Temporal trends among childhood brain tumor biopsies

We sought temporal trends in the demographic, clinical, histologic feature, diagnostic class, and quality of life data over the interval 1930–1979 in the Childhood Brain Tumor Consortium database. The proportion of children younger than eight years old declined from 72% to 55% and the proportion of those older than ten more than doubled from 12% to 27%. The relative frequency of tumors in the supratentorial compartment increased significantly, while infratentorial tumors decreased. We found significant declines in supratentorial ependymomas and pilocytic astrocytomas. Similarly, some infratentorial tumors, especially ependymomas, decreased and brain stem tumors increased. Infratentorial medulloblastoma (primitive neuroectodermal tumor) increased significantly. Some individual histologic features which are markers of anaplasia increased in frequency in both supratentorial and infratentorial tumors. There was a significant increase in biopsies that contained nonneoplastic neural tissue in addition to tumor for both compartments and among supratentorial tumors there was a marked increase in the proportion of cases containing an indistinct neural tissue boundary. The probability of postoperative death declined, but the probability of survival five or ten years after surgery did not improve significantly for children who had tumors in either compartment. Among children who survived five years after the initial craniotomy, the proportion who had significant long term deficits increased. Most of this increase occurred in the last decade (1970–79). In this decade, the proportion of children for whom no deficits were reported five years following operation was 4% if they had a supratentorial tumor and 27% if they had an infratentorial tumor. The proportions of children alive five years following first surgery who had arachnoidal metastases increased significantly for infratentorial tumors.The Childhood Brain Tumor Consortium (Floyd H. Gilles, principal investigator) is composed of the following:     

An ELISA for recombinant Lepidoglyphus destructor, Lep d 2, and the monitoring of exposure to dust mite allergens in farming households

BACKGROUND: Exposure to indoor allergens, such as dust mites, has been recognized as a risk factor for sensitization and symptoms. OBJECTIVE: To develop a two-site ELISA for the determination of Lep d 2 in the reservoir, to measure dust mite allergen exposure (Lep d 2, Der p 1, Der f 1 and Der 2) in farm households, and to investigate whether exposure to these allergens is associated with sensitization, asthma and rhinoconjunctivitis. METHODS: Monoclonal antibodies to recombinant (r)Lep d 2 were produced with standard hybridoma technique. Dust samples from 393 households were analysed for allergen content by two-site ELISA methods. RESULTS: A two-site Lep d 2 ELISA was developed with a detection limit of 0.09 microg/g. The assay was highly reproducible and levels of Lep d 2 showed a strong correlation with the number of Lepidoglyphus mites (r(s): 0.7; P = 0.0002). Lep d 2 was detected in 20% of the homes; levels ranged from 0.09 to 1.7 microg/g of dust. Der p 1 was recorded in 59% of the samples, ranging from 0.055 to 139 microg/g, and Der f 1 and Der 2 in 40% and 50% of the samples, ranging from 0.055 to 24.5 microg/g and 24.3 microg/g, respectively. Dermatophagoides allergens were significantly higher in mattresses than in carpets (P < 0.0001), but this difference was not observed with Lep d 2. A strong relationship between immunoglobulin (Ig)E to rLep d 2 and asthma (OR = 10.4) and rhinoconjunctivitis (OR = 7.5) was seen. Furthermore, sensitization to D. pteronyssinus was significantly associated with asthma (OR: 13.7) and rhinoconjunctivitis (OR: 5.7). CONCLUSION: When assessing mite allergen exposure in rural homes, not only the Der p 1, Der f 1 and Der 2 allergens, but also the Lep d 2 allergen should be taken into consideration.     

Screening for minimal brain dysfunction (MBD/DAMP) at six years of age: results of motor test in relation to perinatal conditions, development and family situation

The aim of this study was to investigate if children aged 6 years of age, classified as having minimal brain dysfunction (MBD) or deficit in attention, motor control and perception (DAMP), exhibit special medical problems, specific developmental features or if special psychosocial conditions exist in the family. The screening program, using the psychoneurological part of the method developed by Gillberg et al., included 234 children who were followed-up prospectively from pregnancy and birth. The results were related to the physical and mental development of the children, to the psychosocial and socioeconomic conditions of the families, to pre- and postnatal conditions and to “reduced optimality score”, as defined by Prechtl. Mental development was assessed by the use of Griffiths' test at 10-14 months and at 4-5 years of age. At the second Griffiths' test, the mother was also interviewed about the presence of aggressiveness and other symptoms of childhood psychopathology in her child, as defined by the DSM-III criteria, and a psychological observation was also made. In addition to screening for MBD/DAMP, at 6 years of age the parents were asked to complete a questionnaire aimed at identifying attention deficit disorder (ADD). No medical or psychological intervention was made before this stage. Fourteen children (9M, 5F) (6%) were identified as having a positive MBD/DAMP screening result. The results of the screening procedure showed a weak correlation with those obtained using the questionnaire based on the DSM-III criteria for ADD. Compared with the rest of the children, those with a positive MBD/DAMP screening result had an increased number of complications during pregnancy but not a reduced optimality score. At 4 years of age the performance on the Griffiths' test was lower and the rate of child psychiatric symptoms such as aggressiveness and signs of the mother having difficulties in setting limits for the child were more common than among the rest of the cohort. No relation was found with the psychosocial or socioeconomic conditions of the family. We conclude that children suspected of having MBD/DAMP at the start of school may have exhibited signs of delayed psychoneurological development and symptoms of psychopathology at 4 years of age.     

Prediction of acute otitis media with symptoms and signs

We carried out a prospective study to analyse if it would be possible to predict the coexistence of acute otitis media on the basis of symptoms and signs of infection. Of the 658 patients admitted to hospital during the period concerned, 197 (29.9%) had otitis media. For each child with otitis, the next patient of the same age was chosen as a control. The risk of having otitis media was increased among patients with cough, rhinitis and earache. All three variables together correctly classified 67% of those not having otitis media and 63% of those with acute otitis, compared with the 50% which would theoretically be achieved by chance alone. Prediction was worst (55%) among patients younger than 2 years of age not having otitis media and best among older patients who had otitis media, i.e. 78%. Prediction on these grounds would have caused significant over-treatment, and one-third of the otitis cases among the youngest group would have been missed. Thus it is important to always examine the ears of a child with an infection in order to reliably exclude the possibility of acute otitis media.     

Validation of a rodent model of Parkinson's disease: Evidence of a therapeutic window for oral Sinemet

Behavioral measures of parkinsonism that are more clinically relevant than rotometry have been developed for rats with severe unilateral dopamine depletions, and the validity of these measures is supported by reports that these parkinsonian symptoms are attenuated by drugs that are effective in the clinical setting. Although the therapeutic gold standard, l-DOPA:carbidopa (Sinemet), effectively attenuates parkinsonian symptoms, the beneficial effects of this drug are limited by the dyskinesias that it produces at higher doses. The range of effective doses, from the minimum dose that produces beneficial effects to the dose that produces intolerable dyskinesias, is referred to as the “therapeutic window”. It would be extremely valuable to assess, preclinically, the effects of novel treatments on the therapeutic window for Sinemet. The results of the present study support the validity of nondrug-induced measures of parkinsonian symptoms in dopamine-depleted rats. Neurological measures revealed large behavioral deficits in the affected forelimb analogous to the deficits exhibited in Parkinson's disease patients, and these deficits were significantly attenuated with some doses of oral Sinemet (30–40 mg/kg). These drug effects on measures of parkinsonism were specific to performance with the affected limb. At slightly higher doses (50 mg/kg), the rats were untestable due to severe dyskinesias. The results of the present study suggest that it is possible to investigate the therapeutic potential of novel treatments as well as their effects on the therapeutic window of oral Sinemet in this rodent model of Parkinson's disease.     

Marital disharmony four and a half years post partum. Effects on parent-child relationships and child development

This longitudinal study of primiparous women concerns factors related to the quality of the marital relationship 4 1/2 years after the birth of the first child. Information was independently collected from the women, their husbands and children. A poor relationship to the partner and impaired mental health in the women post partum were associated with marital disharmony at follow-up. In disharmonious marriages more often than in others parents were estimated to have a rejecting attitude towards their child and the child to have a rejecting attitude towards its parents. Further, in these marriages poor parental relationships of boys were more common than those of girls and socially immature boys as compared to socially immature girls overrepresented.     

Differential response to amphetamine in schizophrenia

Amphetamine added to maintenance therapy with neuroleptic drugs was accompanied by relief of complaints in 32 of 48 chronic schizophrenic patients with a long-standing incapacity for work. In 22 cases this relief was followed by increased work efficiency. These gains were lost at experimental withdrawal of amphetamine. The response to amphetamine varied with type of schizophrenic symptomatology. All current regressive symptoms meant worsening in spite of concomitant neuroleptic treatment, in accordance with the dopamine hypothesis. Non-regressive subjects displaying florid symptoms, however, benefited. Worsening, in a few cases, occurred only in the absence of neuroleptics. A few subjects with negative symptoms only, seemed totally unresponsive. These findings point at variations in sensitivity to dopaminergic stimulation in schizophrenic subjects. Worsening and improvement with amphetamine were each clearly connected with type of symptomatology only when current psychotic or florid non-regressive symptoms were exhibited. In cases with negative symptoms only, the type of response could not be reliably based on clinical data. Studies of autonomic functioning and attention were therefore performed in a sub-sample. Skin conductance level, reactivity and habituation rate were found to be lower in positive responders before amphetamine. After amphetamine there were no such differences. Attention tests showed no initial differences between groups but the performance of positive responders improved with amphetamine.     

Respiratory symptoms and ventilatory performance in workers exposed to grain and grain based food dusts

A health surveillance study of male grain food manufacturingworkers used a respiratory health questionnaire and spirometryto assess the prevalence of work-related respiratory symptomsand impaired ventilatory performance. The prevalence of cough,breathlessness, wheeze and chest tightness was between 8–13%but was 20% for rhinitis. Rhinitis was the most common symptomwith 37% of those reporting rhinitis describing this as work-related.A case-control analysis of workers reporting rhinitis did notidentify any specific occupational activities associated withincreased risk of rhinitis. Smoking habit and all respiratorysymptoms apart from rhinitis had a significant effect upon ventilatoryperformance. Occupational exposure to raw grains, flour, ingredientsand finished food was categorized as high, medium or low ineither continuous or intermediate patterns. Multiple regressionanalysis confirmed the effects of height, age and smoking uponventilatory performance. However, occupational exposure to grain,flour, food ingredients and cooked food dusts had no effectupon ventilatory performance. It is concluded that smoking habitis the major determinant of respiratory symptoms and impairedventilatory function. The excess complaints of rhinitis warrantfurther study but it would appear that the current occupationalexposure limits for grain, flour, food ingredients and cookedfood dusts are adequate to protect workers against impairmentof ventilatory performance.     

Prolonged Psychic Epileptic Seizures: A Study of the Absence Status

Long-lived epileptic seizures associated with spike-and-wave complexes are presently considered to be the absence status, i.e., the generalized nonconvulsive status. EEG radiotelemetry allowed us to record three prolonged seizures of 3 epileptic patients. Clinical manifestations included selective rather than global impairment of higher cortical functions. Clinical impairment appeared only when patients were in a state of activity and if those altered functions were used. EEG abnormalities were diffuse, but among them spike-and-wave complexes were never diffuse. It was impossible to establish close electroclinical correlation. However, the clinical and electrical evolution was roughly isomorphic, i.e., cyclic. Major clinical manifestations were associated with spikes rather than with slow waves. Lastly, patients showed common ictal psychopathological symptoms. The problem of classifying such seizures in either the generalized or partial status is discussed. The role of selective impairment of mental functions in psychopathological symptoms is also dealth with.     

Discontinuation symptoms in users of selective serotonin reuptake inhibitors in clinical practice: tapering versus abrupt discontinuation

Objective Tapering of selective serotonin reuptake inhibitor (SSRI) therapy, as opposed to abrupt discontinuation, has been recommended by several guidelines and in the literature in order to diminish the occurrence of discontinuation symptoms. However, the evidence of a favourable effect of tapering is limited, and it is unclear how patients ought to discontinue SSRIs in daily life. The aim of this study was to examine the way in which patients discontinue SSRI therapy in clinical practice and to compare the effect of tapering with that of abrupt discontinuation on the occurrence of discontinuation symptoms.Methods Patients (n=74) who recently discontinued SSRI therapy completed a questionnaire containing questions about discontinuation symptoms (DESS events), the prescribed SSRI, reasons for discontinuation, way of discontinuation, knowledge of discontinuation symptoms, impact on daily life and patient counseling and education. The number of DESS events was compared among groups (abrupt discontinuation versus tapering; age; male versus female; paroxetine versus other SSRIs; knowledge of discontinuation symptoms at start of therapy versus lack of knowledge).Results A total of 66 patients were eligible for analysis. Of all patients ending SSRI therapy, 21% abruptly discontinued therapy. There was a significant difference in the number of DESS events between abrupt discontinuation and tapering of SSRI therapy (12.0 versus 5.9). There was also a tendency for an adverse effect of lack of knowledge of discontinuation symptoms at the start of therapy on the number of DESS events (8.9 versus 5.5).Conclusion One in five patients abruptly discontinued their SSRI therapy in clinical practice. Abrupt discontinuation caused a larger increase in the number of discontinuation symptoms than tapering. We therefore advise tapering SSRI therapy in clinical practice to prevent unnecessary adverse effects of discontinuation.