Current status of monoclonal antibodies for imaging and therapy of prostate cancer

It is clear that there is significant need for improved staging and therapy of prostate cancer. The attributes and strengths of MoAbs seem particularly well-suited to the setting of prostate cancer. Recent progress in the application of MoAbs to in vivo imaging and therapy is encouraging. Clearly, further such efforts in prostate cancer are warranted.     

Double-blind, placebo-controlled study of the effects of carvedilol in patients with moderate to severe heart failure. The PRECISE Trial. Prospective Randomized Evaluation of Carvedilol on Symptoms and Exercise

BACKGROUND: Carvedilol has improved the symptomatic status of patients with moderate to severe heart failure in single-center studies, but its clinical effects have not been evaluated in large, multicenter trials. METHODS AND RESULTS: We enrolled 278 patients with moderate to severe heart failure (6-minute walk distance, 150 to 450 m) and a left ventricular ejection fraction < or = 0.35 at 31 centers. After an open-label, run-in period, each patient was randomly assigned (double-blind) to either placebo (n = 145) or carvedilol (n = 133; target dose, 25 to 50 mg BID) for 6 months, while background therapy with digoxin, diuretics, and an ACE inhibitor remained constant. Compared with placebo, patients in the carvedilol group had a greater frequency of symptomatic improvement and lower risk of clinical deterioration, as evaluated by changes in the NYHA functional class (P = .014) or by a global assessment of progress judged either by the patient (P = .002) or by the physician (P < .001). In addition, treatment with carvedilol was associated with a significant increase in ejection fraction (P < .001) and a significant decrease in the combined risk of morbidity and mortality (P = .029). In contrast, carvedilol therapy had little effect on indirect measures of patient benefit, including changes in exercise tolerance or quality-of-life scores. The effects of the drug were similar in patients with ischemic heart disease or idiopathic dilated cardiomyopathy as the cause of heart failure. CONCLUSIONS: These findings indicate that, in addition to its favorable effects on survival, carvedilol produces important clinical benefits in patients with moderate to severe heart failure treated with digoxin, diuretics, and an ACE inhibitor.     

The influence of angiotensin-converting enzyme inhibition on renal tubular function in progressive chronic nephropathy

The influence of angiotensin-converting enzyme (ACE) inhibition on renal tubular function in progressive chronic nephropathy was investigated in 69 patients by the lithium clearance (C(Li)) method. Studies were done repeatedly for up to 2 years during a controlled trial on the effect of enalapril on progression of renal failure. The pattern of proteinuria was followed over the first 9 months. At baseline, the glomerular filtration rate (GFR) was 5 to 68 mL/min. Absolute proximal tubular reabsorption rate of fluid (APR), estimated as the difference between GFR and C(Li), was 1 to 54 mL/min. Calculated fractional proximal reabsorption (FPR) was moderately subnormal. During the study, GFR decreased and sodium clearance was unchanged; fractional excretion of sodium therefore increased. In the group of patients randomized to treatment with enalapril (n = 34), GFR at 1 month was 83% (P < 0.001) and C(Li) was 88% (P < 0.01) of the baseline values, APR and FPR had not changed significantly, and potassium clearance was significantly decreased. Through the rest of the study period, APR remained nearly unchanged and FPR even increased in the enalapril group. In the group of patients randomized to treatment with conventional antihypertensive drugs (n = 35), C(Li) was unchanged until severe reduction in GFR, APR and FPR decreased gradually, and potassium clearance was almost unchanged. These differences in tubular function between the two treatment regimens were significant (P < 0.05). An unchanged or increased APR in either treatment regimen was associated with a long-term slower progression of renal failure. Over 9 months, the 24-hour fractional clearance of albumin decreased in the ACE inhibitor group (P < 0.01), whereas the clearances of immunoglobulin G and retinol-binding protein were unchanged in this group. In the conventional group, the fractional clearances of these three plasma proteins all increased. It is concluded that in progressive chronic nephropathy ACE-inhibitor treatment was associated with different adaptive tubular changes in the handling of sodium, water, and protein compared with conventional antihypertensive therapy. During ACE inhibition, the reabsorptive capacity of the proximal tubule appeared to be better preserved, which might be of importance for the beneficial effect of this treatment in chronic renal disease.     

Hepatic transcatheter arterial chemoembolization alternating with systemic protracted continuous infusion 5-fluorouracil for gastrointestinal malignancies metastatic to liver: a phase II trial of the Puget Sound Oncology Consortium (PSOC 1104)

We assessed a regimen of alternating regional and systemic therapy in patients with gastrointestinal malignancies with liver-dominant metastases for feasibility, toxicity, response rate, response duration, patterns of progression, and progression-free and overall survival. Regional therapy comprised selective hepatic transcatheter arterial chemoembolization (TACE) using a suspension of cisplatin and particulate polyvinyl alcohol. This procedure was delivered between cycles of protracted continuous infusion 5-fluorouracil (PCI-5FU) as systemic chemotherapy. Patient eligibility criteria included: (a) having histologically documented adenocarcinoma arising from a gastrointestinal primary site with unresectable liver metastases bidimensionally measurable on computerized tomography scan; (b) age greater than 18 years; and (c) performance status 0-2 (Zubrod). PCI-5FU (250 mg/m2/day) was administered i.v. for 28 days, followed by the first TACE (TACE 1) delivered to the hepatic artery supplying the lobe with the greatest tumor burden. Restaging was performed before TACE 2 and TACE 3, which followed at monthly intervals. PCI-5FU for 21 days was sandwiched between each of the TACE treatments. After the final TACE, maintenance PCI-5FU was given for 28 days of each 35-day cycle until toxicity or progression. Between December 23, 1991, and January 19, 1995, 32 patients were registered in this trial, of whom 27 were eligible; 20 completed one or more treatment cycles and were evaluable for radiographic response. Patients with colorectal liver metastases predominated (74%). Twelve (44%) of 27 patients had failed one or more prior treatment regimens. There were no treatment-related deaths, and hematological and hepatic toxicities were generally manageable and reversible. Two patients, however, developed hepatic abscesses requiring drainage, and one patient developed an infarcted gallbladder, which necessitated cholecystectomy. There were no patients with complete responses; there were 8 (40%) with partial responses, 4 (20%) with minor responses, 2 (10%) with stable disease, and 6 (30%) who progressed on the treatment. The median duration of response for partial responders was 4.2 months (127 days; range, 56-245 days). The median reduction in carcinoembryonic antigen for responders was 87.5%. Two patients underwent subsequent resection of residual metastases; one of them is still alive at 58.4 months follow-up. The predominant site of disease progression was the liver; 25% of the patients progressed in extrahepatic sites. The median overall survival for the whole group is 14.3 months (95% confidence interval, 7.2-16.2). Actuarial overall survival for the whole group at 1 year and 2 years is 57 and 19%, respectively. Alternating systemic PCI-5FU and regional TACE (cisplatin/polyvinyl alcohol) is an active and feasible regimen with manageable toxicities in patients with metastatic gastrointestinal malignancies with liver-dominant disease and merits further investigation. The complications seen were in line with those reported at other specialized centers.     

Clinical evaluation of a posterior composite 10-year report

OBJECTIVE: To determine if the long-term use of continuously infused intrathecal baclofen (ITB) over a 1-year period will control spastic-dystonic hypertonia in patients with traumatic brain injury (TBI). SETTING: Tertiary care outpatient and inpatient rehabilitation center directly attached to a university hospital. SUBJECTS: Persons with TBI and intractable spasticity and dystonia for more than 6 months' duration recruited in a consecutive manner. DESIGN: TBI patients were admitted to the study after screening via a bolus injection of either intrathecal normal saline or 50 microg of baclofen. Data for Ashworth rigidity scores, spasm scores, and deep tendon reflex scores were collected for both the upper extremities (UE) and lower extremities (LE). Patients whose LE Ashworth scores decreased an average of 2 points were then offered implantation of a computer-controlled pump for continuous ITB. Changes over time were assessed statistically via Friedman's analysis for ordinal data and ANOVA for linear data. Differences between set points in time were also assessed via Wilcoxon signed rank. DATA SET: Seventeen patients (average age 29+/-11 yrs) with spasticity and/or dystonia treated over 1 year via a computer-controllable intrathecal delivery system for the delivery of ITB. RESULTS: After 1 year of continuous ITB treatment the average LE Ashworth score decreased from 3.5+/-1.3 (SD) to 1.7+/-0.9 (p < .0001), spasm score from 1.8+/-1.3 to 0.2+/-0.5 (p< .0001), and reflex score from 2.5+/-1.1 to 0.1+/-0.3 (p < .0001). The average UE Ashworth score decreased from 2.9+/-1.5 to 1.6+/-1.0 (p < .0001), spasm score from 1.2+/-1.5 to 0.2+/-0.6 (p < 0.0001), and reflex score from 2.2+/-0.5 to 1.0+/-0.8 (p < .0001). The average ITB dose required to attain these effects at 1 year was 302 microg continuously infused per day. CONCLUSION: Continuous intrathecal infusion of baclofen is capable of maintaining a reduction in spasticity and dystonia in both the upper and lower extremities of TBI patients.     

Mechanism of zeolite A nanocrystal growth from colloids at room temperature

The formation and growth of crystal nuclei of zeolite A from clear solutions at room temperature were studied with low-dose, high-resolution transmission electron microscopy in field emission mode and with in situ dynamic light scattering. Single zeolite A crystals nucleated in amorphous gel particles of 40 to 80 nanometers within 3 days at room temperature. The resulting nanoscale single crystals (10 to 30 nanometers) were embedded in the amorphous gel particles. The gel particles were consumed during further crystal growth at room temperature, forming a colloidal suspension of zeolite A nanocrystals of 40 to 80 nanometers. On heating this suspension at 80 degrees C, solution-mediated transport resulted in additional substantial crystal growth.     

Synthesis of permselective membranes by radiation-induced grafting of N-vinylpyrrolidone onto poly(tetrafluoroethylene–hexafluoropropylene–vinylidene fluoride) (TFB) films

The radiation initiated grafting of N-vinylpyrrolidone (NVP) onto poly(tetrafluoroethylene–hexafluoropropylene–vinylidene fluoride) (TFB) films has been investigated using a direct radiation technique. Different solvents were used for diluting the monomer, and it was found that dioxane is suitable for this grafting system. The influence of other grafting parameters, such as inhibitor, monomer concentration and dose rate, on the rate and yield of grafting was studied. The dependence of the grafting rate on the monomer concentration was found to be of the 1.1 order. Some physicochemical properties, such as swelling, thermal behaviour, mechanical and electrical conductivity, were investigated. A study was made to gain a better understanding of the observed water uptake using IR spectroscopy and scanning electron microscope (SEM) analysis. The possibility of some practical uses, e.g. removal of heavy metals from solution by grafted membranes was investigated. © 1999 Society of Chemical Industry     

The effects of a psychoeducational program on adolescents' activity involvement, self-esteem, and locus of control

Adolescents' participation in extracurricular activities is related to a number of variables, such as higher grade point average, increased self-esteem, and lower absenteeism. This research, part of a larger longitudinal study, was designed to determine whether a short, psychoeducational intervention, the personal empowerment program, would affect adolescents' level of involvement in activities, their self-esteem, or their locus of control. Fifty-two ninth-grade students who were average participators were randomly selected and assigned to either the empowerment program or control group. Students were surveyed six months after the program. Analyses of covariance using pretest scores as the covariates indicated that students who participated in the program maintained their level of activity involvement during the transition to high school, a time when participation generally decreases. The program did not produce significant changes in self-esteem or locus of control. Implications for future research are discussed.     

The effect of 12 months'' treatment with eicosapentaenoic acid in five children with cystic fibrosis

BACKGROUND: The use and indications for laparoscopy have been increasing. As part of this trend, a new algorithm may emerge for pediatric trauma in which laparoscopic techniques are used in hemodynamically stable patients with suspected hollow viscus perforation. CASE REPORT: We present a case in which laparoscopy was successfully used in a pediatric trauma patient as a diagnostic and therapeutic modality. A 4-year-old boy was a back-seat passenger in a head-on collision motor vehicle accident. He was restrained by a lap seat belt. He sustained a concussion, a large forehead laceration and a seat belt abdominal injury. On admission, he complained of abdominal pain. Physical examination revealed a soft, non-distended abdomen with moderate diffuse tenderness. He was hemodynamically stable. Computerized tomography of the abdomen revealed free fluid in the pelvis. No abnormalities were detected in the liver or spleen. Because of clinical deterioration and suspected intestinal perforation, diagnostic laparoscopy was utilized instead of proceeding directly to celiotomy. At laparoscopy a jejunal perforation was found and successfully repaired laparoscopically. Large hematomas were seen in the mesentery, as well as an unsuspected splenic laceration. No active bleeding was found. The patient recovered uneventfully and was discharged 5 days following the surgical procedure. CONCLUSION: This case illustrates the efficacy of using early laparoscopy in children with abdominal trauma when diagnosis is difficult and hollow viscus injury is suspected.