Department of Physiology and Biophysics and Center for Excellence
in Cardiovascular-Renal Research, University of Mississippi Medical
Center, Jackson, Mississippi 39216 - 4505
Vascular resistance and
...arterial pressure are reduced during normal pregnancy, but dangerously
elevated during pregnancy-induced hypertension (PIH), and changes in
nitric oxide (NO) synthesis have been hypothesized as one potential
cause. In support of this hypothesis, chronic inhibition of NO
synthesis in pregnant rats has been shown to cause significant
increases in renal vascular resistance and hypertension; however, the
cellular mechanisms involved are unclear. We tested the hypothesis that
the pregnancy-associated changes in renal vascular resistance reflect
changes in contractility and intracellular Ca 2+
concentration (Ca 2+ i ) of renal
arterial smooth muscle. Smooth muscle cells were isolated from
renal interlobular arteries of virgin and pregnant Sprague-Dawley rats
untreated or treated with the NO synthase inhibitor
nitro- L -arginine methyl ester ( L -NAME; 4 mg · kg 1 · day 1 for 5 days), then loaded with fura 2. In cells of virgin rats incubated in
Hanks' solution (1 mM Ca 2+ ), the basal
Ca 2+ i was 86 ± 6 nM. Phenylephrine
(Phe, 10 5 M) caused a transient increase in
Ca 2+ i to 417 ± 11 nM and maintained
an increase to 183 ± 8 nM and 32 ± 3% cell contraction.
Membrane depolarization by 51 mM KCl, which stimulates Ca 2+
entry from the extracellular space, caused maintained increase in
Ca 2+ i to 292 ± 12 nM and 31 ± 2% contraction. The maintained Phe- and KCl-induced
Ca 2+ i and contractions were reduced in
pregnant rats but significantly enhanced in pregnant rats treated with
L -NAME. Phe- and KCl-induced contraction and
Ca 2+ i were not significantly different
between untreated and L -NAME-treated virgin rats or between
untreated and L -NAME + L -arginine treated pregnant rats. In Ca 2+ -free Hanks', application of Phe or
caffeine (10 mM), to stimulate Ca 2+ release from the
intracellular stores, caused a transient increase in
Ca 2+ i and a small cell contraction that
were not significantly different among the different groups. Thus renal
interlobular smooth muscle of normal pregnant rats exhibits reduction
in Ca 2+ i signaling that involves
Ca 2+ entry from the extracellular space but not
Ca 2+ release from the intracellular stores. The reduced
renal smooth muscle cell contraction and
Ca 2+ i in pregnant rats may explain the
decreased renal vascular resistance associated with normal pregnancy,
whereas the enhanced cell contraction and
Ca 2+ i during inhibition of NO synthesis in
pregnant rats may, in part, explain the increased renal vascular
resistance associated with PIH.
vascular resistance; hypertension; calcium; contraction
Prevention of Infections Associated With Combat-Related Extremity Injuries Murray, Clinton K.; Obremskey, William T.; Hsu, Joseph R. ...
The journal of trauma,
2011-August, 2011-Aug, 2011-08-00, 20110801, Letnik:
71, Številka:
2 Suppl 2, Prevention of Infections Associated With Combat-Related Injuries: Clinical Practice Guidelines Update
Journal Article
During combat operations, extremities continue to be the most common sites of injury with associated high rates of infectious complications. Overall, ∼15% of patients with extremity injuries develop ...osteomyelitis, and ∼17% of those infections relapse or recur. The bacteria infecting these wounds have included multidrug-resistant bacteria such as Acinetobacter baumannii, Pseudomonas aeruginosa, extended-spectrum β-lactamase-producing Klebsiella species and Escherichia coli, and methicillin-resistant Staphylococcus aureus. The goals of extremity injury care are to prevent infection, promote fracture healing, and restore function. In this review, we use a systematic assessment of military and civilian extremity trauma data to provide evidence-based recommendations for the varying management strategies to care for combat-related extremity injuries to decrease infection rates. We emphasize postinjury antimicrobial therapy, debridement and irrigation, and surgical wound management including addressing ongoing areas of controversy and needed research. In addition, we address adjuvants that are increasingly being examined, including local antimicrobial therapy, flap closure, oxygen therapy, negative pressure wound therapy, and wound effluent characterization. This evidence-based medicine review was produced to support the Guidelines for the Prevention of Infections Associated With Combat-Related Injuries2011 Update contained in this supplement of Journal of Trauma.
HYPOTHESIS Certain clinicopathologic factors predict improved survival after cytoreductive surgery and intraperitoneal hyperthermic chemotherapy for peritoneal carcinomatosis. DESIGN Prospective ...clinical trial. SETTING Surgical oncology service at a university academic hospital. PATIENTS A population of 109 consecutive patients with peritoneal carcinomatosis treated between December 1991 and November 1997. INTERVENTION All patients underwent resection of gross disease followed by 2-hour intraoperative perfusion of mitomycin C (20-40 mg) into the peritoneal cavity at a temperature of 40.5°C. MAIN OUTCOME MEASURES Clinicopathologic factors that independently predicted improved overall survival rates. RESULTS Overall survival at 1 and 3 years was 61% and 33%, respectively. With median follow-up of 52 months, median overall survival was 16 months. Four factors were significant independent predictors of improved survival by multivariate analysis: nonadenocarcinoma histologic features (P = .001), the appendix as a primary site (P = .003), the absence of hepatic parenchymal metastases (P = .01), and complete resection of all gross disease (R1/0 resection) (P<.001). Patients with an R1/0 resection vs an incomplete resection of gross disease (R2 resection) had 3-year overall survival of 68% vs 21% (P<.001). CONCLUSIONS Patients with peritoneal carcinomatosis have a uniformly poor prognosis. However, in select patients, the natural history of this disease condition may be altered by using the multimodality approach of cytoreductive surgery and intraperitoneal hyperthermic chemotherapy. These results require confirmation in prospective randomized studies.Arch Surg. 2003;138:26-33-->
The tumor suppressor gene deleted in pancreatic cancer locus 4 (Smad4/DPC4) is inactivated in about 50% of pancreatic adenocarcinomas. The role of DPC4 in the transforming growth factor-beta ...(TGF-beta) receptor-mediated signal transduction cascade in human pancreatic, colon, and breast carcinoma cell lines has been investigated by a number of laboratories. The results demonstrate that Smad4/DPC4 protein functions as a key transcription factor required in regulation of TGF-beta inducible gene expression and subsequent growth inhibition. Many transcription regulators that are involved in cell growth, differentiation, and oncogenesis have been identified and cloned. Yet paradoxically, it is much more difficult to identify the important downstream target genes responsible for the biological effects elicited by these transcription factors. Although numerous attempts have been made and different approaches have been used to identify the target genes, only limited success has been achieved. Our data show that p21waf1 is one of the Smad4/DPC4-regulated downstream target genes and suggest that overexpression of the Smad4/DPC4 gene can bypass TGF-beta receptor activation and reestablish one of the key regulatory controls of cell proliferation. Identification of the Smad-regulated downstream target genes responsible for diverse biological processes that they control will extend our understanding of the mechanism for cell cycle regulation and cell differentiation.
Despite advances in resuscitation and surgical management of combat wounds, infection remains a concerning and potentially preventable complication of combat-related injuries. Interventions currently ...used to prevent these infections have not been either clearly defined or subjected to rigorous clinical trials. Current infection prevention measures and wound management practices are derived from retrospective review of wartime experiences, from civilian trauma data, and from in vitro and animal data. This update to the guidelines published in 2008 incorporates evidence that has become available since 2007. These guidelines focus on care provided within hours to days of injury, chiefly within the combat zone, to those combat-injured patients with open wounds or burns. New in this update are a consolidation of antimicrobial agent recommendations to a backbone of high-dose cefazolin with or without metronidazole for most postinjury indications, and recommendations for redosing of antimicrobial agents, for use of negative pressure wound therapy, and for oxygen supplementation in flight.
We describe individual, area, and provider characteristics associated with care patterns for early-stage breast cancer in Appalachian counties of Kentucky, North Carolina, Ohio, and Pennsylvania.
...Cases of stages I to III breast cancer from 2006 to 2008 were linked to Medicare claims occurring within 1 year of diagnosis. Rates of guideline-concordant endocrine therapy (n = 1,429), chemotherapy (n = 1,480), and radiation therapy (RT) after breast-conserving surgery were studied; RT was studied in women age ≥ 70 years with stage I estrogen receptor (ER) -positive/progesterone receptor (PR) -positive cancer, for whom RT was optional (n = 1,108), and in all others, for whom RT was guideline concordant (n = 1,422). Univariable and multivariable analyses were performed. Independent variables included age, race, county-level economic status, state, surgeon graduation year and volume, comorbidity, diagnosis year, Medicaid/Medicare dual status, histology, tumor size, tumor sequence, positive lymph nodes, ER/PR status, stage, trastuzumab use, and surgery type.
Population mean age was 74 years; 97% were white. For endocrine therapy, chemotherapy, and RT, guideline concordance was 76%, 48%, and 83%, respectively. Where it was optional, 77% received RT. Guideline-concordant endocrine therapy was lower in North Carolina versus Pennsylvania (odds ratio OR, 0.60; 95% CI, 0.41 to 0.88) and higher if surgeon graduated between 1984 and 1988 versus ≥ 1989 (OR, 1.58; 95% CI, 1.06 to 2.34). Guideline-concordant chemotherapy varied significantly by state, county-level economic status, and surgeon volume. In guideline-concordant RT, lower surgeon volume (v highest) predicted RT use (OR, 1.63; 95% CI, 1.61 to 2.36). In optional RT, North Carolina residence (v Pennsylvania; OR, 0.29; 95% CI, 0.17 to 0.48) and counties with higher economic status (OR, 0.61; 95% CI, 0.40 to 0.94) predicated RT omission.
Notable variation in care by geographic and surgical provider characteristics provides targets for further research in underserved areas.
![[Ca2+]i signaling in renal ...](http://api.summon.serialssolutions.com/2.0.0/image/issn/XR4PS5YY4K/0363-6119/small "[Ca2+]i signaling in renal arterial smooth muscle cells of pregnant rat is enhanced during inhibition of NOS")
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