PubMed Health⌕ Search

Biomedical subjects

M E Lynch

Publications and source records attributed to M E Lynch.

At least 19 recordsLinked to original sources
PubMed2005

Preclinical science regarding cannabinoids as analgesics: an overview.

Modern pharmacology of cannabinoids began in 1964 with the isolation and partial synthesis of delta-9-tetrahydrocannabinol, the main psycho-active agent in herbal cannabis. Since then, potent antinociceptive and antihyperalgesic effects of cannabinoid agonists in animal models of acute and chronic pain; the presence of cannabinoid receptors in pain-processing areas of the brain, spinal cord and periphery; and evidence supporting endogenous modulation of pain systems by cannabinoids has provided support that cannabinoids exhibit significant potential as analgesics. The present article presents an overview of the preclinical science.

Analgesics↗
PubMed2005

Guidelines for the use of cannabinoid compounds in chronic pain.

OBJECTIVE: To provide clinicians with guidelines for the use of cannabinoid compounds in the treatment of chronic pain. METHODS: Publications indexed from 1990 to 2005 in the National Library of Medicine Index Medicus were searched through PubMed. A consensus concerning these guidelines was achieved by the authors through review and discussion. RESULTS: There are few clinical trials, case reports or case series concerning the use of cannabinoid compounds in the treatment of chronic pain. There are no randomized clinical trials examining the use of herbal cannabis in the treatment of chronic pain. CONCLUSIONS: A practical approach to the treatment of chronic pain with cannabinoid compounds is presented. Specific suggestions about the off-label dosing of nabilone (Cesamet, Valeant Canada limitee/Limited) and dronabinol (Marinol, Solvay Pharma Inc, Canada) in the treatment of chronic pain are provided.

Analgesics↗
PubMed2004

Patterns of cannabis use among patients with multiple sclerosis.

To estimate the patterns and prevalence of cannabis use among patients with multiple sclerosis (MS), 220 patients were surveyed in Halifax, Nova Scotia. Seventy-two subjects (36%) reported ever having used cannabis for any purpose; 29 respondents (14%) reported continuing use of cannabis for symptom treatment. Medical cannabis use was associated with male gender, tobacco use, and recreational cannabis use. The symptoms reported by medical cannabis users to be most effectively relieved were stress, sleep, mood, stiffness/spasm, and pain.

Administration, Oral↗
PubMed2003

Inhalation efficacy of RFI-641 in an African green monkey model of RSV infection.

Human respiratory syncytial virus (RSV) is a major cause of acute upper and lower respiratory tract infections. RFI-641 is a novel RSV fusion inhibitor with potent in vitro activity. In vivo efficacy of RFI was determined in an African green monkey model of RSV infection involving prophylactic and therapeutic administration by inhalation exposure. Inhalation was with an RFI-641 nebulizer reservoir concentration of 15 mg/ml for 15 minutes (short exposure) or 2 hours (long exposure). Efficacy and RFI-641 exposure was determined by collection of throat swabs, nasal washes and bronchial alveolar lavage (BAL) on selected days. The short-exposure group (15 minutes) exhibited no effect on the nasal, throat or BAL samples. The throat and nasal samples for the long-exposure group failed to show a consistent reduction in viral titers. RFI-641 2 hours exposure-treated monkeys showed a statistically significantly log reduction for BAL samples of 0.73-1.34 PFU/ml (P-value 0.003) over all the sampling days. Analysis indicates that the long-exposure group titer was lower than the control titer on day 7 and when averaged across days. The results of this study demonstrate the ability of RFI-641 to reduce the viral load of RSV after inhalation exposure in the primate model of respiratory infection.

Administration, Inhalation↗
PubMed2001

Antidepressants as analgesics: a review of randomized controlled trials.

This review provides an overview of 59 randomized placebo-controlled trials that examined the analgesic effect of antidepressants. To summarize, there is significant evidence that the tricyclic group of antidepressants is analgesic and that trazodone is not; the data regarding selective serotonin reuptake inhibitors are conflicting. To date, there are no randomized controlled trials examining the potential analgesic action of nefazodone or venlafaxine, but on the basis of initial clinical reports and its structural similarity to other analgesics, venlafaxine shows promise as an analgesic.

Analgesics↗
PubMed2000

Subjective overachievement: individual differences in self-doubt and concern with performance.

We discuss the construct of doubt about one's competence and suggest that doubt can have myriad consequences (e.g., self-handicapping, defensive pessimism). We focus on the effect of self-doubt when it is combined with a concern with performance and assert that this combination leads to the phenomenon of subjective overachievement. In two studies, we present a new 17-item Subjective Overachievement Scale (SOS), which includes two independent subscales measuring individual differences in self-doubt and concern with performance. The first study, consisting of two large samples (Ns = 2,311 and 1,703), provides evidence that the scale has high internal consistency and a clear two-factor structure. Additionally, the subscales have adequate test-retest reliability (Ns = 67 and 115). A second study reveals that the SOS has good convergent and discriminant validity. Both subscales are unrelated to social desirability but exhibit the predicted patterns of associations with other related constructs. The Concern with Performance Subscale is correlated with achievement motivation, whereas the Self-Doubt Subscale is correlated with scales assessing negative affectivity (e.g., self-esteem, social anxiety) and other self-related strategies associated with concerns about one's competence (e.g., self-handicapping, defensive pessimism, impostor phenomenon). The SOS, which combines the two subscales, appears to tap a unique strategy that individuals may use to deal with doubts about their own competence.

Achievement↗
PubMed2000

The effects of prenatal drug exposure, term status, and caregiving on arousal and arousal modulation in 8-week-old infants.

Prenatal exposure to cocaine, as well as other drugs, has been linked with "dysregulation," usually defined as problems in arousal and/or behavioral regulation. This study was designed to describe the physiological basis of dysregulation as a function of prenatal cocaine/polydrug exposure and term status. Eight-week-old infants were selected because they are just developing the ability to modulate arousal. One hundred-eighteen infants (23 preterm control, 27 preterm drug-exposed, 29 full-term control, and 39 full-term drug-exposed) completed a protocol during which heart rate (HR) and respiratory rate (RR) were measured. Drug group differences were found in baseline, arousal (response to stress), and arousal modulation (recovery from stress). A hierarchical multiple regression analysis was conducted to determine the portion of variance attributable to postnatal caregiving environment, term status, and specific drug exposure. Term status accounted for significant variance in arousal (both RR and HR), and in arousal modulation (only RR). Prenatal exposure to cocaine contributed a significant amount of unique variance in HR arousal whereas tobacco contributed significantly to HR arousal modulation. Prenatal drug exposure and preterm status contributed differently to dysregulation as measured by physiological responses.

Adaptation, Psychological↗
PubMed1998

Use of the laryngeal mask airway in the ambulatory setting.

STUDY OBJECTIVE: To determine the utility of the laryngeal mask airway (LMA) in an ambulatory surgery practice. DESIGN: Prospective, longitudinal device (survival) study. SETTING: University-based ambulatory surgery center. PATIENTS: 1,831 ASA physical status I, II, and III outpatients undergoing superficial ambulatory surgery procedures. INTERVENTIONS: Twenty LMA devices were entered into service over a 2-year period and the number of uses, as well as the structural integrity, were assessed at the end of this study period. The serial number on each LMA device was used to track the number of times it was autoclaved, as well as the date that the device failed any of the standardized pre-use tests or was lost. MEASUREMENTS AND MAIN RESULTS: During the 2-year survey, 6,430 general anesthetics were administered at the ambulatory surgery center, with 1,831 (28%) using an LMA device for airway management. At the end of the study period, nine devices were still in use, three had been withdrawn for structural analysis by the manufacturer (after > 100 uses), three failed the pre-use test (after 38-82 uses), and five devices were lost (after 21-162 uses). The structural examination revealed that the tubes were 50% weaker; however, the cuffs, pilot balloons, and values were functioning normally. The median (range) number of uses was 92 (21-195). Thus, the 20 LMA devices evaluated tolerated an average of 92 autoclave cycles each over the 2-year observation period. CONCLUSIONS: To optimize the use of the LMA device in the ambulatory setting, it is necessary to increase awareness that it is a nondisposable piece of equipment and to adhere to the manufacturer's instructions for cleaning, sterilization, and insertion.

Ambulatory Surgical Procedures↗
PubMed1996

Clinical prediction rules to optimize cytotoxin testing for Clostridium difficile in hospitalized patients with diarrhea.

BACKGROUND: Although routine testing of hospitalized patients with diarrhea for Clostridium difficile cytotoxin has been advocated as a high-yield procedure, the rationale for this practice has been questioned. To target a low-yield subgroup for whom routine testing could be deferred, we derived a clinical decision rule for predicting results of the C difficile cytotoxin assay in hospitalized adults with diarrhea. METHODS: We hypothesized a priori that two variables, antibiotic use (within 30 days prior to testing) and history of significant diarrhea (new onset of > 3 partially formed or watery stools per 24 hour period), would be highly predictive of cytotoxin results, and obtained these data on 480 consecutive patients who underwent diagnostic testing for C difficile at a university hospital and affiliated Veterans Affairs medical center. For more detailed modelling, we recorded symptoms, signs, comorbidity, and other potential causes of diarrhea for 68 test positive patients (cases) and 265 randomly selected test negative patients (controls) within the study cohort. RESULTS: The overall prevalence of positive cytotoxin assays was 14%. Prior antibiotic therapy (OR = 9.0, 95% CI 2.1-38.4), significant diarrhea (OR = 2.2, 95% CI 1.1-4.7), and abdominal pain (OR = 1.9, 95% CI 0.96-3.7) were independent predictors of cytotoxin assay results. The model discriminated patients with positive and negative assays with a receiver operating characteristic (ROC) area of 0.68; observed and predicted probabilities of a positive cytotoxin assay were well correlated over the entire range of observed probabilities (r2 = 0.86). A decision rule (defined as positive if prior antibiotic use and either significant diarrhea or abdominal pain are present) demonstrated sensitivity and specificity of 86 and 45%. When applied to the entire dataset (N = 480), a simplified a priori rule, defined as positive if both prior antibiotic use and history of significant diarrhea are present, demonstrated sensitivity, specificity, positive and negative predictive value of 80, 45, 18 and 94%, respectively (6% of those predicted to be cytotoxin-negative actually tested positive). Use of this rule would have averted 39% of cytotoxin assays in our study population. CONCLUSIONS: Patients without prior antibiotic use and either significant diarrhea or abdominal pain are unlikely to have positive C difficile cytotoxin assay results, and may not routinely require cytotoxin testing.

Abdominal Pain↗
PubMed1996

The role of sympathetic activity in neuropathic orofacial pain.

Seventeen patients with neuropathic orofacial pain are presented with reference to precipitating events, pain descriptions, response to treatment, and other aspects of their histories and clinical presentation. Stellate ganglion blocks were done on 14 patients. Ten of 14 patients reported temporary relief of pain with stellate ganglion blocks. Five of these patients noted more prolonged improvement in pain, two reported no change, and two experienced a temporary increase in pain. It is argued that sympathetically maintained pain involving orofacial locations does occur and that stellate ganglion blocks may benefit a subgroup of these patients. It is noted that current diagnostic categories are inadequate to describe a subgroup of these patients. New categories are suggested, and further study is recommended.

Adult↗
PubMed1995

Expanding the caregiving environment for advanced practice neonatal nurses.

Advanced practice neonatal nurses (APNNs) have participated as crucial care providers during the past two decades in supporting the development and implementation of safe, therapeutic interventions for critically ill infants in the neonatal intensive care unit (NICU). This role has been limited primarily to the NICU environment, however, and there has been minimal opportunity for APNNs to participate in caregiving that extends beyond this boundary. This boundary-based practice may no longer be practical as a result of significant changes in health care financing and health care reform. It is important for all neonatal health care providers to consider an expanded scope of practice for the APNN that extends beyond the NICU into the community and home and encompasses caregiving for the neonate and infant within the first year of life.

Health Care Reform↗
PubMed1995

Mice immunized by primary vaginal Candida albicans infection develop acquired vaginal mucosal immunity.

It has been postulated that systemic cell-mediated immunity (CMI) is an important host defense mechanism against Candida infections of the vagina. However, in an estrogen-dependent murine model of experimental vaginal candidiasis, we recently showed that systemic Candida-specific Th1-type CMI induced by immunization with Candida culture filtrate antigen had no effect on vaginal Candida population levels during the course of a vaginal infection. In the present study, mice given a second vaginal inoculation in the presence of peripheral Candida-specific Th1-type CMI induced by prior vaginal infection had anamnestic-type increased delayed-type hypersensitivity (DTH) responses, concomitant with significantly fewer Candida organisms in the vagina than in primary-infected mice. In addition, organisms in secondary-infected mice were fragmented and superficial penetration into the epithelium was reduced. The systemic presence of Candida-specific T suppressor (Ts) cells that significantly suppressed the infection-derived anamnestic DTH reactivity did not abrogate the protective effect in the vagina. Additional experiments showed that vaginally immunized mice were not protected from gastrointestinal or systemic candidiasis and, in contrast to mice with a second vaginal infection, did not demonstrate anamnestic DTH reactivity. These results suggest that a moderate level of local protection against a Candida vaginal infection can be achieved by vaginal immunization but that the protective role of acquired peripheral Candida-specific Th1-type reactivity at the vaginal mucosa appears to be limited.

Animals↗
PubMed1995

Circulating CD4 and CD8 T cells have little impact on host defense against experimental vaginal candidiasis.

The etiology of recurrent vulvovaginal candidiasis in otherwise healthy women of child-bearing age remains an enigma. To date, results from both clinical studies and a murine model of vaginal candidiasis indicate that Candida vaginitis can occur in the presence of Candida-specific Th1-type cell-mediated immunity expressed in the peripheral circulation. The present study was designed to determine the role of circulating CD4 and CD8 cells in primary and secondary vaginal infections with Candida albicans. Vaginal fungal burden, Candida-specific delayed-type hypersensitivity (DTH), and lymph node cell Th1/Th2 cytokine production were monitored in CD4 and/or CD8 cell-depleted mice during persistent primary vaginal infections and secondary vaginal infections against which partial protection was observed. Treatment of mice with anti-CD4 or anti-CD8 antibodies resulted in 90% or greater depletion of the respective cell populations. Mice depleted of CD4 cells had significantly reduced Candida-specific DTH and lymph node cell Th1-type cytokine production during a primary vaginal infection, as well as reduced anamnestic DTH during a secondary vaginal infection. In contrast, mice depleted of CD8 cells showed only reduced gamma interferon production during a primary infection; no alterations in DTH were observed. Despite reductions in DTH and cytokine production, however, CD4 and/or CD8 cell depletion had no effect on vaginal C. albicans burden in mice after a primary or secondary vaginal inoculation. Taken together, these results suggest that while circulating CD4 and CD8 cells contribute to systemic Candida-specific cell-mediated immunity in vaginally infected mice, neither CD4 nor CD8 circulating T cells appear to provide significant host defenses against C. albicans at the vaginal mucosa.

Animals↗
PubMed1995

The assessment and prevalence of affective disorders in advanced cancer.

The assessment of depression in patients with advanced cancer presents a difficult clinical challenge. Reported prevalence rates of depression in cancer patients range from 3.7% to 58%. Studies using structured diagnostic interviews and clearly defined diagnostic criteria are presented. The current literature suggests that among hospitalized cancer patients with significant levels of physical impairment at least 25% suffer from clinically important depression. Risk of suicide and recent literature regarding early wish to die are also discussed.

Canada↗
PubMed1994

Comparison of the effects of salbutamol and clenbuterol on skeletal muscle mass and carcass composition in senescent rats.

Aging decreases skeletal muscle mass and strength, making elderly subjects particularly vulnerable to catabolic effects of age-related diseases. Clenbuterol, a muscle anabolic beta 2-adrenergic agonist, has reduced or restored skeletal muscle losses in experimental catabolic states. However, the doses of clenbuterol used to prevent or reverse muscle wasting in most animal models have exceeded the estimated safe dose in man. Recently, another beta 2-adrenergic agonist, salbuamol (albuterol), has been shown to increase muscle weight and protein content in young rats at a dose similar to that used clinically. In contrast to clenbuterol, salbutamol is currently approved for human use as a bronchodilator in the United States. This study has compared the muscle and protein anabolic effects of salbutamol at a clinically relevant dose with those of clenbuterol at a dose typically used in animal models of muscle wasting. Salbutamol and clenbuterol were administered by implanted osmotic minipumps to Fisher-344 rats aged 3 and 24 months at doses of 1.03 mg and 600 micrograms per kilogram per 24 hours for 3 weeks. The weights of five hindlimb muscles, as well as carcass protein and fat content, were determined. Salbutamol and clenbuterol increased combined hindlimb muscle weight 19% and 28% in young rats, with 19% and 25% increases in old rats. Similarly, these drugs increased gastrocnemius weight and protein content 19% and 24% in young rats, with 19% and 23% increases in old rats. Salbutamol and clenbuterol increased carcass protein content 20% and 30% in young rats, with 12% and 21% increases in old rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Agonists↗
PubMed1994

Effect of clenbuterol on recovery of muscle mass and carcass protein content following dietary protein depletion in young and old rats.

There is a need for new therapeutic agents designed to prevent or restore skeletal muscle loss in frail, elderly subjects resulting from injury or disease and associated catabolic stresses such as malnutrition. Since the beta 2-adrenergic agonist clenbuterol increases skeletal muscle mass in rats, the effect of this agent on recovery of muscle mass and carcass protein content following protein malnutrition was studied in young and old rats. The 3-week period of severe dietary protein restriction reduced body weight 21%, hind-limb muscle weight 24 and 15%, and carcass protein content 31 and 19%, respectively, in 3- and 24-month-old rats. During the 3-week recovery period induced by feeding a complete diet, 10 mg clenbuterol per kg diet increased hind-limb muscle weight 34 and 30% and carcass protein content 27 and 25%, respectively, in 3- and 24-month-old rats. Restoration was complete in animals of both ages fed clenbuterol and incomplete in animals fed the control diet. These observations suggest that clenbuterol or similar beta 2-adrenergic agonists may be useful in hastening the recovery of muscle mass and body protein stores lost because of malnutrition in frail, elderly humans.

Aging↗
PubMed1994

Effects of preinduced Candida-specific systemic cell-mediated immunity on experimental vaginal candidiasis.

It has been postulated that systemic cell-mediated immunity (CMI) is an important host defense factor against recurrent vaginal infections caused by Candida albicans. Using an estrogen-dependent murine model of vaginal candidiasis, we have previously shown that mice inoculated vaginally with C. albicans acquire a persistent vaginal infection and develop Candida-specific Th1-type systemic CMI. In the present study, experimental vaginitis was monitored in the presence of preinduced systemic Candida-specific CMI. Mice immunized systemically with C. albicans culture filtrate antigens (CaCF) in complete Freund's adjuvant (CFA) had Th1-type reactivity similar to that of vaginally infected mice. CaCF given to mice intravenously induced Candida-specific suppressor T (Ts) cells. Mice preimmunized with CaCF-CFA and given a vaginal inoculum of C. albicans had positive delayed-type hypersensitivity (DTH) reactivity from the time of vaginal inoculation through 4 weeks. Conversely, mice infected in the presence of Ts cells had significantly reduced DTH responses throughout the 4-week period in comparison with naive infected mice. However, the presence of Th1-type Candida-specific DTH cells or Ts cells, either induced in mice prior to vaginal inoculation or adoptively transferred at the time of inoculation, had no effect on the vaginal Candida burden through 4 weeks of infection. A similar lack of effects was obtained in animals with lower Candida population levels resulting from a reduction in or absence of exogenous estrogen. These results suggest that systemic Th1-type CMI demonstrable with CaCF is unrelated to protective events at the level of the vaginal mucosa.

Animals↗