Calcium-sensing receptor expression in human adipocytes

The presence of the extracellular calcium-sensing receptor (CaSR) has been demonstrated in numerous cells that are key in the control of serum calcium concentrations, underscoring its relevance in systemic calcium homeostasis. The more recent evidence of its presence in tissues not involved in this function has broadened the spectrum of interest in this protein, now known to regulate diverse cell functions such as proliferation, differentiation, and apoptosis. This study shows the expression of CaSR in human omental adipose tissue, isolated adipocytes, and adipocyte progenitor cells as assessed by RT-PCR and immunoblotting. This is the first report of CaSR being expressed in human adipocytes and adipocyte progenitor cells, opening the possibility to investigate the physiological implications and thus contributing a novel component for adipose tissue biology research.     

Serial dexamethasone suppression tests in depressed patients treated only with electroconvulsive therapy

Several systematic studies have evaluated serial dexamethasone suppression tests (DST) in patients with major depression who were treated with antidepressant medications. DST changes were noted to parallel clinical improvement in most recovering patients. If serial DSTs are a valid state-related correlate of depressive pathophysiology, all types of effective antidepressant treatment should result in DST 'normalization'. However, no treatment modalities other than antidepressant medications have been studied serially with systematic assessments. To test whether serial DSTs reflect clinical progress in depressives treated solely with electroconvulsive therapy (ECT), we studied weekly DSTs and Hamilton Rating Scales for Depression (HRSD) in 22 drug-free depressed patients. We observed progressive DST 'normalization' in most patients and moderately high correlations between weekly DST and HRSD values throughout treatment. Most patients receiving ECT became DST suppressors. In most patients the DST appeared to reflect the severity of depressive pathophysiology, perhaps providing serial feedback to clinicians monitoring the progress of treatment with ECT.     

Bilateral Laparoscopic Adrenalectomy for Adrenocorticotropic Dependent Cushing's Syndrome

Purpose

We report our experience with bilateral laparoscopic adrenalectomy for total adrenal ablation in patients with Cushing's syndrome.

Materials and Methods

Four women (mean age 63 years) with Cushing's syndrome secondary to nonlocalized ectopic adrenocorticotropic hormone production in 3 and pituitary microadenoma after failed transsphenoidal ablation in 1 underwent bilateral transabdominal laparoscopic adrenalectomy. Preoperatively risk was III or IV according to the American Society of Anesthesiologists classification.

Results

In all cases bilateral laparoscopic adrenalectomy was successfully performed. Operative time ranged from 375 to 475 minutes (mean 404) and mean blood loss was 162 cc. All patients resumed oral intake on postoperative day 1, mean number of postoperative parentral narcotic doses was 2.25 and mean postoperative hospital stay was 5.75 days (range 3 to 8). Complications included an abdominal wall hematoma. All patients resumed baseline activity by postoperative day 14.

Conclusions

Our experience in 4 cases of Cushing's syndrome suggests that bilateral laparoscopic adrenalectomy is a safe and effective alternative to open adrenalectomy. Further experience with this technique will likely decrease operative time, and confirm the benefit of a decreased hospital stay and convalescence.     

Mediator function of the human Rad51B–Rad51C complex in Rad51/RPA-catalyzed DNA strand exchange

Five Rad51-like proteins, referred to as Rad51 paralogs, have been described in vertebrates. We show that two of them, Rad51B and Rad51C, are associated in a stable complex. Rad51B-Rad51C complex has ssDNA binding and ssDNA-stimulated ATPase activities. We also examined the functional interaction of Rad51B-Rad51C with Rad51 and RPA. Even though RPA enhances Rad51-catalyzed DNA joint formation via removal of secondary structure in the ssDNA substrate, it can also compete with Rad51 for binding to the substrate, leading to suppressed reaction efficiency. The competition by RPA for substrate binding can be partially alleviated by Rad51B-Rad51C. This recombination mediator function of Rad51B-Rad51C is likely required for the assembly of the Rad51-ssDNA nucleoprotein filament in vivo.     

Clinical predictors of renal mass pathological features

Study Type – Therapy (case series) Level of Evidence 4 What’s known on the subject? and What does the study add? Widespread use of abdominal imaging has changed the landscape of kidney lesions with an increase in serendipitously detected small renal masses (SRMs) that represent a new epidemiological entity that requires further understanding and potentially reconsideration of current treatment schemes. We identified specific preoperative factors associated with renal mass pathological features, and specifically with an increased risk of malignant, potentially aggressive disease. These factors should be considered when evaluating potential candidates for active surveillance and ablative techniques.

OBJECTIVE

? To evaluate the influence of radiographic tumour size and other preoperative variables on the pathological characteristics of the lesion to determine the distribution of pathological features and assess preoperative risk factors for potentially aggressive versus probably indolent renal lesions.

PATIENTS AND METHODS

? Retrospective review of records for 768 patients who underwent surgery for single, sporadic renal mass between 2000 and 2008 in a tertiary academic institution. ? Demographic, radiographic and pathological variables were recorded and analysed with regression analyses for risk factors for potentially aggressive pathological features (malignant pathology, high Fuhrman grade, lymphovascular invasion and extracapsular extension).

RESULTS

? Malignancy was pathologically confirmed in 628 (81.8%) specimens. ? Radiographic size was significantly associated with malignancy (versus benign pathology; OR = 1.13, P= 0.001), high Fuhrman grade (OR = 1.21, P < 0.0001), vascular invasion (OR = 1.19, P < 0.0001) and extracapsular extension (OR = 1.23, P < 0.0001). ? Age, symptomatic presentation, solid appearance and radiographic size were independent predictors of potentially aggressive disease, whereas for male gender (OR = 1.43, P= 0.062) a trend toward statistical significance was noted.

CONCLUSIONS

? Age, male gender, radiographic size and appearance, as well as symptomatic presentation, are associated with an increased risk of malignant, potentially aggressive disease. ? These factors should be considered when evaluating management options for a solitary enhancing renal mass.     

Age adjusted prostate specific antigen and prostate specific antigen velocity cut points in prostate cancer screening

PURPOSE: We identified age adjusted prostate specific antigen and prostate specific antigen velocity cut points for prostate cancer biopsy. MATERIALS AND METHODS: A cohort of 33,643 men was retrieved from the Duke Prostate Center database. Of this group 11,861 men with 2 or more prostate specific antigen values within 2 years were analyzed for age adjusted prostate specific antigen and prostate specific antigen velocity performance in cancer risk assessment using a receiver operating characteristic curve. RESULTS: In the 11,861 men prostate cancer prevalence was 273 (8.0%), 659 (14.9%) and 722 (17.9%) in the groups of men 50 to 59 years old, 60 to 69 and 70 years old or older. In prostate cancer groups median prostate specific antigen and prostate specific antigen velocity in men 50 to 59 vs 70 years old or older were 5.6 vs 8.1 ng/ml and 1.37 vs 1.89 ng/ml per year (<0.0001). In men 50 to 59 years old the sensitivity and specificity were 82.1% and 80.7% at prostate specific antigen 2.5 ng/ml, and 84.3% and 72.4% at prostate specific antigen velocity 0.40 ng/ml per year, higher than those in men 70 years old or older at prostate specific antigen 4.0 ng/ml or prostate specific antigen velocity 0.75 ng/ml per year. Decreasing the prostate specific antigen cut point to 2.0 ng/ml and the prostate specific antigen velocity cut point to 0.40 ng/ml per year in men 50 to 59 years old improved the cancer detection rate but decreased the positive predictive value. CONCLUSIONS: Current biopsy guidelines (prostate specific antigen 4.0 ng/ml or greater, or prostate specific antigen velocity 0.75 ng/ml or greater per year) underestimated cancer risk in men 50 to 59 years old. Prostate specific antigen and prostate specific antigen velocity cut points should be age adjusted. In men 50 to 59 years old prostate specific antigen and prostate specific antigen velocity cut points could be decreased to 2.0 ng/ml and 0.40 ng/ml per year, respectively. Factors of age, sensitivity, specificity, positive predictive value and cancer prevalence are critical for obtaining the desired balance between cancer detection and negative biopsy.     

The effect of frequency doubled double pulse Nd:YAG laser fiber proximity to the target stone on transient cavitation and acoustic emission

PURPOSE: Scant information has been published describing the effect of laser fiber distance from the stone target on the mechanism of calculus fragmentation. Using high speed photography and acoustic emission measurements we characterized the impact of laser fiber proximity on stone comminution. We evaluated the effect of laser fiber distance from the stone target on resultant cavitation bubble formation and shock wave generation. MATERIALS AND METHODS: Stone fragmentation was assessed using a FREDDY (frequency doubled double pulse Nd:YAG) (World of Medicine, Orlando, Florida) laser and a holmium laser. The FREDDY laser was operated using a 420 microm fiber at an output energy of 120 and 160 mJ in single and double pulse settings, and a pulse repetition rate of 1 Hz. The holmium laser was operated using a 200 microm fiber at an output energy of 1 to 3 J and a pulse repetition rate of 1 Hz. The surface of a 1 cm square BegoStone (Bego, Bremen, Germany) attached to an X-Y-Z translational stage was aligned perpendicular to the laser fiber, which was immersed in a Lucite tank filled with water at room temperature. An Imacon 200 high speed camera was used to capture transient cavitation bubbles at a framing rate of up to 1,000,000 frames per second. Acoustic emission signals associated with shock waves generated during the rapid expansion and collapse of the cavitation bubble were measured using a 1 MHz focused ultrasound transducer. RESULTS: At laser fiber distances of 3.0 mm or less cavitation bubbles and shock waves were observed with the FREDDY laser. In contrast to the holmium laser, the bubble size and shock wave intensity of the FREDDY laser was inversely related to the fiber-to-stone distance over the range tested (0.5 to 3.0 mm). CONCLUSIONS: While bubble size was noted to increase with a larger stone-to-fiber distance using the holmium laser, to consistently generate cavitation bubbles and shock waves using the FREDDY laser the laser fiber should be operated within 3.0 mm of the target stone. These findings have significant implications during clinical laser stone fragmentation.