MIR-210 modulates mitochondrial respiration in placenta with preeclampsia.

Preeclampsia (PE) affects 5-8% of all pregnancies and is associated with significant maternal and fetal morbidity and mortality. Placental mitochondrial dysfunction has been reported in PE. MicroRNAs (miRNA) are small non-coding RNAs that regulate gene expression through mRNA degradation and translational repression. MiR-210 has been previously shown to be upregulated in placentas from pregnancies complicated by PE. We hypothesized that placental mitochondrial dysfunction during PE can be mediated by miR-210. Placentas were collected at term from normotensive pregnancies (CTRL) and those complicated by severe PE (n = 6 each) following c-section (no labor). Villous tissue from PE showed significantly increased levels of HIF-1α compared to CTRL with no change in corresponding mRNA expression but with reduced DNA-binding activity. Mitochondrial complex III was significantly decreased in PE along with significantly reduced protein expression in complex I and IV during PE. Among the four miRNAs tested, miR-210 showed significant up regulation in PE and significant downregulation of its target, ISCU mRNA. To understand the role of miR-210 in PE, loss- and gain-of-function studies were performed using primary trophoblasts. Trophoblasts were transfected with miR-210 inhibitor or pre-miR-210 and mitochondrial function was measured using Seahorse Extracellular Flux Analyzer. Cells transfected with pre-miR-210 showed significant reduction in oxygen consumption. In contrast, transfection of trophoblast with AntagomiR-210 was sufficient to prevent the DFO-mediated respiratory deficiency. These data collectively suggest that miR-210 overexpression during PE could be responsible for placental mitochondria dysfunction.

Measurement of mitochondrial respiration in trophoblast culture.

Pregnancy is a state of oxidative stress, which becomes exaggerated under pathological conditions, such as preeclampsia, IUGR, diabetes and obesity, where placental mitochondrial dysfunction is observed. The majority of investigations utilize isolated mitochondria when measuring mitochondrial activity in placenta. However, this does not provide a complete physiological readout of mitochondrial function. This technical note describes a method to measure respiratory function in intact primary syncytiotrophoblast from human term placenta.

[Abdominal aorta injury secondary to closed trauma]. / Lesión de aorta abdominal secundaria a trauma cerrado.

Traumatic injury of the abdominal aorta with total interruption of blood flow is uncommon. When there is total obstruction of the artery, the clinical picture is dramatic. The most frequent mechanism is compression due to the safety belt during a car accident. The patients have absent femoral and distal pulses, associated to neuropathy in the lower limbs. We present a case of abdominal aorta injury secondary to closed trauma and review the causes, presentation forms and management of the injury.

Lesión de aorta abdominal secundaria a trauma cerrado / Abdominal aorta injury secondary to closed trauma

La lesión traumática de la aorta abdominal con interrupción total del flujo sanguíneo es infrecuente. Cuando se produce la obstrucción total de la arteria el cuadro clínico es dramático. El mecanismo más frecuente es la compresión por el cinturón de seguridad durante un accidente automovilístico. Los pacientes se encuentran con pulsos femorales y distales ausentes, asociado a neuropatía en extremidades inferiores. Presentamos un caso de lesión de aorta abdominal secundaria a trauma cerrado y repasamos las causas, formas de presentación y manejo de la lesión

Traumatic injury of the abdominal aorta with total interruption of blood flow is uncommon. When there is total obstruction of the artery, the clinical picture is dramatic. The most frequent mechanism is compression due to the safety belt during a car accident. The patients have absent femoral and distal pulses, associated to neuropathy in the lower limbs. We present a case of abdominal aorta injury secondary to closed trauma and review the causes, presentation forms and management of the injury

Changes in expression of antioxidant enzymes affect cell-mediated LDL oxidation and oxidized LDL-induced apoptosis in mouse aortic cells.

Transgenic mice overexpressing Cu/Zn superoxide dismutase (hSod1Tg(+/0)) or catalase (hCatTg(+/0)) and knockout mice underexpressing manganese superoxide dismutase (Sod2(+/)(-)) or glutathione peroxidase-1 (Gpx1(-/-)) were used to study the effect of antioxidant enzymes on cell-mediated low density lipoprotein (LDL) oxidation and oxidized LDL (oxLDL)-induced apoptosis. Incubation of LDL with mouse aortic segments or smooth muscle cells (SMCs) resulted in a significant increase in LDL oxidation. However, LDL oxidation was significantly reduced when LDL was incubated with aortic segments and SMCs obtained from hSod1Tg(+/0) and hCatTg(+/0) mice compared with those obtained from wild-type mice. In contrast, LDL oxidation was significantly increased when LDL was incubated with aortic segments and SMCs obtained from Sod2(+/)(-) and Gpx1(-/-) mice. CuSO(4)-oxidized LDL increased DNA fragmentation and caspase activities in the primary cultures of mouse aortic SMCs. However, oxLDL-induced DNA fragmentation and caspase activities were reduced 50% in SMCs obtained from hSod1Tg(+/0) and hCatTg(+/0) mice compared with wild-type control mice. In contrast, oxLDL-induced DNA fragmentation and caspase activities were significantly increased in SMCs obtained from Sod2(+/)(-) and Gpx1(-/-) mice. These findings suggest that overexpression of Cu/Zn superoxide dismutase or catalase reduces cell-mediated LDL oxidation and oxLDL-induced apoptosis, whereas underexpression of manganese superoxide dismutase or glutathione peroxidase-1 increases cell-mediated LDL oxidation and oxLDL-induced apoptosis.

Effect of overexpression of human Cu/Zn-SOD on activation-induced lymphocyte proliferation and apoptosis.

The process of lymphocyte proliferation and apoptosis is known to be linked to oxidative stress. In the present study, we have used a new transgenic mouse model to investigate the effect of human Cu/Zn superoxide dismutase (Cu/Zn-SOD) overexpression on activation-induced lymphocytes proliferation and apoptosis. Cu/Zn-SOD activity was 3.5-fold higher in the spleen of the transgenic mice overexpressing Cu/Zn-SOD (Tg-Cu/Zn-SOD) compared to the wild-type littermates. Proliferative response of lymphocytes to lipopolysaccharide (LPS), Concanavalin A (Con A), and anti-CD3 was measured by [3H]-thymidine incorporation. Activation-induced apoptosis was determined by incubating the T cells with anti-CD3 (primary stimulus) for 72 h, followed by restimulation with Con A (secondary stimulus) for various times. Apoptosis was assessed by measuring DNA fragmentation using a spectrofluorimetric assay and monitoring the expression of the specific apoptotic markers (Fas/CD95 receptor and Fas/CD95 ligand (Fas-L) using flow cytometry. There was no significant difference in proliferative response of lymphocytes to LPS, Con A, or anti-CD3 in transgenic mice overexpressing human Cu/Zn superoxide dismutase (Tg-Cu/Zn-SOD) compared to wild-type littermates. In addition, no significant difference was observed in lymphocyte populations and subsets between Tg-Cu/Zn-SOD mice and wild-type littermates. However, splenic T cells from Tg-Cu/Zn-SOD mice exhibited a significantly (p <.05) higher level of activation-induced DNA fragmentation than T cells from wild-type littermates. The increase in DNA fragmentation was paralleled with an increase in the proportion of T cells expressing Fas and Fas-L molecules. The possible consequences of Cu/Zn-SOD overproduction on activation-induced apoptosis are discussed.

Peptide YY Y1 receptor activates mitogen-activated protein kinase and proliferation in gut epithelial cells via the epidermal growth factor receptor.

The G-protein-coupled peptide YY (PYY)/neuropeptide Y Y1 receptor (Y1R) subtype is highly expressed in the proliferative zone of human colonic crypt epithelial cells but biochemical and biological support for growth effects have been lacking. Using a model gut epithelial cell system, we have stably expressed the human Y1R in IEC-6 cells and show that the Y1R does couple to mitogen-activated protein kinase (MAPK) phosphorylation and cell growth. This pathway uses pertussis-toxin-sensitive G-proteins and betagamma subunits, inhibited by co-transfected alpha-transducin. The Src-family tyrosine kinase inhibitor PP1, as well as specific inhibition of the epidermal growth factor receptor tyrosine kinase (EGFR TK) by PD153035, also blocks PYY stimulation of MAPK. This pathway further requires protein kinase C with EGFR TK inhibition blocking PYY-induced protein kinase Cepsilon (PKCepsilon) translocation to the cell membrane. Finally, we show that PYY stimulates growth in Y1R-expressing gut epithelial cells that is dependent on EGFR TK activity. These results demonstrate a novel pathway involving G(i)/G(o) protein, EGFR and PKC to activate MAPK. Further, they support a role for PYY and the Y1R in regulating growth in human colonic epithelium.

Evaluating ambulatory resident practice using an Internet-based system.

To improve faculty participation in providing feedback on resident outpatient practice, we designed and implemented an Internet-based evaluation system. Attending physicians scored residents on 7 questions related to specific practice behaviors, and completed a free-text comment section. Between January and June 1998, 516 evaluations for 107 residents were generated using the Internet-based system, compared with 29 handwritten evaluations for 82 residents between January and June 1997. The number of faculty evaluations was 527 for 121 residents in the second half of 1998. An Internet-based evaluation system can improve faculty compliance with performing evaluations.

Evidence of juxtacrine signaling for transforming growth factor alpha in human endometrium.

To determine the mechanism of signaling for transforming growth factor alpha (TGFalpha) in human endometrium, uterine luminal fluid proteins were retrieved by lavage followed by collection of the adjacent endometrium at hysterectomy. In the endometrium we observed the presence of the full-length transmembrane TGFalpha protein and the phosphorylation of its only known receptor, the epidermal growth factor receptor (EGFR), by immunoprecipitation-Western blot; TGFalpha mRNA via reverse transcription-polymerase chain reaction; and immunolocalization of TGFalpha to the surface endometrium adjacent to the uterine lumen. Despite this demonstration of TGFalpha in functional endometrium, we could not detect measurable amounts of TGFalpha in any of the 16 endometrial washings by either immunoprecipitation-Western blot or by ELISA. Recovery rate for intraluminal fluid spiked with TGFalpha control peptide was 93.4-97%. The inability to detect TGFalpha in intraluminal fluid despite its high concentration in cells directly adjacent to the uterine lumen, along with the absence of any cleaved TGFalpha species identified in the endometrium, suggests that TGFalpha signals its receptor as a transmembrane ligand. Since the EGFR is present in the endometrium and on the surface of embryos, these data are consistent with a juxtacrine mode of signaling for TGFalpha between endometrial cells, and between the luminal surface epithelium and preimplantation embryos.

Will commercial managed care patients accept residents as their primary care providers?

We conducted a telephone survey of patients in a university-based medical practice to determine if there was a difference across payer class in patients' willingness to have supervised housestaff physicians function as their primary care providers. Overall, commercial managed care patients were more likely to object to seeing housestaff physicians than were Medicaid or Medicare patients (50% vs 32% or 23%, respectively). However, prior outpatient care by a resident physician significantly increased patient willingness to be cared for by a resident. This effect of prior care by a resident was noted in the managed care as well as the Medicaid and Medicare populations. Although there may have been self-selection, our data demonstrate that a significant proportion of managed care patients who have had residents as their primary care providers are amenable to continuing this practice.

Laser blepharoplasty: is it safe?

The complications of the "traditional" blepharoplasty have been well outlined; however, very little can be found on the safety of lasers when used for blepharoplasty. In this article, 20 consecutive patients undergoing laser blepharoplasty are examined preoperatively and postoperatively for eye function and ocular injury by an independent ophthalmologist. Follow-up examinations were performed at random times after surgery ranging from 4 to 60 days, with the majority of patients (17 of 20) seen between 4 and 17 days after surgery. Any changes from the preoperative examinations were recorded. Results demonstrated no complications associated with the use of lasers during blepharoplasty. Safety precautions and surgical procedures are outlined. An attempt is made to separate those hazards specific to the laser technique from the "traditional" blepharoplasty procedure.

HIV seropositivity in a burn center's population.

HIV infection in a patient with burn injuries complicates the care of both the patient and the treating burn team. In the patient, HIV slows wound healing and increases the complications seen with burns. For the treating team, HIV is a hazard that infects the large volume of bodily fluids to which the burn team is potentially exposed. At Saint Francis Memorial Hospital, a team of plastic surgeons, infectious disease specialists, medical internists, psychiatrists, social workers, and nurses was established for the care of patients with burn injuries who have HIV. To ascertain the baseline need for this specialized care, we interviewed 103 consecutive patients admitted to the Bothin Burn Center. Those found to be positive by history (3 of 103) were excluded from HIV testing. Of the remaining 100 consecutive patients, all consented to HIV testing. None of these patients, even those with known risk factors, was found to have undiagnosed HIV positivity. We conclude the occult incidence in the population tested is lower than expected, and continued testing is warranted.

Evaluation of an instructional model for emergency ultrasonography.

OBJECTIVE: To evaluate a 4-hour ultrasonography course in the setting of an emergency medicine (EM) training program. METHODS: EM residents and faculty at a large urban center were provided a 4-hour emergency ultrasonography course. Then, during an 18-month period, a nonconsecutive sample of ultrasonographic examinations were videotaped and later reviewed. The interpretations of the emergency, physician examinations were compared with the following reference standards: 1) an official ultrasound performed and interpreted by the departments of radiology or cardiology; 2) an operative report; 3) A CT scan or i.v. pyelogram (IVP); or 4) a cardiologist's or a radiologist's interpretation of the videotaped examinations. RESULTS: Of 258 examinations reviewed, 28 (11%) of these were excluded because the cardiologist or radiologist reviewing the videotape determined them to be "technically limited" studies. Of the remaining 230 examinations, there were: 127 gallbladder studies [disease prevalence = 0.58; sensitivity = 0.89; specificity = 0.80; kappa (kappa) = 0.69; 95% CI: 56-82%]; 39 echocardiograms to rule out pericardial effusions [disease prevalence = 0.15; sensitivity = 0.83; specificity = 0.97 kappa = 0.80; 95% CI: 54-100%]; 25 abdominal ultrasounds to rule out free peritoneal fluid [disease prevalence = 0.32; sensitivity = 0.88; specificity = 0.94; kappa = 0.81; 95% CI: 26-95%]; 16 renal ultrasounds to rule out hydronephrosis [disease prevalence = 0.25; sensitivity = 1.0; specificity = 0.92; kappa = 0.84; 95% CI: 56-100%]; 12 pelvic ultrasounds to rule in an intrauterine pregnancy [disease prevalence = 0.67; sensitivity = 1.0; specificity = 0.75; kappa = 0.80; 95% CI: 43-100%]; and 11 abdominal ultrasounds to rule out abdominal aortic aneurysms [disease prevalence = 0.09; sensitivity = 1.0; 95% CI: 2.5-91%; specificity = 1.0; 95% CI: 68-100%]. CONCLUSIONS: This 4-hour ultrasonography course has potential to serve as a foundation for an instructional model for ultrasonography training in the setting of an EM residency program.

Treatment of thromboembolic complications of fulminant meningococcal septic shock.

A patient report of fulminant meningococcal septic shock is described. The presentation, hospital course, and reconstructive efforts are outlined, and a brief review of meningococcal infection is included. Emphasis is placed on the algorithm used to determine treatment. A 19-year-old Hispanic male presented with all the hallmarks of Waterhouse-Friderichsen syndrome (WFS)-sudden onset, high fever, dyspnea with intermittent cyanosis, shock, disseminated intravascular coagulopathy, and the development of purpura. The pathognomonic feature of WFS-hemorrhage into the adrenal glands-if present, was not extensive, as he did not require steroid supplementation. Though cerebrospinal fluid latex agglutination was negative, his serum was positive for group C Neisseria and admission blood cultures grew Neisseria meningitidis. Thromboembolic complications were systemic with the highest morbidity peripherally in the lower extremities. Care for these injuries involved every rung of the reconstructive ladder-from local wound care and skin grafts to local flaps and microvascular transplantation.

Teaching aesthetic surgery at the resident level.

The field of plastic and reconstructive surgery continues to broaden its scope while other fields continue to narrow theirs. The inability to teach aesthetic surgery is often confounded by the absence of an aesthetic surgery clinic for the chief resident, a reduced number of procedures and cases available, and a lack of faculty staff involvement. A close examination of the 19 western United States-based plastic surgery programs was performed in order to determine the most useful methods in teaching aesthetic surgery. An aesthetic surgery survey was distributed to most recently graduated plastic surgery residents to evaluate their overall experience in aesthetic surgery during residency. Of the 40 residents' surveys, 31 were returned. As anticipated, greater than half (51.6%) of the western United States programs were without a chief resident aesthetic clinic. Also, greater than half of those surveyed (51.6%) felt that the quantity of aesthetic cases was insufficient. The residents' comfort in performing specific operations was quite variable. From data analysis it is apparent there is a greater requirement for "hands-on" experience with aesthetic surgical cases during residency training. Overwhelmingly, the responses indicated the need for a Chief Resident Aesthetic Clinic, greater faculty involvement, and an increased clinic population with attending staff assistance. A 6-month chief resident aesthetic surgery clinic rotation at Saint Francis Memorial Hospital has proven to be very beneficial in teaching all aspects including pre-operative evaluation, surgical technique, and postoperative care of the aesthetic patient.

Chronic hyperpigmentation from a heated mustard compress burn: a case report.

This is a case study of a woman who sustained a second-degree, partial-thickness burn of the midchest and medial breast distribution after the application of a heated mustard compress as a naturopathic remedy for a recent bout of pneumonia. This case study demonstrates the potential for hyperpigmentation and hypertrophic scarring associated with heated mustard burns. A photograph of the presenting burn with the region of hyperpigmentation 3 days after the injury is provided.

The effect of antenatal surgery on craniofacial growth in sheep model.

The purpose of this investigation was to evaluate the effect of antenatal palatal surgery in a sheep model. At 75 to 90 days of gestation, 20 fetuses underwent surgical in utero manipulation of their palates with the incision and elevation of bilateral bipedicled mucoperiosteal flaps. Sixteen of the 20 sheep (80 percent) went on to a normal full-term delivery. The palates and facial appearances were grossly evaluated, and detailed measurements were made of the palates. The data underwent statistical analysis. We were unable to discern any differences between the experimental group and the age-matched controls. Antenatal palatal surgery appeared to have no effect on craniofacial growth and development.

Performance improvement: one model to reduce length of stay.

Dedicated quality professionals are tired of quick fixes, Band-Aids, and other first-aid strategies that offer only temporary relief of nagging problems rather than a long-term cure. Implementing strategies that can produce permanent solutions to crucial problems is a challenge confronted by organizations striving for continuous performance improvement. One vehicle, driven by data and customer requirements, that can help to solve problems and sustain success over time is the storyboard. This article illustrates the use of the storyboard as the framework for reducing length of stay--one of the most important problems facing healthcare organizations today.

Personal protection devices: a case for noisemakers.

The author explores alternative methods for preventing and responding to an attempted assault and presents a convincing argument for the use of noisemakers.