High Prevalence of Asymptomatic Esophageal Motility Disorders among Morbidly Obese Patients

Background: Morbid obesity is becoming more prevalent in the industrialized world. Few data exist regarding the resting lower esophageal sphincter pressure (LESP) and esophageal motility in relationship to body mass index (BMI). Methods: During a 3-year period, 111 of 152 morbidly obese patients seeking bariatric surgery completed esophageal manometric testing and questionnaire regarding esophageal symptoms. Manometric parameters included wave amplitude and duration of esophageal contractions, percentage of peristaltic function, and resting LESP. Questionnaire data included age, sex, medications, prior medical conditions, and esophageal symptoms. Results: 88 (79%) of the patients were female; 23 (21%) were male. The mean age was 39.8 years (± 9.9), the mean BMI was 50.7 kg/m2 (± 9.4). There was a lack of correlation between BMI and LESP (r = 0.04). Abnormal manometric findings were observed in 68/111 (61%) patients: 28 (25%) had only hypotensive lower esophageal sphincter (LESP < 10 mm Hg); 16 (14%) had nutcracker esophagus (amplitude >180 mm Hg), 15 (14%) had nonspecific esophageal motility disorders, 8 (7%) had diffuse esophageal spasm (DES), and 1 (1%) had achalasia. Patients with DES had a significantly higher BMI than those with other motility disorders (P < 0.05). Dysphagia was reported in 7 (6%) patients and chest pain in 1 patient. Heartburn and/or regurgitation (gastroesophageal reflux disease, GERD) was noted in 35 patients (32%), of whom 18 (51%) had a hypotensive resting LES. 40 of 68 patients (59%) with abnormal motility tracings did not report any esophageal symptoms. Conclusion: Morbid obesity per se does not imply an abnormality of LESP. In addition, a majority of morbidly obese patients who were considering bariatric surgery had no esophageal symptoms but were found to have abnormal esophageal manometric patterns. These findings add support to the suggestion that morbidly obese patients may have abnormal visceral sensation.     

Stress among primary teachers: Individuals in organizations

The following article is based on a survey of over 250 class teachers working in 30 primary schools in a large regional authority in Scotland. The study aimed to: (i) establish the prevalence and nature of occupational stress among primary school teachers, and (ii) determine the relationship between stress, anxiety and organizational phenomena. The data were collected by means of a specifically designed questionnaire and standardized measures of psychiatric morbidity. These important data are discussed in terms of their implications for training, organizational change and the direction of future research.     

2009 Japanese Society of Latex Allergy guidelines for the safe management of latex allergy

Latex allergy is an IgE-mediated reaction to natural latex antigen. Operating room equipment frequently includes medical devices, such as surgical gloves, intravenous lines, and urinary catheters, which are made from latex or contain latex. These products can trigger an allergic reaction that can result in anaphylactic shock. Removal of natural rubber and latex-containing products from the operating room and avoidance of external and internal exposure of patients to latex antigen will prevent such allergic reactions. Updated guidelines for the safe management of latex allergy were published in 2009 by the Japanese Society of Latex Allergy. The previous guidelines regarding this topic were published in 2006. The new guidelines consist of 11 chapters that deal with background, exposure to latex antigen and development of sensitization, high-risk groups, natural rubber products, allergic reactions triggered by natural rubber products, diagnosis, latex-fruit syndrome, countermeasures and treatments in emergencies, prevention and safe management in the hospital, countermeasures in daily life, and limits for application of the guidelines. We had a case that required management according to the 2009 guidelines. A 49-year-old male doctor with a history of allergy to latex gloves was scheduled for laparoscopic cholecystectomy under general and epidural anesthesia for recurrent, acute cholecystitis. The anesthesia and operation were performed uneventfully with latex-free medical devices and machines in a latex-safe environment in the operating room under the new guidelines. Safe anesthetic management under the 2009 guidelines should be available for all operations in Japan on patients with latex allergy.     

Prevalence of Loss-of-Function FTO Mutations in Lean and Obese Individuals

OBJECTIVE

Single nucleotide polymorphisms (SNPs) in intron 1 of fat mass– and obesity-associated gene (FTO) are strongly associated with human adiposity, whereas Fto^−/− mice are lean and Fto^+/− mice are resistant to diet-induced obesity. We aimed to determine whether FTO mutations are disproportionately represented in lean or obese humans and to use these mutations to understand structure-function relationships within FTO.

RESEARCH DESIGN AND METHODS

We sequenced all coding exons of FTO in 1,433 severely obese and 1,433 lean individuals. We studied the enzymatic activity of selected nonsynonymous variants.

RESULTS

We identified 33 heterozygous nonsynonymous variants in lean (2.3%) and 35 in obese (2.4%) individuals, with 8 mutations unique to the obese and 11 unique to the lean. Two novel mutations replace absolutely conserved residues: R322Q in the catalytic domain and R96H in the predicted substrate recognition lid. R322Q was unable to catalyze the conversion of 2-oxoglutarate to succinate in the presence or absence of 3-methylthymidine. R96H retained some basal activity, which was not enhanced by 3-methylthymidine. However, both were found in lean and obese individuals.

CONCLUSIONS

Heterozygous, loss-of-function mutations in FTO exist but are found in both lean and obese subjects. Although intron 1 SNPs are unequivocally associated with obesity in multiple populations and murine studies strongly suggest that FTO has a role in energy balance, it appears that loss of one functional copy of FTO in humans is compatible with being either lean or obese. Functional analyses of FTO mutations have given novel insights into structure-function relationships in this enzyme.Genome-wide association studies have revealed that single nucleotide polymorphisms (SNPs) within the first intron of fat mass– and obesity-associated gene (FTO) are strongly associated with adiposity (1–4). These associations have been largely consistent across multiple different ethnicities including Europeans (5–8), Asians (9–11), Hispanics (12,13), and Africans (13,14). At present, it remains unclear whether these SNPs influence the expression or splicing of the FTO gene and/or whether the unequivocal association with obesity is causally related to alterations in expression or function of FTO. If the effect of the intron 1 SNPs is through FTO, it also remains unclear whether the obesity risk SNPs result in a loss or a gain of FTO function. It remains possible that the SNPs influence the expression and/or function of neighboring genes and that such an effect might underlie the association with adiposity. There are several examples in metabolic disease where common variants close to a particular gene are associated with alterations in risk of common phenotypes such as fat mass or risk of obesity, whereas rare loss- or gain-of-function mutations in the same gene are associated with a more severe version of the same metabolic phenotype (e.g., MCR4 [5,15–19], POMC [20,21], BDNF [22–24], and PCSK1 [25,26]). When information is available from both types of variants, clarity of mechanistic understanding is greatly enhanced. To establish whether nonsynonymous variants of FTO might be enriched in either lean or obese subjects, we sequenced the FTO coding region and intron-exon boundaries in a large group of subjects with severe obesity and a similarly sized group of individuals with lifelong leanness. We have recently established that FTO encodes a 2-oxoglutarate (2-OG) Fe²⁺-dependent dioxygenase (27). In this study, we have examined the functional enzymatic properties of naturally occurring variants to gain further insights into structure-function relationships in the human enzyme.     

Type 2 diabetes among Asian Americans: Prevalence and prevention

Type 2 diabetes mellitus (T2DM) is a growing problem among Asian Americans. Based on the Centers for Disease Control, the age-adjusted prevalence of T2DM for Asian Americans is 9%, placing them at “moderate risk”. However differential patterns of disease burden emerge when examining disaggregated data across Asian American ethnic groups; with Filipino, Pacific Islander, Japanese, and South Asian groups consistently described as having the highest prevalence of T2DM. Disentangling and strengthening prevalence data is vital for on-going prevention efforts. The strongest evidence currently available to guide the prevention of T2DM in the United States comes from a large multicenter randomized clinical control trial called the Diabetes Prevention Program, which targets individual lifestyle behavior changes. It has been translated and adopted for some Asian American groups, and shows promise. However stronger study designs and attention to several key methodological considerations will improve the science. Increased attention has also been directed toward population level downstream prevention efforts. Building an infrastructure that includes both individual and population approaches is needed to prevent T2DM among Asian American populations, and is essential for reducing health disparities.