Involvement of pelvic girdle and proximal leg muscles in early oculopharyngeal muscular dystrophy.

Although limb girdle weakness is not part of the major diagnostic criteria of oculopharyngeal muscular dystrophy (OPMD), it has frequently been observed in the Dutch and other OPMD cohorts. In the Dutch cohort, this might be related to the relatively old age or the severity of the genetic defect. This patient-control study (14 OPMD patients and 12 controls) investigated the involvement of limb girdle muscles with a multidimensional approach in early OPMD. We assessed functional abilities, disease impact, physical activity, muscle strength, histopathology and fatty infiltration using questionnaires, actometer, functional tests, manual and quantitative muscle testing, muscle biopsy and muscle MRI. The study showed that involvement of pelvic girdle and proximal leg can be a relatively early feature of OPMD, resulting in impaired daily life activities. The fat fraction of the hip adductors and hamstrings was significantly higher in OPMD patients than in controls. Future studies should include assessment of hip flexors, hip adductors and hamstrings (muscle strength measurements and MRI), functional tests and questionnaires. These findings are important in future diagnostics, management and for the design of outcome measures in trials.

The yield of diagnostic work-up of patients presenting with myalgia, exercise intolerance, or fatigue: A prospective observational study.

Myalgia, fatigue, and exercise intolerance are cause for referral to a neurologist. However, the diagnostic value of history, neurological examination, and ancillary investigations in patients with these symptoms is unknown. This study provides a sound footing for deciding which ancillary investigations should be conducted. A prospective observational study of the diagnostic approach in 187 patients with myalgia, exercise intolerance, or fatigue as their predominant symptom was performed. The primary outcomes were independent contribution of referral letter, history, examination, and ancillary investigations to a myopathy diagnosis. The secondary outcome was diagnostic value of combined ancillary investigations. 27% of patients had a myopathy. Positive family history (OR 3.2), progressive symptoms (OR 2.2), atrophy (OR 9.7), weakness (OR 10.9), and hyporeflexia (OR 4.4) were associated with a myopathy. Positive predictive values for myopathy were calculated for CK (0.32), EMG (0.66), ultrasound (0.47), and muscle biopsy (0.78). All contributed significantly in predicting myopathy. Multivariate analysis yielded a diagnostic algorithm facilitating a more efficient work-up in future patients. CK levels, EMG, ultrasound, and muscle biopsy independently contribute to predicting a myopathy. The diagnostic algorithm shows which combination of ancillary investigations should be employed in different subgroups and when to omit invasive techniques. This algorithm may drastically improve diagnostic efficiency.

Vascular Health in Patients in Remission of Cushing's Syndrome Is Comparable With That in BMI-Matched Controls.

CONTEXT: In active Cushing's syndrome (CS), patients suffer from endothelial dysfunction and premature atherosclerosis. However, it is uncertain to what extent vascular health recovers after long-term remission. This is highly relevant because this topic relates to future development of cardiovascular disease. OBJECTIVE: The objective of the study was to investigate whether micro- and macrovascular health is impaired after long-term remission of CS in patients with no or adequately treated comorbidities. DESIGN AND SETTING: This was a cross-sectional case-control study in two tertiary referral centers. PATIENTS AND MAIN OUTCOME MEASURES: Sixty-three patients (remission of CS for ≥ 4 y) and 63 healthy, well-matched controls were compared. In group A (58 patients and 58 controls), serum biomarkers associated with endothelial dysfunction, intima media thickness, pulse wave velocity, and pulse wave analysis were studied. In group B (14 patients and 14 controls), endothelium-dependent and -independent vasodilatation was studied in conduit arteries (flow mediated dilation of the brachial artery) and forearm skeletal muscle resistance arteries (vasodilator response to intraarterial acetylcholine, sodium-nitroprusside, and NG-monomethyl-L-arginine using venous occlusion plethysmography). RESULTS: There were no significant differences between the outcome measures of vascular health of patients and controls in groups A and B. CONCLUSION: The vascular health of patients in long-term remission of CS seems to be comparable with that of healthy gender-, age-, and body mass index-matched controls, provided that the patients have no, or adequately controlled, comorbidities. Therefore, the effects of hypercortisolism per se on the vasculature may be reversible. This accentuates the need for the stringent treatment of metabolic comorbidities in these patients.

[A man with an image from the past]. / Een man met een beeld uit het verleden.

In the past intrathecal injection of ethiodized oil was used as a radio-opaque contrast agent. Nowadays the intrathecal use of ethiodized oil is very limited, however because of its inert properties it remains visible on radiological investigations even many decades after injection. Therefore, knowledge and recognition of this radiological feature is important since this prevents unnecessary further investigations.

Impaired endothelial function and blood flow in repetitive strain injury.

Repetitive Strain Injury (RSI) is a disabling upper extremity overuse injury that may be associated with pathophysiological changes in the vasculature. In this study we investigated whether RSI is associated with endothelial dysfunction and impaired exercise-induced blood flow in the affected forearm. 10 patients with RSI (age, 40.2 ± 10.3; BMI, 23.8 ± 3.3) and 10 gender- and age-matched control subjects (age, 38.0 ± 12.4; BMI, 22.7 ± 3.4) participated in this study. Brachial artery blood flow was measured at rest and during 3-min periods of isometric handgrip exercise at 15%, 30% and 45% of the individual maximal voluntary contraction. Brachial artery endothelial function was assessed as the flow mediated dilation (FMD), by measuring brachial artery diameter and velocity before and after 5-min ischemic occlusion. We found a lower exercise-induced brachial artery blood flow in patients with RSI than in controls (p=0.04). Brachial artery FMD was significantly lower in patients with RSI than in controls (p<0.01), whilst a lower FMD was also found in patient with unilateral RSI when comparing the affected arm with the non-affected arm (p=0.04). Our results suggest that patients with RSI have an attenuated exercise-induced blood flow and an impaired endothelial function in the affected arm. These findings importantly improve our understanding of the pathophysiological mechanism of RSI.

The impact of obesity on physiological responses during prolonged exercise.

BACKGROUND: Prolonged, moderate-intensity exercise training is routinely prescribed to subjects with obesity. In the general population, this type of exercise can lead to fluid and sodium imbalance. However, little is known whether obesity alters the risk of fluid and sodium imbalances. OBJECTIVE: This study examined physiological responses, such as core body temperature, fluid and sodium balance, in lean (BMI<25), overweight (2530) subjects during prolonged moderate-intensity exercise. SUBJECTS: A total of 93 volunteers (24-80 years), stratified for BMI, participated in the Nijmegen Marches and walked 30-50 km at a self-selected pace. Heart rate and core body temperature were recorded every 5 km. Subjects reported fluid intake, while urine output was measured and sweat rate was calculated. Baseline and post-exercise plasma sodium levels were determined, and urinary specific gravity levels were assessed before and after exercise. RESULTS: BMI groups did not differ in training status preceding the experiment. Exercise duration (8 h 41 ± 1 h 36 min) and intensity (72 ± 9% HR(max)) were comparable across groups, whereas obese subjects tended to have a higher maximum core body temperature than lean controls (P=0.06). Obese subjects demonstrated a significantly higher fluid intake (P<0.001) and sweat rate (P<0.001), but lower urine output (P<0.05) compared with lean subjects. In addition, higher urine specific gravity levels were observed in obese versus lean subjects after exercise (P<0.05). Furthermore, plasma-sodium concentration did not change in lean subjects after exercise, whereas plasma-sodium levels increased significantly (P<0.001) in overweight and obese subjects. Also, overweight and obese subjects demonstrated a significantly larger decrease in body mass after exercise than lean controls (P<0.05). CONCLUSION: Obese subjects demonstrate a larger deviation in markers of fluid and sodium balance than their lean counterparts during prolonged moderate-intensity exercise. These findings suggest that overweight and obese subjects, especially under strenuous environmental conditions, have an increased risk to develop fluid and sodium imbalances.

Hepatic unsaturated fatty acids in patients with non-alcoholic fatty liver disease assessed by 3.0T MR spectroscopy.

RATIONALE AND OBJECTIVE: Non-alcoholic fatty liver disease (NAFLD) is related to the metabolic syndrome and obesity. Proton magnetic resonance spectroscopy ((1)H MRS) is a non-invasive technique to assess hepatic triglyceride content (HTGC) and allows assessment of unsaturated fatty acids (UFA). There is increasing evidence that hepatic UFA are associated with the development of NAFLD. Therefore the objective of this study was to assess hepatic UFA in patients with NAFLD using (1)H MRS. MATERIALS AND METHODS: We included 26 consecutive patients with deranged liver enzymes, with and without type 2 diabetes mellitus (DM2), suspected for NAFLD. Liver function and metabolic parameters were assessed. (1)H MRS measurements were performed at 3.0T. From the (1)H MR spectra two ratios were calculated: ratio 1 (UFA); unsaturated fatty acid peak vs. reference water peak and ratio 2 (HTGC); total fatty acid peak vs. reference water peak. RESULTS: Twenty-six patients were included. In these patients hepatic UFA (ratio 1) correlated with AST/ALT ratio (r=-0.46, p=0.02), glucose levels (r=0.46, p=0.018), HOMA-IR (r=0.59, p=0.004) and HTGC (r=0.81, p<0.001). In diabetic patients (n=12) hepatic UFA correlated with alkaline phosphatase levels (r=0.72, p=0.01), HOMA-IR (r=0.73, p=0.01) and HTGC (r=0.83, p=0.002). Compared to non-diabetic patients with NAFLD, hepatic UFA levels were increased in patients with DM2 and NAFLD (0.032 vs. 0.014, p=0.03). CONCLUSION: Hepatic UFA can be assessed with (1)H MRS. (1)H MRS determined hepatic UFA correlate with clinical and metabolic parameters associated with NAFLD. Hepatic UFA are increased in patients with DM2. This study provides evidence for the use of non-invasive (1)H MRS to assess hepatic UFA in vivo.

Diazoxide-mediated insulin suppression in obese men: a dose-response study.

BACKGROUND: It has been suggested that diazoxide (DZX)-mediated insulin suppression may be useful to promote weight loss in obese subjects. AIM: To assess the DZX-dose range that is safe to use in obese hyperinsulinaemic men. METHODS: Assessment of DZX efficacy and safety was based on plasma glucose and insulin responses to a standardized 500-kcal breakfast, taken on the sixth day of treatment. Basic information regarding the potential efficacy of DZX treatment was first evaluated in an open-label study in five non-obese men. Subsequently, a double-blind, randomized, placebo-controlled study was performed in 12 obese but otherwise healthy men, comparing placebo treatment with DZX in doses of 50, 75 and 100 mg three times daily for 6 days. RESULTS: In non-obese subjects, DZX 50 mg decreased peak insulin levels by +/-28% and raised peak glucose concentration from 7.1 +/- 0.6 to 7.8 +/- 0.6 mmol/l (p < 0.05). DZX 100 mg reduced peak insulin levels by 45% and caused a rise in peak glucose levels from 7.1 +/- 0.6 to 9.0 +/- 0.9 mmol/l (p < 0.05). In obese men, the 50 and 75 mg doses had no significant effects on glucose or insulin levels. DZX 100 mg reduced the peak insulin levels and insulin area under the curve by +/-20% (p < 0.05) but did not affect fasting or postprandial glucose levels. The relatively limited insulin-suppressive effects in obese subjects were attributed to the low plasma DZX levels that were achieved in this group. For comparable doses, plasma DZX levels were about 30% lower in obese than in non-obese men. Plasma DZX levels were highly dependent on dose (p < 0.001) and body weight (p < 0.001). Ninety-two percent of the total variability in DZX levels was explained by these two parameters. CONCLUSION: DZX-mediated insulin suppression is dose dependent in normal and in obese men. However, the efficacy of DZX is much less in obese than in non-obese subjects. This is attributed to weight-dependent differences in distribution volume that lead to markedly lower plasma DZX levels in obese subjects. Weight-adjusted doses will be needed to achieve biologically effective plasma DZX levels. Extrapolation of the data suggests that effective insulin suppression in obese men will at least require a daily dose of 3.2-4.2 mg/kg.