Neonatal depletion of cortical dopamine: effects on dopamine turnover and motor behavior in juvenile and adult rats

Abnormal development of mesoprefrontal dopamine (DA) neurons may contribute to the pathophysiology of schizophrenia. Consistent with this hypothesis, DA nerve terminal density is decreased in the cortex of schizophrenic subjects [M. Akil, J.N. Pierri, R.E. Whitehead, C.L. Edgar, C. Mohila, A.R. Sampson, and D.A. Lewis, Lamina-specific alterations in the dopamine innervation of the prefrontal cortex in schizophrenic subjects, Am. J. Psychiatry, 156 (1999) 1580-1589]. This abnormality may be present early in development, giving rise to dysfunction as an individual matures. The present studies examined the effects of early partial loss of medial prefrontal cortex (mPFC) DA on DA turnover and locomotor behavior in juvenile, pubertal, and adult rats (30, 45, and 60 days of age, respectively). Local infusions of 6-hydroxydopamine on postnatal day (PN) 12-14 produced persistent decreases in basal tissue DA concentrations and increases in 3,4-dihydroxyphenylacetic acid (DOPAC):DA ratios in the mPFC. In the nucleus accumbens of lesioned rats, basal DA concentrations were decreased and DOPAC:DA ratios were increased on PN30, but not PN45 or 60. Footshock (30 min at 0.6 mA) increased DOPAC and DOPAC:DA ratios in the mPFC of PN30 and 60 control rats. These effects were attenuated in age-matched rats previously sustaining approximately 50% loss of mPFC DA on PN12-14. Footshock did not affect DOPAC:DA ratios in the nucleus accumbens of control or lesioned rats. The lesion also failed to alter basal or stress-evoked motor activity. The present data suggest that a decreased density of mPFC DA nerve terminals occurring early in development results in persistent alterations in basal and stress-evoked activity of mesoprefrontal DA neurons, but not mesoaccumbens DA neurons.     

Laparoscopic Heller myotomy provides durable relief from achalasia and salvages failures after botox or dilation

OBJECTIVE: To report outcome after laparoscopic Heller myotomy in a large number of patients. SUMMARY BACKGROUND DATA: Laparoscopic Heller myotomy has been undertaken for over a decade, but most studies involve small numbers of patients with limited follow-up. METHODS: Since 1992, 262 patients have undergone laparoscopic Heller myotomy and been prospectively followed. Concomitant fundoplication was undertaken for a patulous hiatus or large hiatal hernia or to buttress the repair of an esophagotomy until recently when it became routinely applied. With mean follow-up at 32 months, symptoms were scored by patients on a Likert scale (frequency: 0 = Never to 10 = Every time I eat/always; severity: 0 = Not bothersome to 10 = Very bothersome). RESULTS: Before myotomy, 79% received Botox or bag dilation: 52% had Botox, 59% underwent dilation, and 36% had both. Inadvertent esophagotomy occurred in 5%. Concomitant diverticulectomy was undertaken in 4%, and fundoplication was undertaken in 30%. Complications were infrequent. Median length of stay was 1 day. After myotomy, the frequency and severity of symptoms of achalasia and reflux significantly decreased. Eighty-eight percent of patients felt their symptoms were greatly improved or resolved, and 90% felt their outcome was satisfying or better. Ninety-three percent felt they would undergo myotomy again, if necessary. CONCLUSIONS: Laparoscopic Heller myotomy can safely and durably relieve symptoms of dysphagia while also reducing symptoms of reflux. Length of stay is short and patient satisfaction is very high with extended follow-up. Laparoscopic Heller myotomy is strongly encouraged for patients with symptomatic achalasia and is efficacious even after failures of dilation and/or Botox therapy.     

Comparison of posterior capsule opacification rates between hydrophilic and hydrophobic single-piece acrylic intraocular lenses

PURPOSE: To determine the effect of intraocular lens (IOL) material on the development of posterior capsule opacification (PCO) at 1 year. SETTING: Department of Ophthalmology, St. Thomas' Hospital, London, United Kingdom. METHODS: One hundred six eyes of 53 patients with bilateral cataract and no other ocular comorbidity were prospectively randomized to receive a hydrophobic acrylic or hydrophilic acrylic single-piece IOL in the first eye to have surgery. The alternate IOL was implanted in the fellow eye 4 to 6 weeks later. All surgery was performed by a single surgeon. Postoperative follow-up was 1 day, 1 and 6 months, and 1 year. At each visit, the best corrected high- and low-contrast visual acuities were assessed and a high-intensity digital retroillumination photograph was taken. Posterior capsule opacification was assessed from the digital images by a single operator using a dedicated software program and calculated as the percentage area of opacified capsule. RESULTS: One year postoperatively, the median percentage area of PCO was 50.3% in the hydrophilic IOL group and 4.9% in the hydrophobic IOL group (P<.001). The difference in PCO was not accounted for by loss of contact between the capsulorhexis and IOL surface. Further analysis showed that lens epithelial cells tended to invade the posterior capsule at the haptic-optic junction. This was more marked in the hydrophilic IOL group. CONCLUSIONS: The rate of PCO was significantly higher with the hydrophilic IOL. However, the results cannot be attributed to the IOL material alone as they show the importance of both IOL material and design.     

Income inequality and alcohol use: a multilevel analysis of drinking and drunkenness in adolescents in 34 countries

BACKGROUND: Economic inequality has been hypothesized to be a health determinant, independent of poverty and household income. The goal of this study was to explore the contextual influences of income inequality on alcohol use and frequency of drunkenness in adolescents. METHODS: The Health Behaviour in School-aged Children study surveyed 162 305 adolescents (ages 11, 13 and 15 years) in 34 countries, providing self-report data on family affluence, alcohol consumption and episodes of drunkenness. Country-level data on income inequality and overall wealth were retrieved from the United Nations Development Program. RESULTS: Multilevel logistic regression revealed that 11- and 13-year-olds in countries of high income inequality consumed more alcohol than their counterparts in countries of low income inequality (after adjustment for sex, family affluence and country wealth). No such effect on alcohol consumption was found in 15-year-olds. Eleven-year-olds in countries of high income inequality reported more episodes of drunkenness than their counterparts in countries of low income inequality. No such effect of income inequality on drunkenness was found in 13- or 15-year-olds. CONCLUSIONS: Income inequality may have a contextual influence on the use of alcohol among younger adolescents. Findings suggest that economic policies that affect the distribution of wealth within societies may indirectly influence the use of alcohol during early and mid-adolescence.     

Exposure to welding fumes is associated with acute systemic inflammatory responses

Aims: To investigate the acute systemic inflammatory response to welding fume exposure.

Methods: Twenty four welders (42% smokers) and 13 non-exposed controls (23% smokers) were monitored at a welding school. Exposure to fine particulate matter (PM_2.5) was assessed using cyclone samplers. Markers of systemic inflammation, including C-reactive protein (CRP), fibrinogen, and white blood cell (WBC) levels, were determined in peripheral blood samples collected at baseline and after 5.3 (SD 1.0) hours of exposure.

Results: The median PM_2.5 concentration for welders was 1.66 mg/m³, which was significantly greater than that for controls (0.04 mg/m³). Compared to non-smokers, smokers had a significantly higher baseline WBC count, but comparable levels of CRP and fibrinogen. In non-smokers, welding fume exposure was associated with a significant increase in WBC and neutrophil counts immediately following exposure (+0.8x10³/µl, 95% CI 0.1 to 1.6, and +1.0x10³/µl, 95% CI 0.4 to 1.7, respectively). A significant decrease in fibrinogen levels was observed in non-smokers (–32 mg/dl, 95% CI –63 to –1). No significant changes in WBC, neutrophil, and fibrinogen levels were found in smokers. Sixteen hours after welding exposure, CRP levels were found to be significantly increased in both non-smokers and smokers (0.90 mg/l, 95% CI 0.17 to 1.64). PM_2.5 concentrations were found to be significantly associated with absolute neutrophil counts in non-smokers, and CRP levels in both non-smokers and smokers.

Conclusions: High levels of welding fume exposure induce acute systemic inflammation in a relatively young, healthy working population. These results also suggest that smoking may modify the effect of welding fume exposure on specific inflammatory markers.

     

Effect of lignocaine, sodium cromoglycate, and ipratropium bromide in exercise-induced asthma

Eight patients with exercise-induced asthma participated in a single-blind trial comparing the protective effects of inhaled lignocaine (estimated dose 48 mg), sodium cromoglycate (estimated dose 12 mg), and ipratropium bromide (estimated dose 120 μg). Saline was used as control. Effects were assessed from the mean maximal percentage fall in forced expiratory volume in one second (FEV₁) and maximal mid-expiratory flow rates (MMFR) after they had run on a treadmill for eight minutes. There was no significant change in baseline FEV₁ or MMFR before each agent was given. Saline, lignocaine, and sodium cromoglycate did not alter the mean baseline FEV₁ or MMFR significantly. Ipratropium caused bronchodilatation with an increase of 16·3% in the mean FEV₁ (p<0·001) and of 43·4% in the mean MMFR (p<0·05). After exercise the maximal percentage falls in FEV₁ (means and SEM) after saline, lignocaine, sodium cromoglycate, and ipratropium bromide were 38·1% (5·0), 34·5% (6·1), 11·3% (3·7), and 19·3% (7·4) respectively. Similarly, the mean maximal falls in MMFR after saline, lignocaine, sodium cromoglycate, and ipratropium bromide were 54·4% (5·2), 52·9% (7·7), 23·6% (6·6), and 32·1% (10·5) respectively. The inhibitory effects of sodium cromoglycate and ipratropium bromide were significant whereas lignocaine failed to produce an effect. These results suggest that mediator release is an important factor in exercise-induced asthma and that in some patients the effects of the mediators may be on the postsynaptic muscarinic receptors. Local anaesthesia of sensory vagal receptors, on the other hand, does not prevent exercise asthma and these receptors do not appear to have any important role in exercise-induced bronchoconstriction.     

Therapeutic Abortion in a Canadian City

In a city of 200,000, 119 therapeutic abortions were performed during the period 1962 to 1968. Multiple grounds were commonly given for abortion; these often included depression. Very frequently the absence of support from other people was a factor in deciding to perform abortion. Only five psychiatrists were involved in 82 cases seen in psychiatric consultation. Abortions carried out for more conventional medical reasons, including rubella, decreased in 1967 and 1968 but there was an overall increase beginning in 1967. In the later years of the study (1967-68) a higher proportion of patients were single, younger, had had no previous pregnancy and were aborted later in pregnancy; more were sterilized.

A marked increase in abortion rate related particularly to the activity of one of the psychiatrists.

One hundred and sixty-six abortions were performed in 1969; a comparable figure (179) was obtained from one other Canadian centre; another centre had performed more (291); two others, 109 and 63; the combined total for 27 other centres from whom replies were obtained was 186.