Severe obesity and diabetes self-care attitudes, behaviours and burden: implications for weight management from a matched case-controlled study. Results from Diabetes MILES--Australia.

AIMS: To investigate whether diabetes self-care attitudes, behaviours and perceived burden, particularly related to weight management, diet and physical activity, differ between adults with Type 2 diabetes who are severely obese and matched non-severely obese control subjects. METHODS: The 1795 respondents to the Diabetes MILES--Australia national survey had Type 2 diabetes and reported height and weight data, enabling BMI calculation: 530 (30%) were severely obese (BMI ≥ 35 kg/m(2); median BMI = 41.6 kg/m(2)) and these were matched with 530 control subjects (BMI < 35 kg/m(2); median BMI = 28.2 kg/m(2)). Diabetes self-care behaviours, attitudes and burden were measured with the Diabetes Self-Care Inventory-Revised. Within-group and between-group trends were examined. RESULTS: The group with BMI ≥ 35 kg/m(2) was less likely to achieve healthy diet and exercise targets, placed less importance on diet and exercise recommendations, and found the burden of diet and exercise recommendations to be greater than the group with BMI < 35 kg/m(2). The group with BMI ≥ 35 kg/m(2) was more likely to be actively trying to lose weight, but found weight control a greater burden. These issues accentuated with increasing obesity and were greatest in those with BMI > 45 kg/m(2). There were no between-group differences in other aspects of diabetes self-care: self-monitoring of blood glucose, use of medications and smoking. Moderate-to-severe symptoms of depression were independently associated with reduced likelihood of healthy diet and physical activity, and with greater burden associated with diet, physical activity and weight management. CONCLUSIONS: Severely obese people with diabetes demonstrated self-care attitudes, behaviours and burdens that infer barriers to weight loss. However, other important diabetes self-care behaviours are supported equally by severely obese and non-severely obese individuals.

Neutralisation of muscle tumour necrosis factor alpha does not attenuate exercise-induced muscle pain but does improve muscle strength in healthy male volunteers.

OBJECTIVE: Inflammatory mediators, such as tumour necrosis factor alpha (TNFalpha), may contribute to delayed-onset muscle soreness. The effect of neutralising TNFalpha with etanercept, a soluble TNFalpha receptor, on delayed-onset muscle soreness (DOMS) induced in the quadriceps muscle was analysed. DESIGN: On two separate occasions at least 6 weeks apart, etanercept 25 mg or vehicle was given subcutaneously 1 hour before unaccustomed exercise to 12 healthy men in a randomised double-blind cross-over format. To induce DOMS, subjects completed 4 sets of 15 repetitions at 80% of their one-repetition maximum (1RM), using a 45 degrees inclined leg press. Muscle soreness was assessed using a 100-mm visual analogue scale (VAS), and pressure pain threshold (PPT) on the thigh before and 24, 48 and 72 hours after exercise. Changes in the subject's muscle strength were detected by reassessing the subject's 1RM 24, 48 and 72 hours after exercise. RESULTS: Muscle strength decreased 24 and 48 hours after exercise regardless of agent administered (analysis of variance, p<0.001). At 72 hours after exercise, muscle strength was significantly greater (p<0.01) after etanercept than after placebo. The exercise protocol induced significant DOMS for up to 72 hours, as reflected by reduced PPT and increased VAS scores (p<0.001). Etanercept had no effect on PPT or VAS. CONCLUSION: TNFalpha does not affect muscle soreness associated with unaccustomed exercise, but may improve the recovery of muscle function.

An alternative sodium bicarbonate regimen during cardiac arrest and cardiopulmonary resuscitation in a canine model.

We evaluated the effect of frequent, early bolus administration of low-dose sodium bicarbonate (NaHCO3) on blood gas values during ventricular fibrillation and cardiopulmonary resuscitation (CPR) compared with normal saline and standard bolus doses of NaHCO3. This was a randomized laboratory investigation involving 13 mongrel dogs and 18 experiments (5 dogs were used in a crossover manner). Each dog underwent 3 minutes of ventricular fibrillation, followed by 15 minutes of CPR. Animals were randomly assigned to one of three treatments administered early in the resuscitation effort: NaHCO3 0.5 mEq/kg at 5, 10, and 15 minutes of ventricular fibrillation (SB); NaHCO3 1 mEq/kg at 5 minutes and 0.5 mEq/kg at 15 minutes of fibrillation (SB); or 0.9% NaCl 1 ml/kg at 5 minutes and 0.5 ml/kg at 15 minutes of fibrillation (P). A total of 15 experiments were included for analysis. Arterial and venous blood gases were sampled at 4, 8, 13, and 18 minutes of fibrillation. The SB group demonstrated the highest arterial partial pressures of carbon dioxide (pCO2) at each sampling point after NaHCO3, including the 18-minute sample: 42 +/- 12, 29 +/- 11, and 35 +/- 10 torr for SB, P, and B, respectively. In addition, SB produced arterial alkalemia (pH > 7.45) after NaHCO3 administration. The arterial pH at 18 minutes of fibrillation for SB, P, and B was 7.46 +/- 0.14, 7.29 +/- 0.07, and 7.41 +/- 0.1, respectively. Similar trends for pCO2 and pH were observed for venous samples.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of high-dose sodium bicarbonate on the vasopressor effects of epinephrine during cardiopulmonary resuscitation.

We attempted to determine the effect of extreme alkalemia induced by highdose sodium bicarbonate on the vasopressor effects of epinephrine during cardiopulmonary resuscitation (CPR). Subjects in this randomized, blinded study performed in a controlled laboratory environment were 12 mongrel dogs that had had a previous episode of CPR. Each dog underwent 3 minutes of ventricular fibrillation (VF) followed by 7 minutes of closed-chest CPR. Animals were assigned to receive either sodium bicarbonate 3 mEq/kg and epinephrine 0.1 mg/kg, or normal saline 3 ml/kg and epinephrine 0.1 mg/kg. The sodium bicarbonate or normal saline was infused over 2 minutes beginning at 4 minutes of VF (1 min of CPR) followed by bolus epinephrine. Arterial pH in the sodium bicarbonate group was significantly higher at each sampling point (7.7 +/- 0.1 vs 7.29 +/- 0.06 at 1 min after drug, p < 0.001). However, there were no statistically or clinically significant differences in coronary perfusion pressure between the groups at any time: 29 +/- 13 versus 32 +/- 21 mm Hg 1 minute, and 22 +/- 12 versus 26 +/- 19 mm Hg 4 minutes after epinephrine for sodium bicarbonate and normal saline, respectively (p > 0.7). Increased arterial pH (alkalemia) induced by high-dose sodium bicarbonate administration did not improve the vasopressor effects of epinephrine during CPR in this canine model. These results suggest the limited value of administering sodium bicarbonate during CPR to improve the responsiveness to epinephrine.

Effect of vehicle on the nasal absorption of epinephrine during cardiopulmonary resuscitation.

STUDY OBJECTIVES: We have shown in previous studies that epinephrine administered intranasally is a feasible route of administration during cardiopulmonary resuscitation (CPR). To promote the absorption of epinephrine we administered phentolamine prior to epinephrine and used a bile salt as a vehicle to dissolve the epinephrine. The purpose of this study was to compare the effect of two different vehicles (bile salt vs surfactant) in promoting the absorption of nasally administered epinephrine during CPR and to determine their effects on the nasal mucosa. STUDY DESIGN: A randomized, blinded study. SETTING: A controlled laboratory environment. SUBJECTS: Eleven mongrel dogs. INTERVENTIONS: Each dog underwent 3 minutes of unassisted ventricular fibrillation (VF) followed by 7 minutes of VF with CPR. Five minutes after the start of VF, 10 dogs received intranasal phentolamine 0.25 mg/kg/nostril followed 1 minute later by intranasal epinephrine 7.5 mg/kg/nostril. The epinephrine was dissolved in a randomly assigned vehicle consisting of either taurodeoxycholic acid (group A, bile salt) or polyoxyethylene-9-lauryl ether (group B, surfactant). One animal acted as a control and received 0.9% sodium chloride nasally. MEASUREMENTS AND MAIN RESULTS: Data from eight dogs (one control) were included for analysis. Histology of the nasal cavity demonstrated severe multifocal erosion and ulceration of the respiratory epithelium for groups A and B compared with the control. The severity was similar between the two groups. In addition, no significant differences in plasma epinephrine concentrations or blood pressure responses were seen between the groups. CONCLUSION: Based on histology, polyoxyethylene-9-lauryl ether offered no advantage over taurodeoxycholic acid in its effect on the nasal mucosa. The data available for changes in epinephrine concentration and pressure also suggest no difference between the two vehicles in promoting the absorption of epinephrine during CPR in an animal model.

Simplified dosing and monitoring of vancomycin for the burn care clinician.

Vancomycin has excellent activity against Gram-positive bacteria and is often selected for use in the infected burn patient. Because of multiple-compartment pharmacokinetics, vancomycin serum concentrations can decrease dramatically in a short time period following the end of an intravenous infusion. This accounts for the widely divergent recommendations for serum vancomycin peak concentrations, e.g. from 15 mg/l up to 80 mg/l, when the time for blood sampling following the end of intravenous infusion is different. It is in general not necessary to monitor vancomycin peak concentrations, not only because its toxic potential is overrated but also because potential toxicity and therapeutic efficacy are correlated with trough concentrations. Post-distribution 'peak' concentrations are generally only useful for determining the optimal dosing interval for patients with impaired renal function. A dosing and monitoring paradigm for vancomycin therapy in burned adults has been devised for burn care clinicians. It provides suggested dose and dosing intervals based on body weight and creatinine clearance, with specific recommendations for regimen modification based upon the results of trough serum concentration determinations.

Intranasal administration of midazolam to a severely burned child.

This report describes the use of intranasally administered midazolam for sedation in a critically ill burned paediatric patient without venous access. Placement of a central venous catheter was successfully carried out following sedation by this method.

Leukopenia in acute thermal injury: evidence against topical silver sulfadiazine as the causative agent.

White blood cell data from time of admission to 4 days after burn injury was retrospectively reviewed to determine differences in the incidence of leukopenia in patients with burn injuries treated topically with either silver sulfadiazine or silver nitrate. WBC counts decreased in both groups of patients during the first 3 days after burn injury. An incidence of leukopenia (WBC count less than or equal to 5000/mm3) was observed in of 40 (47.5%) patients treated with silver sulfadiazine and in 13 of 30 (43.3%) patients treated with silver nitrate. There was no statistical difference in the incidence of leukopenia between the two treatment groups. These data suggest that silver sulfadiazine may not be the cause of the leukopenia observed early after burn injury.

Treatment of esophageal varices.

The pathophysiology and treatment of esophageal varices are reviewed. The cause of esophageal varices is generally thought to be portal hypertension. The most common cause of portal hypertension in the United States is alcoholic liver disease. Other etiologies of portal hypertension include portal vein thrombosis, schistosomiasis, and inferior vena caval obstruction by tumor or thrombus. Although short-term balloon tamponade and vasopressin infusion will control acute variceal hemorrhage, they do not affect the underlying problem and are not indicated for long-term treatment of esophageal varices. Surgical procedures either ablate varices or lower portal vein pressure. Portal-systemic shunts have emerged as the preferred surgical technique, but the superiority of total versus selective shunts is unclear. Pharmacological management can include administration of vasopressin, somatostatin, verapamil, or isosorbide dinitrate for short-term treatment or verapamil, isosorbide dinitrate, or propranolol for prolonged treatment. Use of sclerotherapy for treatment and prevention of hemorrhage from esophageal varices has grown recently. Because there are several sclerosing agents and combinations of agents available for use, assessing their relative safety and efficacy is difficult. Innovative approaches to management of varices include a shunt procedure involving the left lung, use of a tissue adhesive, and laser treatment. Because of its effectiveness and ease of administration, sclerotherapy appears to be a rational method of treatment for acute hemorrhage from esophageal varices.

Effect of blood and serum on in vitro antibacterial activity of nitrofurazone.

The effect of various volumes of blood and serum on the in vitro antibacterial activity of 0.2% nitrofurazone soluble dressing (NSD) was studied. The antibacterial activity of NSD was tested with an agar well diffusion technique. Zones of inhibition against susceptible strains of Escherichia coli and coagulase-positive Staphylococcus aureus were measured with a micrometer. Bacterial concentrations of 10(5) and 10(8) colony-forming units per milliliter were tested to evaluate a possible effect of inoculum size. Wells contained full-strength (undiluted) NSD or 75%, 50%, or 25% NSD dilutions (w/w) in blood, serum, or 0.9% sodium chloride injection. The mean decrease in inhibition zone size produced by blood and serum was only 7.2%. The diminution of activity, albeit small, was statistically significant. The zones produced were still much larger than those associated with clinical cure. Therefore, the impact of blood and serum on nitrofurazone's in vitro antibacterial activity can best be described as a slight reduction in rather than an elimination of effectiveness. This small reduction in activity is unlikely to be clinically important in patients with burns or other surface wounds that contain blood or serum. An effect of inoculum size was demonstrated for both organisms. Blood and serum produced a small but significant reduction in NSD's antibacterial activity in vitro. Controlled clinical studies are needed to ascertain the clinical importance of these findings.

Influence of rifampin on tocainide pharmacokinetics in humans.

The effects of metabolic enzyme induction by rifampin on the pharmacokinetics of tocainide were studied in eight healthy volunteers. In an open, unrandomized fashion, volunteers received tocainide hydrochloride 600 mg orally. Blood samples were obtained immediately before and at various time intervals up to 48 hours after the dose. Urine samples were collected before and at various intervals up to 72 hours after the dose. Serum and urine samples were assayed for tocainide content by high-performance liquid chromatography. After a four-week washout period, volunteers ingested 300 mg of rifampin by mouth every 12 hours. After 10 doses, subjects received a second oral dose of tocainide hydrochloride 600 mg, and blood and urine samples were collected as before. During the sampling period, subjects continued to ingest rifampin 300 mg orally every 12 hours. Significant differences in elimination rate constant (average increase, 0.0545 to 0.0748 hr-1), elimination half-life (average reduction, 13.2 to 9.4 hours), oral clearance, and area under the concentration-time curve (average reduction, 76.8 to 55.0 mg.hr/L) between the control and rifampin treatment phases were observed. Volume of distribution and renal clearance of tocainide were not significantly different after rifampin treatment. Tocainide appears to be susceptible to significant drug-drug interactions mediated by metabolic enzyme induction.

Comparison of intravenous and intranasal administration of epinephrine during CPR in a canine model.

STUDY OBJECTIVES: Epinephrine improves coronary perfusion pressure during CPR. However, administration of epinephrine during CPR may be delayed or omitted if IV or endotracheal access is not established. Therefore, the objective of this study was to determine if intranasal administration of epinephrine during CPR would provide an alternate route of drug administration that is readily accessible and requires no special technical skills. DESIGN AND SETTING: Randomized blinded study performed in a controlled laboratory environment. TYPE OF PARTICIPANTS: Twenty mongrel dogs weighing 19.5 +/- 4.6 kg. INTERVENTIONS: All dogs received either IV epinephrine 0.015 mg/kg or intranasal epinephrine 14 mg per nostril. Phentolamine (5 mg per nostril) was administered intranasally one minute before nasal administration of epinephrine to improve absorption. Each dog underwent three minutes of ventricular fibrillation followed by seven minutes of CPR with a pneumatic chest compression device. Epinephrine was administered at two minutes into CPR. MEASUREMENTS AND MAIN RESULTS: Seven dogs were excluded because of inadequate baseline coronary perfusion pressure or compression device displacement, leaving a total of 13 dogs for analysis (six IV epinephrine, seven intranasal epinephrine). Baseline coronary perfusion pressure (mean +/- SD) was similar for IV epinephrine and intranasal epinephrine (16.9 +/- 7.1 mm Hg versus 18.2 +/- 13.8 mm Hg, respectively, P = .84). For IV and intranasal epinephrine, coronary perfusion pressure increased to 21.4 +/- 9.2 mm Hg and 24.4 +/- 18.7 mm Hg one minute after epinephrine, respectively (P = .73). Five minutes after epinephrine coronary perfusion pressure was 18.2 +/- 8.7 mm Hg and 24.3 +/- 13.9 mm Hg for IV epinephrine and intranasal epinephrine, respectively (P = .38). The rate of successful resuscitation was similar for both groups, five of seven dogs for intranasal epinephrine and four of six dogs for IV epinephrine (P = .66). CONCLUSION: Intranasal epinephrine has similar effects on coronary perfusion pressure and resuscitation compared with standard-dose IV epinephrine. Therefore, the nasal route for administration of epinephrine appears to be an acceptable alternate method of drug delivery during CPR and compares favorably with standard IV therapy in the canine model. Because of the obvious benefits to human patients, these observations suggest further investigation.

Effect of dose on the nasal absorption of epinephrine during cardiopulmonary resuscitation.

Delay in epinephrine administration during cardiopulmonary resuscitation (CPR) due to technical difficulties in obtaining an access site may be detrimental. To avoid this potential delay, we have previously shown that intranasal administration of phentolamine and epinephrine is a rapidly obtainable and feasible route of administration during CPR. A randomized blinded dose ranging study was performed in a controlled laboratory environment. Thirty mongrel dogs were randomized to one of the following dosage regimens: phentolamine, 0.25 or 2.5 mg/kg/nostril; epinephrine, 0.075, 0.75, or 7.5 mg/kg/nostril. Phentolamine was administered intranasally 1 minute before the intranasal administration of epinephrine to improve absorption. Each dog underwent 3 minutes of ventricular fibrillation followed by 7 minutes of closed chest CPR. Epinephrine was administered was administered at 3 minutes of CPR. Data from 26 dogs were included for analysis. Treatment B (0.25 and 7.5 mg/kg/nostril of phentolamine and epinephrine, respectively) produced the greatest elevation in coronary perfusion pressure (17 +/- 11 vs. 4 +/- 3 mm Hg for the next highest group, P < .003) and in epinephrine plasma concentrations (1,403 +/- 1,400 vs 290 +/- 182 ng/mL for the next highest group, P > .05). In addition, treatment B had the highest resuscitation rate, 100% (5/5) versus 0% to 50% for the other groups (P < .05). These data show that there is a dose response effect, with 0.25 and 7.5 mg/kg/nostril of phentolamine and epinephrine being the optimal dose studied. In addition, when administered in appropriate doses, intranasal epinephrine reaches the systemic circulation and increases coronary perfusion pressure and successful resuscitation during CPR in this canine model.

The effect of sodium bicarbonate administration on the vasopressor effect of high-dose epinephrine during cardiopulmonary resuscitation in swine.

Sodium bicarbonate is administered during cardiopulmonary resuscitation (CPR) for the treatment of systemic acidemia. However, the effect of administering standard-dose sodium bicarbonate on the vasopressor effect of epinephrine is unknown. This study compared the effects of sodium bicarbonate or normal saline on the vasopressor effect of epinephrine in 18 pigs. After 10 minutes of unassisted ventricular fibrillation, CPR was started using a pneumatic chest compression device. Two minutes after the start of CPR, sodium bicarbonate (1 mEq/kg) or normal saline (1 mL/kg) was administered into the right ventricule followed 1 minute later by epinephrine (0.2 mg/kg). Defibrillation was attempted at 8 minutes of CPR (18 minutes of ventricular fibrillation). Results demonstrated no significant differences in aortic systolic, aortic diastolic, or coronary perfusion pressure (CPP) between the two groups (1 minute after epinephrine, CPP was 22.6 +/- 13.3 mm Hg versus 21.1 +/- 20.7 mm Hg for the sodium bicarbonate and normal saline groups, respectively). However, when the data were stratified according to pH < 7.4 and pH > 7.4, the peak change in CPP was 12.7 +/- 21 mm Hg when pH < 7.4 and was 5.2 +/- 7.4 when pH > 7.4 (P = .33). Resuscitation was also similar between the two groups (two of nine for sodium bicarbonate and one of nine for normal saline). In conclusion, the standard recommended dose of sodium bicarbonate did not alter the vasopressor effect of epinephrine or resuscitation compared with normal saline in this closed chest model of ventricular fibrillation and CPR.