Depression without sadness: functional outcomes of nondysphoric depression in later life

OBJECTIVES: We hypothesized that depressive symptoms not meeting full standard criteria for Major Depression would be associated with significant functional impairment among older adults over the course of a 13-year follow-up interval. Specifically, we developed criteria for a form of depression whose core symptoms did not include sadness or dysphoria. DESIGN: Population-based 13-year follow-up survey. SETTING: Community-dwelling adults living in East Baltimore in 1981. PARTICIPANTS: Subjects were the 1612 participants of the Baltimore sample of the Epidemiologic Catchment Area Program aged 50 years and older at the initial interview in 1981. MEASUREMENTS: The subjects were sorted into four categories based on their responses at baseline: (1) persons meeting standard criteria for Major Depression; (2) persons meeting alternative criteria for depression with dysphoria or (3) without dysphoria; and (4) a comparison category of persons not meeting any criteria for depression ("noncases"). The mortality and functional status of each group were compared after a 13-year follow-up interval. RESULTS: Compared with non-cases, participants aged 50 years and older who reported depressive symptoms but who denied sadness or dysphoria (nondysphoric depression) were at increased risk for death (relative risk (RR) = 1.70; 95% confidence interval (CI) (1.09, 2.67)), impairment in activities of daily living (RR = 3.76; 95% CI (1.73, 8.14)), impairment in instrumental activities of daily living (RR = 5.07; 95% CI (2.24, 11.44)), psychologic distress (RR = 3.68; 95% CI (1.47, 9.21)), and cognitive impairment (RR = 3.00; 95% CI (1.31, 6.89)) after a 13-year follow-up interval. The findings were not wholly explained by potentially influential baseline characteristics such as age, education, selected comorbid medical conditions, and functional status. CONCLUSION: Among adults aged 50 years and older, nondysphoric depression may be as important as Major Depression in relation to the development of functional disability and other long-term outcomes.     

Independent effects of food intake and insulin status on insulin-like growth factor-I in young pigs

The successful use of proteins in pharmaceutical and other commercial applications requires close examination of their relative fragility. Because of the resultant enhanced stability, proteins are often formulated in the solid state, even though dehydration tends to alter their structure. Even in the solid form, however, proteins may become inactivated due to various deleterious processes, e.g., aggregation. This review focuses on such mechanisms, with an emphasis on case studies conducted in our laboratory. Proteins which have both disulfide bonds and free thiols may aggregate via thiol-disulfide exchange, and this process may be facilitated by lyophilization-induced structural perturbations. For proteins possessing disulfides but not free thiols, aggregation also may occur when native disulfides are beta-eliminated, thus giving rise to thiol species which can catalyze disulfide scrambling. Other deleterious processes have also been uncovered, including a formaldehyde-mediated aggregation of formalinized vaccines. It is illustrated how knowledge of such deterioration pathways makes possible the rational development of stable solid protein formulations.     

Ocular perforation during retrobulbar and peribulbar injections

BACKGROUND AND OBJECTIVE: To determine the ocular perforations during retrobulbar and peribulbar injections. PATIENTS AND METHODS: Twenty-five ocular perforations between 1976 and 1993 occurred after 13 retrobulbar and 12 peribulbar injections. Eighteen patients (72%) were women. Eighteen eyes were myopic (72%). Risk factors included high myopia in 11 cases (44%), use of Atkinson gaze in 21 cases (84%) and a sharp injection needle. RESULTS: Deep position of the posterior pole was common. Perforation signs comprised vitreous hemorrhage in 25 eyes (100%), subretinal hemorrhage in 19 eyes (76%), retinal breaks along the inferior vascular arcade in 19 eyes (76%), and retinal detachment in 14 eyes (56%). Proliferative vitreoretinopathy developed in 11 eyes (44%). CONCLUSION: Retinal detachment strongly correlated to poor visual outcome.     

Save our children

This paper reports changes in adrenocorticotrophic hormone (ACTH), insulin and insulin-like growth factor-1 (IGF-1) concentrations in cats from a previously published study. The cats were given oral megestrol acetate (MA, 5 mg once daily for 14 days), subcutaneous proligestone (PRG, 100 mg on two occasions one week apart) or subcutaneous saline (1 ml as for PRG). In the cats given saline (n = 6), basal ACTH, insulin and IGF-1 did not change significantly throughout the following seven weeks. The cats given MA (n = 7) developed significant suppression of plasma ACTH concentrations and hyperinsulinaemia during treatment and for two to four weeks after MA dosage ceased. In the cats given PRG (n = 7), plasma ACTH concentrations were not significantly altered although three cats had markedly suppressed values for some time after PRG treatment had ceased. Serum insulin concentrations were not significantly altered in the PRG-treated cats. The results suggest PRG may be a preferable alternative to MA in some situations.     

Altered impulse activity modifies synaptic physiology and mitochondria in crayfish phasic motor neurons

1. Crayfish phasic motor synapses produce large initial excitatory postsynaptic potentials (EPSPs) that fatigue rapidly during high-frequency stimulation. Periodic in vivo stimulation of an identified phasic abdominal extensor motor neuron (axon 3) induced long-term adaptation (LTA) of neuromuscular transmission: initial EPSP amplitude became smaller and synaptic depression was significantly reduced. We tested the hypothesis that activity-induced synaptic fatigue-resistance seen during LTA was dependent upon, or correlated with, mitochondrial oxidative competence. 2. Periodic unilateral conditioning stimulation of axon 3 entering each of two adjacent homologous abdominal segments (segments 2 and 3) increased the synaptic stamina in both "conditioned" axons; mean final EPSP amplitudes, recorded after 20 min of 5-Hz test stimulation, were significantly larger than those measured with the same protocol from contralateral unstimulated axons. 3. During 5-Hz test stimulation of the conditioned axon 3 of segment 3, acute superfusion with 0.8 mM dinitrophenol or 20 mM sodium azide [inhibitors of oxidative adenosinetriphosphate (ATP) synthesis] produced increased synaptic depression. Drug-free saline superfusion of the conditioned axon 3 of segment 2 in these same animals did not affect the increased synaptic fatigue resistance seen in this segment. Thus both successful induction (in axon 3 of saline-perfused segment 2) and attenuation (in axon 3 of drug-perfused segment 3) of the increased synaptic stamina can be demonstrated with this twin-segment conditioning protocol. 4. Confocal microscopic imaging of mitochondrial rhodamine-123 (Rh123) fluorescence was used to assess relative oxidative competence of conditioned and unconditioned phasic axons. Conditioned phasic axons showed significantly higher mean mitochondrial Rh123 fluorescence than contralateral unstimulated axons. In the same preparations that showed increased postconditioning Rh123 fluorescence, the synaptic fatigue resistance measured from conditioned axon 3 was also significantly greater than that recorded from contralateral unstimulated axon 3. 5. Axotomy of the phasic extensor nerve root (containing axon 3), before in vivo conditioning stimulation of its decentralized segment, prevented induction of both the increased synaptic stamina in axon 3 and the enhanced mitochondrial fluorescence in decentralized motor axons of the nerve root. Hence, induction of both changes requires axonal transport of materials between the soma and the motor synapses of axon 3. 5. Axotomy of the phasic extensor nerve root (containing axon 3), before in vivo conditioning stimulation of its decentralized segment, Prevented induction of both the increased synaptic stamina in axon 3 and the enhanced mitochondrial fluorescence in decentralized motor axons of the nerve root Hence, induction of both changes requires axonal transport of materials between the soma and the motor synapses of axon 3 6. Because mitochondrial Rh123 fluorescence is primarily dependent upon the oxidative activity of these organelles, our findings suggest that conditioning stimulation of phasic extensor axon 3 increases its mitochondrial oxidative competence and that the enhanced synaptic stamina seen during LTA in axon 3 is correlated with, and dependent upon, oxidative activity.(ABSTRACT TRUNCATED AT 400 WORDS)     

Donor cell induced CD69 expression and intracellular IL-2 and IL-4 production by peripheral blood lymphocytes isolated from kidney transplant recipients

Flow cytometry assays, which measure CD69 activation and intracellular cytokine production, have been used to measure peripheral blood lymphocyte (PBL) responses to in vitro antigen exposure. In the present study, we show that, in healthy individuals and immunosuppressed kidney transplant recipients, CD69 expression and intracellular cytokine production by peripheral blood T cells compare favorably to thymidine uptake as a measure of PBL response to alloantigen in mixed leukocyte culture (MLC). Heparinized whole blood from 23 healthy individuals was incubated for 24-48 h with 3rd party allogeneic monocytes; blood from twelve kidney transplant recipients was incubated with monocytes from their kidney donor and with monocytes from unrelated individuals. The percentage of T cells expressing surface CD69 or intracellular IL-2 or IL-4 was determined by 3-color flow cytometry. We identified 5 donor-specific response patterns in our kidney transplant group. One transplant recipient was hyporesponsive; his cells did not express CD69 or produce IL-2 in response to either donor or 3rd party allogeneic cells. All other transplant recipients expressed CD69 and IL-2 in response to 3rd party allogeneic cells. Two had no response to donor cells (donor-specific hyporesponsiveness), three had donor-specific anergy (CD69 expression without cytokine production in response to donor cells), five had a donor-specific Thl response (CD69 expression and IL-2 production in response to donor cells), and one had a donor-specific Th2 response (CD69 expression and IL-4 but not IL-2 production in response to donor cells). Rapid measures of donor-specific hyporesponsiveness such as CD69 activation antigen expression and intracellular cytokine production may prove valuable in monitoring lymphocyte function and aid in the long-term management of kidney transplant recipients.