Biomedical subjects

T L Smith

Publications and source records attributed to T L Smith.

At least 73 records · Page 4Linked to original sources

PubMed2000

Autonomic nervous system evaluation of patients with vasomotor rhinitis.

OBJECTIVE: To demonstrate the utility of quantitative neurological laboratory testing of autonomic nervous system dysfunction and to apply this methodology to further study the relation of chronic vasomotor (nonallergic) rhinitis to the autonomic nervous system. METHODS: It has been suspected that vasomotor rhinitis is due either to a hyperactive parasympathetic nervous system or an imbalance between it and the sympathetic nervous system. The exact relation has not been determined. Recently neurological laboratories have been developed in which a battery of tests can be performed to determine reactivity of the autonomic nervous system. RESULTS: Autonomic nervous system testing was performed on 19 patients with symptoms fulfilling the diagnostic criteria for vasomotor rhinitis and the results were compared with 75 sex- and age-matched control subjects. Patients with vasomotor rhinitis had significant abnormalities of their sudomotor, cardiovagal, and adrenergic subscores. Their composite autonomic scale score was significantly impaired at 2.43, as compared with 0.11 for controls (P < .005). CONCLUSION: Autonomic nervous system dysfunction is significant in patients with vasomotor rhinitis. Possible factors that trigger this dysfunction including nasal trauma and extraesophageal manifestations of gastroesophageal reflux are discussed.

Adult↗

PubMed2000

Use of computer-aided surgery for frontal sinus ventilation.

OBJECTIVES: To review our experience and evaluate the utility of computer-aided surgery for frontal sinus and frontal recess disease. STUDY DESIGN: A retrospective review of 31 consecutive patients undergoing computer-aided surgery for frontal sinus ventilation. METHODS: The hospital charts of 31 patients were reviewed. Previous sinonasal procedures, etiology of sinonasal disease, preoperative computed tomography (CT) scan findings, preoperative symptoms, endoscopic and intraoperative findings, type of frontal sinus ventilation procedure, complications, imaging system registration method or accuracy, and postoperative course were noted. RESULTS: In all 31 patients the surgery was successfully completed, and no intracranial or orbital complications were encountered during or after surgery. Six patients required additional surgery including revision transnasal endoscopic frontal sinus ventilation or osteoplastic flaps with fat obliteration. In the six cases requiring additional surgery, disease severity, most commonly, aspirin triad disease, predisposed to failure of frontal sinus ventilation. CONCLUSIONS: Computer-aided surgery is a useful adjunctive device for safe, efficient identification and surgery of the frontal sinus. However, it is not a replacement for sound surgical technique, anatomical knowledge, and experience. In particular, patients with aspirin triad disease with frontal recess and frontal sinus involvement are highly suited for computer-aided surgery and thorough removal of disease, although failures occur despite this technique. The long-term benefit of computer-aided surgery of the frontal sinus has not yet been demonstrated by this or other studies.

Adolescent↗

PubMed2000

Behavioral symptoms and psychiatric diagnoses among 162 children in nonalcoholic or alcoholic families.

OBJECTIVE: People with alcoholic relatives have high rates of alcohol abuse and dependence as adults, but their patterns of problems earlier in life are less clear. Many studies have not controlled for parental disorders other than alcoholism or for parents' socioeconomic status and general life functioning. The authors' goal was to conduct a study controlling for such factors. METHOD: Personal structured interviews and a behavioral checklist were administered to the parents of 162 children 7 years old or older whose fathers had participated in the 15-year follow-up of 453 sons of alcoholics with no history of antisocial personality disorder and sons of nonalcoholic comparison subjects originally selected from a university population. RESULTS: There was no significant relationship between a family history of alcoholism and childhood diagnoses of conduct, oppositional, or attention deficit disorders or with behavioral checklist summary scores. However, children with alcoholic relatives apparently have a slightly higher risk for drug abuse or dependence than those without alcoholic relatives. CONCLUSIONS: Once familial antisocial disorders and familial socioeconomic status are controlled for, a family history of alcoholism does not appear to relate to childhood externalizing disorders.

Adolescent↗

PubMed2000

The 5-year clinical course of high-functioning men with DSM-IV alcohol abuse or dependence.

OBJECTIVE: One goal of diagnostic criteria is to predict the course of clinically relevant future problems. This study evaluated the ability of the DSM-IV categories of alcohol abuse and alcohol dependence to predict the onset and cessation of the 11 DSM-IV abuse/dependence criterion items. METHOD: The DSM-IV categorical approach was used to determine alcohol diagnoses for 435 highly educated young adult men, who constituted 97.3% of the 447 men appropriate for this study. Structured face-to-face follow-up interviews were administered 5 years later. RESULTS: At the beginning of the study, 14.5% (N=63) of the subjects were alcohol dependent, 18.2% (N=79) reported alcohol abuse, and 67.4% (N=293) carried no alcohol diagnosis. Across these three diagnostic groups, 68.3%, 46.8%, and 15.4%, respectively, experienced at least one of the 11 DSM-IV abuse/dependence criterion items over the next 5 years. Only 11.4% of those who reported alcohol abuse went on to develop alcohol dependence. In addition to their diagnosis, characteristics that predicted subsequent problems with alcohol included a family history of alcoholism, higher levels of alcohol intake and a greater number of alcohol problems in the 10 years preceding the diagnosis, and a history of drug use. CONCLUSIONS: Even in this highly educated and high-functioning group of men, alcohol abuse and dependence predicted the onset and cessation of alcohol-related problems.

Adult↗

PubMed2000

Outcomes assessment following treatment of spasmodic dysphonia with botulinum toxin.

Spasmodic dysphonia (SD), a disabling focal dystonia involving the laryngeal musculature, is most commonly treated by the intramuscular injection of botulinum toxin (BTX). Although the treatment is well tolerated and generally produces clinical voice improvement, it has never been statistically shown to alter the patient's perception of voice quality or general health. Declining resources for medical care mandate that treatment outcomes be documented. A prospective analysis of the effects of BTX on the patient's perception of voice and general health was undertaken. The Voice Handicap Index (VHI) and Short Form 36 (SF-36) surveys were administered to patients before treatment and 1 month after. Pretreatment and posttreatment scores were analyzed with a Student's t-test. On the VHI, improvements in the patients' perception of their functional, physical, and emotional voice handicap reached statistical significance (p < or = .0005). On the SF-36, patients had statistically significant improvements in mental health (p < or = .03) and social functioning (p < or = .04). Treatment of SD with BTX significantly lessened the patients' perception of dysphonia. In addition, it improved their social functioning and their perception of their mental health. These outcome measures justify the continued treatment of SD with BTX.

Adult↗

PubMed2000

Results of treatment with hyper-CVAD, a dose-intensive regimen, in adult acute lymphocytic leukemia.

PURPOSE: To evaluate the efficacy and toxicity of Hyper-CVAD (fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone), a dose-intensive regimen, in adult acute lymphocytic leukemia (ALL). PATIENTS AND METHODS: Adults with newly diagnosed ALL referred since 1992 were entered onto the study; treatment was initiated in 204 patients between 1992 and January 1998. No exclusions were made because of older age, poor performance status, organ dysfunction, or active infection. Median age was 39.5 years; 37% were at least 50 years old. Mature B-cell disease (Burkitt type) was present in 9%, T-cell disease in 17%. Leukocytosis of more than 30 x 10(9)/L was found in 26%, Philadelphia chromosome-positive disease in 16% (20% of patients with assessable metaphases), CNS leukemia at the time of diagnosis in 7%, and a mediastinal mass in 7%. Treatment consisted of four cycles of Hyper-CVAD alternating with four cycles of high-dose methotrexate (MTX) and cytarabine therapy, together with intrathecal CNS prophylaxis and supportive care with antibiotic prophylaxis and granulocyte colony-stimulating factor therapy. Maintenance in patients with nonmature B-cell ALL included 2 years of treatment with mercaptopurine, MTX, vincristine, and prednisone (POMP). RESULTS: Overall, 185 patients (91%) achieved complete remission (CR) and 12 (6%) died during induction therapy. Estimated 5-year survival and 5-year CR rates were 39% and 38%, respectively. The incidence of CNS relapse was low (4%). Compared with 222 patients treated with vincristine, doxorubicin, and dexamethasone (VAD) regimens, our patients had a better CR rate (91% v 75%, P <.01) and CR rate after one course (74% v 55%, P <.01) and better survival (P <.01), and a smaller percentage had more than 5% day 14 blasts (34% v 48%, P =.01). Previous prognostic models remained predictive for outcome with Hyper-CVAD therapy. CONCLUSION: Hyper-CVAD therapy is superior to our previous regimens and should be compared with established regimens in adult ALL.

Adolescent↗

PubMed2000

Hangover symptoms in Asian Americans with variations in the aldehyde dehydrogenase (ALDH2) gene.

OBJECTIVE: Hangovers are not experienced by all people and whether they contribute to the development of alcoholism is unclear. One population that might provide some insight into the role of hangover in the etiology of alcohol use disorders is that of individuals of Asian heritage. Certain Asians have lower rates of alcohol use and alcoholism, findings associated with a mutation in the aldehyde dehydrogenase (ALDH2) gene. Asians with ALDH2*2 alleles drink less and are less likely to be alcoholic than Asians without this mutation. Following alcohol ingestion, they exhibit more intense reactions to alcohol and generate higher levels of the metabolite acetaldehyde. This study evaluated hangover symptoms in Asian Americans with variations in the ALDH2 gene. METHOD: Men and women of Chinese, Japanese and Korean heritage (N = 140) were asked about their drinking history and a blood sample was collected for genotyping at the ALDH2 locus. Subjects used a Likert-type scale to estimate their severity of hangover and completed a 13-item hangover scale assessing the frequency of hangover symptoms during the previous 6 months. RESULTS: With abstainers (n = 17) excluded and with the effects of gender and recent drinking history controlled, ALDH2 genotype accounted for a significant amount of additional variability in the estimated severity of hangover score with a similar, but nonsignificant, trend for a five-item subscale score derived from the hangover scale. CONCLUSIONS: These results suggest that Asian Americans with ALDH2*2 alleles may experience more severe hangovers that may contribute, in part, to protection against the development of excessive or problematic drinking in this population.

Adult↗

PubMed2000

Clinical characteristics and family histories of alcoholics with stimulant dependence.

OBJECTIVE: While much is known about the clinical patterns and family histories of individuals with alcoholism or stimulant (cocaine and amphetamine) dependence, there are few data that describe men and women with concomitant alcohol and stimulant dependence. METHOD: As part of the Collaborative Study on the Genetics of Alcoholism, structured interviews were administered to 3,882 (2,432 male) DSM-III-R defined alcohol and/or stimulant dependent subjects. The characteristics and family histories of four groups were compared: Group 1 (26%), with the onset of alcohol before stimulant dependence; Group 2 (10%), with alcohol dependence simultaneously with or after stimulant dependence; Group 3 (58%), with alcohol dependence only; Group 4 (6%), with stimulant dependence only. RESULTS: Individuals with concomitant alcohol and stimulant dependence (Groups 1 and 2) reported more general life problems (e.g., marital instability), a higher rate of antisocial personality disorder and more substance-induced mood disorders, additional drug dependencies and substance-related difficulties than those with dependence on one substance only. People with alcohol dependence before stimulant dependence had the most severe clinical patterns. In addition, alcohol dependence and stimulant dependence were found to breed true in families of subjects with these concomitant disorders. The major findings were confirmed with logistic regression analyses, and were independent of ASPD and gender. CONCLUSIONS: It is important for clinicians to be aware of the severe clinical characteristics of patients with concomitant alcohol and stimulant dependence. In addition, the data consistent with drug-specific heritability in this heterogeneous population may be useful to researchers.

Adult↗

PubMed2000

The relationships of a family history of alcohol dependence, a low level of response to alcohol and six domains of life functioning to the development of alcohol use disorders.

OBJECTIVE: Numerous biological and sociocultural factors have been proposed as potentially important to the risk for alcohol use disorders. This study evaluates the relationships to alcohol abuse or dependence of several additional potential trait and state characteristics when studied in the context of a family history of alcohol dependence (FH) and the level of response (LR) to alcohol. METHOD: Data were generated from the successful 15-year follow-up of 97% of 453 sons of alcohol dependent men and controls; of these, 315 men were appropriate for the current analyses. Personal interviews were used to gather data from the subjects and additional informants to study the relationships among FH, LR as determined 15 years previously, and retrospective ratings over the recent 15 years for six additional domains of life functioning. These were evaluated as correlates of a diagnosis of an alcohol use disorder in both a 3-step hierarchical and a 7-step structured series of regressions for the subjects with complete data. RESULTS: LR, FH and measures from all of the domains except stress had significant zero-order correlations with alcohol abuse or dependence. The hierarchical regression revealed that LR and FH remained significant when considered in the context of the five remaining domains. Both trait-like characteristics (behavioral undercontrol, alcohol expectancies and ways of coping) and state-like domains (nurturance in the social support system and the amount of drinking in the environment) added significantly to the analyses. A heuristic model of the relationship among these variables was tested in a structured series of regressions with a final R2 of 0.22. Future prospective study of the offspring of these subjects will help evaluate potential causal implications of these findings. CONCLUSIONS: Prospective studies, measuring both biological and environmental factors, are needed for optimal understanding of the performance of such characteristics in real-life conditions.

Adaptation, Psychological↗

PubMed2000

Prediction of prognosis following fludarabine used as secondary therapy for chronic lymphocytic leukemia.

A prognostic factor analysis for survival and response was conducted on 374 previously treated patients who were treated with one of four fludarabine regimens. As several prognostic factors were associated with response and survival, multivariate analyses were conducted to identify the combination of factors which best describe the prognosis as regards response to fludarabine and survival. Statistical models to identify the hazard for survival and probability of response were developed. The characteristics which were included in the model predicting for survival were sex, age, number of prior treatments, performance status, hemoglobin level, serum albumin, and alkaline phosphatase levels. The characteristics most strongly associated with response were the hemoglobin levels, serum albumin, and the number of prior treatments. These models can be used to identify risk groups to guide physicians in decision-making and to assist in the design and analysis of clinical trials.

Adult↗

PubMed2000

Terminal deoxynucleotidyl transferase expression in acute myelogenous leukemia and myelodysplasia as determined by flow cytometry.

The significance of terminal deoxynucleotidyl transferase (TdT) expression in acute myelogenous leukemia (AML) remains controversial. Therefore, we studied TdT expression by flow cytometry in 120 previously untreated patients with AML or myelodysplastic syndrome (MDS) to determine the distribution of TdT-positive blasts and the intensity of TdT expression and to seek clinically significant associations. TdT expression measured by flow cytometry (flow TdT%) was heterogeneous, ranging from 0.1% to 87% (median, 8.5%), and 74 patients (62%) had at least 5% TdT-positive blasts. TdT positivity was associated with the M0 or M1 subtype and with expression of CD34 and CD7. No significant correlation was found between TdT expression and type of cytogenetic abnormality or rearrangement of immunoglobulin or T-cell receptor genes. Remission lasted longer in patients with a flow TdT% < 5 than in patients with a flow TdT% > 5 (median, 95 weeks vs 55 weeks, p = 0.02); however, complete remission rates did not differ when patients were classified by initial flow TdT%. Survival was slightly better for patients with flow TdT% less than 5%. Among patients with a flow TdT% > 5%, those with a higher TdT intensity survived longer than those with a lower intensity. These data suggest that quantitative TdT measurement may contribute to prognostic estimate in AML patients.

Adult↗

PubMed2000

Serum beta-2 microglobulin levels are a significant prognostic factor in Philadelphia chromosome-positive chronic myelogenous leukemia.

Our objective was to investigate the prognostic significance of serum beta-2 microglobulin (B2M) levels among patients with chronic myelogenous leukemia (CML). All patients with Philadelphia chromosome-positive early chronic phase CML (i.e., within 1 year of diagnosis) treated with IFN alpha-based therapy at the M. D. Anderson Cancer Center between 1980 and 1997, in whom pretreatment B2M levels were available, were investigated. Two hundred one patients were evaluable. Their median B2M was 2.2 mg/dl (range, 1.1-20 mg/dl). Serum B2M levels were associated with other variables of prognostic significance, including age, spleen size, WBC count, percentage of peripheral and marrow blasts, and percentage of marrow basophils. Patients with B2M levels >2.9 mg/dl (ie., the upper quartile of the distribution) had a significantly lower rate of major cytogenetic response compared to those in the lower three quartiles (20 versus 52%; P < 0.01). They also had a shorter survival, with a 5-year survival rate of 48%, compared with 75% for those in the lower quartiles (P = 0.01). High B2M levels (>2.9 mg/dl) could identify a group of patients with an adverse outcome within patients in stage I disease (P = 0.02). Results for patients in stages 2-4 were inconclusive because of the small number of patients in these groups. We conclude that serum B2M levels are an important, and probably independent, prognostic factor for patients with CML in early chronic phase treated with IFN-based therapy.

Aged↗

PubMed2000

The topoisomerase I inhibitor DX-8951f is active in a severe combined immunodeficient mouse model of human acute myelogenous leukemia.

The severe combined immunodeficient (SCID) mouse model of human acute myelogenous leukemia (AML) is a unique system for preclinical in vivo evaluation of the activity and toxicity of new agents. The topoisomerase I (topo I) inhibitor topotecan is active in patients with AML and myelodysplastic syndromes. DX-8951f is a novel topo I inhibitor with more potent antitumor effects than topotecan or CPT-11 in vitro. To study the in vivo activity of DX-8951f, 6-week-old female SCID mice received injections into the tail vein with 2 x 10(7) exponentially growing KBM-3 cells. In each experiment, three to five sets of five mice were treated with DX-8951f doses ranging from 7.5 to 80 mg/kg and at schedules of 1, 3, and 5 days; a control set of five mice was treated with the drug vehicle alone. One group received DX-8951f on day 7 of the inoculation with KBM-3 (early-treatment group). To study the activity of DX-8951f in advanced disease, a second group was treated 1 month after the inoculation, when the animals were developing symptoms (late-treatment group). The study end point was the duration of survival until death from leukemia, which was assessed clinically and by the presence of the human DQ alpha gene in tissue samples by PCR. Six experiments were conducted with 170 animals. Survival was higher in both the early- and late-treatment groups than in untreated controls, and the treated groups had significantly less central nervous system disease. Significantly improved survival was observed in animals treated early with 60 and 80 mg/kg as a single injection, with 15 and 20 mg/kg over 3 days, and with 7.5 and 10 mg/kg over 5 days. In the late-disease model (treatment starting on days 28-35), improved survival was observed with a single dose of 80 or 20 mg/kg over 5 days. Dose escalation was limited by dilution problems at the 1-day schedule and by toxicity (mainly gastrointestinal) of the prolonged schedules. Both efficacy and toxicity were dose schedule dependent, increasing with higher doses and prolonged exposure. By establishing the antileukemic activity of DX-8951f against human AML transplanted into SCID mice at doses below the LD10, our data provide a rationale for clinical evaluation of the drug in patients with AML and favor the use of prolonged administration.

Animals↗

PubMed1999

Primary refractory and relapsed adult acute lymphoblastic leukemia: characteristics, treatment results, and prognosis with salvage therapy.

BACKGROUND: Relapses continue to be problematic for adults with acute lymphoblastic leukemia (ALL). New therapies generally are first tested in the salvage setting prior to incorporation into frontline regimens. Defining the prognosis at relapse (or at failure of induction) and subsequently predicting outcome would be useful to select the population in whom to test new strategies, rather than attempting traditional reinduction therapy. METHODS: Between March 1980 and March 1997, 314 eligible adults with primary refractory (24%) or primary relapsed (76%) ALL were treated with various chemotherapy or stem cell transplantation (SCT) regimens. The Cox proportional hazards model was used to assess biologic factors and disease history in relation to survival. RESULTS: A complete remission (CR) was achieved in 97 patients (31%), 21% died prior to a response, and 49% were refractory to salvage therapy. Of the 76 patients refractory to induction therapy for their de novo ALL, 26 patients (34%) achieved a CR with salvage therapy. The median overall CR duration was 6 months. The median overall survival was 5 months; 24% of the patients were alive at 1 year, and the projected survival at 5 years was 3%. Nineteen patients were alive at the time of last follow-up, 10 with 6 weeks to 10 years of continuous CR from the time of their first salvage therapy. SCT consolidation in second CR was performed in 25% of patients; 28% of those who received allogeneic SCT remain in continuous CR at 4 months, 2(1/2) years, 3(1/2) years, and 10 years, whereas all 8 who received autologous SCT have relapsed. Favorable factors for longer survival by multivariate analysis were age <40 years, absence of circulating blasts, and first CR duration longer than 1 year. Patients were stratified into 4 risk groups: Group 1, with no unfavorable features or only short initial CR duration; Group 2, with only increased age or peripheral blasts; Group 3, with any 2 unfavorable features; and Group 4, with all 3 unfavorable features. The median survival times for each group were 11, 6, 4, and 2 months, respectively; 1-year survival rates were 44%, 25%, 12%, and 9%, respectively (P < 0.01). The resulting model was also predictive for CR rates; the corresponding CR rates were 47%, 35%, 14%, and 9%, respectively (P < 0.01). CONCLUSIONS: Salvage therapy for adult ALL patients continues to yield poor results, but it is an area of research where it may be possible to discover new agents or strategies to be incorporated into frontline therapy. The prognostic model derived will be utilized prospectively to select patients for new therapeutic strategies involving such novel agents as liposomal compounds, purine nucleoside phosphorylase inhibitors, and monoclonal antibodies.

Adolescent↗

PubMed1999

Risk factors for acute graft-versus-host disease after allogeneic blood stem cell transplantation.

We evaluated demographic characteristics and graft composition as risk factors for acute graft-versus-host disease (GVHD) in 160 adult recipients of HLA-identical allogeneic blood stem cell transplants. The patients received a median nucleated cell dose of 7.9 x 10(8)/kg and median C34(+) cell dose of 5.6 x 10(6)/kg. GVHD prophylaxis consisted of cyclosporine (CSA) and steroids, tacrolimus (FK506) and steroids, or FK506 and methotrexate. Grades 2 to 4 GVHD occurred in 31% (95% CI, 23% to 39%), and grades 3 to 4 GVHD in 14% (95% CI, 8% to 20%). In univariate analyses, GVHD prophylaxis with CSA and high CD34(+) cell doses were significant risk factors for grades 2 to 4 GVHD, but diagnosis, age, use of total body irradiation, donor sex, female donor for male recipient, donor parity, donor alloimmunization, viral serology, nucleated cell dose, CD3(+) cell dose, and CD56(+) cell dose did not alter the incidence of GVHD significantly. With a CD34(+) cell dose less than 8 x 10(6) CD34(+) cells/kg, the risk of grades 2 to 4 GVHD was significantly higher for those who received CSA (39%, 95% CI, 21% to 47%) in comparison with those on FK506 (18%, 95% CI, 10% to 26%) (P =.03), but GVHD prophylaxis regimen had less impact with a higher CD34(+) cell dose (overall grades 2 to 4 GVHD rate 52%, 95% CI, 37% to 67%). GVHD prophylaxis and CD34(+) cell dose are independent risk factors for acute GVHD after allogeneic blood stem cell transplantation.

Adolescent↗

PubMed1999

Increased calcium/calmodulin protein kinase activity in astrocytes chronically exposed to ethanol: influences on glutamate transport.

The effects of ethanol exposures on calcium/calmodulin-dependent protein kinase activity as well as its influence on glutamate uptake were determined in astrocytes prepared from neonatal rat cerebral cortex. Acute 15-min exposure to 100 mM ethanol had no effect on Ca2+/CaM-dependent protein kinase activity. However, chronic exposure to 100 mM ethanol for 4 days elicited a significant increase in the activity of this enzyme with no parallel increase in its expression. Ca2+/CaM-independent kinase activity was less than 1% of the Ca2+/CaM-dependent kinase activity and was unaffected by any of the ethanol exposures. Exposure to 100 mM ethanol for four days also resulted in a significant increase in Na+-dependent [3H]glutamate uptake which was reversed when ethanol-exposed astrocytes were co-incubated with KN-93, a specific inhibitor of Ca2+/CaM kinase. These results suggest that the effects of ethanol on glutamate transport may be mediated in part, by the level of Ca2+/CaM kinase activity.

Amino Acid Transport System X-AG↗

PubMed1999

Selective genotyping for the role of 5-HT2A, 5-HT2C, and GABA alpha 6 receptors and the serotonin transporter in the level of response to alcohol: a pilot study.

BACKGROUND: The vulnerability to alcohol dependence appears to be genetically influenced through a variety of mechanisms. One potentially genetically mediated channel may be a low level of response (LR) to alcohol, which has been seen in children of alcoholics and noted to predict future alcohol abuse and dependence. This pilot study uses a case and control genetic association approach to evaluate the possible role of five genotypes in both LR and alcoholism in informative subgroups of men with high and low LR scores documented 15 years earlier. METHODS: As part of a larger study, 41 men, about 39 years old, were selected from among the first 113, completed 15-year follow-ups in a prospective study. The 17 subjects whose LRs at age 20 were in the lower third were compared on five polymorphisms of four genes with 24 men whose reactions to alcohol had been above the median. RESULTS: The 14 men with the LL genotype of the serotonin transporter (5-HTT) polymorphism and the seven with the Pro/Ser genotype of the GABAA alpha 6 polymorphism had demonstrated lower LR scores at about age 20, and had significantly higher proportions of alcoholics than the other genotypes for those loci. All four subjects with combined LL and Pro/Ser genotypes had developed alcoholism and demonstrated the lowest LR scores overall. There was no evidence that two polymorphisms of the 5-HT2A receptor gene and one of the 5-HT2C receptor gene were related to LR or alcoholism in this sample. CONCLUSIONS: These results are consistent with animal and human studies suggesting a possible role for genetic variation in the GABAA alpha 6 and the serotonin transporter in the reaction to alcohol and the alcoholism risk.

Adult↗

PubMed1999

HIV type 1 V3 domain serotyping and genotyping in Gauteng, Mpumalanga, KwaZulu-Natal, and Western Cape Provinces of South Africa.

More than 20.8 million people are living with HIV/AIDS in sub-Saharan Africa, with southern Africa the worst affected area and accounting for one of the fastest growing AIDS epidemics worldwide. Samples from 81 patients, including 25 from KwaZulu-Natal, 26 from Gauteng, 5 from Mpumalanga, and 25 from Western Cape Province, were serotyped using a competitive V3 peptide enzyme immunoassay (cPEIA). Viral RNA was also isolated from serum and the V3 region amplified by reverse transcriptase polymerase chain reaction (RT-PCR) to obtain a 240-bp product for direct sequencing of 29 samples. CLUSTAL W was used to make multiple sequence alignments. Distance calculation, tree construction methods, and bootstrap analysis were done using TREECON. Subtype C-like V3 loop sequences predominate in all provinces tested in South Africa. Discordant sero- and genotype results were observed in one patient only. The correlation between sero- and genotyping was 96% (24 of 25) in KwaZulu-Natal and 100% in Gauteng and Mpumalanga. In Western Cape Province 18% of patients were identified as sero/genotype B and 82% as sero/genotype C. Our data show that results of the second-generation V3 cPEIA correlated well with V3 sequencing and would be a rapid and affordable screening test to monitor the explosive southern African HIV-1 epidemic.

Adolescent↗