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Biomedical subjects

C A Crowley

Publications and source records attributed to C A Crowley.

8 recordsLinked to original sources
PubMed2001

Phase 2 and 3 clinical trial of oral bexarotene (Targretin capsules) for the treatment of refractory or persistent early-stage cutaneous T-cell lymphoma.

OBJECTIVES: To determine the safety and efficacy of oral bexarotene (Targretin capsules; Ligand Pharmaceuticals Incorporated, San Diego, Calif). DESIGN: The effects of 2 randomized doses of 6.5 mg/m(2) per day (with crossover for progression) vs 650 mg/m(2) per day (later modified to 300 mg/m(2) per day) were evaluated in an open-label, multicenter, phase 2 and 3 study conducted between February 1997 and November 1998. SETTING: Eighteen international cutaneous T-cell lymphoma clinics at academic referral centers. PATIENTS: Fifty-eight patients with biopsy-proven stage IA through IIA cutaneous T-cell lymphoma that was refractory to (or patients were intolerant of) treatment or had reached at least a 6-month response plateau under at least 2 forms of prior therapy (median of 3.5 prior therapies). INTERVENTION: Bexarotene (Targretin capsules) administered once daily with meal for 16 weeks or longer. MAIN OUTCOME MEASURES: Primary end point classification of overall response rate of complete and partial remissions determined by either the Physician's Global Assessment of Clinical Condition or the objective Composite Assessment of Index Lesion Severity. Body surface area, time to response, duration of disease control, time to disease progression, individual index lesion signs and symptoms, and quality of life parameters were secondary outcomes. RESULTS: Responses (> or = 50% improvement) were seen in 3 (20%) of 15 patients with an initial dose at 6.5 mg/m(2) per day (95% confidence interval [CI], 0%-40%), 15 (54%) of 28 patients at 300 mg/m(2) per day (95% CI, 35%-72%), and 10 (67%) of 15 patients at above 300 mg/m(2) per day (95% CI, 43%-91%). The rate of progressive disease was 47%, 21%, and 13% at the same dose levels, respectively. Eight (73%) of 11 patients crossing over from 6.5 mg/m(2) per day to higher doses subsequently responded. The median duration of response from start of therapy could not be estimated for the 15 patients at 300 mg/m(2) per day owing to low relapse rates in 2 patients (13%); at higher doses it was 516 days. The following drug-related adverse effects were reversible and treatable: hypertriglyceridemia (46 patients [79%]), hypercholesterolemia (28 patients [48%]), headache (27 patients [47%]), central hypothyroidism (23 patients [40%]), asthenia (21 patients [36%]), and leukopenia (16 patients [28%]). No cases of drug-related neutropenic fever, sepsis, or death occurred. Pancreatitis occurred in 3 patients with triglyceride levels higher than 14.69 mmol/L (1300 mg/dL), all of whom were taking 300 mg/m(2) or more of oral bexarotene per day. CONCLUSIONS: Bexarotene (Targretin capsules) (the first retinoid X receptor-selective rexinoid) was well tolerated and effective as an oral treatment for 15 (54%) of 28 patients with refractory or persistent early-stage cutaneous T-cell lymphoma at doses of 300 mg/m(2) per day. Hypertriglyceridemia and hypothyroidism require monitoring but are reversible and manageable with concomitant medication.

Administration, Oral↗
PubMed1985

Normal and recombinant human growth hormone administered by constant infusion feminize catechol estrogen formation by rat liver microsomes.

Human GH or recombinant DNA-derived human GH administered to normal mature male rats by constant infusion decreased hepatic 2-hydroxylation of estradiol to female levels, as measured by 3H2O release and isolation of the catechol estrogen product. PRL had no effect under the same conditions. The maximum response to GH was attained at an infusion rate of 0.02 IU/h . kg after 5-7 days, and a significant change was observed within 1-2 days. The effect of GH was primarily on hydroxylation of C-2 of the estrogen, as demonstrated by comparative studies with estradiol labeled with 3H at C-4 or C-6,7, and appeared to be mediated by the cytochrome P-450 system of the liver microsomes. Ascorbic acid at 1 mM did not affect 2-hydroxylation significantly while protecting the catechol estrogen produced from further oxidation. The results indicate that GH has the potential to regulate estrogen metabolism in the liver and provide evidence for another component in the hypothalamic-pituitary-liver axis.

Animals↗
PubMed1984

Subcellular localization of the large subunit of Mo1 (Mo1 alpha; formerly gp 110), a surface glycoprotein associated with neutrophil adhesion.

Mo1 alpha (formerly gp 110) is a neutrophil glycoprotein whose deficiency is associated with abnormalities in several neutrophil functions, including defects in adherence, chemotaxis, and phagocytosis. Examination of whole cells and subcellular components by the use of both immunological and electrophoretic techniques demonstrated that Mo1 alpha was located primarily in the specific granules but that a small portion was present in the plasma membrane, where it is exposed to the extracellular environment and can bind to anti-Mo1 antibody. During degranulation, Mo1 alpha is translocated from the specific granules to the plasma membrane, resulting in a 5-10-fold increase in the surface expression of this glycoprotein. These findings plus previous work suggest that plasma membrane-associated Mo1 alpha is needed for a normal interaction between neutrophils and underlying surfaces, and raise the possibility that the increase in surface adhesiveness of neutrophils that have discharged their specific granules might be due in part to the increase in the amount of Mo1 alpha in the plasma membranes of these degranulated cells.

Animals↗
PubMed1984

Recurrent and metastatic mesoblastic nephroma in infancy.

Local recurrence or metastasis of mesoblastic nephroma is extremely uncommon. The first report of a child with mesoblastic nephroma to have both of these problems is presented. The usual course of mesoblastic nephroma is benign, with nephrectomy being curative. Adjuvant treatment is not necessary and may be lethal. However, a review of the five patients who developed locally recurrent and/or metastatic tumor indicates that chemotherapy and radiotherapy are of benefit and can produce long-term disease-free survival.

Antineoplastic Agents↗
PubMed1982

Studies on the interaction between GP-18-0-deficient neutrophils and vascular endothelium.

A patient whose neutrophils lack the glycoprotein gp-180 shows an increased susceptibility to bacterial infections. Neutrophils from this patient migrate abnormally both in vivo and in vitro. To examine the basis for this abnormality in migration, a study was carried out on the interaction of gp-180-deficient neutrophils with artificial surfaces and with human endothelial cell cultures. Compared with normal neutrophils. gp-180-deficient neutrophils showed decreased adhesion to cold-insoluble globulin-coated plastic surfaces, and their ability to spread on this substratum was greatly impaired. In contrast, gp-180-deficient neutrophils interacted in a normal fashion with endothelial monolayers, attaching to their surfaces and migrating between cell junctions to spread between the monolayers and the subjacent plastic. A normal interaction with endothelium in vivo was implied by the finding that the rise in the neutrophil count in response to epinephrine, an index of the marginated pool, was normal in the gp-180-deficient patient. We conclude that the abnormal function of gp-180-deficient cells is unlikely to be caused by a faulty interaction with the vascular endothelium. We postulate instead that these cells migrate poorly in vivo because of an abnormal interaction with extravascular connective tissue matrix constituents.

Bacterial Infections↗
PubMed1980

An inherited abnormality of neutrophil adhesion. Its genetic transmission and its association with a missing protein.

Neutrophils from a five-year-old boy with recurrent bacterial infections failed to spread on surfaces, leading to a severe defect in chemotaxis and a mild impairment in phagocytosis. Failure to spread was also seen in a fraction of the neutrophils from the patient's mother and sister, but cells from his father and brother were normal. Gel electrophoresis revealed that a protein with a molecular weight of 110,000 daltons (designated gp 110) present in the particulate fraction of normal neutrophils was absent from the patient's cells, and that its levels were below normal in cells from his mother and sister but normal in neutrophils from his father and brother. These findings suggest that gp 110 is necessary for the spreading of neutrophils onto surfaces, that the functional abnormality in the patient's cells is caused by its absence, and that deficiency of gp 110 is an X-linked congenital disease.

Blood Proteins↗
PubMed1979

Extrarenal Wilms' tumor.

Extrarenal Wilms' tumor is a rare entity usually seen as a mass in the retroperitoneal area. It may surround and distort otherwise normal kidneys and ureters. Like many other abdominal masses, its true nature remains uncertain until microscopic examination has been performed after surgery. The tumors appear to behave clinically like intrarenal Wilms' tumors, though in the cases reviewed there was a relatively higher incidence in older patients. The prognosis of extrarenal Wilms' tumor is difficult to evaluate due to the small numbers of cases reported and the differing tumor therapy used. However, those cases treated most recently appear to have a good response to therapy.

Child, Preschool↗