Incidence rates of acute promyelocytic leukemia among Hispanics, blacks, Asians, and non-Hispanic whites in the United States.

Despite significant improvements in the prognosis of acute promyelocytic leukemia brought about by therapeutic advances, understanding of the epidemiology of acute promyelocytic leukemia remains limited. Earlier reports have suggested that Hispanics may have an increased incidence of acute promyelocytic leukemia, but no systematic analysis of national data has yet been reported. We performed a retrospective cohort study, using data from the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute from 1992-2001 in order to compare leukemia incidence rates as a function of race and ethnicity. We identified 709 cases of acute promyelocytic leukemia and analyzed incidence rates by race and sex. Hispanics were not found to have greater lifetime incidence rates than whites, with an incidence relative rate (IRR) of 0.86 that of whites (P=0.17). The age distribution among Hispanics was significantly different from non-Hispanic whites, with greater incidence rates for children ages 1-19 years (IRR=1.9, P=0.02) and adult ages 20-44 years (IRR=1.6, P=0.004). Blacks had lower lifetime incidence rates than non-Hispanic whites (IRR=0.75, P=0.04), Hispanics (IRR=0.64, P=0.007), and Asians (IRR=0.67, P=0.03). Asians did not differ from non-Hispanic whites in lifetime or age-specific incidence rates. These results indicate that while US Hispanics do not have greater lifetime incidence rates of acute promyelocytic leukemia, blacks have lower incidence rates of acute promyelocytic leukemia than Hispanics, non-Hispanic whites, and Asians.     

Effects of estradiol alone and combined with norethisterone acetate on pulse-wave velocity in hypertensive postmenopausal women.

BACKGROUND: Arterial hypertension and postmenopausal reduction of estrogen levels may be involved in modifications of the stiffness of large arteries. OBJECTIVES: To evaluate the pulse-wave velocity (PWV) and indirectly the arterial stiffness in hypertensive postmenopausal women submitted to hormone therapy with estradiol alone or combined with norethisterone acetate. SUBJECTS: Forty-five hypertensive postmenopausal women were double-blindly, randomly assigned to three arms of treatment: placebo (group I); estradiol 2 mg/day (group II); or estradiol 2 mg/day and norethisterone acetate 1 mg/day (group III). METHODS: Arterial stiffness was assessed from PWV measurements of the common carotid and femoral arteries (CF-PWV) and the common carotid and radial arteries (CR-PWV) obtained using the automatic Complior(R) device, taken at baseline and after 12 weeks of treatment. RESULTS: After the 12-week treatment, values of CF-PWV and CR-PWV were not significantly different (p = 0.910 and p = 0.736, respectively) among the groups. Systolic blood pressure showed a positive correlation with CF-PWV in groups II and III (p = 0.02 and p < 0.001, respectively). CONCLUSIONS: PWV and arterial stiffness in postmenopausal hypertensive women did not reduce over a 12-week treatment with estradiol alone compared with the same period of treatment with estradiol combined with norethisterone acetate.     

Vaginal stenosis in patients treated with radiotherapy for carcinoma of the cervix

The aim of our study was to determine the incidence, timing, and severity of vaginal stenosis in patients with carcinoma of the cervix who had received pelvic and/or vaginal radiotherapy as part of their treatment. We also sought to determine if there were any predisposing factors for the development of stenosis. A retrospective chart review was undertaken for all the patients diagnosed with carcinoma of the cervix between January 1, 1990, and December 31, 2000 and treated with pelvic and/or vaginal radiation at Westmead Hospital. Since January 1, 1990, data regarding vaginal stenosis has been prospectively recorded on all the patients. Data collected included patient demographics, stage of disease, treatments administered, and incidence, timing, and severity of vaginal stenosis. One hundred and eighty-eight patients were treated. Mean age was 58.6 years. Thirteen percent of patients had stage IB disease, 45% had stage II disease, 39.5% had stage III disease, and 1.5% had stage IV disease. One hundred and seventy-nine patients returned for follow-up, and data regarding vaginal toxicity were available in 98%. Twenty-seven percent had grade 1 toxicity (partial stenosis or shortening but not complete occlusion), and 11% had grade 2 (complete occlusion). Stenosis of any grade was noted at a mean of 9.6 months and median of 7.5 months (range, 26 days-5.6 years) from completion of treatment. The only prognostic factor associated with increased risk of stenosis was age greater than 50 years (odds ratio 2.26). Vaginal stenosis is a common complication of pelvic and vaginal radiotherapy, occurring in 38% of patients. Stenosis occurs most often in the first year after treatment. Patients over the age of 50 are most at risk.     

Die klassifikatorische und pr?diktive Qualit?t des Merkmals “suicide intent” bei Parasuiziden Eine clusteranalytische Untersuchung Eine clusteranalytische Untersuchung

In einer clusteranalytischen Untersuchung mit 137 Patienten, die einen Parasuizid verübt hatten, wurden 6 Subgruppen unter Berücksichtigung der Klassifikationsvariable “suicide intent” isoliert. Es wurde die Hypothese geprüft, dass sich sowohl die Motivstrukturen als auch die Raten an wiederholten Parasuiziden in Abh?ngigkeit der Clusterl?sung bedeutsam voneinander unterscheiden. Die Ergebnisse unterstützen die Annahme einer zunehmenden Ausdifferenzierung der interpersonell orientierten Motivstrukturen mit sinkendem bzw. einer Einengung der Motivstruktur auf den Todeswunsch mit steigendem “suicide intent”. Es wurden folgende Subgruppen differenziert: eine Suizid-Hochrisikogruppe mit ausschlie?licher Todesintention und -motivation, 2 moderate Suizid-Risikogruppen mit hoher Todesintention und leichten Tendenzen zu interpersoneller Motivation, eine Subgruppe, gekennzeichnet durch eine manipulativ/strategisch orientierte Motivstruktur und auff?llig h?ufigen Parasuizidwiederholungen, eine Subgruppe mit vorrangig appellativ orientierten Motiven, Kontrollverlust und vergleichsweise seltenen Parasuizidwiederholungen und eine Subgruppe mit ambivalenter Motivstruktur (interpersonell und todesorientiert).     

Freezing of gait in postmortem-confirmed atypical parkinsonism.

The frequency and pathophysiology of freezing of gait (FoG) in atypical parkinsonism is unknown. We analysed the frequency of FoG in postmortem-confirmed atypical parkinsonian disorders (APD) comprising corticobasal degeneration (CBD), dementia with Lewy bodies (DLB), multiple system atrophy (MSA), and progressive supranuclear palsy (PSP). Sixty-six patients with pathologically confirmed APD (CBD, n = 13; DLB, n = 14; MSA, n = 15; PSP, n = 24) formed the basis for a multicenter clinicopathological study. Clinical features at first and last clinical visit were abstracted from patient records on standardized forms following strict instructions. At the first visit (median 36 months after symptom onset), 24% of APD had FoG (CBD, 8%; DLB, 21%; PSP, 25%; MSA, 40%). Logistic regression analysis showed a significant association of FoG and urinary incontinence (P = 0.04) at first visit. At last visit, 47% of APD had FoG (CBD, 25%; PSP, 53%; DLB, 54%; MSA, 54%). Clinicopathological correlation based on routine postmortem examination failed to identify a consistent neuropathological substrate of FoG. This study demonstrates that (1) FoG is common in APD, and (2) urinary incontinence is significantly associated with FoG in these disorders. Whether FoG and urinary incontinence share similar neuropathological substrates remains to be determined by future studies.     

Effects of verapamil on the pharmacokinetics and metabolism of epirubicin

Summary Experimental data suggest that multidrug resistance in cancer may be overcome by using an increased dose of anticancer agent(s) in combination with a resistance-modifying agent (RMA). We studied the pharmacokinetics and metabolism of both epirubicin (EPI) and verapamil (VPL) to explore the possible pharmacokinetic interactions between these two drugs. Ten patients with advanced breast cancer were given EPI (40 mg/m² in a daily i.v. bolus for 3 consecutive days), and five of them also received VPL (4×120 mg/daily p.o. for 4 consecutive days). The data indicated a significant interaction between these two drugs that affected their metabolism. The areas under the concentration-time curves (AUC) obtained for epirubicin glucuronide, epirubicinol glucuronide, and both of the 7-deoxy-aglycones were higher in the EPI+VPL group as compared with the EPI group. The AUC, terminal half-life, mean residence time, volume of distribution at steady state, and plasma clearance of EPI alone as compared with EPI+VPL did not differ significantly. These results suggest either an induction of enzymes necessary for drug metabolism or an increase in the liver blood flow, resulting in an enhanced generation of metabolites with time or in an inhibition of excretion processes. Comparisons of the AUC values obtained for EPI and its metabolites after the first, second, and third injections of EPI revealed a cumulative effect for the metabolites that was more pronounced in the EPI+VPL group, being significant (P<0.05) for epirubicin glucuronide in both treatment groups and for epirubicinol glucuronide in the EPI+VPL group. Maximal concentrations of VPL and nor-VPL reached 705±473 and 308±122 ng/ml, respectively, with the steady-state concentrations being 265±42 ng/ml for VPL and 180±12 ng/ml for nor-VPL.This study was supported by the Erich und Gertrud Roggenbuck-Stiftung zur Förderung der Krebsforschung (Hamburg). The anthracycline metabolites were kindly provided by Dr. A. Suarato (Farmitalia, Milano, Italy); nor verapamil was provided by Dr. Traugott (Knoll, Ludwigshafen, Germany)