Effects of ovarian hormones and aging on respiratory sinus arrhythmia and breathing patterns in women

We investigated the effect of ovarian hormones and aging on breathing pattern [pulmonary minute ventilation (V(E))], tidal volume (V(T)), breathing frequency (F(b)), and respiratory sinus arrhythmia (RSA) in women. Recordings of V(E) and electrocardiogram (ECG) were obtained from 23 healthy women (10 premenopausal, 13 postmenopausal) under resting, isocapnic hypoxia (IH), and euoxic hypercapnia (EH) conditions. Premenopausal women were tested on three different days, each day corresponding to a specific phase of the menstrual cycle (follicular, mid-cycle, and luteal); postmenopausal women (PMW) were tested on 1 day only. On each test day, subjects were challenged with IH and EH. The order of the two tests was randomized and separated by at least 1 hour. Due to the low F (b) of several PMW, the band limits for RSA analysis had to be adjusted. The spectral coherence between respiratory flow and ECG RR-interval was used to determine the spectral band. Within the spectral band, there was a consistent phase relationship between the two variables where high values of spectral coherence indicate a well-defined phase relationship between respiratory flow and RR-interval variability. The main findings in this study for RSA are fourfold. First, RSA did not change with different levels of ovarian hormones (progesterone, serum 17beta-estradiol) during the menstrual cycle. Second, RSA was not influenced by hormone replacement therapy. Third, RSA did not change with age. Fourth, RSA did not change with IH and EH-induced changes in breathing patterns. Finally, high individual variability of average RR-interval change per breath was found.     

Mitral valve prolapse: From syndrome to disease

Mitral valve prolapse (MVP) is due to a heterogeneous group of conditions that may affect the mitral valve or the mitral valve apparatus. Although MVP may progress later in life to frank mitral insufficiency requiring mitral valve repair or may predispose to bacterial endocarditis, in most cases it is a benign, idiopathic condition without serious consequences. However, many investigators have documented that MVP is often associated with a constellation of signs and symptoms, which appear to constitute a distinct syndrome. These associated findings include autonomic dysfunction, frequent complaints of chest pain, palpitations, orthostasis, fatigue, dyspnea on exertion and anxiety. Although the risk of significant myocardial dysfunction or bacterial endocarditis appears to be related to patient sex, age and the severity of valvular prolapse and insufficiency, there appears to be little or no relations between the extent of prolapse and the degree of autonomic dysfunction or the severity of symptoms of chest pain, palpitations, dyspnea on exertion and anxiety. The development of uniform diagnostic standards for mental disorders has helped to make it possible to identify several related entities, including generalized anxiety disorder, panic disorder and agoraphobia; patients with these disorders frequently somatize their anxiety and complain of many symptoms which may be seen in patients with MVP. Although several studies have reported an increased frequency of MVP in patients with anxiety disorders, recent studies suggest that the conditions are not linked. Iatrogenic cardiac neurosis is common in both groups of patients. Anxiety disorders and MVP, both common conditions, may occur concommitantly and thereby produce a complicated clinical picture whose end result may be one of long term physical and emotional impairment. It is important for general internists and cardiologists to recognize the often protean manifestations of the anxiety disorders, and to utilize psychiatric consultation as necessary, and conversely, for psychiatrists to recognize how common and usually benign MVP is and to be able to reassure their patients or, when necessary, to send them for cardiac consultation.     

Identification of a new allele, HLA-DRB1*1360, on a DRB5 haplotype in a Brazilian individual

The application of DNA-based methods for human leukocyte antigen (HLA) genotyping has revealed an ever-increasing degree of polymorphism within the HLA-DRB loci and has resulted in the discovery of new alleles. We have identified a new DRB1 allele that was subsequently named DRB1*1360 by the WHO Nomenclature Committee. This allele is unusual for a DRB1*13 allele, as it is present on a DRB5 haplotype rather than the normal DRB3 haplotype found in association with DRB1*13 alleles.     

Expression and modulation of Rho kinase in human pregnant myometrium

There is little information outlining the role of Rho kinase, RhoA, and calcium sensitization in regulation of human uterine contractility during pregnancy. The aims of this study were to investigate the expression of RhoA, and the Rho kinases ROCK I and ROCK II in human pregnant myometrium, to evaluate the effects of Rho kinase inhibition on pregnant human myometrial contractility in vitro, and to compare these effects with those of the calcium channel blocker nifedipine. RT-PCR using primers for RhoA, ROCK I and ROCK II was performed on mRNA isolated from human pregnant myometrium. Isometric recording was performed in isolated myometrial strips obtained at Caesarean section. The effects of the Rho kinase inhibitor Y-27632 (1 nmol/l to 10 mmol/l), and nifedipine (1 nmol/l to 10 mmol/l), on oxytocin (0.5 nmol/l) induced contractions were measured and compared. Expression of RhoA, ROCK I and ROCK II mRNA was identified in human pregnant myometrium (n = 3). Y-27632 exerted a potent relaxant effect on myometrial contractility with a pD(2) value (+/- SEM) of 7.63 +/- 0.38 (n = 6). The maximum net relaxant effect (+/- SEM) was 72.3 +/- 6.1% (n = 6). Corresponding values for nifedipine were 7.24 +/- 0.48 (n = 6; P = 0.469) and 93.40 +/- 3.1% (n = 6; P = 0.028). Rho A/Rho kinase-mediated calcium sensitization may play role in the physiology of human parturition, and pharmacological inhibition of this pathway may therefore provide a novel approach to tocolysis for pre-term labour.     

Circuit factors in the high cardiac output of sepsis

The increase of cardiac output (CO) in sepsis must be matched by an increase in venous return. Our goal was to determine which of the determinants of venous return are responsible in volume-loaded and nonvolume-loaded pigs with endotoxemia. The determinants include stressed volume, venous compliance (C_v), venous resistance (RVR) and right atrial pressure (Pra). We also tested the effect of the nitric oxide (NO) synthase inhibitor, N^ω-nitro- -arginine-methyl ester (L-NAME) after the hemodynamics with endotoxin stabilized.

Pigs were anesthetized and mechanically ventilated. We measured CO by thermodilution, mean circulatory filling pressure (MCFP) by inflating a balloon in the right atrium, blood volume by dye dilution, and C_v by rapid blood infusions. RVR was calculated from MCFP - Pra/CO). After baseline measurements, we infused 10 μg/(kg x h⁻¹) of Escherichia coli endotoxin. Eight animals also received 30 mL × kg⁻¹ of dextran over the 2 hours (volume treated), and seven did not (no volume). After 2 hours we injected 25 mg × kg⁻¹ of the NO synthase inhibitor, L-NAME, and repeated the measurements.

In volume-treated animals, CO increased from 3.9 ± 0.7 to 5.4 ± 0.8 L x min⁻¹ (P < .05), and blood pressure (BP) fell from 118 ± 9 to 76 ± 12 mmHg. MCFP rose, and there was no change in RVR or C_v, whereas capacitance increased (ie, right shift of pressure-volume curve). Cardiac function (ie, Starling curve) did not change. In no-volume animals, CO fell from 4.47 ± 0.64 to 2.50 ± 0.86 L × min⁻¹, BP from 114 ± 10 to 9 13 mmHg and MCFP fell. Systemic vascular resistance did not change. Cardiac function was markedly depressed, and the heart rate increased from 143 ± 13 to 203 ± 30 beats x min⁻¹. L-NAME restored BP in both groups but also increased RVR and depressed cardiac function.

Changes in vascular tone during endotoxemia are dependent on volume status. The increased cardiac output in volume-treated septic animals occurred because of an increase in stressed volume due to the volume given in combination with a dilated vasculature. L-NAME restored arterial tone but decreased CO because of a rise in RVR and decrease in cardiac function.     

Identification of aortic thrombus by magnetic resonance imaging

The unique properties of magnetic resonance imaging result in the potential to differentiate various components of the diseased arterial wall. In this article four cases are presented in which magnetic resonance imaging showed mural aortic thrombus and its anatomic relationship to the visceral and renal arteries. Once thrombus is identified and localized specific operative strategies can be undertaken to prevent recurrent embolic events and/or avoid perioperative thromboembolic complications.     

George Peters Award: How does breast-specific gamma imaging affect the management of patients with newly diagnosed breast cancer?

Background

We sought to determine the number of patients with known breast cancer who were found to have an additional, mammographically occult lesion detected on breast-specific gamma imaging (BSGI).

Methods

An institutional review board-approved review of all patients who underwent BSGI at Beth Israel Medical Center from 2006 to 2008 was performed.

Results

A total of 82 patients underwent BSGI for newly diagnosed breast cancer. Of these, 18 had an additional abnormality, and 17 were biopsied. There were 4 cases of invasive ductal carcinoma, 1 invasive lobular carcinoma, 1 ductal carcinoma in situ, 1 lobular carcinoma in situ, 2 papillomas, and 8 benign biopsies. One patient proceeded directly to mastectomy and an area of ductal carcinoma in situ was found, corresponding to the BSGI.

Conclusions

In our study group, 22% of patients had a surgical change in management based on BSGI findings. BSGI detected additional carcinoma in 9%. BSGI plays an important role in the clinical management of patients with known breast cancer.     

Tubulin binding blocks mitochondrial voltage-dependent anion channel and regulates respiration

Regulation of mitochondrial outer membrane (MOM) permeability has dual importance: in normal metabolite and energy exchange between mitochondria and cytoplasm and thus in control of respiration, and in apoptosis by release of apoptogenic factors into the cytosol. However, the mechanism of this regulation, dependent on the voltage-dependent anion channel (VDAC), the major channel of MOM, remains controversial. A long-standing puzzle is that in permeabilized cells, adenine nucleotide translocase (ANT) is less accessible to cytosolic ADP than in isolated mitochondria. We solve this puzzle by finding a missing player in the regulation of MOM permeability: the cytoskeletal protein tubulin. We show that nanomolar concentrations of dimeric tubulin induce voltage-sensitive reversible closure of VDAC reconstituted into planar phospholipid membranes. Tubulin strikingly increases VDAC voltage sensitivity and at physiological salt conditions could induce VDAC closure at <10 mV transmembrane potentials. Experiments with isolated mitochondria confirm these findings. Tubulin added to isolated mitochondria decreases ADP availability to ANT, partially restoring the low MOM permeability (high apparent K_m for ADP) found in permeabilized cells. Our findings suggest a previously unknown mechanism of regulation of mitochondrial energetics, governed by VDAC and tubulin at the mitochondria–cytosol interface. This tubulin–VDAC interaction requires tubulin anionic C-terminal tail (CTT) peptides. The significance of this interaction may be reflected in the evolutionary conservation of length and anionic charge in CTT throughout eukaryotes, despite wide changes in the exact sequence. Additionally, tubulins that have lost significant length or anionic character are only found in cells that do not have mitochondria.     

Predictors of success after bilateral epididymovasostomy performed during vasectomy reversal: A multi-institutional analysis

IntroductionVasectomy reversal (VR) represents an excellent option for paternity in men who desire to expand their family following vasectomy. Traditional VR via vasovasostomy has a success rate upwards of 90%^1,2 but when sperm or sperm parts are not present in vasal fluid, epididymovasostomy (EV) must be performed instead. Our objective was to determine which factors influence success after bilateral EV.MethodsA prospectively maintained database with data from the U.S. and Canada was used to identify men who underwent bilateral EV at time of VR. Success was defined as motile sperm in any postoperative semen analyses. Multivariable logistic regression was used to identify predictors of success.ResultsA total of 200 men had at least one postoperative semen analysis, and 171 men were included in the analysis. Average age was 44.7 years, with average followup of seven months. Median time elapsed between vasectomy and EV was 15 years (interquartile range [IQR] 10–18). Overall success rate was 50%. Despite the study being adequately powered, factors such as years since vasectomy (odds ratio [OR] 1.01, confidence interval [CI] 0.95–1.06), age (OR 0.96, CI 0.91–1.01), intraoperative presence of motile sperm (OR 0.81, CI 0.41–1.62), and epidydimal fluid characteristics did not predict success.ConclusionsBilateral EV at time of VR is successful in 50% of cases in a multi-institutional, North American cohort. Microsurgeons can be reassured that neither time elapsed nor epididymal fluid characteristics negatively impact success rates as long as sperm or sperm parts are present. Surgeons performing VR should be comfortable and prepared to perform EV if indicated.