Analysis of the polymorphic prion protein gene codon 129 in idiopathic Parkinson's disease.

Idiopathic Parkinson's disease (IPD) is a neurodegenerative disorder of unknown aetiology. Histopathological similarities between IPD and Creutzfeldt-Jakob prion disease (CJD) have been suggested. Homozygosity at polymorphic prion protein gene codon 129 (PRNP129) is a risk factor for developing CJD. Therefore we investigated a putative genetic link between CJD and IPD by studying PRNP129 genotype segregation in 81 patients with IPD. We did not ascertain a different PRNP129 genotype distribution in IPD patients compared to healthy Germans. We found a significant difference in PRNP129 genotype in dependence of the clinical predominance type of IPD. Patients with tremor-dominant IPD presented less frequent a methionine homozygosis at PRNP129 than hypokinetic-rigid IPD patients (30% versus 62.5%; p<0.033). In conclusion, genotype distribution at codon 129 is obviously not essential in determining IPD. But our results may provide first evidence of an association between certain PRNP129 polymorphisms and the clinical presentation of IPD.

Apolipoprotein E and alpha-1-antichymotrypsin polymorphisms in sporadic inclusion body myositis.

Sporadic inclusion body myositis (s-IBM) is a progressive muscle disease of unknown aetiology. Characteristically, intracellular amyloid deposits are detectable, including beta-amyloid precursor protein, phosphorylated tau, alpha1-antichymotrypsin (alpha1-ACT) and apolipoprotein E (ApoE). Polymorphisms and mutations of the encoding genes have been identified in a variety of neurodegenerative diseases including Alzheimer's disease (AD). Beside other factors, polymorphisms may lead to protein accumulation in both diseases. In particular, polymorphisms within the ApoE and alpha1-ACT gene have been implicated in the aetiology of AD and s-IBM. We analysed ApoE and alpha1-ACT gene polymorphisms in 35 s-IBM patients. We could not identify any statistical significant correlation between distinct ApoE and alpha1-ACT genotypes and the risk of developing s-IBM. Additionally, ApoE and alpha1-ACT genotypes seem not to influence the onset age of s-IBM. A combination of different alpha1-ACT and ApoE genotypes appears not to enhance the risk of developing s-IBM. Therefore, allelic variations of alpha1-ACT and ApoE are unlikely to be genetic key factors in the aetiology of s-IBM.

HLA typing and Parkinson's disease.

Idiopathic Parkinson's disease (IPD) is a neurodegenerative disorder of unknown aetiology. Several antigens have been associated with IPD using serological methods. We systematically analysed HLA class I and II alleles in 45 German Caucasian IPD patients using sequence-specific oligonucleotides and sequence-specific primer technology. Applying Bonferroni adjusted p values, we demonstrate a statistically significant increase of the DQB1*06 allele (p = 0.002) in IPD which may indicate an association between IPD and the immune system. Alternatively, HLA alleles might be in linkage disequilibrium with genes located next to the HLA locus.

Expression of the interferon-induced MxA protein in viral encephalitis.

MxA protein accumulates cytoplasmically in response to interferon stimulation, and mediates resistance against several viruses. In order to test whether MxA may serve as a diagnostic tool for viral infections of the central nervous system (CNS), we performed MxA immunohistochemistry on biopsies and autopsies of 57 patients with neurological disorders of known viral and nonviral aetiology. MxA was detectable in all HIV patients with proven opportunistic viral encephalitis, in all patients suffering from isolated viral encephalitis, in one of three HIV patients with cerebral toxoplasmosis, and in one case of micronodular encephalitis. No MxA was detectable in HIV patients with isolated HIV encephalitis or HIV infection accompanied by an opportunistic nonviral disorder. We were unable to show MxA expression in a variety of nonviral inflammatory and noninflammatory disorders of the CNS. Several cases of Rasmussen's encephalitis and multiple sclerosis tested negative, arguing against their possible viral aetiology. Two-colour immunohistochemistry identified macrophages and activated microglia as MxA expressing cells. In all studied cases MxA expression was accompanied by a marked T-cell infiltrate. Therefore, the detection of MxA-protein is a sensitive adjuvant marker for those cases of viral encephalitis which are accompanied by pronounced lymphocytic infiltrates.

[Proximal weakness and exercise-induced pain as initial symptom of oculopharyngeal muscular dystrophy]. / Proximale Schwäche und belastungsabhängige Schmerzen als Erstsymptome einer okulopharyngealen Muskeldystrophie.

A 54-year-old female patient presented with exercise-induced proximal muscle pain and weakness of the lower limbs. One year after the onset of these symptoms she developed bilateral ptosis and dysphagia. Molecular genetic analysis of the poly(A) binding protein 2 gene (PABP2) confirmed the presumptive diagnosis of oculopharyngeal muscular dystrophy (OPMD). Exercise-induced proximal muscle pain and weakness are rarely initial symptoms of OPMD. We discuss therapeutic options and present an overview of the relevant literature.

Randomized, single-blinded comparative study of the efficacy of amoxicillin (40 mg/kg/day) versus standard-dose penicillin V in the treatment of group A streptococcal pharyngitis in children.

A 10-day course of amoxicillin at a dosage of 40 mg per kilogram per day was compared with conventional (lower dosage) penicillin V therapy in the treatment of culture-proven Group A streptococcal pharyngitis in children 3 to 18 years of age in a prospective, randomized, and single-blinded study. Children had to have signs and symptoms compatible with the diagnosis of streptococcal pharyngitis and to have a throat swab positive for Group A streptococci. A second throat culture was obtained 10 to 14 days after the completion of therapy. Serotyping was performed to help differentiate carrier states from reinfections. Of 161 children enrolled, 113 were evaluable; 55 received penicillin and 58 received amoxicillin. At the completion of therapy 70.9% (39/55) of patients in the penicillin group vs 87.9% (51/58) of patients in the amoxicillin group were asymptomatic (clinical cure, P = 0.025). At the completion of therapy, 54.5% (30/55) of patients in the penicillin group vs 79.3% (46/58) of patients in the amoxicillin group had negative throat cultures (bacteriologic cure, P = 0.005). The carrier rate (children who were well but who were still carrying the same serotype of Group A streptococcus) also differed between the groups: 13 (23.6%) in the penicillin group compared with six (10.3%) in the amoxicillin group. Amoxicillin at 40 mg/kg/day was significantly more effective than lower dosages of penicillin V for clinical and bacteriologic cure in the treatment of Group A streptococcal pharyngitis in children. The current perception that penicillin is declining in effectiveness may be due to inadequate dosing.

The effect of prolonged bottle feeding on cow's milk intake and iron stores at 18 months of age.

Thirty-four toddlers were studied in a prospective, convenience sample comparison at their 18-month health supervision visit to examine the effect of prolonged (i.e., to 18 months of age) bottle feeding on both the daily volume of cow's milk intake and the toddler's iron stores (serum ferritin concentrations.) Seventeen toddlers had been weaned from the bottle by approximately 1 year of age, and 17 toddlers who remained on the bottle at 18 months of age were the compared group. The toddlers who remained on the bottle had significantly greater (P < 0.001) cow's milk intake (mean 26.3 oz vs 16.1 oz). The mean ferritin concentrations were lower in the persistent bottle group (17.3 micrograms/L vs 23.4 micrograms/L), but not significantly so. Questioning parents about their toddlers' continued bottle use at 18 months can provide a marker for potentially excessive cow's milk intake.