Use of high-resolution thermography as a validation measure to confirm epidural anesthesia in mice: a cross-over study.

BACKGROUND: Effective epidural anesthesia is confirmed in humans by sensory assessments but these tests are not feasible in mice. We hypothesized that, in mice, infrared thermography would demonstrate selective segmental warming of lower extremities following epidural anesthesia. METHODS: We anesthetized 10 C57BL/6 mice with isoflurane and then inserted a PU-10 epidural catheter under direct surgical microscopy at T11-12. A thermal camera (thermal sensitivity ±0.05°C, pixel resolution 320x240 pixels, and spatial resolution 200 µm) recorded baseline temperature of front and rear paws, tail and ears. Thermography was assessed at baseline and 2, 5, 10, and 15 min after an epidural bolus dose of 50 µL bupivacaine 0.25% or 50 µL saline (control) using a cross-over design with dose order randomized and investigators blinded to study drug. Thermal images were recorded from video and analyzed using FLIR software. Effect over time and maximal effect (Emax) were assessed by repeated measures ANOVA and paired t-tests. Comparisons were between bupivacaine and control, and between lower vs upper extremities. RESULTS: Epidural bupivacaine caused progressive warming of lower compared with upper extremities (P <0.001), typically returning to baseline by 15 min after administration. Mean (±SD) Emax was +3.73 (±1.56) °C for lower extremities compared with 0.56 (±0.68) °C (P=0.03) for upper extremities. Following epidural saline, there was no effect over time (Emax for lower extremities -0.88 (±0.28) °C compared with the upper extremities -0.88 (±0.19) °C (P >0.99). CONCLUSIONS: Thermography is a useful tool to confirm epidural catheter placement in animals for which subjective, non-noxious, sensory measures are impossible.

Predictors of nonresponse to fluid restriction in hyponatraemia due to the syndrome of inappropriate antidiuresis.

BACKGROUND: Fluid restriction (FR), the first-line treatment for hyponatraemia due to the syndrome of inappropriate antidiuresis (SIAD), often does not lead to successful correction of hyponatraemia. Therefore, predictive markers of treatment response are desirable. We evaluated routinely measured serum (s) and urine (u) parameters, s-copeptin and s-mid-regional pro-atrial natriuretic peptide (s-MR-proANP), as possible predictors of FR response. METHODS: In this prospective observational study, we included patients with profound hyponatraemia (s-sodium <125 mmol L-1 ) due to SIAD. Patients were classified as FR responders (increase in s-sodium concentration of >3 mmol L-1 within 24 h) or nonresponders (increase of ≤3 mmol L-1 within 24 h). Initial laboratory parameters were compared between groups with logistic regression analysis. RESULTS: Of 106 SIAD patients analysed, 82 underwent treatment with FR; 48 (59%) patients showed a successful response to FR and 34 (41%) were considered nonresponders. High levels of u-sodium and u-osmolality were significantly associated with nonresponse to FR [odds ratio (OR) 15.0, 95% confidence interval (CI) 2.4-95.8, P = 0.004 and OR 34.8, 95% CI 1.2-1038.8, P = 0.041, respectively). The association of u-sodium and nonresponse remained significant also after adjustment for diuretic use. Lower levels of s-MR-proANP were associated with nonresponse (OR 0.03, 95% CI 0.003-0.3, P = 0.004), whereas s-copeptin was not significantly associated with response to FR. CONCLUSION: Easily measured laboratory parameters, especially u-sodium, correlate with therapeutic response and identify patients most likely to fail to respond to FR. Measurement of these parameters may facilitate early treatment choice in patients with SIAD.

Mid-regional pro-atrial natriuretic peptide and the assessment of volaemic status and differential diagnosis of profound hyponatraemia.

BACKGROUND: Hyponatraemia is common and its differential diagnosis and consequent therapy management is challenging. The differential diagnosis is mainly based on the routine clinical assessment of volume status, which is often misleading. Mid-regional pro-atrial natriuretic peptide (MR-proANP) is associated with extracellular and cardiac fluid volume. METHODS: A total of 227 consecutive patients admitted to the emergency department with profound hypo-osmolar hyponatraemia (Na < 125 mmol L(-1) ) were included in this prospective multicentre observational study conducted in two tertiary centres in Switzerland. A standardized diagnostic evaluation of the underlying cause of hyponatraemia was performed, and an expert panel carefully evaluated volaemic status using clinical criteria. MR-proANP levels were compared between patients with hyponatraemia of different aetiologies and for assessment of volume status. RESULTS: MR-proANP levels were higher in patients with hypervolaemic hyponatraemia compared to patients with hypovolaemic or euvolaemic hyponatraemia (P = 0.0002). The area under the curve (AUC) to predict an excess of extracellular fluid volume, compared to euvolaemia, was 0.73 [95% confidence interval (CI) 0.62-0.84]. Additionally, in multivariate analysis, MR-proANP remained an independent predictor of excess extracellular fluid volume after adjustment for congestive heart failure (P = 0.012). MR-proANP predicted the syndrome of inappropriate antidiuresis (SIAD) versus hypovolaemic and hypervolaemic hyponatraemia with an AUC of 0.77 (95% CI 0.69-0.84). CONCLUSION: MR-proANP is associated with extracellular fluid volume in patients with hyponatraemia and remains an independent predictor of hypervolaemia after adjustment for congestive heart failure. MR-proANP may be a marker for discrimination between the SIAD and hypovolaemic or hypervolaemic hyponatraemia.

Stress hormones predict cerebrovascular re-events after transient ischemic attacks.

BACKGROUND: TIA is a strong predictor of subsequent stroke. The hypothalamic stress hormone copeptin is an accurate prognostic marker in acute ischemic stroke. This study assessed prognostic reliability of 2 distinct stress hormones, copeptin and cortisol, for the risk stratification of re-events in patients with TIA. METHODS: We conducted a prospective study in patients admitted to the emergency department with a TIA. Clinical risk scoring using the ABCD2 score was determined and both hormones were measured in plasma on admission. The primary endpoint was a cerebrovascular re-event within 90 days. RESULTS: We included 107 consecutive patients with TIA. Re-events occurred in 10 patients (9%). Copeptin levels were higher in patients with a re-event compared with patients without re-event (p = 0.02), in contrast to cortisol (p = 0.53). Copeptin revealed a higher area under the receiver operating characteristics curve (AUC) to predict re-events compared to the ABCD2 score (AUC of 0.73 vs 0.43; p < 0.01) and improved its prognostic accuracy (AUC of combined model of 0.77; p = 0.002). CONCLUSION: Measurement of plasma copeptin but not cortisol levels in patients with TIA provides additional prognostic information beyond the ABCD2 clinical risk score alone. If confirmed in future studies, routine copeptin measurement may be an additional tool for risk stratification and targeted resource allocation after TIA.

Biological, psychological and clinical markers of caregiver's stress in impaired elderly with dementia and age-related disease.

Stress refers to the experience, produced through a person-environment transaction, that results in psychological or physiological distress. Everyday stress or hassles have a larger impact on health, in this frame caring for elderly disabled and/or demented persons have been shown to be a chronic role strain. The concept of stress and strain encompasses different levels of individual functioning (physiological, cognitive, affective, social). We studied whether 3 different distressing conditions show (i) different profiles in biological, psychological and clinical indices of stress, and (ii) different response to temporary environmental manipulation. A sample of 29 caregivers of elderly subjects temporarily institutionalized for (i) respite program, (ii) behavioral psychological symptoms of dementia (BPSD) in dementia-control and, (iii) a rehabilitation program after hip fracture, was assessed with clinical, psychological and biological measures. The BPSD appear to be the most powerful distressing factor, both at the beginning and at the end of the study. On the whole, to an improvement of patient's clinical picture, it corresponds only a partial improvement in stress indices of the caregiver. The slope of biological indices don not parallel those of psychological ones. Among psychometric indices, the pattern of recovery differentiate affective and cognitive domains. The "respite" care condition seems to be the less effective in reducing stress in the caregivers. The stress process should be considered in its different domains to allow a tailored intervention.

Patient with an Xp21 contiguous gene deletion syndrome in association with agenesis of the corpus callosum.

The so-called Xp21 contiguous deletion syndrome or complex glycerol kinase deficiency (GKD) usually presents with classical Duchenne muscular dystrophy (DMD) or a milder dystrophic myopathy, adrenal hypoplasia, and GKD. A number of syndromic and nonsyndromic cases of agenesis of the corpus callosum (ACC) also map to that location. To date, none of the cases of complex GKD have been associated with ACC. Here, we report on a patient with a complex phenotype as a result of the Xp21 contiguous deletion syndrome in association with ACC. Biochemical, cytogenetic, and molecular analyses were performed to detect and establish the size of the genomic deletion. It is at least 3 million base pairs in length; however, exact limits could not be determined in the present study. Nevertheless, we suggest the presence of a primary gene involved in the embryogenesis of the corpus callosum between Xp21.1 and Xp22.11.

A further evaluation of the effect of age on striate cortex of the rhesus monkey.

The brains of 14 rhesus monkeys (Macaca mulatta) between 4 and 35 years old were examined to determine the effects of aging on the thickness, neuronal frequency, fine structure, surface area, and volume of striate cortex. The effects of aging were ascertained by comparing the striate cortex in the six monkeys between 4 and 12 years of age with that of the eight monkeys over 25 years of age. The brains of the monkeys were all fixed by vascular perfusion and except for one of the old monkeys, whose age was estimated, the exact ages of all of the monkeys are known. One micron thick sections of plastic embedded cortex from one hemisphere of each monkey were examined by light microscopy to determine the thickness of the striate cortex, and neuronal frequency was determined by counting the numbers of neurons displaying nuclei in 250 microns-wide strips passing through the thickness of the cortex. When young monkeys were compared with the old ones, no differences were found in either the thickness of the cortex or in the numbers of neuronal profiles beneath unit areas of cortical surface. This suggests that neurons are not lost with age, and when the cortices were examined by electron microscopy there was no indication that the cell bodies of neurons are degenerating, except possibly in layer 1. Serial, 30 microns-thick, Nissl stained frozen sections from the other hemisphere of each monkey were used to determine both the surface area and the volume of the striate cortex. Overall, the surface area varied between 702 and 1480 mm2, with a mean value of 956 mm2, but there was no indication that the surface area decreased with age, and the same is true for the volume of striate cortex. The conclusion is that while there is a large variation in the amount of cortex occupied by area 17, there is no indication that its thickness, volume, or number of neurons is altered by age.

[Cytokines and chemokines in child physiopathology]. / Citochine e chemiochine in fisiopatologia infantile.

The paper reviews the modern knowledge of cytokines in physiopathology. Particular interest is expressed in their role in the endocrine system and, for chemokines, their role in the induction of leukocyte chemotaxis and the body's reaction (not only immune) to special situations and stimuli, for example infections (HIV, TBC, etc.), transplant reject, etc.

["Pediatric" forms of Creutzfeldt-Jakob disease (nvCJD)]. / Forme "pediatriche" della malattia di Creutzfeldt-Jacob (nvCJD).

The authors propose the name of pediatric CJD disease (nvCJD) for those forms of this pathology which appear in childhood and adolescence (about twenty cases have been reported in Europe: 1996). The "pediatric form" differs both in terms of age ("teenagers" and also 16-year-old), but also owing to its long course (mean of 14 to 35 months) and the early onset of psychiatric and sensory symptoms. Until a few years ago, discussion of a new pediatric-adolescent form of the disease (new variant of CJD) would have been laughable.