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Biomedical subjects

Catherine Cormier

Publications and source records attributed to Catherine Cormier.

13 recordsLinked to original sources

Unexpected serum parathyroid hormone profiles in some patients with primary hyperparathyroidism.

BACKGROUND: Third-generation parathyroid hormone (PTH) assays have been reported to measure only intact PTH(1-84), in contrast to second-generation assays, which also detect PTH(7-84) fragments. Higher PTH measurements were observed with third- than with second-generation PTH assays in a few patients with either severe primary hyperparathyroidism or parathyroid carcinoma. METHODS: We analyzed biological data [second- and third-generation PTH assays, 25-hydroxyvitamin D (25-OHD), calcium, and phosphate concentrations] obtained before and after surgery for 2 groups of patients selected from a large series of consecutive patients with primary hyperparathyroidism (PHPT): 7 female patients with surgically and histologically confirmed PHPT (group 1) and a matched group (group 2). RESULTS: For group 1 but not group 2, PTH concentrations measured by third-generation PTH assays before surgery were higher than those measured by the second-generation assays. Circulating 25-OHD, calcium, and phosphate concentrations were similar in both groups. In addition, PTH values measured with the third-generation PTH assays in group 1 decreased after surgery. CONCLUSIONS: Our results confirm that third-generation PTH assays do not measure only PTH(1-84). The frequency of this unexpected finding of markedly lower PTH concentrations than previously reported was approximately 5% in patients with PHPT without malignancy. We do not know whether the presence of this unexpected profile is predictive of malignancy.

Adult↗

Evaluating vitamin D status. Implications for preventing and managing osteoporosis and other chronic diseases.

Recent studies have added new dimensions to the fund of knowledge on vitamin D. In addition to the classic role of vitamin D in preventing rickets and osteomalacia, a preventive effect against osteoporotic fractures has been convincingly established, and abundant evidence suggests a role in preventing malignancies and autoimmune diseases. Serum 25-OH-vitamin D assay is a simple test for evaluating vitamin D status. However, recent review articles indicate that current reference ranges for serum 25-OH-vitamin D are too low. An appropriate lower normal limit may be between 50-100 nmol/l (20-40 ng/ml). Standard supplement dosages may fail to provide concentrations above this range.

Fractures, Bone↗

Violent sex offenses: how are they best measured from official records?

In the United States, sexually violent predator (SVP) commitment statutes generally require assessment of an offender's risk of subsequent sexual violence. Current actuarial methods for predicting sexual reoffending were actually designed to predict something else-charges or convictions for offenses deemed sexual based on information obtained from police "rapsheets" alone. This study examined the referral and past offenses of 177 sex offenders. Results showed that police rapsheets (and data based on them) underestimated the number and severity of sexually motivated violent offenses for which sex offenders were actually apprehended. Rapsheet violent offenses seemed a more accurate index of the conduct addressed by SVP legislation than were rapsheet sex offenses. We suggest that, when evaluating sex offenders for SVP status, actuarial instruments designed to predict violent recidivism (as measured by rapsheet violent reoffenses) might be preferable to those designed to predict sexual recidivism (as measured by rapsheet sexual reoffenses).

Adult↗

[Parathyroid hormone in osteoporosis].

Continuous parathyroid hormone secretion caused by primary hyperparathyroidism contributes to osteoporosis. Laboratory tests, in particular the intact PTH assay, make the diagnosis of hyperparathyroidism certain. In hyperparathyroidism, the bone damage primarily affects the cortical bone, especially the proximal one-third of the radius and to a lesser degree the upper femur; the lumbar spine is affected more rarely. Intermittent administration of parathyroid hormone stimulates bone formation and is useful in treating osteoporosis. Subcutaneous injections once daily administration of PTH stimulates bone formation on the surface of trabecular and cortical bone, by preferential stimulation of osteoblastic more than osteoclastic activity.

Femur↗

[Malnutrition and low bone mineralisation in adults with cystic fibrosis].

With striking advances in its treatment, cystic fibrosis has turned into an adult condition. Respiratory complications and exocrine pancreatic insufficiency work together to cause malnutrition which reduces survival. The management of low bone mineralization (osteoporosis, osteomalacia) is necessary not only to limit growth failure in younger patients but still in adulthood. We received the literature on malnutrition and bone diseases in adults with cystic fibrosis.

Adult↗

Practical considerations in PTH testing.

New knowledge concerning PTH biology have accumulated during the past few years. The finding that the so-called "intact" PTH assays measure a "non-1-84" PTH fragment in addition to full-length PTH has led to the development of new assays. These new assays, which were initially thought to measure 1-84 PTH only, have been shown to recognize also another PTH species called "amino-PTH". As the various names given to the different assay methods are highly confusing, there is a need for a simplified nomenclature. A simple way would be to identify the older "intact" PTH assays as second-generation assays and the new assays (Whole, CAP, BioIntact) as third-generation assays. Although of considerable potential interest for the comprehension of PTH physiology, the third-generation PTH assays have not yet proved to be superior to the second-generation assays in clinical practice. There is thus currently no recommendation to switch from the second-generation to the third-generation assays in clinical practice, or to use a ratio derived from the concommitent measurement of PTH with both assay-generation. Because second- and third-generation PTH assays are usually highly correlated, significant differences in the clinical information provided by these methods are unlikely. However, our opinion is that more definitive bone biopsy studies in dialyzed patients selected according to their bone- and calcium-related treatment are still needed to reach a consensus. Finally, we have proposed that PTH reference values should be established in healthy subjects with a normal vitamin D status. This supposes that 25OHD is measured in the reference population beforehand, and that the subjects with vitamin D insufficiency are eliminated from the reference group. Although more complicated than the usual way to establish normative data, we have shown that it decreases the upper limit of normal by 25-35%, enhancing thus the diagnostic sensitivity for hyperparathyroidism without a decrease in specificity.

Chronic Kidney Disease-Mineral and Bone Disorder↗

Third- or second-generation parathyroid hormone assays: a remaining debate in the diagnosis of primary hyperparathyroidism.

BACKGROUND: Since the demonstration that the second-generation PTH assays, also called intact PTH assays, recognize a non-1-84 PTH fragment in addition to the intact 1-84 PTH, new PTH assays defined as third-generation assays have been commercialized. Two previous studies aimed at evaluating whether these third-generation PTH assays improved the diagnostic sensitivity for primary hyperparathyroidism (PHPT), but they yielded opposite results. METHODS: In the present study we compared two second-generation PTH assays (the total intact PTH assay from Scantibodies Laboratory, Inc., and the intact PTH assay from Nichols Institute Diagnostics) with two third-generation assays (the cyclase-activating PTH assay also from Scantibodies Laboratory and the bio-intact PTH assay from Nichols Institute) in a series of 145 consecutive PHPT patients operated in our endocrine surgery department over a 10-month period. A group of 74 healthy subjects served as controls. RESULTS: The diagnostic sensitivities for PHPT of the total intact, the intact, the cyclase-activating, and the bio-intact assays were 93.8%, 97.3%, 84.2%, and 89.0%, respectively, with 95% confidence intervals in the control groups of 10-46, 11-60, 8.4-34, and 9-41 ng/liter, respectively. CONCLUSION: Our findings demonstrate that the diagnostic sensitivities of second- and third-generation PTH assays are similar. Third-generation PTH assays do not therefore improve the diagnosis of elevated serum PTH levels in PHPT, although there are numerical differences among the values.

Aged↗

[Ossification of the common posterior longitudinal ligament of the spine and spinal cord compression in a patient from Senegal].

INTRODUCTION: Ossification of the posterior longitudinal ligament of the spine is a rare cause medullar compression. OBSERVATION: A 50-year-old man from Senegal was referred with recent-onset mechanical lumbar pain with proximal motor deficiency of the lower limbs and somatosensory disorders. Magnetic resonance imaging revealed layered medullar compression, due to anterior cervical and mixed anterior and posterior thoracic ossification. Corticosteroid treatment led to regression of the pain and neurological disorders within a few days. DISCUSSION: This case report of ossification of the posterior longitudinal ligament of the spine appears to be an idiopathic form corresponding to the "Japanese disease" initially thought to be limited to that population.

Anti-Inflammatory Agents↗

Surgery versus medical follow-up in patients with asymptomatic primary hyperparathyroidism: a decision analysis.

OBJECTIVES: To examine the cost-effectiveness of strategies for management of primary asymptomatic hyperparathyroidism: surgical strategies and medical follow-up versus surgery. DESIGN: We used a Markov state-transition decision-analytic model for an hypothetical cohort of 55-year-old women to compare with a lifetime horizon costs and effectiveness of bilateral neck exploration (BNE), unilateral neck exploration (UNE), video-assisted parathyroidectomy (VAP) and lifelong medical follow-up shifting for either BNE or UNE in case of disease progression. METHODS: Data on localization tests, complications and treatment efficacies were derived from a systematic review of the literature. Outcomes were expressed as quality-adjusted life years (QALY). Costs (2002 Euro) discounted at 3% yearly were estimated from the health care system perspective. RESULTS: In the base-case analysis, VAP strategy (VAPS) was the most effective and BNE strategy (BNES) was the least costly. UNE strategy (UNES) had an incremental cost-effectiveness ratio of 2688 Euro/QALY versus BNES and VAPS of 17,250 Euro/QALY in comparison with UNES. Surgical management was more effective than medical follow-up with acceptable incremental cost-effectiveness ratios. VAPS became less effective than UNES over 71 years. Differences between UNES and VAPS were sensitive to success and complication rates, quality-of-life weights and procedural costs. Medical follow-up strategies became the most effective if quality-of-life weight for this condition was higher than 0.99. CONCLUSIONS: Surgery is more effective than medical follow-up at a reasonable cost and can be preferred except in patients choosing medical follow-up. Minimally invasive surgery is cost-effective compared to the traditional surgical approach.

Cost-Benefit Analysis↗

Assay-specific decision limits for two new automated parathyroid hormone and 25-hydroxyvitamin D assays.

BACKGROUND: The recent development of nonradioactive automated assays for serum parathyroid hormone (PTH) and 25-hydroxyvitamin D (25OHD) has made measurement of these two hormones possible in many laboratories. In this study, we compared two new assays for PTH and 25OHD adapted on an automated analyzer, the LIAISON, with two manual immunoassays used worldwide. METHODS: We studied 228 osteoporotic patients, 927 healthy individuals, 38 patients with primary hyperparathyroidism, and 167 hemodialyzed patients. Serum PTH was measured with the Allegro and the LIAISON assays, and 25OHD was measured with DiaSorin RIA and the LIAISON assay. Regression analysis was used to calculate decision thresholds for the LIAISON assays that were equivalent to those of the Allegro PTH and DiaSorin 25OHD assays. RESULTS: The 25OHD concentrations obtained with the LIAISON assay and the RIA in osteoporotic patients were well correlated (r = 0.83; P <0.001). Regression and Bland-Altman analyses suggested that the LIAISON 25OHD assay reads lower than the DiaSorin RIA at low concentrations but higher at high concentrations. However, the cutoff (50 nmol/L) used in our laboratories to define vitamin D insufficiency with the DiaSorin RIA is applicable to the LIAISON 25OHD assay. In 927 healthy individuals, the 3rd-97th percentile intervals were 3-80 ng/L and 13-151 nmol/L for the LIAISON PTH and 25OHD concentrations, respectively. However, 506 individuals (54.6%) were vitamin D-insufficient; we therefore considered only the 421 individuals with a LIAISON 25OHD >50 nmol/L as eligible for the reference population for the LIAISON PTH assay. In this group, the 3rd-97th percentile interval for LIAISON PTH was 3-51 ng/L. Considering upper reference limits of 46 and 51 ng/L for the Allegro and LIAISON assays, respectively, the frequency of above-normal PTH concentrations in patients with primary hyperparathyroidism was similar in both assays. Regression analysis between serum PTH measured by the Allegro and LIAISON assays in 167 hemodialyzed patients and the corresponding Bland-Altman analysis of these data suggest that the LIAISON PTH assay tends to read higher than the Allegro assay at low concentrations but lower at high concentrations (>300 ng/L). CONCLUSIONS: Because clinical decision limits for both PTH and 25OHD should be assay specific, we propose equivalences between these assays and two manual assays used worldwide. These assay-specific decision limits should help potential users of the LIAISON PTH and 25OHD assays.

Autoanalysis↗

Primary hyperparathyroidism and osteoporosis in 2004.

In patients with primary hyperparathyroidism, a definite diagnosis is the first step in the management strategy and relies on appropriately selected and carefully interpreted laboratory tests. Parathyroid hormone assays are being increasingly performed as part of the routine evaluation of osteoporosis. In this setting, laboratory tests are often consistent with primary hyperparathyroidism but should be interpreted with caution. Bone mineral density measurements are useful for assessing the impact of primary hyperparathyroidism. The recommended bone mineral density cutoffs for selecting patients requiring parathyroidectomy were lowered in 2003, and the number of surgically treated patients has increased as a result. Parathyroidectomy remains the treatment of choice given the low mortality associated with this procedure and the absence of pharmacological alternatives suitable for long-term use.

Bone Density↗

Stable expression of the avian retroviral oncoprotein v-Rel in avian, mouse, and dog cell lines.

Overexpression of the retroviral oncoprotein v-Rel can rapidly transform and immortalize a variety of avian cells in culture. However, mammalian models for v-Rel-mediated oncogenesis have been compromised by the fact that high-level expression of v-Rel has been reported to be toxic in many mammalian cell types, including mouse 3T3 cells, Rat-1 cells, and mouse bone marrow cells. In this article, we demonstrate that 3T3 cells can support expression of v-Rel for at least 24 days when infected with a mouse stem cell virus (MSCV) retroviral vector containing v-rel. In retrovirus-infected 3T3 cells, v-Rel is located in the nucleus and can bind to DNA, but does not transform the cells. On the other hand, 3T3 and Rat-2 cells do not express v-Rel after stable transfection with a pcDNA-based v-Rel expression vector. We also show that infection of the IL3-dependent mouse B cell line BaF3 with the MSCV-v-rel vector results in expression of v-Rel, but does not convert these cells to growth factor independence. In contrast to 3T3 cells, the dog osteosarcoma D17 cell line can support a high level of v-Rel expression, after either transfection or infection with a retroviral vector. That is, v-Rel can be stably expressed as a nuclear, DNA-binding protein in D17 cells to approximately the same level as in chicken embryo fibroblasts. These results suggest that the restriction to v-Rel expression in rodent fibroblasts is generally absent in D17 cells and that the type of v-rel expression vector determines whether 3T3 cells can support stable expression of v-Rel. The findings reported here are an essential first step in the development of mammalian systems to study Rel-mediated oncogenesis.

3T3 Cells↗

The use in clinical practice of parathyroid hormone normative values established in vitamin D-sufficient subjects.

We have found recently that excluding subjects with low serum 25OHD has a significant impact on the PTH reference range (10-46 ng/liter instead of 10-65 ng/liter with the same assay). However, before being used routinely, this new range had to be clinically validated. We thus reviewed the chart of 708 consecutive osteopenic patients who were referred to our unit for a biological exploration in search of secondary causes for their low bone mass. They were classified into two groups. Group 1 (n = 360) included the patients for whom no reasons for high PTH were found after examination of their chart. Group 2 (n = 348) included patients with one of the following potential reasons for an increased PTH concentration: hyper- or hypocalcemia, normocalcemic primary hyperparathyroidism (PHPT), renal hypercalciuria, vitamin D insufficiency, chronic renal failure, use of bisphosphonates, and any chronic disease known to potentially alter calcium metabolism. Among the 360 group 1 patients, 15 (4.2%) had a serum PTH level more than 46 ng/liter, which is not different from the theoretical rate of 3% of normal subjects whose serum PTH may be above the 97th centile of the reference (chi(2) = 2.8; NS). Forty-two group 2 patients had a surgically proven PHPT. Among these, serum PTH was </=65 ng/liter in 17 (40.5%) and </=46 ng/liter in 5 (12%). In conclusion, our proposed PTH reference range allows to identify fewer patients with mild surgically proven PHPT who have a normal serum PTH concentration, without inducing an increase in the rate of falsely high PTH.

Adult↗