Pap tests needed for women of all ages.
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Female↗
Biomedical subjects
J M Davis
Publications and source records attributed to J M Davis.
A potential drug interaction between fluoxetine and valproic acid.
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Bipolar Disorder↗
Failure of low dose carbohydrate feeding to attenuate glucoregulatory hormone responses and improve endurance performance.
The effects of ingesting a low dose of CHO on plasma glucose, glucoregulatory hormone responses, and performance during prolonged cycling were investigated. Nine male subjects cycled for 165 min at approximately 67% peak VO2 followed by a two-stage performance ride to exhaustion on two occasions in the laboratory. Every 20 min during exercise, subjects consumed either a flavored water placebo (P) or a dilute carbohydrate beverage (C). Blood samples were collected immediately before, every 20 min throughout, and immediately after exercise. Plasma was analyzed for glucose, lactate, free fatty acids (FFA), and various glucoregulatory hormones. VO2, RER, heart rate, perceived exertion, and exercise performance were also measured. Lactate, FFA, epinephrine, norepinephrine, ACTH, cortisol, and glucagon increased with exercise whereas glucose and insulin decreased (p < or = .05). Except for a small difference in glucose at 158 min of exercise and at exhaustion, no significant differences were found between drinks for any of the variables studied (P > or = .05). Ingestion of 13 g carbohydrate per hour is not sufficient to maintain plasma glucose, attenuate the glucoregulatory hormone response, and improve performance during prolonged moderate intensity cycling.
Adrenocorticotropic Hormone↗
Intracranial self-stimulation motivates treadmill running in rats.
Most animal running models have traditionally used aversive motivators to induce exercise tasks. This study demonstrates treadmill running motivated by reinforcement of intracranial self-stimulation (ICSS), providing an alternative model with which to study physiological responses to exercise. Twenty-nine male Sprague-Dawley rats were stereotaxically implanted with bipolar electrodes aimed at the ventral tegmental area of the brain. After 7 days of operant lever-press training for ICSS, rats that pressed at least 50 presses/min were randomly divided into three conditions: exercise-reinforcing brain stimulation (Ex-St), exercise-aversive shock (Ex-Sh), and sedentary controls (C). Ex-St and Ex-Sh ran for 30 min at 25 m/min at 5% grade for 2 wk with ICSS and electric shock as the motivator, respectively, while C did not run. At the end of 2 wk, Ex-St and Ex-Sh performed an endurance run. Results show that Ex-St ran longer than Ex-Sh [63 +/- 10 vs. 42 +/- 10 (SD) min; P less than 0.05]. HR was higher in Ex-St than in C (P less than 0.05). Rectal temperature increased similarly in both exercise groups. This model provides a highly effective method to motivate treadmill running in rats and as such can be used to characterize physiological responses to exercise without the potentially confounding influence of stress associated with an aversive shock motivator.
Animals↗
Phase I study of combination drug purging for autologous bone marrow transplantation.
In a phase I clinical trial of autologous bone marrow transplantation, we determined the feasibility of ex vivo purging with high concentrations of pharmacologics in combination. Light-density cells isolated from the grafts of 26 patients with acute leukemia or lymphoblastic lymphoma were treated with 4-hydroperoxycyclophosphamide (4-HC; 30 to 60 micrograms/mL), vincristine (Vcr; 1.5 to 3.0 micrograms/mL), and methylprednisolone sodium succinate (MP; 5 mg/mL). All patients received marrow-lethal induction therapy followed by infusion of the treated grafts. Three patients died of transplant-related complications before achieving peripheral blood recovery of greater than 0.5 x 10(9) granulocytes per liter. All other patients achieved this parameter of engraftment at a median of 35 days after marrow infusion. The median time to last platelet transfusion was 45 days. These durations of aplasia were similar to those experienced by other patients receiving density-gradient separated grafts treated with 60 micrograms/mL of 4-HC as a single agent. No patient required infusion of untreated reserve marrow because of engraftment failure. The colony-forming unit-granulocyte macrophage (CFU-GM) content of the grafts after purging predicted these parameters of engraftment. Colony-forming unit-leukemia (CFU-L) cultured from the grafts of 12 of the patients treated for acute lymphoblastic leukemia (ALL) were considerably more sensitive to the combination regimen than to 4-HC alone; the sensitivity of CFU-GM from these patients did not differ between the two regimens. The results of this trial indicate the feasibility of treating autologous bone marrow grafts with high concentrations of pharmacologics in combination. The use of combinations may increase the efficacy of ex vivo purging without increasing the toxicity to normal hematopoietic cells.
Adolescent↗
Barriers to improving diabetes care for blacks.
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Black or African American↗
Eye injury in a podiatrist.
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Eye Injuries, Penetrating↗
Effect of antidepressants and neuroleptics on phosphoinositide metabolism in human platelets.
The effect of tricyclic antidepressants (imipramine, desipramine, amitriptyline) and several other antidepressants like iprindole, a monoamine oxidase inhibitor phenelzine, trazodone and mianserin as well as cocaine (a potent inhibitor of norepinephrine uptake), and neuroleptics (haloperidol, thioridazine, chlorpromazine) on [3H]inositol phosphate formation was investigated in human platelets. Basal and thrombin-induced [3H]inositol monophosphate ([3H]IP1), [3H]inositol bisphosphate ([3H]IP2) and [3H]inositol trisphosphate ([3H]IP3) production were measured in [3H]myoinositol-labeled platelets in the presence of lithium chloride and in the presence or absence of test drugs. Desipramine, imipramine, amitriptyline and iprindole inhibited thrombin-stimulated formation of [3H]IP2 and [3H]IP3 in human platelets but had no significant effect on [3H]IP1 formation. In contrast, trazodone, mianserin, cocaine and phenelzine had no effect on inositol phosphate formation in thrombin-stimulated human platelets. The neuroleptics thioridazine and chlorpromazine also decreased thrombin-stimulated [3H]IP2 and [3H]IP3 production but not [3H]IP1 in human platelets, whereas haloperidol had no significant effect. The effect of antidepressants and neuroleptics on the level of [3H]phosphatidylinositol ([3H]PI), [3H]phosphatidylinositol 4-phosphate ([3H]PIP) and [3H]phosphatidylinositol 4,5-bisphosphate ([3H]PIP2) was also determined. All of the drugs tested except phenelzine and thioridazine increased the accumulation of [3H]PI, [3H]PIP and [3H]PIP2. Thioridazine increased levels of [3H]PI but decreased the level of [3H]PIP and [3H]PIP2, whereas phenelzine had no effect on [3H]PI, [3H]PIP and [3H]PIP2 interconversion in human platelets.(ABSTRACT TRUNCATED AT 250 WORDS)
Antidepressive Agents, Tricyclic↗
Comparisons of the costs of psychotropic medications: an update.
This is an update of a review on the cost of psychotropic drugs. It provides realistic tables to clinicians and patients on the short and long term costs of prescribing and taking medication for psychiatric disorders, and recommendations on how to minimize their expense.
Antidepressive Agents↗
Drug treatment of the neuroleptic malignant syndrome.
We performed a case-controlled analysis on the effectiveness of dantrolene and certain dopamine agonists--bromocriptine, amantadine 3,4-dihydroxyphenylalanine, (DOPA)--for the neuroleptic malignant syndrome (NMS). This was based on a review of all known published studies using as controls those cases not treated with these drugs and/or electroconvulsive therapy. In this control group, the NMS-related death rate was 21 percent. Dantrolene alone reduced the death rate to 8.6 percent, bromocriptine alone to 7.8 percent, and amantadine alone to 5.9 percent. We also stratified patients into five levels of severity based on state of consciousness and temperature and showed that the relative reduction in death rate held up at all levels. The dopamine agonists and dantrolene have a therapeutic effect independent of each other.
Amantadine↗
Experimental studies in rats on the effects of asbestos inhalation coupled with the inhalation of titanium dioxide or quartz.
Rats were exposed for 1 year, with a 2-year follow-up, to dust clouds consisting of a mixture of amosite or chrysotile asbestos with either titanium dioxide or quartz. The addition of titanium dioxide to asbestos did not increase levels of pulmonary fibrosis above the amounts produced by chrysotile or amosite alone. Quartz, however, greatly increased fibrosis above that produced by the asbestos types alone. Both particulate dusts caused an increase in the numbers of pulmonary tumours and mesotheliomas compared to asbestos alone but while tumours in animals treated with asbestos and quartz tended to occur earlier than tumours with asbestos alone, in animals treated with dusts containing titanium dioxide, tumour production occurred later than with asbestos alone. In animals treated with mixtures of asbestos and quartz, there was evidence of increased transport of fibres across the visceral pleural surface and this may be associated with the finding of a higher proportion of pleural mesotheliomas than previously reported in experimental inhalation studies from any laboratory using the main asbestos varieties. The presence of particulate dusts made little difference to the amounts of amosite fibre retained in the lung tissue but, with chrysotile, titanium dioxide appeared to increase retention while quartz reduced it.
Animals↗
Effect of desipramine on inositol phosphate formation and inositol phospholipids in rat brain and human platelets.
To examine the mechanism of action of antidepressant drugs, we studied the effect of desipramine (DMI) in vitro on agonist-stimulated inositol phosphate formation and inositol phospholipids in rat brain and human platelets. We observed that DMI inhibited thrombin-stimulated 3H-inositol bisphosphate (IP2) and 3H-inositol trisphosphate (IP3) but not 3H-inositol monophosphate (IP1) formation in human platelets. DMI also inhibited norepinephrine (NE) and serotonin (5-HT) stimulated 3H-IP1 formation in rat cerebral cortex. DMI increased levels of all three 3H-inositol phospholipids, 3H-phosphatidyl inositol (PI), 3H-PI-4-phosphate (PIP), and 3H-PI 4,5-bisphosphate (PIP2), in both platelets and rat cortex. The decreased formation of inositol phosphates and increased levels of [3H]-PI, [3H]-PIP, and [3H]-PIP2 by DMI appears to be due to the inhibition of the enzyme phospholipase C rather than its effects on receptors. It is thus possible that interaction of tricyclic antidepressant drugs with the PI-signaling system may be related to their mechanism of action.
Animals↗
Effects of unilateral-nondominant vs. bilateral ECT on memory and depression: a preliminary report.
Reported are preliminary results from a randomized, double-blind study comparing the differential effects of unilateral-nondominant (UND) and bilateral (BL) electroconvulsive therapy (ECT) on memory function and clinical efficacy. The study included the serial administration (before, shortly after, and 6 months following a course of ECT) of behavioral ratings and memory tests for dominant and nondominant, anterograde and retrograde memory functions. Thus far, clinical improvement shortly after a course of ECT and 6 months later was significant for the entire sample and did not differ between the UND and BL groups. Most memory ratings worsened significantly after ECT, but returned to baseline levels 6 months later. Surprisingly, the scores generally did not differ between the UND and BL groups at any time point. Clinical implications for choice of administration are discussed.
Aged↗
Leukocyte-mediated epithelial injury in ozone-exposed rat lung.
Both epithelial injury and inflammation are characteristic findings in the centriacinar regions of the lungs of rats exposed to ozone. In humans such effects could lead to long-term lung damage and disease. In animals, neoplastic change in the lungs after exposure to ozone has been described previously. The possible relationships between inflammatory cell recruitment, epithelial injury, and hyperplasia, with special regard to the important role of repair processes in leading to increased incidence of tumors in some species, have been addressed in the present study. We have previously described that leukocytes from lungs inflamed by different agents can injure epithelial cells in vitro. We have suggested that this leukocyte-mediated epithelial injury could enhance epithelial turnover in ozone-exposed lungs and so enhance the likelihood of tumor development. We, therefore, set out to test the hypothesis that bronchoalveolar leukocytes from ozone-exposed lungs can injure epithelial cells in vitro. PVG rats were exposed to 0.2, 0.4, 0.6, and 0.8 parts per million2 (ppm) ozone for seven hours per day for up to four days. On the morning following the last exposure, bronchoalveolar lavage was used to sample the bronchoalveolar leukocytes and the following parameters were assessed: total number, differential leukocyte count, production of oxidants, ability to degrade fibronectin, and ability to injure epithelial cells. In addition to these parameters, which were measured at all concentrations and time points in limited experiments, we also assessed macrophage size in short-term culture and inflammation in histological sections of lungs. Total number of lavageable cells was not affected by ozone inhalation. However, the percentage of macrophages decreased with ozone treatment and the percentage of neutrophils increased on days 1 and 2 at 0.6 and 0.8 ppm ozone. There was no significant effect of ozone exposure on the ability of neutrophils to degrade fibronectin or injure epithelial cells. Production of superoxide anion in response to stimulation with phorbol myristate acetate was significantly decreased by exposure to 0.6 ppm ozone, as described in previous studies. Macrophages from the lungs of rats exposed to ozone were larger than control macrophages.
Animals↗
Mesothelioma dose response following intraperitoneal injection of mineral fibres.
The relationship between injected dose and the development of peritoneal mesotheliomas has been examined in rats using the UTCC standard reference samples of chrysotile, crocidolite and amosite as well as a sample of fibrous erionite from Oregon. Doses injected into the peritoneal cavity ranged from 0.005 to 25 mg and with each dust a clear dose response was found. The proportion of animals developing tumours increased with the amount of dust injected while the tumour induction period was reduced. When times to death from mesothelioma were analysed using standard hazard models, erionite was the most carcinogenic dust by mass followed by chrysotile, amosite and crocidolite. The hazard slopes for erionite, chrysotile and crocidolite, over the range of doses examined, were parallel while the slope for amosite was shallower. The relative hazards for the various dust types were also examined with dose expressed as the number of injected fibres in a range of sizes as measured by SEM. No combination of fibre dimensions was found at which the hazard for the four dust types was equal although when dose was expressed as the number of long fibres injected (> 8 microns in length) the hazard slopes for chrysotile, crocidolite and amosite were relatively close. The hazard level of erionite remained well above the other dust types regardless of how the dose was expressed.
Animals↗
Random regression models for multicenter clinical trials data.
A random-effects regression model is proposed for the analysis of data arising from multicenter clinical trials. Advantages of the random regression model (RRM) in this context include that it allows for varying numbers of subjects within the different centers, it can assess the influence of variables measured both at the level of the subject and at the level of the center on the subject's clinical outcome, and it controls for and estimates the amount of intracenter variation that is present in the data. An example utilizing data collected in the National Institute of Mental Health schizophrenia collaborative study, where subjects were clustered within nine centers, illustrates the usefulness of the statistical model. Other applications and extensions of RRM within a psychiatric framework are discussed.
Humans↗
Steady-state plasma level prediction for haloperidol from a single test dose.
Due to large interindividual variabilities in kinetics of haloperidol (HPDL), empirically adjusting the dose to achieve steady-state plasma levels (Css) is a time consuming process. We report a method to individualize doses to achieve the desired Css from the observed plasma level 24 hours after a single test dose. Twenty-eight acutely psychotic patients, after up to 2 weeks of inhospital drug washout, received a 15-mg oral "test" dose of HPDL and 24- and 48-hour plasma levels were measured. They were then randomly assigned to empirically determined doses of HPDL (2, 4, or 10 mg b.i.d.) to achieve a low, medium, or high Css. The 24-hour plasma level after the test dose, the final Css, and the dose required to achieve that Css were analyzed by a linear regression model. The log Css in terms of the log dose revealed a strong linear relationship (R2 = .78, n = 28), which was further improved by the addition of the 24-hour log plasma level (R2 = .87).
Female↗
Role of the efferent arteriole in tubuloglomerular feedback.
Tubuloglomerular feedback (TGF) is generally regarded as being mediated by a single, humoral vasoconstrictor acting on the afferent arteriole. Examination of the literature reveals, however, that acute activation or blockade of TGF may, under certain circumstances, be associated with vasomotion of the efferent arteriole, either in the same or in the opposite direction as the afferent arteriole. The former appears to be the case particularly when myogenic autoregulation is attenuated, for example, with application of calcium channel blockers. Experiments in which the TGF signal is chronically lost by preventing tubular fluid flow at the macula densa also suggest participation of the efferent arteriole. Under these circumstances, stop flow pressure and single nephron filtration rate increase and glomerular blood flow falls. TGF activity at this stage is modestly enhanced. Taken together, these findings suggest efferent vasoconstriction. After a delay of some hours, vasoconstriction is also apparent in the afferent arteriole. It is not clear whether the mechanism involved in this response is related to the "normal" TGF response. Together, these findings are hard to reconcile with the hypothesis of a single vasoconstrictor acting on the afferent arteriole.
Animals↗