Κυριακή 28 Αυγούστου 2016

Using a pulse oximeter to determine clinical depth of anesthesia—investigation of the utility of the perfusion index

Summary

Background

Peripheral vasodilation is a well-recognized side effect of general anesthesia, and induces changes in the amplitude of the pulse plethysmograph (PPG) waveform. This can be continuously quantitaed using the Perfusion Index (PI), a ratio of the pulsatile to nonpulsatile signal amplitude in the PPG waveform. We hypothesized that the perfusion index would rise with the induction of anesthesia in children, and fall with emergence, and performed a prospective, observational study to test this.

Aim

Our primary aim was to test whether the different clinical stages of anesthesia were associated with changes in the perfusion index, and the secondary aim was to test the correlation between the normalized perfusion index and the MAC value.

Methods

Twenty-one patients between the ages of 1 and 18 undergoing minor procedures with no anticipated painful stimuli were recruited. Patients with significant illnesses were excluded. Data collection commenced with a preinduction baseline, and data were collected continuously, with event marking, until completion of the anesthesia and removal of the pulse oximeter. Data collected included perfusion index, heart rate, and anesthetic gas concentration values. A normalized perfusion index was calculated by subtracting the initial baseline perfusion index value from all perfusion index values, allowing changes, from a standardized initial baseline value of zero, to be analyzed.

Results

During induction, the mean normalized perfusion index rose from 0.0 to 4.2, and then declined to 0.470 when the patients returned to consciousness. P < 0.001 using repeated measures anova test. The normalized perfusion index was correlated with MAC values (r2 = 0.33, 95% CI 0.18–0.47, P < 0.01).

Conclusion

The perfusion index changed significantly during different stages of anesthesia. There is a significant correlation between the perfusion index, measured by pulse oximetry, and the MAC value, in pediatric patients undergoing minor procedures.

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Validation of ultrasonography for non-invasive assessment of diaphragm function in muscular dystrophy

Abstract

Duchenne muscular dystrophy (DMD) is a severe, degenerative muscle disease caused by dystrophin mutations. The mdx mouse is a widely used animal model of DMD. The mdx diaphragm muscle most closely recapitulates key features of DMD muscles, including progressive fibrosis and considerable force loss. Diaphragm function in mdx mice is commonly evaluated by specific force measurements ex vivo. While useful, this method only measures force from a small muscle sample at one time point. Therefore, accurate assessment of diaphragm function in vivo would provide an important advancement to study the time-course of functional decline and treatment benefits. Here, we evaluated an ultrasonography technique for measuring time-dependent changes of diaphragm function in mdx mice. Diaphragm movement amplitude values for mdx mice were considerably lower than WT, decreased from 8 to 18 months of age, and correlated strongly with ex vivo specific force. We then investigated the time-course of diaphragm amplitude changes following administration of an adeno-associated viral vector expressing Flag-micro-dystrophin (AAV-μDys) to young adult mdx mice. Diaphragm amplitude peaked 4 weeks after AAV-μDys administration, and was 26% greater than control mdx mice at this time. This value decreased slightly to 21% above mdx controls after 12 weeks of treatment. Importantly, diaphragm amplitude again correlated strongly with ex vivo specific force. Also, diaphragm amplitude and specific force negatively correlated with fibrosis levels in the muscle. Together, our results validate diaphragm ultrasonography as a reliable technique for assessing time-dependent changes in dystrophic diaphragm function in vivo, and for evaluating potential therapies for DMD.

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Selective accumulation of biotin in arterial chemoreceptors- requirement for carotid body exocytotic dopamine secretion

Key points

  • Biotin, a vitamin whose main role is to be a coenzyme for carboxylases, accumulates at unusually large amounts within cells of the carotid body (CB).
  • In biotin-deficient rats biotin rapidly disappears from the blood; however it remains at relatively high levels in CB glomus cells. The CB contains high levels of mRNA for SLC5a6, a biotin transporter, and SLC19a3, a thiamine transporter regulated by biotin.
  • Animals with biotin deficiency exhibit pronounced metabolic lactic acidosis. Remarkably, glomus cells from these animals have normal electrical and neurochemical properties. However they show a marked decrease in the size of quantal dopaminergic secretory events.
  • Inhibitors of the vesicular monoamine transporter 2 (VMAT2) mimic the effect of biotin deficiency. In biotin-deficient animals, VMAT2 protein expression decreases in parallel with biotin depletion in CB cells.
  • These data suggest that dopamine transport and/or storage in small secretory granules in glomus cells depend on biotin.

Abstract

Biotin is a water-soluble vitamin required for the function of carboxylases as well as for the regulation of gene expression. Here, we report that biotin accumulates in unusually large amounts in cells of arterial chemoreceptors, carotid body (CB) and adrenal medulla (AM). We show in a biotin-deficient rat model that the vitamin rapidly disappears from the blood and other tissues (including the AM), while remaining at relatively high levels in the CB. We have also observed that, in comparison with other peripheral neural tissues, CB cells contain high levels of SLC5a6, a biotin transporter, and SLC19a3, a thiamine transporter regulated by biotin. Biotin-deficient rats show a syndrome characterized by marked weight loss, metabolic lactic acidosis, aciduria and accelerated breathing with normal responsiveness to hypoxia. Remarkably, CB cells from biotin-deficient animals have normal electrophysiological and neurochemical (ATP levels and catecholamine synthesis) properties; however, they exhibit a marked decrease in the size of quantal catecholaminergic secretory events, which is not seen in AM cells. A similar differential secretory dysfunction is observed in CB cells treated with tetrabenazine, a selective inhibitor of the vesicular monoamine transporter 2 (VMAT2). VMAT2 is highly expressed in glomus cells (in comparison with VMAT1) and in biotin-deficient animals VMAT2 protein expression decreases in parallel with the decrease of biotin accumulated in CB cells. These data suggest that biotin has an essential role in the homeostasis of dopaminergic transmission modulating the transport and/or storage of transmitters within small secretory granules in glomus cells.

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De novo Loss of function Mutations in KIAA2022 Are Associated with Epilepsy and Neurodevelopmental Delay in Females

Abstract

Intellectual disability (ID) affects about 3% of the population and has a male gender bias. Of at least 700 genes currently linked to ID, more than 100 have been identified on the X chromosome, including KIAA2022. KIAA2022 is located on Xq13.3 and is expressed in the developing brain. The protein product of KIAA2022, X-linked Intellectual Disability Protein Related to Neurite Extension (XPN), is developmentally regulated and is involved in neuronal migration and cell adhesion. The clinical manifestations of loss-of-function KIAA2022 mutations have been described previously in fifteen males, born from unaffected carrier mothers, but few females. Using whole exome sequencing, we identified a cohort of five unrelated female patients with de novo likely gene damaging variants in KIAA2022 and core phenotypic features of intellectual disability, developmental delay, epilepsy refractory to treatment, and impaired language, of similar severity as reported for male counterparts. This study supports KIAA2022 as a novel cause of X-linked dominant intellectual disability, and broadens the phenotype for KIAA2022 mutations.

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Six year adalimumab efficacy in steroid-dependent Crohn's disease patients: A prospective real life study

Adalimumab is effective in the treatment of Crohn's disease. We have already reported data on the efficacy of adalimumab in 110 steroid-dependent patients. At the end of the study 90 patients (64.5%) maintained clinical remission.

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Six year adalimumab efficacy in steroid-dependent Crohn's disease patients: A prospective real life study

Adalimumab is effective in the treatment of Crohn's disease. We have already reported data on the efficacy of adalimumab in 110 steroid-dependent patients. At the end of the study 90 patients (64.5%) maintained clinical remission.

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Fla. community paramedics to begin seeing patients

By Claire Aronson
The Bradenton Herald

MANATEE COUNTY, Fla. — As a paramedic, Shane Pflieger has been interviewing patients for years as he transports them to the emergency room like a doctor does. But once the patient is transferred to the doctor, his questioning ends.

Now Pflieger, who is one of two Manatee County community paramedics, said he is "going to learn about the where they keep going part."

On a recent morning, Pflieger, along with other community paramedic, Angie Hadlock, were studying textbooks before they went over to Centerstone of Florida for a site visit. They are a couple weeks into the education component of the rollout of the county's new community paramedicine program, which became the newest division in the public safety department at the beginning of August.

"We are going to be working closely with them," Pflieger said of Centerstone.

Community paramedicine will "fill community health care gaps by preventing unnecessary hospitalizations, decreasing hospital re-admissions and increasing access to primary care," according to a program brochure.

"It's a very high profile initiative," said Bob Smith, the county's public safety director. "It's got a pretty extensive amount of partnering with outside agencies. ... The value for us is helping those people with more than current emergency problems. We've got a great amount of resources in this county that can help people in these situations. We just need someone that can take the time to sit down with a patient and point in right direction more than anything else."

By the end of the month, the community paramedics will begin serving one of its target patient populations — those with mental health and substance abuse issues. The community paramedics will help to provide these patients with the available resources in the community.

"We recognize you have a problem. Lets talk about community resources," said James Crutchfield, the county's community paramedicine division chief. "It is important that we commit to these people."

Melissa Larkin-Skinner, chief clinical officer with Centerstone, said she hopes the new program will reduce the number of individuals with mental health and substance abuse problems.

"As a community, we have to find an answer," she said. "I think this is a very innovative approach that we are certainly all hopeful will work. I am certainly excited to see it get started."

Other target populations include patients who experience frequent falls, individuals using the 911 system three or more times within 30 days, those who suffer from congestive heart failure/chronic respiratory conditions and diabetic patients.

"Every month or every other month, we will see another subtype of patient," Crutchfield said.

The state's Strategic Plan encourages the development of community paramedicine programs, according to Crutchfield.

"It is going to be a large topic for awhile," he said. "Our target population and community problems align almost directly with the state vision."

While Manatee County isn't one of the very first community paramedicine programs in the state, there have been others that have started and failed because the program tried to do much at once, which is why Manatee's rollout will be slower, Crutchfield said.

"The idea is to crawl before walk and then walk before run," he said.

With a 9 percent increase in population growth since 2010, there has been a 37 percent increase in 911 call volume since 2008, according to Manatee County Emergency Medical Services data.

"Our population is increasing so call volume is going to increase as well," Crutchfield said. "If you are taking care of patients that are most vulnerable in the community, the need of EMS for those patients decreases."

Community outreach will be a component of the program, such as visiting homeless camps and telling them, for example, that they shouldn't be calling 911 to go to the hospital for a shower, Crutchfield said.

"Those calls will decrease," he said. "If you start addressing preventative type of medicine for people falling, that number changes too. We have to be understanding that may not decrease as some may hope because of more people moving here, so maybe the type of calls change."

A lot of the issues in health care are related to the fact that people overuse emergency rooms because they either can't get into see a primary care physician or they wait until there is an emergency instead of ongoing maintenance of the issue, Larkin-Skinner said.

"They are going to take their medical knowledge into the community to help people," she said. "It is all about trying to change behavior. It is giving them someone that has expertise to be healthier. I also think it shows that somebody cares about them."

A grant is funding the three positions within the division for one year. But continued funding for the program is included in the county's 2016-17 budget, which the commission will consider Sept. 15.

"I think you have to prove need and value," Crutchfield said. "There are so many needs. As we prove our worth, I think it's easy to justify more."



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Scalp-recorded high-frequency oscillations in atypical benign partial epilepsy

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Publication date: October 2016
Source:Clinical Neurophysiology, Volume 127, Issue 10
Author(s): Ping Qian, Hui Li, Jiao Xue, Zhixian Yang
ObjectiveTo investigate how high-frequency oscillations (HFOs) were affected by methylprednisolone treatment and the clinical significance of HFOs in patients with atypical benign partial epilepsy (ABPE).MethodsIn 14 ABPE patients with methylprednisolone treatment, we measured interictal HFOs and spikes during sleep in pre- and post-methylprednisolone scalp electroencephalography (EEG). Patients with benign childhood epilepsy with centrotemporal spikes (BECTS) were taken as control.ResultsBefore methylprednisolone treatment, 10/14 ABPE patients had HFOs, with a mean value of 85.79 per 60s per patient, while 2/14 BECTS patients had HFOs with a mean value of 1.86 per 60s per patient (p=0.006). The 10 ABPE patients with HFOs tended to have more frequent epileptic negative myoclonus/atypical absences than the other 4 ABPE patients without HFOs. Rates reduced by methylprednisolone treatment were statistically significant for both spikes (p=0.027) and HFOs (p=0.005). The percentage of reduction was 41.8% (4653/11,133) and 95% (1141/1202) for spikes and HFOs, respectively.ConclusionProportion and rates of HFOs in ABPE were more prevalent than in BECTS. HFO rates reduced by methylprednisolone treatment might be more significant than spike rates.SignificancePrevalence of HFOs reflected at least some aspect of epileptic severity of ABPE. HFOs were more sensitive to methylprednisolone treatment than spikes.



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