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Preparation, characterization, and evaluation of a monoclonal antibody against the rabbit platelet glycoprotein IIb/IIIa in an experimental angioplasty model.

The deposition of platelets at the site of balloon angioplasty is thought to play a major role in the pathogenesis of restenosis. The antibody AZ-1, which binds to the rabbit platelet glycoprotein IIb/IIIa receptor and inhibits platelet function both in vitro and in vivo, was produced and tested in an experimental model of angioplasty. Atherosclerosis was induced by desiccation injury of the femoral artery, followed by a 28-day diet with 2% cholesterol and 6% peanut oil. Rabbits were randomized to receive an infusion of saline, a single infusion of 0.5 mg/kg of AZ-1, or an infusion of 0.6 mg/kg AZ-1 before angioplasty. The latter group received a second infusion of 0.6 mg/kg 72 hours later. Functional platelet inhibition was demonstrated by prolongation of the bleeding time in all treated animals. Angiography was performed at baseline, immediately after a standardized angioplasty, and again 28 days after angioplasty on a total of 42 vessels. There were no significant differences between the antibody-treated group and the control group in the mean angiographic minimum luminal diameter at any of the time points. There was also no difference in the initial improvement after angioplasty (acute gain), in the decrease in luminal diameter from immediately after angioplasty to 28 days after angioplasty (late loss), or in the overall improvement from before angioplasty to 28 days after angioplasty. Quantitative histological analysis confirmed the lack of a beneficial effect of AZ-1. There were no significant differences in the area of the intima, the media, or the combined intima and media between the antibody-treated groups and the control group. Thus, potent platelet inhibition for up to 6 days after balloon angioplasty using a monoclonal antibody that inhibits platelet aggregation did not reduce the response to vascular injury after balloon angioplasty in this rabbit model of experimental atherosclerosis.

Angioplasty↗

Risk behaviors in maltreated youth placed in foster care: a longitudinal study of protective and vulnerability factors.

OBJECTIVE: Few studies have examined the impact of placement in foster care prospectively to determine what early responses might predict later functioning. The current study examined protective and vulnerability factors in a longitudinal study of youth placed in foster care. METHODOLOGY: A cohort of 214 ethnically-diverse youth, ages 7-12, who entered foster care between May 1990 and October 1991 were recruited for the Time 1 study if they remained in foster care for at least 5 months. For the Time 1 study, youth and their caregivers were interviewed and assessed approximately 6 months following their initial placement. Six years later, as adolescents, the youth were re-interviewed regarding their involvement in four domains of risk behavior. RESULTS: Bivariate analyses indicated that several Time 1 control variables (e.g., age, ethnicity, type of maltreatment, behavior problems) and Time 1 psychosocial predictor variables (i.e., dimensions of social support and self-perception) were related to the Time 2 risk behavior outcomes. Regression analyses with all variables accounted for between 33 and 46% of the variance, with the psychosocial predictor variables, as a group, significant over and above the control variables. CONCLUSIONS: The results suggest that there are some modifiable protective and vulnerability factors present shortly after maltreated youth are placed in foster care that predict their engagement in adolescent risk behaviors 6 years later.

Age Factors↗

Reduction of postischemic immune inflammatory response: an effective strategy for attenuating chronic allograft nephropathy.

BACKGROUND: Ischemia added to the allogeneic background accelerates the cellular mechanisms involved in alloresponsiveness, supporting the influence of early nonspecific inflammatory injury on chronic allograft nephropathy (CAN). The authors hypothesize that reinforcing initial immunosuppressive regimens may prevent immunogenicity derived from postischemic inflammatory responses, attenuating CAN. METHODS: Lewis rats engrafted with Fischer kidneys received for 15 days overimmunosuppressive doses of rapamycin, a standard cyclosporine regimen, or both, and were followed functionally for 24 weeks. Animals were grouped according to the initial immunosuppressant or cold-ischemia period. Grafts were evaluated for acute inflammatory response at 1 week and for chronic histologic damage at 24 weeks. RESULTS: Rats under cyclosporine alone displayed the highest mortality, which was decreased in the long term by reducing cold ischemia or by strengthening immunosuppression. At 24 weeks, all rapamycin-treated groups displayed much less severe tubulointerstitial and vascular damage. The combination of both immunosuppressants offered better functional outcome and a global reduction in chronic histologic damage. After 1 week, ATN and profibrotic features appeared in all 5-hr ischemic animals, indicating that cyclosporine and rapamycin co-treatment did not induce further nephrotoxicity. Treatment with rapamycin, alone or combined with cyclosporine, greatly reduced the severe immune-inflammatory damage, including vessels, shown in cyclosporine-treated ischemic grafts. CONCLUSIONS: Strengthening initial immunosuppression attenuates the intensity and extent of the early postischemic immune-inflammatory response as well as later function and structure of renal allografts. Severe CAN may be prevented by reducing cold ischemia or strengthening immunosuppression. Because the former approach is not always possible, reinforcement of early immunosuppression constitutes an excellent alternative.

Animals↗

Lateralisation of cortical function during cognitive tasks: regional cerebral blood flow studies of normal individuals and patients with schizophrenia.

To assess cognitively-related regional asymmetries of brain function, regional cerebral blood flow (rCBF) was determined by the xenon inhalation method while normal subjects performed 10 different tasks and also while they were at rest. In addition to healthy subjects, patients with schizophrenia were also studied. A total of 447 rCBF studies were carried out during the following conditions: the Wisconsin Card Sort Test, a numbers matching test, a symbols matching test, Raven's Progressive Matrices, an auditory discrimination test, an auditory control task, two versions of a visual continuous performance task, line orientation, semantic classification, and resting. On the whole, those tasks that seem to require or allow for internal verbalisation resulted in the greatest activation of the left hemisphere compared with the right; right hemisphere activation predominated only in the two tasks primarily involving attention and vigilance. Furthermore, a consistent regional topography of normal cerebral functional laterality was seen: under most conditions left prefrontal cortical activity exceeded that of right prefrontal cortex; during all non-auditory tasks, parieto-occipital cortical activity had an opposite pattern-greater right than left. During most conditions the schizophrenic patients displayed the same pattern. While several cognitively specific between-group differences were found, no single cortical region was consistently implicated and no specific direction of abnormal asymmetry predominated. These data suggest that there is a predominant task-independent functional pattern of cortical activity emphasising relatively greater left anterior and right posterior activation. This pattern may reflect the verbal and attentional primacy of these areas, respectively.

Adult↗

Cortical visual areas of the cat project differentially onto the nuclei of the accessory optic system.

Cortical projections to the nuclei of the cat's accessory optic system were demonstrated by anterograde transport and degeneration methods. Areas 21a, 21b, AMLS and PMLS were found to project to the medial, lateral and dorsal terminal accessory optic nuclei. Selective projections from area PLLS to the lateral terminal nucleus and from areas 17 and 18 to the medial terminal nucleus were noted. No terminal labeling was detected following injections of areas ALLS, DLS, 20a, 20b, 19, 7 or the splenial visual area. The accessory optic system has been implicated in the control of optokinetic nystagmus. Additional evidence supports a role for ipsilateral visual cortical projections in mediating optokinetic pursuit in the naso-temporal direction under monocular conditions. Thus the visual cortical projections we describe may partially underlie the observed functional laterality of monocularly elicited optokinetic pursuit in the cat. The present results further indicate that suprasylvian areas AMLS, PMLS and 21 are the cortical regions primarily responsible for descending visual influences on the cat's accessory optic nuclei.

Afferent Pathways↗

Biophysical properties of lipids and dynamic membranes.

The lipid bilayer is a 3D assembly with a rich variety of physical features that modulate cell signaling and protein function. Lateral and transverse forces within the membrane are significant and change rapidly as the membrane is bent or stretched and as new constituents are added, removed or chemically modified. Recent studies have revealed how differences in structure between the two leaflets of the bilayer and between different areas of the bilayer can interact together with membrane deformation to alter the activities of transmembrane channels and peripheral membrane binding proteins. Here, we highlight some recent reports that the physical properties of the membrane can help control the function of transmembrane proteins and the motor-dependent elongation of internal organelles, such as the endoplasmic reticulum.

Animals↗

Impaired NMDA receptor function in mouse olfactory bulb neurons by tetracycline-sensitive NR1 (N598R) expression.

High Ca(2+) permeability and its control by voltage-dependent Mg(2+) block are defining features of NMDA receptors. These features are lost if the principal NR1 subunit carries an asparagine (N) to arginine (R) substitution in a critical channel site at NR1 position 598. NR1(R) expression from a single allele in gene-targeted NR1(+/R) mice is lethal soon after birth, precluding analysis of altered synaptic functions later in life. We therefore employed the forebrain specific alphaCaMKII promoter to drive tTA-mediated tetracycline sensitive transcription of transgenes for NR1(R) and for lacZ as reporter. Transgene expression was observed in cortex, striatum, hippocampus, amygdala and olfactory bulb and was mosaic in all these forebrain regions. It was highest in olfactory bulb granule cells, in most of which Ca(2+) permeability and voltage-dependent Mg(2+) block of NMDA receptors were reduced to different extents. This indicates significant impairment of NMDA receptor function by NR1(R) in presence of the wild-type NR1 complement. Indeed, even though NR1(R) mRNA constituted only 18% of the entire NR1 mRNA population in forebrain, the transgenic mice died during adolescence unless transgene expression was suppressed by doxycycline. Thus, glutamate receptor function can be altered in the mouse by regulated NR1(R) transgene expression.

Amino Acid Substitution↗

Characterizations of a hypomorphic argonaute1 mutant reveal novel AGO1 functions in Arabidopsis lateral organ development.

Genes that encode the ARGONAUTE (AGO) proteins make up a highly conserved family, and several members in the family have been defined to function in posttranscriptional gene silencing (PTGS) in plants, quelling in fungi and RNAi in animals. The Arabidopsis AGO1 gene has been demonstrated to be crucial in multiple RNA silencing pathways (PTGS, microRNA and trans-acting siRNA pathways); however, its biological functions do not seem to be fully addressed. Here we report characterizations of a new hypomorphic ago1 allele, ago1-37, and show novel AGO1 functions important in lateral organ development. We found that double mutants combining ago1-37 with asymmetric leaves1 (as1) or asymmetric leaves2 (as2) produced more severe phenotypes than the single mutants, indicating that AGO1 genetically interacts with AS1 and AS2 for plant development. Similar to the previously characterized mutants rdr6, sgs3 and zippy, which are deficient in the trans-acting siRNA activity, ago1-37 also showed an earlier phase transition from juvenile to adult leaves. Moreover, based on the detailed phenotypic analyses of single and double mutant plants, we found that the AGO1 functions are required for repressing several class I KNOTTED1-like homeobox (KNOX) genes in leaves, and for specifying both adaxial and abaxial identities of the leaf and petal. Our results demonstrate several important AGO1 functions in plant lateral organ development.

Alleles↗

Glucocorticoids suppress beta-cell development and induce hepatic metaplasia in embryonic pancreas.

Elevated glucocorticoids are associated with low birth weight and fetal 'programming' of hypertension and glucose intolerance. In the present paper, we show that treatment of fetal rats with dexamethasone during the last week of gestation reduces the insulin content of their pancreatic beta-cells. We reproduce this effect of dexamethasone in vitro using organ cultures of mouse embryonic pancreas, and show that it is associated with an elevation of expression of the transcription factor C/EBPbeta (CCAAT/enhancer-binding protein beta) and a reduction of the transcription factor Pdx-1 (pancreatic duodenal homeobox-1). Dexamethasone also induces the appearance of hepatocyte-like cells in organ cultures of pancreas, based on the expression of liver markers, albumin, alpha1-antitrypsin and transthyretin. Evidence that C/EBPbeta is responsible for compromising the differentiation and later function of beta-cells is obtained from its effects on the beta-cell-like cell line RIN-5F. Transfection with a constitutive form of C/EBPb suppresses insulin formation, whereas introduction of a dominant-negative inhibitor of C/EBPb has no effect. We conclude that dexamethasone inhibits insulin expression in pancreatic beta-cells via a mechanism involving down-regulation of Pdx-1 and induction of C/EBPbeta. This mechanism may operate in combination with other changes during fetal programming, leading to type 2 diabetes in later life.

Animals↗

Functional and phenotypic analysis of thymocytes in SCID mice. Evidence for functional response transitions before and after the SCID arrest point.

Thymocytes from severe combined immune deficient (SCID) mice undergo developmental arrest at an early stage, before most TCR gene rearrangement. They therefore represent a natural test case to assess those aspects of T cell development that are TCR independent. Multiparameter flow cytometry was used to analyze the array of immature phenotypes present in the SCID thymus at steady state, as defined by the markers CD4, CD5, Sca-1, NK1.1, CD44, heat-stable antigen (HSA), and IL-2R alpha. The results suggest a simple developmental block in SCID mice rather than a program of aberrant differentiation. SCID thymocytes displayed efficient, developmentally regulated functional responses. Approximately 20-25% of the cells, mostly within the IL-2R alpha +HSA+CD44low fraction, could be induced to express IL-2. This IL-2 inducibility was highly dependent on IL-1 costimulation, in agreement with the behavior of normal immature thymocytes. These results formally demonstrate that competence to express IL-2 is developed independently of TCR expression or gene rearrangement. Comparison of the response properties of various SCID thymocyte subsets indicated that IL-2 inducibility is first likely to be acquired at an early (Sca-1++CD44++HSAlow) stage. A later functional transition was revealed by comparing patterns of IL-2R alpha regulation in normal and SCID IL-2R alpha +HSA+CD44low thymocytes. The SCID thymocytes uniformly maintained IL-2R alpha expression on in vitro stimulation, whereas only a minority of the normal cells in the corresponding subset could do so unless IL-1 was also added. The SCID arrest point thus appears to separate the IL-2R alpha +HSA+CD44low stage into distinct early (TCR independent) and late phases. Normal cells that progress beyond the SCID arrest point appear to lose, rather than gain, competence to make various responses, even before they leave the IL-2R alpha +HSA+CD44low stage. A model is proposed in which discrete changes in functional competence define novel transitions in early thymocyte development, at least some of which may be linked to TCR-beta gene rearrangement before positive or negative selection.

Animals↗

Consequences of structural renovascular changes for renal barostat function.

During maximal vasodilatation the renal vascular beds of normotensive control rats (NCR), uninephrectomized NCR (U-NCR), spontaneously hypertensive rats (SHR), and two-kidney, one clip renal hypertensive rats (RHR) have been compared concerning glomerular filtration capacity, total renovascular resistance, and the relationship between perfusion pressure and glomerular filtration rate (GFR). The GFR reflects the important ratio between the preglomerular and postglomerular resistances that is a major determinant of GFR, and during maximal vasodilatation it shows whether, and how, this ratio is altered by differentiated renovascular structural adaptation. In SHR hypertension this ratio soon becomes increased to match the pressure rise as a result of structural changes, which implies a most efficient upward resetting of the renal barostat function. Later the postglomerular resistance is also raised in SHR as a result of structural changes. This adaptation presumably occurs to offset the gradual deterioration in glomerular filtration capacity. In the clipped, "low-pressure" RHR kidney, only the preglomerular resistance is reduced, a local adaptation tending to offset the effect of the artificial inflow hindrance on GFR as a result of structural changes. In the "pressure-exposed" RHR kidney the preglomerular and postglomerular resistances are both equally increased, again as a result of structural changes. In this situation, therefore, resetting of the renal barostat function occurs less efficiently than in SHR. This may explain the observation that arterial pressure readily normalizes in RHR on declipping. The hypertrophic U-NCR kidney shows a proportional and uniform outgrowth of the renovascular bed, thus without altering the pre-postglomerular resistance ratio.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Chemosensory input and lateralization of brain function in the domestic chick.

One-day old domestic chicks (Gallus gallus domesticus) show concentration-dependent behavioural responses to olfactory cues. In the present study we investigated the lateralized olfactory responses of 1-day-old chicks to the odours of eugenol and iso-amyl acetate. In experiment 1 different concentrations of each odour were presented in repeated trials to chicks housed individually. The odours were presented together with a small coloured bead at which the chick pecked. When tested with the highest concentration of eugenol (100% v/v), the chicks demonstrated more head shaking when their left nostril was occluded (RN; right nostril in use) than when their right nostril was occluded (LN; left nostril in use). No such lateralization occurred in response to iso-amyl acetate. This result was confirmed in a second experiment in which the chicks were tested with unscented stimuli, 100% eugenol and 100% isoamyl acetate. In experiment 3 we found that occluding both the chicks' nostrils abolished the head shaking response to eugenol and to iso-amyl acetate. Thus, the chicks' head shaking responses to the odorants eugenol and iso-amyl acetate are mediated primarily by inputs from within the nasal cavity, and not by oral or occular inputs. The present results are consistent with the hypothesis that there is lateralization to olfactory cues and that it is dependent on the involvement of receptors inside the nasal cavity. We suggest that differences in lateralized olfactory responses to different odours are affected by the relative involvement of intranasal olfactory and trigeminal chemoreceptors.

Animals↗

Reduction of motor behavioural deficits in senescence via chronic prolactin or estrogen administration: time course and putative mechanisms of action.

The effects of chronic estrogen (E2), rat prolactin (rPRL), modified ovine prolactin (mPRL) administration on motor behavior (inclined screen performance) and striatal dopamine (DA) (D2subtype) receptor concentrations were examined in senescent (greater than 24 months of age) female rats, mPRL possesses no lactotrophic activity. Administration of either E2 or rPRL was effective in improving both inclined screen performance (increased time that the animal could remain on the screen by 95 and 413 s, respectively, compared to highest pre-injection performance) and striatal D2 receptor concentrations (14 and 20% respectively). These were indications, however, from separate analyses that improvements in inclined screen performance were seen prior to any increases in striatal D2 receptor concentrations. These early performance increases seemed instead to be the result of improved muscarinic receptor control over striatal DA autoreceptor function. Later improvements in inclined screen performance (at 6-7 days after the E2 injections were begun) were more dependent on increased striatal DA receptor concentrations. A second set of experiments which involved the injection of E2 into senescent male as well as female rats indicated that there were no sex differences in improvements in inclined screen performance, and that once the E2 injections were discontinued, performance returned to preadministration levels. The results are discussed in terms of two important processes that may be involved in mediating enhanced inclined screen performance following E2 administration: (1) enhancement of muscarinic receptor regulation of DA autoreceptor function; and (2) increases in striatal DA receptor density.

Aging↗

Long-term results using adjunctive mitomycin C in optic nerve sheath decompression for pseudotumor cerebri.

PURPOSE: Up to 35% of patients undergoing optic nerve sheath decompression (ONSD) for pseudotumor cerebri who show initial improvement in visual function later show deterioration in visual field and acuity. Although repeat surgery can result in subsequent visual improvement, these procedures are technically difficult because of scarring and fibrosis. Attempting to improve the long-term success of ONSD, the authors sought to analyze the long-term success of ONSD by pretreating optic nerve sheaths with mitomycin C before incision. METHODS: Using a standard transconjunctival medial orbitotomy, optic nerve sheaths were exposed and treated for 5 minutes with mitomycin C (0.5 mg/ml)-soaked neurosurgical cottonoids before incision. RESULTS: Both eyes undergoing repeat ONSD with adjunctive mitomycin C had initial improvement and stable visual function for follow-up of more than 3 years. Four eyes that underwent primary ONSD all initially showed improvement in visual field. Three eyes with large cysts or fistulas remained stable. Another eye had gradual decline in visual function. Repeat ONSD in this eye showed no orbital scarring, and lysis of adhesions between dura-arachnoid and optic nerve resulted in improved, stable visual function for 31 months of follow-up. CONCLUSION: Mitomycin C appears to be a safe adjunct to ONSD in a series of six patients followed between 20 and 37 months. Fistulization and cyst formation are associated with improved visual function. Closure of cysts and fistulas may result in worsening visual function due to intersheath adhesions. Repeat surgery shows significantly less orbital scarring and allows for easier and successful repeat surgery. Adjunctive mitomycin C leads to less orbital scarring after ONSD, allowing for easier repeat surgery.

Adult↗

Structural and functional differentiation of sinusoidal endothelial cells during liver organogenesis in humans.

During fetal life, human liver sinusoids, which differentiate between 4 and 12 weeks of gestation from capillaries of the septum transversum, must support an important hematopoietic function and acquire the structural and functional characteristics of adult sinusoids. To gain insight into their differentiation process, we studied the expression of (1) markers of continuous endothelia, absent from adult sinusoidal endothelial cells (PECAM-1, CD34, and 1F10); (2) functional markers of adult sinusoidal endothelial calls (CD4, 1CAM-1, CD32, and CD14); and (3) extracellular matrix components (laminin, tenascin, fibronectin, and thrombospondin) in 37 fetuses of different gestational ages. We identified two successive differentiation events. (1) An early structural differentiation, occurring from 5 to 12 weeks of gestation, was characterized by the loss of continuous endothelial cell markers and a reduction in the perisinusoidal amount of laminin and in the deposition of tenascin, fibronectin, and thrombospondin; at the end of this process, fetal liver sinusoids present structural characteristics comparable to those of the sinuses in adult hematopoietic bone marrow. (2) A later functional differentiation was characterized by the acquisition of the markers of adult sinusoidal endothelial cells, initiating at 10 weeks of gestation and completed by 20 weeks of gestation; this process likely contributes to adapt liver sinusoids to the specific functions of the adult hepatic tissue.

Adult↗

The retinal pigmented epithelium is required for development and maintenance of the mouse neural retina.

BACKGROUND: During development of the vertebrate eye, there is a series of reciprocal cellular interactions that determine the fate of the eye components. Although evidence from organ culture suggests that the retinal pigmented epithelium (RPE) organizes the laminar structure of the differentiated neural retina, no role has been identified for the RPE in early eye development, nor has the later function of RPE been demonstrated in vivo. RESULTS: To investigate the role of RPE cells in eye development, we generated transgenic mice that carry the attenuated diphtheria toxin-A gene; this transgene was driven by the promoter of the gene encoding the tyrosinase-related protein-1, which is specifically expressed in pigment cells. Depending on the expression level of the transgene, the retinal epithelium was ablated before or after its differentiation into a pigmented cell layer. We show that an early ablation (embryonic day E10-11) resulted in disorganization of the retinal layer, immediate arrest of eye growth and subsequent eye resorption. A later ablation (E11.5-12.5) allowed the eye to be maintained during embryogenesis, but the laminar structure of the retina became disrupted by the end of gestation, the vitreous failed to accumulate the adults were anophthalmic or severely microphthalmic. In some microphthalmic eyes, a number of RPE cells escaped ablation and formed patches of pigmented cells; the laminar structure of the retina was maintained immediately adjacent to such pigmented areas but disrupted elsewhere. In both cases--early or late ablation of the RPE--the retina appears to be the primary affected tissue. CONCLUSIONS: We conclude that presence of the RPE is required for the normal development of the eye in vivo. Its presence early in development is necessary for the correct morphogenesis of the neural retina. After the neural retina has started to differentiate, the RPE is still necessary, either directly or indirectly, to maintain the organization of the retinal lamina.

Animals↗

Efficacy of speech aid prostheses for acquired defects of the soft palate and velopharyngeal inadequacy--clinical assessments and cephalometric analysis: a Memorial Sloan-Kettering Study.

BACKGROUND: Restoration of speech after surgical resection for oropharyngeal cancer traditionally includes maxillofacial prosthetic intervention. Relatively few publications with objective speech outcomes exist. The purpose of this study was to evaluate speech outcome relative to the size of the surgical defect, the type of speech prosthesis, and the height and position of the speech bulb in relation to the posterior pharyngeal wall in the nasopharynx. METHODS: Fifty-five patients treated at the Memorial Sloan-Kettering Cancer Center Dental Service who underwent ablative cancer therapy were evaluated. All patients were 4 months or longer after surgery and were using a speech aid or obturator prosthesis at the time of the study. Speech samples for percent intelligibility and perceptual evaluation were collected and analyzed, in addition to aeromechanical measurements of palatopharyngeal function. Lateral cephalograms were taken while wearing the prosthesis using a radiopaque marker placed on the posterior aspect of the prosthesis for evaluating the height and position of the prosthesis obturator-speech bulb component. RESULTS: After adjustment for the differences between listeners, findings revealed that as the percentage of resection of palate or tongue increased, the intelligibility of speech decreased. Aeromechanical assessment of speech was the only outcome measure sensitive to the type of speech prosthesis. The position of the speech bulb component, as well as the angle measured, was correlated with the percent intelligibility. The amount of the prosthesis physically contacting the posterior pharyngeal wall was not significantly associated with any of the functional outcome measures. CONCLUSIONS: Speech aid and obturator prostheses contribute to a higher percentage of intelligible speech. A difference in intelligibility exists in relationship to the position of the prosthesis and the anterior tubercle of the atlas vertebrae (C1), both statistically and clinically. The position for optimal speech could not be specifically located mathematically (ie, 3 mm or 3 degrees inferior to the anterior tubercle of the atlas vertebrae) from the analysis. Subjective ratings of the efficacy of the obturator-speech bulbs by the clinicians did not correspond to the percent intelligibility. A strong statistical and clinical correlation exists supporting the efficacy of speech bulb-obturator intervention after velopharyngeal insufficiency for improved intelligibility of both words and sentences.

Adolescent↗

One-month stability of depression among elderly home-care patients.

OBJECTIVE: Studies in primary care settings have shown that depression is often chronic and associated with negative outcomes among patients with medical illness. The stability of depression among home care recipients has not been investigated. The authors examined the 1-month stability of major depression in a representative sample of elderly adults shortly after their admission to home care. METHODS: A group of 539 subjects over age 65, newly admitted to home care for skilled nursing, were interviewed with the Structured Clinical Interview for DSM-IV (SCID-IV). Depression severity, medical comorbidity, pain, functional status, cognitive status, and recent life events were also assessed. Of 84 subjects who met criteria for major depression (MDD) at baseline, 74 were available for 1-month follow-up interview. RESULTS: At 1-month follow-up, 31 subjects (42%) continued to meet MDD criteria; 20 (27%) achieved partial remission; and 23 (31%) were in full remission. Fewer instrumental activity limitations at baseline, experiencing "a great deal" of pain, and absence of a recent stressful life event were associated with full remission at 1-month follow-up. CONCLUSION: Nearly one-half of newly admitted elderly home care patients who meet criteria for MDD continue to meet full criteria 1 month later. Functional and psychosocial factors affect the short-term course.

Aged↗