Defunct brain stem cardiovascular regulation underlies cardiovascular collapse associated with methamphetamine intoxication

Background  

Intoxication from the psychostimulant methamphetamine (METH) because of cardiovascular collapse is a common cause of death within the abuse population. For obvious reasons, the heart has been taken as the primary target for this METH-induced toxicity. The demonstration that failure of brain stem cardiovascular regulation, rather than the heart, holds the key to cardiovascular collapse induced by the pesticide mevinphos implicates another potential underlying mechanism. The present study evaluated the hypothesis that METH effects acute cardiovascular depression by dampening the functional integrity of baroreflex via an action on brain stem nuclei that are associated with this homeostatic mechanism.     

Renal Sodium and Potassium Excretion in Diseased Cattle Estimated Without Measurement of the Urine Volume

Since measurement of urine volume can disturb the electrolyte excretion, and since such measurement is difficult to carry out on diseased cattle, a method to estimate the renal electrolyte excretion without measurement of urine volume has been tried and discussed. Depending on a constant renal excretion of creatinine, the method allows substitution of measurement of urine cratinine concentration for measurement of urine volume. The largest source of error in the use of this method is alteration in the glomerular filtration rate, and the error of the method is therefore very high in case of cardiovascular collapse (136 and 300 % was found here). The errors found were only 4–18 % in normal or slightly affected animals, and 0–44 % in animals with severe fluid and electrolyte complications without collapse. Apart from cases complicated by cardio-vascular collapse and acute uremia the method seems to be acceptable for clinical estimation of the renal electrolyte excretion.     

Open laparoscopy. Commentary

Open laparoscopy has been receiving increased attention in the US and internationally. However, opinions differ on its appropriate role in laparoscopy services. In the US some surgeons remain comfortable using closed laparoscopy for all patients, including some who have had previous abdominal surgery. Some centers are using more open procedures, especially for training programs and for cases where open laparoscopy may be indicated, as described by Dr. Hasson in this "Bulletin." Others have converted to performing all laparoscopy by the open technique. The Planned Parenthood Federation of America encourages minilaparotomy and open laparoscopy for tubal occlusion n its facilities because of the greater inherent potential for patient safety with these approaches. AVS has not provided open laparoscopy equipment to international programs, although some projects have used an open technique. Neither the World Federation of Health Agencies for the Advancement of Voluntary Surgical Contraception nor the AVS Science Committee has addressed the role of open laparoscopy in international programs. This is due in part to insufficient worldwide experience in open laparoscopy. However, this does not preclude AVS from providing such equipment for open laparoscopy in the future. In the US approximately 300-500 Hasson cannulas have been commercially distributed annually for the past 4-5 years. About 2000 may be currently in use in the US. Therefore, among the 6915 hospitals registered with the American Hospital Association in 1982, a substantial proportion may now provide access to open laparoscopy equipment. Studies in the US are not yet available to fully assess the safety of open laparoscopy. However, general comparisons of complication rates for open and closed laparoscopy may not be appropriate since many surgeons reserve the more complicated cases for open laparoscopy.     

Sensitivity to Intravenous Anaesthetics: A Report of Three Cases

Three patients with sensitivity to an intravenous anaesthetic—thiopentone, propanidid, and Althesin (alphadolone and alphaxalone)—are described. In the cases of thiopentone and Althesin the reaction was characterized by cardiovascular collapse, while bronchospasm also occurred with thiopentone. The reaction to propanidid was a direct skin sensitivity. All patients had a personal or family history of asthma and all had been previously exposed to the offending drug. A leucocyte challenge test showed an allergic response to thiopentone and Althesin in two patients but gave a negative result in the patient with the skin reaction. Allergic reactions can occur to all types of intravenous anaesthetics in a few patients.     

Cyclosporin A Disrupts Notch Signaling and Vascular Lumen Maintenance

Cyclosporin A (CSA) suppresses immune function by blocking the cyclophilin A and calcineurin/NFAT signaling pathways. In addition to immunosuppression, CSA has also been shown to have a wide range of effects in the cardiovascular system including disruption of heart valve development, smooth muscle cell proliferation, and angiogenesis inhibition. Circumstantial evidence has suggested that CSA might control Notch signaling which is also a potent regulator of cardiovascular function. Therefore, the goal of this project was to determine if CSA controls Notch and to dissect the molecular mechanism(s) by which CSA impacts cardiovascular homeostasis. We found that CSA blocked JAG1, but not Dll4 mediated Notch1 NICD cleavage in transfected 293T cells and decreased Notch signaling in zebrafish embryos. CSA suppression of Notch was linked to cyclophilin A but not calcineurin/NFAT inhibition since N-MeVal-4-CsA but not FK506 decreased Notch1 NICD cleavage. To examine the effect of CSA on vascular development and function, double transgenic Fli1-GFP/Gata1-RFP zebrafish embryos were treated with CSA and monitored for vasculogenesis, angiogenesis, and overall cardiovascular function. Vascular patterning was not obviously impacted by CSA treatment and contrary to the anti-angiogenic activity ascribed to CSA, angiogenic sprouting of ISV vessels was normal in CSA treated embryos. Most strikingly, CSA treated embryos exhibited a progressive decline in blood flow that was associated with eventual collapse of vascular luminal structures. Vascular collapse in zebrafish embryos was partially rescued by global Notch inhibition with DAPT suggesting that disruption of normal Notch signaling by CSA may be linked to vascular collapse. However, multiple signaling pathways likely cause the vascular collapse phenotype since both cyclophilin A and calcineurin/NFAT were required for normal vascular function. Collectively, these results show that CSA is a novel inhibitor of Notch signaling and vascular function in zebrafish embryos.     

Bioenergetics failure and oxidative stress in brain stem mediates cardiovascular collapse associated with fatal methamphetamine intoxication

Background

Whereas sudden death, most often associated with cardiovascular collapse, occurs in abusers of the psychostimulant methamphetamine (METH), the underlying mechanism is much less understood. The demonstration that successful resuscitation of an arrested heart depends on maintained functionality of the rostral ventrolateral medulla (RVLM), which is responsible for the maintenance of stable blood pressure, suggests that failure of brain stem cardiovascular regulation, rather than the heart, holds the key to cardiovascular collapse. We tested the hypothesis that cessation of brain stem cardiovascular regulation because of a loss of functionality in RVLM mediated by bioenergetics failure and oxidative stress underlies the cardiovascular collapse elicited by lethal doses of METH.

Methodology/Principal Findings

Survival rate, cardiovascular responses and biochemical or morphological changes in RVLM induced by intravenous administration of METH in Sprague-Dawley rats were investigated. High doses of METH induced significant mortality within 20 min that paralleled concomitant the collapse of arterial pressure or heart rate and loss of functionality in RVLM. There were concurrent increases in the concentration of METH in serum and ventrolateral medulla, along with tissue anoxia, cessation of microvascular perfusion and necrotic cell death in RVLM. Furthermore, mitochondrial respiratory chain enzyme activity or electron transport capacity and ATP production in RVLM were reduced, and mitochondria-derived superoxide anion level was augmented. All those detrimental physiological and biochemical events were reversed on microinjection into RVLM of a mobile electron carrier in the mitochondrial respiratory chain, coenzyme Q10; a mitochondria-targeted antioxidant and superoxide anion scavenger, Mito-TEMPO; or an oxidative stress-induced necrotic cell death inhibitor, IM-54.

Conclusion

We conclude that sustained anoxia and cessation of local blood flow that leads to bioenergetics failure and oxidative stress because of mitochondrial dysfunction, leading to acute necrotic cell death in RVLM underpins cardiovascular collapse elicited by lethal doses of METH.     

Effects of the addition of carbon dioxide on manifestations of acute hypoxia in rats

In pentobarbitalized rats, hypoxia induced by inhalation of O2 8%-N2 92%, produces a transient hyperventilation which is followed by a respiratory depression and an apnea. A cardiovascular collapse is then observed. Correction of the hypocapnia depending on the initial hyperventilation, by inhalation of a gas mixture containing 4% CO2 maintains the hyperventilation and suppresses the cardiovascular collapse. Carbon dioxide activity is both a direct one by stimulation of respiratory centers and an indirect one by increasing the sensitivity of the peripheral arterial chemoreceptors to hypoxia. Four percent carbon dioxide just compensating hypocapnia are sufficient to prevent apnea and vascular collapse. The increase of this concentration up to hypercapnia complicates the interpretation of the results by addition of hypoxic and hypercapnic effects.     

宫腔镜联合腹腔镜在女性不孕症诊治中的应用

摘要目的：探讨宫腔镜联合腹腔镜在女性不孕诊断及治疗中的临床应用价值。方法：回顾性分析60 例我院收治的采用宫腔镜联 合腹腔镜进行诊断和治疗的女性不孕症患者为研究对象,对其临床资料进行分析。结果：宫腔镜联合腹腔镜检查发现,60 例不孕 症患者中,56.7 %的患者患有慢性盆腔炎,16.7 %的患者为子宫内膜异位症,11.7 %的患者为多囊卵巢综合征;单纯腹腔镜检查的 阳性检出率为60.0 %,单纯宫腔镜检查的阳性检出率为28.3 %,宫腔镜联合腹腔镜检查的阳性检出率高达91.7 %,宫腔镜联合腹 腔镜镜检阳性发现率明显高于前二者(P < 0.05)。治疗前,双侧不通、一侧通畅和双侧输卵管通畅的患者分别为38.3 %、48.3 %和 13.3 %,经宫腔镜联合腹腔镜治疗后分别为11.7 %、50.0 %和38.3 %,差异均有统计学意义(P<0.05)。34 例原发性不孕患者,术后 13例妊娠,妊娠率38.2 %;26 例继发性不孕患者,术后15 例妊娠,妊娠率57.7 %;总妊娠率为46.7 %,其中宫外孕2例。结论：宫 腔镜联合腹腔镜检查可帮助明确女性不孕症患者明确原因及发病部位,并可针对病因进行治疗,提高女性不孕症的病因诊断准 确率及治愈率。     

The technique of subclavian vein cannulation

A modification of the technique for subclavian vein cannulation, which avoids the risk of fatal air embolism, is described. Other essential precautions designed to avoid the usual complications are emphasized. The technique as described has been used successfully in over 50 consecutive cases without complications.     

宫腔镜联合腹腔镜在女性不孕症诊治中的应用

目的：探讨宫腔镜联合腹腔镜在女性不孕诊断及治疗中的临床应用价值。方法：回顾性分析60例我院收治的采用宫腔镜联合腹腔镜进行诊断和治疗的女性不孕症患者为研究对象,对其临床资料进行分析。结果：宫腔镜联合腹腔镜检查发现,60例不孕症患者中,56．7％的患者患有慢性盆腔炎,16．7％的患者为子宫内膜异位症,11．7％的患者为多囊卵巢综合征;单纯腹腔镜检查的阳性检出率为60．0％,单纯宫腔镜检查的阳性检出率为28．3％,宫腔镜联合腹腔镜检查的阳性检出率高达91．7％,宫腔镜联合腹腔镜镜栓阳性发现率明显高于前二者（P〈0．05）。治疗前,双侧不通、一侧通畅和双侧输卵管通畅的患者分别为38．3％、48．3％和13．3％,经宫腔镜联合腹腔镜治疗后分别为11．7％、50．o％和38．3％,差异均有统计学意义（P〈0．05）。34例原发性不孕患者,术后13例妊娠,妊娠率38．2％;26例继发性不孕患者,术后15例妊娠,妊娠率57．7％;总妊娠率为46．7％,其中宫外孕2例。结论：宫腔镜联合腹腔镜检查可帮助明确女性不孕症患者明确原因及发病部位,并可针对病因进行治疗,提高女性不孕症的病因诊断准确率及治愈率。     

Noninvasively determined muscle oxygen saturation is an early indicator of central hypovolemia in humans.

Ten healthy human volunteers were subjected to progressive lower body negative pressure (LBNP) to the onset of cardiovascular collapse to compare the response of noninvasively determined skin and fat corrected deep muscle oxygen saturation (SmO2) and pH to standard hemodynamic parameters for early detection of imminent hemodynamic instability. Muscle SmO2 and pH were determined with a novel near infrared spectroscopic (NIRS) technique. Heart rate (HR) was measured continuously via ECG, and arterial blood pressure (BP) and stroke volume (SV) were obtained noninvasively via Finometer and impedance cardiography on a beat-to-beat basis. SmO2 and SV were significantly decreased during the first LBNP level (-15 mmHg), whereas HR and BP were late indicators of impending cardiovascular collapse. SmO2 declined in parallel with SV and inversely with total peripheral resistance, suggesting, in this model, that SmO2 is an early indicator of a reduction in oxygen delivery through vasoconstriction. Muscle pH decreased later, suggesting an imbalance between delivery and demand. Spectroscopic determination of SmO2 is noninvasive and continuous, providing an early indication of impending cardiovascular collapse resulting from progressive reduction in central blood volume.     

Cardiovascular Effects of Peritoneal Insufflation of Carbon Dioxide for Laparoscopy

We have investigated, in 13 artificially ventilated and anaesthetized patients, the cardiovascular effects of peritoneal insufflation of carbon dioxide preparatory to laparoscopy. Stepwise increases of intra-abdominal pressure up to a maximum of 25 cm H₂O were accompanied by increases of airway pressure, intrathoracic pressure, central venous pressure, and femoral venous pressure and by signs of cardiovascular stimulation with mild tachycardia and hypertension. End-tidal carbon dioxide tension rose only slightly. The anaesthetic technique used provided good surgical conditions; our results suggest that it does not impose undue strain on the homoeostatic ability of the patient''s cardiovascular system.     

Managing gynaecological emergencies with laparoscopy.

A consecutive series of 49 women (50 procedures), whose conditions were haemodynamically stable, presenting with acute lower abdominal pain, pelvic tenderness, and either a urine concentration of greater than 50 U/l beta human chorionic gonadotrophin or a pelvic mass shown by ultrasonography were treated with operative laparoscopy under video monitoring (videopelviscopy) as an alternative to laparotomy. Ectopic pregnancy, ovarian and non-ovarian cysts, pelvic adhesions, endometriosis, and fibroids were found, for which salpingotomy, salpingectomy and salpingo-oophorectomy, cystectomy, adhesiolysis, thermocoagulation, and myomectomy were carried out by laparoscopy. In one patient pelviscopy was repeated because of persistent tubal pregnancy after the fimbria was expressed. Laparotomies were carried out on three patients because treatment was not possible by laparoscopy and on a further patient two days after adhesiolysis had been attempted. These were the only serious complications. For the 46 cases (45 patients) in which operative laparoscopy was successful the mean stay in hospital was 1.9 days after operation, and this group of patients returned to normal activities and to work after an average of 2.3 and 2.6 weeks respectively. Most gynaecological emergencies that are managed by laparotomy can be treated by laparoscopy and benefit both patients and the health service.     

A simple model for the two dimensional blood flow in the collapse of veins

Veins in the cardiovascular system may collapse if the internal pressure is less than the external pressure. Such collapse or buckling will have important consequence in terms of the rate of blood flow. Here a steady, parallel unidirectional flow as an exact solution of the continuity and the Navier Stokes equations is constructed. Various stages of the deformation process of the elastic tube (before contact of opposite sides occurring), from an ellipse to a `strongly buckled' configuration, are obtained in analytical forms as a by-product of the calculations. The pressure – area and the pressure – flow rate diagrams computed numerically from the model agree with the trends measured experimentally. Partial Financial Support has been provided by the Research Grants Council Contract HKU 7184/04E.     

Cardiovascular collapse after tracheal ligature in the rat

Tracheal ligature provokes in the Rat a cardiovascular collapse, the animal dying in 4 minutes. Pretreatment with phentolamine, an alpha-adrenergic blocker, increases the systemic arterial hypotension and shortens the survival time.     

腹腔镜切除与内镜联合治疗胃肠道肿瘤的效果观察

目的：分析腹腔镜联合内镜治疗胃肠道肿瘤的可行性和临床效果。方法：对我院收治的行腹腔镜切除与内镜联合治疗的75例胃肠道肿瘤患者的临床资料进行回顾性分析,其中腹腔镜与胃镜联合治疗34例,腹腔镜与肠镜联合治疗41例。总结分析治疗效果。结果：75例患者中有72例手术成功,3例患者因肿瘤位置不佳中转开腹,腹腔镜与胃镜联合平均手术时间（72.8±12.7）min,出血量5~30mL,术后无吻合口瘘、吻合口出血、腹腔感染等并发症,住院时间（7.5±0.5）d。结论：腹腔镜联合内镜治疗胃肠道肿瘤具有创伤小、手术安全的特点,是一种有效、安全的治疗手段,值得临床推广应用。     

325例腹腔镜附件手术的临床分析

目的:评价腹腔镜在附件疾病治疗中的价值及安全性。方法:回顾性分析325例附件良性疾病腹腔镜手术治疗情况。随机选取妇科附件良性肿瘤、异位妊娠、输卵管粘连及伞端不通、卵巢破裂、巧克力囊肿,卵巢冠囊肿等病例;采用腹腔镜手术治疗。术式根据病情不同,采取卵巢(冠)囊肿剥除术、附件切除术、输卵管切除术及造口术。结果:腹腔镜手术占同期手术42．54%,手术成功率100%,发生并发症5例(1．54%)。结论:腹腔镜微创手术,副作用少,适应证掌握得当,妇科大部分附件手术可在腹腔镜下完成。     

Identifying physiological measurements for medical monitoring: implications for autonomous health care in austere environments

In a patient who has lost a significant amount of blood, avoiding cardiovascular collapse and impending circulatory shock depends on the ability to maintain adequate arterial blood pressure in the presence of significant central hypovolemia. Our analysis of hemodynamic, autonomic, and metabolic data obtained from healthy human subjects exposed to progressive reduction in central blood volume and supported by data from trauma patients provide evidence to support the following conclusions: 1. Because of autonomically-mediated compensatory mechanisms, standard vital signs can remain unchanged or change too late, when cardiovascular collapse is imminent. 2. Currently proposed closed-loop resuscitation and oxygen delivery systems controlled by arterial blood pressure and SpO2 may prove inadequate for early intervention decision-support. 3. Continuous capture of PP, ECG R-wave amplitude, indices of HRV, cardiac BRS, and/or muscle PO2 could improve the sensitivity of closed-loop resuscitation and oxygen delivery by providing earlier indications of clinical status.     

Hybridization, species collapse, and species reemergence after disturbance to premating mechanisms of reproductive isolation

There are now a number of well-studied cases in which hybridization between closely related sympatric species has increased, sometimes resulting in the replacement of species pairs by hybrid swarms. Many of these cases have been linked to anthropogenic environmental change, but the mechanisms leading from environmental change to species collapse, and the long-term effects of hybridization on species pairs, remain poorly understood. We used an individual-based stochastic simulation model to explore the conditions under which disturbances that weaken premating barriers to reproduction patterns between sympatric species might lead to increased hybridization and to species collapse. Disturbances often resulted in bouts of hybridization, but in many cases strong reproductive isolation spontaneously reemerged. This was sometimes true even after hybrid swarms had replaced parental species. The reemergence of species pairs was most likely when disturbances were of short duration. Counterintuitively, incipient species pairs were more likely to reemerge after strong but temporary disturbances than after weaker disturbances of the same duration. Even temporary bouts of hybridization often led to substantial homogenization of species pairs. This suggests that ecosystem managers may be able to refill ecological niches, but in general will not be able to resurrect lost species after species collapse.     

Isolation System for General Hospitals

A four-category isolation system has been used for three years. It is based on the principle that different precautions are needed against different diseases. There are three types of source isolation and one of protective isolation. Coloured door cards indicate the main precautions on the front and the main diseases to which they apply on the back. The system encourages application of effective precautions without waste of effort on those that are irrelevant to some diseases.