Continuous negative external pressure (cNEP) reduces respiratory impairment during screening colonoscopy: a pilot study.

BACKGROUND AND STUDY AIMS: Drugs administered during gastrointestinal procedures cause increased collapsibility of the upper airway, which may lead to respiratory impairment. We evaluated the ability of continuous negative external pressure (cNEP) to lessen respiratory impairment during screening colonoscopy. PATIENTS AND METHODS: The initial 24 patients served as controls, while the next 30 received cNEP. cNEP was delivered by a soft silicone collar placed over the anterior neck. The primary endpoint was the frequency of respiratory impairment, defined as either: (i) a decline from baseline of > 4 % in oxygen saturation, or (ii) apnea lasting ≥ 20 seconds. RESULTS: Mean respiratory impairment episodes were 3.50 in the no-cNEP group vs. 1.92 in the cNEP group, a reduction of 45 % (P = 0.022). Apneas ≥ 20 seconds occurred in 74 % of the no-cNEP group and 28 % of the cNEP group (P = 0.002). While 42 % of the no-cNEP group required increased supplemental oxygen, this was true for only 10 % of the cNEP group (P = 0.01). cNEP adverse events were minimal. CONCLUSIONS: During screening colonoscopy, sedation-related respiratory impairment is significantly reduced by cNEP.ClinicalTrials.gov NCT01895062.

Treatment of infantile neuroaxonal dystrophy with RT001: A di-deuterated ethyl ester of linoleic acid: Report of two cases.

BACKGROUND: Infantile neuroaxonal dystrophy (INAD) is a rare, autosomal recessive disease due to defects in PLA2G6 and is associated with lipid peroxidation. RT001 is a di-deuterated form of linoleic acid that protects lipids from oxidative damage. METHODS: We evaluated the pharmacokinetics (PK), safety, and effectiveness of RT001 in two subjects with INAD (subject 1: 34 months; subject 2: 10 months). After screening and baseline evaluations, subjects received 1.8 g of RT001 BD. PK analysis and clinical evaluations were made periodically. MAIN FINDINGS: Plasma levels of deuterated linoleic acid (D2-LA), deuterated arachidonic acid (D2-AA), D2-LA to total LA, and D2-AA to total AA ratios were measured. The targeted plasma D2-LA ratio (>20%) was achieved by month 1 and maintained throughout the study. RBC AA-ratios were 0.11 and 0.18 at 6 months for subjects 1 and 2; respectively. No treatment-related adverse events occurred. Limited slowing of disease progression and some return of lost developmental milestones were seen. CONCLUSIONS: Oral RT001 was administered safely in two subjects with INAD. Early findings suggest that the compound was well tolerated, metabolized and incorporated in the RBC membrane. A clinical trial is underway to assess efficacy.

The natural history of infantile neuroaxonal dystrophy.

BACKGROUND: Infantile neuroaxonal dystrophy (INAD) is a rapidly progressive neurodegenerative disorder of early onset causing premature death. It results from biallelic pathogenic variants in PLA2G6, which encodes a calcium-independent phospholipase A2. OBJECTIVE: We aim to outline the natural history of INAD and provide a comprehensive description of its clinical, radiological, laboratory, and molecular findings. MATERIALS AND METHODS: We comprehensively analyzed the charts of 28 patients: 16 patients from Riyadh, Saudi Arabia, 8 patients from North and South America and 4 patients from Europe with a molecularly confirmed diagnosis of PLA2G6-associated neurodegeneration (PLAN) and a clinical history consistent with INAD. RESULTS: In our cohort, speech impairment and loss of gross motor milestones were the earliest signs of the disease. As the disease progressed, loss of fine motor milestones and bulbar dysfunction were observed. Temporo-frontal function was among the last of the milestones to be lost. Appendicular spastic hypertonia, axial hypotonia, and hyperreflexia were common neurological findings. Other common clinical findings include nystagmus (60.7%), seizures (42.9%), gastrointestinal disease (42.9%), skeletal deformities (35.7%), and strabismus (28.6%). Cerebellar atrophy and elevations in serum AST and LDH levels were consistent features of INAD. There was a statistically significant difference when comparing patients with non-sense/truncating variants compared with missense/in-frame deletions in the time of initial concern (p = 0.04), initial loss of language (p = 0.001), initial loss of fine motor skills (p = 0.009), and initial loss of bulbar skills (p = 0.007). CONCLUSION: INAD is an ultra-rare neurodegenerative disorder that presents in early childhood, with a relentlessly progressive clinical course. Knowledge of the natural history of INAD may serve as a resource for healthcare providers to develop a targeted care plan and may facilitate the design of clinical trials to treat this disease.

Measures of obesity and metabolic syndrome in Indian Americans in northern California.

BACKGROUND: In populations predisposed to cardiovascular disease, type 2 diabetes and visceral obesity, use of additional measurements of waist girth and waist/hip ratio (WHR) can help define risk levels associated with body mass index (BMI) for screening and clinical purposes. PURPOSE: To investigate measures of obesity associated with presence of metabolic syndrome and its risk factors in asymptomatic American adults of Asian Indian origin between 29 and 59 years of age. METHODS: Fifty-six apparently healthy men (43.7 years +/- 7.1, BMI 21-34 kg/m2) and women (43.1 years +/- 6.9, BMI 21-36 kg/m2) were recruited for participation in this cross-sectional study. Height, weight, hip girth, waist girth, and blood pressure were recorded by using standard procedures. Blood samples were taken after an overnight fast and analyzed for measures defined by the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) criteria for the metabolic syndrome. RESULTS: Prevalence of the metabolic syndrome was 33.9% (29-59 years, average BMI 26.1 +/- 3.7 kg/m2). Risk factors most prevalent were low high-density lipoprotein cholesterol (HDL-C) (55%), hypertriglyceridemia (61%), and high blood pressure (50%) in men and low HDL-C (56%), high waist circumference (44%), and high blood pressure (32%) in women. Waist girth of 90.8 +/- 6.8 cm (men) and 75 +/- 3 cm (women), waist/hip ratios (WHRs) of .89 +/- .06 (men) and .76 +/- .03 (women), and BMI values of 24.8 +/- 2.5 kg/m2 (men) and 23.7 +/- 1 kg/m2 (women) were associated with absence of all risk factors associated with metabolic syndrome. Average waist girth (men: 99.6 +/- 8.1 cm, P < .05; women: 95.5 +/- 5.2 cm, P < .001) of those positive was significantly higher than those negative for the metabolic syndrome. Waist girth in women was significantly associated with fasting glucose (r = .40, P < .05), two-hour glucose (r = .57, P < .05), triglyceride (r = .42, P < 05), and HDL-C (r = -.47, P < .05). Waist/ hip ratio (WHR) for women with the metabolic syndrome was significantly higher (.87 +/- .07, P < .05) compared to those without (.79 +/- .05) and most significantly correlated with two-hour glucose (r = .51, P < .05). Body mass index (BMI) in the overweight range for men (28.3 +/- 3 kg/m2, P < .05) and women (30.0 +/- 3.5 kg/m2, P < .05) was associated with metabolic syndrome and significantly correlated with low HDL-C levels in men (r = -.49, CONCLUSION: Prevalence of the metabolic syndrome in Indian Americans aged 29- 59 years using the NCEP ATP III criteria was similar to rates reported in urban populations in India. Low HDL-C, hypertriglyceridemia, high waist circumference, and high blood pressure were most prevalent risk factors in this study. Among obesity measures, waist girth was significantly associated with most risk factors for the syndrome; WHR was most significant for two-hour glucose in women, whereas BMI mostly correlated with HDL-C for men. While BMI < or = 24.9 was associated with absence of all risk factors, BMI in overweight range was associated with presence of metabolic syndrome. These results point to clinical significance of using additional measures of obesity in addition to BMI to determine health risk in this population, particularly in premenopausal Asian Indian women.

Leisure time physical activity and metabolic syndrome in Asian Indian immigrants residing in northern California.

OBJECTIVE: Immigrant Asian Indians possess major lipid and non-lipid risk factors that constitute features characteristic of metabolic syndrome. First-line therapy recognized in risk management of this syndrome is weight reduction and increased physical activity. We investigated the relationship of intensity and duration of leisure time physical activity (LTPA) to physiological indices of metabolic syndrome in Asian Indian immigrants. METHODS: Fifty-six apparently healthy men (43.7 years +/- 7.1; body mass index [BMI] 21-34) and women (43.1 years +/- 6.9; BMI 21-36) were screened to participate in this cross-sectional study. Leisure time physical activity (LTPA) was determined by Minnesota LTPA questionnaire. Anthropometric measurements were recorded by using standard procedures. Blood samples taken after an overnight fast were analyzed for measures defined by the NCEP ATP III criteria for metabolic syndrome. RESULTS: Prevalence of metabolic syndrome was 33.9% (age 29-59 years; average BMI 26.1 +/- 3.7) suggesting development of syndrome at younger age. While participants reported little LTPA, men were more active than women (total activity metabolic index (AMI) per week: 533 vs 204, respectively). In men, moderate activity was associated with a lower prevalence of metabolic syndrome, lower fasting glucose (r=-0.44), 2-hour glucose tolerance (r=-0.40), and lower serum triglyceride (r=-0.63). Only heavy activity was inversely associated with waist girth for both men (r=-0.46) and women (r=-0.41). Leisure activity levels reported by women were not significantly associated with any other risk factors. Low levels of physical activity were associated with prevalence of low high-density lipoprotein cholesterol (HDL-C), but reported LTPA levels were not significantly associated with favorable changes in serum HDL-C or blood pressure in both sexes. CONCLUSION: We provide evidence that Asian Indians who are physically active have a more favorable metabolic syndrome risk factor profile. Results highlight need to encourage physical activity in Asian Indian immigrants, particularly women, to reduce prevalence of metabolic syndrome.

The effect of ambient air temperature on whole-body bioelectrical impedance.

It has previously been shown that extreme changes in ambient air temperature can affect whole-body bioelectrical impedance. The purpose of this study was to determine if more moderate changes in ambient air temperature, such as those experienced in most laboratory settings, would also affect bioelectric impedance analysis (BIA). In addition, to elucidate the mechanism responsible for changes in BIA with ambient air temperature, both skin blood flow (SBF) and the electrode-skin interface temperature were independently manipulated to determine their effect on BIA. During the first part of the study, nine healthy volunteers had their BIA measured in five different ambient air temperatures (15, 20, 25, 30 and 35 degrees C). Mean BIA was 513 ohms under the 15 degrees C condition and decreased significantly (p < 0.05) to 486 ohms in the 35 degrees C trial. However, no significant change was found in mean BIA between the 20 and 25 degrees C trials, which is the temperature range seen in most laboratories. Thus, moderate changes in ambient air temperature have only minor effects on BIA. In the second and third parts of the study, the electrode-skin interface temperature and SBF were independently manipulated using ice packs and electric heating pads placed over the four BIA electrodes. The results showed that BIA was inversely related to SBF (r = -0.95), and strongly suggest that changes in SBF, not electrode-skin interface temperature, are responsible for the changes seen in BIA.

Prognostic significance of post-clopidogrel platelet reactivity assessed by a point-of-care assay on thrombotic events after drug-eluting stent implantation.

AIMS: The aim of this study was to determine whether platelet reactivity on clopidogrel therapy, as measured by a point-of-care platelet function assay, is associated with thrombotic events after percutaneous coronary intervention (PCI) with drug-eluting stents (DESs). METHODS AND RESULTS: Platelet reactivity on clopidogrel (post-treatment reactivity) was measured with the VerifyNow P2Y12 assay (Accumetrics Inc., San Diego, CA, USA) in 380 patients undergoing PCI with sirolimus-eluting stents. Receiver-operating characteristic curve analysis was used to derive the optimal cut-off value for post-treatment reactivity in predicting 6 month out-of-hospital cardiovascular (CV) death, non-fatal MI, or stent thrombosis. The mean post-treatment reactivity was 184 +/- 85 PRU (P2Y12 reaction units). The optimal cut-off for the combined endpoint was a post-treatment reactivity > or =235 PRU [area under the curve 0.711 (95% confidence interval 0.529-0.893), P = 0.03], which was similar to the threshold of the upper tertile (231 PRU). Patients with post-treatment reactivity greater than the cut-off value had significantly higher rates of CV death (2.8 vs. 0%, P = 0.04), stent thrombosis (4.6 vs. 0%, P = 0.004), and the combined endpoint (6.5 vs. 1.0%, P = 0.008). CONCLUSION: High post-treatment platelet reactivity measured with a point-of-care platelet function assay is associated with post-discharge events after PCI with DES, including stent thrombosis. Investigation of alternative clopidogrel dosing regimens to reduce ischaemic events in high-risk patients identified by this assay is warranted.