Sjögren's Syndrome with Chronic Pancreatitis, Sclerosing Cholangitis, and Pulmonary Infiltrations

We report a patient with Sjögren's syndrome and multiple gastrointestinal manifestations who successfully responded to therapy with ursodeoxycholic acid. Our patient had sialoadenitis with dry mouth, dry eyes, arthralgia, chronic pancreatitis, sclerosing cholangitis, and pulmonary inflitrations. The first signs of disease were the symptoms of chronic pancreatitis followed by icterus, caused by extrahepatic bile duct obstruction. Sclerosing cholangitis was diagnosed by liver biopsy and endoscopic retrograde cholangiography. Sialoadenitis, causing dry mouth, was verified by buccal biopsy. Pulmonary infiltrations were seen on standard chest x-ray, and also shown by high-resolution computed tomography examination. Obstructive icterus and even pulmonary infiltration responded successfully to treatment with ursodeoxycholic acid.     

Complete Sequence of a 93.4-kb Contig from Chromosome 3 of Trypanosoma cruzi Containing a Strand-Switch Region

We have initiated large-scale sequencing of the third smallest chromosome of the CL Brener strain of Trypanosoma cruzi and we report here the complete sequence of a contig consisting of three cosmids. This contig covers 93.4 kb and has been found to contain 20–30 novel genes and several repeat elements, including a novel chromosome 3-specific 400-bp repeat sequence. The intergenic sequences were found to be rich in di- and trinucleotide repeats of varying lengths and also contained several known T. cruzi repeat elements. The sequence contains 29 open reading frames (ORFs) longer than 700 bp, the longest being 5157 bp, and a large number of shorter ORFs. Of the long ORFs, seven show homology to known genes in parasites and other organisms, whereas four ORFs were confirmed by sequencing of cDNA clones. Two shorter ORFs were confirmed by a database homology and a cDNA clone, respectively, and one RNA gene was identified. The identified genes include two copies of the gene for alanine-aminotransferase as well as genes for glucose-6-phosphate isomerase, protein kinases and phosphatases, and an ATP synthase subunit. An interesting feature of the sequence was that the genes appear to be organized in two long clusters containing multiple genes on the same strand. The two clusters are transcribed in opposite directions and they are separated by an ~20-kb long, relatively GC-rich sequence, that contains two large repetitive elements as well as a pseudogene for cruzipain and a gene for U2snRNA. It is likely that this strand switch region contains one or more regulatory and promoter regions. The reported sequence provides the first insight into the genome organization of T. cruzi and shows the potential of this approach for rapid identification of novel genes.     

Electrodermal Responsivity in Young Hypotensive and Hypertensive Men

Electrodermal responses were recorded during the presentation of 16 moderately intense (1000 Hz, 90dB) tones in three groups of young men: borderline hypertensives (138/79 mmHg), normotensives (112/65 mmHg), and hypotensives (104/63 mmHg). Electrodermal response habituation was measured as a decline in response over trials, number of trials to a response criterion of three successive nonresponses, and number of inversions of response amplitude (larger responses following smaller responses) in the stimulus sequence. Habituation was fastest in hypotensives. Nonspecific electrodermal responses at rest and during tone presentations were most frequent in borderline hypertensives, least frequent in the hypotensive group, with the normotensive group falling in between. There were no significant differences in electrodermal level. The rapid habituation rate in hypotensives is discussed in terms of cursory information processing associated with impulsive behaviour. The higher nonspecific electrodermal activity in borderline hypertensives is interpreted to indicate increased sympathetic nervous system activity.     

On lossy transform compression of ECG signals with reference to deformation of their parameter values

Electrocardiogram (ECG) signals are the most prominent biomedical signal type used in clinical medicine. Their compression is important and widely researched in the medical informatics community. In the previous literature compression efficacy has been investigated only in the context of how much known or developed methods reduced the storage required by compressed forms of original ECG signals. Sometimes statistical signal evaluations based on, for example, root mean square error were studied. In previous research we developed a refined method for signal compression and tested it jointly with several known techniques for other biomedical signals. Our method of so-called successive approximation quantization used with wavelets was one of the most successful in those tests. In this paper, we studied to what extent these lossy compression methods altered values of medical parameters (medical information) computed from signals. Since the methods are lossy, some information is lost due to the compression when a high enough compression ratio is reached. We found that ECG signals sampled at 400 Hz could be compressed to one fourth of their original storage space, but the values of their medical parameters changed less than 5% due to compression, which indicates reliable results.     

Neuroendocrine and Cardiovascular Stress Reactivity in Middle-Aged Normotensive Adults with Parental History of Cardiovascular Disease

Neuroendocrine and cardiovascular stress reactivity was studied in healthy middle-aged individuals whose parental history included essential hypertension and/or myocardial infarction and a control group without parental history of cardiovascular disease. All subjects completed a rest session (1 hour) and a stress session (1 hour). The stress session included behavioral (mirror image tracing, mental arithmetic, and the Stroop color word conflict test) and physical stressors (the cold pressor test and isometric exercise). Systolic and diastolic blood pressures and heart rate were recorded at baseline before and during all stressors. Specimens for determination of urinary catecholamines and cortisol were sampled after the rest and stress sessions respectively. Generally, a parental history of hypertension but not of myocardial infarction influenced neuroendocrine and cardiovascular stress reactivity. A family history of hypertension was associated with exaggerated epinephrine, norepinephrine, and cortisol excretion during stress and with enhanced heart-rate reactivity to behavioral (mental arithmetic and mirror image tracing) but not to physical stressors (isometric exercise or the cold pressor test). We conclude that individuals with a family history of hypertension tend to display exaggerated cardiovascular and neuroendocrine reactivity to stress.     

Gamma scintigraphic evaluation of the fate of hydroxypropyl methylcellulose capsules in the human gastrointestinal tract

The fate (movement and disintegration) of hard novel hydroxypropyl methylcellulose (HPMC) two-piece capsules in the human gastrointestinal tract was investigated using a gamma scintigraphic imaging method. Two different prolonged-release formulations without an active ingredient were used. The capsules contained different viscosity grades of HPMC powder (HPMC K100 and HPMC K4M). The aim was to determine the main reason why the pharmacokinetic profiles of model drugs change when the diluent was changed to a higher viscosity grade. The results were compared with our previous pharmacokinetic studies with corresponding capsules containing metoclopramide hydrochloride or ibuprofen as a model drug. The first observation was that the HPMC capsules had a tendency to attach to the oesophagus. Therefore, it is recommended that the HPMC capsules as well as gelatine capsules be taken with a sufficient amount of water (150–200 ml) in an upright position and maintaining the upright position for several minutes. The viscosity grade of the HPMC did not affect the transit times of the capsules in the GI tract. The major differences between the two formulations were the complete disintegration times of the capsules and the spreading of the capsules to the large intestine. Most of the HPMC K100-based capsules were completely disintegrated during the 8 h study, whereas the HPMC K4M-based capsules still exhibited plug formations in the large intestine. Also the HPMC K100-based capsules spread better to the ascending colon than the HPMC K4M-based capsules. The faster disintegration of the HPMC K100-based capsules explains the differences in the pharmacokinetic profiles of the model drugs between the HPMC K100- and K4M-based capsules in our previous studies. The main absorption site of the drugs from the capsules studied here is probably the large intestine when taken in a fasting state.     

Modelling the risk of noise-induced hearing loss among military pilots

Noise is a significant risk factor in aviation, especially in military aviation. Even though our earlier studies have shown that the risk of noise-induced hearing loss (NIHL) among military pilots is small and the monitoring of their hearing is effective, we still need to develop methods of assessing the risk of NIHL more effectively at both the general and individual levels. In addition, many other risk factors are considered to contribute to the development of hearing impairment. The novel NoiseScan data management system enables assessment of the risk of developing hearing impairment on the basis of known risk factors. This study investigates the risk of hearing impairment among Finnish Air Force pilots using reasonably accurate noise exposure data and other risk factors for hearing impairment. This risk is also compared with that of industrial workers, whose risk followed the ISO 1999 prediction. Hearing among Finnish military pilots turned out to be better than predicted by the ISO 1999 model. The industrial workers had a larger number of risk factors than the pilots. Owing to the small number of risk factors, the hearing of pilots corresponds to approximately the 80th percentile, being 9-13 dB better than the 50th percentile obtained with the industrial population.     

New polymyxin derivatives that display improved efficacy in animal infection models as compared to polymyxin B and colistin

Polymyxin B and colistin (polymyxin E) are bactericidal pentacationic lipopeptides that act specifically on Gram‐negative bacteria, first by disrupting their outermost permeability barrier, the outer membrane (OM), and then damaging the cytoplasmic membrane. The discovery of both polymyxin B and colistin was published independently by three laboratories as early as in 1947. They were subsequently used in intravenous therapy. Unfortunately, they also exhibit significant and dose‐limiting nephrotoxicity. Therefore, polymyxins were reserved as agents of last‐line defense. The emergence of extremely multiresistant strains has now forced clinicians to reinstate polymyxins in the therapy of severe infections. However, the current dosage regimens lead to insufficient drug concentrations in serum and clinicians have been advised to use larger doses, which further increases the risk of nephrotoxicity. Very recently, the interest in developing better tolerated and more effective polymyxins has grown. This review focuses on describing four development programs that have yielded novel derivatives that are more effective than the old polymyxins in animal infection models. Compounds from three programs are superior to the old polymyxins in the rodent lung infection model with Acinetobacter baumannii and/or Pseudomonas aeruginosa. One of them is also more effective than polymyxin B in A. baumannii mouse thigh infection. The fourth program includes compounds that are approximately tenfold more effective in Escherichia coli murine pyelonephritis than polymyxin B.     

Celiac disease in patients with severe liver disease: gluten-free diet may reverse hepatic failure

BACKGROUND & AIMS: Mild liver abnormalities are common in patients with celiac disease and usually resolve with a gluten-free diet. We investigated the occurrence of celiac disease in patients with severe liver failure. METHODS: Four patients with untreated celiac disease and severe liver disease are described. Further, the occurrence of celiac disease was studied in 185 adults with previous liver transplantation using serum immunoglobulin A endomysial and tissue transglutaminase antibodies in screening. RESULTS: Of the 4 patients with severe liver disease and celiac disease, 1 had congenital liver fibrosis, 1 had massive hepatic steatosis, and 2 had progressive hepatitis without apparent origin. Three were even remitted for consideration of liver transplantation. Hepatic dysfunction reversed in all cases when a gluten-free diet was adopted. In the transplantation group, 8 patients (4.3%) had celiac disease. Six cases were detected before the operation: 3 had primary biliary cirrhosis, 1 had autoimmune hepatitis, 1 had primary sclerosing cholangitis, and 1 had congenital liver fibrosis. Only 1 patient had maintained a long-term strict gluten-free diet. Screening found 2 cases of celiac disease, 1 with autoimmune hepatitis and 1 with secondary sclerosing cholangitis. CONCLUSIONS: The possible presence of celiac disease should be investigated in patients with severe liver disease. Dietary treatment may prevent progression to hepatic failure, even in cases in which liver transplantation is considered.