An increasing trend in health-care professionals notifying children of unhealthy weight status: NHANES 1999-2014.

BACKGROUND: Pediatric obesity prevalence remains at historically high levels. The objective of this study was to examine secular trends in the percentages of overweight/obese children who received notification from a health-care professional (HCP) about their unhealthy weight. METHODS: We analyzed data of 25 570 (including 8639 overweight/obese) children aged 2-18 years collected from seven cross-sectional biennial surveys (National Health and Nutrition Examination Survey, 1999-2014), in which adolescents (16 years and older) and caregivers, mostly biological mothers, of children (2-15 years) were asked 'Has a doctor or other health professional ever told you that you (or your child) were overweight?' RESULTS: Approximately 90% of overweight/obese children visited HCPs at least once in the past 12 months, but only 22.12% (s.e.=1.92) in 1999 to 34.43% (2.35) in 2014 of the overweight/obese children were notified by HCPs about unhealthy weight. The biennial increase in odds of receipt of notification of unhealthy weight was 1.08 (95% confidence interval=(1.04-1.12)). Greater likelihood for receipt of notification was associated with being obese (odds ratio=5.03 (4.29-5.89) vs overweight); black (1.24 (1.06-1.46)) or Hispanic race/ethnicity (1.72 (1.45-2.04) vs white); female sex (1.22 (1.07-1.11) vs boys); and child's insurance status (1.31 (1.08-1.59) vs uninsured). There were increasing odds of being notified with increasing age: 1.00 (reference), 2.24 (2.06-2.62), 3.22 (2.50-4.13) and 4.87 (3.76-6.32) for children 2-5, 6-11, 12-16 and 16+ year old, respectively. The frequency of medical contact was linearly associated with an increased likelihood of being notified. CONCLUSIONS: Notification of child's unhealthy weight by HCPs increased significantly between 1999 and 2014, but the opportunity of clinical intervention remained substantially under-utilized.

A-272651, a nonpeptidic blocker of large-conductance Ca2+-activated K+ channels, modulates bladder smooth muscle contractility and neuronal action potentials.

BACKGROUND AND PURPOSE: The large-conductance Ca(2+)-activated K(+) channel (BK(Ca), K(Ca)1.1) links membrane excitability with intracellular Ca(2+) signaling and plays important roles in smooth muscle contraction, neuronal firing, and neuroendocrine secretion. This study reports the characterization of a novel BK(Ca) channel blocker, 2,4-dimethoxy-N-naphthalen-2-yl-benzamide (A-272651). EXPERIMENTAL APPROACH: (86)Rb(+) efflux in HEK-293 cells expressing BK(Ca) was measured. Effects of A-272651 on BK(Ca) alpha- and BK(Ca) alphabeta1-mediated currents were evaluated by patch-clamp. Effects on contractility were assessed using low-frequency electrical field stimulated pig detrusor and spontaneously contracting guinea pig detrusor. Effects of A-272651 on neuronal activity were determined in rat small diameter dorsal root ganglia (DRG). KEY RESULTS: A-272651 (10 microM) inhibited (86)Rb(+) efflux evoked by NS-1608 in HEK-293 cells expressing BK(Ca) currents. A-272651 concentration-dependently inhibited BK(Ca) currents with IC(50) values of 4.59 microM (Hill coefficient 1.04, measured at +40 mV), and 2.82 microM (Hill coefficient 0.89), respectively, for BK(Ca) alpha and BK(Ca) alphabeta1-mediated currents. Like iberiotoxin, A-272651 enhanced field stimulated twitch responses in pig detrusor and spontaneous contractions in guinea pig detrusor with EC(50) values of 4.05+/-0.05 and 37.95+/-0.12 microM, respectively. In capsaicin-sensitive DRG neurons, application of A-272651 increased action potential firing and prolonged action potential duration. CONCLUSIONS AND IMPLICATIONS: These data demonstrate that A-272651 modulates smooth muscle contractility and neuronal firing properties. Unlike previously reported peptide BK(Ca) blockers, A-272651 represents one of the first small molecule BK(Ca) channel blockers that could serve as a useful tool for further characterization of BK(Ca) channels in physiological and pathological states.

Enantiospecific synthesis of annulated nicotine analogues from D-glutamic acid. 7-Azabicyclo[2.2.1]heptano[2.3-c]pyridines.

The conformationally restricted nicotinoid (1S,4S)-7-methyl-7-azabicyclo[2.2.1]heptano[2,3-c]pyridine dihydrochloride has been prepared enantiospecifically from D-glutamic acid. The method involved a lithium cis-2,6-dimethylpiperidide-mediated intramolecular anionic cyclization of (2S,5R)-N-(tert-butyloxycarbonyl)-5-[3-(4-N-chloropyridinyl]proline methyl ester in tandem with a standard decarboxylation sequence. Reductive amination afforded the desired N-methylated [2.2.1]bicyclonicotinoid. Cyclization of the corresponding iodopyridinylproline methyl ester, obtained via ultrasound-facilitated chloro-iodo exchange, was also effected.

Human natural killer cells: a unique innate immunoregulatory role for the CD56(bright) subset.

During the innate immune response to infection, monocyte-derived cytokines (monokines), stimulate natural killer (NK) cells to produce immunoregulatory cytokines that are important to the host's early defense. Human NK cell subsets can be distinguished by CD56 surface density expression (ie, CD56(bright) and CD56(dim)). In this report, it is shown that CD56(bright) NK cells produce significantly greater levels of interferon-gamma, tumor necrosis factor-beta, granulocyte macrophage-colony-stimulating factor, IL-10, and IL-13 protein in response to monokine stimulation than do CD56(dim) NK cells, which produce negligible amounts of these cytokines. Further, qualitative differences in CD56(bright) NK-derived cytokines are shown to be dependent on the specific monokines present. For example, the monokine IL-15 appears to be required for type 2 cytokine production by CD56(bright) NK cells. It is proposed that human CD56(bright) NK cells have a unique functional role in the innate immune response as the primary source of NK cell-derived immunoregulatory cytokines, regulated in part by differential monokine production.

Cardiac rehabilitation in the United Kingdom. How complete is the provision?

PURPOSE: To bring up-to-date information about all the cardiac rehabilitation (CR) units in the UK, including their staffing and the services they offer, and to determine the numbers and diagnoses of the patients they treat. METHODS: Questionnaire survey to establish the continued functioning of the centers, the disciplines of their staff, the number of patients treated, their diagnoses, and the outcomes measured. RESULTS: 286 centers were identified. Of the 236 who returned their questionnaires, 171 (72%) gave figures of the numbers and diagnoses of their patients. The median number treated in the different programs was 150, with a total of 32,499 patients. Of those, 63% were recovering from myocardial infarction, 25% from coronary artery bypass graft (CABG), and 4% from percutaneous transluminal coronary angioplasty (PTCA). Twenty-four percent of patients were female, 87% were between the ages of 40 and 74, and 10% were older than 75. Of the responders, 80 (34%) performed an exercise test both before and after the course. Of the 171 who gave figures, 113 (66%) measured outcomes. CONCLUSIONS: In the UK, between 14% and 23% of infarct patients, between 33% and 56% of CABG patients, and between 6% and 10% of PTCA patients are enrolled into CR programs.

Cost implications of using inhaled nitric oxide compared with epoprostenol for pulmonary hypertension.

OBJECTIVE: To compare the cost of using intravenous epoprostenol with that of inhaled nitric oxide (NO) for treating episodes of pulmonary hypertension in children with congenital heart disease. DESIGN: An analysis of the cost of epoprostenol and NO use over the previous 18 months was performed. Three 6-month periods were identified, two in which epoprostenol was used and the third in which inhaled NO was introduced for the treatment of pulmonary hypertension. SETTING: A 10-bed pediatric cardiac intensive care unit, Royal Liverpool Children's Hospital, Alder Hey, Liverpool, England. SUBJECTS: Children with congenital heart disease and persistently elevated pulmonary artery pressure following cardiac surgery. MAIN OUTCOME MEASURES: The total duration of use of epoprostenol and inhaled NO was documented. The costs per hour for epoprostenol and inhaled NO were calculated and the annual cost of each agent was estimated. RESULTS: In the two 6-month periods prior to the introduction of inhaled NO, epoprostenol was used on 14 occasions (5 in the first period, 3 in the second). In the last 6-month period, nine children required pulmonary vasodilator therapy on 14 occasions. All nine children were treated successfully with inhaled NO; none were given or needed epoprostenol, as NO always was effective in providing pulmonary vasodilatation. For resistant pulmonary hypertension, increasing the concentration of NO would have been the next therapeutic option. The cost for the two 6-month periods using epoprostenol was $19,483.48 for the drug and $283.25 for equipment costs (total cost $19,766.73). There was no expenditure on epoprostenol in the final 6-month period. The cost of NO was $465. However, the total expenditure, including the delivery and monitoring system, was $4,722.85. CONCLUSIONS: Using inhaled NO in our pediatric cardiac intensive care unit abolished the use of epoprostenol during the reported monitoring period. The cost savings were significant, amounting to 12% of the annual drug budget for the unit. The cost of setting up the inhaled NO delivery system is recouped rapidly. The ease of delivery and measurement of inhaled NO also may have contributed to its increased clinical use.

'Determination' of sugar alcohol and Polydextrose absorption in humans by the breath hydrogen (H2) technique: the stoichiometry of hydrogen production and the interaction between carbohydrates assessed in vivo and in vitro.

The production of hydrogen from substrates and substrate mixture of sugar alcohols and Polydextrose was determined, both in vivo using the breath hydrogen test, and in vitro, using human faecal microorganisms in anaerobic culture. One objective was to test a previous assumption that the stoichiometry of hydrogen production from different alternative carbohydrates is similar. Another objective was to discover whether hydrogen responses from mixtures of substrates were simply additive, or whether interactions occurred. The breath tests were performed in a 10 subject x 10 substrate factorial design with substrates and substrate mixtures (5-11 g) administered in 42 g chocolate confectionery. Incorporation of the alternative carbohydrates lactitol (L), Isomalt (I) and Polydextrose (P) into otherwise conventional confectionery increased breath hydrogen production by approximately 112, 73 and 11%/g respectively. There was no interaction between L and I or between P and I, but a combination of L and P approximately doubled the breath hydrogen anticipated from their individual contributions (P < 0.05). Anaerobic cultures showed a sixfold range in the efficiency of converting individual substrates and mixtures to hydrogen gas (0.003-0.018 kJ H2 per kJ carbohydrate). The positive interaction between L and P, and the lack of interaction between L and I, and between P and I, found in vivo were reproduced in vitro. The work showed that interpretation of the hydrogen breath test is confounded by differing stoichiometries for hydrogen production, by interaction between substrates and by an uncertain extent to which small intestinal hydrolysis yielding species with a fermentation stoichiometry that differs from the parent substrate.

Market value and managerial decisions: implications from a decade of feeder cattle teleauctions.

Data from feeder cattle teleauction sales in Georgia from 1977 to 1988 were analyzed using least squares analysis of variance to detect significant (P less than .05) influential factors on price. The sample was divided into two periods, 1977 to 1982 and 1983 to 1988, to test whether the influence of factors had changed over the time periods. The test of equality was rejected (P less than .01) using a Chow test, thus suggesting a change had occurred. Hereford breeds were discounted in the latter period whereas Angus breeds generated a premium in the earlier period. Treatment for specific diseases resulted in premium prices, as did preconditioning, during the 1983 to 1988 period. The effect of seasonality on prices decreased over the two time periods. The optimal lot size increased from 228 to 280 cattle during the time periods.

Coronary rehabilitation in the community.

Over a five-year period, 162 patients with coronary disease joined a physical rehabilitation course at a community sports centre gymnasium under the supervision of a general practitioner. One hundred and forty-seven patients had suffered a recent or old myocardial infarction and 15 suffered from angina pectoris. One hundred and thirty-eight patients (85 per cent) completed a three-month course of exercises, 16 (10 per cent) defaulted and eight (5 per cent) were withdrawn. One patient died at home during the three-month course. There were no changes in weight, blood pressure or blood fat measurements during the course but predicted maximum oxygen uptake increased by 26.9 per cent and the double product after effort (which is proportional to myocardial oxygen uptake) decreased by 13.6 per cent.We believe that the rehabilitation of patients in community sports centres is safe and effective and should be more widely practised.

Effects of glycogen depletion and pedaling speed on "anaerobic threshold".

Nine male subjects performed continuous incremental exercise on a bicycle ergometer pedaling at 50 and 90 rpm in a normal glycogen state (NG) and at 50 rpm in a glycogen-depleted state (GD) to determine if alterations in pedaling frequency and muscle glycogen content would affect their "anaerobic thresholds." Ventilatory [T(vent)] and lactate [T(lac)] thresholds were identified as the points after which expired minute volume and blood lactate began to increase nonlinearly as a function of work rate. The GD protocol elicited a significant divergence between the two thresholds shifting the T(vent) to a lesser and the T(lac) to a greater work rate relative to the NG state. When the pedaling frequency was increased to 90 rpm in the NG condition, the T(lac) was shifted to a lesser work rate relative to the 50-rpm NG condition. A correlation of only 0.71 was obtained between subjects' T(vent) and T(lac). In subjects of less than 70 kg body wt, the T(lac) came at a work rate 400 kg.m.min-1 less than in subjects of greater than 80 kg body wt despite equivalent O2 uptake. The observation that the T(vent) and T(lac) could be manipulated independently of each other reveals limitations in using the T(vent) to estimate the so-called anaerobic threshold.

Long-term antihypertensive drug treatment and blood pressure control in three hospital hypertension clinics.

Prescribing patterns and blood pressure control have been studied in 1101 patients treated at three specialist hypertension clinics in Britain. Seventy-four per cent of the patients were already receiving treatment at the time they were referred by their general practitioners. Though the initial improvement in blood pressure control was satisfactory, there was often some deterioration of control over the long term. The pressure exceeded 140/90 mmHg in the majority of patients followed for a year or more. During 1971-5 diuretics remained first preference, with increasing use of beta-blockers and a distinct decline in the use of sympathetic neurone blockers both by hospital staff and referring practitioners. Multiple drug treatment was common, nearly half the patients requiring more than one antihypertensive drug. In newly treated patients the frequency of cessation of a particular class of drug because of side effects or lack of efficacy ranged from 6 per cent with diuretics to 57 per cent with adrenergic neurone blocking drugs. Long-term blood pressure control still presents many problems, and the results contrast with the more optimistic interpretations sometimes placed on short-term clinical trials of antihypertensive effect.

Initial care of hypertensive patients. Influence of different types of clinical records.

The initial record of history and clinical findings has been studied in 278 patients attending three hypertension clinics. Half of these were randomly allocated to standard case notes and the other half to a special structured questionnaire record. The investigations carried out in a total of 521 patients with raised arterial pressures were examined. The records derived from the structured questionnaire were much more complete than the standard case notes but the difference was less obvious for a positive record than a negative one. None of the investigations was carried out in all patients, even though it was the policy of the clinics that most of them should be. A possible aetiological diagnosis was made in 28 patients and, at the time of writing, 3 patients had benefited from a surgical operation carried out as a result of investigation. These results raise the question of the quality of the initial care of hypertensive patients and suggest that the structured questionnaires might lead to an improvement. It remains to be established whether all the information collected does influence the outcome in patients with hypertension.

Randomised controlled trial of computer-held medical records in hypertensive patients.

A total of 278 hypertensive patients in three clinics were randomly allocated to have their medical records held in a computer system (136) or on standard hospital notes (142). For the computer system the doctor completed a structured input form, and the information on symptoms, physical findings, and diagnoses was more complete than that in the standard notes. This resulted in certain symptoms and risk factors being recognised more often when the computer system was used. The hypertension clinics' routines were not disrupted by the introduction of a computer-held system, and follow-up consultation times were not affected by the type of records kept, although the first consultation took eight minutes longer when computer documents were completed. The patients remained in the trial for one year and clinical management was assessed from blood pressure control, drop-out rates, and the frequency of performing investigations. These estimates of management showed no significant difference between the two groups, but the attempt to tailor the computer system to help management made the system acceptable to the doctors using it. The computer system continues to be used and is providing data for research into hypertension.

Computer-based hypertension clinic records: a co-operative study.

A computer-based medical record system has been developed to help with research into hypertension and the management of patients with hypertension. Standard medical records are replaced by data collection forms and case notes printed by the computer. A computer-generated document for recording information at follow-up visits contains an up-to-date summary of the important clinical features with warnings of risk factors. A blood-pressure graph and a letter for the general practitioner are produced on request. The system has been used in three clinics for two years and is being tested in general practice. Information on 900 newly-referred patients has been recorded and at present data on 30 to 40 new patients and 160 follow-up visits are added each month.