Recovery of T cell subsets after autologous bone marrow transplantation is mainly due to proliferation of mature T cells in the graft

In 22 patients with malignancies, treated with high-dose chemoradiotherapy and autologous bone marrow transplantation (BMT), peripheral blood T cell subsets and functions were studied. In ten cytomegalovirus (CMV)-negative patients, CD4+ and CD8+ T cells (representing T cells of the helper/inducer phenotype and T cells of the suppressor/cytotoxic phenotype, respectively), recovered slowly and simultaneously. In 12 CMV-positive patients, however, CD8+ T cells recovered more rapidly than CD4+ T cells and rose to increased counts. No T cells with an immature phenotype (CD1+, OKT6+) were observed. Lymphocyte stimulation by herpes simplex virus infected fibroblasts (and by CMV-infected fibroblasts in CMV-positive patients) in contrast remained high and even increased after BMT in both groups. These data indicate that T cell recovery after autologous BMT is mainly due to proliferation of mature T cells present in the BM graft and not to generation of new T cells from T cell precursors.     

Gait dysfunction in mild cognitive impairment syndromes

OBJECTIVES: To conduct a systematic clinical and quantitative assessment of gait in older adults with mild cognitive impairment (MCI) syndromes.
DESIGN: Cross-sectional.
SETTING: Einstein Aging Study, a community-based longitudinal aging study.
PARTICIPANTS: Fifty-four individuals with amnestic MCI (a-MCI), 62 with nonamnestic-MCI (na-MCI), and 295 healthy controls identified from the Einstein Aging Study participants.
MEASUREMENTS: Comparison of clinical and quantitative gait performance in subjects with MCI subtypes with that of cognitively normal older adults.
RESULTS: Neurological gaits were more common in a-MCI (31.5%, P =.008) but not in na-MCI (19.4%, P =.55), than in controls (16.3%). Quantitative gait in multiple parameters was worse in both MCI subtypes than in controls. Factor analysis revealed three independent factors representing pace, rhythm, and variability. Subjects with a-MCI had worse rhythm and variability scores than those with na-MCI and controls. Subjects with na-MCI had worse performance on the pace domain than the other two groups. Subjects with MCI and gait abnormalities had higher disability scores than subjects with MCI without gait abnormalities.
CONCLUSION: Gait dysfunction is common in older individuals with amnestic and nonamnestic subtypes of MCI.     

Primary herpes simplex virus type-2 infection as a cause of liver failure after liver transplantation

We report a case of fatal primary herpes simplex virus type-2 (HSV-2) infection following liver transplantation, which manifested with fever and liver failure in the absence of muco-cutaneous disease. The infection was characterized by high levels of HSV DNA in blood and the patient's inability to mount HSV-specific T-cell responses while showing preserved T-cell responses against cytomegalovirus. The donor was HSV-1 immunoglobulin G (IgG) seronegative and HSV-2 IgG seropositive, whereas the recipient was HSV-1 and HSV-2 IgG seronegative, suggesting that the graft may have been the source of the infection. In HSV-seronegative recipients of grafts from HSV-seropositive donors, HSV infection should be included in the differential diagnosis of a febrile illness, regardless of the absence of muco-cutaneous disease. In this setting, real-time polymerase chain reaction applied to blood samples provides a sensitive, rapid, and quantitative diagnostic tool.     

Bromocriptine as a new therapeutic agent for peripartum cardiomyopathy

Peripartum cardiomyopathy (PPCM) is a poorly understood, rare disorder in which left ventricular systolic dysfunction and symptoms of heart failure occur between the last month of pregnancy and the first 5 months postpartum. Recent data suggest that uncontrolled oxidative stress leads to the activation of the prolactin cleaving enzyme cathepsin D that in turn leads to an increase in a cleaved 16 kDa prolactin. This cleaved form that has an angiostatic and proapoptotic role appears to drive the disease by adversely impacting the endothelium and cardiomyocyte. Bromocriptine that reduces the prolactin production by dopamine agonist actions may improve outcomes in patients with peripartum cardiomyopathy by eliminating the cleaved form of prolactin despite the activation of the cleaving enzyme. In limited case reports and proof of concept studies use of bromocriptine in the early stages has been shown to improve outcomes in patients with peripartum cardiomyopathy. However, larger randomized control study is still awaited.     

Cost-effectiveness of counseling and pedometer use to increase physical activity in the Netherlands: a modeling study

Background

Counseling in combination with pedometer use has proven to be effective in increasing physical activity and improving health outcomes. We investigated the cost-effectiveness of this intervention targeted at one million insufficiently active adults who visit their general practitioner in the Netherlands.

Methods

We used the RIVM chronic disease model to estimate the long-term effects of increased physical activity on the future health care costs and quality adjusted life years (QALY) gained, from a health care perspective.

Results

The intervention resulted in almost 6000 people shifting to more favorable physical-activity levels, and in 5100 life years and 6100 QALYs gained, at an additional total cost of EUR 67.6 million. The incremental cost-effectiveness ratio (ICER) was EUR 13,200 per life year gained and EUR 11,100 per QALY gained. The intervention has a probability of 0.66 to be cost-effective if a QALY gained is valued at the Dutch informal threshold for cost-effectiveness of preventive intervention of EUR 20,000. A sensitivity analysis showed substantial uncertainty of ICER values.

Conclusion

Counseling in combination with pedometer use aiming to increase physical activity may be a cost-effective intervention. However, the intervention only yields relatively small health benefits in the Netherlands.     

The harlequin nail. A marker for smoking cessation

Changes in the human nail frequently serve as an indicator of local and systemic disease. Alterations in the morphology, structure and growth characteristics of the nail accompany chronic cigarette smoking; yellow pigmentation of the nail plate--referred to as the "nicotine sign"--is common. The clubbed yellow nail may indicate the presence of lung cancer. In contrast to the ominous nature of the clubbed yellow nail, we describe a sign that is more propitious: the sudden cessation of smoking due to an intercurrent disease, often a cerebrovascular accident (CVA), leads to the development of a distinct line of demarcation between the distal pigmented nail and the newly emerging proximal nonpigmented nail. We propose the term "harlequin nail" for this curious physical sign. By measurement of the distance between the proximal nail base fold and the line of demarcation, we can deduce the date smoking ceased (and, by inference, the approximate date of a CVA in a patient unable to volunteer this information). This sign also serves as a reminder that the "nicotine nail" remains discolored only because of dynamic restaining of the nail with tobacco by-products.