Citations

Abstract Aim The purpose of the study was to determine the risk of postoperative complications and the functional outcome after a hand-sewn ileal pouch–anal anastomosis (IPAA) for ulcerative colitis using a single J-shaped pouch design. Methods Preoperative function, operative morbidity and long-term functional outcome were assessed prospectively in 1310 patients who underwent IPAA between 1981 and 1994 for ulcerative colitis. Results Three patients died after operation. Postoperative pelvic sepsis rates decreased from 7 per cent in 1981–1985 to 3 per cent in 1991–1994 (P=0·02). After mean follow-up of 6·5 (range 2–15) years, the mean number of stools was 5 per day and 1 per night. Frequent daytime and night-time incontinence occurred in 7 and 12 per cent of patients respectively, and did not change over a 10-year period. The cumulative probability of suffering at least one episode of ‘clinical’ pouchitis was 18 and 48 per cent at 1 and 10 years and the cumulative probability of pouch failure at 1 and 10 years was 2 and 9 per cent respectively. Conclusion These results indicate that increased experience decreases the risk of pouch-related complications and that with time the functional results remain stable, but the failure rate increases.

Purpose: To determine whether (1) tailored nicotine patch therapy that is based on smoking rate can be carried out in a multisite oncology investigative group practice setting, (2) long-term use of bupropion reduces the rate of relapse to smoking in smokers who stop smoking with nicotine patch therapy, and (3) bupropion can initiate smoking abstinence among smokers who have failed to stop smoking after nicotine patch therapy. Participants and Methods: Fourteen North Central Cancer Treatment Group sites recruited generally healthy adult smokers from the general population for nicotine patch therapy and based the patch dosage on smoking rates. At completion of nicotine patch therapy, nonsmoking participants were eligible to be assigned to bupropion or placebo for 6 months (for relapse prevention). and smoking participants were eligible to be assigned to bupropion or placebo for 8 weeks of treatment. Results: Of 578 subjects, 31% were abstinent from smoking at the end of nicotine patch therapy. Of those subjects not smoking at the end of nicotine patch therapy who entered the relapse prevention phase, 28% and 25% were not smoking at 6 months (the end of the medication phase) for bupropion and placebo, respectively (P = .73). For those still smoking at the end of nicotine patch therapy, 3.1% and 0.0% stopped smoking with bupropion or placebo, respectively (P = .12). Conclusion: Tailored nicotine patch therapy for the general population of smokers can be provided in a multisite oncology investigative group setting. Bupropion did not reduce relapse to smoking in smokers who stopped smoking with nicotine patch therapy. Bupropion did not initiate abstinence among smokers who failed to stop smoking with nicotine patch therapy.

Persistent spectral nonphotochemical hole-burning (NPHB) spectroscopy has recently been applied to dye molecules in cells. The sensitivity of NPHB to the nanoenvironment of the probe is well established. It has been shown that NPHB applied to bulk suspensions of cultured human cells can distinguish between normal and cancer cells. Thus, NPHB has potential as a diagnostic cancer tool. For this reason, the methodology is referred to as hole-burning imaging, by analogy with MRI. The optical dephasing time ( T 2 ) of the dye in hole-burning image replaces the proton T 1 relaxation time in MRI. In addition to the T 2 mode of operation, there are four other modes including measurement of the spectral hole growth kinetics (HGK). Reported here is that the selectivity and sensitivity of NPHB operating in the HGK mode allow for distinction between normal and carcinoma cells at the single-cell level. The ovarian cell lines are ovarian surface epithelial cells with temperature-sensitive large T antigens (analogously normal) and ovarian surface epithelial carcinoma (OV167) cells. The mitochondrial specific dye used was rhodamine 800 (Molecular Probes). This carbocationic dye is highly specific for the outer and inner membranes of mitochondria. In line with the results for bulk suspensions of the two cell lines, the hole-burning efficiency for OV167 cells was found to be significantly higher than that for normal cells. Theoretical analysis of the HGK data leads to the conclusion that the degree of structural heterogeneity for the probe–host configurations in OV167 cells is lower than in the normal cells. Possible reasons for this are given.

Purpose: To study the efficacy and safety of percutaneous cisplatin-epinephrine (CDDP-EPI) injectable gel in patients with localized unresectable hepatocellular carcinoma (HCC). Patients and Methods: Eligible patients had histologically proven HCC, no prior treatment except for surgery, and no more than three tumors (each measured ≤ 7 cm, total tumor volume ≤ 200 cm3). They were treated percutaneously under ultrasound or computed tomography (CT) guidance, with up to 10 mL of CDDP-EPI gel (1 mL contains 4 mg of CDDP and 0.1 mg of EPI) per treatment and four treatments in 6 weeks to a maximum of eight treatments. The primary end points were tumor response, defined by change of percentage of tumor necrosis according to CT criteria, and safety. Survival parameters were secondary end points. Results: From June 1997 to April 2000, 58 patients (median age, 65 years) entered the study. All patients were assessable for safety, and 51 were assessable for efficacy. The median number of treatments was four (range, one to eight treatments). Objective response rate was 53% (27 of 51 patients), including 16 complete and 11 partial responses. Of the 27 responders, 14 (52%) subsequently developed progressive disease, but in most of them (93%), a new tumor arose at untreated liver sites. Median survival was 27 months (range, 18.4 to 35.7 months). The 1-, 2-, and 3-year survival rates were 79%, 56%, and 14% respectively. The procedure was well tolerated with only minor side effects. Conclusion: Percutaneous local ablation with CDDP-EPI injectable gel can induce significant tumor necrosis and local control for localized unresectable HCC, and the treatment is well tolerated.

Background— BAY 41-2272 is a recently introduced novel orally available agent that directly stimulates soluble guanylate cyclase (sGC) and sensitizes it to its physiological stimulator, nitric oxide. To date, its therapeutic actions in congestive heart failure (CHF) remain undefined. We characterized the cardiorenal actions of intravenous BAY 41-2272 in a canine model of CHF and compared it to nitroglycerin (NTG). Methods and Results— CHF was induced by rapid ventricular pacing for 10 days. Cardiorenal and humoral function were assessed at baseline and with administration of 2 doses of BAY 41-2272 (2 and 10 μg · kg −1 · min −1 ; n=8) or NTG (1 and 5 μg · kg −1 · min −1 ; n=6). Administration of 10 μg · kg −1 · min −1 BAY 41-2272 reduced mean arterial pressure (113±8 to 94±6 mm Hg; P <0.05), pulmonary artery pressure (29±2 to 25±2 mm Hg; P <0.05), and pulmonary capillary wedge pressure (25±2 to 20±2 mm Hg; P <0.05). Cardiac output (2.1±0.2 to 2.3±0.2 L/min; P <0.05) and renal blood flow (131±17 to 162±18 mL/min; P <0.05) increased. Glomerular filtration rate was maintained. There were no changes in plasma renin activity, angiotensin II, or aldosterone. NTG mediated similar hemodynamic changes and additionally decreased right atrial pressure and pulmonary vascular resistance. Conclusion— The new sGC stimulator BAY 41-2272 potently unloaded the heart, increased cardiac output, and preserved glomerular filtration rate without activation of the renin-angiotensin-aldosterone system in experimental CHF. These beneficial properties make direct sGC stimulation with BAY 41-2272 a promising new strategy for the treatment of cardiovascular diseases such as CHF.

Angiogenesis plays an important role in the biology of multiple myeloma (MM) and has prognostic importance in this disease. Solitary plasmacytoma is a localized plasma cell malignancy that progresses to MM in a significant number of patients. We examined if angiogenesis is increased in solitary plasmacytoma and if it can help identify patients likely to progress to myeloma. We studied angiogenesis in plasmacytoma biopsy samples and bone marrow biopsies from 25 patients. High-grade angiogenesis was present in 64% of plasmacytomas. In contrast, bone marrow angiogenesis was low in all patients. Patients with high-grade angiogenesis in the plasmacytoma sample were more likely to progress to myeloma and had a shorter progression-free survival compared with patients with low-grade angiogenesis (P = .02). Angiogenesis is increased in solitary plasmacytoma and is a significant predictor of progression to myeloma and provides further evidence of its importance in the pathogenesis of myeloma.

OBJECTIVEWe sought to compare methods for determining intrabolus cricopharyngeal pressure as a possible indicator for cricopharyngeal myotomy.STUDY DESIGNWe determined multiple intrabolus pressures in the cricopharyngeal region of 20 normal volunteers, of whom 12 were 20 to 35 years old and 8 were older than 75 years. Data were collected using a commercially available manofluorography system and a 6‐sensor unidirectional solid‐state 2‐ x 4‐mm catheter. Each subject underwent 5 5‐mL and 5 10‐mL liquid barium swallows. Data were analyzed, and young subjects were compared with old subjects.RESULTSThe mean mid‐bolus pressures in young subjects were 5.2 ± 4.9 mm Hg and 7.2 ± 6.5 mm Hg for the 5‐mL and 10‐mL swallows, respectively, and in older subjects, 10.8 ± 8.8 mm Hg and 12.3 ± 7.4 mm Hg. The mean gradient pressures across the 3‐cm cricopharyngeal region in young subjects were 2.02 ± 5.0 mm Hg, and −0.91 ± 4.8 mm Hg for the 5‐mL and 10‐mL swallows, respectively, and for older subjects, 4.38 ± 3.1 mm Hg and 2.82 ± 3.4 mm Hg.CONCLUSIONSCricopharyngeal intrabolus pressures were lower in young than in older subjects. The mid‐bolus pressure and the gradient pressure across the cricopharyngeal region appeared to be the most consistent methods for evaluating intrabolus pressures.SIGNIFICANCEIntrabolus pressure anomalies in the cricopharyngeal region have been proposed as an indicator for selecting patients who would benefit from cricopharyngeal myotomy. The methods of determining intrabolus pressures vary, with resulting variations in recommendations.

Abstract This study examined the prognostic value of circulating peripheral blood plasma cells (PBPCs) in patients with primary systemic amyloidosis (AL). A sensitive slide-based immunofluorescence technique was used to assess 147 patients for circulating PBPCs. Circulating monoclonal plasma cells were quantified as a percentage of circulating cytoplasmic immunoglobulin-positive cells (PBPC%). The absolute circulating plasma cell count was also determined. When analyzed retrospectively, 24 (16%) of 147 patients were found to have detectable circulating PBPCs. Overall survival for patients with high PBPC%'s (> 1%) was poorer (median survival, 10 vs 29 months;P = .002). Similarly, overall survival for patients with high PBPC counts (> 0.5 × 106/L) was significantly poorer (median, 13 vs 31 months;P = .003). Increased percentages of bone marrow plasma cells (BMPC%; P = .0004), increased levels of serum β2-microglobulin (P = .04), and dominant cardiac amyloid involvement (P = .03) also predicted poorer survival. The combined consideration of circulating PBPCs and BMPC% identified low-, intermediate-, and high-risk groups with median survivals of 37.5, 15.5, and 10 months, respectively (P = .0003). Multivariate analysis revealed circulating PBPCs and BMPC% to be independent prognostic factors for survival. Patients with PBPC%'s of 2% or higher were significantly more likely to have a coexisting clinical diagnosis of multiple myeloma (50% vs 12%, P = .008). The prognostic value of circulating PBPCs may help select treatment for patients with AL.