The impact of obesity on esophagectomy: a meta-analysis.

The impact of body mass index (BMI) on postoperative outcomes after curative resection for esophageal cancer has been assessed in many studies worldwide with conflicting conclusions. The aim of this meta-analysis is to evaluate the influence of preoperative BMI on surgical and oncologic outcomes after radical surgery for esophageal cancer, in Western studies. A comprehensive electronic search was performed to identify Western publications reporting BMI and outcomes following surgery for esophageal cancer. Articles that did not report preoperative BMI, postoperative morbidity, and early mortality were excluded. Statistical analysis was performed using the OpenMetaAnalyst software (Version 10.10). One hundred and ninety records were examined and 8 studies were included with a total of 2838 patients. The study population was stratified into two groups: a nonobese group (BMI < 30 kg/m2), containing 2199 patients, and an obese group (BMI ≥ 30 kg/m2), with 639 patients. In the obese group, there was an increased risk (up to 35%) of anastomotic leak (P = 0.003; RR: 0.857, 95% CI: 0.497, 0.867). The obese group showed a significantly more favorable five-year overall survival (P = 0.011). Although there was a significant association between anastomotic leak and obesity, patients with obesity also have a better overall 5-year survival. This meta-analysis demonstrates that patients with obesity should be counseled regarding the specific risks of surgery but they can be reassured that despite these risks overall outcome is satisfactory.

Working memory performance and exposure to pleasant and unpleasant ambient odor: is spatial span special?

Sensory influences on working memory (WM) performance were investigated in 86 healthy adults. Participants were exposed to an ambient pleasant odor (lemon), unpleasant odor (machine oil) or no odor during completion of three WM tests from the Wechsler Memory Scale-III: the letter-number sequencing, spatial span and digit span tests. A significant main effect of odor was found for spatial span but no other task: scores were significantly lower in the unpleasant odor condition than the pleasant odor condition. Significant odor × sex interactions were found for the spatial span, digit span and letter-number sequencing tasks: men's spatial span scores were lower in the unpleasant odor condition than in the control condition, and women's scores were significantly better in the pleasant odor condition than in the unpleasant odor condition. The results suggest that ambient odor may impair or facilitate specific types of WM depending on the task, sex of the participant and affective characteristics of the odor.

A double-blind, placebo-controlled randomised trial evaluating the effect of a polyphenol-rich whole food supplement on PSA progression in men with prostate cancer--the U.K. NCRN Pomi-T study.

BACKGROUND: Polyphenol-rich foods such as pomegranate, green tea, broccoli and turmeric have demonstrated anti-neoplastic effects in laboratory models involving angiogenesis, apoptosis and proliferation. Although some have been investigated in small, phase II studies, this combination has never been evaluated within an adequately powered randomised controlled trial. METHODS: In total, 199 men, average age 74 years, with localised prostate cancer, 60% managed with primary active surveillance (AS) or 40% with watchful waiting (WW) following previous interventions, were randomised (2:1) to receive an oral capsule containing a blend of pomegranate, green tea, broccoli and turmeric, or an identical placebo for 6 months. RESULTS: The median rise in PSA in the food supplement group (FSG) was 14.7% (95% confidence intervals (CIs) 3.4-36.7%), as opposed to 78.5% in the placebo group (PG) (95% CI 48.1-115.5%), difference 63.8% (P=0.0008). In all, 8.2% of men in the FSG and 27.7% in the PG opted to leave surveillance at the end of the intervention (χ2 P=0.014). There were no significant differences within the predetermined subgroups of age, Gleason grade, treatment category or body mass index. There were no differences in cholesterol, blood pressure, blood sugar, C-reactive protein or adverse events. CONCLUSIONS: This study found a significant short-term, favourable effect on the percentage rise in PSA in men managed with AS and WW following ingestion of this well-tolerated, specific blend of concentrated foods. Its influence on decision-making suggests that this intervention is clinically meaningful, but further trials will evaluate longer term clinical effects, and other makers of disease progression.

Diagnosis of bacteriuria by detection of volatile organic compounds in urine using an automated headspace analyzer with multiple conducting polymer sensors.

The Osmetech Microbial Analyzer (OMA) is an automated headspace analyzer fitted with a novel detector system consisting of an array of polymer sensors, each of which responds to different volatile organic compounds. The system can be used for screening clinical urine specimens for significant bacteriuria by sampling urine headspace and subjecting the output of the multiple-detector response to principal component analysis. The OMA readily distinguished artificially infected urine samples from sterile controls. The OMA was then used to analyze 534 unselected clinical urine specimens, of which 21.5% had significant bacteriuria (containing >10(5) CFU of bacteria/ml). The sensitivity and specificity of the OMA compared with conventional culture were 83.5 and 87.6%, respectively. The OMA is a promising automated system for the rapid routine screening of urine specimens, and further clinical trials are in progress.

Paradoxical effects of trichostatin A: inhibition of NF-Y-associated histone acetyltransferase activity, phosphorylation of hGCN5 and downregulation of cyclin A and B1 mRNA.

Trichostatin A (TSA), an inhibitor of histone deacetylase (HDAC), is widely used to study the role of histone acetylation in gene expression, since genes that use histone acetylation as a means of regulating expression may be up regulated when TSA is added. In this study, however, we show that TSA has an unexpected paradoxical effect leading to inhibition of NF-Y-associated histone acetyl transferase (HAT) activity and phosphorylation of the HAT, hGCN5. TSA treatment of cells resulted in diminished levels of NF-Y-associated HAT activity without changes in NF-Y(A) amount. hGCN5 is one of the HATs known to associate with NF-Y. The association of hGCN5 with NF-Y was not altered by TSA treatment. The enzymatic activity of hGCN5 is known to be inhibited by phosphorylation. TSA treatment of Hela cells resulted in phosphorylation of hGCN5. Exposure of the NF-Y immunoprecipitates from TSA-treated cells to a phosphatase resulted in enhanced HAT activity. We have also shown that the mRNA levels of several genes, cyclin B1 and cyclin A, are downregulated by TSA; these effects do not require protein synthesis and the downregulation of cyclin B1 by TSA occurs through transcription. These results suggest that TSA can have contradictory effects, on one hand stimulating HAT activity in general by inhibition of HDACs, but also resulting in inhibition of NF-Y-associated HAT activity and phosphorylation of hGCN5.

Alterations in chandelier neuron axon terminals in the prefrontal cortex of schizophrenic subjects.

OBJECTIVE: Abnormalities in prefrontal cortical gamma-aminobutyric acid (GABA) neurotransmission may contribute to cognitive dysfunction in schizophrenia. The density of chandelier neuron axon terminals (cartridges) immunoreactive for the GABA membrane transporter (GAT-1) has been reported to be reduced in the dorsolateral prefrontal cortex of schizophrenic subjects. Because cartridges regulate the output of pyramidal cells, this study analyzed the laminar distribution of GAT-1-immunoreactive cartridges to determine whether certain subpopulations of pyramidal cells are preferentially affected. METHOD: Measurements were made of the density of GAT-1 -immunoreactive cartridges in layers 2-3a, 3b-4, and 6 of dorsolateral prefrontal cortex area 46 in 30 subjects with schizophrenia, each of whom was matched to one normal and one psychiatric comparison subject. GAT-1-immunoreactive cartridge density was also examined in monkeys chronically treated with haloperidol. RESULTS: Relative to both comparison groups, the schizophrenic subjects had significantly lower GAT-1-immunoreactive cartridge density in layers 2-3a and 3b-4. The decrease was most common and most marked in layers 3b-4, where 80% of the schizophrenic subjects exhibited an average 50.1% decrease in cartridge density in comparison with the matched normal subjects. In contrast, GAT-1-immunoreactive cartridge density was unchanged in the haloperidol-treated monkeys. CONCLUSIONS: These findings demonstrate that the density of GAT-1-immunoreactive cartridges is reduced in the majority of schizophrenic subjects and that this alteration may most prominently affect the function of pyramidal cells located in the middle cortical layers. This abnormality may reflect a number of underlying deficits, including a primary defect in dorsolateral prefrontal cortex circuitry or a secondary response to altered thalamic input to this region.

Chronic neurogenic facial pain: lack of response to intravenous phentolamine.

AIMS: Chronic neurogenic facial pain is commonly resistant to treatment and is often the source of significant patient morbidity. Adrenergic mechanisms are postulated to play a role in producing this type of pain, and adrenergic blocking agents are frequently used in clinical practice for pain control therapy. The analgesic effectiveness of an adrenergic blocking agent, intravenous phentolamine, was compared to saline and intravenous lidocaine in the present study using a single-blind protocol in patients with chronic neurogenic facial pain. METHODS: Thirty patients were studied whose common clinical features included pain for more than 6 months, unilateral trigeminal distribution, constant dysesthesia, and no evidence of pathology or known etiology. Phentolamine (30 mg), lidocaine (100 mg), and saline were each infused over periods of 5 to 10 minutes. Pain ratings were assessed every 4 minutes throughout each study period using a 10-point pain intensity scale. RESULTS: No patient reported subjective improvement of pain during or immediately following phentolamine or saline infusions alone. Sixteen of the 30 patients reported decreased pain following lidocaine infusion. In the majority of the patients, the duration of lidocaine analgesia was less than 30 minutes; however, some patients reported decreased pain for a longer time. CONCLUSION: The results do not support an adrenergic mechanism for chronic neurogenic facial pain. The response to lidocaine, a nonadrenergic, membrane-stabilizing agent, suggests that it may have clinical effectiveness in certain neurogenic facial pain patients.

The dynamics of childhood poverty.

Child poverty rates have remained high since the middle of the 1970s. While several trends, including declines in the number of children per family and increases in parental years of schooling, worked to reduce child poverty rates, several others, including show economic growth, widening economic inequality, and increases in the proportion of children living in mother-only families, had the opposite effect, pushing more children into poverty. Poverty is a common risk: One-third of all children will be poor for at least one year. For many, poverty lasts only a short while, but for a small percentage, poverty persists both throughout childhood and into the adult years. Poverty is not shared equally across different demographic groups. African-American children. Latino children, and children in mother-only families are disproportionately poor. Long-term poverty is even more concentrated than single-year poverty. In 1992, almost 90% of long-term poor children were African-American as compared to all poor children (single-year and long-term poor), of whom 60% were white. Both family structure and the labor market are implicated in long-term childhood poverty. Changes in employment of family members and changes in family composition are each strongly associated with transitions into and out of childhood poverty. Of these, changes in employment are the most important.

The benefits of a shared-care prostate clinic.

OBJECTIVE: To establish a hospital based shared-care clinic to investigate and manage benign prostatic hyperplasia (BPH) with general practitioners (GPs). PATIENTS AND METHODS: During one year, 330 patients referred with suspected prostatic obstruction were investigated in an outreach clinic in a rural cottage hospital by urology department nurses according to a protocol. After this, they were referred directly back to their GPs with recommendations for their management or seen in the urologist's clinic. A questionnaire was completed by the GPs to assess their satisfaction with and attitudes to the clinic. RESULTS: One-third of the patients were referred directly back to their GP, a third were seen routinely and a third seen urgently in the urologist's clinic, usually because a prostate-specific antigen assay indicated the possibility of latent prostatic cancer. A survey confirmed that GP support for the clinic was unanimous whilst patients were reassured by the thoroughness and sensitivity of the clinic's nursing staff. CONCLUSION: The clinic reduced the workload of the GPs and urologists whilst providing a speedy and comprehensive assessment of patients presenting with suspected prostatic obstruction.

Arachidonic acid metabolism in benign and malignant prostatic tissue in vitro: effects of fatty acids and cyclooxygenase inhibitors.

Concentrations of fatty acids (FA) in prostatic tissue of patients with either benign or malignant prostatic disease have previously been shown to be significantly different. In particular, there was a significant reduction in arachidonic acid (AA, C20:4n-6) and docosapentaenoic acid (DPA, C22:5n-6) concentrations in malignant prostatic tissue (PCa) phospholipids (PL). It was suggested that the decreased AA concentration in PCa may be due to its increased metabolism via the cyclooxygenase (CO) and/or lipoxygenase (LO) pathways to produce eicosanoids such as prostaglandins (PGs) and/or leukotrienes (LTs) rather than an impairment in desaturase activity in situ. The eicosanoid production in benign prostatic tissue (BPH) and PCa was determined using [3H]AA. The only eicosanoid produced in significant amounts by either tissue was PGE2 and PCa converted radiolabelled AA to PGE2 at an almost 10-fold higher rate than BPH. PGE2 production from [3H]AA by PCa was investigated in the presence of oleic acid (OA, C18:1n-9), eicosapentaenoic acid (EPA, C20:5n-3), docosahexaenoic acid (DHA, C22:6n-3), dihomo-gamma-linolenic acid (DGLA, C20:3n-6), eicosatetraynoic acid (ETYA) and ketoprofen (KPN) respectively. OA was found to be the most effective inhibitor of PGE2 production by PCa compared with DHA, EPA, ETYA and KPN, while DGLA was the least effective. Diacylglycerol (DAG) formation from labelled AA by PCa was about 4-fold greater than in BPH. Such high levels of DAG may be a means of promoting tumorigenesis through activation of protein kinase C as found with phorbol esters which can be regarded as DAG analogues.

Purification and characterization of a fatty acid binding protein from human prostatic tissue.

Epidemiological studies suggest the existence of a strong relationship between the incidence of prostatic cancer and the intake of dietary lipids in humans. However, very little information is available on intracellular fatty acid metabolism in human prostatic tissue. The objective of this study was to identify and subsequently characterize a fatty acid binding protein of human prostatic tissue. A fatty acid binding protein (FABP) was purified and characterized from human prostatic tissue. The purified FABP had an apparent molecular mass of 15.0 +/- 1.0 kDa as averaged from three different methods, sodium dodecylsulfate-polyacrylamide gel electrophoresis (SDS-PAGE), gel filtration and amino acid analysis. The pI value of the protein was determined to be 6.8. Scatchard analysis of fatty acid binding to the purified FABP from malignant prostatic tissue showed a Kd value of 0.53 +/- 0.02 microM for arachidonic acid (n = 5). The Kd values of FABP purified from benign prostatic tissue were 0.57 +/- 0.02 microM for oleic acid and 0.51 +/- 0.04 microM for arachidonic acid (n = 5). Fatty acid analysis revealed that the level of endogenously bound arachidonic acid was about 2.5-fold higher in FABP from malignant than from benign tissue. In addition, both malignant and benign tissues contained the same concentration of FABP. The concentrations of FABP in malignant and benign tissues were 19.2 +/- 1.8 and 21.4 +/- 2.1 micrograms per mg of total cytosolic protein, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Essential fatty acid distribution in the plasma and tissue phospholipids of patients with benign and malignant prostatic disease.

There is increasing evidence that essential fatty acids (EFA) may have a role to play in the aetiology of some types of cancer although their precise mode of action is unknown. Differences in the metabolism of EFA between patients with benign or malignant prostatic disease may help to elucidate their role in the latter. We have, therefore, measured the concentration of the essential fatty acids, and their metabolites, in the phospholipid fractions of both plasma and tissue, in patients with either benign or malignant prostatic disease. Comparison of the median concentration of fatty acids in each group (n = 10) revealed significant differences between them. The phospholipid component of total lipid was greater in malignant (P less than 0.04, unpaired t-test) than in benign tissue. The concentrations of linoleic acid (LA) and di-homo gamma linolenic acid (DGLA) in plasma and tissue were not different between the two groups of patients, but a significant reduction in arachidonic acid (ARA) (P less than 0.002, Mann-Whitney U-test) and docosapentaenoic acid (DPA) (P = 0.009) concentrations was observed in malignant tissue as compared to benign. Patients with malignant prostatic disease also had a significantly higher concentration of oleic acid in phospholipids from both plasma and prostatic tissue. The stearic to oleic acid ratio was similar in plasma but was significantly reduced in malignant tissue (P = 0.006). We suggest that the decreased arachidonic acid concentration in malignant tissue may be due to its increased metabolism, via the lipoxygenase and cyclooxygenase pathways to produce higher concentrations of eicosanoids, rather than an impairment in desaturase activity in situ.

An unusual, highly aggressive, anaplastic carcinoma of the nasal cavity.

The case of a patient who had a rapidly growing anaplastic carcinoma of the nasal cavity is reported. The patient died from local recurrences, regional lymph nodes, and distant pulmonary metastases within seven months of the initial diagnosis.