Is apoptosis a diagnostic marker of acute myocardial infarction?

OBJECTIVE: To investigate and quantify the presence of apoptosis in early myocardial ischemia in humans. METHODS: Histologic sections from the left and right ventricles of 16 hearts with impending myocardial infarction were stained with terminal deoxynucleotidyl transferase-mediated deoxyuridine 5-triphosphate nick end labeling (TUNEL) method and with antibodies to p53, bcl-2, cpp32, FAS, FAS-L, and bax. DNA electrophoretic analysis was also performed. RESULTS: According to the inclusion criteria, all 16 cases showed morphologic changes consistent with ischemia and/or reperfusion. TUNEL results were positive in 14 of the 16 ischemic areas. Unexpectedly, they were also positive in "remote from ischemia" myocardium of both the left and right ventricles. DNA electrophoretic analysis confirmed the results of TUNEL. Immunohistochemistry was uniformly negative, probably because of autolysis phenomena. CONCLUSIONS: We showed that apoptosis precedes necrosis in humans, but the detection of apoptosis cannot be used as a diagnostic tool, since it can also be triggered by nonischemic events.     

Functioning after a major depressive episode: complete or incomplete recovery?

BACKGROUND: Numerous studies have shown improved functioning after a depression, but often substantial limitations at follow-up remained. The goal of this study is to examine (1) whether functioning returns to pre-morbid levels after a major depressive episode (MDE), (2) predictors of incomplete functional recovery, and (3) how these functional levels relate to those in a non-depressed sample. METHODS: Data were derived from the Netherlands Mental Health Survey and Incidence Study, a prospective general population study with three waves. Psychopathology was measured with the Composite International Diagnostic Interview (CIDI) and functioning with the Short-Form-36 Health Survey (SF-36). One hundred and sixty-five individuals who met criteria for MDE between baseline and third wave, but not in the 12 months preceding baseline and third wave were selected. RESULTS: Mean post-morbid levels of functioning did not differ from pre-morbid levels although this level still differed significantly from the non-depressed sample. Sixty to eighty-five percent of the respondents did better or showed no change on different scales after recovery from MDE. Co-morbid substance use disorder and anxiety disorder, presence of somatic illness, external mastery, low social support and high baseline functioning were predictors of worsened functioning. LIMITATIONS: Lay interviewers used fully structured diagnostic interviews to determine MDE and functioning was measured using self-report. CONCLUSIONS: In general, people who recover from a MDE will also recover from functional impairments. The most important predictors of incomplete functional recovery are clinical and social in nature whereas personality and demographic characteristics are less important.     

"Constitutive" skin pigmentation: a marker of breast cancer risk?

There is much evidence to support a link between oestrogen and breast cancer. Both adult and foetal oestrogen may have this predisposing effect, and between-individual and between-population differences in oestrogen may account for much of the variation in risk for breast cancer. Here we suggest that "constitutive" skin colour in women is a marker for prenatal and adult oestrogen levels such that within ethnic groups light-skinned women have experienced higher in utero and adult oestrogen than dark-skinned women. Scores for 'constitutive' skin pigment may therefore be predictive of risk for breast cancer and low scores could be used to identify individuals at high risk.     

Is serum Cystatin-C a suitable marker of renal function in children?

Cystatin C (Cys-C) is a low-molecular weight (13 kDa) protein that is a member of the cysteine protease family and is produced by all nucleated cells. In normal conditions, serum Cys-C is almost completely filtered by the renal glomerulus and largely catabolized by proximal tubular cells. Since serum Cys-C levels are closely correlated with the glomerular filtration rate (GFR), serum Cys-C assay has been introduced as a marker of renal function in patients with kidney diseases. In this review, we focus on studies reported during the past decade in which serum Cys-C levels have been compared to serum creatinine levels as a marker of GFR in pediatric populations. All but one of these studies showed diagnostic superiority or equivalence of serum Cys-C levels vs serum creatinine levels in children. The recent evidence from clinical trials generally supports the use of serum Cys-C assays as a renal function test in pediatric patients. However, clinicians should be cognizant of extrarenal conditions and pharmacological factors that can influence the results of serum Cys-C assays.     

Is xerostomia a risk factor for cardiovascular morbidity and mortality in maintenance hemodialysis patients?

Xerostomia resulting mostly from hyposalivation and alkaline salivary pH is a frequent but often underappreciated symptom in the diseased population of maintenance hemodialysis (HD) patients. We reviewed also other xerostomia-predisposing factors, its specific dental and oral clinical signs and features, as well as plausibly detrimental dialysis-specific pro-atherosclerotic and cardiovascular consequences. In view of increasing multidisciplinary importance of xerostomia, its general, pharmacological and emerging treatment methods were presented. Special attention was paid to the untoward and often neglected pro-xerostomic effects of multiple common medications and substances; they were listed and described in more detail. The combined therapeutic approach of dentists and nephrologists may effectively alleviate xerostomia and support general health condition of maintenance hemodialysis patients.     

Is pseudomelanosis coli a marker of colonic neuropathy in severely constipated patients?

AIMS: To study relationships between the number of pseudomelanosis coli cells and that of colonic enteric neurons and interstitial cells of Cajal, which are significantly reduced compared with controls in severely constipated patients. Pseudomelanosis coli is frequent in patients using anthraquinone laxatives. It is not known whether the prolonged use of these compounds damages the enteric nervous system in constipated patients. PATIENTS AND METHODS: The relationship between the number of pseudomelanosis coli cells and that of colonic enteric neurons (as well as that of apoptotic enteric neurons) and of interstitial cells of Cajal was assessed by histological and immunohistochemical methods in 16 patients with chronic use of anthraquinone laxatives undergoing surgery for severe constipation unresponsive to medical treatment. No relationship was found between the number of pseudomelanosis coli cells and that of enteric neurons (and that of the apoptotic ones), nor of interstitial cells of Cajal, in either the submucosal or the myenteric plexus. CONCLUSION: The use of anthraquinone laxatives, leading to the appearance of pseudomelanosis coli, is probably not related to the abnormalities of the enteric nervous system found in severely constipated patients.     

Is living in a border region a risk for a high prevalence of resistance?

This study assessed the antimicrobial resistance and population structure of Staphylococcus aureus isolated from general practice (GP) patients and nursing home (NH) residents in the province of Limburg (near the border with Germany and Belgium) in comparison with those obtained in the remaining provinces of the Netherlands. A total of 617 and 418 S. aureus isolates were isolated from 2,691 to 1,351 nasal swabs from GP patients and NH residents, respectively. Quantitative antibiotic susceptibility testing was performed using a microbroth dilution method. Putative methicillin-resistant S. aureus (MRSA) isolates were tested for the presence of the mecA gene and spa typing was performed on all S. aureus isolates. No significant differences in the prevalence of resistance were found between the two groups of GP isolates, but the isolates from the NH residents showed a lower resistance for trimethoprim–sulfamethoxazole (p = 0.003) in Limburg province compared with the remaining provinces in the Netherlands. Among the isolates from NH residents in Limburg province, the prevalence of spa-CC 084 was higher (p = 0.003) and that of spa-CC 002 was lower (p = 0.01) compared with isolates from NHs in the remaining provinces of the Netherlands. We observed no differences in resistance and population structure between S. aureus isolates from GP patients in Limburg and the remaining provinces of the Netherlands, and only a few differences were observed between the NH populations. There was no higher prevalence of resistance among the GP and NH isolates from Limburg compared with the remaining provinces.     

Elevated plasma pentraxin 3: a potential cardiovascular risk factor?

Cardiovascular disease (CVD) is still a primary cause of death in most countries. The pathogenesis of CVD can be influenced by multiple risk factors. Recent studies suggested that the innate immune system may be involved in the development of CVD. Pentraxins are critical components of the innate immune system. Recent researches have demonstrated that elevated plasma pentraxin 3 (PTX3) is associated with cardiovascular events and cardiovascular risk factors. Thus, we hypothesized that elevated plasma PTX3 is a potential cardiovascular risk factor evidenced by the following aspects: (1) PTX3 inhibited angiogenesis and promoted restenosis, (2) the expression of PTX3 increased in advanced atherosclerotic lesions and the blood of patients with ischemic heart disorders, (3) elevated plasma PTX3 levels were associated with adverse cardiovascular outcomes. If the hypothesis is confirmed, PTX3 will be an effective target point to the prevention and treatment of CVD.     

Is there a risk of prion disease after the administration of urinary-derived gonadotrophins?

Concern has been raised recently about the possibility of prion proteins appearing in the urine of animals and, possibly, humans affected by prion disease [scrapie, bovine spongiform encephalopathy (BSE) and Creutzfeldt Jakob disease (CJD)]. A debate has started in which the suggestion has been made that the purification of human urine for the provision of gonadotrophins should be discontinued. The alternative would be to use recombinantly-derived gonadotrophin preparations. The recombinant products, however, rely upon bovine serum during the cell culture process and could potentially also be exposed to abnormal prion proteins. It is reassuring that the different types of gonadotrophin preparations that are currently available are produced with either urine or bovine serum that is sourced from countries that at the present time appear to be free of BSE and new variant CJD. We can therefore be reassured that the gonadotrophins that we use therapeutically appear to be equally safe.     

Is cell death and replacement a factor in aging?

The central theme of the 3rd International Conference on Functional Genomics of Ageing was tissue regeneration as a remedial strategy to address age-related cellular damage and the pathology that ensues. The conference included sessions on maintaining genome integrity and the potential of stem cells to restore function to damaged tissues. In addition to several human syndromes that appear to reflect accelerated ageing, there are now a number of mouse models that prematurely display phenotypes associated with ageing. The intent of this summary presented at the end of the conference was to: (1) discuss various human syndromes and mouse models of accelerated ageing; (2) evaluate whether the phenotypes displayed might result from an elevated rate of cell death coupled with an inability to adequately maintain cell number in various tissues with increasing age; and (3) discuss whether similar events may be occurring during normal ageing, albeit much more slowly.