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Biomedical subjects

E Frank

Publications and source records attributed to E Frank.

At least 199 records · Page 11Linked to original sources

Bipolar depression: an underestimated treatment challenge.

We sought to determine whether depressive and mixed/cycling episodes were as responsive to standardized pharmacotherapeutic interventions as were manic episodes in bipolar 1 patients. As part of the Maintenance Therapies in Bipolar Disorder (MH29618, E. Frank, PI) study, forty-two acutely ill bipolar 1 patients who had been randomly assigned to one of two preliminary phase non-pharmacologic treatment strategies (interpersonal and social rhythm therapy [IPSRT] or a standard medication clinic approach) were treated according to a standardized pharmacotherapeutic protocol. Symptom severity was measured weekly with the Hamilton Depression Rating Scale and the Bech-Rafaelsen Mania Scale in order to assess symptomatic remission. Survival analysis with the proportional hazards model was performed on time to remission. Manic patients were significantly more likely to achieve clinical remission than the depressed patients (100 vs. 59%) and did so significantly more rapidly. The difference in proportion remitting and time to remission between the depressed and mixed/cycling groups was not statistically significant. No significant effect for non-pharmacologic treatment assignment was found. These results point to the need to develop more effective treatments for bipolar depression. They also suggest that psychotherapy has a limited impact in the acute phase treatment of bipolar episodes.

Adult↗

Generalized covariance-adjusted discriminants: perspective and application.

When discriminant analysis is used in practice for assessing the usefulness of diagnostic markers, the lack of control over covariates motivates the need for their adjustment in the analysis. This necessity for adjustment arises especially when the researcher's aim is classification based on a set of diagnostic markers and is not based on a set of covariates for which there exists known heterogeneity among the subjects with respect to the groups under consideration. The traditional covariance-adjusted approach is restrictive for such applications in that they assume linear covariates and a normal distribution for the the feature vector. Further, there is no available method for variable selection in using such covariance-adjusted models. In this paper, we generalize the traditional covariance-adjusted model to a general normal and logistic model, where these generalized models not only relax the distributional assumptions on the feature vector but also allow for nonlinear covariates. Exact and asymptotic tests are also derived for the problem of variable selection for these new models. The methodology is illustrated with both simulated data and an actual data set from a psychiatric study on using the Social Rhythm Metric for patients with anxiety disorders.

Activities of Daily Living↗

Using interpersonal psychotherapy (IPT) in a combined psychotherapy/medication research protocol with depressed elders. A descriptive report with case vignettes.

One hundred eighty subjects at least 60 years of age with recurrent unipolar major depression were recruited to participate in a depression treatment protocol. All patients received drug therapy with nortriptyline (NT) and interpersonal psychotherapy (IPT) with an experienced clinician. Acutely, 81% of subjects showed a full response to combined treatment. In the initial 127 subjects, the most common problem areas in therapy were role transition (41%), interpersonal disputes (34.5%), and grief (23%). Case vignettes are presented and discussed. The combination of IPT and NT showed a powerful antidepressant effect. IPT was readily adaptable to the needs of depressed elders.

Aged↗

Is life stress more likely to provoke depressive episodes in women than in men?

One of the most consistent findings in psychiatric research is that rates of major depression are at least twofold higher among women than among men. Although there is considerable agreement in the literature that life events play a role in producing, triggering, or maintaining episodes of depression, less is known about the relationship among gender, life events, and depression. In the present study, we compared the rates, focus ("interpersonal" vs. "non-interpersonal"), and timing of stressful life experiences reported in rigorous interviews of male and female patients with unipolar recurrent depression and nondepressed contrast subjects. Consistent with hypotheses, female patients were more likely to experience stressful life experiences than their male counterparts; rates of stressful life experiences did not differ between female and male controls. Unexpectedly, rates of interpersonal stress did not differ among males and females regardless of patient or control status. We also found no significant differences in the timing of pre-onset events: stressful events were generally concentrated in the period immediately preceding onset for both men and women. Thus, although these data suggest that life stress may play a larger role in the provocation of recurrent episodes of depression for women than for men, there do not seem to be sex differences in the extent to which interpersonal vs. noninterpersonal events and difficulties are associated with depression onset or in the temporal distribution of events. Implications of these results are discussed in the context of research on other putative factors contributing to gender differences in rates of depression.

Adult↗

Restriction in cell fates of developing spinal cord cells transplanted to neural crest pathways.

At early neural tube stages, individual stem cells can generate neural crest cells as well as dorsal or ventral spinal cord cells. To determine whether this pluripotency is lost as development proceeds, we back-transplanted quail spinal cells from different developmental stages and different spinal locations into the crest migratory pathways of st 16-20 chicken host embryos. The transplanted spinal cells from st 27 dorsal cord and st 18 ventral cord differentiated within the new crest environment into sensory and sympathetic neurons, satellite and Schwann cells, and melanocytes. St 27 ventral cells still generated several crest derivatives but not sensory or sympathetic neurons. This loss in ability to produce neurons correlates with the end of neurogenesis in ventral cord. The end of neurogenesis in the cord, therefore, results from an intrinsic change in the potential of spinal neuroepithelial cells to generate neurons.

Animals↗

Quality of life in elderly patients with recurrent major depression: a factor analysis of the General Life Functioning Scale.

Quality of life profiles measured by the General Life Functioning (GLF) Scale were examined in elderly patients with recurrent major depression, before and during combined treatment with nortriptyline and interpersonal psychotherapy. The study group included 110 patients, 91 recovered and 19 nonrecovered, aged 60 to 80 years, suffering from at least their second lifetime episode of major depression. Repeated measures analysis of covariance (with Hamilton and Beck depression scores as time-dependent covariates) was used to compare the temporal course of overall GLF scores for the recovered and the nonrecovered groups. Factor analysis was used to examine whether the GLF Scale yielded an overall score and measured specific aspects of well-being and coping. There were significant differences in the overall GLF scores between recovered and nonrecovered patients, with the differences increasing from week 8 of treatment onward. Analysis revealed significant improvements in quality of life, as measured by overall GLF scores, over the course of treatment in both recovered and nonrecovered patients. Even when changes in Hamilton and Beck depression ratings were controlled for in the statistical analysis, improvements in GLF scores were found to be greater in recovered than in nonrecovered patients. Thus, the GLF measures more than change in level of depression. Its overall score also has high internal reliability.

Adaptation, Psychological↗

Current and future management of serious skin and skin-structure infections.

The purpose of this study was to compare in a randomized, open-label clinical study, the efficacy and safety of cefepime (1 g every 12 hours) with that of ceftazidime (1 g every 8 hours) in patients with serious skin and skin-structure infections. Of 298 patients enrolled in the study, 130 with serious skin and skin-structure infections were evaluable. Demographics and underlying medical conditions were comparable in both groups. The most common infections were cellulitis, abscesses, ulcers, and postoperative wound infections. The most common pathogens isolated were Staphylococcus aureus, group A streptococci, Enterobacteriaceae, and Pseudomonas aeruginosa. Duration of therapy in the 93 patients treated with cefepime was 3-18 days and in the 37 ceftazidime-treated patients was 4-16 days. Pathogen bacteriologic response rates were high: 92% (124 of 135) of pathogens were eradicated by cefepime and 95% (55 of 58) by ceftazidime. Clinical response rates were satisfactory in 88% (82 of 93) of cefepime-treated patients and in 89% (33 of 37) of ceftazidime-treated patients. Adverse events occurred with similar frequency in both groups. Events probably related to study drugs affected 3% (6 of 198) of patients treated with cefepime and 4% (4 of 100) of ceftazidime-treated patients. Cefepime, a new parenteral cephalosporin administered every 12 hours, is an extremely well tolerated and effective alternative to ceftazidime given every 8 hours for the treatment of serious skin and skin-structure infections.

Bacteria↗

Prevention advice rates of women and men physicians.

BACKGROUND: As the number of women in medicine and the emphasis on prevention and primary care increase in the United States, it is important to know the extent to which female and male physicians advise patients about prevention. It is also important to know whether any gender-based differences are attributable to women's higher rates of choosing primary care specialties. Prior studies have examined only small populations of physicians, limited physician specialties, or few prevention-related outcomes. METHODS: Telephone survey from a systematic random sample of the Physician Masterfile maintained by the American Medical Association. One thousand US physicians (167 women and 833 men); a 48% response rate. Self-reported frequency with which physicians review patients' health behaviors and initiate counseling about unhealthy behaviors. RESULTS: Of the surveyed physicians, 44% stated that they always reviewed the patient health behaviors in question, and 36% usually systematically counseled patients when unhealthy behaviors were known. Female physicians were significantly more likely than were male physicians to report systematic counseling about unhealthy behaviors (52% vs 37.8%, P < .001, chi 2). We also analyzed our data by adjusting for age and including only family and general physicians and internists. After these adjustments, gender-based differences remained in the direction of female physicians being more likely than male physicians to report reviewing patients' health practices and providing systematic counseling, although these differences no longer reached statistical significance. Gender-related differences were greatest for more sensitive behaviors (ie, drug use and sexual behaviors). Primary care physicians were more likely than other physicians to review and counsel patients about health behaviors. This specialty-based difference was more significant among male than among female physicians. CONCLUSIONS: In this random sample, although all physicians counseled patients inconsistently about prevention, female physicians reported systematically counseling patients more than did male physicians, and primary care physicians reviewed and counseled more often than did physicians in other specialties.

Adult↗

Anxiety among widowed elders: is it distinct from depression and grief?

The purpose of this study was to test the validity and utility of distinguishing symptoms of anxiety from those of depression and grief in recently spousally bereaved elders. We also examined pathways from baseline (six months or less post-spousal death) to follow-up (12 and 18 months post-death) levels of anxiety, depression and grief-related symptoms. Baseline and follow-up data were available from 56 recently widowed elderly subjects recruited for an investigation of physiological changes in bereavement. Confirmatory factor analyses indicated that a model in which anxiety was specified as a third factor, apart from depression and grief factors, fit the data well and significantly better than either the one or two factor models. Path analyses revealed that both baseline severity of grief and anxiety had significant lagged effects and predicted follow-up severity of depression. Symptoms of anxiety appeared distinct from those of depression and grief, and the anxiety, depression and grief factors differentially predicted subsequent symptomatology. These findings suggest a need for more specific identification and treatment of anxiety, depression and grief symptoms within the context of late-life spousal bereavement.

Aged↗

Longitudinal effects of nortriptyline on EEG sleep and the likelihood of recurrence in elderly depressed patients.

Our objectives were to determine the effects of nortriptyline and placebo on subjective and EEG sleep measures over 1 year of maintenance therapy in elderly depressed patients and to determine the relationship of such effects to recurrence in nortriptyline or placebo-treated patients during maintenance therapy. EEG and subjective sleep assessments were conducted before and during a maintenance therapy study of patients suffering from major depression. During acute treatment all patients received nortriptyline plus interpersonal psychotherapy (IPT). During maintenance treatment patients were randomly assigned to double-blind treatment in one of four cells: nortriptyline with IPT; nortriptyline with medication clinic (no IPT); placebo with IPT; or placebo with medication clinic. Sleep evaluations were conducted at one point before treatment, one point following remission during continuation nortriptyline/IPT treatment, and at three time points after random assignment to maintenance treatment. The setting was the sleep laboratory of the outpatient depression treatment clinic, and subjects were a convenience sample of media-recruited and clinically referred elderly outpatient depressed patients (n = 72). Complete sleep analyses were conducted for 21 nortriptyline- and 10 placebo-treated patients throughout 1 year of maintenance treatment. The main outcome measures were subjective and EEG sleep measures and the recurrence of major depression. Our results show that nortriptyline acutely and persistently decreased REM sleep, increased phasic REM activity, decreased sleep apnea, and had no effect on periodic limb movements during sleep. Recurrence on maintenance nortriptyline was associated with lower phasic REM activity during early continuation therapy, but EEG sleep measures did not predict recurrence during placebo maintenance therapy. Patients treated with nortriptyline had a lower recurrence rate than those treated with placebo. Better subjective sleep quality and maintenance IPT were associated with a lower rate of recurrence regardless of nortriptyline treatment. It seems that nortriptyline has persistent effects on REM sleep and sleep apnea in elderly depressed patients. Maintenance nortriptyline, maintenance IPT, good subjective sleep quality, and high-phasic REM activity are associated with a reduced likelihood of the recurrence of depression during maintenance therapy.

Aged↗

An updated basal body temperature method.

Basal body temperature (BBT) readings are handicapped as fertility predictors by exogenous influences on women's temperatures, many of which could be adjusted for by the presence of a non-cycling control. We, a married, cohabiting couple, tracked our BBTs for two months. We found substantial temperature covariability. When there were difficult-to-explain changes in the female partner's temperature, similar changes in the male partner's temperature suggested that these fluctuations were not attributable to ovulation. Additionally, a clear mid-cycle widening of our temperature gap suggested that ovulation had occurred. This is a limited trial of a new method. However, the potential for substantially improving the accuracy and usefulness of a globally utilized method, coupled with its inexpensiveness, ease, and painlessness, call for a larger study.

Adult↗

A critical period for the influence of peripheral targets on the central projections of developing sensory neurons.

During development, the projections that sensory neurons make within the spinal cord are influenced by the specific targets they contact in the periphery. If sensory ganglia normally supplying principally cutaneous targets are forced to grow into limb muscles, in early stage tadpoles, many sensory neurons within these ganglia innervate limb muscles and subsequently develop spinal projections appropriate for muscle spindle afferents. If the same procedure is performed with adult frogs, however, these novel projections do not form. In this study, we have determined the developmental stages at which this sensitivity to peripheral targets exists. Axons from sensory neurons in thoracic (largely cutaneous) dorsal root ganglia were re-routed into the front leg at various stages through metamorphosis, and the central spinal projections of these re-routed fibers were assessed with HRP labeling. We found that thoracic sensory axons could be made to project to limb muscles throughout development, but that the central projections of these neurons were only appropriate for spindle afferents if the fibers were re-routed before stage XVIII, shortly before metamorphic climax. Because sensory neurons can regenerate specifically into the appropriate spinal laminae even in adult frogs, these results suggest that changes in either the DRG or the arm musculature occur by stage XVII so that DRG neurons cannot respond to novel peripheral targets.

Afferent Pathways↗

The prophylaxis of depressive episodes in recurrent depression following discontinuation of drug therapy: integrating psychological and biological factors.

Models of long-term treatment in recurrent unipolar illness ideally should integrate both psychological and biological factors. In earlier reports we noted that high treatment specificity (i.e. good-quality maintenance interpersonal psychotherapy) and high delta sleep ratio were each associated with significantly increased wellness intervals in the absence of pharmacotherapy among patients with recurrent unipolar depression. To determine how these specific factors when taken together are related to length of survival time, we examined the concurrent effects of treatment specificity and delta sleep ratio on wellness intervals using survival analysis. We found significant effects of both treatment specificity and delta ratio on survival time. Seventy-three per cent of the patients in the high treatment specificity/high delta ratio group survived the 3-year trial, while 44% of the patients in the low delta ratio but high treatment specificity group survived. None of those rated low on both variables survived. We also found an effect for individual clinicians on treatment specificity and survival time and noted that the prophylactic effect of treatment specificity was maintained even within subsets of therapists grouped by their patients' survival times. Secondary analyses revealed an effect of patient attitudes on treatment specificity and survival time, although, when taken together, treatment specificity was the only variable remaining significantly associated with outcome. We conclude that patients remain well the longest when pre-treatment delta sleep parameters more closely approximate those of non-depressed individuals and when monthly psychotherapy is of higher quality. The key finding is that high specificity is of significant prophylactic benefit even for patients with a biological vulnerability for recurrence. We also conclude that in addition to therapists, patient expectancies contribute to treatment specificity, and high treatment specificity is, in turn, reflected in longer times to recurrence.

Adult↗

Effects of positive and negative life events on time to depression onset: an analysis of additivity and timing.

While the relationship of life events to depression onset has occupied researchers for almost a quarter of a century, few studies have attempted to account for either the temporal patterning of events relative to episode onset, or, the effect of multiple events in a study period. In this report, we attempt to address the issues of timing of events, multiple events (both positive and negative) and multiple aspects (both positivity and negativity) of single events on latency time to depression onset, while simultaneously accounting for possible decay in the effects of events over time. We use the proportional hazards approach to model the effects of life events and consider modelling the change in impact of events with the passage of time. After interviewing 142 recurrent unipolar patients using the Life Events and Difficulties Schedule, we rated severity and positivity of life events reported during the 6-month period prior to onset. As we hypothesized, additional life events occurring after an initial provoking agent level event significantly alter the risk of illness onset. Additional severely threatening events decrease the time to onset, but positive events do not appear to delay onset. Interestingly, seemingly neutral events had a highly significant effect in shortening the time to onset. We note the many limitations imposed on the interpretation of these findings related to the selected group of subjects studied and encourage those who have more generalizable data to apply these methods of analysis.

Adult↗

Life stress and treatment course of recurrent depression: II. Postrecovery associations with attrition, symptom course, and recurrence over 3 years.

Life stress was studied in relation to postrecovery attrition, symptom course, and recurrence of depression over 3 years. Participants were 67 individuals with recurrent depression who had responded to treatment. Life stress was assessed for the prior 12 weeks at acute treatment entry (T1), initial recovery (T2), and after 17 weeks of sustained recovery (T3). Severe life events at T1 predicted greater attrition, a more favorable postrecovery symptom course, and a lower likelihood of recurrence over 3 years. Life stress at T2 was not predictive of outcomes. Finally, undesirable life events at T3 tended to predict a worse symptom course and a higher likelihood of recurrence, particularly for individuals on medication. The findings are discussed in terms of (a) different processes influenced by life stress over time and (b) limitations of existing longitudinal research for studying the effects of life stress over prolonged intervals.

Adult↗

A proposed technique for intraoperative measurement of cervical spine stiffness.

OBJECTIVE: Classically cervical biomechanical data have been obtained using cadaver models. Few methods exist for in vivo measurement of cervical biomechanics. A technique for intraoperative measurement of cervical motion segment stiffness (load-axial displacement) has been developed, enabling load/displacement data to be obtained during surgery at the spinal levels operated on and at adjacent cervical levels. METHODS: The instrument used for measuring motion segment stiffness was a vertebral retractor equipped with displacement and strain transducers and designed to be placed over the shafts of Caspar distraction screws. Stiffness was measured under simulated anterior cervical surgical conditions. RESULTS: A preliminary study deciphering axial cervical spine load/displacement data on 12 cadavers was performed with this instrument. Using a distraction load of 88.8640 N, axial displacements of 2.110 +/- 0.258 mm (mean +/- standard error of the mean) at C3-C4, 2.367 +/- 0.304 mm at C4-C5, and 2.207 +/- 0.238 mm at C5-C6 were found. When data were evaluated for age, there was a significant decrease in stiffness with advancing age in two of the three spinal segments tested (P < 0.05 for C3-C4, P < 0.04 for C4-C5, P < 0.12 for C5-C6), which correlated with previous studies. CONCLUSION: These results suggest that this technique may be useful in assessing intraoperative motion-segment stability.

Adult↗

Near-fatal status asthmaticus induced by nasal insufflation of cocaine.

Asthma and cocaine abuse are both common. While cocaine has been associated with numerous pulmonary complications, only smoking cocaine has been clearly linked to the precipitation of life-threatening exacerbations of asthma. We report a case in which nasal insufflation of cocaine ("snorting") triggered a near-fatal asthmatic attack.

Administration, Intranasal↗