Methamphetamine dependence increases risk of neuropsychological impairment in HIV infected persons.

Both HIV infection and methamphetamine dependence can be associated with brain dysfunction. Little is known, however, about the cognitive effects of concurrent HIV infection and methamphetamine dependence. The present study included 200 participants in 4 groups: HIV infected/methamphetamine dependent (HIV+/METH+), HIV negative/methamphetamine dependent (HIV-/METH+), HIV infected/methamphetamine nondependent (HIV+/METH-), and HIV negative/methamphetamine nondependent (HIV-/METH-). Study groups were comparable for age, education, and ethnicity, although the HIV-/METH- group had significantly more females. A comprehensive, demographically corrected neuropsychological battery was administered yielding a global performance score and scores for seven neurobehavioral domains. Rates of neuropsychological impairment were determined by cutoff scores derived from performances of a separate control group and validated with larger samples of HIV+ and HIV- participants from an independent cohort. Rates of global neuropsychological impairment were higher in the HIV+/METH+ (58%), HIV-/METH+ (40%) and HIV+/METH- (38%) groups compared to the HIV-/METH- (18%) group. Nonparametric analyses revealed a significant monotonic trend for global cognitive status across groups, with least impairment in the control group and highest prevalence of impairment in the group with concurrent HIV infection and methamphetamine dependence. The results indicate that HIV infection and methamphetamine dependence are each associated with neuropsychological deficits, and suggest that these factors in combination are associated with additive deleterious cognitive effects. This additivity may reflect common pathways to neural injury involving both cytotoxic and apoptotic mechanisms.     

The impact of estrogen and progesterone on asthma.

OBJECTIVE: This paper describes evidence of a positive effect of both endogenous and exogenous estrogen and progesterone on lung function across the life span in women. DATA SOURCES: Articles were identified using the keywords asthma, pulmonary function, menarche, menopause, estrogen, progesterone, hormone replacement therapy, oral contraceptives, and menstrual cycle from years 1966 to 2001 in MEDLINE. Additional studies were identified from article reference lists. STUDY SELECTION: Relevant, peer-reviewed original research articles in the English language were selected. RESULTS: Estrogen and/or progesterone may alter pulmonary function and asthma. Premenopausal women experience decreases in pulmonary function and increases in asthma exacerbations and hospitalizations during the premenstrual and menstrual phases. Oral contraceptives and hormone replacement therapy are associated with improved pulmonary function and decrease in asthma exacerbation. Some asthmatic patients experience improved pulmonary function and reduced asthma medication requirement during pregnancy. CONCLUSIONS: Estrogen and progesterone modify airway responsiveness. Further research is needed to elucidate the clinical relevance of estrogen and progesterone in the pathophysiology and therapy of asthma.     

Quantitative MRI of the brain in children with sickle cell disease reveals abnormalities unseen by conventional MRI

Conventional MRI (cMRI) has shown that brain abnormalities without clinical stroke can manifest in patients with sickle cell disease (SCD). We used quantitative MRI (qMRI) and psychometric testing to determine whether brain abnormalities can also be present in patients with SCD who appear normal on cMRI. Patients 4 years of age and older with no clinical evidence of stroke were stratified by cMRI as normal (n = 17) or abnormal (n = 13). Spin-lattice relaxation time (T1) of gray and white matter structures was measured by the precise and accurate inversion recovery (PAIR) qMRI method. Patient cognitive ability was assessed with a standard psychometric instrument (WISC-III or WISC-R). In all 30 patients with SCD, qMRI T1 was lower than in 24 age- and race-matched controls, in cortical gray matter (P < .0006) and caudate (P < .0009), as well as in the ratio of gray-to-white matter T1 (P < .008). In the 17 patients who were shown to be normal by cMRI, qMRI T1 was still lower than in controls, in both cortical gray matter (P < .02) and caudate (P < .004). Histograms of voxel T1 show that the proportion of voxels with T1 values intermediate between gray and white matter (ie, consistent with encephalomalacia) was 9% higher than controls in patients shown to be normal by cMRI (P < .05) and 15% higher than controls in patients shown to be abnormal by cMRI (P < .0005). The full scale intelligence quotient (FSIQ) of all patients with SCD was 75, compared to the FSIQ of 88 in a historical control group of patient siblings (P < .001). The FSIQ of patients shown to be normal by cMRI was 79, significantly lower than the FSIQ of patient siblings (P < .04). The FSIQ of 71 in patients shown to be abnormal by cMRI was significantly lower than both the patient siblings (P < .005) and the patients shown to be normal by cMRI (P < .04). Patients shown to be abnormal by cMRI scored lower than patients shown to be normal by cMRI, specifically on the subtests of vocabulary (P = .003) and information (P = .03). Cognitive impairment is thus significant, even in patients with SCD who were shown to be normal by cMRI, suggesting that cMRI may be insensitive to subtle neurologic damage that can be detected by qMRI. Because cognitive impairment can occur in children normal by cMRI, our findings imply that prophylactic therapy may be needed earlier in the course of SCD to mitigate neurologic damage.     

The Effects of Serum from Patients with Acute Liver Failure on the Growth and Metabolism of Hep G2 Cells

In many bioartificial liver systems currently being designed and evaluated for use in fulminant hepatic failure, direct contact is required between the patient's blood and the liver cells in the device. The efficacy of such devices will be influenced by the interaction of fulminant hepatic failure (FHF) patient serum with the cells. We have found that FHF serum inhibits the growth rate and the synthesis of DNA, RNA, and protein; disturbs glutathione homeostasis; and induces morphological changes in cultured human Hep G2 cells. These interactions should influence the design of bioartificial liver devices based on proliferating cell lines and indicate the requirement to pretreat FHF patient plasma to reduce the toxin load.     

Tick Bites and Lyme Disease in an Endemic Setting: Problematic Use of Serologic Testing and Prophylactic Antibiotic Therapy

Context.— The use of serologic testing to diagnose Lyme disease (LD) is a source of controversy. Expert recommendations also discourage the routine use of antibiotic therapy for prophylaxis of LD following tick bites, but the extent to which physicians in endemic areas have adopted these recommendations is not known. Objective.— To assess the pattern of use of serologic testing and antibiotic therapy for tick bites and LD and associated charges for management in an endemic area. Design.— Active surveillance of patient-physician encounters for tick bites and LD. Setting.— Primary care practices on the Eastern Shore of Maryland. Patients.— Consecutive sample of 232 patients with tick bites, LD (defined by physician diagnosis in medical record), and suspected LD (physician notation of possible, but not definite LD) seen in 1995. Main Outcome Measures.— Serologic testing for LD, test results, antibiotic therapy, and direct costs of management. Results.— Surveillance identified 142 patients (61.2%) with diagnoses of tick bites, 40 patients (17.2%) with LD, and 50 patients (21.6%) with suspected LD. Of the 142 patients seen for tick bites, 95 (67%) underwent serologic testing for LD. Of these, 93 patients had initial negative or equivocal results; 24 (26%) of the 93 had convalescent testing, with 1 seroconversion. Seventy-eight patients (55%) with a diagnosis of tick bite received antibiotic therapy. No patients with tick bite developed clinical LD. Serologic testing for LD was performed for 36 patients (90%) with a diagnosis of LD and 46 patients (92%) with suspected LD. In most cases, antibiotics were prescribed before serologic test results became available. Convalescent testing was not performed for 37 (86%) of the 43 patients with suspected LD who had initial negative or equivocal results. Of these 37 patients, 25 (68%) did not receive antibiotic therapy. Direct charges for treatment of these 232 patients totaled $47595, one third of which was attributable to serologic testing. A total of 32% of direct charges were for patients with tick bites, 48% were for patients with LD, and 20% were for patients with suspected LD. Conclusions.— In this setting, most patients consulting physicians for tick bites received prophylactic antibiotic therapy of unproven efficacy and underwent unnecessary, costly serologic testing. Despite almost universal use in this study, serologic testing for LD did not appear to influence treatment of patients diagnosed as having LD.      

Substitution of the 5-HT1 agonist trifluoromethylphenylpiperazine (TFMPP) for the discriminative stimulus effects of ethanol: effect of training dose

The role of the ethanol training dose on the ability of the selective 5-HT¹ agonist TFMPP (m-trifluoromethylphenylpiperazine) to produce ethanol-like discriminative stimulus effects was evaluated in three groups of rats trained to discriminate 1.0 g/kg (n=5), 1.5 g/kg (n=6) or 2.0 g/kg (n=7) ethanol (IG) from water using a two-lever procedure with food reinforcement available under a fixed ratio 20 (FR 20) schedule. Ethanol generalization gradients were comparable in the three groups, indicating few potency differences in the ethanol stimulus across training dose. However, the ability of TFMPP (0.1–1.7 mg/kg; IP) to substitute for ethanol was dependent on the training dose. TFMPP resulted in partial substitution in the 1.0 g/kg group, complete substitution for 1.5 g/kg group and no substitution in the 2.0 g/kg ethanol training group. The results indicate a serotonergic component to the discriminative stimulus effects of an intermediate dose of ethanol that is not prominent as the dose of ethanol is raised. These data add further support for the hypothesis that ethanol produces a mixed discriminative cue, the components of which are not uniformly amplified when the dose of ethanol is increased.     

Evaluation of a burn prevention program in a public school system.

The "Learn Not to Burn" prevention program is a burn prevention curriculum sponsored by the North Carolina Jaycee Burn Center, the State Department of Public Instruction, and the North Carolina Department of Insurance Fire and Rescue Division. The goal of the program is to reduce burn-related deaths and injuries in North Carolina through burn prevention education by making the "Learn Not to Burn" curriculum available to primary school children across the state at no cost to the schools. The curriculum instrument is a reusable notebook that provides a means for teachers to integrate burn prevention into regular class subject areas. At the time of initiation of this study approximately 70% of the school systems in North Carolina had been provided with the "Learn Not to Burn" curriculum.     

The relationship of life adversity, social support, and coping to hospitalization with major depression.

We evaluated the relationship between life events, social support, coping, and depression in 27 male inpatients meeting the requirements for Research Diagnostic Criteria major depressive disorder and in 35 age- and sex-matched nonpatients. Overall, the hospitalized depressed patients reported significantly more events and difficulties than did the controls, but this difference in statistical significance disappeared after excluding from analysis "non-independent" happenings which could have been brought on by depression. More hospitalized depressed patients (23 of 27, or 85%) than controls (8 of 35, or 22.9%) experienced markedly threatening events and difficulties ("marked adversities") in the 6 months before their interview. The depressed group also reported having significantly fewer social supports, being less satisfied with the emotional component of this support, and using more emotion-focused coping than the controls. A discriminant analysis predicted depressive status from a combination of marked adversities, reduced number of social supports, and greater use of emotion-focused coping. The results indicate that the relationship of life events to depression is complex. The excess number of events might be partly a product of dysfunctional behavior that "produces" depression-related events which might, in turn, exacerbate depression; simultaneously, patients are more likely to experience highly adverse events which might precipitate the depression in the first place. Reduced social supports and the use of emotion-focused coping appear to also be associated with hospitalization for major depression.