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Biomedical subjects

K M Connor

Publications and source records attributed to K M Connor.

12 recordsLinked to original sources
PubMed1999

A pilot study of mirtazapine in post-traumatic stress disorder.

Recently, studies of pharmacotherapy for post-traumatic stress disorder (PTSD) have been focused on serotonin-selective reuptake inhibitors (SSRI), despite a number of treatment-limiting side-effects. Mirtazapine, a novel drug with both noradrenergic and serotonergic properties, may be effective in individuals who demonstrate intolerance to side-effects of and a limited response to SSRIs. Six outpatients with severe, chronic PTSD were treated with mirtazapine, up to 45 mg/day for 8 weeks. Efficacy assessments and side-effect monitoring were performed at baseline and weeks 2, 4, 6 and 8. Fifty percent of the sample demonstrated improvement of 50% or more from baseline using a global rating. In addition, improvements were noted on both interviewer-administered and self-rated scales of PTSD and of depression. The drug was well tolerated with few significant side-effects. Mirtazapine was associated with clinical improvement in 50% of subjects with severe, chronic PTSD, suggesting a need for further investigation in double-blind, placebo-controlled trials.

Adolescent↗
PubMed1998

Generalized anxiety disorder: neurobiological and pharmacotherapeutic perspectives.

The concept of generalized anxiety has evolved over many years, from initial descriptions of "anxiety neurosis" to recognition of generalized anxiety disorder (GAD) as a clinical entity included in the 3rd edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-III) in 1980. Since 1980, the definition of GAD has undergone further change, with modifications in the salience of autonomic and panic like symptoms, duration, and allowance of comorbidity. The importance of these historical considerations lies in the fact that most of our current knowledge about GAD rests on outdated definitions, including most of the literature pertaining to treatment. Indeed, we cannot be sure that the DSM-III definition of GAD bears resemblance to the current concept, and these differences may have profound implications for findings from research. The following two-part report comprises i) a review of the basic neurobiology of GAD, with reference to serotonergic, noradrenergic, neuroendocrine, autonomic imaging, and other systems; and ii) an overview of the current status of pharmacotherapy for GAD.

Anti-Anxiety Agents↗
PubMed1998

Early immunopathological events in experimental ovine paratuberculosis.

An experimental oral infection of neonatal (< 2 weeks old) lambs with a cervine isolate of Mycobacterium avium subspecies paratuberculosis (M.a. paratuberculosis), the causal agent of ruminant paratuberculosis (Johne's disease) was used to investigate bacteriological, histopathological and immunological changes during the early (up to 8 weeks) post-infection phase. In vitro culture for mycobacteria was positive in one faecal and three mesenteric lymph node (MLN) samples from the eight infected lambs. All mycobacterial isolates from MLN were identified as M.a. paratuberculosis by polymerase chain reaction (PCR). Small-to-medium sized focal granulomata were observed in jejunal (JPP) and ileal Peyer's patches (IPP) from four of the eight infected lambs. Compared with controls, JPP from all infected lambs had significantly (p < 0.05) higher proportions of CD8+ and CD2+ lymphocytes, and there were significantly (p < 0.05) fewer cells expressing B lymphocyte-associated markers in IPP and MLN. The T/B cell ratio was significantly (p < 0.05) increased in both JPP and MLN from infected lambs. The expression of a range of genes for cytokines was examined using specific reverse transcriptase PCR (RT-PCR) amplification of messenger RNA (mRNA) template isolated from MLN, JPP and IPP from both groups of animals. Densitometric analyses indicated that, in infected animals, MLN expressed significantly (p < 0.05) more mRNA for TNF-alpha: JPP had significantly increased (p < 0.05) mRNA for GM-CSF and significantly decreased (p < 0.05) mRNA for IL-4 and IFN-gamma. Infected lambs had significantly (p < 0.05) decreased titres of both circulating IgG and gut mycobacteria-associated IgG antibody. Infection was not associated with any consistent changes in lymphocyte reactivity to specific mycobacterial antigens, IFN-gamma release into supernatants from in vitro intestinal lymphocyte cultures or gut IgA antibody levels.

Animals↗
PubMed1998

Discontinuation of clonazepam in the treatment of social phobia.

Patients with social phobia who responded well to 6 months of open-label treatment with clonazepam were assigned to receive either continuation treatment (CT) with clonazepam for another 5 months, or to undergo discontinuation treatment (DT) using a clonazepam taper at the rate of 0.25 mg every 2 weeks, with double-blind placebo substitution. Clinical efficacy was compared between the CT and DT groups using three different social phobia scales. Benzodiazepine withdrawal symptoms were also measured. Relapse rates were 0 and 21.1% in the CT and DT groups, respectively. Subjects in the CT group generally showed a more favorable clinical response at midpoint and/or endpoint, although even in the DT group clinical response remained good. With respect to withdrawal symptoms, the rates were low in both groups (12.5% for CT and 27.7% for DT) with no real evidence suggesting significant withdrawal difficulties. At the end of 11 months of treatment with clonazepam, however, a more rapid withdrawal rate was associated with greater distress. This study offers preliminary evidence to suggest that continuation therapy with clonazepam in the treatment of social phobia is safe and effective, producing a somewhat greater clinical benefit than a slow-taper discontinuation regime. However, even in the DT group, withdrawal symptoms were not found to be a major problem. The study can be taken as supportive of benefit for longterm clonazepam treatment in social phobia, as well as being compatible with a reasonably good outcome after short-term treatment and slow taper.

Adult↗
PubMed1998

Treatment of posttraumatic stress disorder with nefazodone.

Selective serotonin reuptake inhibitors are useful in the treatment of posttraumatic stress disorder (PTSD), but have a number of side-effects which limit their acceptability. A newer serotonergic compound, nefazodone, has a different side-effect profile, thus making it a potentially promising compound to study. Seventeen private practice patients with PTSD were treated with nefazodone up to 600 mg/day for a maximum total treatment period of 12 weeks. All subjects were civilians, and were monitored for efficacy and side-effects at weeks 1, 2, 4, 6, 8 and 12. Nefazodone was associated with statistically significant improvement in mean scores on all six rating scales used to assess change from baseline in PTSD symptoms. Additionally, statistically significant improvement from baseline were seen for the intrusive, avoidant/numbing, and hyperarousal clusters on a global PTSD scale. Early improvements in nightmares and general sleep disturbance were observed. Overall, there was a 43% response rate at endpoint, or 60% in treatment completers, by observer rating. Side-effects (assessed on the Medication Effects Scale) were generally benign. Nefazodone was associated with clinical improvement in this population, and now needs to be studied in double-blind, placebo controlled, protocols.

Adolescent↗
PubMed1998

Bupropion sustained release: a therapeutic overview.

Sustained-release bupropion (bupropion SR) represents a new form of an already known effective antidepressant drug. Its pharmacokinetics, mechanism of action, metabolism, and efficacy are reviewed. Benefit relative to placebo has been demonstrated in two large multicenter trials, with low doses (100 or 150 mg) having been shown to have therapeutic efficacy. An overview of all placebo-controlled trials of bupropion SR is given, and the differential properties of bupropion and serotonergic drugs are described. The concept of a catecholamine-indolamine spectrum is presented, along with its implications for possible differential therapeutics of selective antidepressants.

1-Naphthylamine↗
PubMed1996

Mutagenicity of cosmetic products containing Kathon.

A variety of shampoos, conditioners, skin-care lotions, and other cosmetic products contain the biocide Kathon CG, which is a mixture of two heterocyclic isothiazolinones: methylisothiazolinone and methylchloroisothiazolinone. This mixture and the related biocide, Kathon 886, have been shown to be potent sensitizers and bacterial mutagens. Five cosmetic products that list the components of Kathon on their labels and two that do not were screened for mutagenicity with Salmonella typhimurium TA100 without S-9. Five of these products and Kathon 886 were further evaluated in TA100 without and with S-9. Kathon 886, a cosmetic product that contained Kathon, and thin layer chromatography-separated components of Kathon 886 were identified by GC/MS analysis. Three of the five products that listed Kathon were direct acting mutagens with TA100. The remaining two products were considerably more toxic than the other products and could not be evaluated for mutagenicity. The addition of S-9 reduced toxicity but did not eliminate mutagenicity. The mutagenic evaluation of Kathon 886 resulted in a dose response similar to that seen with some cosmetic products but at a 1,000-fold lower concentration, and activity was also reduced by the addition of S-9 mix. S-9 reduced activity both with and without cofactors present. Thin layer chromatography separation of the components and subsequent identification by GC/MS indicated that methylisothiazolinone was nonmutagenic while methylchloroisothiazolinone was mutagenic. Additionally, a dichlorinated compound was identified which was also mutagenic. In light of these findings and the reported skin sensitization by Kathon CG in various cosmetics, we recommend that additional testing be done to assure the safety of products containing Kathon CG.

Chromatography, Thin Layer↗
PubMed1996

Moredun Bordetella Medium, an improved selective medium for isolation of Bordetella parapertussis.

Bordetella parapertussis, previously thought to be an obligate human respiratory tract pathogen, has been isolated from sheep. Attempts to assess the prevalence of B. parapertussis in conventionally reared sheep by nasal swabbing proved futile with existing selective media because of extensive overgrowth with Mucor spp. and other nasal commensals. Moredun Bordetella Medium (MBM), which contains cycloheximide and spectinomycin at final concentrations of 0.5 mg/ml and 100 mu g/ml, respectively, was developed as an improved selective medium to isolate B. parapertussis from the nasal cavities of conventionally reared sheep. The selective ability of MBM was evaluated with 200 nasal swabs from conventionally reared sheep, and B. parapertussis was recovered from 31.5% of the samples. MBM facilitated the simple and effective isolation of B. parapertussis from ovine nasal swabs and, in successfully excluding overgrowth with other contaminants, proved superior to other test formulations evaluated and to existing conventional media.

Bordetella↗
PubMed1984

Tactile sensory coding during development: signaling capacities of neurons in kitten dorsal column nuclei.

The functional maturation of cuneate neurons was studied using reproducible tactile stimulation procedures and quantitative assessment of coding capacities in anesthetized (N2O/O2 plus barbiturate infusion) or decerebrate cats from six different age groups; neonatal (1-5 days), 10-15, 25-30, 55-63, and 83-90 days, and an adult group. Cuneate neurons were distinguished from input fibers to the nucleus on criteria of spike configuration and time course and on response profiles. Extracellular spike durations underwent a progressive shortening with age, reaching the adult range at approximately 3 mo when background activity levels also reached maturity. Despite an increase in conduction-path length, response latencies decreased to adult values by 25-30 days of age, presumably reflecting the increased conduction velocity in the input fibers. In each age group three functional classes of neurons responsive to tactile stimulation of the footpads were identifiable. One consisted of slowly adapting neurons whose stimulus-response relations resembled those of the adult in responsiveness and dynamic range by 25-30 days postnatal age. The remaining neurons were purely dynamically sensitive, but among them two classes could be distinguished by their differential sensitivity to cutaneous vibration, one receiving rapidly adapting (RA) fiber input the other pacinian corpuscle (PC) input. The combined bandwidth of vibration sensitivity in dynamically sensitive cuneate neurons expands from approximately 5-300 Hz in the neonate to the mature range of 5-1,000 Hz by 1 mo of age. The PC class of cuneate neurons showed an upward shift in peak sensitivity from 30-200 Hz in the neonate to 100-300 Hz at 10-15 days, reaching adult values of 200-600 Hz by 25-30 days. Over this period absolute thresholds dropped by an order of magnitude at 200-500 Hz reflecting the threshold trends in primary PC fibers. During the first 1-2 postnatal months, the capacity of cuneate PC neurons to signal information in a pattern code about vibration frequencies around 300 Hz is restricted because of poor phase locking and low responsiveness, which preclude an impulse periodicity reflecting the vibratory frequency.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMedDate not supplied

A family study of chronic post-traumatic stress disorder following rape trauma.

There is evidence that familial factors serve as determinants of risk for post-traumatic stress disorder (PTSD), especially familial anxiety. This study investigates the relationship between chronic PTSD and family psychiatric morbidity. The sample was drawn from 81 female rape survivors with or without lifetime PTSD, 31 major depressive disorder controls, 20 anxiety disorder controls and 39 healthy controls. First-degree family members were directly interviewed (n = 285) and diagnoses assigned of major depressive, anxiety and alcohol or substance use disorder. Information was also available by family history for 639 relatives. In the directly interviewed sample, no consistently increased morbidity risk was observed for anxiety, PTSD, or alcohol/substance abuse in the rape survivor groups, but there was an increase in depression relative to the anxiety in healthy control groups. When comorbid depression in rape survivor probands was taken into account post hoc, an increased risk for depression was noted in family members of PTSD probands with depression, but not in relatives of PTSD probands without lifetime depression. Among rape survivor probands with non-comorbid PTSD, rates by history of familial anxiety and depression were negligible. In a logistic regression analysis, individual vulnerability to depression served as an independent predictor of chronic PTSD, along with specific trauma-related variables. In the family history group, results were consistent with those obtained from the directly interviewed group. Our findings clearly support the view that PTSD following rape is associated with familial vulnerability to major depression, which may thus serve as a risk factor for developing PTSD. The exact nature of this predisposition calls for further inquiry and there is a need to expand this study to include other PTSD populations. PTSD may on occasion represent a form of depression which is induced and/or modified neurobiologically and phenomenologically by extreme stress. Our findings may be a reflection of the sample composition, the current conceptualization of PTSD, or be related to study limitations.

Adolescent↗