Rapid glucocorticoid mediation of suppressed testosterone biosynthesis in male mice subjected to immobilization stress

Physical and psychosocial stress challenge homeostasis, increasing glucocorticoid secretion (in rodents, corticosterone [CORT]) while decreasing testosterone (T) levels. The dynamics of stress-induced changes in T, CORT, and luteinizing hormone (LH) concentrations in mice have not been investigated previously. In particular, it remains to be established whether there is a rapid effect of CORT that is directly mediated by glucocorticoid receptors (GRs) in the testis. Therefore, serum and intratesticular T, serum CORT, and LH levels were measured during acute immobilization (IMO) stress, using the C57BL/6 strain of mice. The effects of testicular GR blockade were investigated by administration of the GR antagonist, RU486, via intratesticular (IT) or intraperitoneal (IP) injection. CORT levels increased in stressed males starting at 15 minutes, reaching a fivefold higher plateau by 1 hour compared with controls (P < .01). Conversely, starting from 30 minutes on, both serum and intratesticular T levels decreased in stressed males to 30% and 8% of control values, respectively, by 6 hours (P < .01). In contrast, LH was unchanged by IMO stress for up to 6 hours. Intratesticular treatment with RU486 partially prevented the IMO-induced decline in T levels. CORT treatment reduced intracellular cyclic adenosine monophosphate (cAMP) content in Leydig cells by 15 minutes and T production by 30 minutes in vitro. We conclude that 1) the rapid changes in T suggest a suppression of T biosynthesis by glucocorticoid through a nongenomic mechanism, lowering the production of cytoplasmic cAMP; 2) changes in gonadotropic stimulation of Leydig cells are unlikely to explain the suppression of T levels during acute stress; and 3) the results are consistent with a direct inhibitory action of CORT on Leydig cells.     

Possible pathologic involvement of receptor for advanced glycation end products (RAGE) for development of encapsulating peritoneal sclerosis in Japanese CAPD patients

Encapsulating peritoneal sclerosis (EPS) is a serious complication of PD. The cause(s) of EPS are unknown but may include peritonitis and long duration of PD treatment. However, EPS may also develop in some patients without a history of peritonitis or with rather short duration of PD therapy. It has been suggested that an increasing peritoneal solute transport rate (PSTR) as a function of time on PD treatment is a risk factor for EPS development after transfer to hemodialysis, and that high PSTR is associated with an increased peritoneal microvessels surface area. Other putative mechanisms might include advanced glycated end products (AGE) and their receptors, RAGE. The purpose of this study was to investigate genetic variations in PD patients developing EPS in comparison to PD patients without EPS. SNPs in genes related to angiogenesis as well as RAGE were analyzed. Twenty patients (M/F: 12/8, mean age at start of PD 42.2 years, mean duration of PD 8.4 years) who were diagnosed as EPS during the period 1982 - 2002 at Jikei University Hospital and a matched control group (n = 20) of nonEPS PD patients were studied. The following 5 SNPs were analyzed: VEGF 936 C/T, ecNOS -786 T/C, 298 Glu/Asp, and RAGE -374 T/A, and -429 T/C. The SNPs were analyzed by the pyrosequencing method. The C allele (T/C and C/C) in the RAGE -429T/C genotype was not found in any of the EPS patients (EPS, T/T: 20/20 (100%), nonEPS, T/T: 15/20 (75%), T/C: 4/20 (20%), C/C: 1/2 0(5%), nonC allele vs C allele, p = 0.013), although every allele was found in other SNPs. We conclude that these preliminary data show that whereas genotypes directly related to angiogenesis did not differ between EPS and nonEPS patients, it is noteworthy that no patients in the EPS group had a C allele in the RAGE -429T/C genotype. This might indicate a possible genetic contribution to the development of EPS that is related to RAGE.     

The impact of dietary oxalate on kidney stone formation

The role of dietary oxalate in calcium oxalate kidney stone formation remains unclear. However, due to the risk for stone disease that is associated with a low calcium intake, dietary oxalate is believed to be an important contributing factor. In this review, we have examined the available evidence related to the ingestion of dietary oxalate, its intestinal absorption, and its handling by the kidney. The only difference identified to date between normal individuals and those who form stones is in the intestinal absorption of oxalate. Differences in dietary oxalate intake and in renal oxalate excretion are two other parameters that are likely to receive close scrutiny in the near future, because the research tools required for these investigations are now available. Such research, together with more extensive examinations of intestinal oxalate absorption, should help clarify the role of dietary oxalate in stone formation.     

Percutaneous Imaging–Guided Radiofrequency Ablation in Patients With Colorectal Pulmonary Metastases: 1-Year Follow-Up

Background: We assessed the safety and evidence of efficacy of radiofrequency ablation (RFA) for colorectal lung metastases with follow-up to 1 year.Methods: Twenty-three patients had percutaneous RFA for 52 colorectal pulmonary metastases under fluoro-computed tomography (CT). Patients received intravenous conscious sedation and local analgesia with routine hospitalization and monitoring for 24 hours after RFA. Patients had CT scanning at 1 month and then every 3 months, with serum carcinoembryonic antigen assessment monthly and every 3 months.Results: All ablations were technically successful. Tumor diameter ranged from .3 to 4.2 cm. Pneumothorax occurred in 43% (10 of 23) of patients. Six patients required intercostal chest drain placement. Six patients had a second RFA, four for new lesions and two for re-treatment of a previously treated lesion. The median admission was 2.0 days (range, 1–9 days). The median follow-up was 428 days (range, 173–829 days); data are reported to 1 year in this article. Five patients died at 5, 6, 8, 8, and 12 months after RFA from extrapulmonary (n = 1) or widespread (n = 4) disease. One patient developed a malignant pleural effusion at 6 months after RFA. Cavitation was seen in nine treated lesions (17%); all resolved with scar tissue contraction by 12 months. Eighteen patients with CT scan follow-up at 1 year have 40 lesions classified as disappeared (n = 17), decreased (n = 5), stable/same size (n = 4), or increased (n = 14).Conclusions: Percutaneous imaging–guided RFA of multiple colorectal pulmonary metastases is a minimally invasive treatment option with modest morbidity. A significant proportion of patients show good evidence of successful local control at 1 year.     

Complications following placement or extraction of endovascular pacemaker and defibrillator leads--cardiothoracic surgical intervention: case reports

Complications related to the insertion or removal of permanent pacemakers and implantable cardiac defibrillators are rare events. However, when adverse events occur, their severity may be life threatening. Rapid recognition of a problem followed by prompt consultation with a cardiothoracic surgeon is necessary to stabilize potentially catastrophic events. The immediate availability of surgical instruments as well as a formalized algorithm for management is necessary to control hemorrhagic situations. Four case reports illustrate these points.     

Is center specific implantation volume a predictor of clinical outcomes with mechanical circulatory support?

This study examined the relationship between implant center volumes and survival rate for implantation of mechanical circulatory support (MCS) devices. Using the Novacor left ventricular assist system (LVAS) Registry, the study cohort consisted of 1,348 patients with established outcomes from 97 centers stratified by the implant center volume: 1-10 implants (n = 199, 65 centers), 11-25 implants (n = 189, 12 centers), 26-50 implants (n = 445, 13 centers), and more than 51 implants (n = 515, 7 centers). Regression and correlation analyses were performed. Regression analysis found a negative impact on survival for centers performing 1-10 implants, with an odds ratio of 1.73 (95% confidence interval, 1.28-2.34; p < 0.001). Composite results from the first 10 implants of each larger volume center were then compared with the group with 1-10 implants, demonstrating that centers with larger volumes had superior results, even in the early patient experience (61% versus 46% transplanted/weaned, p < 0.001). However, when annualized outcomes (i.e., outcomes by calendar year) were determined for each center, no significant correlation was found between the outcomes and annualized frequency of implantation (R2 = 0.003, n = 422). Although the total number of implants performed at a specific center appeared to impact clinical outcomes, no correlation was found between annualized frequency of implant and clinical outcome.     

Salt appetite: a neurohormonal viewpoint

Sodium is a key component of virtually every mammalian physiological function. As such, many animals have evolved specialized mechanisms for detecting and ameliorating deficits in body sodium, including the development of a robust salt appetite, where normally aversive concentrations of salt are readily consumed during periods of sodium deprivation. Here, we review research spanning more than half a century focusing on the condition and detection of sodium deprivation, the important and unique function of taste in sodium homeostasis, as well as the neurohormonal interactions leading to behaviors aimed at the reversal of sodium deficits. Based on the present literature, we propose a model for the interaction of forebrain and brainstem systems for the mediating circuitry giving rise to salt appetite and discuss the remarkable parallel between what is known about the neurohormonal interactions that regulate salt appetite and those involved in energy homeostasis.