Impact of experimental endogenous gram-negative peritonitis on the pancreas of the rat as evaluated by cationic trypsin-like immunoreactivity in peritoneal fluid and serum and by electron microscopy of pancreatic tissue

Endogenous gram-negative peritonitis leading to septic shock was induced in rats by a defined perforation of the coecum. Cationic trypsin-like immunoreactivity (CTLI) was measured in peritoneal fluid and serum by a radioimmunoassay method. Five, 10, and 15 h after the coecal perforation, CTLI in peritoneal fluid was significantly higher than before the coecal perforation and also higher than in the corresponding control rats. Moreover, CTLI in serum was under the same conditions significantly higher 10 and 15 h after the induction of peritonitis. Gel chromatography of peritoneal fluid and serum during peritonitis showed free CTLI and CTLI bound to both alpha-1-antitrypsin and alpha-2-macroglobulin, whereas only free CTLI could be detected in serum from control rats. These findings were accompanied by local ultrastructural changes in the acinar cells as evaluated by electron microscopy. The pathophysiologic implications of the findings are discussed.     

De novo missense mutations in the NAA10 gene cause severe non-syndromic developmental delay in males and females

Recent studies revealed the power of whole-exome sequencing to identify mutations in sporadic cases with non-syndromic intellectual disability. We now identified de novo missense variants in NAA10 in two unrelated individuals, a boy and a girl, with severe global developmental delay but without any major dysmorphism by trio whole-exome sequencing. Both de novo variants were predicted to be deleterious, and we excluded other variants in this gene. This X-linked gene encodes N-alpha-acetyltransferase 10, the catalytic subunit of the NatA complex involved in multiple cellular processes. A single hypomorphic missense variant p.(Ser37Pro) was previously associated with Ogden syndrome in eight affected males from two different families. This rare disorder is characterized by a highly recognizable phenotype, global developmental delay and results in death during infancy. In an attempt to explain the discrepant phenotype, we used in vitro N-terminal acetylation assays which suggested that the severity of the phenotype correlates with the remaining catalytic activity. The variant in the Ogden syndrome patients exhibited a lower activity than the one seen in the boy with intellectual disability, while the variant in the girl was the most severe exhibiting only residual activity in the acetylation assays used. We propose that N-terminal acetyltransferase deficiency is clinically heterogeneous with the overall catalytic activity determining the phenotypic severity.     

Severe deterioration of newly diagnosed Takayasu arteritis in a patient re-treated with interferon beta-1α for concomitant longstanding multiple sclerosis

A 52-year-old woman with Takayasu arteritis and a known history of multiple sclerosis had been treated with subcutaneous interferon (IFN) beta-1α. After the re-introduction of the IFN beta-1α, the patient had a gradual worsening of the arteritis, with claudication symptoms in the left arm and increased inflammation markers. An evaluation using Doppler ultrasound of the supra-aortic vessels revealed severe stenosis of the left axillary artery. The IFN beta-1α was withdrawn, with prompt clinical and laboratory improvement of the vasculitis.     

Axial Tension Model of Spinal Cord Injury

ABSTRACT

The purpose of this investigation was to determine the safety and efficacy of subtrigonal, periureteral injections of autogenous fat grafts for the treatment of vesicoureteral reflux.

Seven patients (12 renal units) with vesicoureteral reflux were treated with subtrigonal autogenous fat injection. Fat harvesting was obtained from abdominal and thigh subcutaneous tissue. Approximately 2 ml of fat was injected beneath each ureteral orifice with a modified 10 Fr needle through a 23.5 Fr rigid cystoscope. Two of the seven patients experienced durable (six months) resolution of reflux. In three patients, reflux resolved but recurred within three months and another developed recurrent reflux within six months. In one patient with a periureteral diverticulum, proper positioning of the needle tip for effective fat injection was not possible, resulting in persistent reflux. Two of the five patients with persistent reflux demonstrated a diminished grade of reflux on follow-up cystography. Neither complications nor ureteral obstruction have been encountered.

The subtrigonal injection technique can be used with autogenous adipose tissue to treat vesicoureteral reflux. Anatomic variation may determine those patients less likely to enjoy durable results. Clinical success and reabsorption of the fat cannot be predicted or controlled at the present time. The ideal periureteral bulking agent for the treatment of vesicoureteral reflux remains to be determined.     

Low perfusion pressure during CPB may induce cerebral metabolic and ultrastructural changes

Background. Recently we reported on cerebral metabolic changes suggesting ischemia in piglets during nitroprusside-induced low-pressure CPB. We here investigated whether a mean arterial pressure (MAP) of 40–45 mmHg could provoke similar changes by a NO-independent intervention. Methods. Piglets underwent 60 minutes normothermic followed by 90 minutes hypothermic CPB. The LP-group (n=8) had MAP of 40–45 mmHg by phentolamine while the HP-group (n=8) had MAP of 60–80 mmHg by norepinephrine. Cerebral glucose, lactate, pyruvate and glycerol were determined. In the last two animals of each group, cerebral tissue was examined by electron microscopy. Results. Cerebral lactate was higher in the LP-group than the HP-group during normothermic CPB. Compared with baseline, cerebral glucose of the LP-group decreased whereas lactate/pyruvate-ratio, lactate and glycerol-concentrations increased during normothermic CPB. In the HP-group these parameters remained unchanged. Electron microscopy showed 31.2% and 8.3% altered mitochondria in the cortical micrographs taken from the LP- and the HP-group, respectively (p<0.001). Conclusion. MAP below 45 mmHg during CPB was associated with cerebral biochemical and morphological changes consistent with anaerobic metabolism and subcellular injury.     

The association between physical fitness level and number and severity of injury and illness in youth elite athletes

Youth elite athletes often double their training and competition load after enrollment into specialized sport academy high school programs. The least fit athletes may be exposed to an excessive and too rapid increase in training load, with negative adaptations such as injury and illness as a consequence. In this study, our aim was to determine whether these least fit athletes were at greater risk of injury or illness during their first school year. Participants were 166 youth elite athletes (72% boys) from a variety of team, technical, and endurance sports newly enrolled into specialized sport academy high schools. The Oslo Sports Trauma Research Center Questionnaire on Health Problems was used to self‐report injuries and illnesses weekly for 26 weeks. Athletes completed the Ironman Jr physical fitness test battery at baseline, evaluating endurance, strength, agility, and speed properties. We ranked the athletes based on their combined test scores and identified the least fit quartile. The main outcome was the number and severity of health problems, comparing the least fit quartile of athletes to the rest of the cohort. Overall, the least fit quartile of athletes did not report more health problems (mean 3.7, 95% CI 3.0‐4.4) compared with the rest of the cohort (3.6, 3.2‐3.9). In conclusion, we demonstrated no association between low physical fitness level and number and severity of injury and illness in youth elite athletes after enrollment into a specialized sport academy high school program.     

Estimation of the duration of ventricular fibrillation using ECG single feature analysis

The duration of untreated ventricular fibrillation (VF) is of paramount importance for CPR success. Moreover, therapeutic interventions taking into account the interval between cardiac arrest onset and initiation of CPR improve outcome. This study was performed to investigate whether VF feature analysis could be used to estimate the duration of VF in patients with out-of-hospital cardiac arrest. Demographic data recorded according to the Utstein guidelines and ECG recordings of 376 cardiac arrest patients from three European areas were analysed. Ten features in the time and frequency domain derived from different sub-bands of the initial VF ECG (n=127) were evaluated. The correlation between VF ECG features and cardiac arrest times was investigated using Pearson's correlation coefficient in a subset of 40 patients with reliably estimated downtimes and artefact-free initial VF tracings. No significant correlation (p<.05) between any of the VF ECG features and downtime could be found. The duration of cardiac arrest could not be estimated reliably from human VF ECG single feature analysis.     

Tensile strength of spinal ligaments

Spinal ligaments from 41 fresh human male cadavers were tested. The ligaments were tested in situ by sectioning all elements except the one under study. The force deflection curves demonstrated a sigmoidal shape, and the point at which an increase in deflection was obtained with decreasing force was taken as failure. The force and deformation at failure are shown for each ligament as a function of spinal level.     

Approximate minimum bias multichannel spectral estimation for heart rate variability

Spectral decomposition of variations in heart rate permits noninvasive measurement of autonomic nervous activity in humans and animals. Autonomic metrics based on spectral analysis are useful in monitoring clinical conditions such as diabetic neuropathy and reinnervation in heart transplant patients. A persistent problem in deriving such autonomic measures is the prerequisite of an accurate and unbiased power spectrum of heart rate variability (HRV). Numerous parametric and nonparametric power spectrum estimators have been introduced, each with its own advantages and drawbacks. Estimator bias has received little attention, despite the fact that at least one common HRV spectrum estimator, the autoregressive method, is known to exhibit bias even in idealized circumstances. We introduce an approximately minimum bias, nonparametric, multichannel spectrum estimation procedure for HRV and contemporaneous signals. The procedure, which is designed specifically for irregular sampling, does not require data segmentation and provides statistically consistent, low variance multichannel spectrum estimates. Estimator performance on simulated and clinical data is presented and compared with results from autoregressive models and Welch periodograms with and without compensation for irregular sampling. Results indicate that the proposed method exhibits advantages over conventional HRV spectrum estimators. Relative computational complexity of the proposed method is also considered.