PubMed Health⌕ Search

Biomedical subjects

T E Smith

Publications and source records attributed to T E Smith.

At least 19 recordsLinked to original sources
PubMed2002

Case reports - reversal of sensory deficit associated with pain relief after treatment with gabapentin.

Many patients with neuropathic pain have coexistent sensory deficits. Neuropathic pain may be alleviated by a variety of drugs but sensory deficits are assumed to be permanent. In an audit of the effects of gabapentin therapy on patients with neuropathic pain, monthly detailed sensory examinations were performed during the first three months of treatment. Of five patients with sensory deficits who tolerated gabapentin therapy, three showed marked improvement of their sensory deficits associated with pain alleviation. The cases are presented and possible explanations for the observed sensory improvements are discussed. These findings raised exciting neurophysiological questions in addition to being of potential importance to the clinical problem of neurotrophic tissue injury.

Acetates↗
PubMed2002

Benign multicystic mesothelioma: a case report.

Benign multicystic mesothelioma (also known as multilocular peritoneal inclusion cyst) is a rare lesion found on any abdominal peritoneal surface that occurs most frequently in premenopausal women. We report the case of a 36-year- old woman, who presented with a history of generalized abdominal pain, intermittent abdominal bloating, and episodes of loose stools. A pelvic ultrasound revealed a complex cystic mass with fine internal septations. The patient was managed by laparotomy with removal of mass, total abdominal hysterectomy, bilateral salpingo-oophorectomy, omentectomy, and multiple peritoneal biopsies. Final pathology revealed benign multicystic mesothelioma. Although mesothelioma is a rare tumour, it is important for all gynaecologists to recognize its existence, the appearance of this lesion, and its generally benign course. This is especially important as it occurs in young women where fertility considerations must be part of the discussion of any pelvic surgery.

Abdominal Pain↗
PubMed2001

A subset of NSAIDs lower amyloidogenic Abeta42 independently of cyclooxygenase activity.

Epidemiological studies have documented a reduced prevalence of Alzheimer's disease among users of nonsteroidal anti-inflammatory drugs (NSAIDs). It has been proposed that NSAIDs exert their beneficial effects in part by reducing neurotoxic inflammatory responses in the brain, although this mechanism has not been proved. Here we report that the NSAIDs ibuprofen, indomethacin and sulindac sulphide preferentially decrease the highly amyloidogenic Abeta42 peptide (the 42-residue isoform of the amyloid-beta peptide) produced from a variety of cultured cells by as much as 80%. This effect was not seen in all NSAIDs and seems not to be mediated by inhibition of cyclooxygenase (COX) activity, the principal pharmacological target of NSAIDs. Furthermore, short-term administration of ibuprofen to mice that produce mutant beta-amyloid precursor protein (APP) lowered their brain levels of Abeta42. In cultured cells, the decrease in Abeta42 secretion was accompanied by an increase in the Abeta(1-38) isoform, indicating that NSAIDs subtly alter gamma-secretase activity without significantly perturbing other APP processing pathways or Notch cleavage. Our findings suggest that NSAIDs directly affect amyloid pathology in the brain by reducing Abeta42 peptide levels independently of COX activity and that this Abeta42-lowering activity could be optimized to selectively target the pathogenic Abeta42 species.

Alzheimer Disease↗
PubMed2001

Quality of life in schizophrenia: contributions of anxiety and depression.

A number of studies have demonstrated a strong relationship between quality of life in schizophrenia and general psychopathology measures, and moreover, that the positive, negative, and disorganized symptoms are less related to quality of life. The current investigation examined the relationship between quality of life and symptomatology in 63 stabilized outpatients diagnosed with schizophrenia or schizoaffective disorder. Consistent with other findings, more severe depression, as rated on the Brief Psychiatric Rating Scale (BPRS) was associated with lower general life satisfaction and lower satisfaction with daily living, finances, health, and social life. In addition, higher anxiety ratings on the BPRS were associated with less satisfaction with global quality of life, daily activities, family, health and social relationship, even when controlling for positive symptoms, negative symptoms, or depression. No other symptoms of schizophrenia were as strongly associated with subjective quality of life. Anxiety was also significantly correlated with a number of positive and negative symptoms while depression was substantially less related. These findings, suggest that more precise analyses of general psychopathology, and anxiety in particular, may be necessary to further clarify the factors involved in quality of life in schizophrenia. In addition, these findings suggest future directions for theories of affect and treatment in schizophrenia.

Adolescent↗
PubMed2001

Female marmoset monkeys (Callithrix jacchus) can be identified from the chemical composition of their scent marks.

The present study analyzed 42 organic solvent extracts of scent mark pools from five dominant female common marmosets by gas chromatography (GC) and combined GC and mass spectrometry. We determined whether there were qualitative or quantitative differences between the chemical composition of scent marks from individual females. Gas chromatography and mass spectral analysis detected the same 162 chemicals in 86% (36/42) of scent mark pools from five dominant females. This near identical chemical composition of scent marks suggested there were few, if any, qualitative differences between the chemical composition of scent marks from individual females. Instead, quantitative differences in scent may provide the key factor distinguishing individual females. Using the relative concentration of highly volatile chemicals detected by GC in scent marks, linear discriminant analysis classified scent mark pools to their correct donor approximately 91% of the time. Such highly reliable statistical matching of scent to donor suggested that each individual female common marmoset has a unique ratio of highly volatile chemicals in their scent marks which may permit individual identification of females from odors in their scent alone.

Animals↗
PubMed2001

Longitudinal analysis of subjective quality of life in schizophrenia: anxiety as the best symptom predictor.

We examined the relationships among changes in anxiety, depression, core symptoms of schizophrenia, and subjective quality of life (QL) longitudinally. Fifty-three stabilized outpatients diagnosed with schizophrenia or schizoaffective disorder were assessed for QL and symptoms every 3 months for a period of 1 year. Using mixed effects models, we found that changes in anxiety, as rated on the Brief Psychiatric Rating Scale, were inversely associated with general life satisfaction and satisfaction with many specific domains. These relationships were stronger than the relationships of QL and any other core symptoms of schizophrenia, including depression. Anxiety was also related to some positive and negative symptoms. These findings support the notion that more precise analysis of general psychopathology, and anxiety in particular, is important in clarifying the factors involved in QL in schizophrenia. We explain our findings in the context of current theories of affect and suggest implications for the treatment of schizophrenia.

Adult↗
PubMed2000

True recurrence vs. new primary ipsilateral breast tumor relapse: an analysis of clinical and pathologic differences and their implications in natural history, prognoses, and therapeutic management.

PURPOSE: The purpose of this study was to classify all ipsilateral breast tumor relapses (IBTR) in patients treated with conservative surgery and radiation therapy (CS+RT) as either new primary tumors (NP) or true local recurrences (TR) and to assess the prognostic and therapeutic implications of this classification. METHODS AND MATERIALS: Of the 1152 patients who have been treated at Yale-New Haven Hospital before 1990, 136 patients have experienced IBTR as their primary site of failure. These relapses were classified as either NP or TR. Specifically, patients were classified as NP if the recurrence was distinctly different from the primary tumor with respect to the histologic subtype, the recurrence location was in a different location, or if the flow cytometry changed from aneuploid to diploid. This information was determined by a detailed review of each patient's hospital and/or radiotherapy record, mammograms, and pathologic reports. RESULTS: As of 2/99, with a mean follow-up of 14. 2 years, the overall ipsilateral breast relapse-free rate for all 1152 patients was 86% at 10 years. Using the classification scheme outlined above, 60 patient relapses were classified as TR, 70 were classified as NP and 6 were unable to be classified. NP patients had a longer mean time to breast relapse than TR patients (7.3 years vs. 3.7 years, p < 0.0001) and were significantly younger than TR patients (48.9 years vs. 54.5 years, p < 0.01). Patients developed both TR and NP at similar rates until approximately 8 years, when TR rates stabilized but NP rates continued to rise. By 15 years following original diagnosis, the TR rate was 6.8% compared to 13.1% for NP. Of the patients who had been previously tested for BRCA1/2 mutations, 17% (8/52) had deleterious mutations. It is noteworthy that all patients with deleterious mutations had new primary IBTR, while patients without deleterious mutations had both TR and NP (p = 0.06). Ploidy was evenly distributed between TR and NP but NP had a significantly lower S phase fraction (NP 13.1 vs. TR 22.0, p < 0.05). The overall survival following breast relapse was 64% at 10 years and 49% at 15 years. With a mean follow-up of 10.4 years following breast relapse, patients with NP had better 10-year overall survival (TR 55% vs. NP 75%, p < 0.0001), distant disease-free survival (TR 41% vs. NP 85%, p < 0.0001), and cause-specific survival (TR 55% vs. NP 90%, p < 0.0001). CONCLUSION: It appears that a significant portion of patients who experience ipsilateral breast tumor relapse following conservative surgery and radiation therapy have new primary tumors as opposed to true local recurrences. True recurrence and new primary tumor ipsilateral breast tumor relapses have different natural histories, different prognoses, and, in turn, different implications for therapeutic management.

Adult↗
PubMed2000

Presenilin 1 regulates pharmacologically distinct gamma -secretase activities. Implications for the role of presenilin in gamma -secretase cleavage.

Presenilins (PSs) are polytopic membrane proteins that have been implicated as potential therapeutic targets in Alzheimer's disease because of their role in regulating the gamma-secretase cleavage that generates the amyloid beta protein (Abeta). It is not clear how PSs regulate gamma-secretase cleavage, but there is evidence that PSs could be either essential cofactors in the gamma-secretase cleavage, gamma-secretase themselves, or regulators of intracellular trafficking that indirectly influence gamma-secretase cleavage. Using presenilin 1 (PS1) mutants that inhibit Abeta production in conjunction with transmembrane domain mutants of the amyloid protein precursor that are cleaved by pharmacologically distinct gamma-secretases, we show that PS1 regulates multiple pharmacologically distinct gamma-secretase activities as well as inducible alpha-secretase activity. It is likely that PS1 acts indirectly to regulate these activities (as in a trafficking or chaperone role), because these data indicate that for PS1 to be gamma-secretase it must either have multiple active sites or exist in a variety of catalytically active forms that are altered to an equivalent extent by the mutations we have studied.

Amino Acid Sequence↗
PubMed2000

Oxytocin responsivity in mothers of infants: a preliminary study of relationships with blood pressure during laboratory stress and normal ambulatory activity.

The neuropeptide oxytocin (OT) enhances maternal behavior and decreases blood pressure (BP) and stress responses in animals. Thus, the relationship of OT responsivity to BP in 14 breast- and 11 bottle-feeding mothers of infants was examined. Laboratory BP was assessed during baseline, speech preparation, active speech, and recovery on 2 days, 1 in which baseline and speech were separated by 10 min of baby holding and the other by no baby contact. Systolic BP reactivity to speech was lower after baby contact. Plasma OT change from baseline to speech after baby contact defined OT increase, minimal OT change, and OT decrease groups. OT increase mothers were primarily breast-feeders, and they had lower BP throughout both stress sessions and after baby feeding at home than OT decrease mothers, who also had greater BP reactivity to preparation and recovery. These results suggest that oxytocin has antistress and BP-lowering effects in humans.

Adult↗
PubMed2000

Insight, symptoms, and neurocognition in schizophrenia and schizoaffective disorder.

There are conflicting reports in the literature regarding the relationships among impaired insight, symptoms, and neurocognition in schizophrenia. The inconsistent findings likely reflect the multidimensionality of insight in this population, along with variations in study design. We examined 46 individuals with chronic schizophrenia or schizoaffective disorder who were recently discharged from an inpatient unit. Insight was operationalized as awareness of having a mental disorder and awareness and attribution of both current and past symptoms. Positive, negative, disorganized, and depression symptoms were rated, and a neurocognition battery, including measures of visual processing, memory, visuo-spatial ability, and executive functions, was administered. Poor awareness of symptoms was moderately associated with core schizophrenia symptoms, and higher levels of depression were strongly associated with good awareness. Symptom misattribution, more so than symptom unawareness, was associated with deficits in frontal lobe functioning. Finally, different patterns of associations between symptoms, neurocognition, and insight were noted for current symptoms versus past symptoms. The data suggest that insight deficits in schizophrenia are multidimensional, and that investigators should pay careful attention to the choice of measures as well as to phase of illness characteristics in future studies.

Adolescent↗
PubMed2000

Pharmacokinetics of dopamine in healthy male subjects.

BACKGROUND: Dopamine is an agonist of alpha, beta, and dopaminergic receptors with varying hemodynamic effects depending on the dose of drug being administered. The purpose of this study was to measure plasma concentrations of dopamine in a homogeneous group of healthy male subjects to develop a pharmacokinetic model for the drug. Our hypothesis was that dopamine concentrations can be predicted from the infusion dose using a population-based pharmacokinetic model. METHODS: Nine healthy male volunteers aged 23 to 45 yr were studied in a clinical research facility within our academic medical center. After placement of venous and arterial catheters, dopamine was infused at 10 microg x kg(-1) x min(-1) for 10 min, followed by a 30-min washout period. Subsequently, dopamine was infused at 3 microg x kg(-1) x min(-1) for 90 min, followed by another 30-min washout period. Timed arterial blood samples were centrifuged, and the plasma was analyzed by high-performance liquid chromatography. Mixed-effects pharmacokinetic models using NONMEM software (NONMEM Project Group, University of California, San Francisco, CA) were used to determine the optimal compartmental pharmacokinetic model for dopamine. RESULTS: Plasma concentrations of dopamine varied from 12,300 to 201,500 ng/l after 10 min of dopamine infusion at 10 microg x kg(-1) x min(-1). Similarly, steady-state dopamine concentrations varied from 1,880 to 18,300 ng/l in these same subjects receiving 3-microg x kg(-1) x min(-1) infusions for 90 min. A two-compartment model adjusted for body weight was the best model based on the Schwartz-Bayesian criterion. CONCLUSIONS: Despite a homogeneous population of healthy male subjects and weight-based dosing, there was 10- to 75-fold intersubject variability in plasma dopamine concentrations, making standard pharmacokinetic modeling of less utility than for other drugs. The data suggest marked intraindividual and interindividual variability in dopamine distribution and/or metabolism. Thus, plasma dopamine concentrations in patients receiving dopamine infusion at identical rates may vary profoundly. Our data suggest that dosing dopamine based on body weight does not yield predictable blood concentrations.

Adult↗
PubMed2000

Ethical decision making among family therapists and individual therapists.

In this study, we investigated the ethical decision making of 30 individual and 30 family therapists in order to detect the types of decision making used by practicing therapists. Informants responded to three ethical dilemmas. Two of the situations were hypothetical. The third dilemma was a situation the informant had experienced in practice. Each interview was assessed for decision-making style, using content analysis. Kohlberg's justice reasoning and Gilligan's care reasoning provided the conceptual foundations for this analysis. The results suggest that both family and individual therapists prefer care reasoning on all dilemma types. There was significantly more care reasoning demonstrated on the personal dilemma than on the hypothetical dilemmas. Characteristics of informants did not provide clear explanations for the differences found in reasoning.

Adult↗
PubMed2000

Neuropathic pain.

Neuropathic pain is a distressing, poorly understood and under-treated condition. In this review we seek to examine the definition and classification of neuropathic pain, summarize clinically important underlying mechanisms, outline current management strategies and look at future directions for research and therapy.

Analgesics↗
PubMed2000

Adolescents' knowledge and beliefs about pregnancy: the impact of "ENABL".

Finding effective ways to prevent adolescent pregnancy is a concern of public health officials, educators, social workers, parents, and legislators. Numerous programs exist, but there is debate as to whether it is the specific program itself or other factors that are responsible for participants' successful outcomes. Using a quasi-experimental design, this study sought to determine which factors predicted changes in knowledge and beliefs among middle school students (N = 1,450) after exposure to Postponing Sexual Involvement (PSI), the curricular component of Education Now and Babies Later (ENABL), a pregnancy prevention program. It was found that the single most important predictor of improvement in knowledge and beliefs about pregnancy prevention was PSI itself, not background variables. The findings contradict some of the previous studies on factors impacting teenage pregnancy and lend support for the continued examination of ENABL as a promising component of pregnancy prevention efforts.

Adolescent↗
PubMed1999

Interactive risk factors for treatment adherence in a chronic psychotic disorders population.

This study identified the unique and primary contributions of several concurrent risk factors for poor adherence to treatment recommendations in a clinic population of individuals with chronic psychotic disorders, i.e. 48% had DSM-IV diagnoses of schizoaffective disorder, 38% had schizophrenia, paranoid type, 12% had schizophrenia, undifferentiated type, and 2% had affective disorder with psychotic features. The target cohort consisted of 87 consecutive admissions to a continuing day treatment program. As part of a services-oriented quality assurance program, clinical staff completed rating scales for all patients. These included the BASIS-32 rating scale, which consisted of the following five subscales: psychosis; depression/anxiety; impulsive/addictive behavior; relation to self and others; and daily living and role functioning, and the Working Alliance Inventory-short form (therapist version), which consisted of the following three subscales: goal; task; and bond. These data were used to identify risk factors that weaken a patient's adherence to medication and non-medication treatment during the first 2 weeks of treatment in the clinic. Medication treatment consisted of both typical and atypical neuroleptic medications, with most patients being on multiple medications. Correlational analyses suggested that many of the risk factor variables were significantly associated with poor treatment adherence. Regression analyses suggested that the degree of psychoticism was most strongly associated with poor adherence to medication treatment and that difficulties relating to self and others were the strongest predictor of poor adherence to non-medication treatment. A large-sample services research design such as this can begin to determine patterns of associations between previous identified risk factors and poor treatment adherence in individuals with chronic psychotic disorders.

Adult↗
PubMed1999

Selective lithiation of 2-methyloxazoles. Applications to pivotal bond constructions in the phorboxazole nucleus.

[formula: see text] The lithiation of 2-methyloxazoles with alkyllithium and hindered lithium amide bases generally results in the competitive formation of a mixture of 5-lithio- and 2-(lithiomethyl)oxazole isomers. Herein a synthetically useful lithiation method which allows for the selective formation of 2-(lithiomethyl)oxazole is described. Diethylamine has been found to be a kinetically competent proton source that will mediate the equilibration of the kinetically formed 5-lithiooxazole to its more stable 2-(lithiomethyl)oxazole counterpart. Application of this metalation strategy with lithium diethylamide to two important bond constructions relevant to a projected phorboxazole synthesis is presented.

Alkylation↗
PubMed1999

The relative influences of symptoms, insight, and neurocognition on social adjustment in schizophrenia and schizoaffective disorder.

Impaired insight and neurocognitive deficits are commonly seen in schizophrenia. No study to date, however, has documented the relative influences of insight deficits, neurocognitive functioning, and psychotic symptoms on overall social adjustment in this population. This was done in a cohort of individuals recovering from acute exacerbations. Forty-six individuals with schizophrenia or schizoaffective disorder were recruited upon discharge from an inpatient unit. Symptom levels, neurocognitive functioning (information processing, memory, and executive functioning), and symptom awareness were documented, and social adjustment was assessed in three domains: treatment compliance, social behavior, and subjective quality of life. Cross-sectional data from initial assessments are reported. Sequential linear regression analyses identified differential associations between illness characteristics and outcome domains. Treatment compliance was most influenced by insight; social behavior deficits were associated with thought disorder and neurocognitive (working memory and visuo-spatial) impairments; and quality of life was associated with mood disturbances. Outcome is multidimensional in schizophrenia, and there are differential patterns of associations between illness characteristics and domains of social adjustment. Studies such as this can guide clinicians in determining the most appropriate treatments for specific individuals and should also guide researchers in efforts to clarify the processes that underlie treatment response and recovery in schizophrenia.

Adult↗