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T L Smith

Publications and source records attributed to T L Smith.

At least 127 records · Page 7Linked to original sources
PubMed1998

Environmental contamination with vancomycin-resistant enterococci in an outpatient setting.

Eleven cancer patients colonized with vancomycin-resistant enterococci (VRE) were followed as outpatients. Environmental cultures were obtained from clinic rooms before and after patients care. Environmental contamination occurred in 29% of encounters. Superficial disinfection did not eradicate contamination, although more thorough cleaning did. We conclude that environmental VRE contamination occurs in the outpatient setting. Infection control practices, similar to those used in the inpatient setting, may be necessary for outpatient clinics.

Adolescent↗
PubMed1998

The BCR gene recombines preferentially with Alu elements in complex BCR-ABL translocations of chronic myeloid leukaemia.

Chronic myeloid leukaemia (CML) develops when two genes, BCR on chromosome 22 and ABL on chromosome 9, recombine to form a hybrid BCR-ABL gene with leukaemogenic properties. The mechanism which underlies this recombination is unknown, but additional chromosome sites may be involved to form complex BCR-ABL rearrangements. The majority of breakpoints in BCR occur within a 5 kb major breakpoint cluster region, M-Bcr. Here, we show that the 3' part of M-Bcr recombined within, or immediately adjacent to, Alu elements at the additional sites in all five complex BCR-ABL rearrangements that have been examined so far. This is a new finding which suggests that Alu sequences have an affinity for the BCR-ABL recombination process in complex rearrangements, and provides additional evidence for the association of these elements with somatic rearrangements which cause human leukaemia. We further show that sequence motifs similar to IgH switch pentamers and consensus binding sites of the lymphoid-associated Translin protein are present on one or more participating strands at 3'M-Bcr recombination sites. Motifs similar to Translin-binding sites were also identified within the Alu consensus. Expressed sequences mapped close to the breakpoint sites on other chromosomes in three of the five cases examined.

Base Sequence↗
PubMed1998

Endogenous nitric oxide influences arteriovenous anastomosis adrenergic tone in the conscious rabbit ear.

The role of nitric oxide (NO) in the control of arteriovenous anastomoses (AVAs) has not been studied in vivo in a thermoregulatory end organ. In this study, the effect of local inhibition of NO synthesis by NG-nitro-L-arginine methyl ester (L-NAME) on the microvasculature in the rabbit ear (n=12) was observed in vivo through a chronically implanted ear microvascular chamber. Ear cutaneous blood perfusion (CBP), total auricular arterial flow (TAF), and ear temperature were monitored simultaneously with the direct microvascular observations. Results revealed that intrafacial artery infusion of L-NAME produced significant vasoconstriction of arterioles, AVAs, and venules (p < 0.05). A decrease of ear blood perfusion also was demonstrated by changes of CBP, TAF, and surface temperature. The data provide evidence that basal generation of NO influences the vascular resistance in the thermoregulatory end organ. Moreover, endogenous NO production may be more important in regulating the AVA flow than is flow in other parts of the rabbit ear microvasculature. The effects of NO inhibition on ear microvasculature were not abolished by superior cervical ganglionectomy, indicating that NO production in the rabbit ear is not a neurally mediated mechanism. Further study with a short-term rabbit ear preparation showed that inhibition of NO production with L-NAME enhanced microvascular constrictive responses to extraluminal application of norepinephrine. NO thus appears to play a role of basal vasodilator in opposition to the basal adrenergic vasoconstrictor tone in the rabbit ear.

Animals↗
PubMed1998

Contusion of skeletal muscle increases leukocyte-endothelial cell interactions: an intravital-microscopy study in rats.

OBJECTIVE: To investigate the relationship between secondary muscle damage after contusion and the interactions between leukocytes and endothelial cells, which are essential steps in secondary inflammatory response. METHODS: In a randomized animal study, rats were chronically instrumented with dorsal skinfold microvascular chambers and exposed to standardized contusion or sham contusion. Leukocyte rolling and adherence in postcapillary venules before and after muscle contusion or sham contusion were quantitated using in vivo microscopy. RESULTS: The number of rolling leukocytes in the postcapillary venules before contusion was low. At 300 minutes after contusion, the number of rolling and adherent leukocytes in the striated muscle microvasculature was increased significantly (p < or = 0.05) compared with either the baseline precontusion condition or the control group at the same time. CONCLUSION: In the mid-term to long-term stages of skeletal muscle injury associated with contusion, a significant portion of tissue damage is secondary to leukocyte-endothelial cell interactions.

Animals↗
PubMed1998

Clinical relevance of the distinction between alcohol dependence with and without a physiological component.

OBJECTIVE: DSM-IV indicates that diagnoses of substance dependence should be further characterized with regard to the presence of a physiological component, defined by tolerance or withdrawal. This study evaluated the possible meaning of this distinction in alcohol-dependent men and women. METHOD: As part of the Collaborative Study on the Genetics of Alcoholism, structured interviews were carried out with 3,395 DSM-III-R-defined alcohol-dependent individuals divided into 2,949 subjects (86.9%) with evidence of tolerance and/or withdrawal (group 1), 51.3% of whom evidenced withdrawal symptoms, and 446 subjects (13.1%) without a physiological component (group 2). Data were evaluated to determine differences between the two groups. RESULTS: Group 1 reported greater severity of alcohol dependence as demonstrated by a larger maximum number of drinks in 24 hours, more persons reporting binges, more alcohol-related life problems, more relevant DSM-III-R criteria endorsed, more physiological complications, and more alcohol-related emotional/psychiatric symptoms such as depression and anxiety. Each of these severity indicators for problems in group 1 was significant in the presence of the others in a logistic regression, and similar items remained significant when tolerance alone, withdrawal alone, or their combination was used as the criterion for group 1 membership; however, for withdrawal a larger proportion of the variance was explained by the predictor variables. The regression results were independent of gender, proband status, and history of antisocial personality disorder. CONCLUSIONS: The results support the clinical relevance of distinguishing between alcohol-dependent patients with and without a physiological component. The data indicate a potential advantage to limiting that definition to withdrawal only.

Adult↗
PubMed1998

Early treatment decisions with interferon-alfa therapy in early chronic-phase chronic myelogenous leukemia.

PURPOSE: To determine, in patients with Philadelphia chromosome (Ph)-positive chronic myelogenous leukemia (CML) on interferon alfa (IFNalpha), whether combining pretreatment characteristics and early response profiles would distinguish patients with differential benefits that would allow better decisions on subsequent therapy. PATIENTS AND METHODS: A total of 274 patients treated from 1982 through 1990 with IFNalpha regimens were analyzed. A second group of 137 patients treated with IFNalpha and low-dose cytarabine (ara-C) between 1990 and 1994 was later used to confirm the guidelines derived from the original study group analysis. Patients' pretreatment factors and response to IFNalpha therapy at 3, 6, and 12 months were analyzed in relation to subsequent achievement of major cytogenetic response. After univariate analysis of prognostic factors, a multivariate analysis selected, at 6 months, independent pretreatment factors that added to the response status in predicting subsequent outcome. The results were then applied at the 3- and 12-month periods and confirmed in the subsequent population. RESULTS: Response to IFNalpha therapy at 3, 6, and 12 months was a significant predictor of later major cytogenetic response. The presence of splenomegaly > or = 5 cm below the costal margin (BCM) or thrombocytosis > or = 700 x 10(9)/L pretreatment added significant independent prediction to response. At 6 months, patients with a partial hematologic response (PHR) or resistant disease had a less than 10% chance of achieving a later major cytogenetic response, as were those in complete hematologic response (CHR) and who had pretreatment splenomegaly and thrombocytosis. Applying the model at 3 months showed that only patients with < or = PHR and pretreatment splenomegaly or thrombocytosis at 3 months had such a low major cytogenetic response rate. Finally, at 12 months, patients with CHR still had a 15% to 25% chance of having a major cytogenetic response later if they did not have pretreatment splenomegaly and thrombocytosis. CONCLUSION: This analysis allows better selection of patients with Ph-positive CML on IFNalpha therapy for continuation of IFNalpha versus changing therapy early in the course of CML. For treatment programs that choose to change patients to other investigational therapies (eg, intensive chemotherapy and/or autologous stem-cell transplantation [SCT]), baseline outcome expectations are provided for patients continued on IFNalpha therapy, against which the results of new approaches can be compared.

Adolescent↗
PubMed1998

Influence of age and body mass index on gamma-glutamyltransferase activity: a 15-year follow-up evaluation in a community sample.

Most clinicians and researchers view serum gamma-glutamyltransferase (GGT) activity as a measure that can be interpreted equally in patients regardless of their demography. The present study evaluates the concurrent influence of age and body mass index (BMI) on GGT in a sample of 133 high functioning young men, with detailed assessment of the pattern of alcohol use at ages 20 [time 1 (T1)], 30 [time 2 (T2)], and 35 [time 3 (T3)]. GGT increased between T1 and T2 (15.4 +/- 9.65 units/liter vs. 20.1 +/- 12.07 units/liter, t = 4.17, p < 0.001), and between T2 and T3 (20.1 +/- 12.07 units/liter vs. 27.3 +/- 24.69 units/liter, t = 4.11, p < 0.001). Controlling for drinking quantity and frequency did not change the finding. The relationship between GGT and BMI was estimated after splitting the sample into normal (BMI < or = 25 kg/m2) and overweight (BMI > 25 kg/m2) subjects. The correlation between GGT and BMI in normal weight men at T1 was r = 0.15, p = 0.09, at T2 r = 0.00, p = 0.96, and at T3 r = 0.09, p = 0.09. In overweight subjects, correlation at T1 was r = 0.40, p = 0.20, at T2 r = 0.36, p < 0.05, and at T3 r = 0.44, p < 0.001. Controlling for the effect of alcohol consumption and/or age did not alter these conclusions. Testing for the interaction of age, BMI, and alcohol consumption did not yield relevant results. We concluded that GGT is positively related to age in the 20s to late 30s and to BMI in overweight subjects; both relationships of age and BMI were independent of alcohol consumption. The interpretation of GGT should take age and BMI into account when suspecting subclinical alcohol problems in young men.

Adult↗
PubMed1998

Nasopharyngeal carcinoma: evidence for improved survival with combined chemoradiation.

Radiation therapy has been the traditional treatment for nasopharyngeal carcinoma. Patients with advanced disease have a higher rate of locoregional as well as distant metastases, which has warranted the addition of chemotherapy in an attempt to improve survival. This retrospective study was designed to determine the absolute survival of patients with nasopharyngeal cancer treated with radiation alone, compared to that of patients receiving concurrent chemoradiation. Between December 1975 and December 1993 eight patients were treated with radiotherapy alone and 14 patients were treated with concurrent chemoradiation using 5-fluorouracil and cisplatin. Analysis of Kaplan-Meier cumulative absolute survival plots revealed that patients receiving chemoradiation survived longer than those receiving radiation alone (p = 0.0321). Patients with lymphoepithelioma, as opposed to squamous cell carcinoma, and patients younger than 30 years were also found to have longer survival, although these differences were not statistically significant (p = 0.0913 and p 0.04044, respectively).

Adolescent↗
PubMed1998

Proliferative and cytokine responses to class II HER-2/neu-associated peptides in breast cancer patients.

Previous studies have characterized the reactivity of CD8+ CTLs with ovarian and breast cancer. There is little information about the antigens and epitopes recognized by CD4+ T cells in these patients. In this study, we analyzed the ability of T cells from peripheral blood mononuclear cells of breast cancer patients to recognize HER-2/neu (HER-2) peptides. We found that 13 of 18 patients responded by proliferation to at least one of the HER-2 peptides tested. Of these peptides, one designated G89 (HER-2: 777-789) was recognized by T cells from 10 patients. Seven of nine responding patients were HLA-DR4+, suggesting that this peptide is recognized preferentially in association with HLA-DR4. Analysis of the specificity and restriction of the cytokine responses to G89 by G89-stimulated T cells revealed that these cells secreted significantly higher levels of IFN-gamma than interleukin 4 and interleukin 10, suggesting priming for a Th0-T helper 1 response. The same pattern of cytokine responses was observed to the intracellular domain of HER-2 protein, suggesting that G89-stimulated T cells recognized epitopes of the HER-2 protein in association with HLA-DR4. Because HLA-DR4 is present in 25% of humans, characterization of MHC class II-restricted epitopes inducing Th0-T helper 1 responses may provide a basis for the development of multivalent HER-2-based vaccines against breast and ovarian cancer.

Amino Acid Sequence↗
PubMed1998

The evolution of the auditory midlatency response in evaluating unconscious memory formation during general anesthesia.

The inability to objectively evaluate the amnesic status of an anesthetized patient has been a perplexing problem for the anesthesia provider. One approach thought to be effective in evaluating the amnesic status of the anesthetized patient is the auditory midlatency response (AMLR). The AMLR is an electrophysiological response that is recorded from scalp electrodes 10 to 80 ms after the auditory pathways begin to process acoustic stimuli. The response is thought to reflect the anesthetized patient's ability to consolidate an acoustic stimuli into an explicit or implicit memory. This article defines the amnesic state, describes the various components of AMLR, discusses clinical uses of the AMLR as an indicator of memory formation during the anesthetized state, and explains the clinical implications of using the AMLR in the surgical suite. Recent results have noted that the Pa waveform, the first positive deflection of the AMLR, may be the component that may serve as an intraoperative indicator of the anesthetized patient's ability to potentially consolidate an intraoperative acoustic stimuli into a memory. With the establishment of the Pa waveform of the AMLR as a reliable indicator of intraoperative memory formation, the AMLR can then be used to significantly decrease the occurrences of traumatic neurosis in the surgical patient and subsequent medicolegal consequences for the health care team. Thus, the use of the AMLR strives to promote a safer intraoperative environment for both the patient and the anesthesia provider.

Anesthesia, General↗
PubMed1998

Giant pleomorphic adenoma of the parotid gland: case report and review of the literature.

Pleomorphic adenomas account for the majority of parotid masses, typically arising in the tail of the gland and enlarging slowly over time. The vast majority are 2 to 6 cm in size when resected. We report resection of the largest benign mixed tumor recorded in the modern English language literature. An 85-year-old reclusive woman had a 20-year history of an enlarging right periauricular mass that had begun bleeding several days prior to admission. The patient ultimately underwent resection of the mass, which measured 26 cm in diameter, weighed 6.85 kg, and proved on pathologic examination to be a benign mixed tumor without malignant degeneration. The implications of this unusual case for the management of mixed tumors are discussed, and a review of the world literature on giant pleomorphic adenomas is presented.

Adenoma, Pleomorphic↗
PubMed1998

Neutralization of HIV-1 subtypes: implications for vaccine formulations.

More than 20.8 million people are infected with HIV in sub-Saharan Africa, with South Africa having one of the fastest growing HIV-1 epidemics, where an estimated 2.4 million people were infected. Thirty-two sera from 25 patients were tested for their ability to neutralize HTLV-IIIB (IIIB) and four primary isolates representing subtypes B, C, D, and a recombinant gag C/env B type. A CEM-SS cell line-based assay was used and the neutralizing titer was defined as the reciprocal of the highest dilution giving a 50% reduction in p24 antigen production. All isolates were neutralized better by subtype-specific sera, except for the C4714 strain, which was neutralized by both subtype B and C sera. C4714 was neutralized by 18/25 (72%) sera, IIIB by 19/32 (59%) sera, D482 by 7/31(23%) sera, B3245 by 6/29 (21%) sera, and the recombinant B/C1491 isolate by 4/25 (16%) sera. Five sera were unable to neutralize any of the isolates. The V3 region of the isolates used in the neutralization assay was amplified by PCR, directly sequenced, and analyzed to reveal variability between the consensus HIV-1 sequences and the isolates. HIV-1 strain C4714 was neutralized more effectively with the sera tested than the IIIIB laboratory strain. Variability in the amino acid sequence of the V3 region, which can alter the conformation of the V3 loop secondary structure, can influence the neutralization of a particular viral isolate. Vaccine formulations should be broadened to include multiple subtypes, especially C subtypes, which is rapidly spreading worldwide.

AIDS Vaccines↗
PubMed1998

The sleep of abstinent pure primary alcoholic patients: natural course and relationship to relapse.

Sleep in male pure primary alcoholic inpatients was examined at a mean of 16 days (n = 29), 19 weeks (n = 29), 14 months (n = 9), and 27 months (n = 4) of abstinence. Results were as follows: (1) the sleep of abstinent alcoholic patients is short, fragmented, and shallow early in abstinence; (2) a patient's sleep improves slowly over at least the first year of abstinence; however, (3) some facets of a patient's sleep remain abnormal even after 27 months of abstinence; (4) insomnia and sleep fragmentation after approximately 5 months of abstinence may be related to relapse by 14 months. The mechanism underlying the relationship between sleep and withdrawal in alcoholic patients is not well understood, and the issue of treating sleep problems as an adjunct to prevention of relapse warrants further investigation.

Adult↗
PubMed1997

OSM-9, a novel protein with structural similarity to channels, is required for olfaction, mechanosensation, and olfactory adaptation in Caenorhabditis elegans.

Although cyclic nucleotide-gated channels mediate sensory transduction in olfaction and vision, other forms of sensory transduction are independent of these channels. Caenorhabditis elegans cyclic nucleotide-gated channel mutants respond normally to some olfactory stimuli and to osmotic stimuli, suggesting that these chemosensory responses use an alternative sensory transduction pathway. One gene that may act in this pathway is osm-9, which is required for each of these responses as well as a mechanosensory response to nose touch. osm-9 encodes a protein with ankyrin repeats and multiple predicted transmembrane domains that has limited similarity to the Drosophila phototransduction channels transient receptor potential (TRP) and TRP-like (TRPL). The sequence of OSM-9 and other TRP-like genes reveals a previously unsuspected diversity of mammalian and invertebrate genes in this family. osm-9 is required for the activity of the predicted G-protein-coupled odorant receptor ODR-10, which acts in the AWA olfactory neurons; its similarity to other G-protein-regulated transduction channels suggests that OSM-9 is involved in AWA signaling. osm-9:: GFP fusion genes are expressed in a subset of chemosensory, mechanosensory, and osmosensory neurons. osm-9 also affects olfactory adaptation within neurons that require the cyclic nucleotide-gated channel for olfaction; in these neurons, the gene has a regulatory function and not a primary role in sensory transduction.

Adaptation, Physiological↗
PubMed1997

Acute effects of periarterial sympathectomy on the cutaneous microcirculation.

The clinical effects of peripheral sympathectomy on patients with vaso-occlusive disease are often dramatic and include relief of pain, improved quality of life, and healing of ulcers. Peripheral periarterial sympathectomy is known to increase skin temperature and to maximize the nutritional component of peripheral blood flow, but the pathophysiology of vaso-occlusive disease and the physiologic mechanisms of this treatment are unknown. In this study, the acute effects of periarterial sympathectomy were directly observed in a rabbit ear model of digital microcirculation (arterioles, arteriovenous anastomoses, and venules). The effects of periarterial sympathectomy on cutaneous perfusion and total flow were also examined using laser Doppler perfusion imaging and digital temperature measurements. The central auricular artery became dilated (50-100%) immediately after sympathectomy; the arterioles, arteriovenous anastomoses, and venules dilated to 165, 156, and 223%, respectively, at 30 minutes and to 187, 174, and 204%, respectively, at 60 minutes, relative to their baseline diameters prior to sympathectomy. Laser Doppler perfusion imaging values and ear temperatures were noted to increase after sympathectomy (8.9%, 3 degrees C), although the core temperature of the rabbit did not change. Thus, acute periarterial sympathectomy can (a) effectively reduce the vascular tone of the distal microvasculature and (b) increase total microcirculatory perfusion-cutaneous and thermoregulatory-by both venular and arteriolar dilation. Periarterial sympathectomy has the clinical potential to increase nutritional blood flow, thereby ameliorating the signs and symptoms of ischemia associated with thermoregulatory abnormalities. Dilation of the arteriovenous anastomoses, with a subsequent reduction in vascular resistance, may contribute to the increased cutaneous temperature noted after sympathectomy.

Anastomosis, Surgical↗
PubMed1997

Regulation of glutamate uptake in astrocytes continuously exposed to ethanol.

CNS glutamatergic transmission is altered by chronic ethanol intake and may underlie the behavioral hyperactivity associated with ethanol withdrawal. Because astrocytes regulate extracellular glutamate levels, the aim of this investigation was to characterize the effects of in vitro ethanol exposure on Na+-dependent glutamate uptake parameters in astrocytes. Ethanol exposure elicited a time and concentration-dependent increase in the maximal uptake capacity, Vmax, for [3H] glutamate, which was reversed upon withdrawal of ethanol from the media. None of the ethanol exposures had any effect on the Km for this process. In addition, the ethanol-induced increase in Vmax for glutamate was reversed by the protein kinase C inhibitors, calphostin C and bisindolylmaleimide, and was not associated with an increase in the expression of either of the major glutamate transporter proteins, GLT-1 or GLAST.

Animals↗