Metabolism and elimination of rhodamine 123 in the rat

Summary Little is known of the pharmacology of rhodamine 123 (RH-123), an agent reported to have carcinoma-selective experimental antitumor activity. Accordingly, using a high-performance liquid chromatographic assay system with fluorescence detection, we examined the plasma decay and the biliary and urinary elimination of parent drug and metabolites in female Sprague-Dawley rats receiving RH-123 at an intravenous dose (5 mg/kg) equivalent to the therapeutic dose used in murine tumor models. Following drug administration to unconscious animals, plasma levels of drug-associated fluorescence fell in a triphasic manner (t_1/2, 15 min; t_1/2, 1 h; t_1/2, 4.7 h). In plasma, unchanged drug predominated but lower levels of the deacylated metabolite rhodamine 110 (RH-110) and two unknowns were also detectable throughout the study. Drug fluorescence was recovered extensively in both urine and bile. In unconscious animals with ureteral cannulae, urinary excretion (11.4% of the dose in 6 h) occurred predominantly as unchanged RH-123 (97% of the total), with low levels of RH-110 (2.4%) and two unknowns (<0.6% combined) also being present. Similarly dosed conscious animals (without surgical intervention) housed in metabolic cages showed a comparable pattern of urinary excretion, with 11.9% of the drug dose being recovered in 6 h and 21.9%, by 48 h. Biliary drug elimination accounted for 8% of the delivered dose in 6 h in unconscious animals and for 11% by 36 h in conscious animals fitted with biliary cannulae. In contrast to urinary excretion, in which unchanged drug predominated, only 50% of the fluorescence recovered in bile was attributable to RH-123. The remainder was due to a number of products that were detectable throughout the study. Of these, one present at significant levels was identified as a glucuronide conjugate of RH-123, based on the liberation of parent drug when the purified metabolite was incubated with -glucuronidase or hydrolyzed with 1 N hydrochloric acid. Further studies with a radiolabeled form of RH-123 are necessary to establish the identity of the remaining unknowns disclosed in this work.This work was supported in part by research grants CA 44890 (T.W.S.) and CA 37082 (M.I.) from the National Cancer Institute, National Institutes of Health, United States Public Health Service     

Staff stress in AIDS prevention and service organizations: implications for health education practice

The purpose of this study was to identify the frequency of staff stressors and their association with programmatic factors in 51 AIDS prevention and service projects funded by the Robert Wood Johnson Foundation. The methodology included both quantitative (i.e. closed-ended survey questions) and qualitative (i.e. in-depth, open-ended interviews) data to identify the important sources of staff stress. The findings suggest that staff working in AIDS prevention and service projects perceive significant levels of stress regardless of project focus. The most frequently reported staff stresses were too much work, rapid organizational growth, burnout, and problems with staff retention and communication. Among the issues rarely reported as a source of staff stress were too little work, discomfort with the target population and personal health risk concerns. The programmatic factor most often associated with staff stress was obtaining additional funding. Health education interventions need to take a comprehensive approach that includes altering the psychosocial-environmental conditions that give rise to stressors and strengthening the individual and organizational factors that may modify the effects of stress on the AIDS workforce.     

Hodgkin disease: prediction of outcome with 67Ga scintigraphy after one cycle of chemotherapy

PURPOSE: To investigate gallium 67 scintigraphy performed early during treatment as a means to predict outcome and thus to optimize treatment of Hodgkin disease (HD) in the future. MATERIALS AND METHODS: Ninety-eight patients with HD were examined. Thirty-one patients underwent 67Ga scintigraphy after one chemotherapy cycle and 83 patients after a mean 3.5 cycles (range, 2-5 cycles). Sixteen patients underwent 67Ga scintigraphy both after one cycle and at midtreatment. Patients underwent whole-body scintigraphy and single photon emission computed tomography of the torso. Torso computed tomography (CT) was performed after a mean 3.5 cycles (range, 2-6 cycles). Failure-free survival was compared between patients with positive and patients with negative test findings (Kaplan-Meier method), and the significance of the difference was calculated. The association of failure-free survival with various prognostic clinical factors before treatment was compared (log-rank test univariate analysis). RESULTS: Failure-free survival differed significantly (P < .002) between patients with positive and patients with negative 67Ga scintigrams after one chemotherapy cycle but not at midtreatment. Failure-free survival was not significantly different between patients with positive and patients with negative CT scans at midtreatment. Twenty-two (92%) of 24 patients with negative 67Ga scintigrams after one cycle and 64 (82%) of 78 patients with negative scintigrams at midtreatment remained in complete response. In four (57%) of seven patients with positive 67Ga scintigrams after one cycle, treatment failed. CONCLUSION: 67Ga scintigraphy after one cycle of chemotherapy is a good early predictor of outcome of HD.     

Molecular genetics of brain tumors

As many as 40000 patients are newly diagnosed each year as having brain tumors. About half of these are metastatic foci of tumors originating outside the central nervous system, while the other half are primary tumors of central nervous system tissues. These are a diverse group of neoplasms. Currently, primary brain tumors are classified in a manner that reflects their histological appearance and location. The identification of cancer as a disorder of genes, however, has opened the possibility of classifying tumors according to the genetic alterations that underlie their pathogenesis and that regulate their malignant behavior. Two major classes of genes critical for the development of all types of cancer, including brain tumors, are now recognized: tumor suppressor genes, which encode genes that function to inhibit cell proliferation and tumor development, and oncogenes, which encode proteins that stimulate proliferation and mediate biological activities important for invasion, neoangiogenesis, immune escape, and other characteristics of malignancy. While in most cases the specific pathways regulating tumor characteristics such as tumor neoangiogenesis and tissue invasion remain to be defined, recognition of the genetic changes characteristic of individual tumor types should provide opportunities to develop more effective, less toxic therapies.     

Oral condyloma acuminatum associated with human papillomavirus and p53 overexpression mimicking cyclosporine effect in a transplant patient

A case of human papillomavirus-associated condyloma acuminatum in the oral cavity, presumed to be fulminant cyclosporine-induced gingival hyperplasia, is reported in a 55-year-old cardiac transplant patient. Approximately 47 months following the transplant, the patient developed severe hyperplasia of the uvula and oral mucosa, resulting in difficulty swallowing. The histopathologic features of the lesion were typical of those of condyloma acuminatum. In situ hybridization of the paraffin-embedded material revealed infection with human papillomavirus types 6/11. This case lends further support to the putative role of long-term cellular immunosuppression in the development of human papillomavirus-associated squamous lesions. In addition, positive staining for p53 protein raises the possibility of concomitant p53 involvement in the pathogenesis of this oral lesion.     

Pentose shunt activity in developing chick retina and pigment epithelium: A switch in biochemical expression in cultured pigment epithelial cells

Pentose shunt activity in developing chick retina and pigment epithelium was studied by measuring the rate of ¹⁴CO₂ evolution from glucose selectively labelled in the C-1 and C-6 positions. In the retina, shunt activity declines from appreciable levels at stages 29–31 to minimal activity in the 2-week-old hatched chick. Overall retinal metabolism also declines up to stage 45, but dramatically increases again after hatching. Developing chick pigment epithelium has minimal shunt activity at all stages studied. In contrast, cultured chick pigment epithelium has appreciable shunt activity which is constant over a period of several weeks in culture. This appears to be a switch in biochemical differentiation which could form the basis at least in part for subsequent changes in cell types observed in cultured pigment epithelial cells byEguchi and Okada (1973).     

Functions of the Coordination and Maintenance Committee and modifying the ICD-9-CM, Volumes 1 and 2

Balancing the multiple uses of ICD-9-CM with its central purpose as a statistical classification system is the function of the Coordination and Maintenance Committee. This article describes the process to modify diagnosis and procedure codes and how AHIMA members can contribute to improving ICD-9-CM.     

Genetic counseling for the deaf.

Genetic counseling is a process that emphasizes accurate diagnosis of hereditary conditions and communication of information to families. Genetic counseling involves systematic collection of family and medical history, a physical examination by a certified clinical geneticist, sharing of information with the family, and follow-up and support services. The issues that arise in genetic counseling can differ for every family and are often dependent on the degree of deafness present in the family, age of onset, and linguistic and cultural orientation. It is important for the genetic counselor to consider these factors in the provision of genetic services. With the increasing application of molecular genetics to the diagnosis and management of hereditary deafness and the increasing participation of families with deafness in research studies, the involvement of genetic counselors to provide information and education to consumers as well as medical professionals and researchers is becoming even more critical. The success of genetic counseling for the provision of information to families and the delineation of types of hereditary deafness through clinical and laboratory research is dependent on appropriate referrals by medical professionals, including otolaryngologists. A working relationship between otolaryngologists and clinical geneticists for the referral and evaluation of patients with hereditary deafness or deafness of "unknown" etiology is important.