Discovery of genes related to formothion resistance in oriental fruit fly (Bactrocera dorsalis) by a constrained functional genomics analysis.

Artificial selection can provide insights into how insecticide resistance mechanisms evolve in populations. The underlying basis of such phenomena can involve complex interactions of multiple genes, and the resolution of this complexity first necessitates confirmation that specific genes are involved in resistance mechanisms. Here, we used a novel approach invoking a constrained RNA sequencing analysis to refine the discovery of specific genes involved in insecticide resistance. Specifically, for gene discovery, an additional constraint was added to the traditional comparisons of susceptible vs. resistant flies by the incorporation of a line in which insecticide susceptibility was 'recovered' within a resistant line by the removal of insecticide stress. In our analysis, the criterion for the classification of any gene as related to insecticide resistance was based on evidence for differential expression in the resistant line as compared with both the susceptible and recovered lines. The incorporation of this additional constraint reduced the number of differentially expressed genes putatively involved in resistance to 464, compared with more than 1000 that had been identified previously using this same species. In addition, our analysis identified several key genes involved in metabolic detoxification processes that showed up-regulated expression. Furthermore, the involvement of acetylcholinesterase, a known target for modification in insecticide resistance, was associated with three key nonsynonymous amino acid substitutions within our data. In conclusion, the incorporation of an additional constraint using a 'recovered' line for gene discovery provides a higher degree of confidence in genes identified to be involved in insecticide resistance phenomena.

Risk-benefit assessment of oral phosphodiesterase type 5 inhibitors for treatment of erectile dysfunction: a multiple criteria decision analysis.

BACKGROUND: Erectile dysfunction (ED) is a common male sexual disorder worldwide. Three oral phosphodiesterase type 5 inhibitors (PDE5Is) - sildenafil, tadalafil and vardenafil - are available for treatment of ED. This study quantitatively evaluated the therapeutic efficacy and safety of these medications to assist treatment decision making. METHODS: We used multiple criteria decision analysis (MCDA) to assess the totality of risk-benefit of PDE5Is. We created two models: (i) the overall model included 'overall improvement in erections' and 'any adverse events' and (ii) the detailed model included 'erectile function domain', 'ability for sexual intercourse', 'duration of erection last', 'serious adverse events', 'headache', 'flushing' and 'dyspepsia'. We calculated a synthetic utility for each drug accounting for all of its benefits and risks. RESULTS: Considering the overall risk-benefit, vardenafil had the highest synthetic utility among three medications; in the order of synthetic utilities: vardenafil (0.568), tadalafil (0.478) and sildenafil (0.437). However, when specific risk and benefit criteria were assessed, tadalafil had the highest synthetic utility (0.602) according to the conjoint evaluation (synthetic utility for vardenafil is 0.491 and sildenafil is 0.442, respectively). The sensitivity analysis based on the uncertainties of weight on risks of any adverse events (including serious adverse events and headache) suggested our results were robust. CONCLUSIONS: This study provides a useful approach that comprehensively and systematically assesses and compares the risk-benefit of several treatment alternatives. Our study not only rank treatment alternatives by synthetic utilities based on the risk-benefit balance but also compare specific risk and benefit criteria between these medicines. Our results provide valuable evidence that can guide clinicians and patients in making treatment decisions.

Inhaled corticosteroids and the increased risk of pulmonary tuberculosis: a population-based case-control study.

AIMS: The association between inhaled corticosteroid (ICS) use and pulmonary tuberculosis (TB) development is uncertain. We conducted a population-based case-control study to investigate whether ICS use increases the risk of developing TB. METHODS: Tuberculosis patients aged 18 years and older were identified using the National Health Insurance Research Database (NHIRD) in Taiwan between 2002 and 2010. Each TB patient was frequency matched to four control patients according to age, sex and index year. We retrospectively followed up the medications and comorbid medical conditions for the 5 years prior to the index date. We calculated the odds ratios (ORs) and 95% confidence intervals (CIs) of TB development using multiple logistic regression models. RESULTS: Most of the study participants were men (68.7%), and the mean age among the 8091 TB patients and 32,364 comparison participants was 61.3 ± 18.6 years. After adjusting for potential covariates, ICS use caused a 2.04-fold increased risk of developing TB (adjusted OR: 2.04, 95% CI: 1.78-2.33). When considering dose-response and adjusting for potential covariates, ICS and oral corticosteroids (OCS) use remained independent risk factors and exhibited a dose-response relationship of TB development. The multiplicative increased risk of TB was also significant in patients using ICS and OCS compared with patients not using ICS and OCS (adjusted OR: 4.31, 95% CI: 3.39-5.49). Previous TB history exhibited the greatest risk of TB development among the comorbidities (adjusted OR: 8.50, 95% CI: 7.52-9.61). CONCLUSION: Long-term ICS use may increase the risk of TB.

Diagnostic accuracy of dual-source CT coronary angiography in a population unselected for degree of coronary artery calcification and without heart rate modification.

AIM: To assess the ability of coronary angiography performed using dual-source computed tomography (DSCT) to evaluate coronary artery disease (CAD) in a population with unselected heart rates and extensive coronary calcification. MATERIALS AND METHODS: Forty-four patients at intermediate to high risk for CAD underwent both DSCT coronary angiography and invasive coronary angiography (ICA) within 30 days. No beta blockers were administered prior to imaging. Image quality and quantitatively stenosis of all coronary segments with a diameter > or = 1.5mm were accessed. Patients were stratified according to mean heart rate (< 70 versus > or = 70 bpm) and heart rate variability (< 10 versus > or = 10 bpm). DSCT detection of coronary stenosis by segment, vessel, and patient characteristics were compared to the reference standard of ICA. RESULTS: Diagnostic accuracy for all patients was high regarding sensitivity (97%), positive predictive value (PPV, 84.2%), and negative predictive value (NPV, 83.3%) but low regarding specificity (45.5%) with a moderate interobserver agreement (Kappa = 0.50). The accuracy for vessel-based diagnosis was high regarding sensitivity (96.6%), specificity (80.8%), PPV (80.3%), and NPV (96.7%). The segment-based diagnostic results revealed a moderate interobserver agreement for image quality and sensitivity, specificity, PPV and NPV for all segments of 66.9, 97.8, 90.8, and 89.9%, respectively. CONCLUSION: DSCT coronary angiography has high diagnostic accuracy in assessing CAD among patients at intermediate to high risk without using heart rate-modulating premedication. DSCT is not superior to ICA for diagnosis of calcified segments.

Effects of different sources of dietary non-starch polysaccharides on the growth performance, development of digestive tract and activities of pancreatic enzymes in goslings.

1. The purpose of this study was to investigate the effects of different sources of dietary non-starch polysaccharides (NSP) on growth performance, development of gastrointestinal tract, and activities of pancreatic enzymes in goslings from 0 to 21 d of age. 2. A total of 100 one-day-old White Roman female goslings were selected and randomly divided into 5 dietary treatment groups. Each group had 4 replicate cages (100 x 60 x 58 cm) of 5 goslings. Goslings in each group were given one of 5 isoenergetic and isonitrogenous semi-purified diets. Experimental diets were designed to contain 90 g/kg of different sources of dietary NSP from maize (control), barley hull, rice bran, wheat bran, or pectin, respectively, and 97.4 g/kg NSP were supplied by soybean meal. 3. The goslings receiving the pectin diet had significantly higher viscosity in intestinal digesta than the other treatment diets. However, the daily feed intake, daily weight gain, and feed conversion ratio of goslings in the pectin group were significantly lower than those given the other diets. 4. The relative weights of proventriculus, gizzard, liver and pancreas, as well as the relative weights and lengths of various intestinal segments in the goslings that received the pectin diet, were significantly higher than those receiving the other diets. The specific activities (SA) of amylase, lipase, trypsin, and chymotrypsin in the pancreatic tissue of goslings in the pectin group were significantly lower than those in the other groups. 5. Goslings given a soluble NSP source (pectin) diet tended to exhibit inhibited growth and decreased activity of pancreatic enzymes. However, compared with maize, the inclusion of insoluble NSP sources from barley hull, rice bran, and wheat bran did not negatively affect growth and also were not significantly different among the treatment diets.

Heparin-induced thrombocytopenia associated with intra-tumour haemorrhage in cavernous sinus after cardiac myxoma surgery.

Heparin-induced thrombocytopenia (HIT) is a life-threatening disorder that is associated with heparin exposure. The incidence of HIT in patients undergoing cardiac surgery is relatively rare. We present a case of intratumor haemorrhage in the cavernous sinus 1 week after cardiac surgery. The pathogenesis may be venous thrombosis and haemorrhagic infarct caused by HIT following cardiopulmonary bypass surgery. This is a rare case and has not been reported previously.

Abundantly expressed hepatic genes and their differential expression in liver of prelaying and laying geese.

Geese have a short egg-laying period and a low egg production rate. To induce and maintain egg laying, genes related to generating hepatic lipid for yolk deposition should be adequately expressed. Liver mRNA from 6 laying geese was extracted and used for construction of a full-length enriched cDNA library. About 2,400 clones containing gene sequences were determined and National Center for Biotechnology Information Gallus gallus Gene Index databases were used to compare and analyze these sequences. Ten highly expressed genes were selected to determine the differential expression between laying and prelay goose liver. Tissue distribution data showed that very low density apolipoprotein II, liver type fatty acid binding protein, vitellogenin I, and vitellogenin II transcripts were specifically expressed in the liver of laying geese. Ovoinhibitor, preproalbumin, alpha-2-hs-glycoprotein, and vitamin D binding protein mRNA were highly expressed in the liver and to a lesser extent in other tissues. Ovotransferrin mRNA was expressed in liver, ovary, oviduct, shell gland, brain, and adipose tissues. The concentration of transthyretin mRNA was high in the liver and brain. The mRNA concentrations of liver type fatty acid binding protein, alpha-2-hs-glycoprotein, and transthyretin in the livers of laying and prelay geese were not different. The concentrations of hepatic ovotransferrin, ovoinhibitor, preproalbumin, very low density apolipoprotein II, vitellogenin I, vitellogenin II, and vitamin D binding protein mRNA were higher in the liver of laying geese than in prelay geese, suggesting that these genes may be involved in laying function or lipid metabolism related to egg formation.

Prognostic factors of spontaneous intracerebral haemorrhage in haemodialysis patients and predictors of 30-day mortality.

BACKGROUND: The prognostic factors of intracerebral haemorrhage (ICH) in haemodialysis (HD) patients are not fully clear and there is no standard clinical grading scale to predict 30-day mortality. Our aim was to develop such a scale. METHODS: Records of all HD patients with spontaneous ICH presenting to Chang Gung Memorial Hospital in Taiwan during 1994-2004 were reviewed. The study design was a retrospective analysis of data collected from one hospital. Prognostic factors were identified by Student's t-test and chi(2)-test. Independent predictors of 30-day mortality were determined by the logistic regression method. An outcome score based on a combination of these predictors was developed with weighting of independent predictors based on strength of association. RESULTS: The overall 30-day mortality rate was 67.3%. Prognostic factors independently associated with mortality were the Glasgow Coma Scale score (P < 0.001), age >/=70 years (P = 0.032), systolic blood pressure <130 mmHg or >/=200 mmHg (P = 0.016), ICH volume >/=30 mL (P = 0.012), presence of intraventricular haemorrhage (P = 0.004) and serum glucose >/=8.8 mmol/L (P = 0.023). The score was the sum of individual points assigned as follows: Glasgow Coma Scale score 12-15 (0 points), 9-11 (1), 3-8 (4); age <70 years, yes (0), no (2); and systolic blood pressure 130-199 mmHg, yes (0), no (1). The 30-day mortality rate increased steadily with score (P < 0.001). CONCLUSION: The outcome score is a simple clinical grading scale that allows risk stratification of HD patients presenting with ICH. This scale could be used to design treatment protocols and clinical research studies of ICH in HD patients.

Prognostic factors affecting the outcome of early cervical cancer treated with radical hysterectomy and post-operative adjuvant therapy.

The purpose of this study is to investigate the clinical and histological features that may affect the survival of the patients and to evaluate the impact of post-operative adjuvant therapy on the outcomes of patients with stage IB and IIA carcinoma of the cervix. From August 1998 to January 2005, 140 patients with International Federation of Gynecology and Obstetrics stage IB and IIA cervical cancer were treated with radical hysterectomy and post-operative pelvic radiation therapy with or without chemotherapy. The median age was 55 years (range, 29-86 years). Seventy-six patients had stage IB and 64 patients had stage IIA disease. Tumour size was <4 cm in 96 patients and > or = 4 cm in 44 patients. One hundred and eleven patients had histology of squamous cell carcinoma, 12 patients has adenocarcinoma and 17 patients had other histologic types. Depth of stromal invasion was <2/3 in 20 patients and > or = 2/3 in 120 patients. Twenty-three patients had parametrial invasion and 117 patients had no parametrial invasion. Thirteen patients had lymphovascular space invasion and 127 had no lymphovascular space invasion. Nine patients had positive surgical margin and 131 patients had negative margin. Twenty-seven patients had pelvic lymph node metastasis and 113 patients had no pelvic lymph node metastasis. Seventy-five patients received concurrent chemoradiotherapy and 65 patients received radiotherapy alone. The 5-year overall survival (OAS) and disease-free survival were 83% and 72% respectively. In the log rank test, tumour size (P = 0.0235), pararmetrial invasion (P = 0.0121), pelvic lymph node metastasis (P < 0.0001) and adjuvant chemotherapy + radiotherapy (P = 0.0119) were significant prognostic factors for OAS, favouring tumour size <4 cm, absence of parametrial invasion and pelvic lymph node metastasis, and those who received adjuvant chemoradiotherapy. The patients who received radiation with concomitant chemotherapy had a 5-year OAS rate of 90% versus those who received radiotherapy alone, with a rate of 76%. For patients with high-risk early stage cervical cancer who underwent a radical hysterectomy and pelvic lymphadenectomy, adjuvant chemoradiotherapy resulted in better survival than radiotherapy alone. The addition of weekly cisplatin to radiotherapy is recommended. The treatment-related morbidity is tolerable.

Interactions among LRF-1, JunB, c-Jun, and c-Fos define a regulatory program in the G1 phase of liver regeneration.

In regenerating liver, a physiologically normal model of cell growth, LRF-1, JunB, c-Jun, and c-Fos among Jun/Fos/LRF-1 family members are induced posthepatectomy. In liver cells, high levels of c-Fos/c-Jun, c-Fos/JunB, LRF-1/c-Jun, and LRF-1/JunB complexes are present for several hours after the G0/G1 transition, and the relative level of LRF-1/JunB complexes increases during G1. We provide evidence for dramatic differences in promoter-specific activation by LRF-1- and c-Fos-containing complexes. LRF-1 in combination with either Jun protein strongly activates a cyclic AMP response element-containing promoter which c-Fos/Jun does not activate. LRF-1/c-Jun, c-Fos/c-Jun, and c-Fos/JunB activate specific AP-1 and ATF site-containing promoters, and in contrast, LRF-1/JunB potently represses c-Fos- and c-Jun-mediated activation of these promoters. Repression is dependent on a region in LRF-1 that includes amino acids 40 to 84 (domain R) and the basic/leucine zipper domain. As the relative level of LRF-1/JunB complexes increases posthepatectomy, c-Fos/Jun-mediated ATF and AP-1 site activation is likely to decrease with simultaneous transcriptional activation of the many liver-specific genes whose promoters contain cyclic AMP response element sites. Thus, through complex interactions among LRF-1, JunB, c-Jun, and c-Fos, control of delayed gene expression may be established for extended times during the G1 phase of hepatic growth.

The immediate-early growth response in regenerating liver and insulin-stimulated H-35 cells: comparison with serum-stimulated 3T3 cells and identification of 41 novel immediate-early genes.

Liver regeneration provides a unique system for analysis of mitogenesis in intact, fully developed animals. Cellular immediate-early genes likely play an important role in cell cycle regulation and have been extensively studied in mitogen-stimulated fibroblasts lymphocytes but not in liver. We have begun to characterize the immediate-early growth response genes of mitogen-stimulated liver cells, specifically, regenerating liver and insulin-stimulated Reuber H-35 hepatoma cells, and to address differences in growth response between different cell types. Through subtraction and differential screening of cDNA libraries from regenerating liver and insulin-treated H-35 cells, we have extensively characterized 341 differentially expressed clones and identified 52 immediate-early genes. These genes have been partially sequenced and subjected to Northern (RNA) blot analysis, and 41 appear to be novel. Surprisingly, two-thirds of these genes are also expressed in BALB/c 3T3 cells, but only 10 were identified in previous studies of 3T3 cells, and of these, 6 include well-known genes like jun and fos, and only 4 are novel. Approximately one-third of the immediate-early genes identified in mitogen-stimulated liver cells or serum-stimulated NIH 3T3 cells are expressed in a tissue-specific fashion, indicating that cell type-specific regulation of the proliferative response occurs during the immediate-early period. Our findings indicate that the immediate-early response is unusually complex for the first step in a regulatory cascade, suggesting that multiple pathways must be activated. The abundance of immediate-early genes and the highly varied pattern of their expression in different cell types suggest that the tissue specificity of the proliferative response arises from the particular set of these genes expressed in a given tissue.

Rapid induction in regenerating liver of RL/IF-1 (an I kappa B that inhibits NF-kappa B, RelB-p50, and c-Rel-p50) and PHF, a novel kappa B site-binding complex.

The liver is one of the few adult tissues that has the capacity to regenerate following hepatectomy or toxic damage. In examining the early growth response during hepatic regeneration, we found that a highly induced immediate-early gene in regenerating liver encodes RL/IF-1 (regenerating liver inhibitory factor) and is the rat homolog of human MAD-3 and probably of chicken pp40. RL/IF-1 has I kappa B activity of broad specificity in that it inhibits the binding of p50-p65 NF-kappa B, c-Rel-p50, and RelB-p50, but not p50 homodimeric NF-kappa B, to kappa B sites. Like RL/IF-1, several members of the NF-kappa B and rel family of transcription factors are immediate-early genes in regenerating liver and mitogen-treated cells. We examined changes in kappa B site binding activity during liver regeneration and discovered a rapidly induced novel kappa B site-binding complex designated PHF [posthepatectomy factor(s)]. PHF is induced over 1,000-fold within minutes posthepatectomy in a protein synthesis-independent manner, with peak activity at 30 min, and is not induced by sham operation. PHF is distinct from p50-p65 NF-kappa B, which is present only in the inactive form in liver posthepatectomy. Although early PHF complexes do not interact strongly with anti-p50 antibodies, PHF complexes present later (3 to 5 h) posthepatectomy react strongly, suggesting that they contain a p50 NF-kappa B subunit. Unlike p50-p65 NF-kappa B, c-Rel-p50, and RelB-p50 complexes, PHF binding to kappa B sites is not inhibited by RL/IF-1. One role of RL/IF-1 in liver regeneration may be to inhibit p50-p65 NF-kappa B activity present in hepatic cells, allowing for the preferential binding of PHF to kappa B sites. Because PHF is induced immediately posthepatectomy in the absence of de novo protein synthesis, PHF could have a role in the regulation of liver-specific immediate-early genes in regenerating liver.

The differential expression of hepatic genes between prelaying and laying geese.

Suppression subtractive hybridization was used to detect differential expression of genes in the livers of laying and prelaying geese. Liver tissues from prelaying and laying geese were dissected for mRNA extraction. The cDNA, reverse transcribed from liver mRNA of prelaying geese, was subtracted from the cDNA generated from the laying geese (forward subtraction). Five hundred seventy-six clones with possible differentially expressed gene fragments were observed by forward subtraction hybridization. After differential screening using the reverse and forward subtraction cDNA, 164 clones were subjected to gene sequence determination and further analysis. Using Northern analysis, 5 known and 8 unknown genes were shown to be highly expressed in the livers of laying geese compared with prelaying geese. Vitellogenin I, apoVLDL-II, ethanolamine kinase, G-protein gamma-5 subunit, and leucyl-tRNA synthase were highly expressed in the livers of laying geese compared with that from the prelaying geese (P<0.05). The expression of these known genes suggests that their function in the liver of laying geese is primarily involved in lipid and lipoprotein metabolism. Several of these differentially expressed genes were found to be responsive to estrogen stimulation, confirming the involvement of these genes in the egg-laying function of the goose.

The expression of pituitary gland genes in laying geese.

The purpose of this study was to detect differential expression of genes in the pituitary gland in laying geese by suppression subtractive hybridization (SSH). Pituitary glands from prelaying and laying geese were dissected for mRNA extraction. The cDNA from pituitary glands of prelaying geese was subtracted from the cDNA from the pituitary glands of laying geese (forward subtraction); the reverse subtraction was also performed. We screened 384 clones with possible differentially expressed gene fragments by differential screening. Sixty-five clones from the differential screening results were subjected to gene sequencing and further analysis. We found that at least 19 genes were highly expressed in the pituitary glands of laying geese compared with prelaying geese. Among these, 6 genes (including 4 novel genes) were confirmed by virtual Northern analysis. We found that prolactin and visinin-like protein were highly expressed in the pituitary glands of laying geese compared with prelaying geese (P < 0.05). Further investigation is needed to demonstrate specific functions of the novel genes discovered in the current study.

Promoter-specific trans-activation and inhibition mediated by JunB.

Nuclear levels of c-Jun, JunB, c-Fos, and LRF-1 (liver regeneration factor) are high for a large fraction of the G1 phase in regenerating liver and mitogen-stimulated hepatic cells. Previously, JunB was regarded as a less potent transcriptional activator than c-Jun that could also function as a repressor. However, we found that, like c-Jun, JunB alone or LRF-1/JunB strongly transactivates a cAMP-responsive promoter. Unlike c-Jun, JunB represses several AP-1 or activator of transcription factor site-containing promoters, and this inhibition is greatly enhanced in the presence of LRF-1. Here, we identify separate regions of JunB required for trans-activation and repression of these promoters. Deletion analysis shows that the region involved in trans-activation function is highly conserved among all Jun family members and corresponds to activator domain (A1) of c-Jun. In contrast, repression is maximal in the presence of both the DNA-binding domain and a region proximal to the basic region that is highly divergent among Jun proteins. Functional distinctions between Jun proteins during induction of the growth response and tumorigenesis may be accounted for by promoter-specific activation and repression mediated by regional differences in Jun family proteins.

Levels of F2-isoprostanes, F4-neuroprostanes, and total nitrate/nitrite in plasma and cerebrospinal fluid of patients with traumatic brain injury.

Several events occurring during the secondary damage of traumatic brain injury (TBI) can cause oxidative stress. F(2)-isoprostanes (F(2)-IsoPs) and F(4)-neuroprostanes (F(4)-NPs) are specific lipid peroxidation markers generated from arachidonic acid and docosahexaenoic acid, respectively. In this study, we evaluated oxidative stress in patients with moderate and severe TBI. Since sedatives are routinely used to treat TBI patients and propofol has been considered an antioxidant, TBI patients were randomly treated with propofol or midazolam for 72 h postoperation. We postoperatively collected cerebrospinal fluid (CSF) and plasma from 15 TBI patients for 6-10 d and a single specimen of CSF or plasma from 11 controls. Compared with the controls, the TBI patients exhibited elevated levels of F(2)-IsoPs and F(4)-NPs in CSF throughout the postsurgery period regardless of the sedative used. Compared with the group of patients who received midazolam, those who received propofol exhibited markedly augmented levels of plasma F(2)-IsoPs, which were associated with higher F(4)-NPs levels and lower total nitrate/nitrite levels in CSF early in the postsurgery period. Furthermore, the higher CSF F(2)-IsoPs levels correlated with 6-month and 12-month worse outcomes, which were graded according to the Glasgow Outcome Scale. The results demonstrate enhanced oxidative damage in the brain of TBI patients and the association of higher CSF levels of F(2)-IsoPs with a poor outcome. Moreover, propofol treatment might promote lipid peroxidation in the circulation, despite possibly suppressing nitric oxide or peroxynitrite levels in CSF, because of the increased loading of the lipid components from the propofol infusion.

Decreased expression and functionality of NMDA receptor complexes persist in the CA1, but not in the dentate gyrus after transient cerebral ischemia.

The authors investigated the gene expression of the NR2A and NR2B subunits of N-methyl-D-aspartate (NMDA) receptor and the functional electrophysiologic activity of NMDA receptor complexes in the vulnerable CA1 and less vulnerable dentate gyrus subfields of the rat hippocampus at different times after transient cerebral ischemia. Decreased expression for both subtypes was observed in both the CA1 subfield and dentate granule cell layer at early times after challenge; however, the decreased expression in the dentate granule cell layer was reversible because mRNA levels for both the NR2A and NR2B subtypes recovered to, or surpassed, sham-operated mRNA levels by 3 days postchallenge. No recovery of expression for either subtype was observed in the CA1 subfield. The functional activity of NMDA receptor complexes, as assessed by slow field excitatory postsynaptic potentiations (slow f-EPSP) in CA1 pyramidal neurons, was maintained at 6 hours postchallenge; however, this activity was diminished greatly by 24 hours postchallenge, and absent at 7 days postchallenge. A similar pattern was observed for the non-NMDA receptor-mediated fast f-EPSP. In dentate granule neurons, however, no significant change in NMDA receptor-mediated slow f-EPSP from sham control was observed at any time after insult. The non-NMDA receptor-generated fast f-EPSPs also were maintained at all times postinsult in the dentate gyrus. These results illustrate that the activity of NMDA receptors remains functional in dentate granule neurons, but not in the pyramidal neurons of the CA1 subfield, at early and intermediate times after transient cerebral ischemia, and suggest that there is a differential effect of ischemia on the glutamatergic transmission systems in these two hippocampal subfields.

Ocular predictors of the onset of juvenile myopia.

PURPOSE: The purpose of this study was to identify reliable predictors of the onset of juvenile myopia. METHODS: The data from 554 children enrolled in the Orinda Longitudinal Study of Myopia (OLSM) as nonmyopes with baseline data from the third grade were evaluated to develop a predictive profile for later onset of juvenile myopia. Myopia was defined as at least -0.75 D of myopia in the vertical and horizontal meridians of the right eye as measured by cycloplegic autorefraction (n = 45 children). Chosen predictors were refractive error and the ocular components: corneal power, Gullstrand crystalline lens power, and axial length. Sensitivity and specificity were calculated. Receiver operating characteristic (ROC) curves were generated to evaluate and compare these predictors singly and combined. RESULTS: Refractive error, axial length, Gullstrand lens and pod corneal power were all significant predictive factors for the onset of juvenile myopia. The best single predictor of future myopia onset in the right eye was the right eye's cycloplegic autorefraction spherical refractive error value (mean sphere across 10 readings) at baseline. For a cut point of less than +0.75 D hyperopia in the third grade, sensitivity was 86.7% and specificity was 73.3%. The area under the ROC curve for this mean sphere was 0.880. Producing a logistic model combining mean sphere, corneal power, Gullstrand lens power, and axial length results in a slight improvement in predictive ability (area under the ROC curve = 0.893). CONCLUSIONS: Onset of juvenile myopia can be predicted with moderate accuracy using the mean cycloplegic, spherical refractive error in the third grade. Measurement of other ocular components at this age improves predictive ability, albeit incrementally. Further improvements in the prediction of myopia onset will require the use of longitudinal data in addition to one-time measurement of refractive error and the ocular components.

Coronary artery calcium evaluation by electron beam computed tomography and its relation to new cardiovascular events.

Electron beam computed tomography is widely used to screen for coronary artery calcium (CAC). We evaluated the relation of CAC to future cardiovascular disease events in 926 asymptomatic persons (735 men and 191 women, mean age 54 years) who underwent a baseline electron beam computed tomographic scan. All subjects included in this report returned a follow-up questionnaire 2 to 4 years (mean 3.3) after scanning, inquiring about myocardial infarction, stroke, and revascularizations. Sixty percent of men and 40% of women had a positive scan at baseline. Twenty-eight cardiovascular events occurred and were confirmed by blinded medical record review. The presence of CAC (a total calcium score of >0) and increasing score quartiles were related to the occurrence of new myocardial infarction (p <0.05), revascularizations (p <0.001), and total cardiovascular events (p <0.001). Those with scores at or above the median (score of 5) had a relative risk of 4.5 (p <0.01) for new events. From Cox regression models, adjusted for age, gender, and coronary risk factors, the relative risks for those with scores of 81 to 270 and -271 (compared with 0) for cardiovascular events were 4.5 (p <0.05) and 8.8 (p <0.001), respectively. These data support previous reports showing CAC to be a modest predictor of future cardiovascular events.

Usefulness of electron beam computed tomography in children with heterotaxy syndrome.

Children with heterotaxy syndrome frequently have complex cardiac and noncardiac malformations requiring detailed diagnostic evaluation for management planning. Direct delineation of these structures by electron beam computed tomography (EBCT) is validated as a means of diagnosis. From July 1995 to March 1997, 32 patients (16 girls, 16 boys) with clinically impressed heterotaxy syndrome were enrolled in this study. After evaluation by echocardiography, EBCT studies were performed. Interpretation of cardiac anomalies was performed by sequential analysis based on these cross-sectional images. The diagnoses were subsequently confirmed by angiocardiography and surgical findings. Twenty-eight patients had bilateral trifurcated bronchi, and most of these (24 of 28) did not have a spleen. Four patients had bilateral bifurcated bronchi, 2 patients had polysplenia, and the other 2 patients had a lobulated single spleen. We found that laterality could be identified by EBCT in all patients. Comparison of diagnostic yield between echocardiography, catheterization, and EBCT showed that EBCT is superior to echocardiography and catheterization in demonstration of pulmonary venous anatomy and presence of a very small rudimentary ventricle. In addition, associated visceral, bronchopulmonary, mediastinal, and intracardiac anomalies could all be clearly delineated by EBCT at the same time. Thus, EBCT is a promising complementary modality for an overall understanding of heterotaxy syndrome.