A comparison of the responses to recombinant human erythropoietin in normal and uremic subjects.

The erythropoietic response to graded doses of recombinant human erythropoietin (epoetin alfa) was assessed in 24 hemodialysis patients by quantitative ferrokinetic studies, and measurement of the reticulocyte count and plasma levels of transferrin receptor protein. These responses were compared to those of 22 normal subjects. Epoetin alfa was given intravenously at 15, 50 or 150 U/kg every other day for four injections. Three patients with chronic renal failure were restudied after renal function was restored following renal transplantation. The results of these three different measurements of erythroid function showed that the acute response to recombinant human erythropoietin was similar in normal subjects and patients with renal failure. We conclude that chronic uremia does not alter the responsiveness to erythropoietin in vivo.     

Dendrotoxin-sensitive K+ currents contribute to accommodation in murine spiral ganglion neurons

We have previously identified two broad electrophysiological classes of spiral ganglion neuron that differ in their rate of accommodation ( Mo & Davis, 1997 a ). In order to understand the underlying ionic basis of these characteristic firing patterns, we used α-dendrotoxin (α-DTX) to eliminate the contribution of a class of voltage-gated K⁺ channels and assessed its effects on a variety of electrophysiological properties by using the whole-cell configuration of the patch-clamp technique. Exposure to α-DTX caused neurons that initially displayed rapid accommodation to fire continuously during 240 ms depolarizing test pulses within a restricted voltage range. We found a non-monotonic relationship between number of action potentials fired and membrane potential in the presence of α-DTX that peaked at voltages between –40 to –10 mV and declined at more depolarized and hyperpolarized test potentials. The α-DTX-sensitive current had two components that activated in different voltage ranges. Analysis of recordings made from acutely isolated neurons gave estimated half-maximal activation voltages of –63 and 12 mV for the two components. Because α-DTX blocks the Kv1.1, Kv1.2 and Kv1.6 subunits, we examined the action of the Kv1.1-selective blocker dendrotoxin K (DTX-K). We found that this antagonist reproduced the effects of α-DTX on neuronal firing, and that the DTX-K-sensitive current also had two separate components. These data suggest that the transformation from a rapidly adapting to a slowly adapting firing pattern was mediated by the low voltage-activated component of DTX-sensitive current with a potential contribution from the high voltage-activated component at more depolarized potentials. In addition, the effects of DTX-K indicate that Kv1.1 subunits are important constituents of the underlying voltage-gated potassium channels.     

Atributable risk of breast,prostate, and lung cancer in Hawaii due to saturated fat

The dietary data from case-control studies of breast, prostate, and lung cancer in Hawaii revealed that saturated fat was a risk factor for these malignancies. The dietary intakes from the three studies were used to calculate the attributable risk (AR) due to saturated fat. For all ethnic groups combined, the ARs for the highest quartiles of intake were 14.9 percent for female breast cancer, 13.0 percent for prostate cancer, and 23.1 percent for male lung cancer. Our results suggested that a reduction of saturated fat to the lowest quartiles of intake could result in a 10 to 20 percent decrease in risk for these three cancers in Hawaii. We also examined the ethnic-specific risks associated with saturated fat consumption among the Japanese and the Caucasians in the three studies. The ARs for the highest quartiles of intake were notably higher among the Caucasians than the Japanese, primarily due to the difference in their dietary patterns. Although the calculated AR due to saturated fat was higher among the Caucasians than among the Japanese, all persons in the population would derive considerable benefit by reducing their intake of this nutrient.Authors are with the Epidemiology Program, Cancer Research Center of Hawaii, University of Hawaii, 1236 Lauhala Street, Honolulu, HI 96813, USA. Address correspondence to Dr Hankin. This study was supported in part by NIH Grant PO1 CA 33619.     

Chronic Bullous Dermatosis of Childhoo Immonopathologic Studies

Chronic bullous dermatosis of childhood (CBDC) is a distinctive subepidermal blistering disorder that characteristically involves the lower face, neck, lower trunk, and diaper area. Nearly all affected patients have a continuous linear band of IgA at the dermoepidermal junction by direct immunofluorescence and many have circulating IgA antibasement membrane antibodies. Few ultrastructural studies have been performed to determine the location of these IgA autoantibodies. We examined an infant with the typical clinical, histopathologic, and immunopathologic features of CBDC in whom a circulating, lamina lucida-reactive IgA autoantibody was identified with a new, more sensitive, split-skin indirect immunofluorescence technique.     

Tissue collection for correlative studies in childhood cancer clinical trials: ethical considerations and special imperatives.

Federal regulations prescribe distinct protections for children participating in research studies. Procedures for collecting tissue specimens from children solely for research purposes must pose no more than a minor increase over minimum risk, thereby limiting the approvable correlative biologic studies to evaluate molecularly targeted agents in children with cancer. Ethical issues arise when approvable correlative studies are a mandatory component of an early-phase pediatric clinical trial of new anticancer agents. The National Cancer Institute Cancer Therapy Evaluation Program sponsored a workshop in 2002 to discuss tissue collection for correlative biologic studies in early-phase childhood cancer clinical studies of molecularly targeted agents. Workshop participants recommended the following: (1) tissue specimens for correlative studies should provide vital clinical and scientific results to qualify for early-phase pediatric study consideration; (2) parents should receive a realistic appraisal of the risks, requirements, and potential for benefit of phase I protocol participation; (3) investigators should clearly distinguish clinically necessary procedures from research procedures of no benefit to the child to improve correlative study informed consent; and (4) participation in correlative research studies included in clinical trials generally should be voluntary. The need to acquire important biologic data regarding new molecular agents will challenge the ingenuity of pediatric cancer researchers, necessitating the application of highly sensitive laboratory assay methods, new imaging procedures, and preclinical models of childhood cancer. Such innovative methods can allow necessary scientific information to be obtained while simultaneously respecting the protections appropriately afforded to children participating in research studies and minimizing the burden of research participation for children with cancer and their families.     

Anesthesia and/or Sedation for Pulsed Dye Laser Therapy

One of the most exciting developments in pediatric dermatology has been the use of the flashlamp-pumped, 585-nm, pulsed dye laser for treatment of vascular birthmarks. In many cases the results are miraculous. The increase in self-esteem and happiness of many children and adolescents has been overwhelming; for some, depression has been lifted, stuttering has ceased, social involvement has increased, and antidepressants have been discontinued. There are many success stories to tell.
Despite the remarkable effects of the pulsed dye laser and the medical and psychosocial indications for its use, the issue of pain control remains significant. We have no perfect outpatient pediatric anesthetic. Most methods carry either some risk or, if not hazardous, often are not very effective for controlling pain. Needless to say, a diversity of opinions exist on how to manage discomfort from this treatment modality. Therefore, we thought it would be useful to share the experiences and opinions of several dermatologists who have extensive experience with the pulsed dye laser.     

Probe™, a balloon wire: Initial experience

Coronary angioplasty is unsuccessful in <3–5% of cases because the balloon catheter fails to follow a guidewire that has traversed a lesion. Between June 1986 and August 1987, 31 lesions were unable to be crossed with at least two standard angioplasty catheters. Finally, a 2.0-mm-diameter Hartzler LPS (ACS) was utilized and successfully crossed and dilated 16 out of 31 lesions (52%). In the remaining 15 lesions, the Probe^TM (USCI) 2.0 mm diameter × 1.5 cm long balloon wire was able to cross the lesions in 13 (82%) and successfully dilated 12. In one case, lesion rigidity prevented the balloon from expanding at 14 atm. A right coronary artery lesion was attempted in 11 cases, and a left anterior descending and circumflex artery lesion in two patients each. No complications were encountered. In seven out of 12 successful Probe^TM cases, a larger balloon catheter was used to further dilate the artery. This new balloon wire has increased our success rate in severe stenoses and in tortuous vessels with severe distal lesions, in which presently available angioplasty equipment has failed.     

How are health professionals earning their living in Malawi?

Background  

The migration of health professionals from southern Africa to developed nations is negatively affecting the delivery of health care services in the source countries. Oftentimes however, it is the reasons for the out-migration that have been described in the literature. The work and domestic situations of those health professionals continuing to serve in their posts have not been adequately studied.