Profile of gastrointestinal involvement in patients with systemic sclerosis.

Systemic sclerosis (SSc) is a chronic autoimmune connective tissue disease. Of the numerous organ manifestations, involvement of the upper and lower gastrointestinal tract (GIT) appears to be the most frequent with regard to the clinical symptoms. However, as the frequency and clinical relevance of GI involvement in patients with SSc are not known in detail, the German network of the systemic sclerosis (DNSS) has developed a detailed questionnaire to evaluate the extent and profile of gastrointestinal involvement in SSc patients. The multi-symptom questionnaire was used at baseline and after 1 year in registered patients of the DNSS. In addition, the results were compared with gastrointestinal disorders in patients with SSc and other rheumatic diseases, as well as with the medical history of the patients. In total, 90 patients were included in the study. The results of the study show that in reality, a much higher (nearly all) percentage of (98,9%) patients than expected suffer from GI-symptoms, regardless of the stage of their disease. Of these, meteorism (87,8%) was the most common followed by coughing/sore voice (77,8%), heartburn (daytime 68,9%, nighttime 53,3%), diarrhea (67,8%), stomach ache (68,9%) and nausea (61,1%). Although SSc patients were treated according to the respective recommendations, only limited improvements with regard to GI-symptoms could be achieved after 1 year of follow-up. In addition, the study revealed that the multi-symptom questionnaire is a useful tool to contribute to identify the gastrointestinal sequelae in systemic sclerosis.

The registry of the German Network for Systemic Scleroderma: frequency of disease subsets and patterns of organ involvement.

OBJECTIVE: Systemic sclerosis (SSc) is a rare, heterogeneous disease, which affects different organs and therefore requires interdisciplinary diagnostic and therapeutic management. To improve the detection and follow-up of patients presenting with different disease manifestations, an interdisciplinary registry was founded with contributions from different subspecialties involved in the care of patients with SSc. METHODS: A questionnaire was developed to collect a core set of clinical data to determine the current disease status. Patients were grouped into five descriptive disease subsets, i.e. lcSSc, dcSSc, SSc sine scleroderma, overlap-syndrome and UCTD with scleroderma features. RESULTS: Of the 1483 patients, 45.5% of patients had lcSSc and 32.7% dcSSc. Overlap syndrome was diagnosed in 10.9% of patients, while 8.8% had an undifferentiated form. SSc sine scleroderma was present in 1.5% of patients. Organ involvement was markedly different between subsets; pulmonary fibrosis for instance was significantly more frequent in dcSSc (56.1%) than in overlap syndrome (30.6%) or lcSSc (20.8%). Pulmonary hypertension was more common in dcSSc (18.5%) compared with lcSSc (14.9%), overlap syndrome (8.2%) and undifferentiated disease (4.1%). Musculoskeletal involvement was typical for overlap syndromes (67.6%). A family history of rheumatic disease was reported in 17.2% of patients and was associated with early disease onset (P < 0.005). CONCLUSION: In this nationwide register, a descriptive classification of patients with disease manifestations characteristic of SSc in five groups allows to include a broader spectrum of patients with features of SSc.

Predictors of abnormal cardiovascular autonomic function measured by frequence domain analysis of heart rate variability and conventional tests in patients with type 1 diabetes.

OBJECTIVE: Frequency domain analysis of heart rate variability (HRV) is used to assess cardiovascular autonomic function. There are no prospective data on the sensitivity of its various components to glycemia or other diabetes-related risk factors compared with conventional tests and with other complications of diabetes. RESEARCH DESIGN AND METHODS: In 1985, possible risk factors of future complications were determined in 115 children with type 1 diabetes. In 1996, the presence of complications (HRV analysis, conventional tests of autonomic function, urinary albumin excretion rate [UAER], and retinopathy) were assessed in 83 of these patients (age 32 +/- 1 years, duration of diabetes 22 +/- 1 years). RESULTS: Poor glycemic control (measured as lifetime glycemic exposure or HbA1c in 1985) was the most important independent predictor of decreases in all measures of absolute power of HRV (total power [TP] and very low frequency, low frequency [LF], and high frequency [HF] power) and square root of the mean square of R-R interval differences but not of changes of normalized measures or ratios (normalized HF and LF LF/HF). Other significant independent predictors of autonomic dysfunction were late age of onset of diabetes, female sex, and high BMI. To examine the sensitivity of the various tests to glycemia, the patients were divided into tertiles based on lifetime glycemic exposure (A1c months). Glycemic exposure in the tertiles averaged 194 +/- 25 A1c months (20 years of HbA1c 0.8% above normal), 556 +/- 19 A1c months(20 years of HbA1c 2.3% above normal), and 963 +/- 30 A1c months (20 years of HbA1c 4% above normal). Tests of complications that were significantly abnormal in patients already in the lowest tertile and were correlated with glycemia were TP and severity of retinopathy. Of conventional tests, only the ratio of length of R-R intervals during expiration to inspiration (E/I ratio) was significantly related to glycemic exposure, but it required high glycemic exposure (20 years of HbA1c 4% above normal) to be abnormal. UAER was significantly increased only in the highest tertile of glycemic exposure. CONCLUSIONS: TP and retinopathy score were much more sensitive to antecedent glycemia than conventional tests of autonomic function or UAER and were significantly abnormal in patients exposed to approximately 20 years' duration of an HbA1c 0.8% above normal.

EEG in early HIV-1 infection is characterized by anterior dysrhythmicity of low maximal amplitude.

We analyzed the EEGs of 67 HIV-1-infected patients at various stages of the disease and of 35 HIV-1-seronegative controls. The most common EEG abnormality in HIV-1 infection was an increased amount of generalized episodic or persistent, predominantly anterior slow activity, associated with a low level of maximal amplitude. When compared to the controls, a lower maximal amplitude of dominant background activity (p less than 0.001), and more marked generalized (p less than 0.01) and anterior (p less than 0.001) disturbances were already seen in early stages of HIV-1 infection. EEG abnormalities were more severe in patients with advanced HIV-1 infection than in those at early infection (p less than 0.001 to p less than 0.05). The presence of a more marked, posteriorly (p less than 0.01) accentuated, generalized slow activity (p = 0.02) was found more often in patients with T-helper cell counts lower than 0.4 x 10(9) (p = 0.05) than in those with higher numbers of T-helper cells. No clear associations were found between the severity of EEG abnormalities and the duration of HIV-1 infection. Our results suggest that EEG is a sensitive method in detecting subclinical functional cerebral disturbances caused by HIV-1.

Magnetic measurements of pulmonary contamination.

The magnitic determination of pulmonary contamination is based on the remanent magnetization of ferromagnetic contaminating particles. The remanent field of the externally magnetized particles is proportional to their amount and shows their distribution. Although only magnetizable particles are detected with this method, the amount of the inhaled ferromagnetic substance can be used when the total dust exposure of the worker is estimated. In this work five shipyard welders were studied. First the particles disposed to the lungs were externally magnetized and then their distribution was mapped with a sensitive magnetometer. The magnitudes of the remanent fields measured from the welders differed from the fields measured from controls by several orders of magnitude. The radiographic findings showed a good correlation with the magnetic measurements, and further experiments will prove whether this method can partly replace presently used radiological investigations.

[Synthesis of D-ribulose-1,5-diphosphate with immobilized enzymes of Thiobacillus]. / Sintez D-ribulozo-1,5-difosfata immobilizovannoi fermentnoi sistemoi tionovykh bakterii.

Preparative synthesis of D-ribulose-1,5-diphosphate (RuDP) from ribose-5-phosphate and ATP was carried out, using as a catalyst a crude extract of Thiobacillus thiooxidans 58 R immobilized on porous glass. The methods for immobiliztion of crude bacterial extracts, synthesis of RuDP and purification of the resultant product by means of column chromatography on activated charcoal and anionites were developed. The structure of RuDP was identified by 13C-NMR spectroscopy. Stability of two phosphate groups of RuDP during acid and alkaline hydrolysis proved to be different: both phosphate groups were completely removed in 1 N H2SO4 at 100 degrees C whereas only one phosphate group was hydrolysed in 1 N NaOH at 25 degrees C. This finding is at variance with the earlier results of Horecker et al. (1956).

Medical illness, medication use and suicide in seniors: a population-based case-control study.

BACKGROUND: Suicide among seniors is a significant health problem in north America, particularly for men in whom the rates rise steadily after 50 years of age. The goal of this study was to examine elder suicides identified from a large population-based database using case-control methods to determine disease and medication factors related to suicide. METHODS: A population-based 1 : 5 case-control study was conducted comparing seniors aged 66 years and older who had died by suicide with age and sex-matched controls. Case data were obtained through British Columbia (BC) Vital Statistics, whereas controls were randomly selected from the BC Health Insurance Registry. Cases and controls were linked to the provincial PharmaCare database to determine medication use and the provincial Physician Claims and Inpatient Hospitalization databases to determine co-morbidity. RESULTS: Between 1993 and 2002 a total of 602 seniors died by suicide in BC giving an annual rate of 13.2 per 100,000. Firearms were the most common mechanism (28%), followed by hanging/suffocation (25%), self-poisoning (21%), and jumping from height (7%). In the adjusted logistic model, variables related to suicide included: lower socioeconomic status, depression/psychosis, neurosis, stroke, cancer, liver disease, parasuicide, benzodiazepine use, narcotic pain killer use and diuretic use. There was an elevated risk for those prescribed inappropriate benzodiazepines and for those using strong narcotic pain killers. CONCLUSION: This study is consistent with previous studies that have identified a relationship between medical or psychiatric co-morbidity and suicide in seniors. In addition, new and potentially useful information confirms that certain types and dosages of benzodiazepines are harmful to seniors and their use should be avoided.

[Gastrointestinal involvement in systemic sclerosis. An underestimated complication]. / Gastrointestinale Beteiligung bei systemischer Sklerose. Eine häufig verharmloste Komplikation.

Systemic sclerosis (SSc) belongs to the family of autoimmune connective tissue diseases and is still a challenge to every practicing physician. The disorder is characterized by progressing fibrosis of the skin and internal organs, abnormal activation of the immune system, and distinct changes in microcirculation. Although it is rare--with a prevalence of about 20:100000--patients need to be cared for in a daily setting. In general thickening of the skin is the first sign of the disease, so dermatologists are most frequently consulted first. Two subtypes exist, limited and diffuse forms. Both entities usually involve internal organs, and therefore interdisciplinary cooperation is mandatory. The increased morbidity and mortality depend predominantly on the grade of involvement of the affected organs. Therefore it is essential to diagnose systemic sclerosis early and to identify and monitor all complications closely. In this respect gastrointestinal involvement is frequently neglected, owing to its primarily non-life-threatening character, resulting in substantially delayed therapy.

[Systemic sclerosis--a challenge in rheumatology]. / Die systemische Sklerose--Eine rheumatologische Herausforderung.

The connective tissue disease systemic sclerosis (SSc) is still a challenge to every rheumatologist. SSc is characterized by progressing fibrosis of the skin and internal organs, abnormal activation of the immune system and distinct changes in microcirculation. Although it is a rare disease with a prevalence of about 20:100,000 one may come across it in daily practice. SSc is classified into limited and diffuse forms. Both entities usually involve internal organs. Life expectancy is limited and depends predominantly on the extent of the organs involved. Therefore, it is essential to diagnose SSc early and to identify and closely monitor the organs involved.

Connective tissue diseases and pregnancy.

Connective tissue diseases (CTD) such as systemic lupus erythematosus diffuse or limited systemic sclerosis and numerous others affect women frequently during the childbearing period. Every pregnancy in a patient with CTD should be regarded as high-risk pregnancy, and requires intensive monitoring and immediate treatment of clinical problems. For these reasons, for women suffering from CTD, who are pregnant or who intend to become pregnant, an interdisciplinary setting addressing all aspects of rheumatology, ob-gyn and neonatalogy needs to be provided. This setting includes particular diagnostic tools and laboratory parameters prior to and during pregnancy as well as in the post-partal period. Aside overt organ dysfunction, key problems in pregnant CTD patients consist mainly of haemostaseological problems such as antiphospholipid antibodies, neonatal lupus erythematosus, congenital heart block and drug therapy of the underlying disease, which will be outlined in this review.

Abnormal electroencephalogram at diagnosis of insulin-dependent diabetes mellitus may predict severe symptoms of hypoglycemia in children.

OBJECTIVES: To evaluate the predictive value of the electroencephalogram (EEG) at the time of diagnosis of insulin-dependent diabetes mellitus (IDDM) for subsequent hypoglycemic coma and/or convulsion. To study whether such an episode causes long-term EEG abnormalities. STUDY DESIGN: An EEG was recorded in 36 patients with IDDM 2 to 3 weeks after diagnosis (median age, 7.5 years) and was then repeated after an episode of severe hypoglycemia associated with coma and/or convulsion (median age, 13.3 years). Paired EEGs were also recorded in 36 age-matched and IDDM duration-matched control patients who had never experienced severe hypoglycemia. A single EEG was recorded in 36 healthy children, matched with patients' ages at the time of IDDM diagnosis. RESULTS: Patients with severe hypoglycemia had an abnormal initial EEG recording more often than did control patients with IDDM (22.2% vs 2.8%, P =.03). Each of the healthy children had a normal EEG recording. The odds ratio for risk of subsequent coma and/or convulsion during hypoglycemia in patients with abnormal initial EEG recordings was 8 (95% CI, 1.1-354.7). After such an episode, the frequency of the abnormal EEG recordings was not elevated. CONCLUSIONS: EEG at the time of diagnosis of IDDM may be useful in identifying those patients at increased risk for coma and/or convulsion as a result of hypoglycemia. However, a single such episode did not appear to have a deleterious effect on the subsequent EEG.

[Dependence of extracellular proteases synthesis on the growth phase of Pseudomonas fluorescens]. / Zavisimost' sinteza vnekletochnykh proteaz ot fazy rosta u Pseudomonas fluorescens.

The aim of this work was to study the dependence of the synthesis of exocellular proteolytic enzymes on the growth phase of Pseudomonas fluorescens which was cultivated in media containing amino acids as a sole carbon source. In all of the studied cases, the proteolytic activity of the medium increased in parallel to the bacterial growth until the culture reached the stationary growth phase. Chloramphenicol added in the phase of intensive growth ceased the increase of the proteolytic activity of the medium without a noticeable delay in time. This fact indicates that the processes of translation and secretion of exoproteases occur virtually at the same time in the cell of P. fluorescens. The rate of degradation of exocellular proteolytic enzymes was shown to be insignificant in comparison to the rate of their synthesis. Therefore, the increase in the proteolytic activity of the medium directly reflects the rate of synthesis of exoproteases.

[Localization of metabolites which are regulators of extracellular protease synthesis in Pseudomonas fluorescens bacteria]. / O lokalizatsii metabolitov--reguliatorov sinteza vnekletochnykh proteaz u bakterii Pseudomonas fluorescens.

The effect of over forty low molecular weight substrates on the growth and synthesis of exocellular neutral proteases was studied in Pseudomonas fluorescens. Neutral exoproteases were found to be regulated enzymes. Glucose did not repress the synthesis of exocellular proteases; the regulation of their synthesis by amino acids involved the mechanism of induction. The data suggest that the primary intracellular inductors of the synthesis of exoproteases are formed for different groups of amino acids at different levels of their utilization by the cells, viz. at the level of transport and at the level of the first steps in the degradation of their carbon backbones. The paper discusses possible molecular mechanisms for integrating the signal of the primary intracellular inductors, which directly regulate the activity of the operon(s) of neutral exocellular proteases.