Harmful and protective roles of neutrophils in sepsis

The current studies demonstrate protective and harmful effects of neutrophils (PMN) during experimental sepsis after cecal ligation and puncture (CLP). It is known that CLP induces signaling defects in blood PMN. When PMN were depleted 12 h after CLP, there were dramatic reductions in levels of bacteremia, evidence for reduced liver and renal dysfunction, sharp reductions in serum levels of cytokines (IL-1beta, IL-6, IL-10, TNF-alpha, and IL-2), and improved survival. In contrast, PMN depletion before CLP resulted in substantial increases in bacteremia and no evidence for attenuation of liver and renal failure dysfunction. These data suggest that at the onset of sepsis, PMN are important in regulating the levels of bacteremia, whereas after the onset of sepsis, as they lose innate immune functions, their presence is associated with higher levels of bacteremia and intensified organ dysfunction.     

Potential of (18)~F-FDG-PET as a valuable adjunct to clinical and response assessment in rheumatoid arthritis and seronegative spondyloarthropathies

AIM: To evaluate the role of fluorine-18-labeled fluorodeoxyglucose positron emission tomography (18F-FDG PET) in various rheumatic diseases and its potential in the early assessment of treatment response in a limited number of patients. METHODS: This study involved 28 newly diagnosed patients, of these 17 had rheumatoid arthritis (RA) and 11 had seronegative spondyloarthropathy (SSA). In the SSA group, 7 patients had ankylosing spondylitis, 3 had psoriatic arthritis, and one had non-specific SSA. Patients with RA were selected as per the American College of Rheumatology criteria. One hour after FDG injection, a whole body PET scan was performed from the skull vertex to below the knee joints using a GE Advance dedicated PET scanner. Separate scans were acquired for both upper and lower limbs. Post-treatment scans were performed in 9 patients in the RA group (at 6-9 wk from baseline) and in 1 patient with psoriatic arthropathy. The pattern of FDG uptake was analysed visually and quantified as maximum standardized uptake value (SUVmax) in a standard region of interest. Metabolic response on the scan was assessed qualitatively and quantitatively and was correlated with clinical assessment. RESULTS: The qualitative FDG uptake was in agreement with the clinically involved joints, erythrocyte sedimentation rate, C-reactive protein values and the clinical assessment by the rheumatologist. All 17 patients in the RA group showed the highest FDG avidity in painful/swollen/tender joints. The uptake pattern was homogeneous, intense and poly-articular in distribution. Hypermetabolism in the regional nodes (axillary nodes in the case of upper limb joint involvement and inguinal nodes in lower limb joints) was a constant feature in patients with RA. Multiple other extra-articular lesions were also observed including thyroid glands (in associated thyroiditis) and in the subcutaneous nodules. Treatment response was better appreciated using SUVmax values than visual interpretation, when compared with clinical evaluation. Four patients showed a favourable response, while 3 had stable disease and 2 showed disease progression. The resolution of regional nodal uptake (axillary or inguinal nodes based on site of joint involvement) in RA following disease modifying anti-rheumatoid drugs was noteworthy, which could be regarded as an additional parameter for identifying responding patients. In the SSA group, uptake in the affected joint was heterogeneous, low grade and nonsymmetrical. In particular, there was intense tendon and muscular uptake corresponding to symptomatic joints. The patients with psoriatic arthritis showed intense FDG uptake in the joints and soft tissue. CONCLUSION: 18F-FDG PET accurately delineates the ongoing inflammatory activity in various rheumatic diseases (both at articular and extra-articular sites) and relates well to clinical symptoms. Different metabolic patterns on FDG-PET scanning in RA and SSA can have important implications for their diagnosis and management in the future with the support of larger studies. FDG-PET molecular imaging is also a sensitive tool in the early assessment of treatment response, especially when using quantitative information. With these benefits, FDG-PET could play a pivotal clinical role in the management of inflammatory joint disorders in the future.     

MR spectroscopic imaging and diffusion-weighted imaging of prostate cancer with Gleason scores

Purpose:

To investigate functional changes in prostate cancer patients with three pathologically proven different Gleason scores (GS) (3+3, 3+4, and 4+3) using magnetic resonance spectroscopic imaging (MRSI) and diffusion‐weighted imaging (DWI).

Materials and Methods:

In this study MRSI and DWI data were acquired in 41 prostate cancer patients using a 1.5T MRI scanner with a body matrix combined with an endorectal coil. The metabolite ratios of (Cho+Cr)/Cit were calculated from the peak integrals of total choline (Cho), creatine (Cr), and citrate (Cit) in MRSI. Apparent diffusion coefficient (ADC) values were derived from DWI for three groups of Gleason scores. The sensitivity and specificity of MRSI and DWI in patients were calculated using receiver operating characteristic curve (ROC) analysis.

Results:

The mean and standard deviation of (Cho+Cr)/Cit ratios of GS 3+3, GS 3+4, and GS 4+3 were: 0.44 ± 0.02, 0.56 ± 0.06, and 0.88 ± 0.11, respectively. For the DWI, the mean and standard deviation of ADC values in GS 3+3, GS 3+4, and GS 4+3 were: 1.13 ± 0.11, 0.97 ± 0.10, and 0.83 ± 0.08 mm²/sec, respectively. Statistical significances were observed between the GS and metabolite ratio as well as ADC values and GS.

Conclusion:

Combined MRSI and DWI helps identify the presence and the proportion of aggressive cancer (ie, Gleason grade 4) that might not be apparent on biopsy sampling. This information can guide subsequent rebiopsy management, especially for active surveillance programs. J. Magn. Reson. Imaging 2012;36:697–703. © 2012 Wiley Periodicals, Inc.     

Effect of ambasilide, a new class III agent, on plateau currents in isolated guinea pig ventricular myocytes: block of delayed outward potassium current.

The actions of ambasilide (LU-47110) on the action potential and membrane currents of isolated guinea pig ventricular myocytes were studied using voltage clamp techniques. Ambasilide (1 microM) prolonged the action potential (APD) at 20, 50 and 90% repolarization by 11.2 +/- 4.3, 13.8 +/- 3.9 and 13.6 +/- 3.7%, respectively, compared to control (n = 10). APD prolongation was attributed to the block of delayed rectifier outward current (Ik) in a concentration-dependent fashion (0.01-10 microM). The effects on the APD and Ik were both partially reversed after perfusion with drug-free Tyrode's solution. The block of Ik by ambasilide was compared to that by E-4031 (5 microM), a putative selective blocker of that fast, inwardly rectifying component of Ik identified in guinea pig ventricle. E-4031 produced about 65% block of Ik for pulse durations between 80 and 420 msec, but the block decreased as the pulse duration increased further, the block accounting for 34 +/- 5% of Ik at 6.3 sec. In contrast, the percentage of reduction of Ik by 10 microM ambasilide did not produce a consistent magnitude of block over a similar range of short depolarizations, but rather progressively decreased Ik as the pusle duration lengthened. Block at the end of a 2-sec pulse was about 48 +/- 8%, more block than could be attributed to an E-4031-sensitive current block alone. Whereas E-4031 (5 microM) shifted the activation curve of Ik 10 mV toward positive potentials and decreased the slope factor, k, by about 4 mV, ambasilide (5 microM) had no effect on these parameters.(ABSTRACT TRUNCATED AT 250 WORDS)     

Clinical and polysomnographic predictors of severe obstructive sleep apnea in the South Indian population

Background:With the emergence of lifestyle diseases in epidemic proportions, obstructive sleep apnea (OSA) is being increasingly recognized in less developed countries as well.Aim:We sought to study the demographic, clinical, and polysomnographic (PSG) predictors of OSA severity in a cohort of South Indian patients.Results:There were 152 (119 males and 33 females) subjects with a mean age of 53.8 years and body mass index (BMI) of 29.31. Mean AHI was 36.2/h (range: 5.1-110) and 66 subjects had severe OSA. Around 12% had the presenting complaint as insomnia, mainly of sleep maintenance. Of the subjects, 35% had witnessed apneas and 67% had excessive daytime sleepiness (EDS); 40% of patients had ≥2 risk factors. PSG parameters showed short sleep onset latency with a high arousal index. Mean apnea duration was 24.92 s. We found that age >55 years, BMI >25 kg/m², witnessed apneas, EDS, hypertension, dyslipidemia, reduced slow wave sleep duration, mean apnea duration >20 s, and desaturation index >10/h correlated well with OSA severity while the arousal index, sleep latency and efficiency, and exposure to smoking and alcohol showed no association.Conclusions:Older subjects with witnessed apneas are likely to have more severe OSA. Even though overall sleep architecture was similar between the groups, severe OSA had shorter slow wave sleep, longer apneas, and higher nocturnal hypoxemia.     

Production of physician services under fee‐for‐service and blended fee‐for‐service: Evidence from Ontario,Canada

We examine family physicians' responses to financial incentives for medical services in Ontario, Canada. We use administrative data covering 2003–2008, a period during which family physicians could choose between the traditional fee for service (FFS) and blended FFS known as the Family Health Group (FHG) model. Under FHG, FFS physicians are incentivized to provide comprehensive care and after‐hours services. A two‐stage estimation strategy teases out the impact of switching from FFS to FHG on service production. We account for the selection into FHG using a propensity score matching model, and then we use panel‐data regression models to account for observed and unobserved heterogeneity. Our results reveal that switching from FFS to FHG increases comprehensive care, after‐hours, and nonincentivized services by 3%, 15%, and 4% per annum. We also find that blended FFS physicians provide more services by working additional total days as well as the number of days during holidays and weekends. Our results are robust to a variety of specifications and alternative matching methods. We conclude that switching from FFS to blended FFS improves patients' access to after‐hours care, but the incentive to nudge service production at the intensive margin is somewhat limited.     

“Dot sign” in dengue encephalitis

Neuro radiological findings in Dengue encephalitis are non specific. Here we report a case of Dengue encephalitis with transient splenial hyperintensity appearing as dot sign on magnetic resonance imaging of brain.     

Hurdles in stroke thrombolysis: Experience from 100 consecutive ischemic stroke patients

Background:

Acute management of ischemic stroke involves thrombolysis within 4.5 h. For a successful outcome, early recognition of stroke, transportation to the hospital emergency department immediately after stroke, timely imaging, proper diagnosis, and thrombolysis within 4.5 h is of paramount importance.

Aim:

To analyze the obstacles for thrombolysis in acute stroke patients.

Materials and Methods:

The study was conducted in a tertiary care center in South India. A total of hundred consecutive patients of acute ischemic stroke who were not thrombolysed, but otherwise fulfilled the criteria for thrombolysis were evaluated prospectively for various factors that prevented thrombolysis. The constraints to thrombolysis were categorized into: i) Failure of patient to recognize stroke symptoms, ii) patient''s awareness of thrombolysis as a treatment modality for stroke, iii) failure of patient''s relative to recognize stroke, iv) failure of primary care physician to recognize stroke, v) transport delays, vi) lack of neuroimaging and thrombolysis facility, and vii) nonaffordability.

Results:

The biggest hurdle for early hospital presentation is failure of patients to recognize stroke (73%), followed by lack of neuroimaging facility (58%), nonaffordability (56%), failure of patient''s relative to recognize stroke (38%), failure of the primary care physician to recognize stroke (21%), and transport problems (13%). Awareness of thrombolysis as a treatment modality for stroke was seen only in 2%.

Conclusion:

Considering the urgency of therapeutic measures in acute stroke, there is necessity and room for improvement to overcome various hurdles that prevent thrombolysis.     

Relationship of Urologic Complications With Health-Related Quality of Life and Perceived Value of Health in Men and Women With Type 1 Diabetes: The Diabetes Control and Complications Trial/Epidemiology of Interventions and Complications (DCCT/EDIC) Cohort

OBJECTIVE

Limited information exists about the influence of urologic complications on health-related quality of life (HRQOL) in patients with type 1 diabetes.

RESEARCH DESIGN AND METHODS

We studied 664 men and 580 women from the Diabetes Control and Complications Trial/Epidemiology of Interventions and Complications Study: mean ages were 51.6 ± 6.6 and 50.6 ± 7.2 years and duration of diabetes was 29.5 ± 4.8 and 29.8 ± 5.1 years, respectively. We assessed associations of sexual dysfunction, lower urinary tract symptoms (LUTS), and, in women, urinary incontinence (UI) with general quality of life (SF-36), perceived value of health (EuroQol-5), diabetes-related quality of life (Diabetes Quality of Life Scale [DQOL]), and psychiatric symptoms (Symptom Checklist 90-R).

RESULTS

In both men and women, urologic complications adversely affected HRQOL and psychiatric symptoms, even after accounting for history of depression leading to treatment. Multivariable analyses accounting for the presence of diabetic retinopathy, neuropathy, and nephropathy also revealed substantial independent effects. In men, for example, the odds (95% CI) of a low DQOL score (≤25th percentile) were 3.01 (1.90–4.75) times greater with erectile dysfunction and 2.65 (1.68–4.18) times greater with LUTS and in women, 2.04 (1.25–3.35) times greater with sexual dysfunction and 2.71 (1.72–4.27) times greater with UI/LUTS combined compared with men and women without such complications. Similar effects were observed for the other measures.

CONCLUSIONS

Sexual dysfunction and urinary complications with type 1 diabetes are associated with decreased quality of life and perceived value of health and with higher levels of psychiatric symptoms, even after accounting for other diabetes complications and depression treatment.