Angiotensin II increases parathyroid hormone-related protein (PTHrP) and the type 1 PTH/PTHrP receptor in the kidney

Angiotensin II (AngII) participates in the pathogenesis of kidney damage. Parathyroid hormone (PTH)-related protein (PTHrP), a vasodilator and mitogenic agent, is upregulated during renal injury. The aim of this study was to investigate the potential relation between AngII and PTHrP system in the kidney. Different methods were used to find that both rat mesangial and mouse tubuloepithelial cells express PTHrP and the type 1 PTH/PTHrP receptor (PTH1R). In these cells, AngII increased PTHrP mRNA and protein production. In contrast, PTH1R mRNA was increased in mesangial cells and downregulated in tubular cells, but its protein levels were unmodified in both cells. AT(1) antagonist, but not AT(2), abolished AngII effects on PTHrP/PTH1R. The in vivo effect of AngII was further investigated by systemic infusion (a low dose of 50 ng/kg per min) into normal rats. In controls, PTHrP immunostaining was mainly detected in renal tubules. In AngII-infused rats, PTHrP staining increased in renal tubules and appeared in the glomerulus and the renal vessels. After AngII infusion, PTHR1 staining was markedly increased in all these renal structures at day 3 but remained elevated only in tubules at day 7. The AT(1) antagonist, but not the AT(2), significantly diminished AngII-induced PTHrP and PTHR1 overexpression in the renal tissue, associated with a decrease in tubular damage and fibrosis. The results indicate that AngII regulates renal PTHrP/PTH1R system via AT(1) receptors. These findings demonstrate that PTHrP upregulation occurs in association with the mechanisms of AngII-induced kidney injury.     

Arterial switch operation with a single coronary artery

OBJECTIVE: Our purpose was to evaluate the impact of coronary pattern on survival and reintervention in patients who underwent the arterial switch operation with a single coronary artery. METHODS: We conducted a retrospective analysis of 53 patients with a single coronary artery who underwent the arterial switch operation between 1983 and 2000 at Children's Hospital Boston. Recent follow-up information was obtained for 40 of the 46 long-term survivors (mean follow-up 7.3 +/- 4.5 years). RESULTS: Thirty-five patients had a single right coronary artery, with the left coronary artery posterior to the pulmonary artery in 27. Eighteen patients had a single left coronary artery (16 with the right coronary artery anterior to the aorta). Six of 7 total patients who died had a single right coronary artery; all died before 1992. There were 5 early deaths, all with a single right coronary artery, with 4 deaths due to coronary malperfusion. Survivals for all patients were 91% at 6 months and 87% at 1, 5, and 10 years after the arterial switch operation. Survival figures were lower for patients having a single right ostium with the left main coronary artery posterior to the pulmonary artery compared with all other subtypes (P =.02, log-rank test). Seven patients had reintervention, 4 because of right ventricular outflow tract obstruction, 1 for heart transplantation, 1 for mitral valve repair and 1 for pacemaker implantation. Freedom from reintervention for all patients was 96% at 6 months, 92% at 1 year, 86% at 5 years, and 82% at 10 years after the arterial switch operation, with lower rates for patients having a single left ostium with the right coronary artery anterior to the aorta (P =.0003, log-rank test). CONCLUSIONS: In the current era, the arterial switch operation with a single coronary artery can be performed safely irrespective of the coronary anatomy. Risk of reintervention is higher in patients having a single left ostium with the right coronary artery anterior to the aorta.     

Improving results of the modified Fontan operation in patients with heterotaxy syndrome

BACKGROUND: Historically the Fontan operation in patients with single ventricle heterotaxy syndrome and atrial isomerism has been associated with high mortality. We studied whether recent modifications of the surgical technique have improved outcome. METHODS: A retrospective review of 135 patients with heterotaxy syndrome who underwent a Fontan operation between 1981 and 2000 was performed. RESULTS: There were 93 patients with right isomerism and 42 with left isomerism. Anomalies of venous return included 25 patients with extracardiac pulmonary venous connection (19%) and 37 patients with an interrupted inferior vena cava (27%). Thirty-six patients (27%) had at least moderate atrioventricular valve regurgitation. The type of Fontan procedure included 17 patients with an atriopulmonary Fontan connection, 67 with a lateral tunnel modification, 19 with an intraatrial tube graft, 25 with an extracardiac tubegraft, and 7 with an intra-extra atrial tube graft. A fenestration was placed in 93 patients (78%). Early mortality was 19% before 1991, 3% since 1991, and no patient has died early since 1993. Ten-year survivals were 70% for Fontan operations before 1990 and 93% for Fontan operations after 1990. Thirty-two patients (23%) had prolonged pleural effusions. Risk factors for death included anomalous pulmonary venous connection (p = 0.02) and higher preoperative pulmonary vascular resistance (p = 0.002). Sixty-two patients (47%) had some form of early postoperative arrhythmia. At 10 years, freedom from late bradyarrhythmia and late tachyarrhythmia were 78% and 70%, respectively. Preoperative arrhythmias, older age at operation, and anatomic features were each independent predictors of late arrhythmia. CONCLUSIONS: The Fontan operation can now be performed in patients with heterotaxy syndrome with excellent survival. However, morbidity in terms of postoperative arrhythmias and prolonged pleural effusions remains significant. Fontan staging, appropriate choice of Fontan modification, aggressive treatment of concomitant malformations, and use of a baffle fenestration contribute to improved outcome.     

Elderly patients on chronic hemodialysis: Effect of the secondary hyperparathyroidism on the hemoglobin level

In patients on chronic hemodialysis (CHD)hyperparathyroidism (HPTH) is associated withanemia and resistance to erythropoietin (EPO). This study included 86 CHD elderly pts (meanage 74.8 y, mean time on CHD = 50.5 mos); theywere divided into two groups: I (n = 31) – PTH> 250 pg/mL and II (n = 55) – PTH < 250 pg/mL.All these patients had been on CHD for> 6 mos. No differences were found betweengroups in respect to age, sex distribution andtime on CHD. The levels of creatinine, BUN, Ca,Al, Fe, albumin and ferritin were similar.Group I had a higher P level (5.4 vs 4.3 mg/dL,p = 0.001) and Ca x P (53.5 vs 43.7, p =0.009). Also the Hct (31 vs 33.5%, p = 0.008)and the Hb (10.4 vs 11.2 g/dL, p = 0.009) values werelower in Group I. The EPO dose (88 vs 85 U/kg/week,p = ns) was similar in the two groups.Our data showed that elderly patients with HPTHhave lower Hct and Hb levels than do youngerpatients on a similar EPO dose. We believethese patients will need a more aggressivetherapy with calcitriol.     

Anteromedial portal versus transtibial drilling techniques in ACL reconstruction: a blinded cross-sectional study at two- to five-year follow-up

Drilling of the femoral tunnel with the transtibial (TT) technique is widely used in bone-patellar tendon-bone (BPTB) anterior cruciate ligament (ACL) reconstruction. Recent studies suggest higher knee stability with the use of the anteromedial portal (AMP). The purpose of this study was to compare functional and clinical outcomes of BPTB ACL reconstruction using the TT or the AMP technique for drilling the femoral tunnel. All ACL reconstructions between January 2003 and April 2006 were approached for eligibility. Forty-seven patients met inclusion criteria (21 TT group and 26 AMP group). Blinded assessments of IKDC score, knee stability and range of motion, one-leg hop test, mid-quadriceps circumference, VAS for satisfaction with surgery, Lysholm and Tegner scores, and SF-12 questionnaire were obtained for both groups. Data on preoperative and postoperative surgical timing were retrospectively reviewed through the charts. The AMP group demonstrated a significantly lower recovery time from surgery to walking without crutches (p < 0.01), to return to normal life (p < 0.03), to return jogging (p < 0.03), to return training (p < 0.03), and to return to play (p < 0.03). Knee stability values measured with KT-1000, Lachman test, pivot-shift sign, and objective IKDC score assessments were significantly better for the AMP compared to TT group (p < 0.002, p < 0.03, p < 0.02, p < 0.015, respectively). No differences were found for VAS for satisfaction with surgery, Lysholm, Tegner, and SF-12 between both groups. The use of the AMP technique significantly improved the anterior-posterior and rotational knee stability, IKDC scores, and recovery time from surgery compared to the TT technique.     

'Functional' neuroanatomical tract tracing: analysis of changes in gene expression of brain circuits of interest

Neuroanatomical tracing when considered as an isolated method produces relatively straightforward answers. Although single-, double- or even triple-tracing paradigms produce valuable data on the organization of brain circuits, the final outcome often is too simplistic since it is not possible to elucidate the activity of these circuits. In this regard, emerging technologies contribute with additional information about the status of neuronal circuits. The laser-guided capture microdissection microscope (LCM) allows the accurate dissection of small brain areas under the microscope that could be further analyzed for gene expression or proteomics. In order to elucidate the gene expression of a given circuit of interest, we have developed a combination of methods comprising (i) fluorescent non-radioactive in situ hybridization for the detection of vGLUT2 mRNA expression combined with retrograde tracing with Fluoro-Gold (FG; analysis performed under the confocal microscope) and (ii) laser-guided capture microdissection of brain areas containing neurons retrogradely labeled with FG followed by the measurement of changes in mRNA levels encoding for vGLUT2 by real-time PCR. Our goal was to detect changes in gene expression of the thalamostriatal pathway in unilaterally 6-OHDA lesioned rats. Taking advantage of this procedure, we found a three-fold increase in vGLUT2 mRNA expression within thalamic neurons projecting to the dopamine-depleted striatum when compared with the activity of the thalamic neurons innervating the control striatum.     

The generalized quadratic knapsack problem. A neuronal network approach.

The solution of an optimization problem through the continuous Hopfield network (CHN) is based on some energy or Lyapunov function, which decreases as the system evolves until a local minimum value is attained. A new energy function is proposed in this paper so that any 0-1 linear constrains programming with quadratic objective function can be solved. This problem, denoted as the generalized quadratic knapsack problem (GQKP), includes as particular cases well-known problems such as the traveling salesman problem (TSP) and the quadratic assignment problem (QAP). This new energy function generalizes those proposed by other authors. Through this energy function, any GQKP can be solved with an appropriate parameter setting procedure, which is detailed in this paper. As a particular case, and in order to test this generalized energy function, some computational experiments solving the traveling salesman problem are also included.     

Relative localizing value of amygdalo-hippocampal MR biometry in temporal lobe epilepsy

OBJECTIVES: The aims of the study were (i) to examine the localizing value of three MRI quantitative modalities (qMRI) currently used for the analysis of the hippocampus and amygdala in the context of pre-surgical screening and (ii) to propose a step-by-step protocol based on the sensitivity and performance of the different MR techniques. METHODS: Ninety-two adults with chronic mesial temporal lobe epilepsy (TLE) of which 28 underwent amygdalo-hippocampal resection, and 34 age-matched controls were included in the study. High-resolution qMRI was performed at 1.5 T, including a tilted T1-weighted 3D-dataset for volumetry and four-echoes T2 relaxometry (both for hippocampus and amygdala quantifications) and multi-voxel spectroscopy [NAA/(Cho+Cre)] (exclusively in the hippocampus). Individual qMRI data were compared with electroencephalography regarding the localization of the epileptogenic area, with the neuropathological data and with postoperative outcome. MRI pathology was defined based on 99% confidence ellipses. Ten controls were used to assess the quantitative MRI intra- and inter-observer variability for all variables. RESULTS: Volumetric measurements revealed unilateral damage in 77% of the patients, T2-relaxometry in 64% and spectroscopy in 53%. Additional measurements of the amygdalae (T2-relaxometry) allowed us to localize pathology that coexists with that of the hippocampus in 34%, and isolated unilateral amygdala damage in 8% of patients. Volumetry and T2-relaxometry (not spectroscopy) were associated with postoperative outcome, but accurate predictive models were computed based on hippocampal measures only. At least at 1-year follow-up, volumetry predicts outcome correctly in 100% of the cases, whilst T2-relaxometry classified 96.4% (27/28) of these patients. All operated patients had hippocampal sclerosis. CONCLUSIONS: Hippocampal structural damage is equivocally depicted by spectroscopy. For diagnostic and pre-operative evaluation, hippocampal volumetry and T2-relaxometry provide maximal accuracy. Amygdala quantifications are irrelevant in the pre-operative evaluation but may be useful for diagnostic purposes. Of the three qMRI modalities tested, T2-relaxometry provided the best balance between diagnosis accuracy and time-efficiency to lateralize a sclerotic lesion on the majority of the patients. Cases that remain undecided after T2-relaxometry may benefit from additional measurements based on hippocampal volumetry.     

Spinal Posture of Thoracic and Lumbar Spine and Pelvic Tilt in Highly Trained Cyclists

The aim of this study was to evaluate sagittal thoracic and lumbar spinal curvatures and pelvic tilt in elite and master cyclists when standing on the floor, and sitting on a bicycle at three different handlebar-hand positions. A total of 60 elite male cyclists (mean age: 22.95 ± 3.38 years) and 60 master male cyclists (mean age: 34.27 ± 3.05 years) were evaluated. The Spinal Mouse system was used to measure sagittal thoracic and lumbar curvature in standing on the floor and sitting positions on the bicycle at three different handlebar-hand positions (high, medium, and low). The mean values for thoracic and lumbar curvatures and pelvic tilt in the standing position on the floor were 48.17 ± 8.05°, -27.32 ± 7.23°, and 13.65 ± 5.54°, respectively, for elite cyclists and 47.02 ± 9.24°, -25.30 ± 6.29°, and 11.25 ± 5.17° for master cyclists. A high frequency of thoracic hyperkyphosis in the standing position was observed (58.3% in elite cyclists and 53.3% in master cyclists), whereas predominately neutral values were found in the lumbar spine (88.3% and 76.7% in elite and master cyclists, respectively). When sitting on the bicycle, the thoracic curve was at a lower angle in the three handlebar-hand positions with respect to the standing position on the floor in both groups (p < 0.01). The lumbar curve adopted a kyphotic posture. In conclusion, cyclists present a high percentage of thoracic hyperkyphotic postures in standing positions on the floor. However, thoracic hyperkyphosis is not directly related to positions adopted on the bicycle.

Key points

• This study evaluated thoracic and lumbar spinal curvatures and pelvic tilt in elite and master cyclists while standing and sitting on the bicycle.
• Elite and master cyclists showed a high frequency of thoracic hyperkyphosis and neutral lumbar lordosis in standing.
• Cyclists adopted a significantly lower thoracic kyphosis on the bicycle at the three handlebar positions analysed (upper, middle and lower handlebars) than in standing posture. The lumbar spine showed a kyphotic posture.
• The high percentage of standing thoracic hyperkyphosis in both groups of cyclists may be related to factors other than the specific posture adopted while cycling. Lumbar kyphosis on the bicycle may not affect the sagittal configuration of the lumbar spine in standing.