Early Embolization After Carotid Artery Stenting with Mesh-Covered Stent: Role of Diffusion-Weighted Magnetic Resonance Imaging as Pre-procedural Predictor and Discriminant Between Intra- and Post-procedural Events.

OBJECTIVES: To evaluate the incidence and the time of onset of early micro-embolism after CAS (carotid artery stenting) with two different mesh-covered stents and to assess the role of DW-MRI (Diffusion-weighted magnetic resonance imaging) in their prediction. METHODS: Single-institution prospective study including 50 patients (33 male, median age 74 years) who underwent CAS with Roadsaver® or CGuard™. All patients with primary stenosis (37/50, 74%) had carotid plaque DW-MRI pre-procedure, with both qualitative evaluation of the hyperintensity and ADC (apparent diffusion coefficient) measurement of the plaque. All patients had brain DW-MRI pre-procedure, at 1 h, 24 h and 30 days post-procedure to evaluate the appearance of hyperintense lesions over time. Imaging analysis was performed in a double-blinded fashion by two radiologists. RESULTS: There were no statistically significant differences between the two stents both in the incidence at 1 h (P = 0.23) and 24 h (P = 0.36) and in the volume of new DWI hyperintense brain lesions at 24 h (P = 0.27). Thirty-four new asymptomatic lesions in 19 patients (38%) were reported: 4 (11.8%) at 1 h, 30 (88.2%) at 24 h. The 30-day DWI-MR showed complete resolution of all lesions and no evidence of new lesion. The incidence of new lesions at 24 h resulted significantly higher in patients with DWI hyperintense carotid plaques (12/16, 75% vs. 0/21, 0%, P < 0.0001). This result was paralleled by the difference in ADC value (0.83 ± 0.21 vs. 1.42 ± 0.52). CONCLUSION: The majority of early asymptomatic brain lesion occurred during the first 24 h after CAS. Pre-procedure high DWI signal of the plaque was associated with an increased incidence of post-procedure microembolizations.

Preoperative MRI evaluation of lesion-nipple distance in breast cancer patients: thresholds for predicting occult nipple-areola complex involvement.

AIM: To identify clinically occult nipple-areola complex (NAC) involvement using preoperative magnetic resonance imaging (MRI), to inform selection of patients eligible for nipple-sparing mastectomy (NSM) or skin-sparing mastectomy (SSM). MATERIAL AND METHODS: This was a retrospective study of 195 patients, who had preoperative breast MRI (February 2011 to January 2017) before undergoing surgical treatments (NSM or SSM) for newly diagnosed breast cancer. Tumour features at MRI (mass or non-mass lesion, diameter, lesion-NAC distance [LND]) and pathology (lesion diameter, histopathological type, receptor status) were recorded, as well as the type of surgery (NSM/SSM) and presence (NAC+) or absence (NAC-) of tumour at intraoperative evaluation of retroareolar tissue. Mann-Whitney test, Fisher's exact test, logistic regression, and receiver operating characteristic (ROC) curve analysis were used for analysis of NAC+ versus NAC- to assess variables that predict NAC tumoural involvement. RESULTS: Over the study period, NAC+ was proven histologically in 71/200 (35.5%) surgical treatments, while there were 129/200 NAC- (72 NSM and 128 SSM performed). LND at MRI was statistically (p<0.001) lower in NAC+ patients than in NAC- patients. The area under the ROC curve (0.82, 95% confidence interval [CI]: 0.76-0.88) indicated 10 mm as the best cut-off, with sensitivity of 82%, specificity of 72%, and accuracy of 79%. A 5-mm cut-off enhanced sensitivity, whereas a 15-mm cut-off favoured specificity. CONCLUSIONS: MRI is a useful tool for identifying NAC+ patients; a 10-mm cut-off for LND assists selection of patients for NSM, although intraoperative retroareolar tissue examination remains mandatory.

Digital breast tomosynthesis as an adjunct to digital mammography for detecting and characterising invasive lobular cancers: a multi-reader study.

AIM: To examine the interpretive performance of digital breast tomosynthesis (DBT) as an adjunct to digital mammography (DM) compared to DM alone in a series of invasive lobular carcinomas (ILCs) and to assess whether DBT can be used to characterise ILC. MATERIALS AND METHODS: A retrospective, multi-reader study was conducted of 83 mammographic examinations of women with 107 newly diagnosed ILCs ascertained at histology. Consenting women underwent both DM and DBT acquisitions. Twelve radiologists, with varying mammography experience, interpreted DM images alone, reporting lesion location, mammographic features, and malignancy probability using the Breast Imaging-Reporting and Data System (BI-RADS) categories 1-5; they then reviewed DBT images in addition to DM, and reported the same parameters. Statistical analyses compared sensitivity, false-positive rates (FPR), and interpretive performance using the receiver operating characteristics (ROC) curve and the area under the curve (AUC), for reading with DM versus DM plus DBT. RESULTS: Multi-reader pooled ROC analysis for DM plus DBT yielded AUC=0.89 (95% confidence interval [CI]: 0.88-0.91), which was significantly higher (p<0.0001) than DM alone with AUC=0.84 (95% CI: 0.82-0.86). DBT plus DM significantly increased pooled sensitivity (85%) compared to DM alone (70%; p<0.0001). FPR did not vary significantly with the addition of DBT to DM. Interpreting with DBT (compared to DM alone) increased the correct identification of ILCs depicted as architectural distortions (84% versus 65%, respectively) or as masses (89% versus 70%), increasing interpretive performance for both experienced and less-experienced readers; larger gains in AUC were shown for less-experienced radiologists. Multifocal and/or multicentric and bilateral disease was more frequently identified on DM with DBT. CONCLUSION: Adding DBT to DM significantly improved the accuracy of mammographic interpretation for ILCs and contributed to characterising disease extent.

Can DW-MRI, with its ADC values, be a reliable predictor of biopsy outcome in patients with suspected prostate cancer?

PURPOSE: To relate the multiparametric magnetic resonance imaging (mp-MRI) of patients with suspect peripheral prostate cancer (PCa) to the results of the subsequent biopsy: in particular to explore whether DWI and ADC can predict the biopsy outcome and to investigate the relation between ADC and Gleason score (GS). MATERIALS AND METHODS: 175 consecutive patients who underwent 1.5 T mp-MRI followed by prostate biopsy were retrospectively analyzed by two independent radiologists. ADC values were measured in the peripheral suspect lesion areas (ADCSL) and in the contralateral zones (ADCNSL) obtaining ADCnorm = ADCSL/ADCNSL. Results on T2W images, DWI, ADC values, and perfusion studies were matched to their corresponding biopsy. RESULTS: Negative DWI and T2W had 100% negative predictive value (NPV). When DWI was positive, ADCSL > 0.90 × 10 > 0.90 × 10(-3) mm(2)/s (ADCnorm > 0.60) identified by the ROC curve (AUC = 0.80) corresponded to NPV = 85%. In positive biopsies, ADCSL and ADCnorm decreased significantly from GS = 6 to GS ≥ 8 with Spearman coefficient ρ = -0.40 and ROC curve AUC = 0.72. CONCLUSION: mp-MRI allows a reliable prediction of a negative biopsy through the values of DWI, T2W, and ADC. In positive biopsies, there is a moderate correlation between ADC and the various GS levels.

Review: Assessment of completeness of reporting in intervention studies using livestock: an example from pain mitigation interventions in neonatal piglets.

Accurate and complete reporting of study methods, results and interpretation are essential components for any scientific process, allowing end-users to evaluate the internal and external validity of a study. When animals are used in research, excellence in reporting is expected as a matter of continued ethical acceptability of animal use in the sciences. Our primary objective was to assess completeness of reporting for a series of studies relevant to mitigation of pain in neonatal piglets undergoing routine management procedures. Our second objective was to illustrate how authors can report the items in the Reporting guidElines For randomized controLled trials for livEstoCk and food safety (REFLECT) statement using examples from the animal welfare science literature. A total of 52 studies from 40 articles were evaluated using a modified REFLECT statement. No single study reported all REFLECT checklist items. Seven studies reported specific objectives with testable hypotheses. Six studies identified primary or secondary outcomes. Randomization and blinding were considered to be partially reported in 21 and 18 studies, respectively. No studies reported the rationale for sample sizes. Several studies failed to report key design features such as units for measurement, means, standard deviations, standard errors for continuous outcomes or comparative characteristics for categorical outcomes expressed as either rates or proportions. In the discipline of animal welfare science, authors, reviewers and editors are encouraged to use available reporting guidelines to ensure that scientific methods and results are adequately described and free of misrepresentations and inaccuracies. Complete and accurate reporting increases the ability to apply the results of studies to the decision-making process and prevent wastage of financial and animal resources.

Pain management in the neonatal piglet during routine management procedures. Part 2: grading the quality of evidence and the strength of recommendations.

Piglets reared in swine production in the USA undergo painful procedures that include castration, tail docking, teeth clipping, and identification with ear notching or tagging. These procedures are usually performed without pain mitigation. The objective of this project was to develop recommendations for pain mitigation in 1- to 28-day-old piglets undergoing these procedures. The National Pork Board funded project to develop recommendations for pain mitigation in piglets. Recommendation development followed a defined multi-step process that included an evidence summary and estimates of the efficacies of interventions. The results of a systematic review of the interventions were reported in a companion paper. This manuscript describes the recommendation development process and the final recommendations. Recommendations were developed for three interventions (CO2/O2 general anesthesia, non-steroidal anti-inflammatory drugs (NSAIDs), and lidocaine) for use during castration. The ability to make strong recommendations was limited by low-quality evidence and strong certainty about variation in stakeholder values and preferences. The panel strongly recommended against the use of a CO2/O2 general anesthesia mixture, weakly recommended for the use of NSAIDs and weakly recommended against the use of lidocaine for pain mitigation during castration of 1- to 28-day-old piglets.

The effect of timing of oral meloxicam administration on physiological responses in calves after cautery dehorning with local anesthesia.

Dehorning is a painful husbandry procedure that is commonly performed in dairy calves. Parenteral meloxicam combined with local anesthesia mitigates the physiological and behavioral effects of dehorning in calves. The purpose of this study was to determine the influence of timing of oral meloxicam administration on physiological responses in calves after dehorning. Thirty Holstein bull calves, 8 to 10 wk of age (28-70 kg), were randomly assigned to 1 of 3 treatment groups: placebo-treated control group (n=10), calves receiving meloxicam administered orally (1 mg/kg) in powdered milk replacer 12h before cautery dehorning (MEL-PRE; n=10), and calves receiving meloxicam administered as an oral bolus (1 mg/kg) at the time of dehorning (MEL-POST; n=10). Following cautery dehorning, blood samples were collected to measure cortisol, substance P (SP), haptoglobin, ex vivo prostaglandin E2 (PgE2) production after lipopolysaccharide stimulation and meloxicam concentrations. Maximum ocular temperature and mechanical nociceptive threshold (MNT) were also assessed. Data were analyzed using noncompartmental pharmacokinetic analysis and repeated measures ANOVA models. Mean peak meloxicam concentrations were 3.61±0 0.21 and 3.27±0.14 µg/mL with average elimination half-lives of 38.62±5.87 and 35.81±6.26 h for MEL-PRE and MEL-POST, respectively. Serum cortisol concentrations were lower in meloxicam-treated calves compared with control calves at 4 h postdehorning. Substance P concentrations were significantly higher in control calves compared with meloxicam-treated calves at 120 h after dehorning. Prostaglandin E2 concentrations were lower in meloxicam-treated calves compared with control calves. Mechanical nociceptive threshold was higher in control calves at 1h after dehorning, but meloxicam-treated calves tended to have a higher MNT at 6h after dehorning. No effect of timing of meloxicam administration on serum cortisol concentrations, SP concentrations, haptoglobin concentrations, maximum ocular temperature, or MNT was observed. However, PgE2 concentrations in MEL-PRE calves were similar to control calves after 12h postdehorning, whereas MEL-POST calves had lower PgE2 concentrations for 3 d postdehorning. These findings support that meloxicam reduced cortisol, SP, and PgE2 after dehorning, but only PgE2 production was significantly affected by the timing of meloxicam administration.

Effect of castration method on neurohormonal and electroencephalographic stress indicators in Holstein calves of different ages.

As public concern for food animal welfare increases, a need to validate objective pain assessment tools exists in order to formulate animal welfare policies and facilitate regulatory approval of compounds to alleviate pain in livestock in the United States. The aims of this study were (1) to compare the physiological response to pain induced by surgical and nonsurgical (band) castration in calves and (2) to elucidate age-related differences in pain response of calves subjected to different castration methods. Seventy-six Holstein bull calves were blocked by age (≤8-wk and ≥6-mo-old) and randomly assigned to 1 of 4 treatment groups: control (n=20), castration by banding (n=18), cut-and-clamp surgical castration (n=20), and cut-and-pull surgical castration (n=18). Measurements included electroencephalogram, heart rate variability, infrared thermography, electrodermal activity, and concentrations of serum cortisol and plasma substance P before, during, and within 20min following castration. Electroencephalogram recordings showed desynchronization for all treatments, consistent with increased arousal; yet the magnitude of desynchronization was greatest for 6-mo-old calves castrated by cut-and-clamp. Additionally, older calves in the cut-and-pull group showed greater desynchronization than younger calves in the same group. Based on the heart rate variability analysis, 6-mo-old calves in the control or cut-and-pull castration groups showed greater sympathetic tone than younger calves in the same treatment groups. Overall, younger calves showed lower electrodermal activity than older calves. Regardless of treatment, concentrations of cortisol and plasma substance P were greater in 6-mo-old calves relative to their younger counterparts, indicating a more robust response to all treatments in older calves. In summary, neurohormonal and electroencephalographic stress responses of calves to castration were age-specific. Castration by cut-and-clamp showed the most pronounced stress response in 6-mo-old calves. These findings provide evidence that support welfare policies recommending castration at an early age and the use of analgesic compounds at the time of surgical castration especially in older calves. However, the potential long-term negative consequences of early untreated pain must be considered and warrant further investigation.

The pharmacokinetics and effects of meloxicam, gabapentin, and flunixin in postweaning dairy calves following dehorning with local anesthesia.

Approved analgesic compounds in cattle are not currently available in the United States due to the lack of validated pain assessment methods and marker residue depletion studies. In this study, we compared the pharmacokinetic parameters and effect of preemptive analgesics administered to calves subjected to dehorning with local anesthesia. Holstein steers were randomly assigned to receive one of the following treatments per os (PO) or intravenously (IV) (n = 8/group): meloxicam (1 mg/kg PO), gabapentin (15 mg/kg PO), meloxicam (1 mg/kg), and gabapentin (15 mg/kg) PO, flunixin (2.2 mg/kg IV), or a placebo. Plasma drug, haptoglobin, substance P (SP) concentrations, serum cortisol concentrations, ocular thermography, mechanical nociceptive threshold (MNT), and average daily gain (ADG) were evaluated. Data were analyzed using mixed-effects models and noncompartmental pharmacokinetic analysis. Meloxicam, gabapentin, and meloxicam with gabapentin at the present doses did not reduce cortisol concentrations. Analgesic-treated calves had significantly lower plasma SP concentrations and improved ADG compared with controls. Flunixin calves had reduced circulating cortisol compared with controls. Meloxicam-treated calves showed an increase in MNT at two horn bud sites compared with the other treatments. Analgesics improved ADG and reduced biomarkers of pain, but effects differed by compound and route of administration.

A study to compare circulating flunixin, meloxicam and gabapentin concentrations with prostaglandin E2 levels in calves undergoing dehorning.

The purpose of this study was to investigate the pharmacokinetics of intravenous flunixin (2.2 mg/kg b.w.), oral meloxicam (1mg/kg b.w.), oral gabapentin (15 mg/kg b.w.) alone or co-administrated with meloxicam as well as the effects of these compounds on prostaglandin E2 (PGE2) synthesis in calves subjected to surgical dehorning. Plasma samples collected up to 24h after drug administration were analyzed by liquid chromatography/mass spectrometry, whereas blood PGE2 levels were measured by immunoenzymatic assay. In plasma, the terminal half-live of flunixin, meloxicam and gabapentin were 6.0 h (range, 3.4-11.0 h), 16.7h (range, 13.7-21.3h) and 15.3h (range, 11-32.9h), respectively. The co-administration of single doses of gabapentin and meloxicam did not seem to affect the pharmacokinetic profile of the two drugs except for gabapentin that reached significantly (P<0.05) higher maximum serum concentration (Cmax) when co-administered with meloxicam, than when administered alone. At 5, 360 and 720 min after dehorning, a significant (P<0.01) decrease in PGE2 concentration was observed in flunixin-treated animals compared with control calves. Moreover, circulating log PGE2 concentrations were inversely proportional to log flunixin concentrations (R(2)=0.75; P<0.0001). None of the other drugs significantly affected blood PGE2 levels. Further assessment of oral meloxicam and gabapentin in established pain models is required to formulate science based analgesic recommendations to enhance animal well-being after dehorning.

Contrast enhanced ultrasound in atherosclerotic carotid artery disease.

AIM: The traditional morphological parameters for the description of a carotid atherosclerotic plaque (degree of stenosis, echogenicity, systolic peak velocity etc.) are insufficient for the prediction of the risk of embolization. Contrast enhanced ultrasound (CEUS), based on the theory of inflammation and neoangiogenesis, seems to have a great potential for the detection of unstable plaques. The purpose of our work was to compare echogenicity of the plaque (evaluated with the Grey Scale Median; GSM), the degree of stenosis and CEUS with the histopathological findings. METHODS: Patients with indication for internal carotid endarterectomy (CEA) underwent a preoperative imaging study with B-mode echo Doppler Ultrasound and with CEUS. The contrast enhancement of the plaque was described with two parameters: the maximum and mean signal intensity (SImax, SImean). After the surgical operation the removed plaque is sent to the pathology laboratory for the measurement of the neoangiogenesis (vessel density, VD). RESULTS: Fifty-one consecutive patients were enrolled (12 symptomatic, 39 asymptomatic). Analysis pointed out significant differences between symptomatic and asymptomatic patients for: GSM median 14 (I quartile 11.5; III quartile 23) versus 32.5 (27-42.25) (P=0.012); SI (%) SImax 30 (29-35.5) versus 24 (19.7-27) (P<0.001) and SImean 23 (20.5-27) versus 15 (8-18.25) (P<0.001); VD (vessels/mm2) 41.5 (30-70) versus 12.6 (7-18.6) (P<0.001), respectively. Moreover, a cut-off value was determined between the two groups for each parameter: GSM:25, SImax:28%, SImean:20%, and VD: 25/mm2. Combined analysis showed that plaques with greater contrast enhancement had more newly formed capillaries and that plaques with lower GSM values correlated with greater vascularization. CONCLUSION: The study confirms that in vitro neoangiogenesis, contrast enhancement and stability of the plaque are strongly connected and CEUS appears to be one of the most promising tools for the stratification of the carotid plaque vulnerability.

Assessing water-electrolyte changes of hyperglycaemic hyperosmolar coma.

AIM: We reported new methods to accurately estimate salt and water deficits during hyperglycaemic hyperosmolar coma (HC), valid under restricted boundary conditions. The accuracy of these estimates is herein verified over the unrestricted spectrum of abnormalities, to correctly evaluate any patient with just one algorithm that recognizes the boundary conditions pertaining to each abnormality, choosing the appropriate calculations. METHODS: A large number of cases of HC was simulated on computer by subtracting an exhaustive combination of water, sodium and chloride losses coupled to a large variety of gains in glucose. Altered solute concentrations were generated. From these true plasma concentrations generated by the computer, the losses of water and electrolytes were back-calculated with our new computational algorithm, by knowing in addition only the normal total body water and extra-cellular volume. The accuracy of the method was tested by comparing true to calculated values over the entire range of deranged values. In 100 patients admitted to hospital for HC these same computations were performed, where calculated data were validated by comparing them to true data obtained by balance studies performed during correction of the abnormality. RESULTS: Both in simulated and real cases of HC true and calculated data for the changes in Na and volume were significantly correlated (R (2)=0.76 and 0.50, respectively, P<0.01), while their mean values were not significantly different by paired "t" tests (P>0.05 for all). CONCLUSION: Our new computation algorithm, applicable to the bed-side, useful in accurately assessing the average water-electrolyte deficits of HC, can be used to guide correct re-infusion strategies.

Effect of intravenous sodium salicylate administration prior to castration on plasma cortisol and electroencephalography parameters in calves.

Nociception is an unavoidable consequence of many routine management procedures such as castration in cattle. This study investigated electroencephalography (EEG) parameters and cortisol levels in calves receiving intravenous sodium salicylate in response to a castration model. Twelve Holstein calves were randomly assigned to the following groups: (i) castrated, untreated controls, (ii) 50 mg/kg sodium salicylate IV precastration, were blood sampled at 0, 5, 10, 20, 30, 45, 60, 90, 120, 150, 180, 240, 360, and 480 min postcastration. The EEG recording included baseline, castration, immediate recovery (0-5 min after castration), middle recovery (5-10 min after castration), and late recovery (10-20 min after castration). Samples were analyzed by competitive chemiluminescent immunoassay and fluorescence polarization immunoassay for cortisol and salicylate, respectively. EEG visual inspection and spectral analysis were performed. Statistical analyses included anova repeated measures and correlations between response variable. No treatment effect was noted between the two groups for cortisol and EEG measurements, namely an attenuation of acute cortisol response and EEG desynchronization in sodium salicylate group. Time effects were noted for EEG measurements, cortisol and salicylates levels. Significant correlations between cortisol and EEG parameters were noted. These findings have implications for designing effective analgesic regimens, and they suggest that EEG can be useful to monitor pain attributable to castration.

ApoB/apoA-I ratio is better than LDL-C in detecting cardiovascular risk.

BACKGROUND AND AIMS: Cardiovascular (CV) events occur even when LDL-C are <100mg/dL. To improve the detection of CV risk we investigated the apoB/apoA-I ratio versus LDL-C in subjects considered normal glucose tolerant (NGT) by oral glucose tolerance test (OGTT). METHODS AND RESULTS: We enrolled 616 NGT (273 men and 343 women), and we measured insulin resistance, lipid profile, apoB/apoA-I and the factors compounding the metabolic syndrome (MetS). An unfavourable apoB/apoA-I (≥0.9 for males and ≥0.8 for females) was present in 13.9% of 108 patients with LDL-C <100mg/dL: compared to subjects with lower apoB/apoA-I (<0.9 for males and <0.8 for females), they had more elements of MetS and their lipid profile strongly correlated with high CV risk. Out of 314 patients with lower apoB/apoA-I, 40.12% had LDL-C ≥130mg/dL: these retained a more favourable lipid profile than corresponding subjects with elevated apoB/apoA-I ratio. Finally, we found a significant correlation between LDL-C and apoB/apoA-I ratio (r=0.48, p<0.0001). CONCLUSIONS: In NGT with LDL-C <100mg/dL, a higher apoB/apoA-I exhibited an atherogenic lipid profile, indicating that LDL-C alone is insufficient to define CV risk. Independent from LDL-level, when apoB/apoA-I is lower, the lipid profile is, in fact, less atherogenic. This study demonstrates that apoB/apoA-I is at least complementary to LDL-C in identifying the "effective" CV risk profile of asymptomatic NGT subjects.

Computation of Na and water deficit of iso-osmolar dehydration.

BACKGROUND AND AIMS: The presence of altered plasma Na concentration (PNa) allows calculations of changes in water and electrolyte contents, which are not feasible during normonatremic derangements. We have developed a computational algorithm whereby the changes in solute (ΔNa and ΔCl) and solvent (ΔV) contents can be computed exactly when Na is lost entirely as NaCl (or NaHCO(3)) and nearly exactly in all other circumstances, except when the losses of Na and Cl occur in the same proportions as those of the normal plasma concentration of these ions. METHODS: In computer experiments, we simulated different fluid depletions containing 140 mEq/l of Na (which is to say, ΔNa/ΔV ≈ 140), coupled with variable ratios in Na to Cl losses (variable ΔNa/ΔCl). The data were back-calculated with our algorithms from the ensuing plasma ion concentrations (PNa(1), PCl(1) and POAN(1), where subscript (0) and (1) indicate normal and deranged plasma concentration values, respectively, and OAN indicates anions other than Cl), as if they had been measured on patients, and from known normal values (TBW(0), ECV(0), Na(0)). These were compared to the true values used to build the simulations. This procedure was reproduced in 17 patients suffering from iso-osmolar dehydration, where true data were obtained by balance studies. RESULTS: True and calculated data were compared with linear regression analysis. We obtained significant correlations both in computer-simulated and real patients (R(2) = 0.83, p < 0.005 and R(2) = 0.63, p < 0.05, respectively). CONCLUSION: This new math model and its related computational method are useful in the correct evaluation and treatment of iso-osmolar dehydration.

Quantitative assessment of the abnormalities of hyperosmolar coma when glucose excess is larger than Na deficit.

Computing Na and water deficits of hyperosmolar coma (HC) is important in correcting the derangement, to avoid unwanted iatrogenic electrolyte derangements and brain oedema. This paper derives and applies formulas valid when GA (glucose accumulation) >2.DeltaNa (sodium loss), with or without DeltaV (water depletion). We built a model system and wrote the equations describing the relationships between volume and concentration of solutes within the body water compartments. HC was simulated on computer experiments by adding GA in different amounts combined with a large variety of DeltaNa and DeltaV. The ensuing concentrations in Na (PNaNone. (1)) and glucose (PG (1)) were used to identify the condition GA >2 . DeltaNa, DeltaV=0 or not equal 0, and then, with original formulas, to back calculate GA, DeltaNa and DeltaV. These same calculations were applied to 31 patients with HC. The procedure to recognize the conditions under investigation unerringly discarded all simulations except those characterized by GA >2 . DeltaNa, with or without DeltaV. When DeltaV=0, the computations yielded values identical to the true ones for GA and DeltaNa (R (2)=1.00, p<0.0001). When DeltaV was present, the correlation coefficients between calculated and true values were 0.92 (p<0.001) for GA, 0.73 (p<0.001) for DeltaNa, 0.74 (p<0.001) for DeltaV in computer experiments, while they were R (2)>0.47<0.95 (p<0.001) in patient studies. The accuracy in computing solute and water changes demonstrates the validity of our model system of HC, and of the calculation formulas, which can be used to quantitatively evaluate the deficits in Na and volume, as well as the addition of glucose, improving the effectiveness of treatment.

Methods for the quantitative assessment of electrolyte disturbances in hyperglycaemia.

AIM: While empirical calculations are presently used, exact solutions to compute volume and solute changes of hyperosmolar coma (HC) can be obtained by subdividing the patients according to well defined clinical and laboratory conditions. These are represented by PNa(G), the plasma Na concentration that would be present if there were only glucose addition (GA), that discloses prevalent Na depletion when >PNa(1), prevalent water deficit when , = or

Electroencephalography in the diagnosis of hydrocephalus in golden hamsters (Mesocricetus auratus).

The golden hamster (Mesocricetus auratus) is a popular laboratory animal and is used in a multitude of behavioural studies. However, it has been shown that it suffers from different forms of hereditary hydrocephalus, which may result in behavioural changes. This prospective study was designed to look into the usefulness of electroencephalography (EEG) measurements in the diagnosis of hydrocephalus in hamsters. The EEGs of the hydrocephalic hamsters were evaluated double-blind and showed a high-voltage slow wave activity, with a fast activity superimposed onto it. This pattern has already been well described in other hydrocephalic species and differed significantly from the EEGs that were obtained from the normal hamsters. It was concluded from our study that a background activity with an amplitude over 50 muV in combination with a frequency of < or =5 Hz was highly indicative of hydrocephalus in young hamsters. We believe that the EEG could be a very useful diagnostic tool in the screening for hydrocephalus in hamsters.

Metabolic characteristics of glucose intolerance: the critical role of obesity.

INTRODUCTION: Obesity enhances insulin secretion and resistance. We investigated its importance in linking insulin metabolism to glucose intolerance. MATERIAL AND METHODS: We studied 700 subjects referred by general practitioners for possible metabolic abnormalities. Plasma glucose was measured before (FPG) and after (2h-PG) OGTT, together with insulin. Insulin resistance was estimated by HOMA-IR, insulin sensitivity using ISI(gly) and ISI(Stumvoll) indexes, insulin secretion by first (1stPH est) and second phase (2ndPH est) estimates. RESULTS: Sixty three subjects had impaired glucose tolerance (IGT), 132 impaired fasting glucose (IFG), 63 a mixed disorder (IFG/IGT). Insulin resistance was present only in IGT and IFG/IGT. IFG sub-jects had inappropriately low insulin secretionexclusively during fasting. In a stepwise logistic regression analysis BMI>or=27, female sex and hy-pertension were associated to an altered 2h-PG during OGTT, while hypertension and age were linked to alterations in FPG. While overweight prevalence (BMI>or=7) was higher in all glucose intolerance groups, obesity (BMI>or=30) was typical of IGT. Overweight and obesity were related to higher insulin concentration, secretion and resistance. Obese normal glucose tolerant subjects were more insulin resistant than lean IFG patients. DISCUSSION: OGTT is essential to correctly establish the metabolic derangement of glucose intolerance. Obesity is significantly connected with the impairment of insulin metabolism even in subjects with normal FPG. Considering that both obesity and insulin resistance are independently associated to an increased cardiovascular risk, all overweight subjects, even with normal FPG, should be referred for OGTT evaluation to define glucose tolerance status in order to enforce adequate preventive actions.