Brain glucose metabolism in hypothyroidism: a positron emission tomography study before and after thyroid hormone replacement therapy.

CONTEXT: Hypothyroidism is frequently associated with subtle behavioral and psychiatric symptoms. The consequences of inadequate thyroid hormone availability to brain metabolism are poorly understood. OBJECTIVE: This study assessed the relationships between neuropsychiatric symptoms and changes in relative regional cerebral glucose metabolism in hypothyroid patients undergoing thyroid hormone replacement therapy. DESIGN, SETTING, AND OUTCOME MEASURE: Relative regional cerebral glucose metabolism was compared in 13 previously untreated hypothyroid patients and 10 healthy control participants. Effects of thyroid hormone replacement therapy (levothyroxine, 3 months) were assessed using neuropsychiatric measures and positron emission tomography with [(18)F]fluorodeoxyglucose. RESULTS: Before treatment, hypothyroid patients exhibited lower regional activity than control subjects in the bilateral amygdala, hippocampus, and perigenual anterior cingulate cortex (ACC), left subgenual ACC, and right posterior cingulate cortex. Severity of depressive symptoms covaried negatively with pretreatment activity in the bilateral middle frontal gyrus and right subgenual and dorsal ACC. Thyroid hormone replacement therapy abolished pretreatment group differences in regional activity, robustly increased activity in the ventral ACC, and significantly reduced both clinician-rated and self-rated behavioral and psychiatric symptoms. Increased activity within the ventral ACC was associated with reduced somatic complaints, whereas increased activity within the dorsal ACC was associated with reduced depressive symptoms. CONCLUSIONS: Reduction of the behavioral complaints during thyroid hormone therapy is associated with a restoration of metabolic activity in brain areas that are integral to the regulation of affect and cognition. The findings suggest that thyroid hormone modulates regional glucose metabolism and psychiatric symptoms in the mature brain.

Potential adverse effects of amphetamine treatment on brain and behavior: a review.

Amphetamine stimulants have been used medically since early in the twentieth century, but they have a high abuse potential and can be neurotoxic. Although they have long been used effectively to treat attention deficit hyperactivity disorder (ADHD) in children and adolescents, amphetamines are now being prescribed increasingly as maintenance therapy for ADHD and narcolepsy in adults, considerably extending the period of potential exposure. Effects of prolonged stimulant treatment have not been fully explored, and understanding such effects is a research priority. Because the pharmacokinetics of amphetamines differ between children and adults, reevaluation of the potential for adverse effects of chronic treatment of adults is essential. Despite information on the effects of stimulants in laboratory animals, profound species differences in susceptibility to stimulant-induced neurotoxicity underscore the need for systematic studies of prolonged human exposure. Early amphetamine treatment has been linked to slowing in height and weight growth in some children. Because the number of prescriptions for amphetamines has increased several fold over the past decade, an amphetamine-containing formulation is the most commonly prescribed stimulant in North America, and it is noteworthy that amphetamines are also the most abused prescription medications. Although early treatment does not increase risk for substance abuse, few studies have tracked the compliance and usage profiles of individuals who began amphetamine treatment as adults. Overall, there is concern about risk for slowed growth in young patients who are dosed continuously, and for substance abuse in patients first medicated in late adolescence or adulthood. Although most adult patients also use amphetamines effectively and safely, occasional case reports indicate that prescription use can produce marked psychological adverse events, including stimulant-induced psychosis. Assessments of central toxicity and adverse psychological effects during late adulthood and senescence of adults who receive prolonged courses of amphetamine treatment are warranted. Finally, identification of the biological factors that confer risk and those that offer protection is also needed to better specify the parameters of safe, long-term, therapeutic administration of amphetamines to adults.

Sex differences in brain activity during aversive visceral stimulation and its expectation in patients with chronic abdominal pain: a network analysis.

Differences in brain responses to aversive visceral stimuli may underlie previously reported sex differences in symptoms as well as perceptual and emotional responses to such stimuli in patients with irritable bowel syndrome (IBS). The goal of the current study was to identify brain networks activated by expected and delivered aversive visceral stimuli in male and female patients with chronic abdominal pain, and to test for sex differences in the effective connectivity of the circuitry comprising these networks. Network analysis was applied to assess the brain response of 46 IBS patients (22 men and 24 women) recorded using [15O] water positron emission tomography during rest/baseline and expected and delivered aversive rectal distension. Functional connectivity results from partial least squares analyses provided support for the hypothesized involvement of 3 networks corresponding to: 1) visceral afferent information processing (thalamus, insula and dorsal anterior cingulate cortex, orbital frontal cortex), 2) emotional-arousal (amygdala, rostral and subgenual cingulate regions, and locus coeruleus complex) and 3) cortical modulation (frontal and parietal cortices). Effective connectivity results obtained via structural equation modeling indicated that sex-related differences in brain response are largely due to alterations in the effective connectivity of emotional-arousal circuitry rather than visceral afferent processing circuits. Sex differences in the cortico-limbic circuitry involved in emotional-arousal, pain facilitation and autonomic responses may underlie the observed differences in symptoms, and in perceptual and emotional responses to aversive visceral stimuli.

Changes in cerebral glucose metabolism during early abstinence from chronic methamphetamine abuse.

Changes in brain function during the initial weeks of abstinence from chronic methamphetamine abuse may substantially affect clinical outcome, but are not well understood. We used positron emission tomography with [F-18]fluorodeoxyglucose (FDG) to quantify regional cerebral glucose metabolism, an index of brain function, during performance of a vigilance task. A total of 10 methamphetamine-dependent subjects were tested after 5-9 days of abstinence, and after 4 additional weeks of supervised abstinence. A total of 12 healthy control subjects were tested at corresponding times. Global glucose metabolism increased between tests (P=0.01), more in methamphetamine-dependent (10.9%, P=0.02) than control subjects (1.9%, NS). Glucose metabolism did not change in subcortical regions of methamphetamine-dependent subjects, but increased in neocortex, with maximal increase (>20%) in parietal regions. Changes in reaction time and self-reports of negative affect varied more in methamphetamine-dependent than in control subjects, and correlated both with the increase in parietal glucose metabolism, and decrease in relative activity (after scaling to the global mean) in some regions. A robust relationship between change in self-reports of depressive symptoms and relative activity in the ventral striatum may have great relevance to treatment success because of the role of this region in drug abuse-related behaviors. Shifts in cortical-subcortical metabolic balance either reflect new processes that occur during early abstinence, or the unmasking of effects of chronic methamphetamine abuse that are obscured by suppression of cortical glucose metabolism that continues for at least 5-9 days after cessation of methamphetamine self-administration.

Process, efficacy and sample demographics of three approaches to behavioural surveillance for gonorrhoea: case interviews, place surveys, and network studies.

We investigated the process and time required to collect 450 interviews in a project to determine the most efficacious behavioural surveillance approaches to detect changes in gonorrhoea prevalence. In total, 150 respondents were recruited in each method. For each of place surveys (bars), gonorrhoea case interviews, and network studies based on seeds from the case and place interviews, we determined the recruitment rate and process. Urine testing for gonorrhoea and chlamydia took place in the place interviews. We present data from Houston, Texas that illustrate the sample characteristics, recruitment rates, and, where appropriate, infection rates. Data indicate that there was high uptake and a rapid recruitment rate from the place surveys, an intermediate rate from the network studies, and that the gonorrhoea case interviews were the most inefficient accrual method for behavioural surveillance. Sample characteristics and biases in each method are described, and conclusions drawn for the relative efficacy of each method for gonorrhoea behavioural surveillance.

Supraphysiological doses of levothyroxine alter regional cerebral metabolism and improve mood in bipolar depression.

Supplementation of standard treatment with high-dose levothyroxine (L-T(4)) is a novel approach for treatment-refractory bipolar disorders. This study tested for effects on brain function associated with mood alterations in bipolar depressed patients receiving high-dose L-T(4) treatment adjunctive to ongoing medication (antidepressants and mood stabilizers). Regional activity and whole-brain analyses were assessed with positron emission tomography and [(18)F]fluorodeoxyglucose in 10 euthyroid depressed women with bipolar disorder, before and after 7 weeks of open-label adjunctive treatment with supraphysiological doses of L-T(4) (mean dose 320 microg/day). Corresponding measurements were acquired in an age-matched comparison group of 10 healthy women without L-T(4) treatment. The primary biological measures were relative regional activity (with relative brain radioactivity taken as a surrogate index of glucose metabolism) in preselected brain regions and neuroendocrine markers of thyroid function. Treatment-associated changes in regional activity (relative to global activity) were tested against clinical response. Before L-T(4) treatment, the patients exhibited significantly higher activity in the right subgenual cingulate cortex, left thalamus, medial temporal lobe (right amygdala, right hippocampus), right ventral striatum, and cerebellar vermis; and had lower relative activity in the middle frontal gyri bilaterally. Significant behavioral and cerebral metabolic effects accompanied changes in thyroid hormone status. L-T(4) improved mood (remission in seven patients; partial response in three); and decreased relative activity in the right subgenual cingulate cortex, left thalamus, right amygdala, right hippocampus, right dorsal and ventral striatum, and cerebellar vermis. The decrease in relative activity of the left thalamus, left amygdala, left hippocampus, and left ventral striatum was significantly correlated with reduction in depression scores. Results of the whole-brain analyses were generally consistent with the volume of interest results. We conclude that bipolar depressed patients have abnormal function in prefrontal and limbic brain areas. L-T(4) may improve mood by affecting circuits involving these areas, which have been previously implicated in affective disorders.

A stochastic-covariate failure model with an application to case-control analysis.

A stochastic process X(t) is periodically stationary (and ergodic) if, for every k> or =1 and every (t(1),ellipsis,t(k)) in R(k), the sequence of random vectors (X(t(1)+n),ellipsis,X(t(k)+n))n=0,+1, ellipsis, is stationary (and ergodic). For such an ergodic process, let T be a positive random variable defined on the sample space of the process, representing a time of failure. The local failure-rate function is assumed to be of the form up(x),-infinity0 is a small number, tending to 0; and, for each u,T=T(u) is the corresponding failure-time. It is shown that X(T(u)) and uT(u) have, for u-->0, a limiting joint distribution and are, in fact, asymptotically independent. The marginal distributions are explicitly given. Let Y be a random variable whose distribution is the limit of that of X(T(u)). Under the hypothesis that p(x) is unknown or of known functional form but with unknown parameters, it is shown how p(x) can be estimated on the basis of independent copies of the random variable Y. The results are applied to the analysis of a case-control study featuring a 'marker' process X(t) and an 'event-time' T. The event in the study is considered to be particularly rare, and this is reflected in the assumption u-->0. The control-distribution is identified with the average marginal distribution of the (periodically stationary) marker process X(t), and the case-distribution is identified with that of Y. The particular application is a biomedical trial to determine the risk of stroke in terms of the level of an anticoagulant in the blood of the patient.

Gonorrhea in male adolescents and young adults in Newark, New Jersey: implications of risk factors and patient preferences for prevention strategies.

BACKGROUND: Although the national rate of gonorrhea declined 68% from 1975 to 1995, rates remain high in many inner-city areas. In 1995, the gonorrhea rate in Newark, NJ, was five times the US rate. OBJECTIVE: To determine factors associated with acquisition of gonorrhea by men in Newark. STUDY DESIGN: A case-control study conducted at the sexually transmitted disease (STD) clinic in Newark, comparing males 15 to 29 years with culture-confirmed gonorrhea to controls with no STD. RESULTS: Compared with controls, males with gonorrhea more frequently reported at least 1 casual sex partner within the preceding month (adjusted odds ratio [OR], 3.2; 95% CI, 1.8-5.7), sex after using marijuana during the preceding month (OR, 2.4; 95% CI, 1.1-5.3), and a history of incarceration (OR, 2.1; 95% CI, 1.2-3.7). Of males with casual partners, having a new casual sexual relationship (onset within the past month) was particularly risky for gonorrhea (OR, 3.9; 95% CI, 1.2-12.7). Incorrect condom use was highly prevalent for both cases and controls. Many persons with gonorrhea reported that they were not willing to consistently use condoms or to have only one partner. CONCLUSIONS: Sex with casual partners is associated with gonorrhea in males, and may be a difficult practice to change. Condoms are often used incorrectly, if at all, in this population. Prevention strategies, in addition to the promotion of condom use and monogamy, may be necessary.

Impact of switching laboratory tests on reported trends in Chlamydia trachomatis infections.

Improvements in the sensitivity and specificity of laboratory testing methods for Chlamydia trachomatis infections in recent years have created potential problems with interpreting data on chlamydia prevalence trends. A switch to a more sensitive test can result in an increase in chlamydia positivity even with no increase in the true disease prevalence. To examine the impact of switching laboratory testing methods on chlamydia positivity trends among women, the authors analyzed data from chlamydia screening programs in family planning clinics in two geographic areas of the United States. Data from 7,287 tests performed in Philadelphia, Pennsylvania, indicated a 46% increase in positivity (from 4.1% to 6.0%) when the clinics switched from a nucleic acid probe assay to a ligase chain reaction test. Data from 35,306 tests performed in Oregon and Washington State laboratories showed a 21% increase in positivity (from 3.3% to 4.0%) when clinics switched from a direct immunofluorescent antibody testing procedure to an enzyme immunoassay with negative gray zone confirmation. These increases were within ranges consistent with the variability of the testing methods and occurred primarily in asymptomatic women and in women over age 20 years. Any switch in laboratory testing methods must be considered when interpreting data on chlamydial infection trends.

Adherence of human immunodeficiency virus-infected patients to antiretroviral therapy.

The impact of demographic, psychosocial, and medical regimen-related variables on adherence of 123 human immunodeficiency virus (HIV)-infected patients to antiretroviral therapy was assessed by means of refill methodology. Satisfaction with social support (P = .029), problem-focused coping (P = .027), and active-behavioral coping (P = .011) correlated significantly with adherence, whereas loss of motivation (P = .006), hopelessness (P = .16), and avoidant coping (p = .015) correlated with nonadherence. At the 6-month follow-up, the mean CD4 cell count differed significantly among adherent versus nonadherent patients (a mean increase of 78/mm3 vs. a mean decrease of 5/mm3; P = .018). Adherence did not correlate with the number of antiretroviral medications consumed per day (mean, 3.0 vs. 2.5). Non-Caucasian patients were more likely to be nonadherent than Caucasian patients (relative risk, 2.5; 95% confidence interval, 1.2-5.3; P = .013); this difference was not explained by age, education, employment, income, history of intravenous drug use, or medical regimen. Non-Caucasian patients, however, were less satisfied with their social support (P = .04) and informational support (P = .016) and were more likely to utilize emotion-focused coping (P = .01). Thus, satisfaction with social support and coping style significantly impacted adherence and likely accounted for the observed racial difference in adherence among HIV-infected patients.

An epidemic of congenital syphilis in Jefferson County, Texas, 1994-1995: inadequate prenatal syphilis testing after an outbreak in adults.

OBJECTIVES: After a syphilis epidemic in Jefferson County, Texas, in 1993 and 1994, congenital syphilis prevalence and risk factors were determined and local prenatal syphilis screening practices were assessed. METHODS: Medical records were reviewed, pregnant women with syphilis were interviewed, and prenatal care providers were surveyed. RESULTS: Of 91 women, 59 (65%) had infants with congenital syphilis. Among African Americans, the prevalence per 1000 live births was 24.1 in 1994 and 17.9 in 1995. Of the 50 women with at least 2 prenatal care visits who had infants with congenital syphilis, 15 (30%) had received inadequate testing. Only 16% of 31 providers obtained an early third-trimester syphilis test on all patients. CONCLUSIONS: Inadequate prenatal testing contributed to this outbreak of congenital syphilis.

Patterns of recurrence and outcome for patients with clinical stage II non-small-cell lung cancer.

Forty-six patients with pathologic clinical stage II non-small-cell lung carcinoma underwent resection with or without adjuvant radiotherapy from 1989 through 1994. These patients were analyzed to determine patterns of recurrence and survival. Surgery consisted of pneumonectomy for 11 patients, bilobectomy for two patients, lobectomy for 29 patients, and wedge or segmental resection for four patients. Adjuvant radiotherapy was delivered to 29 patients, and the median total dose was 54 Gy (range, 44-60 Gy). Median follow-up time was 23 months for all patients and 25 months for surviving patients. Twenty-six of 46 patients have had recurrence. The site of first recurrence was locoregional for 9 of 46 patients (20%) and distant for 17 of 46 patients (37%). The median time to locoregional recurrence was 18 months for patients treated with radiotherapy and 13 months for patients treated without radiotherapy. An isolated locoregional recurrence (with no simultaneous distant recurrence) was seen in 2 of 28 evaluable patients (7%) treated with radiotherapy compared with 3 of 17 patients (18%) not treated with radiotherapy. For all patients, the 3-year disease-free survival rate was 52%, and the overall survival rate was 52%. Among patients treated with radiotherapy, the 3-year disease-free survival and overall survival rates were 56% and 56%, respectively, compared with 46% and 43%, respectively, for patients who did not receive radiotherapy (p values were not significant). The locoregional recurrence rate was 33% for patients with adenocarcinoma and 15% for those with squamous cell carcinoma. The distant recurrence rates by histologic characteristic were 56% and 20%, respectively. For patients with clinical stage II non-small-cell lung cancer, postoperative radiotherapy appears to improve locoregional control. However, the preponderance of recurrences remains distant. Further study is warranted with special emphasis on control of systemic disease.

Total parenteral nutrition via multilumen catheters does not increase the risk of catheter-related sepsis: a randomized, prospective study.

The purpose of this study was to determine in a randomized, prospective manner whether administration of total parenteral nutrition (TPN) via multilumen catheters increases the risk of catheter-related sepsis (CRS). All patients receiving hyperalimentation during a 24-month period were randomized to receive either a double-lumen catheter (DLC) or a triple-lumen catheter (TLC). A total of 101 catheters were placed in 79 patients, of which 49 were DLCs and 52 were TLCs. The patients with DLCs received a total of 784 days of TPN, whereas patients with TLCs received a total of 754 days of TPN. CRS was associated with one (2.0%) of the 49 DLCs vs. one (1.9%) of the 52 TLCs. In comparison, the rate of CRS associated with single-lumen catheters (historical control) at our institution was 1.4% (P > .90). We conclude that the use of multilumen catheters in TPN therapy does not result in an increased risk of CRS.

Screening women for gonorrhea: demographic screening criteria for general clinical use.

OBJECTIVES: The purpose of this analysis was to derive potential gonorrhea screening criteria for women. METHODS: Data corresponding to 44,366 gonorrhea cultures from women 15 through 44 years of age in Columbus, Ohio, were analyzed. RESULTS: Characteristics that were associated with gonococcal infection and were suitable for screening decisions included patient's age and marital status and previous prevalence of gonorrhea at provider site. Probabilities of infection ranged from .001 for married women 25 through 44 years of age at low-prevalence provider sites to .078 for unmarried women 15 through 19 years of age at high-prevalence sites. CONCLUSIONS: Patient's age and marital status and prevalence of gonorrhea at provider site can be used as indicators to ensure testing of high-prevalence groups.

Trends in the prevalence of chlamydial infections. The impact of community-wide testing.

BACKGROUND: Evaluation of existing testing programs should guide the national effort to expand programs for the prevention of chlamydial infections. The Columbus (Ohio) Health Department instituted community-wide testing for Chlamydia trachomatis in 1988. GOALS: To assess trends in the prevalence of chlamydial infection, the coverage of screening, and concurrent trends in the prevalence of gonorrhea. STUDY DESIGN: This was a cross-sectional study of women 15 to 44 years of age tested for C. trachomatis at over 50 provider sites in Columbus, Ohio, from 1989 to 1992. RESULTS: The prevalence of chlamydial infection among all women tested decreased by 33% from 1989 to 1992. Prevalence decreased least (19%) among black women 15 to 19 years of age, the group with the highest initial prevalence (20.2%), even though 42% of this population in the city was tested. Prevalence did not decrease at all among prenatal patients 15 to 19 years of age. For women tested for both gonorrhea and chlamydia, gonorrhea decreased by 39% during the 4-year period. CONCLUSIONS: Screening appeared to have limited effect on the prevalence of chlamydial infection for groups with highest initial prevalence, despite the relatively high percentage of the population tested. Expanding screening programs to include men and instituting behavioral interventions may be necessary to reduce more rapidly the prevalence of chlamydia among these women.