Neil M. Flynn

Preliminary evidence of reduced cognitive inhibition in methamphetamine-dependent individuals

Chronic methamphetamine abuse is associated with disruption of frontostriatal function involving serotonin and dopamine circuitry. Clinically, methamphetamine-dependent (MD) individuals are highly distractible and have difficulty focussing. Here, we used a computerized single-trial version of the Stroop Test to examine selective attention and priming in MD. Subject groups comprised eight MD men (31.7+/-7.2 years of age), who had used methamphetamine for 15.75+/-8.4 years but were currently abstinent for 2-4 months, and 12 controls (35.7+9.7 years of age). Compared with the control group, the MD group exhibited significantly greater interference (P<0.05) despite intact priming. Error rates did not differ between the groups. This preliminary finding of reduced cognitive inhibition in MD individuals is consistent with the distractibility they show clinically. Furthermore, the dissociation between explicit attentional performance and priming effects suggests that some attentional functions are not as affected by long-term methamphetamine use as others.

Comparisons of Community-Associated Methicillin-Resistant Staphylococcus aureus (MRSA) and Hospital-Associated MSRA Infections in Sacramento, California

ABSTRACT Methicillin-resistant Staphylococcus aureus (MRSA) has long been a common pathogen in healthcare facilities, but in the past decade, it has emerged as a problematic pathogen in the community setting as well. A retrospective case series study of patients from whom MRSA was isolated from December 1, 2003, through May 31, 2004, was conducted at the University of California, Davis, Medical Center. Patient data were collected from electronic medical records and traditional chart reviews to determine whether MRSA acquisition was likely to have been in the community or in the hospital. Antimicrobial susceptibility testing and pulsed-field gel electrophoresis (PFGE) were performed for all confirmed isolates. Skin and soft tissue were the most common infection sites for all MRSA patients. Among the 283 MRSA infections, 127 (44.9%) were defined as community-associated (CA)-MRSA. Ninety-six percent of the CA-MRSA isolates were susceptible to clindamycin. Double-disk diffusion tests were performed to examine inducible clindamycin resistance by erythromycin induction on both CA and hospital-associated (HA) clindamycin-susceptible and erythromycin-resistant isolates. Ten percent (17 of 183) were positive. Most CA-MRSA isolates were identified by PFGE as a unique strain, genotype USA300, which was not genetically related to the predominant genotype, USA100, in the HA-MRSA isolates. Injecting drug users accounted for 49% of CA-MRSA infections but only 19% of the HA-MRSA infections (odds ratio, 4.2; 95% confidence interval, 2.4 to 7.4). Our study shows that a single clone of CA-MRSA accounts for the majority of infections. This strain originated in the community and is not related to MRSA strains from healthcare settings. Injecting drug users could be a major reservoir for CA-MRSA transmission.

Methamphetamine Use and Sexual and Injection Risk Behaviors Among Out-of-Treatment Injection Drug Users

Our primary objective was to examine the relationship between methamphetamine use and sexual risk-taking behaviors--number of sexual partners, frequency of sexual behaviors with regular and casual partners, trading money or drugs for sex, and condom use--among male and female out-of-treatment injection drug users (OTIDUs). As a risk group for human immunodeficiency virus (HIV) transmission, we also investigated injection behaviors by methamphetamine use. Data were collected from 1392 OTIDUs within the California counties of Fresno, Sacramento, and San Diego. Excluded from this cross-sectional survey were male OTIDUs engaging in sex with only or mostly men since 1978. In bivariate analyses, we found that male OTIDUs with a history of methamphetamine use had more sex partners and participated in more acts of anal insertive intercourse with casual partners and vaginal intercourse with regular and casual partners than male OTIDUs never using methamphetamines. In addition, a greater percentage of male OTIDUs using methamphetamines reported trading sex for money or drugs. Methamphetamine-using female OTIDUs participated in more acts of vaginal intercourse with regular male sex partners than female OTIDUs never using methamphetamines. By multivariate logistic regression, we found methamphetamine use related to consistent condom use among male OTIDUs and among male sex partners of female OTIDUs. Discriminant function analyses revealed that sexual risk taking could be differentiated by methamphetamine use among male OTIDUs. Methamphetamine use also correlated with using shared needles or syringes among male and female OTIDUs and was related to not always disinfecting used needles or syringes with bleach. Our findings suggest that methamphetamines may contribute to heterosexual HIV transmission.

Low N-acetyl-aspartate and high choline in the anterior cingulum of recently abstinent methamphetamine-dependent subjects: a preliminary proton MRS study

Studies based on animal models report that methamphetamine (MA) abuse diminishes dopamine (DA) and serotonin innervation in frontal brain regions. In this in vivo human study, we used proton magnetic resonance spectroscopy (MRS), which yields measures of N-acetyl-aspartate (NAA), a marker of living neurons, to examine frontal brain regions possibly affected by methamphetamine dependence (MD). We tested the hypothesis that MD subjects would exhibit abnormally low levels of NAA, referenced to creatine (Cr), in anterior cingulate gray matter. We further hypothesized that the primary visual cortex, which receives relatively less DA innervation than the frontal brain regions, would show normal NAA/Cr ratios in MD subjects. Subjects included nine MD men (mean+/-standard deviation (S.D.)=32.5+/-6.4 years) and nine age-matched control men (mean+/-S.D.=32.7+/-6.8 years). The MD subjects were MA-free for 4-13 weeks. Proton MRS metabolites were expressed as ratios of creatine; the absolute values of which did not distinguish controls and MD subjects. With regard to metabolite ratios, the MD men had significantly lower NAA/Cr in the cingulum (mean+/-standard error (S.E.): control=1.46+/-0.03; MD=1.30+/-0.03; Mann-Whitney P=0.01) but not in the visual cortex (mean+/-S.E.: control=1.64+/-0.06; MD=1.69+/-11; Mann-Whitney P=0.52) relative to controls. These results provide evidence for NAA/Cr deficit that is selective to the anterior cingulum, at least with respect to visual cortex, in MD subjects. The neuronal compromise that these changes reflect may contribute to the attentional deficits and dampened reward system in MD.

Hepatitis C in methadone maintenance patients: prevalence and public policy implications.

Abstract Objective: This study measured the extent and examined implications of hepatitis C (HCV) infection in a methadone maintenance treatment (MMT) population. Method: Four hundred and sixty patients were tested for HCV-Ab, hepatic enzymes and bilirubin, HCV-RNA, and hepatitis B antibody. Results: Overall, 87% of this population had evidence of HCV-Ab. Among drug injectors (IDU), 96% were HCV-Ab positive. Among a subset of Laotian opium-smoking patients prevalence was only 11%. Sixty-two percent of patients with HCV-Ab had detectable HCV-RNA. Only 41% had elevated hepatic enzymes, and 5% had elevated bilirubin levels. All age groups were equally infected. Systemic problems in screening and treating HCV in drug users were identified. Conclusion: HCV infection poses significant long-term health risks for this population. Harm reduction interventions aimed at reducing transmission of HCV and other needle-related infectious disease deserves more consideration.

Sexual Risk Among Injection Drug Users Recruited from Syringe Exchange Programs in California

Objective: The objective of this study was to examine correlates of sexual risk among injection drug users (IDUs). Study: A total of 1445 IDUs were recruited from California syringe exchange programs. Results: Consistent condom use was independently related to being HIV-positive, having multiple sex partners, not having a steady partner, not sharing syringes, and not injecting amphetamines for men; and engaging in sex work, not sharing syringes, and not having a steady partner for women. Having multiple recent sexual partnerships that included a steady partner was related to engaging in sex work, speedball injection, and amphetamine use among men; and younger age, having had a sexually transmitted disease (STD), engaging in sex work, and using alcohol among women. Having heterosexual anal sex was related to having had an STD, having multiple sexual partners, using amphetamines, and syringe-sharing for men; and younger age and amphetamine use for women. Conclusions: Comprehensive prevention interventions addressing multiple sexual and injection risk behaviors are needed for IDUs.

Necrotizing Fasciitis Associated with Injection Drug Use

We studied cases of necrotizing fasciitis among injection drug users (IDUs) and non-IDUs who presented at the University of California Davis Medical Center from 1984 through 1999. Of 107 patients, 59 (55%) were IDUs and 48 (45%) non-IDUs. Among IDUs, 32 (54%) recently injected at the site of infection, and 17 patients (29%) presented with an abscess. Among non-IDUs, 17 (35%) reported a recent insect bite and 9 (19%) reported a wound or abrasion at the site of infection. Overall, seventy cases (65%) had > or = 3 debridements, and 31 patients (29%) had > 5% of their total body surface area debrided. Of all patients with necrotizing fasciitis, 16 (15%) did not survive. Among the 59 IDUs, 6 (10%) did not survive, while among non-IDUs, 10 (21%) did not survive. Our results indicate the need for a high index of suspicion for necrotizing fasciitis among patients presenting with cellulitis, a recent insect bite, wound, or recent injection drug use. Preventive interventions for necrotizing fasciitis among IDUs should include street-based education and treatment for abscesses and cellulitis.

Epidemiology and public health consequences of methamphetamine use in California's Central Valley

Abstract Methamphetamine use is an increasingly serious public health problem in California and other parts of the country. Despite sensationalistic media attention, however, very little is known about users of this clandestinely consumed drug. Employing methods known as Rapid Assessment and Response, the authors describe the epidemiology and public health implications of methamphetamine use in Californias Central Valley, with a focus on Sacramento, which many social indicators suggest has been more severely affected by methamphetamine than any city in the nation. Data sources for this report include interviews with drug users, statistical reports, epidemiologic studies, and local informed expert opinion. In their social demography, methamphetamine users in the Central Valley are in marked contrast to those of coastal cities such as Seattle and San Francisco, being largely heterosexual, and of mixed racial/ethnic heritage. Three-quarters or more initiate their use of the drug while still in their teens, with more than a quarter beginning use before the age of 15. Many of these rapidly gravitate to regular use, and continue using well into their thirties. Methamphetamine users are at much higher risk of infection with HIV than opiate users, particularly if they inject. Partly because methamphetamine enhances libido, users of the drug typically also have many more sexual partners. Not surprisingly, data indicate that methamphetamine users are more likely than heroin users to be HIV-infected. Methamphetamine appears to be less of a street drug than heroin, complicating efforts at street outreach. However, because it is typically used in social settings, a social or diffusion approach to HIV prevention might be particularly promising.

Infusion Carboplatin Treatment of Relapsed and Refractory Acute Leukemia: Evidence of Efficacy With Minimal Extramedullary Toxicity at Intermediate Doses

Carboplatin (CBDCA) is a second-generation platinum analog with prominent myelotoxicity and modest extramedullary toxicity. We performed a phase I study of CBDCA in adult patients with relapsed acute leukemia. Therapy was administered as a five-day continuous infusion. The initial dose of 875 mg/m2 over five days was escalated in 15% increments to a final dose of 2,100 mg/m2 over five days. Twenty-eight patients received 35 induction courses of CBDCA, including two patients who achieved a complete remission (CR) following the first course, and received a second induction course at the time of relapse. Therapy was well tolerated. No grade 3 or 4 extramedullary toxicity was seen. Myelosuppression was regularly observed, with prolonged myelosuppression at 2,100 mg/m2 over five days being the indication to cease dose escalation. Eight of 28 patients (28.5%) responded to CBDCA therapy (six CR, two partial remission [PR]) or ten of 30 initial induction courses (33.3%). Continuous-infusion CBDCA has an advantage over other therapy for acute leukemia because of its highly selective myelotoxicity and minimal gastrointestinal and renal toxicity. A standard phase II study should be undertaken to establish a more accurate response rate.

Oral serum-derived bovine immunoglobulin improves duodenal immune reconstitution and absorption function in patients with HIV enteropathy

Objectives:To examine the impact of serum-derived bovine immunoglobulin, an oral medical food known to neutralize bacterial antigen and reduce intestinal inflammation, on restoration of mucosal immunity and gastrointestinal function in individuals with HIV enteropathy. Design:Open-label trial with intensive 8-week phase of bovine serum immunoglobulin (SBI) 2.5 g twice daily with a 4-week washout period and an optional 9-month extension study. Methods:HIV enteropathy was defined as chronic gastrointestinal symptoms including frequent loose or watery stools despite no identifiable, reversible cause. Upper endoscopy for tissue immunofluorescent antibody assay and disaccharide gut permeability/absorption studies were performed before and after 8 weeks of SBI to test mucosal immunity and gastrointestinal function. Blood was collected for markers of microbial translocation, inflammation, and collagen kinetics. A validated gastrointestinal questionnaire assessed changes in symptoms. Results:All eight participants experienced profound improvement in symptoms with reduced bowel movements/day (P = 0.008) and improvements in stool consistency (P = 0.008). Gut permeability was normal before and after the intervention, but D-xylose absorption increased in seven of eight participants. Mucosal CD4+ lymphocyte densities increased by a median of 139.5 cells/mm2 from 213 to 322 cells/mm2 (P = 0.016). Intestinal-fatty acid binding protein (I-FABP), a marker of enterocyte damage, initially rose in seven of eight participants after 8 weeks (P = 0.039), and then fell below baseline in four of five who continued receiving SBI (P = 0.12). Baseline serum I-FABP levels were negatively correlated with subsequent rise in mucosal CD4+ lymphocyte densities (r = −0.74, P = 0.046). Conclusion:SBI significantly increases intestinal mucosal CD4+ lymphocyte counts, improves duodenal function, and showed evidence of promoting intestinal repair in the setting of HIV enteropathy.