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.     

Diastolic function in children and adolescents on dialysis and after kidney transplantation: an echocardiographic assessment

Thirty-seven children and adolescents on renal replacement therapy (11 on haemodialysis, 14 on continuous ambulatory peritoneal dialysis and 12 after renal transplantation) were studied by echocardiography, echo-Doppler and phonocardiography. Right and left ventricular (R/L V) diastolic functions were measured by transmitral and transtricuspid flow velocities and by LV isovolumic relaxation time (LVIRT). Thirty-seven age- and sex-matched healthy subjects served as controls. R/L V diastolic dysfunction was only observed in the dialysis patients. In these patients LVIRT was prolonged. LV and RV peak inflow velocities were increased both in early (E) and late (A) diastole with a reduction in the E/A ratios. This pattern of diastolic dysfunction is compatible with the combined effects of a hypercirculatory state (volume overload, anaemia, arteriovenous fistula) and an abnormality of cardiac relaxation. The transplant patients showed no major cardiac abnormalities.     

Computational modeling to predict effect of treatment schedule on drug delivery to prostate in humans.

PURPOSE: To evaluate a computational approach that incorporates experimental data in preclinical models to depict doxorubicin human tissue pharmacokinetics. EXPERIMENTAL DESIGN: Beagle dogs were given 2 mg/kg doxorubicin as i.v. bolus, 4-h infusion, or 96-h infusion. Concentrations in plasma, prostate (target tissue), heart (toxicity), and major tissues for disposition were determined and modeled. Model parameters were obtained after the bolus injection with model validation based on the 4-h and 96-h infusion data. Clinical pharmacokinetic data and scale-up gave doxorubicin profiles in human prostate and heart. RESULTS: In agreement with in vitro results, tissues were best modeled with two compartments, one rapidly and one slowly equilibrating. The developed tissue distribution model predicted concentrations for all three administration regimens well, with an average deviation of 34% (median, 29%). Interspecies scale-up to humans showed that the change from a bolus injection to a slow, 96-h infusion (a) had different effects on the drug partition and accumulation in heart and prostate, and (b) lowered the peak concentration in the plasma by approximately 100-fold but had relatively little effect on maximal heart concentration ( approximately 33% lower). The simulated drug exposure in a human prostate was above the exposure required to inhibit tumor proliferation but was 30 to 50 times below that needed for cell death. CONCLUSION: The present study shows a computation-based paradigm for translating in vitro and in vivo preclinical data and to estimate and compare the drug delivery and pharmacokinetics in target tissues after different treatment schedules.     

Intraprostatic chemotherapy: distribution and transport mechanisms.

PURPOSE: The present study evaluated the tissue distribution and targeting advantage of intraprostatic chemotherapy. EXPERIMENTAL DESIGN: We studied the delivery and spatial distribution of a fluorescent drug, doxorubicin, in the prostate of beagle dogs, after intraprostatic or i.v. administration. Drug concentrations were measured using high-performance liquid chromatography and confocal fluorescence microscopy. RESULTS: I.v. and intraprostatic injections yielded qualitatively and quantitatively different doxorubicin distribution in the prostate. A relatively homogeneous distribution was found after i.v. administration, whereas intraprostatic injection yielded a highly heterogeneous distribution with >10-fold higher concentrations localized in a cone-shaped glandular lobule bound by fibromuscular stroma, compared with other parts of the prostate. Compared with i.v. injection, intraprostatic injection yielded, on average, approximately 100-fold higher tissue-to-plasma concentration ratio, ranging from 963-fold near the injection site to 19-fold in the contralateral half of the prostate. The drug distribution within the prostate further suggests an important role for acinar flow in intraprostatic drug transport. CONCLUSIONS: Intraprostatic administration represents a viable option to deliver high drug concentrations within the prostate. The results further suggest the fibromuscular stroma separating the prostatic lobules as a major barrier to drug transport and convective flow as an important drug transport mechanism in the prostate.     

Aesthetic aspects in reconstructive microsurgery

The reconstruction of a part of the body that has lost or inhibited function has been the most important aspect of reconstructive surgery in the past. Because of the existence of better techniques and the patient's wish for social reintegration, the plastic surgeon today is forced to consider the aesthetic results of his work more than in the past. Sometimes microsurgical procedures in reconstructive surgery are the only chance for the patient to be healed or palliated. Experience with more than 350 free tissue transfers gave us the opportunity to estimate the value of a donor flap with respect to the requirements of the receiving site. To satisfy the high aesthetic demands in these cases, it was necessary for the right place and shape the flap to fit as closely as possible, even if further corrections were necessary to achieve a satisfactory result. The transfer of latissimus dorsi and radial forearm flaps to the face and lower leg is discussed in cases of tumorus diseases and severe injuries of young and old patients.Presented to the IXth Congress of the International Society of Aesthetic Plastic Surgery, New York, October 13, 1987