Pharmacokinetics of an immediate and extended release oral morphine formulation utilizing the spheroidal oral drug absorption system in dogs.

This study investigated the pharmacokinetics of a human-labeled oral morphine formulation consisting of both immediate and extended release components in dogs. In a randomized design, 14 dogs were administered either 1 or 2 mg/kg morphine orally. Blood samples were collected up to 24 h post drug administration. Plasma concentrations of morphine were measured using high-pressure liquid chromatography with electrochemical coulometric detection. For both groups, maximal concentration occurred at 3 h post drug administration followed by a gradual decrease in morphine concentration over 24 h. There was substantial variability in morphine concentrations among dogs. The higher dose group produced a greater exposure (higher area-under-the-curve), higher peak concentration, longer half-life and a shorter time to peak concentration (t(max)). The specific oral morphine formulation used in this study produced sustained plasma morphine concentrations over 24 h compared with previous intravenous dosing and immediate-release oral morphine studies. However, the low morphine plasma concentrations and high variability produced from this formulation, suggest that the clinical application of this formulation at the doses evaluated in this study are limited.

Sample size and statistical power in the small-animal analgesia literature.

OBJECTIVE: To document the power and required sample sizes to achieve certain treatment objectives in the veterinary analgesia literature. METHODS: Pubmed's MEDLINE database and selected journals were searched. Only publications produced between 1994 and 2004 that reported 'no difference' between experimental groups in the abstract, results or conclusion sections and those that were randomised, prospective and blinded were reviewed. The data reported in the publications were then subjected to power analyses to determine the power and necessary sample size (to achieve a power of 0.8) to allow detection of 20 per cent, 50 per cent and 80 per cent treatment effects. RESULTS: Twenty-two studies provided sufficient data for analysis. Five out of 22 (23 per cent) had sufficient power to detect a 20 per cent treatment effect, 12 of 22 (54 per cent) had sufficient power to detect a 50 per cent treatment effect and 18 of 22 (82 per cent) had sufficient power to detect an 80 per cent treatment effect. The mean number of animals required per group to document a 20 per cent, 50 per cent and 80 per cent treatment effect were 90, 15 and 7, respectively. CLINICAL SIGNIFICANCE: Publications that report no significant difference between analgesic regimens may have committed a Type II error. The reader may inappropriately conclude that there is no difference between treatments when there may, in fact, be a superior analgesic regimen. Clinical practice based on the principles of evidence-based medicine could therefore result in suboptimal care for patients.

Treatment of hypoxemia during xylazine-tiletamine-zolazepam immobilization of wapiti.

Hypoxemia is a commonly observed complication during the chemical immobilization of wild ruminants. If severe and left untreated, it can predispose animals to arrhythmias, organ failure, and capture myopathy. The following prospective study was designed to measure the degree of hypoxemia in wapiti that were immobilized with a combination of xylazine and tiletamine-zolazepam and to assess the response to nasal oxygen therapy. Pulse oximetry and arterial blood gas analysis were used to assess the degree of hypoxemia prior to nasal insufflation of oxygen and to demonstrate any beneficial effects of this intervention. All wapiti exhibited mild to marked hypoxemia (PaO2 = 43 +/- 11.8 mmHg) prior to treatment and showed marked improvement after 5 minutes of nasal insufflation of oxygen at 10 L/min (PaO2 = 207 +/- 60 mmHg). This inexpensive, noninvasive technique has great benefit in treating clinical hypoxemia under field conditions, and we recommend that nasal insufflation of oxygen be implemented during xylazine-tiletamine-zolazepam-induced immobilization of wapiti and other wild ruminants.

Comparison of analgesic techniques for antler removal in wapiti.

The purpose of this research was to compare the effectiveness of ring block anesthesia (LA) and electroanesthesia (A) for antler removal in elk given a long-acting tranquilizer to remove stress from restraint. Thirty-two male wapiti were given 1 mg/kg body weight of zuclopenthixol acetate; the next day, they were restrained in a hydraulic chute, provided with electroanesthesia or a lidocaine ring block, and had their antlers removed. Behavioral response to antler removal was scored. Significantly more (P = 0.032) animals responded to antler removal in the EA group. Heart rates and arterial pressures were measured by a catheter connected to a physiological monitor. Heart rate increased significantly over time with EA, but not with LA. Heart rate increased from baseline significantly more in the EA group immediately prior to antler removal (P = 0.017), immediately post antler removal (P = 0.001), and at 1 min post antler removal (P = 0.037). It was concluded that EA is not as effective a method of anesthesia as is LA for antler removal.

Suspected tolazoline toxicosis in a llama.

Clinical signs of tolazoline toxicosis developed in a 4-year-old llama that received 2 doses of tolazoline hydrochloride to reverse xylazine-induced sedation. The full first dose (4.3 mg/kg [2.0 mg/lb] of body weight) was erroneously injected i.v., and the second dose was administered half i.v., half i.m. 45 minutes later, because the llama became weak and recumbent. Signs of anxiety, hyperesthesia, profuse salivation, and tachypnea were the first detectable clinical signs of tolazoline toxicosis. Convulsions, hypotension, gastrointestinal tract hypermotility, and diarrhea also developed. The llama was treated successfully with i.v. administration of diazepam, phenylephrine, and lactated Ringer's solution supplemented with potassium chloride and oxygen administered via nasal insufflation. We suggest that the maximum dose of tolazoline administered at any one time to llamas not exceed 2 mg/kg (0.91 mg/lb). Furthermore, tolazoline should be administered slowly i.v. or i.m. to reduce the risk of adverse reactions.

Co-morbidity of lifetime psychiatric disorder among male alcoholic patients.

The lifetime co-morbidity of major psychiatric disorders among male alcoholics was examined with the structured Psychiatric Diagnostic Interview (PDI), which was administered to 928 patients undergoing alcoholism treatment at six Veterans Administration Medical Centers. Thirty-eight percent were positive for alcoholism only; 62% fulfilled inclusive lifetime diagnostic criteria for at least one other additional psychiatric syndrome. Thirty percent satisfied criteria for one additional syndrome; 16% for two additional syndromes; 12% for three; and 4% for four or more disorders in addition to alcoholism. Depression and antisocial personality were the most frequently identified co-occurring syndromes (36% and 24%, respectively) followed by drug abuse and mania (17% each). The additional psychiatric syndromes in this sample were clearly not randomly distributed; instead, certain disorders tended to cluster together such as: drug abuse and antisocial personality; mania and depression; depression and anxiety disorder; and schizophrenia and affective disorder. Implications for classification and treatment are discussed.

Examination of Cloninger's type I and type II alcoholism with a sample of men alcoholics in treatment.

Cloninger's clinical method of classifying alcoholics into two groups (Types I and II) was examined with data obtained from 360 VA hospitalized male alcoholic patients. For operational criteria, the Cloninger clinical method of subtyping alcoholics employs age-of-onset of problem drinking and symptom-clusters supposedly associated with each subtype. Marked overlap was found between the symptom-clusters used to define the two subtypes. Ninety-one percent of the entire sample satisfied criteria for both symptom-clusters. Dividing the sample by early-onset (Type II, less than or equal to 25 years) and late-onset (Type I, greater than 26 years) alcoholism did not substantially reduce the overlap between symptom-clusters; i.e., 96% of the early-onset and 83% of the late-onset subgroups were positive for both symptom-clusters. Only 21 men (6%) could be classified when both age-of-onset and the type-appropriate symptom-cluster were used to separate patients. In hospital settings, at least, these findings suggest that the two-group clinical alcoholism typology proposed by Cloninger basically reflects the age-of-onset of problem drinking.

Subtyping male alcoholics by family history of alcohol abuse and co-occurring psychiatric disorder: a bi-dimensional model.

Six studies of 568 alcoholics in treatment are summarized to illustrate the interactive effects of familial alcoholism, other forms of family psychopathology and the lifetime prevalence of additional psychiatric disorder on the onset and course of male alcoholism. A family history of alcoholism as well as additional co-occurring psychiatric syndromes were associated with (1) earlier onsets of problem drinking, (2) a more virulent course and (3) greater heterogeneity of psychopathology among first degree relatives. A bi-dimensional method of classifying male alcoholics is proposed which combines a family history of abusive drinking and the presence or absence of co-morbid psychiatric disorders. Implications for the clinical researcher and practitioner are briefly discussed.

Primary and secondary depression in alcoholic men: an important distinction?

The primary-secondary depression distinction was investigated in male alcoholic patients from five Veterans Administration Medical Centers. The Psychiatric Diagnostic Interview, a DSM-III-compatible, criterion-referenced, structured interview, was administered to 565 patients admitted to the Alcoholism and Drug Treatment Units. Seventy-eight patients (13.8%) who exhibited only alcoholism and depression were divided into three subgroups based on the temporal onset of depression relative to the onset of alcoholism. Although few statistical differences were found, observed trends suggested more impairment in alcoholic patients with primary depression than in those with concurrent or secondary depression. The findings indicate that the primary-secondary depression distinction may have important clinical relevance and should be made whenever possible.

A comparative study of familial alcoholism.

In a large multicenter study of 568 male alcoholics, structured interviews were used to compare the clinical characteristics of patients with a positive (65%) or negative (35%) family history of abusive drinking among first degree relatives. Alcoholics with a positive family history were found to have: an earlier onset of alcoholism, greater alcoholic severity, more medical and legal problems, a broader range of treatments, an increased lifetime prevalence of additional psychiatric disorders and a greater diversity of psychiatric disturbance among biological relatives. The degree of psychiatric heterogeneity in the patients roughly corresponded to the degree of psychiatric heterogeneity in their families. Assortative mating was proposed as a possible mechanism to account for clinical differences between the familial and nonfamilial alcoholic.

The dropout in alcoholism research: a brief report.

Compared to 148 alcoholic men who were successfully followed up after 1 year in a controlled treatment evaluation study, the 18 treatment dropouts reported somewhat less alcohol impairment due to drinking and lower scores on measures of psychopathology when first seen.

Comparison of three outpatient treatment interventions: a twelve-month follow-up of men alcoholics.

Men inpatient alcoholics (N = 174) from a Veterans Administration medical center who were preselected by employment status were randomly assigned to one of three outpatient treatment interventions: (1) medication only, (2) active support or (3) untreated medical monitoring. Subjects were followed monthly for 1 year, with an 85% 12-month follow-up rate. Although the sample as a whole showed reduced alcohol misuse and improved social functioning after 12 months, the specific form of treatment was unrelated to outcome. These findings suggest that the intensity of the outpatient treatment experience is not related to outcome and that time-consuming interventions are not differentially cost-effective.

Sex-role affiliation among male alcoholics.

Male alcoholic veterans were sex-typed more frequently as feminine than masculine on the PRF ANDRO when compared to college males or older, nonalcoholic veterans (N = 123). Endorsement of passive-feminine characteristics among alcoholics (1) is interpreted to be a consequence, not a cause of the disorder; (2) is considered reversible with the achievement of sustained sobriety; and (3) is a feature that possibly needs to be addressed directly in order to facilitate successful therapeutic interventions.

The psychiatric physical examination - Part I: methodology.

The frequency of medical findings in psychiatric patients is quite high. Regardless, none of the responding psychiatrists in a recent survey do routine physical examinations. In response to this survey, the authors describe a method of rapid physical examination specifically designed for the psychiatric patient. The average duration of the examination in 75 patients was 16.9 minutes. There was no evidence of negative transference or countertransference. The level of competency required was that of a medical student, yet there were 8.2 physical findings per patient with 5.3 physical findings per patient being unknown previously.

The psychiatric physical examination - Part II: findings in 75 unselected psychiatric patients.

The psychiatric physical examination described in the previous paper was done on 75 new psychiatric inpatients. The examiners were one psychiatrist and two psychiatrist-internists. Results confirmed the high frequency of known and unsuspected medical illnesses previously reported in the literature. Additionally, the specific "psychiatric physical examination" confirmed the known psychiatric diagnoses in 76% of the patients and led to consideration of a second or other psychiatric diagnoses in 43% of the patients.

Psychological adjustment and sex-role affiliation in an alcoholic population.

Examined the relationship among sex-role categories and indices of social/personal adjustment and psychiatric symptoms in a male alcoholic (N = 123) population. No significant relationships were found between PRF sex-role categories and measures of distress, mood disturbance and psychiatric symptomatology; nor was sex-role type found to be associated with behaviors common to alcoholism. These findings differ from those of others, which report that less sex-typed males have more adjustment problems. The inability to demonstrate a relationship between maladjustment and the PRF ANDRO typology raises the question whether sex-role affiliation is largely independent of factors suggestive of poor mental health.

Differentiation of alcoholics by family history.

Alcoholics having a family history of alcoholism tended to drink at an earlier age and to have more social and personal problems than do alcoholics not having a family history of alcoholism.