Opposing trends in incidence of esophageal squamous cell carcinoma and adenocarcinoma in a multi-ethnic Asian country

OBJECTIVES: To describe the incidence trends in esophageal squamous cell carcinoma (SCC) and adenocarcinoma among the three major ethnic groups in Singapore from 1968 to 2002. METHODS: Esophageal cancer cases in Singapore citizens and permanent residents obtained from the Singapore Cancer Registry and population data derived from the national census were used to calculate the incidence rates from 1968 to 2002. RESULTS: The age-standardized incidence rates (ASRs) for SCC decreased progressively from 8.31 to 3.85 per 100,000 men (p = 0.017) and from 3.43 to 0.81 per 100,000 women (p = 0.027). The rates fell for all three ethnic groups. The ASR for adenocarcinoma rose from 0 to 0.54 per 100,000 men and from 0.03 to 0.13 per 100,000 women, although these time trends did not achieve statistical significance. The frequency of regular smoking in the population decreased from 23% in 1966/1977 to 12.6% in 2004. The percentage of obesity in adults rose from 4.3% in 1982-1985 to 6.9% in 2004. The frequency of esophagitis in Singapore based on endoscopic findings increased from 3.9% in 1992 to 9.8% in 2001. CONCLUSIONS: The decline in the incidence of SCC is likely to be associated with the known decrease in the frequency of smoking among Singaporeans. In contrast, there appears to be a trend toward an increase in the incidence of adenocarcinoma in Singapore, although the absolute incidence remains relatively low. This may be due to the associated rise in the frequency of reflux esophagitis and obesity in Singapore.     

Autologous myoblast transplantation after myocardial infarction increases the inducibility of ventricular arrhythmias

BACKGROUND: Small scale clinical trials suggested the feasibility and the efficacy of autologous myoblast transplantation to improve ventricular function after myocardial infarction. However, these trials were hampered by unexpected episodes of life-threatening ventricular tachyarrhythmias (VT). We investigated cardiac electrical stability after myoblast transplantation to the myocardium. METHODS AND RESULTS: Seven days after coronary ligation, Wistar rats were randomized into 3 groups: a control group receiving no further treatment, a vehicle group injected with culture medium into the infarcted myocardium, and a myoblast group injected with autologous myoblasts. Holter monitoring did not discriminate the myoblast from the vehicle groups. Programmed Electrical Stimulation (PES) was performed to evaluate further a cardiac substrate for arrhythmia susceptibility. The occurrence of sustained VT during PES was similar in control and vehicle groups (5/17 and 4/19 rats, respectively; p=0.50). In contrast, 13/20 rats (65%) from the myoblast group showed at least one episode of sustained VT during PES (p<0.05 and p<0.005 versus control and vehicle groups). As a further control group, rats injected with autologous bone marrow mononuclear cells into the infarcted myocardium did not show increased susceptibility to PES. CONCLUSIONS: In an infarcted rat model, myoblast transplantation but not bone marrow mononuclear cells or myocardial injection per se induces electrical ventricular instability. Because ventricular arrhythmias are life-threatening disorders, we suggest that such preclinical evaluation should be conducted for any new source of cells to be injected into the myocardium.     

Risk factors for death in acquired immunodeficiency syndrome-associated disseminated histoplasmosis

We performed a retrospective study of 164 human immunodeficiency virus (HIV)-infected patients with disseminated histoplasmosis to identify the risk factors for death. Death occurred in 32% of the cases. Univariate analysis identified the following risk factors: diarrhea (odds ratio [OR] = 3.9, P = 0.001), neurologic manifestations (OR = 5.8, ; P = 0.001), hemoglobin level < 8.0g/dL (OR = 2.7, P = 0.004), urea level 2 times the normal upper limit (OR = 5.0, P < 0.001), creatinine level > 1.5 mg/dL (OR = 2.9, P = 0.005), aspartate aminotransferase (AST) level > 2.5 times the normal upper limit (OR = 3.1, P = 0.01), respiratory insufficiency (OR = 9.7, P < 0.001), sepsis (OR = 20.2, P < 0.001), and acute renal failure (OR = 2.5, P = 0.011). A hemoglobin level < 8.0 g/dL (OR = 3.8, P = 0.008), an AST level >or= 2.5 times the normal limit (OR = 1.0, P = 0.007), acute renal failure (OR = 2.96, P = 0.015), and respiratory insufficiency (OR = 12.2, P = 0.01) were independent risk factors for death.     

Comparison between fatigue, sleep disturbance, and circadian rhythm in cancer inpatients and healthy volunteers: evaluation of diagnostic criteria for cancer-related fatigue

The aim of this study was to evaluate whether diagnostic criteria for cancer-related fatigue syndrome (CRFS) could be rigorously applied to cancer inpatients, and to explore the relationship between subjective fatigue and objective measures of physical activity, sleep, and circadian rhythm. Female cancer patients (n=25) and a comparison group of subjects without cancer (n=25) were studied. Study participants completed a structured interview for CRFS and questionnaires relating to fatigue, psychological symptoms, and quality of life (QoL). Wrist actigraphs worn for 72 hours were used as an objective measure of activity, sleep, and circadian rhythm. Compared to controls, cancer patients were more fatigued, had worse sleep quality, more disrupted circadian rhythms, lower daytime activity levels, and worse QoL. After exclusion of subjects with "probable" mood disorders, the prevalence of CRFS was 56%. Fatigue severity among the cancer patients was significantly correlated with low QoL, depression, constipation, and decreased self-reported physical functioning. It can be concluded that the diagnostic criteria for CRFS can be applied to cancer inpatients but strict application requires a rigorous assessment of psychiatric comorbidity. Despite cancer inpatients having greater impairments of sleep and circadian rhythm, it was found that fatigue severity did not appear to be related to these impairments.     

Drug-related problems on hospital admission: relationship to medication information transfer

BACKGROUND: Patients with end-stage renal disease (ESRD) are at risk for drug-related problems (DRPs), especially on hospital admission. OBJECTIVE: To identify and characterize the DRPs experienced by patients with ESRD on admission and investigate how these DRPs could be related to gaps in medication information transfer. METHODS: Patients with ESRD admitted to the hospital were prospectively identified and clinically assessed by a pharmacist to identify and categorize DRPs on admission. Each DRP was evaluated to determine whether it could have been caused by a gap in medication information transfer. For DRPs caused in this manner, the interface in the information transfer process where the gap may have occurred was determined. RESULTS: A total of 199 DRPs were identified in 47 patients with ESRD over a 12 week period. Ninety-two percent of patients had at least one DRP on admission, with an average of 4.2 +/- 2.2 DRPs per patient. The most common DRP identified was indication for drug therapy--patient requires drug but is not receiving it (51.3%). Of the total DRPs, 130 (65%) were related to gaps in medication information transfer, with 21.5% occurring between the inpatient hospital and the ambulatory clinic pharmacists and 17.7% between the admitting physician and the patient. CONCLUSIONS: Results of this study demonstrate that, in patients with ESRD, DRPs on admission are frequently related to gaps in medication information transfer between healthcare professionals and also between healthcare providers and patients. Improved communication is required at medication information transfer interfaces to prevent these DRPs.     

Ultrastructural features of the lining epithelium of the vas deferens of Agouti paca

The epididymal epithelium of Agouti paca, a wild South American rodent, was basically formed by principal and basal cells. Principal cells were closely related to processes of adsorptive endocytosis, phase-fluid endocytosis and also secretion originating from their cytoplasmic ultrastructural features. Principal cells were also characterized by the presence of vesicles of several shapes, sizes and internalized content occurring in smaller pits, pale small vesicles next to the apical brush border of microvillus, as well as coated vesicles, smooth surface vesicles and great vesicles. Multivesicular bodies, endosomes and lysosomes were mainly observed in supranuclear position. Moreover, presence of an apocrine secretory process was demonstrated by the occurrence of apical cytoplasmic expansions projecting into the vas deferens luminal compartment. Basal flattened cells without luminal surface contact occurred next to the basement membrane of the ductus, and did no exhibit special ultrastructural features.     

DAZ gene copies: evidence of Y chromosome evolution

The DAZ gene, a contributing factor in infertility, lies on the human Y chromosome's AZFc region, whose deletion is a common cause of spermatogenic failure. Y chromosome binary polymorphisms on the non-recombining Y (NRY) region, believed to be a single occurrence on an evolutionary scale, were typed in a sample of fertile and infertile men with known DAZ backgrounds. The Y single-nucleotide polymorphisms (Y-SNPs) with low mutation rates are currently well characterized and permit the construction of a unique phylogeny of haplogroups. DAZ haplotypes were defined using single-nucleotide variant (SNV)/sequence tagged-site (STS) markers to distinguish between the four copies of the gene. The variation of 10 Y chromosome short tandem repeat (STRs) was used to determine the coalescence age of DAZ haplotypes in a comparable time frame similar to that of SNP haplogroups. An association between DAZ haplotypes and Y chromosome haplogroups was found, and our data show that the DAZ gene is not under selective constraints and its evolution depends only on the mutation rate. The same variants were common to fertile and infertile men, although partial DAZ deletions occurred only in infertile men, suggesting that those should only be used as a tool for infertility diagnosis when analysed in combination with haplogroup determinations.     

Synthetic and natural polycations for gene therapy: state of the art and new perspectives

Currently, the major drawback of gene therapy is the gene transfection rate. The two main types of vectors that are used in gene therapy are based on viral or non-viral gene delivery systems. There are several non-viral systems that can be used to transfer foreign genetic material into the human body. In order to do so, the DNA to be transferred must escape the processes that affect the disposition of macromolecules. These processes include the interaction with blood components, vascular endothelial cells and uptake by the reticuloendothelial system. Furthermore, the degradation of therapeutic DNA by serum nucleases is also a potential obstacle for functional delivery to the target cell. Cationic polymers have a great potential for DNA complexation and may be useful as non-viral vectors for gene therapy applications. The objective of this review was to address the state of the art in gene therapy using synthetic and natural polycations and the latest strategies to improve the efficiency of gene transfer into the cell.