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Biomedical subjects

R G Cooke

Publications and source records attributed to R G Cooke.

At least 19 recordsLinked to original sources
PubMed2001

Altered TRPC7 gene expression in bipolar-I disorder.

BACKGROUND: As altered storage-operated calcium (Ca(2+)) entry (SOCE) may affect Ca(2+) homeostasis in bipolar disorder (BD), we determined whether changes occur in the expression of TRPC7 and SERCA2s, proteins implicated or known to be involved in SOCE, in B lymphoblast cell lines (BLCLs) from BD-I patients and comparison subjects. METHODS: mRNA levels were determined in BLCL lysates from BD-I, BD-II, and major depressive disorder patients, and healthy subjects by comparative reverse transcriptase-polymerase chain reaction, and BLCL basal intracellular Ca(2+) concentration ([Ca(2+)]B) was determined by ratiometric spectrophotometry using Fura-2, in aliquots of the same cell lines, at 13-16 passages in culture. RESULTS: TRPC7 mRNA levels were significantly lower in BLCLs from BD-I patients with high BLCL [Ca(2+)]B compared with those showing normal [Ca(2+)]B (-33%, p =.017) and with BD-II patients (-48%, p =.003), major depressive disorder patients (-47%, p =.049) and healthy subjects (-33%, p =.038). [Ca(2+)]B also correlated inversely with TRPC7 mRNA levels in BLCLs from the BD-I group as a whole (r = -.35, p =.027). CONCLUSIONS: Reduced TRPC7 gene expression may be a trait associated with pathophysiological disturbances of Ca(2+) homeostasis in a subgroup of BD-I patients.

Adult↗
PubMed2001

Altered IMPA2 gene expression and calcium homeostasis in bipolar disorder.

Reduced inositol monophosphatase (IMPase) activity and elevated basal intracellular calcium levels ([Ca(2+)](B)) have been reported in B lymphoblast cell lines (BLCLs) from bipolar I affective disorder (BD-I) patients, which may reflect cellular endophenotypes of this disorder. As the PI cycle couples to intracellular Ca(2+) mobilization, these two putative endophenotypes may be related. Using an RT-PCR assay, mRNA levels were estimated for IMPA1 and 2 genes encoding human IMPase 1 and 2, respectively, in BLCLs phenotyped on [Ca(2+)](B), from patients with a DSM-IV diagnosis of BD-I (n = 12 per phenotype) and from age- and sex-matched healthy subjects (n = 12). IMPA2 mRNA levels were significantly lower in BLCLs from male BD-I patients with high [Ca(2+)](B) (n = 6) compared with healthy male subjects (n = 5) (-52%, P = 0.013), male BD-I patients with normal BLCL [Ca(2+)](B) (n = 8) (-42%, P = 0.003) and female BD-I patients with high [Ca(2+)](B) (n = 6) (-59%, P = 0.0004). A significant negative correlation was observed between IMPA2 mRNA levels and [Ca(2+)](B) in BLCLs from male (P = 0.046), but not female BD-I patients. Sex-dependent differences were also evident in postmortem temporal cortex IMPA2 mRNA levels which, in contrast to BLCLs, were significantly higher in male BD-I subjects compared with male controls (P = 0.025, n = 4/group). Collectively, these observations suggest a potential sex-dependent link between abnormalities in IMPA2 expression and calcium homeostasis in the pathophysiology of BD.

Adult↗
PubMed2001

Quality of life: an important dimension in assessing the treatment of depression?

Quality of life is used to assess the overall impact of medical treatments from the patient's perspective. Because depression affects a person's ability to function at work and at home, the evaluation of various treatments must include an assessment of patients' physical, social and psychological status. This paper classifies and evaluates a variety of widely used health-related quality-of-life questionnaires that have potential value as outcome measures in the treatment of depression. The paper also outlines how these measures have been beneficial in the assessment of depressed patients. They reveal differences between patients with depression and control groups, are sensitive to change in status during treatment, have predictive value for outcome measures and provide additional information about timelines for improvement in psychosocial functioning, which may occur at a different rate than changes in other depressive symptoms. Despite the limitations of these questionnaires, they provide an important additional dimension to the evaluation of treatment with antidepressant medications.

Antidepressive Agents↗
PubMed2000

Suppression of oxytocin-induced prostaglandin F2alpha release after intra-uterine nordihydroguariaretic acid administration in ewes.

Intrauterine administration of the 5-lipoxygenase inhibitor nordihydroguariaretic acid (NDGA; 5 mg, bid) on Days 9-14 of the ovine estrous cycle (estrus = Day 0) delayed luteolysis and extended the duration of the estrous cycle (20+/-1, SD, vs. 16+/-1 days; P < 0.01). In control ewes, plasma concentrations of 13,14,dihydro-15-keto prostaglandin F2alpha increased significantly (P < 0.001) following i.v. administration of oxytocin (10 i.u.) on Day 14; in the nordihydroguariaretic acid-treated ewes, however, there was no such increase. In addition, concentrations of endometrial oxytocin receptors were significantly less (P < 0.01) in the nordihydroguariaretic acid-treated ewes (218+/-60 vs. 579+/-66 fmol/mg tissue). These results suggest that 5-lipoxygenase products of arachidonate metabolism may be involved in the control of ovine luteal function.

Animals↗
PubMed2000

The correlates of community functioning in patients with bipolar disorder.

BACKGROUND: Although bipolar disorder is associated with substantial levels of disability, efforts to investigate the correlates of impairment have been meagre. METHODS: Sixty-one euthymic patients with a diagnosis of bipolar disorder were administered a variety of quality of life measures, including a measure of community functioning entitled the Occupational Performance Questionnaire (OPQ). This measure included a Community Functioning Scale (CFS) that provides a rating of adaptive level of functioning that was compared with other clinical and functional indices. RESULTS: The OPQ was found responsive to the assessment of community functioning among euthymic patients, as about one third of the patients did not meet the criteria for adequate level of community functioning. Moreover, a positive history for alcoholism or alcohol abuse and reported current levels of high anxiety were associated with the impairment in community functioning. LIMITATIONS: This study relied on self-report data derived from a measure of community functioning developed specifically for this study. CONCLUSION: Despite the preliminary nature of these findings, further investigation of the functional impairments associated with bipolar disorder is needed.

Adult↗
PubMed2000

Comorbidity of obsessive-compulsive disorder in recovered inpatients with bipolar disorder.

OBJECTIVE: To determine the frequency of obsessive-compulsive disorder (OCD) in inpatient subjects with bipolar disorder (BD) and to examine the clinical characteristics of BD subjects with OCD. METHOD: The sample consisted of 143 inpatient subjects with DSM-III-R BD-I and BD-NOS (BD-II), recovered from a current episode of either depression or mania. Demographic and clinical variables were obtained on the day of admission. Current comorbid conditions including OCD were determined by the Structured Clinical Interview for DSM-III-R Ifollowing recovery from the acute affective episode. RESULTS: The frequency of current OCD was 7% (N = 10). All BD subjects with OCD were BD-II, were male, and had a diagnosis of current dysthymia. They had fewer episodes and a higher incidence of prior suicide attempts than bipolar subjects without OCD. None of the bipolar subjects with OCD fulfilled criteria for cyclothymia. CONCLUSIONS: Our findings suggest that BD-II, OCD, dysthymia, and suicidality cluster together in some subjects with BD. We discuss the clinical implications of our findings.

Adult↗
PubMed2000

Effect of number of episodes on wellbeing and functioning of patients with bipolar disorder.

OBJECTIVE: To examine the relationship between number of episodes and inter-episode functioning in bipolar disorder. METHOD: Sixty-four euthymic subjects with bipolar affective disorder completed the Medical Outcomes Questionnaire Short Form and the Global Assessment of Functioning Scale. Goodness-of-fit models were used to define the relation between episode number and level of function. RESULTS: Non-linear logarithmic and power relations best described the association between number of episodes and outcome. Number of past depressions was a stronger determinant of outcome than past manias. CONCLUSION: Strategies to minimize the number of episodes experienced by patients with bipolar illness must be pursued aggressively if function is to be maintained, with particular attention given to minimizing episodes of depression.

Adolescent↗
PubMed1999

Collagenase and gelatinase messenger ribonucleic acid expression and activity during follicular development in the rat ovary.

Metalloproteinases are members of a family of proteinases that remodel the extracellular matrix throughout the body. To test the hypothesis that metalloproteinases are regulated by gonadotropin-induced changes during follicular growth, rats were injected with eCG (20 IU, s.c.), and ovaries and serum were collected at the time of eCG administration (0 h) and at 6, 12, 24, 36, or 48 h later for analysis of metalloproteinase mRNA expression, metalloproteinase activity, and steroidogenesis. Serum estradiol levels increased from 18.9 pg/ml at 0 h to 503.8 pg/ml at 48 h. Analysis of mRNA expression was performed for collagenase-3, 72-kDa gelatinase, and 92-kDa gelatinase (n = 3-4). For collagenase-3, eCG stimulated a 32-fold increase in collagenase-3 mRNA at 48 h after eCG injection as compared to that in ovaries collected at the time of eCG administration (i.e., 0-h control). The mRNA levels for 72-kDa gelatinase were 2.8-fold compared to 0 h at 36 h after eCG treatment and returned to control levels by 48 h after gonadotropin treatment. Levels of the 92-kDa mRNA expression peaked at 24 h (4. 2-fold compared to 0 h) and returned to control levels by 36 h. Gel zymography revealed 3 gelatinolytic bands corresponding to the gelatinases of approximately 72 kDa, 92 kDa, and 105 kDa. Analysis of metalloproteinase activity as the degradation of collagen or gelatin per ovary showed an increase in gelatinolytic and collagenolytic activity between 12 and 48 h after eCG treatment. In summary, these findings demonstrate that the gonadotropin induction of folliculogenesis results in changes in the metalloproteinases that may be responsible for extracellular matrix remodeling associated with follicular growth.

Animals↗
PubMed1999

Family-of-origin characteristics in bipolar disorder: a controlled study.

OBJECTIVE: To assess the family-of-origin characteristics of patients with bipolar disorder relative to those of control subjects. METHOD: Fifty-six euthymic patients meeting research diagnostic criteria for bipolar disorder and 21 control subjects completed the Family Environment Scale (FES) for the family they grew up with. RESULTS: The 2 groups showed strikingly similar profiles on 10 indices of family functioning or structure. CONCLUSIONS: The results do not support the hypothesis that specific family attributes contribute to the development of bipolar disorder.

Adult↗
PubMed1998

Delayed luteolysis after intra-uterine infusions of nordihydroguaiaretic acid in the ewe.

Intrauterine administration of nordihydroguaiaretic acid (5 mg, bid. NDGA), an inhibitor of the enzyme 5-lipoxygenase, on days 10-14 of the oestrous cycle, maintained luteal function and delayed oestrus in the ewe. The duration (mean +/- SD) of the oestrous cycle in the treatment group (n = 4) was 24 +/- 1 days, which was significantly (P < 0.001) longer than that of 16 +/- 1 days in vehicle-treated controls (n = 4); plasma progesterone concentrations were also significantly (P < 0.01) higher in the treatment group. On days 13 and 14 of the cycle (oestrus = Day 0) in the control group large pulses of 13,14-dihydro-15-keto prostaglandin F2alpha (PGFM) were evident, with mean (+/- SD) maximum concentrations of 232.5 +/- 66 and 415 +/- 309 pg ml(-1), respectively. In the treatment group, however, concentrations of PGFM were below detection level (< 50 pg ml(-1)). Similarly, in the control group, oxytocin release was highly pulsatile, with mean (+/- SD) peak concentrations of 21.8 +/- 5 and 18.5 +/- 6 pg ml(-1) on days 13 and 14, respectively; these were significantly (P < 0.01) higher than values of 7.6 +/- 3 and 6.1 +/- 3 pg ml(-1) in NDGA-treated ewes, where pulses were of relatively low amplitude. These results suggest that 5-lipoxygenase products of arachidonic acid metabolism may be involved in the positive feedback mechanism between luteal oxytocin and uterine PGF2alpha during luteolysis in the ewe.

Animals↗
PubMed1998

Effects of arterial infusions of adrenalin and acetylcholine on luteal secretion of progesterone and oxytocin in goats.

The effects of close intra-arterial infusion of acetylcholine and adrenalin on ovarian secretion of progesterone and oxytocin were examined on Day 10 of the estrous cycle in goats (estrus = Day 0). Acetylcholine (15 micrograms/min) was without effect, but adrenalin (10 micrograms/min) significantly (P < 0.001) raised both progesterone and oxytocin concentrations in ovarian vein plasma. These results show that luteal hormone secretion is enhanced in the goat by beta-adrenergic stimulation and suggest that, as in the sheep and cow, there may be neuroendocrine involvement in the regulation of caprine luteal function.

Acetylcholine↗
PubMed1998

Effect of adrenalin and propranolol on progesterone and oxytocin secretion in vivo during the caprine estrous cycle.

The effects of jugular infusions of adrenalin and the beta-adrenergic receptor antagonist propranolol on plasma concentrations of progesterone and oxytocin were examined at 2 different stages of the caprine estrous cycle. Adrenalin (25 micrograms.kg-1h-1) significantly (P < 0.05) increased oxytocin secretion on Day 3 and Day 10 of the cycle (estrus = Day 0); progesterone concentrations were significantly (P < 0.05) elevated on Day 10 alone. Propranolol had no effect on progesterone secretion yet significantly (P < 0.05) reduced oxytocin concentrations on Day 3. These results suggest that there may be neuroendocrine involvement in the regulation of luteal oxytocin secretion in the goat.

Animals↗
PubMed1998

Gender differences in patients with bipolar disorder influence outcome in the medical outcomes survey (SF-20) subscale scores.

BACKGROUND: The importance of gender on the course and outcome in bipolar disorder (BD) has been widely acknowledged. The limited data suggest that the prevalence is similar between sexes but that the course of illness may be different. This study investigated gender differences in a clinic sample of patients with BD including a measure of subjects' perception of well-being and functioning. METHODS: Euthymic outpatients attending a mood disorders clinic were systematically assessed. Measurements obtained included SADS-LV, Hamilton Depression Ratings scores, Young Mania Rating scores, and Medical Outcome Survey Short Form 20 items and Global Assessment of Functioning. RESULTS: Women with BD have a later onset of mania, are more likely to have a rapid cycling course, experience mixed episodes, experience more depressive episodes and report more overall impairment in all MOS subscale scores with significant impairment in physical health and pain. CONCLUSIONS: Further investigation and replication of these differences need to be addressed including non-euthymic patients and during a longer period of systematic follow-up.

Adult↗
PubMed1997

Relationship between the five-factor model of personality and unipolar, bipolar and schizophrenic patients.

The purpose of this study was to examine personality differences among three different Axis I disorders-recovered patients with unipolar depression (n = 62), euthymic patients with bipolar disorder (n = 34), and patients with schizophrenia in the residual phase of their illness (n = 41) using the five-factor model of personality (FFM). The dimensions of the FFM-Neuroticism (N), Extraversion (E), Openness (O), Agreeableness (A), and Conscientiousness (C)-were measured with composite scores derived from the NEO Personality Inventory (NEO PI) and the Revised NEO Personality Inventory (NEO PI-R). While no group differences emerged on N or C, the bipolar patients scored significantly higher on the Positive Emotion facet (subscale) of E than the unipolar patients. The schizophrenic patients scored lower on the Feelings, Values and Actions facets of O than did the unipolar and bipolar patients. The unipolar patients scored higher on A than the schizophrenic patients.

Adult↗
PubMed1997

Levels of functioning and well-being in recovered psychotic versus nonpsychotic mania.

The aim of the study was to compare psychotic and nonpsychotic bipolar patients on demographic and outcome measures. Sixty two patients with bipolar disorder were divided into groups on the basis of psychosis during an index episode of mania. Groups were compared on demographic, clinical and outcome measures. Psychotic patients were more symptomatic during the index episode, but they did not differ from nonpsychotic patients on ratings of function and well being when euthymic. Psychosis occurring within the context of an exacerbation of mania does not seem to predict a poorer outcome when patients return to the euthymic state. A limitation of the present study is that it involves short-term outcome, but the data can be used to inform patients and family about the possibility of full recovery even in the psychotic form of mania.

Adult↗
PubMed1996

Bipolar disorder, unipolar depression and the Five-Factor Model of personality.

We examined differences between personality characteristics of euthymic bipolar disorder patients (BD) (n = 34) and recovered unipolar depressed patients (UD) (n = 74) using the taxonomy of the Five-Factor Model of personality (FFM) as measured by composite scales derived from the NEO Personality Inventory (NEO PI) and the revised NEO PI (NEO PI-R). Euthymic BD patients scored significantly higher on the Openness (O) dimension and the Positive Emotions facet of the E dimension than did recovered UD patients. For O, euthymic BD patients scored higher on the Feelings facet. These results suggest not only that euthymic BD patients are more likely to experience positive affects than recovered UD patients, but also that euthymic BD patients are more receptive to their positive and negative feelings than are recovered UD patients.

Adult↗
PubMed1996

Comparative evaluation of two self-report Mania Rating Scales.

Two brief patient-rated scales, the Internal State Scale (ISS) and the Self-Report Manic Inventory (SRMI), have been shown to reliably diagnose mania. In the current study we further evaluated the utility of these scales relative to each other and to the observer-rated Young Mania Rating Scale (YMRS), for quantifying the severity of manic/hypomanic symptoms cross-sectionally and over time, in 20 patients with rapid-cycling bipolar disorder. The self-report scales correlated well with each other and with the YMRS, but each covered a somewhat different domain of the manic syndrome. The SRMI and the ISS were more sensitive than the YMRS to the mood fluctuations in the euthymic to hypomanic range observed in our subjects. Used in tandem, the two self-report scales may find application in clinical research with outpatients with bipolar disorder, and as an adjunct to clinical monitoring in this patient population.

Bipolar Disorder↗