Severe Hyperglycemia Immediately After Allogeneic Hematopoietic Stem-Cell Transplantation is Predictive of Acute Graft-Versus-Host Disease

Stress hyperglycemia and acute graft-versus-host disease (GVHD), the major early complication of hematopoietic stem cell transplantation (HSCT), are both associated with excessive release of inflammatory cytokines. We investigated whether new-onset hyperglycemia immediately after HSCT predicts acute GVHD. We studied nondiabetic adult recipients of human leukocyte antigen-matched HSCT (peripheral blood stem cells) for acute leukemia. Using mean morning serum glucose on Days 1–10, we classified hyperglycemia as: mild (6.11–8.33 mmol/L), moderate (8.34–9.98), and severe (minimum of 9.99). Subjects who were GVHD‐free on Day 10 were followed during Days 11–100 for grades II–IV acute GVHD or competing event. Evaluation utilized cumulative incidence-based proportional hazards regression. Subjects (n?=?328) were age 18–74, median of 49 years. Per body mass index (BMI)—25.0 % were obese (BMI, 30–48), 33.8 % overweight (25 to <30), 30.8 % normal weight (21 to <25), and 10.4 % lean (18 to <21). Mild, moderate, or severe hyperglycemia occurred during Days 1–10 in 50.0, 21.3, and 16.8 % of subjects, respectively. Cumulative incidence on Day 100 was 44.8 (±2.8)?% acute GVHD and 7.9 (±1.5)?% competing event. Among normal-to-overweight subjects (n?=?212), severe hyperglycemia developed in 14.2 % (n?=?30) and more than doubled the risk of acute GVHD (hazards ratio, 2.71; 95 % CI, 1.58–4.65—adjusted for donor/recipient characteristics, prophylactic regimen, and mucositis). In contrast, among obese subjects (n?=?82), severe hyperglycemia developed in 30.5 % (n?=?25) but did not significantly affect risk of GVHD. (No lean subjects (n?=?34) developed severe hyperglycemia.) Hyperglycemia that was less than severe had an effect indistinguishable from normoglycemia. In nondiabetic patients, severe hyperglycemia immediately after allogeneic HSCT indicates increased likelihood of acute GVHD. This association is absent in obese patients, who may be primed by obesity-induced inflammation to develop severe hyperglycemia even without experiencing the cytokine storm that is essential to GVHD pathogenesis.     

Left ventricular mass and function with reduced-fat or reduced-carbohydrate hypocaloric diets in overweight and obese subjects

In animals, carbohydrate and fat composition during dietary interventions influenced cardiac metabolism, structure, and function. Because reduced-carbohydrate and reduced-fat hypocaloric diets are commonly used in the treatment of obesity, we investigated whether these interventions differentially affect left ventricular mass, cardiac function, and blood pressure. We randomized 170 overweight and obese subjects (body mass index, 32.9±4.4; range, 26.5-45.4 kg/m(2)) to 6-month hypocaloric diets with either reduced carbohydrate intake or reduced fat intake. We obtained cardiac MRI and ambulatory blood pressure recordings over 24 hours before and after 6 months. Ninety subjects completing the intervention period had a full cardiac MRI data set. Subjects lost 7.3±4.0 kg (7.9±3.8%) with reduced-carbohydrate diet and 6.2±4.2 kg (6.7±4.4%) with reduced-fat diet (P<0.001 within each group; P=not significant between interventions). Caloric restriction led to similar significant decreases in left ventricular mass with low-carbohydrate diets (5.4±5.4 g) or low-fat diets (5.2±4.8 g; P<0.001 within each group; P=not significant between interventions). Systolic and diastolic left ventricular function did not change with either diet. The 24-hour systolic blood pressure decreased similarly with both interventions. Body weight change (β=0.33; P=0.02) and percentage of ingested n-3 polyunsaturated fatty acids (β=-0.27; P=0.03) predicted changes in left ventricular mass. In conclusion, weight loss induced by reduced-fat diets or reduced-carbohydrate diets similarly improved left ventricular mass in overweight and obese subjects over a 6-month period. However, n-3 polyunsaturated fatty acid ingestion may have an independent beneficial effect on left ventricular mass.     

Changes in masticatory mandibular movements in growing individuals: a six-year follow-up

The pattern of mandibular movement during chewing is influenced by several central and peripheral factors. The aim of the present study was to determine whether changes in masticatory function, characterized by mandibular velocity and displacement, occurred during individuals' normal growth. Forty-seven children, 9-15 years of age, were followed over a 6-year period. All had an Angle Class I occlusion with no obvious orthodontic problems. Oral motor function with respect to mandibular displacement, duration, and velocity was monitored 3-dimensionally with an opto-electronic method. The chewing cycle was divided into an opening, closing, and occlusal phase. Total body height was measured. During the follow-up period, all masticatory variables except the 3-dimensional opening distance showed significant changes. The total chewing cycle duration, the opening and occlusal time of the chewing cycle, and the 3-dimensional closing distance increased during the growth period, while the closing time of the chewing cycle, the 2-dimensional lateral and vertical distances and both the opening and closing velocity decreased. The children who grew proportionally most in height during the 6-year period, i.e. the youngest children in the group studied, showed a significantly larger decrease in the opening velocity. From this study it becomes evident that the variables of the chewing cycle undergo a continuous process of change during growth. This is possibly a reflection of anatomical changes, maturation of the central nervous system, and altered functional demands.     

Activation of the cortical pain network by soft tactile stimulation after injection of sumatriptan

The anti-migraine drug sumatriptan often induces unpleasant somatosensory side effects, including a dislike of being touched. With a double-blind cross-over design, we studied the effects of sumatriptan and saline on perception (visual analogue scale) and cortical processing (functional magnetic resonance imaging) of tactile stimulation in healthy subjects. Soft brush stroking on the calf (n=6) was less pleasant (p<0.04) and evoked less activation of posterior insular cortex in the sumatriptan compared to the saline condition. Soft brushing activated pain processing regions (anterior insular, lateral orbitofrontal, and anterior cingulate cortices, and medial thalamus) only in the sumatriptan condition, whereas activation of somatosensory cortices was similar in both conditions. Soft brush stroking on the palm (n=6) was equally pleasant in both conditions. One possible mechanism for the activation of pain processing regions by brush stroking is sensitization of nociceptors by sumatriptan. Another possibility is inhibition of a recently discovered system of low-threshold unmyelinated tactile (CT) afferents that are present in hairy skin only, project to posterior insular cortex, and serve affective aspects of tactile sensation. An inhibition of impulse transmission in the CT system by sumatriptan could disinhibit nociceptive signalling and make light touch less pleasant. This latter alternative is consistent with the observed reduction in posterior insular cortex activation and the selective effects of stimulation on hairy compared to glabrous skin, which are not explained by the nociceptor sensitization account.     

Evaluation of orthodontic treatment, retention and relapse in a 5-year follow-up: a comparison of treatment outcome between a specialist and a post-graduate clinic

The aim of this study was to evaluate and compare orthodontic treatment between a specialist clinic and a post-graduate clinic. A long-term follow-up study was done 5 years after orthodontic treatment ended. Eighty-one individuals treated at the Post-graduate clinic at the Department of Orthodontics, University Clinics of Odontology, G?teborg, and 84 individuals treated at the Orthodontic Specialist Clinic in V?nersborg, the county of V?stra G?taland were examined. The Peer Assessment Rating (PAR) index was used on pre-, post-treatment and 5-year follow-up study casts. The percentage reduction in weighted PAR (WPAR) scores after treatment and at the 5-year follow up did not differ significantly between the clinics. There were significant higher pre-, post-treatment and 5-year follow-up PAR and WPAR scores in patients from the Specialist Clinic as compared with patients from the Post-graduate Clinic. In the whole sample 97.6% of the patients were improved or greatly improved after treatment and 95.8% were still improved or greatly improved 5 years after treatment. Sixty-seven percent of the patients still had retainers in one or both arches at the 5-year follow-up. The WPAR scores are one factor that indicates the high quality of the treatment process in both clinics. The higher post-treatment PAR scores in the Specialist Clinic may be because a larger number of patients were treated only in one jaw at this clinic.