Search for Pompe disease among patients with undetermined myopathies.

OBJECTIVE: Pompe disease is a rare treatable glycogen storage disease with in adults - a limb-girdle muscle weakness. Muscle biopsy may fail to show the typical vacuolar myopathy. We asked if we had un-diagnosed patients with Pompe disease in western Sweden. MATERIAL AND METHODS: We searched the muscle biopsy registry during the time period 1986 until 2006 including 3665 biopsies and included patients at our Neuromuscular Center with unspecified myopathy or limb-girdle muscular dystrophy. The dry blood spot test was used to identify patients with Pompe disease. RESULTS: A total of 82 patients (46 from the biopsy register and 36 from our center) were seen and dry blood spot test was obtained. No patient with Pompe disease was found. The dry blood spot test was low in three cases (11, 16, and 18% of normal) but a second blood sample showed a normal result based on GAA enzyme activity in lymphocytes in all three patients. In one patient with low normal result of the analysis in lymphocytes a genetic test showed no pathogenic mutations. Further investigation gave a definite diagnose of another myopathy in 12 patients. CONCLUSIONS: The prevalence of Pompe disease in western Sweden (3 in 1.27 million or 0.24 per 100.000 inhabitants) is lower than in the Netherlands and New York. Re-evaluation of patients with myopathies but without definite diagnosis is rewarding since 12 of 82 patients in our study had a definite molecular diagnosis after workup.

Adenovirus DNA in Guthrie cards from children who develop acute lymphoblastic leukaemia (ALL).

BACKGROUND: In search of a proposed viral aetiology of childhood acute lymphoblastic leukaemia (ALL), the common species C adenoviruses were analysed in Guthrie cards. METHODS: Guthrie cards from 243 children who later developed ALL and from 486 matched controls were collected and analysed by nested polymerase chain reaction for the presence of adenovirus DNA. RESULTS: Adenovirus DNA was reliably detected from only two subjects, both of whom developed ALL. CONCLUSION: Adenovirus DNA is detected in Guthrie card samples at too low a frequency to reveal an association between adenovirus and the development of leukaemia.

Targeted in vivo expression of nicotinic acetylcholine receptors in mouse brain using lentiviral expression vectors.

Nicotinic acetylcholine receptors (nAChRs) in the brain exhibit diverse functional properties and ubiquitous distribution. Yet, except for providing a receptor for the exogenously applied nicotine of tobacco products, their role in the normal functioning of the brain has remained elusive. We have used a lentiviral expression vector to re-express the beta2 subunit specifically in the ventral tegmental area (VTA) of beta2-/- mice. The viral vector efficiently expresses beta2- subunit protein leading to new nAChR-binding sites. VTA neurons transduced by the lentiviral vector are responsive to intravenous nicotine when analyzed using in vivo electrophysiology. Nicotine-induced dopamine release from the nucleus accumbens (NuAcc) was also restored in re-expressing beta2-/- mice. Intra-VTA injection of nicotine was found to be reinforcing in both wild-type and beta2-subunit re-expressing beta2-/- mice, but not in beta2-/- mice. Furthermore, in the absence of applied nicotine, the spontaneous slow exploratory behavior of the mice was restored, whereas fast navigation did not change. This latter behavioral analysis suggests a role for beta2* nAChR, specifically expressed in the VTA, in mammalian cognitive function.

Sarcoplasmic body myopathy--a rare hereditary myopathy with characteristic inclusions.

OBJECTIVES: To characterise a Swedish family with a rare hereditary myopathy with unique sarcoplasmic inclusion bodies in the muscle biopsy. MATERIALS AND METHODS: Part of the pedigree was described in 1980. Nine new members of the included and the phenotype further characterised through clinical, neurophysiological and radiological investigations. RESULTS: Six of the nine subjects displayed clinical and/or laboratory evidence of myopathy with sarcoplasmic inclusions. CONCLUSIONS: Sarcoplasmic body myopathy is distinguished from other distal myopathies by a more malignant course and early involvement of thenar muscles and hand flexors. Five to ten years after onset the affected subjects develop distal, as well as proximal, weakness and atrophy and the majority require a wheelchair after ten to fifteen years of disease. The disorder is manifested through elevated creatine kinase levels and the presence of the pathognomonic sarcoplasmic inclusions prior to clinical signs and symptoms.

Nicotine reinforcement and cognition restored by targeted expression of nicotinic receptors.

Worldwide, 100 million people are expected to die this century from the consequences of nicotine addiction, but nicotine is also known to enhance cognitive performance. Identifying the molecular mechanisms involved in nicotine reinforcement and cognition is a priority and requires the development of new in vivo experimental paradigms. The ventral tegmental area (VTA) of the midbrain is thought to mediate the reinforcement properties of many drugs of abuse. Here we specifically re-expressed the beta2-subunit of the nicotinic acetylcholine receptor (nAChR) by stereotaxically injecting a lentiviral vector into the VTA of mice carrying beta2-subunit deletions. We demonstrate the efficient re-expression of electrophysiologically responsive, ligand-binding nicotinic acetylcholine receptors in dopamine-containing neurons of the VTA, together with the recovery of nicotine-elicited dopamine release and nicotine self-administration. We also quantified exploratory behaviours of the mice, and showed that beta2-subunit re-expression restored slow exploratory behaviour (a measure of cognitive function) to wild-type levels, but did not affect fast navigation behaviour. We thus demonstrate the sufficient role of the VTA in both nicotine reinforcement and endogenous cholinergic regulation of cognitive functions.

Nitric oxide is involved in nicotine-induced burst firing of rat ventral tegmental area dopamine neurons.

In the present study, using single cell recordings in vivo and intracellular recordings in vitro from midbrain slices, the role of N-methyl-d-aspartate (NMDA) receptor signaling on firing activity in ventral tegmental area dopamine neurons elicited by nicotine was investigated in the rat. In accordance with previous studies, systemic nicotine (0.5 mg/kg s.c.) increased both firing rate and burst firing of dopamine neurons in vivo, and bath-applied nicotine (10 microM) increased firing rate in vitro. The competitive NMDA receptor antagonist CGP39551 (2.5 mg/kg i.p.) inhibited nicotine's effects on burst firing and also attenuated the nicotine-induced increase in firing rate. Moreover, although the nitric oxide (NO)-synthase inhibitor N-nitro-l-arginine-methyl-ester (l-NAME; 5.0 mg/kg i.p.) had no effect on cell firing by itself, it prevented the response to nicotine in vivo. In contrast, l-NAME (100 microM) did not influence nicotine's effect on dopamine cell firing in vitro, suggesting that the effect of l-NAME seen in vivo is dependent on presynaptic afferent input. The present study confirms previous results suggesting that the effect of systemically administered nicotine is in part presynaptic and mediated via NMDA receptors. The data also indicate that NO plays an important role in the previously demonstrated, indirect, glutamate-mediated excitation of these neurons by nicotine. By inference, our results provide additional support for the involvement of NO in nicotine dependence.

Oral sugar clearance and other caries-related factors in patients with myotonic dystrophy.

The aim of the investigation was to try to explain why patients with myotonic dystrophy (MD) have a high caries prevalence. Seventeen MD patients, 15 of whom had been examined 8 years earlier, and 17 matched, healthy controls participated. In connection with this follow-up examination, the oral sugar clearance was evaluated after chewing a glucose tablet. A paraffin-stimulated whole saliva sample was collected for determination of secretion rate, buffer capacity, and numbers of mutans streptococci and lactobacilli. Dietary score, plaque index, oral muscular coordination, and self-cleaning ability were also recorded. For all factors, the MD patients showed less favorable mean values than the controls; the differences between the groups were statistically significant, except for the bacterial counts and the salivary buffer capacity. Thus, the high caries prevalence in MD patients may be explained by longer oral sugar clearance time, lower salivary secretion rate, higher intake frequency of sugar-containing products, higher plaque index, and less pronounced oral muscular coordination and self-cleaning ability than in healthy individuals.

Ultrasound imaging of the masseter muscle in myotonic dystrophy patients.

Ultrasound technique was applied to measure the thickness and examine the internal structure of the masseter muscle in a group of 16 adult patients (nine women and seven men) with myotonic dystrophy (MyD) and 16 healthy individuals matched in age, sex and number of occluding teeth. The masseter thickness was measured bilaterally under both relaxed conditions and during maximal clenching. The error of measurement was found to be small, not exceeding 0.45 mm. The imaging characteristics of the masseter in most of the MyD patients was an obvious atrophy of the muscle with increased echointensity of the intramuscular tissue and loss of the internal structure concerning tendons and fasciae. The mean masseter thickness (+/- SD) in the MyD group was 10.4 (+/- 2.2) mm under relaxed conditions and 11.1 (+/- 2.4) mm during maximal clenching, compared with 13.3 (+/- 2.2) mm and 14.1 (+/- 2.4) mm, respectively, in the healthy group (P < 0.001). In conclusion, our results indicate that, in most of the myotonic dystrophy patients, the masseter muscle is atrophic with obvious signs of degeneration. Ultrasound is a useful method for both qualitative and quantitative evaluation of the condition of the masseter muscle.

Geographical and temporal distribution of Ockelbo disease in Sweden.

The incidence of Ockelbo disease and the prevalence of Ockelbo virus neutralizing antibodies were investigated in a sample of the Swedish population. The disease occurs throughout most of Sweden but with higher incidence and antibody prevalence rates in the central part of the country. It generally affects middle-aged men and women, with equal incidence between sexes, and is uncommon in people younger than 20 years of age. The disease occurs during a short period each year between the third week of July and the first week of October, with a peak during the second half of August. During the 8 years studied (1981-8), an average of 31 Ockelbo patients/year were diagnosed. The antibody prevalence rates in the oldest age groups were 20-40 times higher than the accumulated life-risk of being diagnosed and reported as an Ockelbo disease patient, which suggests that many cases are asymptomatic and/or unreported.

Dental needs of patients with myotonic dystrophy.

The aim of this study was to assess oral health and motoric ability in persons with myotonic dystrophy in comparison with a control group of healthy persons and find out whether an increased need of dental care exists in persons with reduced motoric ability. Twenty-seven persons, mean age 45, with the diagnosis myotonic dystrophy were compared with an age- and sex-matched control group. The dental status was determined from orthopantomograms and bite-wing radiographs. Oral hygiene, using a simplified index, periodontal pocket depth and alveolar bone height were recorded. Additionally, the finger force of the patient was recorded in order to evaluate the muscular capacity. Compared to control persons, persons with myotonic dystrophy had a lower finger force. They also had fewer teeth, higher caries frequency and more plaque, although no difference was found in the alveolar bone support around their remaining teeth. A positive correlation was found between finger force and oral hygiene. Persons with myotonic dystrophy had a decreased ability to maintain good oral hygiene, possibly due to motoric disability, and they had an increased need of dental hygienic care.