Operational dermatology

Military dermatology encompasses all cutaneous manifestations that present to medical officers in a deployed situation, either in peacetime or in war. Medical officers in a field environment cannot avoid facing cutaneous quandaries. This article briefly highlights the omnipresent threat of cutaneous disease. It follows with a cost-effective look at periodically deploying a dermatologist to Bosnia. Volumes of historical data clearly justify the assignment of a dermatologist as a special consultant staff officer to every corps or theater medical staff. Despite this data, only two U.S. Army units in our present table of organization and equipment will have a dermatologist (60L) available for periodic direct-field consultation and teaching. After review of the historical data and the Stabilization Force-Bosnia statistics presented here, the table of organization and equipment restructuring that is required to meet the challenges of tomorrow will be clear. A dermatologist must be deployed as a theater or division consultant.     

Positive effect of prophylactic total parenteral nutrition on long-term outcome of bone marrow transplantation

In a randomized trial we studied the impact of providing total parenteral nutrition (TPN) to bone marrow transplant (BMT) patients during their cytoreductive therapy, and for 4 weeks following BMT, on 8 parameters of outcome. A total of 137 patients over 1 year of age and with normal nutritional status were randomized either to receive TPN starting one week prior to transplant or to receive hydration with a 5% dextrose solution containing electrolytes, minerals, trace elements, and vitamins. TPN was ultimately required by 40 of the 66 control patients when nutritional depletion was documented. Average total calorie and protein intake was significantly higher for the TPN group than for the control group. Minimum follow-up was 1 year and median was 2 years. Overall survival, time to relapse, and disease-free survival were significantly improved in the TPN group. Engraftment, duration of hospitalization, and incidences of acute and chronic graft-vs.-host disease and bacteremia were not different. Thus TPN during BMT had a positive effect on long-term outcome. Prophylactic nutritional therapy appears to be indicated even for well-nourished individuals during cytoreduction and BMT.     

Monosomy 7 associated with pediatric acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS): successful management by allogeneic hematopoietic stem cell transplant (HSCT)

Pediatric acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) with monosomy 7 is associated with poor disease-free survival when treated by conventional chemotherapy, immunosuppression or supportive measures. Hematopoietic stem cell transplant (HSCT) may improve outcomes; however, data to support this are limited. To better understand the curative potential of HSCT in these patients, all cases of AML and MDS with monosomy 7 treated by two transplant programs (1992 to present) were reviewed. A total of 16 patients were treated, all by allogeneic HSCT. Primary diagnoses were MDS (N = 5), therapy-related MDS (N = 3), AML (N = 5) and therapy-related AML (N = 3). In all, 11 patients (69%) survive event-free at 2 years with median follow-up of 986 days (range 330-2011 days). Toxicity caused deaths of the five nonsurviving patients, four of whom were transplanted with active leukemia. Allogeneic HSCT is effective therapy for childhood AML and MDS associated with monosomy 7, particularly for patients with AML in complete remission and MDS.     

Increased sphingomyelin content of plasma lipoproteins in apolipoprotein E knockout mice reflects combined production and catabolic defects and enhances reactivity with mammalian sphingomyelinase.

Apolipoprotein E knockout (apoE0) mice accumulate atherogenic remnant lipoproteins in plasma. We now provide evidence that these particles are enriched in sphingomyelin (SM), and explore the mechanisms and possible pathophysiological consequences of this finding. The phosphatidylcholine/sphingomyelin (PC/SM) ratio was reduced in all lipoproteins in apoE0 mice compared with wild-type (Wt) mice (2.0+/-0.2 vs. 4.7+/-0.5; 2.8+/-0.5 vs. 5.5+/-0.9; 1.9+/-0. 5 vs. 4.6+/-0.5 for VLDL, LDL, and HDL), reflecting 400 and 179% increases in plasma pools of SM and PC, respectively. Turnover studies using [14C]PC/[3H]SM VLDL or HDL showed that the fractional catabolic rate (FCR) of VLDL-SM and HDL-SM were markedly reduced in the apoE0 mice compared with Wt mice, while the FCRs of VLDL-PC and HDL-PC were similar. By contrast, the FCRs of [3H]PC ether and [14C]SM were identical in apoE0 and Wt mice. The production rates of VLDL-SM and HDL-SM in apoE0 mice were much higher than in Wt mice, while the production rates of lipoprotein PC were similar. To assess the underlying mechanisms, we also measured the PC/SM ratio in VLDL and LDL of LDL receptor knockout (LDLr0) and hepatic LDL receptor-related protein knockout/LDLr0 mice, but found no difference with Wt mice. Using S-sphingomyelinase, an enzyme secreted by macrophages and endothelial cells, we found that VLDL and LDL from apoE0, but not from Wt or LDLr0 mice, were significantly aggregated, and that aggregation was not prevented by adding back apoE. We then enriched the apoE0-VLDL and Wt-VLDL with different amounts of SM, and found that VLDL aggregation was enhanced. Thus, the increased SM content of lipoproteins in apoE0 mice is due to combined synthesis and clearance defects. Impaired SM clearance reflects resistance to intravascular enzymes and delayed removal by a non-LDLr, non-LDLr related protein pathway. The increased SM content in slowly cleared remnant lipoproteins may enhance their susceptibility to arterial wall SMase and increase their atherogenic potential.     

The development of corpus callosum microstructure and associations with bimanual task performance in healthy adolescents

Cross-sectional and longitudinal volumetric studies suggest that the corpus callosum (CC) continues to mature structurally from infancy to adulthood. Diffusion tensor imaging (DTI) provides in vivo information about the directional organization of white matter microstructure and shows potential for elucidating even more subtle brain changes during adolescent development. We used DTI to examine CC microstructure in healthy right-handed adolescents (n=92, ages 9-24 years) and correlated the imaging data with motor task performance. The primary DTI variable was fractional anisotropy (FA), which reflects the degree of white matter's directional organization. Participants completed an alternating finger tapping test to assess interhemispheric transfer and motor speed. Task performance was significantly correlated with age. Analyses of variance indicated that 9- to 11-year-olds generally performed worse than each of the older groups. Males outperformed females. Significant positive correlations between age and FA were observed in the splenium of the CC, which interconnects posterior cortical regions. Analyses of variance indicated that individuals older than 18 years had significantly higher FA than 9- to 11-year-olds. FA levels in the genu and splenium correlated significantly with task performance. Regression analyses indicated that bimanual coordination was significantly predicted by age, gender, and splenium FA. Decreases in alternating finger tapping time and increases in FA likely reflect increased myelination in the CC and more efficient neuronal signal transmission. These findings expand upon existing neuroimaging reports of CC development by showing associations between bimanual coordination and white matter microstructural organization in an adolescent sample.