Revised QUICKI provides a strong surrogate estimate of insulin sensitivity when compared with the minimal model

OBJECTIVE: To compare insulin sensitivity (Si) from a frequently sampled intravenous glucose tolerance test (FSIGT) and subsequent minimal model analyses with surrogate measures of insulin sensitivity and resistance and to compare features of the metabolic syndrome between Caucasians and Indian Asians living in the UK. SUBJECTS: In all, 27 healthy male volunteers (14 UK Caucasians and 13 UK Indian Asians), with a mean age of 51.2+/-1.5 y, BMI of 25.8+/-0.6 kg/m(2) and Si of 2.85+/-0.37. MEASUREMENTS: Si was determined from an FSIGT with subsequent minimal model analysis. The concentrations of insulin, glucose and nonesterified fatty acids (NEFA) were analysed in fasting plasma and used to calculate surrogate measure of insulin sensitivity (quantitative insulin sensitivity check index (QUICKI), revised QUICKI) and resistance (homeostasis for insulin resistance (HOMA IR), fasting insulin resistance index (FIRI), Bennetts index, fasting insulin, insulin-to-glucose ratio). Plasma concentrations of triacylglycerol (TAG), total cholesterol, high density cholesterol, (HDL-C) and low density cholesterol, (LDL-C) were also measured in the fasted state. Anthropometric measurements were conducted to determine body-fat distribution. RESULTS: Correlation analysis identified the strongest relationship between Si and the revised QUICKI (r=0.67; P=0.000). Significant associations were also observed between Si and QUICKI (r=0.51; P=0.007), HOMA IR (r=-0.50; P=0.009), FIRI and fasting insulin. The Indian Asian group had lower HDL-C (P=0.001), a higher waist-hip ratio (P=0.01) and were significantly less insulin sensitive (Si) than the Caucasian group (P=0.02). CONCLUSION: The revised QUICKI demonstrated a statistically strong relationship with the minimal model. However, it was unable to differentiate between insulin-sensitive and -resistant groups in this study. Future larger studies in population groups with varying degrees of insulin sensitivity are recommended to investigate the general applicability of the revised QUICKI surrogate technique.     

Secretin Provocation: Gastrin Results in Various Clinical Situations

Our previous secretin provocation studies in normal volunteers and unoperated duodenal ulcer patients suggested that the gastrin rise in gastrinoma may be an exaggeration of the normal response rather than paradoxical. We report further studies in various clinical settings having normogastrinemia (normal, n = 17; unoperated duodenal ulcer, n = 13; primary hyperparathyroidism, n = 7) and hypergastrinemia (postvagotomy, n = 5; hypochlorhydria, n = 7; achlorhydria, n = 10; chronic renal failure, n = 10; gastrinoma, n = 5). Under all nongastrinoma conditions, there were similar gastrin rises of 9-19% between 2 and 5 min after bolus intravenous GIH secretin (2 CU/kg), which fell to baseline by 8 min, except for chronic renal failure. In chronic renal failure, gastrin remained elevated from 7 to 30 min and was significantly different (p less than 0.05) at 10-30 min compared to all other nongastrinoma conditions except hyperparathyroidism. Peak rises occurred within 5 min in all entities, but only three gastrinoma patients had positive secretin provocation tests by the predefined criterion of a gastrin rise greater than 200 pg/ml. The results of secretin provocation in various clinical entities with and without hypergastrinemia further support the hypothesis that the gastrin rise in gastrinoma is an exaggeration of the normal response. The prolonged gastrin rise seen in chronic renal failure may be due to altered renal clearance, inasmuch as other hypergastrinemic states had responses similar to normal and duodenal ulcer.     

Nonoperative Management of a Severe Proximal Rectus Femoris Musculotendinous Injury in a Recreational Athlete: A Case Report

This report describes a severe injury to the proximal rectus femoris (RF) muscle in a 37-year-old recreational athlete. This injury is a relatively rare occurrence in both the general and elite athletic populations. Acute and long-term imaging and functional outcomes are described. This athlete was able to return to full activity without surgical intervention. Follow-up imaging demonstrated gross healing of both complete (or near complete) muscle and tendon tears.

Key High‐efficiency Practices of Emergency Department Providers: A Mixed‐methods Study

Objective

The objective of this study was to determine specific provider practices associated with high provider efficiency in community emergency departments (EDs).

Methods

A mixed‐methods study design was utilized to identify key behaviors associated with efficiency. Stage 1 was a convenience sample of 16 participants (ED medical directors, nurses, advanced practice providers, and physicians) identified provider efficiency behaviors during semistructured interviews. Ninety‐nine behaviors were identified and distilled by a group of three ED clinicians into 18 themes. Stage 2 was an observational study of 35 providers was performed in four (30,000‐ to 55,000‐visit) community EDs during two 4‐hour periods and recorded in minute‐by‐minute observation logs. In Stage 3, each behavior or practice from Stage 1 was assigned a score within each observation period. Behaviors were tested for association with provider efficiency (relative value units/hour) using linear univariate generalized estimating equations with an identity link, clustered on ED site.

Results

Five ED provider practices were found to be positively associated with efficiency: average patient load, using name of team member, conversations with health care team, visits to patient rooms, and running the board. Two behaviors, “inefficiency practices,” demonstrated significant negative correlations: non–work‐related tasks and documentation on patients no longer in the ED.

Conclusions

Average patient load, running the board, conversations with team member, and using names of team members are associated with enhanced provider productivity. Identification of behaviors associated with efficiency can be utilized by medical directors, clinicians, and trainees to improve personal efficiency or counsel team members.

     

Topical methyl nicotinate-induced skin vasodilation in diabetic neuropathy

OBJECTIVE: To evaluate the vasodilation induced by topical application of methyl nicotinate (MN) and to compare it with the vasodilatory response to acetylcholine (ACh) and sodium nitroprusside (SNP) in healthy subjects and diabetic neuropathic patients. RESEARCH DESIGN AND METHODS: Ten diabetic patients with peripheral neuropathy (DN) and 10 age- and sex-matched healthy control subjects (C) were enrolled. The vasodilatory response to topical application of 1% MN and a placebo emulsion at the forearm and dorsum of the foot skin at 5, 15, 30, 60 and 120 min was measured using Laser Doppler Perfusion Imaging. The vasodilatory response to iontophoresis of 1% ACh and 1% SNP solutions was also evaluated. RESULTS: The maximal vasodilatory response to ACh, SNP and MN was similar at the forearm and foot level in the diabetic patients. In the control group, the responses to MN, ACh and SNP were similar on the forearm but in the foot, the MN vasodilatory response was higher when compared to the ACh and SNP responses. MN-related vasodilation was present 5 min after the application, reached its peak at 15-30 min and declined to pre-application levels 120 min afterward. CONCLUSIONS: Topical application of MN at the forearm and foot levels of diabetic neuropathic patients results in skin vasodilation that is comparable to the maximal vasodilation that can be induced by iontophoresis of ACh or SNP and lasts for less than 2 h. Further studies will be required to explore the potential of MN to increase blood flow and to prevent diabetic foot problems in clinical practice.     

Chronic airflow obstruction in Fabry's disease

Seven patients with Fabry's disease, an x-linked sphingolipid storage disorder, were evaluated for the presence and extent of airway obstruction. All were found to have significant obstruction to airflow. In addition, evaluation of their airway epithelial cells obtained by bronchoscopy demonstrated that these cells contained inclusion bodies consistent with deposits of ceramide trihexoside, suggesting that part of their functional obstruction to airflow may be secondary to intrinsic airway disease. Although all of the study population had evidence of airflow obstruction, the impairment was much worse in those who smoked, implying that even mild cigarette smoking is particularly hazardous to patients with Fabry's disease.     

Cardiovascular Effects of the Supraglottic and Super-supraglottic Swallowing Maneuvers in Stroke Patients with Dysphagia

The prolonged voluntary closure of the glottis during the supraglottic and super-supraglottic swallowing techniques may create the Valsalva maneuver. The Valsalva maneuver has been associated with sudden cardiac death and cardiac arrhythmias. This study describes the effects of the supraglottic and super-supraglottic swallowing techniques on the cardiovascular system. Subjects included 23 patients from an acute inpatient rehabilitation hospital. Subject groups included recent stroke, dysphagia, and a history of coronary artery disease (Group 1, N = 11), recent stroke and dysphagia with no known coronary artery disease (Group 2, N = 4), and orthopedic diagnosis with no known dysphagia or coronary artery disease (Group 3, N = 8). Cardiac status was moni-tored for 4 hours during swallowing training, regular therapy sessions, and a meal. For Groups 1 and 2, 86.6% (13 out of 15) of the subjects demonstrated abnormal cardiac findings during the swallowing session including supraventricular tachycardia, premature atrial contractions, and premature ventricular contractions. Arrhythmia subsided within a few minutes after the session and did not occur during other activities. In Group 3 (control group), none of the subjects demonstrated abnormal cardiac findings except for bradycardia in one subject. It is suggested that the supraglottic and super-supraglottic swallow maneuvers may be contraindicated for patients with a history of stroke or coronary artery disease.     

Quantification of experimental myocardial infarction using nuclear magnetic resonance imaging and paramagnetic ion contrast enhancement in excised canine hearts

Determination of myocardial infarct size is important for clinical management of patients with ischemic heart disease and for research on limiting infarct size. Nuclear magnetic resonance (NMR) imaging permits tomographic depiction of the distribution of mobile tissue protons. NMR images have demonstrated high spatial resolution and contrast. To evaluate the potential of this technique in measuring myocardial infarct size, NMR imaging was performed in six canine hearts excised 24 hours after circumflex coronary artery ligation. Before sacrifice, the dogs received i.v. manganous chloride (0.05 mmol/kg). After NMR imaging, the heart were sectioned and the myocardial slices were stained with triphenyl tetrazolium chloride. The pathologically determined infarct size was compared with the infarct size measured by NMR imaging. The correlation was good (regression line slope 1.06; r = 0.94). We conclude that NMR imaging with paramagnetic contrast agents can be used to determine infarct size in excised hearts.     

Correction in trans for Fabry disease: expression, secretion and uptake of alpha-galactosidase A in patient-derived cells driven by a high-titer recombinant retroviral vector.

Fabry disease is an X-linked metabolic disorder due to a deficiency of alpha-galactosidase A (alpha-gal A; EC 3.2.1.22). Patients accumulate glycosphingolipids with terminal alpha-galactosyl residues that come from intracellular synthesis, circulating metabolites, or from the biodegradation Of senescent cells. Patients eventually succumb to renal, cardio-, or cerebrovascular disease. No specific therapy exists. One possible approach to ameliorating this disorder is to target corrective gene transfer therapy to circulating hematopoietic cells. Toward this end, an amphotropic virus-producer cell line has been developed that produces a high titer (>10(6) i.p. per ml) recombinant retrovirus constructed to transduce and correct target cells. Virus-producer cells also demonstrate expression of large amounts of both intracellular and secreted alpha-gal A. To examine the utility of this therapeutic vector, skin fibroblasts from Fabry patients were corrected for the metabolic defect by infection with this recombinant virus and secreted enzyme was observed. Furthermore, the secreted enzyme was found to be taken up by uncorrected cells in a mannose-6-phosphate receptor-dependent manner. In related experiments, immortalized B cell lines from Fabry patients, created as a hematologic delivery test system, were transduced. As with the fibroblasts, transduced patient B cell lines demonstrated both endogenous enzyme correction and a small amount of secretion together with uptake by uncorrected cells. These studies demonstrate that endogenous metabolic correction in transduced cells, combined with secretion, may provide a continuous source of corrective material in trans to unmodified patient bystander cells (metabolic cooperativity).