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Biomedical subjects

C M White

Publications and source records attributed to C M White.

At least 55 records · Page 3Linked to original sources
PubMed1999

Cost-effectiveness of amiodarone for prophylaxis of atrial fibrillation in coronary artery bypass surgery.

The cost-effectiveness of amiodarone prophylaxis of atrial fibrillation (AF) in patients undergoing coronary artery bypass grafting (CABG) was determined. A decision analysis using current hospital data and values from the literature was conducted. Under the base-case scenario, CABG patients received usual care (no prophylaxis) or 2 g of oral amiodarone hydrochloride over one to three days before surgery and 400 mg daily for seven days after surgery. Costs of hospitalization in the intensive care unit (ICU) and the cardiac step-down unit (SDU), cardioversion costs, electrocardiogram costs, drug costs, nursing administration charges, and pharmacy i.v. admixture charges were included. A sensitivity analysis using a Monte Carlo simulation and a one-way sensitivity analysis were performed. The mean cost per AF event avoided was lower in the amiodarone group ($15,750, 95% confidence interval [CI]: $15,591-$15,999) than the control group ($17,426,95% CI: $17,252-$17,600). A majority of the cost difference was due to the cost of hospitalization for patients without AF, the frequency of AF, and the cost of hospitalization in the SDU for patients with AF. For patients treated with amiodarone who did not develop AF, the cost difference was sensitive to changes in the cost of hospitalization and the efficacy of amiodarone. For patients who did develop AF, the cost difference was robust. Prophylaxis of AF with amiodarone in CABG patients was more cost-effective than usual care in the short term from a hospital perspective; the results were sensitive to changes in the cost of hospitalization of patients who did not develop AF and the efficacy of amiodarone.

Amiodarone↗
PubMed1999

Genotype/phenotype correlations in X-linked dominant Charcot-Marie-Tooth disease.

We have studied the relationship between genotype, clinical phenotype, and pathology in 13 families with dominant X-linked Charcot-Marie-Tooth (CMT) neuropathy. Connexin32 (Cx32) gene mutations were spread throughout the coding region and included eight missense mutations, one 8-bp deletion/4-bp insertion frame shifting mutation, two nonsense mutations, and one deletion of the entire coding sequence. One hundred sixteen affected CMTX patients (53 males and 63 females) and 63 unaffected, at-risk individuals were compared by neurological and electrophysiological examinations and analyzed by gender; nerve biopsies were available from seven index cases. It was found that mutations within all regions of the Cx32 gene coding sequence caused an identical clinical phenotype. Male CMTX patients were affected more severely and showed an age-dependent progression of clinical signs and of the pathology; there was, however, variability in the severity of disease expression, irrespective of age, among males within families of defined genotype. All but 10% of female CMTX patients had only mild signs. Motor nerve conduction velocities were moderately slowed (median nerve MNCV: males 34.5 +/- 6.2 m/sec; females 45.8 +/- 7.3 m/sec), and motor and sensory nerve amplitudes were reduced (median nerve CMAP: males 3.7 +/- 3.7 mV; females 7.8 +/- 3.4 mV), with electromyographic evidence of chronic denervation. Differences were significant between gender and between affected and unaffected individuals. In agreement with the electrophysiological observations, pathological studies showed evidence of paranodal demyelination and of a length-related axonal degeneration in motor and sensory nerve fibers. Correlations between genotype and clinical phenotype suggested that missense mutations located within the second transmembrane domain and/or cytoplasmic loop might be associated with milder clinical phenotype, and therefore might be less disruptive of connexin32 gap junction function. Missense, chain-terminating, or deletion mutations in all other locations of the connexin32 protein caused severe forms of CMTX and disease onset in the first decade. Observed variability of disease severity among males within kinships suggests the influence of other modifying factors.

Charcot-Marie-Tooth Disease↗
PubMed1999

Mutation of beta-catenin is an early event in chemically induced mouse hepatocellular carcinogenesis.

beta-catenin activation, and subsequent upregulation of Wnt-signaling, is an important event in the development of certain human and rodent cancers. Recently, mutations in the beta-catenin gene in the region of the serine-threonine glycogen kinase (GSK)-3beta phosphorylation target sites have been identified in hepatocellular neoplasms from humans and transgenic mice. In this study we examined 152 hepatocellular neoplasms from B6C3F1 mice included in five chemical treatment groups and controls for mutations in the beta-catenin gene. Twenty of 29 hepatocellular neoplasms from mice treated with methyleugenol had point mutations at codons 32, 33, 34 or 41, sites which are mutated in colon and other cancers. Likewise, nine of 24 methylene chloride-induced hepatocellular neoplasms and 18 of 42 oxazepam-induced neoplasms exhibited similar mutations. In contrast, only three of 18 vinyl carbamate-induced liver tumors, one of 18 TCDD-induced liver tumors, and two of 22 spontaneous liver neoplasms had mutations in beta-catenin. Thus, there appears to be a chemical specific involvement of beta-catenin activation in mouse hepatocellular carcinogenesis. Expression analyses using Western blot and immunohistochemistry indicate that beta-catenin protein accumulates along cell membranes following mutation. The finding of mutations in both adenomas and carcinomas from diverse chemical treatment groups and the immunostaining of beta-catenin protein in an altered hepatocellular focus suggest that these alterations are early events in mouse hepatocellular carcinogenesis.

Adenoma, Liver Cell↗
PubMed1999

Proximal migration of transanastomotic pancreatic stent following pancreaticoduodenectomy and pancreaticojejunostomy.

BACKGROUND: The use of catheters to stent the pancreaticojejunal anastomosis following pancreaticoduodenectomy is practiced by some surgeons. Their long-term effects in this setting, however, remain unknown. METHODS: A 60-yr-old woman underwent a potentially curative pylorus preserving pancreaticoduodenectomy for Stage I ampullary carcinoma. Roux-en-Y pancreaticojejunostomy was constructed over a short stent. She presented 4 yr later with abdominal pain, steatorrhea, and weight loss. Computed tomography revealed a stent within the proximal pancreatic duct, with gross upstream ductal dilatation and parenchymal features of chronic pancreatitis. RESULTS: Laparotomy revealed no disease recurrence. The stent, removed through a jejunotomy, was occluded. On-table pancreatogram demonstrated a 3-cm proximal duct stricture. Drainage was achieved with a lateral pancreaticojejunostomy (modified Puestow procedure). Recovery was uneventful, with clinical recovery of pancreatic exocrine function at 6 mo follow-up. CONCLUSION: Proximal migration of transanastomotic pancreatic stent with subsequent development of chronic pancreatitis is a potential complication following pancreaticoduodenectomy. It can be managed effectively with stent removal and a lateral pancreaticojejunostomy.

Anastomosis, Roux-en-Y↗
PubMed1999

The meaning of public health nursing: creating 24 hour care in a community in Japan.

This case study describes the strategies and activities of public health nurses to increase the availability of services in a municipality of 36,000 and to transform community attitudes so that those needing services would feel free to use them. Strategies and activities are seen in the context of Japan, Minakuchi Town and the leadership of the chief public health nurse. Practicing in partnership with members of the community, strategies of public health nurses include technical activities (conducting needs assessment and framing program alternatives) and information sharing and health education (e.g. 75 meetings organized with health promoters for residents in the districts of the town). On the basis of the results of Minakuchi Town, viewed as an example of expert public health nursing practice, a general model for public health nursing practice is presented.

Adult↗
PubMed1999

An assessment of the safety of short-term amiodarone therapy in cardiac surgical patients with fentanyl-isoflurane anesthesia.

UNLABELLED: In previously published case reports and a retrospective study, investigators have noted that amiodarone may cause substantial hemodynamic instability when combined with fentanyl-containing anesthesia regimens. We performed the present study to evaluate the safety of short-term amiodarone therapy when combined with a fentanyl-containing anesthesia regimen in a randomized, double-blinded, placebo-controlled format. After institutional approval and written informed consent, patients scheduled to undergo coronary artery bypass grafting or valvular surgery were randomly allocated to receive amiodarone (3.4 g over 5 days or 2.2 g over 24 hours) or placebo before surgery. Four indicators for hemodynamic instability were assessed: 1) a net increase in fluid balance during surgery of >2 L; 2) use of dopamine at a rate >10 microg x kg(-1) x min(-1); 3) use of other vasopressive catecholamines; and 4) use of a phosphodiesterase inhibitor or intraaortic balloon pump. Systolic, diastolic, and central venous pressures were measured before fentanyl administration, before cardiopulmonary bypass (CPB), and after separation from CPB. Overall, 84 patients (45 patients in the amiodarone group, 39 in the placebo group) were enrolled and completed the study. There were no significant differences between the two groups in any indicator for hemodynamic instability or the indicators of instability combined. After CPB, there was a significantly lower systolic blood pressure in the amiodarone group compared with the placebo group (112 +/- 12 vs 117 +/- 14 mm Hg; P = 0.049). However, there was a trend toward smaller IV fluid requirements during surgery in the amiodarone group compared with the placebo group (438 +/- 867 vs 907 +/- 1640 mL; P = 0.09). We found no increased risk of hemodynamic compromise after short-term amiodarone therapy among patients receiving a fentanyl-containing anesthesia regimen during open heart surgery. IMPLICATIONS: In previous retrospective studies and case reports, investigators have identified a possible risk of hemodynamic compromise when patients receiving chronic amiodarone therapy are given anesthesia regimens containing fentanyl. We performed a prospective, randomized, double-blinded study to evaluate the hemodynamic effects of short-term amiodarone therapy during fentanyl-isoflurane anesthesia for open heart surgery. No adverse hemodynamic effects of amiodarone were identified.

Adjuvants, Anesthesia↗
PubMed1999

A comparison of the antifibrillatory effects of desethylamiodarone to amiodarone in a swine model.

We evaluated the effect of two different doses of desethylamiodarone (DEA) and amiodarone on the ventricular fibrillation threshold (VFT). We ascertained the VFT in 24 pigs randomized to intravenous DEA, amiodarone, or vehicle. Ventricular fibrillation was induced by pacing the right ventricle by using a primary drive train at a cycle length of 270 ms for eight beats of 2-ms duration each. A secondary train of 20 pulses of 4-ms duration (100 Hz) immediately followed this over a total duration of 200 ms synchronized to the primary drive train. The intensity of the secondary train stimuli current was initially 2 mA and was increased by 2-mA increments until sustained VF with hemodynamic collapse was induced. The minimal current strength needed to induce sustained VF was defined as the VFT measured in mA. DEA (10 mg/kg) increased the VFT significantly over baseline from 13.5+/-4.9 to 23.2+/-8.8 mA (p = 0.0076). Amiodarone, 10 mg/kg, increased the VFT significantly over baseline (mean +/- SD) from 14.4+/-3.6 to 23.8+/-6.1 mA (p = 0.0016). An additional dose of amiodarone (15 mg/kg) increased the VFT to 38.5+/-15.9 mA, which is significantly greater than the VFT derived from lower-dose amiodarone (p = 0.046). We showed that DEA (10 mg/kg) has a similar antifibrillatory effect as 10 mg/kg of amiodarone. We also demonstrated a dose-dependent effect on VFT for amiodarone.

Amiodarone↗
PubMed1999

Pharmacological effects of HMG CoA reductase inhibitors other than lipoprotein modulation.

The HMG CoA reductase inhibitors reduce levels of low-density lipoproteins, raise high-density lipoproteins, and lower triglycerides. However, there are other pharmacological effects derived from HMG CoA reductase inhibitor therapy. Certain HMG CoA reductase inhibitors affect atherosclerotic plaque composition, endothelial function, platelet and clotting factors, and immune functioning. The unique extrahepatic pharmacological profile of agents in this class has not been fully characterized. All of the HMG CoA reductase inhibitors studied have improved endothelium-dependent vasodilatation. Vascular smooth muscle proliferation is not significantly affected by pravastatin but is by the other agents. Of all the HMG CoA reductase inhibitors, cerivastatin is the most potent inhibitor of vascular smooth muscle proliferation. Pravastatin is the only agent proven to significantly reduce platelet-thrombus formation and fibrinogen levels. Simvastatin has no effect on platelet-thrombus formation or fibrinogen levels, while atorvastatin and lovastatin have been shown to increase fibrinogen in some studies. Plasminogen activator inhibitor-1 levels are decreased by pravastatin, are not affected by atorvastatin, and are significantly increased by lovastatin and simvastatin. Pravastatin also has clinical benefits in transplant medicine as a result of inhibiting natural killer cell function, an effect that has not been explored with other HMG CoA reductase inhibitors.

Animals↗
PubMed1999

The effect of pharmacokinetically guided acute intravenous testosterone administration on electrocardiographic and blood pressure variables.

Previous studies have demonstrated that intravenous testosterone can dilate coronary arteries and increase exercise treadmill time, but the electrocardiographic and hemodynamic effects are unknown. This trial determined the hemodynamic and electrocardiographic effects of dosing intravenous testosterone to achieve a physiologic and a superphysiologic serum testosterone concentration. Twenty men (70.6 +/- 6.2 years) had individualized testosterone bolus and continuous infusions designed to increase the serum testosterone concentration by two (physiologic) and six times baseline (superphysiologic). The men were studied on three occasions when they were randomly allocated to received a placebo, physiologic testosterone regimen, or superphysiologic testosterone regimen. Blood pressures and 12-lead electrocardiograms (ECGs) were taken preinfusion and 28 minutes after initiating the infusion on each visit. The blood pressure (systolic and diastolic) and ECG variables (PR, QRS, QT, QTc, and RR intervals) preinfusion and during the infusion were compared, and the delta changes in the variables were compared between groups. The physiologic testosterone regimen increased the serum testosterone concentration by 2.39 +/- 0.48 times the preinfusion concentration, while the superphysiologic regimen increased it by 6.22 +/- 0.99 times. No significant changes occurred in the blood pressure or ECG variables in any group versus preinfusion values or between the three groups. Exogenously administered intravenous testosterone does not significantly affect the blood pressure or ECG variables when given to achieve physiologic or superphysiologic concentrations.

Aged↗
PubMed1999

Prevention of suboptimal beta-blocker treatment in patients with myocardial infarction.

OBJECTIVE: To review the published data and clinical guidelines on the use of beta-blockers in myocardial infarctions (MIs) and contrast that with actual clinical practice. DATA SOURCES: A MEDLINE search (January 1970-June 1999) was performed to identify all relevant articles. References from these articles were also evaluated for review if deemed important. DATA SYNTHESIS: Intravenous and oral beta-blockers have been proven to improve outcomes in patients with MIs in numerous clinical trials. In current clinical practice, only 15% of MI patients receive intravenous beta-blockers and long-term beta-blocker therapy is used in <40% of patients without contraindications. However, they could be safely administered to 40% and 70% of these patients, respectively. Furthermore, most of these patients are receiving doses far below those found beneficial in clinical trials. Many of the real and perceived contraindications to beta-blockers are reviewed to allow the practitioner to identify patients who are incorrectly excluded from beta-blocker therapy. Also discussed are special clinical situations in which the benefits observed during clinical trials may not apply. CONCLUSIONS: Beta-blockers are valuable drugs in the treatment of peri- and post-MI. In clinical practice, most patients are not treated or are inadequately treated with beta-blockers. Pharmacists should ensure that such patients actually have an absolute contraindication or unusual situation where therapy is not firmly indicated. Patients without absolute contraindications warrant titration to specific target doses or a target heart rate of 55-60 beats/min.

Adrenergic beta-Antagonists↗
PubMed1999

The effect of amiodarone on the ventricular fibrillation threshold.

We evaluated the antifibrillatory effect of two different doses of amiodarone after cardiac arrest with a cardiopulmonary resuscitation (CPR) model in 19 pigs. Ventricular fibrillation was induced by pacing the right ventricle using a primary drive train at a cycle length of 270 msec for 8 beats. The minimum current strength necessary to induce sustained ventricular fibrillation was defined as the ventricular fibrillation threshold (VFT) measured in mA. Three VFT determinations were made at baseline, followed by 9 minutes of continuous CPR with two determinations of VFT, and three after stabilization. The pigs were placed into one of three groups: amiodarone 2 or 5 mg/kg, or placebo. The average poststabilization VFT in each group was compared with the average baseline VFT. Pigs receiving amiodarone 2 mg/kg had significantly higher VFT after stabilization than at baseline (22.88+/-12.76 to 27.10+/-10.18 mA, p=0.048), as did those receiving 5 mg/kg (17.03+/-7.01 to 28.08+/-11.58 mA, p=0.002). The deltaVFT was significantly greater with amiodarone 5 mg/kg than with vehicle (placebo), but not with 2 mg/kg. There were no changes in VFT in any group during CPR versus baseline. When active treatments were combined, the trend was toward better survival in the amiodarone groups (13/13) compared with the placebo group (4/6, p=0.076).

Amiodarone↗
PubMed1999

Prophylactic magnesium to decrease the arrhythmogenic potential of class III antiarrhythmic agents in a rabbit model.

We assessed the prophylactic effect of intravenous magnesium sulfate on the occurrence of torsades de pointes and early after-depolarizations, and on the QT interval (QTc) in an established rabbit model. Ten rabbits were given intravenous methoxamine to slow their heart rates. After 12 minutes five animals received a 60-mg/kg bolus and continuous infusion of magnesium 0.6 mg/kg/minute, and five received equivolume normal saline concurrently with the class III antiarrhythmic agent clofilium 5 mg/kg over 30 minutes. Electrocardiogram lead II and the monophasic action potential were recorded continuously throughout the experiment. The magnesium group experienced significantly less torsades de pointes and early after-depolarizations than the normal saline group (1/5 and 5/5 both parameters, respectively, p=0.048). There were no differences between groups in QT or QTc interval at baseline or at maximum QT or QTc prolongation. Magnesium decreases the occurrence of torsades de pointes without affecting the QT or QTc interval but does decrease the occurrence of early after-depolarizations. These findings must be validated in human studies.

Anesthesia↗
PubMed1999

Familiarity and pronounceability of nouns and names.

Ratings of familiarity and pronounceability were obtained from a random sample of 199 surnames (selected from over 80,000 entries in the Purdue University phone book) and 199 nouns (from the Kucera-Francis, 1967, word database). The distributions of ratings for nouns versus names are substantially different: Nouns were rated as more familiar and easier to pronounce than surnames. Frequency and familiarity were more closely related in the proper name pool than the word pool, although both correlations were modest. Ratings of familiarity and pronounceability were highly related for both groups. A production experiment showed that rated pronounceability was highly related to the time taken to produce a name. These data confirm the common belief that there are differences in the statistical and distributional properties of words as compared to proper names. The value of using frequency and the ratings of familiarity and pronounceability for predicting variations in actual pronunciations of words and names are discussed.

Adult↗
PubMed1999

A review of potential cardiovascular uses of intravenous glucagon administration.

Glucagon is a counter-regulatory hormone that is classically used to treat hypoglycemia. However, it can elicit the generation of cAMP within the myocardium to cause positive inotropic and chronotropic effects without the need for beta-1 adrenoceptor stimulation. Glucagon has been used extensively to treat beta-blocker overdose and has evidence for use in verapamil and imipramine overdose as well. Glucagon has been used as adjunctive therapy in shock situations and heart failure but is inferior to catecholamines. An interesting potential indication for glucagon is in treating postcountershock asystole.

Animals↗