Are Anesthesia and Surgery during Infancy Associated with Decreased White Matter Integrity and Volume during Childhood?

BACKGROUND: Anesthetics have neurotoxic effects in neonatal animals. Relevant human evidence is limited. We sought such evidence in a structural neuroimaging study. METHODS: Two groups of children underwent structural magnetic resonance imaging: patients who, during infancy, had one of four operations commonly performed in otherwise healthy children and comparable, nonexposed control subjects. Total and regional brain tissue composition and volume, as well as regional indicators of white matter integrity (fractional anisotropy and mean diffusivity), were analyzed. RESULTS: Analyses included 17 patients, without potential confounding central nervous system problems or risk factors, who had general anesthesia and surgery during infancy and 17 control subjects (age ranges, 12.3 to 15.2 yr and 12.6 to 15.1 yr, respectively). Whole brain white matter volume, as a percentage of total intracranial volume, was lower for the exposed than the nonexposed group, 37.3 ± 0.4% and 38.9 ± 0.4% (least squares mean ± SE), respectively, a difference of 1.5 percentage points (95% CI, 0.3 to 2.8; P = 0.016). Corresponding decreases were statistically significant for parietal and occipital lobes, infratentorium, and brainstem separately. White matter integrity was lower for the exposed than the nonexposed group in superior cerebellar peduncle, cerebral peduncle, external capsule, cingulum (cingulate gyrus), and fornix (cres) and/or stria terminalis. The groups did not differ in total intracranial, gray matter, and cerebrospinal fluid volumes. CONCLUSIONS: Children who had anesthesia and surgery during infancy showed broadly distributed, decreased white matter integrity and volume. Although the findings may be related to anesthesia and surgery during infancy, other explanations are possible.

Are anesthesia and surgery during infancy associated with altered academic performance during childhood?

BACKGROUND: Although studies in neonatal animals show that anesthetics have neurotoxic effects, relevant human evidence is limited. We examined whether children who had surgery during infancy showed deficits in academic achievement. METHODS: We attempted to contact parents of 577 children who, during infancy, had one of three operations typically performed in otherwise healthy children. We compared scores on academic achievement tests with population norms. RESULTS: Composite scores were available for 287 patients. The mean normal curve equivalent score was 43.0±22.4 (mean±SD), lower than the expected normative value of 50, P<0.0001 by one-sample Student t test; and 35 (12%) had scores below the 5th percentile, more than expected, P<0.00001 by binomial test. Of 133 patients who consented to participate so that their scores could be examined in relation to their medical records, the mean score was 45.9±22.9, P=0.0411; and 15 (11%) scored below the 5th percentile, P=0.0039. Of 58 patients whose medical records showed no central nervous system problems/potential risk factors during infancy, 8 (14%) scored below the 5th percentile, P=0.008; however, the mean score, 47.6±23.4, was not significantly lower than expected, P=0.441. Duration of anesthesia and surgery correlated negatively with scores (r=-0.34, N=58, P=0.0101). CONCLUSIONS: Although the findings are consistent with possible adverse effects of anesthesia and surgery during infancy on subsequent academic achievement, other explanations are possible and further investigations are needed.

Acitretin for lichen amyloidosus.

We present two cases of lichen amyloidosus treated with retinoids. A 57-year-old Vietnamese woman has had extensive generalized recalcitrant lichen amyloidosus for 23 years. Treatment with oral etretinate (25 mg/day) for 3 years, and later oral acitretin (10 mg/day) for the past 10 years, has controlled the pruritus and flattened the hyperkeratotic papules. Whenever the acitretin was ceased her symptoms flared within weeks. On each occasion reintroduction of acitretin was effective within 1-2 months. The second case is that of a 51-year-old Australian Aboriginal woman who had a 2-year history of lichen amyloidosus affecting her lower legs. A 2-month course of oral acitretin (25 mg b.d.) produced a marked improvement in both the pruritus and hyperkeratotic papules. She was then lost to follow up for 2 years, during which time her symptoms recurred.

Vulnerability-specific stress generation: an examination of depressogenic cognitive vulnerability across multiple domains.

BACKGROUND AND OBJECTIVES: Although there is supporting evidence for the stress generation hypothesis (i.e., the tendency for depression-prone individuals to experience more negative dependent events influenced by their behaviors and characteristics), additional research is required to advance current understanding of the specific types of dependent events relevant to this effect. The present study elaborated on the stress generation hypothesis, in which the content of negative dependent events experienced by individuals is contingent upon, and matches, the nature of their particular vulnerabilities. This extension was tested within the context of Cole's competency-based model of depression. DESIGN: Participants (n=185) were assessed at two time-points separated by a four-month interval. METHODS: Self-perceived competence in academic, social, and appearance domains at the initial time-point were examined in relation to negative life events prospectively occurring over the four-month follow-up period, assessed using the "contextual threat" method. RESULTS: Partial support was obtained for vulnerability-specific stress generation. Stress-generation specificity was found for self-perceived competence in appearance and academic domains, but not for self-perceived social competence. CONCLUSIONS: The current findings are consistent with the possibility of a more complex relation between self-perceived social competence and domain-congruent stress generation. Individuals may be more likely to experience negative dependent events in domains matching their specific vulnerabilities.

High Behavioral Approach System (BAS) sensitivity, reward responsiveness, and goal-striving predict first onset of bipolar spectrum disorders: a prospective behavioral high-risk design.

A prospective, behavioral high-risk design provided a theoretically guided examination of vulnerability to first onset of bipolar spectrum disorder based on the Behavioral Approach System (BAS) model. Adolescents (ages 14-19) at an "age of risk" for bipolar disorder onset were screened on BAS sensitivity by interviewers blind to current symptoms, lifetime history, and family history of psychopathology. Participants were selected with high versus moderate levels of BAS sensitivity and administered a lifetime diagnostic interview. Those with a bipolar spectrum disorder, psychosis, or hypomanic episode with onset prior to the BAS sensitivity assessment were excluded. High BAS (n = 171) and moderate BAS (n = 119) sensitivity participants in the final sample completed baseline measures of symptoms, goal-setting, and reward responsiveness and were followed prospectively with semistructured diagnostic interviews every 6 months. Consistent with the vulnerability hypothesis of the BAS model of bipolar disorder, high BAS participants had a greater likelihood, and shorter time to onset, of bipolar spectrum disorder than moderate BAS participants across an average of 12.8 months of follow-up (12.9% vs. 4.2%), controlling for baseline depressive and hypomanic symptoms, and family history of bipolar disorder. High reward responsiveness on a behavioral task and ambitious goal-striving for popular fame and financial success (but not impulsivity) also predicted first onset of bipolar spectrum disorder controlling for the covariates and BAS risk group, and ambitious goal-striving partially mediated the BAS risk group effect. We discuss implications of the findings for the BAS model of bipolar disorder and early intervention efforts.

Effect of the glycemic index of carbohydrates on Acne vulgaris.

Acne vulgaris may be improved by dietary factors that increase insulin sensitivity. We hypothesized that a low-glycemic index diet would improve facial acne severity and insulin sensitivity. Fifty-eight adolescent males (mean age ± standard deviation 16.5 ± 1.0 y and body mass index 23.1 ± 3.5 kg/m(2)) were alternately allocated to high or low glycemic index diets. Severity of inflammatory lesions on the face, insulin sensitivity (homeostasis modeling assessment of insulin resistance), androgens and insulin-like growth factor-1 and its binding proteins were assessed at baseline and at eight weeks, a period corresponding to the school term. Forty-three subjects (n = 23 low glycemic index and n = 20 high glycemic index) completed the study. Diets differed significantly in glycemic index (mean ± standard error of the mean, low glycemic index 51 ± 1 vs. high glycemic index 61 ± 2, p = 0.0002), but not in macronutrient distribution or fiber content. Facial acne improved on both diets (low glycemic index -26 ± 6%, p = 0.0004 and high glycemic index -16 ± 7%, p = 0.01), but differences between diets did not reach significance. Change in insulin sensitivity was not different between diets (low glycemic index 0.2 ± 0.1 and high glycemic index 0.1 ± 0.1, p = 0.60) and did not correlate with change in acne severity (Pearson correlation r = -0.196, p = 0.244). Longer time frames, greater reductions in glycemic load or/and weight loss may be necessary to detect improvements in acne among adolescent boys.

Patterns and density of early tracheal colonization in intensive care unit patients.

OBJECTIVE: The study aimed to describe the patterns and density of early tracheal colonization among intubated patients and to correlate colonization status with levels of antimicrobial peptides and inflammatory cytokines. DESIGN: The was a prospective cohort study. SETTING: The study was conducted in medical and cardiovascular intensive care units of a tertiary referral hospital. PATIENTS: Seventy-four adult patients admitted between March 2003 and May 2006 were recruited for the study. INTERVENTIONS: Tracheal aspirates were collected daily for the first 4 days of intubation using standardized, sterile technique and sent for quantitative culture and cytokines, lactoferrin and lysozyme measurements. MEASUREMENTS AND MAIN RESULTS: The mean acute physiology and chronic health evaluation (APACHE II) score in this cohort was 24 +/- 7. Proportion of subjects colonized by any microorganism increased over the first 4 days of intubation (47%, 60%, 70%, 70%, P = .08), but density of colonization for bacteria or yeast did not change significantly. No known risk factors predicted tracheal colonization on day 1 of intubation. Several patterns of colonization were observed (persistent, transient, new colonization, and clearance of initial colonization).The most common organisms cultured were Candida albicans and coagulase-negative Staphylococcus. Levels of cytokines, lactoferrin, or lysozyme did not change over time and were not correlated with tracheal colonization status. Four subjects (6%) had ventilator-associated pneumonia. CONCLUSIONS: The density of tracheal colonization did not change significantly over the first 4 days of intubation in medical intensive care unit patients. There was no correlation between tracheal colonization and the levels of antimicrobial peptides or cytokines. Several different patterns of colonization may have to be considered while planning interventions to reduce airway colonization.