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Biomedical subjects

T L Smith

Publications and source records attributed to T L Smith.

At least 55 records · Page 3Linked to original sources

Health-related quality-of-life measure enhances acute treatment response prediction in depressed inpatients.

BACKGROUND: Many nonbiological variables are reported to predict treatment response for major depression; however, there is little agreement about which variables are most predictive. METHOD: Inpatient subjects (N = 59) diagnosed with current DSM-IV major depressive disorder completed weekly depressive symptom ratings with the Hamilton Rating Scale for Depression (HAM-D-17) and Beck Depression Inventory (BDI), and weekly health-related quality-of-life (HRQL) ratings with the Quality of Well-Being Scale (QWB). Acute responders were identified by a 50% decrease in HAM-D-17 score from baseline within 4 weeks of medication treatment. Predictor variables were initially chosen from a literature review and then tested for their association with acute treatment response. RESULTS: An initial predictive model including age at first depression, admission BDI score, and melancholia predicted acute treatment response with 69% accuracy and was designated as the benchmark model. Adding the admission QWB index score to the benchmark model did not improve the prediction rate; however, adding the admission QWB subscales for physical and social activity to the benchmark model significantly improved acute treatment response prediction to 86% accuracy (p = .001). CONCLUSION: In addition to being designed for use in cost-effectiveness analyses, the QWB subscales appear to be useful HRQL variables for predicting acute inpatient depression treatment response.

Adult↗

A comparison of correlates of DSM-IV alcohol abuse or dependence among more than 400 sons of alcoholics and controls.

BACKGROUND: Alcohol dependence and abuse are defined as separate disorders. However, relatively few data are available about whether the same characteristics predict both syndromes. METHODS: Complete data were available from the 15 year follow-up of 411 men who originally had been evaluated from a university population at about age 20. Both baseline data gathered prospectively and the retrospective ratings in six domains of life functioning were analyzed for their relationship to the development of alcohol abuse or dependence during the follow-up. RESULTS: Baseline characteristics of a family history of substance use disorders, the quantity and frequency of drinking, the history of alcohol-related problems, and the level of response to alcohol all predicted future alcohol abuse or dependence, but only an alcoholic second-degree relative or a first-degree drug-dependent family member differentially predicted dependence. Logistic regression analyses revealed that similar baseline characteristics combined to predict dependence and, separately, abuse. When the domains of functioning during the 15 years were included, positive alcohol expectancies, poor coping mechanisms, low level of social support, and drinking in the environment contributed to both dependence and abuse, although the relationship was stronger for dependence. CONCLUSIONS: The predictors and correlates of alcohol abuse and dependence in this group of men were similar. Further research in additional populations and on other drugs is needed to determine if the two syndromes overlap sufficiently to be combined.

Adult↗

A genome-wide search for genes that relate to a low level of response to alcohol.

BACKGROUND: The low level of response (LR) to alcohol is genetically influenced in both humans and animals, and a low LR is a characteristic of offspring of alcoholics that has been reported to predict alcoholism 10 and 15 years later. The genes that contribute to a low LR have not yet been identified. METHODS: A 12-item questionnaire that measures LR, the Self Rating of the Effects of Alcohol (SRE) instrument, was filled out by 745 individuals from the Collaborative Study on the Genetics of Alcoholism (COGA) for whom genetic material was available. These subjects were genotyped by using 336 markers with an average heterozygosity of 0.74 and an average intermarker distance of 10.5 cM. Both quantitative and qualitative nonparametric, sib-pair analyses were carried out for the SRE measure related to early drinking experiences. RESULTS: Correlations of SRE scores across related individuals were significant and between 0.16 and 0.22 for most values, compared with nonsignificant correlations of 0.03 or less among unrelated individuals. Linkage analyses performed by using the FIRST 5 variables (first five times alcohol is consumed) identified four chromosomal regions with lod scores > or = 2.0 whose maximum was also near a marker. One of these chromosomal regions previously was linked to alcohol dependence in the COGA sample. CONCLUSIONS: These data document the familial nature of a low LR to alcohol as measured by the SRE and suggest several chromosomal regions that might contribute to the phenomenon.

Alcoholism↗

HER-2/neu overexpression as a poor prognostic factor for patients with metastatic breast cancer undergoing high-dose chemotherapy with autologous stem cell transplantation.

PURPOSE: High-dose chemotherapy with autologous stem cell transplantation (HDCT) produces a high tumor response rate for patients with metastatic breast cancer and have 20% long-term progression-free survival. Overexpression of HER-2/neu oncoprotein predicts outcome in patients with breast cancer given standard-dose chemotherapy. Therefore, we evaluated whether the HER-2/neu overexpression in the primary tumor predicts clinical outcome in patients with metastatic breast cancer given HDCT. EXPERIMENTAL DESIGN: A total of 236 patients were given standard-dose induction chemotherapy followed by stem cell collection; high-dose chemotherapy with cyclophosphamide, thiotepa, and carmustine; and stem cell infusion. HER-2/neu expression was assessed by immunostaining with anti-HER-2/neu e2-4001 monoclonal antibody in 63 patients. RESULTS: Clinical characteristics and survival were similar for patients with known and unknown HER-2/neu status. HER-2/neu was overexpressed in 22 of 63 tumors (35%). There was some tendency for HER-2/neu overexpression to be associated with the absence of estrogen or progesterone receptors. In considering the association of HER-2/neu expression with patient outcomes, HER-2/neu overexpression was associated with generally shorter overall survival (P = 0.02) and progression-free survival (P < 0.01), and this association persisted to a lesser extent after adjustment for differences in important prognostic factors between the two groups. CONCLUSION: We conclude that HER-2/neu overexpression may represent an additional prognostic factor for patients with metastatic breast cancer who undergo HDCT.

Antibodies, Monoclonal↗

Evaluation of word associations as a reliable postoperative indicator of implicit memory formation during the intraoperative period.

Patients expect to receive an anesthetic that prevents the formation of memories during the intraoperative period. Unfortunately, explicit memory formation occurs 40,000 times per year in the United States, while the incidence of implicit memory is thought to be greater. The purpose of the study was to evaluate the effectiveness of word associations as a reliable postoperative indicator of implicit memory formation during the intraoperative period. Forty-eight participants scheduled to undergo general anesthesia for an elective procedure were selected. During the administration of 0.77 +/- .18 microgram/kg per minute of remifentanyl and 0.31 +/- .04 end-tidal volume percent of sevoflurane in air/oxygen, word associations in the form of "Trivial Pursuit" (Hasbro, Inc, Pawtucket, RI) game statements were presented via headphones. Within 24 hours of surgery, each participant was given a postoperative word association test that included the experimental and control word associations. No reports of explicit memory were noted. The experimental word associations were correctly answered 19.3% of the time, while the control word associations were correctly answered 12.8% of the time (P = .014). The findings illustrated that the word association test in the form of Trivial Pursuit game statements/answers may serve as a reliable postoperative indicator of implicit memory formation during the intraoperative period.

Adult↗

Homoharringtonine and low-dose cytarabine in the management of late chronic-phase chronic myelogenous leukemia.

PURPOSE: : To evaluate the efficacy and toxicity profiles of a combination regimen of homoharringtonine (HHT) and low-dose cytarabine (ara-C) in patients with Philadelphia chromosome (Ph)-positive chronic myelogenous leukemia (CML) who had experienced treatment failure with interferon alfa (IFNalpha) therapy. PATIENTS AND METHODS: One hundred five patients were treated: 100 in chronic phase (15 with cytogenetic clonal evolution) and five in accelerated phase. Their median age was 52 years; all had been treated unsuccessfully with IFNalpha; 94% were in late chronic phase; 43% had been exposed to ara-C and 11% had been exposed to HHT. Patients received HHT 2.5 mg/m(2) by continuous infusion daily for 5 days and ara-C 15mg/m(2) daily in two subcutaneous injections for 5 days every 4 weeks. The outcome of the 100 patients in chronic phase was compared with a previous study group of 73 patients treated with HHT alone. RESULTS: Overall, the complete hematologic response (CHR) rate in chronic phase was 72%; the cytogenetic response rate was 32% (major response, 15%; complete response, 5%). Toxicities were acceptable, mostly related to moderate diarrhea (3%), headaches (3%), cardiovascular events (3%),and myelosuppression-associated complications (3% to 14%). With a median follow-up period of 25 months, the estimated 4-year survival rate was 55%. Response rates were identical with HHT plus ara-C versus HHT alone, but the survival was significantly longer with the combination after accounting for differences in the study groups and by multivariate analysis. CONCLUSION: The combination regimen of HHT and ara-C is effective and safe in patients with CML who have experienced treatment failure with IFNalpha and needs to be investigated together with IFNalpha as part of front-line CML therapy. The addition of ara-C did not improve the response rates but may have improved survival, perhaps through suppression of clones related to disease transformation.

Antineoplastic Combined Chemotherapy Protocols↗

Efficiency of spermatogenesis: a comparative approach.

Efficiency of spermatogenesis is the estimated number of spermatozoa produced per day per gram of testicular parenchyma. Spermatogenesis is the process of cell division and cell differentiation by which spermatozoa are produced in testes. Efficiency of spermatogenesis is influenced by species differences in the numerical density of germ cell nuclei and in the life span of these cells. Activities of spermatogonia, spermatocytes, and spermatids partition spermatogenesis into three major divisions (spermatocytogenesis, meiosis, and spermiogenesis, respectively). Spermatocytogenesis involves mitotic germ cell division to produce stem cells and primary spermatocytes. Meiosis involves duplication of chromosomes, exchange of genetic material, and two cell divisions that reduce the chromosome number and yield four spermatids. In spermiogenesis, spherical spermatids differentiate into mature spermatids which are released in the lumen of seminiferous tubules as spermatozoa. Spermatogenesis and germ cell degeneration can be quantified from numbers of germ cells in various developmental steps throughout spermatogenesis. Germ cell degeneration occurs throughout spermatogenesis; however, the greatest impact occurs during spermatocytogenesis and meiosis. There are species and seasonal influences on the developmental steps in spermatogenesis at which germ cell degeneration occurs. Number of Sertoli cells, amount of smooth endoplasmic reticulum of Leydig cells, and the number of missing generations of germ cells within the spermatogenic stage of the cycle influence efficiency of spermatogenesis. Efficiency of spermatogenesis is influenced to the amount of germ cell degeneration, pubertal development, season of the year, and aging of humans and animals.

Aging↗

Randomized trial of high-dose chemotherapy and blood cell autografts for high-risk primary breast carcinoma.

BACKGROUND: Uncontrolled studies have reported encouraging outcomes for patients with high-risk primary breast cancer treated with high-dose chemotherapy and autologous hematopoietic stem cell support. We conducted a prospective randomized trial to compare standard-dose chemotherapy with the same therapy followed by high-dose chemotherapy. PATIENTS AND METHODS: Patients with 10 or more positive axillary lymph nodes after primary breast surgery or patients with four or more positive lymph nodes after four cycles of primary (neoadjuvant) chemotherapy were eligible. All patients were to receive eight cycles of 5-fluorouracil, doxorubicin (Adriamycin), and cyclophosphamide (FAC). Patients were stratified by stage and randomly assigned to receive two cycles of high-dose cyclophosphamide, etoposide, and cisplatin with autologous hematopoietic stem cell support or no additional chemotherapy. Tamoxifen was planned for postmenopausal patients with estrogen receptor-positive tumors and chest wall radiotherapy was planned for all. All P values are from two-sided tests. RESULTS: Seventy-eight patients (48 after primary surgery and 30 after primary chemotherapy) were registered. Thirty-nine patients were randomly assigned to FAC and 39 to FAC followed by high-dose chemotherapy. After a median follow-up of 6.5 years, there have been 41 relapses. In intention-to-treat analyses, estimated 3-year relapse-free survival rates were 62% and 48% for FAC and FAC/high-dose chemotherapy, respectively (P =.35), and 3-year survival rates were 77% and 58%, respectively (P =.23). Overall, there was greater and more frequent morbidity associated with high-dose chemotherapy than with FAC; there was one septic death associated with high-dose chemotherapy. CONCLUSIONS: No relapse-free or overall survival advantage was associated with the use of high-dose chemotherapy, and morbidity was increased with its use. Thus, high-dose chemotherapy is not indicated outside a clinical trial.

Adult↗

Randomized trial of alpha-interferon or dexamethasone as maintenance treatment for multiple myeloma.

In order to assess the role of alpha-interferon or dexamethasone as maintenance therapy for multiple myeloma, 172 consecutive, previously untreated patients with disease of low or intermediate tumor mass received primary therapy with oral melphalan and intermittent, high-dose dexamethasone (MD), repeated monthly. Within 5 months, 84 responding patients were assigned at random to maintenance treatment with alpha-interferon (3 mU s.c. 3 x weekly) or dexamethasone (20 mg/m2 p.o. each morning for 4 days) repeated monthly until relapse. Upon relapse, MD was resumed for 2 cycles and second responses were maintained with 4-day courses of melphalan-dexamethasone until second relapse. Initial response was achieved in 88 patients (51%) after a median 0.7 month and no more than 3 courses of MD, a frequency of response similar to that observed previously with dexamethasone alone. There were identical median remissions of 10 months with interferon or dexamethasone, both maintenance regimens being associated with infrequent, mild, and reversible side effects. Significantly more patients responded again to resumption of MD after disease relapse to interferon (82%) than to dexamethasone (44%) (P = 0.001). The median remission from randomization to melphalan-resistant second relapse was 32 months for patients maintained initially on interferon compared to 19 months for those on dexamethasone (P = 0.01). These findings supported an advantage for interferon in remission maintenance by increasing the frequency of tumor recontrol with later treatment that included dexamethasone.

Adult↗

Role of alpha-1 adrenoceptor subtypes mediating constriction of the rabbit ear thermoregulatory microvasculature.

An acute in vivo preparation of the microvasculature of the rabbit ear was used to evaluate the functional role of alpha1 (alpha1)-adrenoceptor subtypes in thermoregulatory microcirculation. The effect of alpha1-adrenoceptor subtype blockade on phenylephrine-induced vasoconstriction was assessed with the alpha1A, alpha1B, and alpha1D-adrenoceptor-selective antagonists 5-methyl-urapidil (10(-8) M), chloroethylclonidine (10(-5) M), and 8-[2-[4(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspirol[4.5]deca ne-7,9-dione dihydrochloride (BMY7378) (10(-6) M), respectively. The results demonstrated that pretreatment of the ear microvasculature with 5-methyl-urapidil or BMY7378 shifted the phenylephrine concentration-response curve rightward and significantly changed the log of the phenylephrine concentration, causing half-maximum stimulation (EC50) in arterioles (p < 0.05). BMY7378 shifted the phenylephrine concentration-response curve of the arteriovenous anastomoses about 100-fold rightward (p < 0.05). All three alpha1-adrenoceptor antagonists eliminated the vasoconstrictive effects of phenylephrine on venules. The results indicate that the ear microvasculature has a heterogenous distribution of alpha1-adrenoceptor subtypes. The alpha1A and alpha1D-adrenoceptor subtypes appear to have a greater influence on constrictive function in arterioles, whereas the alpha1D-adrenoceptor is the dominant constrictor of arteriovenous anastomoses. In general, the alpha1-adrenoceptor does not play a major vasoconstrictor role in venules. Chloroethylclonidine, an irreversible alpha1B-adrenoceptor antagonist, induced contractile responses in the ear microvasculature, probably due to its alpha2-adrenoceptor agonist effects. This study extended our understanding of the adrenergic receptor control mechanisms of a cutaneous thermoregulatory end organ characterized by two parallel perfusion circuits providing nutritional and thermoregulatory functions.

Animals↗

Midline radiofrequency tissue reduction of the palate for bothersome snoring and sleep-disordered breathing: A clinical trial.

This study is a prospective, nonrandomized clinical trial initiated to assess the safety and efficacy of radiofrequency tissue reduction of the palate for the treatment of bothersome snoring and sleep-disordered breathing. Twelve healthy volunteers with socially disruptive snoring underwent a baseline polysomnogram along with a battery of visual analog scales (VASs) to measure daytime sleepiness, snoring level, pain, and disturbances of speech and swallowing. After radiofrequency tissue reduction of the palate, they were re-evaluated with a mean follow-up after the final procedure of 15.7 +/- 5.1 (mean +/- SD) weeks. As rated by the bed partner, a significant reduction in the level of snoring occurred in all 12 patients, with a mean pretreatment snoring level of 8.3 +/- 2.1 to a mean posttreatment snoring level of 2.1 +/- 1.4. (Student t test, P < 0.0001) These patients required an average of 2.3 treatment sessions each. Nine of 12 had a reduction in snoring from a bothersome level (VAS range 5-10) to a nonbothersome level (VAS range 0-3). Daytime sleepiness as measured by the Epworth Sleepiness Scale (0-24) decreased from 10.8 +/- 4.4 to 8.3 +/- 4.1 (P = 0.011). Posttreatment pain was considered absent or minimal in 11 of 12 patients and was managed with acetaminophen. No significant adverse events or complications were reported.

Adolescent↗

Nitric oxide is a mediator of the late-phase response in an animal model of nasal allergy.

The presence of nitric oxide (NO) in the nose is well documented; however, the role of this molecule in nasal physiology is still poorly understood. Our laboratory has previously demonstrated that NO is a mediator of the immediate secretory response to an intranasal histamine challenge in a rat model of nasal allergy. Histamine challenge, however, does not elicit a late-phase response (LPR). To study the role of NO in the LPR, we developed a model of nasal allergy in which brown Norway rats are actively sensitized to the allergen ovalbumin and later challenged intranasally with either phosphate-buffered saline solution (vehicle), ovalbumin in vehicle, or ovalbumin and the NO synthase inhibitor N -nitro-l -arginine methyl ester. In each experiment, nasal lavage samples were collected 30, 120, 240, and 360 minutes after challenge. Lavage samples were analyzed for albumin content by ELISA, inflammatory cell concentration with a hemocytometer, and evidence of inflammation by light microscopy. Blocking NO synthesis with N -nitro-l -arginine methyl ester significantly inhibited both albumin exudation and inflammatory cell influx into the nasal cavity during the LPR. These data suggest that NO plays a role in the LPR of nasal allergy.

Albumins↗

Arterial reconstruction for radial artery occlusion.

This study was designed to detail the history and symptoms of symptomatic radial artery vaso-occlusive disease and to evaluate the results of radial artery reconstruction. Thirteen patients with symptomatic vaso-occlusive disease of the radial artery unresponsive to management by nonoperative modalities were managed with arterial reconstruction. All cases were treated with reversed interpositional vein grafting from the radial artery in the forearm (end-to-side) to the deep arch distally (end-to-end). Patients completed preoperative and postoperative assessments of symptoms and function, cold sensitivity (cold intolerance), and digital microvascular perfusion (isolated cold stress test evaluation with laser Doppler fluxmetry). At the follow-up examination all vascular grafts were patent, as determined by Allen's testing and Doppler ultrasound. The patients reported symptoms and functional status that demonstrated significant improvement following reconstruction. Microvascular evaluations demonstrated a significant improvement in digital microvascular perfusion as assessed by laser Doppler fluxmetry and digital temperature recordings with a resultant resolution of ischemic pain, numbness, and ulceration.

Adolescent↗

Physician preferences for educational media.

BACKGROUND: Although educational media have expanded in variety, information on physicians' preferences for types of educational media remains limited. METHOD: An assessment form was distributed to 14 medical societies evaluating their members' medical education media preferences and society antimicrobial-resistance educational offerings. RESULTS: These 14 medical societies represent 349,685 physicians. All supported educational offerings, most frequently as professional meetings, followed by audiotapes, computer programs, Internet sites, or print-based self-study materials. Only 5 (36%) societies had measured how many members used their educational offerings. Eight (57%) societies had made antimicrobial resistance an educational priority for their medical societies. Antimicrobial treatment was the most commonly offered educational topic on antimicrobial resistance. CONCLUSIONS: These 14 medical societies help to educate over one half the practicing US physicians. However, less than one half of the societies knew how many of their members used the educational materials they offered, or how their members would prefer to obtain medical education. Understanding how physicians want to obtain medical information potentially could improve the delivery of medical knowledge to physicians.

Attitude of Health Personnel↗

A pilot study of antibiotic cycling in a hematology-oncology unit.

OBJECTIVE: To determine the safety and treatment efficacy of cycling antibiotic regimens for prophylaxis or treatment of patients with profound neutropenia. DESIGN: A prospective, nonrandomized, observational trial. SETTING: A 20-bed adult hematology-oncology inpatient unit at a university referral hospital. PATIENTS: Hospitalized adult patients with chemotherapy- or radiation-induced neutropenia (absolute neutrophil count less than 500 cells/mm3). INTERVENTION: Between July 1994 and January 1996, 295 hospitalized patients were evaluated on an intent-to-treat basis for the cycling protocol. Of these, 271 were eligible and assigned to one of four antibiotic regimens being used at the time of enrollment: (1) ceftazidime+vancomycin; (2) imipenem; (3) aztreonam+cefazolin; (4) ciprofloxacin+clindamycin. Data on infection rates and types, and antibiotic resistance patterns, toxicity, and effectiveness were collected. RESULTS: Twenty-four patients were excluded. Of the 271 evaluable patients, 123 (42%) were able to complete treatment on the assigned regimen. Of the 148 patients (50%) unable to do so, the reasons for failure included persistent fever (79%), breakthrough bacteremia (14%), and drug toxicity (7%). The antibiotic susceptibility profiles over the study period showed no increase in resistance. However, there was a marked increase in enterococcal infections. CONCLUSIONS: Our data show no significant increase in side effects or decrease in efficacy while cycling antibiotics among neutropenic patients and thus support further study of its role.

Adult↗

Reliability of measurements of muscle tone and muscle power in stroke patients.

OBJECTIVES: to establish the reliability of the modified Ashworth scale for measuring muscle tone in a range of muscle groups (elbow, wrist, knee and ankle; flexors and extensors) and of the Medical Research Council scale for measuring muscle power in the same muscle groups and their direct antagonists. DESIGN: a cross-sectional study involving repeated measures by two raters. We estimated reliability using the kappa statistic with quadratic weights (Kw). SETTING: an acute stroke ward, a stroke rehabilitation unit and a continuing care facility. SUBJECTS: people admitted to hospital with an acute stroke-35 patients, median age 73 (interquartile range 65-80), 20 men and 15 women. RESULTS: inter- and intra-rater agreement for the measurement of power was good to very good for all tested muscle groups (Kw = 0.84-0.96, Kw = 0.70-0.96). Inter- and intra-rater agreement for the measurement of tone in the elbow, wrist and knee flexors was good to very good (Kw = 0.73-0.96, Kw = 0.77-0.94). Inter- and intra-rater agreement for the measurement of tone in the ankle plantarflexors was moderate to good (Kw = 0.45-0.51, Kw = 0.59-0.64). CONCLUSIONS: the Medical Research Council scale was reliable in the tested muscle groups. The modified Ashworth scale demonstrated reliability in all tested muscle groups except the ankle plantarflexors. If reliable measurement of tone at the ankle is required for a specific purpose (e.g. to measure the effect of therapeutic intervention), further work will be necessary.

Aged↗