Clusterin expression in cutaneous CD30-positive lymphoproliferative disorders and their histologic simulants

Background:  Clusterin is a ubiquitous 80 kDa heterodimeric glycoprotein previously shown to be expressed on tumor cells of systemic and, to a lesser extent, primary cutaneous anaplastic large cell lymphoma (PC-ALCL). Lymphomatoid papulosis (LyP), an important differential diagnosis of ALCL, has been studied for clusterin expression in only a small number of cases. The aim of this study was to compare clusterin immunostaining patterns in LyP and other cutaneous histologic simulants with those of PC-ALCL.
Methods:  Formalin-fixed, paraffin-embedded sections of PC-ALCL (6), LyP (20), mycosis fungoides with large cell transformation (MF-LCT, 12), pityriasis lichenoides et varioliformis acuta (PLEVA, 12), arthropod bite reaction (ABR, 12) and lymphomatoid reactions (LR, 9) were immunostained for clusterin and evaluated for staining pattern and distribution. All diagnoses were made with clinicopathologic correlation.
Results:  Characteristic dot-like Golgi staining was identified in 10/20 LyP (50%), 4/6 PC-ALCL (67%) and 9/12 MF-LCT (75%). Two of 12 PLEVA (17%), 1 of 12 ABR (8%) and 2 of 8 LR (25%) had lymphocytes (< 25%) with diffuse cytoplasmic staining. Dermal dendritic cells stained strongly for clusterin. High background staining occurred in some cases.
Conclusion:  Clusterin immunostaining does not reliably distinguish between LyP, PC-ALCL or MF-LCT, but could distinguish LyP from its reactive histologic simulants.     

Are hospitals prepared to support newborn survival? – an evaluation of eight first‐referral level hospitals in Kenya*

Objective To assess the availability of resources that support the provision of basic neonatal care in eight first‐referral level (district) hospitals in Kenya. Methods We selected two hospitals each from four of Kenya’s eight provinces with the aim of representing the diversity of this part of the health system in Kenya. We created a checklist of 53 indicator items necessary for providing essential basic care to newborns and assessed their availability at each of the eight hospitals by direct observation, and then compared our observations with the opinions of health workers providing care to newborns on recent availability for some items, using a self‐administered structured questionnaire. Results The hospitals surveyed were often unable to maintain a safe hygienic environment for patients and health care workers; staffing was insufficient and sometimes poorly organised to support the provision of care; some key equipment, laboratory tests, drugs and consumables were not available while patient management guidelines were missing in all sites. Conclusion Hospitals appear relatively poorly prepared to fill their proposed role in ensuring newborn survival. More effective interventions are needed to improve them to meet the special needs of this at‐risk group.     

The genetic and epigenetic basis of ependymoma

Introduction  

Although ependymoma is the third most common pediatric brain tumor, we know little about the genetic/epigenetic basis of its initiation, maintenance, or progression. This is due in part to the heterogeneity of the disease, as well as the small sample size of the cohorts analyzed in most studies.     

A Preliminary Study of the Population-Adjusted Effectiveness of Substance Abuse Prevention Programming: Towards Making IOM Program Types Comparable

The Institute of Medicine distinguishes between programs based on who is targeted: the entire population (universal), those at risk (selective), or persons exhibiting the early stages of use or related problem behavior (indicated). Evaluations suggest that although universal programs can be effective in reducing and preventing substance use, selective and indicated programs are both more effective and have greater cost-benefit ratios. This paper tests these assumptions by comparing the impact of these program types in reducing and preventing substance use at the individual level (i.e., those exposed to intervention services) and in the population (i.e., those exposed and not exposed to intervention services). A meta-analysis was performed on 43 studies of 25 programs to examine program comparability across IOM categories. When examining unadjusted effect sizes at the individual level, universal programs were modestly more successful in reducing tobacco use, but selective and indicated programs were modestly more successful in reducing alcohol and marijuana use. When adjusted to the population level, the average effect sizes for selective and indicated programs were reduced by approximately half. At the population level, universal programs were more successful in reducing tobacco and marijuana use and selective and indicated programs were more successful in reducing alcohol use. Editors’ Strategic Implications: The authors’ focus on the public health value of a prevention strategy is compelling and provides a model for analyses of other strategies and content areas.     

Sildenafil Prevents Cardiovascular Changes after Bone Marrow Fat Embolization in Sheep

Background: Sudden, intraoperative cardiovascular deterioration as a result of pulmonary embolization of bone marrow fat is a potentially fatal complication during total hip and knee arthroplasty, intramedullary nailing, and spine surgery. Anesthetic management is challenging in the presence of increased right ventricular afterload due to pulmonary hypertension. Selective pulmonary vasodilation may be an appropriate prophylactic or therapeutic measure. The effect of sildenafil (phosphodiesterase inhibitor) on cardiovascular deterioration after bone marrow fat embolization was therefore investigated.

Methods: Bone cement (polymethylmethacrylate) was injected into three lumbar vertebrae in 12 sheep. Invasive blood pressures and heart rate were recorded continuously until 60 min after the last injection. Cardiac output and arterial and mixed venous blood gas variables were measured at selected time points. Before the first cement injection, 6 animals received a bolus injection (0.7 mg/kg) of sildenafil, with continuous infusion (0.2 mg [middle dot] kg-1 [middle dot] h-1) thereafter. Postmortem lung and kidney biopsies were taken for semiquantitative analysis of intravascular fat.

Results: Fat embolism was associated with a transient increase (21 +/- 7mmHg) in pulmonary arterial pressure. A transient decrease in arterial blood pressure and temporary increases in central venous pressure and dead space were also observed. No significant changes in any cardiovascular variable were observed after fat embolism in the sildenafil group. There was significantly (P < 0.05) less intravascular fat in the lungs of the sildenafil (median count of 5 emboli per microscopic view) compared with the control group (median count of 1).     

Central Sensitization Theory of Migraine: Clinical Implications

The clinical science of migraine headache continues to evolve. Theories of the pathophysiology of migraine have progressed from the early vascular basis of migraine to more complex current theories that emphasize the centrality of neuronal dysfunction. The most recently articulated theory of migraine is the central sensitization hypothesis, which proposes that altered processing of sensory input in the brainstem, principally the trigeminal nucleus caudalis, could account for many of the temporal and symptomatic features of migraine, as well as its poor response to triptan therapy when such treatment is initiated hours after the onset of pain. Both preclinical and clinical data support the central sensitization theory. A critical clinical implication of this theory is that drugs that are capable of either aborting or arresting the process of central sensitization, most prominently dihydroergotamine, may have a unique role in the treatment of migraine. An additional, and highly practical, implication is based upon the finding that cutaneous allodynia—pain arising from innocuous stimulation of the skin, as in hair brushing or the application of cosmetics—is an easily identifiable marker of central sensitization. Thus, the presence or absence of cutaneous allodynia can be integrated into the routine clinical assessment of migraine and utilized as a determinant of treatment. Future basic and clinical research on central sensitization is likely to be of ongoing importance to the field.     

Changes in fetal presentation in twin pregnancies.

OBJECTIVE: The aim of the study was to describe the occurrence of spontaneous version in twins in the third trimester, as well as the correlation between antepartum and birth presentation. METHODS: Twin pregnancies were divided into four gestational age intervals: 20-23; 24-27; 28-31; and 32-36 weeks. Fetal presentation was categorized as cephalic (C) or non-cephalic (NC). Hospital records were reviewed to determine demographic factors, including mode of conception. Chi-square was used to compare distributions of presentations, and Cramer's V measure of association was used to correlate presentations in individual pregnancies between antepartum intervals and birth. RESULTS: A total of 207 pregnancies were included. The distribution of fetal presentations changed significantly through gestational age intervals (p < 0.001), although they were similar between 32-36 weeks and birth (p = 0.75). Correlation between antepartum and birth presentation in individual pregnancies strengthened throughout the four intervals. No correlation was seen between parity, gender, birthweight, or in vitro fertilization and fetal presentation or rate of spontaneous version.CONCLUSION: Many twins undergo spontaneous version in the third trimester, though there is excellent correlation between presentation at 32-36 weeks and birth. A cephalic presenting twin at > or = 28 weeks is highly likely to be in cephalic presentation at delivery.     

Quantitative immunoblotting assay of blood coagulation factor XII

The immunoblotting technique was applied to the study of Factor XII (F.XII) in plasma. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) of whole plasma followed by electroblotting of the electropherograms to nitrocellulose (NC) membranes and immunologic detection by a double antibody technique was used. ¹²⁵-F.XII was transferred to the NC membrane in amounts proportional to the amount applied to the gel provided that a constant amount of carrier protein was present. Based on this, a quantitative assay was developed using either normal plasma or F.XII dilutions in F.XII-deficient plasma as standards. The measurement of F.XII antigen by immunoblotting was reproducible and gave values similar to those obtained by radial immunodiffusion. Two normal plasma pools contained 26 and 29 μ/ml of F.XII according to the immunoblotting assay. Compared to other immunoassays, immunoblotting has the advantage of directly estimating the apparent molecular weight (MW) of the protein of interest. Thus, we could confirm the normal apparent MW (80,000) of a F.XII-like molecule previously isolated from a cross reacting material (CRM)-positive F.XII-deficient plasma. None of eight CRM-negative F.XII-deficient plasmas showed an 80,000 MW immunoreactive molecule. However, five of these eight plasmas had a faint autoradiographic band at 115,000 MW that was similarly seen in only three out of 43 individual normal plasmas. The nature of this 115,000 MW band remains to be defined.