Biomedical subjects
Publications and source records attributed to E Frank.
This study surveyed 4158 adults residing in two control cities of the Stanford Five-City Project. Analysis of five cross-sectional surveys (conducted in 1979 through 1990) demonstrated improvements in respondents' general cardiovascular disease risk factor knowledge and behaviors. Cholesterol-related knowledge and behavior showed particularly marked improvements.
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This article launches a special WESTERN JOURNAL OF MEDICINE effort to help prevent disease and disability. Erica Frank, MD, MPH, an Assistant Professor in the Department of Community and Preventive Medicine and Department of Medicine, Emory University School of Medicine, and Adjunct Professor at the Emory University School of Public Health, Atlanta, Georgia, will head the endeavor. The goals are to present scientific foundations for prevention and to provide practical ways to improve patients' lives. This first article addresses smoking cessation. We may think that we know it all, but we may not, and patients do not: about 25% of Americans smoke, and more than half of persons who ever smoked began their fatal habit before they were 18 years old. Side-stream smoke affects adults and children adversely, too, causing inflammation, infection, and cancer. Smokers need to stop smoking, and young people need to not start. Dr Frank's review is accompanied by a page for patients. It debunks myths and is designed to be duplicated so patients can leave their physician's office with a new lease on life in hand. Look for future prevention-oriented articles in this series that feature science and patient education.
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The study of nocturnal penile tumescence (NPT) is frequently used to evaluate male erectile dysfunction. Buckling force, a measure of rigidity, is an important part of this evaluation, but its reliability is unknown. Accordingly, we studied the reliability of buckling force measurement and the stability of "maximum buckling force" between consecutive NPT series repeated in the same subject. For individual subjects, we correlated buckling forces for separate episodes of sleep-related tumescence that were of comparable fullness (0-100%) as rated by a technician's visual estimates. For healthy control subjects, test-retest correlations were > 0.8 both within-night and across study series separated by an average of 70 weeks. In depressed men, correlations within nights were > 0.9, but fell to 0.64 across study series separated by an average of 21 weeks. Despite the high reliability of buckling force measurement, we found little stability of "maximum buckling force" between NPT series for individual subjects. Considerable variability in the maximum degree of penile rigidity was seen over time despite a constant level of reported daytime erectile function. We conclude that although penile rigidity is one of the more important variables in the assessment of male erectile dysfunction and can be measured reliably, the instability of maximum rigidity during sleep-related erections suggests that it is, at best, an imprecise correlate of daytime erectile function.
OBJECTIVE: To compare the efficacy of cefuroxime axetil and doxycycline in the treatment of patients with Lyme disease associated with erythema migrans. DESIGN: Randomized, multicenter, investigator-blinded clinical trial with clinical evaluations during treatment (8 to 12 days) and at 1 to 5 days and 1, 3, 6, 9, and 12 months post-treatment. SETTING: Three university referral centers and one private practice. PATIENTS: A total of 123 patients with physician-documented erythema migrans. INTERVENTION: Patients were treated orally for 20 days with either cefuroxime axetil, 500 mg twice daily (63 patients), or doxycycline, 100 mg three times daily (60 patients). MEASUREMENTS: Resolution of erythema migrans and of signs and symptoms related to early Lyme disease as well as prevention of late Lyme disease. RESULTS: A satisfactory clinical outcome (success or improvement) was achieved in 51 of 55 (93%) evaluable patients treated with cefuroxime axetil and in 45 of 51 (88%) patients treated with doxycycline (difference, 5%, 95% Cl, -5% to 14%). The only complication at 1 month post-treatment was Lyme arthritis in one patient who received doxycycline. Of the patients with satisfactory outcomes at 1 month post-treatment who were evaluable at 1 year post-treatment, a satisfactory outcome was achieved in 43 of 48 (90%) and in 35 of 38 (92%) patients treated with cefuroxime axetil and doxycycline, respectively (difference, -2%; Cl, -12% to 7%). Lyme arthritis did not develop in any patient after 1 month post-treatment, whereas peripheral neuropathy was suspected in one patient treated with cefuroxime axetil. Thirty percent of patients treated with cefuroxime axetil and 32% of those treated with doxycycline had one or more drug-related adverse events. Doxycycline was associated with more photo-sensitivity reactions (15% compared with 0%; P = 0.001) and cefuroxime axetil with more diarrhea (21% compared with 7%; P = 0.035) and Jarisch-Herxheimer reactions (29% compared with 8%; P = 0.005). CONCLUSIONS: Cefuroxime axetil is well tolerated and appears to be equally as effective as doxycycline in the treating of early Lyme disease and in preventing the subsequent development of late Lyme disease.
A descriptive study was conducted in a new sample of 51 men with DSM-III-R research diagnostic criteria (RDC) major depression in order to replicate earlier observations that measures of nocturnal penile tumescence (NPT) and penile rigidity are disturbed in depressive states. When compared to both the age-equated patient (n = 34) and normal control (n = 28) groups reported in our 1988 study, the new sample manifested significant abnormalities of NPT and diminished penile rigidity. Such disturbances were not, however, significantly correlated with psychobiological indicators of severe or endogenous depression.
Muscle and cutaneous nerves were individually labeled with DiI in chick embryos to examine the development of sensory afferent arborizations in the spinal cord. Initially, cutaneous and muscle arbors were similar; both types first entered the spinal gray matter at stage 28-29 (embryonic day (E) 6). Differences in projections were first observed by late stage 34 (E8.5): muscle afferent collaterals extended almost unbranched to the level of motoneuronal dendrites while cutaneous afferents branched frequently and remained within the dorsal horn. Projections of putative small caliber axons into laminae 1 and 2, located laterally in the chick, did not develop until E13-14.
Aminomalonic acid (Ama) was first detected in alkaline hydrolysates of proteins in 1984. In this work we describe our search for the origin of aminomalonic acid in alkaline hydrolysates of proteins. We have developed a technique for quantitation of aminomalonic acid based upon gas chromatography/mass spectrometry. Using this technique, we find approximately 0.3 Ama/1000 amino acids in hydrolysates of Escherichia coli protein. We have demonstrated that Ama is not formed from any of the 20 major amino acids during the hydrolysis procedure. Furthermore, the amount of Ama found does not depend on the presence of small amounts of O2 during the hydrolysis. Thus far, we have not been able to demonstrate an artifactual origin for Ama. The results described above suggest that Ama may indeed be a constituent of proteins before the hydrolysis procedure. Possible origins of Ama include errors in protein synthesis and oxidative damage to amino acid residues in proteins.
Sixteen male outpatients with major depression and 20 age-equated healthy controls were awakened from rapid eye movement (REM) sleep between 1:30 and 3:30 AM, and the rapidity of return to REM sleep was determined. The time it took to return to REM sleep was reduced in depressives compared with controls: 61.6 (17.9 SD) min versus 80.6 (24.9 SD) min, respectively (p = 0.01). The time elapsed until the return to REM sleep was significantly correlated with baseline REM latency in controls (but not depressives). In contrast, return to REM time was significantly correlated with depression severity scores in depressives (but not controls). There was no evidence to support the hypothesis that the more rapid return to REM sleep in depression was caused by a slow wave sleep deficit. The mechanism underlying the rapid return of REM sleep in depression thus may be related to a severity-linked disturbance, such as a proposed increase in REM "pressure."
Although spousal bereavement in late life is common and frequently leads to major depression, the boundary between bereavement without a depressive syndrome and bereavement-related depression has been insufficiently studied from a physiological perspective. Because other forms of depression are associated with physiological changes, including sleep, we have attempted to clarify the relationship of bereavement and bereavement-related depression by investigating electroencephalographic (EEG) sleep in 31 elderly volunteers with recent spousal bereavement, stratified by the presence (n = 15) or the absence (n = 16) of major depression (Research Diagnostic Criteria). Entry into the study was limited to volunteers without a personal history of psychiatric disorder. As hypothesized, bereaved subjects with major depression had significantly lower sleep efficiency, more early morning awakening, shorter rapid eye movement (REM) latency, greater REM sleep percent, and lower rates of delta wave generation in the first nonREM (NREM) period, compared with bereaved subjects without depression. Furthermore, the sleep of bereaved subjects with single-episode major depression resembled that of elderly patients with recurrent unipolar major depression (n = 15) on measures noted above. Sleep in bereavement without depression was similar to that of 15 healthy control subjects (neither bereaved nor depressed). These findings suggest that the current DSM-III-R concept of uncomplicated bereavement is not confirmed, as the sleep patterns of subjects who develop a depressive syndrome in the context of bereavement, many of whom might be considered to have "uncomplicated bereavement" by DSM-III-R standards, are identical to sleep patterns found in major depressive episodes. To our knowledge, this is the first study of EEG sleep in spousal bereavement with and without major depression.
After conducting a randomized, 3-year maintenance trial in 128 patients with recurrent depression who had responded to combined short-term and continuation treatment with imipramine hydrochloride and interpersonal psychotherapy, we asked those individuals who survived the 3-year trial receiving active medication (with or without psychotherapy) to continue in a 2-year additional randomized trial of active medication vs placebo. The question was whether maintaining antidepressant medication at the dosage used to treat the acute episode beyond 3 years would continue to provide a significant prophylactic effect compared with medication discontinuation after the 3 years of effective maintenance treatment. Survival analysis demonstrated a highly significant continued prophylactic effect for active imipramine hydrochloride treatment maintained at an average dose of 200 mg. We conclude that active imipramine treatment is an effective means of preventing recurrence beyond 3 years and that patients with previous episodes less than 2 1/2 years apart, therefore, merit continued prophylaxis for at least 5 years.
Shunt malfunction is common and its diagnosis may require invasive testing that may be inaccurate or result in complications. Magnetic resonance imaging (MRI) may prove to be a useful noninvasive test of shunt function as it has been shown that MRI is capable of measuring cerebrospinal fluid (CSF) flows from 2 ml/h to 40 ml/h in model systems. Since flows in functioning shunt systems can be less than 2 ml/h, MRI must be sensitive enough to detect flow in this range in order to be a valid test for shunt function. Continuing previous studies, we have studied MRI flow-related enhancement at flow rates from 0 to 2 ml/h. Multiple spin echo scans (TR2000, TE20) were made through a specialized section of tubing in a model shunt system. The intensity of the MRI signal at points known to demonstrate maximal flow-related enhancement was measured. A linear relationship was demonstrated between signal intensity and flow as low as 0.8 ml/h. These results add support to the concept that MRI is sensitive enough to detect the lowest flows present in functioning shunt systems and therefore may be useful as a noninvasive test of shunt function.
Although the endogenous subtype in depression has long been thought to have prognostic significance, to date no long-term maintenance treatment trial has examined the relative risk of recurrence in patients meeting criteria for this subtype. Following our analysis of the primary hypotheses regarding the relationship between treatment assignment and outcome [Frank et al. (1990) Arch. Gen. Psychiatry 47, 1093-1099], we now examine psychobiologic and maintenance treatment correlates for these recurrent unipolar patients grouped according to melancholic, endogenous but not melancholic, and non-endogenous subtype at index presentation. No differences were observed among the three groups in overall survival time; however, in the 52 patients who received psychotherapy without active medication during the maintenance phase, length of survival was inversely related to endogeneity. Interestingly, no differences were found among the three groups in EEG sleep parameters when studied either at baseline or following recovery.
The recently completed long-term maintenance trial of full-dose imipramine for recurrent unipolar disorder provided an opportunity to examine the extent to which such doses (200-300 mg daily) are associated with persistent and adverse side effects, particularly weight change. In 115 patients we monitored weight change during the three-year maintenance treatment phase to the point of trial completion, recurrence or termination. No differences were noted between individuals receiving active medication (average gain of 5.8 lbs. during an average treatment period of 725 days) versus those randomized to the 'no-drug' cells (average gain of 2.8 lbs. during an average treatment period of 422 days). Numerous other factors such as body mass index, previous weight gain and gender did not play a differential role in establishing why some individuals gained weight during long-term treatment of depression regardless of specific treatment.
Electroencephalographic (EEG) sleep measures have been examined as predictors of therapeutic response in patients with major depression. Although some studies have reported that EEG sleep measures are predictive of a favorable outcome with medications, two recent studies found no differences in the baseline sleep characteristics of responders and nonresponders to psychotherapy. To clarify this issue, we compared baseline EEG sleep in a group of patients with recurrent depression who responded to interpersonal psychotherapy (n = 19) and a comparable group who did not respond (n = 18). Baseline ratings of depression severity did not differ in the groups, but some differences in baseline sleep were noted. Psychotherapy nonresponders had longer sleep latencies, lower sleep efficiency, and increased automated measures of phasic rapid eye movement (REM) activity. In addition, the two groups had different EEG sleep adaptation patterns for REM latency and phasic REM density measures across the two study nights. These preliminary results suggest that baseline EEG sleep patterns, as well as the pattern of laboratory adaptation, may differ for depressed patients who respond to psychotherapy and those who do not.
Electroencephalographic (EEG) sleep studies may help to identify persistent versus episodic biological characteristics of major depressive disorder. This report examines longitudinal EEG sleep studies in depressed patients treated with psychotherapy alone. Nineteen patients were studied during a symptomatic baseline period and again during early remission after treatment with interpersonal psychotherapy (IPT). EEG sleep findings at baseline were not markedly abnormal, but they were similar to those in other published studies of young adult outpatients. No changes were found in visually scored EEG sleep measures between depression and early remission. Automated measures of delta sleep and rapid eye movement (REM) activity showed small state-related changes, with delta activity increasing from baseline to remission, and automated REM measures decreasing. Strong baseline-remission correlations were noted for most sleep measures, including slow wave sleep, phasic REM activity, and automated delta EEG counts; measures of sleep continuity and tonic REM sleep were not strongly correlated. Consistent adaptation effects across nights were observed for sleep continuity and REM measures during each clinical phase. These findings support the hypothesis that most visually scored EEG sleep measures, as well as the sleep adaptation process, are stable through the acute episode of depression, at least into early symptomatic remission. They also suggest that finer-grained automated analyses of delta and REM activity may provide more sensitive tools for examining state-related changes.
Thirty-two outpatient depressives were treated by experienced therapists during a 16- to 20-week, 20- to 24-session cognitive-behavioral therapy (CBT) protocol. Patients were classified as CBT responders (n = 22) or nonresponders (n = 10) on the basis of independent clinical ratings of Hamilton (1960) depression severity. Point and confidence interval estimation procedures yielded results consistent with hypotheses derived from the states-of-mind (SOM; Schwartz & Garamoni, 1986) model. At posttreatment, CBT responders shifted the balance of positivity and negativity to the optimal range, whereas nonresponders remained in a predominantly negative SOM. Response status was related more strongly to change in positivity than in negativity. Findings support the view that clinical response to CBT depends on reducing negativity and increasing positivity until an optimal balance is achieved.