Biomedical subjects

T L Smith

Publications and source records attributed to T L Smith.

At least 199 records · Page 11Linked to original sources

PubMed1994

Levels of retinoblastoma protein expression in newly diagnosed acute myelogenous leukemia.

The relationship between the level of retinoblastoma protein (RB) expression and the survival of 113 newly diagnosed acute myelogenous leukemia (AML) patients was studied. Western blotting was used to determine the level of RB protein present in peripheral blood leukemia cells and results were confirmed in 26 patients by immunohistochemistry. The leukemic cells from 22/113 AML patients (19%) contained RB protein at levels that were equal to or less than the level of RB observed in the mononuclear cell fraction of peripheral blood from normal individuals (Low RB). Levels of RB greater than that of normal blood (Elevated RB) were seen in 91 patients (81%). The median survival of patients with low RB was significantly shorter than that seen in patients with elevated RB, 12 weeks versus 40 weeks (P = .02). Remission induction frequency was 36% in low RB patients compared with 68% in AML patients with elevated RB (P = .01). Multivariate analysis showed that low RB protein level was an independent prognostic factor predictive or poor survival after allowing for other known prognostic factors. These data suggest that a low level of the RB protein at the time of diagnosis is associated with shortened survival in AML patients because of inferior response to conventional therapy. Monitoring of the RB level could identify a subgroup of AML patients with an extremely poor prognosis when treated with chemotherapy alone, who would be eligible for alternative therapeutic strategies.

Adolescent↗

PubMed1994

The relationship between brachytherapy dose and outcome in patients with bulky endocervical tumors treated with radiation alone.

PURPOSE: To evaluate the relationship between brachytherapy dose and outcome in patients treated with external radiotherapy (40 Gy to the whole pelvis) and intracavitary radium therapy for bulky endocervical tumors. METHODS AND MATERIALS: Between 1962 and 1985, 98 patients with Stage IB-IIB bulky endocervical carcinomas (> or = 6 cm in diameter) treated with radiotherapy alone received 40 Gy to the whole pelvis followed by 2 or more intracavitary treatments. Twenty-five patients received < 6000 mg-hr of intracavitary treatment and 73 received > or = 6000 mg-hr (an average dose to point A of approximately 49 Gy). Brachytherapy exposures ranged from 4800-7885 mg-hrs. RESULTS: Patients who received < 6000 mg-hr tended to have unfavorable (narrow) vaginal anatomy (p < 0.01) and to be treated in the later years of the study (p < 0.01). The high-dose group included a somewhat greater proportion of patients with positive lymphangiograms or poor responses to initial external beam treatment. Despite having somewhat more favorable tumors, patients who received less than 6000 mg-hr had a higher rate of pelvic disease recurrence at 5 years (33%) than those who received higher doses (16%) (p = 0.03). Actuarial survival rates at 5 years were 44% and 60% for the low- and high-dose groups, respectively (p = 0.14). Among those who received more than 6000 mg-hr, there was no significant relationship between brachytherapy dose and pelvic disease control. Calculated actuarially, the rate of major (> or = grade 3) complications at 5 years was 23% in the low-dose group and 10% in the high-dose group (p = 0.1). CONCLUSIONS: The relatively high incidence of pelvic disease recurrence and complications in patients who receive less than 6000 mg-hr reflects the narrow therapeutic window for complication-free pelvic disease control in patients with bulky central disease and unfavorable normal tissue anatomy. The results also demonstrate a high pelvic control rate and acceptable morbidity in patients with favorable anatomy treated with high-dose radiotherapy alone.

Brachytherapy↗

PubMed1994

Obesity as an adverse prognostic factor for patients receiving adjuvant chemotherapy for breast cancer.

OBJECTIVE: To determine whether obesity is an independent prognostic factor among women receiving adjuvant chemotherapy for lymph node-positive breast cancer and to determine how obesity relates to other commonly used prognostic indicators. DESIGN: Retrospective review of the clinical characteristics and clinical course of 735 patients with stages II and III primary breast cancer who were treated using three consecutive postoperative adjuvant chemotherapy protocols. Univariate and multivariate analyses were used to determine the prognostic implications of obesity defined by weight and height tables and body mass index. In addition, we analyzed the relation between obesity and other known prognostic indicators for patients with primary breast cancer. SETTING: A comprehensive cancer center. PATIENTS: 735 patients with lymph node-positive primary breast cancer who were treated using three consecutive fluorouracil-doxorubicin-cyclophosphamide-containing adjuvant chemotherapy protocols and for whom complete data on weight, height, standard prognostic factors, and outcome were available. MAIN OUTCOME MEASUREMENTS: Disease-free and overall survival for the entire group and obese and nonobese subgroups. RESULTS: 24 percent of patients were more than 20% overweight. With a median follow-up of 10.7 years, the estimated 10-year, disease-free rate for patients not more than 20% overweight was 54% (95% CI, 50% to 58%) compared with 40% (CI, 33% to 47%) for remaining patients classified as obese. Although obese patients tended to have somewhat less favorable prognoses based on standard prognostic criteria, a proportional-hazards regression model adjusting for other factors indicated that risk for disease recurrence among obese patients was 1.33 times that of the nonobese population (CI, 1.05 to 1.68). CONCLUSIONS: Obesity is an indicator of poor prognosis for patients with primary breast cancer even after the administration of adjuvant chemotherapy. The effect of dietary interventions to reduce body weight on the outcome of breast cancer therapy must be investigated.

Adult↗

PubMed1994

Increased pressure for rapid eye movement sleep at time of hospital admission predicts relapse in nondepressed patients with primary alcoholism at 3-month follow-up.

OBJECTIVE: To determine whether polygraphic sleep recordings, obtained at the time of admission to an inpatient alcohol treatment program, predict abstinence and relapse 3 months following hospital discharge in nondepressed patients with primary alcoholism. DESIGN: Two independent, consecutive cohorts of patients (group 1, n = 28; group 2, n = 17) underwent all-night polygraphic sleep recordings and other clinical evaluations during the first and fourth weeks of a 1-month inpatient treatment program within a Veteran Affairs Medical Center. They were reevaluated 3 months following discharge to the community. None were treated with disulfiram or other medications during or after hospitalization. PATIENTS: All subjects were male veterans with primary alcoholism and without significant preexisting, secondary, or comorbid diagnoses such as major medical problems, depression, antisocial personality, or drug addiction. OUTCOME MEASURES: Relapse was defined as any alcohol consumption between discharge from the hospital and 3-month follow-up. RESULTS: Ten (36%) of 28 patients in group 1 were Relapsers at 3-month follow-up. Relapsers in group 1 showed significantly shorter Rapid Eye Movement (REM) latency, increased Rapid Eye Movement percent (REM%), and increased REM Density during their admission sleep studies compared with Abstainers. To replicate these observations, group 2 was then studied as a validation sample. Six (35%) of 17 patients relapsed. As in group 1, Relapsers had significantly shorter REM latency and increased REM% compared with Abstainers; REM Density was not significantly different in the Relapsers as compared with Abstainers in group 2. Using a principal components analysis based on these three REM sleep measures to determine "REM pressure," three separate discriminant function analyses (DFAs) were calculated: one for each group and one for all patients (n = 45) together. The DFA from group 1 correctly classified 22 (78.6%) of the 28 patients in group 1 and 13 (76.5%) of the 17 patients in group 2 as Relapsers or Abstainers. The DFA from group 2 correctly classified 13 (76.5%) of the 17 patients in group 2 and 23 (82.1%) of the 28 patients in group 1. The DFA formed from both groups together correctly classified 36 (80%) of the 45 patients. When the REM sleep measures at hospital admission and discharge were compared, no statistically significant effect of time was observed. Abstinence and relapse were not consistently related to other clinical measures at the time of hospital admission such as age, duration and severity of alcoholism, marital status, employment, hepatic enzyme levels, cognitive performance, or depression ratings. CONCLUSION: Short REM latency, increased REM%, and, possibly, increased REM Density at the time of admission to a 1-month inpatient alcohol treatment program predict relapse in nondepressed patients with primary alcoholism by 3 months following hospital discharge.

Alcohol Drinking↗

PubMed1994

Decreased microvascular perfusion in the rabbit ear after six hours of ischemia.

The cellular injury produced by reperfusion of ischemic tissue with oxygen-rich blood has been studied in numerous tissues but has not been investigated extensively in thermoregulatory tissue. This study was designed (a) to compare 4 and 6 hours of ischemia to document the evidence of impaired capillary perfusion after resumption of blood flow (reperfusion injury) in a thermoregulatory end organ (the rabbit ear), and (b) to examine, with use of vital capillaroscopy (VC) and laser Doppler flowmetry (LDF), the altered microvascular blood flow in the rabbit ear after ischemia and reperfusion. One ear from each of five rabbits underwent warm ischemia for 4 hours. VC showed no deficits of capillary perfusion in these ears after reperfusion; LDF measurements in both ears also demonstrated no significant difference between control and reperfusion blood flow. One ear from each of eight additional rabbits underwent 6 hours of warm ischemia. LDF values were significantly reduced in the ischemic ear after reperfusion as compared with baseline measurements for that ear and as compared with the control ear. VC showed arrested perfusion and static plasma gaps within three to five capillaries per high-power field (an area of 300 x 500 microns) in the ischemic ear and good perfusion of all vessels in the contralateral control ear. This evidence of reperfusion injury in a thermoregulatory end organ may help to explain the poor functional result that often occurs after replantation of an amputated digit.

Animals↗

PubMed1994

Microvascular response in the rabbit ear to total body cooling: a model for study of human digits.

Conditions such as Raynaud's disease, cold intolerance following digit replantation, and reflex sympathetic dystrophy are all exacerbated by diminished blood flow in the digits. The rabbit ear, being similar to the human digit, is an excellent model for studying microvascular responses during thermoregulation and was used in this study of microcirculatory changes during total-body cold stress. In eight rabbits a window was placed in one ear each, and the underlying vascular beds were photographed with the unanesthetized animal at room temperature (23 degrees C) and in a cold room (6 degrees C). Luminal arterial diameters constricted more than venular diameters during cold stress (39.6% vs. 16.5%, respectively, of the control diameters; P = 0.014). All responses were linear; the slopes of the regression lines were significantly different between arterioles and venules (P < 0.0001). This study suggests that decreased circulation in response to cold is due to decreases in the diameter and number of vessels available for perfusion, as predicted by the Poiseuille equation.

Animals↗

PubMed1994

A rabbit ear model for cold stress testing.

A rabbit ear model resembling the human digit was studied to determine the vascular response of the rabbit ear to a cold stress. Following moderate cooling (10 minutes at 5 degrees - 8 degrees C), auricular blood flow and cutaneous perfusion were reduced. This decrease was reversed by 30 minutes of warming. The response in the rabbit ear to cold stress is similar to that of normal human digits. The similarities between the control of the circulation in human digits and rabbit ears may result from the similarities in digital and auricular vascular receptors and receptor subtypes. Verification of the rabbit model provides an experimental method for obtaining important data regarding digital pathophysiology and the treatment of cold intolerance. Further study with this model will provide clinically relevant information regarding the pathophysiology of digital thermoregulatory abnormalities.

Animals↗

PubMed1994

Nitric oxide synthase is an active enzyme in the spiral ganglion cells of the rat cochlea.

Nitric oxide (NO) mediates the effects of the excitatory amino acids in the central nervous system. Excitatory amino acids, in particular L-glutamate, are thought to be the neurotransmitter(s) present at the cochlear hair cell-afferent nerve synapse. To our knowledge, no studies to date have documented the presence of NO in the cochlea nor attempted to elucidate the role of NO in hearing. Rat cochlea frozen sections were examined for the presence of nitric oxide synthase (NOS) by NADPH diaphorase histochemistry. Vibratome sections of rat cochlea were examined by immunocytochemistry with an antibody to citrulline, an indication of NOS activity. Spiral ganglion cells in the rat cochlea were positive by NADPH diaphorase histochemistry and by anti-citrulline immunocytochemistry. These results indicate that NOS is present and that the enzyme actively produces nitric oxide in the spiral ganglion cells of the rat cochlea. Given our current understanding of neurotransmission in the cochlea, it is reasonable to postulate that the actions of NO in cochlear neuronal tissue are similar to the actions of NO in the CNS and that NO acts as a neurotransmitter/neuromodulator in the cochlea. In addition, because NO has been implicated as a mediator of excitotoxicity in the CNS, NO may play a role in neurotoxicity in the cochlea.

Amino Acid Oxidoreductases↗

PubMed1994

Scanning mutagenesis of the Arc repressor as a functional probe of operator recognition.

Protein-DNA and protein-protein interactions are central to most biological regulation, and yet our understanding of these macromolecular recognition events is still incomplete. Both types of interactions are critical for the function of the Arc repressor. The functional importance of residues in or near its operator DNA-binding surface and dimer-dimer interaction surface has been probed by alanine-scanning mutagenesis. Mutations in three categories cause large binding defects: beta-sheet side chains that directly interact with DNA bases; side chains that link different DNA-binding regions of Arc, and side chains required to maintain the active DNA-binding conformation.

Bacteriophage P22↗

PubMed1994

Growth of tumor derived activated T-cells for the treatment of cancer.

This report describes the production of Tumor Derived Activated Cell cultures (TDAC, also called tumor infiltrating lymphocytes) from patient tumor biopsies and our preliminary experience growing these cells to therapeutic levels using artificial capillary bioreactor cultures. TDAC were successfully grown in medium containing Interleukin 2 from 80% of the 113 tumor biopsies tested. There was no significant difference in success (growth to 1 x 10(9) cells) comparing primary and metastatic tumors. Many of the tumors were shipped to the laboratory from distant sites. Success rate did decrease with the length of time for tumor transport. Interleukin 4 was beneficial in the development of 1 of 4 TDAC cultures which did not grow with IL-2 only. Seventy-seven bioreactor cultures were initiated for 31 patients. On the average, 1.9 x 10(9) TDAC were inoculated per bioreactor; 3.3 x 10(10) were harvested in 22 days. Twelve liters of medium were required per 1 x 10(10) TDAC produced. TDAC cultures contained T cells with variable ratios of CD4 to CD8 cells. Secreted granulocyte monocyte colony stimulating factor, interferon gamma and tumor necrosis factor were measured in the bioreactor cartridge conditioned medium. Twenty three patients were evaluated. Partial responses were observed in 4 patients including a dramatic remission of scalp nodules in a patient with renal cancer. Results showed that therapeutic amounts of TDAC cells may be produced in a reasonable and cost effective manner using artificial capillary bioreactor cultures.

Biopsy↗

PubMed1994

Characteristics of men with alcoholic hallucinosis.

The goal of this study was to evaluate the characteristics of primary alcoholics with alcoholic hallucinosis. Six hundred and forty-three primary alcoholic men were recruited from a 28-day Alcohol and Drug Treatment Program at the San Diego VA Medical Center. Subjects only experiencing perceptual abnormalities during alcohol withdrawal, drug-related hallucinosis, as well as those having abnormal sensations that did not meet criteria for hallucinations were excluded from the present study. The remaining 532 subjects were divided into Group 1 (n = 48), which consisted of subjects with a DSM-IIIR and ICD-10 diagnosis of alcoholic hallucinosis, and Group 2 (n = 484) which consisted of those without any history of hallucinations. A comparison of the two groups revealed that Group 1 men were younger at the onset of alcohol problems, consumed more alcohol per occasion, developed more alcohol-related life problems, and had higher rates of drug experimentation as well as more different types of drugs used. This study suggests that primary alcoholics who consume more drugs and/or alcohol might be at an increased risk for developing alcoholic hallucinosis.

Adult↗

PubMed1994

One-year incidence rate of major depression and other psychiatric disorders in 239 alcoholic men.

The rate of depressive symptoms among alcoholics is high, but many of these syndromes appear to be alcohol-induced mood disorders and might not represent major depressive episodes independent of heavy drinking. The present study examines one aspect of the relationship between alcoholism and depression by evaluating the incidence of new episodes of major depressive disorders among alcohol-dependent men during the year following treatment. One year following discharge from an alcohol treatment program, structured face-to-face interviews were carried out with 239 primary alcoholic men, as well as additional informants. Approximately 4% of the men developed depressive episodes while drinking heavily, but only 2.1% demonstrated major depressions independent of heavy alcohol intake. There was no evidence of an increased incidence of any other major psychiatric disorder during the year of follow-up. These results are consistent with prospective studies of children of alcoholics and of longitudinal evaluations of general population samples. They do not indicate that in the present sample most primary alcohol-dependent men have elevated rates for major depressive disorders independent of alcohol-induced mood syndromes. However, it is likely that in the context of heavy drinking severe, although temporary, depressive episodes are likely to be observed.

Adult↗

PubMed1994

Artifacts associated with acoustic rhinometric assessment of infants and young children: a model study.

The present study was undertaken to determine in model studies whether currently available acoustic rhinometry instrumentation might be used to analyze the nasal cavity configuration of infants and children. A simple nasal cavity model was constructed using eight Lucite inserts that were placed between standard nosepieces provided by the manufacturer and a 35-cm-long polyvinyl chloride pipe closed at its distal end. To simulate the nasal valve, the inserts were 12 mm in length and had apertures ranging in diameter from 2 to 9 mm. A series of experiments was conducted to evaluate the accuracy with which the acoustic rhinometer measured the size of each insert aperture and the configuration of the model system distal to that aperture. Transmission losses caused errors in the area measurement of the insert aperture and the tube distal to the insert. When the insert aperture was < 6 mm in diameter (0.28 cm2), the aperture area was overestimated by > 10%, whereas the area of the distal tube was underestimated by > 10%. As a result of response lags, the acoustic rhinometer also failed to provide an accurate indication of insert length. Finally, oscillation artifacts caused estimates of the distal pipe area to fluctuate. These three systematic errors are described, and their potential impact on acoustic rhinometry in children is discussed.

Acoustics↗

PubMed1994

A comparative study of criteria for subgrouping alcoholics: the primary/secondary diagnostic scheme versus variations of the type 1/type 2 criteria.

OBJECTIVE: This study compared three methods for identifying type 1 and type 2 alcoholism to determine how well the methods agree. It also evaluated the comparability of each of these schemes to the primary/secondary approach to subgrouping alcoholics. METHOD: Fifty male alcoholic inpatients were given diagnoses of primary alcoholism without antisocial personality disorder or primary antisocial personality disorder with secondary alcoholism on the basis of data from structured interviews. Operationalized criteria for type 1 and type 2 alcoholism from three groups of researchers (Gilligan et al., von Knorring et al., and Sullivan et al.) were also used to designate subgroups of the same subjects. RESULTS: Subgroups of subjects classified as having type 1 or type 2 alcoholism according to the criteria of von Knorring et al. and of Sullivan et al. showed good levels of agreement, but the criteria of Gilligan et al. yielded poor agreement with those of the other two schemes. Subgroups with type 1 or type 2 alcoholism according to the criteria of Sullivan et al. showed significant overlap with subgroups diagnosed according to the primary/secondary alcoholism scheme: there was 73% concordance between the type 1 subgroup and the subgroup with primary alcoholism and 73% concordance between the type 2 subgroup and the subgroup with primary antisocial personality disorder and secondary alcoholism. CONCLUSIONS: There is variability in assigning diagnoses of type 1 and type 2 alcoholism with the use of current methods. Also, type 1/type 2 classifications based primarily on age-at-onset factors significantly overlap with the primary/secondary classifications of alcoholics.

Adolescent↗

PubMed1994

Recovery of eustachian tube function and hearing outcome in patients with cleft palate.

Eustachian tube dysfunction is a nearly universal complication of cleft palate, resulting in chronic ear disease and conductive hearing loss. Cleft palate repair is thought to result in recovery of eustachian tube function, but the length of time between repair and recovery of eustachian tube function is not known. Furthermore, the efficacy of tympanostomy tubes in the treatment of eustachian tube dysfunction and hearing sequelae has not been examined in a systematic way. To answer these questions, we performed a retrospective study that used serial audiometric data and tympanometry on 81 patients with cleft palates (162 ears), with follow-up ranging from 1 to 17.3 years. Average time to recovery of eustachian tube function was 6.0 years (range, 1.0 to 10.3 years) after cleft palate surgery. For children followed up for at least 6 years (longest follow-up, 17.3 years), 70% (67 of 85) had normal eustachian tube function at their last follow-up visit. Ears treated with Armstrong tympanostomy tubes required an average of 3.1 tubes per ear until recovery of eustachian tube function, whereas ears treated with Goode T tubes required only 1.1 tubes per ear (p < 0.05). Hearing evaluation revealed that 67% of ears had abnormal hearing thresholds (> 20 dB) before tympanostomy tube placement, whereas only 7.5% of ears demonstrated this loss after tube placement. Furthermore, more than 90% of ears maintained normal thresholds after recovery of eustachian tube function. These data indicate that most children with cleft palates eventually recover normal eustachian tube function after palatoplasty, but for the majority of children, this does not occur for many years.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1994

The prognostic importance of blackouts in young men.

In order to test the commonly held perception that blackouts are an early diagnostic sign of alcoholism, we evaluated a sample of 230 nonalcoholic young men longitudinally over an 8-12 year follow-up period. Consistent with the literature, blackouts were a common occurrence in this cohort, with 26% of the men reporting blackouts by their early twenties, and 30% of the subjects experiencing blackouts over the approximately 10-year follow-up. Alcohol-related amnestic episodes were associated with the quantity and frequency of drinking, and men with blackouts (especially four or more) were more likely to have other problems related to their heavy drinking. Although few alcoholics will report not having had such amnestic spells, blackouts are not sensitive indicators of the risk for developing alcoholism. The data suggest that blackouts should be viewed as an important warning sign of problem drinking, but not as the "hallmark" of alcoholism.

Adolescent↗

PubMed1994

Effect of hamstring stretching on hamstring muscle performance.

The relationship between hamstring flexibility and hamstring muscle performance has not been reported. The purposes of this study were 1) to determine the most effective stretching method for increasing hamstring flexibility and 2) to determine the effects of increasing hamstring flexibility on isokinetic peak torque. Nineteen subjects participated in this study. A two-way analysis of variance was used to compare two stretching techniques: proprioceptive neuromuscular facilitation stretch and static stretch. A one-way repeated measures analysis of variance was used to compare hamstring isokinetic values pre- and poststretching. No significant increase occurred (p < .05) in hamstring flexibility even though increases occurred with each technique: static stretch (+21.3%) and proprioceptive neuromuscular facilitation (+25.7%). Significant increases occurred in peak torque eccentrically at 60 degrees/sec (p < .05, +8.5%) and 120 degrees/sec (p < .05, +13.5%) and concentrically at 120 degrees/sec (p < .05, +11.2%). No significant increase occurred at 60 degrees/sec (p > .05, +2.5%). We concluded that increasing hamstring flexibility was an effective method for increasing hamstring muscle performance at selective isokinetic conditions. Further study is needed to determine if increasing hamstring flexibility will increase performance in closed kinetic chain activities.

Adult↗

PubMed1994

Predictors of drinking and driving in healthy young men: a prospective study.

This paper explores the ability of information about alcohol use and problem patterns in men's early 20s to predict drinking and driving by their early 30s. The sample consisted of 231 healthy young men who were students or nonacademic staff at a university. Subjects were evaluated initially with questionnaires and interviews, and subsequently followed-up using interviews with themselves and with a resource person. The reported rate of drinking and driving at follow-up was nearly 38%. Using logistic regression, the combination of variables that best predicted drinking and driving included prior alcohol-related auto accidents, a measure of typical drinking, and a measure of drinking-related problems. The overall prediction employing this combination was 72%, the specificity was 86%, and the sensitivity was 48%.

Accidents, Traffic↗