Estimates of radiation absorbed dose for intraperitoneally administered iodine-131 radiolabeled B72.3 monoclonal antibody in patients with peritoneal carcinomatoses

Using a newly available model for determining estimates of radiation absorbed dose of radioisotopes administered intraperitoneally, we have calculated absorbed dose to tumor and normal tissues based on a surgically controlled study of radiolabeled antibody distribution. Ten patients with peritoneal carcinomatosis received intraperitoneal injections of the murine monoclonal antibody B72.3 radiolabeled with 131I. Biodistribution studies were performed using nuclear medicine methods until laparotomy at 4-14 days after injection. Surgical biopsies of normal tissues and tumor were obtained. The marrow was predicted to be the critical organ, with maximum tolerated dose [200 rad (2 Gy) to marrow] expected at about 200 mCi (7.4 GBq). In patients with large intraperitoneal tumor deposits, the tumor itself is an important source tissue for radiation exposure to normal tissues. Local "hot-spots" for tumor-absorbed dose were observed, with maximum tumor-absorbed dose calculated at 11,000 rad (11 Gy) per 100 mCi (3.7 GBq) administered intraperitoneal; however, tumor rad dose varied considerably. This may pose serious problems for curative therapy, especially in patients with large tumor burdens.     

24-hour unit dose dispensing of class III-V controlled substances

Methods of controlling controlled substance (CS) inventories in unit dose dispensing systems vary. The two extremes are total floor stock of all CS drugs by the use of declining inventory signout sheets on the nursing unit to controlling only Class II and a few selected class III-V items. The method described herein outlines a systematic approach to controlling items on an individual patient basis consistant with the benefits of unit dose dispensing. A CS card assigned to each patient for each of his required controlled substance medications serves as an audit trail for doses consumed by the patient and provides a declining inventory receipt when returned to the pharmacy.     

Clinical studies of a fast homoarginine-sensitive alkaline phosphatase in patients with cancer

The activity of an isoenzyme of alkaline phosphatase (FHAP) was measured in serum samples obtained from 1692 individual subjects. The median FHAP concentration in patients with untreated or recurrent cancer (2.73 IU/liter) was two-fold higher than in hospitalized control patients with illnesses other than cancer (1.17 IU/liter) and three-fold higher than in healthy control subjects (0.93 IU/liter). Among patients with either breast or colorectal cancer who were clinically disease free following their initial therapy, the median FHAP concentration (1.54 IU/liter) was intermediate between the median FHAP concentration in patients with untreated or recurrent cancer and that of healthy control subjects. In order to illustrate the potential clinical application of FHAP as a diagnostic cancer marker, we have selected a serum FHAP concentration of 2.22 IU/liter as a reference value above which only 3% of healthy control subjects would have a "positive" test. Utilizing this reference value, 58% of the patients in the present study with untreated or recurrent cancer would have a positive FHAP test, whereas only 11%, of hospitalized patients with illnesses other than cancer would have a positive test. These data suggest that FHAP may be equivalent to the carcinoembryonic antigen as a diagnostic cancer marker.     

Professionalism: rise and fall.

Historically, the early professionalization movements in medicine and the law appear as organizational projects which aspire to monopolize income and opportunities in markets of services or labor and to monopolize status and work privileges in occupational hierarchies. Their central task is to standardize training and link it to actual or potential markets of labor or services, a linkage that is structurally effected in the modern university. The second wave of professionalization has different protagonists than the older "market professions": placed in a different structural situation, the bureaucratic professions transform the model of profession (which they adopt as a strategy of collective ascension) into an ideology. The import of the ideology of professionalism is examined in relation to two issues: the relationships between professional occupations and bureaucratic organizations; and the position of professional occupations within the larger structure of inequality. Analysis of the first point requires consideration of the distinctions between professional occupations in the public and private sectors, the use of professional knowledge and the image of profession in bureaucratic organizations, and the specific characteristics of professions that produce their own knowledge. In the discussion of the second point, professional occupations and their ideology are examined in relation to other occupations and to the possibilities of political awareness generated by uncertain professional statuses.     

Individual differences in cocaine-induced locomotor activity in rats: behavioral characteristics, cocaine pharmacokinetics, and the dopamine transporter.

Outbred male Sprague-Dawley rats can be classified as either low or high cocaine responders (LCRs or HCRs, respectively) based on their locomotor response to acute cocaine. Concomitant measurement of dopamine clearance in these rats revealed that the differential behavioral responses are associated with the magnitude of dopamine transporter (DAT) inhibition by cocaine. Here, we investigated several factors that might contribute to cocaine-induced behavioral variability and its association with differential inhibition of DAT function. In rats classified as LCRs or HCRs after 10 mg/kg cocaine injection, we found no differences in (1) novelty-induced locomotion, (2) cocaine levels in dorsal striatum or nucleus accumbens (NAc), (3) DAT number or affinity in NAc, or (4) DAT affinity for cocaine in NAc. In rats given 20 mg/kg cocaine, behavior was more uniform across individuals, but still warranted separation into LCR/HCR categories. Additionally, we analyzed the stability of the LCR/HCR classification made during the first test with 10 or 20 mg/kg cocaine by retesting rats 7 days later with saline or cocaine (10 or 20 mg/kg). Before injection, HCRs were more active relative to LCRs and to their own behavior on the first test day. Following cocaine, LCRs and HCRs exhibited similar drug-induced changes in locomotion, but there were unique effects that depended on the cocaine dose given on the first and second test days. Our results argue against several likely explanations for individual differences in cocaine-induced behavior and highlight the influence of a single cocaine exposure on subsequent behavioral responses to the drug.     

In vitro assessment of the efficacy of thermal therapy in human benign prostatic hyperplasia.

The successful management of BPH with minimally invasive thermal therapies requires a firm understanding of the temperature-time relationship for tissue destruction. In order to accomplish this objective, the present in vitro study assesses the cellular viability of human BPH tissue subjected to an experimental matrix of different temperature-time combinations. Hyperplastic prostate tissue was obtained from 10 radical prostatectomy specimens resected for adenocarcinoma. A portion of hyperplastic tissue from the lateral lobe of each prostate was sectioned into multiple 1 mm thick tissue strips, placed on a coverslip and thermally treated on a controlled temperature copper block with various temperatures (45-70 degrees C) for various times (1-60 min). After heat treatment, the tissue slices were cultured for 72 h and viability was assessed using two independent assays: histology and dye uptake for stromal tissue and using histology alone for the glandular tissue. The hyperplastic human prostate tissue showed a progressive histological increase in irreversible injury with increasing temperature-time severity. The dye uptake and histology results for stromal viability were similar for all temperature-time combinations. In vitro thermal injury showed 85-90% stromal destruction (raw data) of human BPH for temperature-time combinations of 45 degrees C for 60 min, 50 degrees C for 30 min, 55 degrees C for 5 min, 60 degrees C for 2 min and 70 degrees C for 1 min. Apoptosis was also identified in the control and milder treated tissues with the degree of glandular apoptosis (about 20%) more than that seen in the stromal regions (< 5%). The Arrhenius model of injury was fitted to the data for conditions leading to a 90% drop in viability (normalized to control) obtained for stromal tissue. The activation energies (E) were 40.1 and 38.4 kcal/mole for the dye uptake study and histology, respectively, and the corresponding frequency factors (A) were 1.1 x 10(24) and 7.78 x 10(22)/s. This study presents the first temperature-time versus tissue destruction relation for human BPH tissue. Moreover, it supports the concept that higher temperatures can be used for shorter durations to induce tissue injury comparable with the current clinically recommended lower temperature-longer time treatments (i.e. 45 degrees C for 60 min) for transurethral microwave thermotherapy of the prostate.     

Cell-kill modeling of microwave thermotherapy for treatment of benign prostatic hyperplasia

PURPOSE: We investigated whether cell-kill modelling could be used as a mean for predicting the outcome of microwave thermotherapy for benign prostate hyperplasia (BPH). METHODS: The two models--Henriques' damage integral and Jung's compartment model--were implemented in a computer program. Real treatment data for 22 patients with BPH who were in chronic retention were used as input, including measured intraprostatic temperatures and microwave power. To test if modelling gives results that are consistent with actual observations, comparison with transrectal ultrasound (TRUS) measurements of the prostate volume before and after treatment was made. The sensitivity of the computer model for variations in the heat cytotoxicity and the temperature probe location in the adenoma was also tested. RESULTS: The average TRUS volume reduction 3 months after treatment was 26 cc, whereas the corresponding cell kill calculation was 27 cc. The computer model appears to be rather insensitive to minor uncertainties in heat sensitivity and location of the intraprostatic reference temperature sensors. CONCLUSION: Cell-kill modelling appears to give results that are consistent with actual observations. The coagulated tissue volume is calculated in real time during the treatment, thereby providing an immediate prediction of the treatment outcome. By using cell-kill modelling, the endpoint of a treatment can be set individually; e.g., when a certain volume reduction has been achieved.     

Clinical results of microwave thermotherapy for benign prostatic hyperplasia

Transurethral microwave thermotherapy is a truly office procedure without the need for anesthesia for the treatment of lower urinary tract symptoms caused by benign prostatic hyperplasia. Several devices have been developed. Continuous refinement of the procedure led to higher energy protocols and high-intensity dose protocols applying the heat-shock strategy. We report on the clinical results of these protocols. Symptom scores improve around 60%, whereas maximum urinary flow rate improve from an average 9 to 10 mL/sec at baseline to 14 to 15 mL/sec during follow-up. No significant differences have been shown between the outcomes with the different devices. Long-term data show satisfactory results after 4 years. Initial clinical results with the heat-shock strategy show results comparable to those of higher-energy protocols with decreased morbidity. Treatment morbidity of higher energy protocols is moderate and consists mainly of the need for catheterization and a higher percentage of retrograde ejaculation. To improve treatment efficacy, patient selection appears to be most important. Prostate size, bladder outlet obstruction, age, and prostate composition are of predictive value for treatment outcome. Further development of the treatment protocols and refinement of the urethral applicators might enhance outcome.     

Whole body 18FDG-PET and the response of esophageal cancer to induction therapy: results of a prospective trial.

PURPOSE: Whole-body 18F-fluorodeoxyglucose ([18F]FDG) positron emission tomography (PET) imaging before and after induction therapy was prospectively evaluated in patients with esophageal cancer to determine whether changes in PET images could measure response to therapy. PATIENTS AND METHODS: Between April 1997 and April 1999, 39 patients (34 men and five women; median age, 59 years; range, 36 to 76 years) with esophageal cancer were prospectively enrolled in a single-institution clinical trial of staging, including PET, induction therapy, restaging including PET, and esophagectomy. All patients undergoing esophagectomy after induction therapy (n = 17) were followed either to recurrence, to death, or through a disease-free interval of at least 24 months. RESULTS: PET after standard staging studies and before therapy imaged undetected sites of metastatic disease in six patients (15%). Restaging (including PET) after induction therapy did not identify any patients with disease progression or any patients with loco-regionally unresectable disease at exploration. The median decrease in the standardized uptake value (SUV) during induction therapy was 59%. After R0 esophagectomy, the 2-year disease-free and overall survival was 38% and 63%, respectively, among patients who had a less than 60% decrease in SUV, and 67% and 89%, respectively, among patients who had a greater than 60% decrease in SUV (P =.055 and P =.088, respectively). CONCLUSION: Compared with conventional imaging, PET detects additional sites of metastatic disease at initial evaluation. After induction therapy, PET did not add to the estimation of loco-regional resectability and did not detect new distant metastases. However, changes in [18F]FDG PET may predict disease-free and overall survival after induction therapy and resection in patients with esophageal cancer. Further evaluation in larger trials is warranted.