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Biomedical subjects

P De Nayer

Publications and source records attributed to P De Nayer.

At least 19 recordsLinked to original sources

Intense 18-fluorodeoxyglucose uptake by the thymus on PET scan does not necessarily herald recurrence of thyroid carcinoma.

This is the first report of intense fluorodeoxyglucose positron emission tomography (FDG-PET) uptake secondary to thymic hyperplasia during follow-up for thyroid carcinoma. A 36-yr-old woman underwent thyroidectomy for a papillary carcinoma measuring 4 cm in diameter. After two doses of radioiodine, thyroglobulin (Tg) remained detectable following recombinant human TSH (rhTSH) stimulation. A whole body scan (WBS) was negative. On computed tomography (CT) scan, a slightly lobulated thymus was visualized. PET scan showed intense thymic uptake. Following resection, anatomo-pathological analysis showed homogenous hyperplastic thymic gland without neoplastic cells. Two months later, under levothyroxin (L-T4) substitution, Tg was no longer detectable and PET scanning did not show any 18-FDG uptake. This observation suggests that thymic FDG uptake does not necessarily herald recurrence of thyroid carcinoma and must be interpreted with caution in such a setting. Other conditions associated with abnormal uptake by hyperplastic thymus must also be envisaged.

Adult↗

Erectile dysfunction and lower androgenicity in type 1 diabetic patients.

OBJECTIVE: To analyse the clinical characteristics and relevant hormonal profile in type 1 diabetic patients with and without ED. MATERIAL AND METHODS: Fifty one type 1 diabetic patients were studied. ED was assessed by direct interview. Chronic diabetic complications, smoking and alcohol status as well as current use of medications were recorded. Hormonal profile consisted of plasma LH, FSH, prolactin, androstenedione (Delta(4)), dehydroepiandrosterone (DHEA), DHEA-sulfate (DHEA-S), free testosterone (FT), estradiol (E(2)), sex hormone binding globulin (SHBG), dihydrotestosterone (DHT), cortisol, TSH and free thyroxine (FT(4)). RESULTS: ED was present in 24 patients (47%) (group 1), who were older (P<0.001), had a longer diabetes duration (P<0.001) and a higher systolic blood pressure (P=0.017) when compared to the subjects who did not complain (group 2). ED was positively correlated to all diabetes-related complications (P<0.02). Antidepressive drug(s) were more frequent in group 1 (P=0.007), as well as prokinetics (P=0.043) and ACE-inhibitors (P=0.010). HbA(1)c was comparable. Patients with ED had lower levels of Delta(4) (P=0.003), DHEA (P<0.001), DHEA-S (P=0.002), FT (P=0.08) while SHBG (P=0.010) and LH (P=0.022) were higher compared to group 2. Multiple logistic regression analysis showed an independent association of ED with Delta(4) (P=0.016), DHEA-S (P=0.037), SHBG (P=0.001) and insulin dose (P=0.025). There was no significant difference for all other measured hormones. CONCLUSION: ED is impressively prevalent in type 1 diabetes and is associated with age, diabetes duration, chronic complications and decreased androgens.

Age Factors↗

Expression of prostate-specific membrane antigen in transitional cell carcinoma of the bladder: prognostic value?

The expression of Prostate-specific membrane antigen (PSMA) mRNA was assessed in the normal bladder urothelium (n = 9), transitional cell carcinoma (TCC) specimens (n = 52), TCC-derived cell lines (n = 3), and preoperative blood samples from TCC patients (n = 27). Specific PSMA mRNA was found in 100% of normal and malignant tissues and two cell lines. PSMA protein was detected in normal (n = 3) and malignant tissues (n = 4). Using a PSMA-specific substrate, PSMA enzymatic activity was found in two bladder cell lines and correlated with immunostaining. Seven of the 27 TCC preoperative blood samples were positive by reverse transcription-PCR. These preliminary results, obtained on a nonrandomized cohort of patients, correlated with tumor invasion (positive RT-PCR: 0% for pT < or = 2 versus 41% for pT > or = 3) and 2-year survival rate (81% in the PSMA-negative group versus 29% in the PSMA-positive group). Although the clinical usefulness of this assay requires confirmation in larger prospective randomized trials, current preliminary results suggest that a blood-borne PSMA mRNA PCR assay may be a useful tool to predict a poor outcome in TCC patients.

Aged↗

Hormone synthesis and storage in the thyroid of human preterm and term newborns: effect of thyroxine treatment.

Iodine and thyroglobulin concentrations, as well as iodine, T3, T4 and sialic acid contents of thyroglobulin, were measured in thyroid glands collected postmortem from 42 human premature or term newborns and infants. Three groups were considered: very preterm newborns (24-32 postmenstrual weeks, < 5 days postnatal life), preterm and term newborns (34-41 postmenstrual weeks, < 5 days postnatal life) and infants (born at term, postnatal age 1-8 months). Five very preterm and seven preterm newborns received a daily dose of 10 microg/kg L-T4 for at least 3 days. Thyroid weight and sialic acid content of thyroglobulin progressed with maturation. Intrathyroidal concentrations of iodine and thyroglobulin did not increase significantly before the 42nd week of postmenstrual age. The level of thyroglobulin iodination increased during the postnatal life, except in the very preterm neonates. T4 and T3 content of thyroglobulin was directly proportional to its degree of iodination and positively related to its sialic acid content. L-T4 treatment of preterm newborns increased thyroglobulin iodination and T4-T3 content, without increasing thyroglobulin concentration in the thyroid. It was concluded that the storage of thyroglobulin and iodine in the thyroid develops around term birth. This, associated with the resulting rapid theoretical turnover of the intrathyroidal pool of T4 in Tg, could be an important factor of increased risk of neonatal hypothyroxinemia in the premature infants. The L-T4 treatment of preterm newborns does not accelerate the maturational process of the thyroid gland.

Humans↗

Long-term effects of percutaneous estradiol on bone loss and bone metabolism in postmenopausal hysterectomized women.

OBJECTIVE: To determine whether percutaneous estradiol (pE2) (1.5 mg/day) is able to counteract the postmenopausal bone loss in postmenopausal hysterectomized women, in a double-blind study versus oral estriol (E3) (2 mg/day). METHODS: The bone mineral density of the lumbar spine (LS) and of the proximal femur (PF) was measured every 3 months by dual energy X-ray absorptiometry for 2 years in 43 hysterectomized postmenopausal women (21 in the E2 group and 22 in the E3 control group), and in a subset of patients for a 3rd year. The statistical analyses were performed on Macintosh using Stat View II. RESULTS: A significant bone loss of 1.2 (0.4%)% and of 1.3 (0.3)% per year was observed in the control group, respectively at LS and at PF, versus a significant gain of 1.2 (0.5)% per year in the treated group at the LS. No significant change at PF occurred in the treated group. In the 20 patients followed up for a 3rd year on pE2, an increase of 1.2 (0.9) and 2.5 (1.4)% at LS in the 12 former active group patients and the eight formerly control patients, respectively was seen. The same trend was observed at the proximal femur. CONCLUSION: pE2 (1.5 mg E2) is able to counteract the postmenopausal bone loss in hysterectomized women, whereas E3 (2 mg/day administered orally) is unable to maintain bone mass.

Administration, Cutaneous↗

Treated plasma cell lesions of bone with MRI signs of response to treatment: unexpected pathological findings.

Two cases of treated plasma cell lesions of bone are reported for which contrast-enhanced MRI had suggested necrosis, based on lack of enhancement after gadolinium injection, and in which pathologic examinations revealed the presence of extensive viable neoplastic tissue. These cases highlight the need for cautious interpretation of contrast-enhanced MRI signs of response to treatment and inactivity of lesions in the setting of plasma cell neoplasms.

Adult↗

Simple bone cysts treated with aspiration and a single bone marrow injection. A preliminary report.

The results of a single percutaneous aspiration and injection of marrow into active, simple bone cysts are reported in 8 cases. Slow regression of the cyst was consistently observed except in one lesion in the distal tibia. All the patients have been free of symptoms after this treatment after a mean follow up of 31 months. The evolution of the cysts was monitored by a cyst index, cyst diameter measurements and computer assisted densitometric image analysis of serial radiographs.

Bone Cysts↗

Expression of prostate-specific antigen and prostate-specific membrane antigen transcripts in blood cells: implications for the detection of hematogenous prostate cells and standardization.

Circulating prostate cells can be detected in cancer patients by using reverse transcriptase-PCR (RT-PCR) assay for prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSM) mRNA. A quality-control study involving a conventional RT-PCR assay was performed and, surprisingly, detected both transcripts in many negative control cell lines and in normal blood samples. The existence of an illegitimate transcription of the PSA and PSM genes was evidenced by sequence analysis of several PSM and PSA-PCR products. Sequencing indeed demonstrated the presence of a PSA or PSM polymorphism in some but not all the cell lines and patient samples, as well as a heterozygous mutation (G to A; Asp to Asn) in the Jurkat cell line. Moreover, the amount of PSA transcript in MCF-7, a PSA-negative breast line, increased after incubation with cycloheximide. Interestingly, the frequency of positivity was as high as 12% in male samples if only tested once, but dropped to 3% upon multiple testing of the same cDNA. This highlights the stochastic effects in RT-PCR results at high sensitivity, hence the importance of repetitive testing in clinical samples. Decreasing the number of cycles avoided the amplification of illegitimate transcripts but also affected the limit of detection, as evidenced with PSA and PSM cDNA containing plasmids, mixing of LNCap with normal blood samples, and the PSA-PSM-negative K562 cell line. The current data raise the need for a multicentric standardization of the RT-PCR methodology used to amplify PSA and PSM transcripts.

Adult↗

The thyrotrophic role of human chorionic gonadotrophin (hCG) in the early stages of twin (versus single) pregnancies.

OBJECTIVE: Human chorionic gonadotrophin (hCG) is known to possess thyroid-stimulating activity. The aim of the present study was to assess the role of hCG in stimulating the maternal thyroid gland in the early stages of normal gestation. STUDY DESIGN: Thirty euthyroid healthy women were investigated prospectively. In each, conception had been assisted by in vitro fertilization techniques, which allowed for the precise determination of gestational age. Women were subdivided into single (n = 17) and twin (n = 13) pregnancies. Serum intact hCG and its free alpha and beta subunits, TSH and free T4 concentrations were measured at 6, 8, 9, 10, 11, 15, 19, 22 and 32 weeks. RESULTS: In twin pregnancies compared with single pregnancies, peak hCG concentrations (9-11 weeks) were significantly higher (mean +/- SE 171,000 +/- 12,500 vs 65,500 +/- 7600 U/l; P < 0.001), and also much more prolonged. Human CG concentrations above 75,000 U/l lasted for less than 1 week in single, compared with up to 6 weeks in twin pregnancies. Free beta-hCG subunit concentrations paralleled those of intact hCG in both groups. The ratios of free beta-hCG subunit/total hCG were similar in single and twin pregnancies, and did not vary with gestation time. Concerning thyroid function, twin pregnancy was more frequently associated with a lowering of TSH, which was also more profound than in single pregnancies. Furthermore, while free T4 levels remained normal in single pregnancies, they were transiently supranormal (up to 52 pmol/l) in four twin pregnancies. CONCLUSION: In twin pregnancies the placenta produces larger amounts of hCG for a prolonged period of time than in single pregnancies. Both the amplitude and duration of hCG production (i.e. the global exposure of the thyroid gland to hCG) are responsible for increased thyroidal stimulation, leading more frequently to increased free T4 and suppressed TSH levels. The results emphasize the role of hCG in stimulating maternal thyroid function in the first trimester of pregnancy. Even though the production of a variant hCG molecule with potent thyrotrophic activity cannot be excluded, this hypothesis is not required to explain the data. Clinicians should be aware of the frequent occurrence of significant but transient biochemical hyperthyroidism associated with hCG stimulation in the early stages of gestation, particularly in twin pregnancies.

Chorionic Gonadotropin↗

Induced healing of aneurysmal bone cysts by demineralized bone particles. A report of two cases.

Two cases of induced healing of aneurysmal bone cyst (ABC) following intralesional implantation of a bone paste made of autogeneic bone marrow and allogeneic bone powder are reported. The calcaneum in one case and the superior pubic ramus in the other were blown out by an ABC and would have required extensive surgery. Via a minimal exposure, the cyst was partially evacuated and filled with an admixture of a partially demineralized bone particles with bone marrow. Ossification of the peripheral shell was the first sign of healing and was observed within the first 3 postoperative months. Successful healing was observed in both cases. The rationale underlying this intralesional treatment was that the bone grafting material might reverse ABC expansion by promoting ossification through a bone induction mechanism. The concept of this treatment was to retain the ABC tissue, using its own intrinsic osteogenic potential to promote healing. By triggering intralesional new bone formation, the bone paste represented an effective means to reverse the expanding phase of ABC. The particulated bone allograft was easy to handle and to introduced in an irregular cavity. Moreover, as a complete cyst evacuation was not required, a minimal surgical approach could be used so that the risks and morbidity associated with an extensive approach were reduced. Its use is of particular interest in poorly accessible areas like the pelvis and spine.

Adolescent↗

Free to total prostate-specific antigen (PSA) ratio improves the discrimination between prostate cancer and benign prostatic hyperplasia (BPH) in the diagnostic gray zone of 1.8 to 10 ng/mL total PSA.

OBJECTIVES: Improved discrimination between prostate cancer (PC) and benign prostatic hyperplasia (BPH) is clearly needed. Our aim in this study was to evaluate whether the free to total prostate-specific antigen (PSA) ratio would be useful in the gray zone of 1.8-10 ng/mL total PSA range. METHODS: In a consecutive series of 435 clinic patients referred for prostate evaluation, 308 had a total PSA < 10 ng/mL (92 had PC and 216 BPH). Free and total PSA were measured, and the free to total PSA ratio calculated. RESULTS: Total PSA values were significantly different between the two groups. For the 200 patients with a total PSA < 6 ng/mL, no significant difference in total PSA values were seen (P = 0.411), whereas free to total PSA ratios remained statistically different (P < 0.001). Receiver operating characteristic (ROC) curve analysis comparing the performances of total PSA over the ratio of free to total PSA showed a clear advantage for the ratio at all sensitivity levels. CONCLUSIONS: These data demonstrate that in a significant number (n = 308) of prostatic patients in the diagnostic gray zone of 1.8-10 ng/mL total PSA, the routine use of free to total PSA might be advantageous in discriminating between cancer and benign hyperplasia. This advantage remained for total PSA < 4 ng/mL. Further study is warranted to confirm these findings in an unselected population.

Aged↗

Evaluation of a second-generation thyrotropin automated immunoassay.

We evaluated the analytical performance of the Vista automated immunoassay system for human thyrotropin determination. The operating characteristics as well as the analytical performance were assessed. The Vista human thyrotropin immunoassay showed a minimal detection limit of 0.08 mU/l and a functional sensitivity of 0.12 mU/l. The system meets the criteria for second-generation human thyrotropin assays.

Automation↗

Free to total prostate-specific antigen (PSA) ratio is superior to total-PSA in differentiating benign prostate hypertrophy from prostate cancer.

BACKGROUND: Serum prostate-specific antigen (PSA) exists in different molecular forms, and their respective concentration has been proposed as a useful tool to improve discrimination between benign prostatic hypertrophy (BPH) and prostate cancer (PC). METHODS: The relevance of the free to total PSA ratio was prospectively studied in a selected urology clinic population of 420 patients. Total serum PSA ranged from 2.1 to 30 ng/ml; 154 had PC and 266 had BPH. RESULTS: Receiver operating characteristic (ROC) curves were constructed for the total population (total-PSA range from 2.1 to 30 ng/ml) and for the diagnostic gray zone of 2.1-10 ng/ml. For the two groups, the free to total PSA ratio had a higher specificity than total-PSA for all sensitivity levels. Cut-off values were found to, vary with prostate weight. CONCLUSIONS: Although free to total PSA ratio demonstrated better performances than total-PSA, its use in screening appears problematic, due to the low prevalence of prostate cancer.

Aged↗

A randomized trial for the treatment of mild iodine deficiency during pregnancy: maternal and neonatal effects.

One hundred and eighty euthyroid pregnant women were selected at the end of the first trimester of gestation on the basis of biochemical criteria of excessive thyroid stimulation, defined as supranormal serum thyroglobulin (TG > 20 micrograms/L) associated with a low normal free T4 index (< 1.23) and/or an increased T3/T4 ratio (> 25 x 10(-3)). Women were randomized in a double blind protocol into three groups and treated until term with a placebo, 100 micrograms potassium iodide (KI)/day, or 100 micrograms iodide plus 100 micrograms L-T4/day. Parameters of thyroid function, urinary iodine excretion, and thyroid volume were monitored sequentially. Neonatal thyroid parameters, including thyroid volume by echography, were also assessed in the newborns from mothers of the three groups. In women receiving a placebo, the indices of excessive thyroid stimulation worsened as gestation progressed, with low free T4 levels, markedly increased serum TG and T3/T4 ratio. Serum TSH doubled, on the average, and was supranormal in 20% of the cases at term. Urinary iodine excretion levels were low, around 30 micrograms/L at term. The thyroid volume increased, on the average, by 30%, and 16% of the women developed a goiter, confirming the goitrogenic stimulus associated with pregnancy. Moreover, the newborns of these mothers had significantly larger thyroid volumes at birth as well as elevated serum TG levels. In both groups of women receiving an active treatment, the alterations in thyroid function associated with pregnancy were markedly improved. The increase in serum TSH was almost suppressed, serum TG decreased significantly, and changes in thyroid volume were minimized (group receiving KI) or almost suppressed (group receiving KI combined with L-T4). Moreover, in the newborns of the mothers in the two groups receiving an active treatment, serum TG was significantly lower, and thyroid volume at birth was normal. The effects of therapy were clearly more rapid and more marked in the group receiving a combination of T4 and KI than in the women receiving KI alone. The differences could be partly attributed to the slightly higher amount of iodine received by women in the combined treatment. However, the main benefits of the combined treatment were almost certainly attributable to the hormonal effects of the addition of L-T4. Furthermore, the study demonstrated that the administration of T4 did not hamper the beneficial effect of iodine supplementation. In conclusion, the present work emphasizes the potential risk of goitrogenic stimulation in both mother and newborn in the presence of mild iodine deficiency.(ABSTRACT TRUNCATED AT 400 WORDS)

Double-Blind Method↗

Serum levels of intact human chorionic gonadotropin (HCG) and its free alpha and beta subunits, in relation to maternal thyroid stimulation during normal pregnancy.

The main objective of the present study was to present additional evidence of the potentially important thyrotropic role of hCG to regulate the maternal thyroid gland during normal pregnancy. Sequential determinations (first and last trimesters) of intact hCG, free alpha and beta-hCG subunits concentrations (using monoclonal IRMAs), and assessment of parameters of thyroid function and thyroid volume were carried out in 62 pregnant women who exhibited during the first trimester of gestation low TSH levels (< or = 0.20 mU/L), and compared to 276 pregnant women with normal TSH levels. The prevalence of having low serum TSH represented 18% of all pregnancies, with almost one half of cases who transiently had undetectable TSH levels. Lowering of TSH was associated with high hCG levels, and occurred primarily during the first trimester. About 10% of women with low TSH presented transient gestational thyrotoxicosis, frequently associated with vomiting. In comparison to control subjects, women with a suppressed serum TSH had significantly and markedly higher intact hCG and free beta-hCG subunit concentrations. The results suggest that TSH reduction may result from a relative oversecretion of both intact hCG and free beta-hCG subunits, compatible with three hypotheses: a) transient overexpression of the beta-hCG gene, leading to enhanced production of hCG heterodimer; b) increased glycosylation of circulating hCG, with in turn a prolonged half life; c) larger syncytiotrophoblast mass with increased hCG production.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗