A modality-specific somatosensory evoked potential test protocol for clinical evaluation: A feasibility study

ObjectiveWe aimed to establish an objective neurophysiological test protocol that can be used to assess the somatosensory nervous system.MethodsIn order to assess most fiber subtypes of the somatosensory nervous system, repetitive stimuli of seven different modalities (touch, vibration, pinprick, cold, contact heat, laser, and warmth) were synchronized with the electroencephalogram (EEG) and applied on the cheek and dorsum of the hand and dorsum of the foot in 21 healthy subjects and three polyneuropathy (PNP) patients. Latencies and amplitudes of the modalities were assessed and compared. Patients received quantitative sensory testing (QST) as reference.ResultsWe found reproducible evoked potentials recordings for touch, vibration, pinprick, contact-heat, and laser stimuli. The recording of warm-evoked potentials was challenging in young healthy subjects and not applicable in patients. Latencies were shortest within Aβ-fiber-mediated signals and longest within C-fibers. The test protocol detected function loss within the Aβ-fiber and Aδ-fiber-range in PNP patients. This function loss corresponded with QST findings.ConclusionIn this pilot study, we developed a neurophysiological test protocol that can specifically assess most of the somatosensory modalities. Despite technical challenges, initial patient data appear promising regarding a possible future clinical application.SignificanceEstablished and custom-made stimulators were combined to assess different fiber subtypes of the somatosensory nervous system using modality-specific evoked potentials.     

Derivation of internal dose-based thresholds of toxicological concern for occupational inhalation exposure to systemically acting organic chemicals

This study aimed at deriving occupational thresholds of toxicological concern for inhalation exposure to systemically-acting organic chemicals using predicted internal doses. The latter were also used to evaluate the quantitative relationship between occupational exposure limit and internal dose. Three internal dose measures were identified for investigation: (i) the daily area under the venous blood concentration vs. time curve, (ii) the daily rate of the amount of parent chemical metabolized, and (iii) the maximum venous blood concentration at the end of an 8-hr work shift. A dataset of 276 organic chemicals with 8-hr threshold limit values-time-weighted average was compiled along with their molecular structure and Cramer classes (Class I: low toxicity, Class II: intermediate toxicity, Class III: suggestive of significant toxicity). Using a human physiologically-based pharmacokinetic model, the three identified dose metrics were predicted for an 8-hr occupational inhalation exposure to the threshold limit value for each chemical. Distributional analyses of the predicted dose metrics were performed to identify the percentile values corresponding to the occupational thresholds of toxicological concern. Also, simple linear regression analyses were performed to evaluate the relationship between the 8-hr threshold limit value and each of the predicted dose metrics, respectively. No threshold of toxicological concern could be derived for class II due to few chemicals. Based on the daily rate of the amount of parent chemical metabolized, the proposed internal dose-based occupational thresholds of toxicological concern were 5.61?×?10^?2 and 9?×?10^?4 mmol/d at the 10th percentile level for classes I and III, respectively, while they were 4.55?×?10^?1 and 8.5?×?10^?3 mmol/d at the 25th percentile level. Even though high and significant correlations were observed between the 8-hr threshold limit values and the predicted dose metrics, the one with the rate of the amount of chemical metabolized was remarkable regardless of the Cramer class (r² = 0.81; n = 276). The proposed internal dose-based occupational thresholds of toxicological concern are potentially useful for screening-level assessments as well as prioritization within an integrated occupational risk assessment framework.     

ONRAB® oral rabies vaccine is shed from,but does not persist in,captive mammals

ONRAB® is a human adenovirus rabies glycoprotein recombinant vaccine developed to control rabies in wildlife. To support licensing and widespread use of the vaccine, safety studies are needed to assess its potential residual impact on wildlife populations. We examined the persistence of the ONRAB® vaccine virus in captive rabies vector and non-target mammals. This research complements work on important rabies vector species (raccoon, striped skunk, and red fox) but also adds to previous findings with the addition of some non-target species (Virginia opossum, Norway rats, and cotton rats) and a prolonged period of post vaccination monitoring (41 days). Animals were directly inoculated orally with the vaccine and vaccine shedding was monitored using quantitative real-time PCR applied to oral and rectal swabs. ONRAB® DNA was detected in both oral and rectal swabs from 6 h to 3 days post-inoculation in most animals, followed by a resurgence of shedding between days 17 and 34 in some species. Overall, the duration over which ONRAB® DNA was detectable was shorter for non-target mammals, and by day 41, no animal had detectable DNA in either oral or rectal swabs. All target species, as well as cotton rats and laboratory-bred Norway rats, developed robust humoral immune responses as measured by competitive ELISA, with all individuals being seropositive at day 31. Similarly, opossums showed good response (89% seropositive; 8/9), whereas only one of nine wild caught Norway rats was seropositive at day 31. These results support findings of other safety studies suggesting that ONRAB® does not persist in vector and non-target mammals exposed to the vaccine. As such, we interpret these data to reflect a low risk of adverse effects to wild populations following distribution of ONRAB® to control sylvatic rabies.     

The best strategy for red blood cell transfusion in severe burn patients,restrictive or liberal: A randomized controlled trial

IntroductionAlthough blood transfusion is common in burns, data are lacking in appropriate transfusion thresholds. It has been reported that a restrictive blood transfusion policy decreases blood utilization and improves outcomes in critically ill adults, but the impact of a restrictive blood transfusion policy in burn patients is unclear. We decided to investigate the outcome of decreasing the blood transfusion threshold.Material and methodsEighty patients with TBSA > 20% who met our inclusion criteria were included. They were randomly divided into control and intervention groups. The intervention group received packed cells only when Hemoglobin declined to less than 8 g/dL at routine laboratory evaluations. While the control group received packed-cell when hemoglobin was declined to less than 10 g/dl. The total number of the received packed cell before, during and after any surgical procedure was recorded. The outcome was measured by the evaluation of the infection rate and other complications.ResultThe mean hemoglobin level before transfusion was 7.7 ± 0.4 g/dL in the restrictive group and 8.8 ± 0.7 g/dL in the liberal group. The mean number of RBC unit transfusion per patient in the restrictive group was significantly lower than the traditional group (3.28 ± 2.2 units vs. 5.9 ± 3.7 units) (p-value = 0.006). The total number of RBC transfused units varied significantly between the two groups (p-value = 0.014). The number of transfused RBC units outside the operation room showed a significant difference between groups (restrictive: 2.8 ± 1.4 units vs. liberal: 4.4 ± 2.6 units) (p = 0.004). We did not find any significant difference in mortality rate or other outcome measures between groups.ConclusionApplying the restrictive transfusion strategy in thermal burn patients who are highly prone to all kinds of infection, does not adversely impact the patient outcome, and results in significant cost savings to the institution and lower rate of infection. We conclude that the restrictive transfusion practice during burn excision and grafting is well tolerated and effective in reducing the number of transfusions without increasing complications.Clinical Trial Registration ReferenceIRCT20190209042660N1.     

The range of minimum provoking doses in hazelnut-allergic patients as determined by double-blind, placebo-controlled food challenges

BACKGROUND: The risk for allergic reactions depends on the sensitivity of individuals and the quantities of offending food ingested. The sensitivity varies among allergic individuals, as does the threshold dose of a food allergen capable of inducing an allergic reaction. OBJECTIVE: This study aimed at determining the distribution of minimum provoking doses of hazelnut in a hazelnut-allergic population. METHODS: Thirty-one patients with a history of hazelnut-related allergic symptoms, a positive skin prick test to hazelnut and/or an elevated specific IgE level, were included. Double-blind, placebo-controlled food challenges (DBPCFC) were performed with seven increasing doses of dried hazelnut (1 mg to 1 g hazelnut protein) randomly interspersed with seven placebo doses. RESULTS: Twenty-nine patients had a positive challenge. Itching of the oral cavity and/or lips was the first symptom in all cases. Additional gastrointestinal symptoms were reported in five patients and difficulty in swallowing in one patient. Lip swelling was observed in two patients, followed by generalized urticaria in one of these. Threshold doses for eliciting subjective reactions varied from a dose of 1 mg up to 100 mg hazelnut protein (equivalent to 6.4-640 mg hazelnut meal). Extrapolation of the dose-response curve showed that 50% of our hazelnut-allergic population will suffer from an allergic reaction after ingestion of 6 mg (95% CI, 2-11 mg) of hazelnut protein. Objective symptoms were observed in two patients after 1 and 1,000 mg, respectively. CONCLUSION: DBPCFCs demonstrated threshold doses in half of the hazelnut-allergic patients similar to doses previously described to be hidden in consumer products. This stresses the need for careful labelling and strategies to prevent and detect contamination of food products with hazelnut residues.     

高危患者降压治疗:重视控制血压底线

高血压高危患者的降压治疗既需降低血压，又需保持足够血流以保障器官灌注。血压降低过度无疑也有一定风险，因此控制皿压需要底线。高危高血压患者的个体差异大，在降压治疗过程中，临床医生既要以循证医学为鉴，叉须遵循个体化治疗原则，把握好降压幅度和速度，坚持高质量平稳降压，才能更好地保护靶器官，减少心脑血管意外的发生。     

CT scan and threshold vibrometry in the diagnosis of spinocerebellar degenerations

45 patients with spinocerebellar degeneration (SCD) underwent through quantitative investigation of the ventricular and cisternal systems by CT scanning and threshold vibrometry in the limbs to find out whether these parameters could be used for distinguishing mainly spinal from cerebellar forms or from olivopontoce-rebellar atrophy. The increase in the vibration sense threshold and the mild atrophy in the posterior cranial fossa proved typical of spinal forms and the reverse for cerebellar forms. In olivopontocerebellar atrophy enlargement of the cisterns and dilatation of the ventricles always exceeded 85% of normal values.

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Sommario 45 pazienti affetti da degenerazione spinocerebellare (SCD) sono stati sottoposti ad uno studio approfondito di esplorazione quantitativa del sistema ventricolare e cisternale alla TAC e della soglia di percezione vibratoria agli arti per valutare la possibilità di distinguere con questi parametri le forme prevalentemente spinali da quelle cerebellari o delle atrofie olivopontocerebellari. L'aumento della soglia vibratoria e la modesta atrofia in fossa posteriore è risultata tipica delle forme spinali, mentre l'inverso si verifica per le forme cerebellari. Nelle atrofie olivopontocerebellari l'allargamento delle cisterne e la dilatazione dei ventricoli supera quasi sempre l'85% rispetto ai casi normali.

     

血液与非血液灌流行缺血预处理鼠心的电生理实验研究

本实验研究血液与非血液灌流条件下缺血预处理（ＩＰ）对心肌的保护作用。应用离体大鼠Ｌａｎｇｅｎｄｏｒｆ灌流模型，分血液灌流ＩＰ组、非血液（ＫｒｅｂｓＨｅｎｓｅｌｅｉｔ液，ＫＨ液）灌流ＩＰ组及相应的对照组。测量心肌电生理特性等指标。结果与ＫＨ液灌流心脏相似，用血液灌流的大鼠心脏经ＩＰ后，在随后的停灌和复灌期间，心室颤动阈升高，心律失常发生率明显降低。实验结论为在用血液灌流离体大鼠心脏模型上，ＩＰ对心肌的保护作用与用生理溶液灌流的模型基本相同。     

5-羟色胺对大鼠脊髓P物质痛觉调制的影响(英文)

比较SP,5-HT与For诱发的脊髓内c-fos表达的异同,以及它们之间的相互关系,从而进一步了解SP在脊髓痛觉调制中的主要作用.方法:用免疫组织化学法和痛阈测定法.结果:发现大鼠it P物质(sP)10μg和sc5％甲醛(For)150μL诱发的脊髓c-fos表达主要在背角Ⅰ,Ⅱ,Ⅴ及Ⅵ层,同时SP使痛阈降低,For使痛级均数(PIR)升高.5-HT it 20μg引起的c-fos表达较多地分布于背角Ⅲ—Ⅳ层,并可使痛阈升高.5-HT和Fen可分别减弱和增加SP及For诱发的脊髓c-fos表达及痛反应.结论:SP在脊髓内可能主要起致痛作用,5-HT可抑制SP引起的脊髓c-fos表达,从而参与SP的痛觉调制作用.