Echocardiographic evaluation of regurgitant fraction in dogs with subclinical myxomatous mitral valve disease: Method comparison, effects of pimobendan, and reproducibility.

INTRODUCTION/OBJECTIVES: To evaluate regurgitant fraction (RF) using Simpson's method of discs to estimate total stroke volume (RFSMOD_TSV) and using Motion-mode to estimate total stroke volume (RFM-modeTSV) in dogs with subclinical myxomatous mitral valve disease (MMVD). We also sought to evaluate the effects of pimobendan on RF, and to determine the reproducibility of RFSMOD_TSV and RFM-modeTSV. ANIMALS, MATERIALS, AND METHODS: Echocardiography was performed on 57 dogs with MMVD (30 stage B1 and 27 stage B2). Ten dogs received pimobendan for 7-10 days and had a second echocardiogram. Nine dogs underwent six repeated echocardiographic examinations by two operators on three nonconsecutive days within one week for reproducibility analysis. RESULTS: Both RFSMOD_TSV and RFM-modeTSV exhibited a curvilinear relationship with left atrium-to-aortic root ratio. Both RFSMOD_TSV and RFM-modeTSV varied considerably within stage B1 (minimum-maximum: -9.1%-58.2% and -35.7%-66.2%, respectively) and B2 (13.6%-76.2% and 20.1%-85.7%, respectively). Method comparison showed RFSMOD_TSV and RFM-modeTSV were not interchangeable with proportional bias. Pimobendan significantly reduced RFSMOD_TSV (-32.0% ± 23.3%) and RFM-modeTSV (-19.2% ± 10.9%) within the same dog and relative to controls. Good inter-day and between-operator reproducibility was observed for RFSMOD_TSV and RFM-modeTSV based on intraclass correlation coefficients 0.86-0.90 and 0.83-0.90, respectively. Reproducibility coefficients were 19.6%-24.1% and 24.1%-27.0%, respectively. CONCLUSIONS: Use of RF using the total stroke volume method to aid the assessment of dogs with subclinical MMVD might be of clinical value. However, further study is warranted. Based on response to pimobendan and reproducibility analysis, RF SMOD_TSV might be a more reliable technique to quantify RF.

Fractional viscoelastic models for power-law materials.

Soft materials often exhibit a distinctive power-law viscoelastic response arising from broad distribution of time-scales present in their complex internal structure. A promising tool to accurately describe the rheological behaviour of soft materials is fractional calculus. However, its use in the scientific community remains limited due to the unusual notation and non-trivial properties of fractional operators. This review aims to provide a clear and accessible description of fractional viscoelastic models for a broad audience and to demonstrate the ability of these models to deliver a unified approach for the characterisation of power-law materials. The use of a consistent framework for the analysis of rheological data would help classify the empirical behaviours of soft and biological materials, and better understand their response.

Age increases MCP-1 level in association with bariatric surgery operating time and metabolic risk severity.

OBJECTIVE: Assess the role of inflammation on operating time in younger vs. older bariatric surgery patients. METHODS: Fifty-five younger (F: 46, Age: 34.9 ± 4.0 years, body mass index [BMI]: 48.2 ± 1.0 kg m-2) and 48 older (F: 34, Age: 57.0 ± 5.1 years, BMI: 46.8 ± 1.0 kg m-2) adults were studied prior to surgery. Blood pressure, glycaemic control (fasting glucose/insulin, HbA1c), lipids (high-density lipoprotein and triglycerides) and inflammation (monocyte chemoattractant protein-1 [MCP-1]) were assessed. Metabolic risk severity z-scores were calculated from clinical outcomes. Omental adipose biopsies were collected at surgery for MCP-1 protein analysis. Operating time was used to characterize surgical difficulty. RESULTS: Older vs. younger adults had higher HbA1c (P = 0.03). There was no difference in BMI, lipids, metabolic risk severity or insulin between groups, but operating time was longer in older vs. younger individuals (P = 0.04). Circulating MCP-1 was also elevated in older vs. younger adults (P = 0.04) independent of HbA1c, although this was not explained by omental fat. Nevertheless, serum MCP-1 was associated with increased metabolic risk severity (R = 0.27, P = 0.01). In addition, operating time was linked to HbA1c (R = 0.30, P = 0.01) and omental MCP-1 protein (R = 0.31, P < 0.01). CONCLUSIONS: MCP-1 is associated with longer operating time and increased metabolic risk severity in older bariatric patients independent of glycaemic control. Pre-operative treatment of inflammation may be required to enhance surgery effectiveness.

Adenosine A1 receptor antagonist prolongs survival in the hypoxic rat.

The hypothesis that adenosine A1 receptor (A1AdoR) selective antagonism limits cardiac depression and prolongs survival during acute global hypoxia was tested in a postinsult treatment model using KW-3902 ([8-(noradamantan-3-yl)-1,3-dipropylxanthine]), an A1AdoR selective antagonist. Rats were anesthetized, paralyzed, then ventilated with 8% O2 (hypoxia). In protocol I, 5 min after hypoxia, rats were treated with saline, drug vehicle, or KW-3902 (0.1 mg/kg i.v.). In protocol II, KW-3902 treatment occurred 2.5, 5, or 7.5 min after hypoxia. In protocol I, after hypoxia, left ventricular contractility, heart rate, and systemic mean arterial blood pressure decreased rapidly in saline-and vehicle-treated groups. In contrast, KW-3902 significantly attenuated the decline in these variables. Survival time (the time from the commencement of hypoxia until death) was more prolonged with KW-3902 (109.5 +/- 9.1 min) than with saline (37.6 +/- 5.0 min) or vehicle (35.0 +/- 4.2 min) (p < 0.001). In protocol II, survival time increased from 29.2 +/- 5.5 min in the 7.5-min treatment group to 109.5 +/- 9.5 min (5-min group) and 245.9 +/- 26.1 min (2.5-min group; p < 0.001). KW-3902 prolongs survival in this model, presumably by antagonizing A1AdoR-mediated inhibition of cardiac function. Also, treatment efficacy is highly time dependent.

What is gross hematuria? Correlation of subjective and objective assessment.

BACKGROUND: Gross hematuria is a screening test used to help determine the need for radiographic evaluation in patients with blunt trauma. This subjective assessment has not been compared with objective measures, nor has interrater reliability been described. METHODS: We performed a prospective, randomized, controlled study to determine the ability of clinicians to assess gross hematuria. Clinicians were asked to assess samples containing various concentrations of blood diluted in urine for the presence of gross hematuria. RESULTS: Gross hematuria was recognized by more than 95% of clinicians only when samples contained more than 3,500 red blood cells per high-power field. Clinicians' interpretations were independent of profession, specialty, and level of training (p > 0.08). CONCLUSION: Clinicians demonstrate poor sensitivity and interrater reliability identifying gross hematuria by inspection. Clinical studies correlating degrees of hematuria to the need for genitourinary diagnostic evaluation should report both subjective and objective measures to identify a threshold value predictive of renal injury.

The effect of lower-extremity position on cerebrospinal fluid pressures.

OBJECTIVE: To determine the effects of lower-extremity positioning on cerebrospinal fluid opening pressure (CSFp). The authors believed that during lumbar puncture (LP), CSFp does not meaningfully decrease when the lower extremities are extended from flexion, as is often suggested. METHODS: In a convenience sample of adult patients who clinically required LP in an urban emergency department, three sequential CSFp measurements were obtained in either sequence A (knee, hip, and neck flexion [90 degrees ], then extension, then flexion) or sequence B (extension, flexion, then extension) prior to CSF withdrawal. The neck was flexed at 30 degrees when the lower extremities were flexed, while the thoracolumbar spine was kept in the neutral position for all measurements. RESULTS: Nineteen patients were studied in each sequence. Although variable, overall within-patient changes between positions were not clinically meaningful. Mean and 95% confidence intervals (95% CIs) for the decrease in CSFp from position 1 to position 3 (same position) were 0.2 cm H(2)O (1.7%) and 0.9 to -0.6 cm H(2)O (6% to -2.7%), respectively. Changing from flexion to extension decreased pressure measurements by a mean of 0.9 cm H(2)O (2.5%) [95% CI = 2.1 to -0.1 cm H(2)O (7.6% to -2.4%)]. Changing from extension to flexion increased CSFp by a mean of 1.1 cm H(2)O (6.1%) [95% CI = 0.2 to 2.0 cm H(2)O (1.3% to 11.5%)], a statistically but not clinically meaningful change. CONCLUSIONS: Changing lower-extremity position did not meaningfully change mean CSFp. These data do not support the common suggestion that extending the lower extremities during LP meaningfully decreases CSF opening pressures.

Hypertonic saline treatment of severe hyperkalemia in nonnephrectomized dogs.

OBJECTIVES: To determine whether a hypertonic saline bolus improves cardiac conduction or plasma potassium levels more than normal saline infusion within 15 minutes of treatment for severe hyperkalemia. Previously with this model, 8.4% sodium chloride (NaCl) and 8.4% sodium bicarbonate (NaHCO(3)) lowered plasma potassium equally effectively. METHODS: This was a crossover study using ten conditioned dogs (14-20 kg) that received, in random order, each of three intravenous (IV) treatments in separate experiments at least one week apart: 1) 2 mmol/kg of 8.4% NaCl over 5 minutes (bolus); 2) 2 mmol/kg of 0.9% NaCl over one hour (infusion); or 3) no treatment (control). Using isoflurane anesthesia and ventilation (pCO(2) = 35-40 torr), 2 mmol/kg/hr of IV potassium chloride (KCl) was infused until conduction delays (both absent p-waves and >/=20% decrease in ventricular rate in

Antagonism of the cardiodepressant effects of adenosine during acute hypoxia.

OBJECTIVE: To determine whether pharmacologic antagonism of adenosine A1-receptor-mediated cardiovascular changes can improve cardiac function and prolong survival during systemic hypoxia. METHODS: Rats were anesthetized with ketamine, instrumented [including left ventricular (LV) pressure transducing catheters], paralyzed with vecuronium, then ventilated to pCO2 = 35-40 torr. After 10 minutes of equilibration (baseline), treatment commenced with saline (n = 7), NPC-205, an adenosine A1 receptor selective antagonist, at doses of 1 mg/kg (n = 10) or 10 mg/kg (n = 10), or drug vehicle (n = 9). Ten minutes later, inspired oxygen was reduced to 5%. RESULTS: Survival duration (min) post-hypoxia increased in a dose-dependent fashion from 10.4 +/- 1.4 (mean +/- SEM) with vehicle control to 23.0 +/- 4.7 and 41.1 +/- 5.7 with 1 and 10 mg/kg NPC-205, respectively (p < 0.000). Five minutes post-hypoxia, dose-dependent increases were also seen in the percentage of pre-hypoxic values of LV contractility [25.9 +/- 8.1 (vehicle), 39.5 +/- 9.6 (1 mg/kg NPC-205), and 56.5 +/- 8.7 (10 mg/kg NPC-205), p = 0.01], heart rate [60.6 +/- 8.3 (vehicle), 74.7 +/- 8.2 (1 mg/kg NPC-205), and 90.4 +/- 24.1 (10 mg/kg NPC-205), p = 0.02], and blood pressure [16.1 +/- 4.8 (vehicle), 28.8 +/- 8.6 (1 mg/kg NPC-205), and 51.7 +/- 8.2 (10 mg/kg NPC-205), p = 0.004]. CONCLUSIONS: The adenosine A1 selective antagonist prolonged survival in this model. This prolongation was attributed to inhibition of adenosine A1 receptor-mediated decline in cardiac inotropy and chronotropy. Adenosine A1 receptor-selective antagonists show promise as adjunctive therapy for hypoxia-induced cardiac insufficiency by prolonging the treatment window until more definitive resuscitation measures are taken.

Use of an unmanned police car to reduce traffic speed.

OBJECTIVE: Motor vehicle collisions are the most common mechanism of traumatic death. Speeding is often implicated as a causal factor in motor vehicle crashes. One potential intervention, to prevent speeding, is the placement of a roadside unmanned police car. This study sought to answer the following questions: is speeding reduced by this intervention, does this intervention lose effectiveness over time, and when the car is removed, do motorists resume speeding? METHODS: A radarless speed detector was placed on a roadway that had a history of speed-related collisions. Baseline speeds were recorded for 12 days. Thereafter, an unmanned police cruiser was parked near the road, and speeds were recorded for 10 days. The police car was removed, and data collection continued 1 more week. The difference between the proportion of motorists exceeding 45-mph in the baseline period and the decoy intervention period was tested by using a chi2 test. RESULTS: During the baseline surveillance, 72.0% of vehicles (186,578 of 259,074 motorists) had speeds greater than 45 mph. After placement of the unmanned police car, 41.0% of motorists (92,272 of 225,026 motorists) exceeded 45 mph (p < .0001). Over the 10-day study period, when the decoy police car was in place, the percentage of motorists exceeding 45 mph gradually increased from 27.2% to 47.4%. Upon removal of the police car, speeding returned approximately to baseline, with 67.5% of motorists (120,640 of 178,752 motorists) exceeding 45-mph. CONCLUSION: Parking an unmanned police car beside a road was associated with a large reduction in speeding over a 10-day period. Removal of the unmanned police car resulted in a return to preintervention speeding.

Cost-based comparison between perforator flaps and TRAM flaps for breast reconstruction.

More women than ever before are undergoing mastectomies secondary to increased awareness and screening. This increase has also caused a corresponding increase in the number of breast reconstructions requested each year. The increased demand for reconstruction has fueled recent advances in new techniques. Aside from foreign-body reconstruction such as implants, the methods now being used are related to autogenous donations and reconstruction. Transverse rectus abdominis myocutaneous (TRAM) flaps and perforator flaps are currently being used for autogenous breast reconstruction. This study will compare these two techniques on the basis of cost and length of stay. A retrospective study of 49 patients undergoing a total of 64 perforator flap breast reconstructions at Memorial Medical Center in New Orleans, Louisiana, during the 1997 calendar year was used. There were 59 deep inferior epigastric perforator and five gluteal artery perforator breast reconstructions. All patients underwent some form of breast reconstruction and differed only in respect to whether a mastectomy was performed and whether the reconstruction was unilateral or bilateral. Those patients who underwent a mastectomy with immediate perforator flap reconstruction (n = 26) were then compared with patients undergoing mastectomy with immediate TRAM flap reconstruction (n = 154) at the University of Texas M. D. Anderson Cancer Center. The data from the Anderson Study were obtained from material published in Plastic and Reconstructive Surgery in 1996. Comparison of patients was limited to those who underwent mastectomy with immediate breast reconstruction because this was the design of the M. D. Anderson study. This approach allowed a cost and length of stay comparison while keeping other variables relatively similar. Patients in the perforator flap series enjoyed a marginally shorter operating time and a much shorter length of stay. On average, the operative time for all perforator flap reconstructions was approximately 2 hours shorter than for all TRAM flaps. As for length of stay, perforator flap patients were discharged, on average, 3 days after the initial reconstruction. In contrast, TRAM flap patients remained in the hospital for an average of approximately 7 days after the initial reconstruction. The overall total, average cost for the perforator flap reconstruction in this study is $9625, whereas the average cost of all TRAM flaps performed in the Anderson study is $18,070.

Double-blind, randomized study of nalmefene and naloxone in emergency department patients with suspected narcotic overdose.

STUDY OBJECTIVES: To compare the efficacy, safety, and withdrawal symptoms in emergency department patients with suspected narcotic overdose treated with nalmefene, an opioid antagonist with a 4- to 10-hour duration of action, with those treated with naloxone. METHODS: Adults in 9 centers who would otherwise receive naloxone for altered consciousness levels were randomly assigned to receive intravenous study drug (1 mg nalmefene, or 2 mg nalmefene or 2 mg naloxone, double-blinded) every 5 minutes as needed for up to 4 doses in a 4-hour study. Outcomes were 20-minute and 4-hour posttreatment changes in respiratory rates, Neurobehavioral Assessment Scale scores, Opioid Withdrawal Scale scores, and incidences of adverse events. RESULTS: Opioid positivity was recorded for 30 of 63 (1-mg nalmefene), 23 of 55 (2-mg nalmefene), and 24 of 58 (naloxone) cases, 75% of whom also had nonopioid central nervous system depressants. Most patients received only 1 dose of study drug. Similar, clinically meaningful improvements in respiratory rates and Neurobehavioral Assessment Scale scores were seen with all treatments. No statistical differences in efficacy or withdrawal outcomes were seen between treatment groups, and no significant overall time-treatment interactions occurred, in either the entire patient group or among opioid-positive cases (P >.21, all comparisons). Adverse events occurred in 30.9% (2 mg nalmefene), 15.9% (1 mg nalmefene), and 15.5% (naloxone) of patients (P >.08); none were associated with morbidity. CONCLUSION: In this study of patients with varied potential causes of altered consciousness, nalmefene (1 mg and 2 mg) and naloxone (2 mg) appeared to be efficacious, safe, and to yield similar clinical outcomes.

Use of tube condensation as an indicator of endotracheal tube placement.

STUDY OBJECTIVE: To determine whether condensation on the inner surface of the endotracheal tube (vapor trail) is a reliable indicator of intratracheal placement. METHODS: Twenty-seven separate experiments were conducted on 10 conditioned, mongrel dogs weighing 15 to 20 kg each. After induction of anesthesia, an endotracheal tube was placed in the trachea under direct visualization. A second, identical endotracheal tube was then placed in the esophagus. An attending emergency physician, blinded to tube placement, then used a bag-valve apparatus to manually ventilate each endotracheal tube in turn. Five ventilations were performed on each tube, and the presence or absence of condensation on the inner surface of the tube was recorded. A second physician, blinded both to tube placement and to the actions of the first assessor, then repeated the ventilation and assessment of both tubes. RESULTS: Vapor trail was observed in 27 (100%) of 27 endotracheal tubes correctly placed in the trachea (95% confidence interval [CI], 90% to 100%) and in 23 (83%) of 27 tubes placed in the esophagus (95% CI, 66% to 96%). Physicians concurred in all cases. Absence of vapor trail was 15% sensitive (95% CI, 4% to 34%) for indicating incorrect (esophageal) tube placement. CONCLUSION: In this model, condensation on the inner surface of the endotracheal tube was common after placement within the esophagus. If these results are confirmed in human studies, the presence of a vapor trial should not be used as a clinical indicator of correct endotracheal tube placement.

Alkalinization is ineffective for severe hyperkalemia in nonnephrectomized dogs. Hyperkalemia Research Group.

OBJECTIVE: To determine whether alkalinization with sodium bicarbonate (NaHCO3) in near-lethal hyperkalemia either lowers potassium (K) rapidly or shortens duration of cardiac conduction disturbances. METHODS: A controlled canine laboratory investigation of 3 treatments for severe hyperkalemia. Conditioned dogs (n = 8; 17-30 kg) received, in random order, 2 mmol/kg of each of 3 treatments (matched in sodium and water) in separate experiments > or = 1 week apart: 1.05% NaHCO3 over 60 minutes (infusion therapy); 8.4% NaHCO3 over 5 minutes, then 14 mL/kg sterile water over 55 minutes (bolus therapy); 8.4% NaCl over 5 minutes, then 14 mL/kg sterile water over 55 minutes (saline therapy). Prior to administering one of the above therapies, the animals were anesthetized with 0.5-2.5% isoflurane and ventilated to maintain a normal PCO2. After 30 minutes of equilibration, 2 mmol/kg/hr (loading dose) of a 2-mmol/mL KCl solution was given until idioventricular or relative junctional bradycardic dysrhythmias were sustained for 15 minutes. Then KCl was decreased to 1 mmol/kg/hr (maintenance dose) for 2 hours and 45 minutes. Treatment was begun after 45 minutes of maintenance KCl infusion. RESULTS: The pretreatment K level (all studies) was 9.06 +/- 0.82 mmol/L (mean +/- SD). Although the mean K level decreased more after saline therapy than after bolus therapy at every time, differences were neither statistically significant nor clinically important during the first 30 minutes. The means of the differences in decreases (saline minus bolus) were small, 0.26 (95% CI, -0.48 to 1.00) at 15 minutes, 0.16 (95% CI, -0.67 to 0.98) at 30 minutes. Dysrhythmia duration was shorter with bolus therapy than for saline therapy in only 1 of 5 dogs (p = 0.38). CONCLUSIONS: Hypertonic saline bolus lowered plasma K as effectively as NaHCO3 bolus in this animal model within the first 30 minutes. Clinically meaningful decreases due to alkalinization alone within 30 minutes are unlikely.

Posttraumatic osseous tunnel formation causing sciatic nerve entrapment.

Sciatic nerve entrapment in an osseous tunnel has only been reported twice previously. We describe a 19-year-old man evaluated for left lower limb pain and weakness that began one and one half years after sustaining stab wounds to the left buttock and midline back near the T11 vertebrae. The patient had sciatica and demonstrated motor and sensory deficits on physical exam. Electrodiagnostic studies demonstrated a localized injury to the sciatic nerve in the proximal thigh. Radiographic studies of the left pelvis and femur showed an 8 to 10cm linear opacification overshadowing the left femoral head and anatomic neck. An arteriogram of the left leg demonstrated a 3 x 4cm lobulated aneurysm arising from the distal portion of the inferior gluteal artery. Surgical exploration revealed the sciatic nerve to be encased in cylindrical bone. The ectopic bone was removed and the sciatic nerve released. The patient had gradual improvement with a nearly complete neurological recovery by three months after surgery.

Effectiveness and safety of intravenous nalmefene for emergency department patients with suspected narcotic overdose: a pilot study.

STUDY OBJECTIVE: To evaluate the efficacy and safety of nalmefene, an investigational narcotic antagonist that has potential advantages over naloxone because of its four- to eight-hour half-life, in emergency department patients with possible narcotic overdose. DESIGN: Multi-institutional, prospective, phase II, open-label study. TYPE OF PARTICIPANTS: Complete data were available for 53 cases from two teaching hospitals. Men 18 years old or older who would otherwise receive naloxone were eligible (two women were enrolled inadvertently). METHODS: Over four hours, one to ten boluses (median, one) of 0.5 or 1.0 mg nalmefene IV were given as often as every two minutes based on clinical need. Respirations, blood pressure, pulse, pupil size, and overall clinical response were monitored. Overall clinical response (1, no change; 2, partial response; 3, complete response), first assessed at two minutes, was analyzed by the Mann-Whitney U test. RESULTS: Fifteen of 25 (0.5 mg) and nine of 28 (1.0 mg) cases were opiate positive. Twelve of 15 (0.5 mg) and six of nine (1.0 mg) opiate-positive cases had a rapid complete response. Coincident causes of depressed sensorium were identified in the remaining six opiate-positive cases. No difference in initial overall clinical response was seen between 0.5-mg and 1.0-mg opiate-positive cases (P = .59). No deterioration requiring repeat nalmefene occurred in opiate-positive cases, even if methadone (four), codeine (two), or pentazocine (one) was found. No serious adverse events were judged to be related to nalmefene. CONCLUSION: Nalmefene is effective in the reversal of opiate overdose and appears to be safe in the management of patients with altered sensorium.