Quantification of 5-HT1A and 5-HT2A receptor Binding in Depressed Suicide Attempters and Non-Attempters

Objective: To determine serotonin system abnormalities related to major depression or previous suicidal behavior.

Methods: [¹¹C]WAY100635, [¹⁸F]altanserin and positron emission tomography were used to compare 5-HT_1A and 5-HT_2A binding in MDD patients divided into eight past suicide attempters (>4yrs prior to scanning) and eight lifetime non-attempters, and both groups were compared to eight healthy volunteers.

Results: The two receptor types differed in binding pattern across brain regions from each other, but there were no differences in binding between healthy volunteers and the two depressed groups or between depressed suicide attempters and non-attempters. No effects of depression severity or lifetime aggression were observed for either receptor.

Conclusion: Limitations of this study include small sample size and absence of high lethality suicide attempts in the depressed attempter group. No trait-like binding correlations with past suicide attempt or current depression were observed. Given the heterogeneity of nonfatal suicidal behavior, a larger sample study emphasizing higher lethality suicide attempts may find the serotonin biological phenotype seen in suicide decedents.     

Risk stratification in breast cancer screening: Cost-effectiveness and harm-benefit ratios for low-risk and high-risk women

In mammography screening programmes, women are screened according to a one-size-fits-all principle. Tailored screening, based on risk levels, may lead to a better balance of benefits and harms. With microsimulation modelling, we determined optimal mammography screening strategies for women at lower (relative risk [RR] 0.75) and higher (RR 1.8) than average risk of breast cancer, eligible for screening, using the incremental cost-effectiveness ratio (ICER) of current uniform screening in the Netherlands (biennial [B] 50-74) as a threshold ICER. Strategies varied by interval (annual [A], biennial, triennial [T]) and age range. The number of life-years gained (LYG), breast cancer deaths averted, overdiagnosed cases, false-positive mammograms, ICERs and harm-benefit ratios were calculated. Optimal risk-based screening scenarios, below the threshold ICER of €8883/LYG, were T50-71 (€7840/LYG) for low-risk and B40-74 (€6062/LYG) for high-risk women. T50-71 screening in low-risk women resulted in a 33% reduction in false-positive findings, a similar reduction in costs and improved harm-benefit ratios compared to the current screening schedule. B40-74 in high-risk women led to an increase in screening benefit, compared to current B50-74 screening, but a relatively higher increase in false-positive findings. In conclusion, optimal screening consisted of a longer interval and lower stopping age than current uniform screening for low-risk women, and a lower starting age for high-risk women. Extending the interval for women at lower risk from biennial to triennial screening reduced harms and costs while maintaining most of the screening benefit.     

Key Points to Consider When Evaluating Andexxa for Formulary Addition

Neurocritical Care -     

Stemmed femoral knee prostheses: Effects of prosthetic design and fixation on bone loss

Although the revision rates for modern knee prostheses have decreased drastically, the total number of revisions a year is increasing because many more primary knee replacements are being done. At the time of revision, bone loss is common, which compromises prosthetic stability. To improve stability, intramedullary stems are often used. The aim of this study was to estimate the effects of a stem, its diameter and the interface bonding conditions on patterns of the bone remodeling in the distal femur.

We created finite element models of the distal half of a femur in which 4 types of knee prostheses were placed. The bone remodeling process was simulated using a strain-adaptive bone remodeling theory. The amount of such remodeling was determined by calculating the changes in bone mineral density in 9 regions of interest from simulated DEXA scans.

The computer simulation model showed that revision prostheses tend to cause more bone resorption than primary ones, especially in the most distal regions. Predicted long-term bone loss due to a revision prosthesis with a thin stem equalled that around a prosthesis with an intercondylar box. However, strong regional differences were found- the stemmed prostheses having more bone loss in the most distal areas and some bone gain in the more proximal ones. A prosthesis with a thick stem led to an increase in bone loss. When the prosthesis-cement interface was bonded, more bone loss was predicted than with an unbonded interface. These results suggest that a stem which increases stability initially may reduce stability in the long term. This is due to an increase in stress shielding and bone resorption.     

De-novo expression of vascular ecto-5′-nucleotidase and down-regulation of glomerular ecto-ATPase in experimental chronic renal transplant failure

Ischemic injury plays an important role in chronic renal transplant failure (CRTF). Down-regulation of ecto-adenosine triphosphatase (ATPase) in combination with up-regulation of ecto-5'-nucleotidase is a hallmark of ischemic injury. We studied the expression of renal ecto-5'-nucleotidase and ecto-ATPase in experimental renal transplantation. Fisher 344-to-Lewis allografted rats were either treated with an angiotensin-converting enzyme inhibitor (ACEi) or left untreated. Lewis-to-Lewis syngrafted rats served as controls. Untreated allografted rats developed proteinuria, glomerulosclerosis, and mild intimal hyperplasia. ACEi completely prevented focal and segmental glomerulosclerosis (FGS) and proteinuria, but significantly enhanced intimal hyperplasia. Untreated allografted rats revealed marked vascular ecto-5'-nucleotidase activity, which increased with ACEi. Vascular ecto-5'-nucleotidase activity was absent in syngrafted animals. Ecto-5'-nucleotidase activity correlated well with intimal hyperplasia. Glomerular ecto-ATPase expression was significantly reduced in untreated allografted rats compared to syngrafted rats and correlated well with the extent of FGS. ACEi prevented reduction in glomerular ecto-ATPase. We found de-novo expression of ecto-5'-nucleotidase at sites of renal intimal hyperplasia. Glomerular ecto-ATPase expression was markedly reduced in allografted rats and was prevented by ACEi. These enzyme expression patterns suggest local ischemic damage in experimental CRTF.     

The care of advanced cancer exclusive of the relief of pain by drugs

A régime for the care of far advanced cancer patients is elaborated.The following considerations in therapy are discussed: the psychologic approach; nursing care; bedsores; ulcers; odors; discharges; the peculiarities of abdominal cancer; fistulae from hollow viscera; hemorrhage; intractable pain; palliative operations.The importance of treating the exact cause of the discomfort rather than loading the patient with narcotics, is emphasized.