Statistical modeling of hemodynamic changes during orthotopic liver transplantation: predictive value for outcome and effect of marginal donors

Aim

This study analyzed hemodynamic recordings collected on a beat-to-beat basis during orthotopic liver transplantation (OLT). The first aim was to construct a graphic that will represent hemodynamic profile during OLT. The second aim was to compare the intraoperative hemodynamic pattern of survivors versus nonsurvivors and those who received a liver from normal versus marginal donors.

Methods

Hemodynamic data (including cardiac output, cardiac index, stroke volume [SV] and SV index, systemic vascular resistance [SVR] and SVR index, mean arterial pressure, and heart rate) were collected from 100 consecutive adult OLT patients with the use of a lithium dilution cardiac output (LiDCO plus) monitor. A LOESS (Robust Locally Weighted Regression and Smoothing Scatterplots) smoother was used to give a more easily interpreted graph. Patients were grouped with respect to survival at 30 days (survivors vs nonsurvivors) and quality of graft (marginal vs normal).

Results

We constructed graphics that represented all intraopetarive hemodynamic data during OLT for 100 consecutive procedures. It confirmed hyperdynamic circulation during OLT. Statistical analysis did not reveal significant differences regarding intraoperative hemodynamic data between survivors and nonsurvivors, or between patients receiving normal versus marginal grafts.

Conclusion

This study shows changes in the hemodynamic profile during OLT, measured on a beat-to-beat basis. Intraoperative hemodynamic changes did not predict patients who did not survive OLT. Beat-to-beat monitoring did not reveal significant hemodynamic instability following transplantation of marginal grafts.     

Organ donation in Latin America

Recently in Latin America, there has been a strong influence of the "Spanish model" of organ procurement. In 2001, The "Punta Cana Group" was created by Latin American transplantation coordinators with the objective of registering and improving the system of donation and procurement. In many countries there is no universal financial support from the government for medical treatment, including dialysis and transplantation. In other countries there is complete financial support for all of the population, including immunosuppressive drugs. Practically all countries have transplantation laws that follow ethical concepts, such as brain death diagnosis criteria, forms of consent, criteria of allocation, and inhibition of commerce. The rate of potential donors notified in countries that perform transplantations with deceased donors varied from 6 to 47 per million population yearly (pmp/y); The rate of effective donors varied from 1 to 20 pmp. In 2004, the mean rate of effective donors in Latin America was 5.4 pmp. The family refusal rate for the donation of organs varied from 28% in Uruguay to 70% in Peru. In some countries, such as Puerto Rico, Uruguay, and Cuba, it was more than 15 pmp, whereas in others countries deceased donors were practically not used. The number of patients on the waiting list for solid organ transplants in 12 Latin American countries is 55,000. Although the donation rate has increased by 100% during the last 10 years, it is lower than that in Europe (15 pmm/y) or the United States (20 pmp/y).     

Clinical results of revision shoulder arthroplasty for glenoid component loosening

We retrospectively reviewed 32 patients who underwent glenoid revision surgery after total shoulder arthroplasty to compare the results of revision total shoulder arthroplasty with those of revision hemiarthroplasty and to identify factors associated with poor results after revision shoulder arthroplasty for glenoid component loosening. Results were reviewed at a mean follow-up of 4 years (range, 2-8 years). Glenoid reimplantation resulted in significant pain relief (P < .0001), improvement in American Shoulder and Elbow Surgeons (ASES) score (P < .02), and external rotation (24 degrees to 44 degrees , P < .004). Revision to a hemiarthroplasty also resulted in significant pain relief (P < .01) and improvement in ASES score (P < .05). For the treatment of glenoid loosening without glenohumeral instability, both reimplantation of a glenoid component and revision to a hemiarthroplasty improved function, satisfaction, and level of pain. Reimplantation of a new glenoid component offered greater improvements in pain (P < .008) and external rotation (increase of 20 degrees versus 3 degrees , P < .03) compared with hemiarthroplasty. For patients with preoperative glenohumeral instability, revision surgery did not improve motion, function, or pain significantly. Risk factors associated with a poor outcome after revision arthroplasty included persistent glenohumeral instability, rotator cuff tears, and malunion of the greater tuberosity.     

Hormonal and hyperglycemic response in laparoscopic and open cholecystectomy

The aim of the study is to evaluate the intensity of the operative trauma during laparoscopic and open cholecystectomy measured by hormonal (cortisol level) and metabolic (blood sugar level) response. Prospective randomized study was conducted in seventy patients with cholelithiasis. They were divided in two groups: thirty five underwent laparoscopic cholecystectomy and thirty five underwent open cholecystectomy (control group). Mean cortisol concentration and glucose concentration were measured preoperatively and postoperatively after 2, 4, 8, 12, 24 and 48 hours. The examined groups were comparable in age and sex. Preoperative plasma cortisol concentration was within normal range in both groups. Postoperatively plasma cortisol level increased in the laparoscopically operated group, and peak level occurred eight hours after surgery (692.6 +/- 27.2 nmol/L). Peak plasma cortisol level in control group developed 8 hours postoperatively (841.1 +/- 33.2 nmol/L). The mean cortisol concentration was significantly higher (p < 0.05) following open procedure between fourth and 48th postoperative hour. Mean plasma glucose concentrations after laparoscopic and open cholecystectomy were significantly higher (p < 0.05) than preoperative values. The mean glucose concentration during the initial 24 hours was significantly higher (p < 0.05) following open cholecystectomy.     

Directional functional coupling of cerebral rhythms between anterior cingulate and dorsolateral prefrontal areas during rare stimuli: a directed transfer function analysis of human depth EEG signal

What is the neural substrate of our capability to properly react to changes in the environment? It can be hypothesized that the anterior cingulate cortex (ACC) manages repetitive stimuli in routine conditions and alerts the dorsolateral prefrontal cortex (PFC) when stimulation unexpectedly changes. To provide evidence in favor of this hypothesis, intracerebral stereoelectroencephalographic (SEEG) data were recorded from the anterior cingulate and dorsolateral PFC of eight epileptic patients in a standard visual oddball task during presurgical monitoring. Two types of stimuli (200 ms duration) such as the letters O (frequent stimuli; 80% of probability) and X (rare stimuli) were presented in random order, with an interstimulus interval between 2 and 5 s. Subjects had to mentally count the rare (target) stimuli and to press a button with their dominant hand as quickly and accurately as possible. EEG frequency bands of interest were θ (4–8 Hz), α (8–12 Hz), β (14–30 Hz), and γ (30–45 Hz). The directionality of the information flux within the EEG rhythms was indexed by a directed transfer function (DTF). The results showed that compared with the frequent stimuli, the target stimuli induced a statistically significant increase of DTF values from the anterior cingulate to the dorsolateral PFC at the θ rhythms (P < 0.01). These results provide support to the hypothesis that ACC directly or indirectly affects the oscillatory activity of dorsolateral PFC by a selective frequency code under typical oddball conditions. Hum Brain Mapp 2009. © 2007 Wiley‐Liss, Inc.     

Two-photon fluorescence microscopy study of cerebrovascular dynamics in ultrasound-induced blood�Cbrain barrier opening

Blood–brain barrier (BBB) disruption can be achieved with ultrasound (US) and circulating microbubble (MB) contrast agent. Using dorsal US sonication and Definity, an MB contrast agent, responses of the cortical cerebral vasculature to BBB opening were observed with varying acoustic peak negative pressure (0.071 to 0.25 MPa) under two-photon microscope. Wistar rats with a craniotomy were sonicated with a single piezoelectric transducer following the intravenous injection of Texas Red for visualization of vasculature and leakage from BBB opening. Based on time-dependent intensity change in the extravascular area, the leakage was classified into three types: fast, sustained, and slow. Fast leakage was characterized by a rapid increase to peak intensity during sonication, but a decrease afterwards, occurring at all pressures and vessels sizes analyzed in our study. Sustained leakage was indicated by a similar, immediate increase to peak intensity but one that remained elevated for the duration of imaging, occurring at low-to-intermediate pressures. Slow leakage began 5 to 15 minutes after sonication, dominating at low pressures, and was more prevalent among smaller vessels than fast and sustained leakage. Our study showed the possibility of controlling leakage type and vessel size in US-induced BBB opening through varying acoustic pressure.     

Alterations of striatal glutamate transmission in rotenone-treated mice: MRI/MRS in vivo studies

Animal models treated with agricultural chemicals, such as rotenone, reproduce several degenerative features of human central nervous system (CNS) diseases. Glutamate is the most abundant excitatory amino acid transmitter in the mammalian central nervous system and its transmission is implicated in a variety of brain functions including mental behavior and memory. Dysfunction of glutamate neurotransmission in the CNS has been associated with a number of human neurodegenerative diseases, either as a primary or as a secondary factor in the excitotoxic events leading to neuronal death. Since many human CNS disorders do not arise spontaneously in animals, characteristic functional changes have to be mimicked by toxic agents. Candidate environmental toxins bearing any direct or indirect effects on the pathogenesis of human disease are particularly useful. The present longitudinal Magnetic Resonance Imaging (MRI) studies show, for the first time, significant variations in the properties of brain ventricles in a rotenone-treated (2 mg/kg) mouse model over a period of 4 weeks following 3 days of rotenone treatment. Histopathological analysis reveals death of stria terminalis neurons following this short period of rotenone treatment. Furthermore, in vivo voxel localized (1)H MR spectroscopy also shows for the first time significant bio-energetic and metabolic changes as well as temporal alterations in the levels of glutamate in the degenerating striatal region. These studies provide novel insights on the effects of environmental toxins on glutamate and other amino acid neurotransmitters in human neurodegenerative diseases.     

The extrinsic coagulation cascade and tissue factor pathway inhibitor in macrophages: A potential therapeutic opportunity for atherosclerotic thrombosis

Objectives

The coagulation protease cascade plays the central requisite role in initiation of arterial atherothrombosis. However, the relative participation of the extrinsic as compared to the intrinsic pathway is incompletely resolved. We have investigated in vivo the relative importance of the extrinsic and intrinsic pathways to define which is more essential to atherothrombosis and therefore the preferable prophylactic therapeutic target. We further addressed which type of plaque associated macrophage population is associated with the thrombotic propensity of atherosclerotic plaques.

Methods

Both photochemical injury and ferric chloride vascular injury models demonstrated arterial thrombosis formation in ApoE deficient mice. We found that direct interference with the extrinsic pathway, but not the intrinsic pathway, markedly diminished the rate of thrombus formation and occlusion of atherosclerotic carotid arteries following experimental challenge. To explore which plaque macrophage subtype may participate in plaque thrombosis in regard to expression tissue factor pathway inhibitor (TFPI), bone marrow derived macrophages of both M and GM phenotypes expressed tissue factor (TF), but the level of TFPI was much greater in M- type macrophages, which exhibited diminished thrombogenic activity, compared to type GM-macrophages.

Results and conclusions

Our works support the hypothesis that the TF-initiated and direct extrinsic pathway provides the more significant contribution to arterial plaque thrombogenesis. Activation of the TF driven extrinsic pathway can be influenced by differing colony-stimulating factor influenced macrophage TFPI-1 expression. These results advance our understanding of atherothrombosis and identify potential therapeutic targets associated with the extrinsic pathway and with macrophages populating arterial atherosclerotic plaques.     

Effective extraction of diagnostic ECG waveform information using orthonormal basis functions derived from body surface potential maps

A common basis of orthogonal waveform functions was derived from 128 lead body surface potential maps of 405 subjects. Twelve such orthogonal functions or frames were adequate for reconstruction of original ECGs from the beginning of QRS to the end of T. A larger number of frames (18) was required when basis functions were derived separately for QRS (10) and ST-T segments (8). Diagnostic information content of the coefficients of the orthogonal basis functions was evaluated in comparison with Minnesota Code criteria for myocardial infarction and with a more advanced multivariate ECG analysis program (Pipberger Program). This was done by deriving a linear discriminant function for separating normals from ECGs of patients with myocardial infarction and testing the discriminant in a different test population of infarcts and normals. The diagnostic accuracy of orthogonal basis functions was as good as that of Pipberger's program and considerably better than that of the Minnesota Code. The classification method described is insensitive to noise and errors in detecting QRS and T wave onsets and offsets or in selecting proper baseline for amplitude measurements. The robustness and enhanced classification stability with respect to noise and minor wave detection errors is a potential advantage particularly in serial ECG comparison.     

Ictal and peri-ictal oscillations in the human basal ganglia in temporal lobe epilepsy

Preictal, ictal, and postictal oscillations in the basal ganglia were analyzed. Five persons with temporal lobe epilepsy who were candidates for surgery had diagonal depth electrodes implanted in the basal ganglia: four of them in the putamen, and one in the pallidum and caudate. Time-frequency and power spectral analyses were used to analyze the EEG. Significant frequency components of 2-10 Hz were consistently observed in the basal ganglia. The frequency of this component slowed during seizures. There was a significant ictal increase in power spectral density in all frequency ranges. The changes in the basal ganglia were consistent while seizure activity spread over the cortex, and partially persisted after the clinical seizure ended. They were inconsistent in the period after seizure onset. Seizures originating in the mesiotemporal structures can affect physiological rhythms in the basal ganglia. The basal ganglia did not generate epileptiform EEG activity. An inhibitory role for the basal ganglia during temporal lobe seizures is suggested.