Absent peripheral chemosensitivity in Prader-Willi syndrome

1994 ◽  
Vol 77 (5) ◽  
pp. 2231-2236 ◽  
Author(s):  
D. Gozal ◽  
R. Arens ◽  
K. J. Omlin ◽  
S. L. Ward ◽  
T. G. Keens
Keyword(s):  
Body Mass Index ◽  
Body Mass ◽  
Vital Capacity ◽  
Minute Ventilation ◽  
Prader Willi Syndrome ◽  
Peripheral Chemoreceptor ◽  
Afferent Pathways ◽  
Ventilatory Responses ◽  
Control Subjects ◽  
And Control

Abnormalities in ventilatory control during wakefulness and sleep have been observed in patients with Prader-Willi syndrome (PWS). The role of peripheral chemoreceptors in the pathophysiology of abnormal ventilatory responses in PWS is unknown. We studied peripheral chemoreceptor function during wakefulness in 17 genetically confirmed PWS patients [age 27.0 +/- 2.5 (SE) yr; 7 males, 10 females; body mass index 31.1 +/- 1.4 kg/m2] and compared their responses with 17 control subjects matched for age, sex, and body mass index. All PWS and control subjects had normal resting end-tidal PCO2 and arterial O2 saturation while awake. Peripheral chemoreceptor function was assessed by the ventilatory responses to 100% O2 breathing, five tidal breaths of 100% N2, and vital capacity breaths of 15% CO2 in O2. Control subjects decreased minute ventilation (VE) by 15.5 +/- 3.6% during hyperoxia. However, PWS patients increased VE by 17.6 +/- 3.3%, indicating a paradoxical response to hyperoxia (P < 0.00001). After CO2 vital capacity breaths, PWS patients showed no significant change and control subjects showed a marked increase (P < 0.0001) in VE. During N2 breathing, again PWS patients showed no change and control subjects exhibited a marked increase (P < 0.00005) in VE. We conclude that PWS patients have absent peripheral chemoreceptor ventilatory responses. We speculate that the lack of ventilatory responses is due to primary peripheral chemoreceptor dysfunction and/or defective afferent pathways to central controllers.

Peripheral chemoreceptor function in children with the congenital central hypoventilation syndrome

1993 ◽  
Vol 74 (1) ◽  
pp. 379-387 ◽  
Author(s):  
D. Gozal ◽  
C. L. Marcus ◽  
D. Shoseyov ◽  
T. G. Keens
Keyword(s):  
Vital Capacity ◽  
Minute Ventilation ◽  
Acute Hypoxia ◽  
Clinical Manifestations ◽  
Congenital Central Hypoventilation Syndrome ◽  
Tidal Breathing ◽  
Peripheral Chemoreceptor ◽  
Ventilatory Responses ◽  
Central Hypoventilation ◽  
Hypoventilation Syndrome

In children with the congenital central hypoventilation syndrome (CCHS), some patients require mechanical ventilation during sleep, whereas others need respiratory assistance even when awake. The cause of this disparity is unclear. We hypothesized that differences in peripheral chemoreceptor response (PCR) could provide an explanatory mechanism for this disparity in clinical manifestations. PCR was measured in five children with CCHS and five sex- and age-matched controls by measuring the ventilatory responses induced by 100% O2 breathing, five tidal breaths of 100% N2, and vital capacity breaths of 5% and 15% CO2 in O2 and 5% CO2–95% N2. Tidal breathing of 100% O2 resulted in similar ventilatory responses in CCHS patients and controls with various changes dependent on the method of analysis of response used. Acute hypoxia by N2 tidal breathing resulted in a 39.2 +/- 22% increase in respiratory rate in CCHS patients and a 15.1 +/- 11.1% increase in controls (P < 0.05), with similar increases in minute ventilation (VE) of 124 +/- 69% and 85 +/- 11%, respectively. Vital capacity breaths of each of the CO2-containing gas mixtures induced similar increases in VE in CCHS patients and controls. The changes in VE obtained with 15% CO2–85% O2 and with 5% CO2–95% N2 were significantly greater than those with 5% CO2–95% O2, suggesting a dose-dependent response as well as additive effects of hypercapnic and hypoxic stimuli. We conclude that the PCR, when assessed by acute hypoxia, hyperoxia, or hypercapnia, is present and intact in CCHS children who are able to sustain adequate ventilation during wakefulness.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals The cut-off limits of the GH response to GH-releasing hormone-arginine test related to body mass index

2005 ◽  
Vol 153 (2) ◽  
pp. 257-264 ◽  
Author(s):  
Ginevra Corneli ◽  
Carolina Di Somma ◽  
Roberto Baldelli ◽  
Silvia Rovere ◽  
Valentina Gasco ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Body Mass ◽  
Gh Deficiency ◽  
Pituitary Hormone ◽  
Obese Patients ◽  
Releasing Hormone ◽  
Gh Secretion ◽  
Control Subjects ◽  
Optimal Separation ◽  
And Control

Objective: The diagnosis of growth hormone (GH) deficiency (GHD) in adults is based on a reduced peak GH response to provocative tests, such as the insulin tolerance test (ITT) and the GH-releasing hormone-arginine (GHRH-ARG) test. However, the cut-off limits of peak GH response in lean subjects are not reliable in obese patients; this is noteworthy since adult GHD is often associated with obesity. Aim of this study was to evaluate the diagnostic cut-off limits of peak GH response to the GHRH-ARG test in overweight and obese as well as in lean population. Design and methods: The GH responses to the GHRH-ARG test were studied in 322 patients with organic hypothalamic-pituitary disease and in 318 control subjects. Patients were subdivided into two groups on the basis of the number of pituitary hormone deficits, except for GH deficiency: (a) patients with total pituitary hormone deficit (TPHD) and (b) patients without or with no more than two pituitary hormone deficits (PHD). Both patients and control subjects were divided into three subgroups according to body mass index (BMI): lean (BMI <25 kg/m2), overweight (BMI ≥25 and <30 kg/m2) and obese (BMI ≥30 kg/m2). TPHD patients were assumed to be GH deficient, whereas PHD patients may include subjects with either normal or impaired GH secretion. The statistical analysis was carried out by the Receiver-Operating Characteristic curve analysis (Medcalc 7.2). The diagnostic cut-off points were calculated for lean, overweight and obese subjects to provide optimal separation of GH-deficient patients and control subjects according to two criteria: (1) a balance between high sensitivity and high specificity; (2) to provide the highest pair of sensitivity/specificity values for GH deficiency. Results: In the lean population the best pair of values, with highest sensitivity as 98.7% and highest specificity as 83.7%, was found using a peak GH cut-off point of 11.5 μg/l. In the overweight population the best pair of values, 96.7 and 75.5%, respectively, was found using a peak GH cut-off point of 8.0 μg/l. In the obese population the best pair of values, 93.5 and 78.3%, respectively, was found using a peak GH cut-off point of 4.2 μg/l. Applying the above mentioned cut-off points, among PHD patients we found that 80 subjects (72%) were GHD whereas 31 (28%) had normal GH secretion. Conclusions: In conclusion the GHRH-ARG test is a reliable tool for the diagnosis of adult GH deficiency in lean, overweight and obese patients, provided that specific BMI-related cut-off limits are assumed.

Ventilatory Responses During Submaximal Exercise in Children With Prader–Willi Syndrome

2018 ◽  
Vol 30 (3) ◽  
pp. 411-417 ◽  
Author(s):  
Adam M. Hyde ◽  
Robert G. McMurray ◽  
Frank A. Chavoya ◽  
Daniela A. Rubin
Keyword(s):  
Carbon Dioxide ◽  
Body Mass Index ◽  
Oxygen Uptake ◽  
Tidal Volume ◽  
Body Mass ◽  
Metabolic Cost ◽  
Prader Willi Syndrome ◽  
Breathing Frequency ◽  
Ventilatory Responses ◽  
Carbon Dioxide Output

Purpose: Prader–Willi syndrome (PWS) is a genetic neurobehavioral disorder presenting hypothalamic dysfunction and adiposity. At rest, PWS exhibits hypoventilation with hypercapnia. We characterized ventilatory responses in children with PWS during exercise. Methods: Participants were children aged 7–12 years with PWS (n = 8) and without PWS with normal weight (NW; n = 9, body mass index ≤ 85th percentile) or obesity (n = 9, body mass index ≥ 95th percentile). Participants completed three 5-minute ambulatory bouts at 3.2, 4.0, and 4.8 km/h. Oxygen uptake, carbon dioxide output, ventilation, breathing frequency, and tidal volume were recorded. Results: PWS had slightly higher oxygen uptake (L/min) at 3.2 km/h [0.65 (0.46–1.01) vs 0.49 (0.34–0.83)] and at 4.8 km/h [0.89 (0.62–1.20) vs 0.63 (0.45–0.97)] than NW. PWS had higher ventilation (L/min) at 3.2 km/h [16.2 (13.0–26.5) vs 11.5 (8.4–17.5)], at 4.0 km/h [16.4 (13.9–27.9) vs 12.7 (10.3–19.5)], and at 4.8 km/h [19.7 (17.4–31.8) vs 15.2 (9.5–21.6)] than NW. PWS had greater breathing frequency (breaths/min) at 3.2 km/h [38 (29–53) vs 29 (22–35)], at 4.0 km/h [39 (29–58) vs 29 (23–39)], and at 4.8 km/h [39 (33–58) vs 32 (23–42)], but similar tidal volume and ventilation/carbon dioxide output to NW. Conclusion: PWS did not show impaired ventilatory responses to exercise. Hyperventilation in PWS may relate to excessive neural stimulation and metabolic cost.

Decreased Bone Density in Adolescent Girls With Anorexia Nervosa

PEDIATRICS ◽  
1990 ◽  
Vol 86 (3) ◽  
pp. 440-447 ◽  
Author(s):  
Laura K. Bachrach ◽  
David Guido ◽  
Debra Katzman ◽  
Iris F. Litt ◽  
Robert Marcus
Keyword(s):  
Bone Mineral Density ◽  
Body Mass Index ◽  
Anorexia Nervosa ◽  
Bone Density ◽  
Bone Mass ◽  
Body Mass ◽  
Bone Mineral ◽  
Whole Body ◽  
Mineral Density ◽  
Control Subjects

Osteoporosis develops in women with chronic anorexia nervosa. To determine whether bone mass is reduced in younger patients as well, bone density was studied in a group of adolescent patients with anorexia nervosa. With single- and dual-photon absorptiometry, a comparison was made of bone mineral density of midradius, lumbar spine, and whole body in 18 girls (12 to 20 years of age) with anorexia nervosa and 25 healthy control subjects of comparable age. Patients had significantly lower lumbar vertebral bone density than did control subjects (0.830 ± 0.140 vs 1.054 ± 0.139 g/cm2) and significantly lower whole body bone mass (0.700 ± 0.130 vs 0.955 ± 0.130 g/cm2). Midradius bone density was not significantly reduced. Of 18 patients, 12 had bone density greater than 2 standard deviations less than normal values for age. The diagnosis of anorexia nervosa had been made less than 1 year earlier for half of these girls. Body mass index correlated significantly with bone mass in girls who were not anorexic (P &lt; .05, .005, and .0001 for lumbar, radius, and whole body, respectively). Bone mineral correlated significantly with body mass index in patients with anorexia nervosa as well. In addition, age at onset and duration of anorexia nervosa, but not calcium intake, activity level, or duration of amenorrhea correlated significantly with bone mineral density. It was concluded that important deficits of bone mass occur as a frequent and often early complication of anorexia nervosa in adolescence. Whole body is considerably more sensitive than midradius bone density as a measure of cortical bone loss in this illness. Low body mass index is an important predictor of this reduction in bone mass.

Effectiveness of Deep Brain Stimulation in Reducing Body Mass Index and Weight: A Systematic Review

2021 ◽  
pp. 1-11
Author(s):  
William Omar Contreras López ◽  
Paula Alejandra Navarro ◽  
Santiago Crispín
Keyword(s):  
Systematic Review ◽  
Body Mass Index ◽  
Deep Brain Stimulation ◽  
Body Mass ◽  
Brain Stimulation ◽  
The Body ◽  
Health Concern ◽  
Prader Willi Syndrome ◽  
Falling Asleep ◽  
Deep Brain

<b><i>Background:</i></b> Obesity has become a major public health concern worldwide, with current behavioral, pharmacological, and surgical treatments offering varying rates of success and adverse effects. Neurosurgical approaches to treatment of refractory obesity include deep brain stimulation (DBS) on either specific hypothalamic or reward circuitry nuclei, which might contribute to weight reduction through different mechanisms. We aimed to determine the safety and clinical effect of DBS in medical refractory obesity. <b><i>Summary:</i></b> Adhering to PRISMA guidelines, we performed a systematic review to identify all original studies – observational and experimental – in which DBS was performed to treat refractory obesity. From database inception to April 2021, we conducted our search in PubMed, Scopus, and LILACS databases using the following MeSH terms: “Obesity” OR “Prader-Willi Syndrome” AND “Deep Brain Stimulation.” The main outcomes were safety and weight loss measured with the body mass index (BMI). The Grading of Recommendations Assessment, Development, and Evaluation methods were applied to evaluate the quality of evidence. This study protocol was registered with PROSPERO ID: CRD42019132929. Seven studies involving 12 patients met the inclusion criteria; the DBS target was the nucleus accumbens in four (57.1%), the lateral hypothalamic area in two (29.6%), and the ventral hypothalamus in one (14.3%). Further, 33% of participants had obesity secondary to Prader-Willi syndrome (PWS) and 66.6% had primary obesity. The global BMI average at baseline was 46.7 (SD: 9.6, range: 32.2–59.1), and after DBS, 42.8 (SD: 8.8, range: 25–53.9), with a mean difference of 3.9; however, the delta in PWS patients was −2.3 and 10 in those with primary obesity. The incidence of moderate side effects was 33% and included manic symptoms (<i>N</i> = 2), electrode fracture (<i>N</i> = 1), and seizure (<i>N</i> = 1); mild complications (41.6%) included skin infection (<i>N</i> = 2), difficulties falling asleep (<i>N</i> = 1), nausea (<i>N</i> = 1), and anxiety (<i>N</i> = 1). <b><i>Key Messages:</i></b> Despite available small case series and case reports reporting a benefit in the treatment of refractory obesity with DBS, this study emphasizes the need for prospective studies with longer follow-ups in order to further address the efficacy and indications.

scholarly journals The Metabolic Phenotype of Prader-Willi Syndrome (PWS) in Childhood: Heightened Insulin Sensitivity Relative to Body Mass Index

2011 ◽  
Vol 96 (1) ◽  
pp. E225-E232 ◽  
Author(s):  
Andrea M. Haqq ◽  
Michael J. Muehlbauer ◽  
Christopher B. Newgard ◽  
Steven Grambow ◽  
Michael Freemark
Keyword(s):  
Body Mass Index ◽  
Insulin Sensitivity ◽  
Body Mass ◽  
Density Lipoprotein ◽  
High Sensitivity ◽  
Metabolic Phenotype ◽  
Prader Willi Syndrome ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Total Adiponectin

Context: Insulin sensitivity is higher in patients with Prader-Willi syndrome (PWS) than in body mass index-matched obese controls (OCs). Factors contributing to the heightened insulin sensitivity of PWS remain obscure. We compared the fasting levels of various hormones, cytokines, lipids, and liver function tests in 14 PWS patients and 14 OCs with those in 14 age- and gender-matched lean children (LC). We hypothesized that metabolic profiles of children with PWS are comparable with those of LC, but different from those of OCs. Results: Leptin levels were comparable in PWS patients and OCs, suggesting comparable degrees of adiposity. Glucose levels were comparable among groups. However, fasting insulin concentrations and homeostasis model assessment insulin resistance index were lower in PWS patients than in OCs (P &lt; 0.05) and similar to LC. Moreover, high-density lipoprotein levels were lower and triglycerides higher in OCs (P &lt; 0.05) but not PWS patients. Total adiponectin, high-molecular-weight (HMW) adiponectin and the HMW to total adiponectin ratio were higher in PWS patients (P &lt; 0.05) than in OCs and similar to LC. High-sensitivity C-reactive protein and IL-6 levels were higher in OCs than in PWS patients or LC (P &lt; 0.05). Nevertheless, PAI-1 levels were elevated in both OC and PWS patients. There were no group differences in glucagon-like peptide-1, macrophage chemoattractant protein-1, TNFα, IL-2, IL-8, IL-10, IL-12p40, IL-18, resistin, total or low-density lipoprotein cholesterol, aspartate aminotransferase, or alanine aminotransferase. Conclusions: The heightened insulin sensitivity of PWS patients relative to OCs is associated with higher levels of adiponectin and lower levels of high-sensitivity C-reactive protein and IL-6. Future studies will determine whether PWS children are protected from obesity comorbidities such as type 2 diabetes, hyperlipidemia, and nonalcoholic fatty liver disease.

Effects of acute and chronic acetazolamide on resting ventilation and ventilatory responses in men

1993 ◽  
Vol 74 (1) ◽  
pp. 230-237 ◽  
Author(s):  
E. R. Swenson ◽  
J. M. Hughes
Keyword(s):  
Metabolic Acidosis ◽  
Ventilatory Response ◽  
Minute Ventilation ◽  
Respiratory Acidosis ◽  
Acute Effects ◽  
Acid Base Balance ◽  
Ventilatory Control ◽  
Peripheral Chemoreceptor ◽  
Ventilatory Responses ◽  
Base Balance

The effects of acetazolamide (ACTZ) on ventilatory control are thought to be mediated by metabolic acidosis. However, carbonic anhydrase (CA) inhibition within brain and chemoreceptors and tissue respiratory acidosis may also be important. We compared the acute effects of ACTZ (tissue respiratory acidosis and tissue CA inhibition without metabolic acidosis) on ventilation and ventilatory control with chronic ACTZ (acute effects plus metabolic acidosis). Five men were studied 1 h after 500 mg iv ACTZ or 0.9% saline (acute effects) and also after three doses of ACTZ (500 mg po every 6 h; chronic effects). Minute ventilation (VE), steady-state hypercapnic ventilatory response (HCVR), and hypoxic ventilatory response (HVR) were measured with respiratory inductance plethysmography. Resting VE was increased equally by acute and chronic ACTZ. HCVR increased with chronic ACTZ in hyperoxia and even further in hypoxia. In contrast, acute ACTZ had no effect on the HCVR slope in hyperoxia and suppressed its augmentation by hypoxia. HVR was fully suppressed by acute ACTZ but unchanged with chronic ACTZ. ACTZ also slowed the rate of full ventilatory response to CO2. These findings show that CA inhibitors affect ventilatory control in a complex fashion, not only through changes in systemic acid-base balance but also by central and peripheral chemoreceptor inhibition.

scholarly journals Growth hormone treatment in Prader-Willi syndrome patients: systematic review and meta-analysis

2020 ◽  
Vol 4 (1) ◽  
pp. e000630 ◽  
Author(s):  
Caroline de Gouveia Buff Passone ◽  
Ruth Rocha Franco ◽  
Simone Sakura Ito ◽  
Evelinda Trindade ◽  
Michel Polak ◽  
...  
Keyword(s):  
Systematic Review ◽  
Body Mass Index ◽  
Body Mass ◽  
Motor Development ◽  
Randomised Controlled Trials ◽  
Meta Analysis ◽  
Controlled Trials ◽  
Prader Willi Syndrome ◽  
Randomised Controlled ◽  
Rhgh Treatment

BackgroundGrowth hormone (GH) treatment is currently recommended in Prader-Willi syndrome (PWS) patients.ObjectivesTo evaluate the impact (efficacy and safety) of the use of recombinant human GH (rhGH) as a treatment for PWS.MethodWe performed a systematic review and, where possible, meta-analysis for the following outcomes: growth, body mass index, body composition, cognitive function, quality of life, head circumference, motor development/strength, behaviour and adverse effects. We included all PWS patients, with all types of genetic defects and with or without GH deficiency, who participated in rhGH studies performed in infancy, childhood and adolescence, that were either randomised controlled trials (RCTs) (double-blinded or not) or non-randomised controlled trials (NRCTs) (cohort and before and after studies). The databases used were MEDLINE, Embase and Cochrane Central.ResultsIn 16 RCTs and 20 NRCTs selected, the treated group had an improvement in height (1.67 SD scores (SDS); 1.54 to 1.81); body mass index z-scores (−0.67 SDS; −0.87 to −0.47) and fat mass proportion (−6.5% SDS; −8.46 to −4.54) compared with the control group. Data about cognition could not be aggregated.ConclusionBased on high quality evidence, rhGH treatment favoured an improvement of stature, body composition and body mass index, modifying the disease’s natural history; rhGH treatment may also be implicated in improved cognition and motor development in PWS patients at a young age.Ethics and disseminationThe current review was approved by the ethical committee of our institution. The results will be disseminated through conference presentations and publications in peer-reviewed journals.PROSPERO registration numberCRD42019140295

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