[Quality of Glaucoma Care in the Greater Hamburg Area]. / Erfassung der Versorgungsqualität von Glaukompatienten im Großraum Hamburg.

Background There is insufficient data on the quality of health services and health-related quality of life of patients with glaucoma. The purpose of this study was to investigate the extent to which the health services for glaucoma patients in the Greater Hamburg area conform to the guidelines set by the German Ophthalmological Society (DOG). Materials and Methods 196 glaucoma patients were offered an interview-administered questionnaire during their inpatient diurnal IOP measurement. The quality of glaucoma care and examinations recommended by the DOG were analysed. The results of the questionnaire were correlated with glaucoma severity, according to the stage of visual field defects. The correlation to the type of glaucoma was also analysed. Results The frequency of visits to the ophthalmologist was 5.1 per year. Most patients reported quarterly medical consultations. The majority of patients reported short waiting periods, because appointments were made in advance. In 92 % of cases, an intraocular pressure measurement was performed with each medical consultation. Half of the patients stated that their intraocular pressure had been measured at different times of the day. The visual field was tested a mean of 0.9 times per year at the ophthalmology clinic, but 1.4 times per year in the outpatient area. Further measures for glaucoma diagnostic testing were carried out 0.8 times per year at the ophthalmology clinic, and 0.4 times per year in the outpatient area. For the majority of patients, there were no additional costs for outpatient glaucoma diagnostic testing. Only 4 % of patients had to pay more than 100 € per year for these services. Conclusions For the majority of glaucoma patients in the Greater Hamburg area, the glaucoma health services conform to the guidelines set by the German Ophthalmological Society. Intraocular pressure measurements were performed on almost all patients at the regular check-ups and visual fields were examined as recommended. However, for about one-fifth of the patients, regular procedures for optic nerve analysis do not take place. The date of the next appointment was arranged immediately, allowing close follow-up, with little or no additional costs for the majority of patients.

Truncating mutations in FUS/TLS give rise to a more aggressive ALS-phenotype than missense mutations: a clinico-genetic study in Germany.

BACKGROUND AND PURPOSE: Mutations in the FUS/TLS have been associated with amyotrophic lateral sclerosis (ALS) in a few percent of patients. METHODS: We screened 184 familial (FALS) and 200 sporadic German patients with ALS for FUS/TLS mutations by sequence analysis of exons 5, 6 and 13-15. We compared the phenotypes of patients with different FUS/TLS mutations. RESULTS: We identified three missense mutations p.K510R, p.R514G, p.R521H, and the two truncating mutations p.R495X and p.G478LfsX23 in samples from eight pedigrees. Both truncating mutations were associated with young onset and very aggressive disease courses, whereas the p.R521H, p.R514G and in particular the p.K510R mutation showed a milder phenotype with disease durations ranging from 3 years to more than 26 years, the longest reported for a patient with a FUS/TLS mutation. Also, in a pair of monozygous twins with the p.K510R mutation, a remarkable similar disease course was observed. CONCLUSIONS: Mutations in FUS/TLS account for 8.7% (16 of 184) of FALS in Germany. This is a higher prevalence than reported from other countries. Truncating FUS/TLS mutations result in a more severe phenotype than most missense mutations. The wide phenotypic differences have implications for genetic counselling.

[First diagnosis of systemic sclerosis based on ocular complications]. / Erstdiagnosestellung einer systemischen Sklerose anhand okulärer Komplikationen.

BACKGROUND: Systemic sclerosis is a chronic connective tissue disease in which immune system dysfunction alters the structure and function of blood vessels. It is characterized by enhanced tissue fibrosis, which may rapidly affect a large area of the skin as well as internal organs. Dry eye symptoms are the most common ocular findings. CASE REPORT: This case presents a 51-year-old male patient suffering from blurred vision in the left eye. The ophthalmoscopic examination revealed retinal thrombotic microangiopathy in both eyes. Spectral-domain optical coherence tomography (SD OCT) showed a macular edema in the left eye. Although these ocular symptoms do not represent the initial manifestation of the primary disease, correct diagnosis was only made in the context of the retinal findings. CONCLUSION: Retinal microangiopathic lesions can play a seminal role in diagnosing systemic sclerosis.

Disposition of human fibrinopeptide A in normal and nephrectomized rabbits.

The distribution, elimination, and metabolism of human fibrinopeptide A (FPA) were studied in normal and nephrectomized rabbits. The activity of 125-I-labeled desamino-tyrosyl human FPA (DAT-FPA) was followed over 4 hours after i.v. administration. Results show that in normal rabbits (n = 10) DAT-FPA is eliminated from plasma in four phases with half-lives of 30 sec, 3.5 min, 15 min, and 90 min. The distribution of 123-I-labeled DAT-FPA in plasma was determined in 15 control rabbits with scintigraphy over 2 hours. DAT-FPA was distributed primarily in the cardiovascular system, liver, and kidneys. In some animals minimal radioactivity was detected over the gall bladder. Radioactivity accumulated rapidly in the urinary bladder, approximately 50% being recorded after 15 min and 90% after 120 min. In the heart area radioactivity decreased with half-lives of 25 sec, 7.5 min, 25 min, and 180 min. Nephrectomized rabbits had similar initial fast distribution of DAT-FPA after administration of 125-I-labeled (n = 10) and 123-I-labeled peptide (n = 10). The estimated half-life of the slow component was in the order of several hours. The results of the scintigraphic and gel chromatographic studies show that FPA is primarily excreted in the urine. Previously reported half-lives of FPA reflect distribution rather than steady state conditions.

Detection of Mycobacterium avium subsp. paratuberculosis in faeces using different procedures of pre-treatment for real-time PCR in comparison to culture.

One of the most relevant aspects in the diagnosis of paratuberculosis (Johne's disease) in cattle is the availability of a method for the rapid and sensitive detection of Mycobacterium avium subsp. paratuberculosis (MAP) in order to facilitate the prompt removal of pathogen-shedding animals from a herd. To meet this requirement, methods for pre-treatment of bovine faecal samples and subsequent extraction of DNA for detection of MAP by real-time PCR were compared with MAP culture results. A total of 116 bovine faecal samples that showed weak (64.7%), moderate (18.1%) or strong (17.2%) growth of MAP on solid HEY medium were investigated. For PCR, supernatants, sediments or bacterial pellets were obtained from faecal samples by pre-treatment before extraction of MAP DNA based on silica membranes or magnetic particles. Samples then were tested by MAP IS900 and ISMav2 real-time PCR with an analytical sensitivity of 6 and 28 genome equivalents (GE) per mL, respectively. The best results were obtained by including a microfiltration step in the sample pre-treatment in combination with silica membrane-based mini-columns or magnetic particles for DNA extraction. This approach enhanced the detection rate of MAP in IS900 real-time PCR from 58.6% to 84.5% using silica membrane mini-columns and from 61.2% to 64.7% using magnetic particles.

Novel missense and truncating mutations in FUS/TLS in familial ALS.

BACKGROUND: Mutations in the FUS/TLS gene have been associated with familial amyotrophic lateral sclerosis (FALS). METHODS: We analyzed the presence and frequency of C-terminal FUS/TLS mutations in a German amyotrophic lateral sclerosis (ALS) cohort, including 133 patients with sporadic ALS (SALS) and 58 patients with FALS by sequence analysis of exons 13-15. RESULTS: We identified 2 novel heterozygous FUS/TLS mutations in 4 German ALS families including the novel missense mutation K510R and the truncating mutation R495X. The truncating mutation was associated with an aggressive disease course whereas the K510R mutation showed a mild phenotype with disease duration ranging from 6 to 8 years. No mutation was detected in 133 patients with SALS. CONCLUSIONS: Mutations in FUS/TLS account for 7% (4 of 58) of FALS in our German cohort.

Impact of heavy metals on hormonal and immunological factors in women with repeated miscarriages.

In 111 women with repeated miscarriages, the urinary excretion of heavy metals was determined in a challenge test with the chelating agent 2,3-dimercaptopropane-1-sulphonic acid in addition to hormonal, chromosomal, immunological and uterine investigations. The heavy metal excretion was correlated to different immunological (natural killer cells, T cell subpopulations) and hormonal (progesterone, oestradiol, prolactin, thyroid stimulating hormone) parameters. We conclude that heavy metals seem to have a negative impact on ovarian as well as on pituitary function. The heavy metal-induced immunological changes may interfere with the physiological adaptation of the immune system to the state of pregnancy with the result of a miscarriage. The observed heavy metal-induced hormonal and immunological changes may be important factors in the pathogenesis of repeated miscarriages.

Influence of the duration of the oestradiol rise on the success rate in GnRH analogue/HMG-stimulated IVF cycles.

The influence of the duration of the serum oestradiol (E2) rise before human chorionic gonadotrophin (HCG) injection on the outcome of in-vitro fertilization (IVF) cycles was investigated. Two different stimulation protocols were compared. In 218 cycles, the Norfolk protocol for stimulation with human menopausal gonadotrophin (HMG) was used (protocol A). In 235 cycles, pituitary function was suppressed by a single injection of a long-acting GnRH analogue ('Decapeptyl microcapsules') before HMG stimulation was started (protocol B). The overall pregnancy rates were significantly higher with protocol B (22% per puncture, 21% per started cycle) than with protocol A (14% per puncture, 9% per started cycle). For each interval of E2 rise duration (5-11 days), the fertilization rates (per oocyte) and the pregnancy rates (per puncture) were evaluated. There was a clear-cut maximum of the pregnancy rates for 6 and 7 days of E2 rise (21 and 16% respectively) for protocol A. For protocol B, pregnancy rates were generally higher than for protocol A. There was also a maximum of the pregnancy rates for 6 (32%) and 7 (29%) days of E2 rise but this maximum was not as clear-cut as for protocol A. The fertilization rates showed no significant differences for each interval of E2 rise in both groups (between 63 and 89%). Therefore, it is concluded that endometrial maturity, and not the oocyte's ability for fertilization, is the most critical factor for success in IVF cycles.(ABSTRACT TRUNCATED AT 250 WORDS)

Therapeutic vaccine for acute and chronic motor neuron diseases: implications for amyotrophic lateral sclerosis.

Therapeutic vaccination with Copaxone (glatiramer acetate, Cop-1) protects motor neurons against acute and chronic degenerative conditions. In acute degeneration after facial nerve axotomy, the number of surviving motor neurons was almost two times higher in Cop-1-vaccinated mice than in nonvaccinated mice, or in mice injected with PBS emulsified in complete Freund's adjuvant (P < 0.05). In mice that express the mutant human gene Cu/Zn superoxide dismutase G93A (SOD1), and therefore simulate the chronic human motor neuron disease amyotrophic lateral sclerosis, Cop-1 vaccination prolonged life span compared to untreated matched controls, from 211 +/- 7 days (n = 15) to 263 +/- 8 days (n = 14; P < 0.0001). Our studies show that vaccination significantly improved motor activity. In line with the experimentally based concept of protective autoimmunity, these findings suggest that Cop-1 vaccination boosts the local immune response needed to combat destructive self-compounds associated with motor neuron death. Its differential action in CNS autoimmune diseases and neurodegenerative disorders, depending on the regimen used, allows its use as a therapy for either condition. Daily administration of Cop-1 is an approved treatment for multiple sclerosis. The protocol for non-autoimmune neurodegenerative diseases such as amyotrophic lateral sclerosis, remains to be established by future studies.