In order to assess the importance of pertinent perinatal risk factors in causing hearing loss (HI), a retrospective evaluation was made of the records of 146 affected children born in the city of Göteborg between 1970 and 1979. The incidence among six-year-olds born between 1970 and 1974 was 3.8 per 1000 newborns. If only HI of more severe degree was taken into account (above 40dB in the best ear), the remaining incidence was 1.4/1000. Sensorineural HI (SNHI) accounted for 87 per cent of the cases. A positive hereditary tendency for HI was found in 55 per cent. In 61 per cent the origin of the HI was presumably prenatal, either positive heredity alone or in the form of facio-auricular anomalies, syndromes and toxic influences (infection and alcohol) during early pregnancy. Postnatal infections (meningitis, parotitis and secretory otitis media) could be ascertained as causes in about 20 per cent of the cases. For 12 per cent no aetiology could be determined. Perinatal aetiology was probable or possible in about 10 per cent of the children. The frequency of SNHI was found to be increased among survivors of neonatal intensive care, VLBW, LBW and SFD infants. Caesarean section, ventouse and breech delivery were not associated with increased rates, nor were hyperbilirubinaemia, exchange transfusion or birth asphyxia. No cases could be traced to aminoglycoside treatment. Neonatal sepsis/meningitis may have been the cause in two of the 146 cases. Hypoxia as a consequence of apnoea and respiratory distress syndrome necessitating mechanical ventilation appeared to be the major risk-factor in the neonatal period. However, in comparison with genetic predisposition, potentially damaging perinatal factors appeared to be of minor importance.

Absorption as a personality trait refers to the predisposition to get deeply immersed in sensory (e.g., smells, sounds, pictures) or mystical experiences, that is, to experience altered states of consciousness. Absorption is markedly related to constructs openness to experiences, hypnotic suggestibility, imagination, and dissociation. Although absorption was hypothesized to be a risk factor for medically unexplained symptoms (MUS), the construct has yet not been investigated in individually suffering from idiopathic environmental intolerance (IEI), formerly better known as multiple chemical sensitivity (MCS). IEI is a complex condition marked by MUS, which patients attribute to various chemical substances that are typically detectable by their odor (e.g., exhaust emissions, cigarette smoke). The current study investigated whether IEI was related to the personality trait of absorption. In a longitudinal study, 54 subjects with IEI were compared to 44 subjects with a somatoform disorder (SFD), but without IEI, and 54 subjects with neither SFD nor IEI (control group, CG). Self-report measures of somatic symptoms, severity of IEI, and level of absorption were collected both at a first examination and 32 mo later. On both assessments, subjects with IEI and individuals with SFD reported similar highly elevated levels of MUS, compared to CG. In contrast to SFD, IEI was specifically related to elevated absorption scores. IEI was specifically associated with a tendency to experience self-altering states of consciousness. Since absorption is related to both openness to unusual experiences and elevated imaginative involvement, absorption might contribute to IEI via two routes by (1) enhancing the susceptibility for IEI-specific convictions and (2) fostering classical conditioning processes of MUS via enhanced cognitive-imaginative representations of assumed IEI triggers.

BACKGROUND

The flow diverting stent is a new and expansive tool in the endovascular therapy of complex intracranial aneurysms. We present our experience using SILK flow diverter (SFD) in patients with complex intracranial aneurysms, and a cost analysis.

METHODS

Between September 2010 and May 2012, 19 consecutive patients with 29 complex intracranial aneurysms were treated with SFD without the adjunctive use of coils. We retrospectively evaluated the technical aspects, thromboembolic events, adjunctive therapies, and short term results in patients with complex intracranial aneurysms treated with SFD. A cost analysis of patients who were treated with SFD was performed and compared with similar sized aneurysms coiled with stent assisted coiling.

RESULTS

The primary technical success rate was 100%. An adjunctive device was required in two of our patients. The technique related complication rate and the 30 day mortality and morbidity rates were 5% (1/20) and 10% (2/20), respectively. We had a total of 263 patient months of clinical and 166 patient months of imaging follow-up. Follow-up imaging revealed two asymptomatic occlusions of the parent artery. Complete occlusion of the aneurysm with fully patent parent artery was observed in 59% of patients where follow-up images were available. The cost analysis showed that the mean cost of treatment with SFD was significantly cheaper compared with the presumed cost of stent assisted coiling (p<0.001).

CONCLUSIONS

The SFD provides a very feasible, efficient, relatively safe, and cost effective method to treat complex intracranial aneurysms without the use of adjunct coiling.

The vacuolar type proton-translocating ATPase of clathrin-coated vesicles is composed of two large domains: an extramembranous catalytic sector and a transmembranous proton channel. In addition, two polypeptides of 50 and 57 kDa have been found to co-purify with the pump. These proteins, termed SFD (sub-fifty-eight-kDa dimer) activate ATPase activity of the enzyme and couple ATPase activity to proton flow (Xie, X.-S., Crider, B.P., Ma, Y.-M., and Stone, D. K. (1994) J. Biol. Chem. 269, 28509-25815). It has also been reported that the clathrin-coated vesicle proton pump contains AP50, a 50-kDa component of the AP-2 complex responsible for the assembly of clathrin-coated pits, and that AP50 is essential for function of the proton pump (Liu, Q., Feng, Y., and Forgac, M. (1994) J. Biol. Chem. 269, 31592-31597). We demonstrate through the use of anti-AP50 antibody, identical to that of the latter study, that hydroxylapatite chromatography removes AP50 from impure proton pump preparations and that purified proton pump, devoid of AP50, is fully functional. To determine the true molecular identity of SFD, both the 50- and 57-kDa polypeptides were directly sequenced. A polymerase chain reaction-based strategy was used to screen a bovine brain cDNA library, yielding independent full-length clones (SFD-4A and SFD-21); these were identical in their open reading frames and encoded a protein with a predicted mass of 54,187 Da. The SFD-21 clone was then used in a reverse transcription-polymerase chain reaction-based strategy to isolate a related, but distinct, transcript present in bovine brain mRNA. The nucleotide and predicted amino acid sequences of this isolate are identical to SFD-21 except that the isolate contains a 54-base pair insert in the open reading frame, resulting in a protein with a predicted mass of 55,933 Da. Both clones had 16% identity to VMA13 of Saccharomyces cerevisiae. No sequence homology between the SFD clones and AP50 was detectable. Anti-peptide antibodies were generated against an epitope common to the two proteins and to the unique 18-amino acid insert of the larger protein. The former reacted with both components of native SFD, whereas the latter reacted only with the 57-kDa component. We term the 57- and 50-kDa polypeptides SFDalpha and SFDbeta, respectively.

Conidiophore morphogenesis in Aspergillus nidulans occurs in response to developmental signals that result in the activation of brlA, a well-characterized gene that encodes a transcription factor that is central to asexual development. Loss-of-function mutations in flbD and other fluffy loci have previously been shown to result in delayed development and reduced expression of brlA. flbD message is detectable during both hyphal growth and conidiation, and its gene product is similar to the Myb family of transcription factors. To further understand the regulatory pathway to brlA activation and conidiation, we isolated suppressor mutations that rescued development in strains with a flbD null allele. We describe here two new loci, designated sfdA and sfdB for suppressors of flbD, that bypass the requirement of flbD for development. sfd mutant alleles were found to restore developmental timing and brlA expression to strains with flbD deletions. In addition, sfd mutations suppress the developmental defects in strains harboring loss-of-function mutations in fluG, flbA, flbB, flbC, and flbE. All alleles of sfdA and sfdB that we have isolated are recessive to their wild-type alleles in diploids. Strains with mutant sfd alleles in otherwise developmentally wild-type backgrounds have reduced growth phenotypes and develop conidiophores in submerged cultures.

OBJECTIVE

Somatoform disorders (SFD) are defined by symptoms that lack medical explanation. This study examined the type and pattern of patients' causal attributions using a new semistructured interview technique

METHODS

The Causal Attributions Interview allows to assess and weigh 15 common explanations of physical symptoms. Attributions given by 79 patients with SFD were compared with those obtained from 187 chronic pain patients.

RESULTS

The test-retest reliabilities of the interview-elicited attributions were satisfactory to good. SFD patients attributed most of their symptoms to mental/emotional problems (46.9%) and somatic disease (41.1%), while the pain sample preferred physical overloading/exhaustion (56.1%), daily hastiness/time pressure (41.7%), somatic disease (39.6%), and weather influence (39.0%). On average, SFD patients chose 2.57 and pain patients 3.86 different attributions for each symptom. These numbers were substantially larger than those of initial spontaneous attributions. Correspondence analysis revealed underlying dimensions with three groups labeled "environmental," somatic," and "psychological/stress." While pure environmental attributions were rare (1.1%), somatic factors were chosen for 28.3% of the symptoms, psychological/stress for 22.1%, and the combination of both for 25.6%. Approximately 10% were attributed in a multicausal sense to all three groups. Depression was found to correlate positively with psychological/stress and negatively with somatic attributions.

CONCLUSIONS

The results do not support the perspective that SFDs generally result from poor acknowledgement of emotional factors. SFD and chronic pain showed distinguishable attributional patterns.

OBJECTIVE

to assess the effects of an educational program in asthmatic patients, following treatment readjustment.

METHODS

moderate to severe asthmatic adults underwent a run-in period (up to 45 days) in order to optimize their treatment. Patients were then randomized to an educational or control group over a one-year period. Education consisted of five individual sessions covering: pathophysiology of asthma, role of medication and side-effects, asthma triggers and their avoidance, detection of an asthma flare-up, and self-management plan based on symptoms and peak-flow monitoring. MAIN OUTCOME CRITERION: symptom-free days over the study period (SFD).

RESULTS

a total of 72 patients were enrolled (36 in the "education group" and 36 in the "control group"), 54 of whom completed the study. Mean SFD was comparable in the two groups (88% in the education group and 89% in the control group, respectively). When the analysis was restricted to the education group, those patients who complied perfectly with the action plan (n = 5) exhibited a higher SFD, compared to the others (97% vs. 87%, p = 0.009).

CONCLUSIONS

both education and control groups showed high and comparable percentages of SFD. Compliance with self-management plans appears to be an important determining factor in educational programs.

OBJECTIVE

The goal of this work was to implement a recently proposed small field dosimetry formalism [Alfonso et al., Med. Phys. 35(12), 5179-5186 (2008)] for a comprehensive set of diode detectors and provide the required Monte Carlo generated factors to correct measurement.

METHODS

Jaw collimated square small field sizes of side 0.5, 0.6, 0.7, 0.8, 0.9, 1.0, and 3.0 cm normalized to a reference field of 5.0 cm × 5.0 cm were used throughout this study. Initial linac modeling was performed with electron source parameters at 6.0, 6.1, and 6.2 MeV with the Gaussian FWHM decreased in steps of 0.010 cm from 0.150 to 0.100 cm. DOSRZnrc was used to develop models of the IBA stereotactic field diode (SFD) as well as the PTW T60008, T60012, T60016, and T60017 field diodes. Simulations were run and isocentric, detector specific, output ratios (OR(det)) calculated at depths of 1.5, 5.0, and 10.0 cm. This was performed using the following source parameter subset: 6.1 and 6.2 MeV with a FWHM = 0.100, 0.110, and 0.120 cm. The source parameters were finalized by comparing experimental detector specific output ratios with simulation. Simulations were then run with the active volume and surrounding materials set to water and the replacement correction factors calculated according to the newly proposed formalism.

RESULTS

In all cases, the experimental field size widths (at the 50% level) were found to be smaller than the nominal, and therefore, the simulated field sizes were adjusted accordingly. At a FWHM = 0.150 cm simulation produced penumbral widths that were too broad. The fit improved as the FWHM was decreased, yet for all but the smallest field size worsened again at a FWHM = 0.100 cm. The simulated OR(det) were found to be greater than, equivalent to and less than experiment for spot size FWHM = 0.100, 0.110, and 0.120 cm, respectively. This is due to the change in source occlusion as a function of FWHM and field size. The corrections required for the 0.5 cm field size were 0.95 (± 1.0%) for the SFD, T60012 and T60017 diodes and 0.90 (± 1.0%) for the T60008 and T60016 diodes-indicating measured output ratios to be 5% and 10% high, respectively. Our results also revealed the correction factors to be the same within statistical variation at all depths considered.

CONCLUSIONS

A number of general conclusions are evident: (1) small field OR(det) are very sensitive to the simulated source parameters, and therefore, rigorous Monte Carlo linac model commissioning, with respect to measurement, must be pursued prior to use, (2) backscattered dose to the monitor chamber should be included in simulated OR(det) calculations, (3) the corrections required for diode detectors are design dependent and therefore detailed detector modeling is required, and (4) the reported detector specific correction factors may be applied to experimental small field OR(det) consistent with those presented here.

The results from literature concerning some aspects of retinal function in macular degenerations (MDs) were reviewed in order to evaluate whether (a) specific patterns of retinal dysfunction may be linked to different clinical phenotypes, and (b) distinct functional profiles may help in orienting molecular diagnosis of diseases. Examined clinical phenotypes included: Stargardt disease/fundus flavimaculatus (St/FF), age-related maculopathy (ARM) and macular degeneration (AMD), pattern dystrophies (PD), Best vitelliform dystrophy (BVD), Sorsby's fundus dystrophy (SFD), autosomal cone-rod dystrophies (CRD). The following functional tests were evaluated: (1) electroretinogram (ERG) (scotopic and photopic according to ISCEV standards, rod and cone photoresponses, rod and cone b-wave intensity-response function, focal ERGs); (2) dark adaptometry (pre-bleach sensitivity and post-bleach recovery kinetics); (3) fundus reflectometry (pigment density and regeneration kinetics). Specific patterns of retinal dysfunction were identified for St/FF, ARM/AMD, SFD and BVD, whereas partially overlapping profiles were found for PD and CRD. Specific functional patterns were associated with different peripherin/RDS gene mutations, as well as with CRX mutations. Combined analysis of different retinal function tests may help to identify different phenotypes of MD, and to orient molecular diagnosis for selected genotypes.

A total of 2248 infants born at All India Institute of Medical Sciences Hospital, New Delhi were selectively screened for hypoglycemia over a period of 15 months. Hypoglycemia (blood glucose less than 30 mg/dl) was diagnosed in 107 cases (4.8%). Preterm babies had three times increased risk (12.8%) as compared to term babies (3.6%). Small-for-dates (SFDs) and large-for-dates (LFDs) infants were at increased risk of manifesting hypoglycemia (7 and 10 times, respectively) as compared to the appropriate-for-dates (AFDs) babies (2.7%). Approximately two-thirds of the hypoglycemic babies (67.3%) had one or more risk factors including birth asphyxia (24.2%), diabetic mothers (23.8%), respiratory distress (13.9%) and septicemia (11.6%). A total of 59.8% cases were asmyptomatic while the rest had one or more symptoms. The most common symptom observed was lethargy (81.4%), followed by jitteriness (67.4%), respiratory abnormalities (41.9%), hypotonia (39.5%) and seizures (30.2%). The amount of glucose (mg/kg/min) needed to maintain a stable blood sugar in various categories of hypoglycemic babies was observed to be in the following decreasing order of amount; symptomatic babies with seizures (Gp IV), IGDM's/IDM's and symptomatic babies with other features (Gp III), SFDs and LFDs (Gp II) and AFDs (Gp I). Such a categorization of hypoglycemic babies will help to treat them more precisely.

We demonstrate that the switching field distribution (SFD) in arrays of 50 nm to 5 microm Co/Pd elements, with perpendicular anisotropy, can be explained by a distribution of intrinsic anisotropy rather than any fabrication related effects. Further, simulations of coercivity and SFD versus element size allow the distribution of intrinsic anisotropy to be quantified in highly exchanged coupled thin films where the reversal mechanism is one of nucleation followed by rapid domain wall motion.

BACKGROUND

This study examines the relationship between parental bonding, adult attachment, and alexithymia in patients with Somatoform Disorders (SFD). There are few empirical studies to support the clinical hypothesis that alexithymia may be due to disturbances in the early parent-child relationship.

METHODS

In a cross-sectional study, data from 76 patients with SFD were obtained, consisting of questionnaire measures of alexithymia (TAS scale), attachment style (BFKE), and also the German version of the MOPS (Measure of Parental Style), the FDEB scale for measuring perceived parental attitude.

RESULTS

A higher than average prevalence of insecure attachment (n = 67, 88.2%) was found in our sample with SFD and a T-value of 54.3 (9.5) in the TAS total score, 22% reaching clinically significant alexithymia. Regression analyses demonstrated the relationship between the "ambivalent clinging" and "ambivalent withdrawing" attachment style and more marked alexithymia features. Furthermore, alexithymia was positively predicted by "indifference" in the relationship to the father, BDI, and Global severity index (SCL-90-R).

CONCLUSIONS

The results of this study support the hypothesis that alexithymia is associated with perceived parental bonding and attachment style.

OBJECTIVE

The purpose of this work is to assess the variation in performance of various commercially available dosimetry diodes for quantitative small field dosimetry, specifically by intercomparing measurements of SRS cone factors.

METHODS

Measurements were made in 6 MV photon beams with fixed SRS cones for two accelerator-based SRS systems: a Varian Clinac iX (Varian/Zmed cones) at 600 MU/min and a CyberKnife model G4 at 800 MU/min. Measurements were made at 1.5 cm depth in water using the IBA Dosimetry "blue phantom" 3D scanning system, controlled by OMNIPRO-ACCEPT software. Source-to-detector distance was 100 cm for the Clinac, 80 cm for the CyberKnife. Two normalization methods were used for the Clinac, one directly referenced to diode measurements in a 10 cm x 10 cm square field and the other indirectly by "daisy-chaining" diode measurements to ion chamber measurement in the 10 cm x 10 cm reference field through an intermediate 4 cm x 4 cm square field. CyberKnife factors were referenced directly to measurements in the 60 mm reference field. Seven commercial diodes were evaluated: PTW TN60008, TN60012, TN60016, TN60017; IBA Dosimetry SFD; Sun Nuclear EDGE; Exradin SD1 (first generation prototype).

RESULTS

With the exception of the SFD, all the evaluated devices yielded surprisingly consistent results. Standard deviations of Clinac factors for four diodes (SD1, EDGE, TN60008, and TN60012) ranged from approximately 0.50% at 30 mm to 2.0% at 5 mm cones size when referenced directly to the 10 cm x 10 cm measurement. The daisy-chaining strategy reduced the standard deviation to approximately 0.30% at 30 mm and 1.9% at 5 mm. Standard deviations for the same four diodes in the CyberKnife beam ranged up to approximately 1.0% at 5 mm.

CONCLUSIONS

The inter-detector variation is small and appears to be systematic with detector packaging, more inherent filtration producing flatter curves for both the relatively hard Clinac beam and the softer CyberKnife beam. The daisy-chain strategy appears to be of limited value for most of the diodes, but does bring the SFD results into significantly better agreement with the others.

Human telomerase, a cellular reverse transcriptase specifically activated in most malignant tumors and usually inactive in normal somatic cells, plays an important role in immortalization and tumorigenesis. Early reports have indicated that terminal differentiation of various cells is associated with a rapid inhibition of telomerase activity, preceded by a down-regulation of telomerase reverse transcriptase (hTERT) mRNA. Recently, we have shown that telomerase can be repressed by all-trans retinoic acid (ATRA) independently of terminal maturation during long-term ATRA treatment of the maturation-resistant promyelocytic leukemia cell line (NB4-R1), leading to shortening of telomeres and cell death, events overcome by ectopic hTERT expression. Here, we report the isolation of a variant of NB4-R1 cells (NB4-R1(SFD)), which bypasses this death step, because of a re-activated telomerase, despite the continuous presence of ATRA. While unresponsive to a long-term maturation independent regulation of telomerase by ATRA, these cells retain a functional pathway of telomerase down-regulation associated with retinoid-induced maturation. These findings reinforce the notion that two distinct pathways of telomerase regulation by retinoids co-exist in APL cells. Noteworthy, we show that the slow developing mechanism, that causes death of maturation-resistant cells, is subjected to a new type of retinoid-resistance as yet not understood.

OBJECTIVE

To determine the cost effectiveness of duloxetine, a new serotonin norepinephrine reuptake inhibitor, when compared with venlafaxine-XR in treating major depressive disorder.

METHODS

A cost effectiveness analysis, using a decision tree modelled outpatient treatment over 6 months. Analytic perspectives were those of society (all direct and indirect costs) and the Ministry of Health of Ontario (MoH) as payer for all direct costs. Rates of success and dropouts were obtained from a meta-analysis of randomized placebo-controlled trials. Costs were taken from standard lists, adjusted to 2005 Canadian dollars; discounting was not applied. One-way sensitivity analyses were performed on monthly acquisition costs and success rates; Monte-Carlo analysis examined all parameters over 10000 iterations.

RESULTS

From both perspectives, outcomes all numerically favoured venlafaxine-XR (Expected success = 53% and 57%; symptom-free days [SFDs] = 52.72 and 57.03 for duloxetine and venlafaxine-XR, respectively). Total expected costs/patient treated were, Can dollar 7081 and Can dollar 6551 (MoH), Can dollar 20987 and Can dollar 19 997 (societal perspective), for duloxetine and venlafaxine-XR, respectively. Expected costs/SFD were Can dollar134 and Can dollar 115 (MoH) and Can dollar 398 and Can dollar 351 (societal viewpoint) for duloxetine and venlafaxine-XR, respectively. Although results were sensitive to changes in success rate within the 95% CI, Monte-Carlo analyses using the ICER (incremental cost effectiveness ratio) as outcome found venlafaxine-XR was dominant in approximately 78% of scenarios in both perspectives.

CONCLUSIONS

Differences in pharmacoeconomic outcomes found were modest, but in all cases, favoured venlafaxine-XR over duloxetine. Therefore, a possible advantage may exist at the population level in the treatment of major depressive disorder in Canada. Ultimately, a head to head study of the two drugs would be needed to confirm these findings.

To evaluate a potential role of Axl, the high-affinity receptor of growth arrest-specific protein 6 (GAS6) in adiposity, murine embryonic fibroblasts (MEF) derived from mice with genetic deficiency of Axl (Axl(-/-)) or wild-type littermates (Axl(+/+)) were differentiated into mature adipocytes. In addition, Axl(-/-) and Axl(+/+) mice were kept on standard fat diet (SFD) or on high-fat diet (HFD) for 15 weeks. Deficiency of Axl in MEF did not affect differentiation, as shown by a similar uptake of Oil Red O and expression of the adipogenic markers aP2 and peroxisome proliferator activator receptor γ (PPARγ) at the end of the differentiation. In the first 7 weeks of HFD feeding, Axl(-/-) mice gained less weight than their wild-type littermates. Weight gain for both genotypes on either SFD of HFD over 15 weeks was, however, not significantly different, resulting in comparable body weights, as well as subcutaneous (s.c.) and gonadal (GON) fat mass. Adipocyte size in the fat tissues was not affected by Axl deficiency. Gene expression analysis indicated that the absence of Axl in vivo may be compensated for by the other TAM family members Mer and Tyro3. Glucose and insulin tolerance tests (ITT) in Axl(-/-) and Axl(+/+) mice did not reveal significant differences in glucose homeostasis. Thus, Axl deficiency had no significant effect on adipogenesis in vitro or in vivo.

OBJECTIVE

Eprosartan is a selective angiotensin II type I receptor antagonist approved for the treatment of hypertension. In the present studies, eprosartan's ability to provide end-organ protection was evaluated in a model of cardiomyopathy and renal failure in stroke-prone rats (SP).

METHODS

SP were fed a high fat (24.5% in food) and high salt (1% in water) diet (SFD). Eprosartan (60 mg/kg/day) or vehicle (saline control) (n = 25/group) was administered by intraperitoneally-implanted minipumps to these SP on the SFD for 12 weeks. Normal diet fed SP and WKY rats (n = 25/group) were also included for comparison (i.e. served as normal controls). Mortality, hemodynamics, and both renal and cardiac function and histopathology were monitored in all treatment groups.

RESULTS

Eprosartan decreased the severely elevated arterial pressure (-12%; P < 0.05) produced by SFD but did not affect heart rate. Vehicle-treated SP-SFD control rats exhibited significant weight loss (-13%; P < 0.05) and marked mortality (50% by week 6 and 95% by week 9; P < 0.01). Eprosartan-treated SP-SFD rats maintained normal weight, and exhibited zero mortality at week 12 and beyond. Eprosartan prevented the increased urinary protein excretion (P < 0.05) that was observed in vehicle-treated SP-SFD rats. Echocardiographic (i.e. 2-D guided M-mode) evaluation indicated that SP-SFD vehicle control rats exhibited increased septal (+22.2%) and posterior left ventricular wall (+30.0%) thickness, and decreased left ventricular chamber diameter (-15.9%), chamber volume (-32.7%), stroke volume (-48.7%) and ejection fraction (-22.3%), and a remarkable decrease in cardiac output (-59.3%) compared to controls (all P < 0.05). These same parameters in eprosartan-treated SP-SFD rats were normal and differed markedly and consistently from vehicle-treated SP-SFD rats (i.e. treatment prevented pathology; all P < 0.05). Cardiac-gated MRI data confirmed the ability of eprosartan to prevent cardiac pathology/remodeling (P < 0.05). Histopathological analysis of hearts and kidneys indicated that eprosartan treatment significantly reduced end-organ damage (P < 0.01) and provided corroborative evidence that eprosartan reduced remodeling of these organs. Vehicle-treated SP-SFD rats exhibited a 40% increase in the plasma level of pro-atrial natiuretic factor that was reduced to normal by eprosartan (P < 0.05).

CONCLUSIONS

These data demonstrate that eprosartan, at a clinically relevant dose, provides significant end-organ protection in the severely hypertensive stroke-prone rat. It preserves cardiac and renal structural integrity, reduces cardiac hypertrophy and indices of heart failure, maintains normal function of the heart and kidneys, and eliminates premature mortality due to hypertension-induced end-organ failure.

BACKGROUND

Liquid-formula diets (LFDs) are useful in metabolic studies of the cholesterolemic effects of dietary lipids because they can be formulated with accuracy, facilitating precise delivery of fatty acids of interest. However, because of differences in composition and nutrient delivery between LFDs and solid-food diets (SFDs), there is a need to determine differences in their effects.

OBJECTIVE

Our objective was to compare lipid and lipoprotein responses to changes in total fat, saturated fatty acids (SFAs), and cholesterol in subjects consuming an SFD or LFD.

METHODS

Twenty-one healthy subjects consumed controlled diets representative of an average American diet [AAD; 37% of energy from fat (15% from SFAs), and <50 mg cholesterol/MJ] or a National Cholesterol Education Program (NCEP) Step II diet [26% fat (5% from SFAs) and <25 mg cholesterol/MJ]. Other nutrients were similar between diets. Diets were consumed for 23 d in a randomized, crossover design.

RESULTS

For the AAD and NCEP Step II diet, there were no significant differences in lipids and apolipoproteins when the LFD or SFD versions were consumed. In contrast, consumption of the SFD was associated with significantly lower total cholesterol and triacylglycerols than was consumption of the corresponding AAD or Step II LFD (P < 0.05). Subjective ratings of satiety, hunger, and quality of life between diet forms did not differ significantly.

CONCLUSIONS

Both LFDs and SFDs yield quantitatively similar cholesterolemic responses to changes in dietary fat, SFAs, and cholesterol. LFDs may offer advantages because they provide easily administered, complete, balanced nutrition without affecting satiety.

THEORY/OBJECTIVE: Somatoform disorder (SFD) is associated with considerable psychosocial impairment. However, only a few studies have dealt with the course of this clinical subgroup. Therefore, the objective was to identify predictors for the various courses of SFD and medically unexplained symptoms (MUS).

METHODS

We screened 620 consecutive patients in primary care using the Patient Health Questionnaire (PHQ-15). Afterwards, 308 patients were studied in more detail using a diagnostic interview and a set of questionnaires. One year later, we were able to interview 277 participants a second time.

RESULTS

After 1 year, 48.8% of the respondents had a remitted SFD. The following variables proved to be significant predictors of MUS: current depressive episode, negative life events, number of MUS at baseline, attributional style, autonomic sensations and catastrophizing cognitions. The course of SFD could be predicted through current depressive or anxiety disorder, negative life events, functional disability and attributional style.

CONCLUSIONS

Somatoform disorder has a favorable course. The predictors of the courses of SFD and MUS we found can be integrated into previous explanatory models. The coping with MUS or SFD can be seen as a mediating factor.

Expression of thrombospondin-2 (TSP-2), a matricellular protein with anti-angiogenic properties, is modulated in developing adipose tissue. To investigate a potential functional role of TSP-2 in adipose tissue angiogenesis and growth, TSP-2 deficient (TSP-2(-/-)) and wild-type littermate (TSP-2(+/+)) mice were kept on normal chow (standard fat diet (SFD)) or on high fat diet (HFD) for 15 weeks. TSP-2(-/-) mice kept on HFD had a significantly lower total body weight throughout the experimental period. Subcutaneous (SC) and gonadal (GON) fat mass were, however, not different, and their composition in terms of size and density of adipocytes and blood vessels was also comparable in both genotypes. Macrophage infiltration in SC or GON adipose tissues was not affected by TSP-2 deficiency. TSP-2 deficiency had no effect on adipose tissue mRNA expression of gelatinase A (MMP-2), whereas gelatinase B (MMP-9) was downregulated in SC and GON adipose tissues of TSP-2(-/-) mice on HFD. Glucose tolerance and insulin resistance tests were comparable for TSP-2(+/+) and TSP-2(-/-) mice. TSP-2 deficiency was not compensated by increased expression of TSP-1 in the TSP-2(-/-) mice. These data suggest that TSP-2, despite its reported anti-angiogenic properties, does not play an important functional role in adipose tissue related angiogenesis or associated fat development in mice.

OBJECTIVE

To determine risk factors for perinatal asphyxia.

METHODS

Cohort study.

METHODS

Teaching hospital.

METHODS

All consecutive hospital births were evaluated during the study period. Asphyxia was defined on intrapartum and neonatal resuscitation criteria. Maternal, intrapartum and neonatal variables were recorded in all births. Data was analyzed after stratifying for live and stillbirths by univariate and logistic regression analyses.

RESULTS

Amongst 2371 births (55 fetal deaths and 2316 live births), there were 86 cases of perinatal asphyxia (35 fetal deaths and 51 live births), providing an asphyxia rate of 36.3/1000 births. On multivariate analysis, risk factors significantly associated with asphyxia included prolonged second stage labor (OR 9.4), vaginal breech delivery (OR 6.6), elective cesarean delivery (OR 4.6), pregnancy induced hypertension (PIH) (OR 2.7) and fetal growth retardation (SFD) (OR 2.4). Amongst stillborn, the significant univariate factors associated with asphyxia were prolonged second stage labor (RR 1.7) and cord prolapse (RR 1.7).

CONCLUSIONS

There is a need to strengthen intrapartum management and early identification of mothers with PIH or intrauterine growth retardation to reduce asphyxial morbidity and mortality.

OBJECTIVE

Because logistical and financial obstacles impede using large prospective cohort studies, surveillance decisions in occupational settings must often be made without evidence of relative benefits and costs. Using the example of isocyanate induced asthma, the most commonly reported immune mediated occupational asthma, the authors developed a model based approach to evaluate the costs and benefits of surveillance from both an employer and a societal perspective.

METHODS

The authors used a mathematical simulation model of isocyanate asthma to compare annual surveillance to passive case finding. Outcome measures included symptom free days (SFD), quality adjusted life years (QALY), direct costs, productivity losses, and incremental cost effectiveness ratio (CER), measured from the employer and the societal perspectives. Input data were obtained from a variety of published sources.

RESULTS

For 100,000 exposed workers, surveillance resulted in 683 fewer cases of disability over 10 years. Surveillance conferred benefits at an incremental cost of 24,000 dollars/QALY (employer perspective; 13.33 dollars/SFD) and was cost saving from the societal perspective. Results were sensitive to assumptions about sensitisation rate, removal rates, and time to diagnosis, but not to assumptions about therapy costs and disability rates.

CONCLUSIONS

Baseline results placed the CER for surveillance for isocyanate asthma within the acceptable range. Costs from the societal and employer perspective differed substantially with a more attractive CER from the societal perspective, suggesting opportunities for employer/societal cost sharing. The analysis demonstrates the value of a model based approach to evaluate the cost effectiveness of surveillance programmes for isocyanate asthma, and to inform shared decision making among clinicians, patients, employers, and society. Such a modeling approach may be applicable to surveillance programmes for other work related conditions.

The assessment of target organ damage is important in defining the optimal treatment of hypertension and blood pressure-related cardiovascular disease. The aims of the present study were (1) to investigate candidate biomarkers of target organ damage, osteopontin (OPN) and plasminogen activator inhibitor-1 (PAI-1), in models of malignant hypertension with well characterized end-organ pathology; and (2) to evaluate the effects of chronic treatment with a p38 MAPK inhibitor. Gene expression, plasma concentrations, and renal immunohistochemical localization of OPN and PAI-1 were measured in stroke-prone spontaneously hypertensive rats on a salt-fat diet (SFD SHR-SP) and in spontaneously hypertensive rats receiving N(omega)-nitro-L-arginine methyl ester (L-NAME SHR). Plasma concentrations of OPN and PAI-1 increased significantly in SFD SHR-SP and L-NAME SHR as compared with controls, (2.5-4.5-fold for OPN and 2.0-9.0-fold for PAI-1). The plasma levels of OPN and PAI-1 were significantly correlated with the urinary excretion of albumin (p < 0.0001). Elevations in urinary albumin, plasma OPN and PAI-1 were abolished by chronic treatment (4-8 weeks) with a specific p38 MAPK inhibitor, SB-239063AN. OPN immunoreactivity was localized predominantly in the apical portion of tubule epithelium, while PAI-1 immunoreactivity was robust in glomeruli, tubules and renal artery endothelium. Treatment with the p38 MAPK inhibitor significantly reduced OPN and PAI-1 protein expression in target organs. Kidney gene expression was increased for OPN (4.9- and 7.9-fold) and PAI-1 (2.8- and 11.5-fold) in SFD SHR-SP and L-NAME SHR, respectively. In-silico pathway analysis revealed that activation of p38 MAPK was linked to OPN and PAI-1 via SPI, c-fos and c-jun; suggesting that these pathways may play an important role in p38 MAPK-dependent hypertensive renal dysfunction. The results suggest that enhanced OPN and PAI-1 expression reflects end-organ damage in hypertension and that suppression correlates with end-organ protection regardless of overt antihypertensive action.

OBJECTIVE

To study temporal pattern of serum liver enzymes levels in newborns with hepatic injury associated with birth asphyxia (BA).

METHODS

Singleton term newborns with BA and ≤72 hours of age admitted to neonatal intensive care unit were prospectively enrolled. Term newborns with physiological jaundice and without BA were studied as controls. Serum liver enzymes were measured at <24 hours, 24-72 hours, and at 6-12 days of age for cases and at 1-6 days of age for controls. BA was defined by 1 minute Apgar score <7 or delayed or absent cry with hypoxic ischemic encephalopathy. BA-associated liver injury was defined as serum alanine aminotransferase (ALT) elevation beyond +2 standard deviation (ALT>> +2 SD) above the mean of control subjects at any of the three time points.

RESULTS

Sixty controls and 62 cases were enrolled. Thirty-five cases (56%) developed BA-associated liver injury (ALT>81 IU/L). They had higher serum levels of ALT, aspartate aminotransferase, lactate dehydrogenase than the control infants, with peak at 24-72 hours. In controls, serum liver enzyme levels were significantly higher in appropriate-for-date (AFD) babies than small-for-date (SFD) babies. Serum enzyme pattern and extent of elevation were comparable between SFD and AFD babies. Degree of serum liver enzyme elevation had no relationship with severity of hypoxic encephalopathy.

CONCLUSIONS

Serum liver enzyme elevation is common in BA; it peaks at 24-72 hours followed by a sharp decline by 6-12 days of age. Pattern and extent of enzyme elevation are comparable between SFD and AFD babies.