutions in Trinidad during the study period were enrolled. In addition patients attending the surgical out-patient clinic and currently admitted to the ward with a diabetic septic foot was selected for the administration of a questionnaire to determine the major contributing factors. Data on the type of amputation, age, sex, ethnicity, from which an age-standardized mortality rate, was determined for the age group 30-60. RESULTS: Of 822 patient files examined, 515 (80%) of these major amputations were performed on Type 2 diabetics, of which 352 (68%) were AKA and 163 (32%) were BKA. The AKA:BKA ratio for the period 2000-2004 was 2.2:1. There was a significant difference between the mean ages at which females had a major amputation to males (p=0.001). The overall ratio of Africans to South East Asians was 1.5:1 amongst the Type 2 diabetic amputees. For major amputations the average length of stay was found to be 22.5 (0-192) days. The age-standardized rate for the age group 30-60 was 13.85 per 100,000 for 2004. Of 66 deaths, 31 (47%) were septicemia cases and 14 (21%) cardio-respiratory failure cases. Finally, of 97 persons interviewed, the major causative agent for diabetic foot complications and amputations was foot trauma (51%). CONCLUSION: Type 2 diabetic amputation status of Trinidad would seem to have improved as shown by this study. However, steps must be taken to improve patient awareness about prevention and care of the diabetic foot. Doctors must also seek to increase their vigilance when screening diabetic patient in the primary care setting in order to prevent the late detection and treatment of the septic lower limb.     

Should postmenopausal women with rheumatoid arthritis who are starting corticosteroid treatment be screened for osteoporosis? A cost-effectiveness analysis

OBJECTIVE: To evaluate the cost-effectiveness of different strategies for preventing corticosteroid-induced osteoporosis. METHODS: Simulated cohorts of postmenopausal women with rheumatoid arthritis (RA) starting corticosteroid treatment were examined. A Markov decision analysis model was developed to compare different management strategies, including watchful waiting, screen and treat, and empirical treatment. Treatment thresholds for the screen and treat strategy were varied from bone mineral density (BMD) T scores <-1.0 to BMD T scores <-4.0. RESULTS: Compared with a watchful waiting approach, the incremental cost-effectiveness ratio for a strategy of screen and treat with alendronate at a BMD T score of <-1.0 was $92,600 per quality-adjusted life year (QALY) gained. This result was sensitive to the cost and efficacy of osteoporosis therapy and, importantly, to the treatment threshold. At a treatment threshold of a BMD T score <-2.5, the incremental cost-effectiveness ratio of screening and treating was $76,100 per QALY. None of these results differed substantially for women taking estrogen replacement therapy. CONCLUSION: The incremental cost-effectiveness ratio of a strategy of screening and treating postmenopausal female RA patients with BMD T scores of < -1.0, compared with watchful waiting, was greater than that of other well-accepted medical interventions. The cost-effectiveness ratios were more acceptable when a T score treatment threshold of <-2.5 was used. These conclusions are limited by the lack of data on fracture and treatment efficacy in corticosteroid-treated patients.     

Transmissibility of systemic amyloidosis by a prion-like mechanism

The generation of amyloid fibrils from an amyloidogenic polypeptide occurs by a nucleation-dependent process initiated in vitro by seeding the protein solution with preformed fibrils. This phenomenon is evidenced in vivo by the fact that amyloid protein A (AA) amyloidosis in mice is markedly accelerated when the animals are given, in addition to an inflammatory stimulus, an i.v. injection of protein extracted from AA amyloid-laden mouse tissue. Heretofore, the chemical nature of this "amyloid enhancing factor" (AEF) has not been definitively identified. Here we report that the active principle of AEF extracted from the spleen of mice with silver nitrate-induced AA amyloidosis was identified unequivocally as the AA fibril itself. Further, we demonstrated that this material was extremely potent, being active in doses <1 ng, and that it retained its biologic activity over a considerable length of time. Notably, the AEF was also effective when administered orally. Our studies have provided evidence that AA and perhaps other forms of amyloidosis are transmissible diseases, akin to the prion-associated disorders.     

Rationale--Trial to Reduce Cardiovascular Events with Aranesp Therapy (TREAT): evolving the management of cardiovascular risk in patients with chronic kidney disease

BACKGROUND: Patients with chronic kidney disease (CKD) have a high burden of mortality and cardiovascular morbidity. Additional strategies to modulate cardiovascular risk in this population are needed. Data suggest that anemia is a potent and potentially modifiable risk factor for cardiovascular disease in patients with CKD, but these data remain unsubstantiated by any randomized controlled trial (RCT). Furthermore, the clinical practice guidelines for anemia management in patients with CKD are based on limited data. The need for new RCTs to address critical knowledge deficits, particularly with regard to the impact of anemia therapy on cardiovascular disease and survival, is recognized within the guidelines and independent comprehensive reviews of the existing published trial data. STUDY DESIGN: The Trial to Reduce Cardiovascular Events with Aranesp (Amgen Inc, Thousand Oaks, Calif) (darbepoetin alfa) Therapy (TREAT) is a 4000-patient, multicenter, double-blind RCT, designed to determine the impact of anemia therapy with darbepoetin alfa on mortality and nonfatal cardiovascular events in patients with CKD and type 2 diabetes mellitus. Subjects will be randomized in a 1:1 manner to either darbepoetin alfa therapy to a target hemoglobin (Hb) of 13 g/dL or control, consisting of placebo for Hb > or =9 g/dL or darbepoetin alfa for Hb <9 g/dL until Hb is again Hb > or =9 g/dL. TREAT is event-driven and has a composite primary end point comprising time to mortality and nonfatal cardiovascular events, including myocardial infarction, myocardial ischemia, stroke, and heart failure. TREAT will provide data that are critical to evolution of the management of cardiovascular risk in this high-risk population.     

Assessment of quality of life in the treatment of patients with neuropathic fecal incontinence

INTRODUCTION: Development of quality-of-life measures has been the focus of research in colorectal disorders in recent years. The assessment of quality of life for fecal incontinence should be more important than quantitative measurement of soiling. PURPOSE: This study assesses specific patient quality-of-life objectives, categorizes objectives, and correlates these objectives with continence scores. METHODS: One hundred eighteen patients entered into a randomized, controlled trial of biofeedback were assessed using the Direct Questioning of Objectives quality-of-life measure. All objectives were documented, categorized, and correlated with continence scores and analog scales. RESULTS: In patients with neuropathic fecal incontinence, the most frequent quality-of-life group concerned the ability to get out of home, to socialize outside of home, to go shopping, and not to have to worry about the location of the nearest toilet while out of home (34 percent; 123/364). At least one of these four objectives was stated by 72 percent of patients (85/118). Only 31 percent of patients (37/118) nominated an objective related to the physical act of soiling. The ability to travel (29 percent), exercise including walking (25 percent), perform home duties (19 percent), family and relationships (22 percent), and job (13 percent) were less frequently cited by patients. CONCLUSION: Continence scores focus heavily on the physical aspects of incontinence such as soiling and hygiene, aspects which seem to be less important to the patients themselves. It is important, therefore, that assessments of fecal incontinence should include reference to quality of life, and in particular to its impact on activities relating to getting out of the house.