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Biomedical subjects

A Papadopoulos

Publications and source records attributed to A Papadopoulos.

At least 55 records · Page 3Linked to original sources

Prevalence of cryoglobulinemia in chronic hepatitis C virus infection and response to treatment with interferon-alpha.

Chronic hepatitis C virus (HCV) infection is associated with a variety of clinically important extrahepatic abnormalities. We have assessed the prevalence of cryoglobulinemia and of the clinical syndrome associated with it in patients with chronic HCV infection. We also have evaluated the clinical, serologic, and biochemical response to antiviral treatment with interferon-alpha (IFN-alpha). Eighty-one patients with chronic liver disease associated with HCV infection were included. Cryoglobulins were sought in the serum. All patients were examined carefully for clinical manifestations of cryoglobulinemia (e.g., palpable purpura, Raynaud's syndrome, arthritis, peripheral neuropathy, Sjögren's syndrome, glomerulonephritis). Antiviral treatment with IFN-alpha, at a dose of 3 to 5 million units, 3 times weekly, was given to 20 patients with cryoglobulinemia. Cryoglobulins were detected in 45.7% of patients. Signs and symptoms of the clinical syndrome associated with cryoglobulinemia were present in 12.3% of the entire group of patients (27% of the subgroup with detectable cryoglobulins). Patients with cryoglobulinemia were older (mean age, 56 +/- 15 vs. 44 +/- 16 years; p = 0.002) and had a higher rate of cirrhosis (48.6% vs. 18.2%, rate ratio = 4.26, 95% confidence interval = 2.11 to 8.58, p = 0.00005) compared to patients without cryoglobulinemia. Cryoglobulins disappeared from the serum in 13 (65%) of the 20 patients who were treated for 6 to 12 months with IFN-alpha. This effect was affiliated in most patients with resolution of the clinical findings associated with cryoglobulinemia and return of transaminases to normal levels. Recurrence of cryoglobulinemia was observed in two thirds of the patients who were observed after treatment with IFN-alpha. We conclude that cryoglobulins are present in 45.7% of patients with chronic HCV infection. Symptoms or signs or both associated with the presence of cryoglobulins develop in a high proportion (27%) of these patients. Antiviral treatment with IFN-alpha leads to resolution of both cryoglobulinemia and the symptoms associated with it in most patients who also show a biochemical response to antiviral treatment. Recurrence is frequent after treatment withdrawal.

Adult↗

Heat-shock protein 27 (HSP27) and its role in female reproductive organs.

Heat shock, other environmental and pathophysiological stress stimulate synthesis of heat shock proteins (HSP) family. These proteins enable the cell to survive and recover from stressful conditions but as yet incompletely understood mechanisms. Beside its role in thermotolerance, it plays a role in cell proliferation and drug resistance which makes this protein of special clinical interest. Published data suggest that HSP27 is related to estrogen in breast and to estrogen and progesterone in the endometrium. It has been shown that some but not all estrogen positive breast cancers express HSP27, and overexpression has been associated with the degree of tumor differentiation, and response to hormonal therapy (Tamoxifen). In endometrial carcinomas, the presence of HSP27 is correlated with the degree of tumor differentiation as well as with the presence of oestrogen and progesterone receptors. Studies suggest that detection of HSP27 in endometrial carcinoma, should not be considered as a method for identifying hormone-responsive tumors or indicator or presence of estradiol receptors. In the cervix HSP27 is a marker of cell differentiation, and is highly expressed during the process of squamous metaplasia. Expression in the ovary is still controversial and requires further confirmation of recent observations.

Breast↗

Osteoporosis in lung transplantation candidates with end-stage pulmonary disease.

PURPOSE: Fractures, a common complication of cardiac and liver transplantation, have not been reported in association with lung transplantation. However, many patients with end-stage pulmonary disease have multiple risk factors for osteoporosis, and several studies have suggested that osteoporosis before transplantation may increase the risk of fracture after transplantation. Therefore, we evaluated a group of patients with end-stage pulmonary disease who were awaiting lung transplantation to determine the prevalence of osteoporosis. METHODS: Seventy patients (aged 18-70 years) were evaluated consecutively with bone densitometry by dual-energy x-ray absorptiometry. The patients were predominantly Caucasian (96%). Bone mass was expressed as bone mineral density (BMD; g/cm2), as the number of standard deviations (SD) below peak bone mass (T score), and as bone mineral apparent density (BMAD; g/cm3), a measurement that minimizes the effects of bone size on BMD. Spine radiographs were obtained in a subset of 50 consecutive patients to detect vertebral compression fractures. Vitamin D status was assessed with serum concentrations of 25-hydroxyvitamin D. The patients were sorted into groups by pulmonary diagnosis: chronic obstructive pulmonary disease (COPD; n = 28); cystic fibrosis (n = 11); idiopathic pulmonary fibrosis; and other lung diseases (Other; n = 31). RESULTS: In the group as a whole, osteoporosis (T score below -2.5) was present in 30% of the patients at the lumbar spine and 49% at the femoral neck. Osteopenia (T score between -1 and -2.5) was present in an additional 35% at the lumbar spine and 31% at the femoral neck. The average femoral neck T score of patients with COPD and cystic fibrosis fell into the osteoporotic range (-2.7 +/- 0.3 and -2.6 +/- 0.3, respectively), significantly (P < 0.01) below that of the patients in the Other category (-1.5 +/- 0.3). The average lumbar spine T score fell into the osteopenic range in all three groups. Low BMAD in patients with cystic fibrosis confirmed that their low BMD was not due to their smaller body size. The prevalence rate of vertebral fractures was 29% in patients with COPD and 25% in those with cystic fibrosis. Vitamin D deficiency (25-hydroxyvitamin D levels < or = 10 ng/ml) was present in 36% of patients with cystic fibrosis and 20% with COPD and Other lung diseases. Lumbar spine BMD tended to be lower in cystic fibrosis patients with vitamin D deficiency. Patients with exposure to glucocorticoids (n = 46) had significantly more vertebral fractures (P < 0.05) and duration of exposure correlated negatively with lumbar spine BMD (r = -0.398; P = 0.008). COPD and Other patients not on glucocorticoids had mild lumbar spine osteopenia (0.972 +/- 0.06 g/cm2; T = -1.2 +/- 0.6). Very few of the patients on glucocorticoids were on any regimen to prevent osteoporosis. CONCLUSIONS: Osteoporosis and vitamin D deficiency are extremely common in patients with end-stage pulmonary disease. Only 34% of patients had normal lumbar spine BMD and only 22% had normal BMD at the hip. Patients with cystic fibrosis and glucocorticoid-treated patients with COPD were most severely affected. Therapies to prevent bone loss and treat established osteoporosis are uncommonly utilized in glucocorticoid-treated patients with end-stage pulmonary disease. Candidates for lung transplantation should be evaluated for osteoporosis and vitamin D deficiency at the time of acceptance to the transplant waiting list.

Absorptiometry, Photon↗

MRI in the investigation of patients with myelopathy thought to be due to multiple sclerosis.

The role of cerebral and spinal cord MRI was investigated in 65 patients with myelopathy suspected of having demyelinating disease. Cerebral MRI demonstrated lesions compatible with demyelination in 80% and spinal cord MRI in 68.6%. In 28.5% of our patients brain lesions were present with normal spinal cord images, but in 17% spinal cord lesions were depicted with a normal brain MRI. The combination of the two examinations demonstrated lesions in 97% of the patients. The frequency of coexistent cerebral lesions in patients with spinal cord lesions was over 85% in patients with chronic disease but only 28.5% in patients with acute myelitis.

Adolescent↗

Value of Gd-DTPA-enhanced MR imaging of the labyrinth in patients with sudden hearing loss.

Recent reports describe labyrinthine enhancement on MRI as a highly specific sign of labyrinthine disease. This paper reports 44 patients with unilateral sensorineural hearing loss (SNHL) and laboratory evidence of cochlear damage investigated with Gd-enhanced MR imaging. Enhancement of the cochlea was observed in only one patient with a lesion at the fundus of the internal auditory canal (IAC) that extended into the cochlea after Gd-DTPA administration. In one more patient, MR imaging demonstrated large vestibular aqueducts as underlying cause for his hearing loss, but no enhancement of the labyrinth was observed. No abnormal signal intensity on precontrast MR scans nor pathologic enhancement of the membranous labyrinth were identified in the other 42 patients. Gd-enhanced MR imaging appears to be insensitive in demonstrating labyrinthine disease and normal examination findings in a patient with sudden SNHL cannot exclude damage at the cochlear level.

Adolescent↗

The novel monoclonal antibody By114 helps detect the early emergence of a paroxysmal nocturnal hemoglobinuria clone in aplastic anemia.

The newly described monoclonal antibody By114 has been used with flow cytometry to investigate the status of the 90-kD glycosylphosphatidyl-inositol (GPI)-anchored component of CD66 (CD66c) on neutrophils from nine patients with paroxysmal nocturnal hemoglobinuria (PNH), seven with aplastic anemia/PNH, and 63 with aplastic anemia (AA) and a negative Ham's test. We have found that By114 is a sensitive indicator for recognizing patients with PNH and has helped delineate a group of nine patients with aplastic anemia and a negative Ham's test who have evidence of a larger PNH clone than indicated by other monoclonal antibodies (mAbs). By114 is a valuable marker for detecting the emergence of a PNH clone before the Ham's test becomes positive and is a more sensitive detector of deficient GPI-anchored proteins than other mAbs.

Adolescent↗

Correlation between spinal cord MRI and clinical features in patients with demyelinating disease.

Localisation of spinal cord lesions by MRI was correlated with neurological symptoms and signs in 16 patients with clinical and laboratory evidence of multiple sclerosis. There was good correspondence between spinal cord lesions and motor tract signs. On the other hand, superficial or deep sensory disturbances correlated with spinal cord lesions in only about a quarter of the patients. MRI of the spinal cord appeared to explain the myelopathy in 11 patients, while in 3 there was strong clinical evidence of more extensive demyelinating lesions. In 7 of the 16 patients MRI of the brain was normal.

Adolescent↗

Noradrenaline uptake inhibition increases melatonin secretion, a measure of noradrenergic neurotransmission, in depressed patients.

Eight patients with endogenous depression who had received no antidepressant treatment for the previous year were treated with the noradrenaline (NA) uptake inhibitor, desipramine (DMI). Pre-treatment plasma melatonin concentrations were normal. After one day of DMI treatment plasma melatonin concentrations were increased but the response was impaired compared to normal subjects. The acute effect of DMI on plasma melatonin persisted after six weeks of treatment. These findings question the hypothesis that beta adrenoceptors are supersensitive in depression and that antidepressant drugs act by down-regulating these receptors.

Adult↗

Effects of alpha-glucosidase inhibitors on mouth to caecum transit time in humans.

The alpha-glucosidase inhibitors acarbose and miglitol have been successfully used to control postprandial hyperglycaemia in diabetics. They probably work by slowing carbohydrate digestion and absorption, but their effect on mouth to caecum transit time has not been studied. The effect acarbose (100 mg), miglitol (100 mg), and placebo on mouth to caecum transit time (380 kcal breakfast with 20 g of lactulose) was investigated in 18 normal volunteers using breath hydrogen analysis. Both miglitol and acarbose significantly increased breath hydrogen excretion (F2,34 = 6.31, p = 0.005) and shortened the mouth to caecum transit time (F2,34 = 3.49, p = 0.04) after breakfast compared with placebo. There was a significant negative correlation between breath hydrogen excretion and mouth to caecum transit time suggesting that with shorter transit times significantly more carbohydrates were spilled into the colon. These results indicate that alpha-glucosidase inhibitors accelerate mouth to caecum transit time by inducing carbohydrate malabsorption.

1-Deoxynojirimycin↗

Differential diagnosis of space-occupying lesions of the liver with MR imaging.

In a retrospective study of 84 patients who underwent MRI examination of the liver the qualitative parameters margin, shape, internal structure, signal intensity and the presence of a capsule were evaluated in 152 lesions comprising 48 hemangiomas, 54 secondary deposits, 23 hepatomas, 8 simple cysts, 17 hydatid cysts, 1 abscess and 1 focal fatty infiltration. Our main objective was to differentiate hemangiomas from secondary deposits and hepatomas. In hemangiomas the combination of smooth margin (98%) round or oval shape (90%) homogeneity (96%) very high signal intensity on T2-weighted sequence (94%), and the complete absence of capsule helped to distinguish them from secondary deposits and hepatomas in the majority of cases. It is concluded that with MR imaging we can establish the diagnosis of focal lesions of the liver in about 95% of cases.

Adolescent↗

Purification of a human milk protein closely similar to tumor-secreted phosphoproteins and osteopontin.

A wide variety of rodent and human tumor cells secrete antigenically related phosphoproteins with molecular weights (Mr) of approximately 58,000 (hamster), 62,000 (rat, mouse), 67,000 (human) (Senger, D.R. and Perruzzi, C.A. (1985) Cancer Res. 45, 5818-5823). Expression of these phosphoproteins is transformation-related; tumor cells produce at least 10-fold or more of this protein as compared to their normal or untransformed counterparts. N-terminal and internal sequences derived from the rat tumor-secreted phosphoprotein indicate that it is identical to rat osteopontin, a bone protein with an Arg-Gly-Asp cell-binding sequence (Oldberg, A., Franzen, A. and Heinegard, D. (1986) Proc. Natl. Acad. Sci. USA 83, 8819-8823). Antibody raised to the Mr 62,000 rat tumor-secreted phosphoprotein was found to bind Mr 75,000 and Mr 35,000 components of human milk, indicating that milk contains antigenically related proteins. The Mr 75,000 protein, which is present in human milk at concentrations ranging from 3 to 10 micrograms/ml, has been purified to homogeneity. The Mr 35,000 component is apparently derived from the Mr 75,000 protein by proteolytic cleavage, and this cleavage also occurs in vitro in the presence of thrombin. N-terminal and internal amino acid sequences were derived from the Mr 75,000 milk protein and found to be similar (12/21 residues) to N-terminal and internal sequences derived from the rat tumor-secreted phosphoprotein and osteopontin. Moreover, sequence derived from the N-terminus of the human milk protein is identical to that of human bone sialoprotein I (the likely human homolog of rat osteopontin) (Fisher, L.W., Hawkins, G.R., Tuross, N. and Termine, J.D. (1987) J. Biol. Chem. 262, 9702-9708).

Amino Acid Sequence↗

An alpha 2 adrenoceptor antagonist, Org 3770, enhances nocturnal melatonin secretion in man.

Nocturnal plasma melatonin concentration was significantly increased in ten normal volunteers following the administration of an alpha 2 adrenoceptor antagonist, Org 3770 (30 mg). This result supports the existence of an alpha 2 adrenergic influence on melatonin secretion in man and provides a possible clinical neuroendocrine marker of the action of an alpha 2 antagonist.

Adrenergic alpha-Antagonists↗

Purification of cytosolic glutathione transferases from Schistocephalus solidus (plerocercoid): interaction with anthelmintics and products of lipid peroxidation.

Glutathione (GSH) transferase isoenzymes have been partially resolved from the cytosol of Schistocephalus solidus (plerocercoid) by GSH affinity chromatography and chromatofocusing at pH 7-5. The presence of isomeric forms was also suggested by analytical isoelectric focusing and high-performance liquid chromatography (HPLC). Gel filtration and sodium dodecyl sulphate-polyacrylamide gel electrophoresis indicated that GSH transferase forms were dimers with a subunit size of approximately 24 kDa. The major GSH transferase form in S. solidus (plerocercoid) showed greater biochemical relationship to the Mu family of mammalian GSH transferase compared to the mammalian Alpha or Pi families. The major subunit purified by GSH affinity chromatography and reversed-phase HPLC also showed high N-terminal homology with the Mu family. A minor GSH transferase form appeared more biochemically related to the Alpha family with respect to substrate specificity and inhibitor sensitivity. The major GSH transferase was inhibited by haematin-related compounds, bile acids and a number of anthelmintics including members of the benzimidazole and phenol-based class of compounds. The major GSH transferase had conjugating activity with members of the trans, trans-2,4-alkadienal and trans-2-alkenal series, secondary products of lipid peroxidation.

Amino Acid Sequence↗