Matter of life and death: the pharmacological approaches targeting apoptosis in brain diseases

Neurodegenerative diseases that include amyotrophic lateral sclerosis, Huntington's disease, Alzheimer's disease, Parkinson's disease, stroke, brain trauma and spinal cord injury, are associated with the inappropriate activation of a neuronal cell-suicide program called apoptosis. Given that central nervous system tissue has very limited regenerative capacity it is of extreme importance to limit the damage caused by neuronal death. During the past decade, considerable progress has been made in understanding the process of apoptosis and, significantly, a number of studies have shown that a variety of small molecules can activate or inhibit cell death by acting on crucial checkpoints of apoptosis. Here, we review evidence linking apoptosis to brain diseases and discuss how knowledge of the mechanisms of cell death has led to novel therapeutic strategies.     

Cyclooxygenase-2 expression in primary Merkel cell carcinoma

BACKGROUND: Merkel cell carcinoma (MCC) is a highly malignant neuroendocrine skin tumor. The typical course of MCC is rapid progression of the primary tumor and metastatic dissemination to the regional lymph nodes. Thus far, no biological, prognostic marker has been established for this aggressive neoplasm. Cyclooxygenase-2 (Cox-2) is undetectable in most normal tissues, but it is induced in various cell types by inflammation and carcinogenesis. Although the expression and function of Cox-2 have been studied extensively in several carcinomas, little is known about Cox-2 expression in neuroendocrine carcinomas. The aim of the present report was to study Cox-2 expression in MCC and find out whether this expression correlates with outcome. METHODS: Immunohistochemical analysis for Cox-2 was performed on 22 primary MCC samples. RESULTS: Almost 70% of the samples showed positive staining. Protein expression of Cox-2 was sparse and low in intensity. We found a tendency for enhanced Cox-2 expression in tumors located in sun-exposed areas. Cox-2 expression had no significant statistical correlation with clinical parameters. CONCLUSIONS: MCC expresses Cox-2 in low levels, and the expression did not prove to be a prognostic factor. Furthermore, the low expression suggests that the primary treatment option for MCC is not therapeutic inhibition of Cox-2.     

Differential results between self-report and interview-based ratings of risk symptoms of psychosis

Aim: Assessing potential risk of developing psychosis has gained growing attention in recent literature. The selection of suitable assessment methods is the central question for this research endeavour. Whereas prodromal detection instruments are mostly interview‐based instruments, there are short screening instruments for self‐report use. Methods: Difference in psychosis risk scores was tested between self‐report results and interview results, with risk symptoms of psychosis included in PROD screening instrument. Subjects were recruited by an early intervention team in Finland. Results: There was a significant difference between psychosis risk scores based on self‐report versus interview in a sample of adolescents (n = 87; P < 0.001). Conclusions: Results suggest that when using screening instruments, risk scores and risk status may vary by the method the information is collected. Checking self‐report results by an additional interview is recommended for both clinical and scientific uses.     

Working Memory, Attention, Inhibition, and Their Relation to Adaptive Functioning and Behavioral/Emotional Symptoms in School-Aged Children

The present study investigated the development of executive functions (EFs) and their associations with performance and behavior at school in 8–12-year-old children. The EFs were measured by computer-based n-back, Continuous Performance and Go/Nogo tasks. School performance was evaluated by Teacher Report Form (TRF) and behavior by TRF and Child Behavior Checklist. The studied dimensions of EF were cognitive efficiency/speed, working memory/attention and inhibitory control. Strong age effects were found for these cognitive abilities (p values <0.01). Inhibitory control was associated with better adaptive functioning (learning, working hard and behaving well), academic performance and less psychiatric symptoms (p values <0.05), specially in 8–9-year-old children. In this youngest age group low inhibitory control was also associated with teacher-reported inattention (p = 0.042). Low inhibitory control was associated with teacher- and parent-reported internalizing symptoms (p < 0.01). These results suggest that maturational factors may underlie low adaptive functioning and psychiatric symptoms during early school years. Further studies are needed to evaluate the association between inhibition and emotional symptoms.     

Multiple organ failure as a cause of death in patients with severe burns

The aim of this study was to investigate the causes of death in patients with burns using both medicolegal autopsy reports and clinical data collected during treatment to specify irreversible organ dysfunctions leading to death. Burn deaths occurring in the Helsinki Burn Center from 1995 to 2005 were identified in the hospital database. The clinical charts and medicolegal autopsy reports were retrieved and compared. The data were evaluated by plastic surgeons specialized in burn care, an intensivist, and a pathologist, with special reference to organ-specific changes in the autopsy reports. From 1999 to 2005, there were 71 burn deaths in the Helsinki Burn Center of which 40% was caused by multiple organ failure (MOF). Death from untreatable burn injury was recorded in 28 patients, whereas other causes were scarce. MOF patients displayed approximately four organ failures on average, ranging from three to eight. All 28 MOF patients were recorded to have acute renal failure, followed by liver damage, of which four patients had acute or chronic liver failure. Sepsis was always affiliated with MOF as a cause of death. In conclusion, careful examination of MOF as a cause of death revealed several organ failures: four organ failures per patient. Acute renal failure was noted in all MOF patients. Sepsis was always affiliated with MOF.     

Evolving practice of the Helsinki Skin Bank

The purpose of this study is to review the management and running of the Helsinki Skin Bank between the years 2001 and 2008. Further aims were to assess the microbiological safety of the glycerol‐preserved allograft skin and analyse its clinical use. The files of the Helsinki Skin Bank were reviewed for allograft skin harvested from organ donors between 2001 and 2008. Data on harvested skin area and microbiological culture results were collected. The patients receiving allograft were also identified and operation indications analysed. Allograft skin was collected from 115 donors, with a mean of 44 335 cm² per year. No skin batches were discarded. Microbiological cultures of the allograft skin batches were negative in 86 (75%) cases. Thirty‐five donor skin batches were used in 69 operations. The most common indication was ‘Biological dressing on partial‐thickness burns', comprising 52% of cases. The cost per cm² was 0.81€. The use of allograft skin in the Helsinki Skin Bank is microbiologically safe and continues to provide a versatile and useful treatment modality in many major burn cases with few observed complications. As compared with synthetically produced temporary dressings currently available, our allograft skin is also more economical.     

Comparison of premortem clinical diagnosis and autopsy findings in patients with burns

INTRODUCTION: Despite the diagnostic advancements, some clinically important diagnoses remain undetected during intensive care in burn patients. The aim of this study was to compare the premortem clinical diagnoses and autopsy findings. PATIENTS AND METHODS: A retrospective review of all burn deaths during 1995-2005 was conducted. The clinical diagnoses and autopsy reports were reviewed, and diagnostic discrepancies were classified into four categories, according to the impact on the treatment. RESULTS: Overall mortality during the study period was 5.4%. Altogether 74 deaths were recorded, of which 71 were included in the study. Typical patient was a 58-year-old male with flame burn of %TBSA 49, ABSI 10. Clinical diagnostic discrepancies were found in 14.1% of the patients; one diagnostic discrepancy was recorded in each of the patients. Of these diagnostic discrepancies, 8.5% were considered major, and 5.6% would have altered the clinical outcome or therapy, if known at the time. Diagnostic discrepancies consisted of one cardiovascular, seven respiratory and two gastrointestinal missed diagnosis. The most common missed diagnosis was pneumonia. CONCLUSION: This study emphasizes the usefulness of autopsies to provide valuable clinical data for the treatment of burn patients. It also highlights the few missed diagnoses which may occur in burn patients.