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Biomedical subjects

J Rosen

Publications and source records attributed to J Rosen.

At least 55 records · Page 3Linked to original sources
PubMed1998

Computerized endoscopic surgical grasper.

We report a computerized endoscopic surgical grasper with computer control and a force feedback (haptic) user interface. The system uses standard unmodified grasper shafts and tips. The device can control grasping forces either by direct surgeon control, via teleoperation, or under software control. In this paper, we test an automated palpation function in which the grasper measures mechanical properties of the grasped tissue by applying a programmed series of squeezes. Experimental results show the ability to discriminate between the normal tissues of small bowel, lung, spleen, liver, colon, and stomach. We anticipate applications in telesurgery, clinical endoscopic surgery, surgical training, and research.

Endoscopes↗
PubMed1997

Association of plasma homovanillic acid with behavioral symptoms in patients diagnosed with dementia: a preliminary report.

Neuroleptic treatment of psychotic symptoms or agitated behavior in elderly patients diagnosed with dementia is associated with reduced efficacy and increased rates of neuroleptic-induced parkinsonism in comparison to younger patients with schizophrenia. We report the first study to examine the relationship between an in vivo measure of dopaminergic function, plasma homovanillic acid (pHVA), and ratings of psychosis, agitation, and parkinsonism before and after neuroleptic treatment in dementia patients. Pretreatment pHVA was significantly correlated with parkinsonian rigidity, with a trend observed with agitation and hostility. Though mean pHVA did not change during perphenazine treatment, intraindividual change in pHVA at day 15 was correlated with improvement in hostility, with a similar trend for improvement in agitation. These preliminary findings are consistent with reports associating dopaminergic function with agitated, but not psychotic, symptoms in patients diagnosed with dementia, and with a reduced responsivity of dopaminergic systems to neuroleptic treatment in these patients.

Aged↗
PubMed1997

A brain imaging (single photon emission computerized tomography) study of semantic and affective processing in psychopaths.

Psychopaths have been described as human predators who use charm, intimidation, and violence to control others and to satisfy their own needs. Underlying their propensity to violate social norms and expectations is a profound lack of empathy, guilt, or remorse, affective processes that have long resisted scientific investigation. Using brain imaging technology we found that psychopaths differed from nonpsychopaths in the pattern of relative cerebral blood flow during processing of emotional words. The results were consistent with the hypothesis that there are anomalies in the way psychopaths process semantic and affective information.

Adult↗
PubMed1997

In-vivo/in-vitro correlation of four extended release formulations of pseudoephedrine sulfate.

An in-vivo/in-vitro correlation was established for four formulations of pseudoephedrine sulfate modified release tablets exhibiting different in-vivo and in-vitro release rate and absorption characteristics. In-vitro release rate data were obtained for 12 individual tablets of each formulation using the USP Apparatus 2 paddle stirrer at 50 rev min-1 in 1000 ml 0.1 N hydrochloric acid for the first hour followed by 0.1 M phosphate buffer at pH 7.5 for hours 2-16. Inspection of the individual and mean release rate data indicated that the in-vitro release rate of pseudoephedrine sulfate was consistent with the intended design of the four extended release formulations. The in-vivo bioavailability and pharmacokinetics of these formulations were evaluated in 20 healthy volunteers under fasted conditions. Wagner-Nelson analyses of the in-vivo data revealed extended release absorption profiles for all four formulations. Linear regression analyses of the mean percentage of dose absorbed versus the mean in-vitro release resulted in statistically significant correlations (r2 > 0.99, p < 0.0001) for each formulation. Qualitative rank order correlations were observed among all combinations of in-vivo and in-vitro parameters. These data support a Level A correlation between in-vivo absorption profiles and in-vitro release rates of four pseudoephedrine sulfate extended release formulations determined in fasted healthy volunteers.

Adult↗
PubMed1997

Drug migration from the adhesive matrix to the polymer film laminate facestock in a transdermal nitroglycerin system.

The apparent loss of nitroglycerin in a prototype transdermal nitroglycerin system was investigated by attenuated total reflectance infrared (ATR-IR) microspectroscopy and high performance liquid chromatography (HPLC). Several transdermal nitroglycerin lots placed under controlled storage conditions exhibited loss of drug potency (up to 10%) along with the appearance of a defect in the polymer film laminate facestock. A significant loss of nitroglycerin from the transdermal drug/adhesive matrix may reduce the bioavailabilty of nitroglycerin to the patient. ATR-IR analysis confirmed that nitroglycerin migrated from the drug/adhesive matrix to the facestock polyester layer under storage conditions and that nitroglycerin was retained in the facestock polyester layer. An alternate sample extraction solution successfully removed the nitroglycerin from both the adhesive matrix and facestock polyester layer with nearly 100% labeled strength recovered. The relationship between the migration of nitroglycerin into the facestock polyester layer and the appearance of the defect in the facestock aluminum layer is discussed and a nitroglycerin-aluminum metal reaction mechanism is proposed.

Adhesives↗
PubMed1997

Spectroscopic identification of an amorphous-to-crystalline drug transition in a solid dispersion SCH 48461 capsule formulation.

Changes in the dissolution of a solid dispersion capsule formulation composed of amorphous SCH 48461 in a polyethylene glycol 8000 matrix were investigated. SCH 48461 [(3R,4S)-1,4-bis(4-methoxyphenyl)-3-(3-phenylpropyl)-2-azetidinone] is a potent cholesterol absorption inhibitor with low water solubility and low melting point. Several capsule lots placed under controlled storage conditions exhibited a slowing of dissolution as a function of time with large inter-lot and intra-lot dissolution variations. Capsule contents were analyzed by attenuated total reflectance infrared (ATR-IR) microspectroscopy and solid-state cross-polarization, magic angle spinning (CPMAS) 13C-nuclear magnetic resonance (NMR) spectrometry. ATR-IR microspectroscopic analysis showed large IR spectral differences between the lots including the presence of a crystalline drug fraction in lots which exhibited incomplete dissolution. Solid-state CPMAS 13C-NMR analysis confirmed the presence of a crystalline drug fraction in the problematic capsule lots. Both ATR-IR and CPMAS 13C-NMR spectral results produced a rank ordering of the crystalline drug fraction present in the capsule lots that correspond to the dissolution results.

Anticholesteremic Agents↗
PubMed1997

The effects of perphenazine on the concentration of nortriptyline and its hydroxymetabolites in older patients.

Twenty-five older patients who presented with psychotic depression were treated with a combination of nortriptyline and perphenazine. Plasma levels of nortriptyline, E-, and Z-10-OH nortriptyline (E- and Z-10-OH-NT) were measured before and after addition of perphenazine. The mean (+/-SD) initial nortriptyline dose was 59 +/- 24 mg/day, whereas the mean final nortriptyline and perphenazine doses were 56 +/- 24 and 19 +/- 13 mg/day, respectively. The mean plasma level to dose quotient for perphenazine (0.45 +/- 0.34 nM/mg/day) was comparable to the mean quotient reported previously in older psychotic patients treated with perphenazine alone. After addition of perphenazine, the median quotient of nortriptyline plasma level to nortriptyline dose (L/D) increased significantly (from 6.1 to 8.6). This change was inversely correlated with baseline nortriptyline L/D. The median ratio of E-10-OH-NT to nortriptyline plasma level decreased significantly (from 1.6 to 1.3), whereas the median ratio of Z-10-OH-NT to nortriptyline plasma level did not change significantly. These results are consistent with the known inhibition by perphenazine of the cytochrome P450 2D6 (sparteine/debrisoquine hydroxylase), the major enzyme involved in the oxidative metabolism of nortriptyline, mostly through the formation of E-10-OH-NT. This complex alteration in the metabolism of nortriptyline induced by perphenazine emphasizes the relevance of measuring plasma levels not only of nortriptyline but also of its hydroxymetabolites in older patients who are more likely to be sensitive to their differing cardiovascular, anticholinergic, and cognitive effects.

Aged↗
PubMed1997

Control-relevant intervention in the treatment of minor and major depression in a long-term care facility.

The authors assessed the effect of a control-relevant psychosocial intervention in 31 nursing home residents with either major depressive episode or minor depression. An initial group of 22 residents were randomized to either active treatment or waiting list. Four of 11 residents randomized to active treatment were deemed Responders, compared with 0 of 11 on the waiting list (P < 0.05). Of the total of 31 residents who participated in the intervention, 14 (45%) were deemed Responders during the intervention period. For these Responders, the Hamilton Rating Scale for Depression (Ham-D) and Geriatric Depression Scale scores improved significantly during the intervention. The improvement in the Ham-D was not sustained 2 months after intervention was terminated. These findings suggest that a psychosocial intervention enhancing socialization according to each resident's choice had a positive therapeutic impact on almost half of the nursing home residents with major or minor depression. However this effect could not be sustained by the residents without the support of the structured program.

Aged↗
PubMed1997

Effect of sertraline on plasma nortriptyline levels in depressed elderly.

BACKGROUND: Several serotonin selective reuptake inhibitors have been reported to be inhibitors of the cytochrome P450 2D6 (CYP2D6). Thus, they may increase the plasma level of secondary amine tricyclic antidepressants, which are predominantly metabolized through this enzyme. Except for a few case reports, no clinical data document the degree of this drug-drug interaction in elderly depressed patients. METHOD: We systematically examined this interaction by determining the change in plasma nortriptyline levels in 14 elderly depressed patients in whom sertraline was added to nortriptyline. RESULTS: After addition of 50 mg/day of sertraline, the median increase in plasma nortriptyline level over baseline was 2% (range, -26% to 117%; p = .30). In 2 patients (14%), there was an increase of 50% or more. For patients taking higher sertraline doses (N = 7; 100 or 150 mg/day), the median increase in plasma nortriptyline level over baseline was 40% (range, -12% to 239%; p = .08). CONCLUSION: Overall, a modest effect of sertraline was observed on nortriptyline metabolism in these elderly depressed patients. This is consistent with prior reports of a weak inhibition of CYP2D6 by sertraline in vitro and in young healthy volunteers. However, some patients showed a change in plasma nortriptyline level that would be considered clinically significant. Thus, careful monitoring of plasma nortriptyline levels is recommended in all patients treated with a combination of nortriptyline and sertraline.

1-Naphthylamine↗
PubMed1997

Increased G-CSF responsiveness of bone marrow cells from hematopoietic cell phosphatase deficient viable motheaten mice.

The mouse mutation viable motheaten (me(v)) results in defects in the expression and catalytic activity of the cytoplasmic protein tyrosine phosphatase known as hematopoietic cell phosphatase (HCP). This reduction in HCP activity leads to the aberrant regulation of several myeloid and lymphoid cell lineages, including substantial increases in numbers of granulocytes. The differentiation, proliferation, and survival of cells in this lineage are normally supported by granulocyte-colony stimulating factor (G-CSF). In this study we have determined the consequences of the loss of HCP activity in me(v)/me(v) mice on the response of bone marrow cells to G-CSF. Bone marrow from these mice exhibited substantial increases in clonogenic and proliferative responses to G-CSF. These enhanced activities of G-CSF correlated with an increase in the level of immature granulocytic, G-CSF receptor positive cells in the bone marrow. These results suggested the possibility that HCP may regulate the G-CSF receptor by a direct interaction. However, under conditions where the previously described interaction between the erythropoietin receptor and HCP was readily observed, HCP did not detectably associate with the G-CSF receptor.

Animals↗
PubMed1997

Plasma levels of citalopram enantiomers and metabolites in elderly patients.

Ten patients with dementia and significant behavioral disturbances (mean age of 77.2 +/- 8.2 years) received citalopram, 10 mg/day for 3 days, followed by 20 mg/day for 2 weeks. Six of the 10 patients completing 17 days of treatment had a clinically impressive response, as assessed by significant improvement in six target items on the Neurobehavioral Rating Scale. Eight patients were also analyzed by measuring the racemic and enantiomeric plasma levels of citalopram (CIT) and desmethylcitalopram (DCIT). A sensitive high-performance liquid chromatography (HPLC) assay for citalopram enantiomers and metabolites was developed using ultraviolet detection. The lower limit of detection was 10 ng/ml for each enantiomer. Steady-state plasma level ranges were 11.2 to 92.2 ng/ml for the biologically active S(+) citalopram and 12.8 to 95.7 ng/ml for the inactive R(-) enantiomer. For the S and R enantiomers of desmethylcitalopram, plasma levels ranged from 11.0 to 22.0 ng/ml and 9.2 to 22.0 ng/ml, respectively. The racemic citalopram plasma level to dose ratio of 3.50 was higher than the ratio (1.96) reported by Overo (1982) for 55 younger patients. The stereoselective metabolism of the enantiomers for citalopram and desmethylcitalopram (S(+) and R(-) enantiomers) in these older subjects differed from that reported in younger patients, suggesting possible age-associated changes in CYP2C19 activities. We hypothesize that quantification of S(+) citalopram will permit a more accurate examination of dose/response relationships. This measure seems to be especially important for older subjects, given the wide ranges and higher concentrations evident from our preliminary results.

Aged↗
PubMed1997

An open pilot study of citalopram for behavioral disturbances of dementia. Plasma levels and real-time observations.

Citalopram, in European studies, has shown some early promise for treatment of poststroke depression and behavioral complications of dementia. An open pilot study of citalopram was conducted in 16 patients with dementia and behavioral disturbances. Citalopram was well tolerated by 13 of the patients, and 9 had a clinically impressive response. A significant overall mean reduction in disruptive vocalizations was observed by means of a novel technique of computer-assisted real-time observation. The mean citalopram plasma level-to-dose ratio was found to be twice that previously reported in younger patients. These pilot findings should encourage future placebo concentration-controlled trials.

Aged↗
PubMed1997

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↗
PubMed1996

Multiple signaling pathways induced by granulocyte colony-stimulating factor involving activation of JAKs, STAT5, and/or STAT3 are required for regulation of three distinct classes of immediate early genes.

Granulocyte colony-stimulating factor (G-CSF) is the major regulator of proliferation and differentiation of neutrophilic granulocyte precursor cells. G-CSF activates multiple signaling molecules, including the JAK1 and JAK2 kinases and the STAT transcription factors. To investigate G-CSF signaling events regulated by the JAK-STAT pathway, we have generated UT7-epo cells stably expressing either wild-type (wt) G-CSF receptor or a series of C-terminal deletion mutants. Gel mobility shift and immunoprecipitation/Western analysis showed that STAT5 is rapidly activated by G-CSF in cells expressing the wt G-CSF receptor, in addition to the previously reported STAT3 and STAT1. Mutants lacking any tyrosine residues in the cytoplasmic domain maintain their ability to activate STAT5 and STAT1 but cannot activate STAT3, implying that STAT5 and STAT1 activation does not require receptor tyrosine phosphorylation. We also observed significant changes in the ratio of STAT1:STAT3:STAT5 activated by various G-CSF receptor C-terminal deletion mutants. These mutant receptors were further used to investigate the role of JAKs and STATs in G-CSF-mediated responses in these cells. We found that JAK activation correlates with G-CSF-induced cell proliferation, whereas STAT activation is not required. We have also identified three classes of G-CSF immediate early genes, whose activation correlates with the activation of distinct JAK-STAT pathways. Our data show that, whereas c-fos is regulated through a pathway independent of STAT activation, oncostatin M, IRF-1, and egr-1 are regulated by an STAT5-dependent pathway and fibrinogen is regulated by an STAT3-dependent pathway. In conclusion, our results suggest that G-CSF regulates its complex biologic activities by selectively activating distinct early response genes through different JAK-STAT signaling molecules.

Animals↗
PubMed1996

Association of the APOE epsilon 4 allele with clinical subtypes of late life depression.

The APOE genotypes of 45 elderly inpatients with major depression were determined to investigate the relationship of this disorder to irreversible dementia in late life. We specifically tested the hypothesis that the frequency of the APOE epsilon 4 allele is elevated in depressed elders with cognitive impairment or psychotic features, subtypes that have been reported to be at increased risk of developing Alzheimer's disease (AD). The frequency of epsilon 4 allele was not elevated in the overall group of 45 inpatients and, contrary to our expectation, was not associated with cognitive impairment in this group. In contrast, the epsilon 4 allele frequency for the patients with psychotic features was nearly four times that for the patients without psychotic features and nearly double that of elderly controls. These data suggest that elderly depressed inpatients with cognitive impairment are at risk for developing AD by an epsilon 4-independent pathway, while those with psychotic features are at risk for developing AD by an epsilon 4-dependent pathway. These findings suggest that subtypes of idiopathic major depression in late life may serve as landmarks that distinguish separable pathogenetic pathways to AD.

Age of Onset↗