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  • 1
    ISSN: 1432-1203
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary We have studied 72 families with at least one child with cystic fibrosis (CF); they were referred because they had requested pre-natal diagnosis in a future pregnancy. The ΔF508 mutation was found in 108/140 CF chromosomes (77%). In 41/72 families (57%), both parents carried a deleted chromosome and the child was doubly deleted. In only 4 families, 2 of them being consanguineous, did neither parent carry a deleted chromosome. Meconium ileus was associated with children who were ΔF508/ΔF508, ΔF508/non-deleted and non-deleted/ non-deleted.
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  • 2
    ISSN: 1432-1084
    Keywords: Diffuse liver disease ; MRI ; CT ; Ultrasound
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Twenty-nine patients with diffuse liver disease were examined by ultrasound, CT and MRI. MRI was performed using T1- and T2-weighted spin-echo sequences as well as fast gradient-echo-sequences. The paramagnetic contrast agent Gd-DTPA was applied intravenously (0.1 mmol/kg). in patients with hepatitis, MRI could be used in guiding liver biopsies as inflammatory changes were clearly delineated. CT and ultrasound were superior to MRI in the detection of focal or diffuse fatty degeneration. On the other hand MRI was more helpful in differentiating fatty changes and neoplasm. In liver cirrhosis, fibrotic changes were most clearly demonstrated by MRI. In patients suffering from hemochromatosis MRI offers advantages over CT and ultrasound in the diagnosis and follow up due to the paramagnetic properties of iron, resulting in a reduction in signal intensity. In patients with Wilson's disease a characteristic pattern of parenchymal changes was seen. Administration of Gd- DTPA contributes additional information about perfusion conditions in the liver parenchyma, however this information was not of diagnostic relevance in the cases we studied.
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  • 3
    ISSN: 1432-1203
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The N1303K mutation was identified in the second nucleotide binding fold of the cystic fibrosis (CF) gene last year. We have gathered data from laboratories throughout Europe and the United States of America in order to estimate its frequency and to attempt to characterise the clinical manifestations of this mutation. N1303K, identified on 216 of nearly 15000 CF chromosomes tested, accounts for 1.5% of all CF chromosomes. The frequency of the N1303K allele varies significantly between countries and ethnic groups, being more common in Southern than in Northern Europe. This variation is independent of the AF508 allele. It was not found on UK Asian, American Black or Australian chromosomes. N1303K is associated with four different linked marker haplotypes for the polymorphic markers XV-2c, KM.19 and pMP6d-9. Ten patients are homozygous for this mutation, whereas 106 of the remainder carry one of 12 known CF mutations in the other CF allele. We classify N1303K as a “severe” mutation with respect to the pancreas, but can find no correlation between this mutation, in either the homozygous or heterozygous state, and the severity of lung disease.
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  • 4
    ISSN: 1432-1041
    Keywords: Captopril ; sublingual ; pharmacokinetics ; pharmacodynamics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In this study we compared the pharmacokinetics and pharmacodynamics of captopril after sublingual and peroral administration. Single 25 mg doses of captopril were administered sublingually and perorally on two different occasions in a randomised cross-over fashion to eight healthy volunteers aged 22–35 years. The kinetics of unchanged captopril, plasma renin activity (PRA), BP and heart rate were studied over three hours after both peroral and sublingual administration of captopril. Mean pharmacokinetic parameters for unchanged captopril after sublingual administration were: Cmax, 234 ng·ml−1; tmax, 45 min; AUC (0–3 h), 15.1 μg·ml−1. min. Mean pharmacokinetic parameters for unchanged captopril after peroral administration were: Cmax, 228 ng·ml−1; tmax, 75 min; AUC (0–3 h), 17.0 μg·ml−1. min. tmax was significantly shorter when captopril was administered sublingually; all other pharmacokinetic parameters were equivalent. The plasma captopril concentrations achieved post drug administration led to increases in PRA and reductions in BP. tmax for PRA was 86 min for sublingual captopril and 113 min for perorally administered drug. Peak PRA values were, however, not significantly different. BP, as expected, was not reduced dramatically in these healthy volunteer subjects, however, in systolic BP vs time profiles, BP was significantly lower after volunteers received sublingual captopril. Heart rate increased slightly after captopril administration; there were no differences between the two routes of administration. Administration of captopril sublingually, therefore led to a more rapid attainment of plasma captopril concentrations and had a more rapid onset of pharmacological effect when compared with peroral administration.
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  • 5
    ISSN: 1433-8491
    Keywords: Alzheimer's disease ; Aging ; Cytoskeleton ; Glycosylation ; Neuropathology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The ultrastructure of Alzheimer's neurofibrillary tangles is heterogeneous and includes abnormal paired helical filaments (PHF) and various other insoluble structures. Insoluble non-PHF components isolated from neurofibrillary tangles were examined by electron microscopy. Comparison of these fractions with normal assembled neurofilaments and normal brain microtubules revealed scattered profiles which were morphologically (not chemically) identical to structures present in the microtubule, but not in the neurofilament preparations. These results support the notion that insoluble microtubules contribute to the make up of the neurofibrillary tangle. Based on these findings, preliminary experiments were conducted which suggest that non-enzymatic glycosylation may be a pathway leading to insolubility of the microtubules.
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  • 6
    ISSN: 1420-9071
    Keywords: Cardiac output ; cardio-regulatory nerves ; hemodynamics ; neurohormones ; pericardial organ ; Crustacea
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract This report provides the first direct measurements of the stroke volume and total cardiac output of crustacean hearts, as recorded from a semi-isolated in vitro preparation. The responses to mechanical perturbations, changes in preload and afterload, show that these hearts do not possess automatic compensatory Frank-Starling-like mechanisms. Heart rate, reflecting the burst rate of the cardiac ganglion, is minimally affected by stretch. On the other hand, these hearts are exquisitely responsive to the neurohormones of the pericardial organs. Serotonin, CCAP and proctolin all produce positive chronotropic and inotropic effects, but the responses to each are unique. Two FMRFamide peptides were positively chronotropic, but negatively inotropic.
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  • 7
    ISSN: 1433-8726
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Prostate-specific antigen (PSA) is the most accurate serum marker for cancer of the prostate (CaP). However, its sensitivity and specificity are suboptimal, especially at values ranging between 4.1 and 10.0 ng/ml (monoclonal), because benign prostatic hypertrophy and hyperplasia (BPH) and CaP frequently coexist in this range. This study was undertaken to determine the value of incorporating prostate volume measurements with serum PSA levels in a quotient (PSA/volume) entitled PSA density (PSAD). A total of 3140 patients were analyzed and stratified by serum PSA, digital rectal examination (DRE), transrectal prostate ultrasound (TRUS), TRUS volume determination and PSAD. All patients were referred for evaluation and therefore do not represent a screened population. Patients underwent prostate biopsies when abnormalities in TRUS or DRE were detected. Although both PSA and PSAD have statistical significance when the serum PSA value is ≦4.0 ng/ml, neither has clinical significance in differentiating BPH from CaP. At serum levels ranging between 4.1 and 10.0 ng/ml, PSA has no ability to differentiate BPH from CaP, whereas PSAD does so with statistical and clinical significance. When the PSA value is between 10.1 and 20.0 ng/ml, only PSAD is statistically significant. When PSA exceeds 20 ng/ml, PSAD is redundant. We conclude that all patients with an abnormality on DRE or TRUS should undergo prostate biopsy. If the PSA value is ≦4.0 ng/ml, TRUS and PSAD are not warranted and routine biopsy is not recommended. For intermediate PSA levels, 4.1–10.0 ng/ml, TRUS, TRUS prostate volume, and PSAD are important. The use of PSAD provides unique information regarding the need for biopsy and the likelihood of CaP. At PSA levels ranging between 10.1 and 20.0 ng/ml, PSAD will identify those patients who are less likely to have CaP, but all should undergo biopsy. If the PSA value is 〉20 ng/ml, all patients should undergo a biopsy.
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  • 8
    ISSN: 1420-908X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rats were sensitized by i. d. injection in the base of the tail with Freund's complete adjuvant (FCA) and were challenged i. d. in the dorsal skin with mycobacterial antigen. The 24 hour dermal delayed-type hypersensitivity (DTH) response increased up to 10 days after FCA injection followed by a decrease by day 15 which coincided with the development of adjuvant arthritis (AA). Drug studies were performed, using a 4-day dosing schedule, on optimal DTH elicited on day 10, suboptimal DTH elicited on day 15, and AA (day 16). Cyclosporine, leflunomide and prednisolone significantly inhibited day 10 DTH and AA with no effect on day 15 DTH. Indomethacin and tiaprofenic acid significantly inhibited AA with no effect on either DTH response. Chloroquine, levamisole,d-penicillamine, diazepam and RU38468 had no significant effect on DTH or AA. These findings suggest a complex temporal relationship between AA, DTH and drug actions.
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  • 9
    ISSN: 1432-136X
    Keywords: Crustacea ; Amphipoda ; Haemocyanin ; Temperature sensitivity ; l-Lactate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The effect of pH, temperature, and l-lactate on the O2 bindign properties of haemocyanin (Hc) from three talitroidean species i.e., the aquatic Apohyale pugettensis, the semi-terrestrial Megalorchestia californiana, and the semi-/euterrestrial Traskorchestia traskiana was studied. The Hc of A. pugettensis was characterized by a higher O2 affinity (and more pronounced Bohr shift) than the Hc of either M. californiana or T. traskiana. Apohyale was the only species that possessed He that was sensitive to temperature change. Resuspending Hc from each of the three species in a stock Ringer's solution (based on the ionic composition of the haemolymph of T. traskiana) showed that the persistence of the difference in Bohr shift between Apohyale and the other two species was due to differences in the haemocyanins themselves and not attributable to their respective ionic environments. An inverse relationship was found between the cooperativity (n 50) and pH of Hc from T. traskiana and A. pugettensis but not for M. californiana. In each case adding l-lactate increased Hc O2 affinity, but this was most pronounced for A. pugettensis.
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  • 10
    ISSN: 1432-136X
    Keywords: Amphipoda ; Crustacea ; Haemocyanin ; Freezing ; Inorganic effectors ; Urate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The effect of variations in [K], [Ca], [Mg], [NaCl], and [urate] on the in vitro O2 binding properties of haemocyanin (Hc) from three talitroidean species, viz. the aquatic Apohyale pugettensis, the semi-terrestrial Megalorchestia californiana, and the semi-/euterrestrial Traskorchestia traskiana were studied. Freezing altered the cooperativity of Hc from A. pugettensis and M. californiana but not T. traskiana. Variations in [NaCl], [K], and [Mg] had no effect on cither O2 affinity or cooperativity of the Hc except for A. pugettensis Hc where an increase in [Mg] resulted in an increase in both O2 affinity and cooperativity. Increasing [Ca] or [urate] increased O2 affinity of both A. pugettensis and M. californiana but not T. traskiana Hc. These effects were most marked in A. pugettensis. The results suggest a negative correlation between sensitivity to Hc effectors and the degree of terrestrial adaptation of a particular amphipod species.
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