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Biomedical subjects

T L Smith

Publications and source records attributed to T L Smith.

At least 109 records · Page 6Linked to original sources
PubMed1999

Clinical course of breast cancer patients with complete pathologic primary tumor and axillary lymph node response to doxorubicin-based neoadjuvant chemotherapy.

PURPOSE: To assess patient and tumor characteristics associated with a complete pathologic response (pCR) in both the breast and axillary lymph node specimens and the outcome of patients found to have a pCR after neoadjuvant chemotherapy for locally advanced breast cancer (LABC). PATIENTS AND METHODS: Three hundred seventy-two LABC patients received treatment in two prospective neoadjuvant trials using four cycles of doxorubicin-containing chemotherapy. Patients had a total mastectomy with axillary dissection or segmental mastectomy and axillary dissection followed by four or more cycles of additional chemotherapy. Patients then received irradiation treatment of the chest-wall or breast and regional lymphatics. Median follow-up was 58 months (range, 8 to 99 months). RESULTS: The initial nodal status, age, and stage distribution of patients with a pCR were not significantly different from those of patients with less than a pCR (P>.05). Patients with a pCR had initial tumors that were more likely to be estrogen receptor (ER)-negative (P<.01), and anaplastic (P = .01) but of smaller size (P<.01) than those of patients with less than a pCR. Upon multivariate analysis, the effects of ER status and nuclear grade were independent of initial tumor size. Sixteen percent of the patients in this study (n = 60) had a pathologic complete primary tumor response. Twelve percent of patients (n = 43) had no microscopic evidence of invasive cancer in their breast and axillary specimens. A pathologic complete primary tumor response was predictive of a complete axillary lymph node response (P<.01 ). The 5-year overall and disease-free survival rates were significantly higher in the group who had a pCR (89% and 87%, respectively) than in the group who had less than a pCR (64% and 58%, respectively; P<.01). CONCLUSION: Neoadjuvant chemotherapy has the capacity to completely clear the breast and axillary lymph nodes of invasive tumor before surgery. Patients with LABC who have a pCR in the breast and axillary nodes have a significantly improved disease-free survival rate. However, a pCR does not entirely eliminate recurrence. Further efforts should focus on elucidating the molecular mechanisms associated with this response.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

Characteristics of alcohol dependent subjects with very elevated levels of Gamma-Glutamyltransferase (GGT).

OBJECTIVE: This article examines characteristics of a subgroup of alcohol dependent men with very elevated serum Gamma-Glutamyltransferase (GGT) activity. METHOD: GGT was measured in 196 men soon after admission to an inpatient alcohol and drug treatment program. Subjects were split into two groups based on the a priori GGT value of > or =150 U/L for Group 1 (n = 20), and <150 U/L for Group 2 (n = 176). Serum aspartate amino-transferase (AST), serum alanine amino-transferase (ALT) and mean corpuscular volume (MCV), as well as several aspects of the drinking history, were compared cross-sectionally between the two groups. The stability of GGT in the context of drinking was evaluated prospectively over 12 months in a subsample of 35 individuals. RESULTS: Most measures of the drinking pattern and severity of dependence were similar between the two groups, although subjects in Group 1 demonstrated higher levels for AST (p < .01), MCV (p < .01) and ALT (p < .01). Subjects in Group 1 reported more drinking days per month (23.8 +/- 3.98 vs 17.8 +/- 8.71, t = 5.43, p < .001), and more related history of alcoholic liver disease (30.0% vs 8.5%, chi2 = 8.66, p < .01). In the presence of the variables significantly different between the two groups, AST, the number of drinking days per month and the proportion with alcoholic liver disease predicted membership to Group 1, although their influence was moderate (pseudo R between 0.16 and 0.20). The correlation between GGT at intake and follow-up in 35 individuals who returned to drinking was r = .56, p < .001, while two out of three subjects with high GGT at intake were also high at follow-up. CONCLUSIONS: Subjects with very high GGT seem to demonstrate a more intense vulnerability to alcohol, a characteristic which appears to be stable over time.

Adult↗
PubMed1999

Evaluation of the self-rating of the effects of alcohol form in Asian Americans with aldehyde dehydrogenase polymorphisms.

OBJECTIVE: In order to easily assess individual differences in response to alcohol, the Self-Rating of the Effects of Alcohol (SRE) form was recently developed and its psychometric properties tested in primarily white subjects. This study aimed to further evaluate the SRE in a population known to have genetically mediated variability in response to alcohol and risk for alcoholism, Asian Americans with ALDH2 polymorphisms. METHOD: Men and women of Chinese, Japanese or Korean heritage between the ages of 21 and 26 years (N = 156) completed the SRE and a blood sample was drawn for genotyping at the ALDH2 locus. RESULTS: SRE results were available from 137 (78 female) subjects. With the effects of gender, body weight, frequency of recent drinking and quantity of recent drinking controlled, ALDH2 genotype still accounted for a significant amount of variability in SRE score in this Asian-American sample. Evaluation of SRE scores 4.5 or higher indicated that a low response to alcohol was associated with ALDH2*1/2*1 genotype, male gender and Korean heritage, all factors associated with increased risk for alcoholism. CONCLUSIONS: These results provide additional support for the SRE as a valid instrument for assessing individual variability in response to alcohol and as a useful measure for identifying individuals at relatively increased or decreased risk for alcoholism based on level of reaction to alcohol.

Adult↗
PubMed1999

Relationship of auditory middle latency response and stem-word completion test as indicators of implicit memory formation during general anesthesia.

Anesthesia providers are unable to objectively evaluate the amnesic status of an anesthetized patient. One purpose of the study was to evaluate the anesthetized patient's ability to process auditory information while receiving an inhalational or intravenous anesthetic regimen. The other purpose was to examine the relationship of the Pa latency of the auditory middle latency response (AMLR) with the stem-word completion test as an intraoperative indicator of implicit memory formation during general anesthesia. One hundred one adults were randomly assigned in a single-blinded design to either a midazolam or sevoflurane anesthetic regimen. Midazolam was administered at 0.540 microgram/kg per minute with fentanyl and 50% nitrous oxide. The other anesthetic regimen was 1.4% end-tidal concentration of sevoflurane with fentanyl and 50% nitrous oxide. A list of 10 words was repeated 16 times. AMLRs were recorded intraoperatively. The difference between the midazolam groups borderlined statistical significance (P = .07) in illustrating that one may potentially process auditory information while anesthetized. Dissimilar findings were found between the sevoflurane groups (P = .77). An inverse correlation was demonstrated between the midazolam group and Pa latency of the AMLR (r = -0.40, P = .047). Multiple regression of the midazolam group demonstrated that the employment status (r2 = .297, P = .005) and the Pa latency (r2 = .238, P = .003) were the best predictors of the postoperative stem-word completion test (F = 12.61, P = .001). In contrast, no correlation was noted in the sevoflurane group (r = 0.43, P = .07). Thus, the continued evaluation of the AMLR as an intraoperative indicator of implicit memory formation is warranted. With the establishment of the AMLR as an indicator of implicit memory formation during general anesthesia, anesthesia providers could then address the occurrences of traumatic neurosis in the postoperative surgical patient and strive to avoid the medicolegal concerns that may face the healthcare team.

Adult↗
PubMed1999

Clinical characteristics of alcoholism in alcohol-dependent subjects with and without a history of alcohol treatment.

BACKGROUND: Most clinical alcohol research is carried out on alcoholics who are in treatment, usually inpatients. However, most alcohol-dependent men and women never enter treatment, and even fewer ever receive inpatient care. Thus, some generally accepted data on the clinical course of alcoholism, derived from treatment samples, might not generalize to the entire population of alcohol-dependent individuals. This article characterizes the clinical characteristics of alcohol dependence in three groups of alcoholics, based on their histories of treatment for alcohol problems: those without prior rehabilitation; those with only outpatient approaches or Alcoholics Anonymous (AA); and subjects with an inpatient experience. METHODS: Semistructured interviews were administered to 3572 DSM-III-R-defined alcohol-dependent subjects from the Collaborative Study on the Genetics of Alcoholism. The clinical patterns were compared across the three groups of alcoholics: Group 1, never-treated (n = 1582; 44%); Group 2, histories of outpatient or AA only (n = 399; 11%); and Group 3, at least one inpatient experience (n = 1591; 45%). RESULTS: A progression was shown from Groups 1 to 3 for more general life problems (e.g., unemployment, marital instability); higher rates of additional drug dependencies and psychiatric disorders; and more alcohol-related adverse events. Logistic regression analyses revealed that those with no prior treatment were more likely to be women, Caucasian, and employed, and to report a lower rate of divorce/separation, lower levels of alcohol intake, and fewer alcohol problems. Among those who received help, inpatient care was predicted by an opposite profile. CONCLUSIONS: These results indicate that studies using data from inpatient populations may give a skewed picture of the clinical characteristics of alcohol dependence.

Adult↗
PubMed1999

Impact of a stimulant-focused enhanced program on the outcome of alcohol- and/or stimulant-dependent men.

BACKGROUND: The approaches to the treatment of most forms of substance dependence are similar. It is not clear whether specific treatment components need to be added to address specific substances. This study asks two questions: What is the impact of a more intense drug treatment program, and do different substance problems require different treatment interventions? METHODS: The 383 veterans included in this study represent two groups of consecutive inpatient male admissions with current alcohol dependence and/or dependence on amphetamines or cocaine at the inpatient Alcohol and Drug Treatment Program of the Veterans Affairs San Diego Healthcare System. All were interviewed at intake by trained interviewers using a standardized semistructured assessment instrument, and a resource person interview also was conducted with 85% of them. The first group of men received the Standard Treatment Program (STP), whereas the second group received the Enhanced Treatment Program (ETP). The latter included an addition of 10 hr per week of intense treatment aimed at stimulants, including two newly developed manual-driven groups (Relapse Prevention and Interpersonal Counseling), each of which met twice a week. RESULTS: The patient follow-up was 92% at 3 months and 83% at 12 months. Abstinence from substances of abuse for ETP and STP were 63% vs. 49% at 3 months and 43% vs. 24% at 12 months. Logistic regressions demonstrated that treatment type continued to predict outcome even in the context of other potentially predictive variables. CONCLUSIONS: Despite the ETP emphasis on stimulants, both alcohol- and stimulant-dependent men appeared to benefit, suggesting a generic improvement in substance use.

Adolescent↗
PubMed1998

Increased REM sleep density at admission predicts relapse by three months in primary alcoholics with a lifetime diagnosis of secondary depression.

BACKGROUND: Having previously reported that 3-month relapse was associated with increased admission REM pressure in nondepressed primary alcoholics, we hypothesized that baseline polysomnography would predict outcome in primary alcoholics with a lifetime diagnosis of secondary depression. METHODS: Twenty-one primary alcoholics with secondary depression received polysomnography and the Hamilton Depression Rating Scale during the first and fourth weeks of a 1-month inpatient alcohol treatment program. Exclusion criteria included serious illness, current major alcohol withdrawal symptoms, other Axis I diagnoses, sleep apnea, nocturnal myoclonus, and psychoactive substances within 14 days of polysomnography. Relapse was defined as drinking any alcohol between hospital discharge and 3-month follow-up. RESULTS: Relapsers' total sleep time was reduced, and REM density (reflecting REM sleep ocular activity) was increased significantly throughout admission compared with abstainers. Sleep continuity and Hamilton scores improved by discharge in sober and relapsing alcoholics. Factors derived from admission REM latency, REM percent, and REM density predicted sobriety vs. relapse within 3 months after hospital discharge in 76% of patients. Admission REM density was greater, and total sleep time was less in relapsers than in patients sober at 3 months. CONCLUSIONS: Results suggest that increased REM density and decreased total sleep time at about 2-4 weeks of abstinence predict relapse by 3 months in depressed alcoholics.

Adult↗
PubMed1998

Can we detect or predict the presence of occult nodal metastases in patients with squamous carcinoma of the oral tongue?

BACKGROUND: When to do a neck dissection as part of the surgical treatment for a patient with squamous carcinoma of the oral tongue is controversial, particularly when the primary can be resected without entering the neck. If the patient who is at high risk for having occult nodal disease in the neck can be identified, node dissection with the glossectomy could be justified. To better identify patients for this procedure, we correlated various tumor and patient factors along with preoperative diagnostic studies with the presence or absence of pathologically positive nodes in a group of patients who underwent node dissection. METHODS: Ninety-one previously untreated patients with biopsy-proved squamous carcinoma of the oral tongue were prospectively studied. All patients had a glossectomy and neck dissection as their initial treatment. The pathology findings (ie, lymph nodes with squamous cancer) were correlated with many preoperative and intraoperative factors, and a statistical analysis was made. RESULTS: The use of computed tomography and ultrasound was not better than the clinical examination in determining the presence or absence of nodal metastases. The best predictors were depth of muscle invasion, double DNA aneuploidy, and histologic differentiation of the tumor. CONCLUSIONS: All patients with stage T2-T4 squamous cancers of the oral tongue should have an elective dissection of the neck. Patients with T1N0 cancer who have a double DNA-aneuploid tumor, depth of muscle invasion > 4 mm, or have a poorly differentiated cancer should definitely undergo elective neck dissection. Ultrasound and computed tomography are of little value in predicting which patients have positive nodes.

Adult↗
PubMed1998

Effects of peripheral sympathectomy on thermoregulatory vascular control in the rabbit ear.

A rabbit ear model of the human digit was utilized to determine the vascular response to peripheral sympathectomy. Vascular responses were evaluated by subjecting chronically instrumented rabbits to a cold stress before and after sympathectomy surgery. The typical response to cold stress is for ear temperatures and auricular cutaneous perfusion to decrease during the cooling phase of the test and to increase toward baseline levels during the rewarming phase after cold exposure. Following peripheral sympathectomy, ear temperatures were significantly increased during both the cooling and rewarming phase of the cold stress test although overall ear perfusion and skin perfusion were not different from sham-operated rabbits. The responses observed in the rabbit ear following peripheral sympathectomy appear to mimic those noted in patients receiving digital peripheral sympathectomies for the treatment of refractory pain and ulceration. Peripheral sympathectomy may result in clinical improvements in patients because it improves both total digital and nutritional cutaneous blood flow. Peripheral sympathectomy in normal rabbit ears does not result in altered perfusion patterns with cold exposure although ear temperature is significantly higher. This pattern of changes suggests that the distribution of extremity perfusion is altered even though overall extremity perfusion and cutaneous perfusion per se are not significantly different from sham-operated controls. Complete sympathectomy was accompanied by a persistent increase in ear temperature and a dissociation between conductance and microvascular perfusion. Auricular conductance was transiently increased and then decreased to levels below preoperative control values. Microvascular perfusion is decreased immediately following amputation/replantation and thereafter increases.

Animals↗
PubMed1998

Effect of cooling on cutaneous microvascular adrenoceptors in vivo in the rabbit ear.

Previous studies have suggested that moderate cooling increases the responsiveness of vascular alpha2-adrenoceptors. However, limited information is available documenting the influence of temperature changes on adrenoceptor responses in the microvasculature of thermoregulatory organs (e.g., the human digit and the rabbit ear) subjected to a wide range of temperatures. In the present study, the effect of local cooling (24 degrees C) on cutaneous microvascular adrenoceptors in the ear was observed in vivo in male New Zealand White rabbits (total: 66 ears). The rabbit ear was studied in a temperature-controlled tissue bath; the ear preparation was pretreated with terazosin (an alpha1-adrenoceptor antagonist) (10(-5) M) or a combination of terazosin (10(-5) M) and propranolol (a beta-adrenoceptor antagonist) (10(-6) M). The microvascular diameter responses of the ear to norepinephrine (10(-11)-10(-4) M) then were determined at 24 or 34 degrees C, respectively, to determine the influences of low temperature on adrenoceptor responses to norepinephrine stimulation. The results demonstrated that low concentrations of norepinephrine induced vasodilation in arterioles and arteriovenous anastomoses. This vasodilation was followed by vasoconstriction with an increased concentration of norepinephrine in animals with alpha1-adrenergic blockade at 34 degrees C. Moderate tissue cooling increased the microvascular maximal response of the rabbit ear to norepinephrine and abolished the vasodilatation induced by a low concentration of norepinephrine. There was no significant difference in the microvascular response to norepinephrine between the two temperature conditions after simultaneous blockade of alpha1-adrenoceptors and beta-adrenoceptors. Data from the present study indicate that moderate cooling does not enhance the responsiveness of alpha2-adrenoceptors to norepinephrine. In contrast, cooling reduced the beta-adrenergic activity of arterioles and arteriovenous anastomoses after norepinephrine stimulation.

Adrenergic alpha-Agonists↗
PubMed1998

Alpha adrenoceptors in the rabbit ear thermoregulatory microcirculation.

The rabbit ear microcirculation was analyzed in a chronic unanesthetized model to evaluate alpha adrenergic microvascular control in a thermoregulatory end organ. This model allowed direct measurement of microcirculatory responses without the effects of anesthetics or inflammatory responses induced by acute surgical intervention. The ipsilateral facial artery was catheterized for drug injections into the experimental ear. Microvascular diameter changes following stimulation or blockade of adrenoceptor (AR) subtypes were observed directly through a chronic microvascular chamber implanted in the rabbit ear. Vascular alpha1- and alpha2-ARs appear to be distributed differently across the arterioles and AVAs of the rabbit ear. Both alpha1- and alpha2-ARs appear to contribute to vasoconstriction of AVAs in the conscious rabbit ear. In contrast, alpha1-AR's (vs alpha2-ARs) appear to predominate in adrenergically mediated sympathetic vasoconstriction of arterioles.

Adrenergic alpha-Agonists↗
PubMed1998

The effect of transdermal nicotine on digital perfusion in reformed habitual smokers.

The effects of transdermal nicotine-assisted smoking cessation on digital perfusion and health-related quality of life were assessed in 10 chronic smokers. Components of digital blood flow were evaluated by digital temperature and laser Doppler fluxmetry before, during, and after a standardized cold challenge. Nutritional flow was measured by vital capillaroscopy; a quantitative perfusion profile was obtained by laser Doppler perfusion imaging. A battery of validated measures were used to evaluate health-related quality of life. The microvascular response of smokers was evaluated before smoking cessation and at 2 and 7 days after smoking cessation and was compared with the response of nonsmoking controls. Results demonstrated that a (1) cutaneous microvascular perfusion was lower in smokers than nonsmokers, (2) the acute administration of transdermal nicotine did not decrease cutaneous perfusion, (3) smoking cessation and transdermal nicotine normalized digital microvascular perfusion by 7 days, and (4) transdermal nicotine and smoking cessation did not negatively impact health-related quality of life.

Administration, Cutaneous↗