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Biomedical subjects

S Mazumdar

Publications and source records attributed to S Mazumdar.

At least 73 records · Page 4Linked to original sources

The posttreatment illness course of depression in bereaved elders. High relapse/recurrence rates.

Losing close attachments through death in late life is common and can lead to depression. Previous work has shown the clinical benefits of treating these depressions. This article describes the 2-year course of 53 elderly subjects with bereavement-related depression after responding to various treatments. Forty-six patients experienced a full response to acute treatment, but 36% experienced relapse or recurrence. This finding suggests that the treatment response in depressed bereaved older patients is more brittle than expected.

Aged↗

Methodological issues in characterizing treatment response in demented patients with behavioral disturbances.

Despite the proliferation of instruments developed to rate behavioral disturbances associated with dementia, systematic studies of how ratings on these instruments should be analyzed to measure change in disruptive behaviors or distressing symptoms (ie treatment response) are noticeably absent. Using one of these scales, we compared three methods to characterize treatment response in 52 elderly demented inpatients who participated in a standardized neuroleptic trial. While all three analyses identified a statistically significant improvement, they conveyed differently the clinical improvement experienced by the patients. Categorical outcomes communicated the clinical meaning of improvement better than changes in total score; changes in factor scores best revealed the differential impact of treatment on specific behavioral and symptomatic domains. Given the heterogeneity of the problematic behaviors and symptoms exhibited by demented patients included in treatment trials, regardless of the intervention being tested or of the instrument being used to rate behaviors, a focused approach to characterizing treatment response is needed.

Aged↗

Accelerating response in geriatric depression: a pilot study combining sleep deprivation and paroxetine.

Elderly depressed patients often require an average of 12 weeks of pharmacotherapy before attaining remission. The delay between treatment initiation and remission may decrease compliance and prolongs suffering; hence, interventions that decrease the time to onset of antidepressant activity are needed. Our objective was to evaluate, in an open trial, the use of one night of total sleep deprivation combined with paroxetine to accelerate antidepressant response in elderly patients. Thirteen elderly patients with major depression were sleep-deprived for one night and started paroxetine on the night of recovery sleep. Patients were followed for twelve weeks, and clinical improvement was rated using the 17-item Hamilton Depression Rating Scale and a version of the Hamilton modified for sleep deprivation studies. 8/13 (62%) patients experienced significant improvement of depressive symptoms by 2 weeks. Within 12 weeks 11/13 (85%) patients responded to the combination of sleep deprivation and paroxetine. Median response time was 2 weeks. Clinical response at 12 weeks was correlated with changes in Sleep Deprivation Depression Rating Scale Scores between baseline and recovery sleep. In an open trial, the combined use of total sleep deprivation and paroxetine appears to be an effective method for speeding the onset of clinical antidepressant activity in geriatric depression and for improving early recognition of non-response.

Aged↗

Dielectric relaxation study of glycine and valine in water mixture using picosecond time domain reflectometry.

The complex permittivity of glycine and valine in water mixture for various temperatures and concentrations have been measured as a function of frequency between 10 MHz and 10 GHz using (TDR) time domain reflectometry technique. Dielectric parameters ie. static dielectric constant and relaxation time were obtained from the complex permittivity spectra using nonlinear least square fit method. From the values of relaxation time, thermodynamic parameters were determined.

Electrochemistry↗

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↗

Social rhythm stability following late-life spousal bereavement: associations with depression and sleep impairment.

The aim of this study was to investigate changes in social rhythm stability and sleep in spousally bereaved subjects (n = 94) and in nonbereaved elderly control subjects (n = 45). Social rhythm stability and activity level were measured with a diary-like instrument, the Social Rhythm Metric (SRM). We observed that spousal bereavement, per se, was not associated with a lower social rhythm stability or activity level except in the presence of a major depressive episode. We also observed an inverse correlation between severity of depression and social rhythm stability, and a positive correlation between depression and both subjective and objective measures of sleep impairment. Higher social rhythm stability was correlated with better sleep in subjects with high activity levels, but not in subjects with low activity levels. Longitudinal data, including pre-bereavement assessment of social rhythm stability, are necessary to ascertain directional effects, i.e., whether loss of spouse occasions disruption of social rhythms or whether such disruption precedes sleep impairment and depression.

Adjustment Disorders↗

Spectroscopic and mechanistic studies of type-1 and type-2 copper sites in Pseudomonas aeruginosa azurin as obtained by addition of external ligands to mutant His46Gly.

The spectroscopic and mechanistic properties of the Cu-containing active site of azurin from Pseudomonas aeruginosa were investigated by the construction of a mutant in which one of the ligands of the metal, His46, was replaced by a glycine. Although the mutation creates a hole in the interior of the protein, the 3D structure of the protein does not change to any appreciable extent. However, the spectroscopic (optical, resonance Raman, EPR) properties of the mutant protein are strongly affected by the mutation. In the presence of external ligands, the properties of the original wild-type protein are restored to a smaller or larger extent, depending on the ligand. It is concluded that the hole created by the mutation, even though it is completely buried inside the protein, can be filled by external ligands, often resulting in the creation of a mixture of so-called type-1 and type-2 copper sites. Also, the redox properties (midpoint potential, kinetics of reduction/oxidation) appeared to be strongly affected by the mutation and the presence of external ligands. The results are compared with previous results obtained on the mutant His117Gly.

Azurin↗

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 unusual intraocular foreign body.

Retained intraocular cilia embedded in the retina are extremely rare. A report of an unusual case of cilia embedded in posterior retina is presented along with a review of available literature. A 22-year-old male presented with a history of diminished vision and metamorphopsia 1 month after the successful repair of an ocular perforation. Anterior segment examination revealed a sutured superotemporal limbal tear with a surgical iris coloboma and a normally positioned clear lens. Ophthalmoscopic examination revealed a normal optic disc, macular striations and 2 cilia embedded in the retina approximately 2 disc diameters superotemporal to fovea. Vitrectomy with removal of cilia and endolaser was performed. This unusual case shows that cilia may become embedded intraocularly during an ocular perforation and that transvitreal removal may be a preferred mode of therapy with the availability of sophisticated vitreoretinal instrumentation.

Adult↗

Treatment outcome in recurrent major depression: a post hoc comparison of elderly ("young old") and midlife patients.

OBJECTIVE: The authors compared response rates, the temporal course of response to acute treatment, and relapse rates during continuation treatment of elderly and midlife patients with recurrent major depression. METHOD: They analyzed results from two separate controlled studies of maintenance therapies for recurrent major depression, in which 148 elderly patients (mean age = 67.9 years) and 214 midlife patients (mean age = 38.5 years) were treated in open acute and continuation therapy with a combination of interpersonal psychotherapy and a tricyclic antidepressant (nortriptyline for the elderly, imipramine for the midlife patients). In an intent-to-treat analysis, remission rates during acute treatment and relapse rates during continuation treatment were examined. Random regression analysis of weekly Hamilton depression scale ratings was used to compare the temporal course of response. RESULTS: During acute-phase therapy, 78.4% (N = 116) of the elderly patients and 69.6% (N = 149) of the midlife patients had remissions. The midlife patients had a faster reduction of Hamilton depression ratings. Following stabilization, 15.5% of the elderly patients and 6.7% of the midlife patients relapsed. Ultimately, 66.2% of the late-life patients and 57.0% of the midlife patients recovered fully. CONCLUSIONS: Older patients appear to benefit as much as, but perhaps more slowly then, midlife patients from treatment of major depression. Continuation treatment should be vigorous and closely monitored, given the apparently higher relapse rates among the elderly. These conclusions should be viewed as preliminary because of the post hoc nature of the analysis reported here.

Adult↗

Changes in perceived health status of depressed elderly patients treated until remission.

OBJECTIVE: The authors predicted that depressed elderly patients who responded to treatment would rate their baseline health more positively than nonresponders, that responders would again rate their health more positively once they were in remission, and that lower baseline self-ratings of health would predict lack of response to protocol treatment. METHOD: The Perception of Illness Scale was administered to 61 depressed elderly patients at baseline and again upon completion of the acute phase of a depression treatment protocol. A logistic regression was performed to ascertain whether Perception of Illness Scale scores predicted response to protocol treatment. RESULTS: Baseline Perception of Illness Scale scores were poorer among the nonresponders, accurately predicted response or lack of response in 75% of the subjects, and showed before-to after-treatment improvement among the responders. CONCLUSIONS: Patients who initially rated their health as fair to poor were less likely to recover from depression in a standardized treatment protocol. Self-ratings of health improved with resolution of depression.

Age Factors↗

High relapse rate after discontinuation of adjunctive medication for elderly patients with recurrent major depression.

OBJECTIVE: The authors documented outcomes of elderly depressed patients requiring adjunctive medication during acute-phase pharmacotherapy because of slow or partial response to nortriptyline. Twenty-eight patients (17.7%) received inpatient care at some point during acute-phase treatment. METHOD: Rates of response, relapse, and sustained remission were examined in 158 elderly patients with recurrent major depression, grouped by whether they received brief treatment with adjunctive medication (lithium, perphenazine, or paroxetine) (N = 39) or did not (N = 119). RESULTS: The group receiving adjunctive medication had a lower rate of response to acute therapy (64.1% versus 83.2%), a higher relapse rate during continuation therapy (52.0% versus 6.1%), and a lower rate of sustained remission (recovery) (48.7% versus 76.5%) than did the group without augmentation. CONCLUSIONS: Elderly depressed patients requiring augmented pharmacotherapy to achieve remission may need continuation of adjunctive medication to remain well and to avoid early relapse. Alternatively, factors that lead to augmentation in the first place (e.g., heightened anxiety) may also increase the risk of relapse.

Age Factors↗

A retained intraretinal foreign body.

A patient with an 11-mm retained intraretinal foreign body is described. Absence of any history of trauma or foreign body entry with no obvious wound of entry and little damage to the ocular structures makes this case unusual.

Adult↗

pH-induced conformational perturbation in horseradish peroxidase. Picosecond tryptophan fluorescence studies on native and cyanide-modified enzymes.

The fluorescence-decay characteristics of the single tryptophan present in horseradish peroxidase (HRP) have been studied using dye-laser pulses and single-photon counting techniques. The decay was found to be dominated by a picosecond-lifetime component, with small contributions from two other lifetime components in the nanosecond range. The distance of the tryptophan residue was estimated from the fluorescence-energy transfer to the heme moiety using Förster's theory. The tryptophan residue was found to be approximately 1.2 nm from the heme moiety at neutral pH. Detailed analysis of the fluorescence-decay profiles using the maximum-entropy method (MEM) has been carried out. The results of the MEM analysis also showed a maximum amplitude peak at approximately 45 ps (at pH approximately 7) with a very small (< 5%) contribution from two other components. Similar results were obtained with the cyanide derivative of the enzyme (HRPCN) where the major lifetime component was found to be 58 ps at neutral pH. The picosecond component of fluorescence lifetimes of native HRP as well as of HRPCN were found to increase with decrease in pH in the range pH 6-3.5. Moreover, the native enzyme showed significant increase in the magnitude of this fast lifetime component at pH above 8. Such increase in the major lifetime component possibly indicated a conformational perturbation caused by pH change in the enzyme. However, the pH dependence of HRPCN, which is devoid of alkaline transition, showed that the shortest lifetime component remains almost unchanged over the pH range 6-11. This result showed that the alkaline transition in native HRP is associated with a structural change in the distal region of the heme center, which is absent in the cyanide-ligated enzyme. The results have been discussed with respect to understanding the pH-induced effects associated with salt bridge and hydrogen-bonding network in HRP.

Cyanides↗

Maintenance therapies for late-life recurrent major depression: research and review circa 1995.

Major depression in the elderly is often a relapsing, chronic illness with high risk for chronic invalidism, poor treatment compliance, and suicide. In most cases, maintenance treatment to prevent recurrence and to enhance the quality of life is thought to be indicated. We review recent data from our ongoing studies that support both the efficacy and the safety of pharmacotherapeutic and psychotherapeutic maintenance treatments. However, the challenges of conducting maintenance therapy research (particularly with a placebo control) with the elderly are many, involving such areas as recruitment, retention, compliance, choice of outcome measures, and informed consent. We discuss each of these challenges and our responses to them. Finally, we suggest that maintenance therapy trials should be extended in several directions: (a) long-term treatment of bipolar and delusional subtypes in the elderly, as well as depression associated with progressive neurodegenerative disorders such as Alzheimer's dementia; (b) assessment of the benefits and risks of long-term therapy with other than tricyclic and monoamine oxidase inhibitor antidepressant agents, such as selective serotonin reuptake inhibitors; and (c) development of models of long-term course, including the interaction of treatments with medical and psychosocial variables that can have a profound impact on illness onset and offset. These issues are illustrated with a discussion of a new protocol designed to test the acute and maintenance efficacy of antidepressant therapy for depressed patients with Alzheimer's disease.

Alzheimer Disease↗

Conformational change due to reduction of cytochrome-c oxidase in lauryl maltoside: picosecond time-resolved tryptophan fluorescence studies on the native and heat modified enzyme.

Detailed fluorescence studies on bovine heart cytochrome-c oxidase (CcO) has been carried out in lauryl maltoside solution. Steady-state fluorescence of the tryptophan residues of the enzyme showed that the fluorophores are embedded deep inside the hydrophobic protein cavity. Time resolved studies of tryptophan fluorescence of native and heat treated CcO have been carried out in both reduced and oxidised forms using synchronously pumped pulsed picosecond dye laser and single photon counting technique. Decay of the tryptophan fluorescence have been fitted using discrete four exponential model. Amplitude distribution of lifetimes also showed four distinct regions in the analysis of the decay profiles by maximum entropy method (MEM). The results indicate that controlled heat treatment of CcO affects the conformation of the enzyme near the active centers which makes it incapable of active proton pumping while the electron transfer property is still conserved. Reduction of the native CcO is associated with a large conformation change in lauryl maltoside near the active centers which is not observed in case of CcO encapsulated in vesicles. Reduction of the heat treated enzyme was found to have a conformation different from the reduced native CcO.

Electron Transport Complex IV↗

Leng et al. reply.

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Journal Article↗