Reduced brainstem size in children with autism.

Recently, structural brain abnormalities as well as functional abnormalities of the brainstem have been reported in autistic children. The authors undertook an analytic study of the brainstem in autistic children by means of magnetic resonance imaging (MRI). The MRI scans of 29 autistic children were compared with 15 control MRI scans. The autistic children were divided into two groups according to DQ (IQ) level: the DQ (IQ) greater than or equal to 80 group and the DQ (IQ) less than 80 group. The midbrain and pons were measured, and the ratio of the midbrain and pons sizes versus the cranium size were calculated. The brainstem size was found to be significantly smaller in the autistic group. In particular, the reduction in brainstem size tended to be greater in the low DQ (IQ) group when compared with the high DQ (IQ) one, though there was no significant difference (p less than 0.1). This suggests that the brainstem is anatomically altered in autistic children.     

Brainstem auditory evoked potentials in patients with multi-infarct dementia and dementia of the Alzheimer type

Brainstem auditory evoked potentials (BAEPs) were recorded in 25 patients with multi-infarct dementia (MID) (mean age 71.2 years), 16 patients with dementia of the Alzheimer type (DAT) (mean age 70.6 years), and 34 normal subjects (mean age 69.1 years). Both MID and DAT patients showed significant prolonged interpeak latencies between waves I and V (I-V IPLs) compared to normal subjects (p less than .001 and p less than .01, respectively). In patients with MID, both I-III IPLs and III-V IPLs were significantly longer than those of normal subjects (p less than .01 and p less than .01 respectively). On the other hand, only III-V IPLs were significantly prolonged in patients with DAT (p less than .01). There were no significant differences between MID and DAT with regard to any of the IPLs. Present results suggest that the brainstem lesions are located in the auditory pathways in patients with MID and DAT. However, with BAEP measurements, we were not able to discriminate between patients with MID and DAT.     

Gender differences in hypothalamic-pituitary-adrenal (HPA) axis reactivity

The present study was designed to determine whether there are gender differences in hormonal response patterns to HPA axis activation. To this end, two methods of activating the HPA axis were employed: a standardized psychological stress test and a pharmacological challenge. Healthy subjects (mean age 23.4 years, SD 7.0 years) completed a naloxone challenge and/or the modified Trier Social Stress Test (TSST). For the naloxone challenge, two baseline blood samples were obtained. Placebo was then administered (0 min), followed by increasing doses of intravenous naloxone (50, 100, 200 and 400 microg/kg) at 30-min intervals. Post-placebo blood samples were collected at 15-min intervals for 180 min. The TSST consisted of 5 min of public speaking followed by 5 min of mental arithmetic exercises. Three baseline and five post-TSST blood samples were drawn. Eighty subjects (53 male, 27 female) underwent the TSST. Following the psychological stressor, adrenocorticotropin (ACTH) and cortisol responses were significantly greater in male subjects compared to female subjects (z=-2.34, p=0.019 and z=-2.12, p=0.034, respectively). Seventy-two subjects (52 male, 20 female) underwent HPA axis activation induced by naloxone. In contrast to the TSST, cortisol responses to the naloxone challenge were significantly greater in female subjects compared to male subjects (z=4.11, p<0.001). Forty-one subjects (25 male, 16 female) completed both the TSST and naloxone challenge. In this subset, ACTH and cortisol responses to the TSST did not differ significantly by gender, although the effect size was moderate to large. Adrenocorticotropin and cortisol responses to the naloxone challenge were significantly greater in female subjects compared to male subjects (z=2.29, p=0.022 and z=4.34, p<0.001, respectively). In summary, male subjects had greater HPA axis responses to a psychological stressor than female subjects, and females had greater hormonal reactivity than males to pharmacological stimulation with naloxone. Such differences are of interest as potential contributors to gender differences in health risks.     

Prospective study of multiple sclerosis with early onset

Fifty-four subjects (36 females and 18 males) affected by clinically definite multiple sclerosis (MS) and with onset of the disease at 15 years of age or before were prospectively studied in five Italian MS centres. Female/male ratio was 4.7 in subjects with age > or = 12 years, suggesting a role of hormonal changes in triggering MS onset The mean follow-up duration was 10.9+/-5.6 years. The functional systems more frequently involved at onset were the pyramidal and brainstem (both in 28% of cases). The onset was monosymptomatic in 31 subjects (57%). The course was relapsing-remitting in 39 subjects (72%) and relapsing-progressive in 15 (28%). Disability was assessed by the Expanded Disability Status Scale (EDSS): the mean score after 8 years of follow up was 3.5 (+/-2.5). The score was <4 in 68% of cases, between 4 and 6 in 8% of cases, >6 in 24% of cases. Disability after 8 years was highly predicted by disability in the first year (p=0.008). There was a tendency to a worse prognosis in relation to the number of relapses in the first 2 years (p=0.08). The outcome was not influenced by the characteristics of symptoms at onset age and gender.     

Short-latency somatosensory and brainstem auditory evoked potentials in patients with Parkinson's disease

Short-latency somatosensory evoked potentials (SSEPs) and brainstem auditory evoked potentials (BAEPs) were recorded in 44 patients with Parkinson's disease (mean age 67.3 years) and 23 normal subjects (mean age 69.3 years). Patients with Parkinson's disease and normal subjects did not show any significant difference with regard to the interpeak latencies between N13 and N20 central conduction time (CCTs). Likewise, there were no significant differences in CCTs between patients with and without dementia. The interpeak latencies between waves I and V (I-V IPLs) in patients with Parkinson's disease were significantly longer than those of the normal subjects (p less than 0.05). In particular, patients with dementia revealed significant prolongation of I-V IPLs compared to patients without dementia and normal subjects (p less than 0.01, p less than 0.001) although no significant differences were observed between patients without dementia and normal subjects. These results show that auditory brainstem pathways are involved in Parkinson's disease patients with dementia.     

Vertebrobasilar arterial dolichoectasia. Complications and prognosis]

Symptomatic dolichoectasia of the vertebrobasilar system was found in 23 patients (16 males and 7 females, mean age: 62 years) during a 13-year period. Arterial hypertension was noted in 20 cases and associated aortic ectasia in 4. The malformation was identified in all patients on CT completed by angiography in 19, MRI in 7. Autopsy was performed in 5 cases. Fourteen subjects (group 1) presented with a vascular event (ischemic in 13) affecting the brainstem and/or cerebellum. Nine other patients (group 2) had a chronic symptomatology resulting from compression of the cranial nerves, central nervous system and/or CSF pathway. Two patients died of stroke within the first month (rupture of the ectasia in one and occlusion in the other one). The 21 survivors were followed for a mean period of 45.3 months. Eight patients had a stroke, with a significantly higher incidence in group 1 than in group 2 (p less than 0.05). Ten patients (5 in each group) developed progressive dementia possibly resulting from multiple cerebral infarction, hypertensive leucoencephalopathy, and/or hydrocephalus. Twelve patients died during the follow-up (4 of stroke, 6 of profound mental and motor deterioration, one from ruptured ectatic aorta, and the last one of unrecognized cause). The actuarial survival rate was 60% after 3 years of follow-up. Except for the incidence of stroke, inaugural manifestations (stroke vs nervous compression) did not seem to influence the long-term prognosis.     

The middle cerebral artery flow velocities during head-up tilt testing in diabetic patients with autonomic nervous system dysfunction

BACKGROUND: The goal of this study was to examine the effects of diabetes mellitus on the trend of mean arterial velocity (v(m)) in both middle cerebral arteries during head-up tilt (HUT). METHODS: The study was performed in 20 patients, 9 females and 11 males (mean age 51 +/- 12 years) with an average 17-year history of insulin-dependent diabetes mellitus type I or II and a dysfunction of the autonomic nervous system confirmed by cardiocirculatory tests [Valsalva maneuver, deep breathing test, handgrip test, orthostatic test and spectral analysis of heart rate (HR) variability], and 19 age-matched healthy volunteers, 9 females and 10 males (mean age 48 +/- 6.8 years). v(m) was measured by a transcranial Doppler monitoring system during a 5-min baseline period, followed by a 5-min HUT in the upright position (90 degrees ). Mean arterial blood pressure (MAP), HR and end-tidal CO(2) (Et-CO(2)) were monitored concomitantly. RESULTS: In healthy volunteers, v(m) decreased stepwise during the first minute of HUT, reaching a minimum during the last 2 min of the test (v(m): basal 63.0 +/- 11.7 cm/s, 1st min 57.6 +/- 12.2 cm/s, 2nd min 55.9 +/- 12.6 cm/s, 3rd min 53.4 +/- 12.6 cm/s, 4th min 52.1 +/- 12.7 cm/s, 5th min 51.3 +/- 13.5 cm/s). In the supine position, v(m) recovered and reached the resting v(m) values. It declined gradually during HUT and less steeply in diabetic (v(m): basal 54.4 +/- 10.1 cm/s, 1st min 51.96 +/- 9.3 cm/s, 2nd min 50.7 +/- 11.6 cm/s, 3rd min 50.5 +/- 11.4 cm/s, 4th min 49.5 +/- 10.7 cm/s, 5th min 48.8 +/- 11.5 cm/s) than in healthy subjects. v(m) differed significantly (p = 0.00) between rest and HUT in both groups. The differences in MAP, HR and Et-CO(2) during rest and HUT between the groups were not statistically significant (p DeltaMAP = 0.36, p DeltaHR = 0.86, p DeltaEt-CO(2) = 0.97). The results of the analysis of variance of v(m) for repeated measurements between the two groups of subjects were highly significant (p = 0.00). The model of linear regression analysis was significant (p = 0.007). Diabetes was significant in the model (p = 0.00), while DeltaMAP, DeltaHR and DeltaEt-CO(2) were not. CONCLUSIONS: These findings may indicate that vasomotor responses during HUT testing are decreased in diabetic patients.     

MATHEMATICAL EXPRESSION OF RELATIONSHIP BETWEEN AUDITORY BRAINSTEM TRANSMISSION TIME AND AGE

Brainstem transmission time (BTT) was studied in 71 subjects ranging in age from one day to 29 years in order to find a mathematical expression to best describe the relationship between BTT and age. The mathematical function which relates BTT to age is exponential. Using this data, the BTT confidence limit was calculated for subjects from birth through to eight years. Repeated recordings of auditory brainstem responses were performed in several children as they grew older and these verified the normal maturational processes of the brainstem structures in the developing infant and young child.     

Statistics and reinvestigation of the 4/s variant of basic EEG activity (author's transl)

We selected our patients from 1961 to 1973 (60 500 patients, 66 661 EEG recordings) for the 4/s variant of EEG activity according to the characteristics described in the literature. In 1.9% (115 patients) this EEG variant was evident. In addition, 25 out of 50 variant patients from this group were reexamined. In regard to amplitude, local distribution, frequency concentration around 4/s, our findings concur with those of other authors. Slower frequencies of the 4/s variant occur more often at advanced age. The age median was 32.7 years compared with 42.5 years in the rest of the cases examined in the clinic and out patient clinic over a period of 15 years. This age difference is significant (P less than 0.001). The 4/s variant did not occur more often in men than in women. Only the most common clinical diagnosis, vascular headache or migraine (36%), occurred with significantly higher incidence in 4/s variant patients (P less than 0.001). Other clinical diagnoses showed the same distribution in EEG variant patients and other patients of this clinic. EEG reexaminations carried out over a long period of time are an important criterion in evaluating 4/s activity in the posterior regions of the cranium as a--possibly constitutional--4/s variant of basic cerebroelectric activity.     

Chronic (“normal pressure”) hydrocephalus in childhood and adolescence

Normal pressure hydrocephalus (NPH) is generally considered to be a disorder of the adult and geriatric population. Only a few reports have described the possible occurrence of this condition in children. A series of 16 patients aged less than 20 years forms the basis of the present report. Among these 16 patients, 11 had a clearly identified etiologic factor and 7 had had a shunt previously implanted. The majority of patients exhibited at least two elements of the adult's triad of psychomotor retardation (14 cases) and/or psychotic-like symptoms (4 cases), gait anomalies (8 cases), and sphincter disturbances (3 cases). Six patients had their intracranial pressure (ICP) monitored. ICP values were estimated to be within the normal limits for age. All the 16 patients underwent shunting or shunt revision. Surgical results were as follows (mean follow-up 20±17.2 months): a good response to shunting was obtained in 12 cases (cured: 5, improved: 7), while the other 4 patients failed to improve. It seems likely that associated parenchymal disorders have played a major role in therapeutic failures. In children showing ventricular dilation on computed tomographic (CT) analysis and a clinical picture of subtle psychomotor deterioration, it may be difficult to distinguish an active disorder of the CSF dynamics from arrested hydrocephalus. Since intracranial manometry cannot be undertaken as a routine procedure, less invasive methods such as cerebrospinal fluid (CSF) tap test, psychometric or urodynamic tests deserve special attention as reliable predictors of outcome after shunting. Because most patients undergo shunting without prior assessment of their CSF pressure, the term chronic hydrocephalus is proposed as an alternative designation to NPH, since there is little argument for maintaining an instrumentally based definition of the syndrome.Presented at the XIV Congress of the European Society for Paediatric Neurosurgery, Lyon, France, 21–23 September 1994     

Central core disease: Histochemical and ultrastructural study of muscle biopsies of father and daughter

Summary Two cases of central core disease, father and daughter, of a family with dominant autosomal inheritance, are presented, one with bilateral congenital dislocation of the hip. Muscle biopsy was performed in both cases. Oxidative enzymes evidenced only type I fibers, most of them presenting a central core and not uncommonly more than one. On electron microscopy the cores generally appeared well demarcated from the surrounding fibrils and were characterized by lack of mitochondria and abnormalities of the Z line. Transitional aspects from normal fibers to completely unstructured cores were observed, as well as from well structured and unstructured cores. These findings are discussed in the light of the previous literature and particular attention is paid to the problem of differentiation between central core and multicore disease. The pathogenesis of the muscular alteration is also discussed in relation with the possibility of their neurogenic origin. Eventually, the histochemical and ultrastructural similarities between central cores and target fibers are focused.

---

Zusammenfassung Aus einer Familie, in welcher die Erkrankung autosomal dominant vererbt wird, werden Vater und Tochter mit Central Core Disease beschrieben. Bei einem Fall besteht außerdem eine bilaterale congenitale Hüftgelenksluxation. Die in beiden Fällen durchgeführte Muskelbiopsie ergab folgendes: Dargestellt durch den histochemischen Nachweis oxydativer Enzyme fanden sich ausschließlich Typ-I-Fasern, von welchen die meisten ein und nicht selten sogar mehrere Central Core aufwiesen. In der Elektronenmikroskopie erschienen die Cores allgemein gut von den umgebenden Fibrillen abgegrenzt und waren durch das Fehlen von Mitochondrien und Anomalien der Z-Linien charakterisiert. Es wurden Übergänge zwischen normalen Fasern einerseits und vollständig unstrukturierten Cores andererseits beobachtet, wie auch Übergänge von gut strukturierten und unstrukturierten Cores. Die Befunde werden unter Berücksichtigung der einschlägigen Literatur diskutiert. Es wird besonders eingegangen auf das Problem der Unterscheidung zwischen Central Core und Multiple Core und Multiple Core Disease. Die Pathogenese der Muskelveränderung wird im besondern auch im Hinblick auf die mögliche neurogene Verursachung diskutiert. Es wird im weitern auf die histochemischen und ultrastrukturellen Gemeinsamkeiten zwischen Central Cores und Target Fibers eingegangen.

     

Stimulant-related reductions of growth rates in the PATS

OBJECTIVE: To investigate growth of children with attention-deficit/hyperactivity disorder (ADHD) in the Preschool ADHD Treatment Study (PATS) before and after initiation of treatment with methylphenidate at titrated doses (average, 14.2 mg/day) administered three times daily, 7 days/week for asymptotically equal to1 year. METHOD: The heights and weights of 140 children with ADHD were measured up to 29 times in the PATS protocol, starting at an average age of 4.4 years. The relationship between standard (z) scores and time on medication was examined using mixed-effect regression to estimate change in relative size (slope). RESULTS: Average relative size at baseline was significantly (p<.0001) greater than zero for z height (+0.45) and z weight (+0.78), indicating greater than expected height (by 2.04 cm) and weight (by 1.78 kg). During treatment, slopes were significantly (p<.0001) less than zero for z height (-0.304/yr) and z weight (-0.530/yr), indicating reduction of growth rates. For 95 children who remained on medication, annual growth rates were 20.3% less than expected for height (5.41 cm/yr-6.79 cm/yr=-1.38 cm/yr) and 55.2% for weight (1.07 kg/yr-2.39 kg/yr=-1.32 kg/yr). CONCLUSIONS: Risks of reduced growth rates should be balanced against expected benefits when preschool-age children are treated with stimulant medication.     

Neurofibrillary tangle predominant form of senile dementia of Alzheimer type: a rare subtype in very old subjects

In a consecutive autopsy series of 580 demented elderly subject, 256 with the clinical diagnosis of probable/possible Alzheimer's disease (AD), there were 10 cases aged between 80 and 99 years with moderate to severe dementia or confusional state in which neuropathological studies revealed abundant neurofibrillary tangles with predominant involvement of the allocortex (entorhinal region, subiculum, CA 1 sector of hippocampus, amygdala) but no or only very few senile plaques. Small numbers of diffuse deposits of A4 amyloid protein were present in the entorhinal cortex of 3 and in the isocortex of 5 brains, while neuritic plaques were totally absent. Only a few cases of this senile dementia with tangles only or, more correctly, neurofibrillary predominant type of AD corresponding to the limbic stage of neuritic AD pathology have been described in the literature. This rare subtype occurring in very old (over 80 years of age) subjects that does not fall within the currently used neuropathological criteria for diagnosis of AD warrants further clinico-pathological documentation.     

Is neurocysticercosis a risk factor in coexistent intracranial disease? An MRI based study

BACKGROUND: Previous reports have suggested that neurocysticercosis is associated with glioma and Japanese encephalitis, and that it is a risk factor for stroke. OBJECTIVE: To determine if neurocysticercosis has a significant association with, or is a risk factor for, coexistent pathologies such as Japanese encephalitis, glioma, abscess, tuberculoma, or infarction. SUBJECTS: 10 350 patients from the hospital population who underwent 1.5 T cranial magnetic resonance imaging during the previous 12 years were evaluated for the presence of neurocysticercosis and coexisting pathology. DESIGN: Retrospective cohort analysis. RESULTS: The prevalence of neurocysticercosis in cases with dual pathology was significantly less than in a control group (1.1% v 8.3%; z = 11.05; p < 0.001, power of test = 1). Neurocysticercosis lesions were less common (p < 0.05) in the different subgroups of coexistent pathology than in the control group except in the case of Japanese encephalitis, where the difference was non-significant (z = 0.69, p = 0.49). The relative risk was less than 1 in all subgroups except Japanese encephalitis, where it was 1.23. The location of neurocysticercosis lesions and the presence of perilesional oedema did not affect coexistent lesion location or severity on a particular side (p = 0.413 and 0.623 for location and perilesional oedema, respectively). When the above factors were analysed separately in patients with Japanese encephalitis, they also did not affect coexistent lesion location or severity (p = 0.659 and 0.548, respectively). CONCLUSIONS: The coexistence of neurocysticercosis and other lesions may be an incidental observation in a few patients referred from areas of high prevalence and endemicity. It appears unlikely that neurocysticercosis is a risk factor for other intracerebral pathology. The location of neurocysticercosis lesions and whether or not there is surrounding perilesional oedema do not appear to affect the location or severity of coexisting lesions.     

Leukoaraiosis and ventricular enlargement in patients with ischemic stroke

We studied the relationship between ventricular size and nonspecific periventricular lucency on computed tomograms (leukoaraiosis) in 192 patients with ischemic stroke. Leukoaraiosis did not occur in 21 patients less than 50 years of age; ventricular size could not be measured in an additional 29. Leukoaraiosis was graded from 0 to 4 on a semiquantitative scale; bicaudate, frontal horn, and posterior horn indices were used as measures of ventricular size. Patients with leukoaraiosis were older (difference between means 7 years, t = 5.3, df = 140, p less than 0.0001) and had larger bicaudate indices (difference between means 0.023, t = 3.54, df = 140, p = 0.0007) than patients without leukoaraiosis. Multiple regression analysis demonstrated that the effects of age and leukoaraiosis were independent. No effect of lesion type (cortical or lacunar infarct, or both) on bicaudate index could be demonstrated. Larger values for the bicaudate index were associated with a predominantly anterior location of leukoaraiosis. The frontal horn and occipital horn indices increased with age, but we could not find an effect of leukoaraiosis on these indices.     

Factor VII hyperactivity in the elderly

To investigate the age-related increase in coagulation factor VII (FVII) and its significance in the elderly, we measured FVII coagulation activity (FVIIc), FVII antigen (FVIIag), and D-dimer levels in 150 normal subjects ranging in age from 60 to 98 years. We also measured blood lipid fractions and serum cholinesterase activity (ChE), as an indicator of hepatic protein synthesis. FVIIc (141 +/- 36%), FVIIag (136 +/- 28%), and D-dimer (0.150 +/- 0.372 microgram/ml) levels were significantly higher in the elderly than in younger controls (p less than 0.01). Both FVIIc and FVIIag levels were significantly higher in elderly women than in elderly men (p less than 0.01). FVIIc levels significantly correlated with FVIIag levels, but not with D-dimer levels. FVIIag was more closely correlated with ChE levels in both sexes (men: r = 0.425, women: r = 0.365, p less than 0.001) than with the lipid fractions. When the elderly subjects were divided into atherosclerotic and non-atherosclerotic groups, both FVIIc (p less than 0.01) and FVIIag (p less than 0.05) levels were higher in the former group. Moreover, the FVIIc/FVIIag ratio and ChE levels were higher in both the elderly men and women with atherosclerosis. These results suggest that in elderly subjects, especially with atherosclerosis, hepatic FVII synthesis and the activation of FVII zymogen are both accelerated.     

Heparin response and clearance in acute and chronic liver disease

Patients with liver disease are at risk of bleeding due to abnormalities of the clotting system although they must be anticoagulated if they require haemodialysis or haemoperfusion. The anticoagulant of choice is heparin. In this study we have investigated heparin kinetics in patients with fulminant hepatic failure (FHF) after a single intravenous dose of heparin (2,500 units) and found there was an increased clearance of heparin whether measured by its anti-Xa effect (t 1/2 = 27.8 +/- 2.9 min compared to t 1/2 = 50.2 +/- 2.7 min in normal controls p less than 0.001) or by the whole blood activated clotting time (t 1/2 = 23.7 +/- 2.2 min compared to t 1/2 = 37.0 +/- 2.0 min p less than 0.001). There was a decreased peak level of heparin measured by anti-Xa effect (peak level in FHF = 0.48 +/- 0.05 u/ml and in controls = 0.69 +/- 0.04 u/ml, p less than 0.02), but an increased sensitivity to heparin (sensitivity in FHF = 0.072 +/- 0.011 sec/unit, in controls 0.033 +/- 0.003 sec/unit, p less than 0.001). Patients with FHF had very low levels of antithrombin III (AT III), but there was no correlation between this and any parameters of heparin effect or clearance. In a group of patients with chronic liver disease heparin kinetics did not differ from controls despite low levels of AT III. The changes in heparin kinetics in FHF are likely to be complex with the balance between the proteins that act as cofactors, (e.g. AT III) and the proteins that have heparin neutralising activity, controlling the response of added heparin.     

Platelets of habitual smokers have reduced susceptibility to aggregating agent

Platelet aggregation to collagen, and productions of 6-keto-prostaglandin-F1-alpha and thromboxane B2 during aggregation were measured after an overnight fast, involving both food and cigarettes, in 19 clinically healthy habitual smokers (10 or more cigarettes/day) and 23 non-smokers receiving the same diet. The subjects (all males; ages = 21-30 years) were residents of a school hostel. Mean platelet aggregation was significantly lower in smokers than non-smokers (23.2 ohms vs 31.5 ohms, p less than 0.005). Non-smokers had significantly higher mean concentration of 6-keto-prostaglandin-F1-alpha than smokers (109.8 pmol/l vs 92.3 pmol/l, p less than 0.05). The level of thromboxane B2 did not differ significantly between the two groups. These observations suggest that the role of smoking as a risk factor for ischaemic heart disease is unlikely to be related to a direct enhancement of aggregation. On the contrary, the observations seem to suggest that habitual smoking may directly reduce platelet aggregability.     

Relationship between smoking and fibrinolytic system with special reference to t-PA and PA inhibitor

Recently tissue plasminogen activator (t-PA) has been clinically applied to the thrombolytic therapy of myocardial infarction. We investigated relationship between cigarette smoking and fibrinolytic system, namely the plasma level of t-PA antigen, plasminogen activator inhibitor (PAI), and PA activity. Nineteen healthy volunteers were asked to smoke for 10 min. The plasma levels of t-PA antigen, PAI activity, PA activity and catecholamine were measured together with measurement of blood pressure and heart rate before, soon after or 30 min after cigarette smoking. Plasma t-PA antigen after cigarette smoking increased to 8.83 +/- 3.11 ng per ml, significantly higher (p less than 0.005) than 6.35 +/- 1.7 ng/ml before cigarette smoking. Plasma PAI activity after cigarette smoking was 5.52 +/- 2.03 u/ml, significantly higher (p less than 0.05) than 4.18 +/- 1.06 u/ml before smoking. Plasma PA activity after smoking was 6.28 +/- 3.85 u/ml significantly higher (p less than 0.05) than 4. 49 +/- 2.74 u/ml. Furthermore, plasma epinephrine level after smoking increased to 59.1 +/- 52.4 pg/ml (p less than 0.1), compared with 36.2 +/- 22.5 pg/ml before smoking. There was a positive correlation between the rate of increase in plasma t-PA antigen and the rate of increase in plasma epinephrine after smoking. It is suggested that plasma epinephrine was related to the mechanism of increased plasma levels of t-PA in cigarette smoking.     

Serotonin transporter polymorphism (5-HTTLPR) and citalopram effectiveness and side effects in children with depression and/or anxiety disorders

OBJECTIVE: The aim of this study was to examine the association between polymorphism in the serotonin transporter gene and citalopram effectiveness and side effects in children and adolescents with major depressive disorder (MDD) and/or anxiety disorders. METHODS: Outpatients, aged 7- 18 years with a Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision (DSM-IV-TR) MDD and/or anxiety disorder were treated in an 8-week open trial with 20-40 mg/day of citalopram. Subjects were genotyped with respect to short (s) versus long (l) forms of the 5-HTTLPR polymorphism of the serotonin transporter, and the relationship between genotype and outcome and side effects was assessed. RESULTS: Subjects with 5-HTTLPR ss genotype showed a less vigorous response with regard to depressive symptoms measured by the Children's Depression Rating Scale-Revised (CDRS-R) scores over time compared to subjects with sl/ll genotypes (beta = 0.67, z = 2.02, p = 0.04). In addition, the 5-HTTLPR ss group exhibited lower rates of agitation compared to those with sl/ll genotype (6.3% vs. 32.8%, p = 0.05). Also, subjects with 5-HTTLPR ss genotype had consistently higher scores of suicidality at each week compared to the sl/ll group (beta = 0.76, z = 2.04, p = 0.04) as measured by item number 13 of the CDRS-R. CONCLUSIONS: The 5-HTTLPR ss genotype was associated with a poorer clinical response with regard to depressive symptoms as well with fewer reports of agitation. The 5-HTTLPR polymorphism may be a genetic marker of response to citalopram in children and adolescents with depression and/or anxiety.