ANTIEPILEPTIC DRUG CONCENTRATIONS IN PLASMA: Clinical Evaluation of 321 Estimations in 237 Unselected Patients

Two chromatographic methods of estimating plasma concentrations of antiepileptic drugs, designed by the authors and described elsewhere, have been used to examine 321 samples of plasma. The methods have been shown to be simple and to fit satisfactorily into a busy laboratory programme. Results obtained with both methods have been found to agree with those of other workers who used a wide variety of techniques. Ranges of plasma concentrations of four commonly-used drugs have been established. Plasma concentrations do not correlate well with drug doses in individual patients. Negligible plasma concentrations have been found in some patients. Possible metabolic interactions have been revealed.     

Electrophysiological evaluation of central and peripheral neural effects of lead exposure

Lead encephalopathy is more usual in children and has rarely been observed in adults. Peripheral neuropathy on the other hand is of more common occurrence among adults with occupational lead exposure, and has been extensively studied with electrophysiological methods. Although encephalopathy often manifests itself with generalized seizures, usual electroencephalographic (EEG) findings have been diffuse slow wave abnormalities. Paroxysmal abnormalities either focal or generalized spikes and/or sharp waves have been detected in some patients. Evoked potential studies have lately been applied to children or adults with a relatively low level of lead exposure, and minor dose-dependent differences have appeared in comparison to control groups. Subclinical signs of peripheral neuropathy have been detected among human subjects with various levels of lead exposure. Nerve conduction velocities of lead workers have been generally lower, although the means have been within normal limits. Some authors have shown clear correlations between measures of lead exposure and nerve conduction velocities indicating an exposure--effect relationship.     

Femoral nerve involvement in diabetics

Background and purpose:  In this study, the conduction of the femoral nerve has been evaluated in diabetic patients without clinical signs of femoral nerve involvement and in a group of healthy subjects.
Methods:  Forty-eight patients have been included in the study. Patients have been examined in terms of neuropathy and their neuropathy scores have been calculated. In addition to the nerve conduction studies have been performed. The findings of the diabetic patients have been compared with those of the 26 healthy volunteers.
Results:  There has been a statistically significant difference between diabetics and the healthy volunteers in the control group in terms of both femoral nerve motor latency and amplitude. The femoral latencies of patients have significantly been related to the total neuropathy score. A significant difference between diabetic patients without polyneuropathy and the controls was observed with respect to their femoral latencies.
Conclusion:  In our study, femoral nerve conduction abnormalities have been determined in diabetics who clinically did not have femoral nerve involvement. It has been observed that these abnormalities become more evident as the polyneuropathy of the patients becomes more serious. Our study has shown that femoral nerve conductions may increase the sensitivity of the diagnosis of polyneuropathy.     

Cell adhesion molecules in neural development

Adhesive mechanisms have been implicated in several morphogenetic processes during development. In the last decade several molecules mediating specific adhesion between cells and between cells and their environment have been characterized. Possible roles in morphogenesis have been established for some of these molecules. In the brain, four cell-cell adhesion molecules have been characterized: NCAM, L1, the myelin-associated glycoprotein and N-cadherin. Furthermore, a cell-substrate adhesion molecule, cytotactin, and its proteoglycan ligand have been described. We here review the data on structure, localization, developmental regulation and function of these molecules in brain.     

Pre-Columbian indigenous psychopharmacology]

A careful review has been carried out on texts concerning Mexican medicine plants, especially on texts obtained directly from the XVI century Indian reports. The plants utilized for psychiatric purposes have been separated from the huge group of 1 500 medicine plants used by the prehispanic Indians, and have been found about 150 plants which have been classified in the modern way of antipsychotic, antidepressant, minor tranquilizer, hallucinogens, sedatives, hypnotics, brain tonics, stimulants and anticonvulsants. The intention in making this research is to awake the interest of the people in the experimenting field; as experiments have been effected only on hallucinogen up to now, and if these have proved to possess the effects caused to the Indians, supposedly large part of the other plants have the effects according to the indications they have mentioned.     

Psychiatry and chronic pain

Pain and chronic pain have been defined by the International Association for the Study of Pain. Psychological mechanisms are recognized in the production of pain, but their importance has probably been overstated. Selection factors have not been attended to sufficiently, and traditional methods which have been relied upon for the diagnosis of hysterical pain have been misleading. Much emotional change seen with pain is a consequence of the physical disorder. Types of illness, seen by psychiatrists working with patients in pain, are described, and brief comments offered on their management.     

Interventions to alleviate patients' stress: A review

Many events occuring in hospital have been found to be stressful for patients. Interventions aimed at alleviating these reactions have, in the main, been evaluated by psychologists and nurses. Methods used and contrasting approaches are reviewed. Although surgery has been the main event for this research, special investigations, treatments and hospital admission and discharge have also been studied. Outcome criteria have varied with physical measures being used more by nurses. Emphasis has been placed on preventing complications rather than enhancing recovery. Recent work has tended to compare types of intervention. Focused positive reappraisal and information on sensations are provided rather than procedural details as they have been found more successful in alleviating stress.     

Neuroblastoma and fetal exposure to phenytoin in a child without dysmorphic features.

Despite the fact that the teratogenic effects of phenytoin have been suggested in several case reports, the evidence for a possible oncogenic potential of phenytoin has not been widely recognized. Recently, neuroblastoma as well as other neuroectodermal and non-ectodermal tumors has been seen in several children exposed to phenytoin prenatally. Previous cases have been almost uniformly associated with the features of "fetal hydantoin syndrome" and none have been developmentally normal. We report a developmentally-normal boy of 21/2 years with an abdominal neuroblastoma whose mother had been on phenytoin (as well as carbamazepine) throughout gestation. We review the various neoplasms which have been reported in the offspring of mothers receiving phenytoin.     

Semen retrieval in spinal cord injured men.

A fertility programme for spinal cord injured men has been in progress for nearly 5 years. Thirty eight men have been treated in this programme. Electroejaculation, vibration ejaculation and subcutaneous physostigmine have all been used successfully to obtain semen. Semen has been obtained from 21 of 24 men with a lesion at T8 or above, and from 4 of 11 men with lesions below T10. There have been 8 pregnancies from 6 couples.     

Recent advances in the diagnosis,genetics and treatment of restless legs syndrome

Knowledge of restless legs syndrome (RLS) has greatly increased in recent years due to the many advances that have been made in diagnosis, management and genetics. Tools have been developed that facilitate the diagnosis and treatment of RLS, in particular the essential diagnostic criteria for RLS have been refined, severity scales (IRLS, RLS-6, JHSS) have been developed, as have instruments that improve diagnostic accuracy and assess for specific aspects of RLS such as augmentation. These newly developed tools have been used in recent population-based studies, which have provided a greater understanding of the epidemiology of RLS, and also within patient-based trials. As far as the genetics of RLS is concerned, linkage studies in RLS families have revealed eight loci but no causally related sequence variant has yet been identified using this approach. Recent genome-wide association studies have identified variants within intronic or intergenic regions of MEIS1, BTBD9, and MAP2K5/LBXCOR1, and PTPRD, raising new pathological hypotheses for RLS. An overview on therapeutic options and recent trials is given based on evidence-based management strategies for this common disorder.     

The antisocial personality: a review

Definition, understanding, and treatment of antisocial personality disorder continue to present difficulties, but there have been several encouraging developments. Recently published data on antisocial syndromes from several different disciplines have been strikingly consistent and have raised hopes for an integrated understanding of the disorder. In addition, many of the sources of antisocial symptoms have been identified, and certain highly structured therapeutic programs have been effective in modifying antisocial behavior. The paper reviews the latest issues related to diagnosis, symptom presentation, and treatment, as well as pathologic, sociologic, and epidemiologic aspects of the disorder.     

Hemispherectomy for Sturge-Weber syndrome.

Patients with Sturge-Weber disease who have the onset of seizures in infancy invariably face a progressively downhill course which leaves them severely hemiplegic, demented and usually institutionalized because of uncontrolled seizures. During the past 12 years, we have carried out 6 hemispherectomies in infants under 1 year of age who presented with seizures and Sturge-Weber disease. The results have been gratifying. Seizures have stopped, hemipareses have been minimal and intellectual development has been good.     

Instruments measuring family or caregiver burden in severe mental illness

The consequences of psychiatric disorders for family members, usually called family or caregiver burden, have been studied during the last 4 decades. During this period a variety of instruments have been developed to measure the impact of mental illness on family members, but not all instruments have been described systematically in the published literature. The authors review 21 instruments that have been used or developed during the last 10 years, including several that have not previously been reported. The protocols are described in terms of their method and comprehensiveness, precursors and theoretical foundations, and types of psychometric information available. The instruments are assessed for potential use as research tools, and also for application in routine clinical practice.     

Cardiovascular disease and sleep-related erections

Sexual difficulties are highly prevalent in male patients with cardiovascular diseases, such as hypertension, atherosclerosis, and hypercholesterolemia. Recently, several studies have been conducted on the effects of cardiovascular diseases, as well as associated drug and nondrug treatments, on nocturnal penile tumescence (NPT) and other measures of sexual function. Although an overall trend has been observed toward decreased NPT in patients with chronic hypertension and other cardiovascular conditions, design and methodological difficulties have been noted in most studies, and results have been generally inconclusive. Similarly, antihypertensive drugs such as beta-blockers and diuretics have been associated with diminished NPT in several studies, although methodological problems have again been noted. Furthermore, the mechanism of action of antihypertensive drugs on sleep-related erections has not been determined. Most recently, a positive effect of cholesterol-lowering drugs (pravastatin, lovastatin) on NPT has been observed in middle-aged males with chronic hypercholesterolemia. Additional studies of the effects of cardiovascular disease on NPT and other measures of sexual function are needed.     

Isolation of neurosecretory granules containing vasopressin and MSEL-neurophysin from guinea pig neurointermediate pituitary

Neurosecretory granules have been isolated from rat and guinea pig neurointermediate pituitaries and their contents have been analyzed by reverse-phase high-pressure liquid chromatography and polyacrylamide gel electrophoresis. Granule components have been compared with synthetic neurohypophysial hormones and chemically characterized neurophysins. In rat granules, oxytocin, arginine vasopressin and MSEL- and VLDV-neurophysins have been identified. In isolated guinea pig granules, only arginine vasopressin and mature MSEL-neurophysin have been found. From these results it can be concluded that both the "dibasic" cleavage between vasopressin and MSEL-neurophysin and the "monobasic" cleavage between MSEL-neurophysin and copeptin occur within the granule compartment. Previous isolation from frozen guinea pig glands of a partially processed precursor encompassing MSEL-neurophysin and copeptin suggests a two-step processing of the three-domain vasopressin precursor, each involving a distinct enzymic system.     

Disease modification in Parkinson's disease

Several separate gene mutations have now been identified in familial Parkinson's disease and important environmental influences modulating risk for the idiopathic form of the disease have also been recognised. These insights have provided important clues in the development of disease modifying therapies. Some compounds have already been shown to potentially delay disease progression in early clinical trials. The most important challenge, particularly for those drugs that might have a symptomatic effect, is defining appropriate markers that will confirm a neuroprotective effect.     

EEG in migraine: a review of the literature

EEG abnormalities in migraine have been reported by a number of authors during the last 50 years. Prevalences vary considerably in the older literature. A number of unspecific rhythms related to drowsiness or hyperventilation have probably been counted as "abnormal", and the reported numbers of definitely abnormal EEG rhythms have been consistently low. In a few controlled and blinded studies, however, slight excess of various EEG rhythms has been found in migraine patients. Similar prevalences of interictal EEG abnormalities have generally been found in patients with classic and common migraine, but the diagnostic classification may not have been precise enough in some studies. During visual aura, either slow waves, depression of background activity amplitude or normal EEG have been reported. The most definitely abnormal EEGs with unilateral or bilateral delta activity have been recorded during attacks of hemiplegic migraine, and during attacks of migraine with disturbed consciousness. The relationship between migraine and epilepsy has still not been adequately clarified. The connection seems to exist in several small entities (e.g. migraine-like headache as an epileptic manifestation, epileptic seizures triggered by epileptic attacks, and possibly in epilepsies with occipital spike waves), but it is seemingly not "fundamental". Newer methods, i.e. EEG frequency analysis and topographic brain mapping, are promising tools in this field. So far, mostly small studies have been published with somewhat inconsistent results. A pattern of increased alpha rhythm variability (and/or asymmetry) in the headache-free phase seems to emerge, however. Significant asymmetry of alpha and theta during headache has been reported in one topographic brain mapping study. Magnetoencephalographic studies of migraine patients have demonstrated slow wave-shifts (similar to those observed in animals with spreading depression). The EEG patterns observed in migraine patients seem to suggest a possible physiological connection between sleep, hyperventilation and migraine. The study of such relationship may shed new light on migraine pathophysiology.     

The WHO collaborative study on strategies for extending mental health care, II: The development of new research methods

Teams in seven developing countries under sponsorship of the World Health Organization have been carrying out collaborative operational research on providing mental health care through primary health care services. New techniques of identifying mental disorders in children and adults have been developed and tested. Methods of assessing the skills and attitudes of health workers toward mental health work and of gauging community attitudes toward mental illness have also been developed. Results have been directly applied in planning better mental health care. The authors conclude that cross-cultural collaborative research is effective in improving mental health care for those in greatest need.     

Measurement of male and female sexual dysfunction

Measurement approaches for male and female sexual dysfunction have proliferated in recent years, spurred in large part by the development of new treatments for male and female dysfunction. In the past, physiologic measures of penile tumescence and rigidity in males, and vaginal blood flow in females, played an important role in clinical and research studies. More recently, a variety of brief, self-report measures have been developed for assessing male and female function across a variety of sexual domains (eg, desire, arousal, orgasm, satisfaction). These self-report measures have been shown to have a high degree of reliability and validity, and are sensitive to treatment interventions. Accordingly, they are widely employed in clinical trials. Daily diary or sexual event logs have similarly been developed for this purpose. Selfreport measures have been used for clinical screening purposes and for diagnostic assessment of sexual function in a number of studies. Finally, several disease-specific quality of life and treatment satisfaction measures have been developed, which are currently in widespread use in clinical trials of sexual dysfunction.     

Psychiatric and Behavioural Disorders in Children with Epilepsy (ILAE Task Force Report): Epilepsy and psychosis in children and teenagers

Psychosis related to epilepsy or antiepileptic treatment can occur in teenagers and very rarely in children. Postictal, interictal and antiepileptic‐drug‐induced psychosis have all been reported in young people. Whether ictal psychosis occurs in this age group remains open to debate. Neuronal antibody encephalitis such as anti‐NMDA receptor encephalitis can present with seizures and psychosis, both of which can resolve with prompt, appropriate immunotherapy. In addition, there have been several reports in which the terms psychosis or psychotic features have been used loosely to describe behavioural disturbance in children with epilepsy; in these cases there have apparently been no diagnostic features of psychosis, implying that these terms should not have been used. The management of epilepsy‐related psychosis in young people is similar to that in adults. Antipsychotic medication should not be withheld if it is needed on clinical grounds. If the psychosis has been induced by antiepileptic medication then a medication review is necessary.