High-Density Lipoprotein: Is the Good Cholesterol Turning Bad?

Low high-density lipoprotein cholesterol (HDL-C) is the most prevalent lipid abnormality in patients with known coronary heart disease (CHD). Since the 1960 s, epidemiologic studies have shown an inverse relationship between HDL-C levels and risk of developing CHD. This data correlates a 1-mg/dL increase in HDL-C with a 2% to 3% reduction in CHD events. The prevalence of low HDL-C among patients with CHD has prompted multiple trials to increase the concentration or mimic the function of HDL in an attempt to reduce cardiovascular events. This review outlines the cardioprotective functions of HDL-C, describes conditions that modify HDL structure and function, and presents an overview of clinical trials on HDL-raising therapies.     

Recombinant Human Interleukin-1 Receptor Antagonist Provides Cardioprotection During Myocardial Ischemia Reperfusion in the Mouse

Purpose

Acute myocardial infarction (AMI) drives an intense inflammatory response that contributes to infarct healing and cardiac remodeling. Recently, different studies have identified a role of interleukin-1 (IL-1) in the development of adverse cardiac remodeling. However, in animal models of AMI IL-1 has been shown to be cardioprotective in preconditioning, raising the question of clinical safety of therapeutic IL-1 blockade for autoinflammatory diseases or for the prevention or the treatment of AMI. In this study we proposed to evaluate the effects of pretreatment with recombinant human interleukin-1 receptor antagonist (rhIL-1Ra) on ischemia reperfusion (I/R) injury to the heart.

Methods

RhIL-1Ra was given 4?h or 30?min before the surgical induction of I/R. Left ventricular ejection fraction(LVEF) and infarct size were assessed to determine the effects of the drug pretreatment compared to vehicle treated mice.

Results

RhIL-1Ra, given 4?h or 30?min before the onset of the ischemia, showed marked cardioprotection though preservation of the LVEF (no change vs sham operated mice) and the reduction of the infarct size (?40?% vs vehicle-treated mice). No differences were observed between the two groups of rhIL-1Ra treatment.

Conclusions

IL-1 blockade therapies using rhIL-1Ra prior the onset of AMI protects the myocardium and preserves cardiac function.     

Patients cured of acromegaly do not experience improvement of their skull deformities

Purpose

Acromegaly is a rare disease that is associated with many co-morbidities. This condition also causes progressive deformity of the skull which includes frontal bossing and cranial thickening. Surgical and/or medical management can cure this condition in many patients, but it is not understood if patients cured of acromegaly experience regression of their skull deformities.

Methods

We performed a retrospective analysis on patients treated at our dedicated pituitary center from 2009 to 2014. We looked at all MRI images taken during the treatment of these patients and recorded measurements on eight skull dimensions. We then analyzed these measurements for changes over time.

Results

29 patients underwent curative treatment for acromegaly within our timeframe. The mean age for this population was 45.0 years old (range 19–70) and 55.2 % (n = 16) were female. All of these patients were treated with a transsphenoidal resection for a somatotropic pituitary adenoma. 9 (31.1%) of these patients required further medical therapy to be cured. We found statically significant variation in the coronal width of the sella turcica after therapy, which is likely attributable to changes from transsphenoidal surgery. None of the other dimensions had significant variation over time after cure.

Conclusion

Patients cured of acromegaly should not expect natural regression of their skull deformities. Our study suggests that both frontal bossing and cranial thickening do not return to normal after cure.

     

Endobronchial stenting for extrinsic compression caused by pulsatile pulmonary artery in a 4-week-old infant

Respiratory compromise secondary to external vascular compression may complicate the course of infants and neonates undergoing repair of congeni tal heart disease. Management of such complications usually involves prolonged ventilatory support and even additional high-risk surgical procedures. In recent years, endobronchial placement of self-expanding stents became a realistic treatment option, although there is controversy as to which of the many stents available today give the best results. We report the first successful endobronchial placement of a self-expanding stent in a 4-week-old infant. This conservative treatment for extrinsic airway compression led to the rapid extubation and recovery of the patient.     

TIE2-expressing monocytes regulate revascularisation of the ischaemic limb

BackgroundMonocytes (CD14+ cells) expressing the receptor TIE2 are a highly angiogenic subset that are pivotal to neovascularisation in the tumour environment. We hypothesised that TIE2-expressing monocytes (TEMs) are also important in neovascularisation of ischaemic tissues.MethodsFlow cytometry was used to quantify circulating TEMs in 40 patients with critical limb ischaemia (20 age-matched and 20 healthy controls). RT-PCR was used to confirm TIE2 expression in FACS-sorted TEMs. ELISA was used to measure circulating levels of the TIE2 ligand angiopoietin 2 (ANG2). Mice were subjected to hindlimb ischaemia and TEMs quantified. In an additional study, haemopoietic stem/progenitor cells, isolated from Pgk-rtTA-miR-126T transgenic mice, were transduced ex vivo with a TRE-miR-Tie2-OFP lentiviral vector and used to reconstitute lethally irradiated mice. These mice were treated with alternate daily doses of doxycycline to silence Tie2 expression on TEMs, and hindlimb ischaemia (HLI) was induced. Conversely, bone-marrow-derived macrophages (BMDMs) were enforced to express Tie2 using a Pgk-Tie2 lentivirus and delivered into the ischaemic hindlimb. Recovery of ischaemia was measured with laser Doppler.FindingsFlow cytometry revealed a ten-fold higher number of circulating TEMs in patients with critical limb ischaemia than in matched controls (mean 3·52% [SE 0·28] vs 0·39 [0·09], p<0·0001). Revascularisation or amputation resulted in a fall in TEM numbers to control levels (p<0·005). Analysis by RT-PCR confirmed TIE2 mRNA expression in TEMs. Circulating ANG2 levels were two-fold higher in patients with critical limb ischaemia than in controls (mean 4354 pg/mL [SE 661] vs 1973 [247], p<0·05). Circulating CD115+/Tie2+ monocyte numbers were higher following hindlimb ischaemia in mice than in sham controls (p<0·05) and Tie2 expression was upregulated in CD45+/CD11b+/F4/80+ macrophages isolated from ischaemic hindlimbs (p<0·05). Tie2 gene knockdown in TEMs inhibited neovascularisation of the ischaemic hindlimb (p<0·0001). Delivery of Tie2-expressing BMDMs into the ischaemic limb accelerated the recovery of blood flow compared with treatment with control BMDMs.InterpretationOur studies suggest that TEMs are mobilised following ischaemia and contribute to the revascularisation of ischaemic tissue, and that TIE2 is important for the proangiogenic functios of TEMs. TEMs may represent a promising, novel therapeutic target for cell therapy in critically ischaemic tissues.FundingBritish Heart Foundation and Royal College of Surgeons of England.     

Diabetic Foot Disease: Emerging Technologies: Diabetic Peripheral Neuropathy and Gait: Does Footwear Modify This Association?

Background

Gait-related fall risk is the leading cause of mortality among patients with diabetes, especially those older than 65 years. Deterioration in balance and loss of protective sensation in lower extremities contribute significantly to fall risk in patients with diabetic peripheral neuropathy (DPN). This study aimed to explore the impact of neuropathy and foot ulcer on gait.

Methods

We recruited 39 participants (age, 56.9 ± 8.2 years; body mass index, 29.6.3 ± 4.7 kg/m²), including 15 DPN patients without foot ulcers, 16 DPN patients with foot ulcers, and 8 healthy aged-matched controls. Patients with active foot ulcers wore an offloading device during gait examination, including removable cast walker.

Results

Results suggest that neuropathy alters gait mainly by increasing gait initiation, gait variability (coefficient of variation of gait velocity), and double support (DS) time, while reducing knee range of motion and center of mass sway (p < .05). Interestingly, the presence of foot ulcer does not impact gait velocity (p > .1) but enhances some of the gait parameters such as gait variability and DS time.

Conclusions

This study demonstrates that neuropathy deteriorates gait, but the presence of foot ulcers does not alter gait parameters further than neuropathy. In addition, patients with foot ulcers demonstrated a better gait compared with DPN patients without ulcers. We speculate that offloading footwear may be enhancing the somatosensory feedback from sensate skin, thereby positively affecting gait parameters. A study with a larger sample is required to explore the effect of prescribed footwear in the DPN population in order to validate the findings of this research study.     

Relationship between tooth shade value and skin color: an observational study

STATEMENT OF PROBLEM: There is limited scientific information on the relationship between tooth shade and skin color. This lack of knowledge may impact the ability of the prosthodontist to select artificial teeth that complement the facial complexion of the patient. PURPOSE: This observational study explored the possibility of a relationship between tooth shade and skin color. MATERIALS AND METHODS:A total of 119 individuals aged 18 to 80 years participated in this observational study. Two investigators calibrated for examining tooth shade performed all examinations. A Vita-Lumin shade guide was used to examine either the maxillary right or left central incisor, one of which had to be restoration- and caries-free for study inclusion. Tooth shades were divided into 4 categories according to value, and skin tones were divided into 4 categories (fair, fair/medium, medium, and dark) with the use of L'Oreal True Illusion compact makeup shades as a guide. Categorical modeling with chi-square analysis and Fisher's exact tests was used to analyze the data (alpha=.05). RESULTS: No interaction among age, skin color, and tooth shade or gender, skin color, and tooth shade was found; however, age was associated with tooth shade (P<.001). Older persons were more likely to have teeth with lower values (darker). Among those aged 60 and older, 85% had teeth in the medium and low range values compared with 17% of those younger than 31. Significant tooth shade differences were discovered among patients with different skin colors (P<.05). Among those with low values (darker teeth), 50% were of fair complexion and 17% were of dark complexion (P<.001). CONCLUSION: Within the limitations of this study, tooth shade value and skin color were inversely related. Older adults were more likely to have darker teeth (lower value).     

Single-step transvaginal aspiration and drainage for suspected pelvic abscesses refractory to antibiotic therapy.

OBJECTIVE: For treatment of suspected pelvic abscesses, the use of the trocar technique avoids many of the technical challenges of the Seldinger method. The purpose of this study was to evaluate the effectiveness and safety of sonographically guided transvaginal aspiration or drainage with the trocar technique in suspected pelvic abscesses that were refractory to antibiotic treatment. METHODS: We retrospectively reviewed 22 patients with suspected pelvic abscesses refractory to antibiotic therapy who underwent single-step transvaginal pelvic aspiration or drainage between 1995 and 2000. RESULTS: Transvaginal aspiration or drainage was successful in 19 (86%) of the 22 patients. Of the 3 patients in whom aspiration or drainage failed, all ultimately went on to have surgery despite undergoing repeated drainage procedures. Drainage catheters were placed in 15 (68%) of the 22 patients and left in place an average of 3.7 days. Aspiration alone resulted in a 100% success rate, whereas drainage with catheter placement resulted in an 80% success rate. No complications, including bleeding, bowel perforation, and death, were reported in any of the procedures. CONCLUSIONS: Transvaginal ultrasonographically guided aspiration or catheter placement with the trocar technique is a safe and effective treatment for suspected pelvic abscesses refractory to antibiotic therapy.     

Detection of lymphocyte subsets using three-color/single-laser flow cytometry and the fluorescent dye Peridinin chlorophyll-a protein

The fluorescent dye, Peridinin chlorophyll A protein (PerCP) derived from dinoflagellate organisms (Glenodinium sp.) can be excited by a 488 nm laser and emits light with a large Stokes shift and no major spectral overlap with commonly used chromophores such as fluorescein isothiocyanate (FITC) and R-phycoerythrin (PE). PerCP was conjugated directly to various mouse monoclonal antibodies (mAb) specific for human leukocyte markers or to avidin for use with biotinylated-mAb, and used to perform three color single-laser flow cytometry. The efficacy of this method was demonstrated by analyzing the heterogeneity of thymus T lineage subsets and B lymphocyte subsets in blood. CD4–CD8–, CD4+CD8+ and CD4+CD8– or CD4–CD8+ subsets differ in their expression of cell-cell interaction markers including CD18, CD28, CD44 and Leu 8, and activation/subset markers CD45RO, CD45RA and CD26. Some CD5+ peripheral blood B cells, unlike CD5– B cells, expressed CD45RO or high levels of CD54 (ICAM-1) suggesting the CD5+ B cell population contains activated lymphocytes. The availability of such an accessible method for three color analysis will make it possible to do routine three color monitoring of immunologic diseases such as AIDS, and autoimmune or periodontal diseases.     

Validation of a short questionnaire in English and French for use in patients with persistent upper gastrointestinal symptoms despite proton pump inhibitor therapy: the PASS (Proton pump inhibitor Acid Suppression Symptom) test.

BACKGROUND: The management of persistent symptoms during acid suppression therapy in patients with gastroesophageal reflux disease or dyspepsia might be improved if patient-physician communication regarding the presence and character of these persistent symptoms were facilitated. AIM: To validate a short, simple questionnaire (the Proton pump inhibitor [PPI] Acid Suppression Symptom [PASS] test), in English and French, to identify patients with persistent acid-related symptoms during PPI therapy and document their response to a change in therapy. METHODS: Patients with persistent acid-related symptoms on PPI therapy were interviewed to produce a draft, five-item questionnaire; content validity was evaluated by focus groups comprising English- and French-speaking patients. Psychometric validity was subsequently evaluated in a multicentre, family practice-based study of English- and French-speaking patients with persistent acid-related upper gastrointestinal symptoms despite PPI therapy. The PASS test, Global Overall Symptom scale, Gastrointestinal Symptom Rating Scale (GSRS), Quality of Life in Reflux and Dyspepsia questionnaire and Reflux Disease Questionnaire were completed at baseline and repeated after one week while patients continued their original PPI therapy. All patients then received esomeprazole 40 mg once daily for four weeks, after which all questionnaires and an evaluation of overall treatment effect were completed. RESULTS: Content validity was established in 20 English- and 16 French-speaking patients. Psychometric validation in 158 English- and 113 French-speaking patients revealed good-to-excellent test-retest reliability coefficients: 0.76 for English; 0.68 for French. For construct validity, the PASS test showed moderate-to-high correlation with the GSRS scale (0.51 for English; 0.43 for French). After four weeks of therapy, the PASS test score fell to zero in 30% of English- and 33% of French-speaking patients, while the Global Overall Symptom score fell to one (no symptoms) in 32% of patients (English- and French-speaking); the PASS test demonstrated good responsiveness in comparison with the GSRS, Reflux Disease Questionnaire and Quality of Life in Reflux and Dyspepsia questionnaire. CONCLUSION: The five-item PASS test is a valid tool for the evaluation of persistent acid-related symptoms in patients receiving PPI therapy. It demonstrates good content validity, test-retest reliability, responsiveness and construct validity in both English and French forms. The PASS test is a simple, clinically applicable tool for the identification of patients with persistent acid-related symptoms during therapy and the assessment of their responses to a change in therapy.