Brian Lin

Combined and Individual Mitochondrial HSP60 and HSP10 Expression in Cardiac Myocytes Protects Mitochondrial Function and Prevents Apoptotic Cell Deaths Induced by Simulated Ischemia-Reoxygenation

BackgroundThe mitochondrial heat-shock proteins HSP60 and HSP10 form a mitochondrial chaperonin complex, and previous studies have shown that their increased expression exerts a protective effect against ischemic injury when cardiac myocytes are submitted to simulated ischemia. The more detailed mechanisms by which such a protective effect occurs are currently unclear. We wanted to determine whether HSP60 and HSP10 could exert a protection against simulated ischemia and reoxygenation (SI/RO)–induced apoptotic cell death and whether such protection results from decreased mitochondrial cytochrome c release and caspase-3 activation and from the preservation of ATP levels by preservation of the electron transport chain complexes. In addition, we explored whether increased expression of HSP60 or HSP10 by itself exerts a protective effect. Methods and ResultsWe overexpressed HSP60 and HSP10 together or separately in rat neonatal cardiac myocytes using an adenoviral vector and then subjected the myocytes to SI/RO. Cell death and apoptosis in myocytes were quantified by parameters such as enzyme release, DNA fragmentation, and caspase-3 activation. Overexpression of the combination of HSP60 and HSP10 and of HSP60 or HSP10 individually protected myocytes against apoptosis. This protection is accompanied by decreases in mitochondrial cytochrome c release and in caspase-3 activity and increases in ATP recovery and activities of complex III and IV in mitochondria after SI/RO. ConclusionsThese results suggest that mitochondrial chaperonins HSP60 and HSP10 in combination or individually play an important role in maintaining mitochondrial integrity and capacity for ATP generation, which are the crucial factors in determining survival of cardiac myocytes undergoing ischemia/reperfusion injury.

Therapy and outcomes in massive pulmonary embolism from the Emergency Medicine Pulmonary Embolism in the Real World Registry

STUDY AIMnClinical guidelines recommend fibrinolysis or embolectomy for acute massive pulmonary embolism (PE) (MPE). However, actual therapy and outcomes of emergency department (ED) patients with MPE have not previously been reported. We characterize the current management of ED patients with MPE in a US registry.nnnMETHODSnA prospective, observational, multicenter registry of ED patients with confirmed PE was conducted from 2006 to 2008. Massive PE was defined as PE with an initial systolic blood pressure less than 90 mm Hg. We compared inpatient and 30-day mortality, bleeding complications, and recurrent venous thromboembolism.nnnRESULTSnOf 1875 patients enrolled, 58 (3.1%) had MPE. There was no difference in frequency of parenteral anticoagulation (98.3% [95% confidence interval {CI}, 90.5-101.6] vs 98.5% [95% CI, 97.9-99.1], P = .902) between patients with and without MPE. Fibrinolytic therapy and embolectomy were infrequently used but were used more in patients with MPE than in patients without MPE (12.1% [95% CI, 3.7-20.5] vs 2.4% [95% CI, 1.7-3.1], P < .001, and 3.4% [95% CI, 0.0-8.1] vs 0.7% [95% CI, 0.3-1.1], P = .022, respectively). Comparison of outcomes revealed higher all-cause inpatient mortality (13.8% [95% CI, 4.9-22.7] vs 3.0% [95% CI, 2.2-3.8], P < .001), higher risk of inpatient bleeding complications (10.3% [95% CI, 2.5-18.1] vs 3.5% [95% CI, 2.7-4.3], P = .007), and a higher 30-day mortality (14.0% [95% CI, 4.4-23.6] vs 1.8% [95% CI, 1.2-2.4], P < .001) for patients with MPE.nnnCONCLUSIONSnIn a contemporary registry of ED patients, MPE mortality was 4-fold higher than patients without MPE, yet only 12% of the MPE cohort received fibrinolytic therapy. Variability exists between the treatment of MPE and current recommendations.

Myocyte protection by 10 kD heat shock protein (Hsp10) involves the mobile loop and attenuation of the Ras GTP-ase pathway

Heat shock proteins (hsp), hsp60 and hsp10, are involved in the folding of imported mitochondrial proteins and the refolding of denatured proteins after stress. We examined whether hsp10 can reduce myocyte death by its mitochondrial function or by interacting with cytoplasmic signaling pathways. Overexpression of hsp10 by adenoviral infection decreased myocyte death induced by hydrogen peroxide, sodium cyanide, and simulated ischemia and reoxygenation (SI/RO). We generated an adenoviral vector coding for a temperature‐sensitive mutant hsp10 protein (P34H), incapable of cooperatively refolding denatured malate dehydrogenase with hsp60. Overexpression of the hsp10 mutant potentiated SI/RO‐induced myocyte death. Analysis of electron transport chain function revealed increased Complex I capacity with hsp10 overexpression, whereas hsp10(P34H) overexpression decreased Complex II capacity. Hsp10 overexpression preserved both Complex I and II function after SI/RO. Examination of the Ras GTP‐ase signaling pathway indicated that inhibition of Ras was required for protection by hsp10. Constitutive activation of Ras abolished the effects afforded by hsp10 and hsp10(P34H). Hsp10 overexpression inactivated Raf, ERK, and p90Ribosomal kinase (p90RSK) before and after SI/RO. Our results suggest that complex mechanisms are involved in the protection by hsp10 against SI/RO‐induced myocyte death. This mechanism may involve the hsp10 mobile loop and attenuation of the Ras GTP‐ase signaling pathway.

A better way to estimate adult patients' weights.

OBJECTIVEnIn the emergency department (ED), adult patients weights are often crudely estimated before lifesaving interventions. In this study, we evaluate the reliability and accuracy of a method to rapidly calculate patients weight using readily obtainable anthropometric measurements. We compare this method to visual estimates, patient self-report, and measured weight.nnnMETHODSnA convenience sample of adult ED patients in an academic medical center were prospectively enrolled. Midarm circumference and knee height were measured. These values were input in to equations to calculate patients weights. A physician and nurse were then independently asked to estimate the patients weights. Each patient was asked to report his/her own weight before being weighed. Calculated weights using the above equations, visual estimates, and patient reports were compared with actual weights by determining the percentage accurate within 10%. The intraclass correlation coefficient was used to determine the reliability of the estimates with respect to actual weights.nnnRESULTSnWeight was determined within 10% accuracy of actual weight in 69% (95% confidence interval, 63-75) of calculated estimates, 54% (48-61) of physician estimates, 51% (44-57) of nurse estimates, and 86% (81-90) of patient estimates. The weight estimation tool calculated weights more accurately in males (74%, 65-82) than females (65%, 56-73). An analysis of errors revealed that when estimates were inaccurate, approximately half were overestimates and half were underestimates. The correlation coefficient between the calculated estimates and actual weights was 0.89. The correlation coefficient of actual weights with respect to physician estimates, nurse estimates, and doctors estimates were 0.85, 0.78, and 0.95, respectively.nnnCONCLUSIONSnThis technique using readily obtainable measurements estimates weight more accurately than ED providers. The technique correlates well with actual patient weights. When available, patient estimates of their own weight are most accurate.

A Case of Elevated Liver Function Tests After Crown-of-Thorns (Acanthaster planci) Envenomation

Abstract The crown-of-thorns starfish (Acanthaster planci) inhabits coral reefs, largely throughout the Indo-Pacific region. Its dorsal surface is covered with stout thorn-like spines. When handled or stepped on by humans, the spines can puncture the skin, causing an immediate painful reaction, followed by inflammation and possible infection. Initial pain and swelling may last for days. Effects of envenomation on the liver have been demonstrated previously in animal models, but hepatic toxicity has not previously been described in humans. We describe elevated liver enzymes in a 19-year-old female associated with A planci spine puncture wounds. To our knowledge, this is the first documented report of transaminitis in a human after A planci envenomation.

A Novel, Simple Method for Achieving Hemostasis of Fingertip Dermal Avulsion Injuries

BACKGROUNDnDistal fingertip pad dermal avulsion injuries can be challenging for emergency physicians. A common occurrence with these injuries is difficult-to-control bleeding. The nature of these wounds is such that conventional primary closure to achieve hemostasis is not feasible. Often, direct pressure, even for prolonged periods, will not adequately control the bleeding. Currently recommended techniques are inadequate to control bleeding, and commercially available hemostatic products may be more costly and not widely available.nnnOBJECTIVEnTo present a simple method to achieve permanent hemostasis of these injuries using a tourniquet and tissue adhesive glue.nnnPROCEDUREnA tourniquet is placed around the proximal digit, and the digit is exsanguinated and elevated to achieve short-term hemostasis. Several layers of commercially available tissue adhesive glue are applied sequentially over the avulsed region of the digit and allowed to dry. The tourniquet is then removed. A clean, bloodless dressing is created over the avulsed fingertip.nnnCONCLUSIONnThis technique provides a rapid, simple, and likely safe means to control bleeding from a fingertip dermal avulsion injury.

Outcomes in Patients Treated with a Novel, Simple Method for Hemostasis of Dermal Avulsion Injuries

OBJECTIVE: A recently described technique proposes a simple method to achieve permanent hemostasis of distal fingertip dermal avulsion injuries. It is simple to learn and easy to perform with readily available materials found in most emergency departments. However, long-term outcomes for patients treated with this technique have not yet been evaluated. A primary objective of the current article is to provide safety data for the technique using an off-label product indication. SETTING: Emergency department of Kaiser Permanente Medical Center, San Francisco, California. MATERIALS AND METHODS: Six patients were treated in the emergency department for fingertip dermal avulsion injuries using a tourniquet and tissue adhesive glue (Dermabond by Ethicon, Somerville, New Jersey). Patients were subsequently contacted to assess healing and satisfaction with cosmetic outcome through interview and photographs of their wounds at 9 months following the date of injury. RESULTS: All 6 patients were satisfied with the cosmetic outcome of treatment, and none received a diagnosis of serious complications. CONCLUSIONS: This series demonstrates cosmetic outcomes for injuries treated with the technique, highlights potential problems that may be perceived by patients during their clinical course, and creates the groundwork for a larger clinical study examining the use of the technique.