Allogeneic stem-cell transplantation using a reduced-intensity conditioning regimen has the capacity to produce durable remissions and long-term disease-free survival in patients with high-risk acute myeloid leukemia and myelodysplasia.

PURPOSE: The toxicity of allogeneic stem-cell transplantation can be substantially reduced using a reduced-intensity conditioning (RIC) regimen. This has increased the proportion of patients with myeloid malignancies eligible for allogeneic transplantation. However, the capacity of RIC allografts to produce durable remissions in patients with acute myeloid leukemia (AML) and myelodysplasia (MDS) has not yet been defined, and consequently, the role of RIC allografts in the management of these diseases remains conjectural. PATIENTS AND METHODS: Seventy-six patients with high-risk AML or MDS received an allograft using a fludarabine/melphalan RIC regimen incorporating alemtuzumab. The median age of the cohort was 52 years (range, 18 to 71 years). RESULTS: The 100-day transplantation-related mortality rate was 9%, and no patient developed greater than grade 2 graft-versus-host disease. With a median follow-up of 36 months (range, 13 to 70 months), 27 patients were alive and in remission, with 3-year actuarial overall survival (OS) and disease-free survival (DFS) rates of 41% and 37%, respectively. The 3-year OS and DFS rates of patients with AML in complete remission at the time of transplantation were 48% and 42%, respectively. Disease relapse was the most common cause of treatment failure and occurred at a median time of 6 months after transplantation. All but one patient destined to relapse did so within 24 months of transplantation. CONCLUSION: The extended follow-up in this series identifies a high risk of early disease relapse but provides evidence that RIC allografts can produce sustained DFS in a significant number of patients with AML who would be ineligible for allogeneic transplantation with myeloablative conditioning.     

Crack and cocaine use among female prostitutes in Glasgow: Risky business

The experience of cocaine and 'crack' use among participants involved in (n = 19) or exiting (n = 10) prostitution in Glasgow, Scotland, is described. In-depth semi-structured qualitative interviews enquired about their use and experience of using cocaine and their perception of its effect on working practice. Twenty-three of 29 participants had used cocaine and 15 out of 29 had used crack cocaine. In reality, freebase not 'crack' was being self-manufactured from cocaine powder. Participants considered that cocaine use in the city was not restricted to prostitution but was reflected throughout the drug scene generally. One possible reason suggested for this was a perceived reduction in heroin availability at a time when cocaine was increasingly readily available. There was no evidence from participants to suggest that they were first introduced to cocaine through prostitution. Most participants believed that using cocaine did not affect how they worked, however they perceived that other prostitutes were prepared to take more risks to support their cocaine use and had to work longer hours to finance a cocaine habit compared to financing a heroin habit. Only participants recruited from the east end of the city spoke about their desperation for money and the sexual risks that they were prepared to take to buy cocaine. Harm-reduction messages should address the sexual and personal risks that some female prostitutes may be taking to support their cocaine use. Treatment and support services in the city, traditionally established to work with problematic heroin users, need to adapt to the changing drug trends among female drug users, including those involved in prostitution, and offer appropriate treatment options and harm-reduction advice to cocaine users.     

Addressing Environmental Health Concerns near Trecatti Landfill Site,United Kingdom

Residents near the Trecatti landfill site located in South Wales, United Kingdom, expressed concern about odors and health effects they attributed to site emissions. The authors compared routinely collected, population-based, health data from potentially exposed electoral wards (i.e., United Kingdom electoral tracts) with data from both wards nearby, matched for socioeconomic deprivation scores, and with wards where residents were likely to attend the same hospital. Mortality rates were higher for all causes and neoplastic diseases (but not respiratory disease) in the exposed wards, but there was no change in rates after the site opened. Hospital data revealed a transient increase in admissions for asthma during the 3 yr that preceded the peak in odor complaints. The birth prevalence of congenital malformations was raised in the exposed wards, but the authors could not exclude a possible artifact resulting from differences in reporting practices between hospitals. The absence of environmental monitoring in the community during the period of public concern was a significant weakness of this study.     

Specific knock‐down of tissue non‐specific alkaline phosphatase mRNA levels inhibits intracellular lipid accumulation in 3T3‐L1 and HepG2 cells

The use of non‐specific inhibitors of tissue non‐specific alkaline phosphatase (TNSALP) in pre‐adipocytes blocks intracellular lipid accumulation. TNSALP is also expressed in hepatocytes, which are known to accumulate lipid in a similar manner to pre‐adipocytes. The purpose of this study was to use specific silencing of TNSALP mRNA, using short interfering (si) RNA, to investigate the role of TNSALP in intracellular lipid accumulation in 3T3‐L1 and HepG2 cells. Cellular activity of TNSALP was measured using an automated colorimetric assay, and intracellular lipid accumulation was determined using the lipid‐specific dye, Oil Red O. Cells were transfected with siRNA directed against TNSALP mRNA, and expression of the TNSALP gene was determined at selected time points postinduction of lipid droplet formation. Expression of the TNSALP gene was inhibited by a maximum of 88 ± 1.9% (P < 0.005 vs. control) 11 days after initiation of lipid droplet formation in the 3T3‐L1 cells and 80 ± 8.9% (P < 0.05 vs. control) after 4 days in the HepG2 cells. This led to significant inhibition of both TNSALP activity and intracellular lipid accumulation in both cell lines. These data demonstrates that TNSALP plays an important role in the control of lipid droplet formation in both pre‐adipocyte and hepatocyte cell lines.