Arterial wall structure and dynamics in type 2 diabetes mellitus methodological aspects and pathophysiological findings

Type 2 Diabetes Mellitus (DM), or adult-onset diabetes, is being considered as a new pandemic. Cardiovascular disease is the major cause of morbidity and mortality in type 2 DM, due to arterial structure and functional changes. Assessment of arterial structure and biomechanics, by non-invasive methods and parameters, can be used to detect early alterations related to DM. Three markers of vascular disease may help to a better evaluation of vascular dysfunction in type 2 DM patients: carotid intimamedia thickness (IMTc), arterial stiffness, assessed by pulse wave velocity (PWV), and endothelial function, evaluated through the brachial artery flow-mediated dilation (FMD). Among these parameters, IMTc is considered a marker of structural vessel wall properties, and arterial stiffness reflects functional wall properties. Endothelial function represents the arterial way to actively regulate its diameter (smooth muscle-dependent actions) and its visco-elastic properties (wall elasticity and viscosity). IMTc is increased in patients with type 2 DM and other independent risk factors, such as: age, hyperlipidemia and duration of DM. Subjects with DM have shown increased arterial stiffness. Type 2 DM is associated with reductions in FMD (endothelial dysfunction), which has already been reported to be inversely and strongly related to the extent of hyperglycemia. The underlying patho-physiological mechanisms are complex and remain to be fully elucidated. A complete understanding of the association between arterial alterations and early detection, and type 2 DM, may be critical for the primary prevention of DM-related macro-vascular disease.     

A historical analysis of severe head injury

Severe head injury (SHI) is a significant health, social and economic concern rendering a worldwide health problem. This retrospective study was designed to describe the features and outcomes of patients with SHI treated in a single neurosurgical unit (Hospital “12 de Octubre”, Madrid, Spain) over a period approaching 13 years. The subjects enrolled were 895 patients (15 years or older) with non-missile SHI treated over the period January 1987 to August 1999, in whom a computerised tomography scan had been performed within the first 6 h of injury. We considered epidemiological, clinical, analytical, radiological and therapeutic data along with final patient outcomes. The overall mortality rate was 46.8% (419 patients). Of these 419 deaths, 177 (42.2%) occurred within the first 48 h of injury rendering an early death rate of 19.8% (177/895 patients). Despite overall mortality showing a clear decreasing trend by the end of the 1990s, proportions of early deaths (within the first 48 h of injury) dramatically rose in the last 3 years of the study. As a whole, an unfavourable outcome was recorded in 62.6% (560 patients). Despite continued efforts to improve the outcome of patients with SHI, the results of our study are pessimistic in that high mortality and unfavourable outcome rates were recorded in this large series of patients. Although overall mortality has diminished over the years, the number of early deaths has increased.     

Bipolar scissors circumcision is a safe, fast, and bloodless procedure in children

Purpose

The aim of this study is to evaluate bipolar scissors circumcision by comparing it with standard freehand scalpel procedure.

Patients and Methods

Data were analyzed from a prospective, randomized study, comparing 2 different surgical techniques for pediatric circumcision: the bipolar diathermy scissors circumcision technique with those of a conventional scalpel technique. A total of 230 pediatric patients younger than 16 years (115 in each arm of the trial) who were undergoing circumcision were reviewed prospectively. Operative time, surgical bleeding, complications, and postoperative morbidity were analyzed. Differences between bipolar scissors circumcision and conventional surgery were compared.

Results

Median blood loss for bipolar circumcision was 0.2 mL (range, 0-0.8 mL) compared with 2.1 mL in the standard group (range, 0.9-4.2 mL) (P < .001). Operative time in the bipolar diathermy treated group was significantly decreased compared with conventionally treated patients (10.8 ± 1.2 vs 19.1 ± 2.6 minutes; P < .01). Early and late postoperative morbidity were significantly decreased in circumcised patients who underwent the bipolar circumcision technique as compared with those who underwent the conventional approach regardless of the postoperative edema (22 vs 10; P = .02).

Conclusions

Bipolar scissors circumcision approach is an effective and safe procedure alternative to the standard scalpel technique in pediatric circumcision with no significant morbidity.     

Transvaginal Cholecystectomy without Abdominal Ports

Background:

Pioneers in natural orifice transvaginal cholecystectomy are in search of an approach that uses less percutaneous assistance. The approach must be safe and affordable. The authors present a successful cholecystectomy using a technique of transvaginal operative laparoscopy with no abdominal ports.

Methods:

A 24-year-old female patient with gallbladder lithiasis underwent a natural orifice cholecystectomy with only one transvaginal 12-mm port, using a laparoscope with a working channel. We used laparoscopic instruments 5 mm in diameter by 43cm in length (including a needle holder, Maryland dissector clamp, spatula, hook, suction cannula, and clip applier) and assistance with percutaneous marionette leashes.

Results:

The patient stayed in the hospital for 24 hours and was discharged without pain and without scars.

Conclusion:

Transvaginal cholecystectomy performed using an operative laparoscope with a working channel is possible in select cases. This technique requires no abdominal ports and is an alternative to culdolaparoscopy or hybrid transvaginal procedures with flexible endoscopes.     

A broader role for 5ARIs in prostate disease? Existing evidence and emerging benefits

5ARIs are recommended for men who have moderate‐to‐severe lower urinary tract symptoms (LUTS) and benign prostatic enlargement (BPE) secondary to benign prostatic hyperplasia. Studies have confirmed the utility of combining 5ARIs with alpha‐blockers; the MTOPS study showed that risk of overall clinical progression was significantly reduced after 4.5 years with combination therapy (finasteride/doxazosin) in comparison with either monotherapy, while the ongoing CombAT trial (dutasteride/tamsulosin) has for the first time shown benefit in improving symptoms for combination therapy over monotherapies within 12 months of treatment. Data also suggest roles for 5ARIs in prostate cancer. Several studies indicate that treatment with a 5ARI improves the performance of PSA testing for identifying men with prostate cancer, while the PCPT showed a significant reduction in the risk of developing prostate cancer with finasteride. However, widespread use of finasteride in this setting has been tempered by an apparent increase in high‐grade disease observed in the study. The ongoing REDUCE study will provide further insight into prostate cancer prevention with 5ARIs. 5ARI‐containing regimens may have utility as less aggressive treatment options for patients who only have rising PSA after definitive local therapy, and in patients with disease resistant to androgen deprivation therapy who have PSA progression. Current evidence therefore shows that 5ARIs are effective in treating LUTS/BPE and preventing disease progression, and may also have a role in the prevention of prostate cancer. The overlap between BPE and prostate cancer may allow a more unified approach to managing these conditions, with 5ARIs having a central role. Prostate 69: 895–907, 2009. © 2009 Wiley‐Liss, Inc.     

Long‐term accumulation of microglia with proneurogenic phenotype concomitant with persistent neurogenesis in adult subventricular zone after stroke

Neural stem cells (NSCs) in the adult rat subventricular zone (SVZ) generate new striatal neurons during several months after ischemic stroke. Whether the microglial response associated with ischemic injury extends into SVZ and influences neuroblast production is unknown. Here, we demonstrate increased numbers of activated microglia in ipsilateral SVZ concomitant with neuroblast migration into the striatum at 2, 6, and 16 weeks, with maximum at 6 weeks, following 2 h middle cerebral artery occlusion in rats. In the peri‐infarct striatum, numbers of activated microglia peaked already at 2 weeks and declined thereafter. Microglia in SVZ were resident or originated from bone marrow, with maximum proliferation during the first 2 weeks postinsult. In SVZ, microglia exhibited ramified or intermediate morphology, signifying a downregulated inflammatory profile, whereas amoeboid or round phagocytic microglia were frequent in the peri‐infarct striatum. Numbers of microglia expressing markers of antigen‐presenting cells (MHC‐II, CD86) increased in SVZ but very few lymphocytes were detected. Using quantitative PCR, strong short‐ and long‐term increase (at 1 and 6 weeks postinfarct) of insulin‐like growth factor‐1 (IGF‐1) gene expression was detected in SVZ tissue. Elevated numbers of IGF‐1‐expressing microglia were found in SVZ at 2, 6, and 16 weeks after stroke. At 16 weeks, 5% of microglia but no other cells in SVZ expressed the IGF‐1 protein, which mitigates apoptosis and promotes proliferation and differentiation of NSCs. The long‐term accumulation of microglia with proneurogenic phenotype in the SVZ implies a supportive role of these cells for the continuous neurogenesis after stroke. © 2008 Wiley‐Liss, Inc.     

miR-181b negatively regulates activation-induced cytidine deaminase in B cells

Activated B cells reshape their primary antibody repertoire after antigen encounter by two molecular mechanisms: somatic hypermutation (SHM) and class switch recombination (CSR). SHM and CSR are initiated by activation-induced cytidine deaminase (AID) through the deamination of cytosine residues on the immunoglobulin loci, which leads to the generation of DNA mutations or double-strand break intermediates. As a bystander effect, endogenous AID levels can also promote the generation of chromosome translocations, suggesting that the fine tuning of AID expression may be critical to restrict B cell lymphomagenesis. To determine whether microRNAs (miRNAs) play a role in the regulation of AID expression, we performed a functional screening of an miRNA library and identified miRNAs that regulate CSR. One such miRNA, miR-181b, impairs CSR when expressed in activated B cells, and results in the down-regulation of AID mRNA and protein levels. We found that the AID 3' untranslated region contains multiple putative binding sequences for miR-181b and that these sequences can be directly targeted by miR-181b. Overall, our results provide evidence for a new regulatory mechanism that restricts AID activity and can therefore be relevant to prevent B cell malignant transformation.