Benefits experts react to reform.
Explore the source record for details and available documents.
California↗
Biomedical subjects
R Hoffman
Publications and source records attributed to R Hoffman.
Dental benefit plans.
Explore the source record for details and available documents.
American Dental Association↗
Radiosurgery for brain metastases from primary lung carcinoma.
PURPOSE: Brain metastases are a common problem in patients with lung cancer. This retrospective review was performed to describe the efficacy and toxicity of stereotactic radiosurgery for brain metastases from lung carcinoma and to evaluate prognostic factors for survival. PATIENTS AND METHODS: A retrospective review was performed of 113 patients with the diagnosis of lung carcinoma who underwent radiosurgery with or without whole-brain radiotherapy for management of newly diagnosed or recurrent, single, or multiple brain metastases from 1991 through 1998 at the University of California, San Francisco. Freedom from progression and survival were measured from the date of radiosurgery and estimated using the Kaplan-Meier method. Prognostic factors were evaluated with the log-rank test and Cox proportional hazards models. RESULTS: The median patient age at the time of radiosurgery was 59 years (range, 37-82 years), and the median Karnofsky performance score was 90 (range, 50-100). The median survival time from radiosurgery was 12.0 months overall, 13.9 months for 41 patients treated with radiosurgery alone initially, 14.5 months for 19 patients treated with radiosurgery and whole-brain radiotherapy initially, and 10.0 months for 53 patients with recurrent brain metastases. Among newly diagnosed patients, multivariate analysis showed that improved survival was associated with absence of extracranial metastases and fewer brain metastases. Among patients with recurrent brain metastases, improved survival was associated with higher Karnofsky performance score, control of the primary tumor, and fewer metastases. Measured by lesion, 1-year local freedom from progression probabilities were 81% for radiosurgery alone, 86% for radiosurgery and whole-brain radiotherapy, and 65% for radiosurgery performed after recurrence. In patients with newly diagnosed brain metastases, there was a significantly greater risk of developing subsequent brain metastases and of worse overall brain freedom from progression after radiosurgery alone versus radiosurgery and whole-brain radiotherapy. One-year brain freedom from progression probabilities were 13% without salvage therapy and 62% with salvage therapy in the 41 patients treated initially with radiosurgery alone, versus 67% without salvage therapy and 89% with salvage therapy in the 19 patients treated initially with radiosurgery plus whole-brain radiotherapy. DISCUSSION: Radiosurgery is an effective therapy for selected patients with newly diagnosed or recurrent brain metastases from lung carcinoma. Initial whole-brain radiotherapy with radiosurgery appears to improve brain control but not survival. Prospective, randomized trials are needed to further investigate the role of radiosurgery with and without whole-brain radiotherapy for brain metastases.
Adenocarcinoma↗
Hermansky-Pudlak syndrome.
A 55-year-old man had oculocutaneous albinism and a history of frequent bruising following minimal trauma. The simultaneous occurrence of these features was first described by Hermansky and Pudlak in 1959. The Hermansky-Pudlak syndrome follows an autosomal recessive trait and is most frequently found in Puerto Rico and in the Swiss alps. It consists of the triad phenotype of hypopigmentation, prolonged bleeding time due to platelet storage pool deficiency and accumulation of ceroid pigment in lysosomal organelles. Other serious features are pulmonary fibrosis and granulomatous colitis. The disorder is caused by mutations in the HPS1 gene on chromosome 10q23. The HPS1 gene product is involved in the trafficking of melanosomes, platelet dense bodies, and lysosomes.
Diagnosis, Differential↗
Feline preleukemia: an animal model of human disease. 1978.
Explore the source record for details and available documents.
Animals↗
Treatment of alopecia areata in the DEBR model using Cyclosporin A lipid vesicles.
Alopecia areata (AA) is a chronic cutaneous disease with a suspected autoimmune origin. We evaluated the efficacy of 0.5% Cyclosporin A (CyA) in a topically applied liposomal formulation as a potential treatment for AA using the Dundee Experimental Bald Rat (DEBR) model. The vehicle consisted of liposomes (75% phosphatidylcholine, 5% lysophosphatidylcholine, 5% sterol, natural oils) of 10% wt. in ethanol with and without 2% wt. terpenes (d-limonene: citral: cineole, 10:45:45) as a penetration enhancer (PE). Fifteen DEBR were allocated to 3 groups of 5. Groups I, II and III received CyA vesicles with PE, CyA vesicles without PE, and CyA in ethanol respectively. All rats were treated twice a day for 6 weeks within a 4 cm2 area on one bald flank with CyA while the contralateral flank received an equivalent control formulation. Rats in group I exhibited visible hair regrowth on the drug treated site after one week of drug application. Group II rats had visible hair regrowth by the end of the second week. The hair growth was progressive and reached a maximum density at the site of application after six weeks in both groups. Histological examination revealed a reduced inflammatory infiltrate and improved hair follicle morphology within the drug treated area as compared to the contralateral vehicle treated skin. Group III rats showed neither visible signs of hair growth nor reduction of hair follicle inflammation. The results of this proof of concept preliminary study suggest that CyA vesicle formulations with and without PE have promising potential as a topical treatment for AA in humans.
Administration, Cutaneous↗
Feline preleukemia: an animal model of human disease.
In man, hematologic abnormalities precede the development of acute myeloblastic leukemia in about one-third of individuals. This preleukemic state may represent a stage of adult leukemia wherein small numbers of leukemic cells are present and the normal marrow stem cell compartment has not been seriously compromised. A syndrome resembling human preleukemia occurs in cats infected with feline leukemia virus (FeLV). This disorder is characterized by anemia, leukopenia or thrombocytopenia occurring weeks or months prior to the development of feline acute leukemia. The natural occurrence of this syndrome in this domestic animal population makes it a potential model of human preleukemia. Initial poor results of therapy of human preleukemia presently prohibit one from carrying out controlled trials with chemotherapeutic agents in such a group of patients. Preliminary trials with chemo- and/or immunotherapy may be more easily attempted with FeLV infected preleukemic cats.
Animals↗
Numerous growth factors can influence in vitro megakaryocytopoiesis.
At least two classes of human megakaryocyte progenitor cells have been identified: the burst-forming unit megakaryocyte (BFU-MK) and the colony-forming unit megakaryocyte (CFU-MK). The BFU-MK is the most primitive progenitor cell committed to the megakaryocytic lineage. The CFU-MK appears to be a more differentiated megakaryocyte progenitor cell and is thought to be ultimately a descendant of the BFU-MK. A number of recombinant cytokines have recently been shown to be able to promote megakaryocyte colony formation in vitro. Recombinant GM-CSF and IL-3, in particular, have the ability to promote both CFU-MK- and BFU-MK-derived colony stimulatory formation. The activities of these two cytokines on in vitro megakaryocytopoiesis are also additive. Recent results of clinical trials in both primates and humans, in which these glycoproteins were administered in vivo, suggest that these cytokines, both alone and in combination, can enhance in vivo thrombopoiesis and therefore may be potentially useful in the treatment of thrombocytopenic disorders.
Animals↗
Responder T-cell subsets and antigenic stimulus in mixed lymphocyte-hepatocyte culture.
Explore the source record for details and available documents.
Animals↗
Idiopathic diabetes insipidus occurring in a patient with Turner's syndrome.
Explore the source record for details and available documents.
Adult↗
Variable in vitro erythropoiesis in patients with transient erythroblastopenia of childhood.
Transient erythroblastopenia of childhood (TEC) is a pure red cell aplasia which primarily affects children in the infant and toddler age group. The clinical syndrome of TEC is well defined and is characterized by moderate to severe anemia with reticulocytopenia, selective aplasia of the erythroid bone marrow elements, and spontaneous recovery, usually within a month of presentation. We utilized the plasma clot tissue culture technique to explore the defect of erythropoiesis in seven patients with TEC. Culture of bone marrow at diagnosis in four patients revealed an increased erythroid proliferative capacity in one and a decreased capacity in three. The former patient plus three additional patients were found to have a transient serum inhibitor of erythroid colony formation in autologous and allogeneic systems. The three patients with diminished erythroid proliferative capacity had no demonstrable serum inhibitor, and in one patient studied the erythroid proliferative capacity became supernormal after recovery. We conclude that although TEC has a characteristic clinical picture, in vitro studies reveal a variable expression of the erythropoietic defect and support the hypothesis of a heterogeneous pathogenesis of this disorder.
Anemia↗
The proliferative capacity of pure red cell aplasia bone marrow cells.
Pure red cell aplasia (PRCA) is a heterogeneous disorder. Immunologic abnormalities have recently been uncovered suggesting that both cell-mediated and humoral immune mechanisms may be of etiological importance in PRCA. Utilizing a technique for the cloning of bone marrow erythroid precursors, we determined the in vitro proliferative capacity of erythroid cells obtained from 21 patients with PRCA. Bone marrow cells from one group of patients produced normal or increased numbers of erythroid colonies while the in vitro proliferative capacity of bone marrow cells from a second group was characterized by subnormal erythroid colony formation. Sera obtained from the former group was frequently associated with demonstrable serum inhibitors of erythropoiesis, while PRCA in the latter group was probably the consequence of intrinsic erythroid stem cell defects or pathologic cellular interactions with nonerythroid regulatory cells. This survey of a relatively large population of patients with PRCA provides evidence for the multiple causative mechanisms that can be operative in the production of PRCA.
Adolescent↗
The relationship between tumor size and chemosensitivity of murine bladder cancer.
The relationship between tumor size and antitumor efficacy of chemotherapy was quantitated using an i.d. bladder cancer in C3H mice. The fundamental hypothesis was that tumor microenvironmental factors progressively changed with tumor growth, which then influenced the cell killing activity of agents. For all five chemotherapeutic agents examined, the antitumor efficacy progressively decreased as the tumor became larger ("volume effect"). The change in antitumor efficacy was expressed as the treatment delay (days) to cause a 50% reduction in antitumor efficacy (designated as volume effect/50, VE50). The VE50 value of Adriamycin (ADM) was 25.1, cisplatin was 10.4, carboplatin was 5.7, vinblastine was 4.7, and cyclophosphamide (CP) was 3.2 to 4.1 days; indicating the antitumor effect of ADM was least and CP was most influenced by tumor size at the time of treatment.
Animals↗
Surveillance for fetal alcohol syndrome in Colorado.
The authors performed surveillance for fetal alcohol syndrome with an existing birth defects registry. Fetal alcohol syndrome cases were identified from multiple sources using passive surveillance and from two selected medical sites using enhanced surveillance. Between May 1992 and March 1994, a total of 173 cases were identified, and the medical records of the cases were reviewed to determine whether the cases met a surveillance case definition for fetal alcohol syndrome. Of these cases, 37 (21 percent) met either definite (28) or probable (9) criteria for fetal alcohol syndrome, 76 met possible criteria (44 percent), and 60 (35 percent) were defined as not fetal alcohol syndrome. Enhanced surveillance had the highest sensitivity for definite or probable cases, 31 of 37 (84 percent), followed by hospital discharge data, 14 of 37 (38 percent). The authors also compared birth certificate information for 22 definite or probable cases in children born between 1989 and 1992 to birth certificate information for all Colorado births for that period. The proportion of mothers of children with fetal alcohol syndrome was statistically significantly greater (as determined by exact binomial 95 percent confidence limits) than the proportion of all mothers for the following characteristics: black race (0.23 versus 0.05), unmarried (0.55 versus 0.22), not employed during pregnancy (0.86 versus 0.43), and started prenatal care in the third trimester (0.18 versus 0.04). Surveillance for fetal alcohol syndrome can be accomplished with an existing registry system in combination with additional case finding and verification activities. Through followup investigation of reported cases, data can be gathered on the mothers of children with fetal alcohol syndrome. These data could be used to target fetal alcohol syndrome prevention programs.
Alcohol Drinking↗
Reversible inhibition of IL-8 receptor B mRNA expression and proliferation in non-small cell lung cancer by antisense oligonucleotides.
We examined the importance of IL-8 receptor B mRNA expression in the growth of non-small cell lung cancer (NSCLC). Using antisense oligonucleotide ICN 197, we were able to inhibit IL-8 R B mRNA expression in vitro. The sequence specific effect of antisense oligonucleotide and down-regulation of IL-8 R B mRNA was shown by Reverse Transcription Polymerase Chain Reaction (RT-PCR) and Southern blot analysis. The proliferation of treated cells was measured by 3H thymidine incorporation. We found that treatment of NSCLC cells caused reversible growth inhibition and reversible down regulation of IL-8 R B mRNA. Furthermore, we observed that the treatment of nude mice with oligonucleotide ICN 197 inhibited the growth of tumors developed from NSCLC cells injected subcutaneously. Our data in vitro suggest that IL-8 receptor B mRNA expression is required to maintain the proliferative rate of NSCLC. Based on the data in vivo. oligonucleotide ICN 197 may be considered for the development of novel therapeutic treatment for lung cancer.
Animals↗
Early hemopoietic progenitors in the peripheral blood of patients with severe aplastic anemia (SAA) after treatment with antilymphocyte globulin (ALG), cyclosporin-A and G-CSF.
BACKGROUND AND OBJECTIVE: We previously reported that patients with acquired severe aplastic anemia (SAA) treated with antilymphocyte globulin (ALG), 6-methylprednisolone, cyclosporin A (CyA) and granulocyte colony-stimulating factor (G-CSF) can mobilize peripheral blood hemopoietic progenitors (PBHP). The aim of the present study was to assess phenotypic and functional properties of these PBHP. METHODS: We studied seven patients who underwent 43 leukophereses (median 5) between day +30 and +80 following ALG, while in treatment with CyA and G-CSF. Mobilized peripheral blood hemopoietic progenitors were analyzed using surface markers, conventional assays for clonogenic cells (CFU-GM, BFU-E, CFU-GEMM) as well as the recently developed assay for long-term culture initiating cells (LTC-ICs). RESULTS: The proportion of CD34+ cells ranged between 0% and 5.4% (median 0.3%), CD34+DR between 0% and 3.5% (median 0.1%) and CD8+ cells between 3.3% and 56% (median 31%). When light density mononuclear cells (MNC) were plated in vitro, we could grow colony-forming units-granulo-macrophage (CFU-GM) (range 0-45/10(5) MNC; normal controls 21-200/10(5) MNC), burst-forming units-erythroid (BFU-E) (range 0-5/10(5) MNC; normal controls 0-6/10(5) MNC), multipotent colonies (CFU-GEMM) (range 0-3/10(5) MNC; normal controls 0-6/10(5) MNC) and high proliferative potential colony-forming cells (HPP-CFC) (range 0-3.4/10(5) MNC). We studied long-term culture-initiating cells (LTC-ICs) in 18 leukophereses from 4 patients; in 7/18 samples LTC-ICs were grown at low frequency (range 0.4-2/10(6) MNC) (normal controls 5-130/10(6) MNC), and in one patient in the absence of CFU-GM growth. The total yield of LTC-ICs in two patients was 7.64 and 10.5 x 10(2)/kg of body weight. INTERPRETATION AND CONCLUSIONS: This study suggests that cells with the phenotype and in vitro function of early hemopoietic progenitors are found, though in small numbers, in the peripheral blood of patients with SAA after treatment with immunosuppressants and prolonged G-CSF administration. Whether G-CSF-mobilized progenitors contribute to hemopoietic recovery in these patients remains to be determined.
Adolescent↗
Screening for pregnancy and contraceptive use among women admitted to a Denver detoxification center.
OBJECTIVE: To determine the prevalence of pregnancy and contraceptive use among female inpatients at a Denver detoxification center who were at risk of becoming pregnant. METHODS: The authors administered surveys and pregnancy tests to 373 female admissions to the Denver CARES detoxification center between March and September 1996. RESULTS: Most were admitted for alcohol-related reasons, and most reported previous pregnancies. Seven percent of admissions had positive pregnancy tests, and 56% of admissions reported not using contraceptives with every sexual encounter. CONCLUSIONS: Routine assessment of pregnancy status and contraceptive use in women admitted for detoxification, along with on-site family planning services, may be important components of efforts to prevent adverse outcomes associated with substance abuse during pregnancy, including fetal alcohol syndrome.
Adolescent↗