[Assessment of the distribution of nucleic acid intercalators in yeast cells by the pseudospectral image analysis].

The intracellular location of nucleic acid intercalators (NAI) in live (not fixed) Saccharomyces cerevisiae cells has been studied using fluorescence microscopy combined with computer pseudospectral image analysis. Three NAI: the anthracycline anticancer drug doxorubicin and the nucleic acid dyes ethidium bromide (E) and 4',6-diamidino-2-phenylindole (DAPI) were used. All three NAI were shown to be localized in nuclei and mitochondria. In contrast to DAPI, which interacted only with DNA, a large fraction of doxorubicin and ethidium bromide apparently bound to mitochondrial membranes. Upon combined application, a competition between these intercalators for binding sites in the nuclear and mitochondrial DNA occurred. It was concluded that this approach may be used in designing new DNA-targeted drugs and in preliminary studies of their interaction with eukaryotic cells.

Effects of the thyromimetic agent diiodothyropropionic acid on body weight, body mass index, and serum lipoproteins: a pilot prospective, randomized, controlled study.

CONTEXT: Widespread thyroid hormone actions offer the possibility of developing selective thyromimetic analogs with salutary metabolic properties. Consequently, effects of diiodothyropropionic acid (DITPA) on body weight, serum lipoproteins, and bone metabolism markers were studied in a prospective, controlled, double-blind 24-wk trial, which was primarily designed to assess treatment of stable chronic heart failure. DESIGN: Eighty-six patients (aged 66 +/- 11 yr, mean +/- sd) were randomized (1:2) to placebo or an escalating DITPA dose (90 to 180, 270, and 360 mg/d) over 8 wk until serum TSH was less than 0.02 mU/liter. Patients were studied at 2, 4, 6, 8, 16, and 24 wk and after 4 wk off study drug. Only 21 DITPA-treated and 27 placebo patients completed the full 24 wk of therapy. RESULTS: DITPA therapy lowered serum TSH levels and, to a lesser extent, serum T(3) and T(4), but there were no differences in clinical manifestations of thyrotoxicosis or hypothyroidism. Serum total and low-density lipoprotein cholesterol levels both decreased on DITPA; there was a transient decrease in triglycerides and no change in high-density lipoprotein cholesterol. DITPA therapy was associated with significant reduction in body weight, 12.5 lb at 24 wk. Increases in serum osteocalcin, N-telopeptide, and deoxypyridinoline levels were consistent with increased bone turnover on DITPA. CONCLUSION: This investigation of DITPA actions demonstrated its efficacy in reducing body weight and lowering total and low-density lipoprotein cholesterol levels. However, DITPA's adverse effects at doses used resulted in a high dropout rate and potentially dangerous skeletal actions were observed.

Two years of intensive glycemic control and left ventricular function in the Veterans Affairs Cooperative Study in Type 2 Diabetes Mellitus (VA CSDM).

OBJECTIVE: The Veterans Affairs Cooperative Study in Type 2 Diabetes Mellitus (VA CSDM) was a multicenter randomized prospective study of 153 male type 2 diabetic patients to assess the ability to sustain clinically significant glycemic separation between intensive and standard treatment arms. A trend toward an excess of combined cardiovascular events in the intensive treatment arm of this trial was reported earlier. The present analysis was done to evaluate the effect of 2 years of intensive glycemic control on the left ventricular (LV) function. RESEARCH DESIGN AND METHODS: The patients were randomized to intensive step treatment with insulin alone or with sulfonylurea (intensive treatment arm [INT], n = 75) or to standard once-daily insulin injection (standard treatment arm [STD], n = 78) treatment. A total of 136 patients (standard treatment arm [STD], n = 70; INT, n = 66) had radionuclide ventriculography at entry and at 24 months for the assessment of LV function. RESULTS: There was no difference in the mean LV ejection fraction (at entry: STD 57.1+/-9.51%; INT 58.1+/-8.7%; at 24 months: STD 57.3+/-10.8%, INT 59.5+/-10.7%), peak filling rate (at entry: STD 2.6+/-0.7 end diastolic volume per second, INT 2.4+/-0.8 end diastolic volume per second; at 24 months: STD 2.7+/-1.0 end diastolic volume per second, INT 2.5+/-0.7 end diastolic volume per second), or time to peak filling rate (at entry: STD 195.3+/-69.5 ms, INT 185.6 +/-62.4 ms; at 24 months: STD 182.6+/-64.8 ms, INT 179.2+/-61.2 ms) between the 2 treatment arms. A subgroup analysis of 104 patients (STD, n = 53; INT, n = 51) that omitted individuals with intervening cardiac events/revascularization or a change in cardioactive medications also showed no difference in the LV function at entry and at 24 months between the 2 groups. Abnormal LV ejection fraction at baseline predicted cardiac events (interval between cardiac beats [RR] = 2.5). CONCLUSIONS: Two years of intensive glycemic control does not affect the LV systolic or diastolic function in patients with type 2 diabetes.

Predicting recovery from acute asthma in an emergency diagnostic and treatment unit.

OBJECTIVE: Optimal use of emergency diagnostic and treatment unit (EDTU) resources for treatment of acute asthma should be facilitated by the selection of patients with a high probability of discharge from the EDTU. The study goal was to identify characteristics of the patient or exacerbation that could be used to predict recovery of pulmonary function within 12 hours. METHODS: Comprehensive cohort design in an urban public hospital. The subjects were 269 patients with moderately severe asthma exacerbations. Data were collected for historical and presenting features and response to treatment over 12 hours. Two outcomes were examined: 1) discharge from the EDTU and 2) achieving 50% predicted peak expiratory flow rate (PEFR) within 12 hours. RESULTS: The two outcomes showed good concordance. The third-treatment PEFR was found to be predictive of both discharge and reaching 50% predicted PEFR within 12 hours. Since the objective measure of reaching 50% predicted PEFR is more readily defined and thus more generalizable, the authors focused on this outcome when describing prediction zones. Patients with 40% or higher PEFR after third treatment had an 89% probability of reaching 50% predicted in 12 hours, while those with a third-treatment PEFR lower than 32% predicted had only a 22% probability. CONCLUSIONS: A simple objective measure of pulmonary function early in treatment discriminated among those with high, low, and intermediate probabilities of achieving a specified level of PEFR within 12 hours. Awareness of this probability could assist clinicians attempting to predict discharge from the EDTU and facilitate decision making regarding utilization of EDTU resources.

Emergency Department Observation Unit versus hospital inpatient care for a chronic asthmatic population: a randomized trial of health status outcome and cost.

OBJECTIVES: This study was designed to determine if an accelerated treatment protocol administered to acute asthmatics presenting to a Hospital Emergency Department Observation Unit (EDOU) can offset the need for inpatient admissions and reduce total cost per episode of care without sacrificing patient quality of life. METHODS: The authors used a prospective randomized controlled trial comparing postintervention patient quality of life for EDOU care versus standard inpatient care as measured by the standardized Medical Outcomes Study (MOS) SF-36 instrument. Other measures reported include: clinical status as measured by peak flow rates, total cost per treatment arm using microcosting techniques, and relapse-free survival 8 weeks after treatment. Eligible patients (n = 113) were assigned randomly to an EDOU or inpatient care from a consecutive sample of 250 acute asthmatic patients presenting to an urban hospital emergency department who could not resolve their acute asthma exacerbation after 3 hours of emergency department therapy. RESULTS: Patients assigned to the EDOU had lower mean costs of treatment (EDOU = $1,202 versus Hospital Inpatient = $2,247) and higher quality of life outcomes after intervention in five of eight domains measured by the MOS SF-36: Physical Functioning, Role Functioning-Emotional, Social Functioning, Mental Health, and Vitality. No differences were found in clinical outcomes as measured by peak flow rates or postintervention relapse-free survival. Univariate comparative findings were re-examined and confirmed through multivariable analysis when baseline SF-36 scores and postintervention peak expiratory flow rates clinical status were used as covariates. CONCLUSIONS: The study showed that the EDOU was a lower cost and more effective treatment alternative for a refractory asthmatic population presenting to the Emergency Department. Several baseline MOS SF-36 domains proved useful in predicting or validating posttreatment clinical status, relapse, and total costs of care. Outcome SF-36 domain scores were also useful in identifying patients with the most favorable clinical, cost, and relapse rate outcomes at the study endpoint.

Closed fractures of the tibial shaft. A meta-analysis of three methods of treatment.

We reviewed the literature to determine the clinical outcomes of the treatment of closed fractures of the tibial shaft with immobilization in a cast, open reduction with internal fixation, or fixation with an intramedullary rod. We reviewed 2372 reports of comparative trials and uncontrolled studies of series of patients published between 1966 and 1993. Nineteen reports, involving six controlled trials and twenty-seven groups of patients, met our inclusion criteria. A structured questionnaire was used to assess the quality of the literature in terms of the experimental design and the method of assessment of outcome. Outcomes from controlled trials were summarized with odds ratios and risk differences, and outcomes from case series were summarized by the medians of the reported results. The studies that were reviewed generally had few subjects and were poorly designed. The comparative trials showed treatment with a cast to be associated with a lower rate of superficial infection than open reduction and internal fixation (mean difference, -5.81 per cent; p = 0.02) and open reduction and internal fixation to be associated with a higher rate of union by twenty weeks than treatment with a cast (mean difference, -18.07 per cent; p = 0.008). There were no other significant associations. There were insufficient data for us to evaluate any aspect of functional status, level of pain, or other patient-reported outcomes of any of the methods of treatment. The results of the present review suggest that the data from the published literature are inadequate for decision-making with regard to the treatment of closed fractures of the tibia.

The family experiences of narcotic addicts and their subsequent parenting practices.

This survey study of male and female narcotic addicts participating in methadone maintenance programs examined self-reported retrospective data on parental behavior experienced by addicts during their adolescent years. These findings were contrasted with the addicts' self-report of their current parenting practices with their own adolescent children. Results showed addicts as perceiving their mothers as significantly more functional in their parenting practices than their fathers on indices of parental involvement, attachment, and responsibility. Significant parenting differences between addicts and their parents were reported for the three indices mentioned, as well as for parent discipline and punitive actions, with the addicts rating their current parenting practices as more effective than those of their parents. Reported parenting practices were further analyzed in the context of how the ratings of parental functioning were related to problems of drug and alcohol abuse exhibited in the home. Findings are discussed in terms of the implications for prevention and treatment approaches for addicts and their children.

Prediction of relapse within eight weeks after an acute asthma exacerbation in adults.

Associations between historical, presenting, and treatment-related characteristics and relapse within 8 weeks after a moderate to severe asthma exacerbation were studied in a cohort of 284 adult asthmatics. Data were collected prospectively, and a multivariate model was developed and internally validated. Within 10 days, only 8% had relapsed, increasing to 45% by 8 weeks. Three variables that could be identified at the time of discharge were independently associated with relapse. These included: having made three or more visits to an emergency department in the prior 6 months (hazard ratio (HR) = 2.3, 95% CI = 1.6-3.4); difficulty performing work or activities as a result of physical health in the 4 weeks prior (HR = 2.7, 95% CI = 1.6-4.3); discontinuing hospital-based treatment for the exacerbation within 24 hours without having achieved a peak expiratory flow rate of at least 50% of predicted (HR = 2.6, 95% CI = 1.6-4.1). These risk factors may help to identify patients with poorly controlled asthma in need of more intensive and comprehensive management.

A comparison between emergency diagnostic and treatment unit and inpatient care in the management of acute asthma.

BACKGROUND: Emergency diagnostic and treatment units (EDTUs) may provide an alternative to hospitalization for patients with reversible diseases, such as asthma, who fail to adequately respond to emergency department therapy. OBJECTIVE: To evaluate the medical and cost-effectiveness, patient satisfaction, and quality of life of patients receiving EDTU care for acute asthma compared with inpatient care. METHODS: A prospective, randomized clinical trial performed at 2 urban public hospitals enrolled patients with acute asthma (age range, 18-55 years) not meeting discharge criteria after 3 hours of emergency department therapy. Patients were treated with inhaled adrenergic agonists and steroids in an EDTU for up to 9 hours after randomization or with routine therapy in a hospital ward. Patients were followed up for 8 weeks. MAIN OUTCOME MEASURES: Discharge rate from the EDTU, length of stay, relapse rates, days missed from work or school, days incapacitated during waking hours, symptom-free days and nights, nocturnal awakenings, direct medical costs, patients satisfaction, and patient quality of life. RESULTS: The study consisted of 222 patients with asthma. Sixty-five patients (59%) treated in an EDTU were discharged home; the remainder were admitted to the hospital. There were no differences during the follow-up period in relapse rates (P = .74) or in any other morbidities between the EDTU and inpatient groups. There were significant differences in the length of stay, patient satisfaction, and quality of life favoring EDTU care. The mean (+/-SD) cost per patient in the EDTU group was $1202.79 +/- $1343.96, compared with $2247.32 +/- $1110.18 for the control group (P < .001). CONCLUSIONS: Treatment of selected patients with asthma in an EDTU results in the safe discharge of most such patients. This study suggests that quality gains and cost-effective measures can be achieved by the use of such units.

An evaluation of a chest pain diagnostic protocol to exclude acute cardiac ischemia in the emergency department.

BACKGROUND: Although accelerated diagnostic protocols are being increasingly used in emergency departments to diagnose acute cardiac ischemia, there have been no prospective evaluations of a chest pain diagnostic protocol with serial determinations of creatine kinase MB isoenzyme and mandatory exercise electrocardiography (ExECG). METHODS: Prospective cross-sectional study in which chest pain protocol results were compared with final (reference) diagnoses of acute cardiac ischemia (including acute myocardial infarction and unstable angina). Patients in need of hospital admission but at low probability (by a validated algorithm) for acute myocardial infarction were examined for exclusions: known coronary artery disease, cardiac complications, severe comorbidities, or inability to perform exercise testing. A 12-hour diagnostic protocol included serial measurements of creatine kinase MB, ECG, and clinical assessments followed by ExECG for those with negative initial serial testing. Reference diagnoses were established during hospitalization and diagnostic accuracy was assessed. RESULTS: The study group of 317 patients was 54% male and 65% black, and had a mean age of 46.6 years; 9.5% had a final diagnosis of acute cardiac ischemia. For this diagnosis, the protocol had a sensitivity of 90.0% (95% confidence interval, 72.3%-97.4%); specificity, 50.5% (95% confidence interval, 44.6%-56.4%); positive predictive value, 16.0%; and negative predictive value, 98.0%. Creatine kinase MB, serial ECGs, and ExECG each made a contribution to improved sensitivity and accuracy, whereas clinical reassessments were less discriminating, as indicated by protocol's receiver operating characteristic curve. CONCLUSIONS: A chest pain diagnostic protocol achieved high sensitivity and improved specificity over the standard emergency department workup. There were no adverse advents associated with early ExECG.

Feasibility of a rapid diagnostic protocol for an emergency department chest pain unit.

STUDY OBJECTIVE: To evaluate the applicability of a short-stay protocol for exclusion of acute ischemic heart disease without hospital admission and to analyze these results in the context of a conceptual model. METHODS: An observational study of patients who presented with chest pain to the emergency department of an 886-bed inner-city municipal hospital and who needed hospital admission to rule out acute myocardial infarction (AMI). Patients were assessed by ED attending physicians to determine eligibility for an alternative, 12-hour protocol in an ED chest pain observation unit (CPOU) followed by immediate exercise testing. Outcome measures were proportion of patients eligible for the short-stay protocol, risk factor profile, and reasons for exclusion. RESULTS: Of 500 patients screened, 446 had sufficient data points to determine protocol eligibility. Of these, 238 (53.3%; 95% confidence interval [CI], 48.7% to 57.9%) were found to have low probability for AMI. After study exclusion criteria were applied to the patient cohort, 63 patients (14.1%; 95% CI, 10.9% to 17.3%) were eligible for the protocol. The most common reasons for exclusion were history of coronary artery disease (46%) and inability to perform an interpretable exercise tolerance test (42%). CONCLUSION: Although most admitted patients with chest pain (53%) were at low probability for AMI, only a minority (14%) were eligible for a short-stay protocol that required patients to be free of known coronary artery disease and able to perform an exercise tolerance test. Factors affecting the operations and efficiency of a CPOU include clinical characteristics of the target patient population, protocol tests used, and hospital occupancy and reimbursement patterns.

Patient satisfaction with an emergency department chest pain observation unit.

STUDY OBJECTIVE: Patient satisfaction is an essential outcome measure in the diagnosis and treatment of acute chest pain in the emergency department. We compared patient satisfaction with the diagnostic protocol of a chest pain observation unit (CPOU) and standard inpatient hospitalization. METHODS: We prospectively studied patients who presented to the ED with chest pain and were found to have a low risk of acute myocardial infarction (AMI) but who still might have benefited from a diagnostic protocol to rule out AMI. Consenting patients (N = 104) were randomized to the CPOU (experimental) arm or the hospital inpatient (control) arm and assessed for satisfaction by means of an interview before hospital discharge. RESULTS: The CPOU protocol scored higher on four summary ratings of overall patient satisfaction. Correlations between overall satisfaction, number, and type of problems with care, and patient characteristics demonstrated content validity and revealed strengths and improvements that might be made in CPOUs. CONCLUSION: Patients were more satisfied with rapid diagnosis in the CPOU than with inpatient stays for acute chest pain. Our findings add important information to the standard practice of weighing clinical and cost outcomes between two medical care alternatives.

A twin study of the association of post-traumatic stress disorder and combat exposure with long-term socioeconomic status in Vietnam veterans.

This study examines the association between post-traumatic stress disorder (PTSD) and combat exposure with the socioeconomic status of 2210 male monozygotic veteran twin pairs in 1987. In the unadjusted analysis on individuals, modest correlations indicated that those with PTSD were more likely to have been divorced, and less likely to be currently employed or to achieve high status in income, education or occupation. In the crude analysis of veterans not suffering from PTSD, there were small positive correlations between combat level experienced and the likelihood of ever being married, ever being divorced, and the number of years employed at the current job. However, when we examined identical twins discordant for PTSD, and adjusted for pre-military and military service factors, only unemployment remained significant. Likewise, in combat-discordant twins, no significant effects on the socioeconomic indicators were seen. We conclude that PTSD and combat experience in Southeast Asia have not had a major impact on the socioeconomic status of veterans.

Insomnia in Vietnam era veteran twins: influence of genes and combat experience.

Genetic and environmental influences on insomnia were studied in 2,825 pairs of Vietnam era veteran male twins. The self-reported sleep problems studied included trouble falling asleep, trouble staying asleep, waking often, waking tired and a composite sleep scale. Twin correlations for each of the sleep problems were larger in monozygotic than in dizygotic pairs, with heritability estimates ranging from 0.21 to 0.42. There was no effect of common familial environment. Phenotypic correlations for combat experience and sleep problems were small, ranging from 0.00 to 0.09, with no differences seen in monozygotic and dizygotic twins. When the effects of genes and combat exposure were evaluated simultaneously, there was a significant genetic contribution to all sleep measures, but combat exposure was significantly associated only with overall sleep quality, waking often and having trouble staying asleep.

A metabolically stable analog of 1,4,5-inositol trisphosphate activates a novel K+ conductance in pyramidal cells of the rat hippocampal slice.

IP(s)3, a metabolically stable analog of 1,4,5-inositol trisphosphate (IP3), inhibited action potential firing when injected into hippocampal pyramidal cells. This effect was associated with decreased input resistance, a more negative resting potential, outward rectification at depolarized potentials, and an afterhyperpolarization. The response to IP(s)3 was unaffected by antagonists of Na+, Ca2+, and Cl- conductances, but was sensitive to changes in extracellular K+ concentration. The IP(s)3-induced conductance was voltage-dependent, was activated in 10 ms with depolarization, and was blocked by extracellular Ba2+ or intracellular Ca2+ chelation. It was not suppressed by other K+ conductance antagonists. Thus, IP(s)3 may activate a novel K+ conductance in CA1 pyramidal cells. IP3 itself did not elicit this conductance, suggesting it may be rapidly metabolized in these cells.

Calcium-dependent pirenzepine-sensitive muscarinic response in the rat hippocampal slice.

Using intracellular recording techniques in the rat hippocampal slice, we observed that muscarinic agonists produce a transient Ca2+-dependent depolarization that may be related to the phosphatidylinositol cycle. First, it was more readily produced by muscarinic group A agonists, which strongly enhance the breakdown of phosphatidylinositol-4,5-bisphosphate (PIP2) than by group B agonists, which are less efficacious. Second, the Ca2+-dependent response was blocked by pirenzepine (PRZ), a selective muscarinic antagonist that blocks PIP2 breakdown in forebrain. Both group A and group B muscarinic agonists caused equivalent maintained levels of depolarization that were relatively insensitive to PRZ. The data suggest that the Ca2+-dependent response is fundamentally unlike other muscarinic responses that have been described in hippocampus.

Papain effects on rat hippocampal neurons in the slice preparation.

Intracellular recordings were made from the CA1 stratum pyramidale region of rat hippocampal slices. Papain was applied to the cells via bath perfusion, and its effects on membrane properties, synaptic potentials and responses to pressure application of gamma-aminobutyric acid (GABA) were assessed. Papain did not markedly affect neuronal input resistance, resting potential or action potentials with treatment times lasting over one hour. Synaptic potentials were initially enhanced and then gradually abolished, with the fast inhibitory postsynaptic potential being the most sensitive and the late, potassium-dependent hyperpolarization being the most resistant to enzyme. Responses to GABA were enhanced by papain, the GABA-activated conductance increased, and a slow depolarizing wave appeared which resembled the effect caused by pentobarbital on these neurons. This study indicates that the use of papain in the acutely dissociated neuron preparation is not responsible for the dramatic increase in resting input resistance seen in these neurons. The GABA-activated conductance may be affected by the enzyme.

Cholinergic phosphatidylinositol modulation of inhibitory, G protein-linked neurotransmitter actions: electrophysiological studies in rat hippocampus.

In electrophysiological studies using the rat hippocampal slice preparation, cholinergic agonists and phorbol 12,13-diacetate, a stimulator of protein kinase C, block the inhibitory actions of baclofen, a gamma-aminobutyric acid B receptor agonist, and adenosine. Relative potencies of cholinergic agonists in stimulating the phosphatidylinositol system, as measured biochemically, parallel their activity in blocking adenosine assessed electrophysiologically. Electrical stimulation of cholinergic afferents also reverses adenosine's inhibitory action. These findings indicate that stimulation of protein kinase C by the phosphatidylinositol system mediates cholinergic blockade of adenosine and baclofen. As these inhibitory agonists act by way of receptors linked to GTP-binding proteins, protein kinase C's inactivation of the GTP-binding protein involved may account for this cholinergic action.

Sodium-potassium pump inhibitors increase neuronal excitability in the rat hippocampal slice: role of a Ca2+-dependent conductance.

We have used the rat hippocampal slice preparation as a model system for studying the epileptogenic consequences of a reduction in neuronal Na+-K+ pump activity. The cardiac glycosides (CGs) strophanthidin and dihydroouabain were used to inhibit the pump. These drugs had readily reversible effects, provided they were not applied for longer than 15-20 min. Hippocampal CA1 pyramidal cells were studied with intracellular recordings; population spike responses and changes in extracellular potassium concentration ([K+]o) were also measured in some experiments. This investigation focused on the possibility that intrinsic neuronal properties are affected by Na+-K+ pump inhibitors. The CGs altered the CA1 population response evoked by an orthodromic stimulus from a single spike to an epileptiform burst. Measurements of [K+]o showed that doses of CGs sufficient to cause bursting were associated with only minor (less than 1 mM) changes in resting [K+]o. However, the rate of K+ clearance from the extracellular space was moderately slowed, confirming that a decrease in pump activity had occurred. Intracellular recording indicated that CG application resulted in a small depolarization and apparent increase in resting input resistance of CA1 neurons. Although CGs caused a decrease in fast gamma-aminobutyric acid mediated inhibitory postsynaptic potentials (IPSPs), CGs could also enhance the latter part of the epileptiform burst induced by picrotoxin, an antagonist of these IPSPs. Since intrinsic Ca2+ conductances comprise a significant part of the burst, this suggested the possibility that Na+-K+ pump inhibitors affected an intrinsic neuronal conductance. CGs decreased the threshold for activation of Ca2+ spikes (recorded in TTX and TEA) without enhancing the spikes themselves, indicating that a voltage-dependent subthreshold conductance might be involved. The action of CGs on Ca2+ spike threshold could not be mimicked by increasing [K+]o up to 10 mM. A variety of K+ conductance antagonists, including TEA, 4-AP, Ba2+ (in zero Ca2+), and carbachol were ineffective in preventing the CG-induced threshold shift of the Ca2+ spike. The shift was also seen in the presence of a choline-substituted low Na+ saline. Enhancement of a slow inward Ca2+ current is a possible mechanism for the decrease in Ca2+ spike threshold; however, it is impossible to use the Ca2+ spike as an assay when testing the effects of blocking Ca2+ conductances. Therefore, we studied the influence of CGs on the membrane current-voltage (I-V) curve, since persistent voltage-dependent conductances appear as nonlinearities in the I-V plot obtained under current clamp.(ABSTRACT TRUNCATED AT 400 WORDS)