[Physicians' knowledge with regard to the timing of adrenaline administration for anaphylaxis in Japan].

PubMed

Imai, Takanori; Sugizaki, Chizuko; Ebisawa, Motohiro

2013-11-01

Adrenaline administration is a top priority treatment for severe anaphylaxis. A survey with regard to the timing of adrenaline administration for anaphylaxis was conducted among physicians in Japan. The survey was conducted using a questionnaire among physicians who had contributed to a nationwide survey for acute food allergy monitoring in 2011. The questionnaire comprised questions asking physicians whether they possessed registrations as an adrenaline self-injector (ASJ), and timing of adrenaline administration for anaphylaxis. Symptoms of anaphylaxis were categorized into shock or respiratory, gastrointestinal, cutaneous, or laryngeal symptoms. A total of 674 replies were obtained from physicians, and 547 physicians were reported to be registered as ASJs. With regard to time, when patients injected themselves with adrenaline, it resulted in laryngeal (78.4%) and circulatory symptoms (64.4%), whereas when physicians administered adrenaline in patients, it resulted in circulatory (74.8%) and laryngeal symptoms (70.0%). Japanese physicians did not necessarily understand the timing of adrenaline administration. Therefore, it is important to provide appropriate education to these physicians with regard to anaphylaxis and ASJ.

Risk assessment and comparative effectiveness of left ventricular assist device and medical management in ambulatory heart failure patients: design and rationale of the ROADMAP clinical trial.

PubMed

Rogers, Joseph G; Boyle, Andrew J; O'Connell, John B; Horstmanshof, Douglas A; Haas, Donald C; Slaughter, Mark S; Park, Soon J; Farrar, David J; Starling, Randall C

2015-02-01

Mechanical circulatory support is now a proven therapy for the treatment of patients with advanced heart failure and cardiogenic shock. The role for this therapy in patients with less severe heart failure is unknown. The objective of this study is to examine the impact of mechanically assisted circulation using the HeartMate II left ventricular assist device in patients who meet current US Food and Drug Administration-defined criteria for treatment but are not yet receiving intravenous inotropic therapy. This is a prospective, nonrandomized clinical trial of 200 patients treated with either optimal medical management or a mechanical circulatory support device. This trial will be the first prospective clinical evaluation comparing outcomes of patients with advanced ambulatory heart failure treated with either ongoing medical therapy or a left ventricular assist device. It is anticipated to provide novel insights regarding relative outcomes with each treatment and an understanding of patient and provider acceptance of the ventricular assist device therapy. This trial will also provide information regarding the risk of events in "stable" patients with advanced heart failure and guidance for the optimal timing of left ventricular assist device therapy. Copyright © 2014 Elsevier Inc. All rights reserved.

Uncontrolled Donation After Circulatory Determination of Death Donors (uDCDDs) as a Source of Lungs for Transplant

PubMed Central

Egan, T. M.; Requard, J. J.

2017-01-01

In April 2014, the American Journal of Transplantation published a report on the first lung transplant in the United States recovered from an uncontrolled donation after circulatory determination of death donor (uDCDD), assessed by ex vivo lung perfusion (EVLP). The article identified logistical and ethical issues related to introduction of lung transplant from uDCDDs. In an open clinical trial, we have Food and Drug Administration and Institutional Review Board approval to transplant lungs recovered from uDCDDs judged suitable after EVLP. Through this project and other experiences with lung recovery from uDCDDs, we have identified solutions to many logistical challenges and have addressed ethical issues surrounding lung transplant from uDCDDs that were mentioned in this case report. Here, we discuss those challenges, including issues related to recovery of other solid organs from uDCDDs. Despite logistical challenges, uDCDDs could solve the critical shortage of lungs for transplant. Furthermore, by avoiding the deleterious impact of brain death and days of positive pressure ventilation, and by using opportunities to treat lungs in the decedent or during EVLP, lungs recovered from uDCDDs may ultimately prove to be better than lungs currently being transplanted from conventional brain-dead organ donors. PMID:25873272

Drug-sensitive reward in crayfish: an invertebrate model system for the study of SEEKING, reward, addiction, and withdrawal.

PubMed

Huber, Robert; Panksepp, Jules B; Nathaniel, Thomas; Alcaro, Antonio; Panksepp, Jaak

2011-10-01

In mammals, rewarding properties of drugs depend on their capacity to activate appetitive motivational states. With the underlying mechanisms strongly conserved in evolution, invertebrates have recently emerged as a powerful new model in addiction research. In crayfish natural reward has proven surprisingly sensitive to human drugs of abuse, opening an unlikely avenue of research into the basic biological mechanisms of drug addiction. In a series of studies we first examined the presence of natural reward systems in crayfish, then characterized its sensitivity to a wide range of human drugs of abuse. A conditioned place preference (CPP) paradigm was used to demonstrate that crayfish seek out those environments that had previously been paired with the psychostimulants cocaine and amphetamine, and the opioid morphine. The administration of amphetamine exerted its effects at a number of sites, including the stimulation of circuits for active exploratory behaviors (i.e., SEEKING). A further study examined morphine-induced reward, extinction and reinstatement in crayfish. Repeated intra-circulatory infusions of morphine served as a reward when paired with distinct visual or tactile cues. Morphine-induced CPP was extinguished after repeated saline injections. Following this extinction phase, morphine-experienced crayfish were once again challenged with the drug. The priming injections of morphine reinstated CPP at all tested doses, suggesting that morphine-induced CPP is unrelenting. In an exploration of drug-associated behavioral sensitization in crayfish we concurrently mapped measures of locomotion and rewarding properties of morphine. Single and repeated intra-circulatory infusions of morphine resulted in persistent locomotory sensitization, even 5 days following the infusion. Moreover, a single dose of morphine was sufficient to induce long-term behavioral sensitization. CPP for morphine and context-dependent cues could not be disrupted over a drug free period of 5 days. This work demonstrates that crayfish offer a comparative and complementary approach in addiction research. Serving as an invertebrate animal model for the exposure to mammalian drugs of abuse, modularly organized and experimentally accessible nervous systems render crayfish uniquely suited for studying (1) the basic biological mechanisms of drug effects, (2) to explore how the appetitive/seeking disposition is implemented in a simple neural system, and (3) how such a disposition is related to the rewarding action of drugs of abuse. This work aimed to contribute an evolutionary, comparative context to our understanding of a key component in learning, and of natural reward as an important life-sustaining process. Copyright © 2010 Elsevier Ltd. All rights reserved.

Integrating Computer/Multimedia Technology in a High School Biology Curriculum.

ERIC Educational Resources Information Center

Matray, Paul; Proulx, Steve

1995-01-01

Discusses hardware and software used to teach scientific method, ecology, evolution, mitosis and meiosis, photosynthesis, cellular respiration, circulatory and respiratory systems, reproduction and drugs, behavior, and genetics. (MKR)

Comparative systemic toxicity of ropivacaine and bupivacaine in nonpregnant and pregnant ewes.

PubMed

Santos, A C; Arthur, G R; Wlody, D; De Armas, P; Morishima, H O; Finster, M

1995-03-01

Ropivacaine is a new amide local anesthetic, having therapeutic properties similar to those of bupivacaine but with a wider margin of safety. Bupivacaine is probably the most commonly used drug in obstetric epidural analgesia, even though laboratory studies have suggested that pregnancy increases the cardiotoxicity of bupivacaine but not of other local anesthetics. The current study was designed to reevaluate, in a random and blinded fashion, the systemic toxicity of bupivacaine and ropivacaine in nonpregnant and pregnant sheep. Chronically prepared nonpregnant and pregnant ewes were randomized to receive an intravenous infusion of ropivacaine or bupivacaine at a constant rate of 0.5 mg.kg-1.min-1 until circulatory collapse. The investigators were blinded to the identity of local anesthetic. Heart rate, arterial blood pressure, and cardiac rhythm were monitored throughout the study. Arterial blood samples were obtained before infusion and at the onset of toxic manifestations, which appeared in the following sequence: convulsions, hypotension, apnea, and circulatory collapse. Serum drug concentrations and protein binding were determined. Blood pH and gas tensions were measured. There were no significant differences between non-pregnant and pregnant animals in the doses or serum concentrations of either drug required to elicit toxic manifestations. In nonpregnant animals, similar doses and serum concentrations of ropivacaine and bupivacaine were associated with the onset of convulsions and circulatory collapse. In pregnant ewes, greater doses of ropivacaine as compared to bupivacaine were required to produce convulsions (7.5 +/- 0.5 vs. 5.0 +/- 0.6 mg.kg-1) and circulatory collapse (12.9 +/- 0.8 vs. 8.5 +/- 1.2 mg.kg-1). The corresponding serum concentrations of ropivacaine were similar to those of bupivacaine. Pregnancy did not affect the serum protein binding of either drug. The proportion of animals manifesting a malignant ventricular arrhythmia as the terminal event was similar among all groups. The systemic toxicity of ropivacaine or bupivacaine is not enhanced by gestation in sheep. This is in contrast to an earlier study in which the cardiotoxicity of bupivacaine was enhanced during ovine pregnancy. Greater doses of ropivacaine, as compared to bupivacaine, are needed to produce toxic manifestations in pregnant animals.

Nationwide surveillance of circulatory collapse associated with levothyroxine administration in very-low-birthweight infants in Japan.

PubMed

Kawai, Masahiko; Kusuda, Satoshi; Cho, Kazutoshi; Horikawa, Reiko; Takizawa, Fumihiko; Ono, Makoto; Hattori, Tetsuo; Oshiro, Makoto

2012-04-01

Although the administration of levothyroxine sodium (LT4) to premature infants had been considered safe, several cases of late-onset circulatory collapse (LCC) following the administration of LT4 in very-low-birth-weight (VLBW) infants have been reported in Japan since 2008. This study was performed to investigate the incidence of LCC associated with the administration of LT4 to VLBW infants. A questionnaire regarding LCC with or without an association with LT4 administration in VLBW infants from 2006 to 2008, was sent to 212 hospitals belonging to the Japan Neonatologist Association. Data of 8727 VLBW infants were analyzed, and 46 cases of LCC associated with the administration of LT4 were reported in this surveillance. Especially, an analysis for infants weighing between 1000 and 1499 g at birth revealed that the incidence of LCC with the administration of LT4 was higher than that of those without LT4. LT4 is widely used for infants, including VLBW infants, and no major complications have been reported. However, our study revealed that more than a few cases of LCC were associated with the administration of LT4 in VLBW infants. In conclusion, careful attention is necessary when initiating the administration of LT4 to VLBW infants. © 2011 The Authors. Pediatrics International © 2011 Japan Pediatric Society.

[Acute novel drugs poisoning among patients of Nofer Institute of Occupational Medicine in Lodz, Toxicology Unit, hospitalized in the years 2008-2012--epidemiology, clinical state].

PubMed

Sawicka, Joanna; Czyzewska, Sylwia; Winnicka, Renata; Politański, Piotr; Swiderska-Kiełbik, Sylwia; Kołaciński, Zbigniew; Czerniak, Paweł; Krakowiak, Anna

2013-01-01

Intoxication with novel recreational drugs poses significant challenge for medical staff due to diagnostic difficulties, complex clinical pattern, resulting from polyethiology of poisoning and potential risk of life threatening complications. Description of clinical pattern novel drug intoxication. retrospective review of medical records patients hospitalized in the Toxicology Unit (TU) with diagnosis of intoxication with novel recreational drugs. During the period from 2008-2010--431 patients were admitted to TU with mentioned above diagnosis. 159 (36.9%) patients were positive for ethanol with its average concentration in blood 150 mg%. Presence of other substances like amphetamine, cannabinoids, atropine, ephedrine, carbamazepine, benzodiazepines and dextrometorphan was confirmed. The most frequent clinical symptoms observed on admission were: anxiety, agitation, complaints associated with circulatory system and vertigo Average pulse rate and both: diastolic and systolic pressure were within normal limits, however authors noted slight tendency toward tachycardia. One patients died due to multiorgan failure. Average period of hospitalization amounted 2.24 days. Co-poisoning with ethanol was associated with higher frequency of circulatory system disturbances. Clinical pattern of poisoning with novel drugs could partially correspond with mild sympathomime. tic syndrome.

[Indications and possibilities of blockade of the sympathetic nerve].

PubMed

Meyer, J

1987-04-01

Treatment of chronic pain through permanent or temporary interruption of sympathetic activity is marked by great clinical success, but nevertheless there are rather skeptical reports about long-term results of these blocks as therapeutic measures. There are many symptoms and signs of chronic pain, while diagnosis is expensive, the pathogenesis is complex, and the etiology is generally due to multiple factors. Indications for sympathetic blockade depend upon the possible means of access, as in the cervicothoracic, thoracic, lumbar, or sacral regions. General indications are: symptoms not limited segmentally within peripheral body areas; pain resulting from microtraumata and lesions of peripheral nerve branches; and pain caused by intensified sympathetic tone with consequent circulatory disturbances. Peripheral circulatory disturbances are the most common indication for sympathetic blockade, as the block produces a vasomotor reaction that leads to increased capillary circulation. Pain caused by herpes zoster, sudden hearing loss, hyperhidrosis, and pseudesthesia can also be influenced by sympathetic blockade. There are several possibilities for reducing or interrupting sympathetic activity; for us, however, blocking of the sympathetic trunk is the most important. During the last 16 years we performed 15,726 sympathetic blockades on 2385 patients, which included: 3735 stellate ganglion blocks, 6121 blocks of the lumbar sympathetic trunk, 5037 continuous peridural anesthesias, 29 blocks of the thoracic sympathetic trunk, and 12 celiac blocks. In 792 cases sympathetic blocks were performed using neurolytic drugs, in most cases 96% ethyl alcohol and less often 10% ammonium sulphate. Other possibilities, such as enteral administration or infusion of sympatholytic drugs, were not taken into consideration; regional intravascular injection of guanethidine can be recommended, however.(ABSTRACT TRUNCATED AT 250 WORDS)

Donation After Circulatory Death for Liver Transplantation: A Meta-Analysis on the Location of Life Support Withdrawal Affecting Outcomes.

PubMed

Cao, Yiming; Shahrestani, Sara; Chew, Hong Chee; Crawford, Michael; Macdonald, Peter Simon; Laurence, Jerome; Hawthorne, Wayne John; Dhital, Kumud; Pleass, Henry

2016-07-01

Liver transplantation using donation after circulatory death (DCD) donors is associated with inferior outcomes compared to donation after brain death (DBD). Prolonged donor warm ischemic time has been identified as the key factor responsible for this difference. Various aspects of the donor life support withdrawal procedure, including location of withdrawal and administration of antemortem heparin, are thought to play important roles in mitigating the effects of warm ischemia. However, a systematic exploration of these factors is important for more confident integration of these practices into a standard DCD protocol. Medline, EMBASE, and Cochrane libraries were systematically searched and 23 relevant studies identified for analysis. Donation after circulatory death recipients were stratified according to location of life support withdrawal (intensive care unit or operating theater) and use of antemortem heparin. Donation after circulatory death recipients had comparable 1-year patient survival to DBD recipients if the location of withdrawal of life support was the operating theater, but not if the location was the intensive care unit. Likewise, the inferior 1-year graft survival and higher incidence of ischemic cholangiopathy of DCD compared with DBD recipients were improved by withdrawal in operating theater, although higher rates of ischemic cholangiopathy and worse graft survival were still observed in DCD recipients. Furthermore, administering heparin before withdrawal of life support reduced the incidence of primary nonfunction of the allograft. Our evidence suggests that withdrawal in the operating theater and premortem heparin administration improve DCD liver transplant outcomes, thus allowing for the most effective usage of these valuable organs.

78 FR 104 - Advisory Committees; Tentative Schedule of Meetings for 2013

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-02

... Date(s), if needed, to be Committee. determined. Peripheral and Central Nervous System May 22. Drugs... be Devices Panel. determined. Circulatory System Devices Panel....... May 17, May 24, June 27...

21 CFR 101.75 - Health claims: dietary saturated fat and cholesterol and risk of coronary heart disease.

Code of Federal Regulations, 2011 CFR

2011-04-01

... cholesterol and risk of coronary heart disease. 101.75 Section 101.75 Food and Drugs FOOD AND DRUG... risk of coronary heart disease. (a) Relationship between dietary saturated fat and cholesterol and risk of coronary heart disease. (1) Cardiovascular disease means diseases of the heart and circulatory...

21 CFR 101.75 - Health claims: dietary saturated fat and cholesterol and risk of coronary heart disease.

Code of Federal Regulations, 2010 CFR

2010-04-01

... of coronary heart disease. (1) Cardiovascular disease means diseases of the heart and circulatory system. Coronary heart disease is the most common and serious form of cardiovascular disease and refers... cholesterol and risk of coronary heart disease. 101.75 Section 101.75 Food and Drugs FOOD AND DRUG...

21 CFR 101.75 - Health claims: dietary saturated fat and cholesterol and risk of coronary heart disease.

Code of Federal Regulations, 2013 CFR

2013-04-01

... cholesterol and risk of coronary heart disease. 101.75 Section 101.75 Food and Drugs FOOD AND DRUG... risk of coronary heart disease. (a) Relationship between dietary saturated fat and cholesterol and risk of coronary heart disease. (1) Cardiovascular disease means diseases of the heart and circulatory...

21 CFR 101.75 - Health claims: dietary saturated fat and cholesterol and risk of coronary heart disease.

Code of Federal Regulations, 2012 CFR

2012-04-01

... cholesterol and risk of coronary heart disease. 101.75 Section 101.75 Food and Drugs FOOD AND DRUG... risk of coronary heart disease. (a) Relationship between dietary saturated fat and cholesterol and risk of coronary heart disease. (1) Cardiovascular disease means diseases of the heart and circulatory...

21 CFR 101.75 - Health claims: dietary saturated fat and cholesterol and risk of coronary heart disease.

Code of Federal Regulations, 2014 CFR

2014-04-01

... cholesterol and risk of coronary heart disease. 101.75 Section 101.75 Food and Drugs FOOD AND DRUG... risk of coronary heart disease. (a) Relationship between dietary saturated fat and cholesterol and risk of coronary heart disease. (1) Cardiovascular disease means diseases of the heart and circulatory...

Does the use of thiopental provide added cerebral protection during deep hypothermic circulatory arrest?

PubMed Central

Al-Hashimi, Sara; Zaman, Mahvash; Waterworth, Paul; Bilal, Haris

2013-01-01

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was: Does the use of thiopental provide added cerebral protection during deep hypothermic circulatory arrest (DHCA)? Altogether, more than 62 papers were found using the reported search, of which 7 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. Four of the seven papers used thiopental alongside other neuroprotective methods and agents. The methods included the use of ice packs to the head and core systemic hypothermia. Agents used alongside thiopental included nicardipine and mannitol. Thiopental was found to have the ability to lower oxygen consumption, where oxygen consumption was measured using the phosphocreatinine and adenosine triphosphate ratio. The neuroprotective effect of thiopental was evaluated by assessing the electrical activity of the brain during circulatory arrest, by which it was shown to be advantageous. However, other trials suggested that adding thiopental during circulatory arrest did not provide any extra protection to the brain. The timing of thiopental administration is of importance in order to gain positive outcomes, as it's ability to lower the cerebral energy state may result in unfavourable results if added before hypothermic circulatory arrest, where this may lead to an ischaemic event. We conclude that the use of thiopental during deep hypothermic circulatory arrest is beneficial, but if administered too early, it may replete the cerebral energy state before arrest and prove to be detrimental. PMID:23644730

Does the use of thiopental provide added cerebral protection during deep hypothermic circulatory arrest?

PubMed

Al-Hashimi, Sara; Zaman, Mahvash; Waterworth, Paul; Bilal, Haris

2013-08-01

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was: Does the use of thiopental provide added cerebral protection during deep hypothermic circulatory arrest (DHCA)? Altogether, more than 62 papers were found using the reported search, of which 7 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. Four of the seven papers used thiopental alongside other neuroprotective methods and agents. The methods included the use of ice packs to the head and core systemic hypothermia. Agents used alongside thiopental included nicardipine and mannitol. Thiopental was found to have the ability to lower oxygen consumption, where oxygen consumption was measured using the phosphocreatinine and adenosine triphosphate ratio. The neuroprotective effect of thiopental was evaluated by assessing the electrical activity of the brain during circulatory arrest, by which it was shown to be advantageous. However, other trials suggested that adding thiopental during circulatory arrest did not provide any extra protection to the brain. The timing of thiopental administration is of importance in order to gain positive outcomes, as it's ability to lower the cerebral energy state may result in unfavourable results if added before hypothermic circulatory arrest, where this may lead to an ischaemic event. We conclude that the use of thiopental during deep hypothermic circulatory arrest is beneficial, but if administered too early, it may replete the cerebral energy state before arrest and prove to be detrimental.

Prevention of vascular inflammation by nanoparticle targeting of adherent neutrophils

NASA Astrophysics Data System (ADS)

Wang, Zhenjia; Li, Jing; Cho, Jaehyung; Malik, Asrar B.

2014-03-01

Inflammatory diseases such as acute lung injury and ischaemic tissue injury are caused by the adhesion of a type of white blood cell--polymorphonuclear neutrophils--to the lining of the circulatory system or vascular endothelium and unchecked neutrophil transmigration. Nanoparticle-mediated targeting of activated neutrophils on vascular endothelial cells at the site of injury may be a useful means of directly inactivating neutrophil transmigration and hence mitigating vascular inflammation. Here, we report a method employing drug-loaded albumin nanoparticles, which efficiently deliver drugs into neutrophils adherent to the surface of the inflamed endothelium. Using intravital microscopy of tumour necrosis factor-α-challenged mouse cremaster post-capillary venules, we demonstrate that fluorescently tagged albumin nanoparticles are largely internalized by neutrophils adherent to the activated endothelium via cell surface Fcɣ receptors. Administration of albumin nanoparticles loaded with the spleen tyrosine kinase inhibitor, piceatannol, which blocks `outside-in' β2 integrin signalling in leukocytes, detached the adherent neutrophils and elicited their release into the circulation. Thus, internalization of drug-loaded albumin nanoparticles into neutrophils inactivates the pro-inflammatory function of activated neutrophils, thereby offering a promising approach for treating inflammatory diseases resulting from inappropriate neutrophil sequestration and activation.

Uncontrolled Donation After Circulatory Determination of Death Donors (uDCDDs) as a Source of Lungs for Transplant.

PubMed

Egan, T M; Requard, J J

2015-08-01

In April 2014, the American Journal of Transplantation published a report on the first lung transplant in the United States recovered from an uncontrolled donation after circulatory determination of death donor (uDCDD), assessed by ex vivo lung perfusion (EVLP). The article identified logistical and ethical issues related to introduction of lung transplant from uDCDDs. In an open clinical trial, we have Food and Drug Administration and Institutional Review Board approval to transplant lungs recovered from uDCDDs judged suitable after EVLP. Through this project and other experiences with lung recovery from uDCDDs, we have identified solutions to many logistical challenges and have addressed ethical issues surrounding lung transplant from uDCDDs that were mentioned in this case report. Here, we discuss those challenges, including issues related to recovery of other solid organs from uDCDDs. Despite logistical challenges, uDCDDs could solve the critical shortage of lungs for transplant. Furthermore, by avoiding the deleterious impact of brain death and days of positive pressure ventilation, and by using opportunities to treat lungs in the decedent or during EVLP, lungs recovered from uDCDDs may ultimately prove to be better than lungs currently being transplanted from conventional brain-dead organ donors. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

Treatment with epinephrine (adrenaline) in suspected anaphylaxis during anesthesia in Denmark.

PubMed

Garvey, Lene H; Belhage, Bo; Krøigaard, Mogens; Husum, Bent; Malling, Hans-Jørgen; Mosbech, Holger

2011-07-01

Literature on the use of epinephrine in the treatment of anaphylaxis during anesthesia is very limited. The objective of this study was to investigate how often epinephrine is used in the treatment of suspected anaphylaxis during anesthesia in Denmark and whether timing of treatment is important. A retrospective study of 270 patients investigated at the Danish Anaesthesia Allergy Centre after referral due to suspected anaphylaxis during anesthesia was performed. Reactions had been graded by severity: C1, mild reactions; C2, moderate reactions; C3, anaphylactic shock with circulatory instability; C4, cardiac arrest. Use of epinephrine, dosage, route of administration, and time between onset of circulatory instability and epinephrine administration were noted. A total of 122 (45.2%) of referred patients had C3 or C4 reactions; of those, 101 (82.8%) received epinephrine. Route of administration was intravenous in 95 (94%) patients. Median time from onset of reported hypotension to treatment with epinephrine was 10 min (range, 1-70 min). Defining epinephrine treatment less than or equal to 10 min after onset of hypotension as early, and more than 10 min as late, infusion was needed in 12 of 60 patients (20%) treated early versus 12 of 35 patients (34%) treated late (odds ratio, 2.09) (95% confidence interval, 0.81-5.35). Anaphylaxis may be difficult to diagnose during anesthesia, and treatment with epinephrine can be delayed as a consequence. Anaphylaxis should be considered and treated in patients with circulatory instability during anesthesia of no apparent cause who do not respond to the usual treatments.

Catecholaminergic, neuroendocrine and anxiety responses to acute psychological stress in healthy subjects: influence of alprazolam administration.

PubMed

Santagostino, G; Amoretti, G; Frattini, P; Zerbi, F; Cucchi, M L; Preda, S; Corona, G L

1996-01-01

We studied the effect of alprazolam (APZ) in 12 healthy volunteers on the psychological stress-induced activation of emotion and on the pituitary-adrenal, adrenomedullary and sympathoneuronal systems. After 3 days of placebo or APZ (1 mg/day orally) administration, we examined plasma levels of adrenocorticotropic hormone, cortisol, L-3,4 dihydroxyphenylalanine, dopamine, norepinephrine (NE), epinephrine, metanephrine, normetanephrine, homovanillic acid, vanillylmandelic acid, 3-methoxy-4-hydroxy phenyglycol, urinary levels of cortisol and catecholamines, circulatory responses and state anxiety levels in subjects undergoing psychological stress based on viewing horror, violence, danger and war film clips. Film viewing produced modest rises of state anxiety levels, of plasma NE concentration and of diastolic blood pressure in both the placebo and drug groups. APZ significantly reduced anxiety levels at the beginning of the experimental session and caused a decrease of noradrenergic and dopaminergic neurotransmitter and cortisol concentrations. Our data suggest that APZ reduced anxiety related to the expectation of the event, while the circuitry between structures responsible for anxiety and peripheral sympathoneural function was still found to be partly sensitive to film viewing.

Nano carriers for drug transport across the blood-brain barrier.

PubMed

Li, Xinming; Tsibouklis, John; Weng, Tingting; Zhang, Buning; Yin, Guoqiang; Feng, Guangzhu; Cui, Yingde; Savina, Irina N; Mikhalovska, Lyuba I; Sandeman, Susan R; Howel, Carol A; Mikhalovsky, Sergey V

2017-01-01

Effective therapy lies in achieving a therapeutic amount of drug to the proper site in the body and then maintaining the desired drug concentration for a sufficient time interval to be clinically effective for treatment. The blood-brain barrier (BBB) hinders most drugs from entering the central nervous system (CNS) from the blood stream, leading to the difficulty of delivering drugs to the brain via the circulatory system for the treatment, diagnosis and prevention of brain diseases. Several brain drug delivery approaches have been developed, such as intracerebral and intracerebroventricular administration, intranasal delivery and blood-to-brain delivery, as a result of transient BBB disruption induced by biological, chemical or physical stimuli such as zonula occludens toxin, mannitol, magnetic heating and ultrasound, but these approaches showed disadvantages of being dangerous, high cost and unsuitability for most brain diseases and drugs. The strategy of vector-mediated blood-to-brain delivery, which involves improving BBB permeability of the drug-carrier conjugate, can minimize side effects, such as being submicrometre objects that behave as a whole unit in terms of their transport and properties, nanomaterials, are promising carrier vehicles for direct drug transport across the intact BBB as a result of their potential to enter the brain capillary endothelial cells by means of normal endocytosis and transcytosis due to their small size, as well as their possibility of being functionalized with multiple copies of the drug molecule of interest. This review provids a concise discussion of nano carriers for drug transport across the intact BBB, various forms of nanomaterials including inorganic/solid lipid/polymeric nanoparticles, nanoemulsions, quantum dots, nanogels, liposomes, micelles, dendrimers, polymersomes and exosomes are critically evaluated, their mechanisms for drug transport across the BBB are reviewed, and the future directions of this area are fully discussed.

Drug therapy in the prevention of failure of the Fontan circulation: a systematic review.

PubMed

Oldenburger, Nathalie J; Mank, Arenda; Etnel, Jonathan; Takkenberg, Johanna J M; Helbing, Willem A

2016-06-01

The Fontan circulation is the optimal treatment for patients with univentricular hearts. These patients are at high risk of circulatory failure. There is no consensus on the optimal drug treatment for the prevention of failure of the Fontan circulation. The aim of this systematic review was to provide an overview of evidence for drug therapy used in the prevention of Fontan circulatory failure. We searched the Embase database for articles that reported drug therapy in Fontan patients. Studies published between 1997 and 2014 were included if efficacy or safety of medication was assessed, drug therapy aimed to prevent or treat failure of the Fontan circulation, and if the full text was available. Case reports were excluded. A total of nine studies were included with a total of 267 Fontan patients; four studies evaluated the medication sildenafil, one iloprost, three bosentan, and one enalapril. Among all, two sildenafil studies reported improvement in exercise capacity, one in exercise haemodynamics, and one in ventricular performance. In the largest study of bosentan, an increase in exercise capacity was found. Enalapril did not result in improvements. The studies analysed in this review suggest that bosentan, sildenafil, and iloprost may improve exercise capacity at the short term. Given the limitations of the studies, more, larger, placebo-controlled studies with longer follow-up periods are needed to better understand which drug therapies are effective in the prevention of failure of the Fontan circulation.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wexler, J.P.; Davis, L.; Mancini, D.

Cardioactive drugs may effect both the central and peripheral circulatory systems. The effects on the central and peripheral circulatory systems of chronic Captorpril therapy in 7 pts with severe congestive heart failure (CHF) were evaluated simultaneously. Skeletal muscle blood flow (SMBF) determined using 133-Xe washout and a Cd/Te detector, oxygen consumption (VO/sub 2/), and radial artery and femoral vein O/sub 2/ concentration difference (A-V) were determined at rest and peak upright bicycle exercise before (BT) and after (AT) 6-12 weeks of Captopril therapy. In CI pts there was a significant increase in VO/sub 2/ and SMBF AT vs BT. Inmore » contrast, in CNC pts there was no change in VO/sub 2/ and a significant decrease in SMBF AT vs BT. In pts with severe CHF who are CI, there is an apparent fall in peripheral vascular resistance (PVR). In contrast, in CNC pts there is an increase in PVR. This study demonstrates that SMBF determines using 133-Xe is an important method for determining the effects of cardioactive drugs.« less

Results of the destination therapy post-food and drug administration approval study with a continuous flow left ventricular assist device: a prospective study using the INTERMACS registry (Interagency Registry for Mechanically Assisted Circulatory Support).

PubMed

Jorde, Ulrich P; Kushwaha, Sudhir S; Tatooles, Antone J; Naka, Yoshifumi; Bhat, Geetha; Long, James W; Horstmanshof, Douglas A; Kormos, Robert L; Teuteberg, Jeffrey J; Slaughter, Mark S; Birks, Emma J; Farrar, David J; Park, Soon J

2014-05-06

A post-approval (PA) study for destination therapy (DT) was required by the Food and Drug Administration (FDA) to determine whether results with the HeartMate (HM) II (Thoratec, Pleasanton, California) left ventricular assist device (LVAD) in a commercial setting were comparable to results during the DT multicenter pivotal clinical trial. New device technology developed in the clinical research setting requires validation in a real-world setting. The PA study was a prospective evaluation of the first 247 HM II patients identified pre-operatively as eligible for DT in the national INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) registry. Patients were enrolled from January to September 2010 at 61 U.S. centers and followed for 2 years. A historical comparison group included patients (n = 133 at 34 centers) enrolled in the primary data cohort in the DT pivotal trial (TR). Survival rates and adverse events for the PA group were obtained from the INTERMACS registry. Baseline characteristics were similar for PA versus TR. Forty-five percent of PA patients were in INTERMACS profiles 1 to 2 and 28% were in profile 3. Adverse events in the PA group were similar or lower than those in the TR group, including improvements in device-related infection (0.22 vs. 0.47) and post-operative bleeding requiring surgery (0.09 vs. 0.23) events per patient-year. Kaplan-Meier survival at 2 years was 62% (PA group) versus 58% (TR group). PA group survival at 1 and 2 years was 82 ± 5% and 69 ± 6% for INTERMACS profiles 4 to 7 (n = 63) versus 72 ± 3% and 60 ± 4% for profiles 1 to 3 (n = 184). The median length of stay after surgery was reduced by 6 days in the PA group versus the TR group. Results in a commercial patient care setting for the DT population supported the original pivotal clinical trial findings regarding the efficacy and risk profile of the HM II LVAD. Survival was best in patients who were not inotrope-dependent (INTERMACS profiles 4 to 7). Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Dual stimuli polysaccharide nanovesicles for conjugated and physically loaded doxorubicin delivery in breast cancer cells.

PubMed

Pramod, P S; Shah, Ruchira; Jayakannan, Manickam

2015-04-21

The present work reports the development of pH and enzyme dual responsive polysaccharide vesicular nano-scaffolds for the administration of doxorubicin via physical loading and polymer-drug conjugation to breast cancer cells. Dextran was suitably modified with a renewable resource 3-pentadecyl phenol unit through imine and aliphatic ester chemical linkages that acted as pH and esterase enzyme stimuli, respectively. These dual responsive polysaccharide derivatives self-organized into 200 ± 10 nm diameter nano-vesicles in water. The water soluble anticancer drug doxorubicin (DOX·HCl) was encapsulated in the hydrophilic pocket to produce core-loaded polysaccharide vesicles whereas chemical conjugation produced DOX anchored at the hydrophobic layer of the dextran nano-vesicles. In vitro studies revealed that about 70-80% of the drug was retained under circulatory conditions at pH = 7.4 and 37 °C. At a low pH of 6.0 to 5.0 and in the presence of esterase; both imine and ester linkages were cleaved instantaneously to release 100% of the loaded drugs. Cytotoxicity assays on Wild Type Mouse Embryonic Fibroblasts (WTMEFs) confirmed the non-toxicity of the newly developed dextran derivatives at up to 500 μg mL(-1) in PBS. MTT assays on fibroblast cells revealed that DOX·HCl loaded nano-vesicles exhibited better killing abilities than DOX conjugated polymer nano-vesicles. Both DOX loaded and DOX conjugated nano-vesicles were found to show significant killing in breast cancer cells (MCF 7). Confocal microscopy images confirmed the uptake of DOX loaded (or conjugated) nano-vesicles by cells compared to free DOX. Thus, the newly developed pH and enzyme dual responsive polysaccharide vesicular assemblies are potential drug vectors for the administration of DOX in both loaded and chemically conjugated forms for the efficient killing of breast cancer cells.

Simple Model of the Circulation.

ERIC Educational Resources Information Center

Greenway, Clive A.

1980-01-01

Describes a program in BASIC-11 that explores the relationships between various variables in the circulatory system and permits manipulation of several semiindependent variables to model the effects of hemorrhage, drug infusions, etc. A flow chart and accompanying sample printout are provided; the program is listed in the appendix. (CS)

Blackworms, Blood Vessel Pulsations and Drug Effects.

ERIC Educational Resources Information Center

Lesiuk, Nalena M.; Drewes, Charles D.

1999-01-01

Introduces the freshwater oligochaete worm, lumbriculus variegatus (common name: blackworms), an organism that is well suited for classroom study because of its closed circulatory system. Describes a set of simple, fast, noninvasive, and inexpensive methods for observing pulsations of the worm's dorsal blood vessels under baseline conditions, and…

Results of the post-U.S. Food and Drug Administration-approval study with a continuous flow left ventricular assist device as a bridge to heart transplantation: a prospective study using the INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support).

PubMed

Starling, Randall C; Naka, Yoshifumi; Boyle, Andrew J; Gonzalez-Stawinski, Gonzalo; John, Ranjit; Jorde, Ulrich; Russell, Stuart D; Conte, John V; Aaronson, Keith D; McGee, Edwin C; Cotts, William G; DeNofrio, David; Pham, Duc Thinh; Farrar, David J; Pagani, Francis D

2011-05-10

The aim of this study was to determine whether results with the HeartMate (HM) II left ventricular assist device (LVAD) (Thoratec Corporation, Pleasanton, California) in a commercial setting are comparable to other available devices for the same indication. After a multicenter pivotal clinical trial conducted from 2005 to 2008, the U.S. Food and Drug Administration approved the HM II LVAD for bridge to transplantation (BTT). A post-approval study was required by the U.S. Food and Drug Administration to determine whether results with the device in a commercial setting are comparable to other available devices for the same indication. The study was a prospective evaluation of the first 169 consecutive HM II patients enrolled in the national INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) who were listed for transplant or likely to be listed. Patients were enrolled from April through August 2008 at 77 U.S. centers and followed for at least 1 year after implant. A comparison group (COMP) included all patients (n = 169 at 27 centers) enrolled in the INTERMACS registry with other types of LVADs (79% HeartMate XVE, 21% Implantable Ventricular Assist Device [Thoratec Corporation]) for the same BTT indication in the same time period. Survival rates, adverse events, and quality of life with the EuroQol EQ-5D visual analog scale were obtained in the INTERMACS registry. Baseline characteristics were similar, but creatinine and blood urea nitrogen were lower in the HM II versus COMP groups, and there were fewer patients in the highest-risk INTERMACS patient profile Number 1 (24% for HM II vs. 39% for COMP). Adverse event rates were similar or lower for HM II versus COMP for all events. Bleeding was the most frequent adverse event for both groups (1.44 vs. 1.79 events/patient-year). Operative 30-day mortality for HM II was 4% versus 11% for COMP. The percentage of patients reaching transplant, cardiac recovery, or ongoing LVAD support by 6 months was 91% for HM II and 80% for COMP, and the Kaplan-Meier survival for patients remaining on support at 1 year was 85% for HM II versus 70% for COMP. Quality of life was significantly improved at 3 months of support and sustained through 12 months in both groups compared with baseline. The results in a post-market approval, actual patient care setting BTT population support the original findings from the pivotal clinical trial regarding the efficacy and risk profile of the HM II LVAD. These data suggest that dissemination of this technology after approval has been associated with continued excellent results. Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Microgravity

NASA Image and Video Library

1992-03-12

Contributes to many transport and regulatory processes and has multifunctional binding properties which range form various metals, to fatty acids, hormones, and a wide spectrum of therapeutic drugs. The most abundant protein of the circulatory system. It binds and transports an incredible variety of biological and pharmaceutical ligands throughout the blood stream. Principal Investigator was Larry DeLucas.

Mean circulatory filling pressure: its meaning and measurement.

PubMed

Rothe, C F

1993-02-01

The volume-pressure relationship of the vasculature of the body as a whole, its vascular capacitance, requires a measurement of the mean circulatory filling pressure (Pmcf). A change in vascular capacitance induced by reflexes, hormones, or drugs has physiological consequences similar to a rapid change in blood volume and thus strongly influences cardiac output. The Pmcf is defined as the mean vascular pressure that exists after a stop in cardiac output and redistribution of blood, so that all pressures are the same throughout the system. The Pmcf is thus related to the fullness of the circulatory system. A change in Pmcf provides a uniquely useful index of a change in overall venous smooth muscle tone if the blood volume is not concomitantly changed. The Pmcf also provides an estimate of the distending pressure in the small veins and venules, which contain most of the blood in the body and comprise most of the vascular compliance. Thus the Pmcf, which is normally independent of the magnitude of the cardiac output, provides an estimate of the upstream pressure that determines the rate of flow returning to the heart.

Biventricular assist device for scombroid poisoning with refractory myocardial dysfunction: a bridge to recovery.

PubMed

Grinda, Jean-Michel; Bellenfant, Florence; Brivet, François Gilles; Carel, Yvan; Deloche, Alain

2004-09-01

We report the usefulness of biventricular mechanical circulatory support in a 36-yr-old woman with refractory myocardial dysfunction resulting from scombroid poisoning. Case report. Medical and surgical university care units. A previously healthy 36-yr-old woman with severe myocardial dysfunction unresponsive to epinephrine (1.3 microg/kg/min) and dobutamine (18 microg/kg/min) after the ingestion of cooked fresh tuna. Implantation at day 3 of a biventricular assist device consisting of two paracorporeal pneumatic pumps set at 70 beats/min to reach an output of 5.6 L/min during 8 days. The biventricular mechanical circulatory assist device allowed weaning of the inotropic drugs, maintenance of end-organ function, and support of the patient until myocardial recovery. The patient was successfully explanted 11 days after ingestion. Cardiac function had totally recovered, but a stroke was noted. At 3-yrs follow-up, there was no cardiac or neurologic sequela. This report describes severe myocardial dysfunction secondary to scombroid poisoning and demonstrates the usefulness of a mechanical circulatory assist device as a bridge to recovery.

Reduced brachial flow-mediated vasodilation in young adult ex extremely low birth weight preterm: a condition predictive of increased cardiovascular risk?

PubMed

Bassareo, P P; Fanos, V; Puddu, M; Demuru, P; Cadeddu, F; Balzarini, M; Mercuro, G

2010-10-01

Sporadic data present in literature report how preterm birth and low birth weight constitute the risk factors for the development of cardiovascular diseases in later life. To assess the presence of potential alterations to endothelial function in young adults born preterm at extremely low birth weight (<1000 g; ex ELBW). Thirty-two ex-ELBW subjects (10 males [M] and 22 females [F], aged 17-28 years, mean [+/- DS] 20.1 +/- 2.5 years) were compared with 32 healthy, age-matched subjects born at term (C, 9 M and 23 F). 1) pathological conditions known to affect endothelial function; 2) administration of drugs known to affect endothelial function. Endothelial function was assessed by non-invasive finger plethysmography, previously validated by the US Food and Drug Administration (Endopath; Itamar Medical Ltd., Cesarea, Israel). Endothelial function was significantly reduced in ex-ELBW subjects compared to C (1.94 +/- 0.37 vs. 2.68 +/- 0.41, p < 0.0001). Moreover, this function correlated significantly with gestational age (r = 0.56, p < 0.0009) and birth weight (r = 0.63, p < 0.0001). The results obtained reveal a significant decrease in endothelial function of ex-ELBW subjects compared to controls, underlining a probable correlation with preterm birth and low birth weight. Taken together, these results suggest that an ELBW may underlie the onset of early circulatory dysfunction predictive of increased cardiovascular risk.

Fishing anti(lymph)angiogenic drugs with zebrafish.

PubMed

García-Caballero, Melissa; Quesada, Ana R; Medina, Miguel A; Marí-Beffa, Manuel

2018-02-01

Zebrafish, an amenable small teleost fish with a complex mammal-like circulatory system, is being increasingly used for drug screening and toxicity studies. It combines the biological complexity of in vivo models with a higher-throughput screening capability compared with other available animal models. Externally growing, transparent embryos, displaying well-defined blood and lymphatic vessels, allow the inexpensive, rapid, and automatable evaluation of drug candidates that are able to inhibit neovascularisation. Here, we briefly review zebrafish as a model for the screening of anti(lymph)angiogenic drugs, with emphasis on the advantages and limitations of the different zebrafish-based in vivo assays. Copyright © 2017 Elsevier Ltd. All rights reserved.

Dual stimuli polysaccharide nanovesicles for conjugated and physically loaded doxorubicin delivery in breast cancer cells

NASA Astrophysics Data System (ADS)

Pramod, P. S.; Shah, Ruchira; Jayakannan, Manickam

2015-04-01

The present work reports the development of pH and enzyme dual responsive polysaccharide vesicular nano-scaffolds for the administration of doxorubicin via physical loading and polymer-drug conjugation to breast cancer cells. Dextran was suitably modified with a renewable resource 3-pentadecyl phenol unit through imine and aliphatic ester chemical linkages that acted as pH and esterase enzyme stimuli, respectively. These dual responsive polysaccharide derivatives self-organized into 200 +/- 10 nm diameter nano-vesicles in water. The water soluble anticancer drug doxorubicin (DOX.HCl) was encapsulated in the hydrophilic pocket to produce core-loaded polysaccharide vesicles whereas chemical conjugation produced DOX anchored at the hydrophobic layer of the dextran nano-vesicles. In vitro studies revealed that about 70-80% of the drug was retained under circulatory conditions at pH = 7.4 and 37 °C. At a low pH of 6.0 to 5.0 and in the presence of esterase; both imine and ester linkages were cleaved instantaneously to release 100% of the loaded drugs. Cytotoxicity assays on Wild Type Mouse Embryonic Fibroblasts (WTMEFs) confirmed the non-toxicity of the newly developed dextran derivatives at up to 500 μg mL-1 in PBS. MTT assays on fibroblast cells revealed that DOX.HCl loaded nano-vesicles exhibited better killing abilities than DOX conjugated polymer nano-vesicles. Both DOX loaded and DOX conjugated nano-vesicles were found to show significant killing in breast cancer cells (MCF 7). Confocal microscopy images confirmed the uptake of DOX loaded (or conjugated) nano-vesicles by cells compared to free DOX. Thus, the newly developed pH and enzyme dual responsive polysaccharide vesicular assemblies are potential drug vectors for the administration of DOX in both loaded and chemically conjugated forms for the efficient killing of breast cancer cells.The present work reports the development of pH and enzyme dual responsive polysaccharide vesicular nano-scaffolds for the administration of doxorubicin via physical loading and polymer-drug conjugation to breast cancer cells. Dextran was suitably modified with a renewable resource 3-pentadecyl phenol unit through imine and aliphatic ester chemical linkages that acted as pH and esterase enzyme stimuli, respectively. These dual responsive polysaccharide derivatives self-organized into 200 +/- 10 nm diameter nano-vesicles in water. The water soluble anticancer drug doxorubicin (DOX.HCl) was encapsulated in the hydrophilic pocket to produce core-loaded polysaccharide vesicles whereas chemical conjugation produced DOX anchored at the hydrophobic layer of the dextran nano-vesicles. In vitro studies revealed that about 70-80% of the drug was retained under circulatory conditions at pH = 7.4 and 37 °C. At a low pH of 6.0 to 5.0 and in the presence of esterase; both imine and ester linkages were cleaved instantaneously to release 100% of the loaded drugs. Cytotoxicity assays on Wild Type Mouse Embryonic Fibroblasts (WTMEFs) confirmed the non-toxicity of the newly developed dextran derivatives at up to 500 μg mL-1 in PBS. MTT assays on fibroblast cells revealed that DOX.HCl loaded nano-vesicles exhibited better killing abilities than DOX conjugated polymer nano-vesicles. Both DOX loaded and DOX conjugated nano-vesicles were found to show significant killing in breast cancer cells (MCF 7). Confocal microscopy images confirmed the uptake of DOX loaded (or conjugated) nano-vesicles by cells compared to free DOX. Thus, the newly developed pH and enzyme dual responsive polysaccharide vesicular assemblies are potential drug vectors for the administration of DOX in both loaded and chemically conjugated forms for the efficient killing of breast cancer cells. Electronic supplementary information (ESI) available: 13C NMR of DEX-CHO, 2D NMR spectra of DEX-CHO, 1H NMR of DEX-IM, 1H NMR of DEX-IM-DOX conjugated, absorbance spectra of DEX-IM-DOX conjugated, DLS, FE-SEM and TEM image of DEX-CHO-5, emission spectra of pyrene and Nile red with DEX-IM-10, FE-SEM image of DEX-IM-DOX loaded, FE-SEM image of acid treated DEX-IM-5, absorbance spectra of DOX released, in vitro DOX release from drug loaded and conjugated vesicles in the presence of serum (FBS), DLS data depicting stability of DEX-IM vesicles in serum (FBS), 1HNMR, 13C NMR and HR-MS spectra of all intermediates are provided. See DOI: 10.1039/c5nr00799b

Current Challenges in Neonatal Resuscitation: What is the Role of Adrenaline?

PubMed

Antonucci, Roberto; Antonucci, Luca; Locci, Cristian; Porcella, Annalisa; Cuzzolin, Laura

2018-06-19

Adrenaline, also known as epinephrine, is a hormone, neurotransmitter, and medication. It is the best established drug in neonatal resuscitation, but only weak evidence supports current recommendations for its use. Furthermore, the available evidence is partly based on extrapolations from adult studies, and this introduces further uncertainty, especially when considering the unique physiological characteristics of newly born infants. The timing, dose, and route of administration of adrenaline are still debated, even though this medication has been used in neonatal resuscitation for a long time. According to the most recent Neonatal Resuscitation Guidelines from the American Heart Association, adrenaline use is indicated when the heart rate remains < 60 beats per minute despite the establishment of adequate ventilation with 100% oxygen and chest compressions. The aforementioned guidelines recommend intravenous administration (via an umbilical venous catheter) of adrenaline at a dose of 0.01-0.03 mg/kg (1:10,000 concentration). Endotracheal administration of a higher dose (0.05-0.1 mg/kg) may be considered while venous access is being obtained, even if supportive data for endotracheal adrenaline are lacking. The safety and efficacy of intraosseous administration of adrenaline remain to be investigated. This article reviews the evidence on the circulatory effects and tolerability of adrenaline in the newborn, discusses literature data on adrenaline use in neonatal cardiopulmonary resuscitation, and describes international recommendations and outcome data regarding the use of this medication during neonatal resuscitation.

Computer Model of Aspirin bound to Human Serum Albumin

NASA Technical Reports Server (NTRS)

1989-01-01

Contributes to many transport and regulatory processes and has multifunctional binding properties which range form various metals, to fatty acids, hormones, and a wide spectrum of therapeutic drugs. The most abundant protein of the circulatory system. It binds and transports an incredible variety of biological and pharmaceutical ligands throughout the blood stream.

The eye and visual nervous system: anatomy, physiology and toxicology.

PubMed Central

McCaa, C S

1982-01-01

The eyes are at risk to environmental injury by direct exposure to airborne pollutants, to splash injury from chemicals and to exposure via the circulatory system to numerous drugs and bloodborne toxins. In addition, drugs or toxins can destroy vision by damaging the visual nervous system. This review describes the anatomy and physiology of the eye and visual nervous system and includes a discussion of some of the more common toxins affecting vision in man. Images FIGURE 1. FIGURE 2. PMID:7084144

Hemodiafiltration efficacy in treatment of methanol and ethylene glycol poisoning in a 2-year-old girl.

PubMed

Szmigielska, Agnieszka; Szymanik-Grzelak, Hanna; Kuźma-Mroczkowska, Elżbieta; Roszkowska-Blaim, Maria

2015-01-01

Every year about 2.4 million people in USA are exposed to toxic substances. Many of them are children below 6 years of age. Majority of poisonings in children are incidental and related to household products including for example drugs, cleaning products or antifreeze products. Antifreeze solutions contain ethylene glycol and methanol. Treatment of these toxic substances involves ethanol administration, fomepizole, hemodialysis and correction of metabolic acidosis. The aim of the study was to check the efficacy of continuous venovenous hemodiagiltration in intoxication with ethylene glycol and methanol. One year and 7 months old girl after intoxication with ethylene glycol and methanol was treated with continuous venovenous hemodiafiltration instead of hemodialysis because of technical problems (circulatory instability). Intravenous ethanol infusion with hemodialtration resulted in rapid elimination of methanol from the body and significantly reduced blood ethylene glycol level. Continuous venovenous hemodiafiltration can be helpful in treatment of ethylene glycol and methanol intoxication.

Depiction of Trends in Administrative Healthcare Data from Hospital Information System.

PubMed

Kalankesh, Leila R; Pourasghar, Faramarz; Jafarabadi, Mohammad Asghari; Khanehdan, Negar

2015-06-01

administrative healthcare data are among main components of hospital information system. Such data can be analyzed and deployed for a variety of purposes. The principal aim of this research was to depict trends of administrative healthcare data from HIS in a general hospital from March 2011 to March 2014. data set used for this research was extracted from the SQL database of the hospital information system in Razi general hospital located in Marand. The data were saved as CSV (Comma Separated Values) in order to facilitate data cleaning and analysis. The variables of data set included patient's age, gender, final diagnosis, final diagnosis code based on ICD-10 classification system, date of hospitalization, date of discharge, LOS(Length of Stay), ward, and survival status of the patient. Data were analyzed and visualized after applying appropriate cleansing and preparing techniques. morbidity showed a constant trend over three years. Pregnancy, childbirth and the puerperium were the leading category of final diagnosis (about 32.8 %). The diseases of the circulatory system were the second class accounting for 13 percent of the hospitalization cases. The diseases of the digestive system had the third rank (10%). Patients aged between 14 and 44 constituted a higher proportion of total cases. Diseases of the circulatory system was the most common class of diseases among elderly patients (age≥65). The highest rate of mortality was observed among patients with final diagnosis of the circulatory system diseases followed by those with diseases of the respiratory system, and neoplasms. Mortality rate for the ICU and the CCU patients were 62% and 33% respectively. The longest average of LOS (7.3 days) was observed among patients hospitalized in the ICU while patients in the Obstetrics and Gynecology ward had the shortest average of LOS (2.4 days). Multiple regression analysis revealed that LOS was correlated with variables of surgery, gender, and type of payment, ward, the class of final diagnosis and age. this study presents trends in administrative health care data residing in hospital information system of a general public hospital. Patterns in morbidity, mortality and length of stay can inform decision making in health care management. Mining trends in administrative healthcare data can add value to the health care management.

Fatty Acid-Mediated Inhibition of Metal Binding to the Multi-Metal Site on Serum Albumin: Implications for Cardiovascular Disease.

PubMed

Blindauer, Claudia A; Khazaipoul, Siavash; Yu, Ruitao; Stewart, Alan J

2016-01-01

Human serum albumin (HSA) is the major protein in blood plasma and is responsible for circulatory transport of a range of small molecules including fatty acids, metal ions and drugs. We previously identified the major plasma Zn2+ transport site on HSA and revealed that fatty-acid binding (at a distinct site called the FA2 site) and Zn2+ binding are interdependent via an allosteric mechanism. Since binding affinities of long-chain fatty acids exceed those of plasma Zn2+, this means that under certain circumstances the binding of fatty acid molecules to HSA is likely to diminish HSA Zn2+-binding, and hence affects the control of circulatory and cellular Zn2+ dynamics. This relationship between circulatory fatty acid and Zn2+ dynamics is likely to have important physiological and pathological implications, especially since it has been recognised that Zn2+ acts as a signalling agent in many cell types. Fatty acid levels in the blood are dynamic, but most importantly, chronic elevation of plasma fatty acid levels is associated with some metabolic disorders and disease states - including myocardial infarction and other cardiovascular diseases. In this article, we briefly review the metal-binding properties of albumin and highlight the importance of their interplay with fatty acid binding. We also consider the impact of this dynamic link upon levels and speciation of plasma Zn2+, its effect upon cellular Zn2+ homeostasis and its relevance to cardiovascular and circulatory processes in health and disease.

Adverse effects of neuromuscular blockers and their antagonists.

PubMed

Naguib, M; Magboul, M M

1998-02-01

Among all the drugs used for general anaesthesia, neuromuscular blockers appear to play a prominent role in the incidence of severe adverse reactions. It now seems likely that most serious adverse drug reactions occurring during anaesthesia are immunological in type. The frequency of life-threatening anaphylactic or anaphylactoid reactions occurring during anaesthesia has been estimated to be between 1 in 1000 and 1 in 25,000 anaesthetic procedures, with the neuromuscular blockers being involved in 80% of cases. The mortality from such serious reactions is reported to be in the range of 3.4 to 6%. The highly immunogenic drug, suxamethonium chloride (succinylcholine), was found to be the most hazardous agent. Drug-specific immunoglobulin E antibodies to suxamethonium chloride and other neuromuscular blockers have been demonstrated. This sensitivity to neuromuscular blockers seems to be a long-lasting phenomenon. During anaesthesia, the clinical features of an allergic reaction are often masked. Tachycardia and circulatory collapse may be the only signs of an allergic reaction, and they are easily misdiagnosed. Bronchospasm is reported to be present in about 40% of cases. Successful management of these patients includes stabilisation during the acute reaction and avoidance of future reactions. The latter is based on the identification of the causative drug and potentially cross-reacting compounds. The use of suxamethonium chloride is associated with many other adverse effects, such as fasciculations, myalgia, potassium release, changes in the heart rate, increases in intragastric and intraocular pressures, and malignant hyperthermia. Because of the dangers of hyperkalaemic cardiac arrest after suxamethonium chloride administration in children with unrecognised muscular dystrophy, there have now been moves to limit the use of this drug in children. Although neuromuscular blockers are designed to specifically block nicotinic cholinergic receptors at the neuromuscular junction, many bind to muscarinic cholinergic receptors on ganglia and smooth muscle, and alter parasympathetically mediated heart rate and airway calibre. Most benzylisoquinolinium muscle relaxants can induce histamine release, especially when they are administered rapidly, which can lead to disturbances of cardiovascular function. In addition, nondepolarising neuromuscular blockers have been implicated in causing generalised weakness following their long term administration to patients on an intensive care unit. The problem with these adverse drug reactions is their unpredictable nature. Therefore, prompt recognition with appropriate therapy can help to improve the outcome.

Adverse effects of neuromuscular blockers and their antagonists.

PubMed

Naguib, M; Magboul, M M

1998-06-01

Among all the drugs used for general anesthesia, neuromuscular blockers appear to play a prominent role in the incidence of severe adverse reactions. It now seems likely that most serious adverse drug reactions occurring during anesthesia are immunological in type. The frequency of life-threatening anaphylactic or anaphylactoid reactions occurring during anesthesia has been estimated to be between 1 in 1000 and 1 in 25,000 anesthetic procedures, with the neuromuscular blockers being involved in 80% of cases. The mortality from such serious reactions is reported to be in the range of 3.4 to 6%. The highly immunogenic drug, suxamethonium chloride (succinylcholine), was found to be the most hazardous agent. Drug-specific immunoglobulin E antibodies to suxamethonium chloride and other neuromuscular blockers have been demonstrated. This sensitivity to neuromuscular blockers seems to be a long-lasting phenomenon. During anesthesia, the clinical features of an allergic reaction are often masked. Tachycardia and circulatory collapse may be the only signs of an allergic reaction, and they are easily misdiagnosed. Bronchospasm is reported to be present in about 40% of cases. Successful management of these patients includes stabilisation during the acute reaction and avoidance of future reactions. The latter is based on the identification of the causative drug and potentially cross-reacting compounds. The use of suxamethonium chloride is associated with many other adverse effects, such as fasciculations, myalgia, potassium release, changes in the heart rate, increases in intragastric and intraocular pressures, and malignant hyperthermia. Because of the dangers of hyperkalemic cardiac arrest suxamethonium chloride administration in children with unrecognised muscular dystrophy, there have now been moves to limit the use of this drug in children. Although neuromuscular blockers are designed to specifically block nicotinic cholinergic receptors at the neuromuscular junction, many bind to muscarinic cholinergic receptors on ganglia and smooth muscle, and alter parasympathetically mediated heart rate and airway calibre. Most benzylisoquinolinium muscle relaxants can induce histamine release, especially when they are administered rapidly, which can lead to disturbances of cardiovascular function. In addition, nondepolarising neuromuscular blockers have been implicated in causing generalised weakness following their long term administration to patients on an intensive care unit. The problem with these adverse drug reactions is their upredictable nature. Therefore, prompt recognition with appropriate therapy can help to improve the outcome.

Serotonin induces ecdysteroidogenesis and methyl farnesoate synthesis in the mud crab, Scylla serrata.

PubMed

Girish, B P; Swetha, C H; Reddy, P Sreenivasula

2017-09-02

In the current study, we have examined the role of serotonin in regulating the levels of methyl farnesoate and ecdysteroids in the giant mud crab Scylla serrata and validated that serotonin indeed is a reproductive hormone. Administration of serotonin elevated circulatory levels of methyl farnesoate and ecdysteroids in crabs. Since methyl farnesoate and ecdysteroid act through retinoid X receptor (RXR) and ecdysteroid receptor (EcR) respectively and these receptors are involved in the regulation of reproduction in crustaceans, we have determined the mRNA levels of RXR and EcR in hepatopancreas and ovary after serotonin administration. The expression levels of both RXR and EcR increased significantly in the hepatopancreas and ovary of serotonin injected crabs when compared to the controls. In vitro organ culture studies revealed that incubation of Y-orgas and mandibular organ explants in the presence of serotonin resulted in a significant increase in the secretion of ecdysteroids by Y-organs, but without alterations in MF synthesis in mandibular organs. From the above studies it is evident that serotonin stimulates Y organs resulting in increased ecdysteroidogenesis. Though the circulatory levels methyl farnesoate elevated after serotonin administration, organ culture studies revealed serotonin mediated methyl farnesaote synthesis is indirect probably by inhibiting release of mandibular organ inhibiting hormone from eyestalks. Copyright © 2017 Elsevier Inc. All rights reserved.

Albumin-based drug delivery: harnessing nature to cure disease.

PubMed

Larsen, Maja Thim; Kuhlmann, Matthias; Hvam, Michael Lykke; Howard, Kenneth A

2016-01-01

The effectiveness of a drug is dependent on accumulation at the site of action at therapeutic levels, however, challenges such as rapid renal clearance, degradation or non-specific accumulation requires drug delivery enabling technologies. Albumin is a natural transport protein with multiple ligand binding sites, cellular receptor engagement, and a long circulatory half-life due to interaction with the recycling neonatal Fc receptor. Exploitation of these properties promotes albumin as an attractive candidate for half-life extension and targeted intracellular delivery of drugs attached by covalent conjugation, genetic fusions, association or ligand-mediated association. This review will give an overview of albumin-based products with focus on the natural biological properties and molecular interactions that can be harnessed for the design of a next-generation drug delivery platform.

Microgravity

NASA Image and Video Library

1989-02-03

(PCG) Protein Crystal Growth Human Serum Albumin. Contributes to many transport and regulatory processes and has multifunctional binding properties which range from various metals, to fatty acids, hormones, and a wide spectrum of therapeutic drugs. The most abundant protein of the circulatory system. It binds and transports an incredible variety of biological and pharmaceutical ligands throughout the blood stream. Principal Investigator on STS-26 was Larry DeLucas.

Effects of nitroglycerin and nitroprusside on vascular capacitance of anesthetized ganglion-blocked dogs.

PubMed

Ogilvie, R I; Zborowska-Sluis, D

1991-10-01

To determine whether changes in vascular capacitance induced by nitroglycerin (NTG) and nitroprusside were due to changes in compliance or unstressed vascular volume, doses producing similar reductions in arterial pressure (Psa) were studied on separate days in six dogs anesthetized and ventilated with pentobarbital after splenectomy during ganglion blockade with hexamethonium. Mean circulatory filling pressure (Pmcf) was determined during transient circulatory arrest induced by acetylcholine at baseline blood volumes and after increases of 5 and 10 ml/kg. Central blood volumes (CBVs, pulmonary artery to aortic root) were determined from transit times, and separately measured cardiac output (CO) was estimated by thermodilution (right atrium to pulmonary artery). NTG and nitroprusside produced similar reductions in Psa and Pmcf without significantly altering right atrial pressure (Pra), pressure gradient for venous return, or CO. Total vascular compliance was not altered, but total vascular capacitance was increased on an average of 4.0 +/- 1.4 ml/kg after NTG and 3.0 +/- 1.3 ml/kg after nitroprusside by increases in unstressed volume. Both drugs caused a variable reduction in CBV, averaging 2 ml/kg. Thus, both drugs produced a large increase in peripheral venous capacitance by increasing unstressed vascular volume without altering total vascular compliance.

Pediatric Donation After Circulatory Determination of Death: A Scoping Review.

PubMed

Weiss, Matthew J; Hornby, Laura; Witteman, William; Shemie, Sam D

2016-03-01

Although pediatric donation after circulatory determination of death is increasing in frequency, there are no national or international donation after circulatory determination of death guidelines specific to pediatrics. This scoping review was performed to map the pediatric donation after circulatory determination of death literature, identify pediatric donation after circulatory determination of death knowledge gaps, and inform the development of national or regional pediatric donation after circulatory determination of death guidelines. Terms related to pediatric donation after circulatory determination of death were searched in Embase and MEDLINE, as well as the non-MEDLINE sources in PubMed from 1980 to May 2014. Seven thousand five hundred ninety-seven references were discovered and 85 retained for analysis. All references addressing pediatric donation after circulatory determination of death were considered. Exclusion criteria were articles that did not address pediatric patients, animal or laboratory studies, surgical techniques, and local pediatric donation after circulatory determination of death protocols. Narrative reviews and opinion articles were the most frequently discovered reference (25/85) and the few discovered studies were observational or qualitative and almost exclusively retrospective. Retained references were divided into themes and analyzed using qualitative methodology. The main discovered themes were 1) studies estimating the number of potential pediatric donation after circulatory determination of death donors and their impact on donation; 2) ethical issues in pediatric donation after circulatory determination of death; 3) physiology of the dying process after withdrawal of life-sustaining therapy; 4) cardiac pediatric donation after circulatory determination of death; and 5) neonatal pediatric donation after circulatory determination of death. Donor estimates suggest that pediatric donation after circulatory determination of death will remain an event less common than brain death, albeit with the potential to substantially expand the existing organ donation pool. Limited data suggest outcomes comparable with organs donated after neurologic determination of death. Although there is continued debate around ethical aspects of pediatric donation after circulatory determination of death, all pediatric donation after circulatory determination of death publications from professional societies contend that pediatric donation after circulatory determination of death can be practiced ethically. This review provides a comprehensive overview of the published literature related to pediatric donation after circulatory determination of death. In addition to informing the development of pediatric-specific guidelines, this review serves to highlight several important knowledge gaps in this topic.

CHANGES OF ARTERIAL BLOOD PRESSURE IN ACUTE RADIATION DISEASE

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ryzewski, J.

1962-12-01

Acute experiments were done in cats and chronic experiments in dogs. The cats were subjected to whole-body x irradiation with a dose of 1500 r, and were examined on the third day after irradiation, when radiation disease was fully developed. Reflexes from the baro- and chemoreceptors were investigated, and arterial blood pressure was recorded in the irradiated cats after intravenous administration of adrenaline, noradrenaline, serotonin, acetylcholine, histamine, Regitine, atropine, or Pendiomid. Dogs were subjected to whole-body irradiation with 800 r,; changes in arterial blood pressure, which occurred after the administration of neurohormones, were investigated before and after irradiation. Pressor reflexesmore » in irradiated cats, elicited by clamping and unclamping of both common carotid arteries, corresponded to a rise from 129.6 to 141.4 mm Hg, as compared to pressor reflexes in nonirradiated cats from 106.6 to 146. Reflexes from carotid sinus chemoreceptors evoked by 0.5% KCl were also weaker in irradiated cats. The results of both the acute and chronic experiments indicate that circulatory changes occur in radiation disease. The changes mainly involve responses of the circulatory system to neurohormones and stimulation of vascular baro- and chemoreceptors. (TCO)« less

Circulatory Support with Venoarterial ECMO Unsuccessful in Aiding Endogenous Diltiazem Clearance after Overdose.

PubMed

Frazee, Erin N; Lee, Sarah J; Kalimullah, Ejaaz A; Personett, Heather A; Nelson, Darlene R

2014-01-01

Introduction. In cardiovascular collapse from diltiazem poisoning, extracorporeal membrane oxygenation (ECMO) may offer circulatory support sufficient to preserve endogenous hepatic drug clearance. Little is known about patient outcomes and diltiazem toxicokinetics in this setting. Case Report. A 36-year-old woman with a history of myocardial bridging syndrome presented with chest pain for which she self-medicated with 2.4 g of sustained release diltiazem over the course of 8 hours. Hemodynamics and mentation were satisfactory on presentation, but precipitously deteriorated after ICU transfer. She was given fluids, calcium, vasopressors, glucagon, high-dose insulin, and lipid emulsion. Due to circulatory collapse and multiorgan failure including ischemic hepatopathy, she underwent transvenous pacing and emergent initiation of venoarterial ECMO. The peak diltiazem level was 13150 ng/mL (normal 100-200 ng/mL) and it remained elevated at 6340 ng/mL at hour 90. Unfortunately, the patient developed multiple complications which resulted in her death on ICU day 9. Conclusion. This case describes the unsuccessful use of ECMO for diltiazem intoxication. Although past reports suggest that support with ECMO may facilitate endogenous diltiazem clearance, it may be dependent on preserved hepatic function at the time of cannulation, a factor not present in this case.

Three-dimensional structure of human serum albumin

NASA Technical Reports Server (NTRS)

Carter, Daniel C.; He, Xiao-Min; Twigg, Pamela D.; Casale, Elena

1991-01-01

The binding locations to human serum albumin (HSA) of several drug molecules were determined at low resolution using crystallographic methods. The principal binding sites are located within subdomains IIA and IIIA. Preliminary studies suggest that an approach to increasing the in vivo efficacy of drugs which are rendered less effective or ineffective by virtue of their interaction with HSA, would be the use of competitive displacement in drug therapies and/or the development of a general inhibitor to the site within subdomain IIIA. These findings also suggest that the facilitated transfer of various ligands across organ/circulatory interfaces such as liver, kidney, and brain may be associated with binding to the IIIA subdomain.

The outcome of tactile touch on stress parameters in intensive care: a randomized controlled trial.

PubMed

Henricson, Maria; Ersson, Anders; Määttä, Sylvia; Segesten, Kerstin; Berglund, Anna-Lena

2008-11-01

The study aimed to investigate the effects of a five-day tactile touch intervention in order to find new and unconventional measures to moderate the detrimental influence of patients' stressors during intensive care. The hypothesis was that tactile touch would decrease stress indicators such as anxiety, glucose metabolism, blood pressure, heart rate and requirements of sedative drugs and noradrenalin. A randomized controlled trial was undertaken with 44 patients, which were assigned either to tactile touch or standard treatment (a rest hour). Observations of the stress indicators were made before, during and after the intervention or standard treatment. The study showed that tactile touch led to significantly lower levels of anxiety. The circulatory parameters suggested increased circulatory stability indicated by a reduction in noradrenalin requirement. The results need to be further validated through studies with larger sample sizes.

Automation of a portable extracorporeal circulatory support system with adaptive fuzzy controllers.

PubMed

Mendoza García, A; Krane, M; Baumgartner, B; Sprunk, N; Schreiber, U; Eichhorn, S; Lange, R; Knoll, A

2014-08-01

The presented work relates to the procedure followed for the automation of a portable extracorporeal circulatory support system. Such a device may help increase the chances of survival after suffering from cardiogenic shock outside the hospital, additionally a controller can provide of optimal organ perfusion, while reducing the workload of the operator. Animal experiments were carried out for the acquisition of haemodynamic behaviour of the body under extracorporeal circulation. A mathematical model was constructed based on the experimental data, including a cardiovascular model, gas exchange and the administration of medication. As the base of the controller fuzzy logic was used allowing the easy integration of knowledge from trained perfusionists, an adaptive mechanism was included to adapt to the patient's individual response. Initial simulations show the effectiveness of the controller and the improvements of perfusion after adaptation. Copyright © 2014 IPEM. Published by Elsevier Ltd. All rights reserved.

Metabolic Disposition of Osimertinib in Rats, Dogs, and Humans: Insights into a Drug Designed to Bind Covalently to a Cysteine Residue of Epidermal Growth Factor Receptor.

PubMed

Dickinson, Paul A; Cantarini, Mireille V; Collier, Jo; Frewer, Paul; Martin, Scott; Pickup, Kathryn; Ballard, Peter

2016-08-01

Preclinical and clinical studies were conducted to determine the metabolism and pharmacokinetics of osimertinib and key metabolites AZ5104 and AZ7550. Osimertinib was designed to covalently bind to epidermal growth factor receptors, allowing it to achieve nanomolar cellular potency (Finlay et al., 2014). Covalent binding was observed in incubations of radiolabeled osimertinib with human and rat hepatocytes, human and rat plasma, and human serum albumin. Osimertinib, AZ5104, and AZ7550 were predominantly metabolized by CYP3A. Seven metabolites were detected in human hepatocytes, also observed in rat or dog hepatocytes at similar or higher levels. After oral administration of radiolabeled osimertinib to rats, drug-related material was widely distributed, with the highest radioactivity concentrations measured at 6 hours postdose in most tissues; radioactivity was detectable in 42% of tissues 60 days postdose. Concentrations of [(14)C]-radioactivity in blood were lower than in most tissues. After the administration of a single oral dose of 20 mg of radiolabeled osimertinib to healthy male volunteers, ∼19% of the dose was recovered by 3 days postdose. At 84 days postdose, mean total radioactivity recovery was 14.2% and 67.8% of the dose in urine and feces. The most abundant metabolite identified in feces was AZ5104 (∼6% of dose). Osimertinib accounted for ∼1% of total radioactivity in the plasma of non-small cell lung cancer patients after 22 days of 80-mg osimertinib once-daily treatment; the most abundant circulatory metabolites were AZ7550 and AZ5104 (<10% of total osimertinib-related material). Osimertinib is extensively distributed and metabolized in humans and is eliminated primarily via the fecal route. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

[Fulminant liver failure in a patient on carbamazepine and levetiracetam treatment associated with status epilepticus].

PubMed

Skopp, Gisela; Schmitt, Horst Peter; Pedal, Ingo

2006-01-01

A 22-year-old female with a history of developmental delay and seizures successfully treated with carbamazepine and levetiracetam developed fulminant hepatic failure and subsequently died. She had been admitted to the hospital following secondary generalized seizures of 35 min duration. A circulatory shock as well as intoxication was taken into consideration during the clinical course. Autopsy failed to reveal a macroscopically discernible cause of death. Significant findings on microscopic examination included acute tubular necrosis in the kidneys, pre-existing marked accumulation of neutral lipid within the hepatocytes as well as hyperacute liver damage with evidence of almost complete hepatocyte necrosis. Carbamazepine and levetiracetam were simultaneously determined from blood and tissues such as liver, lungs, muscle and kidneys by LC-MS/MS following addition of lamotrigine as an internal standard and liquid-liquid extraction. Validation data are given for levetiracetam. Both carbamazepine and levetiracetam were present in blood at concentrations within or below the therapeutic range, respectively. Moreover, tissue concentrations suggested long-term administration of anticonvulsant drugs, which is in accordance with the medical history. After excessive drug concentrations could be ruled out, the metabolic consequences of a prolonged carbamazepine therapy to cause severe hepatic injury in the present case are discussed. A mechanism of injury to the hepatocytes may be membrane damage by either an increased production of free radicals and/or a decreased free radical scavenging capacity. Following ischemia with reperfusion and during hyperthermia, large amounts of free radicals are formed. Induction of the mixed oxidase activity during longterm administration of carbamazepine may also increase production of free radicals, leaving the hepatic cell more vulnerable to oxidative injury.

[Chapter 2. Transitions in drug-discovery technology and drug-development in Japan (1980-2010)].

PubMed

Sakakibara, Noriko; Yoshioka, Ryuzo; Matsumoto, Kazuo

2014-01-01

In 1970s, the material patent system was introduced in Japan. Since then, many Japanese pharmaceutical companies have endeavored to create original in-house products. From 1980s, many of the innovative products were small molecular drugs and were developed using powerful medicinal-chemical technologies. Among them were antibiotics and effective remedies for the digestive organs and circulatory organs. During this period, Japanese companies were able to launch some blockbuster drugs. At the same time, the pharmaceutical market, which had grown rapidly for two decades, was beginning to level off. From the late 1990s, drug development was slowing down due to the lack of expertise in biotechnology such as genetic engineering. In response to the circumstances, the research and development on biotechnology-based drugs such as antibody drugs have become more dynamic and popular at companies than small molecule drugs. In this paper, the writers reviewed in detail the transitions in drug discovery and development between 1980 and 2010.

Carrot juice ingestion attenuates high fructose-induced circulatory pro-inflammatory mediators in weanling Wistar rats.

PubMed

Mahesh, Malleswarapu; Bharathi, Munugala; Raja Gopal Reddy, Mooli; Pappu, Pranati; Putcha, Uday Kumar; Vajreswari, Ayyalasomayajula; Jeyakumar, Shanmugam M

2017-03-01

Adipose tissue, an endocrine organ, plays a vital role not only in energy homeostasis, but also in the development and/or progression of various metabolic diseases, such as insulin resistance, type 2 diabetes and non-alcoholic fatty liver disease (NAFLD), via several factors and mechanisms, including inflammation. This study tested, whether carrot juice administration affected the adipose tissue development and its inflammatory status in a high fructose diet-induced rat model. For this purpose, male weanling Wistar rats were divided into four groups and fed either control or high fructose diet of AIN-93G composition with or without carrot juice ingestion for an 8 week period. Administration of carrot juice did not affect the adiposity and cell size of visceral fat depot; retroperitoneal white adipose tissue (RPWAT), which was corroborated with unaltered expression of genes involved in adipogenic and lipogenic pathways. However, it significantly reduced the high fructose diet-induced elevation of plasma free fatty acid (FFA) (P ≤ 0.05), macrophage chemoattractant protein 1 (MCP1) (P ≤ 0.01) and high sensitive C-reactive protein (hsCRP) (P ≤ 0.05) levels. Carrot juice administration attenuated the high fructose diet-induced elevation of levels of circulatory FFA and pro-inflammatory mediators; MCP1 and hsCRP without affecting the adiposity and cell size of visceral fat depot; RPWAT. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

Systemic toxicity of ropivacaine during ovine pregnancy.

PubMed

Santos, A C; Arthur, G R; Pedersen, H; Morishima, H O; Finster, M; Covino, B G

1991-07-01

Ropivacaine is a new amide local anesthetic structurally related to bupivacaine and mepivacaine. Its potency and duration of action are similar to those of bupivacaine but its therapeutic index may be greater. Since pregnancy enhances the cardiotoxicity of bupivacaine, the current study was devised to compare the toxicity of ropivacaine in chronically instrumented nonpregnant and pregnant ewes during continuous intravenous infusion of the drug at the rate of 0.5 mg.kg-1.min-1. In all animals, symptoms of local anesthetic toxicity occurred in the usual order--convulsions, hypotension, apnea, and circulatory collapse. There were no significant differences between the two groups of animals in the doses and plasma concentrations of ropivacaine associated with each toxic manifestations. For example, circulatory collapse occurred at a mean dose of 11.3 +/- 1.1 mg.kg-1 in nonpregnant and 12.4 +/- 0.9 mg.kg-1 in pregnant animals, with corresponding plasma concentrations of 7.3 +/- 0.3 and 9.6 +/- 2.1 micrograms.ml-1 (P = not significant). Protein binding of ropivacaine in the concentration range associated with toxic manifestations was similar in sera obtained from nonpregnant and pregnant ewes. In conclusion, ovine pregnancy does not enhance the systemic toxicity of ropivacaine, possibly because of an absence of gestation-related increase in the availability of free drug.

Contemporary Risk Factors and Outcomes of Transfusion-Associated Circulatory Overload.

PubMed

Roubinian, Nareg H; Hendrickson, Jeanne E; Triulzi, Darrell J; Gottschall, Jerome L; Michalkiewicz, Michael; Chowdhury, Dhuly; Kor, Daryl J; Looney, Mark R; Matthay, Michael A; Kleinman, Steven H; Brambilla, Donald; Murphy, Edward L

2018-04-01

Transfusion-associated circulatory overload is characterized by hydrostatic pulmonary edema following blood transfusion. Restrictive transfusion practice may affect the occurrence and severity of transfusion-associated circulatory overload in critically ill patients. We sought to examine contemporary risk factors and outcomes for transfusion-associated circulatory overload. Case-control study. Four tertiary care hospitals. We prospectively enrolled 200 patients with transfusion-associated circulatory overload identified by active surveillance and 405 controls matched by transfusion intensity. None. Among 20,845 transfused patients who received 128,263 blood components from May 2015 until July 2016, transfusion-associated circulatory overload incidence was one case per 100 transfused patients. In addition to cardiovascular comorbidities, multivariable analysis identified the following independent predictors of transfusion-associated circulatory overload: acute kidney injury, emergency surgery, pretransfusion diuretic use, and plasma transfusion-the latter especially in females. Compared with matched controls, transfusion-associated circulatory overload cases were more likely to require mechanical ventilation (71% vs 49%; p < 0.001), experienced longer intensive care and hospital lengths of stay following transfusion, and had higher mortality (21% vs 11%; p = 0.02) even after adjustment for other potentially confounding variables. Despite restrictive transfusion practice, transfusion-associated circulatory overload remains a frequent complication of transfusion and is an independent risk factor for in-hospital morbidity and mortality. In addition to cardiovascular and renal risk factors, plasma transfusion was associated with transfusion-associated circulatory overload after controlling for other covariates. Additional research is needed to examine the benefit of reduced erythrocyte or plasma exposure in patients at high risk for transfusion-associated circulatory overload.

Blacks' Death Rate Due to Circulatory Diseases Is Positively Related to Whites' Explicit Racial Bias.

PubMed

Leitner, Jordan B; Hehman, Eric; Ayduk, Ozlem; Mendoza-Denton, Rodolfo

2016-10-01

Perceptions of racial bias have been linked to poorer circulatory health among Blacks compared with Whites. However, little is known about whether Whites' actual racial bias contributes to this racial disparity in health. We compiled racial-bias data from 1,391,632 Whites and examined whether racial bias in a given county predicted Black-White disparities in circulatory-disease risk (access to health care, diagnosis of a circulatory disease; Study 1) and circulatory-disease-related death rate (Study 2) in the same county. Results revealed that in counties where Whites reported greater racial bias, Blacks (but not Whites) reported decreased access to health care (Study 1). Furthermore, in counties where Whites reported greater racial bias, both Blacks and Whites showed increased death rates due to circulatory diseases, but this relationship was stronger for Blacks than for Whites (Study 2). These results indicate that racial disparities in risk of circulatory disease and in circulatory-disease-related death rate are more pronounced in communities where Whites harbor more explicit racial bias.

Pharmacokinetic consequences of spaceflight

NASA Technical Reports Server (NTRS)

Putcha, L.; Cintron, N. M.

1991-01-01

Spaceflight induces a wide range of physiological and biochemical changes, including disruption of gastrointestinal (GI) function, fluid and electrolyte balance, circulatory dynamics, and organ blood flow, as well as hormonal and metabolic perturbations. Any of these changes can influence the pharmacokinetics and pharmacodynamics of in-flight medication. That spaceflight may alter bioavailability was proposed when drugs prescribed to alleviate space motion sickness (SMS) had little therapeutic effect. Characterization of the pharmacokinetic and/or pharmacodynamic behavior of operationally critical medications is crucial for their effective use in flight; as a first step, we sought to determine whether drugs administered in space actually reach the site of action at concentrations sufficient to elicit the therapeutic response.

Circulatory nucleosome levels are significantly increased in early and late-onset preeclampsia.

PubMed

Zhong, Xiao Yan; Gebhardt, Stefan; Hillermann, Renate; Tofa, Kashefa Carelse; Holzgreve, Wolfgang; Hahn, Sinuhe

2005-08-01

Elevations in circulatory DNA, as measured by real-time PCR, have been observed in pregnancies with manifest preeclampsia. Recent reports have indicated that circulatory nucleosome levels are elevated in the periphery of cancer patients. We have now examined whether circulatory nucleosome levels are similarly elevated in cases with preeclampsia. Maternal plasma samples were prepared from 17 cases with early onset preeclampsia (<34 weeks gestation) with 14 matched normotensive controls, as well as 15 cases late-onset preeclampsia (>34 weeks gestation) with 10 matched normotensive controls. Levels of circulatory nucleosomes were quantified by commercial ELISA (enzyme-linked immunosorbant assay). The level of circulatory nucleosomes was significantly elevated in both study preeclampsia groups, compared to the matched normotensive control group (p = 0.000 and p = 0.001, respectively). Our data suggests that preeclampsia is associated with the elevated presence of circulatory nucleosomes, and that this phenomenon occurs in both early- and late-onset forms of the disorder. Copyright 2005 John Wiley & Sons, Ltd.

[The brain and cytokines - the mutual origin of depression, obesity and cardiovascular diseases?].

PubMed

Ufnal, Marcin; Wolynczyk-Gmaj, Dorota

2011-04-19

Accumulating evidence points to a pivotal role of the brain in the regulation of the circulatory system and energy balance. It has also been found that common civilization diseases such as depression, obesity, hypertension, myocardial infarction or heart failure are accompanied by an increase in concentration of inflammatory mediators in the blood, cerebrospinal fluid and various tissues. Recent studies have revealed that inflammatory mediators that are synthesized peripherally or in the brain may affect the nervous regulation of animal body systems. For example, it has been found that non-specific pro-inflammatory stimuli as well as treatment with several cytokines may cause depressive behavior, disturbances in energy balance and alterations in the circulatory system. On the other hand, knockout of genes for pro-inflammatory cytokines or administration of anti-inflammatory mediators may normalize the pathological changes. In the present manuscript we will review studies that imply the common neuroinflammatory pathogenesis of cardiovascular diseases, depression and energy balance disorders.

Orthostasis test in the practice of the cardiologist

NASA Technical Reports Server (NTRS)

Moskalenko, N. P.; Glezer, M. G.

1980-01-01

The orthostasis test makes it possible to evaluate neurohumoral regulation and reaction of the circulatory system and to detect changes in the function of a number of internal organs (especially the kidney). Simultaneous recording of the ECG in an orthostatic position despite nonspecificity, makes it possible to detect hidden damage (organic or metabolic) or increased sensitivity of the myocardium to stressor sympathetico-adrenal effects, stability of therapeutic effect, and the action mechanism of a number of drugs.

The Impact of Pharmaceutical Expenses and the Use of Flexible Budgets at The Johns Hopkins Hospital

DTIC Science & Technology

1999-12-01

Newborns & Other Neonates, “Blood, Blood Forming Organs, & Immulogical”, Myeloproliferative Diseases & Poorly Diff Neoplasm , Infectious & Parasitic Diseases...1,716.1) Endocrine, Nutritional, & Metabolic (n=412) 3.2 2.2 38 268 (1,807.7) 81.4 2,140 (5,366.3) Myeloproliferative Diseases & Poorly Diff Neoplasm (n...pharmaceutical expenditures were for drugs utilized in six of the twenty-five MDG’s, Myeloproliferative Diseases at 18.5%, Circulatory System at 14.7

User's instructions for the Guyton circulatory dynamics model using the Univac 1110 batch and demand processing (with graphic capabilities)

NASA Technical Reports Server (NTRS)

Archer, G. T.

1974-01-01

The model presents a systems analysis of a human circulatory regulation based almost entirely on experimental data and cumulative present knowledge of the many facets of the circulatory system. The model itself consists of eighteen different major systems that enter into circulatory control. These systems are grouped into sixteen distinct subprograms that are melded together to form the total model. The model develops circulatory and fluid regulation in a simultaneous manner. Thus, the effects of hormonal and autonomic control, electrolyte regulation, and excretory dynamics are all important and are all included in the model.

Vascular and Immunobiology of the Circulatory Sphingosine 1-Phosphate Gradient

PubMed Central

Yanagida, Keisuke; Hla, Timothy

2017-01-01

Vertebrates are endowed with a closed circulatory system, the evolution of which required novel structural and regulatory changes. Furthermore, immune cell trafficking paradigms adapted to the barriers imposed by the closed circulatory system. How did such changes occur mechanistically? We propose that spatial compartmentalization of the lipid mediator sphingosine 1-phosphate (S1P) may be one such mechanism. In vertebrates, S1P is spatially compartmentalized in the blood and lymphatic circulation, thus comprising a sharp S1P gradient across the endothelial barrier. Circulatory S1P has critical roles in maturation and homeostasis of the vascular system as well as in immune cell trafficking. Physiological functions of S1P are tightly linked to shear stress, the key biophysical stimulus from blood flow. Thus, circulatory S1P confinement could be a primordial strategy of vertebrates in the development of a closed circulatory system. This review discusses the cellular and molecular basis of the S1P gradients and aims to interpret its physiological significance as a key feature of the closed circulatory system. PMID:27813829

Microgravity

NASA Image and Video Library

1998-12-01

As the most abundant protein in the circulatory system albumin contributes 80% to colloid osmotic blood pressure. Albumin is also chiefly responsible for the maintenance of blood pH. It is located in every tissue and bodily secretion, with extracellular protein comprising 60% of total albumin. Perhaps the most outstanding property of albumin is its ability to bind reversibly to an incredible variety of ligands. It is widely accepted in the pharmaceutical industry that the overall distribution, metabolism, and efficiency of many drugs are rendered ineffective because of their unusually high affinity for this abundant protein. An understanding of the chemistry of the various classes of pharmaceutical interactions with albumin can suggest new approaches to drug therapy and design. Principal Investigator: Dan Carter/New Century Pharmaceuticals

Repeated suppression of lymphocyte blastogenesis following vaccinations of CPV-immune dogs with modified-live CPV vaccines.

PubMed

Mastro, J M; Axthelm, M; Mathes, L E; Krakowka, S; Ladiges, W; Olsen, R G

1986-09-01

A commercially available modified-live canine parvovirus (CPV) vaccine was evaluated for its immunosuppressive properties in eight random-bred dogs, all with circulatory antibody to CPV. Three of the eight dogs exhibited a significant decrease in lymphocyte blastogenesis after vaccine administration. In these dogs, this decrease in blastogenesis was of short duration and was consistently observed after repeated administrations of the vaccine. Neither gastroenteritis, fever nor leukopenia, signs indicative of virulent canine parvovirus infection, were detected in these animals. In addition, lymphocytes from these dogs lacked Ia antigen expression. This study demonstrated that the immunomodulating effects of ML-CPV is not observed in all animals yet is consistent in affected individuals.

Preparation of silica nanoparticles loaded with nootropics and their in vivo permeation through blood-brain barrier.

PubMed

Jampilek, Josef; Zaruba, Kamil; Oravec, Michal; Kunes, Martin; Babula, Petr; Ulbrich, Pavel; Brezaniova, Ingrid; Opatrilova, Radka; Triska, Jan; Suchy, Pavel

2015-01-01

The blood-brain barrier prevents the passage of many drugs that target the central nervous system. This paper presents the preparation and characterization of silica-based nanocarriers loaded with piracetam, pentoxifylline, and pyridoxine (drugs from the class of nootropics), which are designed to enhance the permeation of the drugs from the circulatory system through the blood-brain barrier. Their permeation was compared with non-nanoparticle drug substances (bulk materials) by means of an in vivo model of rat brain perfusion. The size and morphology of the nanoparticles were characterized by transmission electron microscopy. The content of the drug substances in silica-based nanocarriers was analysed by elemental analysis and UV spectrometry. Microscopic analysis of visualized silica nanocarriers in the perfused brain tissue was performed. The concentration of the drug substances in the tissue was determined by means of UHPLC-DAD/HRMS LTQ Orbitrap XL. It was found that the drug substances in silica-based nanocarriers permeated through the blood brain barrier to the brain tissue, whereas bulk materials were not detected in the brain.

Preparation of Silica Nanoparticles Loaded with Nootropics and Their In Vivo Permeation through Blood-Brain Barrier

PubMed Central

Zaruba, Kamil; Kunes, Martin; Ulbrich, Pavel; Brezaniova, Ingrid; Triska, Jan; Suchy, Pavel

2015-01-01

The blood-brain barrier prevents the passage of many drugs that target the central nervous system. This paper presents the preparation and characterization of silica-based nanocarriers loaded with piracetam, pentoxifylline, and pyridoxine (drugs from the class of nootropics), which are designed to enhance the permeation of the drugs from the circulatory system through the blood-brain barrier. Their permeation was compared with non-nanoparticle drug substances (bulk materials) by means of an in vivo model of rat brain perfusion. The size and morphology of the nanoparticles were characterized by transmission electron microscopy. The content of the drug substances in silica-based nanocarriers was analysed by elemental analysis and UV spectrometry. Microscopic analysis of visualized silica nanocarriers in the perfused brain tissue was performed. The concentration of the drug substances in the tissue was determined by means of UHPLC-DAD/HRMS LTQ Orbitrap XL. It was found that the drug substances in silica-based nanocarriers permeated through the blood brain barrier to the brain tissue, whereas bulk materials were not detected in the brain. PMID:26075264

Ephedrine fails to accelerate the onset of neuromuscular block by vecuronium.

PubMed

Komatsu, Ryu; Nagata, Osamu; Ozaki, Makoto; Sessler, Daniel I

2003-08-01

The onset time of neuromuscular blocking drugs is partially determined by circulatory factors, including muscle blood flow and cardiac output. We thus tested the hypothesis that a bolus of ephedrine accelerates the onset of vecuronium neuromuscular block by increasing cardiac output. A prospective, randomized study was conducted in 53 patients scheduled for elective surgery. After the induction of anesthesia, the ulnar nerve was stimulated supramaximally every 10 s, and the evoked twitch response of the adductor pollicis was recorded with accelerometry. Patients were maintained under anesthesia with continuous infusion of propofol for 10 min and then randomly assigned to ephedrine 210 microg/kg (n = 27) or an equivalent volume of saline (n = 26). The test solution was given 1 min before the administration of 0.1 mg/kg of vecuronium. Cardiac output was monitored with impedance cardiography. Ephedrine, but not saline, increased cardiac index (17%; P = 0.003). Nonetheless, the onset of 90% neuromuscular block was virtually identical in the patients given ephedrine (183 +/- 41 s) and saline (181 +/- 47 s). There was no correlation between cardiac index and onset of the blockade. We conclude that the onset of the vecuronium-induced neuromuscular block is primarily determined by factors other than cardiac output. The combination of ephedrine and vecuronium thus cannot be substituted for rapid-acting nondepolarizing muscle relaxants. Ephedrine increased cardiac index but failed to speed onset of neuromuscular block with vecuronium. We conclude that ephedrine administration does not shorten the onset time of vecuronium.

38 CFR 4.62 - Circulatory disturbances.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 38 Pensions, Bonuses, and Veterans' Relief 1 2010-07-01 2010-07-01 false Circulatory disturbances. 4.62 Section 4.62 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS SCHEDULE FOR RATING DISABILITIES Disability Ratings The Musculoskeletal System § 4.62 Circulatory disturbances...

38 CFR 4.62 - Circulatory disturbances.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 38 Pensions, Bonuses, and Veterans' Relief 1 2014-07-01 2014-07-01 false Circulatory disturbances. 4.62 Section 4.62 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS SCHEDULE FOR RATING DISABILITIES Disability Ratings The Musculoskeletal System § 4.62 Circulatory disturbances...

38 CFR 4.62 - Circulatory disturbances.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 38 Pensions, Bonuses, and Veterans' Relief 1 2013-07-01 2013-07-01 false Circulatory disturbances. 4.62 Section 4.62 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS SCHEDULE FOR RATING DISABILITIES Disability Ratings The Musculoskeletal System § 4.62 Circulatory disturbances...

38 CFR 4.62 - Circulatory disturbances.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 38 Pensions, Bonuses, and Veterans' Relief 1 2011-07-01 2011-07-01 false Circulatory disturbances. 4.62 Section 4.62 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS SCHEDULE FOR RATING DISABILITIES Disability Ratings The Musculoskeletal System § 4.62 Circulatory disturbances...

38 CFR 4.62 - Circulatory disturbances.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 38 Pensions, Bonuses, and Veterans' Relief 1 2012-07-01 2012-07-01 false Circulatory disturbances. 4.62 Section 4.62 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS SCHEDULE FOR RATING DISABILITIES Disability Ratings The Musculoskeletal System § 4.62 Circulatory disturbances...

[The effect of tachykinins microinjections into the solitary tract nucleus on respiration and blood circulation in rats].

PubMed

Chepurnov, S A; Iniushkin, A N

1997-04-01

Administration of substance P and kassinin into the solitary tract nucleus of anesthetized rats induced a dose-dependent increase in ventilation, tidal volume, inspiratory muscle activity, and a decrease in the mean blood pressure and heart rate. Microinjections of peptides caused a decrease in ventilatory response to hypoxia and an inhibition of the Breuer-Hering reflex. The data obtained suggest involvement of tachykinins in the respiratory and circulatory control via the solitary tract nucleus.

Number of Heat Wave Deaths by Diagnosis, Sex, Age Groups, and Area, in Slovenia, 2015 vs. 2003

PubMed Central

Perčič, Simona; Kukec, Andreja; Cegnar, Tanja; Hojs, Ana

2018-01-01

Background: Number of deaths increases during periods of elevated heat. Objectives: To examine whether differences in heat-related deaths between 2003 and 2015 occurred in Slovenia. Materials and Methods: We estimated relative risks for deaths for the observed diagnoses, sex, age, and area, as well as 95% confidence intervals and excess deaths associated with heat waves occurring in 2015 and 2003. For comparison between 2015 and 2003, we calculated relative risks ratio and 95% confidence intervals. Results: Statistically significant in 2015 were the following: age group 75+, all causes of deaths (RR = 1.10, 95% CI 1.00–1.22); all population, circulatory system diseases (RR = 1.14, 95% CI 1.01–1.30) and age group 75+, diseases of circulatory system (RR = 1.17, 95% CI 1.01–1.34). Statistically significant in 2003 were the following: female, age group 5–74, circulatory system diseases (RR = 1.69, 95% CI 1.08–2.62). Discussion: Comparison between 2015 and 2003, all, circulatory system diseases (RRR = 1.25, 95% CI 1.01–1.55); male, circulatory system diseases (RRR = 1.85, 95% CI 1.41–2.43); all, age group 75+ circulatory system diseases (RRR = 1.34, 95% CI 1.07–1.69); male, age group 75+, circulatory system diseases (RRR = 1.52, 95% CI 1.03–2.25) and female, age group 75+, circulatory system diseases (RRR = 1.43, 95% CI 1.08–1.89). Conclusions: Public health efforts are urgent and should address circulatory system causes and old age groups. PMID:29361792

Practice pattern and professional issues of nurse practitioners in mechanical circulatory support programs in the United States: a survey report.

PubMed

Casida, Jesus M; Pastor, Jessica

2012-09-01

Few data-based reports about the role and work environment of advanced practice nurses, specifically nurse practitioners in mechanical circulatory support programs, have been published. To describe the practice pattern and professional issues confronted by nurse practitioners in the rapidly evolving and expanding mechanical circulatory support programs in the United States. A descriptive research design was employed using the data from the 2010 mechanical circulatory support nurses survey. Quantitative and qualitative data that pertained to the demographic and practice profiles as well as barriers and overall issues faced by the nurse practitioners in their clinical practice were analyzed. Nonrandom sample of 48 nurse practitioners from 95 mechanical circulatory support programs nationwide. The practice pattern of nurse practitioners in mechanical circulatory support programs is similar to the practice pattern reported for nurse practitioners in acute and critical care settings. However, only 44% and 10% of nurse practitioners in mechanical circulatory support programs are authorized to admit and transfer patients into and out of the hospital, respectively. High workload, lack of institutional support, knowledge deficit, role ambiguity, lack of professional recognition, and burnout were the common issues faced by the participants in their clinical practice. The results provide preliminary evidence on the practice pattern, restrictions, and work environment issues that may threaten the viability of an mechanical circulatory support program in which nurse practitioners play a crucial role. Implications for clinical practice, research, and policy development are discussed.

[Etiological analysis and individualized treatment of pharyngeal paraesthesia].

PubMed

Lou, Zhengcai; Gong, Xuhong; Lou, Fangyi; He, Lanjuan; Zhu, Qiaoying

2009-07-01

To analyze the nosazontology of pharyngeal paraesthesia and investigate the treatment. Two hundred and twelve misdiagnosed pharyngeal paraesthesia patients were investigated by history inquiry, routine examination, 24-hour esophageal pH monitoring, barium X-ray of the oesophagus, anxieties-athymic private measuring scale, coefficient of variation of the R-R (CVR-R), bioavailable testosterone detection (Bio-T), erection experiment and questionnaire about man climacteric syndrome. The concomitant symptoms and positions of pharyngeal paresthesia were also studied. We adopted individuallized sequential multi-therapy for every patient according to the cause of disease. The cause of disease within 212 cases of pharyngeal paraesthesia included 62 psychic trauma, 32 endocrine system disease, 106 upper gastrointestinal disease, circulatory disease, 9 circulatory disease, 3 idiopathic. With individualized treatment, 110 cases had fully recovered, 63 cases excellence and 31 cases utility, and the efficiency rate was 96.23%. Pharyngeal paraesthesia can be caused by several factors. Thorough examination and comprehensive analysis should be applied to those incurable patient who has been treated for a long time. Short course of treatment and irrational drug use are the main causes of short-term recurrence and unsatisfactory curative effect.

The use of human albumin for the treatment of ascites in patients with liver cirrhosis: item of safety, facts, controversies and perspectives.

PubMed

Facciorusso, Antonio; Nacchiero, Maurizio Cosimo; Rosania, Rosa; Laonigro, Giulio; Longo, Nunzio; Panella, Carmine; Ierardi, Enzo

2011-09-01

Albumin constitutes approximately one half of the proteins in the plasma and plays a pivotal role in modulating the distribution of fluid between body compartments. Hence it is commonly employed in cirrhotic patients in association with diuretics for the treatment of ascites. Nevertheless, its usefulness is controversial in this condition and well-stated only in some circumstances. The item of safety of the drug appears to be convincing due to the accurate cautions in the course of its preparation. Side effects are described in literature only as sporadic events. Indeed, albumin administration is effective to prevent the circulatory dysfunctions after large-volume paracentesis and renal failure and after Spontaneous Bacterial Peritonitis (SBP). Finally albumin represents, associated with vasoconstrictors, the therapeutic gold standard for the hepatorenal-syndrome (HRS). Physiopathological bases of the therapeutic use of albumin in hepatic cirrhosis consist in both hypoalbuminemia and portal hypertension consequences. In fact, cirrhotic patient with ascites, in spite of hydrosaline retention, shows an effective hypovolemia with peripheral arterial vasodilatation and increase in heart rate. Therefore the effectiveness of albumin administration in the treatment of ascites is due to its plasma volume expander property as well as its efficacy in restoring plasmatic oncotic pressure. Trials are in progress in order to define the effectiveness of the prolonged home-administration of human albumin in the treatment and prevention of ascites. Finally, it has been recently demonstrated that the binding, transport and detoxification capacities of human albumin are severely reduced in cirrhotics and this impairment correlates with the degree of liver failure. Therefore, the next challenge will be to determine whether the alterations of non-oncotic properties of albumin are able to forecast mortality in cirrhotics with ascites and exogenous albumin chronic administration will be effective in predicting and preventing such alterations.

Experts' recommendations for the management of cardiogenic shock in children.

PubMed

Brissaud, Olivier; Botte, Astrid; Cambonie, Gilles; Dauger, Stéphane; de Saint Blanquat, Laure; Durand, Philippe; Gournay, Véronique; Guillet, Elodie; Laux, Daniela; Leclerc, Francis; Mauriat, Philippe; Boulain, Thierry; Kuteifan, Khaldoun

2016-12-01

Cardiogenic shock which corresponds to an acute state of circulatory failure due to impairment of myocardial contractility is a very rare disease in children, even more than in adults. To date, no international recommendations regarding its management in critically ill children are available. An experts' recommendations in adult population have recently been made (Levy et al. Ann Intensive Care 5(1):52, 2015; Levy et al. Ann Intensive Care 5(1):26, 2015). We present herein recommendations for the management of cardiogenic shock in children, developed with the grading of recommendations' assessment, development, and evaluation system by an expert group of the Groupe Francophone de Réanimation et Urgences Pédiatriques (French Group for Pediatric Intensive Care and Emergencies). The recommendations cover four major fields of application such as: recognition of early signs of shock and the patient pathway, management principles and therapeutic goals, monitoring hemodynamic and biological variables, and circulatory support (indications, techniques, organization, and transfer criteria). Major principle care for children with cardiogenic shock is primarily based on clinical and echocardiographic assessment. There are few drugs reported as effective in childhood in the medical literature. The use of circulatory support should be facilitated in terms of organization and reflected in the centers that support these children. Children with cardiogenic shock are vulnerable and should be followed regularly by intensivist cardiologists and pediatricians. The experts emphasize the multidisciplinary nature of management of children with cardiogenic shock and the importance of effective communication between emergency medical assistance teams (SAMU), mobile pediatric emergency units (SMUR), pediatric emergency departments, pediatric cardiology and cardiac surgery departments, and pediatric intensive care units.

Impact of Selected Socio-demographic Factors on the Development of Mortality due to Circulatory System Diseases in the Slovak Republic.

PubMed

Gavurová, Beáta; Kubák, Matúš

2017-12-01

We mapped the situation within a group of diseases of the circulatory system (I00-I99) in the Slovak Republic during 1996-2014. We focused mainly on spatiotemporal differences in mortality while controlling for age and sex. We performed binary logistic regression aiming to reveal socio-demographic factors that influence the odds of dying due to diseases of the circulatory system (I00-I99). In our analysis, the dependent variable was death diagnosis and the independent variables were age, region, gender, and marital status. Our findings suggest that odds of dying due to diseases of the circulatory system (I00-I99) increased for every year of age by 5.4%. Within the period from 1996 to 2014, the risk of dying from diseases of the circulatory system decreased by 2% every year. We also documented the fact that being female raised the odds of dying due to diseases of the circulatory system (I00-I99) by 12.9% compared to males. Furthermore, it could be argued that serious differences in terms of regional distribution of deaths caused by diseases of the circulatory system (I00-I99) exist in the Slovak Republic. We present the development of diseases of the circulatory system (I00-I99) in the Slovak Republic. Differences in spatial distribution of deaths are documented as well as related gender differences. Our study can serve as a tool for policy makers and benchmark for professionals. Copyright© by the National Institute of Public Health, Prague 2017.

Radiation-associated circulatory disease mortality in a pooled analysis of 77,275 patients from the Massachusetts and Canadian tuberculosis fluoroscopy cohorts.

PubMed

Tran, Van; Zablotska, Lydia B; Brenner, Alina V; Little, Mark P

2017-03-13

High-dose ionising radiation is associated with circulatory disease. Risks associated with lower-dose (<0.5 Gy) exposures remain unclear, with little information on risk modification by age at exposure, years since exposure or dose-rate. Tuberculosis patients in Canada and Massachusetts received multiple diagnostic x-ray fluoroscopic exposures, over a wide range of ages, many at doses <0.5 Gy. We evaluated risks of circulatory-disease mortality associated with <0.5 Gy radiation exposure in a pooled cohort of 63,707 patients in Canada and 13,568 patients in Massachusetts. Under 0.5 Gy there are increasing trends for all circulatory disease (n = 10,209; excess relative risk/Gy = 0.246; 95% CI 0.036, 0.469; p = 0.021) and for ischaemic heart disease (n = 6410; excess relative risk/Gy = 0.267; 95% CI 0.003, 0.552; p = 0.048). All circulatory-disease and ischaemic-heart-disease risk reduces with increasing time since exposure (p < 0.005). Over the entire dose range, there are negative mortality dose trends for all circulatory disease (p = 0.014) and ischaemic heart disease (p = 0.003), possibly due to competing causes of death over this dose interval.These results confirm and extend earlier findings and strengthen the evidence for circulatory-disease mortality radiation risk at doses <0.5 Gy. The limited information on well-known lifestyle/medical risk factors for circulatory disease implies that confounding of the dose trend cannot be entirely excluded.

76 FR 36548 - Circulatory System Devices Panel of the Medical Devices Advisory Committee; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-22

...] Circulatory System Devices Panel of the Medical Devices Advisory Committee; Notice of Meeting AGENCY: Food and... of Committee: Circulatory System Devices Panel of the Medical Devices Advisory Committee. General... also comes with a sheath, introducer, loader, dilator, balloon (used to pre-dilate the native annulus...

77 FR 25183 - Circulatory System Devices Panel of the Medical Devices Advisory Committee; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-27

...] Circulatory System Devices Panel of the Medical Devices Advisory Committee; Notice of Meeting AGENCY: Food and... of Committee: Circulatory System Devices Panel of the Medical Devices Advisory Committee. General..., introducer, loader, dilator, balloon (used to pre-dilate the native annulus) and a crimper. FDA intends to...

Dependence of pentobarbital kinetics upon the dose of the drug and its pharmacodynamic effects.

PubMed

Kozlowski, K H; Szaykowski, A; Danysz, A

1977-01-01

Pentobarbital (PB), at dose range of 20--50 mg/kg, displays in rabbits non-linear, dose-dependent kinetics. Pharmacokinetics parameters of drug elimination depend largely upon the dose, while the distribution phase is dose-independent. The rate of disappearance of PB from the central compartment (plasma) decreases with the increase of the dose. The analysis of pharmacodynamic parameters has shown that this dose-dependent retardation of PB elimination is probably caused by an impairment of metabolic processes, resulting from disturbance of the circulatory system. A close correlation has been found between the hypotensive effect of PB and the elimination constant, k13, and also between the hypotensive effect and beta.Vd(extrap), a coefficient proportional to the rate of metabolism of PB [23, 29]. The results indicate the necessity of considering the changes in the functional state of the organism, related to the action of a drug, in pharmacokinetic studies.

[Perioperative management of long-term medication].

PubMed

Vogel Kahmann, I; Ruppen, W; Lurati Buse, G; Tsakiris, D A; Bruggisser, M

2011-01-01

Anesthesiologists and surgeons are increasingly faced with patients who are under long-term medication. Some of these drugs can interact with anaesthetics or anaesthesia and/or surgical interventions. As a result, patients may experience complications such as bleeding, ischemia, infection or severe circulatory reactions. On the other hand, perioperative discontinuation of medication is often more dangerous. The proportion of outpatient operations has increased dramatically in recent years and will probably continue to increase. Since the implementation of DRGs (pending in Switzerland, introduced in Germany for some time), the patient enters the hospital the day before operation. This means that the referring physician as well as anesthesiologists and surgeons at an early stage must deal with issues of perioperative pharmacotherapy. This review article is about the management of the major drug classes during the perioperative period. In addition to cardiac and centrally acting drugs and drugs that act on hemostasis and the endocrine system, special cases such as immunosuppressants and herbal remedies are mentioned.

78 FR 55728 - Society of Clinical Research Associates-Food and Drug Administration: Food and Drug...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-11

...: Food and Drug Administration, HHS. ACTION: Notice of public workshop. The Food and Drug Administration... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-N-0001] Society of Clinical Research Associates-Food and Drug Administration: Food and Drug Administration...

US FDA perspective on regulatory issues affecting circulatory assist devices.

PubMed

Sapirstein, Wolf; Chen, Eric; Swain, Julie; Zuckerman, Bram

2006-11-01

There has been a rapid development in mechanical circulatory support systems in the decade since the US FDA first approved a mechanical device to provide the circulatory support lacking from a failing heart. Devices are presently approved for marketing by the FDA to replace a failing ventricle, the Ventricular Assist Device or the entire heart, Total Artificial Heart. Contemporaneous with, and permitted by, improvement in technology and design, devices have evolved from units located extracorporeally to paracorporeal systems and totally implanted devices. Clinical studies have demonstrated a parallel improvement in the homeostatic adequacy of the circulatory support provided. Thus, while the circulatory support was initially tolerated for short periods to permit recovery of cardiac function, this technology eventually provided effective circulatory support for increasing periods that permitted the FDA to approve devices for bridging patients in end-stage cardiac failure awaiting transplant and eventually a device for destination therapy where patients in end-stage heart failure are not cardiac transplant candidates. The approved devices have relied on displacement pumps that mimic the pulsatility of the physiological system. Accelerated development of more compact devices that rely on alternative pump mechanisms have challenged both the FDA and device manufacturers to assure that the regulatory requirements for safety and effectiveness are met for use of mechanical circulatory support systems in expanded target populations. An FDA regulatory perspective is reviewed of what can be a potentially critical healthcare issue.

Aortic arch reconstruction: deep and moderate hypothermic circulatory arrest with selective antegrade cerebral perfusion.

PubMed

Wu, YanWen; Xiao, LiQiong; Yang, Ting; Wang, Lei; Chen, Xin

2017-07-01

To compare the effects of moderate and deep hypothermic circulatory arrest (DHCA) with selective antegrade cerebral perfusion (SACP) during aortic arch surgery in adult patients and to offer the evidence for the detection of the temperature which provides best brain protection in the subjects who accept aortic arch reconstruction surgery. A total of 109 patients undergoing surgery of the aortic arch were divided into the moderate hypothermic circulatory arrest group (Group I) and the deep hypothermic circulatory arrest group (Group II). We recorded the data of the patients and their cardiopulmonary bypass (CPB) time, aortic clamping time, SACP time and postoperative anesthetized recovery time, tracheal intubation time, time in the intensive care unit (ICU) and postoperative neurologic dysfunction. Patient characteristics were similar in the two groups. There were four patients who died in Group II and 1 patient in Group I. There were no significant differences in aortic clamping time of each group (111.4±58.4 vs. 115.9±16.2) min; SACP time (27.4±5.9 vs. 23.5±6.1) min of the moderate hypothermic circulatory arrest group and the deep hypothermic circulatory arrest group; there were significant differences in cardiopulmonary bypass time (207.4±20.9 vs. 263.8±22.6) min, postoperative anesthetized recovery time (19.0±11.1 vs. 36.8±25.3) hours, extubation time (46.4±15.1 vs. 64.4±6.0) hours; length of stay in the intensive care unit (ICU) (4.7±1.7 vs. 8±2.3) days and postoperative neurologic dysfunction in the two groups. Compared to deep hypothermic circulatory arrest, moderate hypothermic circulatory arrest can provide better brain protection and achieve good clinical results.

Simple retrograde cerebral perfusion is as good as complex antegrade cerebral perfusion for hemiarch replacement.

PubMed

Tanaka, Akiko; Estrera, Anthony L

2018-01-01

Cerebral complication is a major concern after aortic arch surgery, which may lead to death. Thus, cerebral protection strategy plays the key role to obtain respectable results in aortic arch repair. Deep hypothermic circulatory arrest was introduced in 1970s to decrease the ischemic insults to the brain. However, safe duration of circulatory arrest time was limited to 30 minutes. The 1990s was the decade of evolution for cerebral protection, in which two adjuncts for deep hypothermic circulatory arrest were introduced: retrograde and antegrade cerebral perfusion (ACP) techniques. These two cerebral perfusion techniques significantly decreased incidence of postoperative neurological dysfunction and mortality after aortic arch surgery. Although there are no large prospective studies that demonstrate which perfusion technique provide better outcomes, multiple retrospective studies implicate that ACP may decrease cerebral complications compared to retrograde cerebral perfusion (RCP) when a long circulatory arrest time is required during aortic arch reconstructions. To date, many surgeons favor ACP over RCP during a complex aortic arch repair, such as total arch replacement and hybrid arch replacement. However, the question is whether the use of ACP is necessary during a short, limited circulatory arrest time, such as hemiarch replacement? There is a paucity of data that proves the advantages of a complex ACP over a simple RCP for a short circulatory arrest time. RCP with deep hypothermic circulatory arrest is the simple, efficient cerebral protection technique with minimal interference to the surgical field-and it potentially allows to flush atheromatous debris out from the arch vessels. Thus, it is the preferred adjunct to deep hypothermic circulatory arrest during hemiarch replacement in our institution.

Simple retrograde cerebral perfusion is as good as complex antegrade cerebral perfusion for hemiarch replacement

PubMed Central

Tanaka, Akiko

2018-01-01

Cerebral complication is a major concern after aortic arch surgery, which may lead to death. Thus, cerebral protection strategy plays the key role to obtain respectable results in aortic arch repair. Deep hypothermic circulatory arrest was introduced in 1970s to decrease the ischemic insults to the brain. However, safe duration of circulatory arrest time was limited to 30 minutes. The 1990s was the decade of evolution for cerebral protection, in which two adjuncts for deep hypothermic circulatory arrest were introduced: retrograde and antegrade cerebral perfusion (ACP) techniques. These two cerebral perfusion techniques significantly decreased incidence of postoperative neurological dysfunction and mortality after aortic arch surgery. Although there are no large prospective studies that demonstrate which perfusion technique provide better outcomes, multiple retrospective studies implicate that ACP may decrease cerebral complications compared to retrograde cerebral perfusion (RCP) when a long circulatory arrest time is required during aortic arch reconstructions. To date, many surgeons favor ACP over RCP during a complex aortic arch repair, such as total arch replacement and hybrid arch replacement. However, the question is whether the use of ACP is necessary during a short, limited circulatory arrest time, such as hemiarch replacement? There is a paucity of data that proves the advantages of a complex ACP over a simple RCP for a short circulatory arrest time. RCP with deep hypothermic circulatory arrest is the simple, efficient cerebral protection technique with minimal interference to the surgical field—and it potentially allows to flush atheromatous debris out from the arch vessels. Thus, it is the preferred adjunct to deep hypothermic circulatory arrest during hemiarch replacement in our institution. PMID:29682460

Yomogin, an inhibitor of nitric oxide production in LPS-activated macrophages.

PubMed

Ryu, J H; Lee, H J; Jeong, Y S; Ryu, S Y; Han, Y N

1998-08-01

In activated macrophages the inducible form of nitric oxide synthase (i-NOS) generates high amounts of toxic mediator, nitric oxide (NO) which contributes to the circulatory failure associated with septic shock. A sesquiterpene lactone compound (yomogin) isolated from medicinal plant Artemisia princeps Pampan inhibited the production of NO in LPS-activated RAW 264.7 cells by suppressing i-NOS enzyme expression. Thus, yomogin may be a useful candidate for the development of new drugs to treat endotoxemia and inflammation accompanied by the overproduction of NO.

The Circulatory System. Instructional Materials in Anatomy and Physiology for Pennsylvania Health Occupations Programs.

ERIC Educational Resources Information Center

National Evaluation Systems, Inc., Amherst, MA.

This instructional modular unit with instructor's guide provides materials on aspects of one of the major systems of the human body--the circulatory system. Its purpose is to introduce the student to the structures and functions of the human circulatory system--and the interrelationships of the two--and to familiarize the student with some of the…

Mathematical circulatory system model

NASA Technical Reports Server (NTRS)

Lakin, William D. (Inventor); Stevens, Scott A. (Inventor)

2010-01-01

A system and method of modeling a circulatory system including a regulatory mechanism parameter. In one embodiment, a regulatory mechanism parameter in a lumped parameter model is represented as a logistic function. In another embodiment, the circulatory system model includes a compliant vessel, the model having a parameter representing a change in pressure due to contraction of smooth muscles of a wall of the vessel.

[Analgesia and sedation in neonatal-pediatric intensive care].

PubMed

Schlünder, C; Houben, F; Hartwig, S; Theisohn, M; Roth, B

1991-01-01

In pediatric intensive care, analgesia and sedation has become increasingly important for newborns as well as prematures in recent years. However, its importance is frequently not well recognized and sedation is confounded with analgesia. In our intensive-care unit (ICU), fentanyl and midazolam have proved to be useful. In newborn and premature infants, fentanyl alone has been sufficient because of its analgesic and sedative action. In a study on 20 newborns and prematures suffering from severe respiratory problems as compared with a historical group that did not receive fentanyl, we could show that in subjects receiving fentanyl, considerably less treatment with sedatives and other analgesics was necessary. Cardiopulmonary tolerance was satisfactory. The highest bilirubin values were reached about 1 day earlier and were slightly higher than those measured in the control group, but oral nutrition could be initiated sooner. In small infants, additional midazolam was given after cardiac surgery. During the first 72 h, we found a correlation between serum levels of midazolam and the depth of sedation; however, after 72 h of medication, the dose had to be raised because of an increase in metabolic clearance. During the concomitant administration of midazolam and fentanyl, significantly less midazolam was needed to achieve appropriate analog-sedation. Prior to the administration of analgesics and sedatives, care should be taken to ensure that circulatory conditions are stable and that there is no hypovolemia, and the drugs must be given slowly during several minutes. Especially in a pediatric ICU, light and noise should be diminished and contact between the parents and the child should be encouraged, even when the child is undergoing mechanical ventilation.

Selective cerebral perfusion prevents abnormalities in glutamate cycling and neuronal apoptosis in a model of infant deep hypothermic circulatory arrest and reperfusion.

PubMed

Kajimoto, Masaki; Ledee, Dolena R; Olson, Aaron K; Isern, Nancy G; Robillard-Frayne, Isabelle; Des Rosiers, Christine; Portman, Michael A

2016-11-01

Deep hypothermic circulatory arrest is often required for the repair of complex congenital cardiac defects in infants. However, deep hypothermic circulatory arrest induces neuroapoptosis associated with later development of neurocognitive abnormalities. Selective cerebral perfusion theoretically provides superior neural protection possibly through modifications in cerebral substrate oxidation and closely integrated glutamate cycling. We tested the hypothesis that selective cerebral perfusion modulates glucose utilization, and ameliorates abnormalities in glutamate flux, which occur in association with neuroapoptosis during deep hypothermic circulatory arrest. Eighteen infant male Yorkshire piglets were assigned randomly to two groups of seven (deep hypothermic circulatory arrest or deep hypothermic circulatory arrest with selective cerebral perfusion for 60 minutes at 18℃) and four control pigs without cardiopulmonary bypass support. Carbon-13-labeled glucose as a metabolic tracer was infused, and gas chromatography-mass spectrometry and nuclear magnetic resonance were used for metabolic analysis in the frontal cortex. Following 2.5 h of cerebral reperfusion, we observed similar cerebral adenosine triphosphate levels, absolute levels of lactate and citric acid cycle intermediates, and carbon-13 enrichment among three groups. However, deep hypothermic circulatory arrest induced significant abnormalities in glutamate cycling resulting in reduced glutamate/glutamine and elevated γ-aminobutyric acid/glutamate along with neuroapoptosis, which were all prevented by selective cerebral perfusion. The data suggest that selective cerebral perfusion prevents these modifications in glutamate/glutamine/γ-aminobutyric acid cycling and protects the cerebral cortex from apoptosis. © The Author(s) 2016.

Prevention of Oxidized Low Density Lipoprotein-Induced Endothelial Cell Injury by DA-PLGA-PEG-cRGD Nanoparticles Combined with Ultrasound

PubMed Central

Li, Zhaojun; Huang, Hui; Huang, Lili; Du, Lianfang; Sun, Ying; Duan, Yourong

2017-01-01

In general, atherosclerosis is considered to be a form of chronic inflammation. Dexamethasone has anti-inflammatory effects in atherosclerosis, but it was not considered for long-term administration on account of a poor pharmacokinetic profile and adverse side effects. Nanoparticles in which drugs can be dissolved, encapsulated, entrapped or chemically attached to the particle surface have abilities to incorporate dexamethasone and to be used as controlled or targeted drug delivery system. Long circulatory polymeric nanoparticles present as an assisting approach for controlled and targeted release of the encapsulated drug at the atherosclerotic site. Polymeric nanoparticles combined with ultrasound (US) are widely applied in cancer treatment due to their time applications, low cost, simplicity, and safety. However, there are few studies on atherosclerosis treatment using polymeric nanoparticles combined with US. In this study, targeted dexamethasone acetate (DA)-loaded poly (lactide-glycolide)-polyethylene glycol-cRGD (PLGA-PEG-cRGD) nanoparticles (DA-PLGA-PEG-cRGD NPs) were prepared by the emulsion-evaporation method using cRGD modified PLGA-PEG polymeric materials (PLGA-PEG-cRGD) prepared as the carrier. The average particle size of DA-PLGA-PEG-cRGD NPs was 221.6 ± 0.9 nm. Morphology of the nanoparticles was spherical and uniformly dispersed. In addition, the DA released profiles suggested that ultrasound could promote drug release from the nanocarriers and accelerate the rate of release. In vitro, the cellular uptake process of fluorescein isothiocyanate (FITC)@DA-PLGA-PEG-cRGD NPs combined with US into the damaged human umbilical vein endothelial cells (HUVECs) indicated that US promoted rapid intracellular uptake of FITC@DA- PLGA-PEG-cRGD NPs. The cell viability of DA-PLGA-PEG-cRGD NPs combined with US reached 91.9% ± 0.2%, which demonstrated that DA-PLGA-PEG-cRGD NPs combined with US had a positive therapeutic effect on damaged HUVECs. Overall, DA-PLGA-PEG-cRGD NPs in combination with US may provide a promising drug delivery system to enhance the therapeutic effects of these chemotherapeutics at the cellular level. PMID:28406431

Prevention of Oxidized Low Density Lipoprotein-Induced Endothelial Cell Injury by DA-PLGA-PEG-cRGD Nanoparticles Combined with Ultrasound.

PubMed

Li, Zhaojun; Huang, Hui; Huang, Lili; Du, Lianfang; Sun, Ying; Duan, Yourong

2017-04-13

In general, atherosclerosis is considered to be a form of chronic inflammation. Dexamethasone has anti-inflammatory effects in atherosclerosis, but it was not considered for long-term administration on account of a poor pharmacokinetic profile and adverse side effects. Nanoparticles in which drugs can be dissolved, encapsulated, entrapped or chemically attached to the particle surface have abilities to incorporate dexamethasone and to be used as controlled or targeted drug delivery system. Long circulatory polymeric nanoparticles present as an assisting approach for controlled and targeted release of the encapsulated drug at the atherosclerotic site. Polymeric nanoparticles combined with ultrasound (US) are widely applied in cancer treatment due to their time applications, low cost, simplicity, and safety. However, there are few studies on atherosclerosis treatment using polymeric nanoparticles combined with US. In this study, targeted dexamethasone acetate (DA)-loaded poly (lactide-glycolide)-polyethylene glycol-cRGD (PLGA-PEG-cRGD) nanoparticles (DA-PLGA-PEG-cRGD NPs) were prepared by the emulsion-evaporation method using cRGD modified PLGA-PEG polymeric materials (PLGA-PEG-cRGD) prepared as the carrier. The average particle size of DA-PLGA-PEG-cRGD NPs was 221.6 ± 0.9 nm. Morphology of the nanoparticles was spherical and uniformly dispersed. In addition, the DA released profiles suggested that ultrasound could promote drug release from the nanocarriers and accelerate the rate of release. In vitro, the cellular uptake process of fluorescein isothiocyanate (FITC)@DA-PLGA-PEG-cRGD NPs combined with US into the damaged human umbilical vein endothelial cells (HUVECs) indicated that US promoted rapid intracellular uptake of FITC@DA- PLGA-PEG-cRGD NPs. The cell viability of DA-PLGA-PEG-cRGD NPs combined with US reached 91.9% ± 0.2%, which demonstrated that DA-PLGA-PEG-cRGD NPs combined with US had a positive therapeutic effect on damaged HUVECs. Overall, DA-PLGA-PEG-cRGD NPs in combination with US may provide a promising drug delivery system to enhance the therapeutic effects of these chemotherapeutics at the cellular level.

Development of regional chemotherapies: feasibility, safety and efficacy in clinical use and preclinical studies

PubMed Central

Cai, Shuang; Bagby, Taryn R; Forrest, M Laird

2011-01-01

Conventional oral and intravenous chemotherapies permeate throughout the body, exposing healthy tissues to similar cytotoxic drug levels as tumors. This leads to significant dose-limiting toxicities that may prevent patients from receiving sufficient treatment to overcome cancers. Therefore, a number of locoregional drug-delivery strategies have been evaluated and implemented in preclinical studies, clinical trials and in practice, in the past decades to minimize systemic toxicities from chemotherapeutic agents and to improve treatment outcomes. Localized treatment is beneficial because many cancers, such as melanoma, peritoneal cancer and breast cancer, advance locally adjacent to the site of the primary tumors prior to their circulatory invasion. In this article, we will review the feasibility, safety and efficacy of multiple localized chemotherapies in clinical use and preclinical development. PMID:22229080

Development and Validation of a Two-Tier Instrument to Examine Understanding of Internal Transport in Plants and the Human Circulatory System

ERIC Educational Resources Information Center

Wang, Jing-Ru

2004-01-01

This study is intended to develop an assessment instrument to investigate students' understandings about internal transport in plants and human circulatory system. A refined process of a two-tier diagnostic test was used to develop the instrument. Finally, three versions of the Internal Transport in Plants and the Human Circulatory System test…

Serotonin and Blood Pressure Regulation

PubMed Central

Morrison, Shaun F.; Davis, Robert Patrick; Barman, Susan M.

2012-01-01

5-Hydroxytryptamine (5-HT; serotonin) was discovered more than 60 years ago as a substance isolated from blood. The neural effects of 5-HT have been well investigated and understood, thanks in part to the pharmacological tools available to dissect the serotonergic system and the development of the frequently prescribed selective serotonin-reuptake inhibitors. By contrast, our understanding of the role of 5-HT in the control and modification of blood pressure pales in comparison. Here we focus on the role of 5-HT in systemic blood pressure control. This review provides an in-depth study of the function and pharmacology of 5-HT in those tissues that can modify blood pressure (blood, vasculature, heart, adrenal gland, kidney, brain), with a focus on the autonomic nervous system that includes mechanisms of action and pharmacology of 5-HT within each system. We compare the change in blood pressure produced in different species by short- and long-term administration of 5-HT or selective serotonin receptor agonists. To further our understanding of the mechanisms through which 5-HT modifies blood pressure, we also describe the blood pressure effects of commonly used drugs that modify the actions of 5-HT. The pharmacology and physiological actions of 5-HT in modifying blood pressure are important, given its involvement in circulatory shock, orthostatic hypotension, serotonin syndrome and hypertension. PMID:22407614

Androgen actions on endothelium functions and cardiovascular diseases

PubMed Central

Cai, Jing-Jing; Wen, Juan; Jiang, Wei-Hong; Lin, Jian; Hong, Yuan; Zhu, Yuan-Shan

2016-01-01

The roles of androgens on cardiovascular physiology and pathophysiology are controversial as both beneficial and detrimental effects have been reported. Although the reasons for this discrepancy are unclear, multiple factors such as genetic and epigenetic variation, sex-specificity, hormone interactions, drug preparation and route of administration may contribute. Recently, growing evidence suggests that androgens exhibit beneficial effects on cardiovascular function though the mechanism remains to be elucidated. Endothelial cells (ECs) which line the interior surface of blood vessels are distributed throughout the circulatory system, and play a crucial role in cardiovascular function. Endothelial progenitor cells (EPCs) are considered an indispensable element for the reconstitution and maintenance of an intact endothelial layer. Endothelial dysfunction is regarded as an initiating step in development of atherosclerosis and cardiovascular diseases. The modulation of endothelial functions by androgens through either genomic or nongenomic signal pathways is one possible mechanism by which androgens act on the cardiovascular system. Obtaining insight into the mechanisms by which androgens affect EC and EPC functions will allow us to determine whether androgens possess beneficial effects on the cardiovascular system. This in turn may be critical in the prevention and therapy of cardiovascular diseases. This article seeks to review recent progress in androgen regulation of endothelial function, the sex-specificity of androgen actions, and its clinical applications in the cardiovascular system. PMID:27168746

Intraoperative care for aortic surgery using circulatory arrest

PubMed Central

Fernández Del Valle, David; González Alvarez, Adrián; Pérez-Lozano, Blanca

2017-01-01

The total circulatory arrest (CA) is necessary to achieve optimal surgical conditions in certain aortic pathologies, especially in those affecting the ascending aorta and aortic arch. During this procedure it is necessary to protect all the organs of ischemia, especially those of the central nervous system and for this purpose several strategies have been developed. The first and most important protective method is systemic hypothermia. The degree of hypothermia and the route of application have been evolving and currently tend to use moderate hypothermia (MH) (20.1–28 °C) associated with unilateral or bilateral selective cerebral perfusion methods. In this way the neurological results are better, the interval of security is greater and the times of extracorporeal circulation are smaller. Even so, it is necessary to take into account that there is the possibility of ischemia in the lower part of the body, especially of the abdominal viscera and the spinal cord, therefore the time of circulatory stop should be limited and not to exceed 80 minutes. Evidence of possible neurological drug protection is very weak and only mannitol, magnesium, and statins can produce some benefit. Inhalational anesthetics and some intravenous seem to have advantages, but more studies would be needed to test their long-term benefit. Other important parameters to be monitored during these procedures are blood glucose, anemia and coagulation disorders and acid-base balance. The recommended monitoring is common in complex cardiovascular procedures and it is of special importance the neurological monitoring that can be performed with several techniques, although currently the most used are Bispectral Index (BIS) and Near-Infrared Spectroscopy (NIRS). It is also essential to monitor the temperature routinely at the nasopharyngeal and bladder level and it is important to control coagulation with rotational thromboelastometry (ROTEM). PMID:28616347

Estimating the Causal Effect of Low Levels of Fine Particulate Matter on Hospitalization.

PubMed

Makar, Maggie; Antonelli, Joseph; Di, Qian; Cutler, David; Schwartz, Joel; Dominici, Francesca

2017-09-01

In 2012, the EPA enacted more stringent National Ambient Air Quality Standards (NAAQS) for fine particulate matter (PM2.5). Few studies have characterized the health effects of air pollution levels lower than the most recent NAAQS for long-term exposure to PM2.5 (now 12 μg/m). We constructed a cohort of 32,119 Medicare beneficiaries residing in 5138 US ZIP codes who were interviewed as part of the Medicare Current Beneficiary Survey (MCBS) between 2002 and 2010 and had 1 year of follow-up. We considered four outcomes: all-cause hospitalizations, hospitalizations for circulatory diseases and respiratory diseases, and death. We found that increasing exposure to PM2.5 from levels lower than 12 μg/m to levels higher than 12 μg/m is associated with increases in all-cause admission rates of 7% (95% CI = 3%, 10%) and in circulatory admission hazard rates of 6% (95% CI = 2%, 9%). When we restricted analysis to enrollees with exposure always lower than 12 μg/m, we found that increasing exposure from levels lower than 8 μg/m to levels higher than 8 μg/m increased all-cause admission hazard rates by 15% (95% CI = 8%, 23%), circulatory by 18% (95% CI = 10%, 27%), and respiratory by 21% (95% CI = 9%, 34%). In a nationally representative sample of Medicare enrollees, changes in exposure to PM2.5, even at levels consistently below standards, are associated with increases in hospital admissions for all causes and cardiovascular and respiratory diseases. The robustness of our results to inclusion of many additional individual level potential confounders adds validity to studies of air pollution that rely entirely on administrative data.

76 FR 82311 - Food and Drug Administration Transparency Initiative: Food and Drug Administration Report on Good...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-30

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2009-N-0247] Food and Drug Administration Transparency Initiative: Food and Drug Administration Report on Good Guidance Practices: Improving Efficiency and Transparency; Availability AGENCY: Food and Drug...

[Powder-induced anaphylactic shock following use of powdered latex gloves during gynecological open laparotomy].

PubMed

Mizuno, Ju; In-nami, Hiroshi; Saegusa, Hiroaki; Kibayashi, Junichiro; Jimbo, Masanori; Kida, Kotaro; Ichiishi, Noriko

2006-06-01

A 42-year-old woman with hysteromyoma underwent total abdominal hysterectomy under general and epidural anesthesia. Three years before, she had undergone resection of lipoma on her left shoulder under local anesthesia uneventfully. She had no previous history of hypersensitivity. General anesthesia was induced by intravenous injection of fentanyl, propofol, and vecuronium followed by inhalation of nitrous oxide, oxygen, and sevoflurane. Lidocaine and fentanyl were injected through a lumbar epidural catheter. After the start of open laparotomy, there was a sudden onset of hypotension. Administrations of ephedrine and phenylephrine, and volume loading were ineffective. Moreover, she showed profound hypotension, tachycardia, oxygen desaturation, decreased endtidal carbon dioxide and increased airway pressure. She broke out in a sweat with flushing on her chest and upper extremities. Therefore, we interrupted the surgery, checked her arterial blood gas analysis, performed echocardiography, and inserted a pulmonary artery catheter. We made a diagnosis of anaphylactic shock and administered methylprednisolone, albumin, epinephrine, norepinephrine, and dopamine to treat the circulatory collapse. The gynecologists changed their surgical gloves from a powdered-latex type to a powder-free latex type, and the surgery was resumed. She responded well to appropriate emergent therapy and all vasopressor drugs were gradually decreased and eventually stopped. After the end of the surgery, she recovered completely from the signs and symptoms of shock. Later, we found a high level of plasma latex protein-specific IgE antibody and confirmed the events as anaphylactic shock due to latex. We assumed that the anaphylactic shock was powder-induced latex allergy following use of powdered latex gloves in this case. Latex allergy should be suspected if an anaphylactic reaction or shock accompanied by circulatory collapse, respiratory failure, and skin symptoms of unknown origin occurs during surgery. As women more often come into contact with household articles containing latex, we suspect that women are prone to developing sensitivity towards latex. We recommend that powder-free or latex-free surgical gloves should be available not only for patients with a high risk of developing latex allergy, but also for patients indicated for gynecological open laparotomy.

Donations After Circulatory Death in Liver Transplant

PubMed Central

Eren, Emre A.; Latchana, Nicholas; Beal, Eliza; Hayes, Don; Whitson, Bryan; Black, Sylvester M.

2017-01-01

The supply of liver grafts for treatment of end-stage liver disease continues to fall short of ongoing demands. Currently, most liver transplants originate from donations after brain death. Enhanced utilization of the present resources is prudent to address the needs of the population. Donation after circulatory or cardiac death is a mechanism whereby the availability of organs can be expanded. Donations after circulatory death pose unique challenges given their exposure to warm ischemia. Technical principles of donations after circulatory death procurement and pertinent studies investigating patient outcomes, graft outcomes, and complications are highlighted in this review. We also review associated risk factors to suggest potential avenues to achieve improved outcomes and reduced complications. Future considerations and alternative techniques of organ preservation are discussed, which may suggest novel strategies to enhance preservation and donor expansion through the use of marginal donors. Ultimately, without effective measures to bolster organ supply, donations after circulatory death should remain a consideration; however, an understanding of inherent risks and limitations is necessary. PMID:27733105

Donations After Circulatory Death in Liver Transplant.

PubMed

Eren, Emre A; Latchana, Nicholas; Beal, Eliza; Hayes, Don; Whitson, Bryan; Black, Sylvester M

2016-10-01

The supply of liver grafts for treatment of end-stage liver disease continues to fall short of ongoing demands. Currently, most liver transplants originate from donations after brain death. Enhanced utilization of the present resources is prudent to address the needs of the population. Donation after circulatory or cardiac death is a mechanism whereby the availability of organs can be expanded. Donations after circulatory death pose unique challenges given their exposure to warm ischemia. Technical principles of donations after circulatory death procurement and pertinent studies investigating patient outcomes, graft outcomes, and complications are highlighted in this review. We also review associated risk factors to suggest potential avenues to achieve improved outcomes and reduced complications. Future considerations and alternative techniques of organ preservation are discussed, which may suggest novel strategies to enhance preservation and donor expansion through the use of marginal donors. Ultimately, without effective measures to bolster organ supply, donations after circulatory death should remain a consideration; however, an understanding of inherent risks and limitations is necessary.

Generation of OH Radical by Ultrasonic Irradiation in Batch and Circulatory Reactor

NASA Astrophysics Data System (ADS)

Fang, Yu; Shimizu, Sayaka; Yamamoto, Takuya; Komarov, Sergey

2018-03-01

Ultrasonic technology has been widely investigated in the past as one of the advance oxidation processes to treat wastewater, in this process acoustic cavitation causes generation of OH radical, which play a vital role in improving the treatment efficiency. In this study, OH radical formation rate was measured in batch and circulatory reactor by using Weissler reaction at various ultrasound output power. It is found that the generation rate in batch reactor is higher than that in circulatory reactor at the same output power. The generation rate tended to be slower when output power exceeds 137W. The optimum condition for circulatory reactor was found to be 137W output and 4L/min flow rate. Results of aluminum foil erosion test revealed a strong dependence of cavitation zone length on the ultrasound output power. This is assumed to be one of the reasons why the generation rate of HO radicals becomes slower at higher output power in circulatory reactor.

Prevention of Hypovolemic Circulatory Collapse by IL-6 Activated Stat3

PubMed Central

Tsimelzon, Anna I.; Mastrangelo, Mary-Ann A.; Hilsenbeck, Susan G.; Poli, Valeria; Tweardy, David J.

2008-01-01

Half of trauma deaths are attributable to hypovolemic circulatory collapse (HCC). We established a model of HCC in rats involving minor trauma plus severe hemorrhagic shock (HS). HCC in this model was accompanied by a 50% reduction in peak acceleration of aortic blood flow and cardiomyocyte apoptosis. HCC and apoptosis increased with increasing duration of hypotension. Apoptosis required resuscitation, which provided an opportunity to intervene therapeutically. Administration of IL-6 completely reversed HCC, prevented cardiac dysfunction and cardiomyocyte apoptosis, reduced mortality 5-fold and activated intracardiac signal transducer and activator of transcription (STAT) 3. Pre-treatment of rats with a selective inhibitor of Stat3, T40214, reduced the IL-6-mediated increase in cardiac Stat3 activity, blocked successful resuscitation by IL-6 and reversed IL-6-mediated protection from cardiac apoptosis. The hearts of mice deficient in the naturally occurring dominant negative isoform of Stat3, Stat3β, were completely resistant to HS-induced apoptosis. Microarray analysis of hearts focusing on apoptosis related genes revealed that expression of 29% of apoptosis related genes was altered in HS vs. sham rats. IL-6 treatment normalized the expression of these genes, while T40214 pretreatment prevented IL-6-mediated normalization. Thus, cardiac dysfunction, cardiomyocyte apoptosis and induction of apoptosis pathway genes are important components of HCC; IL-6 administration prevented HCC by blocking cardiomyocyte apoptosis and induction of apoptosis pathway genes via Stat3 and warrants further study as a resuscitation adjuvant for prevention of HCC and death in trauma patients. PMID:18270592

A literature-based cost analysis of tissue plasminogen activator for prevention of biliary stricture in donation after circulatory death liver transplantation.

PubMed

Jones, J M; Bhutiani, N; Wei, D; Goldstein, L; Jones, C M; Cannon, R M

2018-04-17

This study sought to approximate the cost-effectiveness of tPA utilization for prevention of biliary strictures (PTBS) in donation after circulatory death liver transplantation (DCD-LT). Previously-reported PTBS rates in DCD-LT with and without tPA were used to calculate the number needed to treat (NNT) for prevention of one PTBS. The incremental cost of PTBS was then used to determine the cost effectiveness of tPA for prevention of PTBS. The incidence of PTBS in the setting of tPA administration was 20%, while incidence in patients without tPA use was 43% (p < 0.001). Meta-analysis demonstrated a risk reduction of 15.7%, which translated into a NNT of 6.4. Cost associated with treating 6.4 patients was $50,353. Based on an incremental cost of $81,888 associated with PTBS management, use of tPA in DCD-LT protocols was estimated to save $31,528 per PTBS prevented. Utilization of tPA in DCD-LT protocols represents one possible cost-effective strategy for prevention of PTBS in DCD-LT. Copyright © 2018 Elsevier Inc. All rights reserved.

Cerebral activation of mitogen-activated protein kinases after circulatory arrest and low flow cardiopulmonary bypass.

PubMed

Aharon, Alon S; Mulloy, Matthew R; Drinkwater, Davis C; Lao, Oliver B; Johnson, Mahlon D; Thunder, Megan; Yu, Chang; Chang, Paul

2004-11-01

Mitogen-activated protein kinases (MAPK) are important intermediates in the signal transduction pathways involved in neuronal dysfunction following cerebral ischemia-reperfusion injury. One subfamily, extracellular regulated kinase 1/2, has been heavily implicated in the pathogenesis of post-ischemic neuronal damage. However, the contribution of extracellular regulated kinase 1/2 to neuronal damage following deep hypothermic circulatory arrest and low flow cardiopulmonary bypass is unknown. We attempted to correlate the extent of neuronal damage present following deep hypothermic circulatory arrest and low flow cardiopulmonary bypass with phosphorylated extracellular regulated kinase 1/2 expression in the cerebral vascular endothelium. Piglets underwent normal flow cardiopulmonary bypass (n=4) deep hypothermic circulatory arrest (n=6) and low flow cardiopulmonary bypass (n=5). Brains were harvested following 24 h of post-cardiopulmonary bypass recovery. Cerebral cortical watershed zones, hippocampus, basal ganglia, thalamus, cerebellum, mesencephalon, pons and medulla were evaluated using hematoxylin and eosin staining. A section of ischemic cortex was evaluated by immunohistochemistry with rabbit polyclonal antibodies against phosphorylated extracellular regulated kinase 1/2. Compared to cardiopulmonary bypass controls, the deep hypothermic circulatory arrest and low flow cardiopulmonary bypass piglets exhibited diffuse ischemic changes with overlapping severity and distribution. Significant neuronal damage occurred in the frontal watershed zones and basal ganglia of the deep hypothermic circulatory arrest group (P<0.05). No detectable phosphorylated extracellular regulated kinase 1/2 immunoreactivity was found in the cardiopulmonary bypass controls; however, ERK 1/2 immunoreactivity was present in the cerebral vascular endothelium of the deep hypothermic circulatory arrest and low flow cardiopulmonary bypass groups. Our results indicate that phosphorylated extracellular regulated kinase 1/2 may play a prominent role in early cerebral ischemia-reperfusion injury and endothelial dysfunction. The pharmacologic inhibition of extracellular regulated kinase 1/2 represents a new and exciting opportunity for the modulation of cerebral tolerance to low flow cardiopulmonary bypass and deep hypothermic circulatory arrest.

Immunotherapy for the treatment of drug abuse.

PubMed

Kosten, Thomas; Owens, S Michael

2005-10-01

Antibody therapy (as either active or passive immunization) is designed primarily to prevent drugs of abuse from entering the central nervous system (CNS). Antidrug antibodies reduce rush, euphoria, and drug distribution to the brain at doses that exceed the apparent binding capacity of the antibody. This is accomplished through a pharmacokinetic antagonism, which reduces the amount of drug in the brain, the rate of clearance across the blood-brain barrier, and the volume of drug distribution. Because the antibodies remain primarily in the circulatory system, they have no apparent central nervous system side effects. Active immunization with drug-protein conjugate vaccines has been tested for cocaine, heroin, methamphetamine, and nicotine in animal, with 1 cocaine and 3 nicotine vaccines in Phase 2 human trials. Passive immunization with high affinity monoclonal antibodies has been tested for cocaine, methamphetamine, nicotine, and phencyclidine (PCP) in preclinical animal models. Antibodies have 2 immediate clinical applications in drug abuse treatment: to treat drug overdose and to reduce relapse to drug use in addicted patients. The specificity of the therapies, the lack of addiction liability, minimal side effects, and long-lasting protection against drug use offer major therapeutic benefit over conventional small molecule agonists and antagonists. Immunotherapies can also be combined with other antiaddiction medications and enhance behavioral therapies. Current immunotherapies already show efficacy, but improved antigen design and antibody engineering promise highly specific and rapidly developed treatments for both existing and future addictions.

76 FR 55928 - Food and Drug Administration Health Professional Organizations Conference

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-09

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0002] Food and Drug Administration Health Professional Organizations Conference AGENCY: Food and Drug Administration, HHS. ACTION: Notice of public conference. The Food and Drug Administration (FDA) is announcing a...

75 FR 18219 - Drug and Medical Device Forum on Food and Drug Administration Drug and Device Requirements and...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-09

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0142] Drug and Medical Device Forum on Food and Drug Administration Drug and Device Requirements and Supplier Controls; Public Educational Forum AGENCY: Food and Drug Administration, HHS. ACTION: Notice of public...

The effect of short term treatment with probiotic VSL#3 on various clinical and biochemical parameters in patients with liver cirrhosis.

PubMed

Marlicz, W; Wunsch, E; Mydlowska, M; Milkiewicz, M; Serwin, K; Mularczyk, M; Milkiewicz, P; Raszeja-Wyszomirska, J

2016-12-01

The evidence is mounting that alterations of innate immunity and gut microbiota contribute to chronic liver disease and its complications. Modulation of intestinal microbiota is an emerging therapeutic strategy in hepatology. Probiotics through modulation of intestinal milieu have the potential to affect the course of liver disease. The data concerning the influence of probiotics on various plasma molecules and compounds involved in the pathogenesis of hyperdynamic circulatory state in liver cirrhosis is still not confluent and require further evaluation. In our study twenty patients with compensated and decompensated liver cirrhosis and ten healthy controls received probiotic VSL#3 daily for 28 days. Plasma levels of interleukin 6 (IL-6), vascular endothelial growth factor (VEGF), plasminogen activator inhibitor (PAI), macrophage inflammatory protein 3/α (MIP-3 α/CCL20), monocyte chemotactic protein-1α (MCP-1/CCL2), human myeloperoxidase (MPO), nitric oxide (NO), prostaglandins, thromboxane (TXB 2 ) and big-endothelin were measured at baseline, day 14 and 28 of probiotic administration. The incidence of hepatic encephalopathy was assessed with critical flicker frequency. Changes in clinical, biochemical and microbiological parameters were evaluated. The stage of liver cirrhosis correlated with an increase in plasma levels of pro-inflammatory cytokines (IL-6) and chemotactic chemokines involved in immune cell trafficking (MIP-3α/CCL20). Probiotic administration in patients with liver cirrhosis led to modulation of plasma levels of several molecules and compounds measured (MIP-3α/CCL20, NO, big-endothelin, TXB 2 and MPO). The grade of encephalopathy during the course of probiotic supplementation remained unaffected in both groups of patients. VSL#3 treatment was well tolerated and safe in patients with liver disease. In patients with compensated and decompensated liver cirrhosis, VSL#3 manipulates selected plasma molecules and compounds involved in hyperdynamic circulatory dysfunction. Short term VSL#3 administration affects several clinical and biochemical parameters commonly altered in liver cirrhosis.

Description, validation, and modification of the Guyton model for space-flight applications. Part A. Guyton model of circulatory, fluid and electrolyte control. Part B. Modification of the Guyton model for circulatory, fluid and electrolyte control

NASA Technical Reports Server (NTRS)

Leonard, J. I.

1985-01-01

The mathematical model that has been a cornerstone for the systems analysis of space-flight physiological studies is the Guyton model describing circulatory, fluid and electrolyte regulation. The model and the modifications that are made to permit simulation and analysis of the stress of weightlessness are described.

The Circulatory System [and] Instructor's Guide: The Circulatory System. Health Occupations Education Module: Instructional Materials in Anatomy and Physiology for Pennsylvania Health Occupations Programs.

ERIC Educational Resources Information Center

National Evaluation Systems, Inc., Amherst, MA.

This module on the circulatory system is one of 17 modules designed for individualized instruction in health occupations education programs at both the secondary and postsecondary levels. It is part of an eight-unit subset on anatomy and physiology within the set of 17 modules. Following a preface which explains to the student how to use the…

75 FR 15439 - Food and Drug Administration/Xavier University Global Medical Device Conference

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-29

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0001] Food and Drug Administration/Xavier University Global Medical Device Conference AGENCY: Food and Drug Administration, HHS. ACTION: Notice of public conference. SUMMARY: The Food and Drug Administration (FDA...

78 FR 15957 - Food and Drug Administration/Xavier University Global Medical Device Conference

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-13

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-N-0001] Food and Drug Administration/Xavier University Global Medical Device Conference AGENCY: Food and Drug Administration, HHS. ACTION: Notice of public conference. SUMMARY: The Food and Drug Administration (FDA...

77 FR 10537 - Food and Drug Administration/Xavier University Global Medical Device Conference

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-22

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-N-0001] Food and Drug Administration/Xavier University Global Medical Device Conference AGENCY: Food and Drug Administration, HHS. ACTION: Notice of public conference. SUMMARY: The Food and Drug Administration (FDA...

76 FR 6477 - Industry Exchange Workshop on Food and Drug Administration Drug and Device Requirements; Public...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-04

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0002] Industry Exchange Workshop on Food and Drug Administration Drug and Device Requirements; Public Workshop AGENCY: Food and Drug Administration, HHS. ACTION: Notice of public workshop. SUMMARY: The Food and Drug...

[Atrial fibrillation and prolonged nocturnal cardiac arrests in a patient with obstructive sleep apnea syndrome. Successful correction of disorders by CPAP therapy].

PubMed

Bairambekov, E Sh; Pevzner, A V; Litvin, A Yu; Fomicheva, O A

The case history of a 46-year-old patient with obstructive sleep apnea syndrome was analyzed. The examination revealed fourth-degree obesity, prior myocardial infarction, persistent atrial fibrillation with nocturnal asystoles lasting as long as 14.3 sec. During selected drug therapy and regular application of secondary ventilation (continuous positive airway pressure (CPAP) therapy) used to correct breathing problems, there was a reduction in the signs of circulatory deficiency, cessation of cardiac pauses, and recovery of sinus rhythm. The therapeutic effect persisted during a 24-month follow-up.

75 FR 73107 - Guidance for Industry and Food and Drug Administration Staff; Blood Lancet Labeling; Availability

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-29

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-D-0590] Guidance for Industry and Food and Drug Administration Staff; Blood Lancet Labeling; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is...

77 FR 21784 - Science Board to the Food and Drug Administration; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-11

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No FDA-2012-N-0001] Science Board to the Food and Drug Administration; Notice of Meeting AGENCY: Food and Drug Administration... Food and Drug Administration (FDA). The meeting will be open to the public. Name of Committee: Science...

78 FR 30317 - Science Board to the Food and Drug Administration; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-22

...] Science Board to the Food and Drug Administration; Notice of Meeting AGENCY: Food and Drug Administration... Food and Drug Administration (FDA). The meeting will be open to the public. Name of Committee: Science Board to the Food and Drug Administration (Science Board). General Function of the Committee: The...

78 FR 6332 - Science Board to the Food and Drug Administration; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-30

...] Science Board to the Food and Drug Administration; Notice of Meeting AGENCY: Food and Drug Administration... Food and Drug Administration (FDA). The meeting will be open to the public. Name of Committee: Science Board to the Food and Drug Administration (Science Board). General Function of the Committee: The...

77 FR 51031 - Science Board to the Food and Drug Administration; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-23

...] Science Board to the Food and Drug Administration; Notice of Meeting AGENCY: Food and Drug Administration... Food and Drug Administration (FDA). The meeting will be open to the public. Name of Committee: Science Board to the Food and Drug Administration (Science Board). General Function of the Committee: The...

Risk Factors and Outcomes in Transfusion-associated Circulatory Overload

PubMed Central

Murphy, Edward L.; Kwaan, Nicholas; Looney, Mark R.; Gajic, Ognjen; Hubmayr, Rolf D.; Gropper, Michael A.; Koenigsberg, Monique; Wilson, Greg; Matthay, Michael; Bacchetti, Peter; Toy, Pearl

2013-01-01

BACKGROUND Transfusion-associated circulatory overload is characterized by new respiratory distress and hydrostatic pulmonary edema within 6 hours after blood transfusion, but its risk factors and outcomes are poorly characterized. METHODS Using a case control design, we enrolled 83 patients with severe transfusion-associated circulatory overload identified by active surveillance for hypoxemia and 163 transfused controls at the University of California, San Francisco (UCSF) and Mayo Clinic (Rochester, Minn) hospitals. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using multivariable logistic regression, and survival and length of stay were analyzed using proportional hazard models. RESULTS Transfusion-associated circulatory overload was associated with chronic renal failure (OR 27.0; 95% CI, 5.2–143), a past history of heart failure (OR 6.6; 95% CI, 2.1–21), hemorrhagic shock (OR 113; 95% CI, 14.1–903), number of blood products transfused (OR 1.11 per unit; 95% CI, 1.01–1.22), and fluid balance per hour (OR 9.4 per liter; 95% CI, 3.1–28). Patients with transfusion-associated circulatory overload had significantly increased in-hospital mortality (hazard ratio 3.20; 95% CI, 1.23–8.10) after controlling for Acute Physiology and Chronic Health Evaluation-II (APACHE-II) score, and longer hospital and intensive care unit lengths of stay. CONCLUSIONS The risk of transfusion-associated circulatory overload increases with the number of blood products administered and a positive fluid balance, and in patients with pre-existing heart failure and chronic renal failure. These data, if replicated, could be used to construct predictive algorithms for transfusion-associated circulatory overload, and subsequent modifications of transfusion practice might prevent morbidity and mortality associated with this complication. PMID:23357450

76 FR 25358 - 2011 Parenteral Drug Association/Food and Drug Administration Glass Quality Conference; Public...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-04

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0002] 2011 Parenteral Drug Association/Food and Drug Administration Glass Quality Conference; Public Conference AGENCY: Food and Drug Administration, HHS. ACTION: Notice of public conference. SUMMARY: The Food...

Fetal circulatory responses to oxygen lack.

PubMed

Jensen, A; Berger, R

1991-10-01

The knowledge on fetal and neonatal circulatory physiology accumulated by basic scientists and clinicians over the years has contributed considerably to the recent decline of perinatal morbidity and mortality. This review will summarize the peculiarities of the fetal circulation, the distribution of organ blood flow during normoxemia, and that during oxygen lack caused by various experimental perturbations. Furthermore, the relation between oxygen delivery and tissue metabolism during oxygen lack as well as evidence to support a new concept will be presented along with the principal cardiovascular mechanisms involved. Finally, blood flow and oxygen delivery to the principal fetal organs will be examined and discussed in relation to organ function. The fetal circulatory response to hypoxemia and asphyxia is a centralization of blood flow in favour of the brain, heart, and adrenals and at the expense of almost all peripheral organs, particularly of the lungs, carcass, skin and scalp. This response is qualitatively similar but quantitatively different under various experimental conditions. However, at the nadir of severe acute asphyxia the circulatory centralization cannot be maintained. Then there is circulatory decentralization, and the fetus will experience severe brain damage if not expire unless immediate resuscitation occurs. Future work in this field will have to concentrate on the important questions, what factors determine this collapse of circulatory compensating mechanisms in the fetus, how does it relate to neuronal damage, and how can the fetal brain be pharmacologically protected against the adverse effects of asphyxia.

Interaction between drug delivery vehicles and cells under the effect of shear stress.

PubMed

Godoy-Gallardo, M; Ek, P K; Jansman, M M T; Wohl, B M; Hosta-Rigau, L

2015-09-01

Over the last decades, researchers have developed an ever greater and more ingenious variety of drug delivery vehicles (DDVs). This has made it possible to encapsulate a wide selection of therapeutic agents, ranging from proteins, enzymes, and peptides to hydrophilic and hydrophobic small drugs while, at the same time, allowing for drug release to be triggered through a diverse range of physical and chemical cues. While these advances are impressive, the field has been lacking behind in translating these systems into the clinic, mainly due to low predictability of in vitro and rodent in vivo models. An important factor within the complex and dynamic human in vivo environment is the shear flow observed within our circulatory system and many other tissues. Within this review, recent advances to leverage microfluidic devices to better mimic these conditions through novel in vitro assays are summarized. By grouping the discussion in three prominent classes of DDVs (lipidic and polymeric particles as well as inorganic nanoparticles), we hope to guide researchers within drug delivery into this exciting field and advance a further implementation of these assay systems within the development of DDVs.

77 FR 52744 - Food and Drug Administration/European Medicines Agency Orphan Product Designation and Grant Workshop

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-30

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-N-0001] Food and Drug Administration/European Medicines Agency Orphan Product Designation and Grant Workshop AGENCY: Food and Drug Administration, HHS. ACTION: Notice of meeting. The Food and Drug Administration's (FDA) Office of Orphan Products Development...

76 FR 9027 - Draft Guidance for Industry and Food and Drug Administration Staff on Best Practices for...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-16

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-D-0057] Draft Guidance for Industry and Food and Drug Administration Staff on Best Practices for Conducting and...: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is...

21 CFR 21.20 - Procedures for notice of Food and Drug Administration Privacy Act Record Systems.

Code of Federal Regulations, 2010 CFR

2010-04-01

... Administration Privacy Act Record Systems. 21.20 Section 21.20 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL PROTECTION OF PRIVACY Food and Drug Administration Privacy Act Record Systems § 21.20 Procedures for notice of Food and Drug Administration Privacy Act Record...

78 FR 9928 - Food and Drug Administration Drug Shortages Task Force and Strategic Plan; Request for Comments

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-12

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-N-0124] Food and Drug Administration Drug Shortages Task Force and Strategic Plan; Request for Comments AGENCY: Food and Drug Administration, HHS. ACTION: Notice; request for comments. SUMMARY: To assist the Food...

21 CFR 7.45 - Food and Drug Administration-requested recall.

Code of Federal Regulations, 2010 CFR

2010-04-01

... Industry Responsibilities § 7.45 Food and Drug Administration-requested recall. (a) The Commissioner of... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Food and Drug Administration-requested recall. 7.45 Section 7.45 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES...

21 CFR 20.1 - Testimony by Food and Drug Administration employees.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Testimony by Food and Drug Administration employees. 20.1 Section 20.1 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... laws administered by the Food and Drug Administration, shall give any testimony before any tribunal...

28 CFR 0.102 - Drug enforcement policy coordination.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 28 Judicial Administration 1 2010-07-01 2010-07-01 false Drug enforcement policy coordination. 0... JUSTICE Drug Enforcement Administration § 0.102 Drug enforcement policy coordination. The Administrator of the Drug Enforcement Administration shall report to the Attorney General, through the Deputy Attorney...

28 CFR 0.102 - Drug enforcement policy coordination.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 28 Judicial Administration 1 2014-07-01 2014-07-01 false Drug enforcement policy coordination. 0... JUSTICE Drug Enforcement Administration § 0.102 Drug enforcement policy coordination. The Administrator of the Drug Enforcement Administration shall report to the Attorney General, through the Deputy Attorney...

28 CFR 0.102 - Drug enforcement policy coordination.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 28 Judicial Administration 1 2013-07-01 2013-07-01 false Drug enforcement policy coordination. 0... JUSTICE Drug Enforcement Administration § 0.102 Drug enforcement policy coordination. The Administrator of the Drug Enforcement Administration shall report to the Attorney General, through the Deputy Attorney...

78 FR 35937 - Food and Drug Administration Decisions for Investigational Device Exemption Clinical...

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2013-06-14

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-D-0790] Food and Drug Administration Decisions for Investigational Device Exemption Clinical Investigations; Draft Guidance for Industry and Food and Drug Administration Staff; Availability AGENCY: Food and Drug...

78 FR 15019 - Food and Drug Administration Prescription Drug User Fee Act V Benefit-Risk Plan; Request for...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-08

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-N-0196] Food and Drug Administration Prescription Drug User Fee Act V Benefit-Risk Plan; Request for Comments AGENCY: Food and Drug Administration, HHS. ACTION: Notice, request for comments. SUMMARY: The Food and...

75 FR 29561 - Memorandum of Understanding Between the Food and Drug Administration and Drugs.Com

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-26

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0004] [FDA 225-09-0012] Memorandum of Understanding Between the Food and Drug Administration and Drugs.Com... Administration (FDA) is providing notice of a memorandum of understanding (MOU) between FDA and Drugs.Com. The...

21 CFR 20.2 - Production of records by Food and Drug Administration employees.

Code of Federal Regulations, 2010 CFR

2010-04-01

... upon an officer or employee of the Food and Drug Administration commanding the production of any record... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Production of records by Food and Drug Administration employees. 20.2 Section 20.2 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND...

Canadian Guidelines for Controlled Pediatric Donation After Circulatory Determination of Death-Summary Report.

PubMed

Weiss, Matthew J; Hornby, Laura; Rochwerg, Bram; van Manen, Michael; Dhanani, Sonny; Sivarajan, V Ben; Appleby, Amber; Bennett, Mary; Buchman, Daniel; Farrell, Catherine; Goldberg, Aviva; Greenberg, Rebecca; Singh, Ram; Nakagawa, Thomas A; Witteman, William; Barter, Jill; Beck, Allon; Coughlin, Kevin; Conradi, Alf; Cupido, Cynthia; Dawson, Rosanne; Dipchand, Anne; Freed, Darren; Hornby, Karen; Langlois, Valerie; Mack, Cheryl; Mahoney, Meagan; Manhas, Deepak; Tomlinson, Christopher; Zavalkoff, Samara; Shemie, Sam D

2017-11-01

Create trustworthy, rigorous, national clinical practice guidelines for the practice of pediatric donation after circulatory determination of death in Canada. We followed a process of clinical practice guideline development based on World Health Organization and Canadian Medical Association methods. This included application of Grading of Recommendations Assessment, Development, and Evaluation methodology. Questions requiring recommendations were generated based on 1) 2006 Canadian donation after circulatory determination of death guidelines (not pediatric specific), 2) a multidisciplinary symposium of national and international pediatric donation after circulatory determination of death leaders, and 3) a scoping review of the pediatric donation after circulatory determination of death literature. Input from these sources drove drafting of actionable questions and Good Practice Statements, as defined by the Grading of Recommendations Assessment, Development, and Evaluation group. We performed additional literature reviews for all actionable questions. Evidence was assessed for quality using Grading of Recommendations Assessment, Development, and Evaluation and then formulated into evidence profiles that informed recommendations through the evidence-to-decision framework. Recommendations were revised through consensus among members of seven topic-specific working groups and finalized during meetings of working group leads and the planning committee. External review was provided by pediatric, critical care, and critical care nursing professional societies and patient partners. We generated 63 Good Practice Statements and seven Grading of Recommendations Assessment, Development, and Evaluation recommendations covering 1) ethics, consent, and withdrawal of life-sustaining therapy, 2) eligibility, 3) withdrawal of life-sustaining therapy practices, 4) ante and postmortem interventions, 5) death determination, 6) neonatal pediatric donation after circulatory determination of death, 7) cardiac and innovative pediatric donation after circulatory determination of death, and 8) implementation. For brevity, 48 Good Practice Statement and truncated justification are included in this summary report. The remaining recommendations, detailed methodology, full Grading of Recommendations Assessment, Development, and Evaluation tables, and expanded justifications are available in the full text report. This process showed that rigorous, transparent clinical practice guideline development is possible in the domain of pediatric deceased donation. Application of these recommendations will increase access to pediatric donation after circulatory determination of death across Canada and may serve as a model for future clinical practice guideline development in deceased donation.

Underuse of medication for circulatory disorders among unmarried women and men in Norway?

PubMed

Kravdal, Øystein; Grundy, Emily

2014-11-24

It is well established that unmarried people have higher mortality from circulatory diseases and higher all-cause mortality than the married, and these marital status differences seem to be increasing. However, much remains to be known about the underlying mechanisms. Our objective was to examine marital status differences in the purchase of medication for circulatory diseases, and risk factors for them, which may indicate underuse of such medication by some marital status groups. Using data from registers covering the entire Norwegian population, we analysed marital status differences in the purchase of medicine for eight circulatory disorders by people aged 50-79 in 2004-2008. These differences were compared with those in circulatory disease mortality during 2004-2007, considered as indicating probable differences in disease burden. The unmarried had 1.4-2.8 times higher mortality from the four types of circulatory diseases considered. However, the never-married in particular purchased less medicine for these diseases, or precursor risk factors of these diseases, primarily because of a low chance of making a first purchase. The picture was more mixed for the divorced and widowed. Both groups purchased less of some of these medicines than the married, but, especially in the case of the widowed, relatively more of other types of medicine. In contrast to the never-married, divorced and widowed people were as least as likely as the married to make a first purchase, but adherence rates thereafter, indicated by continuing purchases, were lower. The most plausible interpretation of the findings is that compared with married people, especially the never-married more often have circulatory disorders that are undiagnosed or for which they for other reasons underuse medication. Inadequate use of these potentially very efficient medicines in such a large population group is a serious public health challenge which needs further investigation. It is possible that marital status differences in use of medicines for circulatory disorders combined with an increasing importance of these medicines have contributed to the widening marital status gap in mortality observed in several countries. This also requires further investigation.

Gene expression profile of high-fat diet-fed C57BL/6J mice: in search of potential role of azelaic acid.

PubMed

Muthulakshmi, Shanmugam; Chakrabarti, Alok K; Mukherjee, Sanjay

2015-03-01

High-fat diet (HFD) elevates circulatory fatty acids and influences glucose and fat metabolism. Azelaic acid (AzA), a naturally occurring α,ω-dicarboxylic acid in wheat, rye, barley, oat seeds and sorghum, has been reported to exert antidiabetic effects in HFD-induced type 2 diabetes mellitus (T2DM) C57BL/6J mice. The present study was undertaken to identify the genes that are differentially modulated by treatment with AzA in HFD-fed mice. Mice were fed HFD for 10 weeks and subjected to intragastric administration of 80 mg/kg body weight (BW) of AzA daily along with HFD from 11 to 15 weeks. Lipid profile, adipokines and cytokines were examined in the plasma/liver of mice. Whole genome profiling was performed in the liver of mice using microarray and validated by qRT-PCR, Western blot and immunohistochemical analyses. HFD intake resulted in significantly elevated lipids (except high-density lipoproteins), resistin, tumour necrosis factor alpha and interleukin-6 with marked reduction in adiponectin. Administration of AzA to HFD-fed mice significantly restored the lipids, adipokines and cytokines to near normal. Transcript profiling revealed that HFD intake activated the genes involved in stress response, cell cycle regulation and apoptosis. Treatment with AzA caused increased expression of genes involved in reactive oxygen species (ROS) scavenging, receptor-mediated signalling, transcription, protein modification and insulin signal transduction. AzA activates insulin signal molecules leading to insulin sensitivity. The ability of AzA to modulate the expression of these genes supports the notion that AzA is a promising drug candidate for the treatment of insulin resistance associated with T2DM.

Folate coupled poly(ethyleneglycol) conjugates of anionic poly(amidoamine) dendrimer for inflammatory tissue specific drug delivery.

PubMed

Chandrasekar, Durairaj; Sistla, Ramakrishna; Ahmad, Farhan J; Khar, Roop K; Diwan, Prakash V

2007-07-01

Folate receptor is overexpressed on the activated (but not quiescent) macrophages in both animal models and human patients with naturally occurring rheumatoid arthritis. The aim of this study was to prepare folate targeted poly(ethylene glycol) (PEG) conjugates of anionic dendrimer (G3.5 PAMAM) as targeted drug delivery systems to inflammation and to investigate its biodistribution pattern in arthritic rats. Folate-PEG-PAMAM conjugates, with different degrees of substitution were synthesized by a two-step reaction through a carbodiimide-mediated coupling reaction and loaded with indomethacin. Folate-PEG conjugation increased the drug loading efficiency by 10- to 20-fold and the in vitro release profile indicated controlled release of drug. The plasma pharmacokinetic parameters indicated an increased AUC, circulatory half-life and mean residence time for the folate-PEG conjugates. The tissue distribution studies revealed significantly lesser uptake by stomach for the folate-PEG conjugates, thereby limiting gastric-related side effect. The time-averaged relative drug exposure (r(e)) of the drug in paw for the folate-PEG conjugates ranged from 1.81 to 2.37. The overall drug targeting efficiency (T(e)) was highest for folate-PEG conjugate (3.44) when compared to native dendrimer (1.72). The folate-PEG-PAMAM conjugates are the ideal choice for targeted delivery of antiarthritic drugs to inflammation with reduced side-effects and higher targeting efficiency. Copyright 2007 Wiley Periodicals, Inc.

Administration costs of intravenous biologic drugs for rheumatoid arthritis.

PubMed

Soini, Erkki J; Leussu, Miina; Hallinen, Taru

2013-01-01

Cost-effectiveness studies explicitly reporting infusion times, drug-specific administration costs for infusions or real-payer intravenous drug cost are few in number. Yet, administration costs for infusions are needed in the health economic evaluations assessing intravenously-administered drugs. To estimate the drug-specific administration and total cost of biologic intravenous rheumatoid arthritis (RA) drugs in the adult population and to compare the obtained costs with published cost estimates. Cost price data for the infusions and drugs were systematically collected from the 2011 Finnish price lists. All Finnish hospitals with available price lists were included. Drug administration and total costs (administration cost + drug price) per infusion were analysed separately from the public health care payer's perspective. Further adjustments for drug brand, dose, and hospital type were done using regression methods in order to improve the comparability between drugs. Annual expected drug administration and total costs were estimated. A literature search not limited to RA was performed to obtain the per infusion administration cost estimates used in publications. The published costs were converted to Finnish values using base-year purchasing power parities and indexing to the year 2011. Information from 19 (95%) health districts was obtained (107 analysable prices out of 176 observations). The average drug administration cost for infliximab, rituximab, abatacept, and tocilizumab infusion in RA were €355.91; €561.21; €334.00; and €293.96, respectively. The regression-adjusted (dose, hospital type; using semi-log ordinary least squares) mean administration costs for infliximab and rituximab infusions in RA were €289.12 (95% CI €222.61-375.48) and €542.28 (95% CI €307.23-957.09). The respective expected annual drug administration costs were €2312.96 for infliximab during the first year, €1879.28 for infliximab during the forthcoming years, and €1843.75 for rituximab. The obtained average administration costs per infusion were higher (1.8-3.3 times depending on the drug) than the previously published purchasing power adjusted and indexed average administration costs for infusions in RA. The administration costs of RA infusions vary between drugs, and more effort should be made to find realistic drug-specific estimates for cost-effectiveness evaluations. The frequent assumption of intravenous drug administration costs equalling outpatient visit cost can underestimate the costs.

76 FR 11490 - Withdrawal of Approval of New Animal Drug Applications; Phenylbutazone; Pyrantel; Tylosin...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-02

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0033... AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA... INFORMATION CONTACT: John Bartkowiak, Center for Veterinary Medicine (HFV-212), Food and Drug Administration...

Immune checkpoint inhibitor-related myocarditis.

PubMed

Tajiri, Kazuko; Aonuma, Kazutaka; Sekine, Ikuo

2018-01-01

Immune checkpoint inhibitors have demonstrated significant clinical benefit in many cancers. The clinical benefit afforded by these treatments can be accompanied by a unique and distinct spectrum of adverse events. Recently, several fatal cases of immune checkpoint inhibitor-related myocarditis were reported. Although its frequency is comparatively lower than that of other immune-related adverse events, myocarditis can lead to circulatory collapse and lethal ventricular arrhythmia. Immune checkpoints, cytotoxic T-lymphocyte antigen 4 (CTLA-4) and programmed cell death protein 1 (PD-1), play important roles in establishing peripheral tolerance to the heart. Evidence from studies using genetically engineered mouse models suggests that CTLA-4 signaling terminates proliferation and promotes anergy during the primary response to cardiac self-peptide recognition. PD-1 signaling restrains autoreactive T cells that enter the peripheral tissues and recognize cardiac-peptide, maintaining them in an anergic state. Patients affected by immune checkpoint inhibitor-related myocarditis often experience rapid onset of profound hemodynamic compromise progressing to cardiogenic shock. Early diagnosis is mandatory to address specific therapy and correct the timing of circulatory support. However, the diagnosis of myocarditis is challenging due to the heterogeneity of clinical presentations. Owing to its early onset, nonspecific symptomatology and fulminant progression, especially when these drugs are used in combination, oncologists should be vigilant for immune checkpoint inhibitor-related myocarditis. With many questions yet to be answered, from basic immune biology to clinical management, future research should aim to optimize the use of these drugs by identifying predictive biomarkers of either a response to therapy or the risks of myocarditis development. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

The cell wall components peptidoglycan and lipoteichoic acid from Staphylococcus aureus act in synergy to cause shock and multiple organ failure.

PubMed Central

De Kimpe, S J; Kengatharan, M; Thiemermann, C; Vane, J R

1995-01-01

Although the incidence of Gram-positive sepsis has risen strongly, it is unclear how Gram-positive organisms (without endotoxin) initiate septic shock. We investigated whether two cell wall components from Staphylococcus aureus, peptidoglycan (PepG) and lipoteichoic acid (LTA), can induce the inflammatory response and multiple organ dysfunction syndrome (MODS) associated with septic shock caused by Gram-positive organisms. In cultured macrophages, LTA (10 micrograms/ml), but not PepG (100 micrograms/ml), induces the release of nitric oxide measured as nitrite. PepG, however, caused a 4-fold increase in the production of nitrite elicited by LTA. Furthermore, PepG antibodies inhibited the release of nitrite elicited by killed S. aureus. Administration of both PepG (10 mg/kg; i.v.) and LTA (3 mg/kg; i.v.) in anesthetized rats resulted in the release of tumor necrosis factor alpha and interferon gamma and MODS, as indicated by a decrease in arterial oxygen pressure (lung) and an increase in plasma concentrations of bilirubin and alanine aminotransferase (liver), creatinine and urea (kidney), lipase (pancreas), and creatine kinase (heart or skeletal muscle). There was also the expression of inducible nitric oxide synthase in these organs, circulatory failure, and 50% mortality. These effects were not observed after administration of PepG or LTA alone. Even a high dose of LTA (10 mg/kg) causes only circulatory failure but no MODS. Thus, our results demonstrate that the two bacterial wall components, PepG and LTA, work together to cause systemic inflammation and multiple systems failure associated with Gram-positive organisms. Images Fig. 2 PMID:7479784

Molecular-biological analysis of the effect of methamphetamine on the heart in restrained mice.

PubMed

Shinone, Kotaro; Tomita, Masafumi; Inoue, Hiromasa; Nakagawa, Yasuhisa; Ikemura, Mayumi; Nata, Masayuki

2010-03-01

In order to investigate the interaction in the heart between the administration of methamphetamine (MAP) and restraint of the body following it, we administrated MAP intraperitoneally to mice and restrained them, and then determined the level of mRNA expression of 22 genes in the heart using quantitative RT-PCR method. The mRNA expressions of Nfkbiz, Nr4a1 and Dusp1 changed significantly after the administration of MAP, suggesting the induction of an inflammatory condition such as damage to the myocardium. Moreover, the serum concentrations of inflammatory cytokines such as tumor necrosis factor-alpha, interleukin (IL)-1 beta and IL-6 were significantly increased by the administration of MAP. On the other hand, the mRNA expressions of Rgs2 and Rasd1 were changed by both the administration of MAP and body restraint without interaction, which indicated that these insults affected the circulatory system additively or synergistically. From these results, it is likely that the administration of MAP, followed by body restraint, might cause acute myocardial damage due to the direct myocardial toxic effect of MAP, myocardial hypoxia and/or severe hypertension, which is one of the mechanisms for sudden death in MAP abusers who were restrained due to their excited state. (c) 2010. Published by Elsevier Ireland Ltd.

Drug overdose surveillance using hospital discharge data.

PubMed

Slavova, Svetla; Bunn, Terry L; Talbert, Jeffery

2014-01-01

We compared three methods for identifying drug overdose cases in inpatient hospital discharge data on their ability to classify drug overdoses by intent and drug type(s) involved. We compared three International Classification of Diseases, Ninth Revision, Clinical Modification code-based case definitions using Kentucky hospital discharge data for 2000-2011. The first definition (Definition 1) was based on the external-cause-of-injury (E-code) matrix. The other two definitions were based on the Injury Surveillance Workgroup on Poisoning (ISW7) consensus recommendations for national and state poisoning surveillance using the principal diagnosis or first E-code (Definition 2) or any diagnosis/E-code (Definition 3). Definition 3 identified almost 50% more drug overdose cases than did Definition 1. The increase was largely due to cases with a first-listed E-code describing a drug overdose but a principal diagnosis that was different from drug overdose (e.g., mental disorders, or respiratory or circulatory system failure). Regardless of the definition, more than 53% of the hospitalizations were self-inflicted drug overdoses; benzodiazepines were involved in about 30% of the hospitalizations. The 2011 age-adjusted drug overdose hospitalization rate in Kentucky was 146/100,000 population using Definition 3 and 107/100,000 population using Definition 1. The ISW7 drug overdose definition using any drug poisoning diagnosis/E-code (Definition 3) is potentially the highest sensitivity definition for counting drug overdose hospitalizations, including by intent and drug type(s) involved. As the states enact policies and plan for adequate treatment resources, standardized drug overdose definitions are critical for accurate reporting, trend analysis, policy evaluation, and state-to-state comparison.

[Anatomophysiological bases of drug administration. Dosage forms and routes of administration].

PubMed

Carillo Norte, Juan Antonio; Gañán Presmanes, Yolanda

2010-12-01

The administration of the right dose to the right patient is of paramount importance to obtain an optimal drug response within the scope of clinical pharmacology and tailored medicine. The marketing of safer and more efficient drug entities, along with the development of new drug administration devices provide a major boost for the diagnosis and treatment of diseases, beyond our imagination. However dose adjustment is not enough to produced the desired effect, and drug therapy should include an appropriate route of drug administration. Currently, there are many different and sophisticated methods to incorporate drugs into the patients that nurses should be familiar with. When there is no contraindication, oral route of drug administration is of choice and most frequently used as a physiological pathway of drug intake.

21 CFR 20.120 - Records available in Food and Drug Administration Public Reading Rooms.

Code of Federal Regulations, 2011 CFR

2011-04-01

... Public Reading Rooms. 20.120 Section 20.120 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF....120 Records available in Food and Drug Administration Public Reading Rooms. (a) The Food and Drug Administration operates two public reading rooms. The Freedom of Information Staff's Public Reading Room is...

78 FR 6824 - Considerations Regarding Food and Drug Administration Review and Regulation of Drugs for the...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-31

... Amyotrophic Lateral Sclerosis; Public Hearing AGENCY: Food and Drug Administration, HHS. ACTION: Notice of public hearing; request for comments. SUMMARY: The Food and Drug Administration (FDA or the Agency) is... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-N-0035...

21 CFR 20.120 - Records available in Food and Drug Administration Public Reading Rooms.

Code of Federal Regulations, 2010 CFR

2010-04-01

... Public Reading Rooms. 20.120 Section 20.120 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF....120 Records available in Food and Drug Administration Public Reading Rooms. (a) The Food and Drug Administration operates two public reading rooms. The Freedom of Information Staff's Public Reading Room is...

78 FR 51732 - The Food and Drug Administration/European Medicines Agency Orphan Product Designation and Grant...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-21

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-N-0001] The Food and Drug Administration/European Medicines Agency Orphan Product Designation and Grant Public Workshop AGENCY: Food and Drug Administration, HHS. ACTION: Notice of public workshop. The Food and Drug...

78 FR 36711 - Food and Drug Administration Safety and Innovation Act Title VII-Drug Supply Chain; Standards for...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-19

...: Food and Drug Administration, HHS. ACTION: Notification of public meeting; request for comments. SUMMARY: The Food and Drug Administration (FDA or Agency) is announcing a public meeting regarding FDA's... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Chapter I [Docket Nos...

78 FR 21085 - Establishment of a Public Docket for Administrative Detention Under the Food and Drug...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-09

... Administration Safety and Innovation Act AGENCY: Food and Drug Administration, HHS. ACTION: Establishment of... authority with respect to drugs under the Food and Drug Administration Safety and Innovation Act (FDASIA....regulations.gov . Submit written comments to the Division of Dockets Management (HFA- 305), Food and Drug...

75 FR 386 - Memorandum of Understanding Between the United States Department of Health and Human Services...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-05

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2009-N-0667... Services, Food and Drug Administration, Center for Drug Evaluation and Research and Northeastern University AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA...

75 FR 1274 - Implantation or Injectable Dosage Form New Animal Drugs; Florfenicol and Flunixin

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-11

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 522 [Docket No... AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration... Veterinary Medicine (HFV-130), Food and Drug Administration, 7500 Standish Pl., Rockville, MD 20855, 240-276...

75 FR 13766 - Food and Drug Administration and Process Analytical Technology for Pharma Manufacturing: Food and...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-23

... Administration--Partnering With Industry; Public Conference AGENCY: Food and Drug Administration, HHS. ACTION: Notice of public conference. The Food and Drug Administration (FDA) is announcing a joint conference with... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0001...

28 CFR Appendix B to Part 61 - Drug Enforcement Administration Procedures Relating to the Implementation of the National...

Code of Federal Regulations, 2010 CFR

2010-07-01

... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Drug Enforcement Administration... ENVIRONMENTAL POLICY ACT Pt. 61, App. B Appendix B to Part 61—Drug Enforcement Administration Procedures.... This part applies to all organizational elements of the Drug Enforcement Administration [DEA]. 2...

An observational study of drug administration errors in a Malaysian hospital (study of drug administration errors).

PubMed

Chua, S S; Tea, M H; Rahman, M H A

2009-04-01

Drug administration errors were the second most frequent type of medication errors, after prescribing errors but the latter were often intercepted hence, administration errors were more probably to reach the patients. Therefore, this study was conducted to determine the frequency and types of drug administration errors in a Malaysian hospital ward. This is a prospective study that involved direct, undisguised observations of drug administrations in a hospital ward. A researcher was stationed in the ward under study for 15 days to observe all drug administrations which were recorded in a data collection form and then compared with the drugs prescribed for the patient. A total of 1118 opportunities for errors were observed and 127 administrations had errors. This gave an error rate of 11.4 % [95% confidence interval (CI) 9.5-13.3]. If incorrect time errors were excluded, the error rate reduced to 8.7% (95% CI 7.1-10.4). The most common types of drug administration errors were incorrect time (25.2%), followed by incorrect technique of administration (16.3%) and unauthorized drug errors (14.1%). In terms of clinical significance, 10.4% of the administration errors were considered as potentially life-threatening. Intravenous routes were more likely to be associated with an administration error than oral routes (21.3% vs. 7.9%, P < 0.001). The study indicates that the frequency of drug administration errors in developing countries such as Malaysia is similar to that in the developed countries. Incorrect time errors were also the most common type of drug administration errors. A non-punitive system of reporting medication errors should be established to encourage more information to be documented so that risk management protocol could be developed and implemented.

Health care utilization and costs for diseases of the circulatory system in a corporate setting.

PubMed

Tsai, S P; Bernacki, E J; Reedy, S M; Miller, K E

1988-01-01

This article presents the health care utilization and costs for diseases of the circulatory system among 14,162 employees and their spouses based on medical insurance claims data analysis. Diseases of the circulatory system ranked first among insurance claims and costs accounting for 23% ($4.6 million) of the plan's total health care costs ($19.7 million) for the 1984 policy year. Overall, 57% of these expenditures were for hospital care, the proportion for hospital costs being as high as 64% for heart diseases and as low as 20% for hypertension. Male employees had higher utilization for both in-hospital and out-patient services than females. Utilization rates and costs dramatically increased for individuals 50 years or older. Costs for surgical and diagnostic procedures amounted to 8% of the total costs of circulatory system disorders. This article provides an example of the utility of claims analysis for morbidity surveillance. The analyses and parameters measured herein can be viewed as prerequisites to the development of health care management and health promotion strategies aimed at reducing health care cost for diseases of the circulatory system in a corporate setting.

A Comparative Study of Different Hypothermic Circulatory Arrest Strategies on Aortic Surgery.

ClinicalTrials.gov

2018-03-22

Morality; Hypothermic Circulatory Arrest Time; Aortic-cross Clamping Time; Cardiopulmonary Bypass Time; Operation Time; Re-Thoracotomy; ICU Stay; Mechanical Ventilation Time; Blood Transfusion; Neurological Disorder; Dialysis; Aneurysm; Endoleak; Hospital Stay

76 FR 61366 - Food and Drug Administration Transparency Initiative: Draft Proposals for Public Comment to...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-04

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2009-N-0247] Food and Drug Administration Transparency Initiative: Draft Proposals for Public Comment to Increase...: Food and Drug Administration, HHS. [[Page 61367

77 FR 60125 - Generic Drug Facilities, Sites and Organizations

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-02

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-N-1006] Generic Drug Facilities, Sites and Organizations AGENCY: Food and Drug Administration, HHS. ACTION: Notice of Requirement. SUMMARY: The Food and Drug Administration (FDA) is notifying generic drug facilities...

21 CFR 1316.10 - Administrative probable cause.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 9 2010-04-01 2010-04-01 false Administrative probable cause. 1316.10 Section 1316.10 Food and Drugs DRUG ENFORCEMENT ADMINISTRATION, DEPARTMENT OF JUSTICE ADMINISTRATIVE FUNCTIONS, PRACTICES, AND PROCEDURES Administrative Inspections § 1316.10 Administrative probable cause. If the judge...

[Clinical value of ammonia determination in venous blood in chronic cor pulmonale].

PubMed

Szulc, E J; Sworzyńska, I

1978-01-01

The authors have examined 43 workers of the Warszawa works: 20 healthy persons and 23 with chronic pulmocardiac syndrome. An increased ammonia level in venous blood, above 48 gamma %, was found in those with chronic pulmocardiac syndrome with simultaneous circulatory insufficiency. Ammonia level in the blood of those with chronic pulmocardiac syndrome but without circulatory insufficiency was normal. These studies indicate that the increase of ammonia concentration in venous blood in chronic pulmocardiac syndrome results from disturbance in hepatic cell function, intensified during circulatory insufficiency.

75 FR 73951 - Amendments to General Regulations of the Food and Drug Administration

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-30

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Parts 1, 14, and 17 [Docket No. FDA-2010-N-0560] RIN 0910-AG55 Amendments to General Regulations of the Food and Drug Administration AGENCY: Food and Drug Administration, HHS. ACTION: Direct final rule. SUMMARY: The Food and Drug...

75 FR 73984 - Amendments to General Regulations of the Food and Drug Administration

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-30

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Parts 1, 14, and 17 [Docket No. FDA-2010-N-0560] RIN 0910-AG55 Amendments to General Regulations of the Food and Drug Administration AGENCY: Food and Drug Administration, HHS. ACTION: Proposed rule. SUMMARY: The Food and Drug...

78 FR 102 - Guidance for Industry and Food and Drug Administration Staff; eCopy Program for Medical Device...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-02

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-D-1056] Guidance for Industry and Food and Drug Administration Staff; eCopy Program for Medical Device Submissions; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug...

77 FR 11550 - Draft Guidance for Industry on Notification to Food and Drug Administration of Issues That May...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-27

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-D-0140] Draft Guidance for Industry on Notification to Food and Drug Administration of Issues That May Result in a Prescription Drug Shortage; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice...

77 FR 20826 - Guidance for Industry and Food and Drug Administration Staff; Food and Drug Administration and...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-06

...] Guidance for Industry and Food and Drug Administration Staff; Food and Drug Administration and Industry... Administration (FDA) is announcing the availability of the guidance entitled ``Guidance for Industry and Food and... written requests for single copies of the guidance document entitled ``Guidance for Industry and Food and...

21 CFR 20.20 - Policy on disclosure of Food and Drug Administration records.

Code of Federal Regulations, 2010 CFR

2010-04-01

... Administration records. 20.20 Section 20.20 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... the record will be so used, may be requested when: (1) The requested record is contained in a Privacy... Administration records. (a) The Food and Drug Administration will make the fullest possible disclosure of records...

76 FR 59705 - Guidance for Industry on User Fee Waivers, Reductions, and Refunds for Drug and Biological...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-27

... Drug Information, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New..., and Development (HFM-40), Center for Biologics Evaluation and Research, Food and Drug Administration..., Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 51...

77 FR 61417 - Guidance for Industry on Acute Bacterial Sinusitis: Developing Drugs for Treatment; Availability

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-09

... of Drug Information, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New..., Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 22... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2007-D-0375...

77 FR 64346 - Nonprescription Drugs Advisory Committee; Amendment of Notice

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-19

... for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Building 31... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-N-0001] Nonprescription Drugs Advisory Committee; Amendment of Notice AGENCY: Food and Drug Administration, HHS. ACTION...

75 FR 1275 - New Animal Drugs; Ractopamine

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-11

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 558 [Docket No. FDA-2009-N-0665] New Animal Drugs; Ractopamine AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug regulations to...

78 FR 22553 - Generic Drug Facilities, Sites, and Organizations

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-16

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-N-0391] Generic Drug Facilities, Sites, and Organizations AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is announcing that the generic drug facility self...

75 FR 81455 - New Animal Drugs; Deslorelin

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-28

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Parts 510 and 522 [Docket No. FDA-2010-N-0002] New Animal Drugs; Deslorelin AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug...

76 FR 17025 - New Animal Drugs; Oxytetracycline

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-28

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Parts 520 and 529 [Docket No. FDA-2011-N-0003] New Animal Drugs; Oxytetracycline AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug...

76 FR 57906 - New Animal Drugs; Gamithromycin

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-19

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Parts 522 and 556 [Docket No. FDA-2011-N-0003] New Animal Drugs; Gamithromycin AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug...

77 FR 32897 - New Animal Drugs; Change of Sponsor's Name

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-04

.... FDA-2012-N-0002] New Animal Drugs; Change of Sponsor's Name AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug... 21 CFR Part 510 Administrative practice and procedure, Animal drugs, Labeling, Reporting and...

Effects of sharing information on drug administration errors in pediatric wards: a pre–post intervention study

PubMed Central

Chua, Siew-Siang; Choo, Sim-Mei; Sulaiman, Che Zuraini; Omar, Asma; Thong, Meow-Keong

2017-01-01

Background and purpose Drug administration errors are more likely to reach the patient than other medication errors. The main aim of this study was to determine whether the sharing of information on drug administration errors among health care providers would reduce such problems. Patients and methods This study involved direct, undisguised observations of drug administrations in two pediatric wards of a major teaching hospital in Kuala Lumpur, Malaysia. This study consisted of two phases: Phase 1 (pre-intervention) and Phase 2 (post-intervention). Data were collected by two observers over a 40-day period in both Phase 1 and Phase 2 of the study. Both observers were pharmacy graduates: Observer 1 just completed her undergraduate pharmacy degree, whereas Observer 2 was doing her one-year internship as a provisionally registered pharmacist in the hospital under study. A drug administration error was defined as a discrepancy between the drug regimen received by the patient and that intended by the prescriber and also drug administration procedures that did not follow standard hospital policies and procedures. Results from Phase 1 of the study were analyzed, presented and discussed with the ward staff before commencement of data collection in Phase 2. Results A total of 1,284 and 1,401 doses of drugs were administered in Phase 1 and Phase 2, respectively. The rate of drug administration errors reduced significantly from Phase 1 to Phase 2 (44.3% versus 28.6%, respectively; P<0.001). Logistic regression analysis showed that the adjusted odds of drug administration errors in Phase 1 of the study were almost three times that in Phase 2 (P<0.001). The most common types of errors were incorrect administration technique and incorrect drug preparation. Nasogastric and intravenous routes of drug administration contributed significantly to the rate of drug administration errors. Conclusion This study showed that sharing of the types of errors that had occurred was significantly associated with a reduction in drug administration errors. PMID:28356748

Pathotropic nanoparticles for cancer gene therapy Rexin-G IV: three-year clinical experience.

PubMed

Gordon, Erlinda M; Lopez, Francisco F; Cornelio, Gerardo H; Lorenzo, Conrado C; Levy, John P; Reed, Rebecca A; Liu, Liqiong; Bruckner, Howard W; Hall, Frederick L

2006-11-01

Metastatic cancer is a life-threatening illness with a predictably fatal outcome, thereby representing a major unmet medical need. In 2003, Rexin-G became the world's first targeted injectable vector approved for clinical trials in the treatment of intractable metastatic disease. Uniquely suited, by design, to function within the context of the human circulatory system, Rexin-G is a pathotropic (disease-seeking) gene delivery system bearing a designer killer gene; in essence, a targeted nanoparticle that seeks out and selectively accumulates in metastatic sites upon intravenous infusion. The targeted delivery of the cytocidal gene to primary tumors and metastatic foci, in effective local concentrations, compels both cancer cells and tumor-associated neovasculature to self-destruct, without causing untoward collateral damage to non-target organs. In this study: i) we report the results of three distinctive clinical studies which demonstrate the initial proofs of concept, safety, and efficacy of Rexin-G when used as a single agent for advanced or metastatic cancer, ii) we introduce the quantitative foundations of an innovative personalized treatment regimen, designated the 'Calculus of Parity', based on a patient's calculated tumor burden, iii) we propose a refinement of surrogate end-points commonly used for defining success in cancer therapy, and iv) we map out a strategic plan for the accelerated approval of Rexin-G based on the oncologic Threshold of Credibility paradigm being developed by the Food and Drug Administration.

Devices as destination therapy.

PubMed

Kukuy, Eugene L; Oz, Mehmet C; Rose, Eric A; Naka, Yoshifumi

2003-02-01

The use of circulatory support as destination therapy has been a goal for the treatment of endstage heart failure for several decades. Current investigations are evaluating several circulatory pumps with that particular objective. With continued modification of design, the current and future pumps will become more reliable and provide improved quality of life to patients in need of mechanical circulatory assistance. The new pumps on the horizon specifically address reliability, size, and cost, and are based on the centrifugal system. These devices use the Maglev (Magnetic Levitation) concept that allows for frictionless pumping, low thrombogenicity, minimal noise, and increased durability. Further research with this goal in mind and support from the federal government will be the key to the future use of circulatory assistance as destination therapy for heart failure patients. In addition, the cost-effectiveness of these devices will need to be maintained as the technology improves, as in any new technology that confronts a more intuitive option like the native heart.

76 FR 45402 - Advisory Committee; Medical Imaging Drugs Advisory Committee; Re-Establishment

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-29

..., Advisory committees, Color additives, Drugs, Radiation protection. Therefore, under the Federal Food, Drug... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 14 [Docket No... AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration...

21 CFR 20.107 - Food and Drug Administration manuals.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 1 2012-04-01 2012-04-01 false Food and Drug Administration manuals. 20.107 Section 20.107 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL PUBLIC INFORMATION Availability of Specific Categories of Records § 20.107 Food and Drug...

21 CFR 20.107 - Food and Drug Administration manuals.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 1 2011-04-01 2011-04-01 false Food and Drug Administration manuals. 20.107 Section 20.107 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL PUBLIC INFORMATION Availability of Specific Categories of Records § 20.107 Food and Drug...

21 CFR 20.107 - Food and Drug Administration manuals.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 1 2014-04-01 2014-04-01 false Food and Drug Administration manuals. 20.107 Section 20.107 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL PUBLIC INFORMATION Availability of Specific Categories of Records § 20.107 Food and Drug...

21 CFR 20.107 - Food and Drug Administration manuals.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 1 2013-04-01 2013-04-01 false Food and Drug Administration manuals. 20.107 Section 20.107 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL PUBLIC INFORMATION Availability of Specific Categories of Records § 20.107 Food and Drug...

76 FR 40808 - Oral Dosage Form New Animal Drugs; Amprolium

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-12

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 520 [Docket No. FDA-2011-N-0003] Oral Dosage Form New Animal Drugs; Amprolium AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug...

76 FR 2807 - New Animal Drugs; Change of Sponsor

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-18

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 510 [Docket No. FDA-2010-N-0002] New Animal Drugs; Change of Sponsor AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug regulations to...

76 FR 59023 - Oral Dosage Form New Animal Drugs; Tylosin

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-23

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 520 [Docket No. FDA-2011-N-0003] Oral Dosage Form New Animal Drugs; Tylosin AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug...

75 FR 79295 - New Animal Drugs; Mupirocin

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-20

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Parts 510 and 524 [Docket No. FDA-2010-N-0002] New Animal Drugs; Mupirocin AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug regulations to...

75 FR 67031 - Oral Dosage Form New Animal Drugs; Domperidone

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-01

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 520 [Docket No. FDA-2010-N-0002] Oral Dosage Form New Animal Drugs; Domperidone AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug...

77 FR 3927 - Oral Dosage Form New Animal Drugs; Deracoxib

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-26

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 520 [Docket No. FDA-2011-N-0003] Oral Dosage Form New Animal Drugs; Deracoxib AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug...

78 FR 22 - New Animal Drugs; Meloxicam; Nicarbazin

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-02

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Parts 520 and 558 [Docket No. FDA-2012-N-0002] New Animal Drugs; Meloxicam; Nicarbazin AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug...

76 FR 6326 - New Animal Drugs; Masitinib

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-04

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Parts 510 and 516 [Docket No. FDA-2011-N-0003] New Animal Drugs; Masitinib AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug regulations to...

77 FR 15960 - Oral Dosage Form New Animal Drugs; Pergolide

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-19

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 520 [Docket No. FDA-2011-N-0003] Oral Dosage Form New Animal Drugs; Pergolide AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug...

76 FR 18648 - Oral Dosage Form New Animal Drugs; Robenacoxib

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-05

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 520 [Docket No. FDA-2011-N-0003] Oral Dosage Form New Animal Drugs; Robenacoxib AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug...

76 FR 78149 - Oral Dosage Form New Animal Drugs; Estriol

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-16

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 520 [Docket No. FDA-2011-N-0003] Oral Dosage Form New Animal Drugs; Estriol AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug...

21 CFR 20.107 - Food and Drug Administration manuals.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Food and Drug Administration manuals. 20.107 Section 20.107 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL PUBLIC INFORMATION Availability of Specific Categories of Records § 20.107 Food and Drug...

77 FR 4224 - New Animal Drugs; Change of Sponsor's Name

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-27

.... FDA-2011-N-0003] New Animal Drugs; Change of Sponsor's Name AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug.... 801-808. List of Subjects in 21 CFR Part 510 Administrative practice and procedure, Animal drugs...

78 FR 42088 - Anesthetic and Analgesic Drug Products Advisory Committee; Cancellation

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-15

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-N-0001] Anesthetic and Analgesic Drug Products Advisory Committee; Cancellation AGENCY: Food and Drug Administration..., Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 31...

77 FR 59930 - Clinical Development Programs for Disease-Modifying Agents for Peripheral Neuropathy; Public...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-01

... for comments. SUMMARY: The Food and Drug Administration (FDA), Center for Drug Evaluation and Research... Contacts: Randi Clark, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New..., Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Silver...

78 FR 13686 - Draft Guidance for Industry and Review Staff on Pediatric Information Incorporated Into Human...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-28

... Prescription Drug and Biological Products Labeling; Availability AGENCY: Food and Drug Administration, HHS... (BPCA) and the Pediatric Research Equity Act (PREA), as amended by the Food and Drug Administration... Drug Information, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New...

The sympathetic/parasympathetic imbalance in heart failure with reduced ejection fraction

PubMed Central

Floras, John S.; Ponikowski, Piotr

2015-01-01

Cardiovascular autonomic imbalance, a cardinal phenotype of human heart failure, has adverse implications for symptoms during wakefulness and sleep; for cardiac, renal, and immune function; for exercise capacity; and for lifespan and mode of death. The objectives of this Clinical Review are to summarize current knowledge concerning mechanisms for disturbed parasympathetic and sympathetic circulatory control in heart failure with reduced ejection fraction and its clinical and prognostic implications; to demonstrate the patient-specific nature of abnormalities underlying this common phenotype; and to illustrate how such variation provides opportunities to improve or restore normal sympathetic/parasympathetic balance through personalized drug or device therapy. PMID:25975657

Acute Right Ventricular Dysfunction in Intensive Care Unit

PubMed Central

Domingo, Enric

2017-01-01

The role of the left ventricle in ICU patients with circulatory shock has long been considered. However, acute right ventricle (RV) dysfunction causes and aggravates many common critical diseases (acute respiratory distress syndrome, pulmonary embolism, acute myocardial infarction, and postoperative cardiac surgery). Several supportive therapies, including mechanical ventilation and fluid management, can make RV dysfunction worse, potentially exacerbating shock. We briefly review the epidemiology, pathophysiology, diagnosis, and recommendations to guide management of acute RV dysfunction in ICU patients. Our aim is to clarify the complex effects of mechanical ventilation, fluid therapy, vasoactive drug infusions, and other therapies to resuscitate the critical patient optimally. PMID:29201914

ABO-incompatible blood transfusion and invasive therapeutic approaches during pediatric cardiopulmonary bypass.

PubMed

Aliç, Yasin; Akpek, Elif A; Dönmez, Asli; Ozkan, Süleyman; Perfusionist, Güray Yener; Aslamaci, Sait

2008-10-01

Human error has been identified as a major source of ABO-incompatible blood transfusion which most often results from blood being given to the wrong patient. We present a case of inadvertent administration of ABO-incompatible blood to a 6-mo-old child who underwent congenital heart surgery and discuss the use of invasive therapeutic approaches. Invasive techniques included total circulatory arrest and large-volume exchange transfusion, along with conventional ultrafiltration and plasmapheresis, which could all be performed rapidly and effectively. The combination of standard pharmacologic therapies and alternative invasive techniques after a massive ABO-incompatible blood transfusion led to a favorable outcome in our patient.

78 FR 14557 - Guidance for Industry and Food and Drug Administration Staff: Investigational Device Exemption...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-06

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2009-D-0010] Guidance for Industry and Food and Drug Administration Staff: Investigational Device Exemption Guidance for Retinal Prostheses; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The...

77 FR 49449 - Food and Drug Administration Clinical Trial Requirements, Compliance, and Good Clinical Practice...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-16

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-N-0001] Food and Drug Administration Clinical Trial Requirements, Compliance, and Good Clinical Practice; Public Workshop AGENCY: Food and Drug Administration, HHS. ACTION: Notice of public workshop. The Food...

78 FR 76842 - Food and Drug Administration/American Academy of Ophthalmology Workshop on Developing Novel...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-19

... for Premium Intraocular Lenses; Public Workshop AGENCY: Food and Drug Administration, HHS. ACTION: Notice. The Food and Drug Administration (FDA) is announcing the following public workshop entitled ``FDA... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-N-0001...

75 FR 22819 - Considerations Regarding Food and Drug Administration Review and Regulation of Articles for the...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-30

... Diseases; Public Hearing AGENCY: Food and Drug Administration, HHS. ACTION: Notice of public hearing; request for comment. SUMMARY: The Food and Drug Administration (FDA) is announcing a public hearing... with rare diseases, a recent public law (Agriculture, Rural Development, Food and Drug Administration...

78 FR 54901 - Food and Drug Administration/American Academy of Ophthalmology Workshop on Developing Novel...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-06

... for Premium Intraocular Lenses; Public Workshop AGENCY: Food and Drug Administration, HHS. ACTION: Notice of public workshop. The Food and Drug Administration (FDA) is announcing the following public... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-N-0001...

76 FR 78933 - Food and Drug Administration Clinical Trial Requirements, Regulations, Compliance, and Good...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-20

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0002] Food and Drug Administration Clinical Trial Requirements, Regulations, Compliance, and Good Clinical Practice; Public Workshop AGENCY: Food and Drug Administration, HHS. ACTION: Notice of public workshop. The...

76 FR 17138 - Food and Drug Administration Clinical Trial Requirements, Regulations, Compliance, and Good...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-28

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0002] Food and Drug Administration Clinical Trial Requirements, Regulations, Compliance, and Good Clinical Practice; Public Workshop AGENCY: Food and Drug Administration, HHS. ACTION: Notice of public workshop. The...

75 FR 14448 - Food and Drug Administration Clinical Trial Requirements, Regulations, Compliance, and Good...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-25

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0001] Food and Drug Administration Clinical Trial Requirements, Regulations, Compliance, and Good Clinical Practices; Public Workshop AGENCY: Food and Drug Administration, HHS. ACTION: Notice of public workshop...

77 FR 49448 - Food and Drug Administration Clinical Trial Requirements, Compliance, and Good Clinical Practice...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-16

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-N-0001] Food and Drug Administration Clinical Trial Requirements, Compliance, and Good Clinical Practice; Public Workshop AGENCY: Food and Drug Administration, HHS. ACTION: Notice of public workshop. The Food...

76 FR 6142 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-03

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0598... Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is announcing... CONTACT: Johnny Vilela, Office of Information Management, Food and Drug Administration, 1350 Piccard Dr...

78 FR 12329 - Distinguishing Medical Device Recalls From Product Enhancements; Reporting Requirements; Draft...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-22

... Industry and Food and Drug Administration Staff; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is announcing the availability of the... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-D-0114...

76 FR 789 - Guidance for Industry and Food and Drug Administration Staff; Section 905(j) Reports...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-06

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-D-0635] Guidance for Industry and Food and Drug Administration Staff; Section 905(j) Reports: Demonstrating Substantial Equivalence for Tobacco Products; Availability AGENCY: Food and Drug Administration, HHS. ACTION...

75 FR 47603 - Draft Guidance for Industry and Food and Drug Administration Staff; Recommendations for Premarket...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-06

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-D-0395] Draft Guidance for Industry and Food and Drug Administration Staff; Recommendations for Premarket Notifications for Lamotrigine and Zonisamide Assays; Availability AGENCY: Food and Drug Administration, HHS...

76 FR 50740 - Draft Guidance for Industry and Food and Drug Administration Staff; Procedures for Handling...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-16

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-D-0514] Draft Guidance for Industry and Food and Drug Administration Staff; Procedures for Handling Section 522 Postmarket Surveillance Studies; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice...

75 FR 39537 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-09

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0101...: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is... CONTACT: Elizabeth Berbakos, Office of Information Management, Food and Drug Administration, 1350 Piccard...

77 FR 26162 - Amendments to Sterility Test Requirements for Biological Products

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-03

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Parts 600, 610, and... AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration...), Food and Drug Administration, 1401 Rockville Pike, suite 200N, Rockville, MD 20852- 1448, 301-827-6210...

75 FR 79383 - Unapproved Animal Drugs

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-20

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0528] Unapproved Animal Drugs AGENCY: Food and Drug Administration, HHS. ACTION: Notice; request for comments. SUMMARY: The Food and Drug Administration (FDA, the Agency) is soliciting comments from stakeholders on...

Canadian Guidelines for Controlled Pediatric Donation After Circulatory Determination of Death—Summary Report*

PubMed Central

Hornby, Laura; Rochwerg, Bram; van Manen, Michael; Dhanani, ; Sonny; Sivarajan, V. Ben; Appleby, Amber; Bennett, Mary; Buchman, Daniel; Farrell, Catherine; Goldberg, Aviva; Greenberg, Rebecca; Singh, Ram; Nakagawa, Thomas A.; Witteman, William; Barter, Jill; Beck, Allon; Coughlin, Kevin; Conradi, Alf; Cupido, Cynthia; Dawson, Rosanne; Dipchand, Anne; Freed, Darren; Hornby, Karen; Langlois, Valerie; Mack, Cheryl; Mahoney, Meagan; Manhas, Deepak; Tomlinson, Christopher; Zavalkoff, Samara; Shemie, Sam D.

2017-01-01

Objectives: Create trustworthy, rigorous, national clinical practice guidelines for the practice of pediatric donation after circulatory determination of death in Canada. Methods: We followed a process of clinical practice guideline development based on World Health Organization and Canadian Medical Association methods. This included application of Grading of Recommendations Assessment, Development, and Evaluation methodology. Questions requiring recommendations were generated based on 1) 2006 Canadian donation after circulatory determination of death guidelines (not pediatric specific), 2) a multidisciplinary symposium of national and international pediatric donation after circulatory determination of death leaders, and 3) a scoping review of the pediatric donation after circulatory determination of death literature. Input from these sources drove drafting of actionable questions and Good Practice Statements, as defined by the Grading of Recommendations Assessment, Development, and Evaluation group. We performed additional literature reviews for all actionable questions. Evidence was assessed for quality using Grading of Recommendations Assessment, Development, and Evaluation and then formulated into evidence profiles that informed recommendations through the evidence-to-decision framework. Recommendations were revised through consensus among members of seven topic-specific working groups and finalized during meetings of working group leads and the planning committee. External review was provided by pediatric, critical care, and critical care nursing professional societies and patient partners. Results: We generated 63 Good Practice Statements and seven Grading of Recommendations Assessment, Development, and Evaluation recommendations covering 1) ethics, consent, and withdrawal of life-sustaining therapy, 2) eligibility, 3) withdrawal of life-sustaining therapy practices, 4) ante and postmortem interventions, 5) death determination, 6) neonatal pediatric donation after circulatory determination of death, 7) cardiac and innovative pediatric donation after circulatory determination of death, and 8) implementation. For brevity, 48 Good Practice Statement and truncated justification are included in this summary report. The remaining recommendations, detailed methodology, full Grading of Recommendations Assessment, Development, and Evaluation tables, and expanded justifications are available in the full text report. Conclusions: This process showed that rigorous, transparent clinical practice guideline development is possible in the domain of pediatric deceased donation. Application of these recommendations will increase access to pediatric donation after circulatory determination of death across Canada and may serve as a model for future clinical practice guideline development in deceased donation. PMID:28925929

Outcomes of pediatric patients supported with continuous-flow ventricular assist devices: A report from the Pediatric Interagency Registry for Mechanical Circulatory Support (PediMACS).

PubMed

Rossano, Joseph W; Lorts, Angela; VanderPluym, Christina J; Jeewa, Aamir; Guleserian, Kristine J; Bleiweis, Mark S; Reinhartz, Olaf; Blume, Elizabeth D; Rosenthal, David N; Naftel, David C; Cantor, Ryan S; Kirklin, James K

2016-05-01

Continuous-flow (CF) ventricular assist devices (VADs) have largely replaced pulsatile-flow VADs in adult patients. However, there are few data on CF VADs among pediatric patients. In this study we aimed to describe the overall use, patients' characteristics and outcomes of CF VADs in this population. The Pediatric Interagency Registry for Mechanical Circulatory Support (PediMACS) is a national registry for U.S. Food and Drug Adminstration (FDA)-approved VADs in patients <19 years of age. Patients undergoing placement of durable CF VADs between September 2012 and June 2015 were included and outcomes were compared with those of adults from the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS). CF VADs were implanted in 109 patients at 35 hospitals. The median age at implantation was 15 years (2.8 to 18.9 years) and median weight was 62 kg (range 16 to 141 kg). The underlying disease was cardiomyopathy in 89 (82%) patients. The INTERMACS level at time of implant was Level 1 in 20 (19%), Level 2 in 64 (61%) and Levels 3 to 7 in 21 (20%) patients. Most were implanted as LVADs (n = 102, 94%). Median duration of support was 2.3 months (range <1 day to 28 months). Serious adverse event rates were low, including neurologic dysfunction (early event rate 4.1 per 100 patient-months with 2 late events). Competing outcomes analysis at 6 months post-implant indicated 61% transplanted, 31% alive with device in place and 8% death before transplant. These outcomes compared favorably with the 3,894 adults supported with CF VADs as a bridge to transplant. CF VADs are commonly utilized in older children and adolescents, with excellent survival rates. Further study is needed to understand impact of patient and device characteristics on outcomes in pediatric patients. Copyright © 2016 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Accuracy of manual entry of drug administration data into an anesthesia information management system.

PubMed

Avidan, Alexander; Dotan, Koren; Weissman, Charles; Cohen, Matan J; Levin, Phillip D

2014-11-01

Data on drug administration are entered manually into anesthesia information management systems (AIMS). This study examined whether these data are accurate regarding drug name, dose administered, and time of administration, and whether the stage of anesthesia influences data accuracy. Real-time observational data on drug administration during elective operations were compared with computerized information on drug administration entered by anesthesiologists. A trained observer (K.D.) performed the observations. Data were collected during 57 operations which included 596 separate occasions of drug administration by 22 anesthesiologists. No AIMS records were found for 90 (15.1%) occasions of drug administration (omissions), while there were 11 (1.8%) AIMS records where drug administration was not observed. The AIMS and observer data matched for drug name on 495 of 596 (83.1%) occasions, for dose on 439 of 495 (92.5%) occasions, and for time on 476 of 495 (96.2%) occasions. Amongst the 90 omitted records, 34 (37.8%) were for vasoactive drugs with 24 (27.7%) for small doses of hypnotics. Omissions occurred mostly during maintenance: 50 of 153 (24.6%), followed by induction: 30 of 325 (9.2%) and emergence: 10 of 57 (17.5%) (P < 0.001). Time and dose inaccuracies occurred mainly during induction, followed by maintenance and emergence; time inaccuracies were 7/325 (8.3%), 10/203 (4.9%), and 0/57 (0%), respectively (P = 0.07), and dose inaccuracies were 15/325 (4.6%), 3/203 (1.5%), and 1/57 (1.7%), respectively (P = 0.11). The range of accuracy varies when anesthesiologists manually enter drug administration data into an AIMS. Charting omissions represent the largest cause of inaccuracy, principally by omissions of records for vasopressors and small doses of hypnotic drugs. Manually entered drug administration data are not without errors. Accuracy of entering drug administration data remains the responsibility of the anesthesiologist.

76 FR 79701 - Bristol-Myers Squibb Co. et al.; Withdrawal of Approval of 70 New Drug Applications and 97...

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Oral Delivery of Protein Drugs Bioencapsulated in Plant Cells.

PubMed

Kwon, Kwang-Chul; Daniell, Henry

2016-08-01

Plants cells are now approved by the FDA for cost-effective production of protein drugs (PDs) in large-scale current Good Manufacturing Practice (cGMP) hydroponic growth facilities. In lyophilized plant cells, PDs are stable at ambient temperature for several years, maintaining their folding and efficacy. Upon oral delivery, PDs bioencapsulated in plant cells are protected in the stomach from acids and enzymes but are subsequently released into the gut lumen by microbes that digest the plant cell wall. The large mucosal area of the human intestine offers an ideal system for oral drug delivery. When tags (receptor-binding proteins or cell-penetrating peptides) are fused to PDs, they efficiently cross the intestinal epithelium and are delivered to the circulatory or immune system. Unique tags to deliver PDs to human immune or nonimmune cells have been developed recently. After crossing the epithelium, ubiquitous proteases cleave off tags at engineered sites. PDs are also delivered to the brain or retina by crossing the blood-brain or retinal barriers. This review highlights recent advances in PD delivery to treat Alzheimer's disease, diabetes, hypertension, Gaucher's or ocular diseases, as well as the development of affordable drugs by eliminating prohibitively expensive purification, cold chain and sterile delivery.

Rapid fabrication method of a microneedle mold with controllable needle height and width.

PubMed

Lin, Yen-Heng; Lee, I-Chi; Hsu, Wei-Chieh; Hsu, Ching-Hong; Chang, Kai-Ping; Gao, Shao-Syuan

2016-10-01

The main issue of transdermal drug delivery is that macromolecular drugs cannot diffuse through the stratum corneum of skin. Many studies have pursued micro-sized needles encapsulated with drugs to overcome this problem, as these needles can pierce the stratum corneum and allow drugs to enter the circulatory system of the human body. However, most microneedle fabrication processes are time-consuming and require expensive equipment. In this study, we demonstrate a rapid method for fabricating a microneedle mold using drawing lithography and a UV-cured resin. The mold was filled with a water-soluble material, polyvinylpyrrolidone (PVP), which was then demolded to produce a water-soluble microneedle array. The results of an in vitro skin insertion test using PVP microneedles and pig ear skin demonstrated the feasibility of the microneedle mold. In addition, by controlling the viscosity of the UV-cured resin through various heat treatments, microneedles with different heights and aspect ratios were produced. Compared with other methods, this technology significantly simplifies and accelerates the mold fabrication process. In addition, the required equipment is relatively simple and inexpensive. Through this technology, we can rapidly fabricate microneedle molds with controllable dimensions for various applications.

CIRCULATORY FAILURE DURING NON-INHALED FORMS OF CYANIDE INTOXICATION

PubMed Central

Haouzi, Philippe; Tubbs, Nicole; Rannals, Matthew D.; Judenherc-Haouzi, Annick; Cabell, Larry A.; McDonough, Joe A.; Sonobe, Takashi

2016-01-01

Our objective was to determine how circulatory failure develops following systemic administration of potassium cyanide (KCN). We used a non-inhaled modality of intoxication, wherein the change in breathing pattern would not influence the diffusion of CN into the blood, akin to the effects of ingesting toxic levels of CN. In a group of 300–400 g rats, CN-induced coma (CN IP, 7 mg/kg) produced a central apnea within 2–3 minutes along with a potent and prolonged gasping pattern leading to auto-resuscitation in 38% of the animals. Motor deficits and neuronal necrosis were nevertheless observed in the surviving animals. To clarify the mechanisms leading to potential auto-resuscitation versus asystole, 12 urethane-anesthetized rats were then exposed to the lowest possible levels of CN exposure that would lead to breathing depression within 7–8 minutes; this dose averaged 0.375 mg/kg/min iv. At this level of intoxication, a cardiac depression developed several minutes only after the onset of the apnea, leading to cardiac asystole as PaO2 reached value around 15 Torr, unless breathing was maintained by mechanical ventilation or through spontaneous gasping. Higher levels of KCN exposure in 10 animals provoked a primary cardiac depression, which led to a rapid cardiac arrest by pulseless electrical activity despite the maintenance of PaO2 by mechanical ventilation. These effects were totally unrelated to the potassium contained in KCN. It is concluded that circulatory failure can develop as a direct consequence of CN induced apnea but in a narrow range of exposure. In this “low” range, maintaining pulmonary gas exchange after exposure, through mechanical ventilation (or spontaneous gasping) can reverse cardiac depression and restore spontaneous breathing. At higher level of intoxication, cardiac depression is to be treated as a specific and spontaneously irreversible consequence of CN exposure, leading to a pulseless electrical activity. PMID:27513083

78 FR 44251 - Regulatory Agenda

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2013-07-23

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21 CFR 1316.09 - Application for administrative inspection warrant.

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2010-04-01

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2011-05-26

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2011-06-22

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Naphyrone: a "legal high" not legal any more.

PubMed

Vardakou, Ioanna; Pistos, Constantinos; Dona, Artemis; Spiliopoulou, Chara; Athanaselis, Sotiris

2012-10-01

Naphyrone, also known as naphthylpyrovalerone and O-2482, is a cathinone derivative that has been recently advertized for purchase on a number of websites. Naphyrone belongs to a new class of "designer drugs" that has emerged on the drugs abuse market and has gained popularity as the new "legal high." Legal highs have been circulating for a number of years in Europe and are becoming popular in the United States. They are affordable, widely available, legal to use and possess, and legal to supply. This review presents any available information about safety profile, clinical data, analytical profile, and legislation of this legal high, which is not legal any more. Any available information has been collected by various literature search engines and the World Wide Web. The structure of naphyrone is similar to that of pyrovalerone, a monoamine uptake inhibitor. This new designer drug does not have a long history of use, so there is little evidence of its long-term effects or on the risks from its use. Because of its similarity to other cathinone derivatives, naphyrone is likely to share the same risks, such as anxiety, paranoia, and overstimulation of the heart and circulatory system. Naphyrone was classified as a controlled drug under the UK Misuse of Drugs Act of 1971 (Amendment No. 2) Regulation 2010.

Modeling and control of a brushless DC axial flow ventricular assist device.

PubMed

Giridharan, Guruprasad A; Skliar, Mikhail; Olsen, Donald B; Pantalos, George M

2002-01-01

This article presents an integrated model of the human circulatory system that incorporates circulatory support by a brushless DC axial flow ventricular assist device (VAD), and a feedback VAD controller designed to maintain physiologically sufficient perfusion. The developed integrated model combines a network type model of the circulatory system with a nonlinear dynamic model of the brushless DC pump We show that maintaining a reference differential pressure between the left ventricle and aorta leads to adequate perfusion for different pathologic cases, ranging from normal heart to left heart asystole, and widely varying physical activity scenarios from rest to exercise.

Temporary Mechanical Circulatory Support: A Review of the Options, Indications, and Outcomes

PubMed Central

Gilotra, Nisha A; Stevens, Gerin R

2014-01-01

Cardiogenic shock remains a challenging disease entity and is associated with significant morbidity and mortality. Temporary mechanical circulatory support (MCS) can be implemented in an acute setting to stabilize acutely ill patients with cardiomyopathy in a variety of clinical situations. Currently, several options exist for temporary MCS. We review the indications, contraindications, clinical applications, and evidences for a variety of temporary circulatory support options, including the intra-aortic balloon pump (IABP), extracorporeal membrane oxygenation (ECMO), CentriMag blood pump, and percutaneous ventricular assist devices (pVADs), specifically the TandemHeart and Impella. PMID:25674024

[Application of artificial neural networks in forecasting the number of circulatory system diseases death toll].

PubMed

Zhang, Ying; Shao, Yi; Shang, Kezheng; Wang, Shigong; Wang, Jinyan

2014-09-01

Set up the model of forecasting the number of circulatorys death toll based on back-propagation (BP) artificial neural networks discuss the relationship between the circulatory system diseases death toll meteorological factors and ambient air pollution. The data of tem deaths, meteorological factors, and ambient air pollution within the m 2004 to 2009 in Nanjing were collected. On the basis of analyzing the ficient between CSDDT meteorological factors and ambient air pollution, leutral network model of CSDDT was built for 2004 - 2008 based on factors and ambient air pollution within the same time, and the data of 2009 est the predictive power of the model. There was a closely system diseases relationship between meteorological factors, ambient air pollution and the circulatory system diseases death toll. The ANN model structure was 17 -16 -1, 17 input notes, 16 hidden notes and 1 output note. The training precision was 0. 005 and the final error was 0. 004 999 42 after 487 training steps. The results of forecast show that predict accuracy over 78. 62%. This method is easy to be finished with smaller error, and higher ability on circulatory system death toll on independent prediction, which can provide a new method for forecasting medical-meteorological forecast and have the value of further research.

European cardiovascular mortality over the last three decades: evaluation of time trends, forecasts for 2016.

PubMed

Gaeta, M; Campanella, F; Gentile, L; Schifino, G M; Capasso, L; Bandera, F; Banfi, G; Arpesella, M; Ricci, C

2017-01-01

The circulatory diseases, in particular ischemic heart diseases and stroke, represent the main causes of death worldwide both in high income and in middle and low income countries. Our aim is to provide a comprehensive report to depict the circulatory disease mortality in Europe over the last 30 years and to address the sources of heterogeneity among different countries. Our study was performed using the WHO statistical information system - mortality database - and was restricted to the 28 countries belonging to the European Union (EU-28). We evaluated gender and age time series of all circulatory disease mortality, ischemic heart diseases, cerebrovascular diseases, pulmonary and other circulatory diseases and than we performed forecast for 2016. Mortality heterogeneity was evaluated by countries using the Cochrane Q statistic and the I-squared index. Between 1985 and 2011 SDR for deaths attributable to all circulatory system diseases decreased from 440.9 to 212.0 x 100,000 in EU-28 and a clear uniform reduction was observed. Heterogeneity among countries was found to be consistent, therefore different analysis were carried out considering geographical area. We forecast a reduction in European cardiovascular mortality. Heterogeneity among countries could only in part be explained by both geographical and health expenditure factors.

78 FR 5713 - New Animal Drugs; Cefpodoxime; Meloxicam

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2013-01-28

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76 FR 79198 - Generic Drug User Fee; Public Meeting; Correction

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2011-12-21

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2012-07-27

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21 CFR 1316.07 - Requirement for administrative inspection warrant; exceptions.

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2010-04-01

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78 FR 69133 - Drug Enforcement Administration

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2013-11-18

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75 FR 37818 - Issues in the Design and Conduct of Clinical Trials for Antibacterial Drug Development; Public...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-30

... Moser or Lori Benner, Center for Drug Evaluation and Research, Food and Drug Administration, Office of... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0001... AGENCY: Food and Drug Administration, HHS. ACTION: Notice of public workshop. SUMMARY: The Food and Drug...

Drug Overdose Surveillance Using Hospital Discharge Data

PubMed Central

Bunn, Terry L.; Talbert, Jeffery

2014-01-01

Objectives We compared three methods for identifying drug overdose cases in inpatient hospital discharge data on their ability to classify drug overdoses by intent and drug type(s) involved. Methods We compared three International Classification of Diseases, Ninth Revision, Clinical Modification code-based case definitions using Kentucky hospital discharge data for 2000–2011. The first definition (Definition 1) was based on the external-cause-of-injury (E-code) matrix. The other two definitions were based on the Injury Surveillance Workgroup on Poisoning (ISW7) consensus recommendations for national and state poisoning surveillance using the principal diagnosis or first E-code (Definition 2) or any diagnosis/E-code (Definition 3). Results Definition 3 identified almost 50% more drug overdose cases than did Definition 1. The increase was largely due to cases with a first-listed E-code describing a drug overdose but a principal diagnosis that was different from drug overdose (e.g., mental disorders, or respiratory or circulatory system failure). Regardless of the definition, more than 53% of the hospitalizations were self-inflicted drug overdoses; benzodiazepines were involved in about 30% of the hospitalizations. The 2011 age-adjusted drug overdose hospitalization rate in Kentucky was 146/100,000 population using Definition 3 and 107/100,000 population using Definition 1. Conclusion The ISW7 drug overdose definition using any drug poisoning diagnosis/E-code (Definition 3) is potentially the highest sensitivity definition for counting drug overdose hospitalizations, including by intent and drug type(s) involved. As the states enact policies and plan for adequate treatment resources, standardized drug overdose definitions are critical for accurate reporting, trend analysis, policy evaluation, and state-to-state comparison. PMID:25177055

76 FR 76738 - Generic Drug User Fee; Public Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-08

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0381] Generic Drug User Fee; Public Meeting AGENCY: Food and Drug Administration, HHS. ACTION: Notice of public meeting; request for comments. The Food and Drug Administration (FDA) is announcing a public meeting to...

77 FR 15961 - Oral Dosage Form New Animal Drugs; Phenylpropanolamine

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-19

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 520 [Docket No. FDA-2011-N-0003] Oral Dosage Form New Animal Drugs; Phenylpropanolamine AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal...

77 FR 55414 - New Animal Drugs; Enrofloxacin; Tylvalosin

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-10

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Parts 520, 522, and 556 [Docket No. FDA-2012-N-0002] New Animal Drugs; Enrofloxacin; Tylvalosin AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal...

78 FR 17595 - New Animal Drugs; Changes of Sponsor

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-22

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Parts 510, 520, 522, 524, 529, and 558 [Docket No. FDA-2013-N-0002] New Animal Drugs; Changes of Sponsor AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is...

75 FR 71450 - Oncologic Drugs Advisory Committee; Amendment of Notice

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-23

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0001] Oncologic Drugs Advisory Committee; Amendment of Notice AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is announcing an amendment to the notice of a...

77 FR 37911 - Oncologic Drugs Advisory Committee; Amendment of Notice

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-25

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-N-0001] Oncologic Drugs Advisory Committee; Amendment of Notice AGENCY: Food and Drug Administration, HHS. ACTION: Notice. The Food and Drug Administration (FDA) is announcing an amendment to the notice of meeting of the...

78 FR 21058 - New Animal Drugs; Change of Sponsor

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-09

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Parts 510, 520, 522, 524, 526, 529, and 558 [Docket No. FDA-2013-N-0002] New Animal Drugs; Change of Sponsor AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is...

78 FR 70062 - Withdrawal of Approval of New Animal Drug Applications; Carbarsone; Roxarsone

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-22

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-N-0002] Withdrawal of Approval of New Animal Drug Applications; Carbarsone; Roxarsone AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is withdrawing approval of...

21 CFR 21.3 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 1 2011-04-01 2011-04-01 false Definitions. 21.3 Section 21.3 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL PROTECTION OF PRIVACY General... products regulated by the Food and Drug Administration or with which the Food and Drug Administration has...

21 CFR 21.3 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 1 2012-04-01 2012-04-01 false Definitions. 21.3 Section 21.3 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL PROTECTION OF PRIVACY General... products regulated by the Food and Drug Administration or with which the Food and Drug Administration has...

21 CFR 21.3 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 1 2013-04-01 2013-04-01 false Definitions. 21.3 Section 21.3 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL PROTECTION OF PRIVACY General... products regulated by the Food and Drug Administration or with which the Food and Drug Administration has...

21 CFR 21.3 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 1 2014-04-01 2014-04-01 false Definitions. 21.3 Section 21.3 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL PROTECTION OF PRIVACY General... products regulated by the Food and Drug Administration or with which the Food and Drug Administration has...

77 FR 29216 - New Animal Drugs; Ceftiofur Sodium; Lincomycin Powder; Naracin; Tylosin

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-17

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Parts 510, 520, 522...; Tylosin AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug...: George K. Haibel, Center for Veterinary Medicine (HFV-6), Food and Drug Administration, 7519 Standish Pl...

76 FR 30176 - Dermatologic and Ophthalmic Drugs Advisory Committee; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-24

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0002] Dermatologic and Ophthalmic Drugs Advisory Committee; Notice of Meeting AGENCY: Food and Drug Administration... Food and Drug Administration (FDA). The meeting will be open to the public. Name of Committee...

75 FR 54016 - New Animal Drugs; Change of Sponsor's Name and Address

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-03

.... FDA-2010-N-0002] New Animal Drugs; Change of Sponsor's Name and Address AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal... in 21 CFR Part 510 Administrative practice and procedure, Animal drugs, Labeling, Reporting and...

76 FR 40612 - New Animal Drugs; Change of Sponsor's Name and Address

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-11

.... FDA-2011-N-0003] New Animal Drugs; Change of Sponsor's Name and Address AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal... Administrative practice and procedure, Animal drugs, Labeling, Reporting and recordkeeping requirements...

76 FR 19375 - Safety and Efficacy of Hypnotic Drugs; Public Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-07

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0002] Safety and Efficacy of Hypnotic Drugs; Public Meeting AGENCY: Food and Drug Administration, HHS. ACTION: Notice of public meeting. The Food and Drug Administration (FDA) is announcing a public meeting to...

77 FR 60442 - Withdrawal of Approval of New Animal Drug Applications; Butorphanol; Doxapram; Triamcinolone...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-03

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-N-0981] Withdrawal of Approval of New Animal Drug Applications; Butorphanol; Doxapram; Triamcinolone; Tylosin AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is...

77 FR 14401 - Draft Guidance on Drug Safety Information-FDA's Communication to the Public; Availability

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-09

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2005-D-0339] Draft Guidance on Drug Safety Information--FDA's Communication to the Public; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is...

77 FR 41415 - Single-Ingredient, Immediate-Release Drug Products Containing Oxycodone for Oral Administration...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-13

... INFORMATION CONTACT: Astrid Lopez-Goldberg, Center for Drug Evaluation and Research, Food and Drug... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-N-0563] Single-Ingredient, Immediate-Release Drug Products Containing Oxycodone for Oral Administration and...

78 FR 43209 - Narcolepsy Public Meeting on Patient-Focused Drug Development

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-19

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-N-0815] Narcolepsy Public Meeting on Patient-Focused Drug Development AGENCY: Food and Drug Administration, HHS. ACTION: Notice of public meeting; request for comments. SUMMARY: The Food and Drug Administration (FDA...

78 FR 58313 - Fibromyalgia Public Meeting on Patient-Focused Drug Development

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-23

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-N-1041] Fibromyalgia Public Meeting on Patient-Focused Drug Development AGENCY: Food and Drug Administration, HHS. ACTION: Notice of public meeting; request for comments. SUMMARY: The Food and Drug Administration (FDA...

78 FR 64956 - Endocrinologic and Metabolic Drugs Advisory Committee; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-30

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-N-0001] Endocrinologic and Metabolic Drugs Advisory Committee; Notice of Meeting AGENCY: Food and Drug Administration... Food and Drug Administration (FDA). The meeting will be open to the public. Name of Committee...

75 FR 22146 - Advisory Committee for Reproductive Health Drugs; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-27

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0001] Advisory Committee for Reproductive Health Drugs; Notice of Meeting AGENCY: Food and Drug Administration... Food and Drug Administration (FDA). The meeting will be open to the public. Name of Committee: Advisory...

76 FR 70462 - Advisory Committee for Reproductive Health Drugs; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-14

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0002] Advisory Committee for Reproductive Health Drugs; Notice of Meeting AGENCY: Food and Drug Administration... Food and Drug Administration (FDA). The meeting will be open to the public. Name of Committee: Advisory...

21 CFR 1316.12 - Refusal to allow inspection with an administrative warrant.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 9 2010-04-01 2010-04-01 false Refusal to allow inspection with an administrative warrant. 1316.12 Section 1316.12 Food and Drugs DRUG ENFORCEMENT ADMINISTRATION, DEPARTMENT OF JUSTICE ADMINISTRATIVE FUNCTIONS, PRACTICES, AND PROCEDURES Administrative Inspections § 1316.12 Refusal to allow...

[Chapter 4. Transitions in pharmaceutical market, production and sales in Japan (1980-2010)].

PubMed

Yoshioka, Ryuzo; Matsumoto, Kazuo

2014-01-01

In this paper, the writers reviewed in detail the pharmaceutical market and the shifts in manufacturing and sales including the trade balance in Japan over a thirty-year period from 1980 to 2010. From the 1980s to the 1990s, many innovative pharmaceutical products were developed and launched in the Japanese market. During the same period, some Japanese companies managed to develop their first internationally marketable drugs, which were antibiotics and effective remedies for the digestive and circulatory organs. During this period, Japanese pharmaceutical companies were also able to launch some of blockbuster drugs. For two decades, the pharmaceutical market grew rapidly. For this reason, it can be called "The Growth Period for Pharmaceutical Products" in Japan. After that period, drug development and sales slowed down due to a lack of expertise in genetic engineering and biotechnologies. This situation caused a large deficit in the trade balance for Japanese pharmaceutical products. However, with regard to the trade balance (including technical royalties) for pharmaceutical product technologies, Japan remains in the black even today.

A Simple Model of the Pulmonary Circulation for Hemodynamic Study and Examination.

ERIC Educational Resources Information Center

Gaar, Kermit A., Jr.

1983-01-01

Describes a computer program allowing students to study such circulatory variables as venus return, cardiac output, mean circulatory filling pressure, resistance to venous return, and equilibrium point. Documentation for this Applesoft program (or diskette) is available from author. (JM)

Early Identification of Circulatory Shock in Critical Care Transport

DTIC Science & Technology

2008-09-30

disclosure and community consultation. Early Identification of Circulatory Shock in Critical Care Transport 2 Community consultation for this...in two aircraft types (Eurocopter EC 135 and EC 145), in IFR weather conditions, and during both day and night operations. We calculated the

21 CFR 21.31 - Records stored by the National Archives and Records Administration.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 1 2011-04-01 2011-04-01 false Records stored by the National Archives and Records Administration. 21.31 Section 21.31 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... § 21.31 Records stored by the National Archives and Records Administration. (a) Food and Drug...

75 FR 21000 - Draft Guidance for the Public, Food and Drug Administration Advisory Committee Members, and Food...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-22

...] (formerly Docket No. 02D-0049) Draft Guidance for the Public, Food and Drug Administration Advisory Committee Members, and Food and Drug Administration Staff: Public Availability of Advisory Committee Members... and Drug Administration Amendments Act of 2007, Public Law No. 110-85), and section 701 (21 U.S.C. 371...

77 FR 14404 - Guidance for the Public, Food and Drug Administration (FDA) Advisory Committee Members, and FDA...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-09

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2002-D-0094; (formerly Docket No. 02D-0049)] Guidance for the Public, Food and Drug Administration (FDA) Advisory... Food and Drug Administration (FDA) is announcing the availability of a guidance for the public, FDA...

77 FR 70166 - Provisions of the Food and Drug Administration Safety and Innovation Act Related to Medical Gases...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-23

...; Establishment of a Public Docket AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is establishing a public docket for information pertaining to FDA's... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-N-1090...

75 FR 17418 - Memorandum of Understanding Between the Food and Drug Administration, United States Department of...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-06

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0004] Memorandum of Understanding Between the Food and Drug Administration, United States Department of Health and... understanding (MOU) between the Food and Drug Administration, U.S. Department of Health and Human Services and...

Analysis of Dose Response for Circulatory Disease After Radiotherapy for Benign Disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Little, Mark P., E-mail: mark.little@nih.gov; Kleinerman, Ruth A.; Stovall, Marilyn

Purpose: To assess the shape of the dose-response for various circulatory disease endpoints, and modifiers by age and time since exposure. Methods and Materials: This was an analysis of the US peptic ulcer data testing for heterogeneity of radiogenic risk by circulatory disease endpoint (ischemic heart, cerebrovascular, other circulatory disease). Results: There were significant excess risks for all circulatory disease, with an excess relative risk Gy{sup -1} of 0.082 (95% CI 0.031-0.140), and ischemic heart disease, with an excess relative risk Gy{sup -1} of 0.102 (95% CI 0.039-0.174) (both p = 0.01), and indications of excess risk for stroke. Theremore » were no statistically significant (p > 0.2) differences between risks by endpoint, and few indications of curvature in the dose-response. There were significant (p < 0.001) modifications of relative risk by time since exposure, the magnitude of which did not vary between endpoints (p > 0.2). Risk modifications were similar if analysis was restricted to patients receiving radiation, although the relative risks were slightly larger and the risk of stroke failed to be significant. The slopes of the dose-response were generally consistent with those observed in the Japanese atomic bomb survivors and in occupationally and medically exposed groups. Conclusions: There were excess risks for a variety of circulatory diseases in this dataset, with significant modification of risk by time since exposure. The consistency of the dose-response slopes with those observed in radiotherapeutically treated groups at much higher dose, as well as in lower dose-exposed cohorts such as the Japanese atomic bomb survivors and nuclear workers, implies that there may be little sparing effect of fractionation of dose or low-dose-rate exposure.« less

The European Registry for Patients with Mechanical Circulatory Support (EUROMACS): first annual report.

PubMed

de By, Theo M M H; Mohacsi, Paul; Gummert, Jan; Bushnaq, Hasan; Krabatsch, Thomas; Gustafsson, Finn; Leprince, Pascal; Martinelli, Luigi; Meyns, Bart; Morshuis, Michiel; Netuka, Ivan; Potapov, Evgenij; Zittermann, Armin; Delmo Walter, Eva Maria; Hetzer, Roland

2015-05-01

The European Registry for Patients with Mechanical Circulatory Support (EUROMACS) was founded on 10 December 2009 with the initiative of Roland Hetzer (Deutsches Herzzentrum Berlin, Berlin, Germany) and Jan Gummert (Herz- und Diabeteszentrum Nordrhein-Westfalen, Bad Oeynhausen, Germany) with 15 other founding international members. It aims to promote scientific research to improve care of end-stage heart failure patients with ventricular assist device or a total artificial heart as long-term mechanical circulatory support. Likewise, the organization aims to provide and maintain a registry of device implantation data and long-term follow-up of patients with mechanical circulatory support. Hence, EUROMACS affiliated itself with Dendrite Clinical Systems Ltd to offer its members a software tool that allows input and analysis of patient clinical data on a daily basis. EUROMACS facilitates further scientific studies by offering research groups access to any available data wherein patients and centres are anonymized. Furthermore, EUROMACS aims to stimulate cooperation with clinical and research institutions and with peer associations involved to further its aims. EUROMACS is the only European-based Registry for Patients with Mechanical Circulatory Support with rapid increase in institutional and individual membership. Because of the expeditious data input, the European Association for Cardiothoracic Surgeons saw the need to optimize the data availability and the significance of the registry to improve care of patients with mechanical circulatory support and its potential contribution to scientific intents; hence, the beginning of their alliance in 2012. This first annual report is designed to provide an overview of EUROMACS' structure, its activities, a first data collection and an insight to its scientific contributions. © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Ethical challenges with the left ventricular assist device as a destination therapy

PubMed Central

Rizzieri, Aaron G; Verheijde, Joseph L; Rady, Mohamed Y; McGregor, Joan L

2008-01-01

The left ventricular assist device was originally designed to be surgically implanted as a bridge to transplantation for patients with chronic end-stage heart failure. On the basis of the REMATCH trial, the US Food and Drug Administration and the US Centers for Medicare & Medicaid Services approved permanent implantation of the left ventricular assist device as a destination therapy in Medicare beneficiaries who are not candidates for heart transplantation. The use of the left ventricular assist device as a destination therapy raises certain ethical challenges. Left ventricular assist devices can prolong the survival of average recipients compared with optimal medical management of chronic end-stage heart failure. However, the overall quality of life can be adversely affected in some recipients because of serious infections, neurologic complications, and device malfunction. Left ventricular assist devices alter end-of-life trajectories. The caregivers of recipients may experience significant burden (e.g., poor physical health, depression, anxiety, and posttraumatic stress disorder) from destination therapy with left ventricular assist devices. There are also social and financial ramifications for recipients and their families. We advocate early utilization of a palliative care approach and outline prerequisite conditions so that consenting for the use of a left ventricular assist device as a destination therapy is a well informed process. These conditions include: (1) direct participation of a multidisciplinary care team, including palliative care specialists, (2) a concise plan of care for anticipated device-related complications, (3) careful surveillance and counseling for caregiver burden, (4) advance-care planning for anticipated end-of-life trajectories and timing of device deactivation, and (5) a plan to address the long-term financial burden on patients, families, and caregivers. Short-term mechanical circulatory devices (e.g. percutaneous cardiopulmonary bypass, percutaneous ventricular assist devices, etc.) can be initiated in emergency situations as a bridge to permanent implantation of ventricular assist devices in chronic end-stage heart failure. In the absence of first-person (patient) consent, presumed consent or surrogate consent should be used cautiously for the initiation of short-term mechanical circulatory devices in emergency situations as a bridge to permanent implantation of left ventricular assist devices. Future clinical studies of destination therapy with left ventricular assist devices should include measures of recipients' quality of end-of-life care and caregivers' burden. PMID:18694496

78 FR 27116 - Draft Guidance for Industry on Charging for Investigational Drugs Under an Investigational New...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-09

... Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 51, rm. 2201, Silver Spring, MD... Evaluation and Research, Food and Drug Administration, 1401 Rockville Pike, suite 200N, Rockville, MD 20852...: Colleen L. Locicero, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New...

76 FR 32863 - Guidance for Industry and Investigators on Enforcement of Safety Reporting Requirements for...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-07

..., Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 51...-40), Center for Biologics Evaluation and Research, Food and Drug Administration, 1401 Rockville Pike..., Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 51...

76 FR 48714 - New Animal Drugs; Change of Sponsor; Moxidectin

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-09

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Parts 520, 522, and 524 [Docket No. FDA-2011-N-0003] New Animal Drugs; Change of Sponsor; Moxidectin AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal...

78 FR 70496 - Withdrawal of Approval of New Animal Drug Applications; Arsanilic Acid

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-26

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 558 [Docket No. FDA-2013-N-0002] Withdrawal of Approval of New Animal Drug Applications; Arsanilic Acid AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is...

78 FR 70566 - Withdrawal of Approval of New Animal Drug Applications; Arsanilic Acid

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-26

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-N-0002] Withdrawal of Approval of New Animal Drug Applications; Arsanilic Acid AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is withdrawing approval of a new...

77 FR 9528 - Animal Drugs, Feeds, and Related Products; N-Methyl-2-Pyrrolidone; Correction

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-17

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 500 [Docket No...: Food and Drug Administration, HHS. ACTION: Final rule; correcting amendment. SUMMARY: The Food and Drug...: George K. Haibel, Center for Veterinary Medicine (HFV-6), Food and Drug Administration, 7519 Standish Pl...

75 FR 59732 - Gastrointestinal Drugs Advisory Committee; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-28

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0001] Gastrointestinal Drugs Advisory Committee; Notice of Meeting AGENCY: Food and Drug Administration, HHS. ACTION: Notice. This notice announces a forthcoming meeting of a public advisory committee of the Food and Drug Administration (FDA). The meeting...

78 FR 42381 - Administrative Detention of Drugs Intended for Human or Animal Use

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-15

... drug supply chain. Specifically, FDA will be able to administratively detain drugs encountered during... integrity of the drug supply chain. Specifically, administrative detention is intended to protect the public... better protect the integrity of the drug supply chain. One of those new authorities is section 709, which...

49 CFR 219.602 - FRA Administrator's determination of random drug testing rate.

Code of Federal Regulations, 2012 CFR

2012-10-01

... Random Alcohol and Drug Testing Programs § 219.602 FRA Administrator's determination of random drug... percentage rate for random drug testing must be 50 percent of covered employees. (b) The FRA Administrator's decision to increase or decrease the minimum annual percentage rate for random drug testing is based on the...

49 CFR 219.602 - FRA Administrator's determination of random drug testing rate.

Code of Federal Regulations, 2014 CFR

2014-10-01

... Random Alcohol and Drug Testing Programs § 219.602 FRA Administrator's determination of random drug... percentage rate for random drug testing must be 50 percent of covered employees. (b) The FRA Administrator's decision to increase or decrease the minimum annual percentage rate for random drug testing is based on the...

49 CFR 219.602 - FRA Administrator's determination of random drug testing rate.

Code of Federal Regulations, 2011 CFR

2011-10-01

... Random Alcohol and Drug Testing Programs § 219.602 FRA Administrator's determination of random drug... percentage rate for random drug testing must be 50 percent of covered employees. (b) The FRA Administrator's decision to increase or decrease the minimum annual percentage rate for random drug testing is based on the...

49 CFR 219.602 - FRA Administrator's determination of random drug testing rate.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Random Alcohol and Drug Testing Programs § 219.602 FRA Administrator's determination of random drug... percentage rate for random drug testing must be 50 percent of covered employees. (b) The FRA Administrator's decision to increase or decrease the minimum annual percentage rate for random drug testing is based on the...

49 CFR 219.602 - FRA Administrator's determination of random drug testing rate.

Code of Federal Regulations, 2013 CFR

2013-10-01

... Random Alcohol and Drug Testing Programs § 219.602 FRA Administrator's determination of random drug... percentage rate for random drug testing must be 50 percent of covered employees. (b) The FRA Administrator's decision to increase or decrease the minimum annual percentage rate for random drug testing is based on the...

76 FR 11794 - Drugs for Human Use; Unapproved and Misbranded Oral Drugs Labeled for Prescription Use and...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-03

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0100... Relief of Symptoms of Cold, Cough, or Allergy; Enforcement Action Dates AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is announcing its intention...

75 FR 65495 - Draft Guidance for Industry on Qualification Process for Drug Development Tools; Availability

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-25

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-D-0529...: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is... framework for interactions between the Center for Drug Evaluation and Research (CDER) and DDT sponsors to...

78 FR 24754 - Guidance for Industry on Regulatory Classification of Pharmaceutical Co-Crystals; Availability

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-26

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-D-0800... and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is... this guidance to the Division of Drug Information, Center for Drug Evaluation and Research, Food and...

21 CFR 874.5220 - Ear, nose, and throat drug administration device.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Ear, nose, and throat drug administration device. 874.5220 Section 874.5220 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES EAR, NOSE, AND THROAT DEVICES Therapeutic Devices § 874.5220 Ear, nose...

21 CFR 874.5220 - Ear, nose, and throat drug administration device.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Ear, nose, and throat drug administration device. 874.5220 Section 874.5220 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES EAR, NOSE, AND THROAT DEVICES Therapeutic Devices § 874.5220 Ear, nose...

21 CFR 874.5220 - Ear, nose, and throat drug administration device.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Ear, nose, and throat drug administration device. 874.5220 Section 874.5220 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES EAR, NOSE, AND THROAT DEVICES Therapeutic Devices § 874.5220 Ear, nose...

21 CFR 874.5220 - Ear, nose, and throat drug administration device.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Ear, nose, and throat drug administration device. 874.5220 Section 874.5220 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES EAR, NOSE, AND THROAT DEVICES Therapeutic Devices § 874.5220 Ear, nose...

21 CFR 874.5220 - Ear, nose, and throat drug administration device.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Ear, nose, and throat drug administration device. 874.5220 Section 874.5220 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES EAR, NOSE, AND THROAT DEVICES Therapeutic Devices § 874.5220 Ear, nose...

78 FR 44572 - Draft Guidance for Industry on Pre-Launch Activities Importation Requests; Availability

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-24

..., Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 51..., Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 51... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-D-0836...

75 FR 1060 - Draft Guidance for Industry on Planning for the Effects of High Absenteeism to Ensure...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-08

... Medically Necessary Drug Products; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice... Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 51, rm... Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., WO Bldg. 51, rm. 3359...

77 FR 12852 - Draft Guidance for Industry on Limiting the Use of Certain Phthalates as Excipients in Center for...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-02

... Evaluation and Research- Regulated Products; Availability AGENCY: Food and Drug Administration, HHS. ACTION... Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 51, Rm... Drug Evaluation and Research (HFD-003), Food and Drug Administration, Bldg. 51, Rm. 4154, 10903 New...

Mechanical Circulatory Support Devices for Acute Right Ventricular Failure.

PubMed

Kapur, Navin K; Esposito, Michele L; Bader, Yousef; Morine, Kevin J; Kiernan, Michael S; Pham, Duc Thinh; Burkhoff, Daniel

2017-07-18

Right ventricular (RV) failure remains a major cause of global morbidity and mortality for patients with advanced heart failure, pulmonary hypertension, or acute myocardial infarction and after major cardiac surgery. Over the past 2 decades, percutaneously delivered acute mechanical circulatory support pumps specifically designed to support RV failure have been introduced into clinical practice. RV acute mechanical circulatory support now represents an important step in the management of RV failure and provides an opportunity to rapidly stabilize patients with cardiogenic shock involving the RV. As experience with RV devices grows, their role as mechanical therapies for RV failure will depend less on the technical ability to place the device and more on improved algorithms for identifying RV failure, patient monitoring, and weaning protocols for both isolated RV failure and biventricular failure. In this review, we discuss the pathophysiology of acute RV failure and both the mechanism of action and clinical data exploring the utility of existing RV acute mechanical circulatory support devices. © 2017 American Heart Association, Inc.

21 CFR 21.20 - Procedures for notice of Food and Drug Administration Privacy Act Record Systems.

Code of Federal Regulations, 2011 CFR

2011-04-01

... Administration Privacy Act Record Systems. 21.20 Section 21.20 Food and Drugs FOOD AND DRUG ADMINISTRATION... Act Record Systems § 21.20 Procedures for notice of Food and Drug Administration Privacy Act Record... of each year a notice concerning each Privacy Act Record System as defined in § 21.3(c) that is not...

21 CFR 21.20 - Procedures for notice of Food and Drug Administration Privacy Act Record Systems.

Code of Federal Regulations, 2012 CFR

2012-04-01

... Administration Privacy Act Record Systems. 21.20 Section 21.20 Food and Drugs FOOD AND DRUG ADMINISTRATION... Act Record Systems § 21.20 Procedures for notice of Food and Drug Administration Privacy Act Record... of each year a notice concerning each Privacy Act Record System as defined in § 21.3(c) that is not...

21 CFR 21.20 - Procedures for notice of Food and Drug Administration Privacy Act Record Systems.

Code of Federal Regulations, 2013 CFR

2013-04-01

... Administration Privacy Act Record Systems. 21.20 Section 21.20 Food and Drugs FOOD AND DRUG ADMINISTRATION... Act Record Systems § 21.20 Procedures for notice of Food and Drug Administration Privacy Act Record... of each year a notice concerning each Privacy Act Record System as defined in § 21.3(c) that is not...

21 CFR 21.20 - Procedures for notice of Food and Drug Administration Privacy Act Record Systems.

Code of Federal Regulations, 2014 CFR

2014-04-01

... Administration Privacy Act Record Systems. 21.20 Section 21.20 Food and Drugs FOOD AND DRUG ADMINISTRATION... Act Record Systems § 21.20 Procedures for notice of Food and Drug Administration Privacy Act Record... of each year a notice concerning each Privacy Act Record System as defined in § 21.3(c) that is not...

77 FR 60440 - Clinical Investigator Training Course

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-03

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-N-0001] Clinical Investigator Training Course AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration's (FDA) Center for Drug Evaluation and Research/Office of Medical...

21 CFR 1316.11 - Execution of warrants.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 9 2010-04-01 2010-04-01 false Execution of warrants. 1316.11 Section 1316.11 Food and Drugs DRUG ENFORCEMENT ADMINISTRATION, DEPARTMENT OF JUSTICE ADMINISTRATIVE FUNCTIONS, PRACTICES, AND PROCEDURES Administrative Inspections § 1316.11 Execution of warrants. An administrative...

76 FR 8775 - Agency Information Collection Activities: Proposed Collection; Comments Requested: Drug...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-15

..., Human Resources Division, Drug Enforcement Administration, 8701 Morrissette Drive, Springfield, VA 22152... Administrator, Human Resources Division, Drug Enforcement Administration, 8701 Morrissette Drive, Springfield... Administration (DEA) will be submitting the following information collection request to the Office of Management...

Leg ischaemia before circulatory arrest alters brain leucocyte count and respiratory chain redox state.

PubMed

Yannopoulos, Fredrik S; Arvola, Oiva; Haapanen, Henri; Herajärvi, Johanna; Miinalainen, Ilkka; Jensen, Hanna; Kiviluoma, Kai; Juvonen, Tatu

2014-03-01

Remote ischaemic preconditioning and its neuroprotective abilities are currently under investigation and the method has shown significant effects in several small and large animal studies. In our previous studies, leucocyte filtration during cardiopulmonary bypass reduced cerebrocortical adherent leucocyte count and mitigated cerebral damage after hypothermic circulatory arrest (HCA) in piglets. This study aimed to obtain and assess direct visual data of leucocyte behaviour in cerebral vessels after hypothermic circulatory arrest following remote ischaemic preconditioning. Twelve native stock piglets were randomized into a remote ischaemic preconditioning group (n = 6) and a control group (n = 6). The intervention group underwent hind-leg ischaemia, whereas the control group received a sham-treatment before a 60-min period of hypothermic circulatory arrest. An intravital microscope was used to obtain measurements from the cerebrocortical vessel in vivo. It included three sets of filters: a violet filter to visualize microvascular perfusion and vessel diameter, a green filter for visualization of rhodamine-labelled leucocytes and an ultraviolet filter for reduced nicotinamide adenine dinucleotide (NADH) analysis. The final magnification on the microscope was 400. After the experiment, cerebral and cerebellar biopsies were collected and analysed with transmission electron microscope by a blinded analyst. In the transmission electron microscope analysis, the entire intervention group had normal, unaffected rough endoplasmic reticulum's in their cerebellar tissue, whereas the control group had a mean score of 1.06 (standard deviation 0.41) (P = 0.026). The measured amount of adherent leucocytes was lower in the remote ischaemic preconditioning group. The difference was statistically significant at 5, 15 and 45 min after circulatory arrest. Statistically significant differences were seen also in the recovery phase at 90 and 120 min after reperfusion. Nicotinamide adenine dinucleotide autofluorescence had statistically significant differences at 10 min after cooling and at 120 and 180 min after hypothermic circulatory arrest. Remote ischaemic preconditioning seems to provide better mitochondrial respiratory chain function as indicated by the higher NADH content. It simultaneously provides a reduction of adherent leucocytes in cerebral vessels after hypothermic circulatory arrest. Additionally, it might provide some degree of cellular organ preservation as implied by the electron microscopy results.

21 CFR 20.120 - Records available in Food and Drug Administration Public Reading Rooms.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 1 2013-04-01 2013-04-01 false Records available in Food and Drug Administration Public Reading Rooms. 20.120 Section 20.120 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL PUBLIC INFORMATION Availability of Specific Categories of Records § 20.120 Records available in Food and Drug...

21 CFR 20.120 - Records available in Food and Drug Administration Public Reading Rooms.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 1 2014-04-01 2014-04-01 false Records available in Food and Drug Administration Public Reading Rooms. 20.120 Section 20.120 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL PUBLIC INFORMATION Availability of Specific Categories of Records § 20.120 Records available in Food and Drug...

21 CFR 20.120 - Records available in Food and Drug Administration Public Reading Rooms.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 1 2012-04-01 2012-04-01 false Records available in Food and Drug Administration Public Reading Rooms. 20.120 Section 20.120 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL PUBLIC INFORMATION Availability of Specific Categories of Records § 20.120 Records available in Food and Drug...

The role of extracorporeal membrane oxygenation circulatory support in the 'crash and burn' patient: from implantation to weaning.

PubMed

Ghodsizad, Ali; Koerner, Michael M; Brehm, Christoph E; El-Banayosy, Aly

2014-05-01

In advanced cardiogenic shock, early mechanical circulatory support may prevent multiorgan failure and death. In this article, we are describing our experience with extracorporeal membrane oxygenation (ECMO) application. Venoarterial ECMO has been used successfully as a therapeutic option for patients with advanced cardiogenic shock and cardiac arrest. In this review, based on the daily routine of the Hershey group using ECMO for therapy of advanced cardiogenic shock, the application of ECMO is described. The aim is to share our hands-on experience during emergent implantation and to contribute to the knowledge within the field of mechanical circulatory support.

21 CFR 1316.08 - Consent to inspection.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 9 2010-04-01 2010-04-01 false Consent to inspection. 1316.08 Section 1316.08 Food and Drugs DRUG ENFORCEMENT ADMINISTRATION, DEPARTMENT OF JUSTICE ADMINISTRATIVE FUNCTIONS, PRACTICES, AND PROCEDURES Administrative Inspections § 1316.08 Consent to inspection. (a) An administrative...

21 CFR 20.3 - Certification and authentication of Food and Drug Administration records.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Certification and authentication of Food and Drug... authentication of Food and Drug Administration records. (a) Upon request, the Food and Drug Administration will... or for authentication of records shall be sent in writing to the Freedom of Information Staff (HFI-35...

78 FR 12762 - Joint Meeting of the Medical Imaging Drugs Advisory Committee and the Oncologic Drugs Advisory...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-25

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-N-0001...; Notice of Meeting. AGENCY: Food and Drug Administration, HHS. ACTION: Notice. This notice announces a forthcoming meeting of a public advisory committee of the Food and Drug Administration (FDA). The meeting will...

21 CFR 20.110 - Data and information about Food and Drug Administration employees.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Data and information about Food and Drug Administration employees. 20.110 Section 20.110 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL PUBLIC INFORMATION Availability of Specific Categories of Records § 20.110...

21 CFR 20.108 - Agreements between the Food and Drug Administration and other departments, agencies, and...

Code of Federal Regulations, 2010 CFR

2010-04-01

... Specific Categories of Records § 20.108 Agreements between the Food and Drug Administration and other... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Agreements between the Food and Drug Administration and other departments, agencies, and organizations. 20.108 Section 20.108 Food and Drugs FOOD AND...

76 FR 36133 - Draft Guidances for Industry and Food and Drug Administration Staff: Classification of Products...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-21

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-D-0429] Draft Guidances for Industry and Food and Drug Administration Staff: Classification of Products as Drugs... Action'' in the Definition of Device Under Section 201(h) of the Federal Food, Drug, and Cosmetic Act...

76 FR 45814 - Animal Generic Drug User Fee Rates and Payment Procedures for Fiscal Year 2012

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-01

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0547] Animal Generic Drug User Fee Rates and Payment Procedures for Fiscal Year 2012 AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is announcing the rates and...

Analysis of free drug fractions in serum by ultrafast affinity extraction and two-dimensional affinity chromatography using α1-acid glycoprotein microcolumns.

PubMed

Bi, Cong; Zheng, Xiwei; Hage, David S

2016-02-05

In the circulatory system, many drugs are reversibly bound to serum proteins such as human serum albumin (HSA) and alpha1-acid glycoprotein (AGP), resulting in both free and protein-bound fractions for these drugs. This report examined the use of microcolumns containing immobilized AGP for the measurement of free drug fractions by ultrafast affinity extraction and a two-dimensional affinity system. Several drugs known to bind AGP were used as models to develop and evaluate this approach. Factors considered during the creation of this method included the retention of the drugs on the microcolumns, the injection flow rate, the microcolumn size, and the times at which a second AGP column was placed on-line with the microcolumn. The final system had residence times of only 110-830ms during sample passage through the AGP microcolumns and allowed free drug fractions to be determined within 10-20min when using only 3-10μL of sample per injection. This method was used to measure the free fractions of the model drugs at typical therapeutic levels in serum, giving good agreement with the results obtained by ultrafiltration. This approach was also used to estimate the binding constants for each drug with AGP in serum, even for drugs that had significant interactions with both AGP and HSA in such samples. These results indicated that AGP microcolumns could be used with ultrafast affinity extraction to measure free drug fractions in a label-free manner and to study the binding of drugs with AGP in complex samples such as serum. Copyright © 2015 Elsevier B.V. All rights reserved.

Electroencephalographic Recordings During Withdrawal of Life-Sustaining Therapy Until 30 Minutes After Declaration of Death.

PubMed

Norton, Loretta; Gibson, Raechelle M; Gofton, Teneille; Benson, Carolyn; Dhanani, Sonny; Shemie, Sam D; Hornby, Laura; Ward, Roxanne; Young, G Bryan

2017-03-01

The timing of the circulatory determination of death for organ donation presents a medical and ethical challenge. Concerns have been raised about the timing of electrocerebral inactivity in relation to the cessation of circulatory function in organ donation after cardio-circulatory death. Nonprocessed electroencephalographic (EEG) measures have not been characterized and may provide insight into neurological function during this process. We assessed electrocortical data in relation to cardiac function after withdrawal of life-sustaining therapy and in the postmortem period after cardiac arrest for four patients in a Canadian intensive care unit. Subhairline EEG and cardio-circulatory monitoring including electrocardiogram, arterial blood pressure (ABP), and oxygen saturation were captured. Electrocerebral inactivity preceded the cessation of the cardiac rhythm and ABP in three patients. In one patient, single delta wave bursts persisted following the cessation of both the cardiac rhythm and ABP. There was a significant difference in EEG amplitude between the 30-minute period before and the 5-minute period following ABP cessation for the group, but we did not observe any well-defined EEG states following the early cardiac arrest period. In a case series of four patients, EEG inactivity preceded electrocardiogram and ABP inactivity during the dying process in three patients. Further study of the electroencephalogram during the withdrawal of life sustaining therapies will add clarity to medical, ethical, and legal concerns for donation after circulatory determined death.

Role of mass drug administration in elimination of Plasmodium falciparum malaria: a consensus modelling study.

PubMed

Brady, Oliver J; Slater, Hannah C; Pemberton-Ross, Peter; Wenger, Edward; Maude, Richard J; Ghani, Azra C; Penny, Melissa A; Gerardin, Jaline; White, Lisa J; Chitnis, Nakul; Aguas, Ricardo; Hay, Simon I; Smith, David L; Stuckey, Erin M; Okiro, Emelda A; Smith, Thomas A; Okell, Lucy C

2017-07-01

Mass drug administration for elimination of Plasmodium falciparum malaria is recommended by WHO in some settings. We used consensus modelling to understand how to optimise the effects of mass drug administration in areas with low malaria transmission. We collaborated with researchers doing field trials to establish a standard intervention scenario and standard transmission setting, and we input these parameters into four previously published models. We then varied the number of rounds of mass drug administration, coverage, duration, timing, importation of infection, and pre-administration transmission levels. The outcome of interest was the percentage reduction in annual mean prevalence of P falciparum parasite rate as measured by PCR in the third year after the final round of mass drug administration. The models predicted differing magnitude of the effects of mass drug administration, but consensus answers were reached for several factors. Mass drug administration was predicted to reduce transmission over a longer timescale than accounted for by the prophylactic effect alone. Percentage reduction in transmission was predicted to be higher and last longer at lower baseline transmission levels. Reduction in transmission resulting from mass drug administration was predicted to be temporary, and in the absence of scale-up of other interventions, such as vector control, transmission would return to pre-administration levels. The proportion of the population treated in a year was a key determinant of simulated effectiveness, irrespective of whether people are treated through high coverage in a single round or new individuals are reached by implementation of several rounds. Mass drug administration was predicted to be more effective if continued over 2 years rather than 1 year, and if done at the time of year when transmission is lowest. Mass drug administration has the potential to reduce transmission for a limited time, but is not an effective replacement for existing vector control. Unless elimination is achieved, mass drug administration has to be repeated regularly for sustained effect. Bill & Melinda Gates Foundation. Copyright © 2017 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.

77 FR 76049 - Draft Guidance for Industry on Electronic Source Data in Clinical Investigations; Correction

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-26

..., Office of Planning & Informatics, Center for Drug Evaluation and Research, Food and Drug Administration... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-D-0643...: Food and Drug Administration, HHS. ACTION: Notice; correction. [[Page 76050

78 FR 14304 - Adrian Vela: Debarment Order

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-05

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-N-0777] Adrian Vela: Debarment Order AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is issuing an order under the Federal Food, Drug, and Cosmetic Act (the...

77 FR 39245 - Sami Arshak Yanikian: Debarment Order

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-02

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-N-0063] Sami Arshak Yanikian: Debarment Order AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is issuing an order under the Federal Food, Drug, and...

21 CFR 1316.13 - Frequency of administrative inspections.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 9 2014-04-01 2014-04-01 false Frequency of administrative inspections. 1316.13 Section 1316.13 Food and Drugs DRUG ENFORCEMENT ADMINISTRATION, DEPARTMENT OF JUSTICE ADMINISTRATIVE... as circumstances may require, based in part on the registrant's history of compliance with the...

21 CFR 1316.13 - Frequency of administrative inspections.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 9 2011-04-01 2011-04-01 false Frequency of administrative inspections. 1316.13 Section 1316.13 Food and Drugs DRUG ENFORCEMENT ADMINISTRATION, DEPARTMENT OF JUSTICE ADMINISTRATIVE... as circumstances may require, based in part on the registrant's history of compliance with the...

21 CFR 1316.13 - Frequency of administrative inspections.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 9 2013-04-01 2013-04-01 false Frequency of administrative inspections. 1316.13 Section 1316.13 Food and Drugs DRUG ENFORCEMENT ADMINISTRATION, DEPARTMENT OF JUSTICE ADMINISTRATIVE... as circumstances may require, based in part on the registrant's history of compliance with the...

21 CFR 1316.13 - Frequency of administrative inspections.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 9 2012-04-01 2012-04-01 false Frequency of administrative inspections. 1316.13 Section 1316.13 Food and Drugs DRUG ENFORCEMENT ADMINISTRATION, DEPARTMENT OF JUSTICE ADMINISTRATIVE... as circumstances may require, based in part on the registrant's history of compliance with the...

21 CFR 20.101 - Administrative enforcement records.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Administrative enforcement records. 20.101 Section 20.101 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL PUBLIC INFORMATION Availability of Specific Categories of Records § 20.101 Administrative enforcement...

76 FR 65371 - Schedules of Controlled Substances: Temporary Placement of Three Synthetic Cathinones Into...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-21

... DEPARTMENT OF JUSTICE Drug Enforcement Administration 21 CFR Part 1308 [Docket No. DEA-357...: Drug Enforcement Administration, Department of Justice. ACTION: Final Order. SUMMARY: The Administrator of the Drug Enforcement Administration (DEA) is issuing this final order to temporarily schedule...

76 FR 55616 - Schedules of Controlled Substances: Temporary Placement of Three Synthetic Cathinones Into...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-08

... DEPARTMENT OF JUSTICE Drug Enforcement Administration 21 CFR Part 1308 [Docket No. DEA-357...: Drug Enforcement Administration, Department of Justice. ACTION: Notice of Intent. SUMMARY: The Administrator of the Drug Enforcement Administration (DEA) is issuing this notice of intent to temporarily...

21 CFR 1316.13 - Frequency of administrative inspections.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 9 2010-04-01 2010-04-01 false Frequency of administrative inspections. 1316.13 Section 1316.13 Food and Drugs DRUG ENFORCEMENT ADMINISTRATION, DEPARTMENT OF JUSTICE ADMINISTRATIVE... as circumstances may require, based in part on the registrant's history of compliance with the...

21 CFR 868.5165 - Nitric oxide administration apparatus.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Nitric oxide administration apparatus. 868.5165 Section 868.5165 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5165 Nitric oxide administration...

21 CFR 868.5165 - Nitric oxide administration apparatus.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Nitric oxide administration apparatus. 868.5165 Section 868.5165 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5165 Nitric oxide administration...

Multimodal system designed to reduce errors in recording and administration of drugs in anaesthesia: prospective randomised clinical evaluation.

PubMed

Merry, Alan F; Webster, Craig S; Hannam, Jacqueline; Mitchell, Simon J; Henderson, Robert; Reid, Papaarangi; Edwards, Kylie-Ellen; Jardim, Anisoara; Pak, Nick; Cooper, Jeremy; Hopley, Lara; Frampton, Chris; Short, Timothy G

2011-09-22

To clinically evaluate a new patented multimodal system (SAFERSleep) designed to reduce errors in the recording and administration of drugs in anaesthesia. Prospective randomised open label clinical trial. Five designated operating theatres in a major tertiary referral hospital. Eighty nine consenting anaesthetists managing 1075 cases in which there were 10,764 drug administrations. Use of the new system (which includes customised drug trays and purpose designed drug trolley drawers to promote a well organised anaesthetic workspace and aseptic technique; pre-filled syringes for commonly used anaesthetic drugs; large legible colour coded drug labels; a barcode reader linked to a computer, speakers, and touch screen to provide automatic auditory and visual verification of selected drugs immediately before each administration; automatic compilation of an anaesthetic record; an on-screen and audible warning if an antibiotic has not been administered within 15 minutes of the start of anaesthesia; and certain procedural rules-notably, scanning the label before each drug administration) versus conventional practice in drug administration with a manually compiled anaesthetic record. Primary: composite of errors in the recording and administration of intravenous drugs detected by direct observation and by detailed reconciliation of the contents of used drug vials against recorded administrations; and lapses in responding to an intermittent visual stimulus (vigilance latency task). Secondary: outcomes in patients; analyses of anaesthetists' tasks and assessments of workload; evaluation of the legibility of anaesthetic records; evaluation of compliance with the procedural rules of the new system; and questionnaire based ratings of the respective systems by participants. The overall mean rate of drug errors per 100 administrations was 9.1 (95% confidence interval 6.9 to 11.4) with the new system (one in 11 administrations) and 11.6 (9.3 to 13.9) with conventional methods (one in nine administrations) (P = 0.045 for difference). Most were recording errors, and, though fewer drug administration errors occurred with the new system, the comparison with conventional methods did not reach significance. Rates of errors in drug administration were lower when anaesthetists consistently applied two key principles of the new system (scanning the drug barcode before administering each drug and keeping the voice prompt active) than when they did not: mean 6.0 (3.1 to 8.8) errors per 100 administrations v 9.7 (8.4 to 11.1) respectively (P = 0.004). Lapses in the vigilance latency task occurred in 12% (58/471) of cases with the new system and 9% (40/473) with conventional methods (P = 0.052). The records generated by the new system were more legible, and anaesthetists preferred the new system, particularly in relation to long, complex, and emergency cases. There were no differences between new and conventional systems in respect of outcomes in patients or anaesthetists' workload. The new system was associated with a reduction in errors in the recording and administration of drugs in anaesthesia, attributable mainly to a reduction in recording errors. Automatic compilation of the anaesthetic record increased legibility but also increased lapses in a vigilance latency task and decreased time spent watching monitors. Trial registration Australian New Zealand Clinical Trials Registry No 12608000068369.

Representations of the Human Circulatory System

ERIC Educational Resources Information Center

Lopez-Manjon, Asuncion; Angon, Yolanda Postigo

2009-01-01

There is no agreement about the robustness of intuitive representations of the circulatory system and their susceptibility to change by instruction. In this paper, we analyse to what extent students with varying degrees of biology instruction and different ages (High School Health Science and Social Science students and first and final year…

21 CFR 201.129 - Drugs; exemption for radioactive drugs for research use.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 4 2010-04-01 2010-04-01 false Drugs; exemption for radioactive drugs for research use. 201.129 Section 201.129 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... Drugs; exemption for radioactive drugs for research use. A radioactive drug intended for administration...

Evaluation of drug administration errors in a teaching hospital

PubMed Central

2012-01-01

Background Medication errors can occur at any of the three steps of the medication use process: prescribing, dispensing and administration. We aimed to determine the incidence, type and clinical importance of drug administration errors and to identify risk factors. Methods Prospective study based on disguised observation technique in four wards in a teaching hospital in Paris, France (800 beds). A pharmacist accompanied nurses and witnessed the preparation and administration of drugs to all patients during the three drug rounds on each of six days per ward. Main outcomes were number, type and clinical importance of errors and associated risk factors. Drug administration error rate was calculated with and without wrong time errors. Relationship between the occurrence of errors and potential risk factors were investigated using logistic regression models with random effects. Results Twenty-eight nurses caring for 108 patients were observed. Among 1501 opportunities for error, 415 administrations (430 errors) with one or more errors were detected (27.6%). There were 312 wrong time errors, ten simultaneously with another type of error, resulting in an error rate without wrong time error of 7.5% (113/1501). The most frequently administered drugs were the cardiovascular drugs (425/1501, 28.3%). The highest risks of error in a drug administration were for dermatological drugs. No potentially life-threatening errors were witnessed and 6% of errors were classified as having a serious or significant impact on patients (mainly omission). In multivariate analysis, the occurrence of errors was associated with drug administration route, drug classification (ATC) and the number of patient under the nurse's care. Conclusion Medication administration errors are frequent. The identification of its determinants helps to undertake designed interventions. PMID:22409837

Evaluation of drug administration errors in a teaching hospital.

PubMed

Berdot, Sarah; Sabatier, Brigitte; Gillaizeau, Florence; Caruba, Thibaut; Prognon, Patrice; Durieux, Pierre

2012-03-12

Medication errors can occur at any of the three steps of the medication use process: prescribing, dispensing and administration. We aimed to determine the incidence, type and clinical importance of drug administration errors and to identify risk factors. Prospective study based on disguised observation technique in four wards in a teaching hospital in Paris, France (800 beds). A pharmacist accompanied nurses and witnessed the preparation and administration of drugs to all patients during the three drug rounds on each of six days per ward. Main outcomes were number, type and clinical importance of errors and associated risk factors. Drug administration error rate was calculated with and without wrong time errors. Relationship between the occurrence of errors and potential risk factors were investigated using logistic regression models with random effects. Twenty-eight nurses caring for 108 patients were observed. Among 1501 opportunities for error, 415 administrations (430 errors) with one or more errors were detected (27.6%). There were 312 wrong time errors, ten simultaneously with another type of error, resulting in an error rate without wrong time error of 7.5% (113/1501). The most frequently administered drugs were the cardiovascular drugs (425/1501, 28.3%). The highest risks of error in a drug administration were for dermatological drugs. No potentially life-threatening errors were witnessed and 6% of errors were classified as having a serious or significant impact on patients (mainly omission). In multivariate analysis, the occurrence of errors was associated with drug administration route, drug classification (ATC) and the number of patient under the nurse's care. Medication administration errors are frequent. The identification of its determinants helps to undertake designed interventions.

Impact of homicide and traffic crashes on life expectancy in the largest Latin American country.

PubMed

Auger, Nathalie; Le Serbon, Emilie; Rasella, Davide; Aquino, Rosana; Barreto, Maurício L

2016-09-01

Brazil and Canada are on opposite poles of the spectrum for life expectancy in America. We identified factors underlying Brazil's lower life expectancy relative to Canada, with emphasis on the role of injury compared with other major causes. We computed life expectancy at birth in Brazil and Canada in 2010 and identified the ages and causes of death responsible for the gap between both countries. The main outcome measure was the contribution of homicide and traffic accidents to the gap, compared with other causes of death. Relative to Canada, life expectancy was lower in Brazil by 8.2 years (men) and 5.2 years (women). Injury lowered life expectancy of men in Brazil by 2.2 years, or more than a quarter of the gap, mainly due to homicide and traffic accidents between ages 20 and 64 years. Homicide and traffic accidents contributed more than all circulatory diseases combined. In women, circulatory disease was the most important cause of lower life expectancy. In 2010, homicides and traffic accidents were the principal cause for short life expectancy of men in Brazil. Improving life expectancy in Brazil requires addressing the root causes of inequalities that drive illicit drug trade, violence and accidents. © The Author 2015. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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Hepatoprotective effect of chrysin on prooxidant-antioxidant status during ethanol-induced toxicity in female albino rats.

PubMed

Sathiavelu, Jayanthi; Senapathy, Giftson Jebakkan; Devaraj, Rajkumar; Namasivayam, Nalini

2009-06-01

To evaluate the effect of chrysin, a natural, biologically active compound extracted from many plants, honey and propolis, on the tissue and circulatory antioxidant status, and lipid peroxidation in ethanol-induced hepatotoxicity in rats. Rats were divided into four groups. Groups 1 and 2 received isocaloric glucose. Groups 3 and 4 received 20% ethanol, equivalent to 5 g/kg bodyweight every day. Groups 2 and 4 received chrysin (20 mg/kg bodyweight) dissolved in 0.5% dimethylsulfoxide. The results showed significantly elevated levels of tissue and circulatory thiobarbituric acid reactive substances, conjugated dienes and lipid hydroperoxides, and significantly lowered enzymic and non-enzymic antioxidant activity of superoxide dismutase, catalase and glutathione-related enzymes such as glutathione peroxidase, glutathione reductase, glutathione-S-transferase, reduced glutathione, vitamin C and vitamin E in ethanol-treated rats compared with the control. Chrysin administration to rats with ethanol-induced liver injury significantly decreased the levels of thiobarbituric acid reactive substances, lipid hydroperoxides and conjugated dienes, and significantly elevated the activity of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione-S-transferase and the levels of reduced glutathione, vitamin C and vitamin E in the tissues and circulation compared with those of the unsupplemented ethanol-treated rats. The histological changes observed in the liver and kidney correlated with the biochemical findings. Chrysin offers protection against free radical-mediated oxidative stress in rats with ethanol-induced liver injury.

Shortage of Peritoneal Dialysis Solution and the Food and Drug Administration's Response.

PubMed

Jensen, Valerie; Throckmorton, Douglas C

2015-08-07

Although the number of new drug shortages has been lower in recent years than in the past, severe shortages have occurred that have affected large numbers of patients. A new law entitled the Food and Drug Administration Safety and Innovation Act was enacted in July of 2012, which requires companies to notify the Food and Drug Administration of anticipated shortages. This notification requirement has allowed the Food and Drug Administration to work closely with manufacturers earlier to mitigate and, often, prevent shortages. However, not all shortages are able to be prevented, and the shortage of peritoneal dialysis solution is one that has had a significant effect on patients. The Food and Drug Administration continues to use all available tools to address this shortage with manufacturers, including temporary availability of imported peritoneal dialysis solution from Ireland. Mitigating shortages is a top priority for the Food and Drug Administration, and communication with all stakeholders is essential. Copyright © 2015 by the American Society of Nephrology.

Theological reflections on donation after circulatory death: the wisdom of Paul Ramsey and Moshe Feinstein.

PubMed

Jotkowitz, A

2008-10-01

Due to the worldwide shortage of organs for transplantation, there has been an increased use of organs obtained after circulatory death alone. A protocol for this procedure has recently been approved by a major transplant consortium. This development raises serious moral and ethical concerns. Two renowned theologians of the previous generation, Paul Ramsey and Moshe Feinstein, wrote extensively on the ethical issues relating to transplantation, and their work has much relevance to current moral dilemmas. Their writings relating to definition of death, organ transplantation and the care of the terminally ill are briefly presented, and their potential application to the moral problem of organ donation after circulatory death is discussed.

Solid‐in‐oil nanodispersions for transdermal drug delivery systems

PubMed Central

Kitaoka, Momoko; Wakabayashi, Rie; Kamiya, Noriho

2016-01-01

Abstract Transdermal administration of drugs has advantages over conventional oral administration or administration using injection equipment. The route of administration reduces the opportunity for drug evacuation before systemic circulation, and enables long‐lasting drug administration at a modest body concentration. In addition, the skin is an attractive route for vaccination, because there are many immune cells in the skin. Recently, solid‐in‐oil nanodisperison (S/O) technique has demonstrated to deliver cosmetic and pharmaceutical bioactives efficiently through the skin. S/O nanodispersions are nanosized drug carriers designed to overcome the skin barrier. This review discusses the rationale for preparation of efficient and stable S/O nanodispersions, as well as application examples in cosmetic and pharmaceutical materials including vaccines. Drug administration using a patch is user‐friendly, and may improve patient compliance. The technique is a potent transcutaneous immunization method without needles. PMID:27529824

Solid-in-oil nanodispersions for transdermal drug delivery systems.

PubMed

Kitaoka, Momoko; Wakabayashi, Rie; Kamiya, Noriho; Goto, Masahiro

2016-11-01

Transdermal administration of drugs has advantages over conventional oral administration or administration using injection equipment. The route of administration reduces the opportunity for drug evacuation before systemic circulation, and enables long-lasting drug administration at a modest body concentration. In addition, the skin is an attractive route for vaccination, because there are many immune cells in the skin. Recently, solid-in-oil nanodisperison (S/O) technique has demonstrated to deliver cosmetic and pharmaceutical bioactives efficiently through the skin. S/O nanodispersions are nanosized drug carriers designed to overcome the skin barrier. This review discusses the rationale for preparation of efficient and stable S/O nanodispersions, as well as application examples in cosmetic and pharmaceutical materials including vaccines. Drug administration using a patch is user-friendly, and may improve patient compliance. The technique is a potent transcutaneous immunization method without needles. © 2016 The Authors. Biotechnology Journal published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

21 CFR 19.10 - Food and Drug Administration Conflict of Interest Review Board.

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75 FR 45646 - Design of Clinical Trials of Aerosolized Antimicrobials for the Treatment of Cystic Fibrosis...

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2010-08-03

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77 FR 10536 - Draft and Revised Draft Guidances for Industry Describing Product-Specific Bioequivalence...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-22

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77 FR 74669 - Draft and Revised Draft Guidances for Industry Describing Product-Specific Bioequivalence...

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2012-12-17

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78 FR 15017 - Guidance for Industry: What You Need To Know About Administrative Detention of Foods; Small...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-08

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-D-0643... Compliance Guide; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is announcing the availability of a guidance for industry entitled...

75 FR 11893 - Food and Drug Administration Transparency Task Force; Request for Comments

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-12

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2009-N-0247... Administration, HHS. ACTION: Notice; request for comments. SUMMARY: The Food and Drug Administration (FDA) is soliciting comments from interested persons on ways in which FDA can increase transparency between FDA and...

Evaluation of exercise-respiratory system modifications and preliminary respiratory-circulatory system integration scheme

NASA Technical Reports Server (NTRS)

Gallagher, R. R.

1974-01-01

The respiratory control system, functioning as an independent system, is presented with modifications of the exercise subroutine. These modifications illustrate an improved control of ventilation rates and arterial and compartmental gas tensions. A very elementary approach to describing the interactions of the respiratory and circulatory system is presented.

From Head to Toe: Respiratory, Circulatory, and Skeletal Systems. Book 3.

ERIC Educational Resources Information Center

Wiebe, Arthur, Ed.; And Others

Designed to supplement curricular programs dealing with the human body, this booklet offers an activity-based, student-oriented approach for middle school teachers and students. Twelve activities focus on principles and skills related to the respiratory, circulatory, and skeletal systems. Each activity consists of student sheets and a teacher's…

Donation after brain circulation determination of death.

PubMed

Dalle Ave, Anne L; Bernat, James L

2017-02-23

The fundamental determinant of death in donation after circulatory determination of death is the cessation of brain circulation and function. We therefore propose the term donation after brain circulation determination of death [DBCDD]. In DBCDD, death is determined when the cessation of circulatory function is permanent but before it is irreversible, consistent with medical standards of death determination outside the context of organ donation. Safeguards to prevent error include that: 1] the possibility of auto-resuscitation has elapsed; 2] no brain circulation may resume after the determination of death; 3] complete circulatory cessation is verified; and 4] the cessation of brain function is permanent and complete. Death should be determined by the confirmation of the cessation of systemic circulation; the use of brain death tests is invalid and unnecessary. Because this concept differs from current standards, consensus should be sought among stakeholders. The patient or surrogate should provide informed consent for organ donation by understanding the basis of the declaration of death. In cases of circulatory cessation, such as occurs in DBCDD, death can be defined as the permanent cessation of brain functions, determined by the permanent cessation of brain circulation.

Effect of Panpal pretreatment and antidotal treatment (HI-6 plus benactyzine) on respiratory and circulatory function in soman-poisoned rats.

PubMed

Kassa, J; Fusek, J

1997-10-01

1 The effect of pharmacological pretreatment (pyridostigmine, benactyzine and trihexyphenidyle), designated Panpal, and antidotal treatment (the oxime HI-6 plus benactyzine) in soman poisoning was investigated in a rat model with on-line monitoring of respiratory and circulatory parameters. 2 Soman poisoning caused a high decrease in respiratory rate as well as minute respiratory volume and an increase in mean arterial pressure from 30-120 min following soman challenge. Soman at sublethal dose also significantly inhibited acetylcholinesterase activity in diaphragm and various brain parts. 3 Panpal pretreatment as well as antidotal treatment were effective in improving the respiratory and circulatory function disturbed by soman without the ability to increase significantly soman-inhibited acetylcholinesterase activity in all brain parts studied. 4 The efficacy of combined Panpal pretreatment and antidotal treatment against sublethal soman poisoning was not different from the efficacy of Panpal pretreatment or antidotal treatment alone. 5 The results of this investigation suggest that Panpal pretreatment as well as antidotal treatment are able to restore respiratory and circulatory function in soman-poisoned rats without significant reactivation of brain acetylcholinesterase.

[Clinical exercise testing and the Fick equation: strategic thinking for optimizing diagnosis].

PubMed

Perrault, H; Richard, R

2012-04-01

This article examines the expected exercise-induced changes in the components of the oxygen transport system as described by the Fick equation with a view to enable a critical analysis of a standard incremental exercise test to identify normal and abnormal patterns of responses and generate hypotheses as to potential physiological and/or pathophysiological causes. The text reviews basic physiological principals and provides useful reminders of standard equations that serve to integrate circulatory, respiratory and skeletal muscle functions. More specifically, the article provides a conceptual and quantitative framework linking the exercise-induced increase in whole body oxygen uptake to central circulatory and peripheral circulatory factors with the view to establish the normalcy of response. Thus, the article reviews the exercise response to cardiac output determinants and provides qualitative and quantitative perspective bases for making assumptions on the peripheral circulatory factors and oxygen use. Finally, the article demonstrates the usefulness of exercise testing as an effective integrative physiological approach to develop clinical reasoning or verify pathophysiological outcomes. Copyright © 2012 SPLF. Published by Elsevier Masson SAS. All rights reserved.

Hyperhomocysteinemia impairs regional blood flow: involvements of endothelial and neuronal nitric oxide.

PubMed

Toda, Noboru; Okamura, Tomio

2016-09-01

Increasing evidence support the idea that hyperhomocysteinemia (HHcy) is responsible for pathogenesis underlying cerebral, coronary, renal, and other vascular circulatory disorders and for hypertension. Impaired synthesis of nitric oxide (NO) in the endothelium or increased production of asymmetric dimethylarginine and activated oxygen species are involved in the impairment of vasodilator effects of NO. Impaired circulation in the brain derived from reduced synthesis and actions of NO would be an important triggering factor to dementia and Alzheimer's disease. Reduced actions of NO and brain hypoperfusion trigger increased production of amyloid-β that inhibits endothelial function, thus establishing a vicious cycle for impairing brain circulation. HHcy is involved in the genesis of anginal attack and coronary myocardial infarction. HHcy is also involved in renal circulatory diseases. The homocysteine (Hcy)-induced circulatory failure is promoted by methionine and is prevented by increased folic acid and vitamin B6/B12. Eliminating poor life styles, such as smoking and being sedentary; keeping favorable dietary habits; and early treatment maintaining constitutive NOS functions healthy, reducing oxidative stresses would be beneficial in protecting HHcy-induced circulatory failures.

Advanced Analgesic Drug Delivery and Nanobiotechnology.

PubMed

Stoicea, Nicoleta; Fiorda-Diaz, Juan; Joseph, Nicholas; Shabsigh, Muhammad; Arias-Morales, Carlos; Gonzalez-Zacarias, Alicia A; Mavarez-Martinez, Ana; Marjoribanks, Stephen; Bergese, Sergio D

2017-07-01

Transdermal administration of analgesic medications offers several benefits over alternative routes of administration, including a decreased systemic drug load with fewer side effects, and avoidance of drug degradation by the gastrointestinal tract. Transdermal administration also offers a convenient mode of drug administration over an extended period of time, particularly desirable in pain medicine. A transdermal administration route may also offer increased safety for drugs with a narrow therapeutic window. The primary barrier to transdermal drug absorption is the skin itself. Transdermal nanotechnology offers a novel method of achieving enhanced dermal penetration with an extended delivery profile for analgesic drugs, due to their small size and relatively large surface area. Several materials have been used to enhance drug duration and transdermal penetration. The application of nanotechnology in transdermal delivery of analgesics has raised new questions regarding safety and ethical issues. The small molecular size of nanoparticles enables drug delivery to previously inaccessible body sites. To ensure safety, the interaction of nanoparticles with the human body requires further investigation on an individual drug basis, since different formulations have unique properties and side effects.

Microcapsules and Methods for Making

NASA Technical Reports Server (NTRS)

Morrison, Dennis R. (Inventor); Mosier, Benjamin (Inventor)

1994-01-01

This invention relates to methods for forming multi-lamellar microcapsules of both hydrophilic and hydrophobic immiscible liquid phases using several polymer/solvent systems. Liquid-Liquid diffusion and spontaneous emulsification are controlled by properly timed sequence exposures of immiscible phases in aqueous vehicles dispersed in hydrocarbon solvents containing small quantities of oil, co-surfactants, and glycerides. Water-in-oil and oil-in-water microcapsules are formed containing selected combinations of several types of drugs, co-encapsulated within fluid compartments inside the microcapsule. Commercial applications of the process and the resultant product relate to drug therapy for treating medical conditions such as cancer, circulatory conditions, and other conditions in which pharmaceuticals are advantageously targeted to specific organs, or delivered in combination with other pharmaceuticals. Small microcapsules may be delivered intravenously to diseased organs or clotted vessels. The use of multiple drugs within the same microcapsule structure provides advantages for applications such as chemoembolization treatments and may be used to deliver both chemotherapeutic drugs, against tumor cells, and an immuno-adjuvant or immunological stimulant to enhance the patient's immune response. Active forms of urokinase and other enzymes may be delivered without dilution to the local site of an embolism for dissolving the embolism. Thus, the invention has several potentially valuable commercial applications related to pharmaceutical and medical applications.

77 FR 8262 - Draft Guidance on Investigational New Drug Applications for Positron Emission Tomography Drugs...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-14

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-D-0081] Draft Guidance on Investigational New Drug Applications for Positron Emission Tomography Drugs; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug...

Preclinical Determinants of Drug Choice under Concurrent Schedules of Drug Self-Administration

PubMed Central

Banks, Matthew L.; Negus, S. Stevens

2012-01-01

Drug self-administration procedures have played a critical role in the experimental analysis of psychoactive compounds, such as cocaine, for over 50 years. While there are numerous permutations of this procedure, this paper will specifically focus on choice procedures using concurrent schedules of intravenous drug self-administration. The aims of this paper are to first highlight the evolution of drug choice procedures and then review the subsequent preclinical body of literature utilizing these choice procedures to understand the environmental, pharmacological, and biological determinants of the reinforcing stimulus effects of drugs. A main rationale for this paper is our proposition that choice schedules are underutilized in investigating the reinforcing effects of drugs in assays of drug self-administration. Moreover, we will conclude with potential future directions and unexplored scientific space for the use of drug choice procedures. PMID:23243420

Photoacoustic monitoring of circulating tumor cells released during medical procedures

NASA Astrophysics Data System (ADS)

Juratli, Mazen A.; Sarimollaoglu, Mustafa; Nedosekin, Dmitry A.; Galanzha, Ekaterina; Suen, James Y.; Zharov, Vladimir P.

2013-03-01

Many cancer deaths are related to metastasis to distant organs due to dissemination of circulating tumor cells (CTCs) shed from the primary tumor. For many years, oncologists believed some medical procedures may provoke metastasis; however, no direct evidence has been reported. We have developed a new, noninvasive technology called in vivo photoacoustic (PA) flow cytometry (PAFC), which provides ultrasensitive detection of CTCs. When CTCs with strongly light-absorbing intrinsic melanin pass through a laser beam aimed at a peripheral blood vessel, laser-induced acoustic waves from CTCs were detected using an ultrasound transducer. We focused on melanoma as it is one of the most metastatically aggressive malignancies. The goal of this research was to determine whether melanoma manipulation, like compression, incisional biopsy, or tumor excision, could enhance penetration of cancer cells from the primary tumor into the circulatory system. The ears of nude mice were inoculated with melanoma cells. Blood vessels were monitored for the presence of CTCs using in vivo PAFC. We discovered some medical procedures, like compression of the tumor, biopsy, and surgery may either initiate CTC release in the blood which previously contained no CTCs, or dramatically increased (10-30-fold) CTC counts above the initial level. Our results warn oncologists to use caution during physical examination, and surgery. A preventive anti-CTC therapy during or immediately after surgery, by intravenous drug administration could serve as an option to treat the resulting release of CTCs.

Importance of integrating nanotechnology with pharmacology and physiology for innovative drug delivery and therapy - an illustration with firsthand examples.

PubMed

Zhang, Rui Xue; Li, Jason; Zhang, Tian; Amini, Mohammad A; He, Chunsheng; Lu, Brian; Ahmed, Taksim; Lip, HoYin; Rauth, Andrew M; Wu, Xiao Yu

2018-05-01

Nanotechnology has been applied extensively in drug delivery to improve the therapeutic outcomes of various diseases. Tremendous efforts have been focused on the development of novel nanoparticles and delineation of the physicochemical properties of nanoparticles in relation to their biological fate and functions. However, in the design and evaluation of these nanotechnology-based drug delivery systems, the pharmacology of delivered drugs and the (patho-)physiology of the host have received less attention. In this review, we discuss important pharmacological mechanisms, physiological characteristics, and pathological factors that have been integrated into the design of nanotechnology-enabled drug delivery systems and therapies. Firsthand examples are presented to illustrate the principles and advantages of such integrative design strategies for cancer treatment by exploiting 1) intracellular synergistic interactions of drug-drug and drug-nanomaterial combinations to overcome multidrug-resistant cancer, 2) the blood flow direction of the circulatory system to maximize drug delivery to the tumor neovasculature and cells overexpressing integrin receptors for lung metastases, 3) endogenous lipoproteins to decorate nanocarriers and transport them across the blood-brain barrier for brain metastases, and 4) distinct pathological factors in the tumor microenvironment to develop pH- and oxidative stress-responsive hybrid manganese dioxide nanoparticles for enhanced radiotherapy. Regarding the application in diabetes management, a nanotechnology-enabled closed-loop insulin delivery system was devised to provide dynamic insulin release at a physiologically relevant time scale and glucose levels. These examples, together with other research results, suggest that utilization of the interplay of pharmacology, (patho-)physiology and nanotechnology is a facile approach to develop innovative drug delivery systems and therapies with high efficiency and translational potential.

Development of a hybrid (numerical-hydraulic) circulatory model: prototype testing and its response to IABP assistance.

PubMed

Ferrari, G; Kozarski, M; De Lazzari, C; Górczyńska, K; Tosti, G; Darowski, M

2005-07-01

Merging numerical and physical models of the circulation makes it possible to develop a new class of circulatory models defined as hybrid. This solution reduces the costs, enhances the flexibility and opens the way to many applications ranging from research to education and heart assist devices testing. In the prototype described in this paper, a hydraulic model of systemic arterial tree is connected to a lumped parameters numerical model including pulmonary circulation and the remaining parts of systemic circulation. The hydraulic model consists of a characteristic resistance, of a silicon rubber tube to allow the insertion of an Intra-Aortic Balloon Pump (IABP) and of a lumped parameters compliance. Two electro-hydraulic interfaces, realized by means of gear pumps driven by DC motors, connect the numerical section with both terminals of the hydraulic section. The lumped parameters numerical model and the control system (including analog to digital and digital to analog converters)are developed in LabVIEW environment. The behavior of the model is analyzed by means of the ventricular pressure-volume loops and the time courses of arterial and ventricular pressures and flows in different circulatory conditions. A simulated pathological condition was set to test the IABP and verify the response of the system to this type of mechanical circulatory assistance. The results show that the model can represent hemodynamic relationships in different ventricular and circulatory conditions and is able to react to the IABP assistance.

Belgian modified classification of Maastricht for donors after circulatory death.

PubMed

Evrard, P

2014-11-01

"Non-heart-beating donors," or, in a more recent and international definition, "donors after circulatory death," are a potential and additional group of deceased persons who are able to add organs to the pool. A new classification is proposed on the basis of the result of a consensus of experts issued from all Belgian transplant centers. The first level of definition is simple and based on whether the situation is uncontrolled (categories I and II) or controlled (categories III, IV, and V). In category I, the patient is declared "dead on arrival" and, in category II, there is an "unsuccessful resuscitation" whether it occurred out or in the hospital for both situations. Category III is the most usual situation in which the treating physician and family are "awaiting cardiac arrest" to declare the death of the patient. Category IV is always characterized by "cardiac arrest during brain death." The special situation of the Belgian law allowing the euthanasia is elaborated in category V, "euthanasia," and includes patients who grant access to medically assisted circulatory death. Organ donation after euthanasia is allowed under the scope of donation after circulatory death. This classification conserves the skeleton of the Maastricht one, as it is simple and clear, but classifies easily the different donors after circulatory death types by processes for ethical issues and for the non-medical or non-specialized reader interested in the field. This is also an argument for public consideration and trust in the difficult field of organ donation.

[Importance of mechanical assist devices in acute circulatory arrest].

PubMed

Ferrari, Markus Wolfgang

2016-03-01

Mechanical assist devices are indicated for hemodynamic stabilization in acute circulatory arrest if conventional means of cardiopulmonary resuscitation are unable to re-establish adequate organ perfusion. Their temporary use facilitates further diagnostic and therapeutic options in selected patients, e.g. coronary angiography followed by revascularization.External thorax compression devices allow sufficient cardiac massage in case of preclinical or in-hospital circulatory arrest, especially under complex transfer conditions. These devices perform standardized thorax compressions at a rate of 80-100 per minute. Invasive mechanical support devices are used in the catheter laboratory or in the intensive care unit. Axial turbine pumps, e.g. the Impella, continuously pump blood from the left ventricle into the aortic root. The Impella can also provide right ventricle support by pumping blood from the vena cava into the pulmonary artery. So-called emergency systems or ECMO devices consist of a centrifugal pump and a membrane oxygenator allowing complete takeover of cardiac and pulmonary functions. Withdrawing blood from the right atrium and vena cava, oxygenated blood is returned to the abdominal aorta. Isolated centrifugal pumps provide left heart support without an oxygenator after transseptal insertion of a venous cannula into the left atrium.Mechanical assist devices are indicated for acute organ protection and hemodynamic stabilization for diagnostic and therapeutic measures as well as bridge to myocardial recovery. Future technical developments and better insights into the pathophysiology of mechanical circulatory support will broaden the spectrum of indications of such devices in acute circulatory arrest.

Circulatory Insufficiency and Hypotension Related to the Ductus Arteriosus in Neonates

PubMed Central

Rios, Danielle R.; Bhattacharya, Soume; Levy, Philip T.; McNamara, Patrick J.

2018-01-01

The biological role of the ductus arteriosus (DA) in neonates varies from an innocent bystander role during normal postnatal transition, to a supportive role when there is compromise to either systemic or pulmonary blood flow, to a pathological state in the presence of hemodynamically significant systemic to pulmonary shunts, as occurs in low birth weight infants. Among a wide array of clinical manifestations arising due to the ductal entity, systemic circulatory insufficiency and hypotension are of significant concern as they are particularly challenging to manage. An understanding of the physiologic interplay between the DA and the circulatory system is the key to developing appropriate targeted therapeutic strategies. In this review, we discuss the relationship of systemic hypotension to the DA, emphasizing the importance of critical thinking and a precise individual approach to intensive care support. We particularly focus on the variable states of hypotension arising directly due to a hemodynamically significant DA or seen in the period following successful surgical ligation. In addition, we explore the mechanistic contributions of the ductus to circulatory insufficiency that may manifest during the transitional period, states of maladapted transition (such as acute pulmonary hypertension of the newborn), and congenital heart disease (both ductal dependent and non-ductal dependent lesions). Understanding the dynamic modulator role of the ductus according to the ambient physiology enables a more precise approach to management. We review the pathophysiology, clinical manifestations, diagnosis, monitoring, and therapeutic intervention for the spectrum of DA-related circulatory compromise. PMID:29600242

Rapid and equivalent systemic bioavailability of the antidotes HI-6 and dicobalt edetate via the intraosseous and intravenous routes.

PubMed

Hill, Simon L; Thomas, Simon H L; Flecknell, Paul A; Thomas, Aurelie A; Morris, Chris M; Henderson, David; Dunn, Michael; Blain, Peter G

2015-08-01

Rapid and effective administration of antidotes by emergency medical responders is needed to improve the survival of patients severely poisoned after deliberate release of chemical weapons, but intravenous access is difficult to obtain while wearing personal protective equipment and in casualties with circulatory collapse. To test the hypothesis that rapid and substantial bioavailability of the antidotes HI-6 oxime and dicobalt edetate can be achieved via the intraosseous (IO) route, plasma concentration-time profiles of these antidotes were compared after administration by the intravenous and IO routes in a minipig animal model. 12 male Göttingen minipigs were randomly allocated to receive 7.14 mg/kg of HI-6 (by rapid bolus) then 4.28 mg/kg of dicobalt edetate (over 1 min) via the intravenous or IO route. Plasma concentrations of each antidote were measured over 360 min following administration and plasma concentration-time profiles plotted for each drug by each route. Peak HI-6 and cobalt concentrations occurred within 2 min of administration by both the intravenous and IO routes. Mean areas under the concentration-time curves (SD) to the end of the experiment (area under the concentration-time curve, AUC (0-t)) for cobalt were 430 (47, intravenous) and 445 (40, IO) μg-min/mL (mean difference 15, 95% CI -41 to 70, p=0.568) and for HI-6 were 2739 (1038, intravenous) and 2772 (1629, IO) μg-min/mL (mean difference 0.33, 95% CI -1724 to 1790, p=0.97). Increases in heart rate (by 50 beats/min intravenous and 27 beats/min IO) and BP, (by 67/58 mm Hg intravenous and 78/59 mm Hg IO), were observed after dicobalt edetate, consistent with the known adverse effects of this antidote. This study demonstrates rapid and similar systemic bioavailability of HI-6 and dicobalt edetate when given by the IO and intravenous routes. IO delivery of these antidotes is appropriate in the acute management of patients with organophosphate and cyanide intoxication when the intravenous route is impractical. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

21 CFR 312.140 - Address for correspondence.

Code of Federal Regulations, 2010 CFR

2010-04-01

... submission to the Central Document Room, Center for Drug Evaluation and Research, Food and Drug... Generic Drugs (HFD-600), Center for Drug Evaluation and Research, Food and Drug Administration, Metro Park... Evaluation and Research, Food and Drug Administration, 12229 Wilkins Ave., Rockville, MD 20852. (3) For...

21 CFR 312.140 - Address for correspondence.

Code of Federal Regulations, 2011 CFR

2011-04-01

... submission to the Central Document Room, Center for Drug Evaluation and Research, Food and Drug... Generic Drugs (HFD-600), Center for Drug Evaluation and Research, Food and Drug Administration, Metro Park... Evaluation and Research, Food and Drug Administration, 12229 Wilkins Ave., Rockville, MD 20852. (3) For...

Integrated Immune and Cardiovascular Function in Pancrustacea: Lessons from the Insects.

PubMed

Hillyer, Julián F

2015-11-01

When pathogens invade the insect hemocoel (body cavity) they immediately confront two major forces: immune-responses and circulatory currents. The immune response is mediated by circulating and sessile hemocytes, the fat body, the midgut, and the salivary glands. These tissues drive cellular and humoral immune processes that kill pathogens via phagocytosis, melanization, lysis, encapsulation, and nodulation. Moreover, immune-responses take place within a three-dimensional and dynamic space that is governed by the forces of the circulatory system. The circulation of hemolymph (insect blood) is primarily controlled by the wave-like contraction of a dorsal vessel, which is a muscular tube that extends the length of the insect and is divided into a thoracic aorta and an abdominal heart. Distributed along the heart are valves, called ostia, that allow hemolymph to enter the vessel. Once inside the heart, hemolymph is sequentially propelled to the anterior and to the posterior of the body. During an infection, circulatory currents sweep small pathogens to all regions of the body. As they circulate, pathogens encounter immune factors of the insect that range from soluble cytotoxic peptides to phagocytic hemocytes. A prominent location for these encounters is the surface of the heart. Specifically, periostial hemocytes aggregate in the extracardiac regions that flank the heart's ostia (the periostial regions) and phagocytoze pathogens in areas of high flow of hemolymph. This review summarizes the biology of the immune and circulatory systems of insects, including how these two systems have co-adapted to fight infection. This review also compares the immune and circulatory systems of insects to that of crustaceans, and details how attachment of hemocytes to cardiac tissues and the biology of the lymphoid organ demonstrate that dynamic interactions between the immune and circulatory systems also occur in lineages of crustaceans. © The Author 2015. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved. For permissions please email: journals.permissions@oup.com.

Past speculations of future health technologies: a description of technologies predicted in 15 forecasting studies published between 1986 and 2010

PubMed Central

Doos, Lucy; Packer, Claire; Ward, Derek; Simpson, Sue; Stevens, Andrew

2017-01-01

Objective To describe and classify health technologies predicted in forecasting studies. Design and methods A portrait describing health technologies predicted in 15 forecasting studies published between 1986 and 2010 that were identified in a previous systematic review. Health technologies are classified according to their type, purpose and clinical use; relating these to the original purpose and timing of the forecasting studies. Data sources All health-related technologies predicted in 15 forecasting studies identified in a previously published systematic review. Main outcome measure Outcomes related to (1) each forecasting study including country, year, intention and forecasting methods used and (2) the predicted technologies including technology type, purpose, targeted clinical area and forecast timeframe. Results Of the 896 identified health-related technologies, 685 (76.5%) were health technologies with an explicit or implied health application and included in our study. Of these, 19.1% were diagnostic or imaging tests, 14.3% devices or biomaterials, 12.6% information technology systems, eHealth or mHealth and 12% drugs. The majority of the technologies were intended to treat or manage disease (38.1%) or diagnose or monitor disease (26.1%). The most frequent targeted clinical areas were infectious diseases followed by cancer, circulatory and nervous system disorders. The most frequent technology types were for: infectious diseases—prophylactic vaccines (45.8%), cancer—drugs (40%), circulatory disease—devices and biomaterials (26.3%), and diseases of the nervous system—equally devices and biomaterials (25%) and regenerative medicine (25%). The mean timeframe for forecasting was 11.6 years (range 0–33 years, median=10, SD=6.6). The forecasting timeframe significantly differed by technology type (p=0.002), the intent of the forecasting group (p<0.001) and the methods used (p<001). Conclusion While description and classification of predicted health-related technologies is crucial in preparing healthcare systems for adopting new innovations, further work is needed to test the accuracy of predictions made. PMID:28760796

75 FR 6209 - Guidance for Industry and Food and Drug Administration; Guidance for the Use of Bayesian...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-08

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2006-D-0410] (formerly Docket No. 2006D-0191) Guidance for Industry and Food and Drug Administration; Guidance for the Use of Bayesian Statistics in Medical Device Clinical Trials; Availability AGENCY: Food and Drug...

75 FR 32952 - Draft Guidance for Industry and Food and Drug Administration Staff; “‘Harmful and Potentially...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-10

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-D-0281] Draft Guidance for Industry and Food and Drug Administration Staff; ```Harmful and Potentially Harmful... Food, Drug, and Cosmetic Act.'' This draft guidance provides written guidance to industry and FDA staff...

78 FR 17932 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

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2013-03-25

... Federal Food, Drug, and Cosmetic Act (21 U.S.C. 342(a)(3)). In addition, the current good manufacturing... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-N-0033... AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA...

21 CFR 170.105 - The Food and Drug Administration's (FDA's) determination that a premarket notification for a food...

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 3 2011-04-01 2011-04-01 false The Food and Drug Administration's (FDA's... and Drug Administration's (FDA's) determination that a premarket notification for a food contact substance (FCN) is no longer effective. (a) If data or other information available to FDA, including data...

21 CFR 170.105 - The Food and Drug Administration's (FDA's) determination that a premarket notification for a food...

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 3 2014-04-01 2014-04-01 false The Food and Drug Administration's (FDA's... (CONTINUED) FOOD ADDITIVES Premarket Notifications § 170.105 The Food and Drug Administration's (FDA's... data or other information available to FDA, including data not submitted by the manufacturer or...

21 CFR 170.105 - The Food and Drug Administration's (FDA's) determination that a premarket notification for a food...

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 3 2010-04-01 2009-04-01 true The Food and Drug Administration's (FDA's... and Drug Administration's (FDA's) determination that a premarket notification for a food contact substance (FCN) is no longer effective. (a) If data or other information available to FDA, including data...

21 CFR 170.105 - The Food and Drug Administration's (FDA's) determination that a premarket notification for a food...

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 3 2013-04-01 2013-04-01 false The Food and Drug Administration's (FDA's... and Drug Administration's (FDA's) determination that a premarket notification for a food contact substance (FCN) is no longer effective. (a) If data or other information available to FDA, including data...

21 CFR 170.105 - The Food and Drug Administration's (FDA's) determination that a premarket notification for a food...

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 3 2012-04-01 2012-04-01 false The Food and Drug Administration's (FDA's... and Drug Administration's (FDA's) determination that a premarket notification for a food contact substance (FCN) is no longer effective. (a) If data or other information available to FDA, including data...

21 CFR 118.9 - Administration of the Salmonella Enteritidis (SE) prevention plan.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 2 2012-04-01 2012-04-01 false Administration of the Salmonella Enteritidis (SE) prevention plan. 118.9 Section 118.9 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... EGGS § 118.9 Administration of the Salmonella Enteritidis (SE) prevention plan. You must have one or...

21 CFR 118.9 - Administration of the Salmonella Enteritidis (SE) prevention plan.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 2 2014-04-01 2014-04-01 false Administration of the Salmonella Enteritidis (SE) prevention plan. 118.9 Section 118.9 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... EGGS § 118.9 Administration of the Salmonella Enteritidis (SE) prevention plan. You must have one or...

21 CFR 118.9 - Administration of the Salmonella Enteritidis (SE) prevention plan.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 2 2013-04-01 2013-04-01 false Administration of the Salmonella Enteritidis (SE) prevention plan. 118.9 Section 118.9 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... EGGS § 118.9 Administration of the Salmonella Enteritidis (SE) prevention plan. You must have one or...

21 CFR 118.9 - Administration of the Salmonella Enteritidis (SE) prevention plan.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 2 2011-04-01 2011-04-01 false Administration of the Salmonella Enteritidis (SE) prevention plan. 118.9 Section 118.9 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... EGGS § 118.9 Administration of the Salmonella Enteritidis (SE) prevention plan. You must have one or...

21 CFR 118.9 - Administration of the Salmonella Enteritidis (SE) prevention plan.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 2 2010-04-01 2010-04-01 false Administration of the Salmonella Enteritidis (SE) prevention plan. 118.9 Section 118.9 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... EGGS § 118.9 Administration of the Salmonella Enteritidis (SE) prevention plan. You must have one or...

77 FR 55845 - Science Board to the Food and Drug Administration: Request for Nominations

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-11

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-N-0001... Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is requesting nominations to serve on the Science Board to FDA (Science Board). FDA seeks to include the views of women and men...

21 CFR 172.809 - Curdlan.

Code of Federal Regulations, 2014 CFR

2014-04-01

... FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD ADDITIVES... Additive Safety (HFS-200), Center for Food Safety and Applied Nutrition, Food and Drug Administration, 5100... Safety and Applied Nutrition's Library, Food and Drug Administration, 5100 Paint Branch Pkwy., College...

21 CFR 1316.50 - Appearance; representation; authorization.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 9 2010-04-01 2010-04-01 false Appearance; representation; authorization. 1316.50 Section 1316.50 Food and Drugs DRUG ENFORCEMENT ADMINISTRATION, DEPARTMENT OF JUSTICE ADMINISTRATIVE FUNCTIONS, PRACTICES, AND PROCEDURES Administrative Hearings § 1316.50 Appearance; representation...