Reticular influences on primary and augmenting responses in the somatosensory cortex

The effects of brief, conditioning trains of high-frequency pulses to the midbrain reticular formation (RF) on primary and augmenting responses of somatosensory (SI) cortex were investigated. Testing stimulation was applied to the ventrobasal (VB) thalamus or to the white matter (WM) beneath SI in VB-lesioned animals. The RF-elicited EEG activation was associated with increased firing rates of SI neurons, enhanced probability of early synaptic discharges to VB or WM stimuli, and significantly reduced duration of the suppressed firing period following an afferent VB or WM volley. The diminished latency of the postinhibitory rebound under RF stimulation had the consequence that, within 10/sec shock-train, the second stimulus was delivered following completion of the rebound component and, instead of an augmented potential, generated a field response of primary-type. The dependence of the RF-induced change in augmenting potentials upon the sharpening effect exerted on the preceding inhibitory-rebound sequence was corroborated by analyzing the RF influence on neurons with different time-course of recovery from inhibition. The replacement of augmenting potentials by primary responses under RF stimulation is advanced as the mechanism behind the obliteration of spontaneously developing 'type I' spindle-waves during EEG arousal. The demonstration of RF influences on SI responses to WM stimulation in VB-lesioned animals points out the cortical level of the effects. The reticulo-thalamo-cortical pathways underlying these influences are discussed.     

Comparative study of protamine chloride and sulphate in relation to the heparin rebound phenomenon

The heparin rebound phenomenon is observed when protamine sulphate, but not protamine chloride, is employed for the neutralization of heparin. On investigating the stability of several protamine compounds towards the protaminolytic activity of human plasma, we found that while protamine chloride was stable, both the sulphate and the phosphate were degradeable. The free base showed intermediary stability which persisted upon its conversion to either chloride or sulphate. Likewise, conversion of the sulphate into the chloride by means of an ion exchange column, did not alter its sensitivity. Apparently, the stability of protamine derivatives is not influenced by the specific anion bound to them but is rather acquired in the course of the manufacturing procedures involved in their preparation.     

Withdrawal of intravenous glyceryl trinitrate: absence of rebound phenomena with transition to oral isosorbide dinitrate

1. Glyceryl trinitrate (GTN) is frequently infused intravenously as a component of the management of acute coronary syndromes (ACS). Abrupt cessation of GTN infusion after periods of more than 24 h administration often induces rebound vasoconstriction reflecting 'pseudotolerance'; this is also the basis of the 'zero hour phenomenon' during chronic nitrate therapy. The efficacy of oral nitrate regimens to prevent vasoconstriction following cessation of intravenous GTN has not been previously examined. Therefore, we investigated the effects of transition from intravenous GTN to oral isosorbide dinitrate (ISDN) on a parameter of apparent arterial stiffness in patients with ACS. 2. The effects of GTN infusion at 5 microg/min on augmentation index (AIx) were quantified in patients (n = 10) with stable angina pectoris in order to establish the magnitude of effect on apparent arterial stiffness. 3. This infusion rate of GTN reduced AIx from 23 +/- 10% (SD) to 3 +/- 14% (SD) (P < 0.01). The effect of transition from GTN infusion of greater than 24 h duration to ISDN (10 mg tds) were examined in patients (n = 16) with ACS (unstable angina/non-Q-wave myocardial infarction). No patient developed recurrent angina during the 24 h following cessation of GTN infusion. The level of AIx was 8 +/- 4% (SD) prior to GTN cessation and fell to 5 +/- 6% (SD) on ISDN (P = 0.05). 4. Thus, in patients treated for ACS, transition from intravenous GTN to low dose oral ISDN is associated with an incremental vasodilatation and no evidence of 'rebound' ischaemia.     

Comparison of the new rebound tonometer with Goldmann applanation tonometer in a clinical setting

Purpose: To evaluate the clinical usefulness of a new rebound tonometer, Icare^® PRO (Icare PRO), by comparison with Goldmann applanation tonometry (GAT) in a study on patients with glaucoma. Methods: One hundred and seventy‐two eyes of 86 subjects were enrolled in this study. All of the subjects were examined with an autorefractometer, Icare PRO, slit‐lamp biomicroscope, GAT, ultrasound A‐scan and pachymeter. Three intraocular pressure (IOP) measurements were obtained by Icare PRO and GAT. The intraobserver reliabilities were established by calculating the intraclass correlation coefficients. The Bland–Altman plot was used to compare the Icare PRO and GAT. Results: There was a good correlation between the IOP measurement by GAT and that by Icare PRO (r = 0.6995, p < 0.001). The intraclass correlation coefficients of Icare PRO and GAT were 0.778 and 0.955, respectively. The IOP differences between Icare PRO and GAT (mean: 1.92 mmHg; SD: 3.29 mmHg; 95% limit of agreement: ?4.52 to 8.37 mmHg) did not vary over the wide range of central corneal thickness (p = 0.498), age (p = 0.248), axial length (p = 0.277) or spherical equivalent (p = 0.075). Conclusions: Although IOP with Icare PRO was higher than that with GAT, especially at lower GAT IOP value, Icare PRO was found to be a reliable method and showed a good correlation with GAT. The IOP difference between Icare PRO and GAT was not affected by the central corneal thickness, age, axial length or spherical equivalent. Icare PRO can be expected not only to be a good screening tool but also to be a good substitute for GAT.     

Evidence of the principle of similitude in modern fatal iatrogenic events

Samuel Hahnemann attributed fundamental importance to the principle of similitude, promoting it to a 'natural law'. Observing that enantiopathic or allopathic treatment produced enduring aggravation of the disease symptoms after a brief and transitory initial relief, he systematised homeopathic treatment, prescribing substances that provoke similar symptoms in healthy individual. Based on clinical and experimental observations, he anticipated the concept of homeostasis, dividing the effects of substances into: primary action of the medicine followed by secondary action or reaction of the organism. This reaction, known as the rebound effect or paradoxical action by modern pharmacology, used to awake the curative response of the body when the principle of similitude is applied, is responsible for several iatrogenic diseases when used on the basis of the principle of contraries. This study discusses the role of this paradoxical reaction of the organism in the fatal side effects of four important drugs, used according to the model of enantiopathic treatment of the symptoms. I present evidence relating to acetylsalicylic acid, rofecoxib, antidepressants and long-acting bronchodilators. The consequences of the allopathic treatment could be decreased if health professionals valued homeostasis, minimising the rebound effect of the organism by gradual suspension of palliative drugs.     

Significant link between sCD30 changes and HIV viremia in patients treated with HAART

Elevated sCD30 levels were generally associated with poor prognosis in chronic HIV infection prior to the era of highly active antiretroviral therapy (HAART). Little information is available on sCD30 and HIV-1 viremia. In this study, the association between sCD30 and HIV-1 viremia was investigated in HIV-infected patients who underwent HAART. sCD30 was measured in 276 patients prior (T0) and 6 months after HAART (T6). Standard survival analyses were used to evaluate the prognostic value of sCD30 and sCD30 change from baseline to predict the virological response to HAART. Higher levels (>30 U/ml) of sCD30 prior to HAART were associated with relatively higher viremia (P = 0.0001) and tended to be associated with a lower chance of achieving virological success (P = 0.13). The median T6 sCD30 level in patients who concomitantly had viremia >500 copies/ml was higher than the median sCD30 level of those with viremia rebound among those who achieve initially virological success.     

Effects of Ranitidine on Gastric Vesicles Containing H+, K+-Adenosine Triphosphatase in Rats

Background: To ascertain the mechanism for rebound acid hypersecretion after treatment with an H₂-receptor blocker, we investigated the effects of ranitidine on gastric H⁺, K⁺-adenosine triphosphatase (ATPase) in rats, Methods: Male Wistar rats received ranitidine (1-50mg/kg body weight intraperito-neally twice a day for 5 days). The rats were starved for 15 h after the last treatment and then killed, and gastric vesicles containing H⁺, K⁺-ATPase were prepared. Results: Treatment with ranitidine dose-dependently increased protein content in the gastric vesicular fraction purified from the gastric mucosa without changing total protein content. Ranitidine also increased the content of a 94,000-dalton protein, the catalytic subunit of H⁺, K⁺-ATPase. On the other hand, ranitidine did not affect the specific activity of the enzyme (μmol/min/mg of the gastric vesicular protein). Since gastric vesicles in the fasting state mainly consist of the tubulovesicular membrane, these results suggest that ranitidine administration increases total tubulovesicular H⁺, K⁺-ATPase content (μmol/min/rat) by increasing the number of tubulovesicles per parietal cell. The ranitidine-induced increase in total tubulovesicular H⁺, K⁺-ATPase activity was still evident 1 week after treatment and returned to control level 1 month later. Conclusions: All these findings suggest that the increased content and total activity of tubulovesicular H⁺, K⁺-ATPase after ranitidine treatment may contribute to the mechanism for acid rebound after H₂-blocker therapy.     

Linkage and retention in care and the time to HIV viral suppression and viral rebound – New York City

The success of antiretroviral therapy (ART) as treatment for the individual patient and as prevention requires the achievment and maintenance of human immunodeficiency virus (HIV) viral suppression. Linkage to and retention in care are required for access to ART. We describe the impact of care on viral suppression using routinely reported surveillance data. We included New York City residents ≥13 years of age, diagnosed with HIV/AIDS from 1 July 2005 to 30 June 2009 with a viral load (VL) or CD4 reported within six months of diagnosis and ≥1 VL reported from 1 July 2005 to 30 June 2011. To examine viral rebound, we restricted the analysis to those who achieved viral suppression and had a subsequent VL measure reported by 30 June 2011. Cox proportional hazards models were used to evaluate factors associated with time to viral suppression (VL ≤ 400 copies/mL) and rebound (VL > 1000 copies/mL). Initiation of care within three months of diagnosis (CD4/VL report within three months of diagnosis), female sex, and an initial CD4 < 350 (cells/mm³) at diagnosis significantly increased the likelihood of viral suppression. Irregular care (no CD4/VL reported every six months), younger age, non-white race/ethnicity, having an initial CD4 ≥ 350 at diagnosis, and AIDS diagnosis by 2010 increased the likelihood of rebound. These findings lend support to interventions for improving linkage to and maintenance in regular care as a way to achieve and maintain suppression. Surveillance data represent an ideal means for monitoring engagement in care and viral suppression at the population level.     

孕前BMI和妊娠期糖尿病对儿童脂肪重积聚时相提前的独立和联合效应

目的 探讨孕前BMI、妊娠期糖尿病（GDM）与儿童脂肪重积聚（AR）时相提前的关联。方法 基于已经建立的马鞍山优生优育队列，本研究共纳入2 896对母子对，收集孕妇孕前身高、体重、24~28周GDM情况，在婴儿42天、3月龄、6月龄、9月龄以及1岁后每6个月进行1次随访，连续追踪随访至6岁，获得其身长/高、体重等资料。采用多因素logistic回归分析孕前BMI、GDM与儿童AR时相提前的关联强度，并通过相乘、相加模型分析孕前BMI及GDM对于儿童AR时相提前的发生是否存在交互作用。结果 母亲孕前体重不足、体重正常、超重和肥胖者分别占23.2%（672例）、66.4%（1 923例）、8.7%（251例）和1.7%（50例）；GDM患病率为12.4%。儿童AR年龄为（4.38±1.08）岁，AR时相提前的儿童占39.3%。多因素logistic回归结果显示，孕前超重（OR=1.67，95%CI：1.27~2.19）、肥胖（OR=3.05，95%CI：1.66~5.56）以及孕期患有GDM（OR=1.40，95%CI：1.11~1.76）是AR时相提前发生的危险因素，而孕前体重不足（OR=0.60，95%CI：0.49~0.73）是AR时相提前发生的保护因素。与仅孕前超重/肥胖或孕期患有GDM相比，孕前超重/肥胖与孕期患有GDM并存，AR时相提前的发生风险更高，OR值（95%CI）分别为2.03（1.20~3.44）、3.43（1.06~11.12）。相乘模型和相加模型分析显示，孕前BMI和孕期患有GDM对儿童AR时相提前无交互作用。结论 母亲孕前较高的BMI和孕期患有GDM是儿童AR时相提前发生的独立危险因素，两者并存的风险更高，但无统计学交互作用。     

脂肪重积聚提前与5岁儿童肥胖和代谢各指标关联的队列研究

目的探讨脂肪重积聚(adiposity rebound,AR)提前与5岁儿童肥胖和代谢各指标的关联。方法研究基于已经建立的"马鞍山市优生优育(MABC)",在2013年10月至2015年4月出生的单胎活产儿,连续追踪随访至5岁时的儿童,截至2019年8月份共获得有连续性儿童测量数据≥8次及代谢指标的有720例。采用体格检查以及实验室检测的方法,获得儿童出生情况、身长/身高、体重、腰围、人体成分、代谢指标等信息。使用χ2检验、F检验、t检验、非参数检验、一般线性模型和Logistic回归模型进行分析。结果已有43.47%学龄前儿童界定为AR提前(AR≤4岁)。控制性别后,AR提前组5岁儿童超重/肥胖(OR=2.71,95%CI:1.81~4.05)、腰围超标(OR=1.88,95%CI:1.25~2.82)、体脂肪百分比≥P90(OR=2.09,95%CI:1.26~3.48)的发生风险均上升,差异均有统计学意义(P<0.05);AR提前组5岁儿童胰岛素抵抗和代谢风险因子得分虽高于未提前组,但是差异无统计学意义。5岁儿童肥胖和超重的发生率分别为6.0%和12.8%,且超重肥胖儿童、腰围超标、腰高比超标和体脂百分比≥P90者,胰岛素抵抗和代谢风险因子得分均较高,差异均有统计学意义(P<0.001)。结论 AR提前能增加5岁超重/肥胖、腰围超标和体脂肪百分比超标的风险,且5岁儿童肥胖各指标超标与胰岛素抵抗和代谢风险因子密切相关。