The polymorphism of drugs in powders and tablets. 1. The preparation and characterization of polymorphic modifications of phenobarbital

The characterisation of three phenobarbital modifications by thermic examination procedures (DSC, DTA) is being described. Modification I was obtained by thermic treatment of the brands (modification II) from Hungary and the GDR. The spray product prepared, consisting of very fine hollow spheres, was identified as modification III. Besides the particle size distribution the form of the particle was determined by scanning electron microscopy (REM). The best results regarding saturation solubility and speed of dissolution were found for the spray product.     

Bronchial artery embolization: monitoring with somatosensory evoked potentials. Work in progress

Surgery remains the treatment of choice for massive and recurrent hemoptysis. In some instances, however, immediate surgical intervention is contraindicated. In these situations, bronchial artery embolization (BAE) has proved to be a successful definitive treatment for non-surgical candidates and a palliative therapy in patients requiring hemodynamic stabilization prior to surgery. The most serious complication of BAE is spinal cord ischemia. This relates directly to the potential anastomotic connections between the bronchial circulation and the anterior spinal artery. Somatosensory evoked potentials (SSEPs) have been used in the past to monitor spinal cord ischemia during procedures that threaten the vascularity of the spinal cord. The authors report two cases in which SSEPs were employed to monitor spinal cord ischemia during bronchial artery embolization.     

Glatiramer acetate-specific antibody titres in patients with relapsing / remitting multiple sclerosis and in experimental autoimmune encephalomyelitis

Glatiramer acetate (GA) is an immunomodulatory drug approved for the treatment of clinically isolated syndrome (CIS) and relapsing/remitting multiple sclerosis (RRMS). As an antigen-based therapy, GA induces GA-specific antibodies in treated patients and animals. GA-specific antibodies do not neutralize therapeutic effects on relapses and disability. Rather, it has been suggested that GA-specific antibodies may be associated with improved clinical outcomes. We evaluated antibody responses in eight patients with RRMS treated with GA for 15 months and antibody responses in GA-treated C57BL/6 mice before and after induction of experimental autoimmune encephalomyelitis (EAE). There were no significant differences from pretreatment levels of total IgE or GA-specific IgE in patients with RRMS. Total IgG1, IgG3 and GA-specific IgG4 were significantly increased at 15 months of GA treatment. Antibody type and titre were not associated with clinical outcomes, i.e. expanded disability status scale (EDSS) score, disease burden on magnetic resonance images (MRI) or clinical relapses. In contrast, mice with EAE showed a marked increase in GA-specific IgE and GA-specific IgG1 antibody responses. GA-treated mice demonstrated improved clinical symptoms and lower mortality than untreated controls. Our results suggest that antibody responses to GA are heterogeneous among patients with RRMS, with no apparent association between antibody response and clinical outcomes. Clinical improvements in EAE-induced GA-treated mice suggest that GA-specific IgE and IgG1 may contribute to GA treatment effects in EAE.     

Mutation spectrum and genotype-phenotype analyses in Cowden disease and Bannayan-Zonana syndrome, two hamartoma syndromes with germline PTEN mutation

The tumour suppressor gene PTEN , which maps to 10q23.3 and encodes a 403 amino acid dual specificity phosphatase (protein tyrosine phosphatase; PTPase), was shown recently to play a broad role in human malignancy. Somatic PTEN deletions and mutations were observed in sporadic breast, brain, prostate and kidney cancer cell lines and in several primary tumours such as endometrial carcinomas, malignant melanoma and thyroid tumours. In addition, PTEN was identified as the susceptibility gene for two hamartoma syndromes: Cowden disease (CD; MIM 158350) and Bannayan-Zonana (BZS) or Ruvalcaba-Riley-Smith syndrome (MIM 153480). Constitutive DNA from 37 CD families and seven BZS families was screened for germline PTEN mutations. PTEN mutations were identified in 30 of 37 (81%) CD families, including missense and nonsense point mutations, deletions, insertions, a deletion/insertion and splice site mutations. These mutations were scattered over the entire length of PTEN , with the exception of the first, fourth and last exons. A 'hot spot' for PTEN mutation in CD was identified in exon 5 that contains the PTPase core motif, with 13 of 30 (43%) CD mutations identified in this exon. Seven of 30 (23%) were within the core motif, the majority (five of seven) of which were missense mutations, possibly pointing to the functional significance of this region. Germline PTEN mutations were identified in four of seven (57%) BZS families studied. Interestingly, none of these mutations was observed in the PTPase core motif. It is also worthy of note that a single nonsense point mutation, R233X, was observed in the germline DNA from two unrelated CD families and one BZS family. Genotype-phenotype studies were not performed on this small group of BZS families. However, genotype-phenotype analysis inthe group of CD families revealed two possible associations worthy of follow-up in independent analyses. The first was an association noted in the group of CD families with breast disease. A correlation was observed between the presence/absence of a PTEN mutation and the type of breast involvement (unaffected versus benign versus malignant). Specifically and more directly, an association was also observed between the presence of a PTEN mutation and malignant breast disease. Secondly, there appeared to be an interdependent association between mutations upstream and within the PTPase core motif, the core motif containing the majority of missense mutations, and the involvement of all major organ systems (central nervous system, thyroid, breast, skin and gastrointestinal tract). However, these observations would need to be confirmed by studying a larger number of CD families.      

Polymorphism of drugs in powders and tablets. 6. X-ray diffractometric studies of polymorphic modifications of tolbutamide

The modifications and spray dried products of tolbutamide published in a former article, are investigated furthermore by X-Ray diffraction. The indication of the reflexes in X-Ray diffraction patterns of 2 modifications is performed. Transformations of modification are provable in consequence of thermal stress.     

“Below average” self-assessed school performance and Alzheimer's disease in the Aging,Demographics, and Memory Study

BackgroundA low level of formal education is becoming accepted as a risk factor for Alzheimer's disease (AD). Although increasing attention has been paid to differences in educational quality, no previous studies addressed participants' own characterizations of their overall performance in school. We examined whether self-assessed school performance is associated with AD beyond the effects of educational level alone.MethodsParticipants were drawn from the population-representative Aging, Demographics, and Memory Study (ADAMS, 2000-2002). The ADAMS participants were asked about their performance in school. Possible response options included “above average,” “average,” or “below average.” The ADAMS participants also underwent a full neuropsychological battery, and received a research diagnosis of possible or probable AD.ResultsThe 725 participants (mean age, 81.8 years; 59% female; 16% African-American) varied in self-assessed educational performance: 29% reported “above average,” 64% reported “average,” and 7% reported “below average” school performance. Participants with a lower self-assessed school performance had higher proportions of AD: 11% of participants with “above average” self-assessed performance had AD, as opposed to 12% of participants with “average” performance and 26% of participants with “below average” performance (P < 0.001). After controlling for subjects' years in school, a literacy test score (Wide-Range Achievement Test), age, sex, race/ethnicity, apolipoprotein E-?4 status, socioeconomic status, and self-reported comorbidities, respondents with “below average” self-assessed school performance were four times more likely to have AD compared with those of “average” performance (odds ratio, 4.0; 95% confidence interval, 1.2–14). “Above average” and “average” self-assessed school performance did not increase or decrease the odds of having AD (odds ratio, 0.9; 95% confidence interval, 0.5–1.7).ConclusionsWe suggest an association between “below average” self-assessed school performance and AD beyond the known association with formal education. Efforts to increase cognitive reserve through better school performance, in addition to increasing the number of years of formal education in early life, may be important in reducing vulnerability throughout the life course.     

The crystallography behavior of carbamazepine under compression pressure

In the present paper the crystallographic behavior of the carbamazepine modifications I, II and III were studied under various conditions by means of X-ray powder diffraction, IR-spectroscopy and differential-scanning-calorimetry. It was found that the crystal lattice of the carbamazepine modification I is relative stable to the applied pressure forms, whereas modification II under similar conditions undergoes a polymorphic transformation into carbamazepine modification III, the extent of which depends on compression pressure and storage time of the tablets. In the compression samples of carbamazepine modification III neither IR-spectroscopically nor X-ray-diffractionally an influence of the pressure could be found on growing up of the enantiotrophic modification I.