Chemotherapy reaction induced by ixabepilone,a microtubule stabilizing agent,mimicking extramammary Paget's disease in a patient with breast carcinoma

The histopathologic characteristics of reactions caused by the many novel anticancer agents are under‐recognized. We report a case of a 67‐year‐old female with locally advanced metastatic breast cancer, who initially presented with an extensive reticulated erythematous patch on the trunk caused by intravascular metastases confirmed by a skin biopsy. Owing to disease progression, she was started on ixabepilone, a mitotic inhibitor. While receiving ixabepilone, another skin biopsy was obtained and initially interpreted as extramammary Paget's disease. However, the biopsy showed metaphase arrest of numerous keratinocytes in the basilar and suprabasilar epidermis. Atypical epithelial cells were only present in the intravascular spaces similar to the initial biopsy. Given the temporal association between the initiation of ixabepilone therapy and the epidermal mitotic arrest, a diagnosis of chemotherapy reaction to ixabepilone was rendered. Ixabepilone is an analog of epothilone, a microtubule stabilizer causing mitotic arrest of the cell cycle approved for the treatment of metastatic and locally advanced treatment‐resistant breast cancer. The demonstration of epidermal mitotic arrest caused by ixabepilone is without precedent. The case emphasizes the importance of considering a chemotherapy reaction in the histologic differential diagnosis of epidermal mitotic arrest in a cancer patient receiving chemotherapy.     

Performance of a novel real-time respirator seal integrity monitor on firefighters: Simulated workplace pilot study

Millions of workers, including firefighters, use respiratory protective device. The key aspect in assuring the intended protection level of a respirator is its fit. However, even if the respirator originally fits well, the faceseal may be breached during its use. Until now, there have been no practically viable, inexpensive means to monitor the performance of a respirator during actual use. A novel Respirator Seal Integrity Monitor (ReSIM) was developed and recently evaluated on manikins by our team. The objective of this study was to evaluate the ReSIM effectiveness on respirator-wearing firefighters exposed to aerosols while performing simulated routine operational activities. Initially, 15 subjects were recruited for the study. Following a preliminary investigation that resulted in modifications in the ReSIM prototype and testing protocol, a subset of nine firefighters was chosen for a full-scale evaluation. The testing was conducted in a 24.3-m³ exposure chamber using NaCl as the challenge aerosol. Controlled faceseal leaks were established by opening a solenoid valve for 10, 15, or 20?sec. Leaks were also established as the tested firefighter slightly repositioned the respirator on his/her face. During the testing, the ReSIM measured particles inside a full-face elastomeric respirator with a 72.7% leak detection sensitivity (probability of correct leak identification) and an 84.2% specificity (probability of correct identification of the intervals which are absent of any leak). After adjusting for false negatives and persistent false positives, sensitivity and specificity increased to 83.6% and 92.2%, respectively. The factors causing minor limitations in leak detection sensitivity and specificity can be attributed to variability among subjects, moisture’s effect on the particle sensor, and some in-mask sampling bias. In conclusion, the ReSIM can promptly detect the breach in a respirator faceseal with high sensitivity and specificity. Due to its capability to alert the wearer of possible overexposure to hazardous aerosols, the ReSIM concept has a remarkable potential to be applied in various working environments, where respirators are used.     

Inheritance of nasal dermoid sinus cyst and evidence for association with third ventricle colloid cyst

Purpose  

The purpose of this paper is to study the possible inheritance of nasal dermoid sinus cyst in the Finnish population.     

Child and family health in the era of prevention: new opportunities and challenges

To maintain positive health outcomes over the life course, prevention efforts should begin early in childhood. Two research domains that significantly impact the trajectory of health over the life course are childhood obesity and early trauma and violence. Prevention strategies addressing multiple levels of influence are being adopted in these fields. Childhood obesity prevention efforts no longer focus solely on individuals, but embrace multiple ecological levels, such as family, school, and community. Similarly, research on early trauma and violence has broadened to consider risk and protective factors across domains of influence. Although we have improved our understanding and prevention of these two issues, gaps remain in research, practice, and policy. The purpose of this review is to relay relevant findings that could enhance prevention strategies. We describe early life and multilevel risk factors relevant to these areas of research. We also provide recommendations for future efforts to better ensure good health for generations to come.     

Sex hormone-binding globulin and insulin-like growth factor-binding protein-1 as indicators of metabolic syndrome, cardiovascular risk, and mortality in elderly men

Two binding proteins, SHBG and IGF-binding protein-1 (IGFBP-1), are both down-regulated by insulin and therefore could serve as potential indicators of the metabolic syndrome and hyperinsulinemia-related cardiovascular risk. We compared serum SHBG and IGFBP-1 as potential markers of abnormal glucose tolerance, the metabolic syndrome, diabetes mellitus, cardiovascular risk factors, and total, cardiovascular, and coronary heart disease mortality in elderly men. Of the original cohort of 1711 men, 524 were alive on January 1, 1989, and 413 participated in the 30-yr examination, of whom 335 men, aged 70-89 yr, formed the study group for the present analysis. Low SHBG and IGFBP-1 were both associated with an increased prevalence of abnormal glucose tolerance and the metabolic syndrome, but only SHBG was associated with diabetes mellitus. SHBG was less influenced by body mass index than IGFBP-1. Low SHBG indicated increased cardiovascular and coronary disease mortality; the association remained after adjustment for abnormal glucose tolerance, but not after adjustment for prevalent cardiovascular disease. IGFBP-1 had no association with mortality. It is concluded that low SHBG is a better indicator of increased cardiovascular mortality than low or high IGFBP-1.     

Hereditary hemochromatosis gene (HFE) mutations C282Y, H63D and S65C in patients with idiopathic dilated cardiomyopathy

BACKGROUND: Hereditary hemochromatosis (HH), a common autosomal recessive disease, leads to excessive iron accumulation in some organs, including the heart. It is therefore not surprising that cardiomyopathy is one of the most severe complications of HH. The HFE gene defects have been thought to contribute to idiopathic dilated cardiomyopathy (IDCM) in some patients, even though the results of genotype analyses have so far been contradictory. Hence we set out here to evaluate the prevalence and potential role of HFE mutations in patients with IDCM. METHODS: A total of 91 IDCM patients and 102 controls were subjected to HFE mutation analyses, in which C282Y, H63D and S65C mutations were determined for each patient. We also analyzed the impact of the C282Y and H63D mutations on the left ventricular end-diastolic diameter (LVEDD), left ventricular ejection fraction (LVEF) and New York Heart Association (NYHA) functional classes. RESULTS: The prevalences of heterozygosity for the C282Y, H63D and S65C mutations in the IDCM patients were 13.2%, 22.0% and 2.2%, respectively. LVEDD was significantly higher (P=0.037) in those with the C282Y mutation at the end of the follow-up period than in those with no mutation. CONCLUSIONS: Our data showed no significant deviations in C282Y, H63D and S65C mutation frequencies between the IDCM patients and controls, suggesting that these mutations do not increase the risk of IDCM. Heterozygosity for the C282Y mutation may nevertheless be a modifying factor contributing to LV dilatation and remodeling.     

Mildronate: cardioprotective action through carnitine-lowering effect

Mildronate [3-(2,2,2-trimethylhydrazinium)propionate dihydrate] ameliorates cardiac function during ischemia by modulating myocardial energy metabolism. Biochemical and pharmacological evidence supports the hypothesis that the mechanism of action of mildronate is based on its regulatory effect on carnitine concentration, whereby mildronate treatment shifts the myocardial energy metabolism from fatty acid oxidation to the more favorable glucose oxidation under ischemic conditions. Because mildronate treatment prepares cellular metabolism and membrane structures to survive ischemic stress conditions, it is possible that mildronate could be regarded as an agent of pharmacological preconditioning.     

Antibodies to human heat shock protein 60, hypertension and dyslipidemia. A study of joint effects on coronary risk

OBJECTIVE: High IgA-class (but not IgG-class) Anti-Heat-shock-protein 60 antibody level is a predictor of coronary risk in dyslipidemic middle-aged men. In this paper we studied the joint effects of high Anti-Hsp60-antibody level and the classical coronary risk factors. METHODS: We used nested case-control design and logistic regression analyses. The cases consisted of 233 middle-aged men with myocardial infarction or coronary death during 8.5-year follow-up in Helsinki Heart Study, a coronary primary prevention study with gemfibrozil. The controls were subjects without coronary events, matched for drug treatment and the geographical area. RESULTS: The relative coronary risks (Odds Ratios (ORs); 95% confidence interval) were 1.41 (0.96-2.05) for high IgA-class Anti-Hsp60 antibody level and 1.98 (1.35-2.90) for hypertension, defined as mean arterial pressure >114 mmHg. With simultaneous occurrence of high Anti-Hsp60 antibody level and hypertension, the ORs were 2.32 (1.26-4.27) for systolic and 2.99 (1.63-5.48) for diastolic hypertension. Similar patterns of joint effects were found between high Anti-Hsp60 antibody and lipoprotein cholesterol levels as well as antibodies against oxidized low-density lipoprotein. CONCLUSIONS: Our results suggest that, while high IgA-class Anti-Hsp60 antibody level predicts coronary risk, the effect is modest without simultaneous occurrence of other classical risk factors.     

Double versus single autotransplantation in multiple myeloma; a single center experience of 100 patients

One hundred patients with newly diagnosed multiple myeloma (MM) were treated with high-dose chemotherapy followed by single or double autologous stem cell transplantation (ASCT). Up-front treatment with a double ASCT tended to prolong progression-free and overall survival.