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Biomedical subjects

J J Mooney

Publications and source records attributed to J J Mooney.

At least 19 recordsLinked to original sources

Time trends in a study of 440 mass slayings/rampages occurring in public places.

We looked for variations in the timing of mass slayings/rampages (MS/R) committed in public places by solitary perpetrators. News reports on 440 MS/R from 1920 to 1996 yielded 379 onset times which were examined for temporal patterns. There was a dramatic increase in the number of MS/R from 1966 to 1995. We observed a significant monthly variation with peaks in July-August and December, and a bimodal daily rhythm for MS/R onset with a major peak at 11:00 a.m. and a minor peak at 8:00 p.m. Observed time trends for MS/R could help develop protective programs to reduce stress and violence in public places.

History, 20th Century↗

Signal transduction by platelet adenylate cyclase: alterations in depressed patients may reflect impairment in the coordinated integration of cellular signals (coincidence detection).

BACKGROUND: Adenylate cyclase (AC) responds to distinct but coincident signals from the agonist-stimulated G-protein Gs and the inhibitory G-protein Gi by generating a greater output signal-to-noise ratio--i.e., agonist-stimulated to basal ratio (fold-stimulation)--through coincidence detection than that generated by a single input (Gs) alone. Such coincidence detection by murine brain AC was found to be enhanced during chronic antidepressant treatment with imipramine. METHODS: We examined and compared the basal, agonist-stimulated, and guanosine 5'-3-O-(thio)triphosphate (GTP gamma S) or AlF4 ion postreceptor-stimulated AC activities in mononuclear leukocytes and platelets from the same blood specimens obtained from depressed patients (n = 27) and control subjects (n = 19). RESULTS: In all subjects, the differences (delta GTP gamma S or delta AlF4) between postreceptor measures of AC in mononuclear leukocytes (where AC is regulated by Gs but not by Gi) and platelets (where AC is regulated by both Gs and Gi) were highly significant. In controls, the relationships between delta GTP gamma S or delta AlF4 and basal, agonist-stimulated, and the fold-stimulation of agonist-stimulated platelet AC resembled the regulation of AC by Gi in model-membrane systems. Comparable relationships between delta GTP gamma S or delta AlF4 and basal, agonist-stimulated, and the fold-stimulation of agonist-stimulated platelet AC activities were not observed in depressed patients. CONCLUSIONS: Our results suggest that in controls, platelet AC enzyme activity is determined (in part) by the coordinated integration of signals from Gs and Gi through coincidence detection, while such coincidence detection by platelet AC may be impaired in patients with depressive disorders.

Adenylyl Cyclase Inhibitors↗

Neuronal monoamine reuptake inhibitors enhance in vitro susceptibility to chloroquine in resistant Plasmodium falciparum.

Chloroquine resistance in Plasmodium falciparum was reversed in vitro by the neuronal monoamine reuptake inhibitors and antidepressants desipramine, sertraline, fluoxetine, and norfluoxetine but not by carbamazepine, an antiseizure and mood-stabilizing tricyclic drug resembling desipramine which only weakly inhibits neuronal monoamine reuptake. These findings have important clinical implications for drug combination therapy.

1-Naphthylamine↗

Changes in norepinephrine output following light therapy for fall/winter seasonal depression.

Recurrent fall/winter depressions that remit during spring and summer have been called Seasonal Affective Disorders (SAD) (Wehr and Rosenthal 1989). The pathophysiology of SAD, its relationship to nonseasonal affective disorders, and the mechanism of action of light therapy, which is effective in treating SAD, remain to be elucidated (Depue et al 1989; Jacobsen et al 1987; James et al 1986; Joseph-Vanderpool et al 1991; Skwerer et al 1988, Terman et al 1989). Norepinephrine (NE) may play a role in the mechanisms of action of many antidepressant treatments (Schildkraut 1965) that alter NE metabolism (Schildkraut et al 1964 and 1965) and decrease the urinary output of NE and its metabolites, i.e., "whole-body NE turnover" (WBNET) (Golden et al 1988; Potter et al 1988). The present study explored whether light therapy also reduces the urinary output of NE and its metabolites.

Adult↗

Abnormal flash visual evoked response in melancholia: a replication study.

Grand mean flash visual evoked responses (FVER) were measured in two new groups of depressed patients with melancholia to replicate findings of an abnormal FVER in a previously reported pilot study (Vasile et al 1989). These different, independently collected groups of melancholic patients demonstrated a statistically significant negative deviation of the FVER 224-300 msec poststimulus maximal in the midline centroparietal region when compared with appropriate normative age-matched control groups (n = 56) in each group). We utilized the identical computer-based quantified neurophysiological technique with mapping to analyze the data in all three melancholic patient groups--the pilot group (n = 9) with mean age 73.1 years, an older replication group (n = 14) with mean age 75.5 years, and a younger replication group (n = 15) with mean age 63.8 years. We also studied a group of depressed patients without melancholia (n = 11) with mean age 65.2 years, and found a similar, but less pronounced, alteration of the FVER. Lastly, we studied a group of nondepressed neuropsychiatric patients (n = 10) with mean age 61.9 years and found no abnormality of the FVER. Our data suggest that a gradient of FVER abnormality exists in depressed patients, most prominent, but not limited to elderly melancholic patients.

Aged↗

Intermittent corticosteroid maintenance treatment of psoriasis: a double-blind multicenter trial of augmented betamethasone dipropionate ointment in a pulse dose treatment regimen.

Ninety psoriasis patients, who were either completely cleared of or manifested only a minimal presence of disease signs following 3-4 weeks of twice daily treatment with augmented betamethasone dipropionate (ABD) ointment 0.05%, were enrolled in this multicenter, double-blind, placebo-controlled study. The study was designed to determine if an intermittent pulse dose regimen of ABD ointment could safely and effectively maintain a remission disease status when treatment was applied in three consecutive applications 12 h apart, once a week for a maximum treatment period of 6 months. The disease of 60% of the patients in the active treatment group was successfully controlled for 6 months, while 80% of the placebo-treated patients experienced exacerbation of disease signs. No serious local or systemic treatment-related adverse experiences were reported. ABD ointment 0.05%, when applied using the intermittent treatment regimen described here, was shown to be a clinically beneficial and well-tolerated method of long-term (up to 6 months) maintenance therapy for psoriasis patients.

Administration, Topical↗

Assessment of nasal patency by rhinoscopic measurement of cross sectional nasal airway area: correlation with subjective nasal symptoms.

Assessment of nasal patency by the recording of nasal symptom scores was compared with an objective method of determining nasal airway area using a fiberoptic rhinoscope. Sixty patients with active allergic rhinitis and nasal congestion requiring treatment were studied. Nasal symptoms were recorded and nasal airway area was measured before and at fixed time intervals after administration of either pseudoephedrine or oxymetazoline. Both methods detected a decongestant response to both drugs, and the symptom of congestion correlated with the measured nasal airway area. Rhinoscopic measurement of cross sectional nasal airway area is an objective method that may be used to complement other methods for evaluation of nasal patency.

Adult↗

Urinary 3-methoxy-4-hydroxyphenylglycol and the depression-type score as predictors of differential responses to antidepressants.

Pretreatment 24 hr urinary 3-methoxy-4-hydroxyphenylglycol (MHPG) levels and the Depression-type (D-type) scores (derived from a multivariate discriminant function equation based on levels of urinary catecholamines and metabolites) were examined as possible predictors of antidepressant responses to either imipramine or alprazolam. In the case of imipramine, the responders had significantly lower pretreatment urinary MHPG levels (p = 0.002) and D-type scores (p less than 0.001) than did nonresponders. In contrast, responders to the antidepressant effects of alprazolam had significantly higher pretreatment urinary MHPG levels (p less than 0.05) and D-type scores (p = 0.02) than did nonresponders. For each antidepressant treatment, D-type scores appeared to provide a better separation of responders from nonresponders than did urinary MHPG levels. For each drug, the effect size for the difference in mean log-transformed D-type scores between responders and nonresponders was greater than the effect size for the difference in mean log-transformed MHPG levels. The difference between the effect sizes was statistically significant for imipramine (p = 0.02) and tended toward significance for alprazolam using two-tailed tests. These results suggest that the D-type equation, which was initially derived to separate bipolar manic-depressive depressions from other subgroups of depressive disorders, can also be used to predict differential responses to certain antidepressant drugs in patients with unipolar depressions.

Adult↗

Preatrophy: covert sign of thinned skin.

Overt iatrogenic cutaneous atrophy is easily recognized; however, the earliest signs of such an adverse event may be covert. Preatrophy is proposed as a term to describe the subtle unmasking or normally covert subpapillary vascular channels found by the use of enhanced skin surface magnification techniques. We conducted a randomized double-blind, bilaterally paired comparison clinical trial in patients with chronic plaque psoriasis treated with twice-daily (nonoccluded) superpotent topical steroids for 2 weeks. Occult reversible delicate networks of horizontally oriented vascular channels were found within and surrounding 20% (23/118) of the involved psoriatic plaques during the course of the study. The use of a hand-held magnifying lens (8X), mineral oil, a coverglass, and adequate illumination allow recognition of preatrophy. Preatrophy was more frequently found in women than in men.

Adult↗

Rapid antidepressant response to alprazolam in depressed patients with high catecholamine output and heterologous desensitization of platelet adenylate cyclase.

The present study examined the relationship between 24-hr urinary catecholamine (norepinephrine and epinephrine) output and measures of platelet adenylate cyclase (AC) activity in depressed patients (n = 17) and control subjects (n = 10). In both groups, significant inverse correlations were observed when 24-hr urinary catecholamine levels were examined in relation to measures of both receptor-mediated (prostaglandin D2 and alpha 2-adrenergic) and postreceptor-mediated (NaF) platelet AC enzyme activities, suggesting that circulating catecholamines may regulate platelet AC by heterologous (agonist-nonspecific) desensitization of the AC enzyme complex. Depressed patients who had favorable antidepressant responses to alprazolam had significantly higher pretreatment urinary catecholamine output and lower receptor-mediated platelet AC enzyme activities than control subjects, whereas the nonresponders did not. After 8 days of treatment with alprazolam, urinary catecholamine levels declined significantly. In responders, receptor-mediated measures of platelet AC activity increased significantly by day 8 to values comparable to those in control subjects; but similar changes were not observed in nonresponders. Prior to treatment, responders showed a strict linear relationship between receptor-mediated (prostaglandin D2) and postreceptor-mediated (NaF) stimulation of platelet AC activity through the stimulatory guanine nucleotide regulatory protein (Ns), whereas nonresponders did not. This suggests the presence of two distinct coupling interactions between platelet prostaglandin D2 receptors and the stimulatory guanine nucleotide regulatory protein in responders and nonresponders to the antidepressant effects of alprazolam prior to treatment. The authors propose that catecholamines, possibly acting through prostaglandins, may regulate platelet AC enzyme activity by heterologous desensitization occurring through postreceptor mechanisms.

Adenylyl Cyclases↗

Superpotent topical steroid treatment of psoriasis vulgaris--clinical efficacy and adrenal function.

Multiple clinical and laboratory evaluations, including morning plasma cortisol levels, were done in forty patients having moderate to severe psoriasis vulgaris prior to and during treatment with either betamethasone dipropionate in optimized vehicle or clobetasol-17-propionate ointment. The study was randomized, double-blind, and of parallel group design, lasting 3 weeks. Both drugs were effective (3 of 4 achieving at least 75% or more improvement). Temporary reversible suppression of the hypothalamic-pituitary-adrenal axis, as reflected by low morning plasma cortisol determinations, was found in eight of forty patients (20%). The clinician should respect the potential for superpotent topical steroids to cause laboratory evidence of adrenal suppression.

Administration, Topical↗

Biologic rhythm disorders, depression, and phototherapy. A new hypothesis.

Disturbances of the circadian timing system are implicated in the pathogenesis of numerous clinical syndromes, including sleep and affective disorders. Abnormalities of circadian rhythms can now be directly measured in the clinical laboratory and potentially corrected. Sleep scheduling disorders are most commonly due to phase misalignments between the endogenous circadian pacemaker and the socioenvironmental schedule. Current research is increasing our understanding of the influence of bright light exposure on the circadian timing system and has begun to be used successfully in the management of these conditions. There is substantial evidence that abnormalities of the circadian timing system are associated with depression. However, the application of new biologic rhythm diagnostic techniques would be required to establish whether circadian dysfunction is involved in the pathogenesis of these conditions. We propose a new hypothesis that phototherapy for seasonal depression may act by increasing an abnormally low circadian amplitude in those patients, such as that reported in endogenously depressed patients. The powerful effect of light on the circadian system indicates that phototherapy may become an important tool in the management of disorders of circadian etiology.

Circadian Rhythm↗

Enhanced signal transduction by adenylate cyclase in platelet membranes of patients showing antidepressant responses to alprazolam: preliminary data.

The triazolobenzodiazepine, alprazolam, was administered to 11 depressed patients over a period of six weeks, and six patients showed a favorable antidepressant response. There were no significant differences between responders and nonresponders in age, pretreatment Hamilton Depression Rating Scores, 4 p.m. postdexamethasone plasma cortisol levels, or platelet monoamine oxidase activities. Blood levels of alprazolam were not meaningfully different in responders and nonresponders when measured on treatment day 8. However, on treatment day 8, significantly enhanced prostaglandin D2-stimulated platelet adenylate cyclase activity, greater suppression of prostaglandin D2-stimulated platelet adenylate cyclase activity by epinephrine, and enhanced sodium fluoride-stimulated platelet adenylate cyclase activity were seen in the six patients who went on to respond to alprazolam, but not in the five nonresponders. In contrast, there were no significant changes in prostaglandin D2, (-)-isoproterenol, or fluoride ion-stimulated leukocyte adenylate cyclase activity in responders or nonresponders. No meaningful changes were observed in the mean densities of either the high-affinity platelet alpha 2-adrenergic receptor (for 3H-p-aminoclonidine) or the leukocyte beta-adrenergic receptor (for 3H-dihydroalprenolol) in responders or nonresponders. The present findings, taken in conjunction with findings from other recent studies, suggest that enhanced coupling between certain neurotransmitter or hormone receptors and adenylate cyclase through the guanine nucleotide regulatory proteins may help explain the antidepressant effects of alprazolam and possibly other forms of antidepressant treatment.

Adenylyl Cyclases↗

Skin-surface touch print for diagnosing fungal infections.

The skin-surface touch print is a practical, easily performed and noninvasive method for obtaining a sample of infected stratum corneum or hair. This technique is particularly useful in diagnosing superficial fungal infections. With simple staining, fungal hyphae and spores can be readily visualized microscopically. This technique has been found to be as effective as the potassium hydroxide test.

Adhesives↗