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T L Smith

Publications and source records attributed to T L Smith.

At least 37 records · Page 2Linked to original sources

Troxacitabine, a novel dioxolane nucleoside analog, has activity in patients with advanced leukemia.

PURPOSE: To investigate the toxicity profile, activity, and pharmacokinetics of a novel L-nucleoside analog, troxacitabine (BCH-4556), in patients with advanced leukemia. PATIENTS AND METHODS: Patients with refractory or relapsed acute myeloid (AML) or lymphocytic (ALL) leukemia, myelodysplastic syndromes (MDS), or chronic myelogenous leukemia in blastic phase (CML-BP). Troxacitabine was given as an intravenous infusion over 30 minutes daily for 5 days. The starting dose was 0.72 mg/m(2)/d (3.6 mg/m(2)/course). Courses were given every 3 to 4 weeks according to toxicity and antileukemic efficacy. The dose was escalated by 50% until grade 2 toxicity was observed, and then by 30% to 35% until the dose-limiting toxicity (DLT) was defined. RESULTS: Forty-two patients (AML: 31 patients; MDS: six patients [five MDS + one CMML]; ALL: four patients; CML-BP: one patient) were treated. Median age was 61 years (range, 23 to 79 years), and 29 patients were males. Stomatitis and hand-foot syndrome were the DLTs. The MTD was defined as 8 mg/m(2)/d. The pharmacokinetic behavior of troxacitabine is linear over the dose range of 0.72 to 10.0 m/m(2). Approximately 69% of troxacitabine was excreted as unchanged drug in the urine. Marrow hypoplasia occurred between days 14 and 28 in 73% of AML patients. Three complete remissions and one partial remission were observed in 30 assessable AML patients. One MDS patient achieved a hematologic improvement. A patient with CML-BP achieved a return to chronic phase disease. CONCLUSION: Troxacitabine has a unique metabolic and pharmacokinetic profile and significant antileukemic activity. DLTs were stomatitis and hand-foot syndrome. Troxacitabine merits further study in hematologic malignancies.

Acute Disease↗

Radiofrequency tissue volume reduction: multilesion vs single-lesion treatments for snoring.

OBJECTIVE: To compare the safety and efficacy of single-lesion and multilesion radiofrequency tissue reduction (RFTR) of the soft palate for the treatment of snoring. DESIGN: Prospective, nonrandomized clinical trial. SETTING: University hospital outpatient clinic. PATIENTS: Nonrandomized patients undergoing RFTR to treat socially unacceptable snoring. Of 47 patients, 16 received single-lesion treatments and 31 received multilesion treatments. INTERVENTION: Soft-palate RFTR was performed using a radiofrequency generator. Patients required 1 to 3 treatments based on improvement or withdrawal from the study, and each received 1, 3, or 4 lesions per treatment. Patients who received single-lesion therapy did not cross over into the multilesion group; however, 5 patients in the multilesion group received 4-lesion therapy after a treatment with 3 lesions. MAIN OUTCOME MEASURES: Outcome measures were determined using visual analog scale questionnaires assessing level of snoring (snoring index) and level of pain (pain index) associated with the procedure. Adverse events and complications during treatment were cataloged. Data were collected before the procedure, 6 weeks after each treatment, and an average of 16 months after the last procedure. RESULTS: Single-lesion and multilesion groups showed significant improvement in snoring after RFTR treatments (P<.01 for both). However, compared with the single-lesion group, the multilesion group required fewer treatments (1.94 vs 2.38; P =.05) and was more than twice as likely to be cured after 2 treatments (61% vs 25%; P =.02). A trend toward improved clinical outcomes with increased number of lesions and total energy per treatment was observed when patients treated with 1, 3, or 4 lesions were compared. The 4-lesion group had the most pronounced improvement in snoring index score per treatment, the lowest number of treatments required for cure, and the greatest percentage of patients cured after 2 treatment sessions. Follow-up demonstrated minimal relapse of snoring in the multilesion group at a mean of 16 months. Although there was a statistically significant increase in pain in the multilesion group vs the single-lesion group, this increase did not increase narcotic use or time off work and was considered minimal by reporting patients. CONCLUSION: Multilesion RFTR using higher energy levels per treatment is safe and has increased efficacy without increased complications relative to single-lesion therapy.

Adult↗

Cardiac-specific abrogation of NF- kappa B activation in mice by transdominant expression of a mutant I kappa B alpha.

Nuclear factor-kappaB (NF-kappa B) is a pleiotropic oxidant-sensitive transcription factor that is present in the cytosol in an inactive form complexed to an inhibitory kappaB (I kappa B) monomer. Various stimuli, including ischemia, hypoxia, free radicals, cytokines, and lipopolysaccharide (LPS), activate NF-kappa B by inducing phosphorylation of I kappa B. Phosphorylation of serine residues at positions 32 and 36 is critical for ubiquitination and degradation of I kappa B alpha with consequent migration of NF-kappa B to the nucleus. Although NF-kappa B is thought to contribute to numerous pathophysiologic processes, definitive assessment of its role has been hindered by the inability to achieve specific inhibition in vivo. Pharmacologic inhibitors of NF-kappa B are available, but their utility for in vivo studies is limited by their relative lack of specificity. Targeted ablation of genes encoding NF-kappa B subunits has not been productive in this regard because of fetal lethality in the case of p65 and functional redundancy in the Rel family of proteins. To overcome these limitations, we have created a viable transgenic mouse that expresses a phosphorylation-resistant mutant of I kappa B alpha (I kappa B alpha(S32A,S36A)) under the direction of a cardiac-specific promoter. Several transgenic lines were obtained with copy numbers ranging from one to seven. The mice exhibit normal cardiac morphology and histology. Total myocardial I kappa B alpha protein level is elevated 3.5- to 6.5-fold with a concomitant 50-60% decrease in the level of I kappa B beta. Importantly, expression of I kappa B(S32A,S36A) results in complete abrogation of myocardial NF-kappa B activation in response to tumor necrosis factor- alpha (TNF-alpha) and LPS stimulation. Thus, novel transgenic mice have been created that make it possible to achieve cardiac-specific and selective inhibition of NF-kappa B in vivo. These transgenic mice should be useful in studies of various cardiac pathophysiological phenomena that involve NF-kappa B activation, including ischemic preconditioning, heart failure, septic shock, acute coronary syndromes, cardiac allograft rejection, and apoptosis.

Amino Acid Substitution↗

Expression of erbB/HER receptors, heregulin and P38 in primary breast cancer using quantitative immunohistochemistry.

The purpose of this study was to investigate the frequency of expression of the erbB/HER family of growth factor receptors, their ligand heregulin, and the two different signaling pathways p38 and mitogen-activated protein kinase (MAPK), as well as the status of HER-2 phosphorylation in tumor specimens from patients with primary breast cancer. The level of expression of these proteins was measured by quantitative immunohistochemistry combined with microscope-based image analysis in paraffin-embedded breast cancer tissue from 35 patients. The frequency of expression was: EGFR (51%), HER-2 (54%), P-HER-2 (48%), HER-3 (48%), HER-4 (57%), heregulin (48%), p38 (17%), MAPK (48%). There was evidence of associations among the coexpression of heregulin, EGFR, HER-2, and HER-3. Also, there was evidence of a positive association between P-MAPK and HER-4. HER-3 was expressed at high levels in patients younger than 50 years of age. There was a trend for expression of higher levels of HER-4 in tumors larger than 2 cm. The expression of EGFR, HER-2, heregulin, p38 and MAPK was independent of age, tumor size, number of lymph nodes involved or hormone receptor status. The HER family of growth factor receptors appear to be regulated independently in invasive breast cancer. Assessing the expression of multiple tumor markers by quantitative immuno-histochemistry is feasible. Further research is needed to determine the prognostic and predictive roles of the various associations between HER receptors, their ligands and signal transduction molecules in patients with early-stage breast cancer.

Breast Neoplasms↗

Potential role of the chemokine receptors CXCR3, CCR4, and the integrin alphaEbeta7 in the pathogenesis of psoriasis vulgaris.

Various adhesion molecules have been implicated in T lymphocyte binding to dermal vascular endothelium in psoriasis vulgaris, but the chemotactic signals that promote subsequent homing into the adjacent dermis and overlying epidermis are poorly defined. We studied chemokine receptor (CCR1-CCR5, CXCR1-CXCR3), chemokine (interferon-gamma inducible protein 10 [IP-10]), monokine induced by interferon-gamma (MIG), thymus and activation-regulated chemokine (TARC), macrophage-derived chemokine (MDC), and adhesion molecule (cutaneous lymphocyte antigen [CLA], E-selectin, lymphocyte function-associated antigen-1 [LFA-1], intercellular adhesion molecule-1 [ICAM-1], very late antigen 4 [VLA-4], vascular cell adhesion molecule-1 [VCAM-1], alphaEbeta7, and E-cadherin) expression in psoriasis by immunohistology, flow cytometry, and molecular techniques. CXCR3 and CCR4 were expressed by dermal CD3+ lymphocytes, and their chemokine ligands, IP-10, MIG, TARC, and MDC, were up-regulated in psoriatic lesions. Keratinocytes stimulated with tumor necrosis factor-alpha and interferon-gamma up-regulated expression of IP-10, MIG, and MDC mRNA, whereas dermal endothelial cells, similarly stimulated, up-regulated expression of IP-10, MDC, and TARC mRNA, suggesting that these cell types were sources of the chemokines detected in biopsies. There was enhanced expression of E-selectin, CLA, LFA-1, ICAM-1, VLA-4, VCAM-1, and alphaEbeta7 in psoriatic lesions versus nonlesional skin. Finally, intra-epidermal CLA+ and alphaEbeta7+ T lymphocytes selectively expressed the chemokine receptor CXCR3. Collectively, these data suggest that CXCR3 and CCR4 may be involved in T lymphocyte trafficking to the psoriatic dermis and that CXCR3 is selectively involved in subsequent T cell homing to the overlying epidermis.

Antigens, Differentiation, T-Lymphocyte↗

Thiotepa, busulfan, cyclophosphamide (TBC) and autologous hematopoietic transplantation: an intensive regimen for the treatment of multiple myeloma.

The study was designed to evaluate the efficacy and safety of an intensive, tri-alkylator conditioning regimen, consisting of thiotepa, busulfan and cyclophosphamide (TBC), prior to autologous hematopoietic cell transplantation in patients with multiple myeloma (MM) and to analyze factors associated with outcome. One hundred and twenty patients with MM received high-dose chemotherapy with TBC followed by autologous bone marrow (n = 24) or peripheral blood stem cell (PBSC) transplantation (n = 96). Fifty-four patients had chemosensitive disease and 66 had refractory disease at the time of transplantation. The overall response rate was 81% and the complete remission (CR) rate was 26%. Patients with chemosensitive disease had a CR rate of 52% vs 5% for patients with refractory disease. Multivariable analysis determined disease status at transplant as the factor most likely associated with long survival. Estimated median survival was 48, 35 and 9 months for patients with chemosensitive, primary refractory or disease in refractory relapse, respectively. Short interval from diagnosis to transplant among patients with primary refractory disease and younger age were also favorable prognostic factors for survival. Patients with refractory disease pre-transplant who achieved remission criteria rapidly after treatment had a worse outcome than the slow responders. Treatment-related mortality with the introduction of PBSC and better supportive care was 4.8%. In conclusion, TBC is an effective and relatively well-tolerated intensive conditioning regimen in patients with MM. A more favorable outcome was observed in patients with chemosensitive disease and with early treatment for primary refractory disease. TBC merits further study in these subgroups and comparison with alternative regimens in prospective studies is warranted.

Adult↗

The clinical course of alcohol dependence associated with a low level of response to alcohol.

AIMS: To evaluate the clinical course of specific alcohol-related life problems and the risk for dependence on illicit drugs in individuals with relatively low and high levels of response (LR) to alcohol earlier in life. SUBJECTS: From among 439 men who were part of the 15-year follow-up of sons of alcoholics and controls, 108 were identified as having fulfilled criteria for DSM-III-R alcohol dependence. MEASURES: The LR to alcohol was originally evaluated following the consumption of 0.61 g/kg of ethanol at age 20 by determining the levels of change in subjective feelings of intoxication, body sway and several hormones such as cortisol. From the 453 original subjects, 450 completed a face-to-face 10-year follow-up evaluation, and 439 completed the 15-year protocol. FINDINGS: A comparison of the clinical course of 50 alcohol-dependent men with clearly low LR values at age 20 with that for 42 individuals whose LR scores were above the median revealed few differences. Those with a low LR had a slightly earlier age of onset of alcohol dependence (24.8 +/- 3.41 vs. 26.6 +/- 4.48 years), and this finding was unrelated to the presence of an alcohol-dependent father. Otherwise the members of the two groups demonstrated a similar course of alcohol dependence. There was no relationship between a low LR at age 20 and either the pattern of substances used or the rate of dependence on illicit drugs. CONCLUSIONS: The results indicate that for this sample a low LR to alcohol, while associated with a high risk for alcohol dependence, was not related to most aspects of the course of alcohol problems once dependence developed.

Adult↗

Quality-of-life assessment in patients with unilateral vocal cord paralysis.

OBJECTIVE: Our objective was to identify the impact of unilateral vocal cord paralysis (UVCP) on an individual's quality of life both before and after thyroplasty. STUDY DESIGN AND SETTING: This was a prospective observational outcome study of consecutive patients presenting to a laryngology clinic with UVCP. Participants received The Medical Outcomes Study Short Form 36-Item Health Survey (SF-36), the Voice Handicap Index (VHI), and the Voice Outcome Survey (VOS). Patients underwent medialization laryngoplasty with silastic, with or without arytenoid adduction. Outcome measures were repeated after surgery. RESULTS: A review of 45 patients at presentation revealed statistically significant reductions in quality of life as measured by each survey. Marked improvements were noted after surgery. CONCLUSIONS: Our preoperative data support a profile of significant general health-related and voice-related limitations caused by UVCP. Patient perceptions improved significantly after the surgical treatment of glottal insufficiency. SIGNIFICANCE: The SF-36, VHI, and VOS provide an important complement to traditional endpoints in the analysis of patients with UVCP.

Adult↗

Temperature-controlled radiofrequency tissue volume reduction in the human soft palate.

OBJECTIVE: To validate the use of temperature-controlled radiofrequency energy applied to the soft palate in a multicenter setting for reduction of snoring in a minimally morbid manner. METHODS: Prospective, nonrandomized multicenter study of 113 patients who had a respiratory disturbance index less than 15 and minimum oxygen saturation not less than 85% and who were seeking treatment for habitual disruptive snoring. Patients were given either single or multiple lesions to the soft palate during each treatment session. RESULTS: Patients received 1978 J on average with an overall average of 2.4 treatments. Snoring scores went from an average of 7.8 (visual analog scale (VAS), 0-10) pretreatment to 3.2 posttreatment. Pain was minimal, averaging 1.7 (VAS 0-10) on days 1 to 6. Complications were few and transient, and mild. CONCLUSIONS: The multiple lesion protocol was the most successful; reducing snoring from 7.6 to 2.7, on a VAS with an average of 1232 J delivered over 1.6 treatments. Temperature-controlled radiofrequency was found to be a minimally invasive, well-tolerated procedure that was safe and efficacious in this study group.

Adult↗

Physician preferences for continuing medical education with a focus on the topic of antimicrobial resistance: Society for Healthcare Epidemiology of America.

OBJECTIVE: To determine the type of media preferred for continuing medical education (CME) and to assess the factors that affect physician preferences for CME in general and on the special topic of antimicrobial resistance. DESIGN: A voluntary survey of the membership of the Society for Healthcare Epidemiology of America, Inc. (SHEA). METHODS: SHEA, in collaboration with other medical societies and with technical assistance from the Centers for Disease Control and Prevention, designed and mailed the survey to its membership. The survey included questions about media used, preferred, and of interest to try for CME delivery in general and on the topic of antimicrobial resistance in specific. The survey also included demographic and general questions, such as work environment, percentage of time in direct patient care, and experience treating patients with antimicrobial-resistant pathogens. RESULTS: 225 SHEA members completed the survey. The majority of physicians were in clinical practice (59%) and worked in a hospital (57%). The median year of graduation from medical school was 1979 (range, 1951-1999). CME subject matter (46%) was ranked as the most important factor affecting media preference. Journal articles (52%) were the most frequently used educational medium; local grand rounds (53%) and regional meetings (53%) were the most preferred media. CD-ROM (56%) and the Internet (46%) were selected as media of greatest interest to try. On the topic of antimicrobial resistance, the most frequently used and the preferred medium was journal articles (67% and 87%, respectively). Most (94%) had received an educational update on current antimicrobial resistance issues within the past year. Stratification of the data by graduation date revealed no significant differences in the medical education media used most (F=0.59, degrees of freedom [dfl=4, P=.6715) or preferred by SHEA members in general or on the topic of antimicrobial resistance (F=1.99, df=4, P=.0982). CONCLUSIONS: This study provides an understanding of how physicians learn, prefer to learn, and implement best practices for optimal patient outcomes in decreasing the spread of antimicrobial resistance.

Attitude of Health Personnel↗

Electrosurgery in otolaryngology-head and neck surgery: principles, advances, and complications.

OBJECTIVES/HYPOTHESIS: Electrosurgical instruments are routinely used in many applications by otolaryngologist-head and neck surgeons; and a complete description of their historical development, physics of operation, histological effects, and technological advancements is necessary for our specialty to take full advantage of this instrumentation. Because of the electrical current, heat production, and common use associated with these instruments, compounded by the complex environments in which they are used, potential complications must be considered and are likely underreported in the literature. This thesis describes the important aspects of electrosurgery along with a study of complications so otolaryngologists can use these instruments to their fullest potential while limiting complications. STUDY DESIGN: National survey of electrosurgical complications. METHODS: A survey addressing potential complications of electrosurgery was developed based on a review of the electrosurgical and complications literature. The electrosurgical complications were organized in the following categories: 1) unanticipated direct burns as a result of the active electrode contacting some tissue unintentionally; 2) unintentional burns as a result of capacitive coupling where radiofrequency (RF) current passes through a metallic instrument (such as forceps) and burns tissue in contact with that metallic instrument; 3) fires occurring as a result of electrosurgical instruments; 4) electromagnetic interference with a pacemaker, defibrillator, or cardiac monitoring device; and 5) other complications not included in the previous categories. The survey was mailed to the 620 members of the Society of University of Otolaryngologists. RESULTS: Of the 620 surveys mailed, 35 were returned by the post office for lack of a forwarding address and 296 were returned completed for a response rate of 49.7%. The respondents performed a total of 99,664 cases in the previous year. During that year, 324 complications related to electrosurgical instruments were reported. These included 219 unanticipated direct burns, 48 burns as a result current flow through a metallic retractor or instrument (capacitative coupling), 13 grounding pad burns, 11 fires, 32 cases of electromagnetic interference, and 1 hair loss at an incision site as a result of a cutting electrosurgical instrument. Information regarding the circumstances surrounding these complications and outcome are presented. CONCLUSIONS: Electrosurgery has proliferated since its original application by William T. Bovie and Harvey Cushing in the 1920s. Because surgeons use this technology frequently, a thorough understanding of these instruments and their potential complications is critical to their safe and successful use. Electrosurgical units operate on basic fundamental principles of physics and involve the passage of electrical current through tissue to create the desired tissue effect. With knowledge of the history, physics, techniques, histological effects, and safety issues of electrosurgery, the field will continue to proliferate and electrosurgery will continue to assist surgeons in alleviating human suffering.

Alopecia↗

The silent sinus syndrome: a case series and literature review.

PURPOSE: The purpose of this study is to describe the clinical and pathologic features of a form of chronic maxillary atelectasis referred to as the silent sinus syndrome, which is characterized by progressive enophthalmos secondary to maxillary collapse resulting from maxillary sinus hypoventilation. METHODS: A retrospective medical record analysis was carried out to identify patients with enophthalmos secondary to maxillary collapse. Clinical records, including ophthalmology and otolaryngology evaluations as well as computed tomography scans and operative reports, were carefully examined. A complete literature review for relevant studies was performed to examine possible pathophysiology and similar cases. RESULTS: Four patients with enophthalmos and asymptomatic maxillary sinus disease were identified. On computed tomography, all four of the patients had opacified, partially collapsed maxillary sinuses with osteopenia of the sinus walls and orbital floor displacement resulting in enophthalmos. All four underwent successful functional endoscopic sinus surgery and transconjunctival orbital floor repair. CONCLUSION: In some instances, chronic maxillary atelectasis can present with enophthalmos secondary to collapse of the maxillary sinus. For reasons that are unclear, the sinus component of the disease remains asymptomatic and is discovered only after thorough evaluation of the enophthalmos.

Adult↗

An evolution in the management of sinonasal inverting papilloma.

OBJECTIVE: We reviewed the 15-year experience of our institution (Medical College of Wisconsin, Milwaukee, WI) in managing sinonasal inverting papilloma, examining trends in diagnosis and treatment. STUDY DESIGN: Retrospective. METHODS: Thirty-seven patients with inverting papilloma were treated from 1986 to 1999. Demographic data, clinical presentations, pathological findings, surgical approaches and procedures, and recurrence rates were collected retrospectively. Each lesion was categorized into one of four groups based on computed tomography scans and endoscopic findings. This categorization was developed to compare various surgical approaches for tumors in each group. RESULTS: Thirty-one patients had complete information for inclusion in our study. Nineteen patients were treated endoscopically with an average follow-up of 50 months. Eight patients were in group I, five were in group II, six were in group III, and no patients were in group IV. The recurrence rate for the endoscopic group was 10%. Twelve patients underwent lateral rhinotomy or sublabial degloving approach with an average follow-up of 58 months. Five patients were in group I, three patients were in group II, 1 patient was in group III, and three patients were in group IV. The recurrence rate for the external group was 8%. Difference in recurrence rates (P =.85) was not observed between the endoscopic and external approach groups. Regardless of approach, patients who had primary resection had a recurrence of 0%, whereas those with secondary resection had a recurrence of 17% (P =.10). CONCLUSIONS: Technological advancements have led to a trend of detecting sinonasal inverting papilloma before extension beyond the sinonasal region. Difference in recurrence rates was not observed between the endoscopic and the external approach groups. Recurrence rates are lower for primary resection versus secondary resection, regardless of surgical approach.

Adult↗

Leptin administration improves skeletal muscle insulin responsiveness in diet-induced insulin-resistant rats.

In addition to suppressing appetite, leptin may also modulate insulin secretion and action. Leptin was administered here to insulin-resistant rats to determine its effects on secretagogue-stimulated insulin release, whole body glucose disposal, and insulin-stimulated skeletal muscle glucose uptake and transport. Male Wistar rats were fed either a normal (Con) or a high-fat (HF) diet for 3 or 6 mo. HF rats were then treated with either vehicle (HF), leptin (HF-Lep, 10 mg. kg(-1). day(-1) sc), or food restriction (HF-FR) for 12-15 days. Glucose tolerance and skeletal muscle glucose uptake and transport were significantly impaired in HF compared with Con. Whole body glucose tolerance and rates of insulin-stimulated skeletal muscle glucose uptake and transport in HF-Lep were similar to those of Con and greater than those of HF and HF-FR. The insulin secretory response to either glucose or tolbutamide (a pancreatic beta-cell secretagogue) was not significantly diminished in HF-Lep. Total and plasma membrane skeletal muscle GLUT-4 protein concentrations were similar in Con and HF-Lep and greater than those in HF and HF-FR. The findings suggest that chronic leptin administration reversed a high-fat diet-induced insulin-resistant state, without compromising insulin secretion.

3-O-Methylglucose↗

Five-year clinical course associated with DSM-IV alcohol abuse or dependence in a large group of men and women.

OBJECTIVE: The prognostic validity of the DSM-IV diagnoses of alcohol abuse and alcohol dependence was evaluated by examining the 5-year clinical course associated with those diagnoses in a large group of predominantly blue-collar men and women. METHOD: Personal semistructured interviews were carried out 5 years after an initial evaluation with 1,346 (75%) of the approximately 1,800 men and women participating in the Collaborative Study on the Genetics of Alcoholism who were eligible for follow-up. RESULTS: About two-thirds of the 298 subjects with DSM-IV alcohol dependence at baseline maintained that diagnosis during the 5-year study period. Fifty-five percent of the 288 subjects with DSM-IV alcohol abuse at baseline continued to meet one or more of the 11 DSM-IV abuse/dependence criteria, and 3.5% went on to meet the criteria for dependence at follow-up. Among the 760 subjects with no alcohol diagnosis at baseline, 2.5% met the criteria for alcohol dependence and 12.8% for alcohol abuse at follow-up. Baseline characteristics that predicted the occurrence of any of the 11 DSM-IV abuse/dependence criteria during the 5-year interval included male gender, lack of marital stability, presence of several of the criteria for dependence, and history of illicit drug use. CONCLUSIONS: The data suggest that over 5 years the DSM-IV diagnosis of alcohol dependence predicts a chronic disorder with a relatively severe course, while DSM-IV alcohol abuse predicts a less persistent, milder disorder that does not usually progress to dependence.

Adult↗

Correlates of unpredicted outcomes in sons of alcoholics and controls.

OBJECTIVE: Several risk factors for alcohol abuse and dependence have been identified, including a family history of the disorder and a low response to alcohol. However, not everyone with these attributes develops an alcohol use disorder and some alcoholics have neither characteristic. This article evaluates factors that might have contributed to unexpected outcomes, in a prospective study of sons of alcoholics and controls. METHOD: 411 men with complete data at baseline (Time 1 or T1) and at 15-year (Time 15 or T15) follow-ups were studied using the level of response (LR) to alcohol, the family history (FH) of alcoholism, and additional alcohol and drug-related experiences at T1. T15 data included the development of alcohol abuse or dependence, along with the 15-year functioning in six domains for the subject, as well as the characteristics of his spouse. The men were divided into groups based on the presence of two major risk factors, low LR and FH, after controlling for several other characteristics, including antisocial personality disorder. RESULTS: Rates of alcohol use disorders increased across Group 1 (family history negative [FHN] and no low LR), Group 2 (either family history positive [FHP] or low LR, but not both) and Group 3 (both FHP and low LR). After controlling for FH and LR for Group 1, only T1 drinking quantity and T15 positive alcohol expectancies related to a diagnosis, but explained only 12% of the variance. The results improved to R2's of 0.26 and 0.36 for Groups 2 and 3, with additional predictors including the T1 history of alcohol problems and T15 measures of poor coping mechanisms, higher drinking in the environment and less nurturance in the social support system. CONCLUSIONS: Procedures aimed at discouraging earlier heavier drinking, altering attitudes toward alcohol early in life, teaching appropriate coping methods and developing support systems might help individuals carrying multiple risk factors to become more resilient.

Adaptation, Psychological↗

A preliminary evaluation of the potential usefulness of the diagnoses of polysubstance dependence.

OBJECTIVE: The concept of polysubstance dependence (PD) has been defined several ways over the years. However, few clinicians and researchers appear to use this label in a manner consistent with any of the major diagnostic manuals. This article evaluates the prevalence and characteristics associated with PD in participants in a large collaborative study. METHOD: In DSM-IV, PD characterizes people who do not meet criteria for dependence on any one substance but, when all drugs of abuse are considered have experienced three or more of the seven dependence items across the substances. In this study, structured face-to-face interviews were administered to 8,834 men and women as part of the Collaborative Study on the Genetics of Alcoholism. The 198 subjects (2.2%) with a slightly expanded concept of the DSM-IV disorder were compared with men and women with dependence on alcohol, marijuana or stimulants, subjects with substance abuse and those with no substance use disorder. RESULTS: In this dataset, compared with subjects with a specific substance dependence, those with PD were slightly more educated and less likely to be divorced or separated, and they had fewer substance-related problems. At the same time, those with PD had more substance problems than did subjects who only met criteria for abuse. These basic conclusions were unchanged among the subset of 59 subjects who met the more restricted, classical DSM-IV PD criteria. CONCLUSIONS: The data indicate that, while relatively rare, subjects with PD might differ in potentially important ways from those with dependence or abuse on specific drugs. A large prospective study of a group with carefully defined PD is needed.

Adult↗