Effects of essential fatty acids in iron deficient and sleep-disturbed attention deficit hyperactivity disorder (ADHD) children.

Inattention, hyperactivity and impulsivity constitute the core diagnostic criteria for attention deficit hyperactivity disorder (ADHD) children. Patients generally suffer from sleep disturbance and malnutrition that can account for tiredness during the day, poor concentration, poor eating and depressed mood, along with anemia and an n-3 polyunsaturated acid deficiency. The change of ADHD behavior in children (9-12) was studied, following 10 weeks of treatment with a polyunsaturated acid mixture on six variables: cooperation, mood, concentration, homework preparation, fatigue and sleep quality. Iron status was also examined. Polyunsaturated acid administration was associated with significant improvement in quality of life, ability to concentrate, sleep quality and hemoglobin levels.

Cognitive impairment and reduced life span of oculopharyngeal muscular dystrophy homozygotes.

OBJECTIVE: To assess the evolution and life expectancy in patients with oculopharyngeal muscular dystrophy (OPMD) who are homozygotes for two (GCN)13 expansions in the PABPN1 encoding gene. BACKGROUND: OPMD is particularly frequent among French Canadians (FCs) and Uzbek Jews (UJs), who carry a same size, (GCN)13, PABPN1 mutation. The high rate of consanguinity among UJs together with late disease onset and normal fertility results in homozygous cases. METHODS: For 15 to 20 years, we followed 4 FC and 6 UJ homozygotes with OPMD and compared them with their heterozygous parents and siblings. In addition to clinical evaluation, electrodiagnostic tests, psychological tests, and brain imaging studies were performed. RESULTS: In all (GCN)13-(GCN)13 patients, OPMD started before age 35 years, with bilateral ptosis and dysphagia; external ophthalmoparesis and dysphonia followed within a few years, as well as weakness in proximal limb muscles. All patients had recurrent aspirations and lost weight; 4 patients required surgical interventions to alleviate dysphagia, and 5 required feeding gastrostomies. Most patients were followed by psychiatrists due to cognitive decline, recurrent depression, or psychotic episodes. Six patients died at ages 50, 51, 53, 56, 56, and 57 years. The eldest patient is now 51 years old; she is cachectic and requires special diet and psychiatric care for paranoid psychosis and uninhibited behavior. CONCLUSIONS: Oculopharyngeal muscular dystrophy progresses faster in homozygote compared with heterozygote patients. It is not restricted to the muscles, but also involves the CNS with cognitive decline and psychotic manifestations and leads to a reduced life expectancy.

Onset and progression of disease in familial and sporadic Parkinson's disease.

Lately different and rare genetic forms of Parkinson's disease (PD) have been described. Complete genomic screening has suggested that still undefined multiple genetic factors might underlie the development of PD. The course of PD patients with and without genetic background might be different. We compared the age at onset and progression of PD with (FH) and without (NFH) family history. Two hundred forty PD patients attending the outpatient Movement Disorders Clinic were evaluated. The age of onset (AO), the duration of disease until stage III of Hoehn and Yahr (YST3), until dementia (YDEM) and family history of PD were determined by interview, examination of medical files and of affected family members. Patients with young onset who reported another PD patient among their siblings were tested for parkin mutations. Statistical analysis used ANOVA, Fisher's Least Significant Difference, log-rank and Wilcoxon's tests for Kaplan-Meier survival curves taking stage III and dementia as end-points. Of the 240 patients (age 73.3 +/- 10.9 years), 29 (12%) had positive FH. Six of them carried parkin mutations. The AO was 33.5 +/- 8.1 (range 19-42) years for parkin carriers, 59.3 +/- 11.3 (range 34-76) for FH and 66.5 +/- 11.8 (27-91) years for NFH (P < 0.0001). The three groups were significantly different from each other (alpha = 0.05). Stage III and dementia were reached only in non-parkin patients. YST3 was 12.6 +/- 6.6 years for FH and 6.5 +/- 5.0 years for NFH (P < 0.0001). YDEM was 10.1 +/- 6.0 years for FH versus 4.7 +/- 4.5 years for NFH (P = 0.002). Kaplan-Meier survival analysis revealed faster motor (P = 0.0016) and mental decline (P = 0.02) in NFH versus FH. Our results showed that the AO of PD is younger in patients with FH. Motor and mental deterioration, however, showed a less steep course in familial PD patients.

Acute mania and hemichorea.

A 61-year-old man suddenly became euphoric and talkative. Later the same day, he developed hemichoreic movements of the left limbs. The patient fulfilled the DSM-IV criteria for a manic episode by abnormally and persistently elevated mood, decreased need for sleep, high distractibility, pressured speech, increased goal-directed activity, and hypersexuality. The mood changes persisted for several weeks. Magnetic resonance imaging of the brain showed a right thalamic infarction. The co-occurrence of hemichorea and mania caused by focal thalamic lesion is very rare. It may be explained by dysfunction in basal ganglia thalamocortical circuitry.

Parkin gene causing benign autosomal recessive juvenile parkinsonism.

Autosomal recessive juvenile parkinsonism (AR-JP) is an early-onset parkinsonism caused by exonic deletions or point mutations in the parkingene. The relationship between the type of the genetic defect and the clinical presentation, the response to therapy, and the evolution have not been yet determined. The authors describe a single-basepair deletion at nucleotide 202 in exon 2 of the parkin gene in a kindred with a benign clinical course.

Oculopharyngeal MD among Bukhara Jews is due to a founder (GCG)9 mutation in the PABP2 gene.

OBJECTIVE: To determine whether all cases of oculopharyngeal muscular dystrophy (OPMD) among Bukhara Jews share the same founder mutation. BACKGROUND: Autosomal dominant OPMD is caused by a (GCG)8-13 repeat expansion in the polyadenylation binding protein 2 (PABP2) gene. The disease has a worldwide distribution but is particularly prevalent in Bukhara Jews and in French Canadians, in whom it was introduced by three sisters in 1648. METHODS: We established the size of the PABP2 mutation in 23 Bukhara Jewish patients belonging to eight unrelated families. In all families, we constructed haplotypes for the carrying chromosomes composed of the alleles for eight chromosome 14q polymorphic markers. RESULTS: All patients share a (GCG)9 PABP2 mutation and a four-marker haplotype. Furthermore, a shared intron single nucleotide polymorphism (SNP) in the PABP2 gene 2.6Kb from the mutation was not observed in 22 families with (GCG)9 mutations from nine different countries. The smaller size of the chromosomal region in linkage disequilibrium around the mutation in Bukhara Jews, as compared with French Canadians, suggests a founder effect that occurred more than 350 years ago. Based on the Luria-Delbrück corrected "genetic clock," we estimate that the mutation appeared or was introduced once in the Bukhara Jewish population between AD 872 and 1512 (mean, AD 1243). CONCLUSION: OPMD among Bukhara Jews is the result of a shared, historically distinct, PABP2 (GCG)9 mutation that likely arose or was introduced in this population at the time they first settled in Bukhara and Samarkand during the 13th or 14th centuries.

Fatty acid mixture counters stress changes in cortisol, cholesterol, and impair learning.

A mixture of linoleic and alpha-linolenic acids (free non-esterified unsaturated fatty acids) administered for 3 weeks prior to injection of cortisol (10 mg/kg), or prior to immersion of rats in a 10 degree C saline bath, prevented elevation of blood levels of cortisol and cholesterol and deficits in Morris water maze spatial learning that usually accompany such stressful conditions. Differences from controls on all behavioural and biochemical measures were statistically significant (P < .05). It is proposed that induction of intense stress, and the associated increase in cortisol, cholesterol and other corticosteroids may damage hippocampal structures and help account for the cognitive decline witnessed in Alzheimer's disease and other age-related conditions. The modulation of these consequences by the fatty acid mixture may provide an alternative strategy for the study of stress markers and for the development of other intervention options in humans.

A comparison of dopamine agonists and catechol-O-methyltransferase inhibitors in Parkinson's disease.

To compare the efficacy and tolerability of three dopamine agonists--pergolide (PRG), pramipexole (PRX), and ropinirole (ROP)-and two catechol-O-methyltranferase (COMT) inhibitors-tolcapone (TOL) and entacapone (ENT)-as add-on therapies to levodopa (L-Dopa) in Parkinson's disease, we analyzed randomized, double-blind, placebo-controlled, multicenter studies. To our knowledge, they had not yet been evaluated in comparison with each other. Statistical analyses used odds ratios, numbers needed to harm, and Fisher's inverse chi2 method. Seven studies meeting the inclusion criteria included treatment of 1,756 patients. The common efficacy measures were the reduction of L-Dopa dose and "off' duration. The reported reduction in L-Dopa dose was significant for all drugs in relation to placebo, but was most significant for PRX and ENT (p < 0.0001). The most significant reduction in "off' duration was with PRG, PRX, and ENT (p < 0.001). The common tolerability measures were the percentage of patients withdrawn because of side effects, because of any reason, and because of the development of dyskinesias. Ropinirole, PRX, and ENT caused fewer withdrawals related to side effects. Pergolide was better than other analyzed drugs concerning withdrawals for any reason. All drugs caused more dyskinesias than placebo (p < 0.0001), with overlapping confidence intervals, except for TOL 600 mg, which caused more dyskinesias than dopamine agonists and ENT. Pramipexole and ENT had the best efficacy and tolerability profile in this analysis.

Autosomal-recessive juvenile parkinsonism in a Jewish Yemenite kindred: mutation of Parkin gene.

We report a Jewish family of Yemenite origin in which three brothers born from a consanguineous marriage had juvenile parkinsonism. The DNA samples from three affected brothers and one healthy brother were analyzed for the linkage to markers covering the autosomal-recessive juvenile parkinsonism (AR-JP) locus. A perfect homozygous cosegregation to the markers was found, giving a maximal lod score of 3.11 at D6S1579, D6S305, and D6S411, all of which are 0 cm apart from each other (nonparametric linkage score, 8.041; p = 0.000977). Exon 3 of the Parkin gene was homozygously deleted in all patients. The AR-JP gene also exists in the Jewish population.

Fatty acids and brain peptides.

The role of fatty acids (FA) as a mediator and modulator of central nervous system activity in general, and peptides in particular, is only recently becoming understood. This paper reviews numerous findings concerned with the activity of fatty acids, particularly with their interaction with diverse neurochemical systems and their consequences for better understanding neurotransmitters, hormones and peptides. The effects include FA as precursors in the manufacture of neurochemical elements, including enzymes, neurotransmitters, and hormones. Of particular interest is the important changes in neuronal membrane composition that have been attributed to FA. Such changes may account for the changes in thermoregulation, learning, and other functions that accompany dietary manipulation of FA intake. While the total level of FA has been the object of many investigations, this report addresses the need to focus on the ratio of FA, especially alpha-linolenic/linoleic acid, which has been shown to be a critical factor in a number of research studies.

[Attitudes of family physicians to alternative medicine].

80 Israeli family physicians (51.25% men and 48.75% women) participated in a telephone survey concerning attitudes, practices and experience with alternative medicine. 23.75% reported practicing 1 or more alternative techniques, most commonly acupuncture (28%) and hypnotherapy (24%). 55% had referred at least 1 patient to an alternative practitioner during the preceding month. Physicians who studied in Israel or Western countries referred more patients than graduates of medical schools of Eastern Europe. Specialists referred patients more often than residents. The most common reason for referral was back pain.

Epidemiology and inheritance of oculopharyngeal muscular dystrophy in Israel.

Oculopharyngeal muscular dystrophy (OPMD) is considered frequent among French Canadians. Our previous observations suggested it is common also among the Jews originating from Bukhara in Uzbekistan, many of whom are now living in Israel. One hundred and seventeen OPMD patients were identified in a population of 70,000 people of Bukharian descent, resulting in a calculated minimal prevalence of 1:600. In all but three families age dependent autosomal dominant inheritance was documented. There is some evidence for genetic anticipation. Three young, severely ill, patients from two different families may be homozygotes, their parents being both affected. Bukhara Jews present the second largest known cluster and the prevalence is the highest in the world. The existence of very large families, intermarriage among carriers and probably homozygote offspring may be useful for genetic studies. A 'founder effect' may explain the high prevalence of OPMD in this population.

Essential fatty acids preparation (SR-3) improves Alzheimer's patients quality of life.

In a number of previous reports we showed the salutary effects on rats of SR-3, a compound comprising a 1:4 ratio of n-3 and n-6 fatty acids. Improvements were noted in learning tasks, thermoregulation, recovery from neurotoxins, and seizure protection. Because we were impressed that these effects are related to changes in membrane fluidity and neuronal functioning and because Alzheimer's Disease is also associated with lipid defects, we undertook a short term (4 week) double blind study with 100 Alzheimer patients (60 received SR-3 and 40 in a placebo control). The results indicated improvements in mood, cooperation, appetite, sleep, ability to navigate in the home, and short term memory. Overall improvement was reported for 49 patients, and in no case did a guardian report adverse effects to the compound. While not uniform or permanent, and while no mode of action for SR-3 can be precisely identified at this time, the promising results in quality of life for the patient and caregiver warrant further clinical trials and continued basic research into the neuropsychological substrate of the disease and its response to SR-3.

Essential fatty acid preparation (SR-3) raises the seizure threshold in rats.

The anticonvulsant properties of a mixture of non-esterified alpha-linolenic acid and linoleic acid with a ratio of 1:4 (SR-3) were evaluated in four rat models of epileptic seizures: (1) i.p. injection of a single convulsant dose (50 mg/kg or 100 mg/kg) of pentylenetetrazol; (2) repeated subconvulsant doses of pentylenetetrazol; (3) cortical irritation by intraventricular administration of iron chloride (FeCl3); and (4) audiogenic seizure-prone preparation created by repeated pretreatment with p-cresol. Treatment with SR-3 (about 40 mg/kg i.p.) for a period of 3 weeks prior to challenge was found effective in each of these experimental models and caused up to a 22-fold increase in latency to major motor seizures, up to 84% reduction in the number of rats with seizures, and up to a 97% reduction in the duration of seizures. It is postulated that the anticonvulsant effects of SR-3 may be related to its stabilization of neuronal membranes. SR-3 should be evaluated further as a treatment for epilepsy.

Modulation of learning, pain thresholds, and thermoregulation in the rat by preparations of free purified alpha-linolenic and linoleic acids: determination of the optimal omega 3-to-omega 6 ratio.

Ingested polyunsaturated fatty acids are postulated to lead to changes in central nervous system activity, presumably by altering the lipid composition of neuronal membranes. In support of this hypothesis, we and other investigators have previously demonstrated cognitive effects in rats fed oils that contain both alpha-linolenic acid (18:3 omega 3) and linoleic acid (18:2 omega 6), with the relative content of alpha-linolenic acid being seen as the critical variable. The present study in rats examined the effects of preparations containing different ratios of highly purified free alpha-linolenic acid to linoleic acid (about 25 mg/kg of body weight daily) on learning performance (Morris water tank), pain thresholds (heated plate), and thermoregulatory control of d-amphetamine-induced hypothermia during 4 weeks of treatment. Preparations with omega 3-to-omega 6 ratios ranging from 1:3.5 to 1:5 (specifically a ratio of 1:4) produced significant favorable effects on all of these variables. Although the specific mode of action remains to be elucidated, these results suggest that such preparations of free fatty acids should be evaluated in the treatment of memory disorders and pain conditions.

Aborting seizures by painful stimulation.

It has been well established that serious consequences may result from allowing seizures to continue. The opportunities for early interruption of seizures by medication is often restricted to medical personnel, leaving non-trained bystanders unable to intervene. We were able to interrupt seizures (including status epilepticus) by application of painful dorsiflexion. The mode of action that enables pain to elevate the seizure threshold remains to be elucidated, although the phenomenon is consistent with earlier laboratory studies in experimental epilepsy. The technique may be recommended as an effective and easily learned procedure that may have wide applicability.

The effect of pain on pentylenetetrazol induced seizures.

Repeated administrations of subconvulsive doses of pentylenetetrazol (PTZ) leads to frank convulsions. The number of injections required to bring about such an effect is taken as an index of seizure vulnerability, and was studied in normal rats. This study examined the effect of pain induced by formaline injection or placement on a hot plate on seizure elicitation. The results could be accounted for by the role of arousal and/or endogenous opiates that are generated by the pain induction procedures, wherein the pain appears to provide some elevation of the threshold for seizure vulnerability.