Novel analytical approach to monitoring advanced glycosylation end products in human serum with on-line spectrophotometric and spectrofluorometric detection in a flow system

We proposed a simple analytical procedure for measurement of serum advanced glycosylation end products (AGEs) based on simultaneous detection of low-molecular-mass peptides and AGEs with a flow system and two detectors connected on-line: spectrophotometric for peptides (lambda = 280 nm) and spectrofluorometric for AGEs (lambda ex = 247 nm, lambda em = 440 nm). Sample pretreatment was carried out in microcentrifuge tubes: Serum (20 microL) was deproteinized with trichloroacetic acid (480 microL, 0.15 mol/L) and lipids were extracted with chloroform (100 microL). Twenty microliters of the filtered aqueous layer was injected to the flow system and the relation between fluorescence and absorption signals was measured. A peptide-derived AGE calibrator was used for calibration. Within-day and between-day CVs were 6.7% and 9.1%, respectively, at an AGE concentration corresponding approximately to that in healthy individuals. Mean results (+/-SD) in 10 healthy individuals were 10.1% +/- 1.0%, in 21 patients with diabetes without complications 18.0% +/- 6.2%, in 25 patients with complications 24.1% +/- 15.4%, and in 12 diabetic patients in end-stage renal disease 92% +/- 30%. Comparison with an ELISA procedure (x, in arbitrary units/L) yields a regression equation y = 0.713x + 1.24 (Sy [symbol: see text] x = 6777, r = 0.8477, n = 41).     

Stress urinary incontinence. Our experience with its treatment using the transvaginal colposuspension technique (Raz I and II)

Presentation of our experience in the surgical treatment of urinary stress incontinence, with transvaginal colposuspension techniques, specifically those described by S. Raz and known as Raz I and Raz II. Over a 24-month period, 25 transvaginal colposuspensions (22 Raz I and 3 Raz II) were performed. The results achieved were 21 patients (84%) have recovered, while 4 (16%) remain incontinent, 3 of them referring improvement and 1 without improvement, after a follow-up of 12 to 36 months. With regard to complications, there has been 5 cases (20%) of postoperative retention, one vesical perforation while passing the needles, and a vesicle perforation during vaginal dissection of the retropubic space.     

Thyrotropic action of human chorionic gonadotropin

Hyperthyroidism or increased thyroid function has been reported in many patients with trophoblastic tumors. In these cases, greatly increased human chorionic gonadotropin (hCG) levels and suppressed TSH levels suggest that hCG has thyrotropic activity. Recent investigations have clarified the structural homology not only in the hCG and TSH molecules but also in their receptors, and this homology suggests the basis for the reactivity of hCG with the TSH receptor. The clinical significance of the thyrotropic action of hCG is now also recognized in normal pregnancy and hyperemesis gravidarum. Highly purified hLH binds to recombinant hTSH receptor and is about 10 times as potent as purified hCG in increasing cAMP. The beta-subunits of hCG and hLH share 85% sequence identity in their first 114 amino acids but differ in the carboxy-terminal peptide because hCG beta contains a 31-amino acid extension (beta-CTP). A recombinant mutant hCG that lacks beta-CTP showed almost identical potency to LH on stimulation of recombinant hTSH receptor. If intact hCG were as potent as hLH in regard to its thyrotropic activity, most pregnant women would become thyrotoxic. One of the roles of the beta-CTP may be to prevent overt hyperthyroidism in the first trimester of pregnancy when a large amount of hCG is produced by the placenta. Nicked hCG preparations, obtained from patients with trophoblastic disease or by enzymatic digestion of intact hCG, showed approximately 1.5- to 2-fold stimulation of recombinant hTSH receptor compared with intact hCG. This suggests that the thyrotropic activity of hCG may be influenced by the metabolism of the hCG molecule itself. Deglycosylation and/or desialylation of hCG enhances its thyrotropic potency. Basic hCG isoforms with lower sialic acid content extracted from hydatidiform moles were more potent in activating adenylate cyclase, and showed high bioactivity/immunoactivity (B/I) ratio in CHO cells expressing human TSH receptors. This is consistent with the finding that the beta-CTP truncated hCG with higher thyrotropic potency is substantially deglycosylated and desialylated in the beta-subunit relative to intact hCG because all four O-linked glycosylation sites occur within the missing C-terminal extension. The desialylated hCG variant also interacts directly with recombinant hTSH receptors transfected into human thyroid cancer cells. There is thyroid-stimulating activity in sera of normal pregnant women, and this correlates with serum hCG levels. The thyroid gland of normal pregnant women may be stimulated by hCG to secrete slightly excessive quantities of T4 and induce a slight suppression of TSH, perhaps being about 1 mU/L less than nongravid levels, but not high enough to induce overt hyperthyroidism. Maternal thyroid glands may secrete more thyroid hormone during early pregnancy in response to the thyrotropic activity of hCG that overrides the normal operation of the hypothalamic-pituitary-thyroid feedback system. Biochemical hyperthyroidism associated with hyperemesis gravidarum has been attributed to hCG. In patients with hyperemesis gravidarum, thyrotropic in serum correlated with hCG immunoreactivity, and the severity of vomiting as indicated by clinical and biochemical parameters correlated with the degree of thyroid stimulation. To understand the thyrotropic action of hCG, it is necessary to know whether hCG activates the same domain of the TSH receptor as does TSH. The identification of the molecular structure of the hCG isoform with the highest thyrotropic potency will resolve the enigma of gestational thyrotoxicosis and the hyperthyroidism associated with trophoblastic disease and hCG-producing tumors.     

Entrapment neuropathies

Relative frequency of entrapment neuropathies was studied from amongst the patients referred to an electrodiagnostic medicine laboratory for electrophysiological studies. During the study period electrophysiological procedures were done on 650 patients with various peripheral nerve disorders. The entrapment neuropathies constituted 8.5%. Carpal tunnel syndrome (CTS) was the commonest entrapment neuropathy (83.6%). Diagnosis of CTS was established in 84 Patients referred with the diagnosis of CTS. Electrophysiological tests confirmed the diagnosis of thoracic outlet syndrome in 4 (15.4%) of the 26 patients referred with this diagnosis and in 5 (19.3%) of them the diagnosis turned out to be CTS. Diagnosis of cubital tunnel syndrome was not suspected clinically in all the 3 patients, they were referred with the diagnosis of ulnar neuropathy. In both the patients with tarsal tunnel syndrome the initial diagnosis was peripheral neuropathy.     

Thyroid neoplasm of mid follicular-medullary type; an uncommon, particular and aggressive form: report of 3 cases

Mixed medullary and follicular carcinoma of the thyroid shares secretory and immunohistochemical features of both follicular and parafollicular thyroidal cells. We report three women, aged 34, 63 and 61 old with this type of tumor. Its diagnosis must be bore in mind in patients with thyroidal tumors and a histological appearance of a medullary or undifferentiated carcinoma. An early diagnosis of a mixed medullary and follicular carcinoma of the thyroid is important, considering its special treatment and negative prognosis.     

Engineering education in Europe

This article assesses the present situation of engineering education in Europe, which is attempting to come together at both academic and professional levels. It then describes the measures being adopted to provide an international flavor to the curriculum at the author's own college in France     

Dosimetry of copper-64-labeled monoclonal antibody 1A3 as determined by PET imaging of the torso

We present biodistribution and dosimetry results for 64Cu-benzyl-TETA-MAb 1A3 from 15 human subjects injected with this tracer as determined by serial PET imaging of the torso. METHODS: PET imaging was used to quantify in vivo tracer biodistribution at two time points after injection. Absorbed dosimetry calculated using MIRD-11 and the updated MIRDOSE3 was compared with estimates obtained using rat biodistribution data. RESULTS: By measuring activity concentrations in the torso, and extrapolating for the whole body using standard organ and tissue volumes, we were able to account for 93% of the injected radiopharmaceutical over a range of imaging times from 0 to 36 hr postinjection. Based on PET imaging and the MIRD-11 schema, the liver and spleen are the critical organs with average absorbed doses of 0.12 and 0.10 mGy/MBq (0.44 and 0.39 rad/mCi). The revised MIRDOSE3 scheme yields similar values for these and other organs but also results in a dose of 0.14 mGy/MBq (0.53 rad/mCi) to the heart wall. In the rat, the large intestine is the critical organ at 0.14 mGy/MBq (0.52 rad/mCi), while liver and kidneys each receive 0.11 mGy/MBq (0.41 rad/mCi). Some disparities in absorbed doses determined by these methods are evident but are a result of dissimilar biodistributions in rats and humans. For most organs, rat extrapolated values are higher than the human measurements with PET. CONCLUSION: This study shows that torso PET imaging can quantitatively measure the whole-body biodistribution of a radiopharmaceutical as long as it has relatively slow pharmacokinetics.