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Biomedical subjects

E Frank

Publications and source records attributed to E Frank.

At least 19 recordsLinked to original sources

Comparison of cefuroxime axetil and doxycycline in the treatment of early Lyme disease.

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.

Adolescent

Diminished nocturnal penile tumescence in depression: a replication study.

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.

Adult

Development of cutaneous and proprioceptive afferent projections in the chick spinal cord.

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.

Afferent Pathways

Detection and possible origins of aminomalonic acid in protein hydrolysates.

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.

Amino Acid Sequence

Electroencephalographic sleep in spousal bereavement and bereavement-related depression of late life.

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.

Aged

Five-year outcome for maintenance therapies in recurrent 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.

Adult

Magnetic resonance imaging analysis of extremely slow flow in a model shunt system.

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.

Cerebrospinal Fluid Pressure

Maintenance treatment and psychobiologic correlates of endogenous subtypes.

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.

Adult

Imipramine and weight gain during the long-term treatment of recurrent depression.

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.

Adult

Electroencephalographic sleep studies in depressed outpatients treated with interpersonal psychotherapy: I. Baseline studies in responders and nonresponders.

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.

Adolescent

Electroencephalographic sleep studies in depressed outpatients treated with interpersonal psychotherapy: II. Longitudinal studies at baseline and recovery.

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.

Adolescent

Shifts in affective balance during cognitive therapy of major depression.

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.

Adaptation, Psychological

Life stress and treatment course of recurrent depression: 1. Response during index episode.

Research on treatment course and outcome in depression is mixed with respect to the implications of life stress. Several concerns are addressed in a prospective study of 91 individuals treated for recurrent depression. Specific forms of stress occurring before treatment entry predicted a poor clinical response both after 16 weeks and after a more extended intervention period. Specific forms of stress occurring during the 1st 6 weeks of treatment also predicted poor response after 16 weeks and after the extended intervention period. Severe stress occurring early in treatment predicted a longer time to attain relief for treatment responders. Concepts underlying the idea that stress-related disorders have a better clinical outcome are discussed, and it is proposed that life stress has different implications for individuals with and without recurrent depression.

Adjustment Disorders

Combined pharmacotherapy and psychotherapy in the acute and continuation treatment of elderly patients with recurrent major depression: a preliminary report.

OBJECTIVE: The authors examined the rate of response to the combination of nortriptyline and interpersonal psychotherapy for acute and continuation treatment of elderly patients with recurrent major depression. METHOD: The subjects were 73 elderly patients, 61 of whom completed treatment. Nortriptyline steady-state blood levels were maintained at 80-120 ng/ml, and interpersonal psychotherapy was administered weekly for 9.1 weeks (medium) of acute therapy and was decreased from biweekly to triweekly during 16 weeks of continuation therapy. During acute treatment nonresponding patients also received brief adjunctive pharmacotherapy with lithium or perphenazine. RESULTS: Of the 61 subjects given adequate trials of nortriptyline and interpersonal psychotherapy, 48 (78.7%) achieved full remission (Hamilton depression rating of 10 or lower over 16 weeks of continuation therapy), 10 patients (16.4%) did not respond (Hamilton rating never below 15), and three achieved only partial remission (Hamilton rating of 11-14). Early versus late onset was not associated with a difference in response rate. During the placebo-controlled, double-blind transition to maintenance therapy, 19 (76.0%) of the 25 patients randomly assigned to placebo maintenance conditions showed continued recovery and six relapsed. None of the 24 patients assigned to nortriptyline conditions relapsed. CONCLUSIONS: Use of nortriptyline plus interpersonal psychotherapy for 9.1 weeks (median) of acute and 16 weeks of continuation therapy appears to be associated with good response and relatively low attrition but about a 25% chance of relapse during double-blind discontinuation of nortriptyline. These data require confirmation in a controlled clinical trial of acute and continuation therapy.

Age Factors

Socioeconomic status and health: how education, income, and occupation contribute to risk factors for cardiovascular disease.

BACKGROUND: Socioeconomic status (SES) is usually measured by determining education, income, occupation, or a composite of these dimensions. Although education is the most commonly used measure of SES in epidemiological studies, no investigators in the United States have conducted an empirical analysis quantifying the relative impact of each separate dimension of SES on risk factors for disease. METHODS: Using data on 2380 participants from the Stanford Five-City Project (85% White, non-Hispanic), we examined the independent contribution of education, income, and occupation to a set of cardiovascular disease risk factors (cigarette smoking, systolic and diastolic blood pressure, and total and high-density lipoprotein cholesterol). RESULTS: The relationship between these SES measures and risk factors was strongest and most consistent for education, showing higher risk associated with lower levels of education. Using a forward selection model that allowed for inclusion of all three SES measures after adjustment for age and time of survey, education was the only measure that was significantly associated with the risk factors (P less than .05). CONCLUSION: If economics or time dictate that a single parameter of SES be chosen and if the research hypothesis does not dictate otherwise, higher education may be the best SES predictor of good health.

Adult

Relationship of pharmacologic compliance to long-term prophylaxis in recurrent depression.

This report examines the relationship of long-term medication compliance (as measured by stability of level/dose ratios and total blood level averages) to prophylaxis in recurrent unipolar patients. Of the 53 patients assigned to active imipramine conditions in a long-term maintenance treatment protocol, 42 were evaluated as clearly compliant, 8 were clearly noncompliant, and 3 were not classifiable. We examined a number of demographic and clinical variables in an attempt to find possible predictors of compliance. No differences were observed between compliant and noncompliant patients with respect to sex, age at screening, age at the onset of their recurrent unipolar illness, duration of the index episode, number of previous episodes, bipolar II vs. recurrent unipolar subtype, endogenous vs. nonendogenous subtype, or baseline severity of depression as assessed by the Hamilton Rating Scale for Depression. However, medication compliance was found to be significantly associated with effective prophylaxis. There was a significantly larger proportion (6 of 12) of noncompliant patients among those experiencing a recurrence in one of the two active medication conditions than among those who remained well for 3 years (2 of 28). The value associated with this difference was p = .04. We conclude that effective prophylaxis is strongly related to stability of medication blood levels which fall within the therapeutic range.

Adult