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Biomedical subjects

N Berman

Publications and source records attributed to N Berman.

At least 55 records · Page 3Linked to original sources

Evaluating telephone T.A.L.K.

A telephone communication instrument, Telephone T.A.L.K. (Trust, Assert, Listen, and K.I.S.S.--Know, Inquire, Solve, Stroke), was developed for a pediatric residency program for teaching and assessment purposes. Residents had call reviews with faculty as an intervention. Eight residents had pre-intervention calls and 3 call reviews. At post-intervention, Trust and Listening skills showed significant improvement and Assert and K.I.S.S. near significance. Ranking frequencies of items for calls of 30 residents indicated which items to select for future teaching.

Clinical Competence↗

Exercise training improves left ventricular diastolic filling in patients with dilated cardiomyopathy. Clinical and prognostic implications.

BACKGROUND: Patients with dilated cardiomyopathy (DCM) often have left ventricular (LV) diastolic dysfunction that can precede the development of systolic dysfunction. Recent reports showed that exercise training (ET) improves the exercise capacity of these patients. Although this improvement is primarily due to peripheral adaptations, the contribution of LV diastolic filling has not been well defined. The purpose of this study was to determine whether ET can induce changes in LV diastolic filling that can account for an increase in exercise capacity and whether these changes can influence prognosis. METHODS AND RESULTS: We prospectively studied 55 consecutive patients (mean age, 55 +/- 7 years) with DCM. Patients were randomized into a training group (36 patients) or a control untrained group (19 patients) and matched for clinical and functional characteristics. All patients underwent a pulsed Doppler echocardiographic study, a radionuclide angiographic study, and a cardiopulmonary exercise test before and after a 2-month ET program. On the basis of the Doppler LV diastolic filling pattern at the beginning of the study, patients were prospectively divided into three subgroups: A (restrictive pattern), B ("normal" pattern), and C (abnormal relaxation pattern). In the trained group, peak VO2 (+12%; P < .0001), peak workload (+8.5%; P < .005), and lactic acidosis threshold (+12%; P < .0001) were significantly increased after training without changes in LV ejection fraction. However, only subgroup C demonstrated significant improvement in peak VO2 (+15%; P < .005). No changes were observed in the untrained group. In the trained subgroups a significant increase in rapid filling fraction (RFF), peak filling rate (PFR), peak early filling velocity (E), and E/A ratio was noted. A significant decrease in atrial filling fraction (AFF), peak atrial filling velocity (A), deceleration time of early filling velocity (EDT), and isovolumic relaxation time (IVRT) was observed only in subgroup C. No changes were found in untrained subgroups. A good correlation was found between Doppler and radionuclide LV diastolic filling parameters before and after training (P < .0001). Multiple stepwise regression analysis demonstrated that pretraining E/A ratio (P < .0001) and peak heart rate (P < .0002) were positive predictors of pretraining peak VO2. Posttraining increase in exercise tolerance (P < .0001) and increase in E/A ratio (P < .0001) were the strongest predictors of an increase in peak VO2. The independent predictors of cardiac events were a greater RFF and a shorter IVRT and EDT. Stepwise logistic regression showed that Doppler LV diastolic filling patterns are independent predictors of overall cardiac events (P = .02), and restrictive pattern has a worse prognosis compared with B (P = .04) and C (P = .007). However, ET did not reach statistical significance (P = .54) as a predictor of cardiac events. CONCLUSIONS: These data demonstrate that ET induces significant improvement in exercise capacity only in patients with DCM and a pattern of abnormal LV relaxation. The improvement in peak VO2 is significantly correlated with an increase in peak early filling rate and peak filling rate as well as a decrease in atrial filling rate. Doppler echocardiography may be a valuable tool in the prognostic assessment of patients with DCM who will benefit from exercise training.

Blood Flow Velocity↗

Tobacco prevention education in a pediatric residency program.

OBJECTIVE: To report the impact of a tobacco intervention in a pediatric residency program. DESIGN: Residents and faculty took pretests and posttests and follow-up surveys 6 months later. SETTING: An urban, university-affiliated, county medical center. INTERVENTION: An educational program of three presentations, written materials, and a bulletin board. RESULTS: Significant improvement in counseling and confidence in counseling. Perceptions of barriers to counseling, specifically expertise, time limitation, and doubts regarding counseling effectiveness diminished. Residents changed less than faculty in particular areas. There were no differences between the posttests and the follow-up survey 6 months later. CONCLUSIONS: Pediatric health professionals in an academic setting, given an educational program, will change their behaviors and attitudes about their role in counseling patients about tobacco use.

Adult↗

Clonidine plus haloperidol in the treatment of schizophrenia/psychosis.

Because of the evidence for increased norepinephrine (NE) production in psychotic patients, we studied the effects of combining the alpha 2-adrenergic agonist clonidine with haloperidol for the treatment of schizophrenic psychosis. Twelve hospitalized schizophrenic patients were taken off their antipsychotic medication for 2 to 4 weeks before double-blind treatment with haloperidol (20 mg/day) combined with either clonidine or placebo. The group receiving clonidine was significantly more improved on the thought disorder subscale of the Brief Psychiatric Rating Scale (p = 0.02). The groups differed initially in the level of negative symptoms, but not controlling for this difference statistically by analysis of covariance did not change the finding with regard to the superiority of combining clonidine with haloperidol. We conclude that larger treatment trials of combining haloperidol with clonidine are warranted.

Adrenergic alpha-Agonists↗

Pharmacokinetics, bioefficacy, and safety of sublingual testosterone cyclodextrin in hypogonadal men: comparison to testosterone enanthate--a clinical research center study.

We studied and compared the pharmacokinetics and bioefficacy of two doses of sublingual testosterone cyclodextrin (SLT; 2.5 and 5.0 mg, administered three times per day) with testosterone enanthate (TE; 200 mg) given once every 20 days by im injections over a 60-day study period in 63 hypogonadal men. After SLT administration, serum testosterone (T) levels peaked at 20 min and then fell, reaching baseline levels by 360 min. The calculated half-lives were 60.3 +/- 7.5 and 68.8 +/- 5.0 min after a single dose of 2.5 and 5.0 mg SLT, respectively. The mean area under curve (AUC) of serum T was computed over 20-day periods for the 3 treatment groups. The mean net AUC of serum T after TE administration was about 4- and 2-fold higher than that in the 2.5 and 5 mg groups over the last 20 days. Serum estradiol and dihydrotestosterone followed the same pattern as serum T. Serum estradiol to T ratios decreased after T replacement in all 3 groups, whereas serum dihydrotestosterone to T ratios were not significantly changed by T treatment. Suppression of serum LH and FSH levels was more marked in the patients treated with TE than in those given SLT. Similarly, serum sex hormone-binding globulin levels showed significant decreases with androgen replacement only in the TE and SLT 5.0 mg range groups. There were no significant adverse effects based on comprehensive physical examinations, urea, electrolytes, and renal or liver function tests. Hematocrit levels increased in the TE-treated group, but remained slightly lower than baseline levels in the SLT groups. Serum high density lipoprotein cholesterol showed a small, but significant, decrease with time of treatment in all groups. Despite the differences in the AUC of serum T levels achieved by different androgen replacement therapies, all patients showed significant improvements in sexual motivation and performance, with no significant difference between the treatment groups. We conclude that SLT may be a useful addition to the currently available injectable and transdermal delivery systems for treatment of hypogonadal men. Because of the ease of administration, rapid reversibility of effects, and lower AUC of serum T levels achieved compared to those of TE injections, SLT may be especially suitable for treatment of boys with delayed puberty and older men with androgen deficiency.

Administration, Sublingual↗

Depressive mania versus agitated depression: biogenic amine and hypothalamic-pituitary-adrenocortical function.

The existence of mixed affective states challenges the idea of specific biological abnormalities in depression and mania. We compared biogenic amines and hypothalamic-pituitary-adrenocortical (HPA) function in mixed manic (n = 8), pure manic (n = 11), agitated bipolar depressed (n = 20), and nonagitated bipolar depressed (n = 27) inpatients (Research Diagnostic Criteria). Mixed manics met Research Diagnostic Criteria for primary manic episodes and also met criteria for major depressive episodes except for duration. The norepinephrine metabolite methoxyhydroxy phenthylene glycol (MHPG) was higher in cerebrospinal fluid from mixed manic than from agitated depressed patients, consistent with differences previously reported between the overall samples of depressed and manic patients. Similarly, patients in a mixed state had higher urinary excretion of norepinephrine (NE) and elevated output of NE relative to its metabolites. HPA activity was similar in mixed manic and agitated depressed patients. These data suggest that mixed manics combine certain biological abnormalities considered to be characteristic of mania and of depression.

Adult↗

Lead exposure in vivo alters the fertility potential of sperm in vitro.

Lead is a male reproductive toxicant. We previously reported that in vivo lead exposure results in a suppression of the hypothalamic-pituitary-testicular axis in male rats. This study was designed to assess if lead exposure in vivo alters (1) the ability of sperm to fertilize ova in vitro, (2) the morphology of the spermatozoa, and (3) the relationship of cell types in the testes as evaluated by DNA flow cytometry. Male Sprague-Dawley rats were given access to either lead-free (0.0%) or 0.3% lead acetate-containing water for 14, 30, or 60 days starting at 100 days of age. On the day of termination, sperm harvested from the caudae epididymis were incubated with eggs harvested from superovulated non-lead-treated females and were scored for stages of penetration. Sperm were also studied by electron microscopy. The testes of animals treated for 60 days were processed for DNA flow cytometry. The overall distribution of the stages of fertilization was significantly different between control and lead-treated animals. The lead-treated groups fertilized significantly fewer eggs than did sperm from the control group. Increased duration of exposure to lead acetate did not result in a more significant percentage of eggs not fertilized. No ultrastructural changes were noted in the spermatozoa of animals treated with lead compared to control animals. There were no differences in the histogram patterns of testicular cells collected from lead-treated animals and control animals. We conclude that lead alters sperm function by altering the hormonal control of spermatogenesis rather than by direct toxic action on spermatozoa.

Administration, Oral↗

Drug-induced actions on brain neurotransmitter systems and changes in the behaviors and emotions of depressed patients.

Despite cumulative evidence that the tricyclic drugs result in significant changes in the functioning of brain serotonergic (5-HT) and nordrenergic (NE) systems, such changes have not been found to be associated with recovery from depression. Based upon evidence that the 5-HT and NE systems were associated with different emotions, it was hypothesized that changes in these systems were associated with different components of behavior in drug-responsive patients and not with changes in the "whole" disorder. Findings from this multihospital study of 104 unipolar and bipolar depressed patients showed early drug-associated reductions in anxiety and hostility in treatment responders to precede changes in motor retardation and depressed mood. Adopting this approach of looking for relationships between changes in components of major depression and changes in neurotransmitter system function, decreases in 5-HT and NE metabolite concentrations in cerebrospinal fluid (CSF) in patients treated with tricyclics, were found to be correlated with changes in specific behaviors. Results indicated the following: (1) drug-induced changes in the 5-HT system to be associated with mood aspects, notably anxiety, and depressed mood; changes in NE primarily with the psychomotor, secondarily with the mood components of the depressed state; (2) the pattern of relationships between changes in 5-HT and in mood in the unipolar was different than that in the bipolar subtype. The results indicate that in determining the relationships of biochemical changes to behavioral ones, that it is important to take into account the type of depression (bipolar or unipolar), as well as examining individually and over time those components that make up the disorder of depression. These results support evidence that tricyclics have multiple behavioral actions, that response is mediated through changes in specific behaviors and that this approach warrants further application in prospective studies of antidepressant drug mechanisms and their therapeutic actions.

Amitriptyline↗

Evidence for pancreatic pacemaker for insulin oscillations in low-frequency range.

Circulating insulin concentrations oscillate in regular fashion, with periods that fall into a high-frequency (period of 5-17 min) or low-frequency (period of 50-150 min) range. Only the high-frequency oscillations have so far been reported in vitro, suggesting that these derive from a primary pancreatic source. This study tested whether the low-frequency insulin oscillations could also be identified in vitro. Rat islets of Langerhans were perifused for 20 h using RPMI medium with 5.5 mM glucose. Perifusate fractions were collected at 9.9-min intervals. Mean insulin concentrations at the outset were 21.4 +/- 2.9 microU/ml, increased to 32.5 +/- 4.6 (P < 0.05) between 13 and 17 h after the start of perifusion, and then either leveled off or decreased to baseline. Superimposed on this general trend, we found sustained insulin oscillations with a period of 50-100 min. The mean amplitude was 14.2 +/- 4.2 microU/ml, and the amplitude/mean ratio was 64.6 +/- 12%. Spectral analysis revealed significant peaks at periods that were close to either 50 or 100 min and a smaller peak at 24-37 min. These data, using in vitro methodology and constant glucose concentrations, indicate the presence of sustained, spontaneous, low-frequency, ultradian insulin oscillations in the pancreatic islets. This provides evidence for a pancreatic component that may participate in the previously described in vivo ultradian insulin oscillations. This finding may also provide a mechanism for the apparent escape from glucose entrainment of serum insulin oscillations in non-insulin-dependent diabetes mellitus.

Activity Cycles↗

Cognitive functioning in a mildly to moderately depressed geriatric sample: relationship to chronological age.

The neuropsychological performance of three age cohorts of depressed patients (46-59, 60-69, and 70-85) was compared with the performance of age-matched control subjects to determine whether advancing age potentiates the effect of depression on cognition. Depression and increasing age did not interact to produce more pronounced cognitive deterioration in our unmedicated, medically healthy, well-educated outpatients diagnosed with mild to moderate major depression. Test findings suggest that presence of mild to moderate depression may result in premature "aging" of specific cognitive abilities (such as nonverbal memory, word generation, and categorization), but once the seventh decade is reached, cognition in depressed and nondepressed individuals appears to be comparable.

Age Factors↗

Cerebral abnormalities in myotonic dystrophy. Cerebral blood flow, magnetic resonance imaging, and neuropsychological tests.

OBJECTIVE: To study cerebral abnormalities in myotonic dystrophy (MD) and determine the different patterns of cerebral function in patients with MD with maternal (mMD) vs paternal (pMD) inheritance. DESIGN: Patients with MD and normal controls were studied with neuropsychological testing, magnetic resonance imaging, and single photon emission computed tomography. SETTING: Studies were done at Harbor-UCLA Medical Center, Torrance, Calif. PATIENTS AND OTHER PARTICIPANTS: Twenty-two consecutive-patients with MD, 11 of whom had pMD and eight mMD, and 10 normal controls were studied. Diagnoses were made on the basis of family history, electromyography, and clinical examinations. Normal subjects in the same age distribution were studied for comparisons. RESULTS: We found significantly lower neuropsychological performance and cerebral blood flow in the patients with MD compared with the controls. Patients with mMD had statistically lower scores on IQ tests and more extensive cerebral hypoperfusion when compared with those with pMD. Changes in cerebral blood flow were most severe in the frontal and temporoparietal association cortex. Cerebral blood blow measures strongly correlated with IQ. CONCLUSIONS: Patients with mMD had earlier onset of disease and lower IQs than the pMD group. The pattern of cerebral perfusion in the mMD group was consistent with a diffuse brain injury, while cerebral perfusion in pMD showed more minor changes. These findings emphasize the cognitive differences between mMD and pMD.

Adolescent↗

Specificity of mixed affective states: clinical comparison of dysphoric mania and agitated depression.

To investigate the clinical specificity of mixed affective states, we compared clinical characteristics of mixed (dysphoric) manics to those of agitated depressed patients. The subjects were inpatients studied in the NIMH Clinical Research Branch Collaborative Study on the Psychobiology of Depression, Biological Studies. Behavior and symptom ratings for depressive and manic symptoms were obtained during a 15-day placebo washout period. Patients with agitated depression were compared to those in acute manic episodes with and without prominent depressive symptoms. Mania ratings clearly distinguished agitated depressed from mixed manic patients. Concerning depression and general psychopathology, mixed manics had more severe agitation, hostility and cognitive impairment than did agitated depressed patients. Depressed mood and anxiety did not differ significantly between the two groups. Nurse ratings for depression and anxiety, based on ward behavior, were similar for mixed manics and agitated depressed patients, while physician-interview rated depression and anxiety were higher in agitated depressed patients. These data support the existence of superimposed depressive and manic syndromes in mixed manics.

Anxiety Disorders↗

Sotalol and type IA drugs in combination prevent recurrence of sustained ventricular tachycardia.

OBJECTIVES: This study assessed the efficacy of the combination of sotalol and either quinidine or procainamide in preventing sustained ventricular tachycardia inducibility and recurrence and prospectively evaluated the ability of the drug combination to prevent ventricular tachycardia recurrence when the arrhythmia remained inducible but was modified. BACKGROUND: Individual antiarrhythmic drugs are often ineffective in preventing the induction and recurrence of sustained ventricular tachycardia. Beta-adrenergic blockade and prolongation of refractoriness may be important components of successful antiarrhythmic therapy in patients with ventricular tachycardia. We reasoned that the combination of sotalol, which has beta-adrenergic blocking properties and prolonged ventricular refractoriness, and quinidine or procainamide, two agents that slow conduction and prolong refractory periods, would be effective therapy in such patients. METHODS: We administered low dose sotalol (205 +/- 84 mg/day) plus quinidine sulfate (1,278 +/- 479 mg/day) or procainamide (2,393 +/- 1,423 mg/day) to 50 patients with spontaneous sustained ventricular tachycardia or fibrillation and inducible ventricular tachycardia. RESULTS: In 21 (46%) of 46 patients, ventricular tachycardia was rendered noninducible at electrophysiologic study (group I), and in 17 patients (37%), inducible tachycardia was modified according to prospectively identified criteria (group II), for a combined 83% response rate. Ventricular refractory periods increased from 252 +/- 24 to 316 +/- 28 ms and from 265 +/- 33 to 316 +/- 24 ms in groups I and II, respectively (p < 0.001), but from 234 +/- 19 to only 286 +/- 13 ms in the group of patients with unmodified ventricular tachycardia inducibility (n = 8, group III, p < 0.001). Cycle length of induced ventricular tachycardia slowed from 324 +/- 62 to 432 +/- 70 ms in group II patients (p < 0.001), whereas it slowed less in group III patients (279 +/- 73 to 314 +/- 63 ms, p = NS). Forty-two of the 50 patients (including all patients in groups I and II) were discharged on treatment with the drug combination. After 25 +/- 19 months of follow-up, the actuarial recurrence rate of ventricular tachycardia was 6%, 6% and 11% at 1, 2 and 3 years, respectively. Among patients in whom this drug combination was unsuccessful at electrophysiologic study (group III) and in those who received alternative therapy after combination therapy was discontinued because of side effects, actuarial recurrence rates were 9%, 14% and 32% at 1, 2 and 3 years, respectively. CONCLUSIONS: The combination of sotalol plus quinidine or procainamide markedly prolongs ventricular refractoriness and slows induced ventricular tachycardia in a high proportion of patients. Patients with modified or noninducible tachycardia have a low rate of arrhythmia recurrence in follow-up. This drug combination deserves further evaluation.

Aged↗

Studies of catecholamine metabolism in schizophrenia/psychosis--I.

Acutely psychotic schizophrenic patients not taking antipsychotic medications and control subjects were studied before and during treatment with debrisoquin (DBQ), an inhibitor of monoamine oxidase, which does not penetrate into brain. Homovanillic acid (HVA) and 3-methoxy-4-hydroxyphenylglycol (MHPG) were measured in plasma, urine, and cerebrospinal fluid (CSF). Significant differences between patients and control subjects were more easily discerned during treatment with DBQ. In patients, HVA was increased in plasma but not in urine or CSF, although MHPG was increased in all three fluids. There were many significant correlations between plasma MHPG and HVA levels and clinical ratings of psychoticism. Plasma MHPG correlated positively with both the severity of positive and negative symptoms and plasma HVA correlated only with positive symptom severity. These data suggest that both dopamine and norepinephrine (NE) metabolism are disturbed in acutely psychotic schizophrenic patients; disturbed NE metabolism may relate to negative symptoms as well.

Adult↗

Studies of catecholamine metabolism in schizophrenia/psychosis--II.

Acutely psychotic schizophrenic patients were maintained on debrisoquin (DBQ) throughout 5 weeks of treatment with haloperidol. Treatment with haloperidol caused initial increases in urinary homovanillic acid (HVA) output that returned toward baseline by the 5th week. During haloperidol treatment, plasma levels of HVA tended to decrease, concurrent with increased renal clearance of HVA. Plasma 3-methoxy-4-hydroxyphenylglycol (MHPG) levels and urinary MHPG output both decreased over the course of treatment. The differences in HVA and MHPG metabolism suggest differential effects of treatment on dopamine and norepinephrine systems. Neuroleptic treatment also abolished the marked morning decreases in plasma HVA concentrations (reported in part I).

Adult↗

A mathematical model of oscillatory insulin secretion.

Insulin is secreted in sustained oscillatory fashion from isolated islets of Langerhans. This finding has led to the assumption of an underlying synchronizing process that coordinates insulin oscillations. This assumption was tested by developing a mathematical model of oscillatory insulin secretion in which we included degree of synchrony as a parameter. We first evaluated insulin oscillations in perifused isolated rat islets, using spectral analysis to determine their regularity and frequency. A parsimonious mathematical model was developed to account for these characteristics. The model postulates a group of secretory units discharging at discrete intervals with the same underlying period. Variation from two sources, phase differences between units (synchrony) and regularity within units, is introduced by adding two normally distributed random variables with standard deviations (Sg and Si, respectively) to the secretory period. Sets of 100 simulations for different values of Sg and Si were run. Results of the simulations suggest that the system tolerates a relatively large degree of asynchrony yet still demonstrates regularity of oscillations on spectral analysis. Comparison with perifusion data suggests that a moderate degree of asynchrony between islets can best account for the pattern of insulin oscillations observed. This model provides a theoretical basis for the study of mechanisms for insulin oscillations.

Adenoma↗

Hypothalamic-pituitary-adrenocortical function in mixed and pure mania.

There is little information about hypothalamic-pituitary-adrenocortical (HPA) axis function in mania, particularly in mixed states. We therefore investigated HPA function and its relationship to clinical state in 19 hospitalized manic patients meeting Schedule for Affective Disorders and Schizophrenia - Research Diagnostic Criteria for acute manic episodes, compared patients with and without a mixed presentation, and examined correlations between HPA activity and behavior. Data were available from 13-16 patients. Behavioral and biochemical analyses were conducted during a 15-d placebo period. Patients with mania had elevated cerebrospinal fluid (CSF) and urinary free cortisol excretion compared with healthy subjects, and did not differ from depressed patients in any cortisol measures. Mixed manics had significantly higher morning plasma cortisol, postdexamethasone plasma cortisol and CSF cortisol than pure manics. Five of 7 mixed manics and 3 of 9 pure manics were dexamethasone suppression test (DST) nonsuppressors. Afternoon plasma cortisol and CSF cortisol correlated significantly with depressed mood; urinary free cortisol correlated with anxiety. None of the cortisol measures correlated with mania or agitation scores. These data suggest that increased cortisol secretion is a characteristic of the depressed state in mixed manics, although pure manics may also have increased DST nonsuppression.

Adult↗