Effect of obstruction on longitudinal left ventricular shortening in hypertrophic cardiomyopathy.

OBJECTIVES: We investigated the cause of the midsystolic drop (MSD) in left ventricular (LV) ejection velocities that are observed with hypertrophic cardiomyopathy (HCM) and severe obstruction. BACKGROUND: Dynamic obstruction is an important determinant of symptoms and adverse outcome. The MSD in velocity and flow occurs in patients with gradients >60 mm Hg. The nadir velocity in the LV occurs simultaneously with peak gradient. METHODS: We studied 36 patients with obstructive HCM and an MSD and compared them with 15 patients with HCM and no obstruction and with 25 age-matched normal control subjects. We measured LV ejection velocity proximal and distal to LV obstruction as well as tissue Doppler velocities and time intervals. RESULTS: The duration of contraction of both the septum and lateral wall is shorter in obstructed patients with the MSD than in nonobstructed HCM patients: septal contraction 203 +/- 68 ms vs. 271 +/- 41 ms (p < 0.001). Parallel reduction in the length of shortening was noted: 1.2 +/- 0.6 cm vs. 1.9 +/- 0.4 cm (p < 0.001). The ejection velocity nadir follows the septal and lateral peak velocities by 100 ms and 60 ms, respectively. The velocity nadir occurs as both walls rapidly decelerate to their premature termination: septal deceleration 79 +/- 35 cm/s2 vs. 48 +/- 21 cm/s2 (p < 0.001). With medical abolition of obstruction the MSD disappears and the duration and length of contraction normalizes. CONCLUSIONS: These data indicate that the MSD is caused by premature termination of LV segmental shortening and is a manifestation of systolic dysfunction.     

Enhanced detection of ischemic myocardium by transesophageal dobutamine stress echocardiography: comparison with simultaneous transthoracic echocardiography

The diagnostic accuracy of dobutamine stress echocardiography is limited in patients with poor transthoracic acoustic windows. Transesophageal echocardiography (TEE) overcomes these limitations and thus may increase the clinical usefulness of dobutamine stress echocardiography. The present study was designed to compare the diagnostic accuracies of transesophageal and transthoracic dobutamine stress echocardiography for the identification of coronary artery disease (CAD) in a cohort of patients with a higher incidence of poor acoustic windows. Forty-two male patients (mean age, 66 +/- 9 years) underwent dobutamine stress echocardiography with simultaneous transesophageal and transthoracic imaging. Coronary arteriography was performed in 28 patients (67%). Transesophageal imaging adequately visualized 99.6% of left ventricular segments compared with 76.2% visualized by transthoracic imaging (P < 0.0001). There was substantial agreement between the two techniques for segmental wall motion analysis at baseline (kappa 0.76; 95% CI, 0.70-0.82); however, at peak dobutamine dose, agreement was significantly reduced (kappa 0.62; 95% CI, 0.55-0.69). The sensitivity (88% vs 75%), specificity (100% vs 75%), and positive predictive value (100% vs 80%) for the identification of CAD were all superior for transesophageal imaging. Transesophageal imaging correctly identified 11 of the 12 patients (92%) with multivessel disease compared with 5 patients (42%) identified by transthoracic imaging (P < 0.03). There were no major complications. Transesophageal dobutamine stress echocardiography is a safe, feasible, and accurate technique for the identification and risk stratification of patients with CAD. Transesophageal imaging appears to be superior to transthoracic imaging for identifying both the presence and extent of CAD, specifically in patients with poor acoustic windows.     

Echocardiographic assessment of viable myocardium

Left ventricular function is one of the most important determinates of long-term prognosis in patients with coronary artery disease. In recent years, it has become apparent that left ventricular dysfunction in patients with coronary artery disease is not always an irreversible process stemming from myocardial necrosis and fibrosis. Myocardial tissue can undergo both a state of potential reversible dysfunction because of prolonged sustained ischemia (hibernating myocardium) or episodes of acute ischemia (stunned myocardium). Revascularization of this tissue may improve regional and global left ventricular function and therefore prognosis. Numerous studies have now firmly established dobutamine echocardiography as a safe, reliable, and accurate imaging modality in the assessment of reversible left ventricular dysfunction. Furthermore, dobutamine echocardiography has been shown to have good sensitivity, specificity, and, more importantly, positive predictive accuracy in identifying both acute and chronic reversible left ventricular dysfunction for risk satisfaction and prognosis.     

Improving postoperative pain management in subpectoral tissue expander implant reconstruction of the breast using an elastomeric pump

IntroductionPostoperative pain after breast surgery is one of the major factors contributing to delay in mobilisation and prolonged hospital stay. A retrospective analysis was performed of patients undergoing skin sparing mastectomy and insertion of a subpectoral implant. The aim was to determine whether the use of an elastomeric local anaesthetic pump improved pain control and length of stay.MethodsTwenty-five consecutive patients undergoing the above procedure were sited with an elastomeric local anaesthetic infusion pump intraoperatively, in addition to standard regular and pro re nata analgesia. The control group comprised 25 patients undergoing the same procedure in the same year who received standard analgesia alone. Visual analogue scale scores were recorded for the duration of inpatient stay, as was any further analgesic requirement.ResultsThe median age was 51 years (range: 26–75 years) in the intervention group and 50 years (range: 28–70 years) in the control group. The mean visual analogue scale score was 0.28 (standard deviation [SD]: 0.61) at 24 hours for the intervention group and 1.84 (SD: 0.37) for the control group (p<0.0001). The mean length of stay was 1.8 days (SD: 0.71 days) for the intervention group and 2.28 days (SD: 0.94 days) for the control group (p=0.15). There were no complications involving catheter placement, leakage or toxicity relating to use of the local anaesthetic.ConclusionsThere was significantly reduced pain with the use of the local anaesthetic infusion pump. The elastomeric pump is a step towards enhanced patient recovery after breast surgery in the case of skin sparing mastectomy and subpectoral tissue expander reconstruction.     

Recognizing and improving patient nonadherence to statin therapy

Despite landmark trials demonstrating the benefits of statin therapy for lipid lowering and in the primary and secondary prevention of acute coronary events, many patients do not adhere to medication regimens. Although incremental gains have been made in lowering the absolute levels of total serum cholesterol in the general population, only one third of treated patients are achieving their lipid goals, with fewer than 20% of patients with cardiovascular disease at their target lipid goals. Only half of patients continue taking statins prescribed to them at 6 months, and only 30% to 40% continue taking them at 1 year. Predictors of poor adherence to statins are described, such as female gender and low socioeconomic status. Approaches that are physician focused and patient centered, such as frequent follow-up and serum lipid testing and better education of patients about cardiovascular disease, are suggested to offset a major impediment to achieving the full therapeutic outcomes promised by clinical trials.     

Association between alcohol consumption and both osteoporotic fracture and bone density

Objective

Alcoholism is a risk factor for osteoporotic fractures and low bone density, but the effects of moderate alcohol consumption on bone are unknown. We performed a systematic review and meta-analysis to assess the associations between alcohol consumption and osteoporotic fractures, bone density and bone density loss over time, bone response to estrogen replacement, and bone remodeling.

Methods

MEDLINE, Current Contents, PsychINFO, and Cochrane Libraries were searched for studies published before May 14, 2007. We assessed quality using the internal validity criteria of the US Preventive Services Task Force.

Results

We pooled effect sizes for 2 specific outcomes (hip fracture and bone density) and synthesized data qualitatively for 4 outcomes (non-hip fracture, bone density loss over time, bone response to estrogen replacement, and bone remodeling). Compared with abstainers, persons consuming from more than 0.5 to 1.0 drinks per day had lower hip fracture risk (relative risk = 0.80 [95% confidence interval, 0.71-0.91]), and persons consuming more than 2 drinks per day had higher risk (relative risk = 1.39 [95% confidence interval, 1.08-1.79]). A linear relationship existed between femoral neck bone density and alcohol consumption. Because studies often combined moderate and heavier drinkers in a single category, we could not assess relative associations between alcohol consumption and bone density in moderate compared with heavy drinkers.

Conclusion

Compared with abstainers and heavier drinkers, persons who consume 0.5 to 1.0 drink per day have a lower risk of hip fracture. Although available evidence suggests a favorable effect of alcohol consumption on bone density, a precise range of beneficial alcohol consumption cannot be determined.     

Unilateral pupillary mydriasis from nebulized ipratropium bromide: A false sign of brain herniation in the intensive care unit

Although there are many causes of anisocoria in the intensive care setting, the development of unilateral mydriasis in patients with intracranial hemorrhage or tumor is a neurological emergency, as it may herald the onset of uncal herniation. We describe two patients with a hemiparesis from neurosurgical disorder who subsequently developed a fixed and dilated pupil. The pupillary abnormality was caused by nebulized ipratropium bromide in both cases, and resolved when the medication was discontinued. Nebulized ipratropium may leak from the mask into ipsilateral eye and cause mydriasis in patients with facial weakness. This benign cause of anisocoria in the intensive care setting is distinguished from uncal herniation by the laterality of neurologic findings, and lack of mental status change, ptosis, and extraocular movement impairment.     

Use of a novel hemoadsorption device for cytokine removal as adjuvant therapy in a patient with septic shock with multi-organ dysfunction: A case study

CytoSorb^® (CytoSorbents Corporation, USA) is a novel sorbent hemoadsorption device for cytokine removal. The aim of this study was to examine the clinical use of CytoSorb^® in the management of patient with septic shock. We used this device as an adjuvant to stabilize a young patient with multi-organ failure and severe sepsis with septic shock. A 36-year-old female patient was hospitalized with the complaints of malaise, general body ache, and breathing difficulty and had a medical history of diabetes mellitus type II, hypertension, obstructive sleep apnea, hypothyroidism and morbid obesity. She was diagnosed to have septic shock with multi-organ dysfunction (MODS) and a low perfusion state. CytoSorb^® hemoadsorption column was used as an attempt at blood purification. Acute physiology and chronic health evaluation score, MODS score, and sequential organ failure assessment score were measured before and after the device application. CytoSorb application as an adjuvant therapy could be considered in septic shock.     

Ubiquitin-proteasomal degradation of COX-2 in TGF-β stimulated human endometrial cells is mediated through endoplasmic reticulum mannosidase I

Cyclooxygenase (COX)-2 is a key regulatory enzyme in the production of prostaglandins (PG) during various physiological processes. Mechanisms of COX-2 regulation in human endometrial stromal cells (human endometrial stromal cells) are not fully understood. In this study, we investigate the role of TGF-β in the regulation of COX-2 in human uterine stromal cells. Each TGF-β isoform decreases COX-2 protein level in human uterine stromal cells in Smad2/3-dependent manner. The decrease in COX-2 is accompanied by a decrease in PG synthesis. Knockdown of Smad4 using specific small interfering RNA prevents the decrease in COX-2 protein, confirming that Smad pathway is implicated in the regulation of COX-2 expression in human endometrial stromal cells. Pretreatment with 26S proteasome inhibitor, MG132, significantly restores COX-2 protein and PG synthesis, indicating that COX-2 undergoes proteasomal degradation in the presence of TGF-β. In addition, each TGF-β isoform up-regulates endoplasmic reticulum (ER)-mannosidase I (ERManI) implying that COX-2 degradation is mediated through ER-associated degradation pathway in these cells. Furthermore, inhibition of ERManI activity using the mannosidase inhibitor (kifunensine), or small interfering RNA-mediated knockdown of ERManI, prevents TGF-β-induced COX-2 degradation. Taken together, these studies suggest that TGF-β promotes COX-2 degradation in a Smad-dependent manner by up-regulating the expression of ERManI and thereby enhancing ER-associated degradation and proteasomal degradation pathways.