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Biomedical subjects

R Ellison

Publications and source records attributed to R Ellison.

17 recordsLinked to original sources
PubMed2001

United States multicenter study of arsenic trioxide in relapsed acute promyelocytic leukemia.

PURPOSE: To determine the safety and efficacy of arsenic trioxide (ATO) in patients with relapsed acute promyelocytic leukemia (APL). PATIENTS AND METHODS: Forty patients experiencing first (n = 21) or > or = second (n = 19) relapse were treated with daily infusions of ATO to a maximum of 60 doses or until all leukemic cells in bone marrow were eliminated. Patients who achieved a complete remission (CR) were offered one consolidation course of ATO that began 3 to 4 weeks later. Patients who remained in CR were eligible to receive further cycles of ATO therapy on a maintenance study. RESULTS: Thirty-four patients (85%) achieved a CR. Thirty-one patients (91%) with CRs had posttreatment cytogenetic tests negative for t(15;17). Eighty-six percent of the patients who were assessable by reverse transcriptase polymerase chain reaction converted from positive to negative for the promyelocytic leukemia/retinoic acid receptor-alpha transcript by the completion of their consolidation therapy. Thirty-two patients received consolidation therapy, and 18 received additional ATO as maintenance. Eleven patients underwent allogeneic (n = 8) or autologous (n = 3) transplant after ATO treatment. The 18-month overall and relapse-free survival (RFS) estimates were 66% and 56%, respectively. Twenty patients (50%) had leukocytosis (> 10,000 WBC/microL) during induction therapy. Ten patients developed signs or symptoms suggestive of the APL syndrome and were effectively treated with dexamethasone. Electrocardiographic QT prolongation was common (63%). One patient had an absolute QT interval of > 500 msec and had an asymptomatic 7-beat run of torsades de pointe. Two patients died during induction, neither from drug-related causes. CONCLUSION: This study establishes ATO as a highly effective therapy for patients with relapsed APL.

Adolescent↗
PubMed2000

Diagnosis of malignant melanoma by general practitioners and hospital specialists.

The aim of this study was to audit all malignant melanomas confirmed histologically in the Scarborough Health District over six years, prompted by the continuing rise in incidence rate nationally and relatively high number of malignant melanomas excised by general practitioners (GPs) in this area. A total of 157 malignant melanomas were diagnosed (60% from females and 40% from males) over the six years; primary excisions being carried out by GPs (37%) and hospital specialists (63%). The clinical diagnosis of malignant melanoma was made in 9% of GP cases and 35% of the hospital specialist cases. However another 45.5% of GP cases, and 38% of hospital specialist cases were regarded as suspicious pigmented lesions clinically. The histological diagnosis was of superficial spreading malignant melanoma in 72% of the GP and 69% of the hospital specialist cases. Most of the GP melanomas were excised with a lateral margin of 2 mm or less (71%); around half of the hospital excisions had a margin of over 2 mm (49%). Most melanomas were 2 mm or less in depth (Breslow depth) in both the GP (81%) and hospital specialist (75%) series. Over the six year period (1993-98) the incidence of malignant melanomas has continued to rise, but Breslow depth at diagnosis has not changed significantly. It is therefore important to continue with early recognition of this condition by GPs in the first instance, reduction in its incidence being the long term goal. During five years of the study there were only 67 lesions thought clinically to be malignant melanoma (26 GP and 41 hospital specialist cases), but which proved to be benign histologically.

Clinical Competence↗
PubMed2000

Leukocytosis and the retinoic acid syndrome in patients with acute promyelocytic leukemia treated with arsenic trioxide.

PURPOSE: Arsenic trioxide, like all-trans-retinoic acid (RA), induces differentiation of acute promyelocytic leukemia (APL) cells in vivo. Treatment of APL patients with all-trans RA is commonly associated with leukocytosis, and approximately 50% of patients develop the RA syndrome. We reviewed our clinical experience with arsenic trioxide to determine the incidence of these two phenomena. PATIENTS AND METHODS: Twenty-six patients with relapsed or refractory APL were treated with arsenic trioxide for remission induction at daily doses that ranged from 0.06 to 0.17 mg/kg. RESULTS: Twenty-three patients (88%) achieved complete remission. Leukocytosis was observed in 15 patients (58%). The median baseline leukocyte count for patients with leukocytosis was 3,900 cells/microL (range, 1,200 to 72,300 cells/microL), which was higher than that for patients who did not develop leukocytosis (2,100 cells/microL; range, 500 to 5,400 cells/microL; P =.01). No other cytotoxic therapy was administered, and the leukocytosis resolved in all cases. The RA syndrome was observed in eight patients (31%). Patients who developed leukocytosis were significantly more likely to develop the RA syndrome (P <.001), and no patient without a peak leukocyte count greater than 10,000 cells/microL developed the syndrome. Among the patients with leukocytosis, there was no observed relation between the leukocyte peak and the probability of developing the syndrome (P =.37). CONCLUSION: Induction therapy of APL with all-trans RA and arsenic trioxide is associated with leukocytosis and the RA syndrome. These clinical effects seem to be intrinsically related to the biologic responsiveness and the differentiation process induced by these new agents.

Antineoplastic Agents↗
PubMed1999

Automated purification and quantification of oligonucleotides.

We have developed automated methods for the trityl-on purification and quantification of synthetic oligonucleotides. Oligonucleotide purification is by solid-phase extraction cartridges using Amberchrom CG-50 resin on an XYZ-axis robotic system. Quantification is by OD260nm using an online UV-visible spectrophotometer with sipper. The purification of 20 oligonucleotides requires 5 min of user set-up time, plus 20 min per sample of robot time. For a 15-25-mer at the 40 nmol scale of synthesis, the method gives a yield of 2.8 ODs from a load of 10.1 OD, i.e., a 28% average yield. Oligonucleotides purified by this method have proven to be successful for primers for automated DNA sequencing.

Autoanalysis↗
PubMed1998

Electrophysiological monitoring in clinical trials. Roche Neuropathy Study Group.

Electrophysiological testing remains an important efficacy parameter in clinical neuropathy trials. The quality of nerve conduction studies in reported trials varies greatly, and may be responsible for negative results. We report the utilization of an expert core lab for electrophysiological testing. With the core lab, the variability of repeat testing is comparable to that of a single, excellent laboratory. Motor conduction velocities demonstrated a coefficient of variation of 3% and sensory conduction velocities 4% across 60 study sites. The distal motor evoked potential amplitudes varied by 13% at the ankle, and 10% at the wrist. The sensory potential amplitudes varied by 16% at the ankle, and 11% at the wrist in 60 sites. The overall monitoring rate in all submitted nerve conduction tracings was 36.6%. Our results show that an expert core lab can improve the electrophysiological quality of clinical trial data with the potential to show small changes in nerve conduction velocities and in both motor and sensory potential amplitudes.

Diabetic Neuropathies↗
PubMed1996

Incidence of overestimation and underestimation of hypertension in a large sample of Canadians with mild-to-moderate hypertension.

OBJECTIVE: To determine the prevalence of overestimated and underestimated hypertension in a large sample of Canadians with mild-to-moderate hypertension before and after antihypertensive treatment. DESIGN: Data were retrieved from files of 1019 patients in whom clinic and ambulatory blood pressures had been measured both at the start and at the end of several studies involving various pharmacological antihypertensive agents. METHODS: Overestimation and underestimation of hypertension were calculated from the difference between office and awake ambulatory blood pressure both for systolic and for diastolic values (standard criteria) and also from the difference between observed ambulatory blood pressure and the predicted level estimated from individual office blood pressure by means of a regression equation derived for the group (criteria of Perloff et al.). RESULTS: Approximately 20% of the patients satisfied both sets of criteria for overestimation of systolic and diastolic hypertension before treatment. A significantly greater proportion of women showed overestimation of diastolic hypertension compared with men (approximately 27 and 17%, respectively, P < 0.05) on the basis of either set of criteria. Treatment did not affect the prevalence of overestimation of hypertension for the group as a whole, but the proportion of women in whom diastolic hypertension was overestimated decreased to above 17% after treatment (P < 0.001). The same proportion of patients satisfied the criteria of Perloff et al. for underestimation of hypertension, but only about 10% satisfied the standard criteria for this condition, both before and after treatment. The reproducibility of overestimation or underestimation of hypertension was 30-40%, independently from the criteria used. CONCLUSIONS: About one-fifth of patients display overestimated hypertension and, according to the criteria of Perloff et al., as great a proportion show underestimated hypertension. Thus, as many hypertensive patients may be overmedicated and undermedicated on the basis of clinic blood pressure compared with ambulatory blood pressure measurement.

Journal Article↗
PubMed1995

Problems in the diagnosis of pituitary adenoma (Cushing's syndrome) in horses.

Thyrotropin releasing hormone (TRH) stimulation tests were carried out on a number of horses, including one clinically affected horse whose age and clinical signs suggested that a pituitary adenoma was most unlikely. The results of these tests indicated that, according to criteria published overseas, the majority of these horses had pituitary adenomas. The fact that clinically normal or affected horses may have marked increases in cortisol concentrations indicates that the TRH stimulation test is not suitable for the diagnosis of pituitary adenoma. Other tests, including alterations in glucose metabolism and, if available, ACTH measurements, are probably more useful for diagnosis. However, most diagnoses will probably rely upon the characteristic clinical signs.

Journal Article↗
PubMed1994

Correlation of antiphospholipid antibodies and protein S deficiency with thrombosis in HIV-infected men.

Antiphospholipid antibodies (aPL) and free protein S (PSF) deficiency have been associated with clinical thrombosis. Previous reports described a high prevalence of these abnormalities in HIV-infected individuals, but suggested there was little associated clinical thrombosis. A cohort of 74 HIV-infected men were studied for aPL, PSF deficiency and the development of thrombosis. aPL, predominantly anticardiolipin antibodies (aCL), were detected in 86% and PSF deficiency in 33%. While 42% of men with aPL also had low PSF levels, there was no correlation between aCL titres or most measures of aPL and PSF levels. However, a strong correlation was noted between a subset of aPL that reacted to phosphatidylethanolamine by hexagonal array assay and low PSF levels. There was no significant correlation between aPL, PSF deficiency and clinical features (medication use, opportunistic infection, CD4 cell count) of HIV in 60 patients for whom clinical information was available. The overall incidence of thrombosis in this group was 18%, and thrombosis developed in 6.6% of those followed prospectively over a median follow-up of 12 months. Development of thrombosis was not significantly correlated with aPL or PSF deficiency, but the high prevalence of these abnormalities may necessitate larger study groups to determine the risk associated with these coagulation changes. Study of a larger group with careful analysis of subsets of aPL, especially those associated with low PSF levels, and longer clinical follow-up could identify the HIV-infected individuals at risk for thrombosis.

Adult↗
PubMed1987

Comparative effects of intravenously administered alizapride and prochlorperazine in cisplatin-induced emesis.

A randomized, double blind crossover trial compared the antiemetic effects of alizapride, a benzamide, and prochlorperazine, a phenothiazine, both administered intravenously to 32 patients treated with chemotherapy combinations containing cisplatin. The total dose of alizapride administered to each patient was 14 mg/kg, and of prochlorperazine .56 mg/kg, divided in five doses. Although alizapride resulted in complete protection against emesis in 31% of the patients during their first course of cisplatin therapy, 42% of those who received alizapride had five or more episodes of emesis. Although prochlorperazine was less effective in offering complete protection against emesis, only 15% of the patients receiving this drug vomited more than five times. The duration of emesis during prochlorperazine treatment was also significantly shorter than during alizapride therapy (p less than 0.02). Optimal dosage and pharmacokinetic distribution of both drugs should be investigated further.

Adult↗