Early chronic lymphocytic leukemia: prognostic value of quantitative bone marrow MR imaging findings and correlation with hematologic variables.

PURPOSE: To determine the frequency of abnormal findings from quantitative bone marrow magnetic resonance (MR) imaging in patients with early-stage chronic lymphocytic leukemia, to correlate these findings with clinical parameters, and to compare spontaneous outcome in patients with normal or abnormal MR imaging findings. MATERIALS AND METHODS: In 21 patients with Binet stage A (Rai stage 0-I) disease, bulk T1 values of the vertebral bone marrow were determined and correlated with initial clinical, laboratory, histopathologic, and cytogenetic findings and with treatment-free survival. RESULTS: Bulk T1 values were normal (< 600 msec) in 14 patients and prolonged in seven. Patients with increased T1 had significantly higher blood (P = .017) and bone marrow (P = .015) lymphocytosis. None of the 14 patients with normal T1 values required specific therapy after a median follow-up of 13 months. Of the seven patients with abnormal T1 values, five required treatment after progression to Binet stage B or C disease at a median of 10 months. CONCLUSION: In patients with abnormal quantitative MR imaging findings, treatment-free survival appears to be significantly shorter (P < .001) than in patients with normal MR imaging findings.

Pharmacokinetics of sertindole and dehydrosertindole in volunteers with normal or impaired renal function.

OBJECTIVE: To study the effect of renal impairment on the pharmacokinetics of sertindole. METHODS: A single 4 mg oral dose of sertindole was given to normal subjects (n = 6) and subjects with various degrees of impaired renal function (n = 18) classified into mild, moderate, and severe/hemodialysis based on their creatinine clearance). The relationships between the pharmacokinetic parameters and the degree of renal impairment were investigated using regression analysis with creatinine clearance as an explanatory variable along with body weight. Subjects were also genotyped for CYP2D6-A or 2D6-B mutations. RESULTS: The mean CL/f and t1/2 values of sertindole ranged from 14 to 31 1.h-1 and from 73 to 93 h, respectively, and were not significantly related to creatinine clearances. There was no indication of any influence of creatinine clearance on the fraction of sertindole (0.994-0.995) binding to plasma proteins. The total fraction of the sertindole dose removed by dialysis was less than 0.1% Subjects with B/B genotype (n = 2) for CYP2D6 were associated with a distinctly lower clearance of sertindole (6.3 vs 25.3 1.h-1) than subjects with wt/wt genotype for CYP2D6. CONCLUSIONS: Since the pharmacokinetics of sertindole are unchanged by renal impairment, dosage adjustment does not appear to be necessary for subjects with various degrees of renal insufficiency or subjects with renal failure requiring hemodialysis.

Acute myeloid leukemia: lack of predictive value of sequential quantitative MR imaging during treatment.

PURPOSE: To assess the use of magnetic resonance (MR) imaging in monitoring treatment response in patients with acute myeloid leukemia (AML). MATERIALS AND METHODS: Bulk T1 and T2 were determined with at least four MR imaging examinations (strictly timed) during the first 6 weeks of treatment in 29 patients with AML (age range, 16-75 years; 15 female, and 14 male). Bulk T1 and T2 in responder (n = 22) and nonresponder (n = 7) patients were compared. RESULTS: Relative to pretreatment bulk T1 values, bulk T1 had increased a mean of 11% at week 1 and had decreased a mean of 7% and 39% at weeks 2 and 6, respectively. Values in nonresponder patients were not statistically significantly different (+11%, -14%, -38%). CONCLUSION: MR imaging of lumbar bone marrow in patients with AML demonstrated statistically significant changes in bulk T1 during treatment that correlated with changes in cellularity. However, neither the early increase in bulk T1 nor the rate or magnitude of the subsequent decrease in bulk T1 were indicative of a positive response to treatment.

Development of an institutional policy on artificial hydration and nutrition.

The issues involved in deciding whether to use artificial methods of delivering hydration and nutrition are often very difficult for patients, families, and health care providers. Once private and personal matters, these decisions now frequently involve the judicial system. Five years ago, Hospice of Washington recognized the need for a written policy and wrote the one published here. Its goal is to respect individual preferences and family concerns while addressing the nutrition and hydration needs of dying patients. The policy sets parameters on the issue, provides basic information, and encourages crafting the most fitting resolution to each situation.

Prolonged duration of blood pressure response to enalkiren, the novel dipeptide renin inhibitor, in essential hypertension.

The effects of sustained renin inhibition by repeated administration of enalkiren (A-64662), the novel dipeptide renin inhibitor, were evaluated in a randomized, double-blind, placebo-controlled, parallel-group study of 32 inpatients (eight per group) with essential hypertension who were maintained on a diet containing 60 meq/day sodium. Three different dosage regimens of enalkiren were studied: 1) 1.2 mg/kg quotid., 2) 0.3 mg/kg q.i.d., and 3) 0.1 mg/kg q.i.d. Each patient received an intravenous infusion every 6 hours for 1 week. Placebo infusions were used to mimic the 4 times/day dosing schedule. Blood pressure was measured periodically via 24-hour automated monitoring equipment. Mean plasma renin activity in the patient groups ranged from 1.58 to 2.68 ng angiotensin I/ml/hr. Plasma renin activity was promptly suppressed in all groups receiving enalkiren. Prolonged duration of plasma renin activity suppression (greater than or equal to 24 hours) was demonstrated after the administration of 1.2 mg/kg enalkiren. The 0.3 mg/kg q.i.d. and 1.2 mg/kg quotid. regimens produced statistically significant reductions (p less than or equal to 0.05) in systolic and diastolic blood pressures with clear evidence of persistent antihypertensive activity for 12 hours or more when compared with the placebo group. Despite relatively large reductions in mean systolic and diastolic blood pressure, mean pulse rates were essentially unchanged. The prolonged reduction in blood pressure with enalkiren without evidence of tachyphylaxis after 1 week of treatment suggests that renin inhibitors may emerge as useful therapeutic agents for the treatment of hypertension.

Terazosin, a new selective alpha 1-adrenergic blocking agent. Results of long-term treatment in patients with essential hypertension.

The long-term treatment of essential hypertension with terazosin, a new once-a-day alpha 1-adrenergic blocking agent, was evaluated in 364 hypertensive patients who received total daily doses of 1 to 40 mg for 3 weeks to 56 months. Consistent mean decreases in supine and standing systolic and diastolic blood pressures were observed throughout the study for patients treated with terazosin as monotherapy (supine, 9 to 12/10 to 13 mm Hg; and standing, 12 to 18/11 to 14 mm Hg) or in combination with other antihypertensive agents (supine, 12 to 16/12 to 15 mm Hg; and standing, 16 to 22/13 to 19 mm Hg). The most commonly reported adverse experiences were dizziness, headache, asthenia, cold symptoms, and nasal congestion. Adverse effects and metabolic disorders often associated with diuretics and beta blockers such as sexual dysfunction, hyperglycemia, hyperuricemia, hypokalemia, or adverse lipid effects were seen infrequently during long-term treatment with terazosin as monotherapy. Overall, terazosin was shown to be effective, safe, and well tolerated by most patients.

Extrapyramidal side effects and oral haloperidol: an analysis of explanatory patient and treatment characteristics.

The incidence of extrapyramidal side effects (EPS) was evaluated in 98 patients treated with haloperidol. The incidence of parkinsonism was higher at higher doses of haloperidol and in younger patients. Prophylactic antiparkinsonian medication was effective in younger but not in older patients. However, these medications were more effective in both young and old patients when given after parkinsonism developed. Akathisia was controlled by the benzodiazepine lorazepam in 14 out of 16 patients, while prophylactic antiparkinsonians were ineffective. The present study points to patient characteristics that may be of significance in the development of EPS due to haloperidol.