Blood Pressure Recordings During Hemodialysis Access Interventions: Implications for Acute Management

A retrospective study evaluating the pattern of blood pressure and its related complications before, during, and after percutaneous hemodialysis interventions was performed in patients presenting with asymptomatic hypertension. Hemodialysis patients undergoing percutaneous interventions including tunneled hemodialysis catheter insertion, percutaneous balloon angioplasty and thrombectomy procedure, and stage II hypertension (systolic blood pressure ≥160 mmHg) were included in this analysis. Blood pressure medications were not used while midazolam and fentanyl were routinely administered. Patients were followed for up to 4 weeks to monitor any complications. The mean blood pressure before, during, and after the procedures were 185 ± 18/96 ± 14, 172 ± 22/92 ± 15, and 153 ± 25/87 ± 14, respectively. There was a statistically significant difference between the blood pressure readings before and after the procedure (before = 185 ± 18/96 ± 14, after = 153 ± 25/87 ± 14; p = 0.001). None of the patients had a stroke, myocardial infarction, or acute pulmonary edema before, during, or after the procedure or during the 4‐week follow‐up period. A significant reduction in blood pressure was observed after the procedure without the administration of any antihypertensive medication. These results suggest that the reduction in blood pressure observed after percutaneous dialysis access interventions (particularly in the presence of midazolam and fentanyl) may make it unnecessary to treat asymptomatic hypertension prior to these procedures.     

The influx of neutral amino acids into the porcine brain during development: a positron emission tomography study

Pigs of three different age groups (newborns, 1 week old, 6 weeks old) were used to study the transport of the large neutral amino acids 6-[18F]fluoro-L-DOPA ([18F]FDOPA) and 3-O-methyl-6-[18F]fluoro-L-DOPA ([18F]OMFD) across the blood-brain barrier (BBB) with positron emission tomography (PET). Compartmental modeling of PET data was used to calculate the blood-brain clearance (K1) and the rate constant for the brain-blood transfer (k2) of [18F]FDOPA and [18F]OMFD after i.v. injection. A 40-70% decrease of K1(OMFD), K1(FDOPA) and k2(OMFD) from newborns to juvenile pigs was found whereas k2(FDOPA) did not change. Generally, K1(OMFD) and k2(OMFD) are lower than K1(FDOPA) and k2(FDOPA) in all regions and age groups. The changes cannot be explained by differences in brain perfusion because the measured regional cerebral blood flow did not show major changes during the first 6 weeks after birth. In addition, alterations in plasma amino acids cannot account for the described transport changes. In newborn and juvenile pigs, HPLC measurements were performed. Despite significant changes of single amino acids (decrease: Met, Val, Leu; increase: Tyr), the sum of large neutral amino acids transported by LAT1 remained unchanged. Furthermore, treatment with a selective inhibitor of the LAT1 transporter (BCH) reduced the blood-brain transport of [18F]FDOPA and [18F]OMFD by 35% and 32%, respectively. Additional in-vitro studies using human LAT1 reveal a much lower affinity of FDOPA compared to OMFD or L-DOPA. The data indicate that the transport system(s) for neutral amino acids underlie(s) developmental changes after birth causing a decrease of the blood-brain barrier permeability for those amino acids during brain development. It is suggested that there is no tight coupling between brain amino acid supply and the demands of protein synthesis in the brain tissue.     

Coronary revascularization: off-pump versus on-pump--a comparison of behavior of biochemical cardiac ischemia markers

BACKGROUND: Recently, coronary artery bypass grafting (CABG) on the beating heart with avoidance of extracorporeal circulation (off-pump CABG technique) has been gaining increasing importance in modern cardiac surgery. The object of this prospective study was to compare postoperative kinetic and patterns of cardiac troponin I (cTnI), T (cTnT), and creatine kinase MB (CKMB) activities after off-pump CABG versus conventional on-pump CABG. METHODS: We studied 106 patients who underwent first-time elective on-pump (group I, n = 69, 56 male, 13 female, mean age: 64.3 +/- 9.9 years, mean ejection fraction: 56 +/- 15%) or off-pump (group II, n = 37, 24 male, 13 female, mean age: 68.4 +/- 9.1 years, mean ejection fraction: 57 +/- 13%) CABG surgery via median sternotomy. CTn I and cTnT levels, total creatine kinase (CK) and CK-MB activities in the serum were measured before operation, up on arrival at the ICU and 6, 12, 24, 48 and 120 hours later. Serial 12-lead ECGs were recorded preoperatively and on days 1, 2 and 5. RESULTS: Serum concentrations of cardiac troponins in all patients were preoperatively either not detectable or in the normal range and significantly increased after surgery. In group I, one patient developed a Q wave myocardial infarction, one patient a non-Q wave infarction and two patients a new left bundle branch block on the ECG. One patient of group II developed a new Q-wave myocardial infarction and another patient permanent atrial fibrillation associated with a continuous arrhythmia. All patients with a myocardial infarction in the ECG showed significant elevation of concentrations or activities of these biochemical markers. The median postoperative peak values for cTnI were measured at 24 h in both groups (2.7 micrograms/l, 95%-CI: [2.2, 3.2] in group I and 1.1 micrograms/l, 95%-CI: [0.5, 1.3] in group II). CTnT postoperatively presented an earlier median peak of 0.128 microgram/l at 12 h in group II (95%-CI: [0.041, 0.146]) than in group I at 48 h (0.298 microgram/l, 95%-CI: [0.254, 0.335]). CONCLUSIONS: All patients undergoing CABG surgery with or without extracorporeal circulation postoperatively showed an increase of cardiac troponin levels. After uncomplicated coronary revascularization, patients with the off-pump CABG technique continuously presented lower serum cardiac troponin concentrations than those with the on-pump CABG technique. CTnI showed the same patterns of release in both groups with different median postoperative peak values at 24 h. The patterns off cTnT release following CABC surgery with or without extracorporal circulation were different: CTnT reaches its postoperative peak value in patients with the off-pump CABG technique earlier than those with the on-pump CABG technique (12 h postoperatively versus 48 h).     

Orientation-specific relationship between populations of excitatory and inhibitory lateral connections in the visual cortex of the cat

The topography of lateral excitatory and lateral inhibitory connections was studied in relation to orientation maps obtained in areas 17 and 18. Small iontophoretic injections of biocytin were delivered to the superficial layers in regions where orientation selectivity had been mapped using electrode recordings of single- and multi-unit activity from various cortical depths. Biocytin revealed extensive patchy axonal projections of up to 3.5 mm in both areas while labelled somata occurred chiefly at the injection site, indicating that the labelling was primarily anterograde. Two types of boutons could be clearly distinguished: (i) putative excitatory boutons either en passant or having a short stalk and (ii) inhibitory boutons which were invariably of the basket-type. Three-dimensional reconstructions of all labelled boutons showed that the excitatory and the inhibitory networks had a distinctively different relationship to orientation maps. The overall distribution of connections showed that 53-59% of excitatory and 46-48% of inhibitory connections were at iso-orientation, +/-30 degrees; oblique-orientation, +/-(30-60) degrees, was shown by 30% of excitatory and 28-39% of inhibitory connections; cross-orientation was shown by 11- 17% of excitatory and 15-24% of inhibitory connections. Although excitatory patches occupied mainly iso-orientation locations, interpatch regions representing chiefly non-iso-orientations (oblique + cross orientation) were also innervated. There was considerable overlap between the excitatory and inhibitory network. Nonetheless, inhibitory connections were more common than excitatory connections with non-iso- orientation locations. There was no significant difference between the orientation topography of area 17 and area 18 projections. The results suggest that in general the lateral connectivity system is not orientation specific, but shows a moderate iso-orientation preference for excitation and an even weaker iso-orientation preference for inhibition. The broad orientation spectrum of lateral connections could provide the basis for mechanisms that requiring different orientations, as for example in detecting orientation discontinuities.      

Early detection of sternal dehiscence by conventional chest X-ray

BACKGROUND: Diagnosis of sternal dehiscence after sternotomy for cardiac surgery is still made clinically. The aim of this study was to identify radiographic signs of sternal dehiscence by routine chest X-ray (CXR) in patients with and without clinically diagnosed sternal dehiscence. METHODS: 75 patients (group I: 65 +/- 9.3 years, f/m = 12/63) with clinically diagnosed sternal dehiscence, necessitating surgical revision and 75 patients with uneventful sternal healing (matched to group I by age, sex, preoperative risk factors and surgical procedures; group II: 66 +/- 9.0 years, f/m = 12/63) were included in this study. Serial CXRs immediately after surgery until re-intervention or discharge were analyzed by a radiologist, blind to the date of redo surgery. RESULTS: In 39 patients of group I (52%) vs. 8 (10.7%) in group II, abnormalities in the sternal wire and/or a midsternal stripe could be found (p < 0.0001): rotated wires (p = 0.003), shifted wires (p = 0.043), and ruptured wires (p = 0.312). Seven patients presented with combined wire abnormalities in group I vs. 0 in group II. Midsternal stripe sign could be detected in 26 patients of group I vs. 3 in group II (p < 0.0001). Sternal dehiscence was suspected based on the above mentioned abnormalities as early as three days postoperatively (Q1 = 2; Q3 = 8 days) in 39 patients, whereas clinical diagnosis of sternal dehiscence was delayed up to ten days postoperatively (Q1 = 7; Q3 = 13 days). CONCLUSIONS: Radiographic signs of sternal dehiscence could be detected before the clinical diagnosis was apparent and predicted sternal dehiscence in more than half of the patients.     

Endocrine characterization of the designer steroid methyl-1-testosterone: investigations on tissue-specific anabolic-androgenic potency, side effects, and metabolism

Various products containing rarely characterized anabolic steroids are nowadays marketed as dietary supplements. Herein, the designer steroid methyl-1-testosterone (M1T) (17β-hydroxy-17α-methyl-5α-androst-1-en-3-one) was identified, and its biological activity, potential adverse effects, and metabolism were investigated. The affinity of M1T toward the androgen receptor (AR) was tested in vitro using a yeast AR transactivation assay. Its tissue-specific androgenic and anabolic potency and potential adverse effects were studied in a Hershberger assay (sc or oral), and tissue weights and selected molecular markers were investigated. Determination of M1T and its metabolites was performed by gas chromatography mass spectrometry. In the yeast AR transactivation assay, M1T was characterized as potent androgen. In rats, M1T dose-dependently stimulated prostate and levator ani muscle weight after sc administration. Oral administration had no effect but stimulated proliferation in the prostate and modulated IGF-I and AR expression in the gastrocnemius muscle in a dose-dependent manner. Analysis of tyrosine aminotransferase expression provided evidence for a strong activity of M1T in the liver (much higher after oral administration). In rat urine, 17α-methyl-5α-androstane-3α,17β-diol, M1T, and a hydroxylated metabolite were identified. In humans, M1T was confirmed in urine in addition to its main metabolites 17α-methyl-5α-androst-1-ene-3α,17β-diol and 17α-methyl-5α-androstane-3α,17β-diol. Additionally, the corresponding 17-epimers as well as 17β-hydroxymethyl-17α-methyl-18-nor-5α-androsta-1,13-dien-3-one and its 17-epimer were detected, and their elimination kinetics was monitored. It was demonstrated that M1T is a potent androgenic and anabolic steroid after oral and sc administration. Obviously, this substance shows no selective AR modulator characteristics and might exhibit liver toxicity, especially after oral administration.