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H Klein

Publications and source records attributed to H Klein.

At least 37 records · Page 2Linked to original sources

Requirement for the SRS2 DNA helicase gene in non-homologous end joining in yeast.

Mitotic cells experience double-strand breaks (DSBs) from both exogenous and endogenous sources. Since unrepaired DSBs can result in genome rearrangements or cell death, cells mobilize multiple pathways to repair the DNA damage. In the yeast Saccharomyces cerevisiae, mitotic cells preferentially use a homologous recombination repair pathway. However, when no significant homology to the DSB ends is available, cells utilize a repair process called non-homologous end joining (NHEJ), which can join ends with no homology through resection to uncover microhomologies of a few nucleotides. Although components of the homologous recombination repair system are also involved in NHEJ, the rejoining does not involve all of the homologous recombination repair genes. The SRS2 DNA helicase has been shown to be required for DSB repair when the homologous single-stranded regions are short. Here it is shown that SRS2 is also required for NHEJ, regardless of the cell mating type. Efficient NHEJ of sticky ends requires the Ku70 and Ku80 proteins and the silencing genes SIR2, SIR3 and SIR4. However, NHEJ of blunt ends, while very inefficient, is not further reduced by mutations in YKU70, SIR2, SIR3, SIR4 or SRS2, suggesting that this rejoining process occurs by a different mechanism.

Adenosine Triphosphatases↗

Frequency and intensity of crack use as predictors of women's involvement in HIV-related sexual risk behaviors.

Recent trends in the progression of the AIDS epidemic in the United States indicate that women's rates of acquiring HIV are escalating more rapidly than are men's. Consequently, there has been both an increasing interest in and a need for research targeting substance-abusing women's involvement in HIV risk behaviors. In recent years, strong suggestive evidence has arisen to suggest that women who use crack cocaine are at an elevated risk for acquiring HIV, probably as a result of their involvement in high-risk sexual behaviors. The present study is based on a sample of 1723 women from 22 locales around the United States who used crack cocaine at least once during the previous 30 days but who reported never having injected drugs at any point in their lifetime. Women were divided into four groups based on their frequency and intensity of using crack. In subsequent analyses, this grouping was used to predict the extent to which female crack users engage in five sexual risk behavior measures (number of sexual partners, number of drug-injecting sexual partners, number of times having sexual relations while high on alcohol and/or other drugs, number of times trading sex for drugs and/or money, and proportion of all sexual acts involving the use of protection). The data revealed that the women who used crack with the greatest frequency and the greatest intensity were the most heavily involved in risky sexual behaviors. They differed quite sharply from their lower-intensity and/or lower-frequency crack-using counterparts in terms of their HIV risk behavior involvement and in terms of their actual HIV seroprevalence rates.

Acquired Immunodeficiency Syndrome↗

Arrhythmias in Heart Failure.

Cardiac arrhythmias are very common in the setting of heart failure, with atrial and ventricular arrhythmias often present in the same patient. The risk and the benefit of antiarrhythmic therapies are still a matter of debate. Class I antiarrhythmic drugs should be avoided in patients with heart failure, cardiac ischemia, or previous myocardial infarction. Beta-blocker agents reduce morbidity and decrease mortality in patients suffering from moderate to severe heart failure. Amiodarone may be beneficial in patients with advanced heart failure and increased resting heart rates. This class III drug may be effective to suppress episodes of atrial fibrillation but can also be beneficial in reducing ventricular response by slowing atrioventricular conduction during chronic atrial fibrillation. Implantable cardioverter-defibrillators (ICDs) markedly reduce sudden cardiac death in patients with ventricular tachycardia or ventricular fibrillation. In patients with advanced heart failure, however, the ICD may not markedly extend survival. Recently analyzed data from the Canadian Implantable Defibrillator Study (CIDS), Antiarrhythmics Versus Implantable Defibrillators (AVID) registry, Multicenter Unsustained Tachycardia Trial (MUSTT), and Multicenter Automatic Defibrillator Implantation Trial (MADIT) have consistently shown that it is the sickest patient who benefits the most from ICD therapy. Patients with markedly depressed ejection fraction (<30%), poor New York Heart Association functional class, and advanced age have been identified as those who really need ICD therapy. Studies of implantable cardioverter-defibrillators in patients with moderate to severe heart failure have been launched and will provide necessary answers to the question of whether a reduction in sudden death will translate into a reduction of all-cause mortality. For patients resuscitated from sustained ventricular tachycardia or ventricular fibrillation, an ICD or, in some cases, amiodarone should be considered. Catheter or surgical ablation can be considered for selected patients with ventricular tachycardia.

Journal Article↗

Age-related differences in the expression of receptors for TGF-beta in human osteoblast-like cells in vitro.

The cell surface expression of receptors for TGF-beta was studied in human osteoblasts derived from femoral trabecular bone of a total of 19 patients aged 2-83 years. All cell populations investigated showed a similar profile of expression of TGF-beta receptors (TbetaR) I, II and III (betaglycan). There were no significant differences in cell differentiation or proliferative behaviour between the age groups. The TGF-beta receptor number per cell significantly increased with age, while the receptor affinity tended to decrease. IGF-I did not influence TbetaR expression in vitro. The results indicate an age-dependent and IGF-I independent increase of osteoblastic TGF-beta receptors in human osteoblast-like cells in vitro.

Adolescent↗

Increased expression of P-selectin in patients with chronic atrial fibrillation.

Previous studies have shown that platelets are activated during atrial fibrillation (AF). However, prophylactic therapy with aspirin is not associated with a reduction of thromboembolic complications in patients with AF. Stimulation of platelet thrombin and ADP receptors causes a release of P-selectin, which is not affected by aspirin. The purpose of this study was to assess the influence of AF on platelet P-selectin expression. Blood samples from 30 patients were studied ex vivo. Nineteen patients had chronic AF (> 3 months), 11 patients were in sinus rhythm (SR). P-selectin expression was determined by flow cytometry (antibody binding capacity [BC]) at baseline and after platelet stimulation with adenosine diphosphate (ADP) and thrombin receptor activating peptide (TRAP). To determine the effect of heart rate and atrial pressure (RAP), measurements were repeated after 10 minutes of ventricular pacing (120 beats/min) in patients with SR. P-selectin expression was increased in patients with AF at baseline (AF: 1329 +/- 81 BC vs SR: 968 +/- 108 BC; P < 0.05) and after stimulation with ADP (AF: 1445 +/- 101 BC vs SR: 1061 +/- 109 BC; P < 0.05) and TRAP (AF: 13,783 +/- 2442 BC vs SR: 5977 +/- 800 BC; P < 0.05). RAP (2.0 +/- 0.5 vs 6.0 +/- 0.8 mmHg; P < 0.01) and atrial rate (75 +/- 5 vs 114 +/- 5 beats/min; P < 0.001) increased during ventricular pacing. However, P-selectin levels remained stable. AF was accompanied by increased P-selectin expression. In contrast, increased ventricular rate and elevated atrial pressure alone had no effect on platelet activity. Further studies are needed to determine if platelet ADP receptor inhibitors offer a therapeutic benefit in patients with AF.

Adenosine Diphosphate↗

Serine residues 1177/78/82 of the insulin receptor are required for substrate phosphorylation but not autophosphorylation.

Serine residues of the human insulin receptor (HIR) may be phosphorylated and negatively regulate the insulin signal. We studied the impact of 16 serine residues in HIR by mutation to alanine and co-overexpression in human embryonic kidney (HEK) 293 cells together with the docking proteins insulin receptor substrate (IRS)-1, IRS-2, or (SHC) Src homologous and collagen-like. As a control, IRS-1 was also cotransfected with an HIR with a juxtamembrane deletion (HIR delta JM) and therefore not containing the domain required for interaction with IRS-1. Coexpression of HIR with IRS-1, IRS-2, and SHC strongly enhanced tyrosine phosphorylation of these proteins. A similar increase in tyrosine phosphorylation was observed in cells overexpressing IRS-1, IRS-2, or SHC together with all HIR mutants except HIR delta JM and a mutant carrying exchanges of serines 1177, 1178, and 1182 to alanine (HIR1177/78/82), although this mutant showed normal autophosphorylation. Analysis of total cell lysates with anti-phosphotyrosine antibodies showed that in addition to the overexpressed substrates, other cellular proteins displayed reduced levels of tyrosine phosphorylation in these cells. To study consequences for phosphatidylinositol 3-kinase (PI 3-kinase) activation, we established stable NIH3T3 fibroblast cell lines overexpressing wild-type HIR, HIR1177/78/82, and other HIR mutants as the control. Again, HIR1177/78/82 showed normal autophosphorylation but showed a clear decrease in tyrosine phosphorylation of endogenous IRS-1 and activation of PI 3-kinase. This decrease in kinase activity also occurred in an in vitro kinase assay towards recombinant IRS-1. Finally, we performed a separation of the phosphopeptides by high-performance liquid chromatography and could not detect any differences in the profiles of HIR and HIR1177/78/82. In conclusion, we have defined a region in HIR that is important for substrate phosphorylation but not autophosphorylation. Therefore, this mutant may provide new insights into the mechanism of kinase activation and substrate phosphorylation.

3T3 Cells↗

Text-based discovery in biomedicine: the architecture of the DAD-system.

Current scientific research takes place in highly specialized contexts with poor communication between disciplines as a likely consequence. Knowledge from one discipline may be useful for the other without researchers knowing it. As scientific publications are a condensation of this knowledge, literature-based discovery tools may help the individual scientist to explore new useful domains. We report on the development of the DAD-system, a concept-based Natural Language Processing system for PubMed citations that provides the biomedical researcher such a tool. We describe the general architecture and illustrate its operation by a simulation of a well-known text-based discovery: The favorable effects of fish oil on patients suffering from Raynaud's disease [1].

Drug-Related Side Effects and Adverse Reactions↗

Yeast Rad54 promotes Rad51-dependent homologous DNA pairing via ATP hydrolysis-driven change in DNA double helix conformation.

Saccharomyces cerevisiae RAD54 gene functions in the formation of heteroduplex DNA, a key intermediate in recombination processes. Rad54 is monomeric in solution, but forms a dimer/oligomer on DNA. Rad54 dimer/oligomer alters the conformation of the DNA double helix in an ATP-dependent manner, as revealed by a change in the DNA linking number in a topoisomerase I-linked reaction. DNA conformational alteration does not occur in the presence of non-hydrolyzable ATP analogues, nor when mutant rad54 proteins defective in ATP hydrolysis replace Rad54. Accordingly, the Rad54 ATPase activity is shown to be required for biological function in vivo and for promoting Rad51-mediated homologous DNA pairing in vitro. Taken together, the results are consistent with a model in which a Rad54 dimer/oligomer promotes nascent heteroduplex joint formation via a specific interaction with Rad51 protein and an ability to transiently unwind duplex DNA.

Adenosine Triphosphatases↗

[Alpha 1-protease inhibitor deficiency. Diagnosis, follow-up and therapy options].

DEFINITION: Alpha-1 antitrypsin (alpha-1 proteinase inhibitor) deficiency is characterized by a marked reduction of alpha-1 antitrypsin, the major antiprotease in man. PREVALENCE: Alpha-1 antitrypsin deficiency is one of the most common hereditary diseases in Caucasians of European descent. Alpha-1 antitrypsin deficiency is the underlying disorder in approximately 2% of all patients with chronic obstructive pulmonary disease and lung emphysema. CLINICAL MANIFESTATIONS: Young adults by the age of 30 to 45 years have a high risk for the development of lung emphysema with cough, sputum expectoration and respiratory insufficiency. There is a moderate risk of liver disease. DIAGNOSTIC PROCEDURES AND TREATMENT: The diagnosis is obtained by measurement of alpha-1 antitrypsin serum levels. Recognition of the disorder is important to prevent deterioration of the pulmonary function by early initiation of preventive measures and treatment. Therapeutic options are physiotherapy, antiobstructive medication and antibiotics. The most direct approach is the intravenous augmentation therapy with purified alpha-1 antitrypsin.

Adult↗

Effect of pacing chamber and atrioventricular delay on acute systolic function of paced patients with congestive heart failure. The Pacing Therapies for Congestive Heart Failure Study Group. The Guidant Congestive Heart Failure Research Group.

BACKGROUND: Previous studies of pacing therapy for dilated congestive heart failure (CHF) have not established the relative importance of pacing site, AV delay, and patient heterogeneity on outcome. These variables were compared by a novel technique that evaluated immediate changes in hemodynamic function during brief periods of atrial-synchronous ventricular pacing. METHODS AND RESULTS: Twenty-seven CHF patients with severe left ventricular (LV) systolic dysfunction and LV conduction disorder were implanted with endocardial pacing leads in the right atrium and right ventricle (RV) and an epicardial lead on the LV and instrumented with micromanometer catheters in the LV, aorta, and RV. Patients in normal sinus rhythm were stimulated in the RV, LV, or both ventricles simultaneously (BV) at preselected AV delays in a repeating 5-paced/15-nonpaced beat sequence. Maximum LV pressure derivative (LV+dP/dt) and aortic pulse pressure (PP) changed immediately at pacing onset, increasing at a patient-specific optimal AV delay in 20 patients with wide surface QRS (180+/-22 ms) and decreasing at short AV delays in 5 patients with narrower QRS (128+/-12 ms) (P<0.0001). Overall, BV and LV pacing increased LV+dP/dt and PP more than RV pacing (P<0.01), whereas LV pacing increased LV+dP/dt more than BV pacing (P<0.01). CONCLUSIONS: In this population, CHF patients with sufficiently wide surface QRS benefit from atrial-synchronous ventricular pacing, LV stimulation is required for maximum acute benefit, and the maximum benefit at any site occurs with a patient-specific AV delay.

Aged↗

The Pacing Therapies for Congestive Heart Failure (PATH-CHF) study: rationale, design, and endpoints of a prospective randomized multicenter study.

In conjunction with pharmacologic therapy, pacing has been proposed as a potential treatment to decrease symptoms in patients with moderate-to-severe congestive heart failure (CHF). Uncontrolled studies of pacing therapy for CHF dealing with different pacing sites, modes of pacing, and atrioventricular delays have reported mixed outcomes. The Pacing Therapies in Congestive Heart Failure (PATH-CHF) study is a single-blind, randomized, crossover, controlled trial designed to evaluate the effects of pacing on acute hemodynamic function and to assess chronic clinical benefit in patients with moderate-to-severe CHF. The effect of pacing on oxygen consumption at peak exercise and at anaerobic threshold during cardiopulmonary exercise tests, and on 6-minute walk distance, have been selected as primary endpoints of the study. Secondary endpoints of the trial were changes in New York Heart Association (NYHA) functional class, quality-of-life as assessed by the Minnesota Living with Heart Failure questionnaire, and hospitalization frequency. Finally, changes in ejection fraction, cardiac output, and filling pattern were assessed by echocardiography. The trial was planned to include 53 patients from 7 centers in Europe over a period of 3 years. The study was divided into 2 parts: acute testing and chronic follow-up. The acute study, performed during the pacemaker implantation, involved extensive testing using a custom-designed computer (FLEXSTIM) and a unique burst pacing protocol (FLEXSTIM protocol) to determine the best ventricular pacing sites and the most appropriate atrioventricular delays. The chronic phase consisted of a crossover study designed to test in each patient the best univentricular pacing site and biventricular pacing as assessed by the acute hemodynamic study. The study started with the first implant in 1995 and has, to date, included 42 patients. The study is expected to be completed by the end of 1998. The results of a first interim analysis showed trends toward improvement in all primary and secondary endpoints during the pacing periods compared with no pacing.

Adult↗

Transvenous biventricular pacing for heart failure: can the obstacles be overcome?

Despite increasing evidence of hemodynamic benefit and long-term improvement in clinical status of congestive heart failure (CHF) patients with left ventricular and biventricular pacing, the risks and technical limitations of placing a permanent left ventricular pacing lead have prevented widespread clinical adoption of this therapy. Results of this and other recent investigations suggest it is necessary to target specific sites on the left ventricle to maximize hemodynamic benefit. However, limitations and variations of coronary vein anatomy, as well as patient safety, lead dislodgement, pacing thresholds, lead handling, and ease-of-use issues, present technical challenges for current transvenous permanent pacing lead designs. However, a new transvenous lead system based on an over-the-wire design appears to solve many of these problems and has proved feasible in acute clinical studies.

Animals↗

Potential benefit of biventricular pacing in patients with congestive heart failure and ventricular tachyarrhythmia.

Treatment of congestive heart failure (CHF) aims for symptomatic relief and reduction of mortality both from sudden death and pump failure. The implantable cardioverter defibrillator (ICD) is highly effective in the prevention of sudden death, but no mortality benefit in advanced CHF has yet been shown. Biventricular pacing may lead to functional improvement in selected patients with CHF. Thus, a biventricular pacemaker with defibrillation capabilities may be ideal for patients with advanced CHF. We retrospectively analyzed the data from 384 patients (age 59 +/- 12 years, 322 male and 62 female) with regard to New York Heart Association (NYHA) CHF class, mean QRS duration, mean PR interval, presence of a QRS > 120 msec and incidence of atrial fibrillation at the time of ICD implantation. Based on eligibility criteria from studies in biventricular pacing, we analyzed how many patients may benefit from biventricular pacing. Patients with CHF were older (NYHA class III: 60.9 +/- 9.7, class II: 61.3 +/- 10 versus class I: 50.8 +/- 13.6 years, p < 0.001 each) and mean QRS duration was longer with advanced CHF (NYHA class III 127.8 +/- 30 msec; class II 119.4 +/- 27.7 msec; class 0-1: 103.9 +/- 17.7 msec, p < 0.001, analysis of variance) as was the mean PR interval (NYHA class III 189.9 +/- 33.5 msec; class II 176.1 +/- 29.3 msec; class 0-1 162.7 +/- 45.9 msec, p < 0.001, analysis of variance). The incidence of atrial fibrillation was higher in class III (25.5%) compared with class 0-1 (16.9%) and class II patients (14.1%, p = 0.043, chi-square test). A total of 28 patients (7.3%) fulfilled eligibility criteria for biventricular pacing if NYHA class III patients were considered candidates and 48 (12.5%) if patients with NYHA II CHF and ejection fraction < or = 30% were included. Thus, biventricular pacing may offer a promising therapeutic approach for a significant proportion of patients with CHF at risk for ventricular tachyarrhythmia.

Aged↗

New primary prevention trials of sudden cardiac death in patients with left ventricular dysfunction: SCD-HEFT and MADIT-II.

Primary prevention of sudden arrhythmic death in patients with organic heart disease with poor left ventricular function and/or heart failure is currently a major challenge in cardiology. Amiodarone (with or without beta blockers) and the implantable cardioverter defibrillator (ICD) are considered the 2 major therapeutic tools to prevent sudden arrhythmic death in these patients. Two large trials have been launched to define the prophylactic benefit of the ICD or amiodarone on total mortality in patients that receive optimal heart failure and anti-ischemic treatment but remain at high risk of dying suddenly. The Sudden Cardiac Death in Heart Failure Trial (SCD-Heft) is designed to determine whether amiodarone or the ICD will decrease overall mortality in patients with coronary artery disease or nonischemic cardiomyopathy who are in heart failure New York Heart Association (NYHA) class II or III and have a left ventricular ejection fraction < 35%. The primary endpoint is total mortality; secondary objectives are comparison of arrhythmic and nonarrhythmic mortality and morbidity in the 3 arms as well as quality of life, cost-effectiveness, and incidence of episodes of ventricular tachyarrhythmias. The Multicenter Automatic Defibrillator Implantation Trial (MADIT) II is a follow-up study to the MADIT trial. It examines the prophylactic benefit in coronary artery disease patients with a left ventricular ejection fraction of < 30%, who have had at least 1 myocardial infarction but require no further risk stratification. MADIT II is a sequential design trial that compares ICD versus no ICD therapy. Programmed electrical stimulation to test inducibility of ventricular tachycardia is performed during ICD implantation, and various noninvasive risk markers are tested after randomization. Primary endpoint is total mortality, and secondary objectives are quality-of-life issues as well as cost-effectiveness ratio.

Adult↗

Molecular characterization of an inwardly rectifying K+ channel from HeLa cells.

Previous patch-clamp studies have shown that the potassium permeability of the plasma membrane in HeLa cells, a cell line derived from an epidermoid carcinoma of the cervix, is controlled by various K+-selective pores including an IRK1 type inwardly rectifying K+ channel. We used the sequence previously reported for the human heart Kir2.1 channel to design a RT-PCR strategy for cloning the IRK1 channel in HeLa cells. A full-length clone of 1.3 kb was obtained that was identical to the human cardiac Kir2.1 inward rectifier. The nature of the cloned channel was also confirmed in a Northern blot analysis where a signal of 5.3 kb corresponding to the molecular weight expected for a Kir2.1 channel transcript was identified not only in HeLa cells, but also in WI-38, ECV304 and bovine aortic endothelial cells. The HeLa IRK1 channel cDNA was subcloned in an expression vector (pMT21) and injected into Xenopus oocytes. Cell-attached and inside-out single channel recordings obtained from injected oocytes provided evidence for a voltage-independent K+-selective channel with current/voltage characteristics typical of a strong inward rectifier. The single channel conductance for inward currents measured in 200 mm K2SO4 conditions was estimated at 40 +/- 1 pS (n = 3), for applied voltages ranging from -100 to -160 mV, in agreement with the unitary conductance for the IRK1 channel identified in HeLa cells. In addition, the single channel conductance for inward currents, Gamma, was found to vary as a function of alphaK, the external K+ ion activity, according to Gamma = Gamma0 [alphaK]delta with Gamma0 = 3.3 pS and delta = 0.5. Single channel recordings from injected oocytes also provided evidence of a voltage-dependent block by external Cs+ and Ba2+. The presence of 500 micron Cs+ caused a voltage-dependent flickering, typical of a fast channel blocking process which resulted in a reduction of the channel open probability at increasingly negative membrane potential values. The fractional electrical distance computed for the Cs+ blocking site was greater than 1 indicating a multiple ion channel occupation. In contrast, external Ba2+ at concentrations ranging from 25 to 100 micron caused a slow channel block, consistent with the binding of a single Ba2+ ion at a site located at half the membrane span. It is concluded on the basis of these observations that HeLa cells expressed a Kir2.1 type inwardly rectifying channel likely to be involved in maintaining and regulating the cell resting potential.

Animals↗

Terahertz Spectroscopy of the Amidogen Radical, NH2.

The rotational spectrum of the NH2 radical in its &Xtilde;2B1 ground vibronic state was investigated between 614 and 1003 GHz. One hundred fifty-nine newly observed lines (188 hyperfine components) of six rotational transitions with 0 </= N </= 5 and 0 </= Ka </= 4 were used in the final, global fit of field-free data for the (000) vibrational state. Recent results from Fourier transform far-infrared (FT-FIR), and millimeter- and submillimeter-wave spectroscopy, as well as microwave optical double resonance (MODR) and recent FIR laser sideband data, were also used in the fit. A large set of spectroscopic constants reproduces the input data within experimental uncertainties and permits the precise prediction of low-N, low-Ka transitions of interest for the astrophysical community. In particular, the astrophysically important 111-000 transition of ortho NH2 was observed near 952.57 and 959.50 GHz. Copyright 1999 Academic Press.

Journal Article↗

Project neighborhoods in action: an HIV-related intervention project targeting drug abusers in Washington, DC.

Project Neighborhoods in Action was a human immunodeficiency virus (HIV) outreach and intervention program that was conducted with injection drug users and crack users in several inner-city neighborhoods in the District of Columbia. Study participants were placed randomly in either a standard intervention or an enhanced intervention condition, with more than 800 persons being assigned to each group. Drug use frequency dropped from 15.2 days to 12.4 for alcohol (P<.0001), 2.1 days to 1.6 for marijuana (P<.003), 13.0 days to 8.8 days for crack (P<.0001), 2.4 days to 1.5 days for cocaine (P<.0001), 19.7 days to 15.6 for heroin (P<.0001), and 5.2 days to 3.4 for speedball (P<.0001). Drug injecting decreased from an average of 90.8 times to 66.9 (P<.0001), with both direct sharing and indirect sharing rates decreasing significantly as well (from 2.4 to 1.1 times for the former [P<.002] and from 12.0 to 8.1 times for the latter [P<.0004]). The number of sexual partners dropped from a mean of 1.6 to 1.1 (P<.0001). The number of drug-injecting sexual partners went from 0.3 to 0.2 (P<.01). Having sex while high decreased from 11.2 times to 7.9 (P<.0001). Trading sex for drugs and/or money declined from 1.9 times to 1.3 (P<.001). Protected sex increased from 29.5% to 63.7% (P<.0001), and the number of unprotected sexual acts dropped from 9.6 to 7.2 (P<.0001). Only a few differences were observed for standard versus enhanced intervention respondents, with no particular pattern formed. We were left with the impression that the standard intervention and enhanced intervention used in this program were about equally effective at reducing the involvement of drug abusers in HIV-related risky behaviors.

Adult↗