Axis II psychopathology as a function of Axis I disorders in childhood and adolescence

OBJECTIVE: To examine the occurrence of elevated personality disorder (PD) dimensional scores in a community sample of young adults as a function of the occurrence of Axis I disorders through age 18 years. METHOD: 299 individuals who had been interviewed regarding Axis I disorders twice while in adolescence (first when 14 through 18 years of age) were carefully assessed regarding Axis I and II psychopathology at age 24. RESULTS: The prevalence of PD diagnoses was relatively low (3.8% in participants with a history of Axis I versus 1.7% in participants with no Axis I history). The occurrence of all four Axis I diagnostic categories (major depression, anxiety disorders, disruptive behavior disorders, substance use disorders) in childhood and adolescence was associated with elevated PD dimensional scores. The likelihood of elevated PD dimensional scores increased as a function of the number of Axis I disorders. Elevated PD scores were significantly associated with a negative course of major depression. CONCLUSIONS: Although the rates of PDs were low, the findings suggest a substantial degree of association between early-onset Axis I disorders and Axis II psychopathology in young adulthood. More research is needed to develop assessment and treatment recommendations addressing the early manifestations of PDs.     

The Employee Health Care Value Survey: round one

In a groundbreaking arrangement, a consortium of large employers--the Xerox, GTE, and Digital Equipment Corporations--launched the Employee Health Care Value Survey during fall 1993. Completed by 24,306 employees, this survey was used to develop comparable methods for assessing corporate health care benefit strategies. It also enabled fair comparisons of thirty-two health plans across the country on more than sixty criteria. Variation in performance among plans was substantial, with managed care plans--particularly prepaid group practices and individual practice associations (IPAs)--recording the most favorable rankings on disenrollment, overall satisfaction, and other measures of "bottom-line performance." Variation in enrollees' health among plans was more modest, with indemnity enrollees posing a somewhat greater illness burden to their plans than enrollees of other plan types. The employers and evaluated health plans are now using the results for multiple purposes, including quality improvement initiatives, employee-based plan performance reports, employee contribution strategies, and health promotion programs.     

Homonucleotide tracts, short repeats and CpG/CpNpG motifs are frequent sites for heterogeneous mutations in the neurofibromatosis type 1 (NF1) tumour-suppressor gene

Glutamatergic synaptic potentials induced by micromolar concentrations of the potassium conductance blocker 4-aminopyridine (4-AP) were recorded intracellularly from rat neostriatal neurons in the presence of 10 microM bicuculline (BIC). These synaptic potentials originate from neostriatal cortical and thalamic afferents and were completely blocked by 10 microM 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) plus 100 microM D-2-amino-5-phosphonovaleric acid (2-APV). Their inter-event time intervals could be fitted to exponential distributions, suggesting that they are induced randomly. Their amplitude distributions had most counts around 1 mV and fewer counts with values up to 5 mV. Since input resistance of the recorded neurons is about 40 M omega, the amplitudes agree to quantal size measurements in mammalian central neurons. The action of a D2 agonist, quinpirole, was studied on the frequency of these events. Mean amplitude of synaptic potentials was preserved in the presence of 2-10 microM quinpirole, but the frequency of 4-AP-induced glutamatergic synaptic potentials was reduced in 35% of cases. The effect was blocked by the D2 antagonist sulpiride (10 microM). Input resistance, membrane potential, or firing threshold did not change during quinpirole effect, suggesting a presynaptic site of action for quinpirole in some but not all glutamatergic afferents that make contact on a single cell. The present experiments show that dopaminergic presynaptic modulation of glutamatergic transmission in the neostriatum does not affect all stimulated afferents, suggesting that it is selective towards some of them. This may control the quality and quantity of afferent flow upon neostriatal neurons.     

Phenotype of striatal cells expressing c-Fos following amphetamine treatment of rats with intrastriatal dopaminergic grafts

Activation of the nigrostriatal dopaminergic system by psychostimulants such as amphetamine increases c-Fos expression in the striatum, mostly in the striatonigral substance P-ergic pathway. This effect is greatly reduced in the neostriatum deprived of dopaminergic afferents. Dopaminergic grafts implanted into the denervated neostriatum restore the reactivity of the striatum to amphetamine. However, the number of striatal neurons expressing c-Fos is greatly increased in the graft-bearing striatum compared with the normal striatum. We examined whether this increase in the number of c-Fos-expressing neurons corresponds to the recruitment of a new neuron population, or whether it reflects an increase in the proportion of substance P-ergic neurons exhibiting activation of c-Fos. Adult rats received a unilateral 6-hydroxydopamine lesion of the ascending dopaminergic mesotelencephalic pathway, and a suspension of embryonic mesencephalic neurons was subsequently implanted into the denervated neostriatum. Three months after implantation, animals were injected with d-amphetamine (5 mg/kg) and killed 2 h later. In the first experiment, striatal sections were processed to visualize both c-Fos protein, by immunohistochemistry, and preproenkephalin A or substance P, by in situ hybridization. In the second experiment, c-Fos and neuropeptide Y were visualized on the same sections. In addition, some sections incubated with anti-c-Fos antibody were counterstained with toluidine blue in order to determine whether cholinergic neurons were expressing c-Fos following amphetamine treatment. The density of neurons expressing c-Fos following amphetamine treatment was three-fold higher in the graft-bearing striata than in the striata of control animals. Approximately 75% of the c-Fos expressing cells were substance P-ergic in control animals whereas 6% were enkephalinergic and only a few were neuropeptide Y-ergic or cholinergic. Similar proportions were found in the graft-bearing striatum, signifying that the pattern of activation of c-fos following amphetamine administration is not changed by the graft. Thus, the increased expression of c-Fos predominantly reflects a graft-induced increase in the proportion of neurons expressing c-Fos within the same population of neurons which normally expresses c-Fos in the striatum, i.e. the striatonigral substance P-ergic neurons; there is no recruitment of a new neuronal population. This increased activation of the striatonigral substance P-ergic pathway may underlie the abnormal behavioural reactions brought about by amphetamine-induced stimulation of the implanted dopaminergic neurons.     

Paracetamol poisoning in the north east of England: presentation, early management and outcome

1. Paracetamol is increasingly involved in self-poisoning in the United Kingdom and remains a common cause of fatal poisoning. 2. To document the epidemiology and early management of paracetamol poisoning data were collected on consecutive patients with suspected paracetamol poisoning presenting to 6 hospitals in the North East of England over 12 weeks in 1994. 3. There were 400 presentations (attendance rate 1.14/10(3) population/yr) involving 343 persons (45% male). Paracetamol concentrations at 4 h correlated weakly with reported paracetamol dose (R = 0.49, P < 0.0001) and were similar comparing those treated and not treated by gastric decontamination. 4. In 38 (9%) cases paracetamol concentrations were above the appropriate nomogram treatment line, including 3% and 20% of patients who reported ingesting less than and more than 12 g respectively. In 21 patients acetylcysteine treatment was deferred until admission to the ward, the mean delay involved was 2.8 h. 5. One patient died, from arrhythmias caused by co-ingested dothiepin. 6. Paracetamol poisoning is common. Most cases do not have potentially toxic plasma paracetamol concentrations, but those who do often present late and antidotal treatment may be delayed inappropriately.     

A patient with Wegener''s granulomatosis presenting with a subarachnoid hemorrhage: case report and review of CNS disease associated with Wegener''s granulomatosis

1. Travellers to high altitude often complain of paroxysmal cough, which has not been previously investigated. We recorded overnight cough frequency and cough-receptor sensitivity to inhaled citric acid in a group of climbers travelling to 5300 m or higher. 2. Cough frequency, monitored in ten subjects, increased from a median of 0 coughs at sea level (range 0-1) to 5 coughs at 5000 m (range 0-13) and to over 60 coughs in subjects ascending to 7000 m. Citric acid cough threshold, measured in 42 subjects, was unchanged on arrival at 5300 m compared with sea level (geometric mean difference 1.26, 95% confidence intervals 0.84-1.89, P = 0.25), but was significantly reduced after 6 days, or more, at altitude compared with sea level (geometric mean difference 2.2, 95% confidence intervals 1.54-3.15, P = 0.0002). Cough threshold was not related to symptoms of acute mountain sickness, oxygen saturation, carbon dioxide tension or lung function. 3. These results indicate an increase in cough and cough-receptor sensitivity after some days at altitude. This may be due to respiratory tract damage from breathing cold dry air at increased ventilatory rates. Other explanations, such as sub-clinical pulmonary oedema or an effect on the cough centre of acclimatization to altitude, cannot be excluded.     

Synthetic and model computational studies of molar rotation additivity for interacting chiral centers: a reinvestigation of van't Hoff's principle

When plane-polarized light impinges on a solution of optically active molecules, the polarization of the light that emerges is rotated. This simple phenomenon arises from the interaction of light with matter and is well understood, in principle, van't Hoff's rule of optical superposition correlates the molar rotation with the individual contributions to optical activity of isolated centers of asymmetry. This straightforward empirical additivity rule is rarely used for structure elucidation nowadays because of its limitations in the assessment of conformationally restricted or interacting chiral centers. However, additivity can be used successfully to assign the configuration of complex natural products such as hennoxazole A if appropriate synthetic partial structures are available. Therefore, van't Hoff's principle is a powerful stereochemical complement to natural products' total synthesis. The quest for reliable quantitative methods to calculate the angle of rotation a priori has been underway for a long time. Both classical and quantum methods for calculating molar rotation have been developed. Of particular practical importance for determining the absolute structure of molecules by calculation is the manner in which interactions between multiple chiral centers in a single molecule are included, leading to additive or non-additive optical rotation angles. This problem is addressed here using semi-empirical electronic structure models and the Rosenfeld equation.     

Ornithine decarboxylase activity in muscle, liver, and intestinal tissue of turkeys during a short-term feed withdrawal and following refeeding

The activity of ornithine decarboxylase (ODC), an enzyme associated with cellular growth and protein synthesis, was examined in breast muscle, liver, and intestinal tissues of turkeys during a short-term period of feed withdrawal (FW) and following refeeding. Turkeys from a randombred control line were reared under standard management practices to 3 wk of age in battery brooders. Feed was then withdrawn from FW birds for a 48-h period, after which feed was consumed ad libitum. Control birds consumed feed ad libitum throughout the test period. Tissues were collected from 12 birds per treatment following 24 and 48 h of FW and at 6, 12, 24, and 48 h following refeeding for later determination of tissue ODC activity. Activity of ODC was greater in tissue from the small intestine than in liver tissue and both had greater activity than that exhibited by breast muscle. Short-term FW and refeeding produced differential responses in ODC activity of the three tissues examined. Feed withdrawal resulted in a reduction of ODC activity in intestinal tissue, whereas activity was unaffected for liver or breast muscle tissues. Compensatory increases in ODC activity were observed in liver and intestinal tissues; however, the increase was both more rapid and transitory in small intestine than in liver tissue. The ODC activity in breast muscle was largely unaffected by short-term FW and refeeding. Patterns of ODC activity in liver during FW and refeeding closely resembled patterns observed for absolute and relative liver weight. Thus, the results of the present experiment demonstrate that short-term FW and refeeding influence underlying growth mechanisms of supply organs, such as hepatic and intestinal tissue, in addition to affecting overall growth and muscle development.