The objective of this study was to prepare solid dispersions consisting of baicalein and a carrier with a low glass transition/melting point (Pluronic F68) by spray freeze drying (SFD). We compared these powders to those produced from the conventional solvent evaporation method. In the SFD process, a feeding solution was atomized above the surface of liquid nitrogen following lyophilization, which resulted in instantaneously frozen microparticles. However, solid dispersions prepared by the solvent evaporation method formed a sticky layer on the glass flask with crystalline baicalein separated out from the carrier. The powder samples were characterized by scanning electron microscopy (SEM), powder X-ray diffraction (PXRD), surface area measurement, differential scanning calorimetry, and Fourier transform infrared spectrometry. SEM and PXRD results suggested that the majority of baicalein in the SFD-processed solid dispersion was in the amorphous state, which has a higher specific surface area than pure baicalein. However, the majority of baicalein was recrystallized in the solid dispersion at the same composition prepared by the solvent evaporation method, which showed a similar dissolution rate to the physical mixture. SFD product was physically and chemically stable after being stored at 40 °C with low humidity for 6 months. After enzyme hydrolysis, baicalein in the SFD product displayed a significantly shorter T (max) and higher C (max) than pure baicalein after oral dosing. The relative bioavailability of the SFD product versus pure baicalein determined by comparing the AUC(0-12) was 233%, which demonstrated the significantly improved oral bioavailability of baicalein produced by the SFD technique.

The aim of this study was to investigate two different processes to produce a stable influenza subunit vaccine powder for pulmonary immunization i.e. spray drying (SD) and spray freeze drying (SFD). The formulations were analyzed by proteolytic assay, single radial immunodiffusion assay (SRID), cascade impactor analysis, and immunization studies in Balb/c mice. Proteolytic assay and SRID analysis showed that antigen integrity after SFD was best conserved when the formulation was buffered by Hepes buffer saline (HBS). Surprisingly, antigen integrity after SD was better conserved when the formulation was buffered by phosphate buffer saline (PBS) rather than by HBS. The dispersion from the dry powder inhaler, the Twincer, resulted in a fine particle fraction (aerodynamic particle size <5microm) of 37% and 23% for spray dried and spray freeze dried powders, respectively. Immunogenicity of both vaccine formulations (SFD/HBS and SD/PBS) was similar to conventional liquid formulation after i.m. immunization. In addition, compared to i.m. immunizations, the pulmonary immunization with the dry powders resulted in significantly higher IgG titers. Furthermore, both the formulations remained biochemically and physically stable for at least 3years of storage at 20 degrees C. Our results demonstrate that both optimized formulations are stable and have good inhalation characteristics.

OBJECTIVE

We undertook this study to analyse the pattern of childhood cutaneous tuberculosis prevailing in northern India over the past 25 years and to highlight differences from and similarities to adult tuberculosis.

METHODS

Clinical records of children with cutaneous tuberculosis who attended the Nehru Hospital attached to the Postgraduate Institute of Medical Education and Research, Chandigarh, India, between January 1975 to December 1999 were analysed.

RESULTS

Four hundred and two patients with cutaneous tuberculosis were examined during the 25-year period of observation. These patients formed 0.1% of the total dermatology outpatients. Seventy-five (18.7%) of these 402 cases were children (</= 16 years). There were 32 (42.7%) boys and 43 (57.3%) girls with a boy : girl ratio of 0.74 : 1. The majority of the children, 41 (54.7%) were in the 10-14 years age group. There was no significant boy or girl preponderance in any group other than in scrofuloderma (<em>SFD</em>), where girls significantly outnumbered boys at all ages. Of the various patterns of cutaneous tuberculosis seen, 40 (53.3%) had <em>SFD</em>, 30 (40.0%) had lupus vulgaris (LV), 3 (4.0%) had tuberculosis verrucosa cutis (TVC), 1 (1.3%) child each had tuberculids and tubercular gumma. No child had a tubercular chancre or acute miliary cutaneous tuberculosis. The neck was the commonest site afflicted with <em>SFD</em> and the face was the commonest site affected with LV. No child had generalized lymphadenopathy. Eighteen (60.0%) of the 30 children with LV had regional lymphadenopathy of which 15 (83.3%) had localized disease and 3 (16.7%) had disseminated disease. Of the 16 children with systemic organ involvement, 12 (75.0%) had regional lymphadenopathy. Of the 62 children in whom the data regarding vaccination status was available, 31 (50.0%) had been vaccinated and 31 (50.0%) had not. Among the vaccinated group no child had disseminated disease. Three (9.7%) children in the nonvaccinated group had disseminated disease. Information regarding Mantoux reactivity was available in 71 (94.7%) children, 61 (86.0%) with localized disease and 10 (14.1%) with disseminated disease. Of the 61 children with localized disease, 56 (91.8%) were Mantoux positive and of the 10 children with disseminated disease, only 5 (50.0%) were Mantoux positive >> 10 mm). Histopathologic reports were available for evaluation in all 75 children. Out of 30 cases of LV, 24 (80%) showed classical tuberculous histology. In contrast, out of 40 cases with <em>SFD</em>, only 19 (47.5%) showed classical histology. Classical tuberculous histology was noted in all 3 (100%) cases of TVC and 1 (100%) case each with tuberculids and gumma. Tubercle bacilli could be demonstrated in 4/30 (13.3%) cases with LV and 9/40 (22.5%) cases with <em>SFD</em>. Systemic involvement was seen in 16 (21.3%) children, of whom 3 (18.8%) had LV and 13 (81.3%) <em>SFD</em>. The lungs were the most common organs involved in 8 (50.0%) children followed by bone(s) in 4 (25.0%), abdomen in 2 (12.5%), and both lung and bone in 1 (6.3%) child. In contrast to adults, girls outnumbered boys in the childhood series; <em>SFD</em> was a common form of presentation in contrast to LV and TVC, tuberculous gumma and tuberculids were noted less often. In both children and adults, Mantoux reactivity did not correlate with the extent of the disease; patients with disseminated disease were found to be less often vaccinated with BCG and regional lymphadenopathy was noted more often in patients with disseminated disease.

CONCLUSIONS

In the whole spectrum of cutaneous tuberculosis, there is a proportion of patients with dissemination (systemic involvement) who are of great epidemiological significance as they require a change in the standard therapeutic regimens recommended for cutaneous tuberculosis.

OBJECTIVE

The primary aim of this study was to investigate facial emotion recognition in patients with somatoform disorders (SFD). Also of interest was the extent to which concurrent alexithymia contributed to any changes in emotion recognition accuracy.

METHODS

Twenty patients with SFD and twenty healthy, age, sex and education matched, controls were assessed with the Facially Expressed Emotion Labelling Test of facial emotion recognition and the 26-item Toronto Alexithymia Scale (TAS-26).

RESULTS

Patients with SFD exhibited elevated alexithymia symptoms relative to healthy controls. Patients with SFD also recognized significantly fewer emotional expressions than did the healthy controls. However, the group difference in emotion recognition accuracy became nonsignificant once the influence of alexithymia was controlled for statistically.

CONCLUSIONS

This suggests that the deficit in facial emotion recognition observed in the patients with SFD was most likely a consequence of concurrent alexithymia. Impaired facial emotion recognition observed in the patients with SFD could plausibly have a negative influence on these individuals' social functioning.

Medically unexplained symptoms are the defining feature of somatoform disorders (SFD) as currently included in Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, and the International Classification of Diseases, Tenth Edition. Cognitive, behavioral, biological, and social variables are important to our understanding of SFD. Research in the past decade has highlighted the central role of (a) prolonged attention allocation to bodily sensations, (b) the dysfunctional role of catastrophizing symptoms as signs of severe illness, (c) neuroendocrine alterations, and (d) the influence of illness behavior (e.g., the avoidance of physical activity) on the maintenance and chronicity of SFD. Additionally, conditioning approaches have demonstrated that perceiving somatic discomfort can easily be learned. In addition to current models of etiology and pathogenesis, the existing evidence on the efficacy and effectiveness of psychotherapy for SFD is reviewed. Finally, future directions and some current blind spots in research on SFD are outlined.

BACKGROUND

Allergic Rhinitis is an inflammatory disease which is characterised by burdensome nasal and/or ocular symptoms. This study aimed to assess the impact of symptoms (number of symptom-free days (SFD) and Quality of Life (QoL)) in patients with Seasonal Allergic Rhinitis (SAR) being treated with fluticasone furoate (FF), mometasone furoate (MF) or fluticasone propionate (FP).

METHODS

In a cross-sectional, non-interventional, cohort analysis, primary care physicians and allergy specialists in France, Germany, and Spain were recruited via telephone interviews. Each physician prospectively recruited 4 SAR patients - 2 receiving FF, 1 receiving MF and 1 receiving FP - during June 2009. Patients answered questions on symptoms and completed questionnaires on QoL (mini-rhinoconjunctivitis Quality of Life Questionnaire, RQLQ) and burden of illness (Pittsburgh Sleep Quality Index).

RESULTS

A total of 540 patients were recruited during June 2009. 88 patients were subsequently found to be ineligible and excluded from the analyses. In the 4 weeks prior to assessment, patients reported a mean of 14.58 (±8.42) SFD. Patients receiving FF had more SFD (mean 15.45 ±8.29) than patients receiving MF (adjusted mean difference -1.22, 95% Confidence Interval (CI) [-3.16 to 0.72], p=0.434) or FP (adjusted mean difference -1.95, 95% CI [-3.87 to -0.03], p=0.092), although statistical significance was not achieved. The mean RQLQ score was 1.54 (±1.06). Patients receiving FF had a better quality of life in the previous week (mini-RQLQ score: mean 1.42, ±1.04) than patients receiving MF (adjusted mean difference 0.28, 95% CI [0.03 to 0.52], p=0.052) or FP (adjusted mean difference 0.18, 95% CI [-0.05 to 0.41], p=0.244). Again, none of these results achieved statistical significance.

CONCLUSIONS

At the height of the allergy season, patients with SAR suffer symptoms approximately 50% of the time, and report an impact on their QoL. No significant differences were observed between FF, FP and MF related to SFD or QoL.

BACKGROUND

ClinicalTrials.gov identifier: NCT01199757.

BACKGROUND

Analytic morphometrics provides objective data that may better stratify risk. We investigated morphometrics and outcome among colon cancer patients.

METHODS

An IRB-approved review identified 302 patients undergoing colectomy who had CT scans. These were processed to measure psoas area (PA), density (PD), subcutaneous fat (SFD), visceral fat (VF), and total body fat (TBF). Correlation with complications, recurrence, and survival were obtained by t-tests and linear regression models after adjusting for age and Charlson index.

RESULTS

The best predictor of surgical complications was PD. PMH, Charlson, BMI, and age were not significant when PD was considered. SF area was the single best predictor of a wound infection. While all measures of obesity correlated with outcome, TBF was most predictive. Final multivariate Cox models for survival included age, Charlson score, nodal positivity, and TBF.

CONCLUSIONS

Analytic morphometric analysis provided objective data that stratified complications and outcome better than age, BMI, or co-morbidities.

BACKGROUND

A decision to implement innovative disease management interventions in health plans often requires evidence of clinical benefit and financial impact. The Pediatric Asthma Care Patient Outcomes Research Team II trial evaluated 2 asthma care strategies: a peer leader-based physician behavior change intervention (PLE) and a practice-based redesign called the planned asthma care intervention (PACI).

OBJECTIVE

To estimate the cost-effectiveness of the interventions.

METHODS

This was a 3-arm, cluster randomized trial conducted in 42 primary care practices. A total of 638 children (age range, 3-17 years) with mild to moderate persistent asthma were followed up for 2 years. Practices were randomized to PLE (n = 226), PACI (n = 213), or usual care (n = 199). The primary outcome was symptom-free days (SFDs). Costs included asthma-related health care utilization and intervention costs.

RESULTS

Annual costs per patient were as follows: PACI, USD 1292; PLE, USD 504; and usual care, USD 385. The difference in annual SFDs was 6.5 days (95% confidence interval [CI], -3.6 to 16.9 days) for PLE vs usual care and 13.3 days (95% CI, 2.1-24.7 days) for PACI vs usual care. Compared with usual care, the incremental cost-effectiveness ratio was USD 18 per SFD gained for PLE (95% CI, USD 5.21-dominated) and USD 68 per SFD gained for PACI (95% CI, USD 37.36-361.16).

CONCLUSIONS

Results of this study show that it is possible to increase SFDs in children and move organizations toward guideline recommendations on asthma control in settings where most children are receiving controller medications at baseline. However, the improvements were realized with an increase in the costs associated with asthma care.

We conducted a cost-effectiveness analysis of acute major depressive disorder (MDD) using serotonin-norepinephrine reuptake inhibitors (SNRIs; venlafaxine), selective serotonin reuptake inhibitors (SSRIs; fluoxetine, fluvoxamine, sertraline, paroxetine), or tricyclic antidepressants (TCAs; amitriptyline, imipramine, desipramine, nortriptyline). A decision-tree model over 6 months was constructed using an expert panel. The analytic perspective was that of the Ontario Ministry of Health as payor for all direct costs, which were derived from standard lists and included the cost of the drug as well as those for medical care, laboratory services, hospitalisation and managing adverse events. Success and dropout rates were determined from a meta-analysis of published randomised controlled trials. Medline, Embase, and International Pharmaceutical Abstracts were searched from 1984 to 1996, as were references from retrieved articles and reviews. Inpatients and outpatients were analysed separately. SSRIs were used as backup therapy for patients receiving venlafaxine and TCAs, and SNRIs were used as backup therapy for patients receiving SSRIs. Pharmacoeconomic outcomes were expected cost per success, expected cost per symptom free day (SFD), and incremental cost per success and per SFD. The meta-analysis identified 56 treatment arms from 36 randomised controlled trials involving 2953 patients (2380 outpatients and 573 inpatients). SNRIs had the highest success rates. The respective costs (in 1996 $Can; $Can1 = $US0.74) for outpatients and inpatients are given below. The expected costs per success were $6044 and $17,234 for venlafaxine, $6634 and $20,874 for SSRIs, and $9035 and $20,459 for TCAs in outpatients and inpatients, respectively. The respective expected costs per SFD were $45.92 and $127.31 for venlafaxine, $51.64 and $157.04 for SSRIs, and $70.71 and $152.43 for TCAs. Venlafaxine was dominant for all incremental pharmacoeconomic analyses. Sensitivity analyses indicated that the results were robust for outpatients but somewhat sensitive for inpatients. In conclusion, venlafaxine is a cost-effective drug for the treatment of MDD in adult outpatients and inpatients.

Idiopathic environmental intolerance (IEI), also known as multiple chemical sensitivity (MCS), is defined as a chronic polysymptomatic condition that cannot be explained by an organic disease. Previous studies suggest that IEI may be a variant of somatoform disorders (SFD), because both disorders overlap with respect to symptoms and psychological features of somatization. However, little is known about the short- and medium-term outcome of IEI and psychological outcome predictors. Two clinical groups (IEI and SFD) and a comparison group (CG) were followed through 32 mo to assess both the outcome, and the extent to which trait anxiety and somatic symptom attribution (assessed at first examination) predict outcome presented 12 and 32 mo later. Outcome measures were the number of self-reported IEI symptoms, IEI triggers, IEI-associated functional impairments, and the number of somatoform symptoms. In addition, the course of the 2 syndromes over the 32-mo follow-up period was investigated with standardized screening scales. The 3 diagnostic groups consisted of 46 subjects with IEI, 38 subjects with SFD but without IEI, and 46 subjects (CG) with neither IEI nor SFD. Syndrome stability was high over the 32-mo follow-up period, and at both follow-ups IEI and non-IEI subjects differed on all IEI outcome measures (symptoms, triggers, functional impairments). Both trait anxiety and somatic attribution (the tendency to attribute common somatic complaints to an illness) predicted outcome. In addition, somatic attribution was found to partially mediate the effect of trait anxiety on outcome in the IEI group. In conclusion, these results suggest that IEI is a chronic and disabling condition and that trait anxiety contributes to the maintenance of the disorder via somatic attributions.

OBJECTIVE

The purpose of this prospective study was to evaluate the effects of cognitive-behavioral treatment (CBT) on mental health status and healthcare utilization in patients with somatoform disorders (SFD) of a specialized tertiary care center.

METHODS

According to DSM-IV interviews, 54 patients had somatization disorder (SD), 51 abridged somatization syndrome (SSI-8) and 67 other defined SFD. A clinical non-SFD comparison group consisted of 123 patients. Treatment effects were controlled against the waiting list. Cost calculations for the 2-year periods before and after treatment were based on medical and billing records from health insurance companies.

RESULTS

The SFD patients improved significantly with respect to physical symptom distress, health anxieties, dysfunctional beliefs towards body and health, depression and psychosocial functioning. Their outpatient plus inpatient charges during the 2 years prior to treatment were about 2.2-fold higher than for average patients of the health system. At the 2-year follow-up, we found treatment-related cost offset of 382 (-24.5%) for outpatient and 1098 (-36.7%) for inpatient care. Indirect socioeconomic costs due to days lost from work decreased by 6702 (-35.3%). Per patient savings of 32,174 (-63.9%) were found in a subgroup of somatizing high-utilizers.

CONCLUSIONS

The results encourage including treatment strategies to reduce somatoform illness behavior into clinical practice.

Laser Speckle Imaging (LSI) images interference patterns produced by coherent addition of scattered laser light to map subsurface tissue perfusion. However, the effect of longer path length photons is typically unknown and poses a limitation towards absolute quantification. In this work, LSI is integrated with spatial frequency domain imaging (SFDI) to suppress multiple scattering and absorption effects. First, depth sensitive speckle contrast is shown in phantoms by separating a deep source (4 mm) from a shallow source (2 mm) of speckle contrast by using a high spatial frequency of illumination (0.24 mm(-1)). We develop an SFD adapted correlation diffusion model and show that with high frequency (0.24 mm(-1)) illumination, doubling of absorption contrast results in only a 1% change in speckle contrast versus 25% change using a planar unmodulated (0 mm(-1)) illumination. Similar absorption change is mimicked in vivo imaging a finger occlusion and the relative speckle contrast change from baseline is 10% at 0.26 mm(-1) versus 60% at 0 mm(-1) during a finger occlusion. These results underscore the importance of path length and optical properties in determining speckle contrast. They provide an integrated approach for simultaneous mapping of blood flow (speckle contrast) and oxygenation (optical properties) which can be used to inform tissue metabolism.

OBJECTIVE

Extracellular matrix homeostasis is dependent in part upon a family of matrix metalloproteinases and their specific inhibitors, the tissue inhibitors of metalloproteinases (TIMPs). Recently, gene defects in TIMP-3 have been identified in the affected individuals of several families with Sorsby's fundus dystrophy (SFD). Very little information is available regarding TIMP-3 function or even its existence in the retina or choroid.

METHODS

We used reverse transcription-polymerase chain reaction and Northern analysis to evaluate the expression of TIMP mRNA and Western immunoblots to evaluate TIMP protein produced by select cells of the human retina and choroid. We also used these methods and immunohistochemistry to localize the TIMPs in the retina and choroid.

RESULTS

TIMP-3 transcripts are found in cultured human retinal pigment epithelium (RPE), choroidal microcapillary endothelium and pericytes. RPE cells also express and secrete TIMP-3 protein, which is localized to the extracellular matrix and is not found in culture medium; TIMP-1 and -2 are found almost exclusively in the medium. Immunohistochemistry of human retina/choroid sections shows pronounced TIMP-3 immunostaining in Bruch's membrane, particularly near the surface of the RPE and endothelial cells, presumably in their basement membranes, with minimal staining in other portions of the retina. Immunostaining for TIMP-1 is absent and for TIMP-2 is much less prevalent, but detectable in Bruch's membrane.

CONCLUSIONS

TIMP-1, -2 and -3 exhibit distinctive expression patterns in the retina and choroid. This distribution and expression pattern partially explains why TIMP-3 mutations result in SFD, rather than other retinal pathologies, such as those associated with proliferative diabetic retinopathy.

OBJECTIVE

To investigate the transitory plateaux observed during dark adaptation after partial bleaches in Sorsby's fundus dystrophy (SFD) and in systemic vitamin A deficiency (VAD).

METHODS

Psychophysical dark adaptation functions were measured after bleaching exposures isomerizing from 2% to 99% of the rhodopsin. Narrow-band stimuli of 1.7 degrees diameter and 200 msec duration were presented at an eccentricity of 30 degrees.

RESULTS

After a full bleach, the patients showed typical dark adaptation abnormalities reported for these diseases. The cone recovery was slowed, and the time to the rod-cone break was delayed; the final phase of rod recovery was also slowed but led to a normal final rod threshold. After partial bleaches, short wavelength stimuli produced a biphasic recovery function, with an initial rapid component and plateau, followed by a subsequent break-off and eventual return to prebleach thresholds. Action spectra obtained during the plateaux were consistent with thresholds for shorter wavelength stimuli mediated by rods and thresholds for longer wavelength stimuli mediated by cones. In the patient with VAD, vitamin A supplementation led to accelerated recovery and disappearance of the transitory rod plateaux.

CONCLUSIONS

The biphasic dark adaptation functions resulting from fractional bleaches in SFD and VAD appear superficially similar to the classic biphasic adaptation functions obtained with full bleaches. However, thresholds during the plateaux are lower than the cone threshold, and action spectra indicate rod mediation. These transitory rod plateaux may increase our understanding of the normal visual cycle and its perturbation in retinal disease.

Paclitaxel-loaded biodegradable implants in the form of microfiber discs and sheets were developed using electrospinning technique and investigated against malignant glioma in vitro and in vivo. The fibrous matrices not only provide greater surface area to volume ratio for effective drug release rates but also give the much needed implantability into tumor resected cavity in post-surgical glioma chemotherapy. Poly-(D,L-lactide-co-glycolide) (PLGA) 85:15 co-polymer was used to fabricate microfiber disc (MFD) and microfiber sheet (MFS) and PLGA 50:50 co-polymer was used to fabricate submicrofiber disc (SFD) and submicrofiber sheet (SFS) to avail different drug release properties. All the dosage forms showed sustained paclitaxel release over 80 days in vitro with a small initial burst. Sheets exhibited a relatively higher initial burst compared to discs probably due to the lower compactness. Also, submicrofibers showed higher release against microfiber due to higher surface area to volume ratio and higher degradation rate. Apoptosis study confirmed the advantage of sustained release of paclitaxel from fiber matrices compared to acute Taxol administration. Animal study confirmed inhibited tumor growth of 75, 78, 69 and 71% for MFD, SFD, MFS and SFS treated groups over placebo control groups after 24 days of tumor growth. Thus these implants may play a crucial role in the local chemotherapy of brain tumors.

Protein aggregation and enzyme activity were compared for reconstituted lysozyme particles produced by two cryogenic technologies, spray freezing into liquid (SFL) and spray-freeze drying (SFD). The particles were characterized by enzyme activity measurements, scanning electron microscopy (SEM), light scattering, X-ray photoelectron spectroscopy (XPS) and BET specific surface area analysis. Highly porous microparticle aggregates of protein nanoparticles, observed by SEM, were produced by both processes. The smaller degree of protein aggregation and smaller losses in enzyme activity for the SFL process relative to the SFD process were due primarily to the spraying step. The higher stability of the SFL versus SFD powders was consistent with the smaller surface excess of lysozyme measured by XPS in SFL, resulting from the reduced time of exposure to the air-water interface during atomization. For pure lysozyme, the degree of aggregation and enzyme activity were comparable for lyophilization and SFL, despite the much larger particle surface area for SFL.

The SILK flow diverter (SFD; Balt Extrusion, Montmorency, France) is a flow diverting stent used in the endovascular treatment of intracranial aneurysms. It works on the principle of redirecting flow away from the aneurysm sac, leading to occlusion over time. We present a systematic review on the clinical outcomes and complications of the SFD. A literature search for English language articles were conducted on PubMed, Medline and EMBASE for articles on the treatment of intracranial aneurysms with the SILK flow diverter. The inclusion criteria were n>10, use of SFD only, data on complications and aneurysm occlusion rate (AOR). Eight studies with 285 patients and 317 intracranial aneurysms were included. The mean age was 52.7 years and nearly 80% were women. In terms of angiographic distribution, 86.8% of aneurysms were located in the anterior circulation and 13.2% in the posterior circulation. As for the aneurysm size, 37.9% were classed as small, 44.4% as large and 17.7% as giant. Ischemic complications and parent artery occlusion each occurred in 10% of patients. Aneurysm rupture rate was 3.5%, while the cumulative mortality was 4.9%. The main outcome measure, 12 month AOR, was 81.8% with complete occlusion in 216 out of 264 aneurysms. Use of flow diverters for the treatment of intracranial aneurysm with complex morphologies has gained in popularity over the last few years. Our review suggests that SFD achieves comparable AOR to its contemporary, the Pipeline Embolization Device (ev3 Endovascular, Plymouth, MN, USA) but has a higher rate of higher rate of ischemic complications, aneurysm rupture and mortality.

BACKGROUND

Previous studies suggest that idiopathic environmental intolerance (IEI) is a variant of somatoform disorders (SFDs) or the so-called functional somatic syndromes. Little is known, however, about the stability and the psychological predictors of IEI.

METHODS

This prospective study examined the 1-year stability of somatic symptoms and IEI features in three diagnostic groups: 49 subjects with IEI, 43 subjects with SFD but without IEI, and 54 subjects (control group, CG) with neither IEI nor SFD. The predictive value of typical psychological predictors for somatization was tested using zero-order correlations and multiple linear regression analyses.

RESULTS

Somatic symptoms and IEI features proved to be temporally stable over the 1-year follow-up period. The SFD and IEI groups scored significantly higher than CG on all measures of somatic symptoms and on questionnaires assessing psychological predictors for somatization. Measures of trait negative affectivity (NA), somatic symptom attribution and somatosensory amplification predicted somatic symptom severity within the IEI and SFD groups, both at baseline and 1 year later. The strongest predictors of IEI complaints in the IEI group were somatic attributions, followed by prominent cognitions of environmental threat and a tendency to focus on unpleasant bodily sensations and to consider them as pathological.

CONCLUSIONS

IEI and SFD are highly stable conditions. In both SFD and IEI, NA and the processes of symptom perception, interpretation and attribution contribute substantially to the persistence of typically somatoform symptoms and IEI complaints. Treatment of IEI and SFD should address these psychological factors and mechanisms.

Sorsby's fundus dystrophy (SFD) is an autosomal dominant degenerative disease of the retina, caused by mutations in exon 5 of the gene for tissue inhibitor of metalloproteinases-3 (TIMP-3). The mechanism by which these mutations give rise to the disease phenotype is unknown. In an attempt to identify common properties of these molecules that might underlie the disease phenotype, a range of SFD mutants were expressed from human retinal pigment epithelial (RPE) cells. This showed that resistance to turnover, resulting from intermolecular disulfide bond formation, was a common property of all the SFD mutants examined, providing a possible explanation for the increased deposition of the protein observed in eyes from SFD patients. In contrast, SFD mutants varied in their ability to inhibit cell-surface activation of matrix metalloproteinase-2 (MMP-2), a potent mediator of angiogenesis, ranging from being fully active to totally inactive. These data show that increased deposition of active TIMP-3, rather than dysregulation of metalloproteinase inhibition, is likely to be the primary, initiating event in SFD.

OBJECTIVE

To study fetal heart rate (FHR), its short term variability (STV), average acceleration capacity (AAC), and average deceleration capacity (ADC) throughout uncomplicated gestation, and to perform a preliminary comparison of these FHR parameters between small-for dates (SFD) and control fetuses.

METHODS

Prospective observational study of 7 h FHR-recordings obtained with a fetal-ECG monitor in the second half of uncomplicated pregnancies (n = 90) and pregnancies complicated by fetal SFD (n = 30). FHR and STV were calculated according to established analysis. True beat-to-beat FHR, recorded at 1 ms accuracy, was used to calculate AAC and ADC using Phase Rectified Signal Averaging (PRSA). Mean values of FHR, STV, AAC, and ADC derived from recordings in SFD fetuses were compared with the reference curves.

RESULTS

Compared with the control group the mean z-scores for STV, AAC, and ADC in SFD fetuses were lower by 1.0 SD, 1.5 SD, and 1.7 SD, respectively (p < 0.0001 for all comparisons). In SFD fetuses, both the AAC and ADC z-scores were lower than the STV z-scores (p < 0.02 and p < 0.002, respectively).

CONCLUSIONS

Analysis of the AAC and ADC as recorded with a high resolution fECG recorder may differentiate better between normal and SFD fetuses than STV.

Numerous mediators, believed to play a role in endothelial dysfunction (e.g., neurohormones, cytokines, hypoxia, and stretch), have been shown to activate p38 mitogen-activated protein kinase (MAPK) in a variety of cell types. The purpose of the present study was to examine the regulation of p38 MAPK in endothelium and its role in endothelial dysfunction and salt sensitivity. In cultured human umbilical vein endothelial cells (HUVECs), tumor necrosis factor-alpha and lipopolysaccharide increased phosphorylation of p38 MAPK (P-p38 MAPK) and increased ICAM-1 expression. Preincubation with highly selective p38 MAPK inhibitors, 1-(1,3-dihydroxyprop-2-yl)-4-(4-fluorophenyl)-5-[2-phenoxypyrimidin-4-yl] imidazole (SB-239063AN) or SB-239063, dose dependently reduced intercellular adhesion molecule-1 expression in HUVECs. In spontaneously hypertensive-stroke prone rats (SHR-SP), P-p38 MAPK was localized by immunohistochemistry to the aortic endothelium and adventitia but was undetectable in aortae from normotensive rats. Introduction of a salt/fat diet (SFD) to the SHR-SP strain induced endothelial dysfunction (ex vivo vascular reactivity analysis), albuminuria, and an increase in blood pressure within 4 weeks. Chronic dietary dosing (approx. 100 mg/kg/day) with SB-239063AN inhibited the SFD diet-induced hypertension. In addition, delayed treatment also significantly improved survival and restored nitric oxide-mediated endothelium-dependent relaxation in SFD-SHR-SPs with established endothelial dysfunction. These results suggest an important role for p38 MAPK in endothelial inflammation and dysfunction as well as providing the first evidence for p38 MAPK-dependent hypertension.

Resonance Raman (RR) spectra are reported for the [2Fe-2S] Rieske protein from Thermus thermophilus (TRP) and phthalate dioxygenase from Pseudomonas cepacia (PDO) as a function of pH and excitation wavelength. Depolarization ratio measurements are presented for the RR spectra of spinach ferredoxin (SFD), TRP, and PDO at 74 K. By comparison with previously published RR spectra of SFD, we suggest reasonable assignments for the spectra of TRP and PDO. The spectra of PDO exhibit virtually no pH dependence, while significant changes are observed in TRP spectra upon raising the pH from 7.3 to 10.1. One band near 270 cm-1, which consists of components at 266 cm-1 and 274 cm-1, is attributed to Fe(III)-N(His) stretching motions. We suggest that these two components arise from conformers having a protonated-hydrogen-bonded imidazole (266 cm-1) and deprotonated-hydrogen-bonded imidazolate (274 cm-1) coordinated to the Fe/S cluster and that the relative populations of the two species are pH-dependent; a simple structural model is proposed to account for this behavior in the respiratory-type Rieske proteins. In addition, we have identified RR peaks associated with the bridging and terminal sulfur atoms of the Fe-S-N cluster. The RR excitation profiles of peaks associated with these atoms are indistinguishable from each other in TRP (pH 7.3) and PDO and differ greatly from those of [2Fe-2S] ferrodoxins. The profiles are bimodal with maxima near 490 nm and>> approx. 550 nm. By contrast, bands associated with the Fe-N stretch show a somewhat different enhancement profile. Upon reduction, RR peaks assigned to Fe-N vibrations are no longer observed, with the resulting spectrum being remarkably similar to that reported for reduced adrenodoxin. This indicates that only modes associated with Fe-S bonds are observed and supports the idea that the reducing electron resides on the iron atom coordinated to the two histidine residues. Taken as a whole, the data are consistent with an St2FeSb2Fe[N(His)]t2 structure for the Rieske-type cluster.

This study investigates the feasibility of using the process of spray-freeze drying (SFD) to produce DNA dry powders for non-viral gene delivery. The effect of protective agents was assessed on the stability of DNA dry powders after SFD. The process of SFD had adverse effects on the tertiary structure of DNA with the protective agents of sucrose, trehalose and mannitol. With the protection of these sugars, a band corresponding to the linear form of DNA was observed during gel electrophoresis between the supercoiled form (SC) and the open circular (OC) form. On the contrary, excess cationic condensing polyethyleneimine (PEI), in conjunction with the above sugars, had the ability to provide protection for DNA from degradation after SFD. This is indicated by the reservation in SC and OC forms of DNA during agarose gel electrophoresis. The electrostatic forces between PEI polymer and DNA are critical for providing protection against various stresses generated by the process of SFD. Furthermore, on rehydration, the particle size and zeta potential of PEI/DNA complexes at weight ratios 3:1 of SFD dry powders were well maintained. Also, no transfection activity loss of PEI/DNA complexes at weight ratios 3:1 on NIH/3T3 cells was observed for reconstituted powders as compared with untreated control solutions. These results give a better understanding of preparing stable DNA dry powders by the process of SFD.

Endovascular therapy is now the treatment of choice for intracranial aneurysms (IAs) for its efficacy and safety profile. The use of flow diversion (FD) has recently expanded to cover many types of IAs in various locations. Some institutions even attempt FD as first line treatment for unruptured IAs. The most widely used devices are the pipeline embolization device (PED), the SILK flow diverter (SFD), the flow redirection endoluminal device (FRED), and Surpass. Many questions were raised regarding the long-term complications, the optimal regimen of dual antiplatelet therapy, and the durability of treatment effect. We reviewed the literature to address these questions as well as other concerns on FD when treating IAs.